U.S. patent application number 16/903219 was filed with the patent office on 2020-10-22 for apparatus and method for indicating treatment site locations for phototherapy to the brain.
The applicant listed for this patent is Pthera LLC. Invention is credited to Luis De Taboada, Jackson Streeter.
Application Number | 20200330786 16/903219 |
Document ID | / |
Family ID | 1000004932487 |
Filed Date | 2020-10-22 |
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United States Patent
Application |
20200330786 |
Kind Code |
A1 |
De Taboada; Luis ; et
al. |
October 22, 2020 |
Apparatus and Method for Indicating Treatment Site Locations for
Phototherapy to the Brain
Abstract
An apparatus and method for indicating treatment site locations
for phototherapy to the brain are disclosed. In some embodiments,
the apparatus is a headpiece wearable by a patient. The headpiece
includes a body adapted to be worn over at least a portion of the
patient's scalp and a plurality of position indicators
corresponding to a plurality of treatment site locations at the
patient's scalp where a light source is to be sequentially
positioned such that light from the light source is sequentially
applied to irradiate at least a portion of the patient's brain. At
least one of the position indicators includes an optically
transmissive portion having an area of at least 1 cm.sup.2 through
which the light propagates.
Inventors: |
De Taboada; Luis; (Carlsbad,
CA) ; Streeter; Jackson; (Newberry, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Pthera LLC |
Newark |
DE |
US |
|
|
Family ID: |
1000004932487 |
Appl. No.: |
16/903219 |
Filed: |
June 16, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12703653 |
Feb 10, 2010 |
10695579 |
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16903219 |
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12403824 |
Mar 13, 2009 |
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12703653 |
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12389294 |
Feb 19, 2009 |
10357662 |
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12403824 |
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61037668 |
Mar 18, 2008 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 2005/067 20130101;
A61N 2005/063 20130101; A61N 2005/0647 20130101; A61N 5/0613
20130101; A61N 2005/0629 20130101 |
International
Class: |
A61N 5/06 20060101
A61N005/06 |
Claims
1. An apparatus wearable by a patient, the apparatus comprising: a
body adapted to be worn over at least a portion of a head of the
patient; and a plurality of indicators on the body that identify,
while the body is being worn by the patient, a plurality of
treatment site locations on the head where a light source is to be
positioned and activated such that light from the light source is
applied to irradiate at least a portion of a brain of the patient,
wherein at least one of the indicators comprises an optically
transmissive portion having an area of at least 1 cm.sup.2 through
which the light propagates.
2. The apparatus of claim 1, wherein the optically transmissive
portion has an area in a range between 1 cm.sup.2 and 20
cm.sup.2.
3. (canceled)
4. The apparatus of claim 1, wherein the optically transmissive
portion comprises an aperture through the body.
5. The apparatus of claim 1, wherein adjacent treatment site
locations of the plurality of treatment site locations have areas
which do not overlap one another.
6. The apparatus of claim 1, wherein adjacent treatment site
locations of the plurality of treatment site locations have
perimeters which are spaced from one another.
7. (canceled)
8. The apparatus of claim 1, wherein the body comprises a
stretchable material generally conforming to the head.
9. (canceled)
10. The apparatus of claim 1, wherein the plurality of indicators
are configured to guide an operator to irradiate the head at the
corresponding treatment site locations sequentially one at a time
in a predetermined order.
11. The apparatus of claim 10, wherein the predetermined order is
configured to reduce temperature increases at the head which would
result from sequentially irradiating treatment site locations in
proximity to one another.
12.-33. (canceled)
34. The apparatus of claim 1, wherein the indicators are connected
to each other by a string, tether, elastic, or adhesive.
35. The apparatus of claim 1, wherein the body comprises a first
mating portion configured to releasably mate with a second
complimentary mating portion of the light source or a light
delivery apparatus.
36. The apparatus of claim 35, wherein the first mating portion
comprises a rim bordering the outer perimeter of the plurality of
indicators.
37. The apparatus of claim 36, wherein the plurality of indicators
comprises a pressure sensor positioned around the rim, the pressure
sensor configured to detect a pressure between the first mating
portion and the second mating portion.
38. The apparatus of claim 1, further comprising a retaining member
extending between a first side of the apparatus and a second side
of the apparatus, the retaining member configured to secure the
apparatus to the head of the patient.
39. The apparatus of claim 1, wherein the body comprises a material
that has a high thermal conductivity configured to reduce
temperature increases to the head or skin of the patient at
locations surrounding the plurality of indicators.
40. The apparatus of claim 1, wherein the body has a thickness
between 1 millimeter (mm) and 10 mm.
41. The apparatus of claim 1, further comprising a plurality of
labels substantially covering the plurality of indicators, wherein
at least a portion of each label comprises a portion of the body
configured to be removed from the apparatus when the treatment site
location has been irradiated.
42. The apparatus of claim 1, wherein the optically transmissive
portion comprises a hollow compartment or cavity that does not
extend completely through the plurality of indicators to the
surface of the head.
43. The apparatus of claim 1, wherein the optically transmissive
portion comprises a film.
44. The apparatus of claim 1, wherein the plurality of indicators
comprises a layer of a photochromic material, the layer of the
photochromic material being able to change its color upon
irradiation by the light source.
45. The apparatus of claim 1, wherein the body comprises coupling
joints connecting the plurality of indicators.
Description
CLAIM OF PRIORITY
[0001] This application is a continuation-in-part application of
U.S. patent application Ser. No. 11/385,980, filed Mar. 21, 2006,
which claims the benefit of U.S. Provisional Application No.
60/763,261, filed Jan. 30, 2006. This application is also a
continuation-in-part application of U.S. patent application Ser.
No. 12/403,824, filed Mar. 13, 2009, which is a
continuation-in-part application of U.S. patent application Ser.
No. 12/389,294, filed Feb. 19, 2009, and which claims the benefit
of priority to U.S. Provisional Application No. 61/037,668, filed
Mar. 18, 2008. The entire content of each of these applications is
hereby expressly incorporated herein by reference.
BACKGROUND OF THE INVENTION
Field of the Invention
[0002] The present invention relates in general to phototherapy,
and more particularly, to novel apparatuses and methods for
phototherapy of brain tissue.
Description of the Related Art
[0003] There are numerous neurologic conditions, such as
neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's
disease, amyotrophic lateral sclerosis), Huntington's disease,
demyelinating diseases (e.g., multiple sclerosis), cranial nerve
palsies, traumatic brain injury, stroke, depression, and spinal
cord injury which could possibly benefit from application of
phototherapy. Most of these conditions cause significant morbidity
and mortality and involve tremendous burden to society, families
and caregivers. Many neurologic conditions have no currently
available effective therapies or the therapies that are available
are not adequate to restore functional recovery, sustain quality of
life, or halt disease progression.
[0004] One example of a neurologic condition that remains a major
unmet medical need is stroke, also called cerebrovascular accident
(CVA). Stroke is caused by a sudden disruption of blood flow to a
discrete area of the brain that is brought on by the lodging of a
clot in an artery supplying blood to an area of the brain (called
an ischemic stroke), or by a cerebral hemorrhage due to a ruptured
aneurysm or a burst artery (called a hemorrhagic stroke). There are
over 750.000 stroke victims per year in the United States, and
approximately 85% of all strokes are ischemic and 15% are
hemorrhagic. The consequence of stroke is a loss of function in the
affected brain region and concomitant loss of bodily function in
areas of the body controlled by the affected brain region.
Depending upon the extent and location of the primary insult in the
brain, loss of function varies greatly from mild or severe, and may
be temporary or permanent. Lifestyle factors such as smoking, diet,
level of physical activity and high cholesterol increase the risk
of stroke, and thus stroke is a major cause of human suffering in
developed nations. Stroke is the third leading cause of death in
most developed nations, including the United States.
[0005] Stroke treatment is often restricted to providing basic life
support at the time of the stroke, followed by rehabilitation.
Currently, the only FDA-cleared treatment of ischemic stroke
involves thrombolytic therapy using tissue plasminogen activator
(tPA). However, tPA can only be used within three hours of stroke
onset and has several contraindications, therefore, only a small
percentage of stroke victims receive this drug.
[0006] Traumatic brain injury (TBI) occurs when a sudden physical
trauma (e.g., crush or compression injury in the central nervous
system, including a crush or compression injury of the brain,
spinal cord, nerves or retina, or any acute injury or insult
producing cell death) causes damage to the head. For example, a
sudden and/or violent blow to the head or an object piercing the
skull and entering brain tissue can result in TBI. The extent of
damage to the brain can be severe, however even mild and moderate
TBI has been associated with neurological sequelae that can be long
lasting. Development of neurodegenerative conditions has been
associated with TBI. TBI can result in a sudden disruption of blood
flow to a discrete area of the brain. The consequence of stroke or
TBI can be a loss of function in the affected brain region and
concomitant loss of bodily function in areas of the body controlled
by the affected brain region. Depending upon the extent and
location of the primary insult in the brain, loss of function
varies greatly from mild or severe, and may be temporary or
permanent.
[0007] A high level of interest and clinical need remains in
finding new and improved therapeutic interventions for treatment of
stroke and other neurologic conditions that continue to devastate
millions of lives each year and where few effective therapies
exist.
SUMMARY OF THE INVENTION
[0008] In certain embodiments, an apparatus is wearable by a
patient for treating the patient's brain. The apparatus comprises a
body adapted to be worn over at least a portion of the patient's
scalp. The apparatus further comprises a plurality of indicators
corresponding to a plurality of treatment site locations at the
patient's scalp where a light source is to be sequentially
positioned such that light from the light source is sequentially
applied to irradiate at least a portion of the patient's brain. At
least one of the indicators comprises an optically transmissive
portion of the body having an area of at least 1 cm.sup.2 through
which the light propagates.
[0009] In certain embodiments, an apparatus is wearable by a
patient for treating the patient's brain. The apparatus comprises
means for identifying a plurality of treatment site locations at
the patient's scalp where light is to be applied to irradiate at
least a portion of the patient's brain. The apparatus further
comprises means for indicating to an operator a sequential order
for irradiating the treatment site locations.
[0010] In certain embodiments, a method of treating a patient's
brain comprises noninvasively irradiating a first area of at least
1 cm.sup.2 of the patient's scalp with laser light during a first
time period. The method further comprises noninvasively irradiating
a second area of at least 1 cm.sup.2 of the patient's scalp with
laser light during a second time period, wherein the first area and
the second area do not overlap one another. The first time period
and the second time period do not overlap one another.
[0011] In certain embodiments, a method for denoting a brain
phototherapy procedure comprises identifying a plurality of
treatment site locations at a patient's scalp. The method further
comprises indicating a sequential order for irradiation of the
treatment site locations. At least one of the treatment site
locations has an area of at least 1 cm.sup.2.
[0012] In certain embodiments, a headpiece is wearable by a patient
for treating the patient's brain. The headpiece comprises a
plurality of position indicators configured to indicate
corresponding treatment site locations at which light is to be
applied to non-invasively irradiate at least a portion of the
patient's brain. At least one position indicator of the plurality
of position indicators comprises an optically transmissive region
and a mating portion configured to releasably mate with a
complementary portion of a light source. The headpiece is
configured to conform to at least a portion of the patient's
scalp.
[0013] In certain embodiments, a headpiece is wearable by a patient
for treating the patient's brain. The headpiece comprises a body
configured to generally conform to at least a portion of the
patient's scalp. The headpiece further comprises a plurality of
position indicators configured to indicate corresponding treatment
site locations of the patient's scalp at which light is to be
applied to non-invasively irradiate at least a portion of the
patient's brain. At least one position indicator of the plurality
of position indicators comprising an aperture and a mating portion
configured to releasably mate with a complementary portion of a
light source. The headpiece also comprises a plurality of labels
configured to indicate a predetermined treatment sequence for
sequentially applying light from the light source to the treatment
site locations. The headpiece further comprises a retaining member
extending between a first side of the headpiece and a second side
of the headpiece. The retaining member is configured to secure the
headpiece to the head of the patient.
[0014] In certain embodiments, a system for providing phototherapy
to at least a portion of a patient's brain comprises a light
emitting device and a wearable headpiece. The light source
comprises a light source configured to generate light comprising
one or more wavelengths in a range of about 630 nm to about 1064
nanometers, an output optical element in optical communication with
the light source, and a docking element. The output optical element
is configured to emit at least a portion of the light generated by
the light source. The wearable headpiece comprises a plurality of
position indicators configured to indicate corresponding treatment
site locations of the patient's scalp at which the light is to be
applied to irradiate at least a portion of the patient's brain. At
least one position indicator of the plurality of position
indicators comprises an optically transmissive region and a mating
portion configured to releasably mate with the docking element of
the light emitting device.
[0015] In certain embodiments, a method of providing phototherapy
to at least a portion of a patient's brain comprises positioning a
wearable headpiece on the patient's head. The method further
comprises reversibly mechanically coupling a light source to a
first portion of the headpiece while the headpiece is on the
patient's head, wherein the headpiece applies a first force to the
light source such that light emitted by the light source
non-invasively irradiates at least a first portion of the patient's
brain by propagating through a first treatment site location of the
patient's scalp. The method also comprises removing the light
source from the first portion of the headpiece while the headpiece
remains on the patient's head.
[0016] For purposes of summarizing the present invention, certain
aspects, advantages, and novel features of the present invention
have been described herein above. It is to be understood, however,
that not necessarily all such advantages may be achieved in
accordance with any particular embodiment of the present invention.
Thus, the present invention may be embodied or carried out in a
manner that achieves or optimizes one advantage or group of
advantages as taught herein without necessarily achieving other
advantages as may be taught or suggested herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 schematically illustrates an example beam delivery
apparatus in accordance with certain embodiments described
herein.
[0018] FIG. 2A schematically illustrates a cross-sectional view of
an example output optical assembly in accordance with certain
embodiments described herein.
[0019] FIG. 2B schematically illustrates another example output
optical assembly in accordance with certain embodiments described
herein.
[0020] FIGS. 3A and 3B schematically illustrate the diffusive
effect on the light by the output optical assembly.
[0021] FIGS. 4A and 4B schematically illustrate cross-sectional
views of two example beam delivery apparatuses in accordance with
certain embodiments described herein.
[0022] FIG. 5 schematically illustrates an example fiber alignment
mechanism in accordance with certain embodiments described
herein.
[0023] FIG. 6 schematically illustrates an example mirror
compatible with certain embodiments described herein.
[0024] FIG. 7 schematically illustrates an example first optical
path of light emitted from the optical fiber in accordance with
certain embodiments described herein.
[0025] FIG. 8 schematically illustrates an example second optical
path of radiation received by the sensor.
[0026] FIG. 9A schematically illustrates an example thermoelectric
element and FIG. 9B schematically illustrates two views of an
example thermal conduit in accordance with certain embodiments
described herein.
[0027] FIG. 10A schematically illustrates another example
thermoelectric element and FIG. 10B schematically illustrates two
views of another example thermal conduit in accordance with certain
embodiments described herein.
[0028] FIG. 11A schematically illustrates a cross-sectional view of
an example heat sink and FIG. 11B schematically illustrates another
example heat sink in accordance with certain embodiments described
herein.
[0029] FIGS. 12A and 12B schematically illustrate two example
configurations of the window with the thermoelectric assembly.
[0030] FIG. 13A schematically illustrates an example chassis for
supporting the various components of the beam delivery apparatus
within the housing in accordance with certain embodiments described
herein.
[0031] FIG. 13B schematically illustrates another example chassis
in accordance with certain embodiments described herein.
[0032] FIG. 14A schematically illustrates a cross-sectional view of
an example configuration of the chassis and the housing in
accordance with certain embodiments described herein.
[0033] FIGS. 14B and 14C schematically illustrate another example
configuration of the chassis and the housing in accordance with
certain embodiments described herein.
[0034] FIGS. 15A and 15B schematically illustrate two states of an
example sensor in accordance with certain embodiments described
herein.
[0035] FIGS. 15C and 15D schematically illustrate two states of
another example sensor in accordance with certain embodiments
described herein.
[0036] FIGS. 16A and 16B schematically illustrate two example
configurations of the trigger force spring and trigger force
adjustment mechanism in accordance with certain embodiments
described herein.
[0037] FIG. 17 schematically illustrates an example lens assembly
sensor in accordance with certain embodiments described herein.
[0038] FIG. 18 is a block diagram of a control circuit comprising a
programmable controller for controlling a light source according to
embodiments described herein.
[0039] FIG. 19A is a graph of the transmittance of light through
blood (in arbitrary units) as a function of wavelength.
[0040] FIG. 19B is a graph of the absorption of light by brain
tissue.
[0041] FIG. 19C shows the efficiency of energy delivery as a
function of wavelength.
[0042] FIG. 20 shows measured absorption of 808 nanometer light
through various rat tissues.
[0043] FIGS. 21A-21D schematically illustrate example pulses in
accordance with certain embodiments described herein.
[0044] FIGS. 22A-22C schematically illustrate an embodiment in
which the apparatus is placed in thermal communication sequentially
with a plurality of treatment sites corresponding to portions of
the patient's scalp.
[0045] FIG. 23A schematically illustrates an example apparatus
which is wearable by a patient for treating the patient's
brain.
[0046] FIGS. 23B and 23C schematically illustrate the left-side and
right-side of an example apparatus, respectively, with labels
substantially covering the indicators corresponding to the
treatment sites.
[0047] FIG. 23D schematically illustrates an example labeling
configuration from above a flattened view of the apparatus of FIGS.
23B and 23C.
[0048] FIGS. 23E-23H illustrate an example embodiment of a wearable
apparatus for use in treating the patient's brain with
phototherapy.
[0049] FIGS. 23I-23M illustrate alternative example embodiments of
a wearable apparatus for use in treating the patient's brain with
phototherapy.
[0050] FIG. 24 schematically illustrates an example embodiment of a
wearable headpiece that may be configured to position a light
delivery apparatus.
[0051] FIGS. 25-28 are flow diagrams of example methods for
irradiating a surface with light.
[0052] FIG. 29A is a flow diagram of an example method for
controllably exposing at least one predetermined area of a
patient's scalp to laser light to irradiate the patient's
brain.
[0053] FIG. 29B is a flow diagram of an example method for
providing phototherapy to at least a portion of a patient's brain
using a wearable headpiece.
[0054] FIG. 30 is a flow diagram of another example method for
treating a patient's brain.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0055] Low level light therapy ("LLLT") or phototherapy involves
therapeutic administration of light energy to a patient at lower
irradiances than those used for cutting, cauterizing, or ablating
biological tissue, resulting in desirable biostimulatory effects
while leaving tissue undamaged. In non-invasive phototherapy, it is
desirable to apply an efficacious amount of light energy to the
internal tissue to be treated using light sources positioned
outside the body. (See, e.g., U.S. Pat. Nos. 6,537,304 and
6,918,922, both of which are incorporated in their entireties by
reference herein.)
[0056] Laser therapy has been shown to be effective in a variety of
settings, including treating lymphoedema and muscular trauma, and
carpal tunnel syndrome. Recent studies have shown that
laser-generated infrared radiation is able to penetrate various
tissues, including the brain, and to modify function. In addition,
laser-generated infrared radiation can induce effects including,
but not limited to, angiogenesis, modify growth factor
(transforming growth factor-.beta.) signaling pathways, and enhance
protein synthesis.
[0057] However, absorption of the light energy by intervening
tissue can limit the amount of light energy delivered to the target
tissue site, while heating the intervening tissue. In addition,
scattering of the light energy by intervening tissue can limit the
irradiance (or power density) or energy density delivered to the
target tissue site. Brute force attempts to circumvent these
effects by increasing the power and/or irradiance applied to the
outside surface of the body can result in damage (e.g., burning) of
the intervening tissue. For example, a patient experiencing TBI can
have a significant amount of bleeding within the skull (e.g.,
"blood in the field"), and this blood can absorb the applied light,
thereby inhibiting propagation of light energy to brain tissue
below the blood-filled region and heating up.
[0058] Non-invasive phototherapy methods are circumscribed by
setting selected treatment parameters within specified limits so as
to preferably avoid damaging the intervening tissue. A review of
the existing scientific literature in this field would cast doubt
on whether a set of undamaging, yet efficacious, parameters could
be found for treating neurologic conditions. However, certain
embodiments, as described herein, provide devices and methods which
can achieve this goal.
[0059] Such embodiments may include selecting a wavelength of light
at which the absorption by intervening tissue is below a damaging
level. Such embodiments may also include setting the power output
of the light source at low, yet efficacious, irradiances (e.g.,
between approximately 100 .mu.W/cm.sup.2 to approximately 10
W/cm.sup.2) at the target tissue site, setting the temporal profile
of the light applied to the head (e.g., temporal pulse widths,
temporal pulse shapes, duty cycles, pulse frequencies), and time
periods of application of the light energy at hundreds of
microseconds to minutes to achieve an efficacious energy density at
the target tissue site being treated. Other parameters can also be
varied in the use of phototherapy. These other parameters
contribute to the light energy that is actually delivered to the
treated tissue and may play key roles in the efficacy of
phototherapy. In certain embodiments, the irradiated portion of the
brain can comprise the entire brain.
[0060] In certain embodiments, the target area of the patient's
brain includes the area of injury, e.g., to neurons within the
"zone of danger." In other embodiments, the target area includes
portions of the brain not within the zone of danger. Information
regarding the biomedical mechanisms or reactions involved in
phototherapy is provided by Tiina I. Karu in "Mechanisms of
Low-Power Laser Light Action on Cellular Level", Proceedings of
SPIE Vol. 4159 (2000), Effects of Low-Power Light on Biological
Systems V, Ed. Rachel Lubart, pp. 1-17, and Michael R. Hamblin et
al., "Mechanisms of Low Level Light Therapy," Proc. of SPIE, Vol.
6140, 614001 (2006), each of which is incorporated in its entirety
by reference herein.
[0061] In certain embodiments, the apparatuses and methods of
phototherapy described herein are used to treat physical trauma
(e.g., TBI or ischemic stroke) or other sources of
neurodegeneration. As used herein, the term "neurodegeneration"
refers to the process of cell destruction resulting from primary
destructive events such as stroke or CVA, as well as from
secondary, delayed and progressive destructive mechanisms that are
invoked by cells due to the occurrence of the primary destructive
event. Primary destructive events include disease processes or
physical injury or insult, including stroke, but also include other
diseases and conditions such as multiple sclerosis, amylotrophic
lateral sclerosis, heat stroke, epilepsy, Alzheimer's disease,
dementia resulting from other causes such as AIDS, cerebral
ischemia including focal cerebral ischemia, and physical trauma
such as crush or compression injury in the CNS, including a crush
or compression injury of the brain, spinal cord, nerves or retina,
or any acute injury or insult producing neurodegeneration.
Secondary destructive mechanisms include any mechanism that leads
to the generation and release of neurotoxic molecules, including
but not limited to, apoptosis, depletion of cellular energy stores
because of changes in mitochondrial membrane permeability, release
or failure in the reuptake of excessive glutamate, reperfusion
injury, and activity of cytokines and inflammation. Both primary
and secondary mechanisms contribute to forming a "zone of danger"
for neurons, wherein the neurons in the zone have at least
temporarily survived the primary destructive event, but are at risk
of dying due to processes having delayed effect.
[0062] In certain embodiments, the apparatuses and methods
described herein are used to provide neuroprotection. As used
herein, the term "neuroprotection" refers to a therapeutic strategy
for slowing or preventing the otherwise irreversible loss of
neurons due to neurodegeneration after a primary destructive event,
whether the neurodegeneration loss is due to disease mechanisms
associated with the primary destructive event or secondary
destructive mechanisms.
[0063] In certain embodiments, the apparatuses and methods
described herein are used to improve neurologic function, to
provide neurologic enhancement, or to regain previously lost
neurologic function. The term "neurologic function" as used herein
includes both cognitive function and motor function. The term
"neurologic enhancement" as used herein includes both cognitive
enhancement and motor enhancement. The terms "cognitive
enhancement" and "motor enhancement" as used herein refer to the
improving or heightening of cognitive function and motor function,
respectively.
[0064] The term "cognitive function" as used herein refers to
cognition and cognitive or mental processes or functions, including
those relating to knowing, thinking, learning, perception, memory
(including immediate, recent, or remote memory), and judging.
Symptoms of loss of cognitive function can also include changes in
personality, mood, and behavior of the patient. The term "motor
function" as used herein refers to those bodily functions relating
to muscular movements, primarily conscious muscular movements,
including motor coordination, performance of simple and complex
motor acts, and the like.
[0065] Diseases or conditions affecting neurologic function
include, but are not limited to, Alzheimer's disease, dementia,
AIDS or HIV infection, Cruetzfeldt-Jakob disease, head trauma
(including single-event trauma and long-term trauma such as
multiple concussions or other traumas which may result from
athletic injury), Lewy body disease, Pick's disease, Parkinson's
disease, Huntington's disease, drug or alcohol abuse, brain tumors,
hydrocephalus, kidney or liver disease, stroke, depression, and
other mental diseases which cause disruption in cognitive function,
and neurodegeneration.
Beam Delivery Apparatus
[0066] The phototherapy methods for the treatment of neurologic
conditions (e.g., ischemic stroke, Alzheimer's Disease, Parkinson's
Disease, depression, or TBI) described herein may be practiced and
described using various light delivery systems. Such light delivery
systems may include a low level laser therapy apparatus such as
that shown and described in U.S. Pat. Nos. 6,214,035; 6,267,780;
6,273,905; 6,290,714; 7,303,578; and 7,575,589 and in U.S. Pat.
Appl. Publ. Nos. 2005/0107851 A1 and 2009/0254154 A1, each of which
is incorporated in its entirety by reference herein. For example,
in certain embodiments, the light delivery apparatus can irradiate
a portion of the patient's scalp or skull while cooling the
irradiated portion of the scalp or skull. In certain other
embodiments, the irradiated portion of the patient's scalp or skull
is not cooled while irradiating the portion of the scalp or
skull.
[0067] These previously-disclosed light delivery apparatuses were
described primarily in conjunction with phototherapy treatment of
stroke, however in certain embodiments, such light delivery
apparatuses can also be used for phototherapy treatment of other
neurologic conditions (e.g., Alzheimer's Disease, Parkinson's
Disease, Huntington's Disease, depression, TBI). A patient who has
experienced a TBI may have a portion of their scalp damaged,
thereby exposing a portion of their cranium or skull. In certain
such embodiments, the light delivery apparatus can irradiate an
exposed portion of the cranium or skull without the light
propagating through scalp tissue. Certain embodiments described
herein are compatible with irradiation of the brain with light
applied to at least a portion of the scalp or with light applied to
at least a portion of the cranium or skull without propagating
through the scalp.
[0068] FIG. 1 schematically illustrates an example beam delivery
apparatus 10 in accordance with certain embodiments described
herein. The apparatus 10 comprises a housing 12, a flexible conduit
14 operatively coupled to the housing 12, and at least one status
indicator 16. In certain embodiments, the apparatus 10 comprises an
output optical assembly 20 comprising an emission surface 22
through which a light beam 30 is emitted. The output optical
assembly 20 is configured to be releasably mechanically coupled to
other components of the apparatus 10. The output optical assembly
20 can also be configured to be releasably coupled to a position
indicator of a wearable headpiece, as described further herein.
[0069] In certain embodiments, the housing 12 is sized to be easily
held in one hand (e.g., having a length of approximately 5%
inches). The housing 12 of certain embodiments further comprises
one or more portions 12a, 12b comprising a biocompatible material
since they may contact the operator, the patient, or both. For
example, one or more low durometer elastomer materials (e.g.,
rubber, polymers, thermoplastic resins) can be used in certain
embodiments. The portion 12a is configured to be grasped by a
user's hand during operation of the apparatus 10. The housing 12 of
certain embodiments is configured so that the emission surface 22
can be held in position and sequentially moved by hand to irradiate
selected portions of the patient's skin. In certain embodiments,
the housing 12 comprises one or more recesses or protrusions which
facilitate the housing 12 being gripped by the user. In certain
embodiments, the housing 12 is configured to be placed on a testing
system to measure or monitor the operative parameters of the
apparatus 10. The housing 12 of certain such embodiments comprises
an alignment rib 12c configured to provide a registration
protrusion which mates with a corresponding registration recess on
the testing system to facilitate proper alignment of the emission
surface 22 with the testing system. The housing 12 of certain
embodiments comprises two or more portions (e.g., 2-piece cast
urethane with 60A overmolding or 3-piece Lustran.RTM. with
thermoplastic elastomer overmolding) which fit together to form a
shell in which other operative components are held. In certain
embodiments, the light used by the apparatus 10 can cause eye
damage if viewed by an individual. In such embodiments, the
apparatus 10 can be configured to provide eye protection so as to
avoid viewing of the light by individuals. For example, opaque
materials can be used for the housing 12 and appropriately placed
to block the light from being viewed directly. In addition,
interlocks can be provided so that the light source is not
activated unless the apparatus 10 is in place, or other appropriate
safety measures are taken.
[0070] In certain embodiments, the housing 12 further comprises a
flexible boot 17 generally surrounding the portion of the apparatus
10 which is releasably mounted to the output optical assembly 20.
The boot 17 of certain embodiments provides a barrier to control,
inhibit, prevent, minimize, or reduce contaminants from entering
the housing 12. Thus, by virtue of the boot 17 providing a barrier,
the contamination entering the housing 12 is lower than it would
otherwise be if the boot 17 did not provide a barrier. Example
materials for the flexible boot 17 include but are not limited to,
rubber or another elastomer.
[0071] In certain embodiments, the conduit 14 is configured to
operatively couple the apparatus 10 to various control, power, and
cooling systems that are spaced from the housing 12. In certain
embodiments, the conduit 14 comprises at least one optical fiber
configured to transmit light from a light source to the apparatus
10 to be emitted from the emission surface 22. In certain
embodiments, the conduit 14 further comprises one or more
electrically conductive wires (e.g., one 20-conductor cable, four
6-conductor cables, ground braid) configured to transmit signals
between the apparatus 10 (e.g., trigger switches or temperature
sensors within the apparatus 10) and a control system spaced from
the apparatus 10 and/or to provide electrical power to the
apparatus 10 (e.g., for a thermoelectric cooler) from a power
system. In still other embodiments, the apparatus 10 comprises a
power source (e.g., a battery). In certain embodiments, the conduit
14 comprises one or more coolant tubes (e.g., 0.125-inch inner
diameter) configured to have a coolant (e.g., liquid or gas) flow
to the apparatus 10 from a cooling system. In certain embodiments,
the conduit 14 comprises one or more connectors which are
mechanically coupled to one or more corresponding connectors within
the housing 12. For example, the conduit 14 can comprise an SMA
connector at an end of the optical fiber which is mechanically
coupled to a corresponding SMA mount within the housing 12.
[0072] In certain embodiments, the conduit 14 comprises a
protective sheath around the one or more fibers, wires, and tubes
of the conduit 14. The protective sheath of certain embodiments
controls, inhibits, prevents, minimizes, or reduces light from
exiting the conduit 14 in the event of a failure of the at least
one optical fiber. Thus, by virtue of having the sheath, the light
exiting the conduit 14 upon fiber failure is lower than it would
otherwise be without the sheath. In certain embodiments, the
protective sheath comprises a strain relief apparatus having a
plurality of rigid segments (e.g., stainless steel), with each
segment having a generally cylindrical tubular shape and a
longitudinal axis. Each segment is articulately coupled to
neighboring segments such that an angle between the longitudinal
axes of neighboring segments is limited to be less than a
predetermined angle. In certain embodiments, the protective sheath
allows the conduit 14 to be moved and to bend, but advantageously
limits the radius of curvature of the bend to be sufficiently large
to avoid breaking the one or more fibers, wires, or tubes therein.
In certain embodiments, the sheath comprises a flexible compression
spring (e.g., 4 inches in length) to provide bend relief and/or a
tension line to provide strain relief.
[0073] In certain embodiments, the at least one status indicator 16
comprises one, two, or more light-emitting diodes (LEDs) which are
lit to visually provide the user with information regarding the
status of the apparatus 10. For example, the at least one status
indicator 16 can be used in certain embodiments to indicate when
the laser source is ready to lase pending engagement of the
trigger. In certain embodiments, the LEDs can be lit to show
different colors depending on whether the optical power, electrical
power, or coolant flow being provided to the apparatus 10 are
sufficient for operation of the apparatus 10. In certain
embodiments, the at least one status indicator 16 provides
information regarding whether the output optical assembly 20 is
properly mounted to the apparatus 10. Other types of status
indicators (e.g., flags, sound alarms) are also compatible with
certain embodiments described herein.
[0074] FIG. 2A schematically illustrates a cross-sectional view of
an example output optical assembly 20 in accordance with certain
embodiments described herein. FIG. 2B schematically illustrates
another example output optical assembly 20 in accordance with
certain embodiments described herein. The output optical assembly
20 comprises an optical element 23 comprising the emission surface
22 and a surface 24 facing generally away from the emission surface
22. As used herein, the term "element" is used in its broadest
sense, including, but not limited to, as a reference to a
constituent or distinct part of a composite device. The output
optical assembly 20 further comprises a thermal conduit 25 in
thermal communication with the optical element 23 (e.g., with a
portion of the surface 24). The thermal conduit 25 comprises at
least one surface 26 configured to be in thermal communication with
at least one heat dissipating surface of the apparatus 10 (e.g., a
surface of a cooling mechanism). The output optical assembly 20
further comprises a coupling portion 27 (e.g., spring-loaded 3-pin
bayonet mount or 4-pin bayonet mount) configured to be releasably
attached and detached from the housing 12. In certain embodiments,
the output optical assembly 20 comprises one or more springs which
provide a sufficient force on the at least one surface 26 towards
the at least one heat dissipating surface of the apparatus 10 to
have the desired thermal conductivity between the two. Various
examples of output optical assemblies 20 compatible with certain
embodiments described herein are described more fully in U.S.
patent application Ser. No. 12/233,498, which is incorporated in
its entirety by reference herein.
[0075] In certain embodiments, the output optical assembly 20 is
configured to be placed in thermal communication with the patient's
scalp or skull (e.g., the optical element 23 is configured to
contact the patient's scalp or skull or is configured to be spaced
from the patient's scalp or skull but to contact a thermally
conductive material in contact with the patient's scalp or skull).
In certain embodiments in which the output optical assembly 20 is
cooled, the output optical assembly 20 cools at least a portion of
the patient's scalp or skull (e.g., the portion of the scalp or
skull being irradiated). Thus, in certain embodiments, the output
optical assembly 20 is adapted to control, inhibit, prevent,
minimize, or reduce temperature increases at the scalp or skull
caused by the light. Thus, by virtue of the output optical assembly
20 cooling the portion of the patient's scalp or skull being
irradiated, the temperature of the irradiated portion of the
patient's scalp or skull is lower than it would otherwise be if the
output optical assembly 20 did not cool the irradiated portion of
the scalp or skull. For example, by cooling the irradiated portion
of the patient's scalp or skull using the output optical assembly
20, the temperature of the irradiated portion of the patient's
scalp or skull can be higher than the temperature of the portion of
the patient's scalp or skull if it were not irradiated, but lower
than the temperature of the portion of the patient's scalp or skull
if it were irradiated but not cooled. In certain embodiments, the
patient's scalp comprises hair and skin which cover the patient's
skull. In other embodiments, at least a portion of the hair is
removed prior to the phototherapy treatment, so that the output
optical assembly 20 substantially contacts the skin of the
scalp.
[0076] The optical element 23 of certain embodiments is thermally
conductive, and optically transmissive at wavelengths which are
transmitted by skin. For example, in certain embodiments, the
thermal conductivity of the optical element 23 is sufficient to
remove heat from the irradiated portion of the patient's scalp or
skull, and the optical transmissivity of the optical element 23, at
wavelengths selected to provide the desired irradiance at a target
region of the brain, is sufficient to allow the desired irradiance
of light to propagate through the optical element 23 to irradiate
the patient's scalp or skull. In certain embodiments, the optical
element 23 comprises a rigid material, while in certain other
embodiments, the optical element 23 comprises a low durometer,
thermally conductive, optically transmissive material (e.g., a
flexible bag or container filled with a thermally conductive,
optically transmissive liquid such as water). Example rigid
materials for the optical element 23 include, but are not limited
to, sapphire, diamond, calcium fluoride, and zinc selenide. In
certain embodiments, the optical element 23 has an emission surface
22 configured to face generally towards the surface to be
irradiated (e.g., the patient's scalp or skull). In certain
embodiments, the emission surface 22 is adapted to be placed in
contact with either the irradiated surface or with a substantially
optically transmissive and substantially thermally conductive
material which is in contact with the irradiated surface. The
emission surface 22 of certain embodiments is configured to be in
thermal communication with the surface to be irradiated by the
light beam emitted from the emission surface 22. In certain such
embodiments, the thermal conductivity of the optical element 23 is
sufficiently high to allow heat to flow from the emission surface
22 to the thermal conduit 25 at a sufficient rate to control,
inhibit, prevent, minimize, or reduce damage to the skin or
discomfort to the patient from excessive heating of the skin due to
the irradiation. Thus, by virtue of the thermal conductivity of the
optical element 23, any damage to the skin or discomfort to the
patient can be lower than it would otherwise be if the optical
element 23 did not have a sufficiently high thermal conductivity.
For example, the damage to the skin or discomfort to the patient
can be higher than it would be if the portion of the patient's
scalp were not irradiated, but the damage to the skin or discomfort
to the patient would be lower than it would be if the optical
element 23 did not have a sufficiently high thermal
conductivity.
[0077] In certain embodiments, the optical element 23 has a thermal
conductivity of at least approximately 10 watts/meter-K. In certain
other embodiments, the thermal conductivity of the optical element
23 is at least approximately 15 watts/meter-K. Examples of
materials for the optical element 23 in accordance with certain
embodiments described herein include, but are not limited to,
sapphire which has a thermal conductivity of approximately 23.1
watts/meter-K, and diamond which has a thermal conductivity between
approximately 895 watts/meter-K and approximately 2300
watts/meter-K.
[0078] In certain embodiments, the emission surface 22 is adapted
to conform to the curvature of the scalp or skull. The emission
surface 22 of certain embodiments is concave (e.g., generally
spherical with a radius of curvature of about 100 millimeters). By
fitting to the curvature of the scalp or skull, the emission
surface 22 advantageously controls, inhibits, prevents, minimizes,
or reduces temperature increases at the scalp or skull that would
otherwise result from air-filled gaps between the emission surface
22 and the scalp or skull. Thus, by virtue of the emission surface
22 fitting to the curvature of the portion of the patient's scalp
or skull being irradiated, the temperature of the irradiated
portion of the patient's scalp or skull is lower than it would
otherwise be if the emission surface 22 did not fit to the
curvature of the irradiated portion of the scalp or skull. For
example, by fitting the emission surface 22 to the curvature of the
irradiated portion of the patient's scalp or skull, the temperature
of the irradiated portion of the patient's scalp or skull can be
higher than the temperature of the portion of the patient's scalp
or skull if it were not irradiated, but lower than the temperature
of the portion of the patient's scalp or skull if it were
irradiated but the emission surface 22 did not fit to the portion
of the patient's scalp or skull. The existence of air gaps between
the emission surface 22 and the scalp or skull can reduce the
thermal conductivity between the emission surface 22 and the scalp
or skull, thereby increasing the probability of heating the scalp
or skull by the irradiation.
[0079] In addition, the refractive-index mismatches between such an
air gap and the emission surface 22 and/or the scalp or skull can
cause a portion of the light propagating toward the scalp or skull
to be reflected away from the scalp or skull. In certain
embodiments, the emission surface 22 is placed in contact with the
skin of the scalp or skull so as to advantageously substantially
reduce air gaps between the emission surface 22 and the scalp or
skull in the optical path of the light. In certain other
embodiments in which an intervening material (e.g., a substantially
optically transmissive and substantially thermally conductive gel)
is in contact with the scalp or skull and with the emission surface
22, the emission surface 22 is placed in contact with the
intervening material so as to advantageously avoid creating air
gaps between the emission surface 22 and the intervening material
or between the intervening material and the scalp or skull. In
certain embodiments, the intervening material has a refractive
index at a wavelength of light impinging the scalp which
substantially matches the refractive index of the scalp (e.g.,
about 1.3), thereby reducing any index-mismatch-generated back
reflections between the emission surface 22 and the scalp. Examples
of materials compatible with certain such embodiments described
herein include, but are not limited to, glycerol, water, and silica
gels. Example index-matching gels include, but are not limited to,
those available from Nye Lubricants, Inc. of Fairhaven, Mass.
[0080] In certain embodiments, the emission surface 22 comprises
one or more optical coatings, films, layers, membranes, etc. in the
optical path of the transmitted light which are adapted to reduce
back reflections. By reducing back reflections, the emission
surface 22 increases the amount of light transmitted to the brain
and reduces the need to use higher irradiances which may otherwise
create temperature increases at the scalp or skull.
[0081] In certain embodiments, the output optical assembly 20 is
adapted to diffuse the light prior to reaching the scalp or skull
to advantageously homogenize the light beam prior to reaching the
emission surface 22. Generally, intervening tissues of the scalp
and skull are highly scattering, which can reduce the impact of
non-uniform beam intensity distributions on the illumination of the
patient's cerebral cortex. However, non-uniform beam intensity
distributions with substantial inhomogeneities could result in some
portions of the patient's scalp or skull being heated more than
others (e.g., localized heating where a "hot spot" of the light
beam impinges the patient's scalp or skull). In certain
embodiments, the output optical assembly 20 advantageously
homogenizes the light beam to have a non-uniformity less than
approximately 3 millimeters. FIGS. 3A and 3B schematically
illustrate the diffusive effect on the light by the output optical
assembly 20. An example energy density profile of the light prior
to being transmitted through the output optical assembly 20, as
illustrated by FIG. 3A, is peaked at a particular emission angle.
After being diffused by the output optical assembly 20, as
illustrated by FIG. 3B, the energy density profile of the light
does not have a substantial peak at any particular emission angle,
but is substantially evenly distributed among a range of emission
angles. By diffusing the light, the output optical assembly 20
distributes the light energy substantially evenly over the area to
be illuminated, thereby controlling, inhibiting, preventing,
minimizing, or reducing "hot spots" which would otherwise create
temperature increases at the scalp or skull. Thus, by virtue of the
output optical assembly 20 diffusing the light, the temperature of
the irradiated portion of the patient's scalp or skull is lower
than it would otherwise be if the output optical assembly 20 did
not diffuse the light. For example, by diffusing the light using
the output optical assembly 20, the temperature of the irradiated
portion of the patient's scalp or skull can be higher than the
temperature of the portion of the patient's scalp or skull if it
were not irradiated, but lower than the temperature of the portion
of the patient's scalp or skull if it were irradiated but the light
were not diffused by the output optical assembly 20. In addition,
by diffusing the light prior to reaching the scalp or skull, the
output optical assembly 20 can effectively increase the spot size
of the light impinging the scalp or skull, thereby advantageously
lowering the irradiance at the scalp or skull, as described in U.S.
Pat. No. 7,303,578, which is incorporated in its entirety by
reference herein.
[0082] In certain embodiments, the output optical assembly 20
provides sufficient diffusion of the light such that the irradiance
of the light is less than a maximum tolerable level of the scalp,
skull, or brain. For example, the maximum tolerable level of
certain embodiments is a level at which the patient experiences
discomfort or pain, while in certain other embodiments, the maximum
level is a level at which the patient's scalp or skull is damaged
(e.g., burned). In certain other embodiments, the output optical
assembly 20 provides sufficient diffusion of the light such that
the irradiance of the light equals a therapeutic value at the
subdermal target tissue. The output optical assembly 20 can
comprise example diffusers including, but are not limited to,
holographic diffusers such as those available from Physical Optics
Corp. of Torrance, Calif. and Display Optics P/N SN1333 from
Reflexite Corp. of Avon, Conn.
[0083] In certain embodiments, the output optical assembly 20
provides a reusable interface between the apparatus 10 and the
patient's scalp or skull. In such embodiments, the output optical
assembly 20 can be cleaned or sterilized between uses of the
apparatus 10, particularly between uses by different patients. In
other embodiments, the output optical assembly 20 provides a
disposable and replaceable interface between the apparatus 10 and
the patient's scalp or skull. By using pre-sterilized and
pre-packaged replaceable interfaces, certain embodiments can
advantageously provide sterilized interfaces without undergoing
cleaning or sterilization processing immediately before use.
[0084] In certain embodiments, the output optical assembly 20 is
adapted to apply pressure to at least an irradiated portion of the
scalp. For example, the output optical assembly 20 is capable of
applying pressure to at least an irradiated portion of the scalp
upon a force being applied to the apparatus 10 (e.g., by an
operator of the apparatus 10 pressing the apparatus 10 against the
patient's scalp by hand or by mechanical means to generate force,
such as weights, springs, tension straps). By applying sufficient
pressure, the output optical assembly 20 can blanch the portion of
the scalp by forcing at least some blood out the optical path of
the light energy. (For a general discussion of skin blanching, see,
e.g., A. C. Burton et al., "Relation Between Blood Pressure and
Flow in the Human Forearm," J. Appl. Physiology, Vol. 4, No. 5, pp.
329-339 (1951); A. Matas et al., "Eliminating the Issue of Skin
Color in Assessment of the Blanch Response," Adv. in Skin &
Wound Care, Vol. 14(4, part 1 of 2), pp. 180-188 (July/August
2001); J. Niitsuma et al., "Experimental study of decubitus ulcer
formation in the rabbit ear lobe," J. of Rehab. Res. and Dev., Vol.
40, No. 1, pp. 67-72 (January/February 2003).) The blood removal
resulting from the pressure applied by the output optical assembly
20 to the scalp decreases the corresponding absorption of the light
energy by blood in the scalp. As a result, temperature increases
due to absorption of the light energy by blood at the scalp are
reduced. As a further result, the fraction of the light energy
transmitted to the subdermal target tissue of the brain is
increased. In certain embodiments, a pressure of at least 0.1 pound
per square inch is used to blanch the irradiated portion of the
scalp, while in certain other embodiments, a pressure of at least
one pound per square inch is used to blanch the irradiated portion
of the scalp. In certain embodiments, a pressure of at least about
two pounds per square inch is used to blanch the irradiated portion
of the scalp. Other values or ranges of pressures for blanching the
irradiated portion of the scalp are also compatible with certain
embodiments described herein. The maximum pressure used to blanch
the irradiated portion of the scalp is limited in certain
embodiments by patient comfort levels and tissue damage levels.
[0085] FIGS. 4A and 4B schematically illustrate cross-sectional
views of two example beam delivery apparatuses 10 in accordance
with certain embodiments described herein. In FIGS. 4A and 4B, the
apparatus 10 comprises an output optical assembly 20 having an
emission surface 22 and releasably operatively coupled to the other
components of the apparatus 10. The apparatus 10 comprises an
optical fiber 40, a fiber alignment mechanism 50 operatively
coupled to the optical fiber 40, a mirror 60 in optical
communication with the optical fiber 40, and a window 70 in optical
communication with the mirror 60. During operation of the apparatus
10, light 30 from the optical fiber 40 propagates to the mirror 60
and is reflected by the mirror 60 to propagate through the window
70. The light 30 transmitted through the window 70 propagates
through the output optical assembly 20 along a first optical path
and is emitted from the emission surface 22. In certain
embodiments, the apparatus 10 comprises additional optical elements
(e.g., lenses, diffusers, and/or waveguides) which transmit at
least a portion of the light received via the optical fiber 40 to
the emission surface 22. In certain such embodiments, the
additional optical elements of the apparatus 10 shape, format, or
otherwise modify the light such that the light beam emitted from
the emission surface 22 has the desired beam intensity profile.
[0086] In certain embodiments, the optical fiber 40 comprises a
step-index or graded-index optical fiber. The optical fiber 40 of
certain embodiments is single-mode, while in certain other
embodiments, the optical fiber is multimode. An example optical
fiber 40 compatible with certain embodiments described herein has a
1000-micron diameter and a numerical aperture of approximately
0.22.
[0087] FIG. 5 schematically illustrates an example fiber alignment
mechanism 50 in accordance with certain embodiments described
herein. In certain embodiments, the fiber alignment mechanism 50 is
mechanically coupled to a portion of the optical fiber 40 and is
configured to allow adjustments of the position, tilt, or both of
the end of the optical fiber 40 from which the light is emitted. In
certain embodiments, the fiber alignment mechanism 50 provides an
adjustment range of at least 5 degrees. The fiber alignment
mechanism 50 of FIG. 5 comprises a connector 52 (e.g., SMA
connector) mechanically coupled to the optical fiber 40, a plate 54
(e.g., a kinematic tilt stage) mechanically coupled to the
connector 52, and a plurality of adjustment screws 56 (e.g., 80
turns per inch or 100 turns per inch) adjustably coupled to the
plate 54. By turning the adjustment screws 56, a distance between a
portion of the plate 54 and a corresponding portion of a reference
structure 58 can be adjusted. In certain embodiments, the fiber
alignment mechanism 50 comprises one or more locking screws 59
configured to be tightened so as to fix the plate 54 at a position,
orientation, or both relative to the reference structure 58. Other
configurations of the fiber alignment mechanism 50 are also
compatible with certain embodiments described herein.
[0088] FIG. 6 schematically illustrates an example mirror 60
compatible with certain embodiments described herein. In certain
embodiments, the mirror 60 is substantially reflective of light
emitted from the optical fiber 40 to reflect the light through a
non-zero angle (e.g., 90 degrees). The mirror 60 of certain
embodiments comprises a glass substrate coated on at least one side
by a metal (e.g., gold or aluminum). Examples of mirrors 60
compatible with certain embodiments described herein include, but
are not limited to, a flat, generally planar glass mirror (e.g.,
NT43-886 available from Edmund Optics Inc. of Barrington, N.J.).
The mirror 60 of certain embodiments can be configured to have an
optical power (e.g., the mirror 60 can be concave) and be adapted
to shape, format, or otherwise modify the light to produce a
desired beam intensity profile. In certain embodiments, the mirror
60 is bonded around its perimeter by an adhesive (e.g., OP-29
adhesive available from Dymax Corp. of Torrington, Conn.) to a
support structure 62.
[0089] In certain embodiments, the mirror 60 is partially
transmissive of light emitted from the optical fiber 40. In certain
such embodiments, the support structure 62 comprises an opening and
the apparatus 10 comprises at least one light sensor 64 positioned
to receive light transmitted through the mirror 60 and the opening
of the support structure 62. The at least one light sensor 64 is
configured to generate a signal indicative of the intensity of the
received light, thereby providing a measure of the intensity of the
light reaching the mirror 60. Examples of light sensors 64
compatible with certain embodiments described herein include, but
are not limited to, OPT101 photodiode available from Texas
Instruments of Dallas, Tex. In certain embodiments, a plurality of
light sensors 64 are used to provide operational redundancy to
confirm that light with a sufficient intensity for operation of the
apparatus 10 is being provided by the optical fiber 40. In certain
embodiments, a diffuser 66 is positioned to diffuse the light
transmitted through the mirror 60 before the light impinges the
light sensor 64. In certain embodiments, the light sensor 64 is
protected from stray light by an opaque shroud 68 generally
surrounding the light sensor 64.
[0090] In certain embodiments, the window 70 is substantially
transmissive to infrared radiation. Example windows 70 compatible
with certain embodiments described herein include, but are not
limited to, a flat, generally planar CaF.sub.2 window (e.g.,
TechSpec.RTM. calcium fluoride window available from Edmund Optics
Inc. of Barrington, N.J.).
[0091] In certain embodiments, the window 70 at least partially
bounds a region within the apparatus 10 which contains the mirror
60. The window 70 of certain such embodiments substantially seals
the region against contaminants (e.g., dust, debris) from entering
the region from outside the region. For example, when the output
optical assembly 20 is decoupled from the apparatus 10, the window
70 controls, inhibits, prevents, minimizes, or reduces contaminants
entering the region. Thus, by virtue of the window 70 substantially
sealing the region, the contamination of the region is lower than
it would otherwise be if the window 70 did not substantially seal
the region.
[0092] FIG. 7 schematically illustrates an example first optical
path 32 of light 30 emitted from the optical fiber 40 in accordance
with certain embodiments described herein. The diverging light 30
exiting the optical fiber 40 propagates along the first optical
path 32 towards the mirror 60. The light 30 is reflected by the
mirror 60 and propagates along the first optical path 32 through
the window 70, impinges or is received by the surface 24 of the
optical element 23, and is emitted from the emission surface 22
towards the surface to be irradiated. In certain embodiments, the
mirror 60 reflects the light 30 through an angle of about 90
degrees. In certain embodiments, the mirror 60 is about 2.3 inches
from the face of the optical fiber 40 and the first optical path 32
is about 4.55 inches in length from the fiber output face to the
emission surface 22 of the optical element 23.
[0093] In certain embodiments, the apparatus 10 further comprises a
sensor 80 spaced from the output optical assembly 20. FIG. 8
schematically illustrates an example second optical path 82 of
radiation 84 received by the sensor 80. The sensor 80 is positioned
to receive the radiation 84 from the output optical assembly 20
propagating through the output optical assembly 20 along the second
optical path 82. The first optical path 32 and the second optical
path 82 have a non-zero angle therebetween. In certain embodiments,
the second optical path 82 is co-planar with the first optical path
32, while in certain other embodiments, the first optical path 32
and the second optical path 82 are non-co-planar with one another.
The sensor 80 of certain embodiments receives radiation 84
propagating along the second optical path 82 from at least a
portion of the surface 24 of the optical element 23 during
operation of the apparatus 10.
[0094] The sensor 80 of certain embodiments comprises a temperature
sensor (e.g., thermopile) configured to receive infrared radiation
from a region and to generate a signal indicative of the
temperature of the region. Examples of temperature sensors
compatible with certain embodiments described herein include, but
are not limited to, DX-0496 thermopile available from Dexter
Research Center, Inc. of Dexter, Mich. In certain embodiments, the
field-of-view of the sensor 80 comprises an area of about 0.26
square inches of the surface 24 spaced from the thermal conduit 25
(e.g., by a distance between 0.05 inch and 0.3 inch). In certain
other embodiments, the field-of-view of the sensor 80 comprises an
area of about 0.57 square inches of the surface 24.
[0095] In certain embodiments, the sensor 80 is responsive to the
received radiation 84 by generating a signal indicative of a
temperature of the skin or of a portion of the output optical
assembly 20 (e.g., the optical element 23). In certain such
embodiments, the apparatus 10 further comprises a controller
configured to receive the signal from the sensor 80 and to cause a
warning to be generated, to turn off a source of the light
propagating along the first optical path 32, or both in response to
the signal indicating that the temperature is above a predetermined
threshold temperature (e.g., 42 degrees Celsius).
[0096] The sensor 80 of certain embodiments is not in thermal
communication with the output optical assembly 20. As shown in FIG.
8, the infrared-transmissive window 70 is between the sensor 80 and
the output optical assembly 20. The light 30 propagating along the
first optical path 32 and the infrared radiation 84 propagating
along the second optical path 82 both propagate through the window
70. In certain embodiments, the sensor 80 is wholly or at least
partially within a region of the housing 12 at least partially
bound, and substantially sealed by the window 70 against
contaminants from entering the region from outside the region.
[0097] In certain embodiments, the apparatus 10 is adapted to cool
the irradiated portion of the scalp or skull by removing heat from
the scalp or skull so as to control, inhibit, prevent, minimize, or
reduce temperature increases at the scalp or skull. Thus, by virtue
of the apparatus 10 cooling the irradiated portion of the patient's
scalp or skull, the temperature of the irradiated portion of the
patient's scalp or skull is lower than it would otherwise be if the
apparatus 10 did not cool the irradiated portion of the scalp or
skull. For example, by cooling the irradiated portion of the
patient's scalp or skull using the apparatus 10, the temperature of
the irradiated portion of the patient's scalp or skull can be
higher than the temperature of the portion of the patient's scalp
or skull if it were not irradiated, but lower than the temperature
of the portion of the patient's scalp or skull if it were
irradiated but not cooled. Referring to FIGS. 4A and 4B, in certain
embodiments, the apparatus 10 comprises a thermoelectric assembly
90 and a heat sink 100 in thermal communication with the
thermoelectric assembly 90. In certain embodiments, the
thermoelectric assembly 90 actively cools the patient's scalp or
skull via the output optical assembly 20, thereby advantageously
avoiding large temperature gradients at the patient's scalp or
skull which would otherwise cause discomfort to the patient. In
certain embodiments, the apparatus 10 further comprises one or more
temperature sensors (e.g., thermocouples, thermistors) which
generate electrical signals indicative of the temperature of the
thermoelectric assembly 90.
[0098] In certain embodiments, the thermoelectric assembly 90
comprises at least one thermoelectric element 91 and a thermal
conduit 92. The at least one thermoelectric element 91 of the
thermoelectric assembly 90 is responsive to an electric current
applied to the thermoelectric assembly 90 by cooling at least a
first surface 93 of the thermoelectric assembly 90 and heating at
least a second surface 94 of the thermoelectric assembly 90. The
thermoelectric assembly 90 is configured to be releasably
mechanically coupled to the output optical assembly 20 so as to
have the first surface 93 in thermal communication with the output
optical assembly 20. In certain embodiments, the first surface 93
comprises a surface of the thermal conduit 92 and the second
surface 94 comprises a surface of the thermoelectric element
91.
[0099] FIG. 9A schematically illustrates an example thermoelectric
element 91 and FIG. 9B schematically illustrates two views of an
example thermal conduit 92 in accordance with certain embodiments
described herein. FIG. 10A schematically illustrates another
example thermoelectric element 91 and FIG. 10B schematically
illustrates two views of another example thermal conduit 92 in
accordance with certain embodiments described herein. The
thermoelectric element 91 has a surface 95 configured to be in
thermal communication with a corresponding surface 96 of the
thermal conduit 92 (e.g., by a thermally conductive adhesive). Upon
application of an electric current to the thermoelectric element
91, the second surface 94 is heated and the surface 95 is cooled,
thereby cooling the first surface 93. In certain such embodiments,
the first surface 93 serves as at least one heat dissipating
surface of the apparatus 10 configured to be in thermal
communication with the at least one surface 26 of the thermal
conduit 25 of the output optical assembly 20 (e.g., by contacting
or mating so as to provide a thermally conductive connection
between the thermoelectric assembly 26 and the output optical
assembly 20). By having the thermally conductive output optical
assembly 20 in thermal communication with the thermoelectric
assembly 90, certain embodiments advantageously provide a conduit
for heat conduction away from the treatment site (e.g., the skin).
In certain embodiments, the output optical assembly 20 is pressed
against the patient's skin and transfers heat away from the
treatment site.
[0100] Examples of thermoelectric elements 91 compatible with
certain embodiments described herein include, but are not limited
to, DT12-6, Q.sub.max=60 W, square thermoelectric element available
from Marlow Industries of Dallas, Tex., and Q.sub.max=45 W
toroidal- or donut-shaped thermoelectric element from Ferrotec
Corp. of Bedford, N.H. In certain embodiments, the thermoelectric
element 91 removes heat from the output optical assembly 20 at a
rate in a range of about 0.1 Watt to about 5 Watts or in a range of
about 1 Watt to about 3 Watts. Example temperature controllers for
operating the thermoelectric assembly 90 in accordance with certain
embodiments described herein include, but are not limited to,
MPT-5000 available from Wavelength Electronics, Inc. of Bozeman,
Mont. Example materials for the thermal conduit 92 compatible with
certain embodiments described herein include, but are not limited
to, aluminum and copper. The thermal conduit 92 of certain
embodiments has a thermal mass in a range of about 30 grams to
about 70 grams, and has a thermal length between surface 93 and
surface 96 in a range of about 0.5 inch to about 3.5 inches.
[0101] In certain embodiments, the thermoelectric assembly 90
generally surrounds a first region 97, wherein, during operation of
the apparatus 10, light irradiating a portion of the patient's skin
propagates through the first region 97. As shown in FIGS. 9B and
10B, in certain embodiments, the first region 97 comprises an
aperture through the thermal conduit 92. As shown in FIG. 10B, the
first region 97 in certain embodiments further comprises an
aperture through the thermoelectric element 91. In certain
embodiments, the thermoelectric assembly 90 comprises a plurality
of thermoelectric elements 91 which are spaced from one another and
are distributed to generally surround the first region 97. As used
herein, the term "generally surrounds" has its broadest reasonable
interpretation, including but not limited to, encircles or extends
around at least one margin of the region, or being distributed
around at least one margin of the region with one or more gaps
along the at least one margin.
[0102] FIG. 11A schematically illustrates a cross-sectional view of
an example heat sink 100 and FIG. 11B schematically illustrates
another example heat sink 100 in accordance with certain
embodiments described herein. The heat sink 100 comprises an inlet
101, an outlet 102, and a fluid conduit 103 in fluid communication
with the inlet 101 and the outlet 102. The inlet 101 and the outlet
102 of certain embodiments comprise stainless steel barbs
configured to be connected to tubes (e.g., using nylon or stainless
steel hose barb locks, clamps, or crimps) which provide a coolant
(e.g., water, air, glycerol) to flow through the fluid conduit 103
and to remove heat from the fluid conduit 103. In certain
embodiments, the coolant is provided by a chiller or other heat
transfer device which cools the coolant prior to its being supplied
to the heat sink 100.
[0103] The example heat sink 100 of FIG. 11A is machined from an
aluminum block and has a recess 104 in which the thermoelectric
assembly 90 is placed to provide thermal communication between the
heat sink 100 and the second surface 94 of the thermoelectric
assembly 90. The example heat sink 100 of FIG. 11B comprises a
first portion 105 and a second portion 106 which fit together to
form the coolant conduit 103. In certain embodiments, a thermally
conductive adhesive (e.g., EP1200 thermal adhesive available from
Resinlab, LLC of Germantown, Wis., with a 0.005-inch stainless
steel wire to set the bondline) is used to bond the thermoelectric
assembly 90 and the heat sink 100 together in thermal communication
with one another.
[0104] The output optical assembly 20 comprises a thermally
conductive thermal conduit 25 having at least one surface 26
configured to be in thermal communication with the first surface of
the thermoelectric assembly 90. As shown in FIGS. 2A and 2B, the
thermal conduit 25 generally surrounds a second region 28. During
operation of the apparatus 10, the light propagates through the
first region 97, the second region 28, and the optical element 23.
In certain embodiments, the heat sink 100 generally surrounds a
third region 107, as schematically illustrated by FIG. 11B. During
operation of the apparatus 10 in certain such embodiments, the
light propagates through the third region 107, the first region 97,
the second region 28, and the optical element 23.
[0105] FIGS. 12A and 12B schematically illustrate two example
configurations of the window 70 with the thermoelectric assembly
90. In certain embodiments, the window 70 is in thermal
communication with at least a portion of the thermoelectric
assembly 90 (e.g., bonded to a recess in the thermal conduit 92, as
shown in FIG. 12A, using OP-29 adhesive available from Dymax Corp.
of Torrington, Conn.). In certain embodiments, the window 70 is in
thermal communication with at least a portion of the heat sink 100
(e.g., retained by an o-ring in the heat sink 100), as shown in
FIG. 12B. In certain embodiments, the window 70 is not in thermal
communication with either the thermoelectric assembly 90 or the
heat sink 100.
[0106] FIG. 13A schematically illustrates an example chassis 110
for supporting the various components of the beam delivery
apparatus 10 within the housing 12 in accordance with certain
embodiments described herein. The chassis 110 of FIG. 13A comprises
a single unitary or monolithic piece which is machined to provide
various surfaces and holes used to mount the various components of
the beam delivery apparatus 10. FIG. 13B schematically illustrates
another example chassis 110 in accordance with certain embodiments
described herein. The chassis 110 of FIG. 13B comprises a plurality
of portions which are bolted or pinned together.
[0107] FIG. 14A schematically illustrates a cross-sectional view of
an example configuration of the chassis 110 and the housing 12 in
accordance with certain embodiments described herein. The chassis
110 of certain embodiments is electrically connected to ground,
while in certain other embodiments, the chassis 110 is electrically
insulated from ground (e.g., floating). In certain embodiments, the
chassis 110 is configured to move relative to the housing 12. For
example, the chassis 110 and the housing 12 are mechanically
coupled together by a pivot 112, as schematically illustrated by
FIG. 14A. The optical fiber 40, fiber adjustment apparatus 50,
mirror 60, window 70, sensor 80, and heat sink 100 are each
mechanically coupled to the chassis 110. The output optical
assembly 20 is also mechanically coupled to the chassis 110 via the
thermoelectric assembly 90 and the heat sink 100.
[0108] For the configuration of FIG. 14A, the emission surface 22
of the output optical assembly 20 is placed in thermal
communication (e.g., in contact) with the patient's scalp or skull
by a user pressing the housing 12 towards the scalp or skull. The
pivot 112 allows the chassis 110 to rotate about the pivot 112
relative to the housing 12 (e.g., by an angle between 1 and 2
degrees, or about 1.75 degrees) such that the emission surface 22
moves towards the housing 12 (e.g., by a distance of 0.05-0.3 inch,
or about 0.1 inch). In certain such embodiments, this movement of
the chassis 110, as well as of the fiber adjustment apparatus 50
and the optical fiber 40, results in a flexing of a portion of the
optical fiber 40 (e.g., in proximity to the coupling between the
housing 12 and the conduit 14).
[0109] This flexing of the optical fiber 40 can be undesirable in
certain circumstances, such as when the optical fiber 40 or its
connection to the fiber adjustment apparatus 50 is fragile and
prone to breakage or failure due to repeated flexing. FIGS. 14B and
14C schematically illustrate another example configuration of the
chassis 110 and the housing 12 in accordance with certain
embodiments described herein. The chassis 110 comprises a first
chassis element 120 and a second chassis element 122 mechanically
coupled to the first chassis element 120 such that the first
chassis element 120 and the second chassis element 122 can move
relative to one another. For example, in certain embodiments, the
apparatus 10 further comprises a hinge 124 (e.g., a pivot or
flexible portion) about which the first chassis element 120 and the
second chassis element 122 are configured to deflect relative to
one another.
[0110] In certain embodiments, the first chassis element 120 is
mechanically coupled to the housing 12, and the optical fiber 40,
fiber adjustment apparatus 50, mirror 60, and sensor 80 (each shown
in dotted lines in FIG. 14C) are mechanically coupled to the first
chassis element 120. The second chassis element 122 is mechanically
coupled to the window 70, thermoelectric assembly 90, and the heat
sink 100 (each shown in dotted lines in FIG. 14C). The output
optical assembly 20 is also mechanically coupled to the second
chassis element 122 via the thermoelectric assembly 90 and the heat
sink 100. Thus, in certain such embodiments, a first portion of the
apparatus 10 comprises the housing 12, first chassis element 120,
optical fiber 40, fiber adjustment apparatus 50, mirror 60, and
sensor 80, and a second portion of the apparatus 10 comprises the
second chassis element 122, window 70, thermoelectric assembly 90,
heat sink 100, and output optical assembly 20. The second portion
is mechanically coupled to the first portion and is in optical
communication with the first portion. The second portion is
configured to be placed in thermal communication with the patient's
skin such that the light from the first portion propagates through
the second portion during operation of the apparatus 10. The first
portion and the second portion are configured to move relative to
one another in response to the second portion being placed in
thermal communication with the patient's skin.
[0111] In certain embodiments, the second portion comprises the
output optical assembly 20 and the first portion and the second
portion are configured to deflect relative to one another by a
non-zero angle. In certain embodiments, this deflection occurs upon
the output optical assembly 20 applying a pressure to a portion of
the patient's scalp sufficient to at least partially blanch the
portion of the patient's scalp. In certain embodiments, this
deflection occurs upon the output optical assembly 20 being placed
in thermal communication with the patient's scalp or skull. In
certain embodiments, the apparatus 10 further comprises a spring
mechanically coupled to the first portion and the second portion.
The spring provides a restoring force in response to movement of
the first portion and the second portion relative to one
another.
[0112] For the configuration of FIGS. 14B and 14C, the emission
surface 22 of the output optical assembly 20 is placed in thermal
communication (e.g., in contact) with the patient's scalp or skull
by a user pressing the housing 12 towards the scalp or skull. The
hinge 124 allows the second portion (e.g., including the second
chassis element 122) to rotate about the hinge 124 relative to the
first portion (e.g., including the first chassis element 120). This
rotation can be by an angle between 1 and 3 degrees, or about 2.3
degrees) such that the emission surface 22 moves towards the
housing 12 (e.g., by a distance of 0.05-0.3 inch, or about 0.08
inch). In certain such embodiments in which the first portion
comprises the optical fiber 40, deflection of the first portion and
the second portion relative to one another controls, inhibits,
prevents, minimizes, or reduces flexing or movement of the optical
fiber 40 (e.g., to control, inhibit, prevent, minimize, or reduce
damage to the optical fiber 40). Thus, by virtue of the movement of
the first and second portions relative to one another, the flexing,
movement, or damage of the optical fiber 40 is lower than it would
otherwise be if the first and second portions did not move relative
to one another.
[0113] In certain embodiments, the relative movement of the output
optical assembly 20 and the mirror 60 can result in the light beam
30 being at least partially occluded or "clipped" by the thermal
conduit 25 of the output optical assembly 20. For example, for a
light beam diameter of 30 millimeters, the light beam 30 is not
clipped by the thermal conduit 25. For larger light beam diameters,
the light beam 30 is partially occluded by the thermal conduit 25.
For a light beam diameter of 31 millimeters, about 0.02% of the
light beam area is occluded, and for 32 millimeters, about 1.56% of
the light beam area is occluded, resulting in an estimated power
loss of less than about 0.08%.
[0114] In certain embodiments, the apparatus 10 further comprises a
sensor 130 configured to detect movement of the first portion and
the second portion relative to one another (e.g., movement of the
first chassis element 120 and the second chassis element 122
relative to one another). The sensor 130 is configured to transmit
a signal to a controller configured to receive the signal and to
control a light source in response to the signal, where the light
source is configured to generate the light used by the apparatus 10
irradiate the patient's scalp or skull. In certain embodiments, the
sensor 130 transmits the signal to the controller upon detecting
that the movement between the first portion and the second portion
is larger than a predetermined threshold value. In this way, the
sensor 130 serves as a trigger switch which is used to trigger the
apparatus 10 (e.g., providing the apparatus 10 with light upon the
sensor 130 detecting the predetermined amount of movement between
the first portion and the second portion indicative of the
apparatus 10 being in a condition for use). The trigger switch of
certain embodiments is actuated by pressing the output optical
assembly 20 against a surface. The light source providing light to
the apparatus 10 is responsive to the trigger switch by emitting
light only when the trigger switch is actuated. Therefore, in
certain such embodiments, to utilize the apparatus 10, the output
optical assembly 20 is pressed against the patient's skin, such as
described above.
[0115] FIGS. 15A and 15B schematically illustrate two states of an
example sensor 130 in accordance with certain embodiments described
herein. The sensor 130 comprises at least one trigger flag 132
mechanically coupled to the first portion (e.g., the housing 12)
and at least one optical switch 134 mechanically coupled to the
second portion (e.g., the second chassis element 122). For example,
the at least one optical switch 134 of certain embodiments
comprises one, two, or more EE-SX-1035 optical switches available
from Omron Electronics Components LLC of Schaumburg, Ill. In a
first state, the trigger flag 132 is displaced away from a sensor
light beam which is detected by the optical switch 134. Upon
pressing the output optical assembly 20 in thermal communication
with the patient's scalp or skull, the optical switch 134 moves
relative to the trigger flag 132 (e.g., by a distance of about 0.07
inch) such that the trigger flag 132 intercepts the sensor light
beam such that it is no longer detected by the optical switch 134.
In response to this second state, the sensor 130 generates a
corresponding signal. In certain other embodiments, the trigger
flag 132 can be positioned to intercept the sensor light beam in
the first state and to not intercept the sensor light beam in the
second state.
[0116] FIGS. 15C and 15D schematically illustrate two states of
another example sensor 130 in accordance with certain embodiments
described herein. The sensor 130 comprises a reflective element 135
mechanically coupled to the first portion (e.g., the first chassis
element 120) and at least one light source/detector pair 136
mechanically coupled to the second portion (e.g., the second
chassis element 122). For example, the at least one light
source/detector pair 136a, 136b of certain embodiments comprises
one, two, or more QRE1113GR reflective sensors available from
Fairchild Semiconductor Corp. of San Jose, Calif. In a first state,
the reflective surface 135 is a first distance away from the light
source/detector pair 136a, 136b such that a sensor light beam from
the source 136a is reflected from the surface 135 but is not
detected by the detector 136b. Upon pressing the output optical
assembly 20 in thermal communication with the patient's scalp or
skull, the reflective surface 135 moves (e.g., by a distance of
about 0.04 inch) to be a second distance away from the light
source/detector pair 136a, 136b such that the sensor light beam
from the source 136a is reflected from the surface 135 and is
detected by the detector 136b. In response to this second state,
the sensor 130 generates a corresponding signal. In certain
embodiments, the sensor 130 further comprises a shroud 137
configured to protect the detector 136b from stray light. In
certain other embodiments, the reflective surface 135 can be
positioned to reflect the sensor light beam to the detector 136b in
the first state and to not reflect the sensor light beam to the
detector 136b in the second state.
[0117] In certain embodiments, the apparatus 10 further comprises
an adjustment mechanism configured to set the predetermined
threshold value, to change the predetermined threshold value, or
both. In certain such embodiments, the adjustment mechanism
comprises a set screw which changes the relative positions of the
two portions of the sensor 130 which move relative to one another.
Certain embodiments further comprise a stop configured to limit a
range of movement of the first portion and the second portion
relative to one another.
[0118] In certain embodiments, the apparatus 10 comprises a trigger
force spring 140 and a trigger force adjustment mechanism 142.
FIGS. 16A and 16B schematically illustrate two example
configurations of the trigger force spring 140 and trigger force
adjustment mechanism 142 in accordance with certain embodiments
described herein. The trigger force spring 140 is mechanically
coupled to the first portion (e.g., the first chassis element 120)
and the second portion (e.g., the second chassis element 122) and
provides a restoring force when the first portion and the second
portion are moved relative to one another. The trigger force
adjustment mechanism 142 of FIG. 16A comprises one or more shims
(e.g., each shim providing about 100 grams of adjustment) placed
between the spring 140 and at least one of the first portion and
the second portion. The trigger force adjustment mechanism 142 of
FIG. 16B comprises one, two, or more adjustment set screws. In
either configuration, the trigger force adjustment mechanism 142
compresses the spring 140 to adjust the amount of force which will
move the first and second portions relative to one another by a
sufficient amount to trigger the apparatus 10. In certain
embodiments, the trigger force adjustment mechanism 142 is set such
that the apparatus 10 is triggered by a pressure applied to the
emission surface 22 towards the housing 12 of at least 0.1 pound
per square inch, at least one pound per square inch, or at least
about two pounds per square inch.
[0119] In certain embodiments, the apparatus 10 further comprises a
lens assembly sensor 150 configured to detect the presence of the
output optical assembly 20 mounted on the apparatus 10. FIG. 17
schematically illustrates an example lens assembly sensor 150 in
accordance with certain embodiments described herein. For example,
the lens assembly sensor 150 of certain embodiments comprises at
least one reflective surface 152 and at least one light
source/detector pair 154a, 154b (e.g., one, two, or more QRE1113GR
reflective sensors available from Fairchild Semiconductor Corp. of
San Jose, Calif.). The reflective surface 152 moves relative to the
light source/detector pair 154a, 154b upon mounting the output
optical assembly 20 to be in thermal communication with the thermal
conduit 92. For example, when the output optical assembly 20 is
mounted, the bayonet is pulled downward. In response to this
movement, the sensor 150 generates a corresponding signal. In
certain embodiments, the sensor 150 further comprises a shroud 156
configured to protect the detector 154b from stray light.
Control Circuit
[0120] FIG. 18 is a block diagram of a control circuit 200
comprising a programmable controller 205 for controlling a light
source 207 according to embodiments described herein. The control
circuit 200 is configured to adjust the power of the light energy
generated by the light source 207 such that the light emitted from
the emission surface 22 generates a predetermined surface
irradiance at the scalp or skull corresponding to a predetermined
energy delivery profile, such as a predetermined subsurface
irradiance, to the target area of the brain.
[0121] In certain embodiments, the programmable controller 205
comprises a logic circuit 210, a clock 212 coupled to the logic
circuit 210, and an interface 214 coupled to the logic circuit 210.
The clock 212 of certain embodiments provides a timing signal to
the logic circuit 210 so that the logic circuit 210 can monitor and
control timing intervals of the applied light. Examples of timing
intervals include, but are not limited to, total treatment times,
pulsewidth times for pulses of applied light, and time intervals
between pulses of applied light. In certain embodiments, the light
source 207 can be selectively turned on and off to reduce the
thermal load on the scalp or skull and to deliver a selected
irradiance to particular areas of the brain.
[0122] The interface 214 of certain embodiments provides signals to
the logic circuit 210 which the logic circuit 210 uses to control
the applied light. The interface 214 can comprise a user interface
or an interface to a sensor monitoring at least one parameter of
the treatment. In certain such embodiments, the programmable
controller 126 is responsive to signals from the sensor to
preferably adjust the treatment parameters to optimize the measured
response. The programmable controller 126 can thus provide
closed-loop monitoring and adjustment of various treatment
parameters to optimize the phototherapy. The signals provided by
the interface 214 from a user are indicative of parameters that may
include, but are not limited to, patient characteristics (e.g.,
skin type, fat percentage), selected applied irradiances, target
time intervals, and irradiance/timing profiles for the applied
light.
[0123] In certain embodiments, the logic circuit 210 is coupled to
a light source driver 220. The light source driver 220 is coupled
to a power supply 230, which in certain embodiments comprises a
battery and in other embodiments comprises an alternating current
source. The light source driver 220 is also coupled to the light
source 207. The logic circuit 210 is responsive to the signal from
the clock 212 and to user input from the user interface 214 to
transmit a control signal to the light source driver 220. In
response to the control signal from the logic circuit 210, the
light source driver 220 adjust and controls the power applied to
the light source. Other control circuits besides the control
circuit 200 of FIG. 18 are compatible with embodiments described
herein.
[0124] In certain embodiments, the logic circuit 110 is responsive
to signals from a sensor monitoring at least one parameter of the
treatment to control the applied light. For example, certain
embodiments comprise a temperature sensor in thermal communication
with the scalp or skull to provide information regarding the
temperature of the scalp or skull to the logic circuit 210. In such
embodiments, the logic circuit 210 is responsive to the information
from the temperature sensor to transmit a control signal to the
light source driver 220 so as to adjust the parameters of the
applied light to maintain the scalp or skull temperature below a
predetermined level. Other embodiments include example biomedical
sensors including, but not limited to, a blood flow sensor, a blood
gas (e.g., oxygenation) sensor, an ATP production sensor, or a
cellular activity sensor. Such biomedical sensors can provide
real-time feedback information to the logic circuit 210. In certain
such embodiments, the logic circuit 110 is responsive to signals
from the sensors to preferably adjust the parameters of the applied
light to optimize the measured response. The logic circuit 110 can
thus provide closed-loop monitoring and adjustment of various
parameters of the applied light to optimize the phototherapy.
Light Parameters
[0125] The various parameters of the light beam emitted from the
emission surface 22 are advantageously selected to provide
treatment while controlling, inhibiting, preventing, minimizing, or
reducing injury or discomfort to the patient due to heating of the
scalp or skull by the light. While discussed separately, these
various parameters below can be combined with one another within
the disclosed values in accordance with embodiments described
herein.
Wavelength
[0126] In certain embodiments, light in the visible to
near-infrared wavelength range is used to irradiate the patient's
scalp or skull. In certain embodiments, the light is substantially
monochromatic (i.e., light having one wavelength, or light having a
narrow band of wavelengths). So that the amount of light
transmitted to the brain is maximized, the wavelength of the light
is selected in certain embodiments to be at or near a transmission
peak (or at or near an absorption minimum) for the intervening
tissue. In certain such embodiments, the wavelength corresponds to
a peak in the transmission spectrum of tissue at about 820
nanometers. In certain other embodiments, the light comprises one
or more wavelengths between about 630 nanometers and about 1064
nanometers, between about 600 nanometers and about 980 nanometers,
between about 780 nanometers and about 840 nanometers, between
about 805 nanometers and about 820 nanometers, or includes
wavelengths of about 785, 790, 795, 800, 805, 810, 815, 820, 825,
or 830 nanometers. An intermediate wavelength in a range between
approximately 730 nanometers and approximately 750 nanometers
(e.g., about 739 nanometers) appears to be suitable for penetrating
the skull, although other wavelengths are also suitable and may be
used. In other embodiments, a plurality of wavelengths is used
(e.g. applied concurrently or sequentially). In certain
embodiments, the light has a wavelength distribution peaked at a
peak wavelength and has a linewidth less than +10 nanometers from
the peak wavelength. In certain such embodiments, the light has a
linewidth less than 4 nanometers, full width at 90% of energy. In
certain embodiments, the center wavelength is (808.+-.10)
nanometers with a spectral linewidth less than 4 nanometers, full
width at 90% of energy.
[0127] In certain embodiments, the light is generated by a light
source comprising one or more laser diodes, which each provide
coherent light. In embodiments in which the light from the light
source is coherent, the emitted light may produce "speckling" due
to coherent interference of the light. This speckling comprises
intensity spikes which are created by wavefront interference
effects and can occur in proximity to the target tissue being
treated. For example, while the average irradiance or power density
may be approximately 10 mW/cm.sup.2, the power density of one such
intensity spike in proximity to the brain tissue to be treated may
be approximately 300 mW/cm.sup.2. In certain embodiments, this
increased power density due to speckling can improve the efficacy
of treatments using coherent light over those using incoherent
light for illumination of deeper tissues. In addition, the
speckling can provide the increased power density without
overheating the tissue being irradiated. The light within the
speckle fields or islands containing these intensity spikes is
polarized, and in certain embodiments, this polarized light
provides enhanced efficacy beyond that for unpolarized light of the
same intensity or irradiance.
[0128] In certain embodiments, the light source includes at least
one continuously emitting GaAlAs laser diode having a wavelength of
about 830 nanometers. In another embodiment, the light source
comprises a laser source having a wavelength of about 808
nanometers. In still other embodiments, the light source includes
at least one vertical cavity surface-emitting laser (VCSEL) diode.
Other light sources compatible with embodiments described herein
include, but are not limited to, light-emitting diodes (LEDs) and
filtered lamps.
[0129] In certain embodiments, the one or more wavelengths are
selected so as to work with one or more chromophores within the
target tissue. Without being bound by theory or by a specific
mechanism, it is believed that irradiation of chromophores
increases the production of ATP in the target tissue and/or
controls, inhibits, prevents, minimizes, or reduces apoptosis of
the injured tissues, thereby producing beneficial effects, as
described more fully below.
[0130] Some chromophores, such as water or hemoglobin, are
ubiquitous and absorb light to such a degree that little or no
penetration of light energy into a tissue occurs. For example,
water absorbs light above approximately 1300 nanometers. Thus
energy in this range has little ability to penetrate tissue due to
the water content. However, water is transparent or nearly
transparent in wavelengths between 300 and 1300 nanometers. Another
example is hemoglobin, which absorbs heavily in the region between
300 and 670 nanometers, but is reasonably transparent above 670
nanometers.
[0131] Based on these broad assumptions, one can define an "IR
window" into the body. Within the window, there are certain
wavelengths that are more or less likely to penetrate. This
discussion does not include wavelength dependent scattering effects
of intervening tissues.
[0132] The absorption/transmittance of various tissues have been
directly measured to determine the utility of various wavelengths.
FIG. 19A is a graph of the transmittance of light through blood (in
arbitrary units) as a function of wavelength. Blood absorbs less in
the region above 700 nanometers, and is particularly transparent at
wavelengths above 780 nanometers. Wavelengths below 700 nanometers
are heavily absorbed, and are not likely to be useful
therapeutically (except for topical indications).
[0133] FIG. 19B is a graph of the absorption of light by brain
tissue. Absorption in the brain is strong for wavelengths between
620 and 980 nanometers. This range is also where the copper centers
in mitochondria absorb. The brain is particularly rich in
mitochondria as it is a very active tissue metabolically (the brain
accounts for 20% of blood flow and oxygen consumption). As such,
the absorption of light in the 620 to 980 nanometer range is
expected if a photostimulative effect is to take place.
[0134] By combining FIGS. 19A and 19B, the efficiency of energy
delivery as a function of wavelength can be calculated, as shown in
FIG. 19C. Wavelengths between 780 and 880 nanometers are preferable
(efficiency of 0.6 or greater) for targeting the brain. The peak
efficiency is about 800 to 830 nanometers (efficiency of 1.0 or
greater). These wavelengths are not absorbed by water or
hemoglobin, and are likely to penetrate to the brain. Once these
wavelengths reach the brain, they will be absorbed by the brain and
converted to useful energy.
[0135] These effects have been directly demonstrated in rat
tissues. The absorption of 808 nanometer light was measured through
various rat tissues, as shown in FIG. 20. Soft tissues such as skin
and fat absorb little light. Muscle, richer in mitochondria,
absorbs more light. Even bone is fairly transparent. However, as
noted above, brain tissue, as well as spinal cord tissue, absorb
808 nanometer light well.
Irradiance or Power Density
[0136] In certain embodiments, the light beam has a time-averaged
irradiance or power density at the emission surface 22 of the
output optical assembly 20 between about 10 mW/cm.sup.2 to about 10
W/cm.sup.2, between about 100 mW/cm.sup.2 to about 1000
mW/cm.sup.2, between about 500 mW/cm.sup.2 to about 1 W/cm.sup.2,
or between about 650 mW/cm.sup.2 to about 750 mW/cm.sup.2 across
the cross-sectional area of the light beam. For a pulsed light
beam, the time-averaged irradiance is averaged over a time period
long compared to the temporal pulse widths of the pulses (e.g.,
averaged over a fraction of a second longer than the temporal pulse
width, over 1 second, or over multiple seconds). For a
continuous-wave (CW) light beam with time-varying irradiance, the
time-averaged irradiance can be an average of the instantaneous
irradiance averaged over a time period longer than a characteristic
time period of fluctuations of the light beam. In certain
embodiments, a duty cycle in a range between 1% and 80%, between
10% and 30%, or about 20% can be used with a peak irradiance at the
emission surface 22 of the output optical assembly 20 between about
12.5 mW/cm.sup.2 to about 1000 W/cm.sup.2, between about 50
mW/cm.sup.2 to about 50 W/cm.sup.2, between about 500 mW/cm.sup.2
to about 5000 mW/cm.sup.2, between about 2500 mW/cm.sup.2 to about
5 W/cm.sup.2, or between about 3.25 W/cm.sup.2 to about 3.75
W/cm.sup.2 across the cross-sectional area of the light beam. In
certain embodiments, the pulsed light beam has an energy or fluence
(e.g., peak irradiance multiplied by the temporal pulsewidth) at
the emission surface 22 of the output optical assembly 20 between
about 12.5 .mu.J/cm.sup.2 to about 1 .mu.J/cm.sup.2, between about
50 .mu.J/cm.sup.2 to about 50 mJ/cm.sup.2, between about 500
.mu.J/cm.sup.2 to about 5 mJ/cm.sup.2, between about 2.5
mJ/cm.sup.2 to about 5 mJ/cm.sup.2, or between about 3.25
mJ/cm.sup.2 to about 3.75 mJ/cm.sup.2.
[0137] The cross-sectional area of the light beam of certain
embodiments (e.g., multimode beams) can be approximated using an
approximation of the beam intensity distribution. For example, as
described more fully below, measurements of the beam intensity
distribution can be approximated by a Gaussian (1/e.sup.2
measurements) or by a "top hat" distribution and a selected
perimeter of the beam intensity distribution can be used to define
a bound of the area of the light beam. In certain embodiments, the
irradiance at the emission surface 22 is selected to provide the
desired irradiances at the subdermal target tissue. The irradiance
of the light beam is preferably controllably variable so that the
emitted light energy can be adjusted to provide a selected
irradiance at the subdermal tissue being treated. In certain
embodiments, the light beam emitted from the emission surface 22 is
continuous with a total radiant power in a range of about 4 Watts
to about 6 Watts. In certain embodiments, the radiant power of the
light beam is 5 Watts 20% (CW). In certain embodiments, the peak
power for pulsed light is in a range of about 10 Watts to about 30
Watts (e.g., 20 Watts). In certain embodiments, the peak power for
pulsed light multiplied by the duty cycle of the pulsed light
yields an average radiant power in a range of about 4 Watts to
about 6 Watts (e.g., 5 Watts).
[0138] In certain embodiments, the time-averaged irradiance at the
subdermal target tissue (e.g., at a depth of approximately 2
centimeters below the dura) is at least about 0.01 mW/cm.sup.2 and
up to about 1 W/cm.sup.2 at the level of the tissue. In various
embodiments, the time-averaged subsurface irradiance at the target
tissue is at least about 0.01, 0.05, 0.1, 0.5, 1, 5, 10, 15, 20,
30, 40, 50, 60, 70, 80, or 90 mW/cm.sup.2, depending on the desired
clinical performance. In certain embodiments, the time-averaged
subsurface irradiance at the target tissue is about 0.01
mW/cm.sup.2 to about 100 mW/cm.sup.2, about 0.01 mW/cm.sup.2 to
about 50 mW/cm.sup.2, about 2 mW/cm.sup.2 to about 20 mW/cm.sup.2,
or about 5 mW/cm.sup.2 to about 25 mW/cm.sup.2. In certain
embodiments, a duty cycle in a range between 1% and 80%, between
10% and 30%, or about 20% can be used with a peak irradiance at the
target tissue of 0.05 mW/cm.sup.2 to about 500 mW/cm.sup.2, about
0.05 mW/cm.sup.2 to about 250 mW/cm.sup.2, about 10 mW/cm.sup.2 to
about 100 mW/cm.sup.2, or about 25 mW/cm.sup.2 to about 125
mW/cm.sup.2.
[0139] In certain embodiments, the irradiance of the light beam is
selected to provide a predetermined irradiance at the subdermal
target tissue (e.g., at a depth of approximately 2 centimeters from
the dura). The selection of the appropriate irradiance of the light
beam emitted from the emission surface to use to achieve a desired
subdermal irradiance preferably includes consideration of
scattering by intervening tissue. Further information regarding the
scattering of light by tissue is provided by U.S. Pat. No.
7,303,578, which is incorporated in its entirety by reference
herein, and V. Tuchin in "Tissue Optics: Light Scattering Methods
and Instruments for Medical Diagnosis," SPIE Press (2000),
Bellingham, Wash., pp. 3-11, which is incorporated in its entirety
by reference herein.
[0140] Phototherapy for the treatment of neurologic conditions
(e.g., ischemic stroke, Alzheimer's Disease, Parkinson's Disease,
depression, or TBI) is based in part on the discovery that
irradiance or power density (i.e., power per unit area or number of
photons per unit area per unit time) and energy density (i.e.,
energy per unit area or number of photons per unit area) of the
light energy applied to tissue appear to be significant factors in
determining the relative efficacy of low level phototherapy. This
discovery is particularly applicable with respect to treating and
saving surviving but endangered neurons in a zone of danger
surrounding the primary injury. Certain embodiments described
herein are based at least in part on the finding that, given a
selected wavelength of light energy, it is the irradiance and/or
the energy density of the light delivered to tissue (as opposed to
the total power or total energy delivered to the tissue) that
appears to be important factors in determining the relative
efficacy of phototherapy.
[0141] Without being bound by theory or by a specific mechanism, it
is believed that light energy delivered within a certain range of
irradiances and energy densities provides the desired
biostimulative effect on the intracellular environment, such that
proper function is returned to previously nonfunctioning or poorly
functioning mitochondria in at-risk neurons. The biostimulative
effect may include interactions with chromophores within the target
tissue, which facilitate production of ATP and/or controls,
inhibits, prevents, minimizes, or reduces apoptosis of the injured
cells which have experienced decreased blood flow (e.g., due to the
stroke or TBI). Because strokes and TBI correspond to interruptions
of blood flow to portions of the brain, it is thought that any
effects of increasing blood flow by phototherapy are of less
importance in the efficacy of phototherapy for stroke or TBI
victims. Further information regarding the role of irradiance and
exposure time is described by Hans H. F. I. van Breugel and P. R.
Dop Bar in "Power Density and Exposure Time of He--Ne Laser
Irradiation Are More Important Than Total Energy Dose in
Photo-Biomodulation of Human Fibroblasts In Vitro," Lasers in
Surgery and Medicine, Volume 12, pp. 528-537 (1992), which is
incorporated in its entirety by reference herein. In addition, the
significance of the irradiance used in phototherapy with regard to
the devices and methods used in phototherapy of brain tissue, are
described more fully in U.S. Pat. No. 7,303,578 and in U.S. Patent
Appl. Publ. Nos. 2005/0107851 A1, 2007/0179570 A1, and 2007/0179571
A1, each of which is incorporated in its entirety by reference
herein. While these previous discussions of irradiance were
primarily in conjunction with phototherapy of stroke, they apply as
well to phototherapy of TBI. For example, in certain embodiments,
to obtain a desired average power density at the brain for treating
TBI, higher total power at the scalp or skull can be used in
conjunction with a larger spot size at the scalp or skull. Thus, by
increasing the spot size at the scalp or skull, a desired average
power density at the brain can be achieved with lower power
densities at the scalp or skull which can reduce the possibility of
overheating the scalp, skull, or brain.
[0142] In certain embodiments, delivering the neuroprotective
amount of light energy includes selecting a surface irradiance of
the light energy at the scalp or skull corresponding to the
predetermined irradiance at the target area of the brain. As
described above, light propagating through tissue is scattered and
absorbed by the tissue. Calculations of the irradiance to be
applied to the scalp or skull so as to deliver a predetermined
irradiance to the selected target area of the brain preferably take
into account the attenuation of the light energy as it propagates
through the skin and other tissues, such as bone and brain tissue.
Factors known to affect the attenuation of light propagating to the
brain from the scalp or skull include, but are not limited to, skin
pigmentation, the presence, type, and color of hair over the area
to be treated, amount of fat tissue, the presence of bruised
tissue, skull thickness, patient's age and gender, and the location
of the target area of the brain, particularly the depth of the area
relative to the surface of the scalp or skull. (For a general
discussion of the absorption of light by melanins in the body, see,
e.g., "Optical Absorption Spectra of Melanins--a Comparison of
Theoretical and Experimental Results,"
accelrys.com/references/case-studies/melanins_partII.pdf.) The
higher the level of skin pigmentation, the higher the irradiance
applied to the scalp to deliver a predetermined irradiance of light
energy to a subsurface site of the brain. The target area of the
patient's brain can be previously identified such as by using
standard medical imaging techniques.
[0143] The irradiance selected to be applied to the target area of
the patient's brain depends on a number of factors, including, but
not limited to, the wavelength of the applied light, the type of
CVA (ischemic or hemorrhagic), and the patient's clinical
condition, including the extent of the affected brain area. The
irradiance or power density of light energy to be delivered to the
target area of the patient's brain may also be adjusted to be
combined with any other therapeutic agent or agents, especially
pharmaceutical neuroprotective agents, to achieve the desired
biological effect. In such embodiments, the selected irradiance can
also depend on the additional therapeutic agent or agents
chosen.
Temporal PulseKwidth, Temporal Pulseshape, Duty Cycle, Repetition
Rate, and Irradiance Per Pulse
[0144] FIG. 21A schematically illustrates a generalized temporal
profile of a pulsed light beam in accordance with certain
embodiments described herein. The temporal profile comprises a
plurality of pulses (P.sub.1, P.sub.2, . . . , P.sub.i), each pulse
having a temporal pulsewidth during which the instantaneous
intensity or irradiance I(t) of the pulse is substantially
non-zero. For example, for the pulsed light beam of FIG. 21A, pulse
P.sub.1 has a temporal pulsewidth from time t=0 to time t=T.sub.1,
pulse P.sub.2 has a temporal pulsewidth from time t=T.sub.2 to time
t=T.sub.3, and pulse P.sub.i has a temporal pulsewidth from time
t=T.sub.i to time t=T.sub.i+1. The temporal pulsewidth can also be
referred to as the "pulse ON time." The pulses are temporally
spaced from one another by periods of time during which the
intensity or irradiance of the beam is substantially zero. For
example, pulse P.sub.1 is spaced in time from pulse P.sub.2 by a
time t=T.sub.2-T.sub.1. The time between pulses can also be
referred to as the "pulse OFF time." In certain embodiments, the
pulse ON times of the pulses are substantially equal to one
another, while in certain other embodiments, the pulse ON times
differ from one another. In certain embodiments, the pulse OFF
times between the pulses are substantially equal to one another,
while in certain other embodiments, the pulse OFF times between the
pulses differ from one another. As used herein, the term "duty
cycle" has its broadest reasonable interpretation, including but
not limited to, the pulse ON time divided by the sum of the pulse
ON time and the pulse OFF time. For a pulsed light beam, the duty
cycle is less than one. The values of the duty cycle and the
temporal pulsewidth fully define the repetition rate of the pulsed
light beam.
[0145] Each of the pulses can have a temporal pulseshape which
describes the instantaneous intensity or irradiance of the pulse
I(t) as a function of time. For example, as shown in FIG. 21A, the
temporal pulseshapes of the pulsed light beam are irregular, and
are not the same among the various pulses. In certain embodiments,
the temporal pulseshapes of the pulsed light beam are substantially
the same among the various pulses. For example, as schematically
shown in FIG. 21B, the pulses can have a square temporal
pulseshape, with each pulse having a substantially constant
instantaneous irradiance over the pulse ON time. In certain
embodiments, the peak irradiances of the pulses differ from one
another (see, e.g., FIGS. 21A and 21B), while in certain other
embodiments, the peak irradiances of the pulses are substantially
equal to one another (see, e.g., FIGS. 21C and 21D). Various other
temporal pulseshapes (e.g., triangular, trapezoidal) are also
compatible with certain embodiments described herein. FIG. 21C
schematically illustrates a plurality of trapezoidal pulses in
which each pulse has a rise time (e.g., corresponding to the time
between an instantaneous irradiance of zero and a peak irradiance
of the pulse) and a fall time (e.g., corresponding to the time
between the peak irradiance of the pulse and an instantaneous
irradiance of zero). In certain embodiments, the rise time and the
fall time can be expressed relative to a specified fraction of the
peak irradiance of the pulse (e.g., time to rise/fall to 50% of the
peak irradiance of the pulse).
[0146] As used herein, the term "peak irradiance" of a pulse
P.sub.1 has its broadest reasonable interpretation, including but
not limited to, the maximum value of the instantaneous irradiance
I(t) during the temporal pulsewidth of the pulse. In certain
embodiments, the instantaneous irradiance is changing during the
temporal pulsewidth of the pulse (see, e.g., FIGS. 21A and 21C),
while in certain other embodiments, the instantaneous irradiance is
substantially constant during the temporal pulsewidth of the pulse
(see, e.g., FIGS. 21B and 21D).
[0147] As used herein, the term "pulse irradiance" I.sub.P.sub.i of
a pulse P.sub.i has its broadest reasonable interpretation,
including but not limited to, the integral of the instantaneous
irradiance I(t) of the pulse P.sub.i over the temporal pulsewidth
of the pulse:
I P i = .intg. T i T i + 1 I ( t ) dt / ( T i + 1 - T i ) .
##EQU00001##
As used herein, the term "total irradiance" I.sub.TOTAL has its
broadest reasonable interpretation, including but not limited to,
the sum of the pulse irradiances of the pulses:
I TOTAL = i = 0 N I P i . ##EQU00002##
As used herein, the term "time-averaged irradiance" I.sub.AVE has
its broadest reasonable interpretation, including but not limited
to, the integral of the instantaneous irradiance I(t) over a period
of time T large compared to the temporal pulsewidths of the
pulses:
I AVE = .intg. 0 T I ( t ) dt / T . ##EQU00003##
The integral
.intg. 0 T I ( t ) dt ##EQU00004##
provides the energy of the pulsed light beam.
[0148] For example, for a plurality of square pulses with different
pulse irradiances I.sub.P.sub.i and different temporal pulsewidths
.DELTA.T.sub.i, the time-averaged irradiance over a time T
equals
I AVE = 1 T i I P i .DELTA. T i . ##EQU00005##
For another example, for a plurality of square pulses with equal
pulse irradiances I.sub.P, with equal temporal pulsewidths, and
equal pulse OFF times (having a duty cycle D), the time-averaged
irradiance equals I.sub.AVE=I.sub.PD. For example, as shown in FIG.
21D, the time-averaged irradiance (shown as a dashed line) is less
than the pulse irradiance of the pulses.
[0149] The pulse irradiances and the duty cycle can be selected to
provide a predetermined time-averaged irradiance. In certain
embodiments in which the time-averaged irradiance is equal to the
irradiance of a continuous-wave (CW) light beam, the pulsed light
beam and the CW light beam have the same number of photons or flux
as one another. For example, a pulsed light beam with a pulse
irradiance of 5 mW/cm.sup.2 and a duty cycle of 20% provides the
same number of photons as a CW light beam having an irradiance of 1
mW/cm.sup.2. However, in contrast to a CW light beam, the
parameters of the pulsed light beam can be selected to deliver the
photons in a manner which achieve results which are not obtainable
using CW light beams.
[0150] For example, for hair removal, tattoo removal, or wrinkle
smoothing, pulsed light beams have previously been used to achieve
selective photothermolysis in which a selected portion of the skin
is exposed to sufficiently high temperatures to damage the hair
follicles (e.g., temperatures greater than 60 degrees Celsius), to
ablate the tattoo ink (e.g., temperatures much greater than 60
degrees Celsius), or to shrink the collagen molecules (e.g.,
temperatures between 60-70 degrees Celsius), respectively, while
keeping the other portions of skin at sufficiently low temperatures
to avoid unwanted damage or discomfort. The parameters of these
pulsed light beams are selected to achieve the desired elevated
temperature at the selected portion of the skin by absorption of
the light by the selected chromophore while allowing heat to
dissipate (characterized by a thermal relaxation time) during the
pulse OFF times to keep other areas of skin at lower temperatures.
As described by J. Lepselter et al., "Biological and clinical
aspects in laser hair removal," J. Dermatological Treatment, Vol.
15, pp. 72-83 (2004), the pulse ON time for hair removal is
selected to be between the thermal relaxation time for the
epidermis (about 3-10 milliseconds) and the thermal relaxation time
for the hair follicle (about 40-100 milliseconds). In this way, the
hair follicle can be heated to sufficiently high temperatures to
damage the follicle without causing excessive damage to the
surrounding skin.
[0151] In contrast to these treatments which are based on creating
thermal damage to at least a portion of the skin, certain
embodiments described herein utilize pulse parameters which do not
create thermal damage to at least a portion of the skin. In certain
embodiments, one or more of the temporal pulsewidth, temporal
pulseshape, duty cycle, repetition rate, and pulse irradiance of
the pulsed light beam are selected such that no portion of the skin
is heated to a temperature greater than 60 degrees Celsius, greater
than 55 degrees Celsius, greater than 50 degrees Celsius, or
greater than 45 degrees Celsius. In certain embodiments, one or
more of the temporal pulsewidth, temporal pulseshape, duty cycle,
repetition rate, and pulse irradiance of the pulsed light beam are
selected such that no portion of the skin is heated to a
temperature greater than 30 degrees Celsius above its baseline
temperature, greater than 20 degrees Celsius above its baseline
temperature, or greater than 10 degrees Celsius above its baseline
temperature. In certain embodiments, one or more of the temporal
pulsewidth, temporal pulseshape, duty cycle, repetition rate, and
pulse irradiance of the pulsed light beam are selected such that no
portion of the brain is heated to a temperature greater than 5
degrees Celsius above its baseline temperature, greater than 3
degrees Celsius above its baseline temperature, or greater than 1
degree Celsius above its baseline temperature. As used herein, the
term "baseline temperature" has its broadest reasonable
interpretation, including but not limited to, the temperature at
which the tissue would have if it were not irradiated by the light.
In contrast to previous low-light level therapies, the pulsed light
beam has an average radiant power in the range of about 1 Watt to
about 6 Watts or in a range of about 4 Watt to about 6 Watts.
[0152] In certain embodiments, the pulse parameters are selected to
achieve other effects beyond those which are achievable using CW
light beams. For example, while CW irradiation of brain cells in
vivo provides an efficacious treatment of stroke, the use of CW
irradiation for the treatment of TBI is more difficult, owing in
part to the excess blood within the region of the scalp, skull, or
cranium to be irradiated (e.g., due to intercranial bleeding). This
excess blood may be between the light source and the target brain
tissue to be irradiated, resulting in higher absorption of the
light applied to the scalp or skull before it can propagate to the
target tissue. This absorption can reduce the amount of light
reaching the target tissue and can unduly heat the intervening
tissue to an undesirable level.
[0153] In certain embodiments described herein, pulsed irradiation
may provide a more efficacious treatment. The pulsed irradiation
can provide higher peak irradiances for shorter times, thereby
providing more power to propagate to the target tissue while
allowing thermal relaxation of the intervening tissue and blood
between pulses to avoid unduly heating the intervening tissue. The
time scale for the thermal relaxation is typically in the range of
a few milliseconds. For example, the thermal relaxation time
constant (e.g., the time for tissue to cool from an elevated
temperature to one-half the elevated temperature) of human skin is
about 3-10 milliseconds, while the thermal relaxation time constant
of human hair follicles is about 40-100 milliseconds. Thus,
previous applications of pulsed light to the body for hair removal
have optimized temporal pulsewidths of greater than 40 milliseconds
with time between pulses of hundreds of milliseconds.
[0154] However, while pulsed light of this time scale
advantageously reduces the heating of intervening tissue and blood,
it does not provide an optimum amount of efficaciousness as
compared to other time scales. In certain embodiments described
herein, the patient's scalp or skull is irradiated with pulsed
light having parameters which are not optimized to reduce thermal
effects, but instead are optimized to stimulate, to excite, to
induce, or to otherwise support one or more intercellular or
intracellular biological processes which are involved in the
survival, regeneration, or restoration of performance or viability
of brain cells. Thus, in certain such embodiments, the selected
temporal profile can result in temperatures of the irradiated
tissue which are higher than those resulting from other temporal
profiles, but which are more efficacious than these other temporal
profiles. In certain embodiments, the pulsing parameters are
selected to utilize the kinetics of the biological processes rather
than optimizing the thermal relaxation of the tissue. In certain
embodiments, the pulsed light beam has a temporal profile (e.g.,
peak irradiance per pulse, a temporal pulse width, and a pulse duty
cycle) selected to modulate membrane potentials in order to
enhance, restore, or promote cell survival, cell function, or both
of the irradiated brain cells following the traumatic brain injury.
For example, in certain embodiments, the pulsed light has a
temporal profile which supports one or more intercellular or
intracellular biological processes involved in the survival or
regeneration of brain cells, but does not optimize the thermal
relaxation of the irradiated tissue. In certain embodiments, the
brain cells survive longer after the irradiation as compared to
their survival if the irradiation did not occur. For example, the
light of certain embodiments can have a protective effect on the
brain cells, or can cause a regeneration process in the brain
cells.
[0155] In certain embodiments, the temporal profile (e.g., peak
irradiance, temporal pulse width, and duty cycle) are selected to
utilize the kinetics of the biological processes while maintaining
the irradiated portion of the scalp or skull at or below a
predetermined temperature. This predetermined temperature is higher
than the optimized temperature which could be achieved for other
temporal profiles (e.g., other values of the peak irradiance,
temporal pulse width, and duty cycle) which are optimized to
minimize the temperature increase of surrounding tissue due to the
irradiation. For example, a temporal profile having a peak
irradiance of 10 W/cm.sup.2 and a duty cycle of 20% has a
time-averaged irradiance of 2 W/cm.sup.2. Such a pulsed light beam
provides the same number of photons to the irradiated surface as
does a continuous-wave (CW) light beam with an irradiance of 2
W/cm.sup.2. However, because of the "dark time" between pulses, the
pulsed light beam can result in a lower temperature increase than
does the CW light beam. To minimize the temperature increase of the
irradiated portion of the scalp or skull, the temporal pulse width
and the duty cycle can be selected to allow a significant portion
of the heat generated per pulse to dissipate before the next pulse
reaches the irradiated portion. In certain embodiments described
herein, rather than optimizing the beam temporal parameters to
minimize the temperature increase, the temporal parameters are
selected to effectively correspond to or to be sufficiently close
to the timing of the biomolecular processes involved in the
absorption of the photons to provide an increased efficacy. Rather
than having a temporal pulse width on the order of hundreds of
microseconds, certain embodiments described herein utilize a
temporal pulse width which does not optimize the thermal relaxation
of the irradiated tissue (e.g., milliseconds, tens of milliseconds,
hundreds of milliseconds). Since these pulse widths are
significantly longer than the thermal relaxation time scale, the
resulting temperature increases are larger than those of smaller
pulse widths, but still less than that of CW light beams due to the
heat dissipation the time between the pulses.
[0156] A number of studies have investigated the effects of in
vitro irradiation of cells using pulsed light on various aspects of
the cells. A study of the action mechanisms of incoherent pulsed
radiation at a wavelength of 820 nanometers (pulse repetition
frequency of 10 Hz, pulse width of 20 milliseconds, dark period
between pulses of 80 milliseconds, and duty factor (pulse duration
to pulse period ratio) of 20%) on in vitro cellular adhesion has
found that pulsed infrared radiation at 820 nanometers increases
the cell-matrix attachment. (T. I. Karu et al., "Cell Attachment to
Extracellular Matrices is Modulated by Pulsed Radiation at 820 nm
and Chemicals that Modify the Activity of Enzymes in the Plasma
Membrane," Lasers in Surgery and Medicine, Vol. 29, pp. 274-281
(2001) which is incorporated in its entirety by reference herein.)
It was hypothesized in this study that the modulation of the
monovalent ion fluxes through the plasma membrane, and not the
release of arachidonic acid, is involved in the cellular signaling
pathways activated by irradiation at 820 nanometers. A study of
light-induced changes to the membrane conductance of ventral
photoreceptor cells found behavior which was dependent on the pulse
parameters, indicative of two light-induced membrane processes. (J.
E. Lisman et al., "Two Light-Induced Processes in the Photoreceptor
Cells of Limulus Ventral Eye," J. Gen. Physiology, Vol. 58, pp.
544-561 (1971), which is incorporated in its entirety by reference
herein.) Studies of laser-activated electron injection into
oxidized cytochrome c oxidase observed kinetics which establish the
reaction sequence of the proton pump mechanism and some of its
thermodynamic properties have time constants on the order of a few
milliseconds. (I. Belevich et al., "Exploring the proton pump
mechanism of cytochrome c oxidase in real time," Proc. Nat'l Acad.
Sci., Vol. 104, pp. 2685-2690 (2007); I. Belevich et al.,
"Proton-coupled electron transfer drives the proton pump of
cytochrome c oxidase," Nature, Vol. 440, pp. 829-832 (2006), both
of which are incorporated in its entirety by reference herein.) An
in vivo study of neural activation based on pulsed infrared light
proposed a photo-thermal effect from transient tissue temperature
changes resulting in direct or indirect activation of transmembrane
ion channels causing propagation of the action potential. (J. Wells
et al., "Biophysical mechanisms responsible for pulsed low-level
laser excitation of neural tissue," Proc. SPIE, Vol. 6084, pp.
60840X (2006), which is incorporated in its entirety by reference
herein.)
[0157] In certain embodiments, the temporal profile of the pulsed
light beam comprises a peak irradiance, a temporal pulse width, a
temporal pulse shape, a duty cycle, and a pulse repetition rate or
frequency. In certain embodiments in which the pulsed light beam is
transmitted through a region of the scalp or skull containing an
excess amount of hemorrhagic blood due to the at least one physical
trauma (e.g., due to intercranial bleeding), at least one of the
peak irradiance, temporal pulse width, temporal pulse shape, duty
cycle, and pulse repetition rate or frequency is selected to
provide a time-averaged irradiance (averaged over a time period
including a plurality of pulses) at the emission surface 22 of the
output optical assembly 20 between about 10 mW/cm.sup.2 to about 10
W/cm.sup.2, between about 100 mW/cm.sup.2 to about 1000
mW/cm.sup.2, between about 500 mW/cm.sup.2 to about 1 W/cm.sup.2,
or between about 650 mW/cm.sup.2 to about 750 mW/cm.sup.2 across
the cross-sectional area of the light beam. In certain such
embodiments, the time-averaged irradiance at the brain cells being
treated (e.g., at a depth of approximately 2 centimeters below the
dura) is greater than 0.01 mW/cm.sup.2.
[0158] In certain embodiments, the peak irradiance per pulse across
the cross-sectional area of the light beam at the emission surface
22 of the output optical assembly 20 is in a range between about 10
mW/cm.sup.2 to about 10 W/cm.sup.2, between about 100 mW/cm.sup.2
to about 1000 mW/cm.sup.2, between about 500 mW/cm.sup.2 to about 1
W/cm.sup.2, between about 650 mW/cm.sup.2 to about 750 mW/cm.sup.2,
between about 20 mW/cm.sup.2 to about 20 W/cm.sup.2, between about
200 mW/cm.sup.2 to about 2000 mW/cm.sup.2, between about 1
W/cm.sup.2 to about 2 W/cm.sup.2 between about 1300 mW/cm.sup.2 to
about 1500 mW/cm.sup.2, between about 1 W/cm.sup.2 to about 1000
W/cm.sup.2, between about 10 W/cm.sup.2 to about 100 W/cm.sup.2,
between about 50 W/cm.sup.2 to about 100 W/cm.sup.2, or between
about 65 W/cm.sup.2 to about 75 W/cm.sup.2. In certain embodiments,
the temporal pulse shape is generally rectangular, generally
triangular, or any other shape. In certain embodiments, the pulses
have a rise time (e.g., from 10% of the peak irradiance to 90% of
the peak irradiance) less than 1% of the pulse ON time, or a fall
time (e.g., from 90% of the peak irradiance to 10% of the peak
irradiance) less than 1% of the pulse ON time.
[0159] In certain embodiments, the pulses have a temporal
pulsewidth (e.g., pulse ON time) in a range between about 0.001
millisecond and about 150 seconds, between about 0.01 millisecond
and about 10 seconds, between about 0.1 millisecond and about 1
second, between about 0.5 millisecond and about 100 milliseconds,
between about 2 milliseconds and about 20 milliseconds, or between
about 1 millisecond and about 10 milliseconds. In certain
embodiments, the pulse width is about 0.5, 1, 2, 4, 6, 8, 10, 15,
20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220,
240, 260, 280, or 300 milliseconds. In certain embodiments, the
temporal pulsewidth is in a range between about 0.1 millisecond and
150 seconds.
[0160] In certain embodiments, the time between pulses (e.g., pulse
OFF time) is in a range between about 0.01 millisecond and about
150 seconds, between about 0.1 millisecond and about 100
millisecond, between about 4 milliseconds and about 1 second,
between about 8 milliseconds and about 500 milliseconds, between
about 8 milliseconds and about 80 milliseconds, or between about 10
milliseconds and about 200 milliseconds. In certain embodiments,
the time between pulses is about 4, 8, 10, 20, 50, 100, 200, 500,
700, or 1000 milliseconds.
[0161] In certain embodiments, the pulse duty cycle is in a range
between about 1% and about 80% or in a range between about 10% and
about 30%. In certain embodiments, the pulse duty cycle is about
10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90%.
Beam Size and Beam Profile
[0162] In certain embodiments, the light beam emitted from the
output optical assembly 20 has a nominal diameter in a range of
about 10 millimeters to about 40 millimeters, in a range of about
20 millimeters to about 35 millimeters, or equal to about 30
millimeters. In certain embodiments, the cross-sectional area is
generally circular with a radius in a range of about 1 centimeter
to about 2 centimeters. In certain embodiments, the light beam
emitted from the emission surface 22 has a cross-sectional area
greater than about 2 cm.sup.2 or in a range of about 2 cm.sup.2 to
about 20 cm.sup.2 at the emission surface 22 of the optical element
23. In certain embodiments, the output optical element 23 has an
aperture diameter of less than 33 millimeters.
[0163] As used herein, the beam diameter is defined to be the
largest chord of the perimeter of the area of the scalp or skull
irradiated by the light beam at an intensity of at least 1/e.sup.2
of the maximum intensity of the light beam. The perimeter of the
light beam used to determine the diameter of the beam is defined in
certain embodiments to be those points at which the intensity of
the light beam is 1/e.sup.2 of the maximum intensity of the light
beam. The maximum-useful diameter of certain embodiments is limited
by the size of the patient's head and by the heating of the
patient's head by the irradiation. The minimum-useful diameter of
certain embodiments is limited by heating and by the total number
of treatment sites that could be practically implemented. For
example, to cover the patient's skull with a beam having a small
beam diameter would correspondingly use a large number of treatment
sites. In certain embodiments, the time of irradiation per
treatment site can be adjusted accordingly to achieve a desired
exposure dose.
[0164] Specifying the total flux inside a circular aperture with a
specified radius centered on the exit aperture ("encircled energy")
is a method of specifying the power (irradiance) distribution over
the light beam emitted from the emission surface 22. The "encircled
energy" can be used to ensure that the light beam is not too
concentrated, too large, or too small. In certain embodiments, the
light beam emitted from the emission surface has a total radiant
power, and the light beam has a total flux inside a 20-millimeter
diameter cross-sectional circle centered on the light beam at the
emission surface 22 which is no more than 75% of the total radiant
power. In certain such embodiments, the light beam has a total flux
inside a 26-millimeter diameter cross-sectional circle centered on
the light beam at the emission surface 22 which is no less than 50%
of the total radiant power.
[0165] In certain embodiments, the beam intensity profile has a
semi-Gaussian profile, while in certain other embodiments, the beam
intensity profile has a "top hat" profile. In certain embodiments,
the light beam is substantially without high flux regions or "hot
spots" in the beam intensity profile in which the local flux,
averaged over a 3 millimeter by 3 millimeter area, is more than 10%
larger than the average flux. Certain embodiments of the apparatus
10 advantageously generate a light beam substantially without hot
spots, thereby avoiding large temperature gradients at the
patient's skin which would otherwise cause discomfort to the
patient.
Divergence
[0166] In certain embodiments, the beam divergence emitted from the
emission surface 22 is significantly less than the scattering angle
of light inside the body tissue being irradiated, which is
typically several degrees. In certain embodiments, the light beam
has a divergence angle greater than zero and less than 35
degrees.
[0167] As the distance between a light source and an observer
increases, the diameter of the source becomes less relevant to
considerations of the beam divergence. For example, an end of the
optical fiber 40 providing the light has a diameter of about 1
millimeter. At a close distance, observing from a specific
location, light rays from the edges of the optical fiber end can
arrive at the observation point with significantly different
angles. However, as the observation point moves away from the light
source, this angular discrepancy is reduced and the source appears
more like a point source.
[0168] In certain embodiments, with the output optical assembly 20
mounted onto the apparatus 10, the optical distance between the
emission surface 22 and the end of the optical fiber 40 is about
82.7 millimeters. The beam divergence dictated by the numerical
aperture of the optical fiber 40 and the exit aperture of the
optical element 23 is about 23 degrees. In certain embodiments,
with the output optical assembly 20 not mounted onto the apparatus
10, the optical distance between the window 70 and the end of the
optical fiber is about 57.5 millimeters, and the beam divergence
dictated by the numerical aperture of the optical fiber 40 and the
exit aperture of the window 70 is about 16 degrees. With a source
diameter of about 1 millimeter, the angular ambiguity in the beam
divergence is about 0.35 degree. Thus, the angular ambiguity is
much less than the beam divergence angle regardless of whether the
output optical assembly 20 is mounted or not onto the apparatus 10,
so the optical fiber 40 can be treated as a point source. In
certain such embodiments, the beam divergence or radiant intensity
(e.g., measured in Watts/steradian) can be calculated directly from
the beam profile or from the irradiance.
Treatment Time
[0169] In certain embodiments, the treatment per treatment site
proceeds continuously for a period of about 10 seconds to about 2
hours, for a period of about 1 to about 10 minutes, or for a period
of about 1 to 5 minutes. For example, the treatment time per
treatment site in certain embodiments is about two minutes. In
other embodiments, the light energy is delivered for at least one
treatment period of at least about five minutes, or for at least
one treatment period of at least ten minutes. The minimum treatment
time of certain embodiments is limited by the biological response
time (which is on the order of microseconds). The maximum treatment
time of certain embodiments is limited by heating and by practical
treatment times (e.g., completing treatment within about 24 hours
of stroke onset). The light energy can be pulsed during the
treatment period or the light energy can be continuously applied
during the treatment period. If the light is pulsed, the pulses can
be 2 milliseconds long and occur at a frequency of 100 Hz, although
longer pulselengths and lower frequencies can be used, or at least
about 10 nanosecond long and occur at a frequency of up to about
100 kHz.
[0170] In certain embodiments, the treatment may be terminated
after one treatment period, while in other embodiments, the
treatment may be repeated for at least two treatment periods. The
time between subsequent treatment periods can be at least about
five minutes, at least two in a 24-hour period, at least about 1 to
2 days, or at least about one week. The length of treatment time
and frequency of treatment periods can depend on several factors,
including the functional recovery of the patient and the results of
imaging analysis of the injury (e.g., infarct). In certain
embodiments, one or more treatment parameters can be adjusted in
response to a feedback signal from a device (e.g., magnetic
resonance imaging) monitoring the patient.
Cooling Parameters
[0171] In certain embodiments, the apparatus 10 comprises an output
optical element 23 in optical communication with a source of light.
The output optical element 23 comprises an emission surface 22
configured to emit a light beam in accordance with the light
parameters disclosed above. In certain embodiments the apparatus 10
further comprises a thermally conductive portion configured to be
placed in thermal communication with the irradiated portion of the
patient's scalp or skull and to remove heat from the irradiated
portion of the patient's scalp or skull. In certain embodiments,
the thermally conductive portion comprises the output optical
element 23. The thermally conductive portion of certain embodiments
is releasably coupled to the output optical element 23.
[0172] In certain embodiments, the thermally conductive portion
removes heat from the irradiated portion of the patient's scalp or
skull. This cooling of the scalp or skull can to improve the
comfort of the patient, by controlling, inhibiting, preventing,
minimizing, or reducing temperature increases at the scalp or skull
due to the irradiation. Thus, by virtue of the cooling of the
portion of the patient's scalp or skull being irradiated, the
temperature of the irradiated portion of the patient's scalp or
skull is lower than it would otherwise be if the irradiated portion
of the scalp or skull were not cooled. For example, by cooling the
irradiated portion of the patient's scalp or skull, the temperature
of the irradiated portion of the patient's scalp or skull can be
higher than the temperature of the portion of the patient's scalp
or skull if it were not irradiated, but lower than the temperature
of the portion of the patient's scalp or skull if it were
irradiated but not cooled. In addition, this cooling of the scalp
or skull can be to perform double-blind studies of the efficacy of
the phototherapy treatment by masking any heating of the scalp or
skull due to the irradiation. (See, e.g., B. Catanzaro et al.,
"Managing Tissue Heating in Laser Therapy to Enable Double-Blind
Clinical Study," Mechanisms for Low-Light Therapy, Proc. of the
SPIE, Vol. 6140, pp. 199-208 (2006).)
[0173] In certain embodiments, heat is removed from the irradiated
portion of the patient's scalp or skull by the thermally conductive
portion at a rate in a range of about 0.1 Watt to about 5 Watts or
in a range of about 1 Watt to about 3 Watts. In certain
embodiments, the thermally conductive portion is configured to
maintain the temperature of the irradiated portion of the patient's
scalp or skull to be less than 42 degrees Celsius. The thermally
conductive portion of certain embodiments is in thermal
communication with the emission surface 22 and is configured to
maintain the temperature of the emission surface to be in a range
of 18 degrees Celsius to 25 degrees Celsius under a heat load of 2
Watts. For a general description of cooling of the scalp, see,
e.g., F. E. M. Janssen et al., "Modeling of temperature and
perfusion during scalp cooling," Phys. Med. Biol., Vol. 50, pp.
4065-4073 (2005). In certain embodiments in which pulsed light is
used, the rate of heat removal can be less, or cooling may not be
utilized for certain ranges of pulsed dosimetries and timing.
Pressure Parameters
[0174] In certain embodiments, the apparatus 10 is configured to
have the thermally conductive portion move relative to a second
portion of the apparatus 10 upon a pressure being applied to the
thermally conductive portion above a predetermined threshold
pressure in a direction of movement of the thermally conductive
portion relative to the second portion of the apparatus 10. The
predetermined threshold pressure is sufficient to have the
thermally conductive portion in thermal communication with the
portion of the patient's scalp or skull. In certain such
embodiments, the apparatus 10 comprises a sensor configured to be
responsive to the movement of the thermally conductive portion
relative to the second portion by generating a signal (e.g.,
binary, analog, or digital) indicative of the movement.
[0175] In certain such embodiments, the sensor 130 in conjunction
with the trigger force spring 140 and the trigger force adjustment
mechanism 142 provides a mechanism for detecting whether the
apparatus 10 is being applied to the patient's scalp or skull with
a pressure above the predetermined threshold pressure. In certain
such embodiments, the sensor 130 detects movement between the first
portion of the apparatus 10 and the second portion of the apparatus
10 upon placing the emission surface 22 in thermal communication
with the patient's scalp or skull with sufficient pressure to
overcome the restoring force of the trigger force spring 140. Upon
applying the threshold pressure to the emission surface 22 move the
first and second portions relative to one another, the sensor 130
detects the movement and generates a corresponding signal. In
certain embodiments, the apparatus 10 further comprises a
controller operatively coupled to the light source and to the
sensor 130. The controller is configured to receive the signal from
the sensor 130 and to turn on the light source in response to the
signal being indicative of the pressure being above the
predetermined threshold pressure.
[0176] In certain embodiments, the threshold pressure is set to be
a pressure which results in blanching of the portion of the
patient's scalp to be irradiated. In certain embodiments, the
threshold pressure is 0.1 pound per square inch, while in certain
other embodiments, the threshold pressure is one pound per square
inch or about two pounds per square inch.
[0177] In certain embodiments in which pulsed light is used, the
amount of blanching can be less, or blanching may not be utilized
for certain ranges of pulsed dosimetries and timing. For example,
in certain embodiments, the patient may have a heightened
sensitivity to pressure applied to the scalp or skull (e.g., a TBI
patient). Thus, in certain embodiments, the apparatus 10 does not
apply sufficient pressure to the scalp of the patient (e.g.,
applies no pressure to the patient's scalp) to blanch the
irradiated portion of the scalp during the irradiation. In certain
other embodiments in which some amount of blanching of the
irradiated portion of the scalp is desired, the maximum pressure
used to blanch the irradiated portion of the scalp is limited by
patient comfort levels and tissue damage levels. For example, the
cranium or skull of a TB1 patient may have cracks or breaks such
that the brain would be adversely affected if pressure were applied
to the scalp. The amount of pressure used, if any, is determined at
least in part, on the amount of pressure that the patient can
withstand without additional damage being done by the application
of pressure.
Irradiating Multiple Portions of the Scalp or Skull
[0178] FIGS. 22A-22C schematically illustrate an embodiment in
which the apparatus 10 is placed in thermal communication
sequentially with a plurality of treatment sites corresponding to
portions of the patient's scalp. In certain such embodiments, the
light emitted from the emission surface 22 propagates through the
scalp to the brain and disperses in a direction generally parallel
to the scalp, as shown in FIG. 22A. In certain embodiments in which
the patient is suffering from a TBI, one or more of the treatment
sites has a portion of the skull exposed and at least a portion of
the light is applied to the exposed portion of the skull without
propagating through scalp tissue. In certain embodiments, the
treatment sites of the patient's scalp do not overlap one another.
The treatment sites (e.g., twenty treatment sites) are preferably
spaced sufficiently far apart from one another such that the light
emitted from the emission surface 22 to irradiate a treatment site
of the patient's scalp is transmitted through intervening tissue to
irradiate an area of the patient's brain which overlaps one or more
areas of the target tissue of the patient's brain irradiated by the
light emitted from the emission surface 22 when a neighboring
treatment site of the patient's scalp is irradiated. FIG. 22B
schematically illustrates this overlap as the overlap of circular
spots 160 across the target tissue at a reference depth at or below
the surface of the brain. FIG. 22C schematically illustrates this
overlap as a graph of the irradiance at the reference depth of the
brain along the line L-L of FIGS. 22A and 22B. Summing the
irradiances from the neighboring treatment sites (shown as a dashed
line in FIG. 22C) serves to provide a more uniform light
distribution at the target tissue to be treated. In such
embodiments, the summed irradiance is preferably less than a damage
threshold of the brain and above an efficacy threshold. In certain
embodiments, portions of the brain irradiated by irradiating the
treatment sites at the scalp do not overlap one another. In certain
such embodiments, the treatment sites at the scalp are positioned
so as to irradiate as much of the cortex as possible.
Example Wearable Apparatus
[0179] FIG. 23A schematically illustrates an example apparatus 500
which is wearable by a patient for treating the patient's brain.
The apparatus 500 comprises a body 510 and a plurality of
indicators 520. The body 510 is adapted to be worn over at least a
portion of the patient's scalp when the apparatus 500 is worn by
the patient. The plurality of indicators 520 correspond to a
plurality of treatment site locations at the patient's scalp where
light is to be applied to irradiate at least a portion of the
patient's brain. At least one indicator 520 comprises an optically
transmissive portion which is substantially transmissive (e.g.,
substantially transparent or substantially translucent) to light
emitted from the emission surface 22 to irradiate at least a
portion of the patient's brain.
[0180] In certain embodiments, at least one of the indicators 520
denotes a position within an area of the patient's scalp
corresponding to a treatment site location. In certain such
embodiments, the position is the center of the area of the
patient's scalp. The adjacent treatment sites of certain
embodiments have areas which do not overlap one another or have
perimeters which are spaced from one another. In certain such
embodiments, the perimeters are spaced from one another by at least
10 millimeters or at least 25 millimeters.
[0181] In certain embodiments, the optically transmissive portion
of the at least one indicator 520 comprises an opening or aperture
through the body 510 at which the beam delivery apparatus 10 can be
placed to irradiate the portion of the patient's scalp exposed by
the hole or aperture. In other embodiments, the optically
transmissive portion comprises a hollow compartment or cavity that
does not extend completely through the indicator 520 to the surface
of the scalp or skull. For example, the indicator 520 can include a
mylar film to prevent contact between a light source and the
patient, thereby avoiding potential contamination of a contact
portion of the light source by contacting the patient. The use of
the mylar or other suitable protective film advantageously enables
the light source (or at least the contact portion of the light
source) to be reused for multiple patients. In other embodiments,
the light source or a contact portion of the light source can be
disposed after a single use.
[0182] In certain embodiments, the optically transmissive portion
has a substantially circular perimeter and a diameter in a range
between 20 millimeters and 50 millimeters or in a range between 25
millimeters and 35 millimeters. In certain embodiments, the
optically transmissive portion has a substantially elliptical
perimeter with a minor axis greater than 20 millimeters and a major
axis less than 50 millimeters. Other shapes of the optically
transmissive portion are also compatible with certain embodiments
described herein.
[0183] In certain embodiments, the plurality of indicators 520
comprises at least about 10 indicators 520 distributed across the
patient's scalp, while in certain other embodiments, the plurality
of indicators 520 comprises 20 indicators 520. In certain other
embodiments, the plurality of indicators 520 comprises between 15
and 25 indicators 520. In certain embodiments, the optically
transmissive portion of each indicator 520 has an area of at least
1 cm.sup.2, in a range between 1 cm.sup.2 and 20 cm.sup.2, or in a
range between 5 cm.sup.2 and 10 cm.sup.2.
[0184] In certain embodiments, the body 510 comprises a hood, while
in other embodiments, the body 510 comprises a cap or has another
configuration which is wearable on the patient's head and serves as
a support for orienting the indicators 520 on the patient's head.
In certain embodiments, the body 510 comprises a stretchable or
pliant material which generally conforms to the patient's scalp. In
certain embodiments, the body 510 comprises nylon-backed
polychloroprene or Tyvek.RTM.. In certain embodiments, the body 510
is available in different sizes (e.g., small, medium, large) to
accommodate different sizes of heads. In certain embodiments, the
body 510 is disposable after a single use to advantageously avoid
spreading infection or disease between subsequent patients.
[0185] The indicators 520 of certain embodiments are configured to
guide an operator to irradiate the patient's scalp at the
corresponding treatment site locations sequentially one at a time
in a predetermined order.
[0186] FIGS. 23B and 23C schematically illustrate the left-side and
right-side of the example apparatus 500, respectively, with labels
522 substantially covering the indicators 520 corresponding to the
treatment sites. In certain embodiments, the labels 522 are
advantageously used to keep track of which treatment sites have
been irradiated and which treatment sites are yet to be irradiated.
In certain such embodiments, at least a portion of each label 522
comprises a portion of the body (e.g., a pull-off tab or flap)
which is configured to be removed from the apparatus 500 when the
treatment site corresponding to the indicator 520 has been
irradiated. In certain embodiments, the labels 522 comprise
removable portions of the body 510 which cover the corresponding
indicator 520. In certain such embodiments, prior to irradiating
the treatment site location corresponding to the indicator 520, the
corresponding label 522 can be removed to allow access to the
underlying portion of the patient's scalp.
[0187] In certain embodiments, the label 522 has a code sequence
which the operator enters into the controller prior to irradiation
so as to inform the controller of which treatment site is next to
be irradiated. In certain other embodiments, each label 522
comprises a bar code or a radio-frequency identification device
(RFID) which is readable by a sensor electrically coupled to the
controller. The controller of such embodiments keeps track of which
treatment sites have been irradiated, and in certain such
embodiments, the controller only actuates the light source when the
beam delivery apparatus 10 is in optical and thermal communication
with the proper treatment site of the patient's scalp.
[0188] FIG. 23D schematically illustrates an example labeling
configuration from above a flattened view of the apparatus 500 of
FIGS. 23B and 23C. The labeling convention of FIG. 23D is
compatible with irradiation of both halves or hemispheres of the
patient's brain. Other labeling conventions are also compatible
with embodiments described herein.
[0189] In certain embodiments, the labels 522 are advantageously
used to guide an operator to irradiate the patient's brain at the
various treatment sites sequentially at each of the treatment sites
one at a time through the indicators 520 in a predetermined order
by optically and thermally coupling the beam delivery apparatus 10
to sequential treatment sites corresponding to the indicators 520.
For example, for the labeling configuration of FIG. 23D, the
operator can first irradiate treatment site "1," followed by
treatment sites "2," "3," "4," etc. to sequentially irradiate each
of the twenty treatment sites one at a time. In certain such
embodiments, the predetermined order of the treatment sites is
selected to advantageously reduce temperature increases which would
result from sequentially irradiating treatment sites in proximity
to one another.
[0190] In certain embodiments, the predetermined order comprises
irradiation of a first treatment site location on a first side of
the patient's scalp (e.g., site "2" of FIG. 23D), then irradiation
of a second treatment site location on a second side of the
patient's scalp (e.g., site "3" of FIG. 23D), then irradiation of a
third treatment site location on the first side of the patient's
scalp (e.g., site "4" of FIG. 23D). In certain such embodiments,
the predetermined order further comprises irradiation of a fourth
treatment site location on the second side of the patient's scalp
after irradiation of the third treatment site location. In certain
embodiments, two sequentially irradiated treatment site locations
are separated from one another by at least 25 millimeters.
[0191] For example, in certain embodiments, the predetermined order
comprises at least a portion of the following sequence of treatment
sites:
[0192] 1. Right anterior frontal
[0193] 2. Left lateral frontal
[0194] 3. Right anteroinferior parietal
[0195] 4. Left posterior mid-parietal
[0196] 5. Right superior parietal
[0197] 6. Right lateral frontal
[0198] 7. Left anterior frontal
[0199] 8. Left posterior superior parietal
[0200] 9. Left posteroinferior parietal
[0201] 10. Right posteroinferior parietal
[0202] 11. Right posterior superior parietal
[0203] 12. Right anterior mid-parietal
[0204] 13. Left anteroinferior parietal
[0205] 14. Left anterosuperior frontal
[0206] 15. Left superior occipital
[0207] 16. Left anterior mid-parietal
[0208] 17. Right posterior mid-parietal
[0209] 18. Right anterosuperior frontal
[0210] 19. Right superior occipital
[0211] 20. Left superior parietal
[0212] For example, the predetermined order of certain embodiments
comprises two, three, four, or more of these treatment sites in the
relative order listed above. The sequence of treatment sites of
certain embodiments comprises two, three, four, or more of these
treatment sites in a relative order which is the reverse of the
sequence listed above. While certain embodiments utilize at least a
portion of the relative order listed above without irradiation at
an additional treatment site between two sequentially listed
treatment sites, certain other embodiments utilize at least a
portion of the relative order listed above with one or more
additional treatment sites between two of the sequentially listed
treatment sites. In certain embodiments, the exact anatomic
locations of each treatment site may be adjusted from those listed
above to account for variations among the sizes of the heads of the
patients (e.g., very large or very small). Thus, in certain
embodiments, there is some variability regarding the locations of
the treatment sites for any given individual.
[0213] In certain embodiments, the apparatus 500 serves as a
template for marking the patient's scalp to indicate the treatment
site locations. The apertures of the apparatus 500 can be used to
guide a user to place marks on the patient's scalp, and the
apparatus 500 can then be removed from the patient's scalp before
the beam delivery apparatus 10 is applied to the scalp for
irradiating the patient's brain. The marks remain on the patient's
scalp to guide the operator while the patient's brain is
irradiated.
[0214] FIG. 23E schematically illustrates a top perspective view of
another example embodiment of the wearable apparatus 500. The
wearable apparatus 500 includes a body 510 comprising five panels
(a lower left panel 524, an upper left panel 526, a midline panel
528, an upper right panel 530, and a lower right panel 532) and
retention assembly 512. The panels of the wearable apparatus 500
include one or more position indicators 520 that correspond to
respective treatment site locations at the patient's scalp where
light is to be applied to irradiate at least a portion of the
patient's brain. The midline panel 528 advantageously does not
include any position indicators 520. The position indicators 520
can each include a label 522 with a number or other indicia to
indicate a sequence of treatment. At least a portion of the label
522 can be removed to form an opening or aperture at which the beam
delivery apparatus 10 can be placed to irradiate the portion of the
patient's scalp exposed by the hole or aperture.
[0215] The retention assembly 512 can include a retaining member
that extends from one side of the apparatus 500 to the other side
(e.g., a chin strap). The retaining member can be formed of a
unitary strap element or two strap elements that couple together
via a coupling mechanism (not shown). The coupling mechanism can
comprise any suitable means of coupling two strap elements together
(e.g., Velcro strips, buckles, snaps, hooks, latches, clips,
buttons, ties, or the like). Other embodiments do not include the
retention assembly 512.
[0216] FIG. 23F illustrates the lower left panel 524, the upper
left panel 526, the upper right panel 530 and the lower right panel
532. The width of the lower left panel 524 and the lower right
panel 532 (denoted in FIG. 23F by "W.sub.1") can be approximately
10 cm. The length of the lower left panel 524 and the lower right
panel 532 (denoted in FIG. 23F by "L.sub.1") can be approximately
20 cm. The length of the upper left panel 526 and the upper right
panel 530 (denoted in FIG. 23F by "L.sub.2") can be between 30 and
35 cm. The width of the upper left panel 526 and the upper right
panel 530 (denoted in FIG. 23F by "W.sub.2") can be between about 4
and 6 cm. As shown in FIG. 23F, one or more of the panels (e.g.,
the upper left panel 526) includes a label indicating the front of
the body 510 and a label indicating a size of the body 510. The
panels include slits 534 that can be sewn together during assembly,
thereby providing a contour which is configured to at least
partially conform to the shape of the patient's scalp. More or
fewer panels can be included in alternative embodiments.
[0217] FIG. 23G illustrates a magnified view of a seam 536 between
the upper right panel 530 and the lower right panel 532. The panels
of the body 510 can comprise Tyvek.RTM. material. The Tyvek.RTM.
panels can be sewn together using a #306 Union Special needle, a
#14 Singer needle, or the like. As shown, a panel can comprise one
or more separate portions (e.g., portions separated by the slits
534) that are sewn together to form a curved shape from a flat
panel. The needle used can be a flat tipped needle or a round-point
needle. The stitches can be spaced so as to include three to five
stitches per inch. Any suitable thread type can be used (for
example, glace thread of short staple cotton). In certain
embodiments, the maximum overlap between panels or portions of a
panel is about two millimeters and the maximum gap between panels
or portions of a panel is about two millimeters. In other
embodiments, the panels of the body comprise suitable materials
other than Tyvek.RTM. material, such as fiber-based (natural and/or
synthetic) materials and/or polymeric materials.
[0218] FIG. 23H illustrates a rear view of the wearable apparatus
500B. As shown in FIG. 23H, the wearable apparatus 500B further
includes a folded perimeter portion 538 that extends around the
bottom of the wearable apparatus 500B. The peripheral portions of
the panels can be inserted within the folded perimeter portion 538
and the edges of the folded perimeter portion 538 can be sewn
together to retain the panels. The retention assembly 512 can also
be attached at the perimeter portion 538. The width of the
perimeter portion 538 can be about fifteen millimeters. The
perimeter portion 538 can comprise elastic-type material (e.g., an
elastic band). The elastic material can be configured to aid in
securing the body 510 to the head of the patient and can allow for
an adjustable fit for different sized heads.
[0219] FIG. 23I schematically illustrates another example
embodiment of the wearable apparatus 500. The wearable apparatus
500 includes a body 510 and a plurality of position indicators 520.
The body 510 can comprise a single, unitary element that is not
separated into individual panels. The body 510 can comprise a
stretchable or pliant material which generally conforms to the
patient's scalp, such as neoprene, chloroprene, rubber, silicone,
thermoplastic resins, other elastomeric materials, and/or the like.
In other embodiments, the body 510 can be formed of a rigid or
substantially rigid material in order to prevent movement during
irradiation, such as polyethylene, polystyrene, polyvinyl chloride,
polytetrafluoroethylene, other plastic or polymeric materials,
and/or the like. In some embodiments, the body 510 comprises one or
more biocompatible materials.
[0220] The body 510 can advantageously comprise a material that has
relatively high thermal conductivity in order to reduce temperature
increases to the patient's scalp or skin at locations surrounding
the position indicators 520, such as diamond, sapphire, calcium
fluoride, and/or the like. The body 510 can have a thickness
between one and ten millimeters; however, other thicknesses can be
used as desired and/or required.
[0221] The position indicators 520 can be coupled to the body 510
using any suitable adhesive or coupling method or device, such as
epoxy, sutures, welding, molding, adhesive, interference fits,
and/or the like. In certain embodiments, the position indicators
520 can provide indicia of orientation of the wearable apparatus
500 relative to the patient's scalp. For example, the position
indicators 520 that cover the right hemisphere of the brain can be
a different color than the position indicators 520 that cover the
left hemisphere of the brain.
[0222] The position indicators 520 can comprise any suitable
polymer or combination of polymers, such as thermoplastics,
thermosets, and elastomers. The polymers used can be selected based
on strength, flexibility, and/or other properties. In certain
embodiments, the position indicators 520 can be formed of two or
more distinct materials (not shown). For example, an inner member
of the position indicators 520 can be formed of one material and an
outer member can be formed of another material. The outer member
can comprise a material having a lower durometer value than the
inner member, or vice-versa.
[0223] FIG. 23J illustrates another example embodiment of the
wearable apparatus 500. In certain embodiments, the wearable
apparatus 500 comprises a plurality of labels 522 with each label
522 in proximity to a corresponding position indicator 520. The
labels 522 advantageously provide one or more numbers, letters, or
symbols (e.g., bar codes) to each of the position indicators 520 to
distinguish the various position indicators 520 from one another.
Other indicia are possible for the labels 522, such as varying
colors, patterns, and the like. In certain such embodiments, the
labels 522 are mechanically coupled to the corresponding indicators
so as to be visible to users of the light source or light delivery
apparatus.
[0224] The labels 522 can advantageously be used to keep track of
which treatment sites have been irradiated and which treatment
sites have yet to be irradiated. The labels 522 can also indicate a
sequence of treatment, as described further above in connection
with FIGS. 23B-23D. In certain embodiments, the labels 522 can be
removable or detachable. For example, a label 522 can be removed
from its respective indicator 520 immediately before the treatment
site corresponding to the indicator 520 is irradiated. In other
embodiments, the labels 522 are integral with the wearable
apparatus 500 and are not configured to be removed during
treatment, as illustrated by the labels 522 of the wearable
apparatus 500 shown in FIG. 23K. The wearable apparatus 500 of FIG.
23K is described in detail in U.S. Pat. Appl. Pub. No.
2007/0179570, which is incorporated by reference herein in its
entirety.
[0225] In other embodiments, a photochromic layer can be positioned
to cover one or more of the treatment sites corresponding to the
plurality of position indicators 520. The photochromic layer can be
substantially optically transmissive to light used for the
phototherapy treatment described herein. In certain embodiments,
the photochromic layer can change colors upon being irradiated by
light. The photochromic layer can advantageously be used to
indicate to a user which treatment sites have been irradiated and
which treatment sites have not. In certain embodiments, the
photochromic layer comprises one or more photochromic dyes (such as
spirooxazines, diarylethenes, axobenzenes, quinones, and the like)
and/or silver or zinc halides. Some photochromic dyes can be more
biocompatible than others. As such, the biocompatibility of the
photochromic dyes can be taken into account in selecting
photochromic dyes for use. However, photochromic dyes with low
biocompatibility properties can be selected for other reasons that
may outweigh biocompatibility. In other embodiments, one or more
flexible polymers having low glass transition properties (such as
siloxanes or polybutyl acrylate) can be attached to the
photochromic dyes. In certain embodiments, the flexible polymers
are biocompatible.
[0226] In certain embodiments, the position indicators 520 are
connected to each other via coupling joints. FIG. 23L illustrates
another example embodiment of the wearable apparatus 500 in which
coupling joints 525 mechanically couple the position indicators 520
to one another. The position indicators 520 and the coupling joints
525 can be formed as one integral piece during the molding process.
In other embodiments, the position indicators 520 can be coupled
together using the coupling joints 525 after the initial molding
process. In embodiments where the position indicators 520 are
coupled together after the initial molding process, the coupling
joints 525 can comprise complementary mating portions that snap
together with the position indicators 520 or with each other. In
embodiments where the position indicators 520 are formed
individually and the wearable apparatus 500 is not formed as an
integral unit during the molding process, the position indicators
520 can be connected by string, tether, elastic, adhesive, and/or
the like with or without the coupling joints 525. The coupling
joints 525 can be formed of the same materials as are the position
indicators 520 or of different materials. The use of coupling
joints 525 in certain embodiments increases the amount of open
space of the wearable apparatus 500, thereby reducing the potential
for heat retention within the wearable apparatus 500. The absence
of the body 510 in certain embodiments advantageously minimizes the
heat loads transferred to the patients' scalp, brain, or skull.
[0227] FIG. 23L illustrates an example embodiment of the wearable
headpiece wherein the position indicators 520 and the coupling
joints 525 are formed as an integral headpiece unit during the
molding process. FIG. 23M illustrates an example embodiment of the
wearable apparatus 500 in which the position indicators 520 are
formed of individual units that are connected together by a tether
or connection element 540 (e.g., string) to form the wearable
apparatus 500. The embodiment of FIG. 23M can advantageously reduce
the cost of manufacture of the wearable apparatus 500.
[0228] In certain embodiments, a wearable headpiece can be
configured to provide a force to position a light source (e.g.,
beam delivery apparatus 10) relative to the patient's scalp. In
certain embodiments, the wearable headpiece is configured to
provide an amount of force which is sufficient to maintain a
sufficiently effective interface between the light source and the
patient's scalp for one or more of the following: sufficient
uniformity across the irradiated area to permit a substantially
equal distribution of light to a target region of a patient's
brain; sufficient optical communication to permit the light from
the light source to propagate to the patient's scalp without an
undue amount of absorption or reflection; sufficient thermal
communication to permit a substantial amount of heat transport from
the patient's scalp to the light source; sufficient pressure
applied to the patient's scalp to substantially blanch the
irradiated portion of the patient's scalp. For example, the
wearable headpiece can provide one or more mating interfaces to
"lock" the light source at one or more desired treatment sites,
thereby preventing movement of the light source relative to the
patient's brain while irradiating the patient's brain with the
light source.
[0229] In certain embodiments, the force of the "lock" provided by
the headpiece is sufficient to hold the light source in place
without any additional structures or personnel holding the light
source. In certain other embodiments, the force of the "lock"
provided by the headpiece is only sufficient to hold the light
source in place when used in conjunction with other structures or
personnel holding the light source (e.g., supporting the bulk of
the weight of the light source). In certain such embodiments, if
the other structure or personnel ceased holding the light source,
the light source would fall away from the patient's scalp since the
force of the "lock" provided by the headpiece alone is insufficient
to hold the light source in place. The headpiece can be configured
to conform to at least a portion of the patient's head (e.g., scalp
and/or forehead). Any of the embodiments illustrated in FIGS.
23A-23M can be adapted to form a wearable headpiece configured to
receive a mating portion of a light source or light delivery
apparatus.
[0230] FIG. 24 schematically illustrates an example headpiece 550
in accordance with certain embodiments described herein. In certain
embodiments, the headpiece 550 is configured to conform to at least
a portion of the patient's scalp and comprises a plurality of
position indicators 555 configured to indicate corresponding
treatment site locations at which light is to be applied to
non-invasively irradiate at least a portion of the patient's brain.
The plurality of position indicators 555 can be arranged about a
patient's head and can be configured to provide a force to position
a light source to irradiate a treatment site location. At least one
of the position indicators 555 includes an optically transmissive
region 560 and a mating portion 565 configured to releasably mate
with a complementary mating portion of a light source or a light
delivery apparatus.
[0231] In certain embodiments, the plurality of position indicators
555 comprises at least three position indicators 555 distributed
across the patient's scalp, forehead, and/or neck. In other
embodiments, the wearable headpiece 550 comprises between four and
thirty position indicators 555. The position indicators 555 can be
spaced such that adjacent position indicators 555 have perimeters
that do not overlap one another. In certain embodiments, the
perimeters are spaced from one another by at least five
millimeters, at least ten millimeters or at least twenty-five
millimeters. The position indicators 555 can be integrally or
mechanically coupled. FIG. 24 illustrates an integral connection
575A and a mechanical connection 575B. In some embodiments, all of
the position indicators 555 are integrally coupled. In other
embodiments, all of the position indicators 555 are mechanically
coupled. The integral connection 575A can be formed, for example,
during a molding process during manufacture. The mechanical
connection can comprise any suitable mechanical connection device
or method, such as snap-fit members, adhesive members, glue, epoxy,
welding, interference fits, and/or the like.
[0232] In certain embodiments, the optically transmissive region
560 has a substantially circular perimeter and a diameter in a
range between twenty millimeters and fifty millimeters or in a
range between twenty-five millimeters and thirty-five millimeters.
In other embodiments, the optically transmissive region 560 has a
substantially elliptical perimeter with a minor axis greater than
twenty millimeters and a major axis less than fifty millimeters.
Other shapes of the optically transmissive region 560 are also
possible. The optically transmissive region 560 can be shaped to
conform with the shape of a mating portion of a light delivery
apparatus (such as the beam delivery apparatus 10 described
herein). In certain embodiments, the optically transmissive region
560 has an area of at least 1 cm.sup.2, in a range between 1
cm.sup.2 and 20 cm.sup.2, or in a range between 5 cm.sup.2 and 10
cm.sup.2.
[0233] The mating portion 565 can comprise any mechanism or
structure for releasably mating, or mechanically coupling, with a
light delivery apparatus (e.g., any of the light delivery
apparatuses described herein). The mating portion 565 can be
configured to retain the light delivery apparatus in a
substantially fixed position so as to produce a substantially equal
distribution of light from an emission surface of the light source
to a target region of irradiation. The mating portion 565 can
prevent excessive tilting of the light delivery apparatus relative
to the patient's scalp during irradiation. In certain embodiments,
by maintaining a substantially even contact or spacing between the
light delivery apparatus and the patient's skull, the mating
portion 565 and can prevent uneven variations in temperature under
the emission surface of the light delivery apparatus.
[0234] In certain embodiments, the mating portion 565 comprises a
rim bordering the outer perimeter of the aperture or opening. The
rim can have a height between about one millimeter and about
fifteen millimeters. In certain embodiments, the rim can have a
height between three and eight millimeters. The rim can act as a
positioning sleeve for an optical element of a light delivery
apparatus to fit into (e.g., via friction fit).
[0235] The mating portion 565 can be formed of rigid, semi-rigid,
or flexible material. In certain embodiments, the mating portion
565 is formed of molded plastic. The molded plastic can be composed
of any suitable polymer or combination of polymers, such as
thermoplastics, thermosets, and elastomers. The polymers used can
be selected based on strength, flexibility, and/or other
properties. In other embodiments, the mating portion 565 is formed
of rubber or other elastomer materials. In certain embodiments, the
mating portion 565 can be formed of two or more distinct materials.
For example, an inner member of the mating portion 565 can be
formed of one material and an outer member can be formed of another
material. The outer member can comprise a material having a lower
durometer value than the inner member or vice versa.
[0236] In certain embodiments, the rim of the mating portion 565 is
sized and shaped to reversibly mechanically couple a mating portion
of a light delivery apparatus to the mating portion 565 via
friction fit. For example, the rim can be sized and shaped to
receive, via friction fit, the output optical assembly 20 of the
beam delivery apparatus 10 of FIG. 1. In some embodiments, the
inner surface of the rim can be textured to enhance engagement
between the mating portions of the rim and the light delivery
apparatus. In other embodiments, the inner surface of the rim can
be formed of a material, such as a rubber or other elastomer, to
increase friction with the mating portion of the light delivery
apparatus.
[0237] In certain embodiments, the rim of the mating portion 565
can be slotted, grooved, notched, indented, recessed or the like to
releasably mate with a complementary mating portion (e.g., docking
element) of the light delivery apparatus, which may have
protrusions, tabs, rivets, or the like. In some embodiments, the
rim includes one or more recesses or slots sized and shaped to mate
with one or more protrusions formed on the complementary mating
portion of the light delivery apparatus. In other embodiments, the
rim includes one or more protrusions and the light delivery
apparatus includes one or more complementary recesses or slots. In
certain embodiments, the complementary mating portion of the light
delivery apparatus mates with the mating portion 565 of the
position indicator 555 via snap-fit members.
[0238] In still other embodiments, the rim of the mating portion
565 can be threaded so as to receive a complementary threaded
portion of the light delivery apparatus. Any other suitable means
of releasably coupling the light delivery apparatus to the position
indicator 555 can be used in accordance with various embodiments
described herein.
[0239] In alternative embodiments, the position indicators 555 can
include a substantially transmissive (e.g., substantially
transparent or substantially translucent) bag comprising a flexible
material (which can be biocompatible), such as the bags described
in connection with FIGS. 22A-22C of U.S. Pat. Appl. Pub. No.
2007/0179570, which is incorporated in its entirety by reference
herein. The bags can provide a mating interface between the light
delivery apparatus and the surface of the patient's scalp, skin, or
skull.
[0240] In certain embodiments, the bags can be configured to be
raised above the surface of the scalp, skin or skull while the
headpiece 550 is worn by the patient so as to prevent heating of
the bag by the body prior to treatment. The bag can configured to
move to be in thermal communication with the scalp upon the light
delivery apparatus being mated to the position indicator 555. For
example, the emission surface of the light delivery apparatus can
be brought into contact with the bag and the bag can be depressed
by the light delivery apparatus to conform to the surface of the
patient's scalp, skin, or skull. The bag can be used to ensure even
pressure and to reduce air gaps and back reflections. The bag can
also prevent uneven temperature fluctuations at the treatment site.
In some embodiments, the bag can include pressure sensors to
provide an indication of adequate blanching of the treatment site.
In other embodiments, pressure sensors can be positioned about the
periphery of the position indicators. Any suitable pressure sensor
or pressure sensor can be used, including but not limited to,
miniature flush diaphragm sensors, flat plate sensors, and/or the
like.
[0241] In other embodiments, the substantially transmissive bag can
be provided with the light delivery apparatus. For example, the
substantially transmissive bag can be coupled to a contact/emission
surface of the light delivery apparatus and brought into contact
with the patient's scalp or skull when inserted within a position
indicator 555.
[0242] In certain embodiments, the position indicators 555 can be
used to provide feedback to an operator of the light delivery
apparatus. For example, the light delivery apparatus can include
one or more mating sensors that do not allow the light delivery
apparatus to be activated until the light delivery apparatus is in
sufficient contact with a mating portion 565 of a position
indicator 555 of the headpiece 550, which may be indicative of a
satisfactory mating condition.
[0243] In certain embodiments, the mating sensors comprise pressure
sensors (not shown). In other embodiments, the mating sensors
comprise proximity sensors. In certain embodiments, the light
delivery apparatus comprises four quadrant-spaced sensors, thereby
ensuring even pressure of the emission surface against the surface
of the patient's scalp or forehead before activation of the output
optical element of the light delivery apparatus.
[0244] The light delivery apparatus can include one or more LEDs
configured to provide an indication to an operator that sufficient
contact with the mating portion 565 of a position indicator 555 has
occurred. The mating indication can also comprise an audible
indication (such as a click or a beep).
[0245] In certain embodiments, the light delivery apparatus can be
mated (e.g., "locked") to a first position indicator and can then
be activated to irradiate a first treatment site corresponding to
the first position indicator for a first period of time. The light
delivery apparatus can then be removed while the headpiece 550 is
still being worn and mated to a second position indicator, with the
light delivery apparatus being activated to irradiate a second
treatment site corresponding to the second position indicator for a
second period of time upon sufficient contact. The process can be
repeated for each of the position indicators, as described in more
detail herein.
[0246] In certain embodiments, the light delivery apparatus is held
in the mated position by an external support. The external support
can be used to prevent a force from being exerted on the patient's
head and/or neck due to the weight of the light delivery apparatus.
The external support can be provided whether the body 510 and/or
the mating portion 565 is rigid or flexible. In certain
embodiments, the external support is provided by the hand of a
person administering the treatment. In other embodiments, the
external support is provided by an external support structure that
provides a force to maintain the light delivery apparatus in a
mated position (e.g., a wall, a tension and/or anchor system,
etc.). In still other embodiments, the light delivery apparatus is
provided by a mechanism that introduces little or no load to the
patient's head and/or neck, such as a mechanical arm that extends
from a structure that is fixed to a wall, ceiling, or floor. In yet
other embodiments, the light delivery apparatus is substantially
lightweight such that no external support is required.
[0247] In certain embodiments, the mating portion 565 is configured
such that the light delivery apparatus is automatically released
from the mating portion 565 when the external support is removed.
For example, if a person administering the treatment accidentally
lets go of the light delivery apparatus during the treatment
procedure, the mated light delivery apparatus can be automatically
released or disconnected from the mating portion 565 to avoid the
exertion of unwanted force on the patient's head and/or neck or on
the wearable headpiece 550 itself.
[0248] In certain embodiments, the light delivery apparatus can
automatically shut off, or terminate, delivery of light when a loss
of support (or an excessive load) is detected. The loss of external
support can be detected by one or more pressure, touch, force,
and/or light sensors, detectors, and/or transducers, for example.
In other embodiments, the mating/locking mechanism is released or
disconnected if an angle of incidence deviates beyond a
predetermined threshold angle. The automatic release and/or
termination of light delivery can be implemented whether support is
provided externally or by the wearable headpiece 550 itself. Such
sensors can comprise a dead-man's switch, a kill switch, or other
safety device or mechanism.
Methods of Light Delivery
[0249] FIGS. 25-28 are flow diagrams of example methods for
irradiating a surface with light. As described more fully below,
the methods are described by referring to the beam delivery
apparatus 10 and components thereof, as described herein. Other
configurations of a beam delivery apparatus are also compatible
with the methods in accordance with embodiments described
herein.
[0250] The method 610 of FIG. 25 comprises providing a beam
delivery apparatus 10 in an operational block 612. The beam
delivery apparatus 10 comprises a first portion and a second
portion mechanically coupled to the first portion and in optical
communication with the first portion, wherein the first portion and
the second portion are configured to move relative to one another,
as described more fully above. The method 610 further comprises
placing the second portion in thermal communication with the
surface in an operational block 614 (e.g., releasably operatively
coupling the second portion to the surface). The method 610 further
comprises irradiating the surface such that the light from the
first portion propagates through the second portion in an
operational block 616. The method 610 further comprises moving the
first portion and the second portion relative to one another in
response to the second portion being placed in thermal
communication with the surface in an operational block 618.
[0251] The method 620 of FIG. 26 comprises providing an optical
element 23 in an operational block 622. The optical element 23
comprises a substantially optically transmissive and substantially
thermally conductive material, and the optical element 23 has a
first surface 22 and a second surface 24, as described more fully
above. The method 620 further comprises placing the first surface
22 in thermal communication with the irradiated surface in an
operational block 624 (e.g., releasably operatively coupling the
first surface 22 to the irradiated surface). The method 620 further
comprises propagating the light along a first optical path 32
through the second surface 24 and through the first surface 22 to
the irradiated surface in an operational block 626. The method 620
further comprises detecting radiation propagating along a second
optical path 82 from at least a portion of the second surface 24,
wherein the first optical path 32 and the second optical path 82
have a non-zero angle therebetween in an operational block 628. In
certain embodiments, the first surface 22 and the second surface 24
face in generally opposite directions, and the first surface 22 is
not along the second optical path 82.
[0252] The method 630 of FIG. 27 comprises providing a
thermoelectric assembly 90 in an operational block 632. The
thermoelectric assembly 90 comprises a first surface 93 and a
second surface 94, and the thermoelectric assembly 90 generally
surrounds a first region 97, as described more fully above. The
method 630 further comprises providing an output optical assembly
20 in an operational block 633. The method 630 further comprises
releasably mechanically coupling the first surface 93 of the
thermoelectric assembly 90 to the output optical assembly 20 so
that the first surface 93 is in thermal communication with the
output optical assembly 20 in an operational block 634. The method
630 further comprises cooling the first surface 93 and heating the
second surface 94 in an operational block 636. The method 630
further comprises propagating light through the first region 97 to
impinge the irradiated surface in an operational block 638. In
certain embodiments, the first surface 22 and the second surface 24
face in generally opposite directions, and the first surface 22 is
not along the second optical path 82.
[0253] In certain embodiments, the output optical assembly 20
comprises an optical element 23 and a thermally conductive portion
25 generally surrounding a second region 28. The thermally
conductive portion 25 is in thermal communication with the optical
element 23. In certain such embodiments, releasably mechanically
coupling the first surface 93 to the output optical assembly 20
comprises releasably mechanically coupling the first surface 93 to
the thermally conductive portion 25. In certain such embodiments,
the method 630 further comprises placing the optical element 23 in
thermal communication with the irradiated surface and propagating
the light comprises transmitting the light through the first region
97, the second region 28, and the optical element 23 to impinge the
irradiated surface. In certain embodiments, the method 630 further
comprises providing a heat sink 100 in thermal communication with
the second surface 94 of the thermoelectric assembly 90. The heat
sink 100 generally surrounds a third region 107, and propagating
the light comprises transmitting the light through the third region
107, the first region 97, the second region 28, and the optical
element 23.
[0254] The method 640 of FIG. 28 comprises emitting a light beam
from an emission surface 22 of an optical element 23 in an
operational block 642. The light beam at the emission surface 22
has one or more wavelengths in a range of about 630 nanometers to
about 1064 nanometers, a cross-sectional area greater than about 2
cm.sup.2, and a time-averaged irradiance in a range of about 10
mW/cm.sup.2 to about 10 W/cm.sup.2 across the cross-sectional area,
as described more fully above. The method 640 further comprises
removing heat from the emission surface 22 at a rate in a range of
about 0.1 Watt to about 5 Watts in an operational block 644. The
method 640 further comprises impinging the irradiated surface with
the light beam in an operational block 646.
[0255] The method 640 of certain embodiments further comprises
placing the emission surface 22 in thermal communication with the
irradiated surface (e.g., using the emission surface 22 to apply
pressure to the irradiated surface by applying a force to the
emission surface 22 in a direction generally towards the irradiated
surface, the pressure greater than about 0.1 pound per square inch
or about equal to 2 pounds per square inch).
[0256] In certain embodiments, impinging the irradiated surface
with the light beam is performed for a time period of 10 seconds to
two hours, for a time period of 60 seconds to 600 seconds, or for a
time period of about 120 seconds. In certain embodiments, the steps
of the operational blocks 642, 644, and 646 are performed
concurrently. The method 640 of certain embodiments further
comprises moving the emission surface 22 from a first position at
which a first portion of the irradiated surface is impinged by the
light beam to a second position, and repeating the steps of the
operational blocks 642, 644, and 646 so as to impinge a second
portion of the irradiated surface by light emitted from the
emission surface 22. The first portion and the second portion do
not overlap one another in certain embodiments. This method can be
repeated so as to impinge twenty portions of the irradiated surface
by light emitted from the emission surface 22. In certain such
embodiments, the twenty portions of the irradiated surface do not
overlap one another. However, the portions of the patient's brain
irradiated by impinging these twenty portions of the patient's
scalp do overlap one another in certain embodiments.
[0257] The irradiated surface of certain embodiments of the methods
described above in reference to FIGS. 25-28 comprises a portion of
the patient's scalp or skull. In certain other embodiments, the
surface irradiated by the light comprises a portion of a
light-detection system configured to measure one or more parameters
of light irradiating the surface (e.g., irradiance, total power,
beam size, beam profile, beam uniformity). In certain such
embodiments, the method further comprises measuring the one or more
parameters of the light from the apparatus 10 impinging the
surface. For example, the light-detection system can comprise a
portion of the apparatus 10 configured to test the light beam
emitted from the emission surface 22 immediately prior to treatment
of the patient. In this way, the light-detection system can be used
to ensure that the light beam applied to the patient's scalp or
skull has the desired treatment parameters.
[0258] In certain embodiments, a patient is treated by identifying
a plurality of treatment sites (e.g., at least about 10) on the
patient's scalp or skull, directing a light beam to each of the
treatment sites, and irradiating each treatment site with the light
beam. As described more fully below, in certain embodiments, the
treatment sites are identified using an apparatus comprising a
plurality of indicators, each of which corresponds to a treatment
site location. In certain such embodiments, the treatment sites are
sequentially irradiated by a light beam from the emission surface.
In certain other embodiments, the treatment sites are instead
identified by other indicia. For example, each of the treatment
sites can be identified by markings made on the scalp, or by
structures placed in proximity to the scalp or skull. Each of the
treatment sites can then be irradiated. In certain embodiments,
each of the treatment sites is irradiated by a light beam from the
emission surface while the emission surface is in contact with the
scalp or skull or in contact with an intervening optically
transmissive element which contacts the scalp or skull. In certain
other embodiments, the scalp or skull is not contacted by either
the emission surface or an intervening element. In certain
embodiments, each of the treatment sites is irradiated using a
single beam delivery apparatus which is sequentially moved from one
treatment site to another. In certain other embodiments, a
plurality of beam delivery apparatuses are used to irradiate
multiple treatment sites concurrently. In certain such embodiments,
the number of beam delivery apparatuses is fewer than the number of
treatments sites, and the plurality of beam delivery apparatuses
are sequentially moved to sequentially irradiate the treatment
sites.
[0259] FIG. 29A is a flow diagram of an example method 700 for
controllably exposing at least one predetermined area of a
patient's scalp or skull to laser light to irradiate the patient's
brain. As described more fully below, the method 700 is described
by referring to the wearable apparatus 500 and the beam delivery
apparatus 10 described herein. Other configurations of a wearable
apparatus 500 and a beam delivery apparatus 10 are also compatible
with the method 700 in accordance with embodiments described
herein.
[0260] The method 700 comprises providing a beam delivery apparatus
10 in an operational block 710. In certain embodiments, the beam
delivery apparatus 10 comprises an emission surface 22 configured
to emit a light beam. Other configurations of the beam delivery
apparatus 10 besides those described above are also compatible with
certain embodiments described herein.
[0261] The method 700 further comprises placing a wearable
apparatus 500 over the patient's scalp in an operational block 720.
The apparatus 500 comprises a body 510 and a plurality of
indicators 520. In certain embodiments, each indicator 520 is
substantially transmissive to the light beam emitted from the
emission surface 22. Other configurations of the wearable apparatus
500 besides those described above are also compatible with certain
embodiments described herein.
[0262] The method 700 further comprises placing the emission
surface 22 in thermal communication with a treatment site of the
patient's scalp or skull to be irradiated in an operational block
730. The method 700 further comprises irradiating the treatment
site with light emitted by the emission surface 22 in an
operational block 740. In certain embodiments, the light beam is
transmitted through the indicator 520.
[0263] In certain embodiments, providing the light emitting
apparatus 600 in the operational block 710 comprises preparing the
beam delivery apparatus 10 for use to treat the patient. In certain
embodiments, preparing the beam delivery apparatus 10 comprises
cleaning the portion of the beam delivery apparatus 10 through
which laser light is outputted. In certain embodiments, preparing
the beam delivery apparatus 10 comprises verifying a power
calibration of laser light outputted from the beam delivery
apparatus 10. Such verification can comprise measuring the light
intensity output from the beam delivery apparatus 10 and comparing
the measured intensity to an expected intensity level.
[0264] In certain embodiments, placing the wearable apparatus 500
over the patient's scalp in the operational block 720 comprises
preparing the patient's scalp for treatment. For example, in
certain embodiments, preparing the patient's scalp for treatment
comprises removing hair from the predetermined areas of the
patient's scalp to be irradiated. Removing the hair (e.g., by
shaving) advantageously reduces heating of the patient's scalp by
hair which absorbs laser light from the beam delivery apparatus 10.
In certain embodiments, placing the wearable apparatus 500 over the
patient's scalp in the operational block 720 comprises positioning
the wearable apparatus 500 so that each indicator 520 is in
position to indicate a corresponding portion of the patient's scalp
or skull to be irradiated.
[0265] In certain embodiments, placing the emission surface 22 in
thermal communication with the treatment site in the operational
block 730 comprises pressing the emission surface 22 to the
treatment site. In certain embodiments, by pressing the emission
surface 22 against the treatment site in this way, pressure is
applied to the portion of the patient's scalp of the treatment site
so as to advantageously blanch the portion of the patient's scalp
to be irradiated.
[0266] In certain embodiments, irradiating the treatment site of
the patient's scalp or skull in the operational block 740 comprises
triggering the emission of light from the emission surface 22 by
pressing the emission surface 22 against the treatment site with a
predetermined level of pressure. In certain embodiments, the
emission of light from the emission surface 22 continues only if a
predetermined level of pressure is maintained by pressing the
emission surface 22 against the treatment site. In certain
embodiments, light is emitted from the emission surface 22 to the
treatment site for a predetermined period of time.
[0267] In certain embodiments, the method further comprises
irradiating additional treatment sites of the patient's scalp or
skull during a treatment process. For example, after irradiating a
first treatment site corresponding to a first indicator, as
described above, the emission surface 22 can be placed in contact
with a second indicator corresponding to a second treatment site
and irradiating the second treatment site with light emitted by the
emission surface 22. The various treatment sites of the patient's
scalp or skull can be irradiated sequentially to one another in a
predetermined sequence. In certain embodiments, the predetermined
sequence is represented by the indicators of the wearable apparatus
500. In certain such embodiments, the beam delivery apparatus 10
comprises an interlock system which interfaces with the indicators
of the wearable apparatus 500 to prevent the various treatment
sites from being irradiated out of the predetermined sequence.
[0268] FIG. 29B is a flow diagram of an example method 750 for
providing phototherapy to at least a portion of a patient's brain.
As described more fully below, the method 750 is described by
referring to the wearable headpiece 550 and a light source (e.g.,
the beam delivery apparatus 10) described herein. Other
configurations of a wearable headpiece 550 and a light source are
also compatible with the method 750 in accordance with embodiments
described herein.
[0269] The method 750 comprises providing a light source (e.g.,
beam delivery apparatus 10) in an operational block 755. In certain
embodiments, the light source comprises an emission surface
configured to emit a light beam.
[0270] The method 750 further comprises placing a wearable
headpiece 550 over the patient's scalp in an operational block 760.
The headpiece 550 comprises a plurality of position indicators 555.
In certain embodiments, at least one of the position indicators 555
includes an optically transmissive region that is substantially
transmissive to the light emitted from the emission surface of the
light source and a mating portion that is configured to releasably
mate with a complementary portion of the light source. Other
configurations of the wearable headpiece 550 besides those
described above are also compatible with certain embodiments
described herein.
[0271] The method 750 further comprises reversibly mechanically
coupling the light source to a first portion of the headpiece 550
while the headpiece 550 is on the patient's head in an operational
block 765. The mechanical coupling can occur via friction fit,
threading, snap-fit members, or any other suitable coupling means.
The method 750 further comprises irradiating a first treatment site
with light emitted by the emission surface of the light source
while the light source is mechanically coupled to the first portion
of the headpiece 550 in an operation block 770. The first portion
of the headpiece 550 applies a first force to the light source such
that light emitted by the light source non-invasively irradiates at
least a first portion of the patient's brain by propagating through
the first treatment site of the patient's scalp.
[0272] The method 750 further comprises decoupling the light source
from the first portion of the headpiece 550 while the headpiece 550
remains on the patient's head in an operational block 775. In
certain embodiments, the method 750 further comprises irradiating
additional treatment sites of the patient's scalp or skull during a
treatment process. For example, operational blocks 765 through 775
can be repeated at a second portion of the headpiece 550 by
reversibly mechanically coupling the light source to a second
portion of the headpiece 550 while the headpiece 550 is on the
patient's head, wherein the headpiece 550 applies a second force to
the light source such that light emitted by the light source while
the light source is mechanically coupled to the second portion of
the headpiece 550 non-invasively irradiates at least a second
portion of the patient's brain by propagating through a second
treatment site of the patient's scalp and then decoupling the light
source from the second portion of the headpiece 550 while the
headpiece 550 remains on the patient's head.
[0273] In certain embodiments, the first portion of the patient's
brain and the second portion of the patient's brain at least
partially overlap one another and the first treatment site and the
second treatment site do not at least partially overlap one
another. In certain embodiments, the first portion of the headpiece
550 is a first position indicator 555 and the second portion of the
headpiece 550 is a second position indicator 555.
[0274] In certain embodiments, the method 750 comprises verifying
(e.g., through the use of pressure sensors) that a sufficient
pressure exists between a mating portion of the light source and
the first portion of the headpiece 550 before irradiating the first
treatment site at operational block 770. In other embodiments,
multiple light sources can be reversibly mechanically coupled to
portions of the headpiece 550 simultaneously.
[0275] FIG. 30 is a flow diagram of another example method 800 for
treating a patient's brain. The method 800 is described below by
referring to the wearable apparatus 500 and the beam delivery
apparatus 10 described herein. Other configurations of a wearable
apparatus 500 and a beam delivery apparatus 10 are also compatible
with the method 700 in accordance with embodiments described
herein.
[0276] The method 800 comprises noninvasively irradiating a first
area of at least 1 cm.sup.2 of the patient's scalp or skull with
laser light during a first time period in an operational block 810.
The method 800 further comprises noninvasively irradiating a second
area of at least 1 cm.sup.2 of the patient's scalp or skull with
laser light during a second time period in an operational block
820. The first area and the second area do not overlap one another,
and the first time period and the second time period do not overlap
one another. In certain embodiments, the first area and the second
area are spaced from one another by at least 10 millimeters. In
certain embodiments, the first area is over a first hemisphere of
the brain, and the second area is over a second hemisphere of the
brain.
[0277] In certain embodiments, the method 800 further comprises
identifying the first area and the second area by placing a
template over the patient's scalp. The template comprises a first
indicator of the first area and a second indicator of the second
area. For example, the first indicator can comprise a first opening
in the template and the second indicator can comprise a second
opening in the template. In certain embodiments, the method 800
further comprises placing a laser light source at a first position
to noninvasively irradiate the first area and moving the laser
light source to a second position to noninvasively irradiate the
second area.
[0278] In certain embodiments, the method 800 further comprises
increasing the transmissivity of the first area to the laser light
and increasing the transmissivity of the second area to the laser
light. Increasing the transmissivity of the first area can comprise
applying pressure to the first area to at least partially blanch
the first area, removing hair from the first area prior to
noninvasively irradiating the first area, applying an
index-matching material to the first area, or a combination of two
or more of these measures. Increasing the transmissivity of the
second area can comprise applying pressure to the second area to at
least partially blanch the second area, removing hair from the
second area prior to noninvasively irradiating the second area,
applying an index-matching material to the second area, or a
combination of two or more of these measures.
[0279] FIG. 38 is a flow diagram of an example method 900 for
treating a patient's brain in accordance with certain embodiments
described herein. The method 900 comprises providing a patient in
an operational block 910 whose brain has experienced at least one
neurologic disorder (e.g., Alzheimer's Disease, Parkinson's
Disease, Huntington's disease, depression) or physical trauma
(e.g., an ischemic stroke or a traumatic brain injury) resulting in
a blood flow reduction to at least some brain cells of the patient.
The method 900 further comprises irradiating at least a portion of
the patient's scalp or skull with a pulsed light beam comprising a
plurality of pulses transmitted through the patient's skull in an
operational block 920. The pulsed light beam has a temporal profile
which supports one or more intercellular or intracellular
biological processes involved in the survival or regeneration of
brain cells. For example, the pulsed light beam of certain
embodiments comprises an average irradiance per pulse and a
temporal profile comprising a temporal pulse width and a duty cycle
sufficient to penetrate the skull to modulate membrane potentials,
thereby enhancing cell survival (e.g., to cause increased neuron
survival), cell function, or both of the irradiated brain
cells.
[0280] In certain embodiments, providing the patient comprises
identifying a patient whose brain has experienced at least one
neurologic disorder or physical trauma. In certain such
embodiments, identifying the patient comprises communicating with
the patient, or with another person with knowledge regarding the
patient's health or experiences, and determining whether the
patient has experienced a neurologic disorder or a physical trauma
to the brain. In certain other embodiments, identifying the patient
comprises examining the patient's body (e.g., head or skull) for
evidence of the patient having experienced a physical trauma to the
brain. This examination in certain embodiments includes use of
invasive or non-invasive medical devices, techniques, or probes
(e.g., a magnetic resonance imaging device). In certain other
embodiments, identifying the patient comprises administering a test
of the patient's mental faculties (e.g., to determine the patient's
abilities on a neurologic function scale) for evidence indicating
that the patient has experienced a neurologic disorder or a
physical trauma to the brain. Persons skilled in the art are able
to identify the patient in accordance with various embodiments
described herein. In certain embodiments, providing the patient
comprises receiving information regarding the results of a previous
identification (e.g., communication, examination, or test
administration) of the patient as one who has experienced at least
one neurologic disorder or physical trauma.
[0281] In certain embodiments, irradiating at least a portion of
the patient's scalp or skull with a pulsed light beam comprises
generating the pulsed light beam and directing the pulsed light
beam to irradiate at least a portion of the patient's scalp or
skull. The pulsed light beam of certain embodiments has a
wavelength, time-averaged irradiance, beam size, beam profile,
divergence, temporal pulse width, duty cycle, repetition rate, and
peak irradiance per pulse, as described herein. Various light
delivery apparatuses can be used to generate the pulsed light beam
and to direct the pulsed light beam towards the patient's scalp or
skull, including but not limited to, the apparatus disclosed herein
or by U.S. Pat. Nos. 6,214,035; 6,267,780; 6,273,905; 6,290,714;
7,303,578; and 7,575,589 and in U.S. Pat. Appl. Publ. Nos.
2005/0107851 A1 and 2009/0254154 A1, each of which is incorporated
in its entirety by reference herein.
[0282] In certain embodiments, irradiating at least a portion of
the patient's scalp or skull comprises identifying one or more
treatment sites (e.g., at least 10, between 2 and 100, or between
15 and 25) and sequentially irradiating the treatment sites with
the pulsed light beam. In certain embodiments, the one or more
treatment sites are identified as described herein (e.g., by an
apparatus worn by the patient and comprising one or more apertures,
by markings made on the scalp, or by structures placed in proximity
to the scalp or skull). In certain embodiments, each treatment site
is irradiated by an apparatus in contact with the scalp or skull or
not in contact with the scalp or skull as described herein. In
certain such embodiments, the irradiated portion of the scalp is
blanched during the irradiation, is not blanched during the
irradiation, is cooled during the irradiation, or is not cooled
during the irradiation.
[0283] In certain embodiments, the patient's scalp is prepared for
treatment prior to irradiation. For example, in certain
embodiments, preparing the patient's scalp for treatment comprises
removing at least a portion of the hair or substantially all the
hair from the predetermined areas of the patient's scalp to be
irradiated. Removing the hair (e.g., by shaving so that the
irradiated portion of the scalp is substantially free of hair)
advantageously reduces heating of the patient's scalp by hair which
absorbs the light from the light emitting apparatus. In certain
other embodiments, the hair is not shaved or otherwise removed
prior to irradiation. For example, irradiating the patient's scalp
can be performed using pulsed light with wavelengths, temporal
pulse widths, and duty cycles which avoid adverse heating of the
patient's scalp due to absorption of light by the hair.
[0284] In certain embodiments, the parameters of the pulsed light
beam used to irradiate the patient's scalp or skull are selected to
perform one or more of the following: (i) to cause increased neuron
survival of the brain cells following at least one physical trauma,
(ii) to support one or more intercellular or intracellular
biological processes involved in the survival or regeneration of
brain cells, or (iii) to modulate membrane potentials in order to
enhance, restore, or promote cell survival, cell function, or both
of the irradiated brain cells following a traumatic brain injury.
In one example such embodiment, the pulsed light beam at the
emission surface of the apparatus has a beam diameter in a range
between 10 millimeters and 40 millimeters, an average irradiance
per pulse in a range between 10 mW/cm.sup.2 and 10 W/cm.sup.2, one
or more wavelengths in a range between 780 nanometers and 840
nanometers, and a temporal pulsewidth in a range between 0.1
millisecond and 150 seconds or between 0.1 millisecond and 300
milliseconds. The duty cycle of certain embodiments can be in a
range between 10% and 30%. Other ranges of these parameters of the
pulsed light beam can be selected in accordance with various other
embodiments described herein.
Neurologic Function Scales
[0285] Neurologic function scales can be used to quantify or
otherwise characterize the efficacy of various embodiments
described herein. Neurologic function scales generally use a number
of levels or points, each point corresponding to an aspect of the
patient's condition. The number of points for a patient can be used
to quantify the patient's condition, and improvements in the
patient's condition can be expressed by changes of the number of
points. One example neurologic function scale is the National
Institute of Health Stroke Scale (NIHSS) which can be used for
short-term measurements of efficacy (e.g., at 24 hours). The NIHSS
is a comprehensive and objective scale which utilizes a
seven-minute physical exam, a 13 item scale, and 42 points. Zero
points corresponds to a normal exam, 42 points (the maximum)
corresponds to basically comatose, and over 15-20 points indicates
that the effects of the stroke are particularly severe. The NIHSS
has previously been used for tPA trials in the treatment of
ischemic stroke, with a 4-point change over 24 hours and an overall
score of 0 or 1 at three months indicative of a favorable outcome.
Other neurologic function scales include, but are not limited to,
modified Rankin Scale (mRS), Barthel Index (BI), Glasgow Outcome,
Glasgow Coma Scale, Canadian Neurologic Scale, and stroke impact
scales such as SIS-3 and SIS-16. In some scales, an improvement in
the patient's condition is indicated by a reduction in the number
of points. For example, the mRS has six points total, with zero
corresponding to normal functioning, and six corresponding to
death. In other scales, an improvement in the patient's condition
is indicated by an increase in the number of points. For example,
in the Glasgow Outcome which has five points, zero corresponds to
death and five corresponds to full recovery. In certain
embodiments, two or more of the neurologic function scales can be
used in combination with one another, and can provide longer-term
measurements of efficacy (e.g., at three months).
[0286] For stroke, the U.S. Food and Drug Administration (FDA) and
the neurologic community have expressed interest in clinical
patient outcomes at 90 days post stroke. Two of the most common and
accepted instruments for measuring efficacy are the NIHSS and mRS.
The FDA is flexible in the way that neurologic function scales can
be used. For example, it is acceptable to use the mRS (i) in
dichotomized fashion with success at score of 0-1 or (ii) it can be
analyzed looking at shifts in the scale showing improvement of
patients along the five-point scale.
[0287] In certain embodiments described herein, a patient
exhibiting symptoms of an ischemic stroke is treated by irradiating
a plurality of treatment sites on the patient's scalp. The
irradiation is performed utilizing irradiation parameters (e.g.,
wavelength, irradiance, time period of irradiation, etc.) which,
when applied to members of a treated group of patients, produce at
least a 2% average difference between the treated group and a
placebo group on at least one neurologic function scale analyzed in
dichotomized or any other fashion and selected from the group
consisting of: NIHSS, mRS, BI, Glasgow Outcome, Glasgow Coma Scale,
Canadian Neurologic Scale, SIS-3, and SIS-16. Certain other
embodiments produce at least a 4% average difference, at least a 6%
average difference, or at least a 10% average difference between
treated and placebo groups on at least one of the neurologic
function scales analyzed in dichotomized or any other fashion and
selected from the group consisting of: NIHSS, mRS, BI, Glasgow
Outcome, Glasgow Coma Scale, Canadian Neurologic Scale, SIS-3, and
SIS-16. In certain embodiments, the irradiation of the patient's
scalp produces a change in the patient's condition. In certain such
embodiments, the change in the patient's condition corresponds to a
change in the number of points indicative of the patient's
condition. In certain such embodiments, the irradiation produces a
change of one point, a change of two points, a change of three
points, or a change of more than three points on a neurologic
function scale.
[0288] Various studies have been conducted to provide information
regarding the interaction of laser light with the human body and
the effectiveness and safety of transcranial light therapy (TLT).
For example, (i) power density measurements have been made to
determine the transmission of laser light having a wavelength of
approximately 808 nanometers through successive layers of human
brain tissue; (ii) in vivo thermal measurements have been made to
determine the heating effect in living tissue of laser light having
a wavelength of approximately 808 nanometers; (iii) NEST-1 and
NEST-2 phototherapy trials ("Infrared laser therapy for ischemic
stroke: a new treatment strategy: Results of the NeuroThera
Effectiveness and Safety Trial-1 (NEST-1)," Stroke, 2007;
38:1843-1849, incorporated in its entirety by reference herein, and
"Effectiveness and safety of transcranial laser therapy for acute
ischemic stroke," Stroke, 2009:40:1359-1364, which is incorporated
in its entirety by reference herein), suggest the safety and
efficacy of transcranial light therapy (TLT) for treatment of
humans with ischemic stroke; (iv) examination of continuous wave
(CW) and pulse wave (PW) NILT delivery frequency settings to
determine optimally efficacious treatment regimens using the RSCEM
(see, P. A. Lapchak, L. De Taboada, "Transcranial near infrared
laser treatment (NILT) increases cortical adenosine-5'-triphosphate
(ATP) content following embolic strokes in rabbits," Brain
Research, Vol. 1306, pp. 100-105 (2010), which is incorporated in
its entirety by reference herein; (v) study of low-level laser
therapy (LLLT) for TBI using the mouse closed-head injury (CHI)
model by studying the neurobehavioral and histological outcome of
the traumatized mice (see, A. Oron et al., "Low-Level Laser Therapy
Applied Transcranially to Mice following Traumatic Brain Injury
Significantly Reduces Long-Term Neurological Deficits," Journal of
Neurotrauma, Volume 24, Number 4, 2007 which is incorporated in its
entirety by reference herein); and (vi) study of infrared
Transcranial Laser Therapy (TLT) for efficacy in an amyloid
precursor peptide (APP) transgenic mouse model of Alzheimer's
Disease (AD). These various studies are described more fully in
U.S. Pat. Appl. Publ. No. US 2009/0254154 A1, which is incorporated
in its entirety by reference herein.
[0289] The explanations and illustrations presented herein are
intended to acquaint others skilled in the art with the invention,
its principles, and its practical application. Those skilled in the
art may adapt and apply the invention in its numerous forms, as may
be best suited to the requirements of a particular use.
Accordingly, the specific embodiments of the present invention as
set forth are not intended as being exhaustive or limiting of the
invention.
* * * * *