U.S. patent application number 11/766037 was filed with the patent office on 2008-01-03 for method of treating or preventing depression.
Invention is credited to Jackson Streeter, Luis De Taboada.
Application Number | 20080004565 11/766037 |
Document ID | / |
Family ID | 34865136 |
Filed Date | 2008-01-03 |
United States Patent
Application |
20080004565 |
Kind Code |
A1 |
Streeter; Jackson ; et
al. |
January 3, 2008 |
METHOD OF TREATING OR PREVENTING DEPRESSION
Abstract
A method of treating or preventing depression is provided. The
method includes non-invasively irradiating at least a portion of a
patient's brain with electromagnetic radiation having a power
density between 0.01 mW/cm.sup.2 and 100 mW/cm.sup.2 at a depth of
approximately 2 centimeters below the dura.
Inventors: |
Streeter; Jackson; (Reno,
NV) ; Taboada; Luis De; (Carlsbad, CA) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE
CA
92614
US
|
Family ID: |
34865136 |
Appl. No.: |
11/766037 |
Filed: |
June 20, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11038770 |
Jan 19, 2005 |
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11766037 |
Jun 20, 2007 |
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10764986 |
Jan 26, 2004 |
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11766037 |
Jun 20, 2007 |
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60537190 |
Jan 19, 2004 |
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60442693 |
Jan 24, 2003 |
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Current U.S.
Class: |
604/20 |
Current CPC
Class: |
A61N 7/00 20130101; A61N
2005/007 20130101; A61N 2005/0659 20130101; A61N 2005/067 20130101;
A61N 1/40 20130101; A61N 5/0622 20130101; A61N 2005/0652 20130101;
A61N 2005/0647 20130101; A61N 5/0613 20130101; A61N 5/0617
20130101 |
Class at
Publication: |
604/020 |
International
Class: |
A61N 1/30 20060101
A61N001/30 |
Claims
1. A method of treating or preventing depression, the method
comprising: non-invasively irradiating at least a portion of a
patient's brain with electromagnetic radiation having a power
density between 0.01 mW/cm.sup.2 and 100 mW/cm.sup.2 at a depth of
approximately 2 centimeters below the dura.
2. The method of claim 1, wherein the power density and a
wavelength of the electromagnetic radiation are sufficient to cause
a neurotrophic effect and/or regulation of neurotransmitters.
3. The method of claim 1, wherein non-invasively irradiating causes
a diminishment or elimination of depression and its symptoms.
4. The method of claim 1, wherein the electromagnetic radiation has
a power density of at least about 0.1 mW/cm.sup.2 at a depth of
approximately 2 centimeters below the dura.
5. The method of claim 1, wherein the electromagnetic radiation has
a power density of at least about 10 mW/cm.sup.2 at a depth of
approximately 2 centimeters below the dura.
6. The method of claim 1, wherein the electromagnetic radiation has
a wavelength between about 630 nanometers and about 1064
nanometers.
7. The method of claim 1, wherein the electromagnetic radiation has
a wavelength between about 780 nanometers and about 840
nanometers.
8. The method of claim 1, wherein the electromagnetic radiation has
a power density between about 10 mW/cm.sup.2 and about 10
W/cm.sup.2 at the surface of the scalp.
9. The method of claim 1, further comprising delivering the
electromagnetic radiation for at least one treatment period of at
least about ten minutes.
10. The method of claim 1, further comprising delivering the
electromagnetic radiation for at least one treatment period for at
least about five minutes.
11. The method of claim 10, wherein the electromagnetic radiation
is pulsed during the treatment period.
12. The method of claim 10, wherein the electromagnetic radiation
is continuous during the treatment period.
13. The method of claim 10, wherein the electromagnetic radiation
is delivered in five or more treatment periods occurring over the
course of at least one week.
14. A method of treating or preventing depression, the method
comprising: causing a neurotrophic effect and/or regulation of
neurotransmitters by non-invasively irradiating at least a portion
of a patient's brain with electromagnetic radiation during at least
one treatment period, the electromagnetic radiation having a power
density between 0.01 mW/cm.sup.2 and 100 mW/cm.sup.2 at a depth of
approximately 2 centimeters below the dura.
15. The method of claim 14, wherein the electromagnetic radiation
has a wavelength between about 630 nanometers and about 1064
nanometers.
16. The method of claim 14, wherein non-invasively irradiating is
performed for five or more treatment periods occurring over the
course of at least one week, each treatment period having a
duration of at least about five minutes.
17. The method of claim 14, wherein the electromagnetic radiation
is pulsed during the at least one treatment period.
18. The method of claim 14, wherein the electromagnetic radiation
is continuously applied during the at least one treatment
period.
19. A method of treating or preventing depression, the method
comprising: irradiating at least a portion of a patient's brain
with electromagnetic radiation transmitted through the scalp, the
electromagnetic radiation having a power density between 0.01
mW/cm.sup.2 and 100 mW/cm.sup.2 at a depth of approximately 2
centimeters below the dura.
20. The method of claim 19, wherein the scalp is cooled while
irradiating at least the portion of the patient's brain.
Description
RELATED APPLICATION INFORMATION
[0001] This application is a continuation of U.S. patent
application Ser. No. 11/038,770, filed Jan. 19, 2005 and which
claims the benefit of U.S. Provisional Application No. 60/537,190
filed Jan. 19, 2004, and which is a continuation-in-part of U.S.
application Ser. No. 10/764,986, filed Jan. 26, 2004, which claims
the benefit of U.S. Provisional Application No. 60/442,693 filed
Jan. 24, 2003. The disclosures of U.S. patent application Ser. Nos.
11/038,770 and 10/764,986 and U.S. Provisional Application Nos.
60/537,190 and 60/442,693 are hereby incorporated by reference in
their entireties.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates in general to treatment of
depression and depressive symptoms, and more particularly, to of
treatment using phototherapy of brain tissue.
[0004] 2. Description of the Related Art
[0005] In the U.S., it is believed that approximately 10% of people
suffer from depression at any one time, and 20%-25% suffer an
episode of depression at some point during their lifetimes. The
disease affects people of all ages, including children, adults, and
the elderly, and disproportionally affects women, with about twice
as many women as men suffering from depression at some point in
their lives. Additionally, persons who suffer one episode of major
depression are much more likely to have additional episodes than
those who have not experienced serious depression.
[0006] There are several types of depression which vary in severity
and average episode length. Two of the most common types are major
depression and chronic depression or Dysthmia. Chronic depression
is generally a less severe form of depression, having milder but
longer lasting symptoms than major depression. The symptoms of both
types of depression are essentially the same, and include sadness,
loss of energy, feelings of hopelessness, difficulty concentrating,
insomnia, and irritability. Individuals suffering depression are
also more likely to engage in drug or alcohol abuse, and if
untreated, depression can lead to violence, including suicide.
[0007] All types of depression, including major and chronic
depression, are commonly treated by one or both of antidepressant
medication and psychotherapy. Other forms of treatment, such as
electroconvulsive therapy (ECT) are also used, albeit less
frequently. There are several types of antidepressant medications
presently available, including tricyclic antidepressants (TCAs),
monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake
inhibitors (SSRIs), and selective norepinephrine reuptake
inhibitors (SSNRIs). Although the widely prescribed SSRIs cause
fewer severe side effects than the older TCA and MAOI drugs, they
are not without their own unpleasant effects, including dizziness,
insomnia, and reduced sexual desire and performance. Despite their
widespread use, antidepressant medications are only moderately
successful, helping only about 70% of the people who take them.
[0008] Against this background, a high level of interest remains in
finding new and improved methods for the treatment of depression
that exhibit higher rates of effectiveness and fewer side effects
of available drug therapy.
SUMMARY OF THE INVENTION
[0009] In accordance with one embodiment, there is provided a
method for treating depression comprising irradiating at least a
portion of a patient's brain with light energy having an
efficacious power density and wavelength. The light energy is
sufficient to cause a diminishment or elimination of depression and
its symptoms, and/or delays, reduces, or eliminates the onset of
depression or depressive symptoms. It is believed that the
radiation causes an upregulation of endogenous compounds in the
brain, including neurotrophic factors, that serve to enhance neural
growth, neurogenesis, and/or plasticity of neural function that
cause the beneficial effects in the brain, and/or that the
radiation results in a more normal balance of neurotransmitters in
the brain.
[0010] Other embodiments also each provide a method for treating,
preventing, or reducing the symptoms of depression. Such methods
preferably result in the upregulation of endogenous compounds
useful in treating depression, reducing the symptoms or severity of
depression, or preventing depression, including neurotrophic
factors that cause or promote neurogenesis, neural growth, and/or
plasticity of neural function. One such method comprises
introducing light of an efficacious power density onto brain tissue
by directing light through the scalp of a patient. Directing the
light comprises providing a sufficiently large spot size on said
scalp to reduce the power density at the scalp below the damage
threshold of scalp tissue, while producing sufficient optical power
at the scalp to achieve said efficacious power density at the brain
tissue. Another such method comprises directing an efficacious
power density of light through the scalp of the patient to a target
area of the brain and/or to the cortex of the brain concurrently
with applying an efficacious amount of ultrasonic energy or an
electromagnetic field to the brain. Yet another method comprises
introducing light of an efficacious power density onto a target
area of the brain and/or to the cortex of the brain by directing
light through the scalp of the patient. The light has a plurality
of wavelengths and the efficacious power density is at least 0.01
mW/cm.sup.2 at the target area.
[0011] In preferred embodiments, the methods utilize a therapy
apparatus for treating a patient's brain. One suitable therapy
apparatus comprises a light source having an output emission area
positioned to irradiate a portion of the brain with an efficacious
power density and wavelength of light. The therapy apparatus
further comprises an element interposed between the light source
and the patient's scalp. The element is adapted to inhibit
temperature increases at the scalp caused by the light.
[0012] Another suitable therapy apparatus comprises a light source
positioned to irradiate at least a portion of a patient's head with
light. The light has a wavelength and power density which
penetrates the cranium to deliver an efficacious amount of light to
brain tissue. The therapy apparatus further comprises a material
which inhibits temperature increases of the head.
[0013] Another suitable therapy apparatus comprises a light source
adapted to irradiate at least a portion of the brain with an
efficacious power density and wavelength of light. The therapy
apparatus further comprises an element adapted to inhibit
temperature increases at the scalp. At least a portion of the
element is in an optical path of the light from the light source to
the scalp.
[0014] Another suitable therapy apparatus comprises a light source
adapted to irradiate at least a portion of the brain with an
efficacious power density and wavelength of light. The therapy
apparatus further comprises a controller for energizing said light
source so as to selectively produce a plurality of different
irradiation patterns on the patient's scalp. Each of said
irradiation patterns is comprised of at least one illumination area
that is small compared to the patient's scalp, and at least one
non-illuminated area.
[0015] Another suitable therapy apparatus comprises a light source
adapted to irradiate at least a portion of the brain with an
efficacious power density and wavelength of light. The therapy
apparatus further comprises a biomedical sensor configured to
provide real-time feedback information. The therapy apparatus
further comprises a controller coupled to the light source and the
biomedical sensor. The controller is configured to adjust said
light source in response to the real-time feedback information.
[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 a therapy apparatus
comprising a cap which fits securely over the patient's head.
[0018] FIG. 2 schematically illustrates a fragmentary
cross-sectional view taken along the lines 2-2 of FIG. 1, showing
one embodiment of a portion of a therapy apparatus comprising an
element and its relationship to the scalp and brain.
[0019] FIG. 3 schematically illustrates an embodiment with an
element comprising a container coupled to an inlet conduit and an
outlet conduit for the transport of a flowing material through the
element.
[0020] FIG. 4A schematically illustrates a fragmentary
cross-sectional view taken along the lines 2-2 of FIG. 1, showing
another embodiment of a portion of a therapy apparatus comprising
an element with a portion contacting the scalp and a portion spaced
away from the scalp.
[0021] FIG. 4B schematically illustrates a fragmentary
cross-sectional view taken along the lines 2-2 of FIG. 1, showing
an embodiment of a portion of a therapy apparatus comprising a
plurality of light sources and an element with portions contacting
the scalp and portions spaced away from the scalp.
[0022] FIGS. 5A and 5B schematically illustrate cross-sectional
views of two embodiments of the element in accordance with FIG. 4B
taken along the line 4-4.
[0023] FIGS. 6A-6C schematically illustrate an embodiment in which
the light sources are spaced away from the scalp.
[0024] FIGS. 7A and 7B schematically illustrate the diffusive
effect on the light by the element.
[0025] FIGS. 8A and 8B schematically illustrate two light beams
having different cross-sections impinging a patient's scalp and
propagating through the patient's head to irradiate a portion of
the patient's brain tissue.
[0026] FIG. 9A schematically illustrates a therapy apparatus
comprising a cap and a light source comprising a light blanket.
[0027] FIGS. 9B and 9C schematically illustrate two embodiments of
the light blanket.
[0028] FIG. 10 schematically illustrates a therapy apparatus
comprising a flexible strap and a housing.
[0029] FIG. 11 schematically illustrates a therapy apparatus
comprising a handheld probe.
[0030] FIG. 12 is a block diagram of a control circuit comprising a
programmable controller.
[0031] FIG. 13 schematically illustrates a therapy apparatus
comprising a light source and a controller.
[0032] FIG. 14 schematically illustrates a light source comprising
a laser diode and a galvometer with a mirror and a plurality of
motors.
[0033] FIGS. 15A and 15B schematically illustrate two irradiation
patterns that are spatially shifted relative to each other.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0034] It has recently been proposed that depression is caused by
the action of stress hormones. Stress hormones such as
corticotrophin-releasing hormone (CRH) result in a decrease in
compounds called neurotrophic factors that are responsible for
neurogenesis and neural growth, including the growth of neural
projections such as dendrites and axons, as well as a decrease in
the flexibility of synapses.
[0035] Accordingly, therapy that results in the upregulation of
neurotrophic factors and other endogenous compounds that cause or
assist neurogenesis and neural growth should be useful in treating
depression, reducing the symptoms or severity of depression, or
preventing depression. Therapy that causes the regulation of
neurotransmitters in the brain such that their concentrations are
at more normal levels, much like the various pharmacological
therapies, should also be useful against depression. Low level
light therapy ("LLLT") or phototherapy administered to the brain is
believed to achieve these desired effects.
[0036] Low level light therapy or phototherapy involves therapeutic
administration of light energy to a patient at lower power outputs
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. No. 6,537,304 to Oron and U.S. patent
application Ser. Nos. 10/353,130, 10/682,379 filed Oct. 9, 2003,
and 10/938,423 filed Sep. 10, 2004, all of which are hereby
incorporated by reference in their entireties.) 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 power density or energy density
delivered to the target tissue site. Brute force attempts to
circumvent these effects by increasing the power and/or power
density applied to the outside surface of the body can result in
damage (e.g., burning) of the intervening tissue.
[0037] 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. However, certain embodiments, as described herein,
provide devices and methods which can achieve this goal.
[0038] 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 very low, yet efficacious, power densities
(e.g., between approximately 100 .mu.W/cm.sup.2 to approximately 10
W/cm.sup.2) at the target tissue site, and time periods of
application of the light energy at a few seconds to minutes to
achieve an efficacious energy density at the target tissue site
being treated, such target tissue being on the cortex or being
within the brain. 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.
Element to Inhibit Temperature Increases at the Scalp
[0039] FIGS. 1 and 2 schematically illustrate an embodiment of a
therapy apparatus 10 for treating a patient's brain 20. The therapy
apparatus 10 comprises a light source 40 having an output emission
area 41 positioned to irradiate a portion of the brain 20 with an
efficacious power density and wavelength of light. The therapy
apparatus 10 further comprises an element 50 interposed between the
light source 40 and the patient's scalp 30. The element 50 is
adapted to inhibit temperature increases at the scalp 30 caused by
the light.
[0040] 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. In certain
embodiments, the element 50 is adapted to contact at least a
portion of the patient's scalp 30, as schematically illustrated in
FIGS. 1-4. In certain such embodiments, the element 50 is in
thermal communication with and covers at least a portion of the
scalp 30. In other embodiments, the element 50 is spaced away from
the scalp 30 and does not contact the scalp 30.
[0041] In certain embodiments, the light passes through the element
50 prior to reaching the scalp 30 such that the element 50 is in
the optical path of light propagating from the light source 40,
through the scalp 30, through the bones, tissues, and fluids of the
head (schematically illustrated in FIG. 1 by the region 22), to the
brain 20. In certain embodiments, the light passes through a
transmissive medium of the element 50, while in other embodiments,
the light passes through an aperture of the element 50. As
described more fully below, the element 50 may be utilized with
various embodiments of the therapy apparatus 10.
[0042] In certain embodiments, the light source 40 is disposed on
the interior surface of a cap 60 which fits securely over the
patient's head. The cap 60 provides structural integrity for the
therapy apparatus 10 and holds the light source 40 and element 50
in place. Exemplary materials for the cap 60 include, but are not
limited to, metal, plastic, or other materials with appropriate
structural integrity. The cap 60 may include an inner lining 62
comprising a stretchable fabric or mesh material, such as Lycra or
nylon. In certain embodiments, the light source 40 is adapted to be
removably attached to the cap 60 in a plurality of positions so
that the output emission area 41 of the light source 40 can be
advantageously placed in a selected position for treatment of any
portion of the brain 20. In other embodiments, the light source 40
can be an integral portion of the cap 60.
[0043] The light source 40 illustrated by FIGS. 1 and 2 comprises
at least one power conduit 64 coupled to a power source (not
shown). In some embodiments, the power conduit 64 comprises an
electrical conduit which is adapted to transmit electrical signals
and power to an emitter (e.g., laser diode or light-emitting
diode). In certain embodiments, the power conduit 64 comprises an
optical conduit (e.g., optical waveguide) which transmits optical
signals and power to the output emission area 41 of the light
source 40. In certain such embodiments, the light source 40
comprises optical elements (e.g., lenses, diffusers, and/or
waveguides) which transmit at least a portion of the optical power
received via the optical conduit 64. In still other embodiments,
the therapy apparatus 10 contains a power source (e.g., a battery)
and the power conduit 64 is substantially internal to the therapy
apparatus 10.
[0044] In certain embodiments, the patient's scalp 30 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 therapy apparatus 10
substantially contacts the skin of the scalp 30.
[0045] In certain embodiments, the element 50 is adapted to contact
the patient's scalp 30, thereby providing an interface between the
therapy apparatus 10 and the patient's scalp 30. In certain such
embodiments, the element 50 is coupled to the light source 40 and
in other such embodiments, the element is also adapted to conform
to the scalp 30, as schematically illustrated in FIG. 1. In this
way, the element 50 positions the output emission area 41 of the
light source 40 relative to the scalp 30. In certain such
embodiments, the element 50 is mechanically adjustable so as to
adjust the position of the light source 40 relative to the scalp
30. By fitting to the scalp 30 and holding the light source 40 in
place, the element 50 inhibits temperature increases at the scalp
30 that would otherwise result from misplacement of the light
source 40 relative to the scalp 30. In addition, in certain
embodiments, the element 50 is mechanically adjustable so as to fit
the therapy apparatus 10 to the patient's scalp 30.
[0046] In certain embodiments, the element 50 provides a reusable
interface between the therapy apparatus 10 and the patient's scalp
30. In such embodiments, the element 50 can be cleaned or
sterilized between uses of the therapy apparatus, particularly
between uses by different patients. In other embodiments, the
element 50 provides a disposable and replaceable interface between
the therapy apparatus 10 and the patient's scalp 30. 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.
[0047] In certain embodiments, the element 50 comprises a container
(e.g., a cavity or bag) containing a material (e.g., gel). The
container can be flexible and adapted to conform to the contours of
the scalp 30. Other exemplary materials contained in the container
of the element 50 include, but are not limited to, thermal exchange
materials such as glycerol and water. The element 50 of certain
embodiments substantially covers the entire scalp 30 of the
patient, as schematically illustrated in FIG. 2. In other
embodiments, the element 50 only covers a localized portion of the
scalp 30 in proximity to the irradiated portion of the scalp
30.
[0048] In certain embodiments, at least a portion of the element 50
is within an optical path of the light from the light source 40 to
the scalp 30. In such embodiments, the element 50 is substantially
optically transmissive at a wavelength of the light emitted by the
output emission area 41 of the light source 40 and is adapted to
reduce back reflections of the light. By reducing back reflections,
the element 50 increases the amount of light transmitted to the
brain 20 and reduces the need to use a higher power light source 40
which may otherwise create temperature increases at the scalp 30.
In certain such embodiments, the element 50 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.
[0049] In certain such embodiments, the element 50 reduces back
reflections by fitting to the scalp 30 so as to substantially
reduce air gaps between the scalp 30 and the element 50 in the
optical path of the light. The refractive-index mismatches between
such an air gap and the element 50 and/or the scalp 30 would
otherwise result in at least a portion of the light propagating
from the light source 40 to the brain 20 to be reflected back
towards the light source 40.
[0050] In addition, certain embodiments of the element 50 comprise
a material having, at a wavelength of light emitted by the light
source 40, a refractive index which substantially matches the
refractive index of the scalp 30 (e.g., about 1.3), thereby
reducing any index-mismatch-generated back reflections between the
element 50 and the scalp 30. Examples of materials with refractive
indices compatible with embodiments described herein include, but
are not limited to, glycerol, water, and silica gels. Exemplary
index-matching gels include, but are not limited to, those
available from Nye Lubricants, Inc. of Fairhaven, Mass.
[0051] In certain embodiments, the element 50 is adapted to cool
the scalp 30 by removing heat from the scalp 30 so as to inhibit
temperature increases at the scalp 30. In certain such embodiments,
the element 50 comprises a reservoir (e.g., a chamber or a conduit)
adapted to contain a coolant. The coolant flows through the
reservoir near the scalp 30. The scalp 30 heats the coolant, which
flows away from the scalp 30, thereby removing heat from the scalp
30 by active cooling. The coolant in certain embodiments circulates
between the element 50 and a heat transfer device, such as a
chiller, whereby the coolant is heated by the scalp 30 and is
cooled by the heat transfer device. Exemplary materials for the
coolant include, but are not limited to, water or air.
[0052] In certain embodiments, the element 50 comprises a container
51 (e.g., a flexible bag) coupled to an inlet conduit 52 and an
outlet conduit 53, as schematically illustrated in FIG. 3. A
flowing material (e.g., water, air, or glycerol) can flow into the
container 51 from the inlet conduit 52, absorb heat from the scalp
30, and flow out of the container 51 through the outlet conduit 53.
Certain such embodiments can provide a mechanical fit of the
container 51 to the scalp 30 and sufficient thermal coupling to
prevent excessive heating of the scalp 30 by the light. In certain
embodiments, the container 51 can be disposable and replacement
containers 51 can be used for subsequent patients.
[0053] In still other embodiments, the element 50 comprises a
container (e.g., a flexible bag) containing a material which does
not flow out of the container but is thermally coupled to the scalp
30 so as to remove heat from the scalp 30 by passive cooling.
Exemplary materials include, but are not limited to, water,
glycerol, and gel. In certain such embodiments, the non-flowing
material can be pre-cooled (e.g., by placement in a refrigerator)
prior to the phototherapy treatment to facilitate cooling of the
scalp 30.
[0054] In certain embodiments, the element 50 is adapted to apply
pressure to at least a portion of the scalp 30. By applying
sufficient pressure, the element 50 can blanch the portion of the
scalp 30 by forcing at least some blood out the optical path of the
light energy. The blood removal resulting from the pressure applied
by the element 50 to the scalp 30 decreases the corresponding
absorption of the light energy by blood in the scalp 30. As a
result, temperature increases due to absorption of the light energy
by blood at the scalp 30 are reduced. As a further result, the
fraction of the light energy transmitted to the subdermal target
tissue of the brain 20 is increased.
[0055] FIGS. 4A and 4B schematically illustrate embodiments of the
element 50 adapted to facilitate the blanching of the scalp 30. In
the cross-sectional view of a portion of the therapy apparatus 10
schematically illustrated in FIG. 4A, certain element portions 72
contact the patient's scalp 30 and other element portions 74 are
spaced away from the scalp 30. The element portions 72 contacting
the scalp 30 provide an optical path for light to propagate from
the light source 40 to the scalp 30. The element portions 72
contacting the scalp 30 also apply pressure to the scalp 30,
thereby forcing blood out from beneath the element portion 72. FIG.
4B schematically illustrates a similar view of an embodiment in
which the light source 40 comprises a plurality of light sources
40a, 40b, 40c.
[0056] FIG. 5A schematically illustrates one embodiment of the
cross-section along the line 4-4 of FIG. 4B. The element portions
72 contacting the scalp 30 comprise ridges extending along one
direction, and the element portions 74 spaced away from the scalp
30 comprise troughs extending along the same direction. In certain
embodiments, the ridges are substantially parallel to one another
and the troughs are substantially parallel to one another. FIG. 5B
schematically illustrates another embodiment of the cross-section
along the line 4-4 of FIG. 4B. The element portions 72 contacting
the scalp 30 comprise a plurality of projections in the form of a
grid or array. More specifically, the portions 72 are rectangular
and are separated by element portions 74 spaced away from the scalp
30, which form troughs extending in two substantially perpendicular
directions. The portions 72 of the element 50 contacting the scalp
30 can be a substantial fraction of the total area of the element
50 or of the scalp 30.
[0057] FIGS. 6A-6C schematically illustrate an embodiment in which
the light sources 40 are spaced away from the scalp 30. In certain
such embodiments, the light emitted by the light sources 40
propagates from the light sources 40 through the scalp 30 to the
brain 20 and disperses in a direction generally parallel to the
scalp 30, as shown in FIG. 6A. The light sources 40 are preferably
spaced sufficiently far apart from one another such that the light
emitted from each light source 40 overlaps with the light emitted
from the neighboring light sources 40 at the brain 20. FIG. 6B
schematically illustrates this overlap as the overlap of circular
spots 42 at a reference depth at or below the surface of the brain
20. FIG. 6C schematically illustrates this overlap as a graph of
the power density at the reference depth of the brain 20 along the
line L-L of FIGS. 6A and 6B. Summing the power densities from the
neighboring light sources 40 (shown as a dashed line in FIG. 6C)
serves to provide a more uniform light distribution at the tissue
to be treated. In such embodiments, the summed power density is
preferably less than a damage threshold of the brain 20 and above
an efficacy threshold.
[0058] In certain embodiments, the element 50 is adapted to diffuse
the light prior to reaching the scalp 30. FIGS. 7A and 7B
schematically illustrate the diffusive effect on the light by the
element 50. An exemplary energy density profile of the light
emitted by a light source 40, as illustrated by FIG. 7A, is peaked
at a particular emission angle. After being diffused by the element
50, as illustrated by FIG. 7B, 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 emitted by the light source
40, the element 50 distributes the light energy substantially
evenly over the area to be illuminated, thereby inhibiting "hot
spots" which would otherwise create temperature increases at the
scalp 30. In addition, by diffusing the light prior to its reaching
the scalp 30, the element 50 can effectively increase the spot size
of the light impinging the scalp 30, thereby advantageously
lowering the power density at the scalp 30, as described more fully
below. In addition, in embodiments with multiple light sources 40,
the element 50 can diffuse the light to alter the total light
output distribution to reduce inhomogeneities.
[0059] In certain embodiments, the element 50 provides sufficient
diffusion of the light such that the power density of the light is
less than a maximum tolerable level of the scalp 30 and brain 20.
In certain other embodiments, the element 50 provides sufficient
diffusion of the light such that the power density of the light
equals a therapeutic value at the target tissue. The element 50 can
comprise exemplary 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.
Power Density
[0060] Phototherapy for the treatment of depression is based in
part on the discovery that 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. Preferred methods described herein are based at
least in part on the finding that, given a selected wavelength of
light energy, it is the power density 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.
[0061] Without being bound by theory, it is believed that light
energy delivered within a certain range of power densities and
energy densities provides the desired biostimulative effect on the
intracellular environment, such that upregulation of neurotrophic
factors occurs which results in neurogenesis, the growth of
existing neurons and the possible growth of new neurons, as well as
supporting plasticity in neural functioning, including at the
synapse level, the suppression of which is thought to be
instrumental in depression. It is further believed that the light
energy may assist in the regulation of one or more
neurotransmitters, including increasing the level of serotonin
and/or norepinephrine, so that a more normal balance of
neurotransmitters is achieved. The biostimulative effect may
include stimulation of the mitochondria by interaction of the light
with chromophores within the target tissue, which facilitate
production of ATP thereby feeding energy to injured or stressed
cells. Further information regarding the role of power density 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.
[0062] The significance of the power density used in phototherapy
has ramifications with regard to the devices and methods used in
phototherapy of brain tissue, as schematically illustrated by FIGS.
8A and 8B, which show the effects of scattering by intervening
tissue. Further information regarding the scattering of light by
tissue is provided by 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.
[0063] FIG. 8A schematically illustrates a light beam 80 impinging
a portion 90 of a patient's scalp 30 and propagating through the
patient's head to irradiate a portion 100 of the patient's brain
tissue 20. In the exemplary embodiment of FIG. 8A, the light beam
80 impinging the scalp 30 is collimated and has a circular
cross-section with a radius of 2 cm and a cross-sectional area of
approximately 12.5 cm.sup.2. For comparison purposes, FIG. 8B
schematically illustrates a light beam 82 having a significantly
smaller cross-section impinging a smaller portion 92 of the scalp
30 to irradiate a portion 102 of the brain tissue 20. The light
beam 82 impinging the scalp 30 in FIG. 8B is collimated and has a
circular cross-section with a radius of 1 cm and a cross-sectional
area of approximately 3.1 cm.sup.2. The collimations,
cross-sections, and radii of the light beams 80, 82 illustrated in
FIGS. 8A and 8B are exemplary; other light beams with other
parameters are also compatible with embodiments described herein.
In particular, similar considerations apply to focussed beams or
diverging beams, as they are similarly scattered by the intervening
tissue.
[0064] As shown in FIGS. 8A and 8B, the cross-sections of the light
beams 80, 82 become larger while propagating through the head due
to scattering from interactions with tissue of the head. Assuming
that the angle of dispersion is 15 degrees and the irradiated brain
tissue 20 is 2.5 cm below the scalp 30, the resulting area of the
portion 100 of brain tissue 20 irradiated by the light beam 80 in
FIG. 8A is approximately 22.4 cm.sup.2. Similarly, the resulting
area of the portion 102 of brain tissue 20 irradiated by the light
beam 82 in FIG. 8B is approximately 8.8 cm.sup.2.
[0065] Irradiating the portion 100 of the brain tissue 20 with a
power density of 10 mW/cm.sup.2 corresponds to a total power within
the portion 100 of approximately 224 mW (10 mW/cm.sup.2.times.22.4
cm.sup.2). Assuming only approximately 5% of the light beam 80 is
transmitted between the scalp 30 and the brain tissue 20, the
incident light beam 80 at the scalp 30 will have a total power of
approximately 4480 mW (224 mW/0.05) and a power density of
approximately 35.8 mW/cm.sup.2 (4480 mW/12.5 cm.sup.2). Similarly,
irradiating the portion 102 of the brain tissue 20 with a power
density of 10 mW/cm.sup.2 corresponds to a total power within the
portion 102 of approximately 88 mW (10 mW/cm.sup.2.times.8.8
cm.sup.2), and with the same 5% transmittance, the incident light
beam 82 at the scalp 30 will have a total power of approximately
1760 mW (88 mW/0.05) and a power density of approximately 568
mW/cm.sup.2 (1760 mW/3.1 cm.sup.2). These calculations are
summarized in Table 1. TABLE-US-00001 TABLE 1 2 cm Spot Size 1 cm
Spot Size (FIG. 8A) (FIG. 8B) Scalp: Area 12.5 cm.sup.2 3.1
cm.sup.2 Total power 4480 mW 1760 mW Power density 358 mW/cm.sup.2
568 mW/cm.sup.2 Brain: Area 22.4 cm.sup.2 8.8 cm.sup.2 Total power
224 mW 88 mW Power density 10 mW/cm.sup.2 10 mW/cm.sup.2
[0066] These exemplary calculations illustrate that to obtain a
desired power density at the brain 20, higher total power at the
scalp 30 can be used in conjunction with a larger spot size at the
scalp 30. Thus, by increasing the spot size at the scalp 30, a
desired power density at the brain 20 can be achieved with lower
power densities at the scalp 30 which can reduce the possibility of
overheating the scalp 30. In certain embodiments, the light can be
directed through an aperture to define the illumination of the
scalp 30 to a selected smaller area.
Light Source
[0067] The light source 40 preferably generates light in the
visible to near-infrared wavelength range. In certain embodiments,
the light source 40 comprises one or more laser diodes, which each
provide coherent light. In embodiments in which the light from the
light source 40 is coherent, the emitted light may produce
"speckling" due to coherent interference of the light. This
speckling comprises intensity spikes which are created by
constructive interference and can occur in proximity to the target
tissue being treated. For example, while the average 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.
[0068] In other embodiments, the light source 40 provides
incoherent light. Exemplary light sources 40 of incoherent light
include, but are not limited to, incandescent lamps or
light-emitting diodes. A heat sink can be used with the light
source 40 (for either coherent or incoherent sources) to remove
heat from the light source 40 and to inhibit temperature increases
at the scalp 30.
[0069] In certain embodiments, the light source 40 generates light
which 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 other embodiments, the
wavelength of the light is preferably between about 630 nanometers
and about 1064 nanometers, more preferably between about 780
nanometers and about 840 nanometers, and most preferably includes
wavelengths of about 790, 800, 810, 820, or 830 nanometers. It has
also been found that an intermediate wavelength of about 739
nanometers appears to be suitable for penetrating the skull,
although other wavelengths are also suitable and may be used.
[0070] In other embodiments, the light source 40 generates light
having a plurality of wavelengths. In certain such embodiments,
each wavelength is selected so as to work with one or more
chromophores within the target tissue. Without being bound by
theory, it is believed that irradiation of chromophores increases
the production of ATP in the target tissue, thereby producing
beneficial effects. In certain embodiments, the light source 40 is
adapted to generate light having a first wavelength concurrently
with light having a second wavelength. In certain other
embodiments, the light source 40 is adapted to generate light
having a first wavelength sequentially with light having a second
wavelength.
[0071] In certain embodiments, the light source 40 includes at
least one continuously emitting GaAlAs laser diode having a
wavelength of about 830 nanometers. In another embodiment, the
light source 40 comprises a laser source having a wavelength of
about 808 nanometers. In still other embodiments, the light source
40 includes at least one vertical cavity surface-emitting laser
(VCSEL) diode. Other light sources 40 compatible with embodiments
described herein include, but are not limited to, light-emitting
diodes (LEDs) and filtered lamps.
[0072] The light source 40 is capable of emitting light energy at a
power sufficient to achieve a predetermined power density at the
subdermal target tissue (e.g., at a depth of approximately 2
centimeters from the dura). It is presently believed that
phototherapy of tissue is most effective when irradiating the
target tissue with power densities of light of at least about 0.01
mW/cm.sup.2 and up to about 1 W/cm.sup.2. In various embodiments,
the subsurface power density 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,
respectively, depending on the desired clinical performance. In
certain embodiments, the subsurface power density is preferably
about 0.01 mW/cm.sup.2 to about 100 mW/cm.sup.2, more preferably
about 0.01 mW/cm.sup.2 to about 50 mW/cm.sup.2, and most preferably
about 2 mW/cm.sup.2 to about 20 mW/cm.sup.2. It is believed that
these subsurface power densities are especially effective at
producing the desired biostimulative effects on the tissue being
treated.
[0073] Taking into account the attenuation of energy as it
propagates from the skin surface, through body tissue, bone, and
fluids, to the subdermal target tissue, surface power densities
preferably between about 10 mW/cm.sup.2 to about 10 W/cm.sup.2, or
more preferably between about 100 mW/cm.sup.2 to about 500
mW/cm.sup.2, will typically be used to attain the selected power
densities at the subdermal target tissue. To achieve such surface
power densities, the light source 40 is preferably capable of
emitting light energy having a total power output of at least about
25 mW to about 100 W. In various embodiments, the total power
output is limited to be no more than about 30, 50, 75, 100, 150,
200, 250, 300, 400, or 500 mW, respectively. In certain
embodiments, the light source 40 comprises a plurality of sources
used in combination to provide the total power output. The actual
power output of the light source 40 is preferably controllably
variable. In this way, the power of the light energy emitted can be
adjusted in accordance with a selected power density at the
subdermal tissue being treated.
[0074] Certain embodiments utilize a light source 40 that includes
only a single laser diode that is capable of providing about 25 mW
to about 100 W of total power output at the skin surface. In
certain such embodiments, the laser diode can be optically coupled
to the scalp 30 via an optical fiber or can be configured to
provide a sufficiently large spot size to avoid power densities
which would burn or otherwise damage the scalp 30. In other
embodiments, the light source 40 utilizes a plurality of sources
(e.g., laser diodes) arranged in a grid or array that together are
capable of providing at least about 25 mW to about 100 W of total
power output at the skin surface. The light source 40 of other
embodiments may also comprise sources having power capacities
outside of these limits.
[0075] FIG. 9A schematically illustrates another embodiment of the
therapy apparatus 10 which comprises the cap 60 and a light source
comprising a light-emitting blanket 110. FIG. 9B schematically
illustrates an embodiment of the blanket 110 comprising a flexible
substrate 111 (e.g., flexible circuit board), a power conduit
interface 112, and a sheet formed by optical fibers 114 positioned
in a fan-like configuration. FIG. 9C schematically illustrates an
embodiment of the blanket 110 comprising a flexible substrate 111,
a power conduit interface 112, and a sheet formed by optical fibers
114 woven into a mesh. The blanket 110 is preferably positioned
within the cap 60 so as to cover an area of the scalp 30
corresponding to a portion of the brain 20 to be treated.
[0076] In certain such embodiments, the power conduit interface 112
is adapted to be coupled to an optical fiber conduit 64 which
provides optical power to the blanket 110. The optical power
interface 112 of certain embodiments comprises a beam splitter or
other optical device which distributes the incoming optical power
among the various optical fibers 114. In other embodiments, the
power conduit interface 112 is adapted to be coupled to an
electrical conduit which provides electrical power to the blanket
110. In certain such embodiments, the power conduit interface 112
comprises one or more laser diodes, the output of which is
distributed among the various optical fibers 114 of the blanket
110. In certain other embodiments, the blanket 110 comprises an
electroluminescent sheet which responds to electrical signals from
the power conduit interface 112 by emitting light. In such
embodiments, the power conduit interface 112 comprises circuitry
adapted to distribute the electrical signals to appropriate
portions of the electroluminescent sheet.
[0077] The side of the blanket 110 nearer the scalp 30 is
preferably provided with a light scattering surface, such as a
roughened surface to increase the amount of light scattered out of
the blanket 110 towards the scalp 30. The side of the blanket 110
further from the scalp 30 is preferably covered by a reflective
coating so that light emitted away from the scalp 30 is reflected
back towards the scalp 30. This configuration is similar to
configurations used for the "back illumination" of liquid-crystal
displays (LCDs). Other configurations of the blanket 110 are
compatible with embodiments described herein.
[0078] In certain embodiments, the light source 40 generates light
which cause eye damage if viewed by an individual. In such
embodiments, the apparatus 50 can be configured to provide eye
protection so as to avoid viewing of the light by individuals. For
example, opaque materials can be appropriately placed to block the
light from being viewed directly. In addition, interlocks can be
provided so that the light source 40 is not activated unless the
apparatus 50 is in place, or other appropriate safety measures are
taken.
Light Delivery Apparatuses
[0079] The phototherapy methods for the treatment of depression
described herein may be practiced and described using, for example,
a low level laser therapy apparatus such as that shown and
described in U.S. Pat. No. 6,214,035, U.S. Pat. No. 6,267,780, U.S.
Pat. No. 6,273,905 and U.S. Pat. No. 6,290,714, which are all
incorporated in their entirety by reference herein, as are the
references incorporated by reference therein.
[0080] Another suitable phototherapy apparatus in accordance with
embodiments described here is illustrated in FIG. 10. The
illustrated therapy apparatus 10 includes a light source 40, an
element 50, and a flexible strap 120 adapted for securing the
therapy apparatus 10 over an area of the patient's head. The light
source 40 can be disposed on the strap 120 itself, or in a housing
122 coupled to the strap 120. The light source 40 preferably
comprises a plurality of diodes 40a, 40b, capable of emitting light
energy having a wavelength in the visible to near-infrared
wavelength range. The element 50 is adapted to be positioned
between the light source 40 and the patient's scalp 30.
[0081] The therapy apparatus 10 further includes a power supply
(not shown) operatively coupled to the light source 40, and a
programmable controller 126 operatively coupled to the light source
40 and to the power supply. The programmable controller 126 is
configured to control the light source 40 so as to deliver a
predetermined power density to the brain tissue 20. In certain
embodiments, as schematically illustrated in FIG. 10, the light
source 40 comprises the programmable controller 126. In other
embodiments the programmable controller 126 is a separate component
of the therapy apparatus 10.
[0082] In certain embodiments, the strap 120 comprises a loop of
elastomeric material sized appropriately to fit snugly onto the
patient's scalp 30. In other embodiments, the strap 120 comprises
an elastomeric material to which is secured any suitable securing
means 130, such as mating Velcro strips, buckles, snaps, hooks,
buttons, ties, or the like. The precise configuration of the strap
120 is subject only to the limitation that the strap 120 is capable
of maintaining the light source 40 in a selected position so that
light energy emitted by the light source 40 is directed towards the
targeted brain tissue 20.
[0083] In the exemplary embodiment illustrated in FIG. 10, the
housing 122 comprises a layer of flexible plastic or fabric that is
secured to the strap 120. In other embodiments, the housing 122
comprises a plate or an enlarged portion of the strap 120. Various
strap configurations and spatial distributions of the light sources
40 are compatible with embodiments described herein so that the
therapy apparatus 10 can treat selected portions of brain
tissue.
[0084] In still other embodiments, the therapy apparatus 10 for
delivering the light energy includes a handheld probe 140, as
schematically illustrated in FIG. 11. The probe 140 includes a
light source 40 and an element 50 as described herein.
[0085] FIG. 12 is a block diagram of a control circuit 200
comprising a programmable controller 126 according to embodiments
described herein. The control circuit 200 is configured to adjust
the power of the light energy emitted by the light source 40 to
generate a predetermined surface power density at the scalp 30
corresponding to a predetermined energy delivery profile, such as a
predetermined subsurface power density, to the target area of the
brain 20.
[0086] In certain embodiments, the programmable controller 126
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
sources 40 can be selectively turned on and off to reduce the
thermal load on the scalp 30 and to deliver a selected power
density to particular areas of the brain 20.
[0087] 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 power densities,
target time intervals, and power density/timing profiles for the
applied light.
[0088] 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 40. 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 sources 40. Other control circuits besides the control
circuit 200 of FIG. 12 are compatible with embodiments described
herein.
[0089] 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 thermally coupled to the
scalp 30 to provide information regarding the temperature of the
scalp 30 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 temperature below a predetermined level. Other embodiments
include exemplary 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.
[0090] In certain embodiments, as schematically illustrated in FIG.
13, the therapy apparatus 310 comprises a light source 340 adapted
to irradiate a portion of the patient's brain 20 with an
efficacious power density and wavelength of light. The therapy
apparatus 310 further comprises a controller 360 for energizing
said light source 340, so as to selectively produce a plurality of
different irradiation patterns on the patient's scalp 30. Each of
the irradiation patterns is comprised of a least one illuminated
area that is small compared to the patient's scalp 30, and at least
one non-illuminated area.
[0091] In certain embodiments, the light source 340 includes an
apparatus for adjusting the emitted light to irradiate different
portions of the scalp 30. In certain such embodiments, the
apparatus physically moves the light source 40 relative to the
scalp 30. In other embodiments, the apparatus does not move the
light source 40, but redirects the emitted light to different
portions of the scalp 30. In an exemplary embodiment, as
schematically illustrated in FIG. 14, the light source 340
comprises a laser diode 342 and a galvometer 344, both of which are
electrically coupled to the controller 360. The galvometer 344
comprises a mirror 346 mounted onto an assembly 348 which is
adjustable by a plurality of motors 350. Light emitted by the laser
diode 342 is directed toward the mirror 346 and is reflected to
selected portions of the patient's scalp 30 by selectively moving
the mirror 346 and selectively activating the laser diode 342. In
certain embodiments, the therapy apparatus 310 comprises an element
50 adapted to inhibit temperature increases at the scalp 30 as
described herein.
[0092] FIG. 15A schematically illustrates an irradiation pattern
370 in accordance with embodiments described herein. The
irradiation pattern 370 comprises at least one illuminated area 372
and at least one non-illuminated area 374. In certain embodiments,
the irradiation pattern 370 is generated by scanning the mirror 346
so that the light impinges the patient's scalp 30 in the
illuminated area 372 but not in the non-illuminated area 374.
Certain embodiments modify the illuminated area 372 and the
non-illuminated area 374 as a function of time.
[0093] This selective irradiation can be used to reduce the thermal
load on particular locations of the scalp 30 by moving the light
from one illuminated area 372 to another. For example, by
irradiating the scalp 30 with the irradiation pattern 370
schematically illustrated in FIG. 15A, the illuminated areas 372 of
the scalp 30 are heated by interaction with the light, and the
non-illuminated areas 374 are not heated. By subsequently
irradiating the scalp 30 with the complementary irradiation pattern
370' schematically illustrated in FIG. 15B, the previously
non-illuminated areas 374 are now illuminated areas 372', and the
previously illuminated areas 372 are now non-illuminated areas
374'. A comparison of the illuminated areas 372 of the irradiation
pattern 370 of FIG. 15A with the illuminated area 372' of the
irradiation pattern 370' of FIG. 15B shows that the illuminated
areas 372, 372' do not significantly overlap one another. In this
way, the thermal load at the scalp 30 due to the absorption of the
light can be distributed across the scalp 30, thereby avoiding
unduly heating one or more portions of the scalp 30.
Methods of Light Delivery
[0094] Preferred methods of phototherapy are based at least in part
on the finding described above that, for a selected wavelength, the
power density (light intensity or power per unit area, in
W/cm.sup.2) or the energy density (energy per unit area, in
J/cm.sup.2, or power density multiplied by the exposure time) of
the light energy delivered to tissue is an important factor in
determining the relative efficacy of the phototherapy, and efficacy
is not as directly related to the total power or the total energy
delivered to the tissue. In the methods described herein, power
density or energy density as delivered to a portion of the
patient's brain 20, including but not limited to the cortex,
appears to be an important factor in using phototherapy to
upregulate neurotrophic compounds and/or regulate
neurotransmitters. Certain embodiments apply optimal power
densities or energy densities to the intended target tissue, within
acceptable margins of error.
[0095] As used herein, the term "neurotrophic benefits" refers to a
therapeutic strategy for slowing, reversing or preventing
depression and/or its symptoms by causing an upregulation of
neurotrophic factors in the brain. Neurotrophic factors include
those which result in or assist: (i) neurogenesis, the creation
and/or growth of new neural cells; (ii) neural growth, the growth
of existing neural cells and/or portions thereof, such as axons or
dendrites; and (iii) plasticity of neural function, the ability to
create and/or revise neural pathways in the brain and CNS for a
given function or functions.
[0096] As used herein, the term "depression-effective" as used
herein refers to a characteristic of an amount of light energy,
wherein the amount is a power density of the light energy measured
in mW/cm.sup.2. A depression-effective amount of light energy
achieves the goal of causing a diminishment or elimination of
depression and its symptoms, and/or delays, reduces, or eliminates
the onset of depression or depressive symptoms. It is believed that
these effects are caused by an upregulation of endogenous compounds
in the brain, including neurotrophic factors, that serve to enhance
neural growth, neurogenesis, and/or plasticity of neural function;
and/or they are caused by regulation of the presence,
concentration, and/or balance of neurotransmitters in the
brain.
[0097] Thus, one method for the treatment of depression in a
patient in need of such treatment involves delivering a
depression-effective amount of light energy having a wavelength in
the visible to near-infrared wavelength range to a target area of
the patient's brain 20. In certain embodiments, the target area of
the patient's brain 20 includes the hippocampus, believed to be
instrumental in depression and its symptoms. In other embodiments,
the target area includes other portions of the brain 20 not within
the hippocampus. The light energy delivered preferably causes
neurotrophic benefits and/or regulation of neurotransmitters.
Additional 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, which is
incorporated in its entirety by reference herein.
[0098] In certain embodiments, delivering the depression effective
amount of light energy includes selecting a surface power density
of the light energy at the scalp 30 corresponding to the
predetermined power density at the target area of the brain 20. As
described above, light propagating through tissue is scattered and
absorbed by the tissue. Calculations of the power density to be
applied to the scalp 30 so as to deliver a predetermined power
density to the selected target area of the brain 20 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 20 from the scalp 30 include, but are not limited to, skin
pigmentation, the presence and color of hair over the area to be
treated, amount of fat tissue, the presence of bruised tissue,
skull thickness, and the location of the target area of the brain
20, particularly the depth of the area relative to the surface of
the scalp 30. For example, to obtain a desired power density of 50
mW/cm.sup.2 in the brain 20 at a depth of 3 cm below the surface of
the scalp 30, phototherapy may utilize an applied power density of
500 mW/cm.sup.2. The higher the level of skin pigmentation, the
higher the power density applied to the scalp 30 to deliver a
predetermined power density of light energy to a subsurface site of
the brain 20.
[0099] In certain embodiments, treating a patient comprises placing
the therapy apparatus 10 in contact with the scalp 30 and adjacent
a target area of the patient's brain 20. The target area of the
patient's brain 20 can be previously identified such as by using
standard medical imaging techniques. In certain embodiments,
treatment further includes calculating a surface power density at
the scalp 30 which corresponds to a preselected power density at
the target area of the patient's brain 20. The calculation of
certain embodiments includes factors that affect the penetration of
the light energy and thus the power density at the target area.
These factors include, but are not limited to, the thickness of the
patient's skull, type of hair and hair coloration, skin coloration
and pigmentation, patient's age, patient's gender, and the distance
to the target area within or on the surface of the brain 20. The
power density and other parameters of the applied light are then
adjusted according to the results of the calculation.
[0100] The power density selected to be applied to the target area
of the patient's brain 20 depends on a number of factors,
including, but not limited to, the wavelength of the applied light,
and the patient's clinical condition. The power density of light
energy to be delivered to the target area of the patient's brain 20
may also be adjusted to be combined with any other therapeutic
agent or agents, such as antidepressants, to achieve the desired
biological effect. In such embodiments, the selected power density
can also depend on the additional therapeutic agent or agents
chosen.
[0101] In preferred embodiments, the treatment proceeds
continuously for a period of about 10 seconds to about 2 hours,
more preferably for a period of about 1 to about 10 minutes, and
most preferably for a period of about 1 to 5 minutes. In other
embodiments, the light energy is preferably delivered for at least
one treatment period of at least about five minutes, and more
preferably for at least one treatment period of at least ten
minutes. The light energy can be pulsed during the treatment period
or the light energy can be continuously applied during the
treatment period.
[0102] In most circumstances, the treatment is repeated for several
treatment periods. The time between subsequent treatment periods is
preferably at least about five minutes, more preferably at least
about 1 to 2 days, and but may be as long as one week or more. In
certain embodiments in which treatment is performed over the course
of multiple days, the apparatus 10 is wearable over multiple
concurrent days (e.g., embodiments of FIGS. 1, 3, 9A, 10, and 13).
The length of treatment time and frequency of treatment periods can
depend on several factors, including the recovery of the patient.
Because it may take one week or more to achieve outwardly
noticeable neurotrophic benefits, treatment preferably proceeds
over the course of several weeks. In certain embodiments, such as
in patients who suffer from chronic depression or dysthmia,
treatment periods may be repeated and continued for an extended
period of time. In some embodiments, treatment may commence
following a traumatic or stressful event or other event or
situation that may trigger depression in individuals so as to
counteract the influence of stress hormones that may cause
depressive changes in the brain and cause an episode of
depression.
[0103] During the treatment, the light energy may be continuously
provided, or it may be pulsed. If the light is pulsed, the pulses
are preferably at least about 10 nanosecond long and occur at a
frequency of up to about 100 kHz. Continuous wave light may also be
used.
[0104] In certain embodiments, the phototherapy is combined with
other types of treatments for an improved therapeutic effect.
Treatment can comprise directing light through the scalp of the
patient to a target area of the brain concurrently with applying an
electromagnetic field to the brain. In such embodiments, the light
has an efficacious power density at the target area and the
electromagnetic field has an efficacious field strength. For
example, the apparatus 50 can also include systems for
electromagnetic treatment, e.g., as described in U.S. Pat. No.
6,042,531 issued to Holcomb, which is incorporated in its entirety
by reference herein. In certain embodiments, the electromagnetic
field comprises a magnetic field, while in other embodiments, the
electromagnetic field comprises a radio-frequency (RF) field. As
another example, treatment can comprise directing an efficacious
power density of light through the scalp of the patient to a target
area of the brain concurrently with applying an efficacious amount
of ultrasonic energy to the brain. Such a system can include
systems for ultrasonic treatment, e.g., as described in U.S. Pat.
No. 5,054,470 issued to Fry et al., which is incorporated in its
entirety by reference herein.
[0105] 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.
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