U.S. patent application number 13/871979 was filed with the patent office on 2013-09-12 for systems and methods for sidesstream dark field imaging.
This patent application is currently assigned to MicroVision Medical Holding BV. The applicant listed for this patent is MICROVISION MEDICAL HOLDING BV. Invention is credited to Can Ince.
Application Number | 20130237860 13/871979 |
Document ID | / |
Family ID | 34426048 |
Filed Date | 2013-09-12 |
United States Patent
Application |
20130237860 |
Kind Code |
A1 |
Ince; Can |
September 12, 2013 |
SYSTEMS AND METHODS FOR SIDESSTREAM DARK FIELD IMAGING
Abstract
The present application discloses systems and methods for the
comprehensive monitoring of the microcirculation in order to assess
the ultimate efficacy of the cardiovascular system in delivering
adequate amounts of oxygen to the organ cells. In some cases,
system embodiments may utilize reflectance avoidance by reflectance
filtering, such as OPS imaging or Mainstream Dark Field imaging, or
by Sidestream Dark Field imaging, which utilizes external direct
light on the tip of the light guide to achieve reflectance
avoidance whereby incident and reflected light do not travel down
the same pathway.
Inventors: |
Ince; Can; (Leiden,
NL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MICROVISION MEDICAL HOLDING BV |
Ansterdam |
|
NL |
|
|
Assignee: |
MicroVision Medical Holding
BV
Ansterdam
NL
|
Family ID: |
34426048 |
Appl. No.: |
13/871979 |
Filed: |
April 26, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13273118 |
Oct 13, 2011 |
8452384 |
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13871979 |
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10956610 |
Oct 1, 2004 |
8064976 |
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13273118 |
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60557792 |
Mar 29, 2004 |
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60508347 |
Oct 3, 2003 |
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Current U.S.
Class: |
600/479 ;
600/476 |
Current CPC
Class: |
A61B 5/412 20130101;
A61B 5/0075 20130101; A61B 5/004 20130101; A61B 5/02007 20130101;
A61B 5/0261 20130101; A61B 5/14556 20130101; A61B 5/72 20130101;
A61B 5/0071 20130101 |
Class at
Publication: |
600/479 ;
600/476 |
International
Class: |
A61B 5/00 20060101
A61B005/00; A61B 5/02 20060101 A61B005/02 |
Claims
1. A handheld system for sidestream dark field analysis of tissue
beneath a tissue surface, comprising: an elongate body portion
including an imaging passage extending along a length of the
elongate body portion; one or more illumination passages which are
disposed radially about the imaging passage within the elongate
body portion and which are optically isolated from the imaging
passage along an entire length of the imaging passage for surface
reflection avoidance or reduction when an examination tip of the
elongate body portion is proximate the tissue surface; a plurality
of light sources which are disposed in optical communication with
the one or more illumination passages and which are configured to
project light onto a first tissue site via the one or more
illumination passages; and an analysis section optically coupled to
the imaging passage and configured to capture data of tissue
beneath the tissue surface from a second tissue site different from
and adjacent to the first tissue site.
2. The system of claim 1 further comprising at least one isolation
surface which is configured to optically isolate an illumination
field of the first tissue site from an imaging field of the second
tissue site.
3. The system of claim 1 further comprising a disposable detachable
cap disposed over a distal portion of the elongate body portion
having a distal window configured to allow illumination and imaging
therethrough.
4. The system of claim 1 further comprising an annular spacer
disposed on the distal end of the elongate body portion configured
to minimize mechanical contact by the distal portion of the body
portion with the second tissue site.
5. The system of claim 1 wherein the light sources comprise light
emitting diodes.
6. The system of claim 5 wherein the light emitting diodes comprise
green light emitting diodes.
7. The system of claim 1 further comprising a handle secured to the
elongate body portion and configured to be held by a user.
8. The system of claim 1 wherein the analysis section comprises an
image capture device.
9. The system of claim 8 wherein the image capture device comprises
a camera.
10. The system of claim 1 wherein the analysis section comprises a
spectrophotometry module.
11. The system of claim 1 wherein the analysis section comprises a
fluorescence imaging module.
12. A method of analyzing tissue in a patient, comprising:
providing a system for side stream dark field imaging of tissue
beneath a tissue surface, including: an elongate body portion
including an imaging passage extending along a length of the
elongate body portion, one or more illumination passages which are
disposed radially about the imaging passage within the elongate
body portion and which are optically isolated from the imaging
passage along an entire length of the imaging passage for surface
reflection avoidance or reduction when an examination tip of the
elongate body portion is proximate the tissue surface, one or more
light sources which are disposed in optical communication with the
one or more illumination passages and which are configured to
project light onto a first tissue site via the one or more
illumination passages, and an analysis section optically coupled to
the imaging passage; emitting light from the one or more light
sources onto the first tissue site; gathering light from a second
tissue site through the imaging passage with the analysis section
and imaging tissue beneath a surface of the second tissue site; and
analyzing light gathered from the second tissue site through the
imaging passage and determining a clinical parameter of the
patient.
13. The method of claim 12 wherein analyzing light gathered from
the second tissue site comprises fluorescence imaging.
14. The method of claim 13 wherein analyzing light gathered from
the second tissue site comprises annexing fluorescence imaging.
15. The method of claim 12 wherein emitting light from the one or
more light sources comprises emitting light from one or more light
emitting diodes.
16. The method of claim 12 wherein emitting light from the one or
more light sources comprises emitting light from one or more green
light emitting diodes.
17. The method of claim 12 wherein gathering light from a second
tissue site through the imaging passage with the analysis section
comprises gathering light from sublingual tissue.
18. The method of claim 12 wherein gathering light from a second
tissue site through the imaging passage with the analysis section
comprises gathering light from microcapillaries.
19. A method of analyzing tissue in a patient, comprising: emitting
light from one or more light sources of a system for side stream
dark field imaging through one or more illumination passages of the
system which are disposed radially about an imaging passage within
an elongate body portion of the system and which are optically
isolated from the imaging passage along an entire length of the
imaging passage and onto a first tissue site; gathering light from
a second tissue site through the imaging passage with an analysis
section of the system and imaging tissue beneath a surface of the
second tissue site; and analyzing light gathered from the second
tissue site through the imaging passage and determining a clinical
parameter of the patient.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent
application Ser. No. 13/273,118, filed on Oct. 13, 2011, and naming
Can Ince as inventor, which is a continuation of U.S. patent
application Ser. No. 10/956,610, now U.S. Pat. No. 8,064,976, filed
on Oct. 1, 2004, and naming Can Ince as inventor, which claims
priority to U.S. Provisional Patent Application Ser. No.
60/508,347, filed on Oct. 3, 2003, and naming Can Ince as inventor,
and which also claims priority to U.S. Provisional Patent
Application Ser. No. 60/557,792, filed on Mar. 29, 2004, and naming
Can Ince as inventor, all of which are incorporated by reference
herein in their entirety.
BACKGROUND
[0002] Currently, physicians typically monitor a number of systemic
(e.g. the macrocirculation) hemodynamic parameters when diagnosing
and monitoring of the hemodynamic condition of patients. For
example, blood flow and pressure are regularly monitored. In
addition, a blood sample may be withdrawn from the patient to
determine the oxygenation of the red blood cells as well as the
oxygen carrying capacity of the circulating blood. Furthermore, a
biopsy may be required to determine the functional state of tissue
cells (e.g. the oxygenation and viability of tissue cells) of the
organ system.
[0003] While monitoring these macrohemodynamic parameters has
proven successful in diagnosing and monitoring a number of
conditions, several shortcomings have been identified. For example,
examining macrocirculatory parameters provides little or no
information relative to the microcirculatory (i.e. hemodynamics and
structure of blood vessels smaller than 250 microns)
characteristics of patients. Current research has shown that
distress at the microcirculatory level involved in a large number
of disease states is not discoverable by monitoring
macrocirculation. As such, diseases or other complications evident
through microcirculatory monitoring may go undetected and
untreated.
[0004] It is believed, for example, that improved clinical
observation of the microcirculation of human organs would be
extremely useful in assessing states of shock such as septic,
hypovolemic, cardiogenic and obstructive shock in patients and in
guiding resuscitation therapies aimed at correcting this condition.
In particular, it has been found that the active recruitment of the
microcirculation maybe an important component of resuscitation.
Additionally, improved clinical observation of the microcirculation
would be helpful in observing gross circulatory abnormalities in
pathologies such as tumors and cardiovascular disease.
[0005] To fully monitor the function of the microcirculation, that
is the structure and perfusion of vessels smaller than 250
micrometers, in addition to measuring blood flow it is important to
measure and asses whether the blood cells are successful in
transporting their oxygen to the microcirculation and thereafter to
the surrounding tissue cells. Of particular importance is the
assessment of the perfusion of the capillaries, which are between
approximately 5 to 10 micrometers, because it is at this level that
oxygen is transported by the red blood cells to the tissue cells of
the organ for the purposes of respiration and survival. Monitoring
the functional state of the microcirculation can thus be regarded
as monitoring the ultimate efficacy and function of the
cardiovascular system to deliver adequate amounts of oxygen to the
organ cells.
[0006] It is believed, for example, that improved and comprehensive
imaging of the properties of the microcirculation would be helpful
in observing and assessing the beneficial effects of therapy during
the resuscitation of shock patients. An accurate assessment of both
blood flow and oxygen availability at the level of the
microcirculation could thus provide a clinical tool with which to
guide resuscitation. A comprehensive way to monitor the
microcirculation could generally provide an improved clinical
diagnostic tool for evaluating and monitoring the functional state
of the microcirculation in the peri-operative phase of
treatment.
[0007] To date, there have been limits to a comprehensive
monitoring of the microcirculation in order to provide the benefits
discussed above. Specifically, several factors have limited the
ability to evaluate the oxygen transport variables of the
microcirculation comprehensively. For example, devices which
contact the surface of the microcirculation inhibit their ability
to obtain quantitative information about blood flow in the various
categories of micro-vessels in the microcirculation by impeding
flow due to exerted pressure. Furthermore, current devices and
techniques for imaging the microcirculation do not provide the
additional needed information about the oxygen availability in the
microcirculation or about the adequacy of oxygenation of the tissue
cells. This information would be very helpful in assessing the
functional state of the microcirculation, specifically its function
in allowing adequate transport of oxygen to the tissue cells. Thus,
there is a need for an improved system and method for a more
effective and a more comprehensive clinical observation of the
microcirculation which includes these parameters.
SUMMARY
[0008] The system and method disclosed herein provides
comprehensive information about the microcirculation by providing
multiple modes of optical spectroscopy and imaging in a manner
which does not influence the microcirculation. In one aspect, the
system avoids reflection of light from the tissue in the various
imaging modes. This reflectance avoidance can be provided by
reflectance filtering, such as orthogonal polarization or
cross-polarization of light or dark field imaging, or by sidestream
dark field imaging, wherein, for example, incident and reflected
light may not travel down the same pathway.
[0009] In order to image flowing cells in the microcirculation,
light has to be illuminated on to the surface of the organs, which
is the substrate, and a magnifying lens may be used. Use of a
specific wavelength of light (e.g. green light) may allow for
better observation of the contrasting red blood cells due to the
absorption characteristics of the hemoglobin (hereinafter Hb) in
the red blood cells. However, surface reflections from the
substrate can interfere with the ability to clearly visualize the
underlying microcirculation structures and the flowing blood cells
therein. Filtering out of these surface reflection by various
methods allows visualization of the blood flow in the underlying
microcirculation on organ surfaces by measurement of the images of
the moving cells. Reflectance filtering can be achieved by a number
of techniques which are known to those of skill in the art. The
system and method disclosed herein may utilize some of these known
techniques, but some novel ones are disclosed as well.
[0010] In some embodiments, the system and method utilizes
reflectance avoidance by known techniques of reflectance filtering,
such as: 1) OPS imaging, whereby illuminating light and reflected
light travel down the same light guide; or 2) Mainstream Dark Field
imaging, whereby illuminating light and reflected travel down the
same light guide but peripheral illumination is achieved by
directing the light through, for example, a hole in a 45.degree.
mirror or design of a lens in the illuminating pathway, which
impedes transmission of the light through the middle, and/or a lens
which poorly allows transmission of the light through the centre is
put in the pathway of the light to achieve the same effect.
[0011] In other embodiments, a novel method of reflectance
avoidance is disclosed which is an alternative to reflectance
filtering. This novel approach, referred to herein as Sidestream
Dark Field imaging (hereinafter SDF), utilizes external direct
light on the tip of the light guide to achieve reflectance
avoidance whereby incident and reflected light do not travel down
the same pathway. This form of imaging can be provided in
combination with a hand-held microscope. A feature of SDF imaging
is that illuminated light and reflected light travel via
independent pathways. With this modality, the illumination can be
placed directly on the tissue and the observations can be made
adjacent to it without light crossing over between two paths. The
illuminating light source is typically placed on or near contact
with the tissue. The scattering of the reflected light is thus
outside of the image as most light cross over is below the tissue
surface. To date, Mainstream Dark Field imaging has been described
as a way of improving contrast and lowering surface reflectance,
but it typically utilizes illumination and reflectance light paths
that travel up and back the same pathway. In the past, SDF
illumination has been applied by ring illumination to improve
epi-illumination. It is believed, however, that it has not been
applied to achieve true dark field illumination by illuminating one
segment of a substrate and observing in another segment images of
the microcirculation and its flowing cells. It is believed that SDF
imaging has characteristics which make it superior to other modes
of imaging.
[0012] The foregoing reflectance avoidance imaging systems, whether
they utilize OPS, Mainstream Dark Field illumination, or SDF
illumination, can be used to enable the comprehensive evaluation of
the functional state of the microcirculation. This is achieved by
an analysis of the moving cells in the images, which permits the
quantitative measurement of red blood cell flow in the capillaries,
as well as in the larger vessels of the microcirculation. This
measurement is believed to represent a truly sensitive measurement
which is indicative of cardiovascular disease and dysfunction.
Laser Doppler measurements, for example, provide an over all flux
of moving particles in an unidentified compartment of the
circulation, but do not have the specificity for measurement of
cellular perfusion of these smallest capillaries.
[0013] The system and method disclosed herein, in providing
reflectance avoidance in combination with optical magnification,
provides a superior method of measurement of the functional state
(e.g. perfusion/oxygenation) of the microcirculation. Next to the
measurement of perfusion, morphological characteristics of the
microcirculation, such as functional capillary density and
micro-vessel morphology, can be measured using reflectance
avoidance imaging. Homogeneous perfusion of the capillaries is a
prerequisite for normal function of the microcirculation and
abnormal perfusion or diminished capillary perfusion is considered
an early and sensitive indicator of cardiovascular disease and
failure.
[0014] The present application thus relates to a variety of imaging
systems for analyzing the reflectance of an examination substrate.
While the imaging system disclosed herein may be used to analyze
the reflectance characteristics of a variety of substrates, it is
particularly well suited for non-invasively imaging the
micro-circulation with a tissue sample.
[0015] In one embodiment, the present application discloses a
system for imaging the reflectance of a substrate and includes a
light source, a light transport body configured to project light
from the light source to an examination substrate and transmit
light reflected and scattered by the examination substrate, an
analysis section in optical communication with the light transport
body and having an orthogonal polarization spectral imaging module
or any other of the reflectance avoidance imaging systems, and at
least one of a reflectance spectrophotometry module and a
fluorescence imaging module.
[0016] In an alternate embodiment, the present application
discloses an orthogonal polarization imaging system and includes a
light source configured to emit white light, a first polarizer to
polarize the white light, a light transport body to transport the
polarized light to an examination substrate and reflect light from
an examination substrate, a second polarizer to filter the light
reflected and scattered by the examination substrate, a filter bank
containing at least one wavelength filter to filter the reflected
light, and an image capture device in optical communication with
the light transport body and configured to image the reflected
light.
[0017] In still yet another embodiment, the present application
discloses a method of imaging the reflectance of a substrate and
includes illuminating an examination substrate with light,
transmitting a portion of light reflected by the examination
substrate to a reflectance spectrophotometer, determining a
concentration of hemoglobin within the examination substrate based
on a spectral characteristic of the examination substrate with the
reflectance spectrophotometer, transmitting a portion of the light
reflected by the examination substrate to an orthogonal
polarization spectral imaging module, and measuring a flow through
a vessel within the examination substrate with an orthogonal
polarization spectral imaging module.
[0018] In one embodiment, the present application discloses a novel
manner of applying dark field imaging on the tip of a light guide
to provide clear images of the microcirculation on human organ
surfaces. This can be accomplished by putting light emitting diodes
(LED's) around the tip of the light guide in combination with a
separator so that the illuminating light does not enter the
reflection light guide directly by surface reflection, but via the
internal structures inside the substrate. This modality of
reflectance avoidance is a form of dark field imaging which we have
called Sidestream Dark Field or SDF imaging and provides remarkably
clear images of the microcirculation.
[0019] In some embodiments, reflectance avoidance imaging is used
to obtain a microcirculatory perfusion index as well as a
heterogeneity of flow index in a device that does not impact flow
patterns. This may be accomplished by using non-contact modes such
as, for example, using a long focal length, immobilizing the device
and substrate by suction at the tip, or utilizing a spacer between
the tissue and the light emitting tip.
[0020] In one such embodiment, a novel, "castle" type of spacer is
utilized to provide distance from the examining substrate and to
avoid pressure of the tip on the substrate. In another embodiment,
a needle camera is utilized with a spacer to provide a dark field
illumination device. In yet another embodiment, a suction device is
used with reflectance avoidance imaging techniques.
[0021] In another embodiment, a distance spacer is used to achieve
reliable capillary perfusion measurements whereby the tip of the
image guide does not impede flow in the microcirculation by
pressure. In yet another embodiment, reflectance avoidance imaging
is used in combination with a space through which fluid, drugs or
gasses can be perfused.
[0022] In one embodiment, a disposable tip attaches to the end of
the device and is removed by a release mechanism so that it can be
disposed of without having to touch the disposable.
[0023] The utilization of reflectance avoidance in the present
invention provides an improved method of observing microcirculatory
hemodynamics and functional morphology. Image analysis can provide
a plurality of clinical parameters which will have utility for
various clinical conditions. The method and device will assist in
providing a perfusion index such as a measure of functional
capillary density, which is the number of perfused micro-vessels
showing per field observed. Other parameters include the
distribution and heterogeneity of micro-vascular flow, torsion and
functional morphology of the blood vessels, the distribution of
diameters of blood vessels, white blood cell kinetics, abnormal red
blood cell kinetics (e.g. the presence of micro-vascular
coagulation, sludging or adhesion).
[0024] For a comprehensive assessment of the functional state of
the microcirculation, it may be preferable to have more than just
perfusion information. It would also be useful to have Information
about the amount of oxygen bound to the Hb, which can be provided
by reflectance spectrophotometry, and information as to whether the
tissue cells are getting sufficient amount of oxygen, which can be
provided by measuring tissue CO.sub.2 by sensing the CO.sub.2 in
the inside of the disposable, using, for example, CO.sub.2
sensitive fluorescence quenching dyes. The light guide can then be
used to excite the dye with a pulse of light and a detector which
measures the CO.sub.2 dependent quenching of fluorescence life time
would provide the measurement. Also, mitochondrial energy states by
NADH via fluorescence imaging can be obtained. Information may be
obtained about whether there is movement of the red blood cells in
the microcirculation, whether the red blood cells are transporting
oxygen (i.e. Hb saturation), and whether the tissue cells are
getting enough oxygen (tissue CO.sub.2 measurement and/or NADH
fluorescence imaging).
[0025] In some embodiments, reflectance spectrophotometry in
conjunction with reflectance avoidance is used to assess the
adequacy of oxygen availability. This may provide for the
assessment of microcirculatory oxygen transport. In some
embodiments this can be accomplished by an analysis of the full
reflected spectrum of light (e.g. 400-700 nm). In other embodiments
it is accomplished by an analysis of discrete wavelengths outputs
of a color sensitive imaging device. Microcirculatory Hb
saturation, microcirculatory Hb concentration, and microcirculatory
hematocrit can all be measured.
[0026] In some embodiments, the SDF imaging technique is combined
with the use of different wavelengths LED's wherein the images are
normalized and Beer Lambert equations are applied.
[0027] In some embodiments, NADH fluorescence imaging is used to
measure the adequacy of the need for mitochondrial oxygen. This can
be used to assess tissue cell dysoxia.
[0028] In some embodiments, fluorescence spectroscopy is used for
tissue cell diagnostics using endogenous molecules, reporter genes
or external indicator dyes. With appropriate filters, apoptosis can
be detected (e.g. via annexin fluorescence), green fluorescent
labeled cells used in gene therapy could be located in terms of
their efficacy in homing in on the target.
[0029] In one embodiment, a method of imaging the microcirculation
by avoiding surface reflections is combined with reflectance
spectrophotometry, Raman spectroscopy, fluorescence spectroscopy
and/or other types of spectroscopic modalities, such as light
scatter measurements or optical coherence tomography.
[0030] In some embodiments, the device is a light guide based
system wherein emission and excitation light travels via light
guides. In some embodiments, the images are detected at the tip
with a tip camera. The device may have a fused silicon lens which
will allow 360 nm to pass in order to enable NADH fluorescence
imaging. The device can be either hand held or a flexible
endoscopic type.
[0031] In addition, to direct contact imaging, the reflectance
avoidance imaging system disclosed herein may also be capable of
operating in a non-contact mode which makes use of a spacer to
avoid pressure in the tissue surface which may impede blood flow
therethrough. Various spacer options exist, including;
[0032] a. plastic upside down cup attached as disposable;
[0033] b. a doughnut shaped spacer (which can be inflatable) with
an upside down situation/cup;
[0034] c. a device (e.g. a plug for around the scope end), such as
a concentric ring with suction ports, for providing suction through
little holes around the perimeter of the scope thereby immobilizing
the perimeter but leaving the microcirculation in the field of view
unstressed; or
[0035] d. a transparent cushion either solid, air inflatable or
filled with fluid.
[0036] What is also disclosed is a non-contacting tip for
endoscopic use. In one embodiment, long focus distance imaging can
be used to observe retinal microcirculation. This modality can be
used to monitor eye diseases and as a monitoring tool during
surgery to monitor brain function non-invasively. In the retinal
application imaging light can be pulsed and small clips of moving
images used for monitoring, thus minimizing retinal light
exposure.
[0037] In one embodiment, the system is configured to operate in a
no contact mode without use of a spacer. Thus, the system may be
used during brain surgery or heart surgery. Any movement of the
object surface can be corrected by image processing either on-line
or after a delay.
[0038] In one embodiment the light guide system has an L-shape at
the end. Here a 45.degree. mirror creates the bend and LED
illumination, using SDF, imaging is present at the tip, with or
without a spacer and/or suction module. This embodiment may be used
to inspect the sides of hollow spaces such as is present in the
digestive track.
[0039] In another embodiment, large objective magnification may be
used. For example, image processing software may be used to
immobilize or stabilize the images, thereby allowing for better
image processing of the movements.
[0040] In still another embodiment, magnification of the substrate
image can be influenced in several ways. For example, different
lenses may be used (different spacer on the tip), or movement of
exiting lenses by an opto-mechanical system, or in the electronic
mode a larger number of pixel CCD or CMOS chips, which are known to
those of skill in the art, or a larger density of pixels in the
chip can be utilized. Movement of the CCD or CMOS can also be used
to influence magnification.
[0041] In still another embodiment, any number of specified color
cameras may be used with the present system. For example, a choice
of color or combination of colors would allow images to be
generated of the saturation of the Hb of the red blood cells in the
microcirculation. A further embodiment involves looking at only the
red output of a color camera and to filter out of the rest of the
image. This would result in red cells moving in a white
background.
[0042] Use of a high speed rate (i.e. higher than video rate) can
be used for obtaining a proper velocity measurement in conditions
in which red blood cells are moving faster than the video rate.
[0043] In some embodiments, a CO.sub.2 measurement of the tissue in
the field of view can be made simultaneously with a reflectance
avoidance flow measurement and an oxygen availability measurement,
such as with spectrophotometry, as a measure of tissue
wellness.
[0044] In one embodiment, a disposable spacer (e.g. upside down
cup) may be employed. In this embodiment, a CO.sub.2 sensing dye
can be impregnated with which CO.sub.2 can be sensed within the cup
environment. The dye works to provide a fluorescence decay
measurement and the excitation and emission light of this dye in
the disposable tip can be measured through the light guide. The
CO.sub.2 measurement can be combined with a reflectance avoidance
flow measurement, such as an OPS or SDF imaging based perfusion
measurement. Furthermore, a CO.sub.2 probe may be inserted into the
nose of a patient to assess tissue pCO2 and combine this
information with simultaneously measured perfusion (e.g. by OPS or
SDF imaging) and oxygen availability (spectrophotometry) measured
sublingually. In another embodiment, the CO.sub.2 probe may be used
rectally. These measurements may be made continuously. The sensor
may be embedded within a pliable of cushioning material. For
example, the sensor may be positioned within a sponge so as to trap
and sense the CO.sub.2 sufficiently.
[0045] The CO.sub.2 sensor can be used in the nose and/or rectally
as alternative locations for a separate sensor which is then
integrated in the measurement. This can be in single or in multi
mode. The latter technique, which makes use of more than one
CO.sub.2 sensor, will give information about regional
heterogeneity. Using multi locations is believed to be a new use of
a CO.sub.2 measurement.
[0046] In some embodiments, a laser can be included as a
therapeutic modality. This can be accomplished, for example, by the
use of dark field illumination in which the laser goes through the
hole in the slanted mirror. In this embodiment, reflectance
avoidance imaging is combined with the use of the laser for
photodynamic therapy (e.g. for cancer) or to coagulate
micro-vessels in port wine stains or other cosmetic corrective
procedures.
[0047] In another embodiment, reflectance avoidance imaging is used
to observe the microstructure of the wound, and temperature is
sensed by a solid state or thermo-sensitive color sensor as well as
by optical spectroscopy to measure the water content. It is thereby
that wound perfusion (via e.g. OPS or SDF imaging), wound
temperature and edema (water content) will give a comprehensive
measurement of the phase of wound healing and allow assessment of
the response to therapy.
[0048] In the photodynamic embodiment (where the patient receives a
photosensitive drug) it is possible to apply fluorescence in
combination with reflectance avoidance for detection of the drug
(which accumulates in tumors) or for enhanced fluorescence in ALA
induced protoporphyring fluorescence. Combining a therapeutic laser
in the device would make it possible to deliver photodynamic
therapy directly to the area of high fluorescence.
[0049] Alternative illumination modalities may include pulsing the
LED illumination in combination with synchronization with a camera
for the measurement of high blood flow velocities. Another
alternative includes the use of an optical foil, acting as a light
guide, or other material which may be wrapped around the tip of the
probe providing illumination from the side of the tip as an
alternative way of illuminating the object and accomplishing
reflectance avoidance. This is similar to the method which is
accomplished by the use of optical fibers placed around the out
side of the scope.
[0050] Other embodiments which include laser therapies include the
use of reflectance avoidance imaging to verify the effectiveness
and allow for the accurate titration of laser doses. A second
example is the use of photodynamic therapy for on-line treatment of
photosensitized tumors.
[0051] In another embodiment, a custom spacer is disclosed in which
it is possible to introduce a drug or gas to the field of
observation and measure the reactivity of the blood vessels (i.e.
losses of which are an indication of poor function). This spacer
could be a suction spacer which would provide space in the field of
view to ensure that there is no contact with the tip and also
provide space to inject a drug (for microcirculatory
responsiveness) or for calibration that may be needed for the
embodiment which utilizes a CO.sub.2 sensor placed in the probe.
Drugs which can be considered challenges to the microcirculation
are vasodilators acting on specific locations of the
microcirculation e.g. acetyl choline, lidocaine or nitrate. Others
include vasopressors, such as noradrenaline or dobutamine. This
modality can also be used in local treatment of tumors by
application of a topical administration of a chemotherapeutic
drug.
[0052] Measuring the reactivity of the blood circulation to
challenges (also given systemically) via, for example, trend
measurements, yield parameters which give additional information
than a snap shot analysis. Response to therapy of the
microcirculation can be monitored continuously providing on-line
information about the functional state of the microcirculation
during illness.
[0053] A further challenge can be induced through a specialized
spacer which applies a momentary suction pulse and measures the
time of microcirculatory refill.
[0054] In some embodiments multi-wavelength imaging can be used for
the measurement and analysis of Hb saturation images. The object is
sequentially or simultaneously illuminated by specific colored
LED's, placed in SDF mode, which are chosen at specific wavelengths
along the absorption spectrum of Hb, such that when combined in a
composite image they provide an image of the distribution of Hb
saturation (or Hb concentration or Hematocrit) of the cells of the
microcirculation. A second embodiment for achieving the same
objective utilizes white light. The reflected light is then split
by a multi-wavelength optical member which may consist of mirrors
and filters which project two or more images each at a different
wavelength onto the imaging device to allow reconstituted
saturation images to be made.
[0055] In one embodiment the use of fluorescence SDF imaging
(endogenous leucocyte fluorescence), or observing light scatter, to
view differences between cells moving in the circulation (i.e.
leucocytes scatter more light than red blood cells) and combining
such imaging, with or without filtering of special wavelengths,
optical conditions permit the observation and quantification of the
amount of leucocytes flowing in the microcirculation. Such a
measurement would allow quantification of the immune status of the
observed field of view by counting the amount of leucocytes and or
observing the kinetics of cell sticking or rolling.
[0056] In one embodiment, annexin fluorescence can be used for the
detection of apoptotic cells. A combination of fluorescence
techniques includes but is not limited to annexin-labeled cells
which will allow for the visualization of apoptotic cells which are
directed to programmed cell death, a precursor to necrosis and cell
death. These measurements may be important in assessing cell
failure in cardiovascular disease, sepsis and in identification and
staging of the severity of cancer, or other stages of diseases such
as inflammatory bowel disease. In this application fluorescence
labeled annexin is administered to the patient, or applied
topically to the site of interest and utilizes the fluorescence
mode of the scope. In the fluorescence mode of the scope we
describe a hand tool (a fluorescence boroscope) such as described
for the reflectance avoidance imaging but in which fluorescence
modality is utilized. Reflectance avoidance imaging can be used to
improve fluorescence imaging, by filtering or avoiding surface
reflections, and can be applied in the boroscope application or
also in fluorescence endoscopy where, to date, the combination of
fluorescence and reflectance avoidance imaging has not been
disclosed.
[0057] In this embodiment, the appropriate choice of filters can be
used to image mitochondrial energy states (NADH levels) through the
use of fluorescence. NADH in vivo fluorescence imaging involves
dual wavelength fluorescence combined with reflectance avoidance
imaging to correct for changes in absorption in the image, which
can be caused by variation in Hb (which is an absorber) in the
vessels in the image (results in heterogeneous images). In
addition, fluorescence spectrophotometry may be combined with
reflectance avoidance imaging to allow cell diagnostics during
surgery directly at the bedside. Tissue cell diagnostics will
target the functional state of the mitochondria by measurement of
the energy of the mitochondria by NADH fluorescence, the gold
standard for assessment of tissue dysoxia. Such fluorescence
imaging can also be used in conjunction with diagnostic dyes for
identification of apoptosis or tumor cells and reporter genes
during gene therapy. Combination of fluorescence dyes and cell
labeling techniques can be used by this modality (with appropriate
filters) to observe and quantify the degree of degradation of the
glycocalix lining of the endothelia cells. This observation
provides a microcirculatory indication of the severity of
cardiovascular disease. Finally measurement of the time course of
transport through the microcirculation of a pulse of fluorescent
dye allows microcirculatory flow at the capillary level to be
quantified when detected by fluorescence.
[0058] In some embodiments, reflectance avoidance imaging will be
combined with Raman spectroscopy, thereby combining
microcirculatory reflectance avoidance imaging with information
about the constituents of the tissues.
[0059] The above embodiments can be used in an endoscopy mode. For
example, dark field endoscopy, OPS imaging, and\or side
illumination can be used to make observations in the gastric tract,
with for example, the L-tip device discussed above. Polarization
can be achieved at the tip of a flexible endoscope. Dark field
illumination can be used in the same way by concentric
illumination. A light conducting foil can be used at the outside. A
45.degree. mirror can be included at the tip for observation of the
sides of the gastric tubes. Thin scopes can be made for
pediatrics.
[0060] In some embodiments, optical coherence tomography can be
used for measurement of optical path-length using Beer Lambert as a
quantitative measurement.
[0061] Sublingual Near Infra-red Spectroscopy can be used in the
transmission mode or in the reflectance mode to measure total
oxygenation of the tongue.
[0062] The foregoing methodologies for comprehensive imaging of the
microcirculation provide a useful clinical tool in assessing states
of shock such as septic, hypovolemic, cardiogenic, and obstructive
shock in patients and in guiding resuscitation therapies.
[0063] Other objects, features, and advantages of the imaging
system and method disclosed herein will become apparent from a
consideration of the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0064] The imaging system of the present application will be
explained in more detail by way of the accompanying drawings,
wherein:
[0065] FIG. 1 shows a block diagram of an embodiment of an imaging
system for analyzing light reflected from an examination
substrate;
[0066] FIG. 2 shows a block diagram of an embodiment of an
analyzing section of an imaging system;
[0067] FIG. 3 shows a schematic diagram of an embodiment of a light
transport section configured to project light on and receive
reflected light from an examination substrate;
[0068] FIG. 4A shows a perspective view of an embodiment of a light
transport body of a light transport section;
[0069] FIG. 4B shows a perspective view of an alternate embodiment
of a light transport body of a light transport section;
[0070] FIG. 4C shows a perspective view of another embodiment of a
light transport body of a light transport section;
[0071] FIG. 4D shows a perspective view of still another embodiment
of a light transport body of a light transport section;
[0072] FIG. 5 shows a schematic diagram of another embodiment of a
light transport section configured to project light on and receive
reflected light from an examination substrate;
[0073] FIG. 6 shows a side view of an alternate embodiment of a
light transport body of a light transport section;
[0074] FIG. 7 shows side view of an embodiment of a spacer device
coupled to an embodiment of a light transport body;
[0075] FIG. 8 shows a side view of another embodiment of a spacer
device coupled to an embodiment of a light transport body;
[0076] FIG. 9 shows a side view of an embodiment of a spacer device
configured to couple to an examination substrate coupled to an
embodiment of a light transport body;
[0077] FIG. 10 shows a bottom view of an embodiment of the spacer
device shown in FIG. 9;
[0078] FIG. 11 shows a cross sectional view of an embodiment of an
imaging system for analyzing reflected light;
[0079] FIG. 12 shows a side view of an optical system for use in
the an imaging system for analyzing reflected light shown in FIG.
10;
[0080] FIG. 13 shows a cross sectional view of an embodiment of an
imaging system for analyzing reflected light having an internal
light source positioned therein;
[0081] FIG. 14 shows a side cross-sectional view of an embodiment
of an imaging system configured to permit side stream dark field
imaging of an area;
[0082] FIG. 15 shows a perspective view of the distal portion of an
embodiment of the imaging system shown in FIG. 14;
[0083] FIG. 16 shows a cross sectional view of an embodiment of an
imaging system having one or more illumination sources located
within illumination passages formed in a body;
[0084] FIG. 17 shows a cross sectional view of an embodiment of an
imaging system having a body coupled to handle portion;
[0085] FIG. 18 shows a schematic diagram of an embodiment of an
imaging system for projecting light to a substrate and collecting
light therefrom for analysis;
[0086] FIG. 19 shows a perspective view of the distal portion of
the imaging system shown in FIG. 18;
[0087] FIG. 20 shows a perspective view of the distal portion of
another embodiment of imaging system shown in FIG. 18;
[0088] FIG. 21 shows a side cross sectional view of an embodiment
of an imaging system wherein the distal portion thereof is in
contact with an examination substrate;
[0089] FIG. 22 shows a side cross sectional view of an embodiment
of an imaging system wherein the distal portion includes an
engaging device thereon;
[0090] FIG. 23 shows a side cross sectional view of an embodiment
of an imaging system wherein the distal portion is not in contact
with the examination substrate;
[0091] FIG. 24 shows a block diagram of diagram of an embodiment of
an imaging system for imaging microcirculation within a structure
and analyzing light reflected from an examination substrate;
[0092] FIG. 25 shows a cross sectional view of an embodiment of a
cap device which may be affixed to a body of an imaging system;
[0093] FIG. 26 shows a perspective view of embodiment of an imaging
system configured for sub-surface imaging of an area; and
[0094] FIG. 27 shows a side cross sectional view of the imaging
system shown in FIG. 26.
DETAILED DESCRIPTION
[0095] FIG. 1 shows a block diagram of an embodiment of a
reflectance imaging system. The imaging system 10 includes an
analyzing section 12 and a light transport section 14 configured to
project light on and/or receive reflected light from an examination
substrate 16. In one embodiment the light transport section 14 may
include an internal light source 18 therein configured to provide
light of at least one selected wavelength and/or polarization to
the examination substrate 16. Optionally, the internal light source
18 may be used with or may comprise a source of white or full
spectral light thereby enabling spectral analysis of light
reflected by the examination substrate 16. In an alternate
embodiment, an external light source 20 may be in optical
communication with the light transport section 14 and configured to
illuminate the examination substrate 16. Optionally, the imaging
system 10 may include both an internal light source 18 and an
external light source 20. As such, the internal and external light
sources may have the same or different wavelengths and/or
polarizations. In another embodiment, an ancillary illuminator 22
may be used to illuminate the examination substrate 16. As shown,
the ancillary illuminator 22 directly illuminates the examination
substrate thereby foregoing the light transport section 14. The
various components of the analyzing section 12 and the light
transport section 14 will be described in greater detail below.
[0096] Referring again to FIG. 1, in one embodiment the analyzing
section 12 includes any number of modules configured to analyze
light reflected from the examination substrate 16 and transported
to the analyzing section 12 by the light transport section 14. In
the illustrated embodiment, the analyzing section 12 includes an
orthogonal polarization spectral (OPS) imaging module 30, a
reflectance spectrophotometry (RFS) module 32, and a fluorescence
(FLS) imaging module 34. Any number of additional modules 36 may be
included in the analyzing section 12. Exemplary additional modules
include, without limitation, Raman spectroscopy modules, optical
coherence tomography modules, dark field imaging including side
stream dark field imaging (See below), and various light scattering
measurement modules.
[0097] As shown in FIGS. 1 and 2, the OPS imaging module 30
receives a light sample 40 from a beam director 98. The light
sample comprises light reflected from the examination substrate 16
and transmitted to the beam director 98 by the light transport
section 14. As such, the OPS imaging module 30 is configured to
image the examination substrate 16 using wither dark field or
non-dark filed illumination. Thereafter, the light sample 40 may
encounter a polarizing section 42 having one or more optical
polarizers therein. The polarizing section 42 permits only light of
a selected or desired polarization to transmit therethrough,
thereby filtering the light reflected by the examination substrate
16 and improving image quality. IN an alternate embodiment, the OPS
imaging module 30 may incorporate a variety of other optical
devices or methodologies to optimize image quality. The polarized
light 44 is then incident upon a filtering section 46 having one or
more optical filters therein. For example, in one embodiment the
filtering section 46 contains at least one narrow band pass filter
therein configured to permit light within a desired wavelength
range to be transmitted therethrough. Exemplary narrow band pass
filters include, without limitation, from about 380 nm to about 450
nm (violet filter), from about 445 nm to about 510 nm (blue
filter), from about 495 nm to about 580 nm (green filter), from
about 575 nm to about 595 nm (yellow filter), from about 590 nm to
about 625 nm (orange filter), from about 615 nm to about 710 nm
(red filter), and from about 690 nm to about 910 nm (color or photo
infrared filter). Optionally, the OPS imaging section 30 may
include filters enabling ultraviolet radiation to transmit
therethrough. In an alternate embodiment, the filtering section 46
receives light from the light transport section 14 prior to the
light sample 40 being polarized.
[0098] Referring again to FIG. 2, the filtered light 48 is then
transmitted from the filtering section 46 to an image capture
device 50. Exemplary image capture devices 46 include, without
limitations, charge coupled devices (CCD) and photomultiplier
devices. For example, in one embodiment a CCD chip having about
1000 by 1000 pixel resolution or higher may be used. Optionally,
images captured at various wavelengths may be captured and compared
to permit image normalization. In an alternate embodiment, an image
capture device 50 may be utilized to correct for motion effects and
aberrations. The image capture device 50 forms an image of light
reflected from the examination substrate 16 and transmitted to the
OPS imaging section 30 by the light transport section 14. (See FIG.
1). In the illustrated embodiment, the image capture device 46 is
in communication with a processor and display device 52. The
processor and display device 52 may be used to process information
from the image capture device 50 and display the information in any
number of ways. Exemplary processor and display devices include,
without limitations, computers and display terminals.
[0099] As shown in FIG. 2, the OPS section 30 may include a light
modulator 54 and/or an OPS optics suite 56. The light modulator 54
may be used to segment the sample light 40, thereby providing a
stroboscopic effect thereto. Exemplary light modulators 54 include,
without limitations, light choppers, shutters, and light valves
including liquid crystal light valves. An OPS optics suite 56 may
be used to focus, defocus, collimate, or otherwise refine the light
sample 40 transmitting through the OPS imaging section 30.
Exemplary components which may be used within the OPS optics suite
56 include, without limitations, mirrors, positive lenses, negative
lenses, acromats, compound lenses, astigmats, windows, flats,
adaptive optics, holographical optical elements, spatial filters,
pinholes, collimators, stages, and beam splitters. The light
modulator 54 and the OPS optics suite 56 may be positioned at
various locations within the OPS imaging section 30.
[0100] Referring again to FIG. 2, the reflectance spectrophotometry
module 32 includes a spectrophotometer 70 coupled to a RFS image
processor 72 for computing and displaying spectral characteristics
of the light reflected from the examination substrate 16. (See FIG.
1). For example, full spectrum (e.g. white) light is used to
illuminate an examination substrate. Thereafter, the light
reflected by the examination substrate 16 may be captured and the
spectral characteristics thereof may be examined to measure a
variety of characteristics of the examination substrate 16,
including, without limitation, hemoglobin saturation and hematocrit
concentration. Exemplary RFS image processors 72 include, without
limitation, CCD and CMOS chips and photo-multiplier devices coupled
to processors and display monitors. As such, the spectrophotometer
70 is in optical communication with the light transport section 14.
In one embodiment, an RFS optics suite 74 may be used to process
and refine the light received from the light transport section 14.
Exemplary components which may be used within the RFS optics suite
74 include, without limitations, mirrors, positive lenses, negative
lenses, acromats, compound lenses, astigmats, windows, flats,
adaptive optics, holographical optical elements, spatial filters,
pinholes, collimators, stages, wavelength filters, emission
filters, and beam splitters.
[0101] As shown in FIG. 2, the fluorescence imaging module 34
includes a fluorescence imaging system 90 and a fluorescence image
capture device 92. Exemplary fluorescence imaging systems 90 may
include variety of optical components including, without
limitation, microscopes, filter wheels, shutters, and optical
filters. For example, green, yellow, and clear optical filters may
be included. In one embodiment, the fluorescence imaging system 90
is configured to detect fluorescence from ultraviolet (UV) to
infrared (IR) wavelengths. The fluorescence image capture device 92
may include a variety of devices including, without limitation, CCD
chips and photomultiplier devices. Optionally, the fluorescence
imaging module 34 may include a fluorescence optical suite 94 to
refine or otherwise alter the light entering the fluorescence
module 34. Exemplary components which may be used within the
fluorescence optical suite 94 include, without limitations,
mirrors, positive lenses, negative lenses, acromats, compound
lenses, astigmats, windows, flats, adaptive optics, holographical
optical elements, spatial filters, pinholes, collimators, stages,
wavelength filters, emission filters, and beam splitters.
[0102] Referring again to FIG. 2, a beam director 98 may be
included within or proximate to the analyzing section 12 and
configured to direct light from the light transport section 14 to
the OPS imaging module 30, the reflectance spectrophotometry module
32, and/or the fluorescence imaging module 34. Exemplary beam
directors 98 include, without limitation, mirrors including
dichroic mirror or elements and dark field mirrors, beam splitters,
optical switches, movable or spinning geometric mirrors, corner
cubes, prisms, and optical gratings. For example, in one embodiment
the beam director 98 comprises a beam splitter directing fifty
percent of the incoming light to the OPS imaging module 30 and 50
percent of the incoming light to the reflectance spectrophotometry
module 32. In an alternate embodiment, the beam director 98
comprises a mirror having a non-reflecting area formed thereon,
thereby reflecting a portion of light to the spectrophotometer and
permitting dark field illumination to the OPS imaging module 30
and/or fluorescence imaging module 34. Optionally, the beam
director 98 may comprise a spinning or moving mirrored polygon
configured to reflect light from the light transport section 14 to
the OPS imaging module 30, the reflectance spectrophotometer module
32, and/or the fluorescence imaging module 34. In another
embodiment, the beam director 98 may be selectively actuated by the
user to direct light to at least one of the OPS imaging module 30,
the reflectance spectrophotometer module 32, the fluorescence
imaging module 34, and/or any additional modules 34 coupled to or
in optical communication with the analyzing section 12.
[0103] In one embodiment of the imaging system 10, the OPS imaging
module 30 is coupled to the light transport section 14, while the
reflectance spectrophotometer module 32 and/or the fluorescence
imaging module 34 are positioned external to the imaging system 10
in optical communication therewith. A beam director 98 is
positioned within the OPS module 30 and configured to direct a
percentage (e.g. fifty percent) of the light received by the
analyzing section 12 along an optical path to the reflectance
spectrophotometer module 32 and the fluorescence imaging module 34,
while the remaining light is directed to the OPS imaging module 30.
An external beam director (not shown) may be used to further divide
the directed light between the reflectance spectrophotometer module
32 and the fluorescence imaging module 34.
[0104] FIGS. 1 and 3 show an embodiment of a light transport
section 14 of an imaging system 10. In the illustrated embodiment,
the light source 20 is positioned proximate to a first lens 100. A
variety of light sources may be used to illuminate the examination
substrate 16, including, without limitation, incandescent lamps,
gas discharge lamps, dye lasers, solid state devices such as light
emitting diodes, laser diodes, gas lasers, excimer lasers, solid
states lasers, and chemical lasers. For example, in one embodiment
the external light source 20 comprises an incandescent lamp
configured to irradiate the examination surface 16 with white
light. In an alternate embodiment, the external light source 20
comprises a mercury lamp thereby stimulating fluorescence in the
tissue of the examination substrate 16. In still another
embodiment, the light source 20 comprises one or more LEDs
configured to illuminate the examination substrate 16 with light of
a discreet wavelength. In still another embodiment, the light
transport section 14 may include a number of light sources. For
example, a white light source and a UV light source could be used
simultaneously. When using multiple light sources a shutter or beam
splitter may be used to operate the system with a desired light
source. For example, to operate the system using the white light
source a shutter could be positioned to prevent the UV light from
entering the light transport section 14. Thereafter, the user may
actuate the shutter to illuminate the examination substrate 16 with
the UV light rather than white light. In an alternate embodiment, a
laser source may be coupled to or in optical communication with the
imaging system 10 to treat the examination substrate 16. For
example, the laser source may be used to treat microcirculatory
disorders including, without limitation, cancerous tissue, skin
discolorations, and/or tissue lesions. Optionally, the imaging
system 10 may be operated without a first lens 100.
[0105] Referring again to FIGS. 1 and 3, light emitted by the
external light source 20 is incident on a polarizer 102 configured
to polarize light to a desired orientation. Thereafter, polarized
light rays 104A, 104B, and 104C are incident on a light director
106 configured to direct light rays 104A', and 104B' to the
examination substrate 16. In the illustrated embodiment, the light
director 106 includes a non-reflective or dark field spot 108
formed thereon, thereby permitting light ray 104C to proceed
therethrough and be absorbed by a beam dump or absorber 110.
Exemplary light directors include, without limitation, beam
splitters, dichroic junctions, and mirrors.
[0106] A light guide 112 in optical communication with the light
source 20 receives and transmits light rays 104'A, 104B' to the
examination substrate 16. In the embodiment illustrated in FIG. 3,
the light guide 112 includes an illumination segment 114 and a
reflectance segment 116. The illumination segment 114 transmits
light to the examination substrate 16 for illumination, while the
reflectance segment 116 transmits reflected light from the
examination substrate 16 to the beam director 98 of the analyzing
section 12. Exemplary light guides include, for example,
boroscopes, endoscopes, liquid light guides, polymer light guides,
glass light guides, tubular bodies, and single or bundled optical
fibers. For example, FIGS. 4A-4D show several embodiments of light
guides 112 which may be used with in the light transport section
14. As shown in FIG. 4A, the light guide 112 may include polymer
illumination and reflectance segments 114, 116, respectively. The
reflectance segment 116 may be optically isolated from the
illumination segment 114, for example, by an internal cladding 115.
Similarly, the illumination segment 114 may include an external
cladding 117 thereon. As shown in FIG. 4B, the reflectance segment
116 may be comprised of a bundle of optical fibers while the
illumination segment 114 comprises a polymer light guide. In the
alternative, FIG. 4C shows a light guide 112 having an illumination
segment 114 constructed of a bundle of optical fibers and having a
polymer reflectance segment 116 therein. FIG. 4D shows another
embodiment wherein the illumination segment 114 and the reflectance
segment 116 are constructed from a bundle of optical fibers.
[0107] As shown in FIG. 3, a lens or lens system 118 may be
included within the light transport section 14 to focus the light
rays 104A', 104B'. The focal point 120 of the lens system 118 may
be located above, at the surface of, or below the surface of the
examination substrate 16. Optionally, the lens system 118 may
include a reflector or other device configured to project
illuminating light at any angle relative to the longitudinal axis
of the light transport body 14. For example, the lens system 118
may permit a user to project light at an angle of about 90 degrees
relative to the longitudinal axis of the light transport body 14.
As shown, the distal tip 137 of the light transport body 14 is
positioned a distance D from the examination substrate 16. As a
result, the light transport body 14 does not contact the
examination substrate 16 thereby permitting the unimpeded flow of
material through the examination substrate 16. As such, the imaging
system 10 permits the user to measure the flow of a material
through the examination substrate 16 in real time. Light 122
reflected from the examination substrate 16 is captured by the lens
118 and transmitted through the reflectance segment 116 and the
dark field spot 108 of the light director 106 to the beam director
98 analyzing section 12. Optionally, a polarizer (not shown) may be
positioned proximate to the distal tip 137 of the light transport
body 14 and configured to polarize light prior to illuminating the
examination substrate 16.
[0108] FIG. 5 shows an alternate embodiment of a light transport
section 14. As shown, an internal light source 18 may be used to
illuminate the examination substrate 16. For example, one or more
LEDs may be used to illuminate an examination substrate 16 with a
discreet wavelength of light. In an alternate embodiment, the
internal light source 18 may comprises LEDs of different color,
thereby illuminating the examination substrate 16 with light of
multiple discreet wavelengths or with full spectrum light for
additional treatment (e.g. laser ablation). Multiple wavelength
LED's can also be used to generate images of the distribution of Hb
saturation in an SDF imaging modality. Those skilled in the art
will appreciate that the use of LEDs as a light source enables the
imaging system 10 to be powered by a battery or other low-power
power supply relative to previous systems. For example, the imaging
system 10 may be powered by coupling the imaging system 10 to a
universal serial port of a personal computer. One or more internal
lenses 130 may, but need not be, included within the light
transport section 14 and positioned proximate to the internal light
source 18. Similarly, one or more optical polarizers or filters 132
may be positioned proximate to the internal lenses 130. The
internal light sources 18 emit rays 134A, 134B which are
transmitted to the examination substrate 16 by the illumination
segment 136 of the light guide 138. An examination lens system 140
may be used to focus the light rays 134A, 134B to the examination
substrate 16. A focal point 142 of the lens system 140 may be
located above, at the surface of, or below the surface of the
examination substrate 16. Thereafter, light rays 144 reflected by
the examination substrate 16 are collected by the lens system 140
and transmitted to the beam director 98 of the analyzing section 12
by the reflectance segment 146 formed within the light guide
138.
[0109] FIG. 6 shows an alternate embodiment of a light guide 150.
As shown, the light guide 150 includes an illuminating segment 152
having a focused or curved distal tip 154, thereby directing light
rays to a focal point within an examination substrate (not shown).
The reflectance segment 156 is configured to transmit light from
the examination substrate 16 to the analyzing section 12 (See FIG.
1).
[0110] FIGS. 7 and 8 show embodiments of spacer devices which may
be affixed to the distal end or distal section of the light guide.
FIG. 7 shows a light guide 160 having a spacer 162 attached
thereto. In the illustrated embodiment, the distal section of the
light guide 160 may include one or more lock members 164 thereon to
securely couple the spacer 164 to the light guide 160. As such, the
spacer 160 may include a locking member recess 166 to accommodate
the locking members 164. The spacer 162 ensures that the light
guide 160 remains at least a distance d from the examination
substrate 16. FIG. 8 shows an alternate embodiment of a spacer 172
coupled to a light guide 170. The spacers 162, 172 may be
manufactured from a variety of materials including, without
limitation, plastic, rubber, elastomer, silicon, or any other
biologically compatible material. In one embodiment, the spacer
162, 172 are disposable.
[0111] FIGS. 9 and 10 show an embodiment of a light guide 180
having an alternate embodiment of a spacer 182 attached thereto.
The spacer 182 includes a vacuum port 184 attachable to a source of
vacuum (not shown). The spacer 182 includes a spacer aperture 186
for irradiating the examination substrate (not shown). The spacer
182 includes one or more attachment orifices 188 thereon which are
in communication with the vacuum port 184. The attachment orifices
188 are formed between an exterior wall 190 and an interior wall
192 of the spacer body 194 and are isolated from the spacer
aperture 186. As such, the spacer 180 is configured to couple to
the examination substrate (not shown) when the vacuum source is
actuated without adversely effecting the irradiation of the
examination surface. As such, the spacer 180 may be rigid or, in
the alternative, may be constructed of a compliant material for use
within or on compliant organs or structures. Like the embodiments
described above, the spacer 182 may be manufactured from a variety
of materials and may be disposable. One or more additional ports
may be formed on the spacer body 194 for the administration of
medicinal or therapeutic agents.
[0112] FIGS. 11 and 12 show an embodiment of an imaging system 200.
As shown, the imaging system 200 includes an illumination body 202
and a reflectance body 204. The illumination body 202 defines an
optics recess 206 configured to receive an optical system 208
therein. The optical system 208 includes a first spacer 210, a
first dark field mirror 212, a filter spacer 213, and a filter bank
214. In the illustrated embodiment, the filter bank 214 includes a
clear filter 216, a yellow filter, 218, a green filter 220, and a
white filter 222. A second spacer 224 is positioned proximate to
the filter bank 214. A third spacer 226 is positioned between the
second spacer 224 and a lens 228. A fourth, fifth, and sixth
spacers 230, 232, and 234, respectively, are positioned proximate
thereto. A second dark field filter 236 is positioned between the
sixth spacer 234 and the seventh spacer 238.
[0113] Referring again to FIG. 11, the reflectance body 204
includes a light director 240 therein. The light reflector 240
includes a non-reflective area 242 formed thereon. In addition, the
reflectance body 204 includes an examination tip 244 which is
configured to be positioned proximate to the examination substrate
(not shown). A polarizer and/or filter 246 and an image capture
device 248 may be positioned within the analyzing section 250 of
the reflectance body 204. During use, a light source 252 projects
light which is filtered and focused by the optical system 208
located within the illumination body 202. The light from the light
source 252 is directed by the light director 240 to the examination
substrate (not shown) located proximate to the examination tip 244.
Light reflected by the examination substrate (not shown) is
transmitted to the analyzing section 250 by the light guide 256,
where the light is depolarized and analyzed.
[0114] FIG. 13 shows another embodiment of an imaging system. As
shown, the imaging system 300 includes an illumination body 302 and
a reflectance body 304. The illumination body 302 defines an optics
recess 306 configured to receive an optical system 308 therein. The
optical system 308 includes a first lens 310 and a second lens 312.
Positioned proximate to the first lens 310 is an internal light
source 318. In the illustrated embodiment, the internal light
source 318 comprises a number of LEDs configured to project light
through the optical system 308. One or more reflectors 316 may be
used to ensure that the light is transmitted through the
illumination body 302.
[0115] As shown in FIG. 13, the reflectance body 304 includes a
light director 340 therein. The light reflector 240 includes a
non-reflective area 342 formed thereon. In addition, the
reflectance body 304 includes an examination tip 344 which is
configured to be positioned proximate to the examination substrate
(not shown). A beam director 398 and an image capture device 348
may be positioned within the analyzing section 350 of the
reflectance body 304. During use, the light source 318 projects
light which is focused by the optical system 308 located within the
illumination body 302. The light from the light source 318 is
directed by the light director 340 to the examination substrate
(not shown) located proximate to the examination tip 344. Light
reflected by the examination substrate (not shown) is transmitted
to the analyzing section 350 by the light guide 356, where the
light is analyzed. As shown, the analyzing section 350 may include
one or more filters or polarizers 360 therein.
[0116] As shown in FIGS. 3-5, at least one light source may be used
to illuminate structures located below the surface of a substrate.
FIGS. 14 and 15 show alternate embodiments of imaging systems
useful in imaging sub-surface structures while avoiding or reducing
the effects of surface reflection. FIG. 14 shows an imaging system
400 comprising a body 402 having one or more imaging passages 404
formed therein. One or more illumination passages 406 may be formed
within the body 402 and may be optically isolated from the imaging
passage 404. In one embodiment, the body is rigid. In an alternate
embodiment, the body 402 is flexible. For example, the body 402 may
comprise a catheter body. Optionally, the body 402 may include an
additional lumen formed therein. For example, an additional lumen
may be positioned within the body 402 and may be used to deliver
therapeutic agents to a treatment site. In another embodiment, an
additional lumen may be used to deliver a vacuum force to a
treatment site. In the illustrated embodiment, the illumination
passage 406 is positioned radially about imaging passage 404. In
the illustrated embodiment, the illumination passage 406 encircles
the imaging passage 404. In an alternate embodiment, the
illumination passage 406 may be positioned anywhere within the body
402. As shown, the illumination passage 406 is optically isolated
from the imaging passage 404. Therefore, illuminating energy
transported through the illumination passage 406 is prevented from
entering the imaging passage 404. As such, the present systems
permits side stream dark field imaging (hereinafter SDF). As shown
in FIG. 14, a feature of SDF imaging is that the illuminated light
412A and 412B and the reflected light 414 travel via independent
pathways. Thus, the illumination can be placed directly on the
tissue and the observations can be made adjacent to it without
light crossing over between two paths.
[0117] Referring again to FIG. 14, at least one illumination source
may be positioned within the illumination passage 406. In one
embodiment, the illumination source 410 comprises one or more LED's
configured to project a selected wavelength to the substrate 420.
In an alternate embodiment, the illumination source 410 comprises a
plurality of LED's configured to project multiple wavelengths to
the substrate 420. For example, as shown in FIG. 14 a first
illumination source 410A configured to project light to the
substrate 420 is positioned at the distal portion 418 of the body
402. Similarly, a second illumination source 410B is positioned at
the distal portion 418 of the body 402. As such, the first and
second illumination sources 410A, 410B are positioned proximate to
the substrate 420 under examination. Optionally, any number of
illumination sources may be positioned within the body 402.
Exemplary illumination sources include, without limitation, LED's,
LLED's, incandescent bulbs, laser light sources, etc.
[0118] FIG. 15 shows a perspective view of the distal portion of an
alternate embodiment of the imaging device 400 shown in FIG. 14. As
shown, the body 402 includes an imaging passage 404 and at least
one illumination passage 406 optically isolated from the imaging
passage 404. One or more illumination devices 410 are located
within the illumination passage 406 and positioned proximate to the
distal portion 418 of the body 402. As such, during use the
illumination source are positioned proximate to the substrate
420.
[0119] FIG. 16 shows a cross sectional view of the distal portion
of an embodiment of an imaging device. As shown, The body 402
defines an imaging passage 404 and an illumination passage 406
therein. Like the previous embodiments, the illumination passage
406 is optically isolated from the imaging passage 404. In the
illustrated embodiment, the illumination passage 406 terminates
proximate to the distal portion 418 of the body 402. Optionally,
the illumination passage 406 may continue through the length of the
body 402. As such, the illumination passage 406 may include one or
more optical fibers configured to deliver illuminating energy to
the substrate 420 from a remote location. In the illustrated
embodiment, one or more illumination sources 410 are positioned
within the illumination passage 406. For example, one or more LED's
may be positioned within the illumination passage 406. Like the
previous embodiments shown in FIGS. 14 and 15, the illumination
passage 406 is optically isolated from the imaging passage 404.
Optionally, at least one conduit 424 may traverse through the body
402 thereby coupling the illumination source 410 to a source of
power. In the illustrated embodiment at least one lens 422 is
positioned within the imaging passage 404 thereby transmitting an
image received from a substrate 420 to an image capture device 416.
(See FIG. 14). Optionally, the imaging system shown in FIGS. 14-16
may be used without a lens 422.
[0120] With reference to FIG. 14, during use, the first
illumination source 410A projects illuminating energy 412A to the
substrate 420. Similarly, the second illumination source 410B
projects illuminating energy 412B to the substrate 420. As shown in
FIG. 14, the illumination energies 412A, 412B are optically
isolated from the imaging passage 404. The first and second
illumination energies 412A, 412B may be the same or differing
wavelengths. Further, as the first and second illumination sources
410A, 410B are positioned at the distal portion of the body 402
proximate to the substrate 420, surface reflections therefrom are
reduced or eliminated. As shown, a sub-surface image 414 is
transported by the imaging passage 404 from the substrate 420 to an
image capture device 416. Exemplary image capture devices include,
without limitation, CCD devices, cameras, spectrophotometers,
photomultiplier devices, analyzers, computers, etc. Optionally, one
or more lenses 422 may be positioned within the image passage 404
or body 402 to focus illumination energy 412 to the substrate 420
or to assist in the transport of an image 414 from the substrate
420 to the image capture device 420416, or both. As stated above,
the optical isolation of the illumination energy from the image
received from the substrate reduces or eliminates the effects of
surface reflections while enabling SDF imaging in addition to a
variety of alternate imaging modalities or spectroscopic
examination of an area.
[0121] FIG. 17 shows an alternate embodiment of an SDF imaging
system. As shown, the SDF imaging system 450 comprises a body 452
defining an imaging passage 454 and an illumination passage 456
optically isolated from the imaging passage 454. The illumination
passage 456 includes one or more illumination sources 460 therein.
Exemplary illumination sources 460 include, without limitation,
LED's, LLEDs, and incandescent bulbs. As shown, the illumination
sources 460 are located proximate to the distal portion 462 of the
body 452. Optionally, the illumination sources 460 may be located
some distance from the examination area. As such, illuminating
energy may be transported to the examination area through fiber
optic conduits positioned within the body 452. Like the previous
embodiments, the body 402 may be rigid or flexible. In the
illustrated embodiment, a cap device 464 is positioned over the
body 452. In one embodiment, the cap device 464 may comprise an
optically transparent disposable cap device 464 configured to be
detachably coupled to the body 452. During use the cap device 464
may protect the body 402 from biological materials and
contaminants. As such, the cap device 464 may be sterile.
[0122] Referring again to FIG. 17, at least one lens 466 may be
positioned within the imaging passage 454. The imaging passage 454
is in optical communication with an imaging capture device 468. The
image capture device 468 may comprise any of devices useful in
capturing and analyzing an image received from a substrate. For
example, the image capture device 468 may comprise a CCD device,
photomultiplier, computer, spectrophotometer, and the like.
Further, a focusing device 470 may be included within the body 452
or the image capture device 468. Exemplary focusing devices
include, without limitation, additional lenses, mechanical drives
or positioners, and the like. Optionally, the SDF imaging system
450 may further include a handle 472 to assist a user in
positioning the device. Further, the SDF imaging system 450 may be
configured to be coupled to a computer, power source, etc.
[0123] FIG. 18 shows an alternate embodiment of an imaging system.
As shown, the imaging system 500 includes a body 502 defining an
imaging passage 504 and at least one illumination passage 506
optically isolated from the imaging passage 504. The illumination
passage 506 includes one or more illumination sources 510 therein.
As shown, the illumination sources 510 are located proximate to the
distal portion 518 of the body 502, however, the illumination
source may be located anywhere on the body 502. Optionally, a cap
device (not shown) may be positioned over the body 502. For
example, the cap device (not shown) may comprise an optically
transparent disposable device configured to be detachably coupled
to the body 502.
[0124] Referring again to FIG. 18, at least one lens 522 may be
positioned within the imaging passage 504. The imaging passage 504
is in optical communication with at least one image capture device
516. In the illustrated embodiment, a first image capture device
516A and a second image capture device 516B may be used with the
system. Further, one or more optical modulators 526 may be
positioned within the image passage 504 and configured to modulate
imaging signals from the substrate 520. Exemplary optical
modulators 526 include, without limitation, mirrors, band pass
plates, polarizers, gratings, and the like. The image capture
devices 516A, 516B may comprise any number of devices useful in
capturing and analyzing an image received from a substrate. For
example, the image capture devices 516A, 516B may comprise CCD
devices, spectrophotometers, spectrum analyzers, and the like.
[0125] As shown in the FIGS. 18 and 19, the illumination sources
510 may comprise LED's of a single wavelength. In the alternative,
the illumination sources 510 may be configured to irradiate light
of multiple wavelengths. For example, FIG. 19 shows a device having
a first illumination source 510A irradiating at a first wavelength
and a second illumination source 510B irradiating at a second
wavelength. FIG. 20 shows a device having a first illumination
source 510A, a second illumination source 510B, and a third
illumination source 510C, each illumination source irradiating at a
different wavelength. As such, the system may be configured to
perform a number of imaging and analyzing procedures with a single
device. For example, a first wavelength may be projected to the
substrate and used for SDF microcirculation imaging within the
underlying vasculature, while a second wavelength may be projected
to the substrate and used for detecting oxygen saturation within a
blood flow. In short any number of wavelengths of illuminating
energy may be projected from the illumination sources 510 and used
for any number of analytical processes. For example, the imaging
system 500 may be configured to permit imaging of the
microcirculation and spectroscopic examination of an area with a
single device.
[0126] Referring to FIGS. 18 and 21, during use the distal portion
518 of the body 502 may be in contact with the substrate 520 under
examination. As such, the illumination source(s) 510 may be
positioned in close proximity to the substrate 520. Optionally, the
distal portion 518 may include one or more engaging devices 528
coupled to the body 504 or the cap device (not shown). For example,
as shown in FIG. 22, the engaging device 528 may comprise an
inflatable device configured to dissipate a pressure applied to the
substrate 520 by the distal portion 518 of the body 502. In an
alternate embodiment, shown in FIG. 23, the distal portion 518 may
be positioned proximate to, but not in contact with, the substrate
520. As such, the illumination sources 510 may be configured to
project illuminating energy 512A, 512B to the substrate 520.
Optionally, one or more lenses may be in optical communication with
the illumination source(s) 510 to aid in the projection of
illumination energy 512A, 512B to the substrate 520.
[0127] FIG. 24 shows a block diagram of an embodiment of an imaging
and analyzing system. As shown, the imaging system 600 includes an
analyzing section 602, a light transport section 604, and a light
delivery section 606 configured to deliver light to and receive
information from a substrate 608. As stated above, the analyzing
section 602 may include any number of analyzing modules configured
to process information received from the substrate 608. In the
illustrated embodiment, the analyzing section 602 includes an OPS
imaging module 620, a dark filed illumination module 622, a
reflectance spectrophotometry module 624, an additional processor
module 626, a fluorescence module 628, and/or a fluorescence
lifetime module 630. The additional processor module 626 may
include one more processing module including, without limitation,
Raman spectroscopy devices, fluorescence decay processors, PpIX
analyzers, and/or OCT (Hb sat) analyzers, and/or CO2 analyzers.
Referring to FIGS. 18 and 21, the analyzing section 602 may be
configured to receive imaging information from the substrate 520
via the imaging passage 504 formed within the body 502. Those
skilled in the art will appreciate that the present system enables
a user to selectively analyze a substrate using multiple imaging
modalities, spectrophotometry modalities, and similar analyzing
methods using a single device coupled to multiple analyzers.
[0128] The light transport section 604 may comprise a body 634
configured to transport light to and from the substrate 608. For
example, the body 634 may include an image passage 504 and an
optically isolated illumination passage 506 as shown in FIG. 18.
Further, the light transport section 604 may include one or more
internal illumination sources 636 positioned therein and configured
to irradiate the substrate 608. Optionally, one or more optical
elements 634 may be positioned within the body 632. Further, the
body 632 may be configured to receive and transport light from an
external light source 638 to the substrate 608.
[0129] Referring again to FIG. 24, the light delivery section 606
may comprise a direct illumination source 640 configured to be
positioned proximate to the substrate 608 and providing direct
illumination thereto. As such, the direct illumination source 640
is optically isolated from an image received from the substrate
608. Exemplary direct illumination sources 640 include LLED's,
LED's, and the like. Further, one or more white light illumination
sources 642 may be used to illuminate the substrate 608. In one
embodiment, the light delivery section 606 may be configured to
deliver materials to or receive materials 644 from the substrate
608. For example, the light delivery section 606 may be configured
to infuse therapeutic agents to the substrate 608. Optionally, the
light delivery section 606 may include one or more engaging devices
646 positioned thereon to assist in positioning the system during
use.
[0130] As stated above, the preceding imaging and analyzing systems
disclosed herein may include one or more cap devices 464 which may
be detachably coupled to the body 452. (See FIG. 17). Generally,
the cap device 464 may comprise optically transparent materials
configured to protect the body 452 during use. As such, the cap
device 464 may be disposable. FIG. 25 shows an alternate embodiment
of a cap device 714. As shown in FIG. 25, the imaging device 700
includes a body 702 having an imaging passage 704 and an
illumination passage 706 optically isolated from the imaging
passage 704 formed therein. The illumination passage 706 may
include one or more conduits 708 coupled to one or more
illumination sources 710 located therein. As shown in FIG. 25, one
or more lenses 712 may be positioned within the imaging passage
704. A cap device 714 may be coupled to the body 702. The cap
device 714 includes an illumination field 716 optically isolated
from an imaging relief 718. In the illustrated embodiment, the
illumination field 716 is positioned proximate to the illumination
sources 710 located within the body 702. Similarly, the imaging
relief 718 is positioned proximate to the imaging passage 704. At
least one isolation surface 720 optically isolates the illumination
field 716 from the imaging relief 718. For example, in the
illustrated embodiment the isolation surface 720 include a
reflective foil 722 thereon which is configured to prevent light
from illumination sources 710 from directly entering the imaging
passage 704 without first engaging a substrate under examination.
Alternate isolation materials may be used on the isolation surface
722 including, without limitation, dyes, foils, impregnations, etc.
Optionally, the cap device 714 may be disposable and may be
configured to detachably couple to the body 702.
[0131] FIG. 26 shows yet another embodiment of a reflectance
avoidance imaging system. As shown, the reflectance avoidance
imaging system 810 includes an imaging device 812 having a spacer
or tissue engaging tip 814 attached thereto. The imaging device 812
includes a body 816 having a distal portion 818 configured to
receive and engage the spacer 814. In one embodiment, the spacer
814 is detachably coupled to the body 816. Optionally, the spacer
814 may be non-detachably coupled to the body 816.
[0132] Referring again to FIG. 26, the imaging body 816 includes
one or more conduits formed therein. In the illustrated embodiment,
the body 816 includes an imaging conduit 820 configured to project
light from a light source (not shown) to a work surface. In
addition, the imaging conduit 820 collects light reflected from the
work surface and transports the reflected light to a sensor suite
(not shown) in communication therewith. Exemplary sensor suites
include, without limitation, a CCD or any other type of imaging or
sensing device, spectral photometers, and the like. Optionally, a
secondary imaging conduit 822 may be positioned within the body
816. For example, the secondary imaging conduit 822 may be
configured to measure CO.sub.2 within tissue through the use of a
CO.sub.2 sensing dye. The CO.sub.2 sensing dye enables the
measurement of fluorescence decay and may utilize light received
from and transmitted through the imaging conduit 820. Optionally,
one or more additional conduits 824 may be positioned within the
body 816. For example, any number of fluid conduits may be formed
within the body 816.
[0133] The spacer 814 includes a spacer body 830 having a coupling
portion 832 configured to engage and couple the distal portion 818
of the body 816. The spacer body 830 further defines an orifice 834
which is in communication with the coupling portion 832. In the
illustrated embodiment, the spacer body 830 includes thread members
836 and attachment devices 838 formed or otherwise disposed thereon
to enable the spacer body 830 to couple to the body 816. Any number
or type of thread members 836 and attachment devices 838 may be
used to couple the spacer body 830 to the imaging device 812. The
distal portion of the spacer body 830 includes a flange 840
defining the orifice 834. In the illustrated embodiment, the flange
840 includes one or more vacuum ports 842 portioned thereon,
thereby permitting the flange 840 to engage or couple to the a work
surface.
[0134] In the illustrated embodiment, the spacer 814 includes one
or more vacuum ports 842 which enable the spacer 184 to engage the
work surface. Optionally, the spacer body 814 may be configured to
avoid contacting the work surface. For example, the spacer body 814
may include an optical system comprised of one or more lenses to
enable the imaging device 812 to project and receive light to and
from a work surface from a distance without contacting the work
surface. For example the optical system may include a zoom lens
system.
[0135] Further, the spacer 814 may be formed in any variety of
shapes and size. For example, the spacer may include a
doughnut-shaped spaces. Furthermore, the spacer 814 may include a
bladder or cushion filled with any variety of fluids. Optionally,
the fluid may be optically transparent.
[0136] FIG. 27 shows a cross sectional view of an embodiment of a
reflectance avoidance imaging system 810. As shown, the body 816
includes the imaging conduit 820, the secondary imaging conduit
822, and the addition conduit 824 formed therein. In addition,
vacuum conduits 856 and 858 are formed within the body 816 and a
couple to a vacuum source. (not shown) The spacer 814 includes
vacuum conduits 870 and 872 which are in communication with the
vacuum conduits 856 and 858 of the body 816 and the vacuum ports
842 formed on the spacer 814. Optionally, one or more attachment
members 862 may be positioned on the body 816 to further enable
coupling of the spacer 814 to the body 816.
[0137] In addition to the novel imaging devices described above,
the present application describes a method of imaging and
determining various biological parameters non-invasively and, if
needed, treating an affected area. For example, when operating the
above-described system in an OPS imaging mode, flow though the
capillaries and related circulatory structures may be examined be
viewing red blood flow therethrough. To operate the system in an
OPS imaging mode, the user irradiates the examination substrate
with white light. The white light is polarized by a polarizer prior
to illuminating the examination substrate. Reflected light is
captured by the light guide and transmitted to the polarizing
section 42 of the OPS imaging module 30 (See FIG. 2). Light
reflected by the system optics and the patient's tissue surface
undergoes a polarization shift as a function of scattering and,
thus, is cancelled by the polarizing section 42. As such,
sub-surface reflected light fails to undergo a polarization shift
and will be captured by the image capture device 50, thereby
enabling sub-surface imaging. Optionally, OPS imaging may be
accomplished in combination with dark field illumination.
[0138] Similarly, the imaging system described herein may be used
to perform reflectance spectrophotometry using the reflectance
spectrophotometry module. A spectrophotometer may be used with the
present imaging system to examine the spectral reflectance of the
tissue surface. Light from a light source illuminates an
examination substrate. The light may comprise an internal light
source 18, external light source 20, and/or an ancillary light
source 22. (See FIG. 1). Light reflected by the examination
substrate 16 is captured by a light transport section 14 and
transmitted to a reflectance spectrophotometry module. The spectral
characteristic of the reflected light may then be examined and used
to determine the hemoglobin saturation, and/or hematocrit
concentration within the surface of an organ under
investigation.
[0139] Lastly, the imaging system described herein may be used to
determine the oxygenation and/or functional state of a tissue cell
using the fluorescence imaging module. For example, an examination
area may be illuminated with UV light thereby targeting the
mitochondrial energy state therein. For example, light having a
wavelength of about 360 nm may be used to illuminate the
examination substrate. Thereafter, light reflected by the substrate
may be captured by the light transport section 14 and transmitted
to the analyzing section 12. (See FIG. 1) The captured light may
undergo a lambda shift from 360 nm to about 460 nm. Thereafter, a
fluorescence imaging module 34 may analyze the reflected light for
to determine the presence of NADH in the cells, thereby showing
availability of oxygen within the cells.
[0140] The OPS imaging processor 52, RFS processor 72, and
fluorescence imaging processor 92 may each contain any number of
formulas, algorithms, models, databases, look-up tables, or related
information to compute and display their respective reflectance
measurements. For example, Beers-Lambert law may be used to
determine the concentration of material in the examination
substrate based on the absorbance of the light by the examination
substrate.
[0141] Also disclosed herein is a method of comprehensively
monitoring the microcirculation of a patient. The method may
include using any of the aforementioned imaging systems disclosed
herein. In one embodiment, the method includes illuminating a
tissue substrate, avoiding the reflection of light from the surface
of the tissue substrate, receiving light from the tissue substrate,
utilizing some of the received light to image microcirculatory flow
in the tissue substrate, utilizing some of the received light to
determine oxygen availability in the microcirculation, and
utilizing some of the received light to determine the adequacy of
oxygenation of the tissue cells.
[0142] In one embodiment, the aforementioned method may include
utilizing the microcirculatory flow information, the oxygen
availability information, and the adequacy of oxygenation of tissue
cells information, making an early and sensitive determination
regarding states of shock, such as septic, hypovolemic, cardiogenic
and obstructive septic shock, in patients, and guiding
resuscitation therapies aimed at correcting this condition.
[0143] In another embodiment the aforementioned method may also
include utilizing the microcirculatory flow information, the oxygen
availability information, and the adequacy of oxygenation of tissue
cells information, and making an early and sensitive determination
regarding cardiovascular disease and failure of the patient.
[0144] In closing, it is understood that the embodiments of the
invention disclosed herein are illustrative of the principals of
the invention. Other modifications may be employed which are within
the scope of the present invention. Accordingly, the present
invention is not limited to that precisely as shown and described
in the present disclosure.
* * * * *