U.S. patent application number 16/165222 was filed with the patent office on 2019-09-19 for apparatus, systems, and methods for mapping of tissue oxygenation.
This patent application is currently assigned to SURGISENSE CORPORATION. The applicant listed for this patent is SURGISENSE CORPORATION. Invention is credited to Gregory Scott Fischer, Justin Thomas Knowles, Jason Matthew Zand.
Application Number | 20190282146 16/165222 |
Document ID | / |
Family ID | 54208660 |
Filed Date | 2019-09-19 |
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United States Patent
Application |
20190282146 |
Kind Code |
A1 |
Zand; Jason Matthew ; et
al. |
September 19, 2019 |
APPARATUS, SYSTEMS, AND METHODS FOR MAPPING OF TISSUE
OXYGENATION
Abstract
Apparatus, systems, and methods are provided that generate in
vivo maps of oxygenation measurements of biological tissue. These
may include surgical instruments and stand-alone imaging systems
with incorporated oxygen sensing capability. Oxygenation maps can
be determined via fluorescent or phosphorescent lifetime imaging of
an injectable probe with an oxygen-dependent optical response.
Probe configuration and methods and apparatus of injecting the
probe into the tissue are provided. Methods and apparatus for
temperature compensation of temperature-dependent lifetime
measurements are provided to improve oxygenation measurement
accuracy. Oxygen maps may be registered with visible light images
to assist in assessing tissue viability or localize anomalies in
the tissue. Resulting oxygen images may be used for various
applications including, but not limited to, guiding surgical
procedures such as colorectal resection through use of
intraoperative sensing, enhanced endoscopic imaging for identifying
suspect lesions during colonoscopy, and external imaging of tissue
such as assessing peripheral vascular disease.
Inventors: |
Zand; Jason Matthew;
(Washington, DC) ; Fischer; Gregory Scott;
(Jamaica Plain, MA) ; Knowles; Justin Thomas;
(Fairfax, VA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SURGISENSE CORPORATION |
BETHESDA |
MD |
US |
|
|
Assignee: |
SURGISENSE CORPORATION
BETHESDA
MD
|
Family ID: |
54208660 |
Appl. No.: |
16/165222 |
Filed: |
October 19, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
14679707 |
Apr 6, 2015 |
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16165222 |
|
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62061079 |
Oct 7, 2014 |
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61975742 |
Apr 5, 2014 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 1/00009 20130101;
A61B 5/1459 20130101; A61B 2560/0247 20130101; A61B 1/0005
20130101; A61B 5/0084 20130101; A61B 5/015 20130101; A61B 5/14556
20130101; A61B 5/0071 20130101; A61B 1/0125 20130101; A61B 1/018
20130101; A61B 1/0676 20130101; A61B 1/043 20130101; A61B 1/005
20130101; A61B 5/0035 20130101 |
International
Class: |
A61B 5/1455 20060101
A61B005/1455; A61B 1/04 20060101 A61B001/04; A61B 1/00 20060101
A61B001/00; A61B 1/018 20060101 A61B001/018; A61B 5/01 20060101
A61B005/01; A61B 1/005 20060101 A61B001/005; A61B 1/06 20060101
A61B001/06; A61B 5/00 20060101 A61B005/00; A61B 1/012 20060101
A61B001/012 |
Goverment Interests
GOVERNMENT INTEREST
[0002] This invention was made, in whole or in part, with
Government Support under National Institutes of Health grant
CA153571. The Government has certain rights in the invention.
Claims
1. An imaging system that resolves and maps a physiologic
condition, or proxy thereof; the imaging system utilizing
information obtained from two or more sensing modalities to resolve
said physiologic condition or proxy thereof; the sensing modalities
used in conjunction provide improved accuracy of absolute
measurements of said physiologic condition or measurement.
2.-20. (canceled)
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application No. 61/975,742, filed Apr. 5, 2014, and U.S.
Provisional Patent Application No. 62/061,079, filed Oct. 7, 2014,
each of which is hereby incorporated herein by reference in its
entirety.
TECHNICAL FIELD
[0003] The present invention relates to surgical instruments and
medical imaging systems, and the molecular agents used by the
instruments and systems; specifically to surgical instruments and
imaging systems with sensors used to detect properties of
biological tissue, and a system for exploiting the information
gathered by the sensors. A sensing system can be configured to
obtain a mapping of physiologic properties of tissue at multiple
locations. Further, information from multiple sensing modalities
can be used together to enable improved measurement accuracy.
BACKGROUND
[0004] A living organism is made up of cells. Cells are the
smallest structures capable of maintaining life and reproducing.
Cells have differing structures to perform different tasks. A
tissue is an organization of a great many similar cells with
varying amounts and kinds of nonliving, intercellular substances
between them. An organ is an organization of several different
kinds of tissues so arranged that together they can perform a
special function.
[0005] Surgery is defined as a branch of medicine concerned with
diseases requiring operative procedures.
[0006] Ninety five percent of the time colorectal cancer develops
by a well understood series of genetic mutations over a 10-15 year
time frame beginning as a growth, or polyp. Over their lifetime,
approximately one third to one half of adults will develop one or
more polyps, approximately ten percent of which will continue to
become cancer. Therefore the overwhelming majority of colorectal
cancers can be avoided by identification and removal of polyps at
an early stage before malignant conversion. Endoscopy is the
predominant means by which the US population is screened for benign
and malignant polyps. While colonoscopy can detect up to 95% of
cancerous lesions, polyps are missed approximately 25% of the time,
even utilizing current "enhanced endoscopy" technology.
BRIEF SUMMARY OF THE INVENTION
[0007] The present invention relates to medical devices and systems
capable of measuring physiologic properties of tissue. In one
embodiment of the system, tissue oxygenation is assessed utilizing
the technique of oxygen dependent quenching of phosphorescence.
Whereby phosphorescence is produced from native biologic tissue, or
via an injected phosphorescent oxygen sensing molecular probe. In
alternative embodiments, other phosphors or molecular markers may
be used to localize specific targets or assess other physiologic
parameters. Techniques and instrument configurations for assessing
oxygenation are disclosed in PCT Patent Application No.
PCT/US14/31267 titled Apparatus, Systems and Methods for
Determining Tissue Oxygenation, the disclosure of which is
incorporated herein by reference in its entirety.
[0008] The present invention includes an imaging system that
resolves and maps a physiologic condition, or proxy thereof. The
imaging system utilizing information obtained from two or more
sensing modalities to resolve the physiologic condition. The
additional modalities used in conjunction provide improved accuracy
of absolute measurements in the physiologic condition or
measurement. One embodiment of the invention takes the form of a
multi-modality imaging system, wherein one modality assesses the
phosphorescent and/or fluorescent lifetime decay of a medium and
another modality assesses temperature at or near the medium. In one
configuration, the medium is an injectable probe with a
phosphorescent lifetime that relates to
nearby/resident/proximate/field oxygen concentration/tension of the
subject biologic tissue; the temperature measurement allows for
selection of a precise temperature-dependent calibration
coefficient of the probe's lifetime used to more accurately resolve
oxygenation.
[0009] An embodiment of the imaging system comprises an optical
sensor configured for detection and measurement of the lifetime of
the decay of light emitted by a phosphorescent and/or fluorescent
medium resulting from illumination of the medium at one or more
excitation wavelengths, and further comprising a temperature sensor
for detecting the temperature at one or more points in the field of
view of the optical sensor. The system further comprising a
processor configured to use temperature measurement to compensate
for temperature-dependent lifetime variation of the phosphorescent
and/or fluorescent response. An embodiment of the invention
includes a phosphorescent lifetime imaging (PLI) system, wherein
the system comprises both an optical detector for mapping
phosphorescent lifetime and an optical detector for detecting
temperature. The system additionally capable of registering the
temperature and lifetime images, and utilizing both phosphorescent
lifetime and temperature at each mapped point to determine the
corresponding oxygenation concentration(s) in the subject
tissue.
[0010] An embodiment of the present invention includes an imaging
system configured for generating a map of biologic tissue
oxygenation based on phosphorescent lifetime of an injectable probe
in a region. The system comprising an optical sensor such as a
camera-based device configured for detecting the lifetime of the
phosphorescent decay of the phosphorescent probe in the region, and
further comprising a temperature sensor configured to map the
temperature of the region. In one configuration, the temperature
sensor is a thermal imaging camera. The correspondence between
measurement locations by both sensors in the region are identified
so as to compensate for temperature-dependent calibration from
lifetime to oxygenation.
[0011] An embodiment of the present invention is an endoscopic
system (such as, but not limited to, a colonoscopic system)
configured for measuring tissue oxygenation based on quenching of
the phosphorescent/fluorescent lifetime of an injectable
phosphorescent/fluorescent probe by surrounding oxygen, and
generating a map of the oxygenation. The endoscopy system further
comprises a means of detecting temperature in the region
corresponding to the map of oxygenation, wherein the oxygen-sensing
endoscopic system is configured to compensate for
temperature-dependent parameters of the oxygenation measurements
based on thermal measurements of the temperature detectors. Another
embodiment of the invention takes the form of a sensing system that
operates independently from a scope such as an endoscope or
colonoscope, and operates in conjunction with the scope. The system
is configured to map both phosphorescent lifetime and temperature
at the tip of the scope and use the temperature maps in conjunction
with the phosphorescent lifetime maps to generate
temperature-compensated absolute tissue oxygenation maps. One
configuration of the independently operating sensing system takes
the form of an oxygen sensing system that incorporates a micro
camera-based thermal imaging cameras. An alternate configuration of
the independently operating sensing system takes the form of an
oxygen sensing system comprising a thermal camera coupled to a
coherent fiber optic imaging bundle with transmission in the
infrared range that enables remote sensing of temperature.
[0012] An embodiment of the present invention includes an imaging
system based on a probe using phosphorescence and/or fluorescence.
The probe may be a nanosensor molecule, quantum dots, or other
molecular tag or marker. The probe may be injectable systemically
or locally, or otherwise introduced into the body. An alternate
embodiment of the imaging system is configured to image natural, or
auto-fluorescence of tissue. The imaging system further comprising
a means for measuring at least one or more physiologic or
environmental parameters and using the measurement to adjust the
calibration of the final measurement image to compensate for the
environmental or physiologic parameters. The environmental and
physiologic parameters may include at least one of: temperature,
pH, concentration of other compounds of absorbers present,
measurements of additional probes, and measurement of a reference
probe or probe with a secondary reference emission. An embodiment
of the imaging system is configured to generate an image
representing a physiologic parameter based on a phosphorescence
and/or fluorescence response from an introduced probe or from
naturally occurring interactions. The system is capable of
utilizing temperature or other environmental or physiologic
parameter to compensate for the measurement represented in the
image.
[0013] An embodiment of the present invention describes a system
and method for generating and combining images in an image overlay
or other augmented reality view. The present invention includes an
approach for overlay of physiologic parameters on endoscopic video
images. It further comprises a method for registering oxygenation
maps (or maps of other physiologic properties) with visible light
or other video images. An embodiment of the present invention
incorporates a method for registering oxygenation maps or the
corresponding precursor lifetime maps to thermal maps/images, and
utilizing the registered temperature information to compensate for
temperature-dependent variation in oxygenation measurements. One
method for the registration includes acquiring images from multiple
cameras using wavelengths of light, such as those in the near
infrared (NIR) band, that are detected by each camera (such as a
visible light endoscopy camera and physiologic parameter sensing
cameras), and using the mutual information and/or other features
between the images for registration. Included in this invention is
an embodiment of the invention where at least two of the following
are registered using the approach: thermal image, visible light
image, and phosphorescent lifetime image. In one configuration of
the present invention, an endoscopic imaging instrument is
configured to map tissue oxygenation of the gastrointestinal
tract.
[0014] The system is further configured to identify suspect
lesions, such as pre-cancerous polyps or lesions. Incorporated is a
method for distinguishing lesions such as polyps from healthy
intestinal wall tissue utilizing pattern matching of static images
of phosphorescent lifetime or oxygenation. Static images refer to
individually captured images, as opposed to a time series of
images; static images may be continuously updated. An alternate
method for distinguishing lesions from healthy tissue utilizes
dynamic changes in lifetime of a time series of images. Included in
the present invention is an instrument configured to map tissue
oxygenation and use the information to guide localization at least
one of non-cancerous, pre-cancerous, or cancerous lesions. A
further embodiment is an endoscopic imaging system configured to
generate a map of tissue oxygenation wherein the oxygenation map
guides localization of the lesions. The system incorporates a
method for identifying potentially suspect lesions (such as polyps)
through mapping of the tissue oxygenation, and optionally
generating an alert. An endoscopic imaging instrument configured to
map tissue oxygenation of the intestinal wall. The system further
configured to identify suspect lesions, such as pre-cancerous
polyps. One configuration of the system incorporates a method for
distinguishing polyp from healthy intestinal wall tissue utilizing
pattern matching of static images of phosphorescent lifetime or
oxygenation. An alternate method for distinguishing polyp from
healthy intestinal wall tissue utilizes dynamic changes in lifetime
of a time series of images. A further configuration of the system
also incorporates contouring, segmentation, and boundary detection.
The detection may incorporate techniques such as active contour
models, level set methods, edge detection, or others. An approach
for using histograms of the oxygenation within the identified
region to further identify or classify properties of the lesion is
also included. In an alternate configuration, the system is
configured for detecting anatomy utilizing phosphorescence lifetime
imaging (or related approach), and may be further configured to
determine the location of and/or highlight vasculature.
[0015] An embodiment of the invention includes a sensing scope that
is integrated into or an accessory to a standard endoscopic system.
The scope may couple with or be introduced through a working
channel or instrument port on a traditional endoscope. Further, the
sensing scope being capable of providing multi-modality imaging,
including but not limited to, phosphorescent and/or fluorescent
lifetime, visible light images, and temperature measurements. The
invention further includes a method for tracking features and
maintaining alignment of an acquired oxygen map (or other property)
after removal of, or disabling of, a sensing instrument or scope.
The method maintains the location identified on a visible light
image such that the image may be used to guide an intervention,
such as biopsy or removal of a lesion. The method further maintains
location data of the lesion using registration techniques to allow
for movement of the visible light scope during the
intervention.
[0016] One embodiment incorporates an adapter or coupler for
interfacing with a preexisting or standard endoscopy system,
wherein the coupler introduces modulated light for the sensing
system through the existing light channels. Further, an adapter
enables thermal imaging through introduced or preexisting imaging
channels, wherein the channels may be rigid light guides or
flexible fiber optic bundles. One embodiment incorporates a
flexible endoscopy device wherein a flexible coherent fiberoptic
bundle that may be utilized for both infrared thermal imaging and
illumination. An alternate embodiment is contemplated wherein a
flexible coherent fiberoptic bundle may be utilized for both PLI
and thermal imaging. The fiber bundles may be configured to have
sufficiently high transmission of infrared radiation corresponding
to the sensitive wavelengths of thermal imagers (i.e., up to
approximately 15 um). An embodiment comprises a flexible endoscopy
system where an illumination fiber bundle is multiplexed to enable
its use in both illumination and sensing. The fiber may be used for
white light illumination or photo-excitation of a light emitting
probe. The fiber may be used for receiving a white light image,
phosphorescent emission image, or infrared thermal image.
[0017] An embodiment of the present invention teaches a
camera-based phosphorescent lifetime imaging system, wherein the
light source for exciting the phosphorescent probe also comprises
such as broadband white light emitters. The system capable of both
providing visible light images and PLI measurements, wherein output
from the light sources may be modulated as required. Further
contemplated is a camera-based phosphorescent lifetime imaging
system, wherein a light source for exciting the phosphorescent
probe comprises emitters circumferentially located around the
camera lens. The circumferentially located emitters, referred to as
the ring light, enable directed light to the region of interest in
the camera's field of view. The ring light may incorporate one or
more lenses. The ring light may incorporate both light sources for
exciting the phosphorescent response and for providing visible
light. An alternate embodiment is contemplated where the combined
light source is externally located and directed at the region of
interest, and in one further embodiment the light source is mounted
alongside or incorporated into procedure/operating room (OR)
lights.
[0018] The present invention teaches the use of at least two unique
probe types together in a medium, wherein one serves as a reference
to compensate the readings of the other for improved accuracy. In
one embodiment of the approach a temperature-dependent probe, not
affected significantly by other factors, is introduced alongside an
oxygen-sensitive probe and the response of the
temperature-dependent, substantially oxygen insensitive probe is
used to compensate for measurements of the oxygen-sensitive probe.
In one configuration, a fluorescent or phosphorescent probe that
has a temperature dependent decay lifetime that is introduced
alongside an oxygen-sensitive probe, wherein the two probes have
distinctly different excitation and/or emission wavelengths. In
another embodiment, two oxygen-dependent probe types with different
temperature dependence are introduced, and the lifetimes from the
probes are used to accurately produce an oxygenation measurement
that is robust to temperature variations, wherein the two probes
have distinctly different excitation and/or emission wavelengths. A
further embodiment wherein two probes are mixed and of a
configuration that allows a substantially similar distribution in
the tissue upon injection. The probes may be of the same structure
with different core materials having different spectral and
temporal response characteristics. The lifetime of the two probes
may be read in an alternating pattern, or one may be read
repeatedly for real-time sensing while the other read at a reduced
rate for temperature compensation.
[0019] The present invention also can include a surgical stapler
anvil with incorporated oxygen sensing capabilities based upon
phosphorescent lifetime. A further embodiment wherein the anvil
comprises a camera that is utilized in the sensing. One
configuration of the surgical stapler anvil incorporates oxygen
mapping capabilities at two or more points based upon
phosphorescent lifetime. A further embodiment wherein the anvil
incorporates temperature sensing, and the temperature map is used
to compensate for the map of oxygen measurements. A sensing
instrument with integrated needles for microinjection of a probe is
taught in the present invention. One configuration further
comprises an injector that couples with a surgical stapler anvil to
inject a medium into tissue at or near the anvil's working surface
(i.e., staple form surface); the medium containing one or more
phosphorescent oxygen sensing probe variants. The invention also
includes a standalone instrument with incorporated oxygen sensing
capabilities based upon phosphorescent lifetime that couples to
surgical stapler anvil to assess oxygenation of tissue at or near
the anvil's working surface (i.e., staple form surface). The
instrument containing one or more sensors configured to rotate or
otherwise fully image the anastomosis. Also included is an
interrogator wand with an integrated injector for delivering probe
and/or sensing tissue oxygenation. The injector may enable
injection internal to the tissue, such as inside a colonic wall, or
external injection, such as externally through a colonic wall. The
instruments further comprising a means for measuring temperature of
tissue at the working surface. In a further embodiment of the
invention, a camera-based phosphorescent lifetime imaging system
comprises a means for attaching an anvil of a surgical stapler,
wherein the attachment is through a quick-release type coupler to
the anvil. The system is configured to generate an oxygenation map
of the anastomosis during surgery. The system further comprising a
thermal imaging camera imaging substantially the same region as the
PLI system and using the measurements to enhance accuracy of
oxygenation measurements.
[0020] One embodiment of the current invention is based upon a
small secondary imaging system, such as a CMOS micro-camera, which
fits down the working channel of an existing colonoscope to
generate an oxygen map of the colonic wall. The system displays the
map and/or highlights suspicious lesions using graphic overlay on
synchronously acquired traditional scope video images. If a
suspicious lesion is identified the system will allow for exchange
of the oxygen mapping camera for another instrument, while
retaining/tracking the lesion highlighted on the video monitor.
Oxygen mapping in one embodiment will be realized using
phosphorescent lifetime imaging (PLI) of an oxygen-sensitive,
systemically injected molecular probe. In one embodiment of the
present invention, temperature sensing is coupled with PLI to
generate a temperature-compensated map of oxygen concentration. The
invention is not restricted to only coupling with a colonoscope to
assess cancerous lesions in colonic wall tissue; the present
invention includes all scope and camera types and configurations
including flexible and rigid, monitoring or visualization of all
internal and external tissues, and identification of any type of
variation in the parameters of the tissue.
[0021] One representative application of the present invention is
in the creation and monitoring of tissue flaps. Cancer of various
types, i.e., breast, skin, etc., often cause removal of significant
volumes of tissue during an attempt at curative resection.
Traumatic injury may result in severed limbs or avulsed portions of
tissue. The resulting tissue loss is often replaced by native
tissue transposed from other parts of the patient's body. Free
tissue flaps are flaps that are completely removed from their
native position along with the supplying vascular pedicle. The free
flap vasculature is then reconnected to vessels near the tissue
void. The vascular anastomosis may fail due to leakage, stricture,
or occlusion from inappropriate clot formation. The present
invention enables resolution of flap oxygenation through a map of
the tissue oxygenation, both for the intra-operative confirmation
of tissue perfusion, and post-operative monitoring. Current
technology is limited to qualitative measures of blood flow. The
present invention presents real time quantitative assessment of
tissue oxygenation. An embodiment of the invention couples a
camera-based phosphorescent lifetime detector with a thermal
imaging camera, wherein a registered temperature map is used to
correct for the calibration coefficients used to convert
phosphorescent lifetime to oxygen concentration. A similar
configuration may be used for monitoring both internal and external
tissue. Another example application is in diagnosing, assessing, or
monitoring the treatment of peripheral vascular disease (PVD).
[0022] Other potential applications include but are not limited to
the monitoring/recording of a transplanted organ or appendage,
intra-cranial, intra-thecal, intra-ocular, intra-otic, intra-nasal,
intra-sinusoidal, intra-pharyngeal, intra-laryngeal,
intra-esophageal, intra-tracheal, intra-thoracic, intra-bronchial,
intra-pericardial, intra-cardiac, intra-vascular, intra-abdominal,
intra-gastric, intra-cholecystic, intra-enteric, intra-colonic,
intra-rectal, intra-cystic, intra-ureteral, intra-uterine,
intra-vaginal, intra-scrotal; intra-cerebral, intra-pulmonic,
intra-hepatic, intra-pancreatic, intra-renal, intra-adrenal,
intra-lienal, intra-ovarian, intra-testicular, intra-penal,
intra-muscular, intra-osseous, and intra-dermal
physiologic/biomechanical parameters.
[0023] Additional features, advantages, and embodiments of the
invention are set forth or apparent from consideration of the
following detailed description, drawings and claims. Moreover, it
is to be understood that both the foregoing summary of the
invention and the following detailed description are exemplary and
intended to provide further explanation without limiting the scope
of the invention as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] FIG. 1 shows a representation of the components of one
embodiment of the present invention.
[0025] FIG. 2a shows an embodiment of the present invention wherein
the system generates a graphic overlay to identify lesion location
on synchronously acquired endoscopic video images.
[0026] FIG. 2b shows a representative oxygen map overlaid on
endoscopic video images.
[0027] FIG. 3 shows an embodiment where the oxygen mapping system
couples with a traditional endoscopic imaging system.
[0028] FIG. 4 shows a close-up view of one embodiment of the
micro-camera endoscopic imaging system that fits within the
instrument channel working port of an endoscope.
[0029] FIG. 5 shows a coupler that enables injection of modulated
excitation light from an external control unit into the light path
of a traditional endoscopic imaging system.
[0030] FIG. 6a shows an embodiment wherein a microcamera-based
secondary imaging system fits inside the working port of a scope
with a dedicated light channel.
[0031] FIG. 6b shows an embodiment wherein a microcamera-based
secondary imaging system fits inside the working port of a scope
where light is injected along the pre-existing light path.
[0032] FIG. 6c shows an embodiment wherein a fiberoptic light path
of a secondary imaging system fits inside the working port of a
scope where light is injected along the pre-existing light
path.
[0033] FIG. 7a shows a schematic drawing of one embodiment of the
present invention wherein an external sensing camera system is used
for generating measurements.
[0034] FIG. 7b shows a schematic of one embodiment of the oxygen
mapping system configured for coupling with an endoscope.
[0035] FIG. 7c shows a representative oxygen mapping system
configured for small animal trails with a rigid endoscope.
[0036] FIG. 8 depicts an embodiment of the system wherein a
microcamera device passes through the working channel instrument
port of an endoscope.
[0037] FIG. 9 shows a timing diagram of one embodiment of the
sensing system using a frequency domain approach.
[0038] FIG. 10a depicts a surgical stapler anvil with integrated
sensors.
[0039] FIG. 10b shows a close-up view of a surgical stapler anvil
working surface with integrated sensors.
[0040] FIG. 11a depicts an embodiment of a medical device with
integrated sensors taking the form of a sensing clip.
[0041] FIG. 11b depicts an embodiment of a medical device with
integrated sensors taking the form of a minimally invasive surgical
instrument.
[0042] FIG. 12 depicts a cross-sectional view of an embodiment of a
self-contained sensing instrument that detachably couples with an
anvil of a surgical stapler.
[0043] FIG. 13a depicts an embodiment of an imaging system with a
light source capable of selectively illuminating a region of
tissue.
[0044] FIG. 13b shows a light source with an extension arm that
allows it to extend and rotate.
[0045] FIG. 14a shows an injector system that couples to a surgical
stapler anvil.
[0046] FIG. 14b shows a cross-sectional view of an embodiment of an
injector.
[0047] FIG. 14c shows another embodiment of an injector system that
couples to a surgical stapler anvil.
[0048] FIG. 15 shows a representative application of the injector
and sensing anvil in colorectal resection procedure.
[0049] FIG. 16a shows a representative embodiment of an imaging
system configured to assess fluorescent and or phosphorescent
lifetime.
[0050] FIG. 16b shows a representative embodiment of an imaging
system configured to assess fluorescent and or phosphorescent
lifetime of tissue at the site of an anastomosis.
DETAILED DESCRIPTION OF THE INVENTION
[0051] Tissue parameters can be measured by a variety of methods.
One technique utilized by the present invention measures tissue
oxygenation levels via utilizing oxygen dependent quenching of
phosphorescence via a systemic or locally injected phosphorescent
oxygen sensing molecular probe for oxygen measurements as disclosed
in U.S. Pat. Nos. 4,947,850, 5,837,865, 6,362,175, 6,165,741,
6,274,086, 7,575,890 and US Patent Application Publication No.
2013/0224874, which disclose measurement methods, the disclosures
of which are incorporated herein by reference in their entireties.
The phosphorescent oxygen sensing probe comprises a phosphorescent
metalloporphyrin core encapsulated inside hydrophobic dendrimers,
which form a protecting shell that isolates the chromophore from
direct contact with the environment, controls oxygen diffusion, and
enables control over the probe's dynamic range and sensitivity. The
metalloporphyrin core can be constructed with different elements.
Palladium and platinum are two elements that can be utilized. An
advantage of a platinum based core over a palladium based core is
its quantum efficiency. The increase in the quantum efficiency of
the phosphor allows for a significant increase of light output when
compared to the Pd based molecule; more light returned per molecule
allows for the use of fewer molecules to achieve the same signal
returned to the device. Alternatively, injection of the same amount
of molecule enables the use of less sensitive (less expensive)
photo-detectors. Peripheral PEGylation of the dendritic branches
ensures high aqueous solubility of the probe whilst preventing
interactions with biological macromolecules. The overall size of
the molecular probe affects the probe's ability to be cleared by
the kidney. Faster clearance limits the agent's exposure to the
patient. The size can be varied through the modification of the
dendrimer length, number of dendrimers, and the size of PEGs/extent
of PEGylation.
[0052] In one embodiment of the probe, the core,
Pd-meso-tetra-(3,5-dicarboxyphenyl)tetrabenzoporphyrin (PdTBP), is
encapsulated by eight generation 2 poly-arylglycine (AG2) dendrons;
each of which are PEGylated with monomethoxy-polyethyleneglycol
amine (PEG-NH2) groups (Av. MW 1,000 Da), having on average 21-22
monomeric --(CH2CH2O)-- units. The molecular weight of the probe
dendrimer was found to be in the range of .about.26,000-44,000 Da
with a maximum of 35,354 Da as determined by MALDI mass
spectroscopy. The phosphorescence quenching method relies on the
ability of molecular oxygen (O2) to quench phosphorescence of
excited triplet state molecules in the environment. In biological
systems phosphorescence quenching by oxygen occurs in a diffusion
controlled fashion and is highly specific to O2, since O2 is the
only small-molecule dynamic quencher present in sufficiently high
concentrations. The dependence of the phosphorescence lifetime
(.tau.) on the partial pressure of oxygen (pO2) through the range
of biological concentrations is well described by the Stern-Volmer
equation: 1/.tau.=1/.tau.0+kq.times.pO2, where .tau. is the
phosphorescence lifetime at a specified oxygen pressure pO2, TO is
the phosphorescence lifetime in the absence of oxygen (pO2=0), and
kq is the quenching constant. One molecular oxygen probe has a
quenching constant, kq, of approximately 326 mmHg.sup.-1 s.sup.-1,
and a TO of 210 .mu.s over the range of physiologic pH, 6.2-7.8,
and constant temperature of 36.5.degree. C.
[0053] The calibration parameters of the probe, kq and TO, change
linearly with respect to temperature. The quenching constant, kq,
increases from 211 mm Hg s.sup.-1 to 338 mmHg.sup.-1 s.sup.-1 with
the rise of temperature from 22.degree. C. to 38.degree. C., which
corresponds to the temperature coefficient of 7.8 mm Hg.sup.-1
s.sup.-1/.degree. C. The absorption spectrum of the probe has
maxima at approximately 448 nm and 637 nm with a phosphorescence
emission maximum of 813 nm. Excitation at multiple wavelengths
confers an application specific advantage of being able to
interrogate and distinguish tissue properties at differing
penetration depths or layers. A combination of multiple pO2 values
in a field of view will manifest itself as a combination of
lifetimes (a sum of exponential decays); multiple pO2 values and
corresponding concentrations can be determined through means
described herein.
[0054] Due to the dependence of measured phosphorescent lifetime on
temperature, it is critical to assess the temperature at the
measurement site and use that information to apply the appropriate
relationship between phosphorescent lifetime and oxygen
concentration. By measuring the temperature at a measurement point,
the appropriate temperature-dependent quenching coefficient kq may
be selected to allow improved accuracy of oxygen concentration
measurement at that point. Although average temperature of a
measurement region may be used to improve accuracy, further
location-dependent compensation may be obtained through mapping the
temperature at multiple points and relating the correspondence of
those points to lifetime measurements when converting to oxygen
concentration. Note that oxygen concentration and oxygenation may
be used interchangeably in this disclosure and both relate to the
amount of oxygen present in the tissue.
[0055] An embodiment of the invention is intended to detect a
quantitative difference in interstitial tissue oxygenation of
non-cancerous, pre-cancerous, and cancerous lesions when measured
against the surrounding normal tissue. A specific embodiment
further described aims to identify the lesions in the
gastrointestinal tract. One application of the invention is
directed toward enhancing the detection of pre-cancerous colonic
polyps. Through the mapping of interstitial tissue oxygenation,
during video colonoscopy, the invention aims to improve detection
of pre-neoplastic, and neoplastic lesions during screening
colonoscopy when compared to traditional white light and "enhanced"
endoscopic techniques. Furthermore the invention aims to
differentiate lesions of various malignant potential based on
patterns of tissue oxygenation. Note for the purposes of this
application, "white light" and "visible light" imaging may be used
interchangeably. By simultaneously mapping the temperature in the
same region of interest, we can improve sensing accuracy by using a
temperature-dependent calibration of lifetime to tissue
oxygenation. Note that for the purpose of this application,
phosphorescent lifetime images/imaging (PLI) refer to the precursor
used for calculating a physiologic parameter such as oxygenation
and may be an actual calibrated lifetime such as measured in
microseconds, or may be represented by related raw data including
clock cycles, camera frames, phase delay, or other measurement
parameters.
[0056] There is currently no clinically practical method of
quantitatively assessing tissue oxygenation during colonoscopy or
method of exploiting such information to improve polyp detection.
The approaches may also be used for various other tissue imaging,
including but not limited to, gastrointestinal imaging to guide
surgical procedures such as a colonic or rectal anastomosis. The
term imaging refers to taking measurements at multiple locations.
This includes, but is not limited to, a 2D map such as a
camera-based sensor or an array of discrete points such as multiple
sensor elements on an instrument.
[0057] FIG. 1 shows a representation of the components of one
embodiment of the present invention, an endoscopic system 100
comprising an oxygen sensing molecular probe 101, a phosphorescent
lifetime imaging interface 103, and a secondary camera 105. The
system aids in the detection of non-cancerous, pre-cancerous, and
cancerous lesions through exploitation of oxygen differences that
exist between healthy tissue and lesions. The system generates
quantitative oxygen mappings of the gastrointestinal tract. An
example of a lesion is a colonic polyp found in the colon. The
oxygen-sensitive phosphorescent oxygen sensing probe 101 is a
nanosensor that is injected systemically into the bloodstream or
locally into the tissue interstitial space. The phosphorescent
lifetime imaging interface 103 determines tissue oxygenation based
on the optical response (related to oxygen-dependent quenching of
phosphorescent lifetime) of the phosphorescent probe 101.
Phosphorescent lifetimes are imaged by a secondary camera 105 which
is passed through the working channel of a traditional scope, such
as a colonoscope. In one embodiment, the secondary imaging system
105 is small micro-camera endoscope that is inserted into the
proximal end of a working channel of a traditional colonoscope and
passed to the distal end of the colonoscope. The camera may be
integrated into a flexible cannula and may be a single use or
limited lifetime device. In another embodiment, the secondary
imaging system comprises a fiberoptic imaging bundle that is
inserted into the proximal end of a working channel and passed
distally. The proximal end of the imaging bundle is coupled to a
camera. In another embodiment the proximal end of the imaging
bundle is coupled to an image intensifier which is coupled to a
camera. The camera itself may employ image intensifying optics. The
light passing into or out of the imaging bundle may pass though
optical filters. The system may further comprise a thermal imaging
system capable of mapping the temperature in the region of
oxygenation measurement. In one embodiment, infrared radiation is
passed through a coherent fiberoptic bundle to a thermal imaging
camera. The fiber optic bundle may be the same as that used in the
secondary imaging system, a bundle also used for illumination, or
an alternate bundle.
[0058] The present invention includes configurations of
oxygen-dependent quenching molecular probes 101 that enables
controlled dwell time in the body or a portion thereof. Controlled
variation of the size and shape of the probe affect dwell time and
clearance rates. In one embodiment, the probe is excreted from the
body in under 24 hours. The molecular probe 101 may be integrated
into or coupled with fully or partially bioabsorbable beads or
other objects so as to maintain sufficient probe at a site for an
extended period following injection. An alternate approach of
maintaining the probes at a site or directing the probes towards a
site includes coupling a molecular probe with a magnetic carrier
for control of its position or to maintain sufficient probe at a
site for an extended period. The present invention may also
incorporate phosphors and other markers for various physiologic
parameters other than oxygenation, such as glucose levels, pH,
lactate, or disease markers. The measurement of multiple
physiologic parameters can occur simultaneously.
[0059] FIG. 2a depicts an embodiment of the present invention
wherein the system generates a graphic overlay (205, 211)
identifying the location of lesions, including polyp or other
abnormalities, or vasculature (203, 209) in subject tissue onto
synchronously acquired endoscopic video images 201. The tissue 201
represents colonic tissue, however the endoscopic system can be
used to image any biological tissue. FIG. 2b shows an embodiment of
the overlay that presents a map of tissue oxygenation (221, 233),
which may appear as a false color semi-transparent overlay 219. In
other embodiments, other physiological properties may be displayed
along with corresponding anatomical imaging. The system is capable
of measuring oxygenation through some visual occlusions such as
tissue folds, and is capable of localizing lesions typically hidden
behind folds 215 or other obstructions. In one embodiment, the
system automatically identifies suspect lesions (203, 209) and
generates an overlay that highlights suspicious lesions (205, 211)
based on resolved oxygenation (221, 223); the overlay may be one of
a generic mark (e.g., a crosshair or box such as in FIG. 2a), an
outline of the lesion, a probability map, and an overlaid oxygen
map as shown in FIG. 2b. This identification process may
incorporate statistical data in assessing whether the measurements
indicate the presence of a non-cancerous, pre-cancerous, or
cancerous lesion, or other features of interest. The colon lesions
can include, but are not limited to, inflammatory, hyperplastic,
adenomatous or tubulovillous polyps. It may further incorporate a
level of certainty associated with the assessment. The overlaid
oxygen map (or other property) may be registered to the endoscope
video so as to ensure alignment. In a further embodiment, the
features in the endoscope video are tracked through an
interactively updated image-based registration process, so as to
maintain the image overlay even if the secondary imaging
system/camera system is removed (such as to insert an instrument
down the working channel). In one embodiment a sensor such as
electromagnetic tracking sensor or an inertial measurement sensor
is used to monitor the absolute position or relative change in
position of the imaging system. The system may be configured to
automatically detect a lesion or other physiologic structure based
on oxygenation, and may be rendered in false colors (i.e., color
map) representing measurements in live oxygen map video feeds or
static images. The system may be configured to detect and localize
vasculature, and in one configuration use this information to guide
a surgical intervention. Such guidance may be used to help localize
a vessel, and may be used to avoid unintentional damage to the
vessel.
[0060] FIG. 3 shows an embodiment of the present invention where
the oxygen mapping system includes an oxygen mapping system control
unit 301 that couples seamlessly with commercially available
endoscope interface units including the control unit 303 and light
source 305 (which may be combined or separate components). A
coupler 309 in the light path can be used to inject the required
modulated light coming from the secondary light source 311 into the
existing illumination fiber bundle 315 and pass through irrigation
or other connections as necessary through the flexible endoscope
319. If a suspicious lesion is identified the system can allow for
exchange of the oxygen mapping camera 323 for another instrument,
while retaining/tracking the lesion highlighted on the video
monitor. Oxygen mapping can be realized using oxygen dependent
quenching of phosphorescence utilizing a systemically injected
molecular probe. In one embodiment, the secondary video feed 323
can be used for PLI imaging and may take the form of electrical
connections to a microcamera at the distal tip of a catheter. In an
alternate embodiment, the secondary video feed 323 may take the
form of a coherent fiberoptic bundle directing light to an imaging
system inside the oxygen mapping system control unit. The imaging
system may be a microcamera (such as a CMOS image sensor), a
traditional camera (such as a CMOS or CCD camera unit) or may be an
intensified scientific imaging system as further described in this
disclosure. In one embodiment, the oxygen mapping system also
comprises temperature measurement capabilities. In one
configuration, a coherent fiberoptic bundle capable of passing
infrared light can be used for thermal imaging; the fiberoptic
bundle may be an independent bundle, a multiplexed use of an
illumination fiber bundle, or a multiplexed use of the oxygen
mapping secondary imaging system's fiber bundle. In an alternate
configuration, a discrete point temperature such as a thermocouple
can be used to assess the tissue temperature at the imaging site.
In a still further configuration, an external sensing system for
measuring core body temperature can feed into the PLI system.
[0061] FIG. 4 shows a close-up view of one embodiment of the
micro-camera endoscope 401 that fits within the instrument channel
working port 403 of an endoscopic scope 405 such as a colonoscope.
Incident light is emitted through optical fibers 409 or integrated
light sources such as LEDs that elicits a phosphorescent,
fluorescent, or other light re-emitting response from the target
tissue or object. A camera 413, such as a micro CMOS sensor which
may include the control circuitry, is placed proximal to an optical
filter 415 that removes incident light (long pass filter), leaving
the re-emitted light. The sensing approach may be time domain,
frequency domain, or an alternate method. Using a time domain
method may eliminate the need for, or reduce the required optical
density of, the filter 415. A wide angle lens 419 may be used to
obtain a wide field of view. Microlenses may be incorporated onto
the camera sensor. The camera 413 and lenses 419 may be configured
so as to provide an angled view of the tissue. A micro thermal
imaging camera may be further incorporated for assessing tissue
temperature at the imaging site. The camera may be an independent
device, or a combined imager capable of both PLI and temperature
mapping. Additional approaches known in the fields for temperature
measurement at one or more points may also be incorporated. The
camera or cameras pass their data out along cables 423. The
secondary imaging system can be contained in a flexible outer
sheath 427.
[0062] One embodiment of a PLI system based upon either distal
imaging (e.g., a microcamera at the tip) or proximal imaging (e.g.,
fiber bundle to external camera) can provide an ultra-wide view
angle. By providing a large view angle, it can be possible to
visualize behind objects such as a polyp, tissue fold, stenosis, or
anastomosis. The distal end of the imaging system may be able to be
actively flexed so as to provide sufficient view to see the rear
side of an object. This embodiment may incorporate pre-bent shape
memory alloys so as to provide a predefined curved shape when
extended. In one embodiment, a cylindrical prism-like device is
used to generate a very large angle of refraction and thus a
greater than 180 degree view. In another configuration, stacked
layers of high index of refraction medium are utilized to create an
ultra-wide view angle lens.
[0063] In one embodiment of the present invention, a medium can
contain fluorescent or phosphorescent oxygen sensing molecular
probe. A light source may be a narrow band light source such as an
LED or laser, or may be a broadband source such as a white light
source. The peak emission wavelength of the narrowband source can
be selected to be at or near an absorption peak of the molecular
probe in the medium. An optical filter may be used to further
restrict incident light to wavelengths in or near the absorption
wavelength region of the molecular probe. The molecular probe can
re-emit light which then optionally passes through a filter to
isolate the emission light from the incident light. A light
detector can sense the intensity of received light. In one
configuration, a detector can be a single point detector such as a
PD, APD, SiPM, or similar device. In an alternate configuration, a
detector can be a multi-point detector or image sensor such as a
camera or an array of single point detectors. The camera may be
CCD, CMOS, or other technology and may be directly at the tissue
contacting surface of instrument or optically coupled at a remote
location such as through an optical fiber bundle. The array of
single point detectors may be PD array, SiPM array, linear CCD or
other technology. The light source may be directed over a broad
area or precisely directed at a point of interest and scanned. The
light detector may be directed over an area or precisely directed
and scanned. In one configuration, a processor commands light
pulses from a light source and analyzes the time response of the
signal received by the detector using time domain signal processing
techniques. In an alternate configuration, the processor can
command modulated light such as a sinusoidal intensity profile from
one or more light source and can analyze the measured signal from
the detector to determine the phase lag through frequency domain
signal processing techniques. In one configuration the medium can
contain a phosphorescent molecular probe. The probe phosphoresces
when excited by wavelengths of light in the probe's absorption
band(s). The phosphorescent lifetime can be responsive to the
oxygen content in the vicinity of the probe due to oxygen's ability
to quench the phosphorescence. The relationship between oxygenation
and phosphorescent lifetime may follow the Stern-Volmer
relationship. Time domain or frequency domain techniques may be
used by the signal processor to quantitatively resolve the
corresponding oxygen content or concentration in a single location
or multiple locations of the tissue. The term "resolve" is intended
to be interpreted broadly to mean to calculate, compute, determine,
assess, or acquire the solution for oxygen content or concentration
in the target tissue. An exemplary implementation of the time
domain or frequency domain techniques is disclosed in U.S. Pat. No.
6,701,168, which is incorporated herein by reference in its
entirety. Oxygen content may be represented as a number or shown as
a map of oxygenation on an instrument or an external display unit.
The oxygen content may be used to predict the likelihood of success
or failure of the surgical procedure, or guide a surgical
procedure. An exemplary implementation of predictive or guidance
techniques is disclosed in US Patent Publication No. 2009/0054908
A1. In one embodiment, the instrument is an endoscopic imaging
system. In another embodiment, the instrument is an adjunct to a
surgical instrument, such as an accessory to a surgical stapler
anvil.
[0064] FIG. 5 demonstrates one embodiment of a coupler 501 that can
enable injection of modulated light along an optical path 503 (such
as a fiber optic cable) from an external control unit 505 into the
light path 509 of an existing endoscope system 511. Light path 509
typically passes white light from a standard endoscopy light source
within or associated with endoscope camera controller 511. This
enables multiplexing the optical fibers 515 of a traditional
endoscope 519 so as to allow white light for traditional video
imaging and modulated wave-length specific light for incorporating
sensing such as PLI. Light source couple 523 mates with the light
port 509 of the endoscopy light source. In one embodiment, a
motorized mirror unit 527 can switch between the white light input
source 523 and the modulated light source from the oxygen mapping
system 503. In an alternate embodiment, solid state or MEMs
switching or mirrors such as a DLP-like device may be used.
Endoscope coupling 529 can couple to a standard endoscope 519 to
pass the combined light output into light path 515.
[0065] FIGS. 6a and 6b show embodiments of the system, wherein a
microcamera endoscope or fiberoptic scope 601 can fit inside the
working port of a traditional commercially available or custom-made
scope 603. A light coupler 607 as described in FIG. 5 can inject
light from the PLI control unit 611 into the existing scope
illumination/light fibers 613. FIG. 6a shows a dedicated light
channel for the PLI system and a shutter unit for the scope
interface. FIG. 6b shows an alternate embodiment where light is
injected along the existing light path 613.
[0066] FIG. 6c depicts an embodiment of the imaging system wherein
a coherent fiberoptic imaging bundle 621 is configured to pass down
the working channel/port 623 of an endoscope 603. Endoscope 603 may
be a fiber optic imaging flexible endoscope or a flexible endoscope
with an integrated microcamera at the distal end 625. The secondary
imaging fiber bundle 621 couples with an imaging system 631. In one
embodiment, imaging system 631 comprises a gated image intensifier
and a sensitive, high-speed camera. The imaging system 631 can be
coupled with the phosphorescent lifetime imaging system 635. The
PLI system 635 controls camera exposure timing, intensifier gating,
and modulation of light source 639. The excitation light from the
modulated source 639 may be combined with the visible light source
643 of a traditional, commercially available endoscope controller
645 with coupler 607 and fed into the scope 603 via optical fibers
613. The video feed of the camera control unit 649 from a
traditional commercial endoscopic imaging system 645 can transmit
endoscopic video images to the PLI system 611. An image processing
unit 653 of the PLI system 611 can register the video images from
the phosphorescent lifetime imaging and the white light endoscopy
imaging. The video images from the commercial endoscope system 645
may be white light video only, or may be a combination of white
light images as well as infrared images.
[0067] The use of infrared (IR) images based on illumination from a
light source 637 (shown in FIG. 6a and FIG. 6b, which may also be
applied to the embodiment described in FIG. 6c) fed into a coupler
641 along with modulated light 639 can enable common features to be
visible in both images captured by the camera unit 649 and imager
631 to assist in registration. A visual output of the PLI system
611 can be displayed on an internal or external display 657, and
may incorporate teachings described in FIG. 2a and FIG. 2b. Note
that the detailed description provided for FIG. 6c also applies to
FIG. 6a, FIG. 6b, and other embodiments of the present
invention.
[0068] FIG. 7a shows a schematic drawing of one embodiment of the
present invention wherein an external sensing camera system 701 can
be used for generating measurements. The system may couple directly
to a lens, such as for external imaging or open surgical
procedures, or it may couple to a rigid or flexible endoscope 705.
In one embodiment, the subject can be systemically injected with
the oxygen-dependent phosphorescent probe and is then imaged with
the system to obtain oxygen maps as well as video images of subject
tissue. A light source 709 is used to illuminate and excite the
probe in the subject's tissue 711; alternatively fluorescence or
phosphorescence of the tissue itself may be detected by direct
illumination with or without a molecular probe. This light source
709 may include multiple wavelengths for exciting different
molecular probes, different absorption peaks of the molecular
probe(s), and for varying light penetration depth (representative
wavelengths shown in FIG. 7a are not intended to be exclusive of
other wavelengths). Discrete wavelengths as well as broadband
sources may be used. Light sources may be LEDs, Lasers, or other
sources. The sources may be modulated by a light control system 715
to enable time domain, frequency domain, or other sensing
techniques. A splitter 721 can be used to direct the light between
an imaging camera 723 (such as a visible light camera) to obtain
white light endoscopic images, and the sensing camera 701. In one
embodiment, the sensing camera is a high speed intensified
scientific camera 701. A filter 763 can allow passage of only
re-emitted light from the probe, or native tissue to the sensing
camera. The splitter 721 may be a beam splitter, an adjustable
mirror, or another way to split the light. In one configuration,
the light can be split based on wavelength to send re-emitted
phosphoresced IR light to the sensing camera while visible light
can be directed towards the imaging camera. FIG. 7b shows details
of one embodiment of the system. FIG. 7c depicts one embodiment of
the system in a preclinical trial. The device may be used
clinically in humans, for veterinary applications, or in laboratory
scenarios.
[0069] In one embodiment, a processor can interface with the
sensing camera 701, the imaging camera 723, and the light source
709. In one embodiment, a computing system 731 can be connected to
the sensing camera 701, and a processor of the computing system 731
can perform calculations on the collected image data. Calculations
may be used to determine and map fluorescent or phosphorescent
lifetime, or a related parameter. The processor of the computing
system 731 may be a microprocessor and/or a graphics processing
unit (GPU). In an alternate configuration, data from the one or
more cameras is passed into a field programmable gate array (FPGA),
and the FPGA is configured to perform some or all of the data
processing such as determining and mapping fluorescent or
phosphorescent lifetime, or a related parameter. One embodiment of
the current invention incorporates a gated image intensifier
coupled to a high speed imaging sensor. The imaging sensor is
communicatively coupled to an FPGA. The FPGA controls the imaging
(including exposure timing) and the gating of the image
intensifier. The FPGA can also control a pulsed or modulated light
source. The FPGA can control the timing and image acquisition. The
FPGA also performs image processing on the acquired images. In one
embodiment, the FPGA determines a map of the phosphorescent or
fluorescent lifetime for each measurement cycle. One approach to
the calculation is to assess the exponential decay time constant
for each pixel. Performing onboard calculation in the FPGA reduces
the need for high-speed data transfer, and thus an embodiment may
have an output of oxygen or lifetime maps at a frame rate similar
to typical endoscopic cameras over a traditional communication
channel such as USB, Ethernet, Firewire, standard PC video such as
VGA or HDMI, composite video, component video, or similar.
[0070] FIG. 7b shows a schematic of one embodiment of the oxygen
mapping system configured for coupling with an endoscope 741 which
may be rigid or flexible. Light source 743 feeds into the
endoscope's illumination port, and may contain white light and
modulated/pulsed excitation light. An adapter (such as C-mount
endoscope adapter) 745 can couple to lens tubes 747 including
focusing optics 749. A splitter box (such as a cube holder) 751 can
contain a splitter 753 which may take the form of a
wavelength-dependent hot (IR) mirror splitter. Focusing optics
including adjustable lens tubes and adapters can couple one output
of splitter 751 to a visible light endoscopy camera 757. The other
output of the splitter can pass through focusing optics 761 and a
longpass or bandpass optical filter 763 to reach the sensing camera
765. The longpass filter can effectively remove incident light
allowing passage of only re-emitted light. The wavelength
selectivity of the filters would be dependent on the optical
absorption and emission properties of the probe as well as the
incident light sources used. The sensing camera can be used for
phosphorescent lifetime imaging and may take a form as described in
FIG. 7a.
[0071] FIG. 7c shows a representative oxygen mapping system
configured for small animal trails with a rigid endoscope 771. The
scope 771 can also contain or can be coupled with an insufflation
channel 773. A multi-wavelength LED light source 775 comprising
remotely selectable white light and pulsed/modulated light couples
to the illumination port of scope 771. A lens assembly and splitter
with filter block 777 (as described in FIG. 7b) couples the scope
771 to the sensing imaging systems 781 and the visible light
imaging system 783. In this embodiment, sensing imaging system 781
is an IR-sensitive intensified camera with high-speed gating. A
control unit such as a data acquisition system (DAQ) 787 provides
for illumination waveform and camera sync control, and may be
coupled to a control computer 791. The illumination of light source
775 can be controlled by the modulated light driver 789. The term
modulated light can refer to pulsed light in the case of time
domain approaches and sinusoidal input in the case of frequency
domain approaches. A display of computer 791 can show the white
light video endoscope output 793 and the calculated oxygen and/or
phosphorescent lifetime map 795. For experimental evaluation, a gas
mixer 797 enables control of the subject's inspired O2
concentration.
[0072] FIG. 8 depicts an embodiment of the system wherein a
microcamera device 803 passes through the working channel
instrument port of an endoscope to its distal tip 807 to image a
subject tissue 809. This embodiment can be compatible with coupling
to both fiber and integrated video scopes. This embodiment can
operate similarly to that of FIG. 7a except that the camera 803 can
be located at the distal tip 807 of the scope. The depicted system
shows a phosphorescent lifetime imaging control system connected to
the microcamera and a light coupler 811 for injecting light into
the illumination port 815 of the scope. The PLI control system 819
can control the camera controller 821, light source 825, and map
generation functionality 829. In one embodiment, it can also
acquire visible light images from an external camera unit or
another source, registers a map of tissue oxygenation or a proxy
thereof to the video image, and displays the tissue oxygenation or
other information through an augmented reality image overlay.
[0073] FIG. 9 shows an exemplary timing diagram of one embodiment
of the sensing system. The figure depicts a frequency domain
approach to sensing wherein excitation light is modulated 901 at a
frequency with a period T mod=1/f mod identified as 903 and the
system acquires timed images during the repeated periods Ts
identified as 905. Ts is defined as: Ts(k)=k*N*T mod+k*dq for each
increment k, where: k=sample number (starting at 0), N=number of
periods between sampling (based on camera frame rate), T mod=period
length of excitation modulation sine wave (l/fmod), dq=increment
along period for each subsequent sample (equivalent to sampling
interval), and q=k*dq=offset from start of period at the current
cycle to trigger sampling. The light modulation waveform (upper
plot) is made up of a sine wave 901 with frequency f mod for the
number of samples desired*N. Each period is staggered by a small
amount q identified as 909 to sweep the imaging trigger 913 through
the full range of the periodic response. The camera triggering
waveform 921 (lower plot) is made up of a pulse train with rising
edge at times Ts(k) for each sample k. Multiple accumulation or
integrations may be performed by synchronizing the shutter or gate
with a portion of the period. This portion can be shifted
incrementally to acquire the whole waveform. The phase lag induced
in the waveform can then be related to oxygenation. Multiple
frequencies may be used to enable more robust measurements, assist
in removing incident light that made it through the filter, or
determine an oxygenation spectrum. In an alternate embodiment, a
time varying frequency such as a linear chirp signal is used to
excite the probe to obtain information from a large number of
frequencies. The acquisition may be taken sequentially over
multiple repetitions of the period or it may be acquired with a
high speed camera unit. Scanning or binning of camera sensor pixels
may be used to obtain fast imaging of a small subset of the field
of view. In another embodiment, a similar approach may be used for
time domain measurements. In this approach, multiple points along
the optical response decay after an excitation pulse are read out
over a series of repeated excitations at a time varying phase
delay. Included is an approach for reduced sample rate or frame
rate requirements through synchronized, gated imaging of multiple
sequential periods. A further approach provides for where multiple
acquisitions or accumulations for a given period may be summed
together to increase the measured signal or improve the signal to
noise ratio (SNR) for that period.
[0074] Included in the present invention are algorithms for
determining oxygenation based on a frequency domain approaches. The
approaches can include a single modulated light excitation
frequency, two frequencies to reduce the effect of residual
excitation light, or multiple frequencies to resolve the presence
and quantity of multiple oxygenation level (i.e., a map of the
spectrum of oxygenation). An embodiment includes an approach where
frequency is adjusted to maintain an approximately fixed phase. The
invention can include an optimization process for determining the
optimum frequencies for acquisition. In an embodiment, oxygenation
calculation can be based on time domain approaches and maximum
entropy approaches. An alternate embodiment can utilize two photon
excitation techniques.
[0075] The invention includes an approach for time domain
oxygenation measurements, wherein temperature measurement
information can be incorporated into the conversion from measured
phosphorescent lifetime to oxygenation. Further included is an
approach for frequency domain oxygenation measurements, wherein
temperature measurement information can be incorporated into the
conversion from measured phase of the phosphorescent response to
oxygenation.
[0076] FIG. 10a depicts a surgical instrument with integrated
sensors. In one embodiment, a surgical stapler anvil 1001 or an
adjunct device that couples to the anvil, incorporates sensors. The
sensors 1005 on the anvil's working surface 1021 (the surface which
forms the staple crimp) may include light emitters and receivers
for performing phosphorescent lifetime imaging of tissue on the
working surface of the instrument. One embodiment of a sensing
anvil 1001 comprises sensor elements 1005 located in cutouts 1007
of anvil face. The sensing anvil contains control electronics
coupled to a wireless transceiver 1009 powered by an onboard
battery 1011. The sensing componentry is encapsulated inside of a
cap 1013.
[0077] FIG. 10b shows a close-up view of the anvil working surface
1021. In one configuration LED light sources 1025 and photodiodes
1027 are interleaved in cutouts 1007 between staple forms. Pressure
sensors 1031 are also in cutouts 1007 to assess tissue interaction
forces. One embodiment of the instrument further comprises one or
more temperature sensors 1033, such as a thermocouple or resistance
temperature detector (RTD). In one configuration, the temperature
sensors may be interleaved between stable forms 1029, distributed
circumferentially around the anvil face 1021 and, or located in the
cutouts 1007 between the staple forms. In an alternate
configuration, a camera can be integrated into the sensing anvil so
as to image the tissue through fiberoptics or other light guides.
This embodiment can be functionally similar to the microcamera
endoscope previously described. In a further alternate embodiment,
a sensor can sweep across the device to take measurements at
multiple points.
[0078] FIG. 11a depicts an embodiment of a medical device with
integrated sensors taking the form of a sensing clip. In an
embodiment, the clip 1101 can be configured to enclose and sense
across intestinal tissue. The tissue can be placed between upper
surface 1103 and compression surface 1105. A clasp 1107 can hold
the sensor closed around the tissue, while a tissue compression
bladder or balloon 1105 can compress the tissue to a specified
pressure through air or fluid connection 1109. One or more sensors
1111 are positioned along the tissue contacting portion of surface
1103. In one configuration, a linear array of oxygenation sensors
can generate a linear 2D map or a 3D array of oxygenations within
the tissue. The sensors 1111 can comprise light emitters and
receivers for PLI measurement. The sensors can further comprise one
or more temperature sensors, that may be associated with each
measurement point to enable temperature compensation of the
oxygenation measurement. The sensors interface with control
electronics (including LED or laser drivers and photodetector
amplifiers) and microcontroller or other processor 1113 and can be
powered by onboard battery 1115. The system can communicate
wirelessly using a wireless transceiver 1117. The sensing system
can be enclosed with encapsulant and/or cap 1119. FIG. 11b depicts
an embodiment of a medical device with integrated sensors taking
the form of a minimally invasive surgical instrument configured as
a endoscopic wand 1141. The sensing head 1143 can comprise an array
of sensors 1145 that interface with control electronics 1149. The
array of sensors on the instrument can comprise one or more of the
following: oxygenation sensors, pressure sensors, and temperature
sensors.
[0079] The present invention includes various sensing surgical
instrument and imaging system configurations. One or more sensing
surgical instruments may be used in conjunction with an imaging
system. In one use of the system, an endoscopic PLI system (such as
described in FIG. 3) is used inside the colon, a wand-like device
(such as in FIG. 11b) can be used on the outside surface, and an
sensing anvil (such as described in FIG. 10a) can be used to assess
tissue oxygenation at the site of an anastomosis. The sensors may
communicate wirelessly with a base station. This base station may
also comprise the PLI imaging system.
[0080] FIG. 12 depicts a cross-sectional view of an embodiment of a
medical device 1201 with integrated sensors. This embodiment can
contain one or more sensor elements in a self-contained instrument
that detachably couples with the anvil 1203 of a surgical stapler.
The body 1205 of the instrument 1201 acts as a grip or handle with
a tissue contacting surface 1209 that compresses tissue 1211
against the face 1213 of the anvil 1203. In one configuration,
tissue 1211 is the site on the proximal end of intestinal tissue
such as colon tissue where an anastomosis is to be performed. The
head of anvil 1203 can be inserted into intestinal tissue 1215
(e.g., the proximal end of a colorectal anastomosis) and a purse
string type closure 1217 can cinch tissue 1211 against the anvil
stalk 1221. The anvil stalk 1221 can be inserted into the stalk
coupler cavity 1223 to align the anvil with the device 1201.
Alternatively, the stalk coupler 1223 (mating member) is a pin
(spike) similar to that at the distal end of a circular surgical
stapler that inserts into the anvil stalk 1221. In one embodiment,
the tissue contacting surface 1209 can act as a sensor window and
can be substantially optically clear to allow optical sensing
through the sensor window. The tissue contacting surface 1209 may
include one or more pressure sensor elements 1229 to allow a
processor 1231 to determine tissue compression pressure. The tissue
compression pressure may be used to gate oxygenation measurements
of the device.
[0081] In one embodiment, an internal structure 1235 within the
outer housing 1205 can rotate one or more sensor elements 1239 to
create a comprehensive reading circumferentially around the
anastomosis. In one embodiment, the rotating sensor elements 1239
can comprise at least one light source and one photodetector. The
sensors may be used for oximetry, fluorescent imaging,
phosphorescent lifetime imaging, or other approaches to optical
sensing. In a further embodiment, the light source can be an LED
configured to excite a phosphorescent response in an oxygen sensing
phosphorescent probe and the photodetector can be a photodiode
configured to detect the phosphorescent response of the probe. The
rotating sensor element 1239 may also comprise one or more
temperature sensors, such as a thermocouple or resistance
temperature detector (RTD). The temperature sensors may also be
fixed to the body 1205 and non-rotating. A signal processor 1231
can control the one or more light sources and receives and analyzes
signals from the photo detector(s). The signal processor 1231 may
be used to determine phosphorescent lifetime. In order to obtain a
set of readings (i.e., an oxygen map) around the anastomosis tissue
1211, the internal structure 1235 can rotate about axis 1245. In
one embodiment the rotation can be by a motor or other rotary
actuator 1241, and in another embodiment the internal structure can
be manually rotated. An angle sensor 1243 can be used to determine
the rotation angle of the internal structure 1235 with respect to
the outer housing 1205. In an alternate configuration, a stepper
motor can be used and relative rotation angle can be inferred from
the motion control signals. In one embodiment the internal
structure 1235 is a re-useable, durable instrument, and the outer
housing 1205 is disposable and single use. The signal processor
1231 can utilize the optical sensor elements to generate
measurements at defined rotation angles, or records the angles at
the time of a reading. The signal processor 1231 can reconstruct a
map of measurements corresponding to the sensor element positions
at the time the readings were taken. In one embodiment, a 360
degree map of tissue oxygenation can be generated for the surface
of an intestinal anastomosis by rotating the sensing elements 1239
and taking readings at discrete intervals. In one embodiment, a
wireless transceiver 1247 transmits data to a base station and may
receive commands from the base station. One or more indicators 1251
may be used to display status of the instrument and/or of the
tissue being measured. The sensing instrument 1201 may be powered
by an internal battery 1255.
[0082] In one embodiment, if a region of tissue is determined to be
faulty/abnormal and require attention (e.g., poor oxygenation), the
rotating sensing structure can rotate to indicate the faulty
position. In a further embodiment, the instrument can align and
then illuminate a region of tissue with compromised oxygenation to
notify the user. The embodiment described here generally refers to
an instrument with at least one sensor element 1239 that couples
with another surgical instrument (such as a circular stapler anvil
1203 or housing) and takes one or more sensor readings on the
tissue surface 1211. In a more specific configuration, the sensor
elements can be configured for PLI and can rotate to determine an
oxygen map of the intestinal tissue on the surface of a circular
stapler anvil 1213 at the proposed site of an anastomosis 1211.
Readings may be taken at a plethora of rotation angles, and may be
taken at a plethora of radial distances. The radial placement may
be at one or more of: inside the staple forms, at the anvil forms
(along the proposed staple line), and outside the staple forms.
[0083] The device may be used internal to the body cavity or
external to the body cavity. The device may incorporate an injector
unit or may work in conjunction with an independent injector unit.
The instrument may have an external mark or indicator to facilitate
system alignment with an external anatomic structure such as the
anti-mesenteric side of the intestine. The external mark or
indicator can be mechanically, electrically, or magnetically
registered to the internal system electronics to allow for
positional awareness of the system with externally aligned anatomy.
The instrument may have an integrated mating member 1223 to enable
a stable, positive couple (connection) to the anvil or housing. In
one embodiment the mating member can take the form of the spike on
the stapler to which the anvil is paired, which mates with the
anvil stalk. The positive connection can be configured to allow for
stability during instrument operation, yet easy release of the
anvil once instrument operation is complete. The easy release
functionality prevents tissue injury during the uncoupling of the
anvil from the instrument. The mating member may be fixed or
movably coupled to the instrument. In one embodiment the mating
member can be placed along the central axis of the instrument to
removably couple to the anvil stalk. The mating member has a
central bore that accepts a coaxial rod which allows for travel
along the axis. The mating member may be mechanically coupled to
the instrument by a constant force spring, or motorized slide such
as a linear stage or solenoid to allow for precise control of the
tissue interaction forces, such as the contact pressure exerted on
the tissue between the anvil and the instrument's tissue contacting
surface. The instrument may have integrated interaction force
sensors which allow the processor to regulate the interaction force
to a set range by actuation of the motorized slide. Similarly the
processor may indicate a condition to the end user responsive to
the magnitude of the transduced interaction force.
[0084] In one configuration of the present invention, the device
can be configured to sense oxygenation in multi-layered tissue, or
to discriminate oxygenation at different depths of tissue. Using a
phosphorescent oxygen sensing probe having multiple absorption
wavelengths in a medium, the device can irradiate and excite a
subset of the probe injected into the tissue based on the
excitation wavelength emitted from the device since the penetration
depth in tissue is wavelength-dependent. Oxygenation can be
discriminated at two or more depths or layers by exciting the
tissue sequentially with multiple emission wavelengths at or near
absorption peaks, and determining the corresponding quenched
lifetime response. Sensing the deeper values will be a summation of
multiple layers, oxygenation at deeper layers can be determined by
accounting for the sensed oxygen at shallower layers. In an
alternative approach, the phosphorescent decay of various
oxygenation levels in heterogeneous luminescence systems (i.e.
mixed oxygenations within the tissue sample) can be determined
through deconvolution methods to produce a spectrum of oxygenation.
In one embodiment of a sensing medical device, a plethora of
sinusoidally modulated excitation light outputs are generated
(either simultaneously, separately, or combined into a time varying
frequency signal such as a chirp) and frequency domain techniques
are utilized to determine the spectrum of phase lag of the received
signal from an injected phosphorescent medium. By determining the
relative contributions of each phase lag, a quantitative spectrum
of tissue oxygenation may be generated. In another embodiment, time
domain techniques can be utilized to determine the time response of
the medium to a pulse of light. Multiple exponential fitting of the
decay can be used to generate a quantitative spectrum of tissue
oxygenation.
[0085] The system described in FIG. 12 teaches a stand-alone
sensing instrument for taking circumferential measurements of
tissue; the instrument described can rotate so as to allow a
maximal number of measurement points with a minimal number of
sensing elements. However, it should be understood that a plurality
of fixed sensing elements, such as described in FIG. 10a, may also
be utilized in a similar configuration for the instrument 1201.
Also, the methods described herein can be applicable to multiple
configurations of a sensing instrument and should not be construed
as limited only to the configuration shown in FIG. 12.
[0086] FIG. 13a depicts an embodiment of an imaging system with a
light source capable of selectively illuminating a region of
tissue. The imaging system 1301 can be endoscopic and in one
embodiment can be a flexible endoscope such as a colonoscope that
is inserted transanally into colon tissue 1303 at the distal end of
an anastomosis junction. The imaging system may be used to image
and assess the viability of an anastomosis 1305 (such as through
mapping the oxygenation on one or both sides). The imaging system
1301 is configured such that it can be used to image the
light-remitted from an injected phosphorescent or fluorescent probe
in the anastomosis surface 1307 and the proximal side 1309 of an
anastomosis, and the anastomosis surface 1311 and the distal side
1313 of an anastomosis. The imaging system 1301 comprises a light
source 1321 that is used to provide illumination 1323 to excite a
light re-emitting probe residing in the distal 1311 and/or proximal
1307 tissue of the anastomosis 1305. The excited probe then
re-emits a phosphorescent or fluorescent response which is imaged
by an imager 1325. Imager 1325 may take the form of a camera
embedded in the distal end of imaging system 1301 and coupled to
control electronics and/or a signal processor 1327. In an alternate
embodiment, imager 1325 is the tip of a coherent fiber optic bundle
which conveys light to a remote camera. The light received by
imager 1325 is focused through lens 1329, which may also
incorporate optical filtering.
[0087] FIG. 13b depicts the imaging system 1301 with a retrograde
or retro-view light source extended. The light source 1341 has an
extension arm 1341 that allows it to extend and rotate. The arm
1341 may comprise pre-bent Nitinol wire enabling defined curvature
by extending and retracting the wire. In one embodiment, the light
source is configured to provide both forward (as shown in FIG. 13a)
and retrograde (as shown in FIG. 13b) illumination of a tissue
location inside a lumen. In a further configuration, the light
source is configured to illuminate the proximal 1307 and distal
1311 surfaces of an intestinal anastomosis 1305.
[0088] A method of determining and differentiating tissue
oxygenation at multiple tissue layers includes: 1) injecting a
phosphorescent oxygen-sensitive probe (or other light re-emitting
probe) into the tissue locally or systemically, 2) inserting
imaging system 1301 at the tip of rigid or flexible shaft 1347 into
the lumen of tissue 1323, 3) illuminating the anastomosis on the
distal surface 1311 (as shown in FIG. 13a) with a light 1323 at an
absorption wavelength of the phosphorescent probe that has a
shallow penetration depth in tissue (such as blue to UV range that
will not significantly penetrate beyond the distal tissue 1311), 4)
using the imager 1325 (such as a CCD, CMOS, or fiber bundle to a
camera system) to acquire signals, and use an onboard or external
signal processor 1327 to generate an oxygen map of the distal
surface 1311, 5) extending the light source 1321 along curved arm
1341 (or an additional/alternate light source), 6) illuminating the
anastomosis on the proximal surface 1307 (as shown in FIG. 13b)
with a light 1343 at an absorption wavelength of the phosphorescent
probe that again has a shallow penetration depth in tissue (blue to
UV range), and 7) using the imager (such as a CCD, CMOS, or fiber
bundle to a camera system) to acquire signals and use an onboard or
external signal processor to generate an oxygen map of the proximal
surface. The described method enables measurement of tissue
oxygenation at a shallow depth of approximately the thickness of
the intestinal wall, thus by illuminating from the proximal side,
only (or substantially only) the probe in the proximal side is
excited. When illuminated from the distal side, only (or
substantially only) the probe in the distal side is excited. The
phosphorescent response is in the red to IR range and will
penetrate through the tissue on either or both sides to the imager.
In an alternate embodiment, the light source 1321 contains emitters
for at least two wavelengths. One wavelength is at an absorption
peak of the probe that has poor tissue penetration and is used to
image only the distal side, and another wavelength is at an
absorption peak of the probe that has high tissue penetration depth
and is used to illuminate both layers. By measuring the oxygenation
of the distal tissue and the combination of both layers, the signal
processor discriminates the distal and proximal layer
oxygenations.
[0089] The invention described in FIG. 13a and FIG. 13b may be
configured with either an internal imager or an external imager
1325 coupled through a coherent fiber optic bundle. In either case,
an image processor 1327, used to generate oxygen maps may be
located externally; for the internal camera the signal processing
may be onboard, external, or a combination thereof. The light
source 1321 may be an electronic emitter located at the instrument
tip, or it may be located externally and optically coupled to the
instrument tip through fiber optic bundles or other means. The
light source may be configured to illuminate either side of an
anastomosis so as to discriminate the oxygenation from both the
proximal and distal sides. One or more temperature sensors 1351 may
be integrated into the imaging system instrument 1301, or
temperature may be assessed though fiberoptic coupling to an
external thermal imager. The temperature information may be used to
compensate for/calibrate the temperature-dependent phosphorescent
lifetime to subject tissue oxygenation.
[0090] FIG. 13b shows a retrograde light source to selectively
illuminate a region of tissue. A configuration of the retrograde
light source is capable of illuminating the distal or proximal side
of an intestinal anastomosis to excite an oxygen sensing molecular
probe in only one side at a time. A further configuration where
light source comprises a coherent fiber optic bundle capable of
transmitting infrared light, and the fiber bundle may be used to
both provide illumination of the tissue and to transmit light from
the tissue to a thermal imaging system for temperature mapping. The
antero/retrograde imaging system may be configured to generate PLI
measurements from both the distal and proximal sides of an
intestinal anastomosis as described. An embodiment of the system is
capable of multi-modality sensing, and in one embodiment
incorporates thermal imaging capabilities. In one embodiment, the
instrument takes the form of an imaging system with a large field
of view configured for generating oxygen maps on the far side of an
anastomosis with a forward facing or substantially forward facing
camera. The system can be configured with prisms or stacked high
index of refraction elements to generate a large field of view. The
present invention teaches a method for distinguishing physiologic
properties in various layers using an injectable probe and a light
source that selectively illuminates the layers. In a further method
an antero/retrograde light source selectively illuminates the front
or rear surface of a tissue.
[0091] FIG. 14a shows an injector system 1401 that couples to a
surgical stapler anvil 1403. This injector 1401 is used to inject a
medium 1405 into intestinal tissue containing the anvil. The
handheld device couples with a syringe 1407 filled with the medium
1405. The syringe may be filled with a single injection or multiple
doses of medium 1405. The syringe may also be an injector capable
of providing multiple metered doses either with a traditional
simple plunger 1409, or a manual or powered metered injector.
Internal fluid channels 1413 bring the medium 1405 from the syringe
1407 through an internal Luer lock, or slip tip fitting 1415 to the
needles 1417. Tissue resides between the handheld device body
tissue contacting surface 1421 and the working surface of anvil
1403. The anvil's stalk 1423 connects and is aligned with the
instrument 1401 through anvil stalk coupler 1425. In one
configuration, the alignment includes keying the anvil stalk's 1423
rotation such that the needle injection points 1417 align with the
sensor locations of a sensing version of anvil 1403 as described in
FIG. 10a and FIG. 10b. Small needles 1413 protrude into the tissue.
As shown in FIG. 14b, the needles 1417 have one or more lateral
holes 1431 and a solid tip to direct the medium into the tissue.
The tissue contacting surface of the device body 1435 may have a
contoured surface to apply different compression to the tissue
against the anvil working surface 1437 at different locations to
further direct the medium. In one embodiment, the surface is sloped
to direct the medium radially outwards from the needles which have
holes pointed outwards. In terms of radial placement, needles may
be used to inject the medium inside the staple forms 1439, at the
staple forms, or outside the staple forms. In one embodiment, the
medium may contain a phosphorescent oxygen sensing probe and the
oxygenation is detected from a sensing anvil (such as described in
FIG. 10a and FIG. 10b), a standalone device (such as described in
FIG. 12), and/or a imaging system (such as described in FIG. 13a
and FIG. 13b). FIG. 14c shows an alternate embodiment of the
injector unit 1443 that mates with a circular surgical stapler 1403
to inject the medium circumferentially into the tissue around the
working surface of the anvil. A handle 1445 attaches to the body of
the injector 1443. Syringe 147 connects to fluid channels 1447
through a Luer lock, or slip tip connector 1449. The use of a
standard fluid fitting 1449 enables pre-prepared, pre-filled
syringed 1407.
[0092] FIG. 15 shows a configuration of the present invention
wherein the system is configured to assess oxygenation of a
colorectal anastomosis. The colon 1501 is divided during surgery,
and a sensing surgical stapler anvil 1503 (hidden from view inside
the colon), such as described in FIG. 10a and FIG. 10b is inserted
into the proximal end 1505 of the transected colon 1501. An
injector 1511 (such as described in FIG. 14a, FIG. 4b, and FIG.
14c) injects oxygen-sensitive phosphorescent probe 1513 through
needles 1521 into the colonic tissue 1523 of the site of the
anastomosis at or near the proximal end 1505. The sensing anvil
1503 measures oxygenation at one or more points at the site of the
anastomotic surface 1523. In one embodiment, the sensing anvil 1503
measures oxygenation with twelve banks of sensors interleaved
between the staple forms configured for phosphorescent lifetime
sensing. In a further embodiment, temperature sensors are also
integrated into the sensing anvil 1503 for temperature compensation
of the oxygenation measurements. As shown in FIG. 15, the distal
end 1505 of the transected colon 1501 is left free, however an
alternate configuration of the present invention can be adapted for
injecting and sensing both the proximal 1505 and distal 1507 ends
of colon 1501. FIG. 10 shows a representative procedure for lower
anterior resection (LAR), but the present invention includes
applications to all colorectal and coloanal resections, as well as
other gastrointestinal procedures and other locations in the
body.
[0093] In one embodiment, pressure sensors are incorporated into
the sensing anvil 1503 to detect compression pressure of the tissue
in the anastomosis 1523, and may further be used to standardize
tissue compression pressure. In one method of use, the sensing
anvil 1503 is activated to generate oxygenation maps of the
anastomosis at various points in the procedure. In a representative
example the sensing anvil can interrogate the proximal anastomotic
tissue 1523 before creation of the anastomosis, during the
approximation of the proximal 1523 and distal 1507 tissue, and
immediately after firing the stapler, joining tissue and creating
the anastomosis. This information may be used to guide the surgical
procedure so as to affect a corrective action. Alternatively, the
results may be used to classify the patient's risk of anastomotic
failure and assist the operative team in the decision to fashion a
temporary or permanent ostomy.
[0094] FIG. 16a shows a representative embodiment of an imaging
system configured to assess fluorescent and or phosphorescent
lifetime. In one embodiment, the system is configured to detect
tissue oxygenation through phosphorescent lifetime imaging of an
oxygen-sensitive probe injected into a tissue. In one
configuration, the PLI system comprises a highly sensitive, low
noise, high speed scientific camera 1601 coupled to a high speed
gated image intensifier 1603; however in other embodiments lower
cost traditional camera-based or other imaging systems may be
utilized. The intensifier 1603 and the camera 1601 are coupled to
an interface unit 1605, via coupling 1607, which controls the
timing of the intensifier gating and the camera exposure, as well
as streams images from the camera to a processor for analysis. In
one embodiment, a computer is used for camera interfacing and image
processing, and a computer-controlled data acquisition device
provides timing control by acting as a dynamic delay generator
(DDG). The intensifier 1603 and the camera 1601 may be separate
components, or may be integrated into an intensified camera.
Further, as described in FIG. 7a, FIG. 7b, and FIG. 7c, some or all
of the functionality of the control interface unit 1605 may be
combined into the camera. In one embodiment, a combined intensified
camera comprises an FPGA or processor for preprocessing images,
thus reducing the bandwidth requirements of connection 1607 to an
external interface unit 1605.
[0095] The camera system comprises a lens 1611 to focus on a region
of interest of the tissue, wherein the probe 1615 resides (either
through local or system injection). In an overhead type system, the
lens 1611 will focus on either an external tissue or a visible
tissue in open surgery. The lens receives re-emitted light 1637
from the probe 1615 that was excited by excitation light 1633. The
re-emitted light is selectively passed through filter 1639 to the
lens 1611. In this configuration, the system may be attached to a
mounting arm 1619 such as a ceiling mounted or floor mounted boom
arm. The system may also be attached to a counterbalanced mounting
arms similar to that of a surgical microscope, and further the head
may have actuation so as to enable control of its position and
alignment through robotic means. In an alternate configuration, the
imaging system shown is a handheld unit configured to readily allow
snap shots of tissue oxygenation similar to the use of a standard
point and shoot camera.
[0096] The imaging system incorporates an illuminator light source
1631 to excite the probe 1615 in the tissue 1613. The illuminator
1631 light is modulated, and may be a pulsed light for time domain
measurements or a sinusoidal excitation for frequency domain
measurements. In one configuration, the illuminator 1631 contains a
plethora of light emitters that form a circumferential ring around
the optical axis of the camera lens 1611. The illumination light
1633 is focused into the same target region as the camera lens. In
one embodiment, the illuminator contains multiple wavelengths of
light emitters so as to provide excitation of the probe 1615 at
multiple wavelengths or selectively excite multiple different probe
types. Further, the illuminator 1631 may comprise both excitation
light and visible light which are switched or multiplexed so as to
enable clear visualization of the anatomy interleaved with
oxygenation imaging. In another configuration, the illuminator may
be an independent light source aimed at the target tissue and not
necessarily aligned along the optical axis of the camera.
[0097] In one embodiment, the imaging system further comprises a
means of assessing the temperature of the tissue containing the
probe. Assessment of the subject tissue temperature, allows for
temperature compensation of the temperature-dependent
phosphorescent decay of the probe. The use of temperature
measurements enables enhanced accuracy and robustness of absolute
oxygen concentration measurements that are invariant to tissue
temperature. Other physiologic and environmental factors may also
be similarly measured to compensate for the lifetime to oxygen
concentration calculation. In one embodiment, temperature is sensed
at one or more discrete points through contact (e.g., thermocouple,
RTD) or non-contact (e.g., optical) means. In one configuration, a
thermal imager 1641 is coupled with the imaging system to create a
temperature map of substantially the same region as the camera
performing lifetime sensing. The thermal imaging camera 1641 may be
rigidly coupled to the camera system 1601 via a mechanical coupler
1643. Registration may be performed to determine the correspondence
between points in the lifetime image and the temperature map. This
correspondence may be performed in real-time utilizing image-based
registration techniques, or it may be performed a priori for a
given configuration. One embodiment of the present invention
incorporates a camera-based PLI system coupled with an infrared
thermal imaging camera to detect both phosphorescent lifetime and
temperature. Temperature and lifetime of a given pixel or region
are both utilized in the determination of the corresponding
oxygenation. In one approach, temperature is explicitly calculated
and used directly with an a priori known temperature coefficient of
the phosphorescent quenching process in calculating the conversion
of phosphorescent lifetime to oxygenation. Thermal imager 1641 may
incorporate polarizing or other filters to minimize/reduce infrared
reflection.
[0098] The PLI system may comprise a laser or other alignment
device affixed to a camera system 1601 and/or a light source 1631
to assist in directing the alignment to a desired field of view
1615. The alignment device may be one of a point source, cross
hairs, and shaped to represent a region. The PLI system may also
comprise an electromechanically actuated head in place of or
coupled to arm 1619. The actuated head may be a robotic device. In
one embodiment, the head is configured for dynamic tracking of a
target or region of interest due to motion/misalignment.
[0099] The imaging system described in FIG. 16a may be used for a
variety of applications. In one application, it is utilized for
imaging gastrointestinal tissue such as colorectal tissue during
colorectal cancer resection. It may be further used for assessing
oxygenation and/or perfusion in tissue during organ transplants or
vascular surgery. One use of the system is for assessing the
viability of skin flaps by measuring their oxygenation. In one
method of use, this system assesses the oxygenation of peripheral
anatomy and utilizes the oxygenation to screen for peripheral
vascular disease and/or guide interventions for peripheral vascular
disease. The system of the method may be a boom-mounted imager, a
handheld imaging instrument, or an alternate configuration. The
system may generate individual images or multiple images over a
specified time course at a specified repetition rate. The absolute
tissue oxygenation and/or time-dependent variation in oxygenation
may be presented.
[0100] FIG. 16b shows a further representative embodiment of the
imaging system described in FIG. 16a configured to assess
fluorescent and or phosphorescent lifetime of tissue at the site of
an anastomosis, specifically a colonic tissue anastomosis as
previously described. The system can additionally be used to image
other gastrointestinal anastomoses of other organs such as, but not
limited to esophagus, stomach, and small intestine. In one
configuration, the imaging system assesses the phosphorescent
lifetime of an injected oxygen-sensitive probe. The probe 1651 is
injected into colorectal tissue 1653 (typically the proximal end as
described in FIG. 15) which has a surgical stapler anvil 1655
inserted into it in preparation for a surgical anastomosis. Anvil
1655 may be a traditional non-sensing anvil, or a sensing anvil as
described in FIG. 10a and FIG. 10b. The probe 1651 is injected into
the tissue 1653 utilizing an injector, such as that described in
FIG. 14a, FIG. 15b, and FIG. 14c, or other means. The tissue in
contact with the working surface (i.e. anvil's staple form surface)
contains the probe and is directed towards the optical axis of the
imaging system 1601. The imaging system further comprises an
alignment guide 1659 that is coaxial with the optical axis of the
camera 1601, intensifier 1603, and lens 1611. The alignment guide
may be repeatably attached and removed from the lens 1611 via a
quick-connect fitting 1661. A coupler 1655, which may be a
quick-connect type connection, joins the alignment guide 1659 with
the stalk 1667 of the surgical stapler anvil 1655. This system
ensures that the proximal end of an anastomosis 1671 is fully
imaged with the PLI system. In one embodiment, the PLI system
further comprises a thermal imager 1641 to determine the
temperature of the same tissue imaged by the PLI as described in
FIG. 16b. The temperature may be used to compensate for the
temperature-dependent phosphorescent lifetime in the conversion of
lifetime to oxygen concentration. Temperature measurement may be
performed via an imaging system of the target region, utilizing an
injectable probe that aids in assessing temperature, contact
measurement of the temperature, or other means.
[0101] In one method of use, the system in FIG. 16b generates an
oxygen map of the proximal end of the anastomosis after resection
and prior to joining with the distal end, and the information is
used to guide the procedure. The guidance may incorporate
corrective action such as additional dissection to reduce tension
and improve blood supply. The system in FIG. 16a, which may be the
same system as described in FIG. 16b with the alignment guide
removed, may then be used for imaging the distal and/or proximal
ends externally. The system may also be used in conjunction with a
sensing anvil, such as that described in FIG. 10a and FIG. 10b.
[0102] The present invention includes, but is not limited to,
sensing and mapping of tissue oxygenation based upon phosphorescent
lifetime. This sensing technology may be used in conjunction with
other technologies. The sensing technology associated with the
invention may sense mechanical or biological properties. The
sensing instruments may include one or more sensing modalities. The
sensing modalities may include mechanical, optical, chemical,
electrical, or other means for generating a signal indicative of a
property of a subject tissue. In one embodiment, the sensing
elements measure oxygenation through the use of a medium containing
a phosphorescent probe or phosphor delivered into tissue. Other
embodiments measure oxygenation through oximetry-based techniques.
Further embodiments measure perfusion or flow rates through the
time response of a fluorescent or phosphorescent medium introduced
into the tissue.
[0103] Accordingly, one embodiment includes sensing surgical
instruments and associated probes, injectors, processing, and
visualization; the instruments capable of performing phosphorescent
lifetime sensing at a plethora of discrete points, and using the
phosphorescent lifetime measurements to generate
temperature-compensated oxygen maps.
[0104] Another embodiment includes imaging systems and associated
probes, injectors, processing, and visualization; the imaging
systems capable of performing phosphorescent lifetime imaging of an
array of points, and using the phosphorescent lifetime measurements
to generate temperature-compensated oxygen maps; wherein, the
oxygen maps are registered to endoscopic video images and used to
identify suspect regions based on oxygenation measurements.
[0105] In an embodiment, the sensing components are incorporated
into, or coupled to, a surgical instrument. Instruments may include
traditional open, laparoscopic, endoscopic, bronchoscopic,
otoscopic, opthalmoscopic, laryngoscopic, cystoscopic, colposcopic,
intravascular, intraluminal, robotic, or other minimally invasive
tools such as a purpose-built tissue interrogator or instrumented
standard instrument such as a grasper, needle driver, stapler, clip
applier, catheter, scissor, cautery, or retractor. Instruments may
also include interrogators or other devices that may or may not be
minimally invasive. In alternate embodiments, the sensing
components are incorporated into a primary or secondary imaging
system for endoscopy.
[0106] This imaging system may be used for diagnostic procedures,
or for monitoring or guiding surgery. The technology may be
incorporated into or associated with rigid or flexible endoscopy
equipment. The technology may be further coupled with endoscopy
equipment based upon light transmission through lenses or optical
fibers, or it may be integrated with digital imaging systems with
microcameras at the distal end. In a further embodiment, the
imaging system disclosed in this invention may be a standalone
camera-based system. This camera based system may be used for
external monitoring of tissue (such as skin flaps), for internal
imaging through either open surgical procedures or minimally
invasive endoscopic procedures, for precision mapping of retinal
oxygenation, used in conjunction with robotic surgery, or other
means. As previously noted, this invention includes phosphorescent
lifetime imaging of a phosphor with an oxygen-dependent quenching
of phosphorescent response to an excitation. The invention also
include sensing other physiologic parameters, sensing using other
fluorescent or phosphorescent probes, measuring inherent
fluorescent or phosphorescent response from tissue, or imaging an
imaging agent or other biomarker or tag such as quantum dots.
Optical sensing elements include but are not limited to light
emitters including light emitting diodes (LEDs) and laser diodes,
and light receivers including photodiodes (including avalanche
photodiodes, photomultiplier tubes, silicon photomultipliers, and
similar enhanced sensitivity detectors), photodiode arrays, CCD
arrays (including enhanced sensitivity detectors such as electron
multiplying EMCCDs), CMOS sensors, cameras, holographic imaging
systems, image intensifiers (which may be coupled with or
integrated into other detectors), and spectrometers.
[0107] The optical sensing elements are configured to measure at
least one of tissue oxygenation, oxygen delivery, oxygen
utilization, tissue characterization, and tissue general health
using oximetry, phosphorescent techniques, or spectroscopic
techniques, and at least one of tissue perfusion, tissue flow
dynamics, tissue oxygen content, tissue chemical composition,
tissue immunologic activity, tissue pathogen concentration, or
tissue water content using fluorescence or phosphorescent based
techniques. The fluorescence and phosphorescence based techniques
include but are not limited to the following: monitoring and
analyzing the intensity and time course of a fluorescent response
responsive to the injection or activation of a fluorescent medium,
determining oxygen quantities by measuring oxygen-dependent
quenching of fluorescent or phosphorescent radiation using a
sensitive material such as Ruthenium by both intensity and time
resolved methods, determining oxygen concentration based on the
quenching time response of injectable oxygen sensitive
phosphorescent probes, and determining the target tissue property
by quantitative fluorescent or phosphorescent methods including the
use of quantum dots, or other biomarkers incorporating light
re-emitting properties. In one configuration the device senses
perfusion using Fluorescein, or IC Green, or other imaging agent.
In one other configuration the device senses oxygen quenching of
native tissue phosphorescence.
[0108] Included in this invention is a method for gating signal
acquisition of a phosphorescent lifetime imaging system to
physiologic parameters. Measurement of tissue oxygenation or other
tissue characteristics can be measured in a gated fashion to
standardize the measurement and allow for comparison. One
representative example of the gated image acquisition is triggered
with pulse and/or respiratory and/or peristaltic motion. Gated
acquisition may also be based on measurements of peristalsis,
respiratory motion, cardiac motion, cardiac output or pulsatile
flow, EEG readings, EMG readings, motion sensors, or other inputs.
A further method captures PLI measurements gated with at least one
or respiration, cardiac output (i.e. pulse), peristalsis, or other
internal or external motion. A further method provides for
dynamically comparing PLI measurements at two or more time points
in a physiologic cycle. One method determines the gate cycle from
images acquired by the PLI system, and a further method provides
for determining the cardiac cycle gate based off of images acquired
of vasculature.
[0109] In one configuration of the present invention, the
instrument is configured to sense oxygenation in multi-layered
tissue, or to discriminate oxygenation at different depths of
tissue. Using a phosphorescent oxygen sensing probe having multiple
absorption wavelengths, the instrument can irradiate and excite a
subset of the probe injected into tissue based on the excitation
wavelength emitted from device since the penetration depth in
tissue is wavelength-dependent. Oxygenation is discriminated at two
or more depths or layers by exciting the tissue sequentially with
multiple emission wavelengths at or near absorption peaks, and
determining the corresponding quenching response. Sensing the
deeper values will be a summation of multiple layers, oxygenation
at deeper layers can be determined by accounting for the sensed
oxygen at shallower layers. In an alternative approach, the
phosphorescent decay of various oxygenation levels in heterogeneous
luminescence systems (i.e. mixed oxygenations within the tissue
sample) can be determined through deconvolution methods to produce
a spectrum of oxygenation.
[0110] The present invention includes a medical imaging system,
probes, and methods for assessment of phosphorescent or fluorescent
lifetime of an injectable probe or natural auto fluorescence. In
one configuration, at least one sensor is configured to obtain
biological tissue oxygenation at a plethora of points utilizing the
technique of oxygen dependent quenching of phosphorescence of an
injectable probe. In another embodiment, the present invention
measures lifetime of a marker or other probe in or on the body. In
a further embodiment, lifetime of phosphorescence or fluorescence
produced from native biologic tissue is assessed. Included in the
present invention is a system and method for performing
microinjection of a probe or imaging agent from tip of an endoscope
or other instrument at one or more points; and a device for
performing microinjection of a probe or imaging agent into tissue
circumferentially at the working surface of a surgical stapler
anvil.
[0111] The embodiments described above demonstrate how oxygen
sensitive probes can be utilized with an imaging system for oxygen
mapping of tissue. These embodiments are for meant as illustrative
purposes. The described sensing configurations and approaches can
be adapted to provide the described functionalities for other
surgical instruments. Further, the techniques discussed should not
be construed to be limited to use only with phosphorescent oxygen
sensing probes.
[0112] The present invention can be practiced by employing
conventional materials, methodology and equipment. Accordingly, the
details of such materials, equipment and methodology are not set
forth herein in detail. In the previous descriptions, numerous
specific details are set forth, such as specific materials,
structures, chemicals, processes, etc., in order to provide a
thorough understanding of the present invention. However, it should
be recognized that the present invention can be practiced without
resorting to the details specifically set forth. In other
instances, well known processing structures have not been described
in detail, in order not to unnecessarily obscure the present
invention.
[0113] Only exemplary embodiments of the present invention and but
a few examples of its versatility are shown and described in the
present disclosure. It is to be understood that the present
invention is capable of use in various other combinations and
environments and is capable of changes or modifications within the
scope of the inventive concept as expressed herein.
[0114] Although the foregoing description is directed to the
preferred embodiments of the invention, it is noted that other
variations and modifications will be apparent to those skilled in
the art, and may be made without departing from the spirit or scope
of the invention. Moreover, features described in connection with
one embodiment of the invention may be used in conjunction with
other embodiments, even if not explicitly stated above.
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