U.S. patent application number 13/591629 was filed with the patent office on 2012-12-13 for remote oximetry monitoring system and method.
Invention is credited to David A. Benaron, Michael R. Fierro, Ilian H. Parachikov.
Application Number | 20120316411 13/591629 |
Document ID | / |
Family ID | 37695273 |
Filed Date | 2012-12-13 |
United States Patent
Application |
20120316411 |
Kind Code |
A1 |
Benaron; David A. ; et
al. |
December 13, 2012 |
Remote oximetry monitoring system and method
Abstract
A medical monitoring system in which information related to
ischemia or an oxygenation to be determined is transmitted by a
sending unit (167) using radiofrequency signals to a receiver
(183), and the results are displayed on an external and remote
monitor (313). The entire device may be encapsulated by a
biocompatible shell (102) to permit implantation.
Inventors: |
Benaron; David A.; (Portola
Valley, CA) ; Parachikov; Ilian H.; (Belmont, CA)
; Fierro; Michael R.; (Los Gatos, CA) |
Family ID: |
37695273 |
Appl. No.: |
13/591629 |
Filed: |
August 22, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12858396 |
Aug 17, 2010 |
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13591629 |
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11193071 |
Jul 29, 2005 |
7813778 |
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12858396 |
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Current U.S.
Class: |
600/339 |
Current CPC
Class: |
A61B 5/1459 20130101;
A61B 5/0261 20130101; A61B 5/412 20130101; A61B 5/14542 20130101;
A61B 5/0031 20130101 |
Class at
Publication: |
600/339 |
International
Class: |
A61B 5/1459 20060101
A61B005/1459 |
Claims
1-13. (canceled)
14. A medical information system for monitoring of living tissue at
a distance comprising: (a) a medical device configured to generate
at least one measure that is a function of oxygenation or ischemia;
and, (b) a sending unit coupled to the device and configured to
send out a transmission based on the measure. (c) a receiver
arranged to receive the transmission; and, (d) a display arranged
to show a result based on the transmission received.
15. A medical information system for monitoring of tissue
oxygenation at a distance comprising: (a) a tissue oximeter
configured to generate at least one measure that is a function of
tissue oxygenation; (b) a sending unit coupled to the oximeter and
configured to send out a transmission based on the measure; (c) a
receiver arranged to receive the transmission; and, (d) a display
arranged to show at least one tissue oxygenation based upon the
transmission received.
16. The system of claim 15, wherein the receiver and the display
are configured to operate as an external monitor.
17. The system of claim 15, wherein the receiver or the sending
unit is configured to communicate using at least a reception or
transmission via radiofrequency.
18. The system of claim 17, wherein the receiver or the sending
unit is a cell phone.
19. The system of claim 15, wherein the receiver or sending unit is
configured to communicate using at least a reception or
transmission via wire.
20. A method monitoring oxygenation at a distance including the
steps of: generating a measure that is a function of tissue
ischemia or oxygenation; transmitting data representing the
measure; receiving the data; and, displaying a result that is a
function of the tissue ischemia or oxygenation based upon the
received data.
21. The method of claim 20, wherein the receiving or transmitting
is achieved using at least a reception or transmission via
radiofrequency.
22. The method of claim 21, wherein a cell phone is configured to
achieve the reception or transmission via radiofrequency.
23. A medical information software application, said application
configured to operate in a remote monitoring device with a
receiving unit and a display, said receiving unit operatively
configured to receive data from a sending unit configured to
transmit data representing a biometric measure of oxygenation, and
said application further configured to output to the display a
result that is a function of tissue ischemia or oxygenation based
upon the received data.
24. The application of claim 23 wherein the application further
includes an alarm function for alerting when the result is beyond
predetermined limits.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to implantable devices and
methods for providing localized measurements of tissue ischemia,
and more particularly relates to the embedding of a visible light
source, a sensor, a power source, and a transmitter into a
long-term implantable shell for the purpose of performing real-time
spectroscopic analysis of in vivo tissue perfusion sensitive to
local tissue ischemia.
BACKGROUND OF THE INVENTION
[0002] The clinical detection of ischemia--an insufficient delivery
of oxygen to meet a tissue's metabolic needs--is unreliable.
Ischemia is especially difficult to detect when the ischemia is due
to a localized interruption of blood flow--such as during a heart
attack or stroke. Existing laboratory tests for ischemia, such as
serum enzyme-leakage tests (e.g., for tests for cardiac isoenzymes
after a heart attack) or EKG electrical tests, are insensitive
indicators of such local tissue ischemia, especially during the
early stages. Similarly, blood tests are also insensitive to local
ischemia, as the ischemia is a result of low oxygenation in a local
tissue, which is reflected in the local capillary oxygenation, not
in the oxygenation of the arterial or venous blood when measured in
the large central arteries and veins. Noninvasive imaging of
ischemia lacks the immediacy that allows for early intervention or
real-time feedback to other devices such as pacemakers.
[0003] Non-implantable ischemia sensors are known. For example,
U.S. Pat. No. 6,532,381 teaches the detection of ischemia using
externally measured electrical (EKG) monitoring and microprocessor
control. However, such devices monitoring multiple external sites
using wire leads placed upon the chest wall are not designed for
implantability, which requires that issues of size, power
consumption, biocompatibility, and robustness over time be
optimized alongside sensing performance, a non-trivial task.
[0004] Implantable sensors are also well known. However,
implantable sensors designed to detect ischemia are rare in the
art, and none of these detect tissue ischemia directly. For
example, U.S. Pat. No. 5,135,004, US Appn 2004/0122478, and WO
00/64534 predict the presence of ischemia based upon the electrical
(EKG), blood pressure, local pH, and/or physical (acceleration
during contraction) characteristics of the heart, while U.S. Pat.
No. 6,527,729 discloses an implantable acoustic sensor that
responds to heart failure by changes in the sound of the heartbeat.
Further, U.S. Pat. No. 5,199,428 and US Appn. 2004/0220460 teach
implantable devices to monitor blood oxygenation (venous blood and
arterial blood, respectively), in the latter case specifically
rejecting local tissue saturation from encapsulation, thus teaching
away from direct tissue monitoring. For reasons to be outlined in
more detail later, such non-tissue blood oxygenation (whether
arterial or venous) is insensitive to tissue ischemia, and is at
best an indirect measure of tissue ischemia. For each of the
devices above, then, ischemia is measured only by indirect and
unreliable indicators of ischemia, such as by indicators of cardiac
electrical, mechanical, and acoustic dysfunction. Another point to
consider is that organs other than the heart are frequent sites of
ischemia (such as in the kidney, liver, or gut), and the prior art
is not directed to these other organs at all. Therefore, none of
the above devices detect local tissue ischemia directly, nor can
they be applied generally to any organ without regard to site.
[0005] All of the above devices are limited by being either
non-implantable, by being at best an indirect measures of local
tissue ischemia, or by being restricted to use in just one organ
such as the heart due to the indirect measures of ischemia (such as
sound or movement) which they employ.
[0006] None of the prior devices or methods allow for a direct
detection of local tissue ischemia in a broad array of target sites
using a long-term or short-term implantable system sensitive to
local ischemia,
[0007] Such a system has not been previously described, nor
successfully commercialized.
SUMMARY OF THE INVENTION
[0008] The inventors have discovered that the site at which tissue
ischemia occurs is always local, and that local tissue physiology
in nearly every case will attempt to compensate for this local
ischemia, producing a direct depression then partial compensation
on the capillary hemoglobin saturation. This local effect is often
not measurable using standard blood monitoring, and capitalizing on
this local capillary effect allows for the design a highly
localized, fully-implantable ischemia detector.
[0009] A salient feature of the present invention is that the
detection and treatment of ischemia is aided by use of an
implantable ischemia sensor.
[0010] Accordingly, an object of the present invention is to
provide a fully-implantable ischemia detector.
[0011] In one aspect the invention provides a direct, quantitative
measure or index of local tissue ischemia.
[0012] In another aspect the invention provides a short-term
implantation, such as optical fibers within the heart muscle after
bypass surgery, or an implant in the lung tissue for short-term
monitoring after a transplant, or even a swallowable device for
detecting ischemia in the gut as it passes through the enteric
system.
[0013] The improved ischemia detection system as described has many
advantages one or more of which are descipled below. While a number
of advantages are set forth for illustrative purposes only, these
advantages are not intended to limit the scope of the claims in any
way.
[0014] One advantage is that a physician or surgeon can obtain
real-time feedback regarding local tissue ischemia in high-risk
patients, and to respond accordingly, while any injury remains
reversible.
[0015] Another advantage is that this system may be safely deployed
within a living body.
[0016] Another advantage is that the system can be actively coupled
to a therapeutic device, such as a pacemaker, to provide feedback
to the pacing function, or passively coupled to a therapeutic
device, such as applied to a stent to monitor stent performance
over time.
[0017] Another advantage is that the system may be constructed to
detect ischemia using light, which allows for simple, safe, and
non-electrical transmission of the measuring photons as
required.
[0018] Another advantage is that the detection can be in the tissue
itself, rather than removed from the site of ischemia. Sources of
local tissue signals include but are not limited to capillary
hemoglobin (not in the arterial or venous circulation but locally
in the capillaries in the tissue), myoglobin (which is
extravascular and within muscle cells in the tissue itself) and
cytochrome (which is intracellular within the mitochondria of the
cells of the tissue itself).
[0019] Another advantage is that use of broadband light can allow
for determination of tissue ischemia using spectroscopy, and in
particular differential spectroscopy, which allows for compensation
of light scattering by tissues.
[0020] A final advantage is that ischemia sensing may be used to
enable detection of many types of disease, such as tissue
rejection, tissue infection, vessel leakage, vessel occlusion, and
the like, many of which produce ischemia as an aspect of the
disease.
[0021] There is provided an implantable device or system with
broadband light source for generating light, and for delivering
this light to a sample for the purpose of enabling spectroscopic
ischemia detection. In some embodiments, the system uses a
phosphor-coated white LED to produce continuous, broadband light
from 400 nm to 700 nm, which is transmitted directly to a target
site. Scattered light returning from the target is detected by a
wavelength-sensitive detector, and a signal related to ischemia is
generated using this wavelength-sensitive information via
spectroscopic analysis. Finally, this signal is sent out from the
device using radiofrequency (RF) transmission. Implantable systems
incorporating the ischemia detection system and medical methods of
use are described.
[0022] The breadth of uses and advantages of the present invention
are best understood by example, and by a detailed explanation of
the workings of a constructed apparatus, now in operation and
tested in animals. These and other advantages of the invention will
become apparent when viewed in light of the accompanying drawings,
examples, and detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] The following drawings are provided:
[0024] FIG. 1 is a schematic diagram of an implantable tissue
ischemia detector incorporating a white LED and constructed in
accordance with embodiments of the invention.
[0025] FIG. 2 is a schematic of an external coil, for powering the
implantable device and for receiving a signal related to the
presence or degree of tissue ischemia, attached to an external
monitor system.
[0026] FIGS. 3A to 3E shows five exemplary schematics of the
optical sensor unit.
[0027] FIG. 4 shows data from the colon of a live subject during
periods of low systemic blood flow, which led to local ischemia, as
collected and analyzed in real time by a medical monitor
constructed in accordance with embodiments of the invention.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
[0028] For the purposes of this invention, the following
definitions are provided. These definitions are intended to be
illustrative and exemplary. They are not intended to restrictively
limit, by the absence of any specific illustrative example, the
common-sense breadth of meaning of the terms to those skilled in
the art. These definitions are as follows:
[0029] Implantable: Intended for implantation internally in a
living body, such as into or between internal tissues. Implantable
devices typically must be biocompatible (i.e., have a biocompatible
exterior), or else the host subject's immune system will attack the
implanted object or the device will have a toxic effect upon the
host.
[0030] Implantable does not require any fixed duration. Implantable
as used herein can mean short-term implantation, such as removable
fibers inserted in the heart or lung, or a swallowable device such
as an gastrointestinal ischemia monitor. Implantable as used herein
may also be a long-term implantation, such as a pacemaker feedback
system which monitors the heart or muscle, or a liver-based MEMS
device that monitors for rejection.
[0031] Fully-Implantable: Complete implantation into a living body,
without a physical connection to the external body.
Fully-implantable devices may contain an embedded power supply,
receive power from another implanted device (such as a pacemaker),
or receive power from an external source such as via transcutaneous
inductive coupling. Fully-implantable devices may still communicate
with receivers external to the body via non-physical means, such as
electromagnetic waves from RFID chips. An implantable system may be
embedded long-term, such as buried deep within a body to monitor
for organ rejection or cardiac ischemia. An implantable system may
also be used short-term only, such as a swallowable pill that
monitors for ischemic ulcers or polyps in the esophagus, stomach,
intestines, and colon, and is passed via the rectum when the
scanning is complete in a few hours to a few days.
[0032] Tissue: Material from a living animal, plant, viral, or
bacterial subject, with an emphasis on mammals, especially
humans.
[0033] Perfusion: The flow of blood to a tissue or region, which
differs from tissue ischemia in that low flow does not guarantee
ischemia.
[0034] Blood Oxygenation: The saturation of the hemoglobin in
arterial and venous blood, which differs from tissue ischemia.
Arterial blood can be 100% oxygenated, yet a blood clot in the
coronary artery will produce severe ischemia despite the 100%
arterial saturation. Similarly, a local occlusion may produce
lethal local ischemia, while the average venous oxygenation is not
lowered detectably due to the small contribution of that local
tissue to the overall venous blood oxygenation.
[0035] Ischemia: A local condition of tissue in which the delivery
of oxygen to the tissue is locally inadequate to meet its metabolic
needs. Such conditions vary from tissue to tissue. For example, the
brain has a high metabolic rate and is easily made ischemic, even
during simple tasks such as deep thought and insight, unless there
is a local and rapid increase in the baseline blood flow and oxygen
delivery to the metabolizing cortical tissues. In contrast, the
growing fetus is in a relative hibernation state, with very low
oxygen needs in most tissues, and is more difficult to make
ischemic. Early and mild ischemia is often evidenced by increases
in the amount of oxygen extracted from the blood being delivered to
the capillary bed, resulting in decreased tissue oxygenation. Later
stage ischemia is evidenced by lactic acid formation and disturbed
cellular metabolism that occurs when the simple compensatory
mechanisms of the tissue (increase oxygen extraction, increase
flow) are no longer sufficient to protect the tissue from the
rising ischemia. Ischemia is therefore distinguished from perfusion
(i.e., blood flow) in that low blood flow does not guarantee
ischemia (such as during tissue cooling or in the fetus), nor does
high flow rule out ischemia (such as during sepsis, fever, or
intense work). Ischemia is a co-existing condition in many
different types of illnesses, including sepsis, tissue rejection,
heart attack, stroke, organ failure, diabetic disease, and other
conditions.
[0036] Target: A material to be detected, imaged, or studied. In
the accompanying examples, one target site is the intestine.
[0037] Target Signal: A sensed signal specific to the target. This
signal may be enhanced through use of a contrast agent. This signal
may be produced by scattering, absorbance, phosphorescence,
fluorescence, Raman effects, or other known spectroscopy
techniques.
[0038] Visible Light: Electromagnetic radiation from blue to
yellow, namely with wavelengths between 400 nm and 625 microns, but
especially those green to orange wavelengths between 475 and 600 nm
where the absorbance by capillary hemoglobin (not in the arterial
or venous circulation but locally in the capillaries in the
tissue), myoglobin (which is extravascular and within muscle cells
in the tissue itself) and cytochrome (which is intracellular within
the mitochondria of the tissue itself) is the strongest.
[0039] Broadband Light: Light produced over a wide range of
wavelengths sufficient to perform solution of multiple simultaneous
spectroscopic equations. For tissue, a width of at least 40 nm is
likely to be needed, while in the preferred embodiment a broadband
white LED produces light from 400 nm to beyond 700 nm.
[0040] LED: A light emitting diode.
[0041] White LED: A broadband, visible wavelength LED, often
comprised of a blue LED and a blue-absorbing broad-emitting
phosphor that emits over a wide range of visible wavelengths. Other
phosphors can be substituted. As used in the examples herein, any
broadband LED could be used, even if not emitting over a full
(white) spectrum. For example, a green LED emitting over a FWHM
range of 100 nm would be considered to be broadband.
[0042] Light Source: A source of illuminating photons. It may be
composed of a simple light bulb, a laser, a flash lamp, an LED, a
white LED, or another light source or combination of sources, or it
may be a complex form including but not limited to, a light emitter
such as a bulb or light emitting diode, one or more filter
elements, a transmission element such as an integrated optical
fiber, a guidance element such as a reflective prism or internal
lens, and other elements intended to enhance the optical coupling
of the light from the source to the tissue or sample under study.
The light may be generated using electrical input (such as with an
LED), optical input (such as a fluorescent dye in a fiber
responding to light), or any other source of energy, internal or
external to the source. The light source may be continuously on,
pulsed, or even analyzed as time-, frequency-, or
spatially-resolved. The light emitter may comprise a single or
multiple light emitting elements, such as a combination of
different light emitting diodes to produce a spectrum of light.
[0043] Light Detector or Light Sensor: A detector that generates a
measurable signal in response to the light incident on the
detector.
[0044] Optical Coupling: The arrangement of two elements such that
light exiting the first element interacts, at least in part, with
the second element. This may be free-space (unaided) transmission
through air or space, or may require use of intervening optical
elements such as lenses, filters, fused fiber expanders,
collimators, concentrators, collectors, optical fibers, prisms,
mirrors, or mirrored surfaces and the like.
[0045] Embodiments of the device and system will now be
described.
[0046] FIG. 1 shows device 101 implanted into the chest wall of
patient 98. Of note, patient 98 is shown for illustrative purposes,
and is not considered a part of the invention. A cut-away schematic
of device 101 showing the interior of implantable device 101 is
shown at the top of FIG. 1. Device 101 is surrounded by
biocompatible exterior 102. Typically, exterior 102 is constructed
from approved Class VI materials as recognized by the U.S. FDA or
other medical device regulatory agencies, such as polyethylene or
surgical steel. Portions of the sensor, power supply, light source,
or transmitter may protrude as needed from this shell within the
spirit of this invention, provided that the protruding parts
themselves are biocompatible.
[0047] Within device 101, light source 103 is illustrated in its
component parts. In some embodiments, broad spectrum white light is
emitted by a high conversion-efficiency white LED source 105 (in
this case, The LED Light, model T1-3/4-20W-a, Fallon, Nev.). In the
exemplary embodiments, diode source 105 is embedded into a plastic
beam-shaping mount using optical clear epoxy 111 to allow light
generated in LED 105 to be collimated, thus remaining at a
near-constant diameter after passing through optical window 115 to
leave device 101. Light then is able to pass forward as shown by
light path vectors 119, with at least a portion of this light
optically coupled to target region 125. Note that while target
region 125 may be in some instances a living tissue, the tissue
itself is not considered to be a claimed part of this
invention.
[0048] A portion of the light reaching target 125 is absorbed by
ischemia in the tissue and another portion is backscattered and
returns as to device 101, as shown by light path vectors 128, to
optical collection window 141. Collection window 141 in this
embodiment is a glass, plastic, or quartz window, but can
alternatively be merely an aperture, or even be a lens, as
required. Light then strikes sensor 155, where it is sensed and
detected.
[0049] Sensor 155 may comprise a number of discrete detectors
configured to be wavelength-sensitive, or may be a continuous CCD
spectrometer, with entry of light by wavelength controlled by
gratings, filters, or wavelength-specific optical fibers. In any
event, sensor 155 transmits an ischemia signal related to the
detected light backscattered from target 125, producing an
electrical signal sent via wires 161 and 163 a sending unit 167,
such as a transmitter chip. The signal transmitted by the sending
unit 167 is received by the receiver 183 where it can be further
processed to provide a display.
[0050] In one embodiment, light source 103 also has two electrical
connections 175 and 176, connecting light source 103 to power
source 179. In one embodiment, power source 179 is an inductive
power supply, capable of receiving an inductive field from
externally powered coil and RFID receiver 183 (FIG. 2) placed
outside of the body, in order to produce power for device 101 as
required. Note that external powered coil 183 is shown for the
purposes of example and illustration, but is not considered a
required part of this invention. Alternatively, source 179 could
merely be a long-lived implantable battery, in which case an
external powered coil may not be required at all.
[0051] Operation of the device may now be described.
[0052] Device 101 is implanted in a patient, for example in the
chest wall of a patient undergoing coronary artery repair for heart
disease. The device may measure the muscle directly, or it can be
placed at a distance. In the latter case, vectors 119 are fiber
optics extended from device 101 and into close proximity to the
target heart muscle, sufficient for optical coupling. Then the
patient is allowed to heal after surgery, and the implantable
device is left inside the patient's body, without a direct physical
connection to the outside world.
[0053] In this example, device 101 is normally powered down and in
a resting (off) state. At some point, it is desired to test the
target heart muscle for the presence of ischemia. As shown in FIG.
2 , external inductive coil 183 is connected to external monitor is
brought into close proximity to the chest wall over the site of
implantation of device 101. Referring back to FIG. 1, through
inductive coupling external coil 183 induces a current in inductive
power source 179 located within device 101, producing sufficient
power for device 101 to power up and turn on. Light source 103
begins to illuminate the target 125, in this case heart muscle.
Sensor 155, which is an embedded spectrophotometer in some
embodiments, receives backscattered light, resolves the incoming
light by wavelength, a marker of ischemia. The result of this
determination is sent to sending unit 167, which in the exemplary
embodiment is an RF transmitter that sends the sensed signals to
external RFID receiver 184. There, the signal received by receiver
184 may be processed for the oxygenation of the hemoglobin in the
terminal capillary beds, a marker of ischemia, by external monitor
313, as shown in the data collected and plotted under the Example
section, below. An example of a system for indicating oxygenation
is described in U.S. Pat. No. 5,987,346, incorporated herein by
reference.
[0054] Once the measurement is completed, external coil 183 is
moved away from device 101, and device 101 powers down and returns
to a resting state.
[0055] In an alternative embodiment, power source 179 may be
charged during proximity to external coil, or have an internal
battery source, allowing device 101 to operate when external coil
179 is not present. Sending unit 167 may then transmit without
being directly queried, such as in response to a dangerous level of
ischemia.
[0056] The light sensor which resolves the incoming light by
wavelength and sends a signal to the sending unit has been
mentioned, and will now be more fully described with reference to
FIGS. 3A to 3E. In one form, FIG. 3A, the sensor 155 is merely
single photodiode 411 and processing electronics 413. Photodiode
411 is made wavelength sensitive through the design of LED 105 as a
cluster of LEDs of different wavelengths, each emitting at a
different time or modulation frequency to allow decoding of the
illuminating wavelength by photodiode 411 and processing unit
electronics 413. Alternatively, sensor 155 may comprise a set of
different photodiodes 421A through 421N, FIG. 3B, each with filters
425A through 425N, allowing each photodiode to be sensitive to only
one wavelength range, again allowing decoding of the sensed light
by wavelength by processing unit electronics 427. Alternatively
again, sensor 155 may be single photodiode 431 with electronically
variable filter 433, FIG. 3C, allowing the wavelength transmitted
to be selected and processed by processing unit electronics
435.
[0057] Still referring to FIGS. 3A to 3E, in other configurations,
sensor 155 may be CCD chip 441 with filter window 443, FIG. 3D,
that varies over its length, allowing only certain wavelengths to
reach each portion of CCD 441, allowing decoding of the
illuminating wavelength by processing unit electronics 447.
Finally, in the preferred embodiment, FIG. 3E, sensor 155 comprises
CCD chip 451 with optical fibers 453 attached to CCD 451 in a
linear array. Fibers 453 are manufactured such that each fiber has
a different interference coating on end 454, allowing each fiber to
transmit a different narrow wavelength range, allowing decoding of
the illuminating wavelength by processing unit electronics 457.
Fibers 453 are biocompatible and can extend outside of device case
102, allowing device 101 to be placed remotely the target to be
monitored, and for the free end of fibers 453 to be placed in
proximity to target 125.
EXAMPLE
[0058] The breadth of uses of the present invention is best
understood by example. This example is by no means intended to be
inclusive of all uses and applications of the apparatus, merely to
serve as a case study by which a person, skilled in the art, can
better appreciate the methods of utilizing, and the scope of, such
a device.
[0059] In this example, an optical sensor, similar in basis of
operation to device 101, is implanted into abdomen of a patient
undergoing colon surgery. In this case, the animal receives
heart-lung bypass, such that the blood flow and oxygen content of
the blood is exactly controlled by a bypass specialist rather than
by the animal's own heart and lungs, affording the ability to
create and resolve ischemia at will. An aortic Doppler probe is
placed, which measures the delivery of blood to tissue. In this
case, when the rate of the pump is lowered to zero flow, ischemia
must exist in the tissues being monitored.
[0060] Analysis of the tissue ischemia is performed by broadband,
visible light, differential spectroscopy. In this technique, the
first differential (for example) of the wavelength vs. intensity
curve sent from the sending unit is processed to remove many of the
effects caused by light scattering by the local tissue, and the
resultant signal is analyzed using a least-squares minimization of
the fitting error to known components of the tissue (such as
myoglobin, capillary hemoglobin, or cytochromes).
[0061] The signal that is measured is a function of the presence,
absence, or risk, or degree of ischemia. This can have clinical
implications and applications in many different medical areas, such
as impending risk of tissue death (as seen in the colon study
above), impending risk of organ rejection (as inflammation results
in increased total blood content, while potentially reducing
oxygenation) cardiac function (as improved cardiac function is
associated with a body-wide improvement in tissue ischemia as well
as a likely improvement in myocardial ischemia), treatment efficacy
for arterial or venous vascular disease (as the real-time effects
of such interventions on tissue oxygenation adequacy can be used as
a treatment signal to guide chemical and physical interventions),
risk of renal damage (as kidney failure is often the result of
acute or chronic reduced oxygen delivery), risk of brain injury (as
stroke is often the result of acute and chronic reduced oxygen
delivery), risk of colon death (as the colon does not have a large
capacity to increase blood and oxygen delivery in times of stress
over baseline), risk of limb amputation (as limbs with good
capillary saturation are more likely to heal and not require
amputation), risk of ulcer healing (as G.I. and diabetic ulcers are
more likely to heal if ischemia is not the only ongoing problem),
and risk of critical limb ischemia (as limb salvage is always
better if possible, but delays resolution of ischemia and presents
a risk to the patient if delayed when amputation is required).
[0062] As shown in FIG. 4, the creation of graded ischemia is
detected by the present invention. In graph 601, the flow detected
by the Doppler probe is plotted on horizontal axis 603 versus the
presence of ischemia as detected by the present invention using
optical spectroscopy plotted on vertical axis 607. Data are plotted
as means with standard error bars 613. As can be seen on graph 601,
when the blood flow to the gut is reduced to zero, the detection of
the presence of ischemia rises to 100%, shown at data point
617.
[0063] It is important to note that the measurement of
flow/perfusion alone, or the measurement of blood oxygenation (not
tissue oxygenation, but oxygenation of the arterial blood) alone
are not sufficient to detect the condition of ischemia. Ischemia is
diagnosed by low local tissue oxygenation, not blood oxygenation or
flow. In some cases, arterial blood may be well oxygenated, but the
delivery of this arterial blood to the tissue is insufficient (such
as with a blood clot); in this case the tissue is indeed ischemia
while the arterial blood oxygenation is normal. Blood flow also
differs from a direct measure of ischemia. For example, in a cooled
patient on heart-lung bypass, blood flow may be very, very low;
however, the cooled tissues, whose oxygen need has been reduced by
the low temperature, are not ischemic. Similarly, a chronically
ischemic heart "hibernates" in order to reduce its own oxygen need,
and may not be ischemic at reduced flow. In the above animal study
example, flow was controlled sufficiently to allow for a low or
zero flow to be consistent with ischemia, but such conclusions
cannot be always made so clearly in the living non-experimental
subject.
[0064] Also, in the example above, power was provided to the device
externally. However, as noted earlier, an integrated battery or set
of batteries can provide power from within the device, reducing
cost of the connection tip. An added advantage of this
battery-based approach is that it removes the need for electrical
connection to the light source, as an added safety feature.
[0065] In this example, the signal detected from the tissue was a
hemoglobin absorbance signal derived from the capillary bed. While
absorbance is ideal for hemoglobin analysis, as described in the
preferred embodiment, other interactions may be preferable for
other measurements. The interaction with the illuminating light
that provides the contrast can include absorbance, polarization,
optical rotation, scattering, fluorescence, Raman effects,
phosphorescence, or fluorescence decay, and measures of a contrast
effect may reasonably include one or more of these effects. Other
tissue components could be measured, including NADH, NADPH,
cytochromes in their oxidized and reduced forms, or even ischemia
or oxygen sensitive dyes. Next, when monitoring muscle such as the
heart, myoglobin is another protein whose saturation is related to
the presence or absence of ischemia. In such cases, a combination
of hemoglobin in the capillaries as well as myoglobin in the heart,
or just myoglobin in the heart myocytes, can serve as a marker of
ischemia. Last, an injectable dye, sensitive to local ischemia, can
be used to generate an optical signal directly related to the
presence of ischemia, such as by changing color in response to
mitochondrial membrane charge or in response to intracellular pH.
Such use of dyes to label cells in vivo with optical dyes has been
demonstrated in vivo by several groups, and the coupling of an
ischemia sensitive dye to use of the present invention to detect
ischemia (and conditions which are a function of ischemia) would
fall within the spirit of the present invention.
[0066] We have discovered an implantable ischemia detector for
detecting local tissue ischemia in a quantitative and enabling
manner in a broad array of target sites. In some embodiments a
device is provided comprising a phosphor-coated white LED and
integrated collimating optics conFig.d to produce continuous,
broadband light from 400 nm to 700 nm in a collimated beam, which
is then directly transmitted to a target site. Light backscattered
by the target site is collected by a sensor, allowing for a direct
measure of ischemia to be determined, and subsequently transmitted
by a sending unit. Power is provided by an internal power source,
which may in turn be itself powered by an external inductive coil
that is brought in proximity to the implanted device in order to
provide energy as needed. The entire implantable device is
encapsulated by a biocompatible shell to add long-term safety while
implanted. Used alone, or in combination with an estimate of
arterial oxygenation, venous oxygenation, or even of blood flow,
this device allows for an index of ischemia to be determined
without additional invasiveness beyond the initial implantation.
The present device may be interrogated using inductive technology
and RF coupling. Implantable devices incorporating the ischemia
system, and medical methods of use, are described. This device has
immediate application to several important problems, both medical
and industrial, and thus constitutes an important advance in the
art.
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