U.S. patent application number 12/101906 was filed with the patent office on 2008-08-07 for broadband solid-state spectroscopy illuminator and method.
Invention is credited to David A. Benaron, Michael R. Fierro, Illian H. Parachikov.
Application Number | 20080188727 12/101906 |
Document ID | / |
Family ID | 28674623 |
Filed Date | 2008-08-07 |
United States Patent
Application |
20080188727 |
Kind Code |
A1 |
Benaron; David A. ; et
al. |
August 7, 2008 |
Broadband solid-state spectroscopy illuminator and method
Abstract
An improved spectroscopy illuminator (103) for generating
broadband light and for delivering the light to a sample with an
improved delivery efficiency, for higher optical density and/or
reduced thermal transfer uses a solid-state broadband white LED
(107) to produce broadband light (114), which is then transmitted
to a sample region (125), such as a living tissue or blood in vivo
or a biological sample in a spectrophotometer target region. The
solid-state source keeps both the illuminator and sample cool
during operation, allowing the illuminator to be integrated into
the tip of a medical probe, a medical system such as an oximeter,
or other monitoring systems or devices making measurements based on
light scattering, absorbance, fluorescence, phosphorescence, Raman
effects, use of a contrast agent, or other known spectroscopy
techniques. Systems incorporating the improved illuminator, and
methods of use are also disclosed.
Inventors: |
Benaron; David A.; (Portola
Valley, CA) ; Parachikov; Illian H.; (Belmont,
CA) ; Fierro; Michael R.; (Los Gatos, CA) |
Correspondence
Address: |
MORGAN, LEWIS & BOCKIUS, LLP.
2 PALO ALTO SQUARE, 3000 EL CAMINO REAL
PALO ALTO
CA
94306
US
|
Family ID: |
28674623 |
Appl. No.: |
12/101906 |
Filed: |
April 11, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11820809 |
Jun 20, 2007 |
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12101906 |
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11451681 |
Jun 12, 2006 |
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11820809 |
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10651541 |
Aug 29, 2003 |
7062306 |
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11451681 |
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10119998 |
Apr 9, 2002 |
6711426 |
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10651541 |
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Current U.S.
Class: |
600/323 ;
600/477; 600/509 |
Current CPC
Class: |
A61B 5/0075 20130101;
A61B 5/0084 20130101; G01J 3/10 20130101; A61B 5/1459 20130101;
A61B 1/00165 20130101; A61B 5/412 20130101; G01N 2201/062 20130101;
A61B 5/42 20130101; A61B 5/14558 20130101 |
Class at
Publication: |
600/323 ;
600/509; 600/477 |
International
Class: |
A61B 5/1455 20060101
A61B005/1455; A61B 5/0402 20060101 A61B005/0402 |
Claims
1-23. (canceled)
24. A broadband illuminator for use in illuminating spectroscopy
samples comprising at least one solid-state broadband light source,
wherein the broadband spectroscopy source emits useable light over
a wavelength range of 40 nm or more.
25. A broadband illuminator for use in illuminating spectroscopy
samples comprising at least one solid-state broadband light source,
wherein the broadband spectroscopy source emits useable light over
a wavelength range of at least 100 nm.
26. A broadband illuminator for use in illuminating spectroscopy
samples comprising at least one solid-state broadband light source,
wherein the solid-state broadband light source emits useable light
over a wavelength range of at least 100 nm, and wherein said
solid-state broadband light source is a broadband LED.
27. The illuminator of claim 24, 25 or 26, wherein said illuminator
is incorporated into a device or system.
28. The illuminator of claim 27, wherein the device or system is
configured to enable an analysis performed using at least a portion
of the light returning after interaction with the sample.
29. The illuminator of claim 27, where said device or system is
selected from the group of devices or systems consisting of:
spectrophotometers, microdevices, microchip, lab-on-a-chip, or
other small optical device with space and size constraints,
disposable optical devices, or other optical spectroscopy devices
and systems.
30. The illuminator of claim 28, further comprising an analysis
system configured to perform the analysis by solution of multiple
simultaneous spectroscopic equations.
31. The illuminator of claim 24, 25, or 26, further wherein said
illuminator is incorporated into a medical device or a medical
system.
32. The illuminator of claim 31, wherein the medical device or
medical system is selected from the group of medical devices and
systems consisting of: probes for medical endoscopic use,
targetable injection needles, catheters, needles, catheters with
extendable needles, nibblers, devices with jaws, scissors, probes
that measure colon oxygenation, probes that measure by pulse
oximetry, probes that measure arterial oxygenation, probes that
measure oxygen delivery to the body's core organs, probes that
measure in the gastrointestinal system including could reasonably
include the oropharynx, nasopharynx, esophagus, stomach, duodenum,
ileum, colon, or other gastrointestinal tissues.
33. The illuminator of claim 31, wherein the medical device is a
probe configured for use in measuring oxygenation.
34. The illuminator of claim 31, wherein the medical device is an
oximeter probe.
35. The illuminator of claim 31, wherein the medical device is a
probe is configured to monitor any one or more of: met-hemoglobin,
carboxy-hemoglobin, and other blood components.
36. The illuminator of claim 36, wherein the monitoring of
met-hemoglobin, carboxy-hemoglobin, and other blood components is
achieved by pulse oximetry.
37. The illuminator of claim 31, wherein the medical device is
configured to identify tissue by type or state.
38. The illuminator of claim 24, 25 or 26, wherein the illuminator
is a medical device configured for use inside, or in contact with,
living tissue.
39. The illuminator of claim 24, 25, or 26, wherein the illuminator
is incorporated into a spectrophotometer.
40. The illuminator of claim 24, 25, or 26, wherein the light is
pulsed.
41. The illuminator of claim 24, 25, or 26, wherein the illuminator
is incorporated into a system where the light is analyzed as
time-resolved, frequency-resolved, or spatially-resolved.
42. The illuminator of claim 26, wherein the broadband LED is
comprised of multiple light emitting elements to produce a
broadband and continuous spectrum of light.
43. The illuminator of claim 42 wherein the multiple light emitting
elements are comprised of a combination of different light emitting
diodes.
44. The illuminator of claim 43 wherein each of the multiple LEDs
operate in at least one wavelength band.
45. The illuminator of claim 26, wherein the broadband LED is a
white LED
46. The illuminator of claim 26, wherein the broadband LED
comprises a blue LED and a phosphor.
47. The illuminator of claim 26, wherein the broadband LED
comprises an LED and a fluorescent dye.
48. The illuminator of claim 24, 25, or 26, wherein the illuminator
operates to produce at least a portion of its light in the infrared
spectrum.
49. The illuminator of claim 24, 25, or 26, wherein the illuminator
operates to produce at least a portion of its light in the
ultraviolet spectrum.
50. The illuminator of claim 24, 25, or 26, further comprising a
target signal, where said target signal is enhanced, produced, or
detected, at least in part, by one or more of the following: light
absorbance, polarization, optical rotation, scattering,
fluorescence, Raman effects, phosphorescence, fluorescence decay,
re-emission, use of a contrast agent, dye shift, or other
spectroscopy techniques.
51. The illuminator of claim 24, 25, or 26, wherein the illuminator
is incorporated into a pulse oximeter.
52. The illuminator of claim 24, 25 , or 26, wherein the
illuminator is incorporated into a medical device that analyzes
hemoglobins selected from the list of hemoglobins consisting of:
methemoglobin, carboxyhemoglobin, and hemoglobins blood
components.
53. A spectroscopy method comprising: illuminating a sample with a
broadband illumination from a broadband solid-state illuminator,
wherein said broadband illuminator emits useable light over a
wavelength range of at least 100 nm; and performing optical
spectroscopy.
54. The method of claim 53, wherein the illuminator is a broadband
LED.
55. A spectroscopy method wherein illumination of a sample is
achieved using a broadband LED.
56. The method of claim 53 or 55, wherein performing optical
spectroscopy further includes: obtaining a target signal, where
said target signal is enhanced, produced, or detected, at least in
part, by one or more of the following methods: light absorbance,
polarization, optical rotation, scattering, fluorescence, Raman
effects, phosphorescence, fluorescence decay, re-emission, use of a
contrast agent, dye shift, or other spectroscopy techniques.
57. The method of claim 54, wherein the broadband LED is comprised
of multiple light emitting elements to produce a broadband and
continuous spectrum of light.
58. The method of claim 57 wherein the multiple light emitting
elements are comprised of a combination of different light emitting
diodes.
59. The method of claim 58 wherein each of the multiple LEDs
operate in at least one wavelength band;
60. The method of claim 54 wherein the broadband LED is a white
LED.
61. The method of claim 53 or 55, wherein the illuminator is
incorporated into a pulse oximeter.
62. The method of claim 53 or 55, wherein the illuminator is
incorporated into a medical device that analyzes hemoglobins and
further including the step of monitoring hemoglobins selected from
the list of hemoglobins consisting of met-hemoglobin,
carboxy-hemoglobin, and other hemoglobins.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 11/451,681 filed on Jun. 12, 2006, relating to
the detection of local tissue ischemia, which is a
continuation-in-part of U.S. patent application Ser. No. 10/651,541
filed on Aug. 29, 2003, now U.S. Pat. No. 7,062,306; which is a
continuation of U.S. patent application Ser. No. 10/119,998 filed
on Apr. 9, 2002, now U.S. Pat. No. 6,711,426, the disclosures of
all of which are incorporated in full by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to devices and methods for
providing, simultaneously or near-simultaneously, spectroscopic
analysis from more than one somatic site, and more particularly
relates to the determination of a difference-weighted analysis
wherein the near-simultaneous determination of two (or more)
spectroscopically-determined somatic oxygenation saturation values
is performed in a manner allowing for the direct and
near-simultaneous comparison of these two (or more) somatic
saturation values, by direct mutual inspection or computational
means, in order to provide synergistic and added medical value
above that provided by each individual value considered separately.
In another aspect, the present invention provides real-time
spectroscopic analysis of in-vivo tissue perfusion from more than
one somatic site that is sensitive to local tissue ischemia and
insensitive to regional arterial and venous oxygenation.
BACKGROUND OF THE INVENTION
[0003] Ischemia, defined as a reduction in blood flow, can be due
to local causes (e.g., due to vascular occlusion or increased
metabolism such as a tumor), global causes (e.g., due to body-wide
reduced blood flow from reduced cardiac output), or both. However,
discriminating the source of changes in tissue oxygenation can be
difficult, considering values at each site individually.
[0004] Collecting spectroscopic values from two different sites
(e.g., organ versus organ, or two sites within the same organ), and
considering or analyzing these together as a difference-weighted
measure, can add medical value. For example, a growing difference
between a stable and normal cheek tissue oximetry, and a falling
colon tissue oximetry, points to a colon-centered pathology rather
than to a global cause such as impending cardiac failure.
Similarly, a widening difference-weighted measurement between a
pulse and tissue oximeter (estimates of arterial and venous
saturation, respectively), helps pinpoint the source of the change
as cardiovascular pathology, rather than increasing pulmonary
failure. Last, a widening spatial gradient, such as a
difference-weighted value between a pair of sensors that is scanned
over a single breast, reduces the noise from organ-wide regional
gradients and highlights local inhomogeneities associated with
tumors such as breast cancer. Each of these three exemplary
difference-weighted values add medical value above what the
absolute values, considered alone and separately, would merit.
[0005] The noninvasive spectroscopic monitoring of hemoglobin
saturation in vivo is known in the art. The great majority of such
known devices and methods monitor only at one site (U.S. Pat. No.
6,662,033, WO/2003/003914); such devices do not allow for mutual or
computational determination of a difference-weighted value. A few
devices and methods in the art teach monitoring at more than one
sites. For example, U.S. Pat. No. 6,615,065 describes dual
monitoring of the brain, wherein the two sensors are applied to a
head of the test subject, taking advantage of the unique
hemispheric and non-somatic structure of the brain, to monitor two
mutually separate regions within a brain of the test subject, with
the two values being simultaneously displayed to allow a user to
observationally and mutually compare the two. No computational
comparison is taught. Further, the '065 patent teaches that it is
the unique, hemispheric structure of the brain that allows the
device of '065 to operate, and thus the device would not be
suitable for somatic monitoring. In contrast, clinicians recognize
that the non-brain (the "somatic") regional of the body constitute
an advantageous early warning system not present in the brain, and
are some of the first key tissues to be shut down by the body
during impending failure of oxygen delivery to tissue. Similarly,
U.S. Patent Application Publication no. 2006/0105319 describes the
measuring of two values, arterial and venous. However, again no
computational comparison is taught, and one of these values is
determined through invasive blood sample, not from
spectrophotometric measurement of tissue itself.
[0006] All of the above devices are limited to being single
measures of oxygenation, are limited or optimized by design or
omission to non-somatic tissue, and/or do not allow direct and
near-simultaneous mutual comparison or computational processing of
at least two somatic values obtained by spectrophotometric
measures.
[0007] None of the prior devices or methods allow for a
difference-weighted spectroscopy that facilitates simultaneous or
near-simultaneous comparison of spectroscopic values from two
somatic regions or sites by inspection or computation. Such a
system has hot been previously described, nor successfully
commercialized. Thus, further developments are needed.
SUMMARY AND OBJECTS OF THE INVENTION
[0008] The inventors have discovered that certain diseases
(vascular ischemia, cancer) are frequently localized, and by
comparing at least two somatic values--either multiple sites or
times--within the body, resulting in a more sensitive detection of
such local conditions.
[0009] A salient feature of the present invention is that the
detection and treatment of diseases such as somatic ischemia or
cancer is aided by use of at least two measurements--either by
multiple somatic sensors monitoring at least two nearby or distant
regions or by dual measurements made by a single sensor over space
or time--allowing a direct comparison of these different
spectroscopic values by mutual inspection or computation.
[0010] In one aspect, the present invention provides a somatic
monitoring apparatus comprising: a first and second sensor, each
configured to generate, based upon light produced and/or detected
by each sensor, first and second somatic output signals that are a
function of each somatic target site, and a difference unit for
comparing said first and second signals, and for generating a
difference-weighted output signal based upon this comparison.
[0011] In other embodiments, this dual-sensor somatic tissue
ischemia monitoring apparatus generates an output signal that is a
function of the presence or degree of local tissue ischemia or
cancer at a first and second target site, with a display unit
configured to display or allow near or substantially simultaneous
comparison of said signals at the two target sites. This can be
expanded to N sensors, with comparisons of a first through Nth
output signals via a difference unit configured to compare at least
two of said first through Nth somatic signals, and to generate a
difference-weighted output signal based upon said comparison.
[0012] In yet another aspect, the difference measurement can be
generated using a single sensor moved through space (allowing
comparison of two sites with one detector), or used over time (such
as reporting changes with time), or even measuring both arterial
and tissue oximetry measurements using one probe (allow
arteriovenous differences to be detected).
[0013] In embodiments of the present invention, we provide both
apparatus and methods for the dual, N, and signal sensor
approaches. In one embodiment of the invention there is provided a
device with dual somatic spectroscopic monitoring sites, including
two solid state broadband light sources and sensors for generating,
delivering, and detecting light from at least two target sites, for
the purpose of allowing a direct comparison of the spectroscopic
values by mutual inspection or computation, thereby adding medical
value. In another example, the system uses dual phosphor-coated
white LED's to produce continuous, broadband, visible light from
400 nm to 700 nm at two somatic sites. Scattered light returning
from each target is detected by a wavelength-sensitive detector,
and two signals, one from each site, is generated using this
wavelength-sensitive information via spectroscopic analysis. The
values are displayed or computed in a manner to allow direct
comparison of the spectroscopic values by mutual inspection or
computation. Systems incorporating the difference-weighted somatic
spectroscopic system arid medical methods of use are described.
[0014] Some embodiments the present invention further provide a
device for detecting local ischemia in a tissue at one or more
tissue sites, characterized in that the device is configured such
that wavelengths of light are selectively emitted, and the
selective wavelengths are substantially transmitted through
capillaries in tissue while being substantially absorbed by
arterial and venous vessels in the tissue.
[0015] As will be understood by the detailed description below, the
somatic monitoring apparatus provides one or more advantages. For
example, by way of illustration and in no way limiting the
invention, one advantage is that the system and method may be
constructed to detect ischemia, cancer, or changes in
perfusion.
[0016] Another exemplary advantage is that a physician or surgeon
can obtain improved real-time feedback regarding local tissue
ischemia, cancer, or perfusion in high-risk patients, and to
respond accordingly.
[0017] Another exemplary advantage is that ischemia (low delivery
of oxygen to tissues) can be differentiated from pulmonary-induced
hypoxemia (low arterial saturation).
[0018] Yet another exemplary advantage is that local changes in
oximetry (vascular disease) can be differentiated from mixed or
global changes (low cardiac output).
[0019] Another advantage is that the detector of the present
invention may 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, based upon the
detection and degree of local ischemia. 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.
[0020] 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 tested in human
subjects. 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
[0021] 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 device. These and other advantages of
the present invention will become apparent upon consideration of
the following detailed description, taken in conjunction with the
accompanying drawings, in which like reference characters refer to
like parts throughout, and in which:
[0022] FIG. 1 a schematic diagram of a difference-weighted
spectroscopy system incorporating a white LED and constructed in
accordance with embodiments of the present invention;
[0023] FIG. 2 shows a medical monitor system constructed in
accordance with embodiments the present invention;
[0024] FIG. 3A shows a pulsatile broadband signal intensity using a
single probe monitor constructed to monitor both arterial and
capillary saturation in accordance with some embodiments of the
present invention;
[0025] FIG. 3B shows a peak systolic and trough diastolic pulse
oximetry signal measured using a single probe difference monitor
constructed in accordance with some embodiments of the present
invention; and
[0026] FIG. 4 shows an exemplary sensor probe having one light and
two (dual) monitoring fibers for monitoring two closely located
sites, in this case located at different depths in a tissue,
according to some embodiments of the present invention.
DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
Definitions
[0027] For the purposes of this invention, the following
definitions are provided for illustration purposes. These
definitions are not intended to limit the scope of the
invention:
[0028] Head or Cranial: Associated with the Head or Skull,
respectively, as opposed to the body tissue (c.f., Somatic, below).
Stedman's Medical Dictionary, 27th edition, states that cranial is
"Relating to the cranium or head." Blood perfusion to the brain and
head, via the carotid supply, can be very different than to somatic
tissues, such as liver, intestine, heart, kidney, and others.
[0029] Somatic: Tissue in the body and central organs, as opposed
to the brain (c.f., brain). Stedman's Medical Dictionary, 27th
edition, states that this is "[r]elating to the soma or trunk".
Organs within the body are considered somatic tissues, and include
the liver, spleen, intestine, heart, kidney, muscle, and pancreas.
Oxygenation and measures in somatic tissues are central to
monitoring for sufficiency of oxygen delivery to tissue in the body
as a whole.
[0030] Ischemia: A condition in which the perfusion of a tissue is
locally inadequate to meet its metabolic needs. Ischemia is
distinguished from low blood flow per se in that low blood flow
alone does not guarantee ischemia (such as during tissue cooling on
which flow can be low without significant ischemia), nor does high
flow rule out or prevent ischemia (such as during sepsis or when
the blood delivered does not contain adequate oxygen). Ischemia is
a co-existing condition in many different types of illnesses,
including infection (sepsis), tissue rejection (host vs. graft
disease), heart attack (myocardial ischemia), stroke (cerebral
ischemia), acute or chronic organ failure, diabetic peripheral
vascular disease, and other conditions.
[0031] Perfusion: The flow of blood or other perfusate per unit
volume of tissue, as in ventilation/perfusion ratio. Reduction in
perfusion is a major clinical problem, and it is associated with,
but not equivalent to, ischemia.
[0032] Difference-Weighted: A measurement that is formed from the
direct or indirect comparison of two or more oxygenation values,
such as somatic venous saturation at organ A to somatic venous
saturation of organ B. Another difference measurement is the
difference between arterial and venous saturation such as described
in detail in co-pending U.S. patent application Ser. No.
11/451,681. Another difference measure is the comparison of a
measured value to a baseline or historical value.
[0033] Spectroscopy. Measurement of material, including tissue,
using light. Such measures can involve a spectrum composed of only
a few wavelengths, such as two discrete wavelengths, or can involve
a spectrum recorded over a range using a broadband light source,
and a wavelength-resolved detector.
[0034] One embodiment of the device will now be described. This
device has been built in prototype form, tested in the laboratory
under experimental conditions, and tested on animals under Animal
Study Review Board approval, as shown in some of the data which
follow the initial description of one embodiment of the system.
[0035] A cut-away schematic showing the interior of spectroscopic
device or apparatus 101 according to embodiments of the present
invention is shown in FIG. 1. Device 101 is preferably surrounded
by soft silicone exterior shell 102, permitting a good grip while
scanning device 101 across a target region, or for implantation for
chronic monitoring. Typically, exterior shell 102 is constructed
from approved Class VI biocompatible materials as recognized by the
U.S. FDA or other medical device regulatory agencies. Portions of
sensor 155, power source 179, light source LED A 103A and LED B
103B, or other components may protrude as needed from this shell
within the spirit of this invention, provided that the protruding
parts themselves are biocompatible as required.
[0036] Within device 101, source LED 103A is illustrated in its
component parts. Broad spectrum white light is emitted by a high
conversion-efficiency white LED 105 (e.g., The LED Light, model
T1-3/4-20W-a, Fallon, Nev.). Source 105 is itself embedded into a
plastic beam-shaping mount using optical clear epoxy 111 to allow
light generated in diode 105 to be collimated, thus remaining at a
near-constant diameter after passing through optical window 115A 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 first target region 123A in target 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.
[0037] A portion of the light reaching region 123A of target 125 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.
[0038] Similarly, within device 101, there is a second light
source, LED 103B is illustrated in its component parts, constructed
in much the same manner as LED 103A, however light this time exits
by optical window 115B, to strike second target region 123B in
target 125. Again, a portion of the light reaching region 123B is
backscattered and returns to device 101 via light path vector 128,
to optical collection window 141, striking sensor 155.
[0039] Sensor 155 may be comprised of a number of discrete
detectors configured to be wavelength-sensitive, or maybe 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 to the
unit that determines a weighted difference, difference unit
167.
[0040] Light source 103A and 103B could be instead multiple, with
up to N light sources, constructed as described; or in a varying
manner. In any event, Light source 103A and 103B also has two
electrical connections 175 and 176, connecting light sources 103A
and 103B to power source 179. In this embodiment, power source 179
is an inductive power supply, capable of receiving an inductive
field from externally powered coil and RFID receiver. Such coils
and receivers are well known.
[0041] Operation of the device may now be described.
[0042] Device 101 is scanned across a breast, for example in a
patient being screened for breast cancer. The device may measure
the various components of the breast such as lipid and water,
and/or it may measure tissue hemoglobin saturation. It may be
placed on the breast 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.
[0043] 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. Power source 179
located within device 101, produces sufficient power for device 101
to power up and turn on. Light sources 103A, 103B, and others if
present, begin to illuminate the target 125, in this case heart
muscle. Sensor 155, which is an embedded spectrophotometer,
receives backscattered light, resolves the incoming light by
wavelength, a marker of ischemia. Under control Of lines 175 and
176, LED 103A is first scanned, with an estimated tissue saturation
(as determined by tissue oximeters arranged as known in the art,
for example, the commercially available T-Stat model 303 Tissue
Oximeter may be used, whose design and methods are incorporated
into this specification by reference) of 72%. Next, under control
of lines 175 and 176, LED 103B is illuminated, producing an
estimated tissue saturation of 72%. There values are sent to
difference Unit 167, and the difference is found to be zero, which
is the median value one expects in normal tissue without
cancer.
[0044] Once the measurement is completed, device 101 powers down
and returns to a resting state.
[0045] 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. Difference unit 167 may then transmit without
being directly queried, such as in response to a dangerous level of
ischemia.
[0046] The breadth of uses and the basis of the present invention
is best understood by example; and thus the detailed description
will be further illustrated by the following examples. These
examples are 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.
EXAMPLE 1
Simultaneous Two-Site Two-Organ Somatic Difference Monitoring
[0047] In this example, a clinical application related to ischemia
is described. Here, a surgeon is repairing the aorta. There are
several reasons why the local tissue oxygenation may fail. For
example, the patient is under anesthesia, and a general depression
(reduction) of cardiac output may occur. If so, the delivery of
oxygen to all parts of the body will fall. On the other hand, if
the blood vessel supplying the colon, which arises in part from the
aorta, is occluded, then the saturation to the colon will fall, but
not the saturation to the cheek. Therefore, by looking at the
saturation of both the cheek and colon at substantially the same
time, or by displaying a difference between the two values, the
cause of the drop in local oxygenation may be determined to be
either local and due to the vascular repair (e.g., large
difference, in this case the absolute value of |.DELTA.0
saturation|>10%) which is an indication of local ischemia, or
systemic and due to hypotension or cardiac failure (e.g., small
difference, in this case the absolute value of |.DELTA.
saturation|<10%), which is an indication of systemic
ischemia
[0048] This is shown in the following table:
TABLE-US-00001 TABLE 1 The difference (.DELTA.) between check and
colon oxygenation is small (|<10%|) under normal conditions, and
during system- wide, whole-body, global reductions in heart output,
hematocrit, or oxygenation from the lungs. In contrast, a large
difference between check and colon oxygenation (|>10%|) is a
sign of disparate flow, and likely of local ischemia. Cheek
(Buccal) Gut (Colon) .DELTA. Local Site Oxygenation Oxygenation
Cheek - Colon Ischemia? Normal 76% 71% +5% No Low He art 42% 48%
-6% No Output Bad Colon 76% 22% +44% YES Artery
[0049] A device displaying two values, simultaneously or
near-simultaneously measured, as well as a difference-weighted
value display, is shown in FIG. 2 according to some embodiments of
the present invention. Monitor or display 313 has two somatic
probes 183 and 185 attached, each placed at difference sites. This
number of probes could, for other embodiments, be any number of N
probes, where N is two or more, within the spirit of the invention.
Monitor 313 displays the results of these two sites of measurement,
as well as a veno-venous(or .DELTA.) difference of 64%. In other
embodiments, the display of N values itself allows a user to
manually and directly compare the two values, adding medical value,
or alternatively, only the difference-weighted value alone could be
displayed, within the spirit of the invention. In view of this
large, calculated veno-venous difference, alert 322 is displayed to
the user.
[0050] Note that near-simultaneous display of the measurement of
two or more somatic sites, in this case somatic tissue oxygenation
as compared at two sites using a dual-site somatic tissue oximeter
constructed in accordance with the present invention, allows either
a direct, mutual comparison by an observer of these two displayed
values, or a calculation or computation, and then display of, this
difference-weighted value. Each of these, dual display for direct,
mutual inspection, or calculation of a processed, weighted
difference, can be a useful difference-weighted measurement.
Further, it is noted that this difference-weighted value is
inherently advantageous, adding medical value and relevance to
either value taken alone and singly, such as by allowing detection
of a local or regional ischemia with better precision, or faster
recognition of an ischemic event, or by allowing more rapid
identification of the source (cardiac/pulmonary) of the low
oxygenation, among advantages illustrated herein. Other advantages,
not discussed here, may be learned, and are incorporated into the
broad list of medical advantages intended within the scope of the
present invention. It is not intended that the medical advantages
be subject to limitation by omission of such additional
advantages.
EXAMPLE 2
Simultaneous Two-Site Single-Organ Somatic Difference
Monitoring
[0051] In the example above, two different organs were studied. In
this example, the monitoring of a single organ, the breast, is
described. It is toward this Example that the embodiment of FIG. 1
is directed.
[0052] In breast cancer, the detection of angiogenesis, the
proliferation of new blood vessels, is a key feature of cancer that
lets the cancer gain the ability to grow and spread. However, the
background variation in blood content in the breast between women
of different ages and breast composition makes the use of a
single-site blood-content threshold less useful than it could
otherwise be. That is, the range of normal blood content in breast
tissue between different women is so large that the increase in
blood due to cancer can be lost in that broad range.
[0053] To illustrate this, consider data from women with breast
cancer. By looking at the difference measurement of the oxygenation
at one location on the breast as compared to another
near-simultaneously or simultaneously measured point of the breast,
and by displaying this difference, local tumor ischemia can be
detected to be present (large local difference, in this case the
absolute value of .DELTA. saturation>10%) or not present (small
difference, in this case the absolute value of .DELTA.
saturation<10%), as shown:
TABLE-US-00002 TABLE 2 The difference in oxygenation between two
nearby regions of the human breast is small under normal
circumstances. A tumor produces a local region of a high gradient
of change in oxygenation (and also in deoxyhemoglobin content).
This difference can be lost in the local variations (sites A and B,
two sites within each region), but there is a large difference that
is a sign of a tumor when one sensor is near the tumor, and the
other is actually over the tumor. Breast Site A Breast Site B
.DELTA. Site Local Site Saturation Saturation A - B Ischemia?
Normal 1 76% 74% +2% No Normal 2 71% 68% +3% No Normal 3 63% 66%
-3% No Tumor 4 78% 66% +12% YES
[0054] This Site A vs. Site B comparison gains utility because the
local variations in oxygenation within a region (at two sites) are
small, but the variations between patients is large. In Error!
Reference source not found. 2, the range of normals above is 15%,
but by looking at differences between sites, only one patient is
seen to have cancer.
EXAMPLE 3
Multi-Site Single-Organ Somatic Difference Monitoring
[0055] In the above example, pairs of data were taken, one pair at
a time. In this example, instead of plotting values from a single
pair, embodiments of the present invention provide for plotting
real time difference values from many measures at many sites.
[0056] Again, using data from human subjects with and without
breast cancer, the following table can be generated. Such
differences can be found by having a difference in spatial
separation at two points, as shown as the difference (delta) values
at 5 sites labeled A-E on each subject, as follows:
TABLE-US-00003 TABLE 3 The Spatial difference at multiple sites by
plotting differences, reduces the noise in breast tissue
saturation, and allows simple detection of tumor near site C of
Patient Tumor 4, in which the saturation difference has a negative
then positive deflection (or vice-versa) during scanning. Patient
.DELTA. Site A .DELTA. Site B .DELTA. Site C .DELTA. Site D .DELTA.
Site E Normal 1 2% 4% -3% 5% -3% Normal 2 0% -2% 3% 2% -3% Normal 3
1% 4% -1% -4% -1% Tumor 4 -1% -4% -18% 13% 3%
[0057] Alternatively, the above differences can be found by a
single emitter/detector pair that is scanned over the tissue. Using
a 3-D positional sensor (X-Y-Z) or 2-D surface motion sensor (such
as the motion detection pad from an optical mouse, based upon a LED
and CCD to detect translation across a surface), measures can
betaken a multiple real-time instances during motion, and the delta
value calculated from the different positions of the detector. So,
at time zero there is no delta, while at time 1 the delta is the
time 1 value minus the time 0 value, at time 2 the delta is the
time 2 value minus time 1, and so on.
EXAMPLE 4
Difference Abdominal Monitoring For Necrotizing Colitis
Detection
[0058] In this example, the monitoring of the premature newborn
abdomen is described. A baseline probe is placed over another
tissue, such as the buccal mucosa.
[0059] As a probe is scanned across the abdomen of normal infants
and across one with a regional portion of bowel with low
oxygenation, the following table is created:
TABLE-US-00004 TABLE 4 The difference display allows the values
abnormal for the oxygenation status to show ischemic necrotizing
enterocolitis at sites C and D of patient Ischemia 4 to be
displayed and/or detected. Patient .DELTA. Site A .DELTA. Site B
.DELTA. Site C .DELTA. Site D .DELTA. Site D Normal 1 -4% 3% -3%
-6% 1% Normal 2 0% 6% 2% -4% -2% Normal 3 -4% 0% 2% 3% 5% Ischemia
4 3% 5% -22% -37% -10%
[0060] In each of these cases, the medical accuracy and value of
these measurement comes from or is enhanced by the simultaneous
measurement of two or more somatic sites.
[0061] It goes without saying that other configurations and
embodiments shall fall within the spirit of the invention, provided
that two or more measures in the body are provided more or less
simultaneously. For example, the reverse situation, in which one or
more sensors and a single light source is used is well within the
spirit of the invention, as are multiple sensors and multiple
sources, provided that more than one location is measured more or
less contemporaneously, to allow an enhanced value from
simultaneous measures.
[0062] Last, an advantage is simply that the user can use one
monitor at multiple sites, without having to purchase multiple
monitors.
EXAMPLE 5
Single or Dual Site Arterio-Venous Difference Monitoring
[0063] In prior examples, venous or tissue oxygenation values were
compared. In this example, arterial and venous values are compared
according to another aspect of the present invention.
[0064] We have shown that the difference between a pulse oximeter
and a tissue oximeter, one showing arterial and the other showing
venous saturation, allows ischemia (low tissue oxygen delivery) and
hypoxemia (low arterial blood saturation) be distinguished as
described in more detail in co-pending parent application U.S. Ser.
No. 11/451,681, the entire disclosure of which is hereby
incorporated by reference. Embodiments of the present invention
employ this difference arterial and venous saturation into a
real-time calculation, and make it possible for real-time
monitoring previously not available.
[0065] In the table below, values of tissue and arterial values
measured in animals are summarized. By making this a real-time
calculation, these values could be demonstrated in real time,
rather than determined after the fact, as had been performed in
these earlier data:
TABLE-US-00005 TABLE 5 The difference display allows the
differences, here calculated after the fact by separate measures,
to be displayed. Values for Normoxia, Hypoxemic Hypoxia, and
Ischemic Hypoxia (low flow and delivery) to be distinguished in
animal and human models (from Benaron et al, Anesthesiology, 2004).
Normoxia Hypoxemic Hypoxia Ischemic Hypoxia Subject (.DELTA.
saturation %) (.DELTA. saturation %) (.DELTA. saturation %) Human
21-29% 16% 51-91% Animal 25-28% 22-38% 66-83%
[0066] In this example, this table can be incorporated into monitor
313 of FIG. 2, in which the difference value of 64% is used to turn
on ischemic hypoxia alert 322. Again, by making this a real-time
calculation, these values could be demonstrated in realtime, rather
than determined after the fact, as had been performed in these
earlier data.
[0067] In some embodiments, a device is provided with dual somatic
spectroscopic monitoring sites where light sources and sensors
generate and detect light from at least two tissue target sites and
are configured to emit light at selective wavelengths where the
selective wavelengths are substantially transmitted through
capillaries in tissue while being substantially absorbed by
arterial and venous vessels in the tissue. This aspect is described
in detail in co-pending U.S. patent application Ser. No. 11/451,681
filed on Jun. 12, 2006, the entire disclosure of which is hereby
incorporated by reference. More specifically, in some embodiments
the device of the present invention is configured to operate at a
wavelength range, such as a range of 400 to 600 nm, and more
specifically blue to green visible illuminating light (at around
500 nm). The inventors have discovered that this range of
wavelengths penetrates larger vessels very poorly while being
relatively highly transmitted by the capillaries, thus allowing
sensitivity of the ischemia measurement at the two or more tissue
sites to be increased. This is wavelength range is taught away from
by oximetry art, which instead is focused on the advantages of near
infrared light. This locally-weighted and microvascular-weighted
measurements to detect ischemia in a local portion of a target
tissue site may be utilized to determine the difference in
measurements between two or more somatic monitoring sites. A
locally-weighted measurement, as used herein, is a measurement that
is weighted toward the condition of a local tissue near a sensor
probe,, rather than the blood flowing in the larger vessels that is
not in physiological contact, e.g., capable of direct and
significant oxygen exchange, with that local tissue. A
microvascular-weighted measurement is a measurement that is
weighted toward the smallest vessels, such as those having 20
microns or smaller, rather than to the blood flowing in the larger
vessels that is not in physiologic contact with the local
tissue.
[0068] Due to the deep penetration of large vessels by infrared
(and red) light, using infrared or red light to measure light
transmittance and absorbance through tissue reflects a wide range
of vessel sizes and results in measurements that are not
substantially locally-weighted or microvascularly-weighted. In
contrast, a blue-green weighted measurement penetrates larger
vessels poorly but capillaries well, and does not travel to
sufficient depths that would force inclusion of many large vessels.
That is, using blue-green light to measure light transmittance and
absorbance through tissue results in a substantially
locally-weighted and microvascular-weighted measurement. This is
non-obvious and counterintuitive to the prior art, which tends to
teach the use of infrared light for its tissue-penetrating ability
and against the use of the shallow-penetrating blue end of the
visible spectrum.
[0069] Another aspect of the arterial-venous approach is that it
can be performed using the present invention, in the absence of a
pulse oximeter, but with the a dual or single site multispectral or
broadband tissue oximeter alone. This was first measured by one of
the inventors in the present invention in the 1990's, and has now
been further developed and an enabling embodiment invented using
the device as disclosed in the present invention, with measurement
even using a single probe over time produces multispectral pulse
oximetry plethysmograph 403, as reflected in data collected from a
human subject in FIG. 3A. The intensity of the signal changes for a
wide range of wavelengths over time, between a minimum to a maximum
intensity, in a pulsatile manner. The maximum absorbance occurs
during the period the tissue is most filled with blood (usually
near the peak of systolic arterial blood pressure, but sometimes
associated with the transmitted pressure of a ventilator breath, or
other blood volume changes), which corresponds to local pulsatile
absorbance maximum 411. Similarly, as the tissue blood content
falls, there is a minimum absorbance during the period the tissue
is least filled with blood (usually near the end of the diastolic
arterial blood pressure resting phase, but sometimes associated
with the release of pressure of a ventilator breath, or other
changes), which corresponds to local pulsatile absorbance minimum
419.
[0070] The important issues of the combined measurement of the
pulse and tissue oximetry signals here are several-fold. First, by
measuring both the venous and the arterial signal, the difference
measurement can be obtained using a single probe, or by two tissue
oximetry probes, wherein the arterial pulsations can be analyzed
using conventional or proprietary pulse oximetry techniques
(computer analysis of the difference signal, ratios at wavelengths,
or even using self-adjusting variable-weight signal extraction
technologies). Such a difference spectrum is illustrated for
broadband pulse oximetry in FIG. 3B, where systolic peak absorbance
signal 424 and diastolic trough absorbance signal 426 can be
subtracted to produce delta signal 432. Delta signal 432 may then
be further analyzed to determine an arterial saturation estimate.
Unsubtracted peak absorbance signal 424 and diastolic trough
absorbance signal 426 can then be analyzed (separately or as an
average) to yield a conventional tissue capillary oximetry signal,
as disclosed in this, invention. The difference weighted measure
here is then the arterial minus the venous signal, as described
earlier in this example.
[0071] The ability to generate a perfusion measurement warrants
some attention here. The magnitude of variation in with time of
delta signal 432 (either in absolute terms, as a fraction of the
total hemoglobin signal, or as a volume-corrected signal) can be
used as a perfusion index. Another measure of perfusion is the A-V
difference itself, which given a fixed amount of oxygen extraction
by the tissue, widens as the inverse of the A-V (or pulse minus
tissue) difference. For example, if the perfusion falls in half,
and the arterial saturation is 100%, one would expect the tissue
saturation to fall from 70% (30% difference) to 40% (60%
difference, or twice 30%), in the absence of other physiological
corrections. Combination of magnitude of time-varying delta signal
432 and A-V difference measures, additionally even including other
measures such as laser Doppler capillary velocity that are known in
the art or correction of these signals for blood volume determined
optically, could be used to generate a more accurate or robust
perfusion index, all optically determined or even augmented with
other flow-sensitive methods such as ultrasound Doppler.
EXAMPLE 6
Layer-Stripping Difference Monitoring for Colon Ischemia
[0072] In the prior examples, oxygenation values were compared
using a simple subtraction. In this example embodiments of the
present invention provide an apparatus or device comprising a probe
with a single light source and two detection fibers at different
distances is used to monitor colon during interventional surgery.
Alternatively, the apparatus may be comprised of a probe with two
light sources and one detection fiber, or separate detection fibers
and separate light sources. Other arrangements may be used by those
of skill in the art, all of which are within the spirit of the
present invention.
[0073] When colon or intestine is joined at surgery, the joined
site is called the anastomosis. Leakage at the joining site, called
anastomotic leakage, occurs after surgery in 5%-14% of patients
undergoing esophageal, gastric, intestinal, and colon anastomosis,
typically several days to weeks after surgery. Leakage results in
gut and colon contents spilling into normally sterile body
cavities, and results in prolonged hospitalizations, sepsis, and
death. However, it is currently not predictable at the time of
surgery which patients will go on to leak, preventing additional
and known steps to be taken in the operating room that could help
avoid future leakage.
[0074] A high-specificity mucosal, intraoperative ischemia
detection system would permit real-time detection of patients at
risk for leakage, allowing for real-time surgical attempts at
correction of the problem. Leakage is, of course, multi-factorial,
but the cause of a leak is frequently local ischemia caused by poor
local perfusion, difficult access with insufficient "good" bowel to
sew to, preexisting infection, and difficult location that leads to
poor local perfusion. These each lead in turn leads to breakdown
and leakage at the site of anastomosis. By identifying the subset
of patients with poor perfusion and likely leak, those patients
would be able to be the focus of more invasive procedures,
procedures that would not be justified if used in all patients, but
certainly justified in patents at high risk for leak.
[0075] We tested the ability of this system to detect colon
ischemia, and found that in open surgery, the top few millimeters
oxygenate from the air, even if the gut is truly ischemic.
Therefore we constructed a scanner, such as that shown in FIG. 1,
in which optical illumination occurs at two difference locations,
and measurement is made through one fiber. Equivalently, one light
could be used, with two different measurement fibers, as shown in
FIG. 4. Here, light source 617 contains central light detection
fiber 623, as well as peripheral light detection fiber 626.
[0076] Using the device as constructed in FIG. 4, as attached to
monitor 313 of FIG. 2, spectra were collected at two separations,
and then the saturation was deduced using a standard radiological
approach called layer stripping, in which the effect of the
overlying layer is removed from the underlying layer. In this
embodiment, monitor 313 comprises a difference unit programmed with
software know in the art for performing layer stripping. In this
approach, it is not the saturation values that are subtracted, but
rather by collecting and mathematically removing the
narrowly-spaced spectrum (collected from light source 617 and
central fiber 623) from the spectrum collected from the more widely
spaced pair (light source 617 and peripheral fiber 626), a common
data analysis tool called layer stripping in radiology, and then
reanalyzing the remaining spectrum for oxygen saturation, deeper
ischemia in the breast or other target tissue can reliably be
detected, as shown:
TABLE-US-00006 TABLE 6 The difference, in this case calculated by
removing the spectra collected from the deeper-collected spectrum,
and then reanalyzing the values, allows the deeper oxygenation to
be determined, thus showing tissues which may not heal in
anastomosis Narrow Deep Color Deep Actual Tissue Measured Pair Only
Pair Only Difference Ischemia? Ischemia Under 80% 40% 09% Yes
Oxygenated Surface Normal Under Ischemic 45% 62% 69% No Surface
Normal Tissue Under 70% 65% 63% No Normal Mucosa
[0077] In patients with ischemia, the surgical procedure can then
be changed by this value, and conversely those with normal values
may be allowed to undergo higher risk procedures. For example, if
the ischemic site is the anastomosis of two regions of a colon, and
the saturation is low, then the tissue should not be sewn together,
as it will not heal. One may also use this approach to study the
effect of surgical staples on ischemia, in order to determine that
surgical staple lines are too tight to heal well.
[0078] We have discovered a dual or multiple somatic measurement
difference method that allows for more sensitive detection of local
ischemia and or local cancer using oximetry measurements. As
described above, in some embodiments the apparatus comprises two
phosphor-coated LED's and integrated collimating optics constructed
in accordance with the present invention to produce light at two or
more target sites. Light backscattered by each target site is
collected by the same or multiple sensors, allowing for an index or
measure of ischemia to be determined, and subsequently transmitted
to a comparison unit that additional compares the two results. This
device has immediate application to several important problems,
both medical and industrial, and thus constitutes an important
advance in the art.
* * * * *