US6201989B1
Expired / Lapsed
US
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Methods and apparatus for detecting the rejection of transplanted tissue
Assignee: Biomax Technologies Inc
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Filing: 1998-03-12
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Granted: 2001-03-13
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Expires: 2018-03-12
Abstract
Abstract Methods and apparatus for detecting the possible rejection of a transplanted tissue by a host. The transplanted tissue is subjected to illumination with light to induce fluorescence. The light can be ultraviolet light, visible light or infrared light, which can be used alone or in any combination, which means one, two or three forms of light may be used together. The induced fluorescence is collected and analyzed, then compared with fluorescence that is obtained using the same procedure for a known, healthy tissue that is the same type of tissue as the transplanted tissue. Also provided are methods and apparatus related to the determination of probe orientation and the need for biopsy.
Inventors
- 👤 Peter D. Whitehead
- 👤 Calum E. MacAulay
- 👤 Nicholas B. MacKinnon
- 👤 Haishan Zeng
- 👤 Christopher R. Thompson
- 👤 Bruce M. McManus
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 00:18
CPC Classifications
A; A61; A61B; A61B10/00; A61B10/02; A61B10/06; A61B5/00; A61B5/0059; A61B5/0071; A61B5/0075; A61B5/0082; A61B5/0084; A61B5/41; A61B5/413; A61B5/414; A61B5/416; A61B5/68; A61B5/6846; A61B5/6847; A61B5/6848; A61B17/00; A61B17/28; A61B17/29; A61B2017/2926; A61B2017/2932; A61B2017/2933; A61B2017/2934; A61B90/00; A61B90/36; A61B90/361; A61B2090/3614; A61B90/37; A61B2090/373; A61B5/0062; A61B5/0066; A61B5/0086; A61B5/72; A61B5/7271; A61B5/7285
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
177 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of a same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the method is implemented using a catheter or endoscope that comprises at least one illumination light guide that conducts light to the transplanted tissue to illuminate the transplanted tissue and at least one collection light guide that collects fluorescence from the transplanted tissue, and wherein the method further comprises collecting a plurality of transplant fluorescence signatures, wherein at least two of the plurality of transplant fluorescence signatures comprise a significant fluorescence contribution from a plurality of selected different depths of the transplanted tissue to provide at least two different fluorescence signatures.
Claim 2
Independent Claim
177 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of a same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the method is implemented using a catheter or endoscope that comprises at least one illumination light guide that conducts light to the transplanted tissue to illuminate the transplanted tissue and at least one collection light guide that collects fluorescence from the transplanted tissue, and wherein the method further comprises collecting a plurality of transplant fluorescence signatures, wherein at least two of the plurality of transplant fluorescence signatures comprise a significant fluorescence contribution from a plurality of selected different depths of the transplanted tissue to provide at least two different fluorescence signatures.
Claim 3
Dependent Claim
70 words
The method of claim 1 wherein the catheter or endoscope comprises at least a first collection light guide and a second collection light guide each of which is spaced a different distance from its associated illumination light guide, and wherein the collection of the at least two different fluorescence signatures comprises collecting light using each of the first collection light guide and the second collection guide during the collecting steps.
Claim 4
Dependent Claim
28 words
The method of claim 2 wherein the illumination light guide associated with the first collection light guide and the second collection light guide is a single light guide.
Claim 5
Dependent Claim
27 words
The method of claim 1 wherein the step of comparing comprises comparing the wavelength of maximum intensity of the transplant fluorescence signature with the healthy fluorescence signature.
Claim 6
Independent Claim
99 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the transplanted tissue is illuminated with light that does not comprise UV light.
Claim 7
Independent Claim
99 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the transplanted tissue is illuminated with light that does not comprise UV light.
Claim 8
Independent Claim
99 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the transplanted tissue is illuminated with light that consists essentially of blue light.
Claim 9
Independent Claim
99 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the transplanted tissue is illuminated with light that consists essentially of blue light.
Claim 10
Independent Claim
103 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the transplanted tissue is illuminated with light that consists essentially of a wavelength of about 442 nm.
Claim 11
Independent Claim
103 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the transplanted tissue is illuminated with light that consists essentially of a wavelength of about 442 nm.
Claim 12
Independent Claim
112 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the step of illuminating comprises illuminating light from an illumination light guide, and the step of collecting comprises collecting the fluorescence in a collection light guide.
Claim 13
Independent Claim
112 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the step of illuminating comprises illuminating light from an illumination light guide, and the step of collecting comprises collecting the fluorescence in a collection light guide.
Claim 14
Independent Claim
106 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the steps of illuminating and collecting are performed in vivo during a single diastole of a heartbeat of the host.
Claim 15
Independent Claim
106 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the steps of illuminating and collecting are performed in vivo during a single diastole of a heartbeat of the host.
Claim 16
Dependent Claim
26 words
The method of claim 9 wherein the steps of illuminating and collecting during a single diastole are initiated using one or more signals of an electrocardiogram.
Claim 17
Dependent Claim
26 words
The method of claim 9 wherein the steps of illuminating and collecting during a single diastole are initiated using a blood pressure pulse of the host.
Claim 18
Dependent Claim
22 words
The method of claim 11 wherein the blood pressure pulse is measured using a blood pressure monitor located externally to the host.
Claim 19
Dependent Claim
16 words
The method of claim 12 wherein the wavelength bands are measured by broad band optical detectors.
Claim 20
Dependent Claim
16 words
The method of claim 11 wherein the blood pressure pulse is measured by a pulse oximeter.
Claim 21
Dependent Claim
21 words
The method of claim 14 wherein the method further comprises selecting a specific spectral region using an optical band pass filter.
Claim 22
Independent Claim
109 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the step of comparing comprises comparing a full width at half maximum (FWHM) of the transplant fluorescence signature with the healthy fluorescence signature.
Claim 23
Independent Claim
109 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the step of comparing comprises comparing a full width at half maximum (FWHM) of the transplant fluorescence signature with the healthy fluorescence signature.
Claim 24
Independent Claim
114 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the step of comparing comprises comparing a ratio of the integrated intensity of two or more wavelength bands of the transplant fluorescence signature with the healthy fluorescence signature.
Claim 25
Independent Claim
114 words
A method for determining whether a transplanted tissue comprises one or more characteristics indicative of rejection by a host, the method comprising: a) illuminating the transplanted tissue under conditions suitable to cause the transplanted tissue to fluoresce; b) collecting the fluorescence to provide a transplant fluorescence signature; and c) comparing the transplant fluorescence signature with a known fluorescence signature representative of the same type of tissue as the transplanted tissue, and therefrom determining whether the transplanted tissue exhibits one or more characteristics indicative of rejection, wherein the step of comparing comprises comparing a ratio of the integrated intensity of two or more wavelength bands of the transplant fluorescence signature with the healthy fluorescence signature.
Claim 26
Independent Claim
27 words
The method of any one of claims 1 to 8 or 16 to 4 wherein the transplanted tissue is illuminated and the fluorescence is collected in vivo.
Claim 27
Independent Claim
16 words
The method of any one of claims 1 - 4 wherein the host is a human.
Claim 28
Independent Claim
21 words
The method of any one of claims 1 - 4 wherein at least one step of the method is computer implemented.
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