Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1998-10-09
2001-09-11
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
Reexamination Certificate
active
06289236
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to distinguishing inflamed bladder tissue from cancerous bladder tissue.
Transitional cell carcinoma (TCC) of the bladder is one of the more common cancers of both men and women in the United States. In 1995, for example, approximately 50,000 new cases were diagnosed, and about 11,000 individuals died of the disease.
In approximately 50 to 65% of cases, TCC lesions are superficial at presentation; however, despite apparently adequate transurethral resection of the tumor, the recurrence rate is about 55 to 70%. Since early malignant and dysplastic lesions are often invisible or barely visible, random biopsies are often recommended in addition to resection of the visible tumor to more accurately diagnose and/or stage the bladder tumor.
Diagnosis and staging of early stage bladder dysplasia can be complicated by the presence of inflamed tissue in the bladder. The similar appearance of inflamed tissue and the early stages of bladder cancer, such as carcinoma in situ, can make it difficult to distinguish between these lesions and cancerous cells. Thus, early malignant and dysplastic lesions can be overlooked because their appearance is similar to that of inflamed tissue.
SUMMARY OF THE INVENTION
The invention is based on the discovery that healthy bladder tissue, inflamed bladder tissue, and cancerous bladder tissue, each have distinct autofluorescence emission profiles centered at about 385 and 455 nm when illuminated with radiation centered at about 337 nm. Accordingly, the invention features methods and an apparatus for detecting cancerous tissue and distinguishing inflamed and cancerous tissue.
In general, the invention features methods for distinguishing cancerous tissue from inflamed tissue in a patient by (a) exposing a target tissue suspected of containing inflamed or cancerous tissue to incident radiation; (b) detecting autofluorescence emitted at a first and second wavelength upon irradiation of the target tissue with the incident radiation; and (c) comparing the autofluorescence emitted at the first wavelength with the autofluorescence emitted at the second wavelength. A decrease in autofluorescence at the first wavelength compared to autofluorescence emitted at the second wavelength indicates cancerous cells within the target tissue.
The incident radiation can have a wavelength between, e.g., 325 and 350 nm, 330 nm and 343 nm, 335 and 340 nm, or can be 337 nm. The emitted autofluorescence at the first wavelength can be between, e.g., 370 and 400 nm, 377 and 393 nm, or can be about 385 nm. The emitted fluorescence at the second wavelength can be between e.g., 440 and 470 nm, 450 and 460 nm, or can be centered at about 455 nm.
The patient can be, e.g., a human, a non-human primate, dog, cat, cow, or horse. The tissue can be an epithelial tissue, e.g., bladder, colon, cervix, esophagus, or lung.
The method can be performed in the presence of a sensitizing agent, or without a sensitizing agent.
In some embodiments, the incident radiation is one that causes collagen and reduced nicotine adenine dinucleotide phosphate (NADPH) or reduced nicotine adenine dinucleotide (NADH) to autofluoresce. The radiation emitted at the first wavelength can be a wavelength where the autofluoresence is dominated by collagen autofluoresence, and the radiation emitted at the second wavelength is a wavelength which is dominated by NADPH or NADH autofluoresence.
In another aspect, the invention provides an apparatus for distinguishing cancerous and inflamed tissue, where the apparatus has (a) a light source; (b) a first detector to detect autofluoresence emitted from the irradiated target tissue at a first wavelength; (c) a second detector to detect autofluoresence emitted from the irradiated target tissue at a second wavelength; and (d) an analyzer that compares a threshold value to the ratio of the autofluoresence at the first wavelength and the autofluoresence at the second wavelength. A ratio below the threshold value indicates that the analyzed tissue is cancerous, and a ratio above the threshold indicates that the analyzed tissue is inflamed. The threshold value can be adjusted to, e.g., 0.9, 1, 1.01, 1.1, 1.3, or 1.78, depending on the desired degree of specificity and sensitivity. A low threshold value will result in fewer tissues being scored as cancerous, while a high threshold value will result in more samples being scored as noncancerous.
In yet another aspect, the invention provides a method for distinguishing cancerous tissue from inflamed tissue in a patient by (a) exposing a target tissue suspected of containing inflamed or cancerous tissue to incident radiation; (b) detecting autofluoresence emitted at a first and second wavelength upon irradiation of the target tissue with the incident radiation; and (c) comparing a threshold value to a ratio of the autofluoresence at the first wavelength and the autofluoresence at the second wavelength. A ratio below the threshold value indicates that the analyzed tissue is cancerous, and a ratio above the threshold indicates that the analyzed tissue is inflamed.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
The invention offers important advantages. First, cancerous lesions can be detected and distinguished from inflammatory lesions in vivo with the advantage that the number of biopsies from non-malignant tissues can be decreased or eliminated. In addition, the method does not require the use of systemic or topically applied sensitizing agents.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.
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Deutsch Thomas F.
Koenig Frank
McGovern Francis J.
Schomacker Kevin T.
Fish & Richardson P.C.
Lateef Marvin M.
Mantis Mercader Eleni
The General Hospital Corporation
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