Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2000-03-06
2004-02-24
Smith, Ruth S. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C604S027000, C604S048000
Reexamination Certificate
active
06697666
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to apparatus and methods for investigating epithelial lined viscus, and more particularly to apparatus and methods for characterizing normal and dysplastic tissue of the endocervical canal.
The most prevalent of preinvasive conditions of the female lower genital tract is cervical intraepithelial neoplasia (CIN). The traditional definition calls it a spectrum of intraepithelial changes that begins as a generally well differentiated intraepithelial neoplasm, which has traditionally been classified as a very mild dysplasia, and ends with invasive carcinoma. Neoplastic changes are confined to the squamous epithelium and include nuclear pleomorphism, loss of polarity, and presence of abnormal mitoses. CIN is graded 1 to 3, based on the amount of undifferentiated cells present from the basement membrane to the surface epithelium. When one third of that distance is involved, the grade is 1; when more than one third and up to two thirds is involved, the grade is 2; when more than two thirds is involved, the grade is 3. Full-thickness involvement from the surface epithelium to the basement membrane is referred to as carcinoma in situ (CIS). The median transit time from CIN to CIS depends on the grade of CIN: for grade 1 CIN, the time is approximately 6 years; for grade 2 CIN, approximately 2 years; and for grade 3, approximately 1 year. Despite some debate in the past about CIN and CIS representing two distinct entities, it is currently believed that CIN and CIS are part of a spectrum of disease that leads to invasive cancer of the cervix. The diagnosis and treatment of CIN are thus part of the prevention of invasive cervical cancer. An accepted method to classify cervical tissues is the new Bethesda system as presented in Wright et al. , “Pathology of the Female Genital Tract,” 156-177, Springer-Verlag, (1994). In accordance with that system, lesions with HPV and CIN are classified as squamous intraepithelial lesions (SILs) where they may be further separated as high grade SIL (CIN II, CIN III, CIS) and low grade SIL (CIN I, HPV). Normal, metaplastic and non-specific inflammation tissues are classified as non-SILs.
Cervical intraepithelial neoplasia is usually detected by screening Pap smears from asymptomatic women. Patients with abnormal Pap smears are referred for colposcopy and possibly biopsy. Acetic acid is applied to the cervix, and areas with abnormal DNA content, such as those with CIN, turn white. The colposcope, a mounted magnifying lens, is used to direct biopsies of the abnormal white areas. Abnormal configurations of blood vessels, called vascular atypia, signal disordered growth and help the clinician know which other areas require biopsy. An appropriate evaluation of the abnormal Pap smear involves review of the referral and repeat Pap smears, endocervical curettage, and multiple biopsies of the aceto white areas; the results of such analysis will indicate whether the patient has CIN.
While the predictive accuracy of colposcopy is a matter of debate in the field with some researchers finding excellent overall accuracy with others finding accuracy to be poor for CIN but good for condyloma.
Recently, there has been intensive research to explore the use of optical spectroscopy for the diagnosis of disease in human tissue. Several studies have successfully demonstrated the use of fluorescence, infrared absorption and Raman spectroscopies for disease diagnosis in various organ systems. Auto and dye induced fluorescence have shown promise in recognizing atherosclerosis and various types of cancers. Many groups have utilized autofluorescence for differentiation of normal and abnormal tissues from the human breast and lung, urinary bladder and gastrointestinal tract.
Copending application Ser. No. 08/666,021, filed Jul. 19, 1996, assigned to the same assignee as the present application, discloses a system that uses fluorescence spectroscopy to discriminate diseased (pre-cancerous and cancerous) from non diseased (normal tissues and inflammation) tissue as well as differentiate cancer and high grade pre-cancers from low grade precancerous lesions of the human cervix in vivo. This system provides more effective patient management, as 1) fluorescence measurements, and hence diagnostic information, can be obtained in real time and 2) the technique is non-invasive. In vitro studies in which fluorescence was measured from cervical biopsies over the UV and visible regions of the spectrum have shown that the fluorescence intensity of histologically abnormal cervix is significantly lower than that of the normal cervix from the same patient. In accordance with the above-referenced copending application, the system includes a fiber optic probe, illumination source and optical multi channel analyzer. The probe is inserted through the vaginal canal until its tip is flush with the surface of the cervix. The probe delivers light at specific excitation wavelengths and collects fluorescence from the entire emission wavelength range from a predetermined area of the cervix. During colposcopy, spectra are collected from each colposcopically abnormal area of the cervix prior to biopsy and from 1 to 4 colposcopically normal areas. Using this system, laser induced fluorescence acquired from human cervical tissues in vivo at 337, 380 and 460 nm excitation is analyzed to identify cervical intraepithelial neoplasia (CIN).
A limitation of previous colposcopic and fluorescence spectroscopic systems is that they are not capable of sampling the endocervix. It is known that atypical colposcopic tissue patterns occur with some frequency at the transformation zone between the squamous and columnar epithelium in the endocervical canal. See, Burke L, Antonioli D A and Ducatman B S.
Colposcopy, Text and Atlas,
pp. 47, 48, 61 and 62, Appleton and Large, Norwalk Conn. (1991) This transformation zone (also known as the squamocolumnar junction) is often located well within the endocervical canal and is not easily subjected to colposcopy or fluorescence spectroscopy using existing systems which are intended primarily to assess the ectocervix. In addition, cervical lesions that exist on the ectocervix often extend into the endocervical canal, and characterization of the lesion within the endocervical canal is often an important matter.
It would therefore be desirable to provide a means to subject the endocervical canal, including the transformation zone, to fluorescence spectroscopy.
SUMMARY OF THE INVENTION
The present invention avoids the above noted drawbacks of the prior art by providing a method and apparatus for characterizing tissue of epithelial lined viscus including, for example, the endocervical canal. In particular, in accordance with a method embodying the present invention, endocervical canal tissue is characterized in vivo, by illuminating endocervical canal tissue in vivo with electromagnetic radiation wavelengths to produce a plurality of fluorescence intensity spectra, detecting a plurality of emission wavelengths from the fluorescence intensity spectra, and characterizing the endocervical canal tissue as a function of the emission wavelengths. The characterizing step may distinguish squamous epithelium and columnar epithelium tissue, normal squamous and abnormal tissue, normal columnar epithelium and abnormal tissue, inflamed and abnormal tissue, low grade SIL and high grade SIL tissue, or normal and high grade SIL tissue.
In addition, the illuminating and detecting steps may comprise, illuminating a substantially cylindrical area of the endocervical canal tissue, and detecting the plurality of emission wavelengths from selected portions of the cylindrical area. The illuminating and detecting steps may further comprise illuminating an area of the endocervical canal in a vicinity of a single pixel, and detecting the plurality of emission wavelengths from the single pixel, and repeating the illuminating and detecting steps to substantially cover the cylindrical surface. In another embodiment, the illuminating and detecting steps may further
Mitchell Michele Follen
Richards-Kortum Rebecca
Utzinger Urs
Board of Regents , The University of Texas System
Fulbright & Jaworski LLP
Smith Ruth S.
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