Characterization of Raman Spectra Measured in Vivo for the Detection of Cervical Dysplasia

Raman spectroscopy has been shown to have the potential for providing differential diagnosis in the cervix with high sensitivity and specificity in previous studies. The research presented here further evaluates the potential of near-infrared Raman spectroscopy to detect cervical dysplasia in a clinical setting. Using a portable system, Raman spectra were collected from the cervix of 79 patients using clinically feasible integration times (5 seconds on most patients). Multiple Raman measurements were taken from colposcopically normal and abnormal areas prior to the excision of tissue. Data were processed to extract Raman spectra from measured signal, which includes fluorescence and noise. The resulting spectra were correlated with the corresponding histopathologic diagnosis to determine empirical differences between different diagnostic categories. Using histology as the gold standard, logistic regression discrimination algorithms were developed to distinguish between normal ectocervix, squamous metaplasia, and high-grade dysplasia using independent training and validation sets of data. An unbiased estimate of the accuracy of the model indicates that Raman spectroscopy can distinguish between high-grade dysplasia and benign tissue with sensitivity of 89% and specificity of 81%, while colposcopy in expert hands was able to discriminate with a sensitivity and specificity of 87% and 72%.

[1]  S. Lam,et al.  Near‐infrared Raman spectroscopy for optical diagnosis of lung cancer , 2003, International journal of cancer.

[2]  R Richards-Kortum,et al.  Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications , 1999, Lasers in surgery and medicine.

[3]  H. Barr,et al.  Raman Spectroscopy for Early Detection of Laryngeal Malignancy: Preliminary Results , 2000, The Laryngoscope.

[4]  K. Nakamoto,et al.  Introductory Raman Spectroscopy , 1994 .

[5]  A. Mahadevan-Jansen,et al.  Near‐Infrared Raman Spectroscopy for In Vitro Detection of Cervical Precancers , 1998 .

[6]  R. Richards-Kortum,et al.  Raman spectroscopy for the detection of cancers and precancers. , 1996, Journal of biomedical optics.

[7]  R Richards-Kortum,et al.  Cervical fluorescence of normal women , 1999, Lasers in surgery and medicine.

[8]  L. Choo-Smith,et al.  Discriminating Vital Tumor from Necrotic Tissue in Human Glioblastoma Tissue Samples by Raman Spectroscopy , 2002, Laboratory Investigation.

[9]  Scott B. Cantor,et al.  COLPOSCOPY FOR THE DIAGNOSIS OF SQUAMOUS INTRAEPITHELIAL LESIONS: A META‐ANALYSIS , 1998, Obstetrics and gynecology.

[10]  A. Mahadevan-Jansen,et al.  Automated Method for Subtraction of Fluorescence from Biological Raman Spectra , 2003, Applied spectroscopy.

[11]  H. Bruining,et al.  In vitro and in vivo Raman spectroscopy of human skin. , 1998, Biospectroscopy.

[12]  Gregg Staerkel,et al.  Cervical Precancer Detection Using a Multivariate Statistical Algorithm Based on Laser‐Induced Fluorescence Spectra at Multiple Excitation Wavelengths , 1996, Photochemistry and photobiology.

[13]  Brian C Wilson,et al.  Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polyps. , 2003, Gastrointestinal endoscopy.

[14]  Irene Georgakoudi,et al.  Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo. , 2002, American journal of obstetrics and gynecology.

[15]  Anita Mahadevan-Jansen,et al.  Organotypic Raft Cultures as an Effective In Vitro Tool for Understanding Raman Spectral Analysis of Tissue¶ , 2003 .

[16]  Michele Follen,et al.  Autofluorescence Microscopy of Fresh Cervical‐Tissue Sections Reveals Alterations in Tissue Biochemistry with Dysplasia ¶ , 2001 .

[17]  Michele Follen,et al.  Autofluorescence Patterns in Short-Term Cultures of Normal Cervical Tissue , 2000, Photochemistry and photobiology.

[18]  S. Datta,et al.  Setting the Target for a Better Cervical Screening Test: Characteristics of a Cost‐Effective Test for Cervical Neoplasia Screening , 2000, Journal of lower genital tract disease.

[19]  T. B. Bakker Schut,et al.  Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy. , 2002, The Journal of investigative dermatology.

[20]  L Burke,et al.  Identification of cervical intraepithelial neoplasia (CIN) using UV‐excited fluorescence and diffuse‐reflectance tissue spectroscopy , 2001, Lasers in surgery and medicine.

[21]  N. Ramanujam Fluorescence spectroscopy of neoplastic and non-neoplastic tissues. , 2000, Neoplasia.

[22]  N Stone,et al.  Raman Spectral Mapping in the Assessment of Axillary Lymph Nodes in Breast Cancer , 2003, Technology in cancer research & treatment.

[23]  H. Bruining,et al.  In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles. , 2001, The Journal of investigative dermatology.

[24]  R. Richards-Kortum,et al.  Near-Infrared Raman Spectroscopy for in vivo Detection of Cervical Precancers , 2001, Photochemistry and photobiology.

[25]  R. Richards-Kortum,et al.  Cost‐Effectiveness Analysis of Diagnosis and Management of Cervical Squamous Intraepithelial Lesions , 1998, Obstetrics and gynecology.

[26]  Brian C. Wilson,et al.  Study of Fiber-Optic Probes for in vivo Medical Raman Spectroscopy , 1999 .

[27]  N. Stone,et al.  The use of Raman spectroscopy to identify and characterize transitional cell carcinoma in vitro , 2004, BJU international.

[28]  Vic Hasselblad,et al.  Accuracy of the Papanicolaou Test in Screening for and Follow-up of Cervical Cytologic Abnormalities , 2000, Annals of Internal Medicine.

[29]  R. Dasari,et al.  Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo , 2002 .

[30]  N Stone,et al.  The use of Raman spectroscopy to identify and grade prostatic adenocarcinoma in vitro , 2003, British Journal of Cancer.

[31]  J. Roodenburg,et al.  In vivo detection of dysplastic tissue by Raman spectroscopy. , 2000, Analytical chemistry.

[32]  Brian C. Wilson,et al.  In vivo Near-infrared Raman Spectroscopy: Demonstration of Feasibility During Clinical Gastrointestinal Endoscopy¶ , 2000, Photochemistry and photobiology.

[33]  Hugh Barr,et al.  Near‐infrared Raman spectroscopy for the classification of epithelial pre‐cancers and cancers , 2002 .

[34]  R Richards-Kortum,et al.  Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications. , 2001, Journal of biomedical optics.