Joseph Ng

High wavenumber Raman spectroscopy for in vivo detection of cervical dysplasia.

Raman spectroscopy is a vibrational spectroscopic technique capable of optically probing the biomolecular changes associated with neoplastic transformation. The purpose of this study was to apply near-infrared (NIR) Raman spectroscopy in the high wavenumber (HW) region (2800-3700 cm(-1)) for in vivo detection of cervical dysplasia. A rapid-acquisition NIR Raman spectroscopy system associated with a ball-lens fiber-optic Raman probe was developed for in vivo spectroscopic measurements at 785 nm excitation. A total of 92 in vivo HW Raman spectra (46 normal, 46 dysplasia) were acquired from 46 patients with Pap smear abnormalities of the cervix. Significant difference in Raman intensities of prominent Raman bands at 2850 and 2885 cm(-1) (CH(2) stretching of lipids), 2940 cm(-1) (CH(3) stretching of proteins), and the broad Raman band of water (peaking at 3400 cm(-1) in the 3100-3700 cm(-1) range) were observed in normal and dysplasia cervical tissue. The diagnostic algorithms based on principal components analysis and linear discriminant analysis together with the leave-one-patient-out cross-validation method on in vivo HW Raman spectra yielded a diagnostic sensitivity of 93.5% and specificity of 97.8% for dysplasia tissue identification. This study demonstrates for the first time that HW Raman spectroscopy has the potential for the noninvasive, in vivo diagnosis and detection of precancer of the cervix.

Simultaneous fingerprint and high-wavenumber confocal Raman spectroscopy enhances early detection of cervical precancer in vivo.

Raman spectroscopy is a vibrational spectroscopic technique capable of nondestructively probing endogenous biomolecules and their changes associated with dysplastic transformation in the tissue. The main objectives of this study are (i) to develop a simultaneous fingerprint (FP) and high-wavenumber (HW) confocal Raman spectroscopy and (ii) to investigate its diagnostic utility for improving in vivo diagnosis of cervical precancer (dysplasia). We have successfully developed an integrated FP/HW confocal Raman diagnostic system with a ball-lens Raman probe for simultaneous acquistion of FP/HW Raman signals of the cervix in vivo within 1 s. A total of 476 in vivo FP/HW Raman spectra (356 normal and 120 precancer) are acquired from 44 patients at clinical colposcopy. The distinctive Raman spectral differences between normal and dysplastic cervical tissue are observed at ~854, 937, 1001, 1095, 1253, 1313, 1445, 1654, 2946, and 3400 cm(-1) mainly related to proteins, lipids, glycogen, nucleic acids and water content in tissue. Multivariate diagnostic algorithms developed based on partial least-squares-discriminant analysis (PLS-DA) together with the leave-one-patient-out, cross-validation yield the diagnostic sensitivities of 84.2%, 76.7%, and 85.0%, respectively; specificities of 78.9%, 73.3%, and 81.7%, respectively; and overall diagnostic accuracies of 80.3%, 74.2%, and 82.6%, respectively, using FP, HW, and integrated FP/HW Raman spectroscopic techniques for in vivo diagnosis of cervical precancer. Receiver operating characteristic (ROC) analysis further confirms the best performance of the integrated FP/HW confocal Raman technique, compared to FP or HW Raman spectroscopy alone. This work demonstrates, for the first time, that the simultaneous FP/HW confocal Raman spectroscopy has the potential to be a clinically powerful tool for improving early diagnosis and detection of cervical precancer in vivo during clinical colposcopic examination.

In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques

This study aimed to evaluate the clinical utility of applying near-infrared (NIR) Raman spectroscopy and genetic algorithm-partial least squares-discriminant analysis (GA-PLS-DA) to identify biomolecular changes of cervical tissues associated with dysplastic transformation during colposcopic examination. A total of 105 in vivo Raman spectra were measured from 57 cervical sites (35 normal and 22 precancer sites) of 29 patients recruited, in which 65 spectra were from normal sites, while 40 spectra were from cervical precancerous lesions (i.e., 7 low-grade CIN and 33 high-grade CIN). The GA feature selection technique incorporated with PLS was utilized to study the significant biochemical Raman bands for differentiation between normal and precancer cervical tissues. The GA-PLS-DA algorithm with double cross-validation (dCV) identified seven diagnostically significant Raman bands in the ranges of 925-935, 979-999, 1080-1090, 1240-1260, 1320-1340, 1400-1420, and 1625-1645 cm(-1) related to proteins, nucleic acids and lipids in tissue, and yielded a diagnostic accuracy of 82.9% (sensitivity of 72.5% (29/40) and specificity of 89.2% (58/65)) for precancer detection. The results of this exploratory study suggest that Raman spectroscopy in conjunction with GA-PLS-DA and dCV methods has the potential to provide clinically significant discrimination between normal and precancer cervical tissues at the molecular level.

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Cervical dysplasia: Assessing methylation status (Methylight) of CCNA1, DAPK1, HS3ST2, PAX1 and TFPI2 to improve diagnostic accuracy

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