Abstract
Raman spectroscopy is a vibrational spectroscopic technique capable of optically probing the compositional,
conformational, and structural changes in the tissue associated with disease progression. The main goal of this work is to
develop an integrated fingerprint (FP) and high wavenumber (HW) in vivo confocal Raman spectroscopy for
simultaneous FP/HW tissue Raman spectral measurements. This work further explores the potential of integrated FP/HW
Raman spectroscopy developed as a diagnostic tool for in vivo detection of cervical precancer. A total of 473 in vivo
integrated FP/HW Raman spectra (340 normal and 133 precancer) were acquired from 35 patients within 1 s during
clinical colposcopy. The major tissue Raman peaks are noticed around 854, 937, 1001, 1095, 1253, 1313, 1445, 1654,
2946 and 3400 cm-1, related to the molecular changes (e.g., proteins, lipids, glycogen, nucleic acids, water, etc.) that
accompany the dysplastic transformation of tissue. The FP (800 - 1800 cm-1), HW (2800 - 3800 cm-1) and the integrated
FP/HW Raman spectra were analyzed using partial least squares-discriminant analysis (PLS-DA) together with the
leave-one patient-out, cross-validation. The developed PLS-DA classification models and receiver operating
characteristics (ROC) curves for the FP, HW and integrated FP/HW spectroscopy further discloses that the performance
of integrated FP/HW Raman spectroscopy is superior to that of all others in discriminating the dysplastic cervix. The
results of this work indicate that the co-contributions of underlying rich biochemical information revealed by the
complementary spectral modalities (FP and HW Raman) can improve the in vivo early diagnosis of cervical precancer at
clinical colposcopy
