Non-invasive analysis of hormonal variations and effect of postmenopausal Vagifem treatment on women using in vivo high wavenumber confocal Raman spectroscopy

Abstract

This study aims to evaluate the feasibility of applying high wavenumber (HW) confocal Raman spectroscopy for non-invasive assessment of menopause-related hormonal changes in the cervix as well as for determining the effect of Vagifem(®) treatment on postmenopausal women with atrophic cervix. A rapid HW confocal Raman spectroscopy system coupled with a ball lens fiber-optic Raman probe was utilized for in vivo cervical tissue Raman measurements at 785 nm excitation. A total of 164 in vivo HW Raman spectra (premenopausal (n = 104), postmenopausal-prevagifem (n = 34), postmenopausal-postvagifem (n = 26)) were measured from the normal cervix of 26 patients undergoing colposcopy. We established the biochemical basis of premenopausal, postmenopausal-prevagifem and postmenopausal-postvagifem cervix using semiquantitative biomolecular modeling derived from Raman-active biochemicals (i.e., lipids, proteins and water) that play a critical role in HW Raman spectral changes associated with the menopausal process. The diagnostic algorithms developed based on partial least squares-discriminant analysis (PLS-DA) together with leave-one patient-out, cross-validation yielded the diagnostic sensitivities of 88.5%, 91.2% and 88.5%, and specificities of 91.7%, 90.8% and 99.3%, respectively, for non-invasive in vivo discrimination among premenopausal, postmenopausal-prevagifem and postmenopausal-postvagifem cervix. This work demonstrates for the first time that HW confocal Raman spectroscopy in conjunction with biomolecular modeling can be a powerful diagnostic tool for identifying hormone/menopause-related variations in the native squamous epithelium of normal cervix, as well as for assessing the effect of Vagifem treatment on postmenopausal atrophic cervix in vivo during clinical colposcopic inspections.

Integrated Mueller-matrix near-infrared imaging and point-wise spectroscopy improves colonic cancer detection

“…The enhanced metabolic rate in colonic cancer [36] contributes to the increased water content as water provides the conversion of mechanical energy developed by contractile proteins into the chemical energy useful in cell process [37]. The increased water for the cancerous colonic tissue has also been observed in other cancer tissues (e.g., esophagus [28], stomach [38], cervix [39][40][41] and brain [42]) by using Raman spectroscopy [4,28,[38][39][40][41][42]. We have also found the decreased DR of hemoglobin band (940 nm) for the colonic cancer, signifying the increased hemoglobin content associated with colonic cancer tissue.…”

Current Advances in the Application of Raman Spectroscopy for Molecular Diagnosis of Cervical Cancer

“…A study by Duraipandian et al used HW Raman spectroscopy to noninvasively assess, in vivo , the effect of Vagifem (oestrogen therapy) treatment in women [ 48 ]. A bimolecular Raman spectroscopy model could not only successfully identify hormone/menopausal related changes in cervical epithelium, but also assess the effect of Vagifem treatment during colposcopic inspections as the protein and lipid Raman signals increase after treatment and start to resemble premenopausal values [ 48 ].…”

In vivo Raman spectral analysis of impaired cervical remodeling in a mouse model of delayed parturition

“…Raman spectroscopy was first applied to the in vivo cervix in the context of cervical dysplasia detection 46 . While conducting optimization of cervical dysplasia detection algorithms, it was discovered that Raman spectroscopy is sensitive to the effects of hormonal status on healthy cervical tissue 47–49 . These findings led to the investigation of longitudinal biochemical changes that can be measured by Raman spectroscopy in the cervix during pregnancy in vivo , both in mouse models and human subjects 31, 50 .…”