Clinical study of noninvasivein vivomelanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

Abstract

Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

Raman active components of skin cancer

“…Since in situ constituents are extracted from skin in their natural state, without any further processing, they can better represent the skin microenvironment that cannot be recapitulated in a synthetic environment. Second, our model was validated by a previous in vivo clinical screening study [12] acquired by a Raman optical fiber probe [27]. Currently, the only biophysical Raman skin cancer model was based on excised fragments of BCC and melanoma skin tissues [9].…”

“…In vivo human skin spectra came from our previous skin cancer screening study [12]. Data were collected from an optical fiber probe [27] integrated in a multimodal spectroscopy system [28] on different sites, such as scalp, nose, earlobe, shoulder and thigh.…”

“…Recent advances in near-infrared lasers, optical filters, fiber optics and CCD cameras have greatly improved its sensitivity in detecting the chemical composition of biological tissues. In the most recent decade, the Raman optical fiber probe has allowed for fast and accurate cancer diagnostics, including ex vivo study of breast [4,5], prostate [6], lung [7] and skin [8,9], and in vivo study of breast [10], cervical [11], and skin [2,12]. Recent clinical studies from our group [12] and others [2] have demonstrated that RS has high diagnostic accuracy in discriminating skin melanoma from nonmelanoma pigmented lesions.…”

“…Furthermore, we applied the model for the first time to in vivo human skin cancer screening data that covers a wide range of normal, nonmelanoma and melanoma skin cancers and precancers [12]. Previous Raman models of human skin were either built for ex vivo tissue specimens [9] or in vivo normal skin [22]; however, Raman biophysical models have not been applied to in vivo skin cancer screening to interpret biophysical changes between pathologies.…”

Influence of water content on Raman spectroscopy characterization of skin sample

“…For example, Zhao et al reported that the diagnostic specificity for fixed sensitivity of 0.99-0.90 was improved from 0.17-0.65 to 0.20-0.75 with wave-number selection based on a leave-one-out cross-selection procedure [13]. Lim et al suggested that a combination of three fiber-opticbased optical spectroscopy modalities (diffuse optical spectroscopy, laser-induced fluorescence spectroscopy, and Raman spectroscopy) is necessary for accurate and noninvasive diagnosis of both melanoma and non-melanoma skin cancers in vivo [14].…”