Spectral diagnosis of skin cancer

The number of skin cancer cases reported in the United States is increasing every year and nearly equals the total cancer cases detected from every other part of the body. Current detection strategies of skin cancers include a visual examination followed by a tissue biopsy. This procedure is subjective, invasive and time-consuming. Therefore, considering the number of cancer cases reported and the number biopsies performed, there is a critical need for a non-invasive diagnostic aid to help clinicians reduce the significantly large numbers of unnecessary biopsies. This dissertation presents a quantitative method based on optical spectroscopy for performing a non-invasive ‘optical biopsy’ of melanoma and non-melanoma skin cancers. We have developed the hardware, software and optical algorithms necessary to implement such a device. First, we present a novel lookup table-based model for determining the optical properties of tissue that is valid for fiber-based probe geometries with close source-detector separations and in highly absorbing tissue. These optical properties are quantitative parameters that can be correlated with the physiology of tissue. Second, we present experimental validation of the effects of microvasculature pigment packaging on diffuse reflectance spectra. We have conducted experiments using microfluidic devices over a physiologically relevant range of optical properties and blood vessel sizes. Third, we present the development of a probe-based portable and clinically compatible instrument capable of in vivo spectral measurements. The instrument combines two modalities – diffuse reflectance and intrinsic fluorescence spectroscopy – to provide complementary information regarding tissue morphology, function and biochemical composition. Finally, we present the results of a pilot clinical study using our portable instrument to determine the accuracy of spectral diagnosis of non-melanoma skin cancers. Our results show that the mean optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different from each other and can potentially be used as biomarkers for non-invasive diagnosis of skin cancer.