Classification of tissue biopsies by Raman spectroscopy guided by quantitative phase imaging and its application to bladder cancer

We present a multimodal label-free optical measurement approach for analyzing sliced tissue biopsies by a unique combination of quantitative phase imaging and localized Raman spectroscopy. First, label-free quantitative phase imaging of the entire unstained tissue slice is performed using automated scanning. Then, pixel-wise segmentation of the tissue layers is performed by a kernelled structural support vector machine based on Haralick texture features, which are extracted from the quantitative phase profile, and used to find the best locations for performing the label-free localized Raman measurements. We use this multimodal label-free measurement approach for segmenting the urothelium in benign and malignant bladder cancer tissues by quantitative phase imaging, followed by location-guided Raman spectroscopy measurements. We then use sparse multinomial logistic regression (SMLR) on the Raman spectroscopy measurements to classify the tissue types, demonstrating that the prior segmentation of the urothelium done by label-free quantitative phase imaging improves the Raman spectra classification accuracy from 85.7% to 94.7%.