Combining the Tactile Resonance Method and Raman Spectroscopy for Tissue Characterization towards Prostate Cancer Detection

Doctoral thesis, 2011

Prostate cancer (PCa) is the most common male cancer in Europe and the US, and only lung and colorectal cancer have a higher mortality among European men. In Sweden, PCa is the most common cause of cancer-related death for men.The overall aim of this thesis was to explore the need for new and complementary methods for PCa detection and to take the first step towards a novel approach: combining the tactile resonance method (TRM) and Raman spectroscopy (RS). First, the main methods for PCa detection were reviewed. Second, to establish a robust protocol for RS experiments in vitro, the effects of snap-freezing and laser illumination on porcine prostate tissue were studied using RS and multivariate statistics. Third, measurements on porcine and human tissue were performed to compare the TRM and RS data via multivariate techniques, and to assess the accuracy of classifying healthy and cancerous tissue using a support vector machine algorithm.It was concluded through the literature review that the gold standard for PCa detection and diagnosis, the prostate specific antigen test and systematic biopsy, have low sensitivity and specificity. Indolent and aggressive tumors cannot be reliably differentiated, and many men are therefore treated either unnecessarily or too late. Clinical benefits of the state–of–the–art in PCa imaging – advanced ultrasound and MR techniques – have still not been convincingly shown. There is a need for complementary and cost-effective detection methods. TRM and RS are promising techniques, but hitherto their potential for PCa detection have only been investigated in vitro.In the RS study no evidence of tissue degradation due to 830 nm laser illumination at an irradiance of â?? 3 · 1010 W mâ??2 were found. Snap-freezing and subsequent storage at â??80â??C gave rise to subtle but significant changes in Raman spectra, most likely related to alterations in the protein structure. The major changes due to PCa do not seem to be related to the protein structure, hence snap-freezing may be applied in our experiments.The combined measurements on porcine and human prostate tissue showed that RS provided additional discriminatory power to TRM. The classification accuracy for healthy porcine prostate tissue, and for healthy and cancerous human prostate tissue, was > 73%. This shows the power of the support vector machine applied to the combined data.In summary, this work indicates that an instrument combining TRM and RS is a promising complementary method for PCa detection. Snap-freezing of samples may be used in future RS studies of PCa. A combined instrument could be used for tumor-border demarcation during surgery, and potentially for guiding prostate biopsies towards lesions suspicious for cancer. All of this should provide a more secure diagnosis and consequently more efficient treatment of the patient.