Dual-modality probe intended for prostate cancer detection combining Raman spectroscopy and tactile resonance technology--discrimination of normal human prostate tissues ex vivo.

Prostate cancer is the most common cancer for men in the western world. For the first time, a dual-modality probe, combining Raman spectroscopy and tactile resonance technology, has been used for assessment of fresh human prostate tissue. The study investigates the potential of the dual-modality probe by testing its ability to differentiate prostate tissue types ex vivo. Measurements on four prostates show that the tactile resonance modality was able to discriminate soft epithelial tissue and stiff stroma (p < 0.05). The Raman spectra exhibited a strong fluorescent background at the current experimental settings. However, stroma could be discerned from epithelia by integrating the value of the spectral background. Combining both parameters by a stepwise analysis resulted in 100% sensitivity and 91% specificity. Although no cancer tissue was analysed, the results are promising for further development of the instrument and method for discriminating prostate tissues and cancer.

Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterization.

The tactile resonance method (TRM) and Raman spectroscopy (RS) are promising for tissue characterization in vivo. Our goal is to combine these techniques into one instrument, to use TRM for swift scanning, and RS for increasing the diagnostic power. The aim of this study was to determine the classification accuracy, using support vector machines, for measurements on porcine tissue and also produce preliminary data on human prostate tissue. This was done by developing a new experimental set-up combining micro-scale TRM-scanning haptic microscopy (SHM)-for assessing stiffness on a micro-scale, with fibre optic RS measurements for assessing biochemical content. We compared the accuracy using SHM alone versus SHM combined with RS, for different degrees of tissue homogeneity. The cross-validation classification accuracy for healthy porcine tissue types using SHM alone was 65-81%, and when RS was added it increased to 81-87%. The accuracy for healthy and cancerous human tissue was 67-70% when only SHM was used, and increased to 72-77% for the combined measurements. This shows that the potential for swift and accurate classification of healthy and cancerous prostate tissue is high. This is promising for developing a tool for probing the surgical margins during prostate cancer surgery.

Technologies for localization and diagnosis of prostate cancer.

The gold standard for detecting prostate cancer (PCa), systematic biopsy, lacks sensitivity as well as grading accuracy. PSA screening leads to over-treatment of many men, and it is unclear whether screening reduces PCa mortality. This review provides an understanding of the difficulties of localizing and diagnosing PCa. It summarizes recent developments of ultrasound (including elastography) and MRI, and discusses some alternative experimental techniques, such as resonance sensor technology and vibrational spectroscopy. A comparison between the different methods is presented. It is concluded that new ultrasound techniques are promising for targeted biopsy procedures, in order to detect more clinically significant cancers while reducing the number of cores. MRI advances are very promising, but MRI remains expensive and MR-guided biopsy is complex. Resonance sensor technology and vibrational spectroscopy have shown promising results in vitro. There is a need for large prospective multicentre trials that unambiguously prove the clinical benefits of these new techniques.

Neuroglobin and cytoglobin as potential enzyme or substrate.

The possible enzymatic activities of neuro- and cytoglobin as well as their potential function as substrates in enzymatic reactions were studied. Neuro- and cytoglobin are found to show no appreciable superoxide dismutase, catalase, and peroxidase activities. However, the internal disulfide bond (CD7-D5) of human neuroglobin can be reduced by thioredoxin reductase. Furthermore, our in vivo and in vitro studies show that Escherichia coli cells contain an enzymatic reducing system that keeps the heme iron atom of neuroglobin in the Fe(2+) form in the presence of dioxygen despite the high autoxidation rate of the molecule. This reducing system needs a low-molecular-weight compound as co-factor. In vitro tests show that both NADH and NADPH can play this role. Furthermore, the reducing system is not specific for neuroglobin but allows the reduction of the ferric forms of other globins such as cytoglobin and myoglobin. A similar reducing system is present in eukaryotic tissue protein extracts.

A combined micro-resonance Raman and absorption set-up enabling in vivo studies under varying physiological conditions: The nerve globin in the nerve cord of Aphrodite aculeata.

We hereby report on the design of a set-up combining micro-resonance Raman and absorption spectroscopy with a microfluidic system. The set-up enabled us to study the nerve globin of Aphrodite aculeata in the functional isolated nerve cord under varying physiological conditions for extended periods of time. The oxygenation cycle of the organism was triggered by utilizing the microfluidic system that allowed for a fast switch between aerobic and anaerobic conditions. The nerve globin was found to very easily shift from a penta-coordinated high spin ferrous form to the oxy state upon a change from anaerobic to aerobic conditions. The observed fast reaction to varying O(2) concentrations supports an oxygen-carrying and/or -storing function of the nerve globin. In addition, by combining resonance Raman and absorption spectroscopy, the physiological response could be distinguished from light-induced effects.