Prostate cancer has received significant attention as it is common but difficult to diagnose and treat. Many of the methods that are used are unreliable. The project aims to develop a combination sensor to localise cancer of the prostate. The instrument combines Raman spectroscopy and resonance sensor technology and the hope is that it will prove a good alternative to tissue samples or PSA tests
The purpose of the project is to develop a new method for detection of prostate cancer that can be used during surgical removal and more accurately localise cancer boundaries and determine the level of aggressiveness of the cancer, than existing methods. The aims are to first explore the individual capacity of a micro tactile scanner (MTS) and fibre optic Raman spectroscopy to detect cancer cells and determine the aggressiveness of the cancer. With aggressiveness we mean the ability of the cancer to grow and to metastasize, i.e. to spread and develop new tumours. After the individual capacities have been determined, we want to combine the tactile resonance sensor technique with Raman spectroscopy into a combined probe – a diagnostic tool for fast and detailed detection of cancer, its aggressiveness and its boundaries towards non-cancerous tissue.
We have excellent experimental facilities in our lab with an MTS system and a fibre optic Raman system. Both setups can today be operated in parallel with an accurate XYZ arrangement. Furthermore we have an intense cooperation with the Japanese group introducing the tactile mapping system as well as long lasting cooperation with the department of pathology at Umeå University. Hence we have unique competence and opportunity to combine the two methods into one combined sensor for reliable cancer detection on both the microscopic and macroscopic level. The first goal is to compare the information from both techniques by studying data obtained with the MTS and the fibre optic Raman probe on the same sites on a sample. Therefore comparative experiments will be carried out. The goal of these experiments is to improve the statistical evaluation and comparison of the information and to create a software tool box with automated read out. In these experiments the MTS-system with the ultra-thin resonance sensor tip will be scanned over a thin slice of prostate tissue measuring the resonance shift at pre-programmed positions. Subsequently fibre optic Raman spectra will be recorded at the same spots. Information coming from both read outs will be compared by linear regression analysis and other statistical means. The advantage of using this approach is that the sampling area of both methods will be similar, which simplifies the statistical evaluation. Some promising data is revealed in the Results paragraph below. A further goal is to compare the stiffness of a growing tumour with the molecular alteration on the cellular level. By linking biomechanical with biochemical information we can learn more about the progression of cancer. We can define parameters related to the tumours aggressiveness and to the ability to metastasize, which will have tremendous impact on cancer treatment. Validation is done with morphometric methods revealing the actual tissue composition. The final aim with the suggested project is to combine a cylindrical resonance sensor with a fibre optic Raman probe into one combination probe head. At this stage, performance and sensitivity of the resonance sensor element and the Raman probe have been carefully evaluated individually. For the combination probe a tactile resonance sensor, consisting of a cylindrical piezoelectric element made of PZT (Lead Zirconate Titanate) with an outer diameter of 5 mm and an inner-hole diameter of 3 mm is used . Through the channel, an optical fibre bundle arranged in a thin steel tube is introduced. The fibre bundle consists of one excitation fibre to transfer the laser light for Raman spectrometry onto the sample and eight recollection fibres to accumulate the Raman scattered photons . Raman probes with high throughput can today be manufactured with an outer diameter of less than 1 mm (see the Instrumentations chapter). The ultra-thin Raman probe is moulded inside the PZT element using a special rubber and a smart geometry to minimize disturbance of the PZT vibration. The idea is to use the combined probe by first scanning the tissue for stiffness changes with the resonance part of the sensor and where hardened areas, or interfaces between areas with different hardness, are detected, Raman spectra are measured by laser illumination of the tissue at the probe site. By doing so, unnecessary laser exposure can be avoided and detailed information on the microscopic level is only collected at relevant places. The first clinical application of a combined Raman and resonance sensor will be during surgical removal of prostate cancer on humans. The goal is to in situ detect the boundary between cancer and non-cancer tissue. By doing so the whole tumor and thus all cancer cells can be removed with high precision to avoid reoccurring of the disease. The tissue is exposed to air and hence great care has to be taken in order to prevent drying out of the tissue. Hence, the laser should be used as little as possible, i.e. only at critical points at the boundary between healthy and malignant prostate tissue. The gross significant regions can be determined by the resonance part of the sensor whereas the boundaries can be localized minutely by the Raman part of the sensor.