Raman spectroscopy in neurosurgery

Abstract: Brain tumors or brain cancer is a disease than affects people of all ages. The median age of a person living with a brain tumor is 60 years, it is however a disease that affects children and young adults in high grade. Brain cancer is the second most common type of cancer among children and is also the most common cause of cancer related death among this group. To ensure that the damages on the brain is as small as possible, it is important that a tumor can be diagnosed and removed as early as possible. Previous methods of diagnosis is based on biopsy where a part of the tumor is removed and examinated by a pathologist. This is a time consuming process that also is biased by the human factor, there is therefore a need for a method that can be used \textit{in situ} with an unbiased result. One method that have shown great promise is photensitation with 5-Aminolevoluic acid (5-ALA). However, this method have shown to only work properly on tumors of high malignancy in adults. As a comlpiment to photosentisation, Raman spectroscopy have shown good promise in previous studies.  This study was conducted to investigate the use of Raman spectroscopy as a tool for \textit{in situ} brain tumor diagnostics. The use of Raman spectroscopy was tested by comparing two previously performed studies, where they looked at a number of Raman bands from biological markers that are known to change in cancerous tissue as well as the intensity ratio between some Raman bands.  A measurement system for Raman spectroscopy was designed and built at Luleå University of Technology where the system were evaluated on tissue samples from conventional meat i.e. pork and beef to ensure that is was possible to achieve spectroscopic information of protein and lipid content in tissue. The measurement system was then transported to Linköpings University where the measurements on six brain tissue samples where performed. The samples came from five different tumors of which one tumor was thought to come from a high malignant tumor based on preliminary histopathological analysis and four from low malignant or benign tumors. Two samples where obtained from the high malignant tumor that was photosentisized with 5-Aminolevoluic acid and one of the samples where illuminated with blue light prior to the Raman spectroscopic measurements.  The spectroscopic data was pre-processed before analysis using conventional methods. The analysed spectra from the brain tissue samples showed presence of the Raman bands associated with brain tissue. It was also possible to see Raman bands associated with 5-ALA in the samples that had been photosentisized, however when the tissue had been illuminated with blue light it was also possible to see distinct Raman bands associated with brain tissue. One tissue sample also showed presence of reduced Neuroglobin (NGB). The composition of NGB is also known to change in tumorous tissue and could therefore be used in future work as a biological marker for brain tumors. When comparing the results obtained in this study with the two previously performed, one of the studies showed that two samples were from a tumor of high malignancy and the other from low malignant or benign tumors. This result was in accordance with the preliminary histopathological assessment of the brain tissue samples. When comparing the results to the other study, the results where contradictory and indicated that all tissue samples where from low malignant or benign tumors.  The conclusion of this work is that Raman spectroscopy is possible to use as a tool for brain tumor diagnostics. It would be desirable to use this method in combination with 5-ALA staining since the Raman bands from brain tissue could be resolved when the tissue had been illuminated with blue light.