Investigation Of Microstructure In Glioblastoma Based On Multiphoton Microscopy

In the United States,brain and nervous system tumors account for 3% of all cancer deaths.Glioma is the most common brain tumor in adults and caused by the irregular growth of glial cells in the cerebral cortex which is characterized by diffuse infiltration around the cerebral cortex.Inadequate resection and recurrence due to invasion of brain tumors and limited intracranial space,severely affecting patient survival.Therefore,the intraoperative in situ diagnosis of residual brain tumors is essential to the best personalized treatment.However,the current clinical diagnostic techniques are deficient in resolution and time-consuming,which make it impossible to accurately diagnose glioma in real time and provide clear pathological information of microstructural changes.In this paper,in order to demonstrate MPM have the ability to clearly identify the microstructure of glioblastoma(GBM)and its value for intraoperative diagnosis and subsequent treatment,the architectural feature in GBM were investigated based on MPM.GBM is the most malignant glioma.First,imaging of brain and brain tumor samples was performed by MPM,the results show that MPM can effectively detect brain tumor cells,the change of extracellular matrix collagen component in tumor microenviroment.two quantitative indicators,nuclear-to-cytoplasmic ratio and collagen content can be extracted to differentiate brain glioma from healthy brain tissues.Secondly,the fresh specimens and histological slices without any staining or labelling were used to perform MPM imaging based on intrinsic SHG and TPEF signals of fibrillar collagens in GBM.We demonstrated that there was fibrillar collagen deposition in the adventitia of remodelled large blood vessels and in the glomeruloid vascular structure in GBM.This method not only can be employed to perform a retrospective study in unstained histological slices but also has the potential to apply for in vivo brain imaging to understand correlations between malignancy of gliomas and fibrillar collagen deposition.Lastly,we further studied the vascular structure of GBM base on MPM,the results showed that the abundant irregular size blood vessels in GBM.It has also been demonstrated that the MPM is capable of identifying several specific vascular patterns.And quantitative resultsshow that they have large differences in collagen content,indicating that the quantitative difference in collagen content can be used as a potential indicator to determine the different types of blood vessels in GBM.