Photodynamic intraoperative diagnosis of braintumors

Objective: This project investigates the potential of fluorescent activity of photosensitisers, which are currently used for intraoperative photodynamic therapy (PDT), to be used for intraoperative photodynamic diagnosis (PDD) of brain tumours. This would allow a more radical resection of the tumour, a circumstance which has great impact on survival of the patients. Introduction: Malignant brain tumours are lethal with a median survival time of 15 months despite all available treatment. A radical resection is hardly possibly because of infiltration of tumour into normal brain tissue and poor differentiation tumour/normal brain. Because of the high selective uptake into malignant tissue and the fluorescence activity of photosensitizer (PS), malignant tissue and its borderline can be differentiated from normal tissue by fluorescence. When stimulated at the appropriate wavelength photosensitisers have the ability not only to fluoresce but also to be phototoxic. This concept of intraoperative fluorescence diagnosis followed by immediate photodynamic therapy is a logical approach to the treatment of infiltrating diffuse malignant gliomas. Fluorescence diagnosis mediated by PS such as delta Amino LeavulinicAcid (5-ALA) and meta- Tetra HydroxyPhenylChlorin (mTHPC) has demonstrated a high selectivity and specificity for bladder tumours and skin lesions and recently for brain tumours. Methods: After obtaining informed consent the patients presenting with high grade gliomas are sensitised by mTHPC prior to operation: A Xenonfight is used for inducing fluorescence. The fluorescence activity will be recorded by a CCD camera , processed by a PC and visualised on-line. The fluorescence signal will further be analysed by a spectrophotometer for chlorine specificity for better distinction between malignant tissues and normal brain, a fact which is especially important in low grade gliomas. The fluorescence signal will be coupled to the operating microscope, which allows on-line real-time microsurgical resection. Summary: After successful completion of this project, we expect intraoperative PDD to become a important tool for neurosurgeons with impact on other specialities. Intraoperative fluorescence allows intraoperative on-line diagnostic and the probability of radical resection is therefore significantly higher. In cam where tumour has to be left because of invasion of functional structures, this remaining portion of the tumour can be treated photodynamically followed immediately after fluorescence diagnosis. This diagnostic and therapeutic concept can be summarised in " to see and to treat". Photodynamic diagnosis bears furthermore the potential to replace neuronavigation to some extent in the near future. Since 1983 the Department for Neurosurgery, Innsbruck, is engaged heavily in the experimental and clinical development of photodynamic application in neurosurgery and is highly acknowledged.