Fluorescence-guided resections of malignant gliomas using 5-ALA

It is generally accepted that the completeness of resection in malignant gliomas should be as complete as possible. Maximal cytoreductive surgery is generally performed aiming at removing at least that part of the tumor that accumulates a contrast agent for magnetic resonance imaging (contrast-enhanced MRI) (1;2). Complete resection of contrast enhancing tumor regions as judged by post-operative MRI is only achieved in a minority of patients (3-6), one of the reasons for this being the difficulty in detecting contrast-enhancing tumor margins intraoperatively (3). Much effort has been put into the development of methods to improve intraoperative tumor detection, such as neuronavigation (7), ultrasound (8), interventional CT (9) or nuclear magnetic resonance imaging (MRI) (10). A direct optical identification of glioma tissue is suggested to be possible by fluorescence imaging of ALA-induced PpIX (11;12). Five-aminolevulinic acid (ALA) is a natural biochemical precursor of hemoglobin. Exogenous administration of ALA elicits the synthesis and accumulation of fluorescent porphyrins in various epithelia and cancerous tissues (13;14). Malignant glioma tissue has also been demonstrated to specifically synthesize and accumulate porphyrins, mainly PpIX in response to ALA administration. PpIX shows red fluorescence when excited with violet-blue light and can be visualized after appropriate modifications to a standard neurosurgical microscope (15). The resulting fluorescence has been under investigation as an intra-operative marker for residual malignant glioma tissue with the aim of improving the surgical treatment of these tumors (11;15).