Abstract

Abstract Background Stereotactic brain tumor biopsies represent a standard neurosurgical technique enabling a precise histopathological tumor diagnosis which is of utmost importance for optimal further treatment allocation. However, non-diagnostic biopsies are not uncommon in routine clinical practice. To overcome this shortcoming, serial biopsies or intraoperative histopathology are typically performed prolonging the operating times and potentially increasing the risk of complications. Recently, the value of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence for visualization of diagnostic tumor tissue was demonstrated in navigation-guided brain tumor biopsies. However, a not negligible proportion of brain tumors lack visible fluorescence. In some of these tumors, a subvisual concentration of PpIX could be detected by spectroscopic analysis. Thus, detection of such subvisual PpIX accumulation in tumor samples in biopsies by the new “Fluorescence Lifetime Imaging” (FLIM) technique might lead to further improvement of this approach. Material and Methods Patients that underwent navigation-guided biopsy of a suspected brain tumor were eligible for inclusion in this study. After administration of 5-ALA, the tissue samples were checked for visible fluorescence during the navigation-guided stereotactic biopsy with a sterile microscope. In each sample the observed fluorescence signal was documented. Additionally, the tissue samples were investigated ex-vivo by FLIM for detection of PpIX accumulation. In each case, a histopathological diagnosis was established according to the WHO classification of CNS tumors. Results A total number of 20 tissue samples could be retrieved in 16 patients with suspected brain tumors. The biopsy with assistance of 5-ALA was feasible in all patients and no relevant side effects occurred. Visible PpIX fluorescence could be observed in 75% of cases. In contrast, 25% of samples did not show visible fluorescence. In one specimen, no fluorescence signal could be evaluated as the sample was covered by too much blood. However, significant accumulation of PpIX could be detected by FLIM in all samples in which evaluation was possible (n=19). A final histopathological diagnosis was feasible in all patients. Conclusion Fluorescence Lifetime Imaging is a promising new technique for improved detection of brain tumor tissue during navigation-guided biopsies. Thus, this new technique might lead in future to reduced operating times and complication rate by minimizing the cases that need serial biopsies or intraoperative histopathology.

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