Abstract Introduction Brain tumor needle biopsy interventions are inflicted with non-diagnostic or biased sampling in up to 25% and hemorrhage, including asymptomatic cases, in up to 60%. To identify diagnostic tissue and sites with increased microcirculation, intraoperative optical techniques have been suggested. The aim of this study was to investigate the clinical implications of in situ optical guidance in frameless navigated tumor biopsies. Methods Real-time feedback on protoporphyrin IX (PpIX) fluorescence, microcirculation, and gray-whiteness was given before tissue sampling (272 positions) in 20 patients along 21 trajectories in total. The primary variables of investigation were fluorescence in relation to neuropathological findings and gadolinium (Gd) enhancement, increased cerebral microcirculation in relation to bleeding incidence, number of trajectories, and impact on operation time. Results PpIX fluorescence was detected in Glioblastoma IDH-wildtype CNS WHO grade 4 (n=12), Primary diffuse large B-cell lymphoma (n=3), astrocytoma IDH-mutated CNS WHO grade 4 (n=1) (Ki67 indices ≥15%). For two patients, no PpIX fluorescence or Gd was found, although samples contained tumorous tissue (Ki67 index 6%). Increased microcirculation was found along nine trajectories (34 sites), located in cortical, tumorous, or tentorium regions. Postoperative bleedings (n=10, nine asymptomatic) were related to skull opening or tissue sampling. The present study strengthens the proposed independence from intraoperative neuropathology as PpIX fluorescence is detected. Objective real-time feedback resulted in fewer trajectories compared to previous studies indicating reduced operation time. Conclusions The integrated optical guidance system provides real-time feedback in situ, increasing certainty and precision of diagnostic tissue before sampling during frameless brain tumor biopsies.
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