Konfokale Laser Endomikroskopie zeigt mikroskopische Gewebemorphologie zur intraoperativen Qualitäts-Analyse von Hirntumor-Biopsien

Brain tumor biopsies in cases with equivocal patient history or MRI findings inherently carry a risk for inconclusive results or neurological deficits. This results in a constant need for innovation to tackle both issues. Confocal laser endomicroscopy (CLE) is an emerging technology that enables real-time assessment of tissue micro-morphology during surgery. Hence, we aimed to evaluate the utility of CLE for quality assessment of demanding brain tumor biopsies.

The study was conducted on 19 patients undergoing brain tumor biopsies with equivocal MRI findings. Sodium fluorescein (Na-F; 5 mg per kg bodyweight) was administered as a contrast agent at the time of skin incision and CLE imaging was performed on freshly biopsied tissue ex vivo (n=1-8 per case). The CLE images were visually inspected by the neurosurgeon and the neuropathologist for signal intensity and tissue features, including cell size and density. Subsequently, the biopsies were transferred for frozen section pathology and diagnostic histopathological workup.

Imaging was performed in median 28 min (range 20-53 min) after administration of Na-F. On average, 147 images were acquired on each biopsy (range 54-331). Time series allowed to differentiate cellular patterns from contaminations with erythrocytes that were moving across the field of interest. In 13/19 cases, a strong fluorescence signal of Na-F was seen together with additional image features (e.g. increased cell density and pleomorphic cells) allowing a preliminary diagnosis. If the Na-F signal was subtle, micromorphological abnormalities could still be identified and the specimen was subsequently considered sufficient for histopathology. Typically, strong Na-F fluorescence was found in glioblastoma and lymphoma and brain metastases, while a subtle Na-F signal accounted for a broad spectrum of entities such as multiple sclerosis or low-grade glioma. It is noteworthy, that those results might be skewed considering the demanding selection of cases. Importantly, histopathological workup was not affected by CLE imaging and a definite diagnosis was possible in all cases.

CLE with Na-F is a valuable tool for intraoperative quality assessment of demanding brain tumor biopsies and frequently allows for assignment of a preliminary diagnosis. Immediate histopathological evaluation enables intraoperative adaptation in biopsy location and sample amount, therefore reducing the likelihood of inconclusive biopsies and neurological deficits.