Scidot-50. A Rat Model for Laser Interstitial Thermal Therapy for Glioblastoma: Effects on Peri-Ablation Blood-Brain Barrier and Implications for Post-Ablation Chemotherapy

Abstract

Laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas, brain tumors in eloquent regions or otherwise inaccessible to traditional open surgery. LITT offers quicker recovery and shorter hospital stays as additional advantages. A laser fiberoptic catheter is positioned in the body of the tumor under magnetic resonance imaging (MRI) guidance via a twist drill hole in the skull. Using MR thermometry, the tumor is ablated by laser heating to lethal temperatures. The peri-ablation zones get heated to sub-lethal temperatures and subsequently recover. It has been reported in humans that opening of the blood-brain barrier (BBB) occurs, lasting several weeks after ablation. We have adapted Visualase®, a clinically available LITT system, for use in a rat glioblastoma model. Athymic female rats (n=7) were implanted with U251 tumor cells in one brain hemisphere. Tumor growth was monitored using MRI. When tumors reached about 4 mm in diameter, they were ablated under supervision of MR diffusion-weighted MRI, sparing the surrounding normal brain tissue. Contrast-enhanced MRI data were obtained before LITT, immediately after and at post-LITT 24 h. The brains were processed for histopathology and stained with hematoxylin and eosin (H&E) for visualizing the extent of the tumor and for major histocompatibility complex (MHC) to identify the human-derived U251 cells. All rats survived the LITT procedure. A ring of contrast enhancement around ablation perimeter was observed immediately after, and also at 24 h. H&E data showed near-complete ablation of the tumors. However, MHC staining showed U251 cells still remaining in the ablation vicinity. These data suggest this model is useful for examining the temporal and spatial development of peri-ablation BBB opening following LITT. Concurrent timing of post-ablation chemotherapy to the development and presence of post-LITT BBB opening may aid in efficient targeting of remaining tumor cells.