Introduction: Laser interstitial thermal therapy (LITT) is a minimally invasive, cytoreductive treatment used for recurrent glioblastoma (GBM). Gadolinium enhancement is typically observed in peri-ablation zone after LITT for GBM in humans, indicating blood brain barrier (BBB) breakdown locally. However, the magnitude and temporal progress of this BBB breakdown are not known. This study investigated the temporal and spatial alterations in post-LITT blood-brain barrier (BBB) permeability using a rat GBM model.
Methods: Athymic rats underwent LITT after implantation of a U251 orthotopic xenograft tumor (n=6). At sacrifice they were injected with fluorescent tracers Evans blue (~68 kDa after binding to plasma albumin) and dextran (40 kDa). Tumor extent was estimated using magnetic resonance imaging (MRI) and its vascular properties measured by dynamic contrast enhanced MRI (DCE-MRI) with Magnevist (~1000 Da) as contrast agent. A Visualase LITT system (Medtronic Inc.) was used for ablation under diffusion-weighted imaging (DWI). Laser power was set at 2 W for 40±10 s. Insertion of the laser fiber without firing was performed in sham controls. Post-LITT imaging was done at 24 h and then at weekly intervals until sacrifice.
Results: Immediate post-ablation MRI showed a ring of peri-ablation zone contrast enhancement. The spatial extent of enhancement decreased over 4 weeks and by weeks 5 and 6 was restricted to the original tumor location. Histologically, LITT led to a clearly demarcated ablation area with edematous, but normal appearing neuropil in the peri-ablation zone. Fluorescence imaging showed peri-ablation areas with dextran leakage and isolated spots with Evans blue leakage and its uptake by cells in the vicinity.
Conclusions: These data suggest that post-ablation BBB opening leads to extravasation of blood-borne tracers. Whether it can be exploited for delivering chemotherapy to remaining tumor cells is the subject for further investigation.
Patient Care: Laser ablation may provide a method for improving delivery of chemotherapy improving the treatment of high grade glioma
Learning Objectives: Understand the BBB breakdown associated with laser ablation