A translational, preclinical model of image-guided laser interstitial thermal therapy for glioma cytoreduction with implications for testing therapies

Document Type

Conference Proceeding

Publication Date

6-11-2023

Publication Title

J Cereb Blood Flow Metab

Abstract

Background: In vivo models of glioblastoma (GBM) are necessary for preclinical therapy testing. Animal models that parallel the clinical scenario of image-guided GBM cytoablation are presently unavailable. Aim: We have adapted image-guided, laser interstitial thermal therapy (LITT) for a preclinical GBM model with the aim of measuring tumor status and its vascular kinetics, acutely as surrogate biomarkers for ablation efficacy and longitudinally to assess GBM recurrence. Method: Athymic female rats were implanted with U251N tumor cells (n=20). When tumors reached ∼4mm in diameter, they were ablated using a Visualase LITT system under diffusion-weighted MRI guidance. Five unablated tumor-bearing rats served as controls. MRI data were acquired at 24 h, and 2 and 4 weeks post-LITT. Rats were sacrificed for histopathology at 24 h, 2 and 4 weeks and the brain sections stained for hematoxylin and eosin (H&E) and human major histocompatibility complex (MHC) to measure the extent of tumor and to identify U251 tumor cells that are of human origin. Results: Sham controls were euthanized due to increased tumor burden by 2 weeks. LITT group showed little tumor tissue at post-LITT 24 h, evidence of recurrence at 2 weeks and significant regrowth at 4 weeks. MRI parameters showed elevated tumoral vascular permeability, Ktrans, values at pre-LITT imaging, that significantly decreased at 24 h and continued to be very low for the next 2 weeks. However, peri-ablation regions showed elevated Ktrans values at post-LITT 24 h suggesting increased bloodbrain barrier (BBB) permeability in ablation periphery (Fig. 1). A significant increase in Ktrans at 2 and 4 weeks coincided with glioma recurrence. Conclusions: A new preclinical image-guided GBM ablation model is presented. MRI was efficient in evaluating GBM cytoreduction and its subsequent recurrence. The recurrent tumor presented with radiological and histological features that were similar to recurrent human GBM.

PubMed ID

Not assigned.

Volume

43

Issue

1

First Page

S158

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