Abstract
Abstract Image-guided laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas and tumors in eloquent loci. We have adapted this technique to develop an image-guided glioblastoma (GBM) ablation model, its recurrence and have tested the efficacy of imaging biomarkers in evaluating tumor ablation and recurrence. The cytopathology and molecular signatures of the primary and recurrent tumors were compared. Immune-compromised female rats were implanted with U251N tumor cells in one brain hemisphere (n=20). Tumor growth was monitored using magnetic resonance imaging (MRI). When tumors reached about 4 mm in diameter, they were ablated using a clinical LITT system (Visualase®), under MRI guidance. Five other rats implanted with U251N tumors were used as unablated controls. MRI data were acquired at 24 h post-LITT, and at 2 and 4 weeks. Rats were sacrificed for histopathology at 2 and 4 weeks, and brain sections stained for hematoxylin and eosin, human major histocompatibility complex, Ki67, a cell proliferation marker and sex determining region Y)-box 2 (SOX2), a stem cell transcription factor. An additional cohort of rats with primary (n=4) and post-LITT recurrent (n=4) U251N tumors were used for analysis of their molecular composition using RNA-Seq approach. In the treated groups, MRI showed little tumor tissue at 24 h, evidence of recurrence at 2 weeks and significant tumor tissue at 4 weeks. Tumor DCE-MRI parameters showed elevated intra-tumoral vascular permeability (i.e., Ktrans) values at pre-LITT imaging, that shifted to peri-ablation periphery at 24 h. A trend of progressive decrease in Ktrans was seen until 1-week post-ablation. Increasing Ktrans values at 2 weeks and after 4 weeks coincided with tumor recurrence. RNA-Seq data showed that cell cycle, cellular movement and inflammatory disease genes were the most differentially expressed genes in the recurrent tumors suggesting increased infiltration may primarily underlie treatment resistance.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.