Evaluation of sonobiopsy feasibility and safety in a mouse model of diffuse intrinsic pontine glioma

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of pediatric brain cancer mortality, emphasizing the need for precise molecular diagnosis to advance therapeutic development. The tumor's location in the brainstem poses challenges for invasive biopsy, prompting the exploration of liquid biopsies. However, both blood-based and cerebrospinal fluid (CSF)-based liquid biopsies exhibit limited sensitivity in diagnosing DIPG. Sonobiopsy, an innovative technique utilizing focused ultrasound and microbubbles, aims to enhance the sensitivity of liquid biopsies. This study assessed the feasibility and safety of sonobiopsy in a DIPG mouse model. The model was established by intracranial injection of enhanced green-fluorescent-protein (eGFP) transduced DIPG tumor cells. Mice were divided into sonobiopsy and conventional liquid biopsy groups. Sonobiopsy, employing MRI-guided focused ultrasound and microbubbles, demonstrated increases in plasma and CSF eGFP DNA, RNA, and protein concentrations compared to conventional liquid biopsy. The enrichment effect varied based on the biomarker type. No observed hemorrhage or tissue damage attributed to sonication suggests the safety of this approach. These results affirm the feasibility and safety of sonobiopsy in enriching DIPG-specific biomarkers in both plasma and CSF, suggesting sonobiopsy as a promising noninvasive molecular diagnostic tool for DIPG.