LAUSR

Neovascularization together with aberrant vasculature is a hallmark of glioblastomas. Understanding tumor vasculature can have a pivotal role in planning therapeutics approaches. The objective of this study was to investigate morphological, vasculature and blood flow changes induced by aggressive tumor growth, using in vivo imaging - magnetic resonance imaging (MRI) and functional ultrasound (fUS) imaging in a mouse model of orthotopic glioma. Female NMRI nude mice were xenografted orthotopically with U-87 MG, a human glioblastoma, cells (5 × 104) at the age of 8 weeks. Four weeks after implantation the mice we anesthetized with isoflurane and scanned with 11.7 T small animal MRI (Bruker) for tumor volumetry. Thereafter, the mice were imaged with Iconeus One imaging system (Iconeus, Paris, France) for structural information of brain vasculature and relative cerebral blood volume (rCBV) changes. High resolution vascular imaging was performed after intravenous injection of microbubble contrast agent (SonoVue, sulphur hexafluoride microbubbles). The average tumor size was 58.8 ± 27.6 mm3 (mean ± SD, n=7) four weeks after implantation. Aberrant vasculature could be visualized with structural fUS imaging as and the necrotic core of the tumor could be observed. A reduced rCBF was observed in ipsilateral hemisphere on the relative power doppler signal timeseries as a lower amplitude and faster decay compared to contralateral side. As a summary, in vivo fUS imaging is a noninvasive tool to visualize vascular changes induced by aggressive brain tumor growth which are not detectable with conventional imaging methods (CT, MRI, PET, SPECT) and can provide a novel readout for efficacy studies. Citation Format: Jussi Rytkönen, Kimmo Lehtimäki, Taina-Kaisa Stenius, Riikka Immonen, Ari Suhonen, Artem Shatillo. In vivo imaging of vascular pathology in mouse orthotopic glioma model using functional ultrasound [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB155.