Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat

Abstract

Blood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2 * w, gadolinium (Gd) enhanced T1w] is used to monitor the effects of pFUS+MB on BBBO and/or assess whether sonication results in parenchymal damage. This study employed multimodal MRI techniques and 18 F-Fludeoxyglucose (FDG) PET to evaluate the effects of single and multiple weekly pFUS+MB sessions on morphology and glucose utilization levels in the rat cortex and hippocampus. pFUS was performed with 0.548 MHz transducer with a slow infusion over 1 min of Optison TM (5-8 × 10 7 MB) in nine focal points in cortex and four in hippocampus. During pFUS+MB treatment, Gd-T1w was performed at 3 T to confirm BBBO, along with subsequent T2w, T2 * w, DTI and glucose CEST (glucoCEST)-weighted imaging by high field 9.4 T and compared with FDG-PET and immunohistochemistry. Animals receiving a single pFUS+MB exhibited minimal hypointense voxels on T2 * w. Brains receiving multiple pFUS+MB treatments demonstrated persistent T2w and T2 * abnormalities associated with changes in DTI and glucoCEST when compared to contralateral parenchyma. Decreased glucoCEST contrast was substantiated by FDG-PET in cortex following multiple sonications. Immunohistochemistry showed significantly dilated vessels and decreased neuronal glucose transporter (GLUT3) expression in sonicated cortex and hippocampus without changes in neuronal counts. These results suggest the importance to standardize MRI protocols in concert with advanced imaging techniques when evaluating long term effects of pFUS+MB BBBO in clinical trials for neurological diseases.

Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain

“…Numerous studies have demonstrated the usefulness of magnetic resonance imaging (MRI) techniques in animal experiments, which is important for pathogenesis researches, drug developments, and so on (Bible et al, 2012 ; Kim et al, 2012 ; Wang et al, 2012 , 2018 ; Li et al, 2015 ; Liang et al, 2020 ; Tu et al, 2020 ). Manganese-enhanced MRI (MEMRI), a new MRI technique, could detect the active neurons and trace neuronal pathway by monitoring manganese ions (Mn 2+ ) in vivo (Aoki et al, 2004 ; Koretsky and Silva, 2004 ).…”