In vivo MRI assessment of the pharmacological opening of the blood brain barrier by intraperitoneal mannitol injection in mice

摘要

Hyperosmolar mannitol administration is used in the clinical and preclinical setting to deliver therapeutic agents across the Blood Brain Barrier (BBB). In most rodent studies, invasive intracarotid mannitol administration is performed. Here, we use dynamic Rapid Steady State (RSS)-MRI1 with the low-molecular weight contrast agent Gd-DOTA and a long observation interval to assess BBB opening upon intraperitoneal (ip) injection of mannitol. Subjects and Methods: Acquisitions were performed at 7T with a 72 mm volume resonator for emission and a 2 9 2 elements phased array surface cryoprobe. Female Swiss mice (n = 5) underwent dynamic T_1-weighted RSS-MRI~1 over 2 h, with ip Gd-DOTA injection (10 mmol/kg) at 5 min and ip mannitol injection (2.5 g/kg, 20%) at 20 min. RSS MRI was performed with a 3D inversion recovery prepared fast gradient echo sequence (TR/TI/TR_(echo)/TE/α = 750/295/ 5/1.5 ms/10°, 300 repetitions, matrix 64x64x33, resolution 230x230x500 mm~3). Time parameters are optimized to null the signal from brain parenchyma and blood (T_1>1 s). Heuristic parameters such as delay and initial slope of signal increase were determined in key brain regions to study the effects of mannitol.