Quantitative imaging of blood brain barrier permeability following repetitive mild head injury

Objectives: The study was designed to evaluate the vulnerability of the blood brain barrier (BBB) to single and repetitive mild head injury using a novel imaging protocol quantitative ultra-short time-to-echo contrast-enhanced magnetic resonance imaging (QUTE-CE MRI) to quantitate changes in microvascular permeability Methods: A closed-head momentum exchange model was used to produce one or three mild head injuries in male rats as compared to non-injured controls. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on BBB permeability in 173 different brain areas. Areas of increased permeability were confirmed by extravasation of labelled dextran. Results: Head injuries occurred without neuroradiological signs of structural brain damage. A single mild head injury increased BBB permeability in cortical areas immediately beneath the site of impact, while three head injuries within 48 hrs of each other compromised a broader area of the brain distal to the site of impact and affecting much of the basal ganglia. Interpretation: QUTE-CE when combined with a rat MRI atlas and computational analysis can identify site-specific increases in BBB permeability across the entire brain following repetitive, mild head injury. QUTE-CE can be readily used in the clinic to provide quantitative non-invasive method for assessing the severity of BBB injury within hours of head injury. Data: At the beginning of each imaging session, a high-resolution anatomical data set was collected using the RARE pulse sequence with following parameters, 35 slice of 0.7 mm thickness; field of view [FOV] 3 cm; 256 × 256; repetition time [TR] 3900 msec; effective echo time [TE] 48 msec; number of excitations (NEX) 3; 6 min 14 sec acquisition time. The QUTE-CE MRI image parameters are: TE = 13 µs, TR=4 ms, flip angle (FA) = 15°, RF pulse bandwidth of 200 kHz. A 3 x 3 x 3 cm3 FOV was used with a matrix size of 180 x 180 x 180 to produce 167 µm isotropic resolution. The data converted to Nifti Format. For each data set there is independent folder that includes scans from 9 animals R1 to R10 excluding R6. Each folder has baseline scan and post contrast agent (SPION) scan. Filenames are indicative of scans