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.研究目的：本研究旨在通过一种新型成像方案——定量超短回波时间对比增强磁共振成像（quantitative ultra-short time-to-echo contrast-enhanced magnetic resonance imaging, QUTE-CE MRI），评估单次及重复性轻度颅脑损伤对血脑屏障（blood brain barrier, BBB）的通透性损伤情况，以定量分析微血管通透性的变化。 研究方法：本研究采用闭合式动量交换模型，对雄性大鼠制造单次或三次轻度颅脑损伤，并设置未损伤对照组作为对照。作为定量血管生物标志物的QUTE-CE技术可生成包含超过50万个体素的血管造影图像，这些图像配准至大鼠三维磁共振脑图谱，可提供173个不同脑区中BBB通透性的位点特异性信息。通透性升高的脑区通过标记葡聚糖的外渗实验得到了验证。 研究结果：所有颅脑损伤模型均未出现脑结构性损伤的神经放射学征象。单次轻度颅脑损伤可使撞击位点正下方的皮层区域BBB通透性升高；而在48小时内连续三次颅脑损伤则会累及撞击位点远端的更大范围脑区，并累及大部分基底神经节。 研究解读：将QUTE-CE技术与大鼠磁共振脑图谱及计算分析相结合，可在重复性轻度颅脑损伤后，识别全脑范围内BBB通透性的位点特异性升高。QUTE-CE技术可便捷地应用于临床，为颅脑损伤后数小时内评估BBB损伤严重程度提供一种定量无创的检测方法。 数据集详情：每次成像实验开始前，均采用RARE脉冲序列采集高分辨率解剖数据集，具体参数如下：35层切片，层厚0.7 mm；视野（field of view, FOV）3 cm；矩阵尺寸256 × 256；重复时间（repetition time, TR）3900毫秒；有效回波时间（echo time, TE）48毫秒；激励次数（number of excitations, NEX）3；采集时长6分14秒。 QUTE-CE磁共振成像参数如下：TE=13微秒，TR=4毫秒，翻转角（flip angle, FA）=15°，射频脉冲带宽200 kHz。采用3×3×3 cm³的视野，矩阵尺寸为180×180×180，可获得167微米的各向同性分辨率。 所有数据均转换为NIfTI格式。每个数据集对应一个独立文件夹，包含9只大鼠的扫描数据（编号R1至R10，排除R6）。每个文件夹中包含基线扫描及对比剂（超顺磁性氧化铁，SPION）注射后的扫描数据。文件名可反映扫描类型。