Varatharaj Aravinthan, Jacob Carmen, Darekar Angela, Yuen Brian, Cramer Stig, Larsson Henrik, Galea Ian
Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Imaging Neurosci (Camb). 2024 Oct 22;2:1-16. doi: 10.1162/imag_a_00324. eCollection 2024 Oct 1.
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to quantify the blood-brain barrier (BBB) permeability-surface area product. Serial measurements can indicate changes in BBB health, of interest to the study of normal physiology, neurological disease, and the effect of therapeutics. We performed a scan-rescan study to inform both sample size calculation for future studies and an appropriate reference change value for patient care. The final dataset included 28 healthy individuals (mean age 53.0 years, 82% female) scanned twice with mean interval 9.9 weeks. DCE-MRI was performed at 3T using a 3D gradient echo sequence with whole brain coverage, T1 mapping using variable flip angles, and a 16-min dynamic sequence with a 3.2-s time resolution. Segmentation of white and grey matter (WM/GM) was performed using a 3D magnetization-prepared gradient echo image. The influx constant K was calculated using the Patlak method. The primary outcome was the within-subject coefficient of variation (CV) of K in both WM and GM. K values followed biological expectations in relation to known GM/WM differences in cerebral blood volume (CBV) and consequently vascular surface area. Subject-derived arterial input functions showed marked within-subject variability which were significantly reduced by using a venous input function (CV of area under the curve 46 vs. 12%, p < 0.001). Use of the venous input function significantly improved the CV of K in both WM (30 vs. 59%, p < 0.001) and GM (21 vs. 53%, p < 0.001). Further improvement was obtained using motion correction, scaling the venous input function by the artery, and using the median rather than the mean of individual voxel data. The final method gave CV of 27% and 17% in WM and GM, respectively. No further improvement was obtained by replacing the subject-derived input function by one standard population input function. CV of K was shown to be highly sensitive to dynamic sequence duration, with shorter measurement periods giving marked deterioration especially in WM. In conclusion, measurement variability of 3D brain DCE-MRI is sensitive to analysis method and a large precision improvement is obtained using a venous input function.
动态对比增强磁共振成像（DCE-MRI）用于量化血脑屏障（BBB）的通透表面积乘积。连续测量可显示BBB健康状况的变化，这对于正常生理学、神经疾病研究以及治疗效果研究具有重要意义。我们进行了一项重测研究，以确定未来研究的样本量计算方法以及适用于患者护理的参考变化值。最终数据集包括28名健康个体（平均年龄53.0岁，82%为女性），平均间隔9.9周进行了两次扫描。DCE-MRI在3T条件下使用全脑覆盖的三维梯度回波序列、可变翻转角的T1映射以及时间分辨率为3.2秒的16分钟动态序列进行。使用三维磁化准备梯度回波图像对白质和灰质（WM/GM）进行分割。采用Patlak方法计算流入常数K。主要结果是WM和GM中K的受试者内变异系数（CV）。K值符合生物学预期，与已知的GM/WM脑血容量（CBV）差异以及相应的血管表面积差异相关。受试者来源的动脉输入函数显示出显著的受试者内变异性，通过使用静脉输入函数可显著降低（曲线下面积的CV分别为46%和12%，p<0.001）。使用静脉输入函数显著改善了WM（30%对59%，p<0.001）和GM（21%对53%，p<0.001）中K的CV。通过运动校正、将静脉输入函数按动脉进行缩放以及使用体素数据的中位数而非平均值，进一步提高了CV。最终方法在WM和GM中的CV分别为27%和17%。用一种标准的群体输入函数替代受试者来源的输入函数未获得进一步改善。结果表明，K的CV对动态序列持续时间高度敏感，测量时间越短，尤其是在WM中，变差越明显。总之，三维脑DCE-MRI的测量变异性对分析方法敏感，使用静脉输入函数可大幅提高精度。
