Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
The Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Magn Reson Med. 2018 Oct;80(4):1507-1520. doi: 10.1002/mrm.27141. Epub 2018 Mar 1.
Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water.
The central principle is that by measuring arterially labeled blood spins that are drained into cerebral veins, water extraction fraction (E) and permeability-surface-area product (PS) of BBB can be determined. Four studies were performed. We first demonstrated the proof-of-principle using conventional ASL with very long post-labeling delays (PLD). Next, a new sequence, dubbed water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), and its Look-Locker (LL) version were developed. Finally, we demonstrated that the sensitivity of the technique can be significantly enhanced by acquiring the data under mild hypercapnia.
By combining a strong background suppression with long PLDs (2500-4500 ms), ASL spins were reliably detected in the superior sagittal sinus (SSS), demonstrating the feasibility of measuring this signal. The WEPCAST sequence eliminated partial voluming effects of tissue perfusion and allowed quantitative estimation of E = 95.5 ± 1.1% and PS = 188.9 ± 13.4 mL/100 g/min, which were in good agreement with literature reports. LL-WEPCAST sequence shortened the scan time from 19 min to 5 min while providing results consistent with multiple single-PLD acquisitions. Mild hypercapnia increased SNR by 78 ± 25% without causing a discomfort in participants.
A new non-contrast technique for the assessment of global BBB permeability was developed, which may have important clinical applications.
许多脑部疾病都与血脑屏障 (BBB) 及其通透性的改变有关。目前使用对比剂的方法主要对 BBB 对大分子的主要渗漏敏感，但可能无法检测到 BBB 通透性的细微变化。本研究旨在开发一种新的非对比 MRI 技术，用于评估 BBB 对水的通透性。
其中心原则是通过测量流入脑静脉的动脉标记血自旋，可以确定 BBB 的水提取分数 (E) 和渗透率表面积乘积 (PS)。进行了四项研究。我们首先使用非常长的标记后延迟 (PLD) 的传统 ASL 证明了原理的可行性。接下来，开发了一种新的序列，称为水提取与相位对比动脉自旋标记 (WEPCAST)，及其 Look-Locker (LL) 版本。最后，我们证明通过在轻度高碳酸血症下采集数据，可以显著提高该技术的灵敏度。
通过结合强背景抑制和长 PLD（2500-4500 ms），可以在矢状窦上 (SSS) 可靠地检测到 ASL 自旋，证明了测量此信号的可行性。WEPCAST 序列消除了组织灌注的部分容积效应，并允许定量估计 E=95.5±1.1%和 PS=188.9±13.4 mL/100 g/min，这与文献报道一致。LL-WEPCAST 序列将扫描时间从 19 分钟缩短到 5 分钟，同时提供了与多个单 PLD 采集一致的结果。轻度高碳酸血症使 SNR 增加了 78±25%，而不会引起参与者不适。
开发了一种新的非对比技术来评估全局 BBB 通透性，这可能具有重要的临床应用价值。
