Nagaraja Tavarekere N, Knight Robert A, Ewing James R, Karki Kishor, Nagesh Vijaya, Fenstermacher Joseph D
Department of Anesthesiology, Henry Ford Hospital, Detroit, MI, USA.
Methods Mol Biol. 2011;686:193-212. doi: 10.1007/978-1-60761-938-3_8.
Breakdown of the blood-brain barrier (BBB) is present in several neurological disorders such as stroke, brain tumors, and multiple sclerosis. Noninvasive evaluation of BBB breakdown is important for monitoring disease progression and evaluating therapeutic efficacy in such disorders. One of the few techniques available for noninvasively and repeatedly localizing and quantifying BBB damage is magnetic resonance imaging (MRI). This usually involves the intravenous administration of a gadolinium-containing MR contrast agent (MRCA) such as Gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), followed by dynamic contrast-enhanced MR imaging (DCE-MRI) of brain and blood, and analysis of the resultant data to derive indices of blood-to-brain transfer. There are two advantages to this approach. First, measurements can be made repeatedly in the same animal; for instance, they can be made before drug treatment and then again after treatment to assess efficacy. Secondly, MRI studies can be multiparametric. That is, MRI can be used to assess not only a blood-to-brain transfer or influx rate constant (Ki or K1) by DCE-MRI but also complementary parameters such as: (1) cerebral blood flow (CBF), done in our hands by arterial spin-tagging (AST) methods; (2) magnetization transfer (MT) parameters, most notably T1sat, which appear to reflect brain water-protein interactions plus BBB and tissue dysfunction; (3) the apparent diffusion coefficient of water (ADCw) and/or diffusion tensor, which is a function of the size and tortuosity of the extracellular space; and (4) the transverse relaxation time by T2-weighted imaging, which demarcates areas of tissue abnormality in many cases. The accuracy and reliability of two of these multiparametric MRI measures, CBF by AST and DCE-MRI determined influx of Gd-DTPA, have been established by nearly congruent quantitative autoradiographic (QAR) studies with appropriate radiotracers. In addition, some of their linkages to local pathology have been shown via corresponding light microscopy and fluorescence imaging. This chapter describes: (1) multiparametric MRI techniques with emphasis on DCE-MRI and AST-MRI; (2) the measurement of the blood-to-brain influx rate constant and CBF; and (3) the role of each in determining BBB permeability.
血脑屏障（BBB）的破坏存在于多种神经系统疾病中，如中风、脑肿瘤和多发性硬化症。对BBB破坏进行无创评估对于监测此类疾病的进展和评估治疗效果非常重要。磁共振成像（MRI）是少数可用于无创且反复定位和量化BBB损伤的技术之一。这通常包括静脉注射含钆的磁共振造影剂（MRCA），如钆-二乙三胺五乙酸（Gd-DTPA），随后对脑和血液进行动态对比增强磁共振成像（DCE-MRI），并分析所得数据以得出血脑转运指数。这种方法有两个优点。首先，可以在同一只动物身上反复进行测量；例如，可以在药物治疗前进行测量，然后在治疗后再次测量以评估疗效。其次，MRI研究可以是多参数的。也就是说，MRI不仅可用于通过DCE-MRI评估血脑转运或流入速率常数（Ki或K1），还可用于评估补充参数，如：（1）脑血流量（CBF），在我们的研究中通过动脉自旋标记（AST）方法进行测量；（2）磁化传递（MT）参数，最显著的是T1sat，它似乎反映了脑水-蛋白质相互作用以及BBB和组织功能障碍；（3）水的表观扩散系数（ADCw）和/或扩散张量，它是细胞外间隙大小和曲折度的函数；（4）通过T2加权成像得到的横向弛豫时间，在许多情况下它可划分组织异常区域。通过使用适当放射性示踪剂的几乎一致的定量放射自显影（QAR）研究，已证实了这两种多参数MRI测量方法的准确性和可靠性，即通过AST测量的CBF和通过DCE-MRI确定的Gd-DTPA流入量。此外，通过相应的光学显微镜和荧光成像已显示了它们与局部病理学的一些联系。本章描述：（1）多参数MRI技术，重点是DCE-MRI和AST-MRI；（2）血脑流入速率常数和CBF的测量；（3）各参数在确定BBB通透性中的作用。
