Pak Rebecca W, Hadjiabadi Darian H, Senarathna Janaka, Agarwal Shruti, Thakor Nitish V, Pillai Jay J, Pathak Arvind P
1 Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, USA.
2 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA.
J Cereb Blood Flow Metab. 2017 Nov;37(11):3475-3487. doi: 10.1177/0271678X17707398. Epub 2017 May 11.
Functional magnetic resonance imaging (fMRI) serves as a critical tool for presurgical mapping of eloquent cortex and changes in neurological function in patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling remains intact during brain tumor progression, and that measured changes in cerebral blood flow (CBF) are correlated with neuronal function. Recent preclinical and clinical studies have demonstrated that even low-grade brain tumors can exhibit neurovascular uncoupling (NVU), which can confound interpretation of fMRI data. Therefore, to avoid neurosurgical complications, it is crucial to understand the biophysical basis of NVU and its impact on fMRI. Here we review the physiology of the neurovascular unit, how it is remodeled, and functionally altered by brain cancer cells. We first discuss the latest findings about the components of the neurovascular unit. Next, we synthesize results from preclinical and clinical studies to illustrate how brain tumor induced NVU affects fMRI data interpretation. We examine advances in functional imaging methods that permit the clinical evaluation of brain tumors with NVU. Finally, we discuss how the suppression of anomalous tumor blood vessel formation with antiangiogenic therapies can "normalize" the brain tumor vasculature, and potentially restore neurovascular coupling.
功能磁共振成像（fMRI）是术前绘制明确皮层以及诊断为脑肿瘤患者神经功能变化的关键工具。然而，fMRI所依据的血氧水平依赖（BOLD）对比机制假定在脑肿瘤进展过程中神经血管耦合保持完整，并且所测量的脑血流量（CBF）变化与神经元功能相关。最近的临床前和临床研究表明，即使是低级别脑肿瘤也可表现出神经血管解耦（NVU），这会混淆fMRI数据的解释。因此，为避免神经外科并发症，了解NVU的生物物理基础及其对fMRI的影响至关重要。在此，我们综述神经血管单元的生理学、它如何被重塑以及被脑癌细胞功能改变。我们首先讨论关于神经血管单元组成部分的最新发现。接下来，我们综合临床前和临床研究结果以说明脑肿瘤诱导的NVU如何影响fMRI数据解释。我们研究允许对伴有NVU的脑肿瘤进行临床评估的功能成像方法进展。最后，我们讨论用抗血管生成疗法抑制异常肿瘤血管形成如何能够“使”脑肿瘤血管系统“正常化”，并有可能恢复神经血管耦合。
