Croall Iain D, Lohner Valerie, Moynihan Barry, Khan Usman, Hassan Ahamad, O'Brien John T, Morris Robin G, Tozer Daniel J, Cambridge Victoria C, Harkness Kirsty, Werring David J, Blamire Andrew M, Ford Gary A, Barrick Thomas R, Markus Hugh S
Department of Clinical Neuroscience, Stroke Research Group, University of Cambridge, Cambridge, U.K.
Neurosciences Research Centre, St. George's, University of London, London, U.K.
Clin Sci (Lond). 2017 Jun 7;131(12):1361-1373. doi: 10.1042/CS20170146. Print 2017 Jun 1.
Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.
扩散张量成像（DTI）指标，如分数各向异性（FA）和平均扩散率（MD），因其与认知等结果相关，已被提议作为脑小血管疾病（SVD）的临床试验标志物。然而，对此进行研究的主要是单中心研究。由于临床试验可能是多中心的，因此需要进一步研究以确定在多中心环境中是否能检测到与认知具有相似强度的关联。作为 PRESERVE DTI 子研究的一部分，在六个地点招募了 109 名有症状腔隙性脑梗死且 MRI 显示有融合性白质高信号（WMH）的患者（平均年龄 = 68 岁）。在处理缺失数据后，五个地点的五台扫描仪型号（西门子和飞利浦）提供了 3T-MRI 扫描，同时进行了神经心理学和生活质量（QoL）评估。从 DTI 直方图分析中提取 FA 中位数和 MD 峰值高度。进行了多元线性回归，包括将归一化脑体积、WMH 病变负荷和腔隙数量作为协变量，以研究 FA 和 MD 与认知及 QoL 的关联。所有白质的 DTI 指标与整体认知（标准化β = 0.268）、心理灵活性（β = 0.306）、语言流畅性（β = 0.376）和蒙特利尔认知评估（MoCA）（β = 0.273）显著相关。这些关联的强度与系统文献综述中先前单中心研究报告的强度相当。在这项多中心研究中，我们证实了 DTI 参数与认知之间的关联，其强度与先前单中心研究中发现的相似。本研究支持在多中心研究中使用 DTI 指标作为疾病进展的生物标志物。
