Zeestraten Eva Anna, Benjamin Philip, Lambert Christian, Lawrence Andrew John, Williams Owen Alan, Morris Robin Guy, Barrick Thomas Richard, Markus Hugh Stephen
Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom.
Department of Radiology, Charing Cross Hospital campus, Imperial College NHS trust, London, United Kingdom.
PLoS One. 2016 Jan 25;11(1):e0147836. doi: 10.1371/journal.pone.0147836. eCollection 2016.
Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD.
脑小血管病（SVD）是血管性认知障碍的主要原因，会导致严重残疾并降低生活质量。认知测试在纵向研究中已被证明对变化不敏感，因此，在临床试验中需要敏感的替代标志物来监测疾病进展并评估治疗效果。在这方面，扩散张量成像（DTI）被认为具有巨大潜力。然而，从DTI中得出的各种参数的敏感性尚不清楚。我们旨在评估DTI标志物检测SVD进展的差异敏感性，并估计基于DTI数据评估旨在阻止病情恶化的治疗干预所需的样本量。我们对99例有症状的SVD患者进行了研究，这些患者被定义为临床腔隙综合征，MRI证实有相应梗死以及在3年随访期内有融合性白质高信号。我们使用线性混合效应模型评估DTI直方图参数的变化并计算样本量估计值。在三年的随访期内，我们观察到白质组织中各向异性分数下降，扩散率增加，且大多数参数发生了显著变化。平均扩散率峰值高度是SVD进展最敏感的标志物，因为它的样本量估计值最小。这表明使用DTI直方图分析可以敏感地监测疾病进展，并证实了DTI作为SVD替代标志物的潜力。
