Sadeghi Neda, Hutchinson Elizabeth, Van Ryzin Carol, FitzGibbon Edmond J, Butman John A, Webb Bryn D, Facio Flavia, Brooks Brian P, Collins Francis S, Jabs Ethylin Wang, Engle Elizabeth C, Manoli Irini, Pierpaoli Carlo
Quantitative Medical Imaging Section, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85719, USA.
Brain Commun. 2020;2(1):fcaa014. doi: 10.1093/braincomms/fcaa014. Epub 2020 Feb 14.
In this study, we used a novel imaging technique, DTI (diffusion tensor imaging)-driven tensor-based morphometry, to investigate brain anatomy in subjects diagnosed with Moebius syndrome ( = 21), other congenital facial weakness disorders ( = 9) and healthy controls ( = 15). First, we selected a subgroup of subjects who satisfied the minimum diagnostic criteria for Moebius syndrome with only mild additional neurological findings. Compared to controls, in this cohort, we found a small region of highly significant volumetric reduction in the paramedian pontine reticular formation and the medial longitudinal fasciculus, important structures for the initiation and coordination of conjugate horizontal gaze. Subsequently, we tested if volume measurements from this region could help differentiate individual subjects of the different cohorts that were included in our study. We found that this region allowed discriminating Moebius syndrome subjects from congenital facial weakness disorders and healthy controls with high sensitivity (94%) and specificity (89%). Interestingly, this region was normal in congenital facial weakness subjects with oculomotor deficits of myopathic origin, who would have been classified as Moebius on the basis of purely clinical diagnostic criteria, indicating a potential role for diffusion MRI morphometry for differential diagnosis in this condition. When the entire Moebius syndrome cohort was compared to healthy controls, in addition to this 'landmark' region, other areas of significantly reduced volume in the brainstem emerged, including the location of the nuclei and fibres of cranial nerve VI (abducens nerve), and fibres of cranial nerve VII (facial nerve), and a more rostral portion of the medial longitudinal fasciculus. The high sensitivity and specificity of DTI-driven tensor-based morphometry in reliably detecting very small areas of volumetric abnormality found in this study suggest broader applications of this analysis in personalized medicine to detect hypoplasia or atrophy of small pathways and/or brainstem nuclei in other neurological disorders.
在本研究中，我们使用了一种新型成像技术——基于扩散张量成像（DTI）的张量形态测量法，来研究被诊断为莫比乌斯综合征（n = 21）、其他先天性面部肌无力疾病（n = 9）以及健康对照者（n = 15）的大脑解剖结构。首先，我们选择了一组仅伴有轻度其他神经学表现且满足莫比乌斯综合征最低诊断标准的受试者。与对照组相比，在这一队列中，我们发现脑桥旁正中网状结构和内侧纵束有一个体积显著减小的小区域，这两个结构对于共轭水平凝视的启动和协调很重要。随后，我们测试了该区域的体积测量值是否有助于区分我们研究中纳入的不同队列的个体受试者。我们发现该区域能够以高敏感性（94%）和特异性（89%）将莫比乌斯综合征受试者与先天性面部肌无力疾病受试者及健康对照者区分开来。有趣的是，在具有肌病性动眼神经缺陷的先天性面部肌无力受试者中，该区域是正常的，而基于纯粹的临床诊断标准，这些受试者会被归类为莫比乌斯综合征，这表明扩散磁共振成像形态测量法在这种情况下的鉴别诊断中可能具有潜在作用。当将整个莫比乌斯综合征队列与健康对照者进行比较时，除了这个“标志性”区域外，脑干中还出现了其他体积显著减小的区域，包括展神经核和纤维、面神经纤维以及内侧纵束更靠前的部分。本研究中基于DTI的张量形态测量法在可靠检测非常小的体积异常区域方面的高敏感性和特异性表明，这种分析方法在个性化医学中有更广泛的应用，可用于检测其他神经系统疾病中小通路和/或脑干核的发育不全或萎缩。
