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In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7
NeuroImage: Clinical ( IF 4.2 ) Pub Date : 2021-01-19 , DOI: 10.1016/j.nicl.2021.102561
Jacob A Parker 1 , Shabbir H Merchant 2 , Sanaz Attaripour-Isfahani 3 , Hyun Joo Cho 4 , Patrick McGurrin 1 , Brian P Brooks 5 , Albert R La Spada 6 , Mark Hallett 1 , Laryssa A Huryn 5 , Silvina G Horovitz 1
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Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive cerebellar ataxia and retinal degeneration. Increasing loss of visual function complicates the use of clinical scales to track the progression of motor symptoms, hampering our ability to develop accurate biomarkers of disease progression, and thus test the efficacy of potential treatments. We aimed to identify imaging measures of neurodegeneration, which may more accurately reflect SCA7 severity and progression. While common structural MRI techniques have been previously used for this purpose, they can be biased by neurodegeneration-driven increases in extracellular CSF-like water. In a cross-sectional study, we analyzed diffusion tensor imaging (DTI) data collected from a cohort of 13 SCA7 patients and 14 healthy volunteers using: 1) a diffusion tensor-based image registration technique, and 2) a dual-compartment DTI model to control for the potential increase in extracellular CSF-like water. These methodologies allowed us to assess both volumetric and microstructural abnormalities in both white and gray matter brain-wide in SCA7 patients for the first time. To measure tissue volume, we performed diffusion tensor-based morphometry (DTBM) using the tensor-based registration. To assess tissue microstructure, we computed the parenchymal mean diffusivity (pMD) and parenchymal fractional anisotropy (pFA) using the dual compartment model. This model also enabled us to estimate the parenchymal volume fraction (pVF), a measure of parenchymal tissue volume within a given voxel. While DTBM and pVF revealed tissue loss primarily in the brainstem, cerebellum, thalamus, and major motor white matter tracts in patients (p < 0.05, FWE corrected; Hedge’s g > 1), pMD and pFA detected microstructural abnormalities in virtually all tissues brain-wide (p < 0.05, FWE corrected; Hedge’s g > 1). The Scale for the Assessment and Rating of Ataxia trended towards correlation with cerebellar pVF (r = −0.66, p = 0.104, FDR corrected) and global white matter pFA (r = −0.64, p = 0.104, FDR corrected). These results advance our understanding of neurodegeneration in living SCA7 patients by providing the first voxel-wise characterization of white matter volume loss and gray matter microstructural abnormalities. Moving forward, this comprehensive approach could be applied to characterize the full spatiotemporal pattern of neurodegeneration in SCA7, and potentially develop an accurate imaging biomarker of disease progression.



中文翻译:

体内评估7型脊髓小脑共济失调的神经变性

脊髓小脑共济失调7型(SCA7)是一种神经退行性疾病,其特征是进行性小脑共济失调和视网膜变性。越来越多的视觉功能丧失使临床量表难以追踪运动症状的进展,从而阻碍了我们开发疾病进展的准确生物标志物的能力,从而测试了潜在疗法的疗效。我们旨在确定神经退行性变的影像学指标,它可以更准确地反映SCA7的严重程度和进展。尽管先前已将通用的MRI技术用于此目的,但它们可能会受到神经变性驱动的细胞外CSF样水增加的影响。在一项横断面研究中,我们使用以下方法分析了从13例SCA7患者和14例健康志愿者中收集的扩散张量成像(DTI)数据:1)基于扩散张量的图像配准技术,以及2)双室DTI模型,以控制细胞外CSF样水的潜在增加。这些方法使我们能够首次评估SCA7患者全脑的白质和灰质的体积和微结构异常。为了测量组织体积,我们使用基于张量的配准进行了基于扩散张量的形态测定(DTBM)。为了评估组织的微观结构,我们使用双室模型计算了实质平均扩散率(pMD)和实质分数各向异性(pFA)。该模型还使我们能够估计实质体积分数(pVF),这是给定体素内实质组织体积的量度。虽然DTBM和pVF揭示组织损失主要发生在脑干,小脑,丘脑,p  <0.05,FWE校正;Hedge's g  > 1),pMD和pFA几乎检测到全脑所有组织的微结构异常(p  <0.05,经FWE校正; Hedge's g > 1)。共济失调评估和评定量表趋向于与小脑pVF(r = -0.66,p = 0.104,FDR校正)和整体白质pFA(r = -0.64,p = 0.104,FDR校正)相关。这些结果通过提供白质体积减少和灰质微结构异常的第一个体素化特征,提高了我们对SCA7患者神经变性的理解。展望未来,这种综合方法可用于表征SCA7中神经变性的完整时空模式,并有可能开发出疾病进展的精确影像生物标记。

更新日期:2021-01-29
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