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Multimodal MRI staging for tracking progression and clinical-imaging correlation in sporadic Creutzfeldt-Jakob disease
NeuroImage: Clinical ( IF 4.2 ) Pub Date : 2020-12-11 , DOI: 10.1016/j.nicl.2020.102523
Simone Sacco 1 , Matteo Paoletti 2 , Adam M Staffaroni 3 , Huicong Kang 4 , Julio Rojas 3 , Gabe Marx 3 , Sheng-Yang Goh 3 , Maria Luisa Mandelli 3 , Isabel E Allen 5 , Joel H Kramer 3 , Stefano Bastianello 6 , Roland G Henry 7 , Howie J Rosen 3 , Eduardo Caverzasi 7 , Michael D Geschwind 3
Affiliation  

Diffusion imaging is very useful for the diagnosis of sporadic Creutzfeldt-Jakob disease, but it has limitations in tracking disease progression as mean diffusivity changes non-linearly across the disease course. We previously showed that mean diffusivity changes across the disease course follow a quasi J-shaped curve, characterized by decreased values in earlier phases and increasing values later in the disease course. Understanding how MRI metrics change over-time, as well as their correlations with clinical deficits are crucial steps in developing radiological biomarkers for trials. Specifically, as mean diffusivity does not change linearly and atrophy mainly occurs in later stages, neither alone is likely to be a sufficient biomarker throughout the disease course. We therefore developed a model combining mean diffusivity and Volume loss (MRI Disease-Staging) to take into account mean diffusivity’s non-linearity. We then assessed the associations between clinical outcomes and mean diffusivity alone, Volume alone and finally MRI Disease-Staging.

In 37 sporadic Creutzfeldt-Jakob disease subjects and 30 age- and sex-matched healthy controls, high angular resolution diffusion and high-resolution T1 imaging was performed cross-sectionally to compute z-scores for mean diffusivity (MD) and Volume. Average MD and Volume were extracted from 41 GM volume of interest (VOI) per hemisphere, within the images registered to the Montreal Neurological Institute (MNI) space. Each subject’s volume of interest was classified as either “involved” or “not involved” using a statistical threshold of ± 2 standard deviation (SD) for mean diffusivity changes and/or −2 SD for Volume. Volumes of interest were MRI Disease-Staged as: 0 = no abnormalities; 1 = decreased mean diffusivity only; 2 = decreased mean diffusivity and Volume; 3 = normal (“pseudo-normalized”) mean diffusivity, reduced Volume; 4 = increased mean diffusivity, reduced Volume. We correlated Volume, MD and MRI Disease-Staging with several clinical outcomes (scales, score and symptoms) using 4 major regions of interest (Total, Cortical, Subcortical and Cerebellar gray matter) or smaller regions pre-specified based on known neuroanatomical correlates.

Volume and MD z-scores correlated inversely with each other in all four major ROIs (cortical, subcortical, cerebellar and total) highlighting that ROIs with lower Volumes had higher MD and vice-versa. Regarding correlations with symptoms and scores, higher MD correlated with worse Mini-Mental State Examination and Barthel scores in cortical and cerebellar gray matter, but subjects with cortical sensory deficits showed lower MD in the primary sensory cortex. Volume loss correlated with lower Mini-Mental State Examination, Barthel scores and pyramidal signs. Interestingly, for both Volume and MD, changes within the cerebellar ROI showed strong correlations with both MMSE and Barthel. Supporting using a combination of MD and Volume to track sCJD progression, MRI Disease-Staging showed correlations with more clinical outcomes than Volume or MD alone, specifically with Mini-Mental State Examination, Barthel score, pyramidal signs, higher cortical sensory deficits, as well as executive and visual-spatial deficits. Additionally, when subjects in the cohort were subdivided into tertiles based on their Barthel scores and their percentile of disease duration/course (“Time-Ratio”), subjects in the lowest (most impaired) Barthel tertile showed a much greater proportion of more advanced MRI Disease-Stages than the those in the highest tertile. Similarly, subjects in the last Time-Ratio tertile (last tertile of disease) showed a much greater proportion of more advanced MRI Disease-Stages than the earliest tertile. Therefore, in later disease stages, as measured by time or Barthel, there is overall more Volume loss and increasing MD.

A combined multiparametric quantitative MRI Disease-Staging is a useful tool to track sporadic Creutzfeldt-Jakob- disease progression radiologically.



中文翻译:

用于追踪散发性克雅氏病进展和临床影像相关性的多模式 MRI 分期

扩散成像对于诊断散发性克雅氏病非常有用,但它在跟踪疾病进展方面存在局限性,因为平均扩散率在整个病程中呈非线性变化。我们之前表明,整个病程中的平均扩散率变化遵循准 J 形曲线,其特征是早期阶段的值降低,而病程后期的值增加。了解 MRI 指标如何随时间变化,以及它们与临床缺陷的相关性是开发用于试验的放射生物标志物的关键步骤。具体而言,由于平均扩散率不会线性变化并且萎缩主要发生在后期阶段,因此两者都不可能成为整个疾病过程中的充分生物标志物。因此,我们开发了一个结合平均扩散率和体积损失(MRI 疾病分期)的模型,以考虑平均扩散率的非线性。然后,我们评估了临床结果与单独的平均扩散系数、单独的体积以及最后的 MRI 疾病分期之间的关联。

在 37 名散发性克雅氏病受试者和 30 名年龄和性别匹配的健康对照中,横断面进行了高角分辨率扩散和高分辨率 T1 成像,以计算平均扩散率 (MD) 和体积的 z 分数。在注册到蒙特利尔神经学研究所 (MNI) 空间的图像中,从每个半球的 41 个 GM 感兴趣体积 (VOI) 中提取平均 MD 和体积。使用平均扩散率变化的 ± 2 标准差 (SD) 和/或体积的 -2 SD 的统计阈值,将每个受试者的感兴趣体积分类为“涉及”或“不涉及”。感兴趣的体积被 MRI 疾病分期为:0 = 无异常;1 = 仅降低平均扩散率;2 = 平均扩散率和体积降低;3 = 正常(“伪标准化”)平均扩散率,减少体积;4 = 平均扩散系数增加,体积减小。我们使用 4 个主要感兴趣区域(总、皮质、皮质下和小脑灰质)或根据已知的神经解剖相关性预先指定的较小区域,将体积、MD 和 MRI 疾病分期与几种临床结果(量表、评分和症状)相关联。

体积和 MD z 分数在所有四个主要 ROI(皮质、皮质下、小脑和总)中彼此呈负相关,突出表明具有较低体积的 ROI 具有较高的 MD,反之亦然。关于与症状和评分的相关性,较高的 MD 与较差的迷你精神状态检查和皮质和小脑灰质的 Barthel 评分相关,但具有皮质感觉缺陷的受试者在初级感觉皮层中显示较低的 MD。容量减少与较低的简易精神状态检查、Barthel 评分和锥体征相关。有趣的是,对于体积和 MD,小脑 ROI 内的变化显示与 MMSE 和 Barthel 有很强的相关性。支持使用 MD 和体积的组合来跟踪 sCJD 进展,MRI 疾病分期显示与单独的体积或 MD 相比更多临床结果的相关性,特别是迷你精神状态检查、Barthel 评分、锥体征、更高的皮质感觉缺陷,以及执行和视觉空间缺陷。此外,当队列中的受试者根据他们的 Barthel 评分和疾病持续时间/病程的百分位数(“时间比”)被细分为三分位数时,最低(最受损)Barthel 三分位数的受试者显示出更大比例的更晚期MRI 疾病分期比最高三分位的那些。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。锥体征、更高的皮质感觉缺陷,以及执行和视觉空间缺陷。此外,当队列中的受试者根据他们的 Barthel 评分和他们的疾病持续时间/病程百分位数(“时间比”)被细分为三分位数时,最低(最受损)Barthel 三分位数的受试者显示出更大比例的更晚期MRI 疾病分期比最高三分位的那些。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。锥体征、更高的皮质感觉缺陷,以及执行和视觉空间缺陷。此外,当队列中的受试者根据他们的 Barthel 评分和他们的疾病持续时间/病程百分位数(“时间比”)被细分为三分位数时,最低(最受损)Barthel 三分位数的受试者显示出更大比例的更晚期MRI 疾病分期比最高三分位的那些。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。当队列中的受试者根据他们的 Barthel 评分和他们的疾病持续时间/病程百分位数(“时间比”)被细分为三分位数时,最低(最受损)Barthel 三分位数的受试者显示出更大比例的更晚期 MRI 疾病-阶段比最高三分位数的阶段。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。当队列中的受试者根据他们的 Barthel 评分和他们的疾病持续时间/病程百分位数(“时间比”)被细分为三分位数时,最低(最受损)Barthel 三分位数的受试者显示出更大比例的更晚期 MRI 疾病-阶段比最高三分位数的阶段。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。最低(最受损)Barthel 三分位数的受试者比最高三分位数的受试者显示出更大比例的更晚期 MRI 疾病阶段。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。最低(最受损)Barthel 三分位数的受试者比最高三分位数的受试者显示出更大比例的更晚期 MRI 疾病阶段。类似地,最后一个时间比三分位数(疾病的最后一个三分位数)中的受试者显示出比最早的三分位数更大比例的更晚期 MRI 疾病阶段。因此,在疾病的后期阶段,按时间或 Barthel 衡量,总体上有更多的体积损失和增加的 MD。

组合的多参数定量 MRI 疾病分期是一种有用的工具,可以通过放射学追踪散发性克雅氏病的进展。

更新日期:2020-12-11
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