Bede Peter, Hardiman Orla
a Quantitative Neuroimaging Group, Academic Unit of Neurology , Biomedical Sciences Institute, Trinity College Dublin , Dublin , Ireland and.
b Department of Neurology , Beaumont Hospital , Dublin , Ireland.
Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):232-241. doi: 10.1080/21678421.2017.1407795. Epub 2017 Dec 7.
Cross-sectional imaging studies offer valuable pathological insights into the neurodegenerative changes of amyotrophic lateral sclerosis. However, clinical trials urgently require sensitive monitoring markers that can detect subtle progressive changes over relatively short periods of time. We have conducted a three time-point longitudinal study to explore anatomical patterns of disease spread and to determine whether MRI metrics capture longitudinal changes over four and eight-month intervals.
Thirty-two ALS patients were enrolled into a multiparametric imaging study to evaluate progressive cortical thickness, grey matter density and white matter alterations. Whole-brain and region-of-interest analyses were conducted in the precentral gyrus, corticospinal tracts, corpus callosum and cerebellum. Additionally, pre-symptomatic changes were explored in patients with no bulbar or lower limb disability.
Our findings suggest that considerable white matter degeneration can be detected early in the course of the disease which shows limited progression over time, whereas grey matter pathology is relatively limited at baseline and exhibits relentless progression. Moreover, progressive presymptomatic structural changes can be identified in the bulbar and lower limb representations of the precentral gyrus.
Our longitudinal imaging study confirms that MRI metrics readily capture progressive changes in ALS. Our data also indicate that white matter metrics are of potential use as diagnostic markers, and grey matter measures may be superior as monitoring biomarkers. One of the most interesting findings of our study is the gradually progressive cerebellar grey matter degeneration throughout the three time-points.
横断面成像研究为肌萎缩侧索硬化症的神经退行性变化提供了有价值的病理学见解。然而，临床试验迫切需要能够在相对较短时间内检测到细微进展变化的敏感监测标志物。我们进行了一项三个时间点的纵向研究，以探索疾病传播的解剖模式，并确定MRI指标是否能捕捉到四个月和八个月间隔内的纵向变化。
32例肌萎缩侧索硬化症患者纳入一项多参数成像研究，以评估皮质厚度、灰质密度和白质的进展性改变。在中央前回、皮质脊髓束、胼胝体和小脑中进行全脑和感兴趣区域分析。此外，还对无延髓或下肢残疾的患者进行了症状前变化的探索。
我们的研究结果表明，在疾病早期即可检测到明显的白质变性，且随时间进展有限，而灰质病变在基线时相对有限，并呈持续进展。此外，在中央前回的延髓和下肢代表区可识别出症状前的进展性结构变化。
我们的纵向成像研究证实，MRI指标能轻易捕捉到肌萎缩侧索硬化症的进展性变化。我们的数据还表明，白质指标有作为诊断标志物的潜在用途，而灰质测量作为监测生物标志物可能更具优势。我们研究中最有趣的发现之一是在三个时间点上逐渐进展的小脑灰质变性。
