From the Translational Imaging in Neurology (ThINk) Basel (A.C., M.O.-P., P.-J.L., M.W., M.B., L.M.-G., X.C., L.K., C.G.), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel; Department of Neurology (A.C., M.O.-P., P.-J.L., M.W., M.B., L.M.-G., X.C., J.K., L.K., C.G.), University Hospital Basel; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) (A.C., M.O.-P., P.-J.L., M.W., M.B., L.M.-G., X.C., J.K., L.K., C.G.), University Hospital Basel and University of Basel, Switzerland; Dipartimento di Scienze della Salute, (A.C., M.P.S.), Università degli Studi di Genova, Italy; Division of Radiological Physics (M.W.), Department of Radiology, University Hospital Basel; Laboratory for Research in Neuroimaging (A.L.), Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne; Neuropsychology and Behavioral Neurology Unit (P.C.), Division of Cognitive and Molecular Neuroscience, University of Basel, Switzerland; and IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy.
Neurol Neuroimmunol Neuroinflamm. 2024 Nov;11(6):e200299. doi: 10.1212/NXI.0000000000200299. Epub 2024 Sep 13.
In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI).
Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity.
Compared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change () = -1.50; = 0.041] and increase in quantitative T1 ( = 0.92; < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion ( = -0.067; = 0.039) and QSM ( = -0.077; = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy.
These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.
在多发性硬化症（MS）患者中，丘脑会在疾病进程中发生萎缩。然而，目前对于导致体积损失的机制以及微结构丘脑病理学与疾病进展之间的关系，我们知之甚少。本项横断面和纵向研究旨在使用先进的多参数定量磁共振成像（qMRI）全面描述 MS 患者丘脑微结构内的活体病理变化。
我们使用定量 T1、磁化传递饱和、多壳层扩散和定量磁化率映射（QSM）对 183 名 MS 患者和 105 名健康对照者（HCs）的丘脑微结构完整性进行了评估。在 2 年的随访期间，对 127 名 MS 患者和 73 名 HCs 进行了相同的 qMRI 检查。MS 患者的纳入标准包括活动复发缓解型 MS（RRMS）或不活动进展型 MS（PMS）疾病进程。我们比较了 MS 患者和 HCs 之间以及不同疾病表型之间的丘脑改变。此外，该研究还调查了丘脑损伤与疾病严重程度的临床和常规 MRI 测量值之间的关系。
与 HCs 相比，MS 患者表现出明显的丘脑改变，提示微结构和宏观结构损伤、脱髓鞘和铁稳态失调。这些改变不仅局限于局灶性丘脑病变，还广泛影响正常的丘脑组织弥散性病变。在随访期间，MS 患者的髓鞘体积分数呈加速下降趋势（年化百分比变化的平均差异（ ）=-1.50； = 0.041），定量 T1 值呈升高趋势（ = 0.92； < 0.0001），提示脱髓鞘和神经退行性过程加剧。MS 患者与 HCs 之间的差异主要是由 PMS 亚组驱动的，其中丘脑退行性变明显加速，甚至与 RRMS 患者相比也是如此。丘脑 qMRI 改变与常规 MRI、临床和认知疾病负担测量值之间存在广泛相关性。随访期间的残疾进展与加速的丘脑退行性变相关，这表现为弥散度（ = -0.067； = 0.039）和 QSM（ = -0.077； = 0.027）变化增强。即使考虑到包括白质病变负荷和大脑及丘脑萎缩在内的其他既定标志物，丘脑 qMRI 指标仍可作为神经和认知残疾的重要预测指标。
这些发现深入了解了 MS 患者的丘脑病理学，强调了丘脑损伤的临床相关性及其与疾病进展的关系。先进的 qMRI 生物标志物在指导旨在减轻丘脑神经退行性过程的干预措施方面具有很大的潜力。
