Salman Fahad, Bergsland Niels, Dwyer Michael G, Reeves Jack A, Ramesh Abhisri, Jakimovski Dejan, Weinstock-Guttman Bianca, Zivadinov Robert, Schweser Ferdinand
Buffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States; Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Buffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Neuroimage Clin. 2025 Mar 26;46:103771. doi: 10.1016/j.nicl.2025.103771.
Studies of thalamic iron levels in multiple sclerosis (MS) have yielded variable findings, potentially due to differences in study cohorts. For example, studies in relatively young cohorts (average ages below 40 years) have reported elevated susceptibility in people with MS (pwMS), whereas studies in older cohorts (above 40 years) found decreased susceptibility.
To test the "early-rise late-decline" hypothesis, which posits that age differences in study cohorts are responsible for conflicting findings regarding thalamic susceptibility in MS.
We chose to replicate one of the previous studies that showed evidence of elevated thalamic iron concentrations in younger pwMS (Rudko et al., 2014). We also replicated a study involving older pwMS (Pudlac et al., 2020) to serve as a control. We assessed thalamic susceptibility using the QSM processing and analysis methodology outlined by Rudko et al. RESULTS: Although cohort characteristics, QSM processing, and analytical methods were closely matched, we found significantly lower thalamic susceptibility in the younger pwMS compared to controls (-1.1 ± 7.8 vs. 5.4 ± 6.1 ppb; effect sizes: -0.35 to -0.91). Study outcomes were robust across a wide range of regularization parameters, with effect size differences influenced by background field removal regularization. A similar pattern was observed in the older cohort, where thalamic susceptibility was again lower in pwMS compared to controls (4.0 ± 9.5 vs. 9.6 ± 10.7 ppb; effect size: -0.55).
Our findings contradict the "early rise" hypothesis of thalamic iron levels in pwMS. The consistency of our results across multiple analyses suggests that QSM processing artifacts are unlikely to explain previous reports of increased thalamic iron. Instead, these variations may stem from demographic or clinical differences, such as geographical factors and treatment regimens.
对多发性硬化症（MS）患者丘脑铁水平的研究结果存在差异，这可能是由于研究队列的不同。例如，在相对年轻的队列（平均年龄低于40岁）中进行的研究报告称，MS患者（pwMS）的易感性升高，而在年龄较大的队列（40岁以上）中进行的研究则发现易感性降低。
检验“早期升高后期下降”假说，该假说认为研究队列中的年龄差异是导致MS患者丘脑易感性研究结果相互矛盾的原因。
我们选择重复之前的一项研究，该研究显示年轻的pwMS患者丘脑铁浓度升高（Rudko等人，2014年）。我们还重复了一项涉及年龄较大的pwMS患者的研究（Pudlac等人，2020年）作为对照。我们使用Rudko等人概述的QSM处理和分析方法评估丘脑易感性。结果：尽管队列特征、QSM处理和分析方法密切匹配，但我们发现年轻的pwMS患者的丘脑易感性显著低于对照组（-1.1±7.8 vs. 5.4±6.1 ppb；效应大小：-0.35至-0.91）。研究结果在广泛的正则化参数范围内都很稳健，效应大小差异受背景场去除正则化的影响。在年龄较大的队列中也观察到了类似的模式，其中pwMS患者的丘脑易感性再次低于对照组（4.0±9.5 vs. 9.6±10.7 ppb；效应大小：-0.55）。
我们的研究结果与pwMS患者丘脑铁水平的“早期升高”假说相矛盾。我们在多次分析中结果的一致性表明，QSM处理伪影不太可能解释先前关于丘脑铁增加的报告。相反，这些差异可能源于人口统计学或临床差异，如地理因素和治疗方案。
