Chaganti Joga R, Talekar Tanush K, Brew Bruce James
Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA.
Advanced Post-Processing Laboratory For Functional MRI and DTI, The Jefferson Integrated Magnetic Resonance Imaging Center (JIMRIC), Thomas Jefferson University, Philadelphia, PA, 19107, USA.
BMC Neurol. 2025 Mar 19;25(1):112. doi: 10.1186/s12883-025-04133-4.
The glymphatic system, a waste clearance pathway, has been implicated in several neurological conditions associated with neuroinflammation. COVID-19 associated neurocognitive impairment, part of the post-acute sequelae of SARS-CoV-2 infection (PASC), is strongly associated with neuroinflammation and disrupted blood-brain barrier (BBB). Several studies have implicated a synergistic interaction between the glymphatic system dysfunction and BBB disruption. In this proof-of-concept study, we investigated the role of the MRI metric diffusion along the perivascular spaces DTI (DTI-ALPS) in patients with PASC and correlated this with the BBB capillary permeability metric- K trans derived from Dynamic contrast enhanced (DCE) perfusion.
14 subjects with PASC who had persisting symptoms of anosmia, ageusia, fatigue, and cognitive impairment (CI) and ten healthy age and sex matched controls were recruited. All PASC subjects underwent routine and advanced MR brain imaging at two time points, (3 months +/- 2 weeks) after initial infection - referred as Time Point 1 (TP-1) - and 10 repeated the MRI scan 12 months (+/- 2 weeks) later - referred as Time Point 2 (TP-2), while the controls had MR imaging done only at TP-1. All had mild neurocognitive impairment. In the final analysis we included those who had DTI study at both time points (n-10). MR imaging included DCE perfusion and DTI in addition to anatomical imaging.
Given the small size of the sample and nonnormality of data in the descriptive analyses, nonparametric analyses were used for group comparisons. A two-sample Wilcoxon rank sum test was used to show the differences in DTI-ALPS between the patients and controls in the predefined regions of interest. Spearman's correlation coefficient (rho) was used to assess the correlation between DTI-ALPS index with K trans.
There was significant reduction in the DTI-ALPS index between the patients and controls in the left hemisphere (z = 2.04, p < 0.04). However, there was no significant change over time in the index. There was a strong inverse correlation between the central white matter K trans and DTI-ALPS index (rho = 0.66, p < 0.03).
Our study indicates that disordered para vascular drainage, a marker for glymphatic system and BBB damage may contribute to neurocognitive impairment (NCI) among patients with PASC. The DTI-ALPS index, which does not require contrast injection, has the potential to serve as a non-invasive biomarker.
类淋巴系统是一种废物清除途径，与多种与神经炎症相关的神经系统疾病有关。新型冠状病毒肺炎相关神经认知障碍是严重急性呼吸综合征冠状病毒2感染（PASC）的急性后遗症的一部分，与神经炎症和血脑屏障（BBB）破坏密切相关。多项研究表明类淋巴系统功能障碍与血脑屏障破坏之间存在协同相互作用。在这项概念验证研究中，我们调查了磁共振成像指标沿血管周围间隙扩散张量成像（DTI-ALPS）在PASC患者中的作用，并将其与动态对比增强（DCE）灌注衍生的血脑屏障毛细血管通透性指标Ktrans相关联。
招募了14名有嗅觉减退、味觉减退、疲劳和认知障碍（CI）持续症状的PASC患者以及10名年龄和性别匹配的健康对照者。所有PASC患者在初始感染后两个时间点（3个月±2周）——称为时间点1（TP-1）——以及10名患者在12个月后（±2周）重复进行磁共振成像扫描——称为时间点2（TP-2），进行常规和高级脑部磁共振成像检查，而对照组仅在TP-1进行磁共振成像检查。所有患者均有轻度神经认知障碍。在最终分析中，我们纳入了在两个时间点都进行了DTI研究的患者（n = 10）。磁共振成像除了解剖成像外，还包括DCE灌注和DTI。
鉴于样本量小且描述性分析中的数据不呈正态分布，采用非参数分析进行组间比较。采用两样本Wilcoxon秩和检验来显示患者和对照组在预定义感兴趣区域的DTI-ALPS差异。采用Spearman相关系数（rho）评估DTI-ALPS指数与Ktrans之间的相关性。
患者和对照组之间左半球的DTI-ALPS指数显著降低（z = 2.04，p < 0.04）。然而，该指数随时间没有显著变化。中央白质Ktrans与DTI-ALPS指数之间存在强烈的负相关（rho = 0.66，p < 0.03）。
我们的研究表明，类淋巴系统和血脑屏障损伤的标志物——血管周围引流紊乱可能导致PASC患者的神经认知障碍（NCI）。无需注射造影剂的DTI-ALPS指数有潜力作为一种非侵入性生物标志物。
