Introduction

White matter damage in the visual pathway is common in multiple sclerosis (MS) and is associated with retinal thinning, although the underlying mechanism of association remains unclear. The goal of this work was to evaluate the presence and extent of white matter tract integrity (WMTI) alterations in the optic radiation (OR) in people with MS and to investigate the association between WMTI metrics and retinal thinning in the eyes of MS patients without a history of optic neuritis (ON) as measured by optical coherence tomography (OCT). We hypothesized that WMTI metrics would reflect axonal damage that occurs in the OR in MS, and that axonal alterations revealed by WMTI would be associated with retinal thinning.

Methods

Twenty-nine MS patients without previous ON in at least one eye and twenty-nine age-matched healthy controls (HC) were scanned on a dedicated high-gradient 3-Tesla MRI scanner with 300 mT/m maximum gradient strength using a multi-shell diffusion MRI protocol (b = 800, 1500, 2400 s/mm²). The patients were divided into two subgroups according to history without ON (N = 18) or with ON in one eye (N = 11). Diffusion tensor imaging (DTI) metrics and WMTI metrics derived from diffusion kurtosis imaging were assessed in normal-appearing white matter (NAWM) of the OR and in focal lesions. Retinal thickness in the eyes of MS patients was measured by OCT. Student’s t-test was used to assess group differences between MRI metrics. Linear regression was used to study the relationship between OCT metrics, including retinal nerve fiber layer (RNFL) and combined ganglion cell and inner plexiform layer thickness (GCL/IPL), visual acuity measures and DTI and WMTI metrics.

Results

OR NAWM in MS showed significantly decreased axonal water fraction (AWF) compared to HC (0.36 vs 0.39, p < 0.001), with similar trends observed in AWF of lesions compared to NAWM (0.27 vs 0.36, p < 0.001). Fractional anisotropy (FA) was lower in OR NAWM of MS patients compared to HC (0.49 vs 0.52, p < 0.001). In patients without ON, AWF was the only diffusion MRI metric that was significantly associated with average RNFL (r = 0.68, p = 0.005), adjusting for age, sex and disease duration and correcting for multiple comparisons. Of all the DTI and WMTI metrics, AWF was the strongest and most significant predictor of average RNFL thickness in MS patients without ON. There was no significant correlation between visual acuity scores and DTI or WMTI metrics after correction for multiple comparisons.

Conclusion

Axonal damage may be the substrate of previously observed DTI alterations in the OR, as supported by the significant reduction in AWF within both NAWM and lesions of the OR in MS. Our results support the concept that axonal damage is widespread throughout the visual pathway in MS and may be mediated through trans-synaptic degeneration.

中文翻译：

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通过白质束完整性指标评估的视辐射中的轴突损伤与多发性硬化症中的视网膜变薄有关。

介绍

视觉通路中的白质损伤在多发性硬化症（MS）中很常见，并且与视网膜变薄有关，尽管其潜在的相关机制尚不清楚。这项工作的目的是评估MS患者视光辐射（OR）中白质道完整性（WMTI）改变的存在和程度，并调查WMTI指标与MS患者眼中视网膜变薄之间的关系。通过光学相干断层扫描（OCT）测量的视神经炎（ON）病史。我们假设WMTI指标将反映发生在MS手术室中的轴突损伤，并且WMTI揭示的轴突改变将与视网膜变薄有关。

方法

在专用的高梯度3-Tesla MRI扫描仪上使用至少30只双眼，最大梯度强度为300 mT / m的专用高梯度3特斯拉MRI扫描仪扫描了29例至少在一只眼中未曾接受过ON手术的MS患者和29例年龄相匹配的健康对照。壳扩散MRI协议（b  = 800、1500、2400 s / mm ²）。根据病史，将患者分为两个亚组：无ON（N = 18）或一只眼睛有ON（N = 11）。在正常或正常的白质（NAWM）以及局灶性病变中评估了扩散张量成像得出的扩散张量成像（DTI）指标和WMTI指标。通过OCT测量MS患者眼中的视网膜厚度。学生Ť-test用于评估MRI指标之间的组差异。线性回归用于研究OCT指标之间的关系，包括视网膜神经纤维层（RNFL）以及神经节细胞和内丛状复合层厚度​​（GCL / IPL）的组合，视敏度指标以及DTI和WMTI指标。

结果

与HC相比，MS中的OR NAWM显示轴突水分数（AWF）显着降低（0.36 vs 0.39，p <0.001），与NAWM相比，病变的AWF观察到相似的趋势（0.27 vs 0.36，p <0.001）。MS患者的OR NAWM的分数各向异性（FA）低于HC（0.49 vs 0.52，p <0.001）。在没有ON的患者中，AWF是唯一与平均RNFL显着相关的弥散MRI指标（r = 0.68，p = 0.005），可以调整年龄，性别和疾病持续时间，并可以进行多次比较校正。在所有DTI和WMTI指标中，AWF是无ON的MS患者平均RNFL厚度的最强和最重要的预测指标。进行多次比较校正后，视敏度得分与DTI或WMTI指标之间没有显着相关性。

结论

轴突损伤可能是先前在OR中观察到的DTI改变的底物，NAWM中的AWF显着降低和MS中OR的病变都支持了轴突损伤。我们的研究结果支持了轴突损伤在MS的整个视觉通路中广泛分布并且可能通过跨突触变性介导的概念。