Watershed regions are more susceptible to tissue microstructural injury in multiple sclerosis.

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae299
Ahmad A Toubasi, Junzhong Xu, Jarrod J Eisma, Salma AshShareef, Caroline Gheen, Taegan Vinarsky, Pragnya Adapa, Shailee Shah, James Eaton, Richard D Dortch, Manus J Donahue, Francesca Bagnato
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引用次数: 0

Abstract

Histopathologic studies report higher concentrations of multiple sclerosis white matter lesions in watershed areas of the brain, suggesting that areas with relatively lower oxygen levels may be more vulnerable to disease. However, it is unknown at what point in the disease course lesion predilection for watershed territories begins. Accordingly, we studied a cohort of people with newly diagnosed disease and asked whether (1) white matter lesions disproportionally localize to watershed-regions and (2) the degree of microstructural injury in watershed-lesions is more severe. Fifty-four participants, i.e. 38 newly diagnosed people with multiple sclerosis, clinically isolated syndrome or radiologically isolated syndrome, and 16 age- and sex-matched healthy controls underwent brain magnetic resonance imaging. T1-weighted and T2-weighted fluid-attenuated inversion recovery sequences, selective inversion recovery quantitative magnetisation transfer images, and the multi-compartment diffusion imaging with the spherical mean technique were acquired. We computed the macromolecular-to-free pool size ratio, and the apparent axonal volume fraction maps to indirectly estimate myelin and axonal integrity, respectively. We produced a flow territory atlas in each subject's native T2-weighted fluid-attenuated inversion recovery images using a T1-weighted magnetic resonance imaging template in the Montreal Neurological Institute 152 space. Lesion location relative to the watershed, non-watershed and mixed brain vascular territories was annotated. The same process was performed on the T2-weighted fluid-attenuated inversion recovery images of the healthy controls using 294 regions of interest. Generalized linear mixed models for continuous outcomes were used to assess differences in size, pool size ratio and axonal volume fraction between lesions/regions of interests (in healthy controls) situated in different vascular territories. In patients, we assessed 758 T2-lesions and 356 chronic black holes (cBHs). The watershed-territories had higher relative and absolute concentrations of T2-lesions (P≤0.041) and cBHs (P≤0.036) compared to either non-watershed- or mixed-zones. T2-lesions in watershed-areas also had lower pool size ratio relative to T2-lesions in either non-watershed- or mixed-zones (P = 0.039). These results retained significance in the sub-cohort of people without vascular comorbidities and when accounting for periventricular lesions. In healthy controls, axonal volume fraction was higher only in mixed-areas regions of interest compared to non-watershed-ones (P = 0.008). No differences in pool size ratio were seen. We provide in vivo evidence that there is an association between arterial vascularisation of the brain and multiple sclerosis-induced tissue injury as early as the time of disease diagnosis. Our findings underline the importance of oxygen delivery and healthy arterial vascularisation to prevent lesion formation and foster a better outcome in multiple sclerosis.

多发性硬化症患者的分水岭区域更容易受到组织微结构损伤的影响。
组织病理学研究报告显示,大脑分水岭区域的多发性硬化症白质病变更为集中,这表明氧气水平相对较低的区域可能更容易患病。然而,我们还不知道病变偏爱分水岭区域始于病程的哪个阶段。因此,我们对一组新确诊的患者进行了研究,并询问:(1) 白质病变是否不成比例地发生在分水岭区域;(2) 分水岭病变的微结构损伤程度是否更严重。54名参与者,即38名新确诊的多发性硬化症、临床孤立综合征或放射学孤立综合征患者,以及16名年龄和性别匹配的健康对照者接受了脑磁共振成像检查。我们采集了 T1 加权和 T2 加权流体衰减反转恢复序列、选择性反转恢复定量磁化转移图像以及球面平均技术多室弥散成像。我们计算了大分子与自由池大小比和轴突表观体积分数图,以分别间接估计髓鞘和轴突的完整性。我们使用蒙特利尔神经研究所 152 空间的 T1 加权磁共振成像模板,在每个受试者的原始 T2 加权流体衰减反转恢复图像中制作了血流区域图谱。病变位置与分水岭、非分水岭和混合脑血管区域的相对位置被标注出来。使用 294 个感兴趣区对健康对照组的 T2 加权流体加权反转复原图像进行了同样的处理。我们使用连续结果的广义线性混合模型来评估位于不同血管区域的病变/感兴趣区(健康对照组)在大小、集合大小比和轴突体积分数方面的差异。在患者中,我们评估了 758 个 T2- 病变和 356 个慢性黑洞(cBHs)。与非分水岭区或混合区相比,分水岭区的 T2- 病变(P≤0.041)和 cBHs(P≤0.036)的相对浓度和绝对浓度更高。与非分水岭区或混合区的 T2-裂隙相比,分水岭区的 T2-裂隙的池大小比也较低(P = 0.039)。这些结果在没有血管合并症的亚群中以及考虑到脑室周围病变时仍具有重要意义。在健康对照组中,只有混合区的轴突体积分数高于非水流区(P = 0.008)。在集合大小比方面没有发现差异。我们提供的体内证据表明,早在疾病诊断时,脑动脉血管化就与多发性硬化引起的组织损伤有关。我们的研究结果强调了氧气输送和健康的动脉血管化对防止病变形成和改善多发性硬化症预后的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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