Background

Choroid plexuses (CPs) have been suggested as a key gateway for inflammation in experimental autoimmune encephalitis, but in vivo evidence of their involvement in multiple sclerosis (MS) is lacking.

Purpose

To assess CP volumetric and inflammatory changes in patients with MS versus healthy control participants.

Materials and Methods

This was a secondary analysis of 97 patients (61 with relapsing-remitting MS [RRMS] and 36 with progressive MS) and 44 healthy control participants who participated in three prospective 3.0-T brain MRI studies between May 2009 and September 2017. A subgroup of 37 patients and 19 healthy control participants also underwent translocator protein fluorine 18 (¹⁸F)–DPA-714 PET for neuroinflammation. Relapses and disability scores were collected at baseline and over 2 years. CPs were manually segmented on three-dimensional T1-weighted images; other brain volumes were additionally segmented. Volumes were expressed as a ratio of intracranial volume. The ¹⁸F-DPA-714 distribution volume ratio was quantified in parenchymal regions, whereas standardized uptake value was used for CP inflammation. Multivariable linear regression analyses were performed to assess CP volumetric and inflammatory differences between patients with MS and healthy control participants and correlations between CP volume and lesion load, brain volumes, ¹⁸F-DPA-714 uptake, and annualized relapse rate.

Results

Ninety-seven patients with MS (mean age, 42 years ± 12 [standard deviation]; 49 women) and 44 healthy control participants (mean age, 39 years ± 14; 23 women) underwent MRI. Thirty-seven patients with MS and 19 healthy control participants underwent PET. CPs were 35% larger in patients with MS (mean value, 15.9 × 10⁻⁴ ± 4.5) than in healthy control participants (mean value, 11.8 × 10⁻⁴ ± 3.8; P = .004). Subgroup analysis confirmed greater CP volume in patients with RRMS (mean value, 15.5 × 10⁻⁴ ± 4.6; P = .008) than in healthy control participants. CP enlargement was greater in patients with active lesions at MRI (mean volume, 18.2 × 10⁻⁴ ± 4.9 in patients with lesions that enhanced with gadolinium vs 14.9 × 10⁻⁴ ± 4 in patients with lesions that did not enhance with gadolinium; P < .001) and correlated with white matter lesion load (r = 0.39; 95% CI: 0.20, 0.55; P < .001) and ¹⁸F-DPA-714 binding in the thalami (r = 0.44; 95% CI: 0.22, 0.72; P = .04) and normal-appearing white matter (r = 0.5; 95% CI: 0.20, 0.71; P = .005). Moreover, it correlated with annualized relapse rate in patients with RRMS (r = 0.37; 95% CI: 0.1, 0.55; P = .005). Finally, patients with MS showed 18.5% higher CP ¹⁸F-DPA-714 uptake than control participants (mean value, 0.778 ± 0.23 vs 0.635 ± 0.15, respectively; P = .01). CP volume in patients with RRMS (r = 0.57; 95% CI: 0.37, 0.73; P = .009) correlated with higher ¹⁸F-DPA-714 uptake.

Conclusion

Choroid plexuses (CPs) are enlarged and inflamed in patients with multiple sclerosis (MS), particularly in those with relapsing-remitting MS with inflammatory profiles; CP volumetric analysis could represent an MS imaging marker.

© RSNA, 2021

EudraCT no. 2008-004174-40; clinical trial registration nos. NCT02305264 and NCT01651520

Online supplemental material is available for this article.

中文翻译：

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炎性多发性硬化症中的脉络丛扩大：3.0-T MRI 和易位蛋白 PET 评估

背景

脉络丛 (CP) 被认为是实验性自身免疫性脑炎炎症的关键途径，但缺乏它们参与多发性硬化 (MS) 的体内证据。

目的

评估 MS 患者与健康对照参与者的 CP 体积和炎症变化。

材料和方法

这是对 2009 年 5 月至 2017 年 9 月期间参加三项前瞻性 3.0-T 脑 MRI 研究的 97 名患者（61 名患有复发缓解型 MS [RRMS]，36 名患有进行性 MS）和 44 名健康对照参与者的二次分析。 37 名患者和 19 名健康对照参与者也接受了易位蛋白氟 18 ( ¹⁸ F)-DPA-714 PET 治疗神经炎症。在基线和 2 年内收集复发和残疾评分。在三维 T1 加权图像上手动分割 CP；其他脑容量也被额外分割。体积表示为颅内体积的比率。在¹⁸F-DPA-714 分布体积比在实质区域量化，而标准化摄取值用于 CP 炎症。进行多变量线性回归分析以评估 MS 患者和健康对照参与者之间的 CP 体积和炎症差异，以及 CP 体积与病变负荷、脑体积、¹⁸ F-DPA-714 摄取和年复发率之间的相关性。

结果

97 名 MS 患者（平均年龄，42 岁 ± 12 [标准差]；49 名女性）和 44 名健康对照参与者（平均年龄，39 岁 ± 14；23 名女性）接受了 MRI。37 名 MS 患者和 19 名健康对照参与者接受了 PET。MS 患者的 CP（平均值，15.9 × 10 ^-4 ± 4.5）比健康对照参与者（平均值，11.8 × 10 ^-4 ± 3.8；P = .004）大 35% 。亚组分析证实，RRMS 患者的 CP 体积（平均值，15.5 × 10 ^-4 ± 4.6；P = .008）比健康对照参与者更大。MRI 显示活动性病变患者的 CP 增大更大（平均体积，18.2 × 10 ^-4钆增强的病灶患者为± 4.9，而钆未增强的病灶患者为14.9 × 10 ^-4 ± 4；P < .001) 并与白质病变负荷相关 ( r = 0.39; 95% CI: 0.20, 0.55; P < .001) 和¹⁸ F-DPA-714 在丘脑中的结合 ( r = 0.44; 95% CI: 0.22, 0.72; P = .04) 和正常外观的白质 ( r = 0.5; 95% CI: 0.20, 0.71; P = .005)。此外，它与 RRMS 患者的年复发率相关（r = 0.37；95% CI：0.1, 0.55；P = .005）。最后，MS 患者的 CP 高出 18.5%¹⁸ F-DPA-714 摄取量比对照组参与者高（平均值分别为 0.778 ± 0.23 和 0.635 ± 0.15；P = .01）。RRMS 患者的 CP 体积 ( r = 0.57; 95% CI: 0.37, 0.73; P = .009) 与较高的¹⁸ F-DPA-714 摄取相关。

结论

多发性硬化症 (MS) 患者的脉络丛 (CP) 扩大和发炎，尤其是那些具有炎症特征的复发缓解型 MS 患者；CP 体积分析可以代表 MS 成像标记。

©北美放射学会，2021

EudraCT 没有。2008-004174-40；临床试验注册号 NCT02305264 和 NCT01651520

本文提供了在线补充材料。