Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Penn Statistics in Imaging and Visualization Endeavor, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ann Neurol. 2023 Oct;94(4):736-744. doi: 10.1002/ana.26727. Epub 2023 Jul 11.
To determine early magnetic resonance imaging (MRI) features of new multiple sclerosis (MS) lesions that will develop into paramagnetic rim lesions (PRLs), which have been associated with progressive tissue injury in MS.
New contrast-enhancing lesions observed on routine clinical MRI were imaged at 7 T within 4 weeks of observation, and 3 and 6 months later. The 6-month MRI was used to classify PRL status (PRL or non-PRL). The relationship between early lesion characteristics and subsequent PRL status was assessed using generalized linear mixed effects models. Random forest classification was performed to classify early predictors of subsequent PRL status.
From 93 contrast-enhancing lesions in 23 MS patients, 37 lesions developed into a PRL. In lesions that developed into PRLs compared with those that did not, the average lesion T on the initial 7 T MRI was 1994 ms compared with 1,670 ms (p-value <0.001), and the average volume was 168.7 mL compared with 44 mL (p-value <0.001) in lesions that did not. These volume differences were also found on 3 T scans (p-value <0.001), and for intensity-normalized T -w (p-value = 0.011) and fluid-attenuated inversion recovery (p-value = 0.005). The area under the receiver operating characteristic curve for the random forest classification with leave-one-out cross-validation was found to be 0.86 using initial 7 T features.
New MS lesions that evolve into PRLs can be identified early in lesion evolution. These findings suggest that biological mechanisms underlying PRL development begin early, which has important implications for clinical trials targeting PRLs development and subsequent therapeutics. ANN NEUROL 2023;94:736-744.
确定新多发性硬化症(MS)病灶中将会发展为顺磁性边缘病灶(PRL)的早期磁共振成像(MRI)特征,这些病灶与 MS 中的进行性组织损伤有关。
在观察后 4 周内,在 7T 下对常规临床 MRI 观察到的新增强病灶进行成像,并在 3 个月和 6 个月后再次成像。使用 6 个月 MRI 对 PRL 状态(PRL 或非 PRL)进行分类。使用广义线性混合效应模型评估早期病灶特征与随后 PRL 状态之间的关系。采用随机森林分类法对随后 PRL 状态的早期预测因子进行分类。
在 23 名 MS 患者的 93 个增强病灶中,有 37 个病灶发展为 PRL。与未发展为 PRL 的病灶相比,在发展为 PRL 的病灶中,初始 7T MRI 上的平均病灶 T 值为 1994ms,而未发展为 PRL 的病灶为 1670ms(p 值<0.001),平均体积为 168.7mL,而未发展为 PRL 的病灶为 44mL(p 值<0.001)。在 3T 扫描中也发现了这些体积差异(p 值<0.001),以及强度归一化 T1-w(p 值=0.011)和液体衰减反转恢复(p 值=0.005)。通过留一交叉验证的随机森林分类法,初始 7T 特征的受试者工作特征曲线下面积为 0.86。
在病灶演变的早期,可以识别出发展为 PRL 的新 MS 病灶。这些发现表明,PRL 发展的生物学机制很早就开始了,这对靶向 PRL 发展和随后治疗的临床试验具有重要意义。