目的:髓磷脂和铁在多发性硬化(MS)病变的髓鞘再生过程中起重要作用。χ分离,一种新的生物物理模型,应用于多回波T2*-数据和T2-数据,估计髓鞘和铁对获得的敏感性信号的贡献。我们使用此方法研究了MS患者和健康个体的病变和非病变脑区的髓磷脂和铁水平。
方法:这项前瞻性MS队列研究包括符合2017年麦当劳标准的MS患者和健康个体,18岁或以上,没有其他神经系统合并症.参与者在基线和2年后接受MRI检查,包括多回波GRE-(T2*)和FAST-(T2)序列。使用χ分离,我们生成了髓鞘敏感和铁敏感的药敏图谱.白质病变(WMLs),皮质病变(CLs),周围正常出现的白质(NAWM),在流体衰减反演恢复和磁化制备的2幅快速梯度回波图像上分割正常出现的灰质,分别。横断面组比较使用Wilcoxon秩和检验,纵向分析应用Wilcoxon符号秩检验。与临床结果的关联(疾病表型,年龄,性别,疾病持续时间,通过扩展残疾状况量表[EDSS]测量残疾,神经丝轻链水平,和T2-病变数量和体积)使用线性回归模型进行评估。
结果:168名MS患者(中位[四分位距(IQR)]年龄47.0[21.7]岁;101名妇女;6,898例WMLs,775个CLs)和103个健康个体(年龄33.0[10.5]岁,57名妇女),108和62被随访,中位数为2年,分别(IQR0.1;5,030WML,485CLS)。在基线,与相应的NAWM(髓鞘0.030[0.012];铁0.019[0.011]ppm;两者均p<0.001)相比,WML具有较低的髓鞘(中值0.025[IQR0.015]百万分率[ppm])和铁(0.017[0.015]ppm)。两年后,髓鞘(0.027[0.014]ppm)和铁均增加(0.018[0.015]ppm;均p<0.001).年龄较小(p<0.001,b=-5.111×10-5),较低的残疾(p=0.04,b=-2.352×10-5),和复发缓解表型(RRMS,0.003[0.01]vs原发性进行性0.002[IQR0.01],p<0.001;与次级渐进0.0004[IQR0.01]相比,p<0.001)在基线时与髓鞘再生相关。髓鞘的增加与通过EDSS测量的临床改善相关(p=0.015,b=-6.686×10-4)。
结论:χ分离,一个新的数学模型应用于多回波T2*图像和T2图像显示,年轻的RRMS患者低残疾表现出较高的髓鞘再生能力,这与2年随访期间的临床残疾相关。
OBJECTIVE: Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals.
METHODS: This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models.
RESULTS: Of 168 patients with MS (median [interquartile range (IQR)] age 47.0 [21.7] years; 101 women; 6,898 WMLs, 775 CLs) and 103 healthy individuals (age 33.0 [10.5] years, 57 women), 108 and 62 were followed for a median of 2 years, respectively (IQR 0.1; 5,030 WMLs, 485 CLs). At baseline, WMLs had lower myelin (median 0.025 [IQR 0.015] parts per million [ppm]) and iron (0.017 [0.015] ppm) than the corresponding NAWM (myelin 0.030 [0.012]; iron 0.019 [0.011] ppm; both p < 0.001). After 2 years, both myelin (0.027 [0.014] ppm) and iron had increased (0.018 [0.015] ppm; both p < 0.001). Younger age (p < 0.001, b = -5.111 × 10-5), lower disability (p = 0.04, b = -2.352 × 10-5), and relapsing-remitting phenotype (RRMS, 0.003 [0.01] vs primary progressive 0.002 [IQR 0.01], p < 0.001; vs secondary progressive 0.0004 [IQR 0.01], p < 0.001) at baseline were associated with remyelination. Increment of myelin correlated with clinical improvement measured by EDSS (p = 0.015, b = -6.686 × 10-4).
CONCLUSIONS: χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.