Defining multiple sclerosis subtypes using machine learning

Author:

Eshaghi ArmanORCID,Young Alexandra,Wijertane Peter,Prados Ferran,Arnold Douglas L.,Narayanan Sridar,Guttmann Charles R. G.,Barkhof Frederik,Alexander Daniel C,Thompson Alan J,Chard Declan,Ciccarelli Olga

Abstract

AbstractMultiple sclerosis (MS) is subdivided into four phenotypes on the basis of medical history and clinical symptoms. These phenotypes are defined retrospectively and lack clear pathobiological underpinning. Since Magnetic Resonance Imaging (MRI) better reflects disease pathology than clinical symptoms, we aimed to explore MRI-driven subtypes of MS based on pathological changes visible on MRI using unsupervised machine learning. In separate train and external validation sets we looked at a total of 21,170 patient-years of data from 15 randomised controlled trials and three observational cohorts to explore MRI-driven subtypes and test whether these subtypes had differential clinical outcomes. We processed MRI data to obtain measures of brain volumes, lesion volumes, and normal appearing white matter T1/T2. We identified three MRI-driven subtypes who were similar in how they accumulated MRI abnormality. Based on the earliest abnormalities suggested by our model they were called: cortex-led, normal appearing white matter-led, and lesion-led subtypes. In the external validation datasets, the lesion-led subtype showed a faster disability progression and higher disease activity than the cortex-led subtype. In all datasets, MRI-driven subtypes were associated with disability progression (βSubtype=0.04, p=0.02; βStage=-0.06, p<0.001), whilst clinical phenotypes and baseline disability were not. Only the lesion-led subtype showed a significant treatment response in three progressive multiple sclerosis randomised controlled trials (−66%, p=0.009) and in three relapsing remitting multiple sclerosis trials (−89%, p=0.04). Our results show that MRI-driven subtyping using machine learning can prospectively enrich clinical trials with patients who are most likely to respond to treatments.

Publisher

Cold Spring Harbor Laboratory

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3