Evolution of Chronic Lesion Tissue in RRMS patients: An association with disease progression

Background and Objective This study examines the long-term changes in Chronic Lesion Tissue (CLT) among relapsing and remitting MS (RRMS) patients, focusing on its impact on clinical and radiological disease progression indicators. Methods The study involved 72 MS patients with at least a 5-year follow-up. Annual assessments used 3D FLAIR, pre- and post-contrast 3D T1, and diffusion-weighted MRI. Lesion segmentation was conducted using iQ-MSTM software, while brain structures were segmented using AssemblyNet. Volumetric changes in CLT were tracked using a custom-designed pipeline. Results Throughout the follow-up period, the volume of CLT in the entire cohort increased continuously and steadily, averaging 7.75±8.2% or 315±465 mm³ per year. Patients with expanding CLT experienced significantly faster brain atrophy, affecting both white and grey matter, particularly in the brain’s central area. Expanded CLT was also associated with higher and worsening EDSS scores, in contrast to the stable CLT group, where EDSS remained unchanged. Conclusion This study demonstrates that, over a period of up to 7 years, patient-specific enlargement of CLT, where present, progresses at a constant rate and significantly influences disease progression. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported by the National Multiple Sclerosis Society (NMSS), Multiple Sclerosis Research Australia (MSRA) and Sydney Medical School. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by University of Sydney and Macquarie University Human Research Ethics Committees and followed the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors