MRI Characteristics of Chronic MS Lesions by Phase Rim Detection and/or Slowly Expanding Properties

Objective: To evaluate the colocalization of phase rim lesions (PRLs) and slowly expanding lesions (SELs) and compare normalized magnetization transfer ratio (nMTR) and diffusion tensor imaging radial diffusivity (DTI-RD) in PRLs and SELs in patients with relapsing multiple sclerosis (RMS). Background: PRLs, as detected on susceptibility-weighted phase images, have been associated with chronic active MS lesions. SELs have been posited as a marker of chronic active MS lesions that can be assessed using only conventional MRI sequences; however, their correspondence with PRLs is unknown. Design/Methods: PRLs were detected at Week 72 in a subset of RMS patients from the AFFINITY trial [NCT03222973] (N=44) using standardized 3-Tesla Siemens 3D isotropic multi-echo Spoiled Gradient T2*. SELs were detected as areas of baseline T2 lesions that showed constant and concentric expansion from baseline to Week 72, using longitudinal T1- and T2-weighted acquisitions. Results: More than twice as many SELs were detected as PRLs. Thirty-seven percent of PRLs (44/118) colocalized with SELs while 16 % (42/267) of SELs colocalized with PRLs. Moderate correlation of SEL and PRL counts across patients was observed (r=0.69). SELs colocalizing with PRLs appeared to be larger in size than those lesions that were PRL+/SEL− or PRL−/SEL+. Chronic lesions that were detected as both PRL+/SEL+ had lowest nMTR and higher DTI-RD, compared to PRL+/SEL− and PRL−/SEL+. Conclusions: White matter lesions defined as SELs and PRLs show only partial correspondence and only a minority of SELs are associated with phase rims and vice versa. SELs and PRLs that colocalized may represent the most severe subset of chronic active white matter lesions. Ongoing investigations of SELs and PRLs may help to clarify MRI lesion subtypes and lead to more sensitive markers of MS disease progression. Support: This study is funded by Biogen Disclosure: Colm Elliott has received personal compensation for serving as an employee of NeuroRx Research. Dr. Belachew has received personal compensation for serving as an employee of Biogen Inc. Dr. Belachew has received stock or an ownership interest from Biogen Inc. Elizabeth Fisher has received personal compensation for serving as an employee of Biogen. Elizabeth Fisher has received stock or an ownership interest from Biogen. Elizabeth Fisher has received intellectual property interests from a discovery or technology relating to health care. Bing Zhu has received personal compensation for serving as an employee of Biogen. Bing Zhu has received stock or an ownership interest from Biogen. Dawei Liu has received personal compensation for serving as an employee of Biogen. Dawei Liu has received stock or an ownership interest from Biogen. Li Zhu has received personal compensation for serving as an employee of Biogen. Jun Ke has received personal compensation for serving as an employee of Biogen. Zahra Karimaghaloo has received personal compensation for serving as an employee of NeuroRx. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GENeuro. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Receptos/Celgene. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received stock or an ownership interest from NeuroRx. The institution of Dr. Arnold has received research support from Novartis. The institution of Dr. Arnold has received research support from Immunotec. David Rudko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroRx Research Inc. Dumitru Fetco has nothing to disclose. Daniel Bradley has nothing to disclose.