To explore the relationship between chronic QSM rim+ lesions and both cognitive function (CF) and EDSS in patients with MS.

Quantitative susceptibility mapping (QSM), an imaging technique sensitive to brain iron, has been used to identify multiple sclerosis (MS) lesions with a rim of iron-laden active microglia/macrophages. These lesions may relate to progressive pathology, and assessing their impact on disability is crucial to validate potential treatment targets.

150 patients with CIS (n=9, 6.0%), RRMS (n=136, n=90.7%), and SPMS (n=5, n=3.3%) were enrolled. The Brief International Cognitive Assessment for Multiple Sclerosis assessed CF. A multivariate multivariable linear model was implemented to test the association between the vector of clinical measures (SDMT, CVLT2, BVMTR, and EDSS) and the number of QSM rim+ lesions per patient. 

The 150 patients had a mean age of 42.6±10.3 years, disease duration of 10.3±7.3 years, and EDSS of 1.4±1.7. A total of 126 QSM rim+ lesions were identified among 53 patients (35.3%). Patients were categorized into 4 groups according to the number of rim+ lesions observed on QSM: 0 rim+ (n=97, 64.67%), 1 rim+ (n=22, 14.67%), 2 rim+ (n=15, 10.0%), or ≥ 3 rim+ (n=16, 10.67%). Total lesion volume (TLV) increased with increasing numbers of rim+ lesions (3.7 cm³, 6.7 cm³, 11.3 cm³ and 12.7 cm³, respectively). The interaction term between TLV and number of rim+ lesions was statistically significant (p=.028). TLV and number of rim+ lesions interacted such that MS patients with ≥ 3 rim + lesions had worse scores on all assessments: SDMT (p=0.036), CVLT2 (p=.004), BVMTR (p=.067), and EDSS (p=.011).

QSM rim+ lesions were associated with physical and cognitive disability; however, this relationship was also closely associated with TLV. Our results promote the use of QSM to identify chronic active lesions and as a tool to understand mechanisms of injury leading to disease progression.