Innate immunity plays a pivotal role in the pathophysiology of multiple sclerosis (MS) and important cell types involved in this process are CNS resident monocytes (microglia) and blood-derived macrophages. Chronic CNS inflammation in the MS lesion is maintained, in part, with iron-laden pro-inflammatory microglia/macrophages (m/M) at the rim of chronic active MS lesions. These lesions are felt to contribute to a more aggressive phenotype of the disease; thus, represents a novel treatment target to reduce disease progression in MS. Identification of the subset of these lesions with a paramagnetic rim has been the focus of several in vivo studies evaluating the cross-sectional association of these lesions with disability, however further work is required to advance the development of this potential treatment biomarker. Utilizing quantitative susceptibility mapping (QSM) to measure chronic active lesions, our group has focused on generating tools to identify and quantify lesion-based chronic innate immune activity. In this talk, I will review imaging approaches to identify chronic lesion-based inflammation and the impact of chronic active lesions on the disease course. I will further propose a novel application of QSM to quantify the inflammatory trajectory within chronic active lesions and provide a new treatment target in MS for current or novel immune modulators