Imaging properties of astrocytic activation in Multiple Sclerosis using MRI and structural tensors

Motivation: Astrocytic activation is a key-mechanism in neuroinflammation,yet its properties in Multiple Sclerosis(MS) are not fully understood. MRI shows promise towards that goal. Goal(s): Inflammation-activated astrocytes upregulate their iron uptake:We investigate potential QSM-sensitivity in this process on MS lesions and associations between astrocytic activation patterns and tissue directionality. Approach: Lesion blocks of 2 QSM-hyperintense and2 QSM-hypo/isointense lesions from 3 different post-mortem MS patients brains, were stained for MBP,GFAP,and CR3-43. Structural-tensor analysis and atlas-based-DWI evaluated GFAP stain directionality. Results: QSM-hypointense lesions showed low astrocytic activation(GFAP) and macrophages/microglia(CR3/43). QSM-hyperintense lesions had perilesional macrophage/microglia accumulation and astrocytic activation. This activation,followed patterns aligned -in-plane- with local fiber orientations. Impact: We provide initial evidence that QSM contrast might also be sensitive to astrocytic activation in MS lesions and surrounding NAWM. The paternalistic activation of astrocytes which resembles local WM axonal directionality introduces a completely novel viewpoint in MS disease progression.