Investigating the relationship between multi-scale perfusion and white matter microstructural integrity in patients with relapsing-remitting MS

BACKGROUND: Multiple sclerosis is characterized by the formation of central nervous system demyelinating lesions with microvasculature inflammation. OBJECTIVE: Evaluate how lesion cerebral perfusion relates to white matter microstructural integrity in patients with RRMS using perfusion MRI and myelin-related T(1)-weighted to T(2)-weighted (T(1)w/T(2)w) ratios. METHODS: Forty-eight patients with RRMS were imaged with dynamic susceptibility contrast imaging using SAGE (spin- and gradient-echo) to calculate global and capillary-sized perfusion parameters, including cerebral blood flow (CBF), volume (CBV), and mean transit time (MTT). T(1)w/T(2)w ratios were used to indirectly assess white matter microstructural integrity. RESULTS: For global perfusion metrics, CBF was reduced 28.4% in lesion regions of interest (ROIs) compared to normal appearing white matter (NAWM), CBV was reduced 25.9% in lesion ROIs compared to NAWM, and MTT increased 12.9%. For capillary perfusion metrics (via spin-echo (SE)), CBF-SE was reduced 35.7% in lesion ROIs compared to NAWM, CBV-SE was reduced 35.2% in lesion ROIs compared to NAWM, and MTT-SE increased 9.1%. Capillary-level CBF was correlated (ρ = 0.34, p = 0.024) with white matter microstructural integrity in lesion ROIs. CONCLUSION: This study demonstrates that lesion perfusion is reduced at both the global and capillary level and capillary-associated hypoperfusion is associated with reduced white matter microstructural integrity in RRMS.