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Updated: Oct 25, 2025

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Investigating the relationship between multi-scale perfusion and white matter microstructural integrity in patients
Nicholas J Sisco1, Aimee Borazanci1, Richard Dortch1
1Division of Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, USA.
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 T1-weighted to T2-weighted (T1w/T2w) 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). T1w/T2w 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.
Insights
Multiple sclerosis lesions show reduced blood flow at global and capillary levels. This reduced capillary perfusion is linked to decreased white matter integrity in patients with relapsing-remitting MS.
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Multiple sclerosis (MS) involves central nervous system demyelination and inflammation.
- Understanding lesion pathophysiology is crucial for MS management.
Purpose of the Study:
- To investigate the relationship between cerebral perfusion in MS lesions and white matter microstructural integrity.
- Utilize perfusion MRI and myelin-related T1w/T2w ratios for assessment.
Main Methods:
- 48 relapsing-remitting MS (RRMS) patients underwent dynamic susceptibility contrast imaging (SAGE).
- Global and capillary perfusion parameters (CBF, CBV, MTT) were calculated.
- T1w/T2w ratios served as a proxy for white matter microstructural integrity.
Main Results:
- Lesions showed significantly reduced global cerebral blood flow (CBF) and cerebral blood volume (CBV), with increased mean transit time (MTT) compared to normal-appearing white matter (NAWM).
- Capillary-level perfusion metrics revealed even greater reductions in CBF-SE and CBV-SE, alongside increased MTT-SE.
- A significant correlation was found between capillary-level CBF and white matter microstructural integrity within lesion regions.
Conclusions:
- Cerebral perfusion is impaired in MS lesions at both global and capillary levels.
- Reduced capillary perfusion (hypoperfusion) is associated with compromised white matter microstructural integrity in RRMS.
- Findings highlight the importance of capillary-level perfusion in MS lesion pathology.

