Lian Li, Michael Chopp, Siamak P Nejad-Davarani, Kourosh Jafari-Khouzani, Suresh C Patel, John Budaj, Mei Lu, Stanton B Elias, Mirela Cerghet and Quan Jiang
Objective
Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components in the
pathophysiology of multiple sclerosis (MS) lesions. However, the roles of stratified lesions with distinct degrees of
hemodynamic and structural injury in disease states remain to be explored. We tested the hypothesis that
hemodynamic and structural impairment, as assessed by cerebral blood volume (CBV) and fractional anisotropy
(FA), respectively, characterizes the extent of tissue injury, and the load of lesion with substantial tissue destruction
would reflect the disease status and therefore, would be related to clinical disability.
Methods
Seven relapsing-remitting MS patients and seven healthy controls underwent perfusion, diffusion and
conventional MRI scans. Based on T2-FLAIR and T1-weighted image, WM plaques were classified. After image
coregistration, values of CBV and FA were estimated in three distinct lesion types (active, T1-hypointense and T1-
isointense lesion) and compared with those obtained in WM from controls. A total of 1135 lesions were evaluated.
Brain volumetric measurement and correlative analysis between brain atrophy, lesion volume and clinical disability
were also performed.
Results
Compared with normal WM, significantly reduced CBV and FA were present in the T1-hypointense lesion, while
insignificant changes in both parameters were exhibited in the T1-isointense lesion. However, increased CBV but
significantly decreased FA was detected in the active lesion. A close spatial relationship between active and T1-
hypointense lesion was observed. Lesion load represented by T1-hypointense plus active lesion volume significantly
correlated with brain atrophy, which, in turn, significantly correlated with the severity of clinical disability.
Conclusion
A distinct combination of CBV and FA characterizes the status of a specific lesion type. A severe structural
impairment does not solely occur in the T1-hypointense lesion, but is also associated with the active lesion. The
burden of the lesion with extensive structural damage provides an image index, indicative of disease status.
