Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis

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Abstract
Background: Ischemic leukoaraiosis (ILA) refers to diffuse T2-weighted white matter hyperintensity in the context of a previous clinical lacunar stroke. Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it is not known whether hypoperfusion is confined to lesions or extends into normal-appearing white matter. Demonstrating changes in normal-appearing white matter would provide clues to the importance of hypoperfusion in pathogenesis and would be an obvious target for therapies aimed at restoring white matter blood flow. Methods: Twenty-one patients with ILA, and 16 age-matched control subjects, underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined both within and outside areas of T2-weighted hyperintensity in both periventricular white matter and the centrum semiovale. Results: CBF of normal-appearing white matter was reduced in periventricular regions (for patients with ILA, 17.9 ± 5.6 mL/100 g/min; for controls, 21.6 ± 5.1 mL/100 g/min; p = 0.046). CBF in gray matter and normal-appearing white matter of the centrum semiovale did not differ significantly between groups. In normal-appearing white matter in patients, CBF was higher in the centrum semiovale than periventricular white matter, with a similar trend in control subjects. Conclusions: Hypoperfusion may be an early feature in the development of periventricular lesions in ILA and may play a direct pathogenic role. Serial studies are now needed to determine whether these changes herald the appearance of new lesions and represent ‘at risk’ white matter, and to determine whether pharmacological agents can restore perfusion of normal-appearing white matter.