Cerebral amyloid angiopathy is associated with a high prevalence of markers of small-vessel disease, including white matter hyperintensities and cerebral microbleeds and is a major cause of lobar intracerebral hemorrhage and cognitive impairment in the elderly.
“Because CAA is a relatively homogeneous small-vessel disease of the brain, we wondered whether other markers, such as mean diffusivity, as measured by diffusion tensor imaging would be predictive of either the severity of CAA or cognitive impairment prior to large hemorrhages associated with CAA,” said Dr. Anand Viswanathan of the hemorrhagic stroke research program and the stroke service at Massachusetts General Hospital in Boston.
Diffusion tensor imaging (DTI) has already been used in a number of other small-vessel diseases to detect microstructural changes in cerebral tissue—even in areas that appear normal on conventional MRI. Dr. Viswanathan and his colleagues had previously studied patients with another small-vessel disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and had found a strong correlation between the apparent diffusion coefficient (ADC)—an average measure of water diffusion in all directions in brain tissue—and functional changes (see images). In fact, ADC changes were much more predictive of functional impairment than were white matter changes on fluid-attentuated inversion recovery (FLAIR) imaging, which are typically seen quite early in this disease process (Stroke 2007;38:1786-90).
For the current study, the researchers recruited subjects from an ongoing single-center, prospective longitudinal cohort study of CAA. The patients had to be at least 55 years of age at the time of presentation and have a symptomatic lobar intracerebral hemorrhage (ICH). They had MRI with diffusion-weighted sequences within 90 days of the index event. Those with other potential causes of ICH were excluded (Stroke 2008;39:1988-92).
Under the Boston Criteria, 5 of the patients had definite CAA with tissue diagnosis, 19 had probable, and 25 had possible. Pre-ICH cognitive function was assessed after an interview with patients and informants and review of medical records and results of a standardized questionnaire. Pre-ICH cognitive impairment was defined as the presence of deficits in memory or other cognitive areas sufficient to interfere with tasks of daily living before ICH.
Images were acquired with a 1.5T-scanner and included diffusion-weighted, FLAIR, and gradient echo. Mean ADC was determined for the hemisphere contralateral to the hema- toma. Seven of 10 patients (70%) with pre-ICH cognitive impairment had a diagnosis of probable CAA, compared with 11 of 38 (29%) without pre-ICH cognitive impairment. Patients with pre-ICH cognitive impairment had greater mean ADC values, compared with those without pre-ICH cognitive impairment.
After adjustment for age and amount of visible cerebral atrophy, only the mean ADC was independently associated with pre-ICH cognitive impairment. The effect of visible cerebral atrophy on pre-ICH cognitive impairment wasn't significant. “ADC changes [seem to] occur even in normal-appearing white matter, as [shown] by conventional FLAIR imaging, suggesting DTI may be more sensitive [for detecting] tissue changes in CAA and other small-vessel diseases in the brain,” Dr. Viswanathan said.
FLAIR imaging reveals areas of white matter hyperintensities in this patient with CAA.
Left to right: T1-weighted images show degree of brain atrophy, FLAIR shows WMH, and ADC maps show tissue microstructural changes. Images courtesy Dr. Anand Viswanathan