Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy

Abstract

Objective: We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA).

Methods: We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at "simulated" hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained.

Results: Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1-9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23-1.46) than simulated lesions (1.14, 95% CI 1.07-1.22, p < 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p < 0.0001). Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p = 0.003).

Conclusions: Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA.

Figure 1. Methods for image analysis

Baseline (A) and follow-up (B) T2* MRIs are reviewed by a rater blinded to the Pittsburgh compound B (PiB) PET scans, new bleeds are identified and mapped on the follow-up MRI (arrow, C). At the last step, follow-up T2* MRI and PiB-PET scans are coregistered for every patient and mean distribution volume ratio values are calculated for each bleed from the corresponding areas on PET (arrow, D).

Figure 2. Appearance of an intracerebral hemorrhage at a location with baseline high amyloid deposition

Arrows point to an area with high Pittsburgh compound B (PiB) retention on baseline PET (A), without hemorrhage on initial T2* MRI scan (B), and where a hemorrhage appears on the 13-month follow-up T2* MRI (C). GRE = gradient echo.

Figure 3. Linear falloff of distribution volume ratio (DVR) values around incident microbleeds

Amyloid deposition decreases at increasing distances from the sites of incident bleeds. The centers and immediate peripheries of actual bleeds have higher Pittsburgh compound B retention when compared to the corresponding shells in and around simulated bleeds.

Figure 4. Correlation between mean superior frontal/parasagittal distribution volume ratio (DVR) and incident microbleed counts

The number of new microbleeds correlated with mean DVR in a superior frontal/parasagittal region of interest (ρ = 0.76, p = 0.007).