Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy

Abstract

Advanced cerebrovascular β-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cerebral microbleeds, but the precise relationship between CAA burden and microbleeds is undefined. We used T2*-weighted magnetic resonance imaging (MRI) and noninvasive amyloid imaging with Pittsburgh Compound B (PiB) to analyze the spatial relationship between CAA and microbleeds. On coregistered positron emission tomography (PET) and MRI images, PiB retention was increased at microbleed sites compared to simulated control lesions (p = 0.002) and declined with increasing distance from the microbleed (p < 0.0001). These findings indicate that microbleeds occur preferentially in local regions of concentrated amyloid and support therapeutic strategies aimed at reducing vascular amyloid deposition.

Figure 1

Cerebral microbleeds and Pittsburgh Compound B retention. T2*-weighted MRI (panel A) illustrates the characteristic hypointense lesions indicative of CMB. This image is co-registered to a map of PiB-PET Distribution Volume Ratio (panel B); the locations of some CMB are shown by arrows. Changes in PiB signal with increasing distance from the CMB are finally measured in concentric shells (panel C). Note that the shells are truncated at the edges of brain parenchyma to ensure that values were not obtained from non-brain tissue.

Figure 2

PiB retention in concentric shells surrounding cerebral microbleeds. Mean PiB DVR values and standard errors are derived from a piecewise linear mixed effects models (see Methods). DVR declines with increasing distance from the center (p<0.0001) and is significantly greater than the corresponding values for simulated lesions in center (p=0.002), shell 1 (p=0.007), and shell 2 (p=0.03).