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Review
. 2011 Jul;7(4):367-85.
doi: 10.1016/j.jalz.2011.05.2351.

Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup

Reisa A Sperling  1 , Clifford R Jack Jr, Sandra E Black, Matthew P Frosch, Steven M Greenberg, Bradley T Hyman, Philip Scheltens, Maria C Carrillo, William Thies, Martin M Bednar, Ronald S Black, H Robert Brashear, Michael Grundman, Eric R Siemers, Howard H Feldman, Rachel J Schindler
Affiliations
Review

Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup

Reisa A Sperling et al. Alzheimers Dement. 2011 Jul.

Abstract

Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened a working group to review the publicly available trial data, attempts at developing animal models, and the literature on the natural history and pathology of related conditions. The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recoverysequences thought to represent "vasogenic edema" and/or sulcal effusion (ARIA-E), as well as signal hypointensities on GRE/T2* thought to represent hemosiderin deposits (ARIA-H), including microhemorrhage and superficial siderosis. The etiology of ARIA remains unclear but the prevailing data support vascular amyloid as a common pathophysiological mechanism leading to increased vascular permeability. The workgroup proposes recommendations for the detection and monitoring of ARIA in ongoing AD clinical trials, as well as directions for future research.

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Figures

Figure 1
Figure 1
ARIA-E as seen on FLAIR images from a monoclonal antibody trial demonstrating increased MR signal in multiple regions of the right hemisphere affecting both gray and white matter.
Figure 2
Figure 2
ARIA-E detected on FLAIR images from a monoclonal antibody trial study demonstrating increased MR signal in sulci, thought to represent proteinaceous fluid tracking in the leptomeninges and sulcal spaces.
Figure 3
Figure 3
Microhemorrhage and superficial siderosis Left: White arrows indicate multiple 1–3mm dark foci in the right inferior temporal and occipital lobes, typical of the appearance of mH. Red arrow indicates inferior sagittal sinus, and yellow arrow indicates susceptibility artifact, as vascular structures and artifacts can sometimes mimic the appearance of mH and siderosis. Right: White arrows indicate curvilinear dark sulci in the right frontal lobe, typical of the appearance of superficial siderosis. Both images were acquired at 1.5T with a 2D long TE (30ms) GRE sequence.
Figure 4
Figure 4. Conspicuity Depends on Technique. SWI vs T2* GRE
SWI image (left) compared to T2* image of same patient on same day on the right. Note, there are 4 more MB detected on the SWI image
Figure 5
Figure 5
Relationship between ARIA-E and ARIA-H. Left: FLAIR image demonstrating ARIA-E with increased signal in white and gray matter and sulcal effacement in right frontal and parietal regions. Right: GRE image showing mH in right parietal region only.
Figure 6
Figure 6
Spontaneous CAA-related inflammation. MR images show VE-like appearance (left) with resolution following course of corticosteroids (center). Pathology image (right) shows white matter rarefaction without necrosis.
Figure 7
Figure 7
Cerebral microhemorrhages in association with advanced CAA
See this image and copyright information in PMC

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