MR imaging features of amyloid-related imaging abnormalities

Abstract

Background and purpose: AD is one of the few leading causes of death without a disease-modifying drug; however, hopeful agents are in various phases of development. MR imaging abnormalities, collectively referred to as amyloid-related imaging abnormalities, have been reported for several agents that target cerebral Aβ burden. ARIA includes ARIA-E, parenchymal or sulcal hyperintensities on FLAIR indicative of parenchymal edema or sulcal effusions, and ARIA-H, hypointense regions on gradient recalled-echo/T2* indicative of hemosiderin deposition. This report describes imaging characteristics of ARIA-E and ARIA-H identified during studies of bapineuzumab, a humanized monoclonal antibody against Aβ.

Materials and methods: Two neuroradiologists with knowledge of imaging changes reflective of ARIA reviewed MR imaging scans from 210 bapineuzumab-treated patients derived from 3 phase 2 studies. Each central reader interpreted the studies independently, and discrepancies were resolved by consensus. The inter-reader κ was 0.76, with 94% agreement between neuroradiologists regarding the presence or absence of ARIA-E in individual patients.

Results: Thirty-six patients were identified with incident ARIA-E (17.1%, 36/210) and 26 with incident ARIA-H (12.4%, 26/210); of those with incident ARIA-H, 24 had incident microhemorrhages and 2 had incident large superficial hemosiderin deposits.

Conclusions: In 49% of cases of ARIA-E, there was the associated appearance of ARIA-H. In treated patients without ARIA-E, the risk for incident blood products was 4%. This association between ARIA-E and ARIA-H may suggest a common pathophysiologic mechanism. Familiarity with ARIA should permit radiologists and clinicians to recognize and communicate ARIA findings more reliably for optimal patient management.

Fig 1.

ARIA-E (effusion); sulcal FLAIR hyperintensity. FLAIR MR imaging at baseline (A) and week 19 (B). On the follow-up surveillance scan (week 19), sulcal FLAIR hyperintensity developed in the right frontal region (arrow). No associated signal abnormality was identified on other imaging sequences, including T1 and gradient recalled-echo/T2* imaging (not shown). Because the imaging appearance mimicked that of a subarachnoid hemorrhage, CT and lumbar puncture were performed, both of which had normal findings, revealing no evidence of blood products.

Fig 2.

ARIA-E (edema and effusion); parenchymal and sulcal FLAIR hyperintensity. FLAIR sequences at baseline (A), week 19 (B), and week 32 (C). By week 19 (6 weeks after the second dose of bapineuzumab), a zone of cortical swelling, sulcal effacement, and parenchymal hyperintensity has developed in the right temporal-occipital lobe. A small sulcal effusion and faint overlying linear leptomeningeal hyperintensity (arrows) help define the area of abnormality. By week 32, these findings have largely resolved. As is typically the case with bapineuzumab-related ARIA, the patient remained asymptomatic throughout all imaging time points.

Fig 3.

ARIA-E (edema); week 19 parenchymal FLAIR hyperintensity. Week 19 FLAIR (A) and corresponding DWI (B) and week 19 gadolinium (C). On the surveillance scan for week 19 (A), several large regions of parenchymal edema develop, principally in the bifrontal and left temporal regions, which resolve on follow-up (not shown). Week 19 DWI reveals minimal T2 shinethrough (B), but no ADC abnormality (not shown). With gadolinium, there is no frank enhancement with only mild prominence of overlying cortical vasculature, in keeping with nonspecific cerebral swelling (C).

Fig 4.

ARIA-E (edema) with incident ARIA-H (microhemorrhages). FLAIR and corresponding gradient recalled-echo/T2* sequences of the same patient, at baseline (A and B) and week 19 (C and D). By week 19 (6 weeks after the second dose of bapineuzumab), significant right-hemispheric edema has developed. As is characteristic of ARIA-E, despite the extensive parenchymal changes, DWI and ADC findings remained normal (not shown), confirming these findings as reflecting vasogenic as opposed to cytotoxic edema. On the corresponding gradient recalled-echo/T2* images, there is concomitant development of several punctate microhemorrhages in the right parietal region (circle). On subsequent imaging, the cerebral edema resolved while the microhemorrhages remained stable (not shown). In general, the severity of ARIA changes was associated with both Apolipoprotein ε4 allele status and drug dosage. As such, this patient was an Apolipoprotein ε4 homozygote and in the highest drug-dose arm.

Fig 5.

ARIA-E (edema) with incident ARIA-H (superficial hemosiderin deposits). Gradient recalled-echo/T2* and corresponding FLAIR sequences from the same patient, at baseline (A), week 19 (B), and week 28 (C). By week 19 (B), several regions of parenchymal edema have developed, including bifrontal regions and the right parieto-occipital lobe. On the corresponding gradient recalled-echo/T2* images, by week 19, there is concomitant development of several superficial linear areas of blood-degradation products (arrows) in the bifrontal regions (≥10 mm). By week 28, the FLAIR changes relating to ARIA-E have resolved, with blood products re-demonstrated.