Cerebral Amyloid Angiopathy MRI Predicts Acute and Future Stroke in Vessel Wall Enhancement on Black-Blood

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients. MATERIALS AND METHODS: This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on preand postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy–positive and age-matched negative participants using a prevalenceand bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P, .20. RESULTS: Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalenceand bias-corrected kappa was 0.82 (95% CI, 0.71–0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio 1⁄4 1.5; 95% CI, 1.1–2.2; P 1⁄4 .022), age (prevalence ratio 1⁄4 1.02; 95% CI, 1.0–1.05; P 1⁄4 .036), time between symptoms and MR imaging (prevalence ratio1⁄4 0.9; 95% CI, 0.8–0.9; P, .001), and smoking (prevalence ratio1⁄4 0.7; 95% CI, 0.5–1.0; P 1⁄4 .042) with c-statistic 1⁄4 0.92 (95% CI, 0.84–0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%–67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement–positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%–84.0%) versus 32.2% (95% CI, 14.4%–62.3%) ischemic strokes per year, chi-square 1⁄4 4.9, P 1⁄4 .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio 1⁄4 3.4; 95% CI, 1.0–12.0; P 1⁄4 .053) and vessel wall enhancement (hazard ratio 1⁄4 2.5; 95% CI, 0.9–7.0; P 1⁄4 .080). CONCLUSIONS: Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy. ABBREVIATIONS: CAA 1⁄4 cerebral amyloid angiopathy; HR 1⁄4 hazard ratio; PR 1⁄4 prevalence ratio; VWE 1⁄4 vessel wall enhancement; vwMRI 1⁄4 vessel wall MR imaging; AIS 1⁄4 acute ischemic stroke; SPACE 1⁄4 sampling perfection with application-optimized contrasts by using different flip angle evolutions Vessel wall enhancement (VWE) can be detected using vessel wall MR imaging (vwMRI) using flow-suppressed, contrastenhanced black-blood T1-weighted sequences. In the setting of intracranial atherosclerosis, VWE is a known independent risk factor for acute ischemic stroke (AIS). Other pathologies also affect the vessel wall, including vasculitis, reversible cerebral vasoconstriction syndrome, and Moyamoya disease and their findings on vwMRI that have been previously described. Very recently, a case series found VWE in 2 of 5 patients (40%) with cerebral amyloid angiopathy (CAA). Although this small study showed Received October 12, 2020; accepted after revision December 11. From the Department of Radiology (J.S.M., A.S., M.D.A., S.-E.K.), Utah Center for Advanced Imaging Research; Utah, and Departments of Pathology (J.A.S.), Neurosurgery (S.T.M.), Internal Medicine (G.J.S.), and Neurology (L.D.D., A.H.d.H.), University of Utah, Salt Lake City, Utah Gregory J. Stoddard performed statistical analyses. This work was supported by the American Heart Association Scientist Development Grant 17SDG33460420 (McNally), NIH/NINDS K23NS105924 (A.H.H.), a grant from the National Institutes of Health R01 HL127582 (S.-E.K., J.S.M.). This investigation was supported by the University of Utah Population Health Research (PHR) Foundation, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR002538 (G.J.S., formerly 5UL1TR001067-05, 8UL1TR000105 and UL1RR025764). Please address correspondence to Scott McNally, MD, PhD, University of Utah, Department of Radiology, 30 North 1900 East #1A071, Salt Lake City, UT 84132-2140; e-mail: scott.mcnally@hsc.utah.edu Indicates open access to non-subscribers at www.ajnr.org Indicates article with online supplemental data. http://dx.doi.org/10.3174/ajnr.A7047 AJNR Am J Neuroradiol : 2021 www.ajnr.org 1 Published March 18, 2021 as 10.3174/ajnr.A7047 Copyright 2021 by American Society of Neuroradiology. that VWE can occur in patients with noninflammatory CAA, its neurologic impact is unknown. In addition to lobar hemorrhage, CAA is an important cause of transient neurologic complaints (amyloid spells), cognitive impairment, and ischemic infarcts. The pathogenesis of CAA is complex and related to amyloid-b deposition in the smallto medium-sized vessel walls, resulting in necrosis, vessel rupture, or thrombosis. Because of this, imaging techniques that highlight vessel wall pathology, such as vwMRI, may have diagnostic and prognostic impact in patients with CAA. Brain imaging currently plays a vital role in CAA diagnosis using the modified Boston criteria. The most common acute imaging finding in patients with CAA is hemorrhage from vessel rupture. Microinfarcts can be seen in animal models of CAA and are present in 30%–60% of patients with CAA, contributing to cortical thinning. CAA imaging criteria depend primarily on the presence of prior hemorrhage on susceptibility-weighted sequences, including siderosis and microhemorrhages in lobar, corticalor subcortical locations. CAA disproportionately affects older adults, with increasing prevalence after age 60 years. Because of this, the modified Boston criteria for CAA use a threshold of 55 years or older. Patients with CAA often undergo work-up for acute neurologic deficits concerning for ischemic stroke, which can be detected on MR imaging. Evaluation of ischemic stroke risk in patients with CAA has important diagnostic and prognostic impact because it is a significant contributor to cognitive decline. These patients have complex medical histories, and because vessel wall pathology may not easily be seen with lumen imaging, this necessitates further evaluation with vessel wall imaging techniques. Because of their complicated nature, neurology consultation and vwMRI are often performed in the work-up of patients with CAA at our institution. In light of this and given the importance of VWE in a variety of intracranial vasculopathies, our goal was to determine the association of VWEwith AIS in patients with CAA undergoing vwMRI during stroke work-up. In this study, we evaluated both acute concurrent and future ischemic stroke risk while controlling for potential cerebrovascular confounders. Our hypothesis was that in patients with CAA, VWE would be associated with both concurrent and future ischemic stroke. MATERIALS AND METHODS The data in this manuscript are available upon reasonable request. Study Design and Cohort Institutional review board approval was obtained before this retrospective study at our academic center from 2015 to 2019 in patients undergoing vwMRI for acute neurologic deficits concerning for ischemic stroke. Because of the retrospective nature, informed consent was not required by the institutional review board. In this protocol, all patients with CAA included had probable or possible CAA (based on modified Boston criteria and microhemorrhages detected before vwMRI) and documented acute focal neurologic deficits warranting vwMRI during the stroke work-up. All patients with CAA admitted under the neurology team with suspected stroke during this time period underwent vwMRI work-up per protocol. Although a few scans exhibited mild motion artifacts, none was sufficient to exclude any participants from interpretation. Chart review was used to determine age, sex, and other potential cerebrovascular confounders at the time of vwMRI. CAA Diagnosis Patients diagnosed with probable or possible CAA were included in this study. Modified Boston criteria were used by a vascular neurologist to diagnose CAA. Briefly, modified Boston criteria for probable CAA included age 55 years or older, appropriate clinical history, and MR imaging findings demonstrating either 1) multiple hemorrhages restricted to lobar, cortical, or corticosubcortical regions of varying sizes or ages without another cause or 2) a single lobar, cortical, or corticosubcortical hemorrhage and focal (#3 sulci) or disseminated (.3 sulci) cortical superficial siderosis without another cause. Cases of possible CAA were also included based on the modified Boston criteria definition: single lobar, cortical, or corticosubcortical hemorrhage without other cause. Twelve of our CAA cases were also confirmed with biopsy. vwMRI Protocol All MR imaging was obtained at 3T on Verio, Trio, or Prisma platforms (Siemens) with standard head coils and a standard contrast dose of MultiHance (Bracco), 0.1mmol/kg. Sequences included those in the Online Supplemental Data. The sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE; Siemens) sequences were acquired with delay alternating with nutation for tailored excitation flow suppression. Images were obtained in this order—precontrast: DWI, SWI, TOF, T2 SPACE, T1 SPACE and postcontrast: TOF and T1 SPACE. Brain Parenchymal Findings Both acute and future ischemic stroke were determined using the American Heart Association definition of CNS infarction as previously described. Briefly, acute or future ischemic stroke was defined by brain cell death attributable to ischemia based on 1) imaging evidence of cerebral infarction or 2) clinical sym