Vessel Wall Magnetic Resonance Imaging Biomarkers of Symptomatic Intracranial Atherosclerosis: A Meta-Analysis

Abstract

Background and purpose: Intracranial atherosclerotic disease is a common cause of stroke worldwide. Intracranial vessel wall magnetic resonance imaging may be able to identify imaging biomarkers of symptomatic plaque. We performed a meta-analysis to evaluate the strength of association of imaging features of symptomatic plaque leading to downstream ischemic events. Effects on the strength of association were also assessed accounting for possible sources of bias and variability related to study design and magnetic resonance parameters.

Methods: PubMed, Scopus, Web of Science, EMBASE, and Cochrane databases were searched up to October 2019. Two independent reviewers extracted data on study design, vessel wall magnetic resonance imaging techniques, and imaging end points. Per-lesion odds ratios (OR) were calculated and pooled using a bivariate random-effects model. Subgroup analyses, sensitivity analysis, and evaluation of publication bias were also performed.

Results: Twenty-one articles met inclusion criteria (1750 lesions; 1542 subjects). Plaque enhancement (OR, 7.42 [95% CI, 3.35-16.43]), positive remodeling (OR, 5.60 [95% CI, 2.23-14.03]), T1 hyperintensity (OR, 2.05 [95% CI, 1.27-3.32]), and surface irregularity (OR, 4.50 [95% CI, 1.39-8.57]) were significantly associated with downstream ischemic events. T2 signal intensity was not significant (P=0.59). Plaque enhancement was significantly associated with downstream ischemic events in all subgroup analyses and showed stronger associations when measured in retrospectively designed studies (P=0.02), by a radiologist as a rater (P<0.001), and on lower vessel wall magnetic resonance imaging spatial resolution sequences (P=0.02).

Conclusions: Plaque enhancement, positive remodeling, T1 hyperintensity, and surface irregularity emerged as strong imaging biomarkers of symptomatic plaque in patients with ischemic events. Plaque enhancement remained significant accounting for sources of bias and variability in both study design and instrument. Future studies evaluating plaque enhancement as a predictive marker for stroke recurrence with larger sample sizes would be valuable.

Keywords: atherosclerosis; biomarker; magnetic resonance imaging; meta-analysis; publication bias.

Conflict of interest statement

Conflicts of Interest/Disclosures: Dr. Scott Kasner reports grants and personal fees from WL Gore, grants and personal fees from Medtronic, and grants and personal fees from Bristol Myers Squibb outside the submitted work.

Figures

Figure 1:. Literature search

Figure 2:. Forest plots of imaging biomarkers of symptomatic plaque

Forest plots of pooled data are graphically shown for 4 imaging endpoints. The vertical line represents an odds ratio of 1 (no effect). Squares represent point estimates of a study’s effect size; square sizes are proportional to the inverse of the variance of the estimate. Horizontal lines represent 95% CIs. Diamonds represent pooled estimates with the diamond width representing 95% CIs. *Mean/weighted mean ± standard deviation or median [interquartile range]; if measured stenosis not reported, stenosis inclusion criterion noted in parentheses. Abbreviations: PD, proton density; MCA, middle cerebral artery; BA, basilar artery; ICA, internal carotid artery; COW, circle of Willis; NR, not reported

Figure 3:. VWI imaging features of symptomatic plaque

(A) Coronal postcontrast VWI shows MCA plaque enhancement (arrowhead; inset: pre-contrast VWI). (B) Axial precontrast VWI shows positive wall remodeling (arrowhead) associated with a MCA plaque. Note the absence of severe luminal narrowing. (C) Coronal precontrast VWI shows T1 hyperintensity (arrowhead) of a left MCA plaque. (D) Sagittal precontrast VWI image of a basilar artery shows plaque surface irregularity (arrowheads along long-axis of basilar artery).

Figure 4:. Plaque enhancement in subjects with transient ischemic attack versus cerebral infarct

Forest plots of plaque enhancement by group. Dotted diamonds represent respective group pooled statistics. Solid black diamond represents overall group (TIA and cerebral infarct) pooled statistic.