Characterization of Asymptomatic Intracranial Atherosclerosis using 3D High Resolution Contrast-enhanced MRI
Huan Yang1,2, Xuefeng Zhang1,3, Li Liu1, Qing Hao4, Victor Urrutia4, Qin Qin1,5, Bruce A. Wasserman1, and Ye Qiao1

1The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins Hospital, Baltimore, MD, United States, 2Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, People's Republic of, 3Inner Mongolia Autonomous Region People's Hospital, Inner Mongolia, China, People's Republic of, 4Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, United States, 5F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States


Although most of strokes occur in asymptomatic patients, most studies have been conducted in symptomatic cohort. Here we aimed to characterize ICAD in stroke-free participants and compare with stroke patients using 3D high-resolution contrast-enhanced BBMRI. Nineteen asymptomatic and 15 stroke patients were included and underwent a standardized protocol which contains 3D TOF MRA and pre- and post-contrast 3D BBMRI imaging. Plaque enhancement was categorized, and morphology and signal-based measurements were compared. The results showed that asymptomatic plaques demonstrated lower contrast-enhancement compared with symptomatic plaques. Contrast-enhancement of ICAD may serve as a marker for plaque stability, providing insight into stroke risk.


Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke worldwide and associated with a high risk of recurrent stoke1. It is a chronic disease and tends to progress silently over years, providing an opportunity for diagnosis before events occur. Although 77% of strokes occur in asymptomatic patients, most studies have been conducted in symptomatic ICAD patients or patients referred for a family history of stroke2. Therefore, the detection and characterization of ICAD in its asymptomatic stage may provide insight into stroke risk and primary prevention of stroke. Recent development of 3D high-resolution black-blood MRI imaging (BBMRI) allows for screening ICAD and provides reliable plaque measurements, even before causing luminal narrowing3. The plaque enhancement on 3D BBMRI entailed after gadolinium contrast is associated with culprit plaques (i.e., responsible for downstream ischemic events)4, while its role in stroke-free individuals remains unknown. Therefore, we aimed to characterize ICAD in an asymptomatic population using 3D high-resolution contrast-enhanced BBMRI and compare with those from stroke patients.


Participants for this study were drawn from those who attended the fifth visit (2011 to 2013) of the Atherosclerosis Risk in Communities (ARIC) study, a community-based prospective study initiated in 1987-1989. Nineteen asymptomatic participants with identified ICAD (9 male; mean age 78.8 ± 6.3 years) were recruited based on the previous BBMRI/MRA in ARIC visit 5. All MRI scans were performed on a 3T MRI Achieva scanner using a 32-channel head coil. High-resolution intracranial vessel wall imaging was acquired based on a standardized protocol 5 that included 3D time-of-flight (TOF) MRA and pre- and post-contrast 3D BBMRI imaging. The 3D TOF MRA was acquired in a transverse plane with the following parameters: TR/TE/flip angle, 23 ms/3.5 ms/25°; FOV, 160 mm x 160 mm; acquired resolution, 0.55×0.55×1.1 mm3 and scan time of approximately 6 minutes. The 3D BBMRI sequence was performed by using an anti-driven based variable-flip-angle TSE sequence (ADE-BBMRI) in a coronal plane (50-mm-thick slab) optimized for flow suppression and wall delineation. The following parameters were used: TR/TE, 2000ms/37ms; TSE factor, 60 including 4 startup echoes; echo spacing, 6.1ms; sense factor, 2; half scan factor (partial Fourier) of 0.6; oversampling factor, 1.2; number of averages, 1; acquired resolution, 0.5x0.5x0.5 mm3; scan time, 5.4 minutes. The ADE-BBMRI sequence was repeated with a TR of 1000ms for T1 weighted contrast in axial plane (80-mm-thick slab) to approximate the same scan time. Gadovist (gadobutrol) was administered intravenously (0.1 mmol/kg) and the BBMRI images were repeated five minutes after contrast administration. Fifteen stroke patients recruited from the local hospital and underwent the standardized protocol were included for comparison. Plaque enhancement was categorized on BBMRI based on the previous criteria4 (Figure 1). Morphology- (stenosis, plaque size, normalized wall index (NWI)) and signal-based (contrast-enhancement (%CE), signal heterogeneity) measurements were compared between two groups.


The clinical and plaque characteristics of the study population are shown in Figure 2. A total of 86 plaques were identified in 19 ARIC participants (mean, 4.7/person), and 70 identified in 15 stroke patients (mean, 4.5/person). Non-enhanced plaques (grade 0) were more frequently identified in ARIC participants compared with those from stroke patients (ARIC, 63% versus Stroke, 20%, p<0.01). In stroke patients, all culprit plaques showed enhanced (40% grade 1, 60% grade 2), whereas the non-enhancement was exclusively observed in non-culprit plaques (Figure 3). Quantitative measurements were performed in 15 pairs of asymptomatic and culprit plaques, matched with degree of stenosis and the plaque location (MCA, 2; ACA, 1; ICA, 6; PCA, 1; BA, 3; VA, 2). Asymptomatic plaques demonstrated lower %CE and smaller NWI than culprit plaques (%CE, 12.1±4.0 vs. 34.1±8.0, p< 0.001; NWI, 56.0±7.9 vs. 69.6±21.4, p =0.052 (marginally significant), respectively). There were no difference identified for other measurements between two groups.


Contrast-enhancement of ICAD demonstrated distinct differences between asymptomatic and symptomatic groups, and may serve as a marker of its stability, providing insight into stroke risk.


Gadolinium contrast enhancement is thought to relate to the plaque inflammation and neovascularization, both of which facilitate the accumulation of the contrast agent within the atherosclerotic plaque. However, it can also occur after the plaque rupture, because of the denudated endothelium layer with an increased permeability. Most current studies of ICAD have underwent BBMRI after the stroke, which limited our ability to discern the exact mechanism accounting for contrast enhancement. To our knowledge, this was the first study to investigate the contrast enhancement in an asymptomatic population using the 3T high resolution contrast-enhanced MRI.


This work is supported by NIH NHLBI R00HL106232


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Categorize plaque enhancement on 3D BB-MRI. A and B, Grade 0 enhancement of an asymptomatic plaque with left internal carotid artery stenosis in an 83-year-old asymptomatic man. C and D, Grade 2 enhancement of a culprit plaque with right internal carotid artery stenosis in a 61-year-old stroke woman.

Demographic, Clinical, and Plaque Characteristics of Study Population

Enhancement Grade of Plaques in Asymptomatic Participants and Stroke Patients

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)