Introduction: Approximately one-fifth of all strokes and transient ischemic attacks affected posterior circulation, supplied by the vertebrobasilar artery system. Diabetes mellitus (DM) is preferentially associated with an increased risk of stroke in the posterior circulation(1). Pathology study suggested DM may increase inflammation and neovascularization, contributing to the development of intraplaque hemorrhage in human diabetic atherosclerosis(2). High-resolution vessel wall magnetic resonance imaging (HR-VWI) allows for identification of high-risk plaque features including T1 hyperintensity and plaque enhancement, and provides reliable assessment of plaque morphology. Complementary to HR-VWI, computed tomographic angiography (CTA) could provide incremental value in the assessment of plaque vulnerability and enable the quantification of vascular calcification. Therefore, we aimed to compare the differences in vertebrobasilar plaque features of DM patients with non-DM patients using a multi-modality imaging approach.
Methods: From April 2017 to June 2021, all patients who underwent both HR-VWI and CTA were retrospectively reviewed. The inclusion criteria were (1) presence of transient ischemic attack or stroke in the territory of posterior circulation; (2) HR-VWI and CTA examinations within a time interval of 4 weeks after the onset of neurological symptoms. DM patients were divided into 2 subgroups by the level of glycated hemoglobin (HbA1c) (≥7.0% as high-HbA1c group vs. ＜7.0% as low-HbA1c group) and diabetes duration (shorter [ 0-9 years] vs. longer [＞10 years]). All MRI and MRA exams were performed on a 3T MR imaging scanner (Ingenia; Philips Healthcare) with a 16-channel head coil. The standardized imaging protocol included DWI, time-of-flight magnetic resonance angiography or phase-contrast magnetic resonance angiography, pre-and post-contrast T1-weighted HR-VWI. The HR-VWI sequence was performed using a volumetric isotropic turbo spin-echo acquisition (VISTA; Philips Healthcare) in coronal and axial planes for comprehensive intracranial artery coverage and optimal blood suppression. The following parameters were used: TR/TE, 425ms/19ms; field of view, 220×220 mm; matrix, 316×312; TSE factor, 28 including 2 startup echoes; oversampling factor, 1.3; number of average, 2; SENSE factor, 2; echo spacing, 6.3 ms; acquired resolution, 0.7×0.7×1.1 mm3; and scan time, 6.1 minutes. Plaque morphological measurements included lumen area, outer wall area, normal wall index, maximum wall thickness, minimum wall thickness, eccentricity index and remodeling index. Signal characteristics including plaque enhancement and T1 hyperintensity were analyzed based on the previous criteria(3, 4). CTA protocol was conducted on a 128-slice dual-source CT scanner (SOMATOM Definition Flash, Siemens healthiness, Forchheim, Germany). Same reconstruction parameters were used for single phase CTA and 4D multi-phase CTA (a section thickness of 1.0 mm; an interval of 0.7 mm). Calcification was defined as the presence of hyperdensity with a CT attenuation of 130 HU or greater. Spotty calcification was defined as a lesion of calcium deposition with a length below 3 mm and within an arc of less than 90°. The calcification volume was quantified semiautomatically using Medical Imaging Interaction Toolkit (MITK, open-source software, https://www.mitk.org).
Results: A total of 148 patients were included and 75 patients were diagnosed with diabetes mellitus. DM patients were more likely to have a history of prior stroke (49% vs. 33%, p=0.034) compared to non-DM patients. Diabetic patients had more presence of T1 hyperintensity, calcification and spotty calcification, as well as higher calcification volume (all p＜0.05) compared with non-diabetic patients. Multivariable logistic regression model demonstrated that the associations of T1 hyperintensity (OR, 2.40 [95% CI, 1.03 to 5.77], p=0.045) and number of spotty calcifications (β, 0.37 [95% CI, 0.01 to 0.73], p=0.047) with the presence of DM were statistically significant after adjusting for baseline characteristics. Compared with patients with the low-HbA1c level, patients with the high-HbA1c level demonstrated significantly more presence of T1 hyperintensity (44% vs. 20%, p=0.047).
Conclusion: Symptomatic diabetic patients have a higher incidence of T1 hyperintensity and larger calcification burden than those without diabetes mellitus, indicating that diabetic patients may be associated with more advanced plaque features in the posterior circulation.
Discussion: In the present study, DM patients demonstrated a higher prevalence of T1 hyperintensity and spotty calcification presence and larger calcification burden than non-DM patients in the vertebrobasilar artery. Culprit plaques in diabetics demonstrated more presence of spotty calcification than those in non-diabetics, with an expected increase number of 0.37 per plaque. Hyperglycemia could accelerate inflammation and oxidative stress, promoting plaque calcification in both intima and media(5). Spotty calcification could represent an active state of the dynamic process of atherosclerosis. Overall, the number of spotty calcifications in the vertebrobasilar artery was relatively paucity, in agreement with the recent case-control study by Zhao et al(6). As a recognized high-risk plaque feature, IPH originates from the disruption of incomplete neovessels, aggravated by inflammation. Our study was in consistent with the pathologic observations reported increased neovascularization and IPH grade in diabetic plaques(7). The diabetic-specific features of plaque vulnerability may indicate the association between DM and its preference for posterior circulation ischemic stroke.

Acknowledgements

This work was supported by the Natural Science Foundation of Shandong Province (grant no.ZR2018BH029, ZR2020QH266), National Natural Science Foundation of China (grant no.82000771), and Academic Promotion Programme of Shandong First Medical University (no.2019QL023).