Plaque Evolution and Vessel Wall Remodeling of Intracranial Arteries: A Prospective, Longitudinal Vessel Wall MRI Study.

BACKGROUND: Progression of intracranial atherosclerotic disease (ICAD) is associated with ischemic stroke events and can be quantified with three-dimensional (3D) intracranial vessel wall (IVW) MRI. However, longitudinal 3D IVW studies are limited and ICAD evolution remains relatively unknown. PURPOSE: To evaluate ICAD changes longitudinally and to characterize the imaging patterns of atherosclerotic plaque evolution. STUDY TYPE: Prospective. POPULATION: 37 patients (69 ± 12 years old, 12 females) with angiography confirmed ICAD. FIELD STRENGTH/SEQUENCE: 3.0T/3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each patient underwent baseline and 1-year follow-up IVW. Then, IVW data from both time points were jointly preprocessed using a multitime point, multicontrast, and multiplanar viewing workflow (known as MOCHA). Lumen and outer wall of plaques were traced and measured, and plaques were then categorized into progression, stable, and regression groups based on changes in plaque wall thickness. Patient demographic and clinical data were collected. Culprit plaques were identified based on cerebral ischemic infarcts. STATISTICAL TESTS: Generalized estimating equations-based linear and logistic regressions were used to assess associations between vascular risk factors, medications, luminal stenosis, IVW plaque imaging features, and longitudinal changes. A two-sided P-value<0.05 was considered statistically significant. RESULTS: Diabetes was significantly associated with ICAD progression, resulting in 6.6% decrease in lumen area and 6.7% increase in wall thickness at 1-year follow-up. After accounting for arterial segments, baseline contrast enhancement predicted plaque progression (odds ratio = 3.61). Culprit plaques experienced an average luminal expansion of 10.9% after 1 year. 74% of the plaques remained stable during follow-up. The regression group (18 plaques) showed significant increase in minimum lumen area (from 7.4 to 8.3 mm2), while the progression group (13 plaques) showed significant decrease in minimum lumen area (from 5.4 to 4.3 mm2). DATA CONCLUSION: Longitudinal 3D IVW showed ICAD remodeling on the lumen side. Culprit plaques demonstrated longitudinal luminal expansion compared with their non-culprit counterparts. Baseline plaque contrast enhancement and diabetes mellitus were found to be significantly associated with ICAD changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Angiography-based hemodynamic features predict recurrent ischemic events after angioplasty and stenting of intracranial vertebrobasilar atherosclerotic stenosis.

OBJECTIVES: To assess the predictive value of hemodynamic features for stroke relapse in patients with intracranial vertebrobasilar atherosclerotic stenosis treated with percutaneous transluminal angioplasty and stenting (PTAS) using quantitative digital subtraction angiography (q-DSA). METHODS: In this retrospective longitudinal study, patients with intracranial vertebrobasilar atherosclerotic stenosis and who underwent PTAS treatment between January 2012 and May 2020 were enrolled. The q-DSA assessment was performed before and after PTAS. ROIs 1-4 were placed along the vertebral artery, proximal and distal basilar artery, and posterior cerebral artery; ROIs 5-8 were in 5 mm and 10 mm proximal and distal to the lesion, respectively. Relative time to peak (rTTP) was defined as the difference in TTP between ROIs. Cox regression analyses were performed to determine risk factors for recurrent stroke. RESULTS: A total of 137 patients (mean age, 62 years ± 10 [standard deviation], 83.2% males) were included, and 26 (19.0%) patients had stroke relapse during follow-up (median time of 42.6 months [interquartile range, 19.7-60.7]). Preprocedural rTTP4-1 (adjusted hazard ratio (HR) = 2.270; 95% CI 1.371-3.758; p = 0.001) and preprocedural rTTP8-5 (adjusted HR = 0.240; 95% CI 0.088-0.658; p = 0.006) were independently associated with the recurrent stroke. These hemodynamic parameters provided an incremental prognostic value for stroke relapse (AUC, 0.817 [0.704-0.931]; the net reclassification index, 0.431 [0.057-0.625]; and the integrated discrimination index, 0.140 [0.035-0.292]). CONCLUSIONS: In patients with intracranial vertebrobasilar atherosclerosis treated with PTAS, preprocedural prolonged TTP of the target vessel and shortened trans-stenotic TTP difference were associated with stroke relapse. Q-DSA-defined hemodynamic parameters provided incremental predictive value over conventional parameters for stroke recurrence. CLINICAL RELEVANCE STATEMENT: Quantitative DSA analysis enables intuitive observation and semi-quantitative evaluation of peri-therapeutic cerebral blood flow. More importantly, quantitative DSA-defined hemodynamic parameters have the potential for risk stratification of patients with intracranial atherosclerotic stenosis. KEY POINTS: Semi-quantitative angiography-based parameters can reflect pre- and postprocedural subtle changes in blood flow in patients with intracranial atherosclerotic stenosis. Although angioplasty procedures can significantly improve blood flow status, patients with more restricted baseline blood flow still show a higher risk of stroke recurrence. Angiography-based hemodynamic features possess prognostic value and can serve as clinical markers to assess stroke risk of patients with intracranial atherosclerotic stenosis.

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

BACKGROUND AND PURPOSE: Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. METHODS: Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. RESULTS: A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). CONCLUSIONS: Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

Self-expanding intracranial drug-eluting stent system in patients with symptomatic intracranial atherosclerotic stenosis: initial experience and midterm angiographic follow-up.

BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke worldwide. In patients undergoing endovascular treatment for ICAS, in-stent restenosis (ISR) is associated with ischemic stroke recurrence. OBJECTIVE: Intracranial drug-eluting self-expanding stent systems (COMETIU; Sinomed Neurovita Technology Inc., CHN) are new devices for treating ICAS. This study evaluated the perioperative experience and medium-term outcomes of COMETIU in 16 patients. METHODS: We prospectively analyzed 16 patients with ICAS (≥ 70% stenosis) who underwent intravascular therapy between September 4, 2022, and February 1, 2023. The primary outcome was the incidence of ISR at 6 months postoperatively. The secondary efficacy outcomes were device and technical success rates. The secondary safety outcomes included stroke or death within 30 days after the procedure and the cumulative annual rate of recurrent ischemic stroke in the target-vessel territory from 31 days to 6 months and 1 year. RESULTS: A total of 16 patients with 16 intracranial atherosclerotic lesions were treated with 16 COMETIUs. All procedures were performed under general anesthesia with 100% device and technical success rates, with no cases of periprocedural stroke or death. The mean radiographic follow-up duration was at least 6 months postoperatively, and all patients presented for radiographic and clinical follow-up. There were no reported ischemic or hemorrhagic strokes. Angiographic follow-up for all patients revealed no cases of ISR. CONCLUSION: COMETIU is safe and effective for treating ICAS, with minimal risk during the procedure and a low rate of ISR during medium-term follow-up.

Balloon angioplasty as first-choice recanalization strategy for intracranial atherosclerosis-related emergent large vessel occlusion with small clot burden.

PURPOSE: The optimal primary recanalization strategy for intracranial atherosclerosis-related emergent large vessel occlusion (ICAS-ELVO) remains controversial. We aimed to explore the safety and efficacy of balloon angioplasty as the first-choice recanalization strategy for ICAS-ELVO with small clot burden. METHODS: Consecutive ICAS-ELVO patients presenting with microcatheter "first-pass effect" during endovascular treatment (EVT) were retrospectively analyzed. Patients were divided into preferred balloon angioplasty (PBA) and preferred mechanical thrombectomy (PMT) groups based on the first-choice recanalization strategy. The reperfusion and clinical outcomes between the two groups were compared. RESULTS: Seventy-six patients with ICAS-ELVO involving the microcatheter "first-pass effect" during EVT were enrolled. Compared with patients in the PMT group, those in the PBA group were associated with (i) a higher rate of first-pass recanalization (54.0% vs. 28.9%, p = .010) and complete reperfusion (expanded thrombolysis in cerebral ischemia ≥ 2c; 76.0% vs. 53.8%, p = .049), (ii) shorter puncture-to-recanalization time (49.5 min vs. 89.0 min, p < .001), (iii) lower operation costs (¥48,499.5 vs. ¥ 99,086.0, p < .001), and (iv) better 90-day functional outcomes (modified Rankin scale:0-1; 44.0% vs. 19.2%, p = .032). Logistic regression analysis revealed that balloon angioplasty as the first-choice recanalization strategy was an independent predictor of 90-day excellent functional outcomes for ICAS-ELVO patients with microcatheter "first-pass effect" (adjusted odds ratio = 6.01, 95% confidence interval: 1.15-31.51, p = .034). CONCLUSION: Direct balloon angioplasty potentially improves 90-day functional outcomes for ICAS-ELVO patients with small clot burden, and may be a more appropriate first-choice recanalization strategy than mechanical thrombectomy for these patients.

Indications, operative techniques, and outcomes of occipital artery-vertebral artery bypass: an institutional series.

PURPOSE: Posterior circulation cerebral bypasses often show higher risks and lower patency. Only few reports discussed occipital artery (OA)-vertebral artery (VA) bypasses. We present our illustrative cases to address current gaps in the literature on OA-VA bypass. METHODS: A single-center retrospective review was conducted to include all institutional cases of OA-VA bypass, discussing the technique and outcomes. RESULTS: Four institutional cases undergoing a total of 5 bypasses were evaluated, including 3 males and 1 female, with median age of 65 years (range, 62-73). All patients had vertebrobasilar insufficiency (VBI) with recurrent strokes/TIAs due to intracranial atherosclerosis, leading to unilateral VA stenosis with contralateral occlusion (1, 25%), bilateral VA stenosis (1, 25%) or occlusion (1, 25%). Medical management included aspirin for all cases (100%), with clopidogrel in 3 (75%). Surgery was performed through a far lateral approach, connecting the OA to the VA-3 segment, with no inter-positional graft. One patient underwent contralateral OA-VA bypass 6 months after the prior surgery due to worsening of the contralateral VA stenosis. Bypass patency was confirmed in all cases with post-operative angiography. All patients had clinical improvement, with one case of wound dehiscence managed conservatively. All patients were alive at last follow-up (median 7.0 months; range: 1.5-18). CONCLUSION: OA-VA bypass is a challenging yet effective strategy in selected patients with VBI. Current literature lacks unique definitions of surgical indications and techniques, which we addressed in our series. Surgical education should focus on expanding the microsurgery anatomy knowledge.

Rare RNF213 variants is related to early-onset intracranial atherosclerosis: A Chinese community-based study.

BACKGROUND: The relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population. METHODS: The present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value. RESULTS: Ninety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (ß = 0.150, P = 0.025) and numerical count of variants (ß = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (ß = 0.154, P = 0.014) and variant count (ß = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors. CONCLUSIONS: Rare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.

Short-term glycemic variability and intracranial atherosclerotic plaque stability assessed by high-resolution MR vessel wall imaging in type 2 diabetes mellitus.

OBJECTIVE: To investigate the relationship between short-term glycemic variability in patients with T2DM and the vulnerability of intracranial atherosclerotic plaques using HR-MR-VWI. MATERIALS AND METHODS: In total, 203 patients with acute ischemic stroke (AIS)/transient ischemia (TIA) combined with T2DM were enrolled. All of them underwent HR-MR-VWI during the period between July 2020 and July 2023. 203 patients were divided into groups with higher (1,5-AG≤ 30.7 µmol/L) and lower (1,5-AG> 30.7 µmol/L) short-term glycemic variability. Patients were also divided into the T1WI and non-T1WI hyperintensity groups. Associated factors(FBG, HbA1c, and 1,5-AG)for the T1WI hyperintensity were analyzed by binary logistic regression. We used the area under the curve (AUC), while the sensitivity and specificity were calculated at the optimal threshold. The Delong test was employed to compare the quality of the AUC of the predictors. RESULTS: The group with higher short-term glycemic variability had a higher incidence of the hyperintensity on T1WI, higher degree of enhancement, higher degree of stenosis and smaller lumen area (P < 0.05). The T1WI hyperintensity group had higher HbA1c levels, higher hemoglobin levels and lower 1,5-AG levels(P < 0.05). 1,5-AG (OR = 0.971, 95 % CI: 0.954∼0.988, P = 0.001), HbA1c (OR=1.305, 95 % CI: 1.065∼1.598, P = 0.01) and male sex (OR = 2.048, 95 % CI: 1.016∼4.128, P = 0.045)/(OR=2.102, 95 % CI: 1.058∼4.177, P = 0.034) were independent risk factors for the hyperintensity on T1WI. 1,5-AG demonstrated enhanced performance and yielded the highest AUC of the receiver operator characteristic curve (AUC = 0.726), with sensitivity and specificity values of 0.727 and 0.635 respectively. CONCLUSION: 1,5-AG, HbA1c and male sex are independent predictors of intracranial plaques with T1WI hyperintensity, the greater short-term glycemic variability, the higher incidence of vulnerable plaques.

Clinical and perfusion imaging characteristics of acute large vessel occlusion in intracranial atherosclerosis.

OBJECTIVES: This study aimed to compare clinical and perfusion imaging profiles in acute ischemic stroke with large vessel occlusion (AIS-LVO) between patients with intracranial atherosclerotic disease (ICAD) and non-ICAD who underwent endovascular treatment (EVT). METHODS: Data from AIS-LVO patients over the anterior circulation undergoing EVT across two stroke centers were retrospectively analyzed. Clinical profiles and perfusion parameters from automated processing of perfusion imaging were compared between ICAD and non-ICAD groups. Ischemic core was defined as relative cerebral blood flow < 30 % on CT perfusion or apparent diffusion coefficient ≤ 620 × 10-6 mm2/s on MR diffusion weighted imaging. RESULTS: A total of 111 patients were included (46 ICAD, 65 non-ICAD). The ICAD group exhibited a higher male proportion (60.9 % vs. 35.4 %), more M1 segment occlusions (78.3 % vs. 56.9 %), lower atrial fibrillation rates (17.4 % vs. 63.1 %), and lower baseline NIH Stroke Scale (NIHSS) scores (median [IQR]: 13 [8.75-18] vs. 15 [10-21]) at presentation compared to non-ICAD (all p < 0.05). However, there was no difference in NIHSS scores at discharge or in good functional outcomes (modified Rankin Scale 0-2) at 3 months between the two groups. ICAD patients also had smaller median ischemic core volumes (0 [IQR 0-9.7] vs. 4.4 [0-21.6] ml, p = 0.038), smaller median Tmax >6s tissue volulmes (89.3 [IQR 51.1-147.1] vs. 124.4 [80.5-178.6] ml, p = 0.017) and lower median HIR (hypoperfusion intensity ratio defined as Tmax >10s divided by Tmax >6s; 0.28 [IQR 0.09-0.42] vs. 0.44 [0.24-0.60], p = 0.003). Higher baseline NIHSS scores correlated with larger Tmax >6s lesion volumes as well as higher HIR value in non-ICAD patients, but not in ICAD patients. CONCLUSIONS: In anterior circulation of AIS-LVO, ICAD patients exhibited distinct clinical presentations and perfusion imaging characteristics when compared to non-ICAD patients. Perfusion imaging profiles may serve as indicators for identifying ICAD patients before EVT.

Immune Markers Are Associated With Asymptomatic Intracranial Large Artery Stenosis and Future Vascular Events in NOMAS.

BACKGROUND: Inflammation contributes to atherosclerosis but is incompletely characterized in intracranial large artery stenosis (ICAS). We hypothesized that immune markers would be associated with ICAS and modify the risk ICAS confers on future vascular events. METHODS: This study included a subsample of stroke-free participants in the prospective NOMAS (Northern Manhattan Study), who had blood samples analyzed with a 60-plex immunoassay (collected from 1993 to 2001) and ICAS assessment with time-of-flight magnetic resonance angiography (obtained from 2003 to 2008). We dichotomized ICAS as either ≥50% stenosis or not (including no ICAS). We ascertained post-magnetic resonance imaging vascular events. We used least absolute shrinkage and selection operator procedures to select immune markers independently associated with ICAS. Then, we grouped selected immune markers into a derived composite Z score. Using proportional odds regression, we quantified the association of the composite immune marker Z score, ICAS, and risk of vascular events. RESULTS: Among 1211 participants (mean age, 71±9 years; 59% women; 65% Hispanic participants), 8% had ≥50% ICAS. Using least absolute shrinkage and selection operator regression, we identified CXCL9 (C-X-C motif chemokine ligand 9), HGF (hepatocyte growth factor), resistin, SCF (stem cell factor), and VEGF-A(vascular endothelial growth factor A) to have the strongest positive relationships with ≥50% ICAS in fully adjusted models. Selected markers were used to derive a composite immune marker Z score. Over an average follow-up of 12 years, we found that each unit increase in immune marker Z scores was associated with an 8% (95% CI, 1.05-1.11), 11% (95% CI, 1.06-1.16), and 5% (95% CI, 1.01-1.09) increased hazard of death, vascular death, and any vascular event, respectively, in adjusted models. We did not find a significant interaction between immune marker Z scores and ICAS in their relationship with any longitudinal outcome. CONCLUSIONS: Among a diverse stroke-free population, selected serum immune markers were associated with ICAS and future vascular events. Further study is needed to better understand their role in the pathogenesis of ICAS and as a potential therapeutic target in stroke prevention.

The CASSISS Randomized Clinical Trial.

The CASSISS trial (China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis), recently published in JAMA, is the most recent of several randomized controlled trials that have failed to show a benefit of percutaneous angioplasty and stenting over medical therapy for the prevention of stroke due to intracranial atherosclerotic stenosis. Current practice guidelines recommended that percutaneous angioplasty and stenting should not be performed routinely as a treatment for stroke prevention in patients with intracranial atherosclerotic stenosis. The CASSISS trial reinforces those recommendations and will not change practice, but it may provide some important lessons for future trial design.

Large Vessel Occlusion Stroke due to Intracranial Atherosclerotic Disease: Identification, Medical and Interventional Treatment, and Outcomes.

Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies.

Triglyceride-glucose index, symptomatic intracranial artery stenosis and recurrence risk in minor stroke patients with hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index, a simple measure of insulin resistance, is associated with intracranial atherosclerosis (ICAS) and stroke. In hypertensive populations, this association may be pronounced. The aim was to investigate the relationship between TyG and symptomatic intracranial atherosclerosis (sICAS) and recurrence risk in ischemic stroke patients with hypertension. METHODS: This prospective, multicenter cohort study included patients with acute minor ischemic stroke with a preadmission diagnosis of hypertension from September 2019 to November 2021 with a 3-month follow-up. The presence of sICAS was determined by a combination of clinical manifestations, the location of the infarction, and the corresponding artery with moderate-to-severe stenosis. ICAS burden was determined by the degree and number of ICAS occurrences. Fasting blood glucose (FBG) and triglyceride (TG) were measured to calculate TyG. The main outcome was ischemic stroke recurrence during the 90-day follow-up. Multivariate regression models were used to explore the association of TyG, sICAS, and ICAS burden with stroke recurrence. RESULTS: There were 1281 patients with a mean age of 61.6 ± 11.6 years; 70.1% were male, and 26.4% were diagnosed with sICAS. There were 117 patients who experienced stroke recurrence during follow-up. Patients were categorized according to quartiles of TyG. After adjusting for confounders, the risk of sICAS was greater (OR 1.59, 95% CI 1.04-2.43, p = 0.033) and the risk of stroke recurrence was significantly higher (HR 2.02, 95% CI 1.07-3.84, p = 0.025) in the fourth TyG quartile than in the first quartile. The restricted cubic spline (RCS) plot revealed a linear relationship between TyG and sICAS, and the threshold value for TyG was 8.4. Patients were then dichotomized into low and high TyG groups by the threshold. Patients with high TyG combined with sICAS had a higher risk of recurrence (HR 2.54, 95% CI 1.39-4.65) than patients with low TyG without sICAS. An interaction effect on stroke recurrence between TyG and sICAS was found (p = 0.043). CONCLUSION: TyG is a significant risk factor for sICAS in hypertensive patients, and there is a synergistic effect of sICAS and higher TyG on ischemic stroke recurrence. TRIAL REGISTRATION NUMBER: The study was registered on 16 August 2019 at https://www.chictr.org.cn/showprojen.aspx?proj=41160 (No. ChiCTR1900025214).

Plaque modification and stabilization after drug-coated balloon angioplasty for intracranial atherosclerotic lesions.

OBJECTIVES: A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). We aimed to evaluate changes of vessel wall features of ICAD lesions after DCB treatment by using vessel wall MRI (VWMRI). METHODS: We retrospectively included patients with symptomatic ICAD who underwent DCB angioplasty alone. The incidences of stenosis of the lumen area, vessel wall thickening, hyperintense plaques, and prominent wall enhancement were compared between the baseline and follow-up VWMRI. RESULTS: There were 29 ICAD lesions from 29 patients, of which 22 were stenosis and 7 were occlusion. The median interval between DCB treatment and follow-up VWMRI was 4.1 [3.3, 6.7] months. After DCB treatment, follow-up VWMRI showed a significant decrease in the stenosis degree of the lumen area (83% [71%, 96%] vs 15% [3%, 41%], p < 0.001). Thirty-eight percent (11/29) of the patients observed normal appearance of the target vessel wall on follow-up VWMRI. In the stenosis group, the prevalence of hyperintense plaques decreased from 66.7% (14/21) at baseline to 23.8% (5/21) at follow-up, and prominent wall enhancement decreased from 66.7% (14/21) at baseline to 19.0%(4/21) at follow-up. The incidence of hyperintense plaques (p = 0.028) and vessel wall thickening (p = 0.018) tended to decrease with follow-up time. Although not significant (p = 0.106), a similar trend was observed between the incidence of prominent wall enhancement and follow-up time. CONCLUSION: Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions. KEY POINTS: • A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). • Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions.

Improved characterization of lenticulostriate arteries using compressed sensing time-of-flight at 7T.

OBJECTIVES: To evaluate the feasibility of 0.2-mm isotropic lenticulostriate arteries (LSAs) imaging using compressed sensing time-of-flight (CS TOF) at around 10 min on 7T, and compare the delineation and characterization of LSAs using conventional TOF and CS TOF. METHODS: Thirty healthy volunteers were examined with CS TOF and conventional TOF at 7T for around 10 min each. CS TOF was optimized to achieve 0.2-mm isotropic LSA imaging. The numbers of LSA stems and branches were counted and compared on a vascular skeleton. The length and distance were measured and compared on the most prominent branch in each hemisphere. Another patient with intracranial artery stenosis was studied to compare LSA delineation in CS TOF and digital subtraction angiography (DSA). RESULTS: The number of stems visualized with CS TOF was significantly higher than with conventional TOF in both left (p = 0.002, ICC = 0.884) and right (p < 0.001, ICC = 0.938) hemispheres. The number of branches visualized by conventional TOF was significantly lower than that by CS TOF in both left (p < 0.001, ICC = 0.893) and right (p < 0.001, ICC = 0.896) hemispheres. The lengths were statistically higher in CS TOF than in conventional TOF (left: p < 0.001, ICC = 0.868; right: p < 0.001, ICC = 0.876). CONCLUSIONS: The high-resolution CS TOF improves the delineation and characterization of LSAs over conventional TOF. High-resolution LSA imaging using CS TOF can be a promising tool for clinical research and applications in patients with neurologic diseases. KEY POINTS: • 0.2-mm isotropic LSA imaging for around 10 min using CS TOF at 7T is feasible. • More stems and branches of LSAs with longer lengths can be delineated with CS TOF than with conventional TOF at the same scan time. • High-resolution CS TOF can be a promising tool for research and applications on LSA.

Association of intracranial atherosclerosis with cerebral small vessel disease in a community-based population.

BACKGROUND AND PURPOSE: The purpose of this study was to explore the relationship between intracranial atherosclerosis and cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents of Lishui, China in the PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study were involved. Intracranial atherosclerosis was grouped by the severity of intracranial artery plaques with stenosis and burden. Four imaging markers including lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMBs), and perivascular spaces (PVS) as well as the CSVD burden scores were assessed. Logistic regression or ordinal logistic regression models with odds ratio (OR) or common OR (cOR) were used to estimate the relationship between intracranial atherosclerosis and CSVD markers and burdens. RESULTS: The mean age was 61.20 ± 6.68 years, and 1424 (46.52%) were men among 3061 participants included at baseline. Intracranial atherosclerotic burden was associated with the severity of the lacunes (OR = 4.18, 95% confidence interval [CI] = 1.83-9.58), modified WMH burden (cOR = 1.94, 95% CI = 1.01-3.71), presence of CMBs (OR = 2.28, 95% CI = 1.05-4.94), and CMB burden (OR = 2.23, 95% CI = 1.03-4.80). However, it was not associated with the WMH burden and PVS. Intracranial atherosclerotic burden was associated with CSVD burden (Wardlaw: cOR = 2.73, 95% CI = 1.48-5.05; Rothwell: cOR = 2.70, 95% CI = 1.47-4.95). The association between intracranial atherosclerosis and CSVD was obvious in participants with both anterior and posterior circulation artery stenosis. CONCLUSIONS: Based on a Chinese community population, there may be an association between intracranial atherosclerosis and CSVD, but its mechanism in relation to vascular risk factors still needs to be clarified.

High-resolution magnetic resonance imaging of acute intracranial artery thrombus.

BACKGROUND AND PURPOSE: The development of high-resolution magnetic resonance imaging (HR-MRI) has enabled submillimeter-level evaluation of intracranial artery plaque and luminal thrombus. We sought to investigate the value of HR-MRI in assessing the pathogenesis of acute intracranial artery thrombus. METHODS: We examined the presence of intracranial thrombus on three-dimensional T1-weighted HR-MRI in acute ischemic stroke patients with intracranial artery occlusion on magnetic resonance angiography. We defined two thrombus-related HR-MRI features (peri-thrombus plaque and distal residual flow beyond the thrombus) and analyzed their association with potential embolic sources. RESULTS: Luminal thrombus and a shrunken artery without luminal thrombus were detected in 162 (96.4%) and six (3.6%) of 168 patients with intracranial artery occlusion, respectively. Among 111 patients with culprit major artery thrombus, peri-thrombus plaques were observed in 46.8% and distal residual flow beyond the thrombus in 64.0%. Patients with peri-thrombus plaque had a higher prevalence of diabetes (44.2% vs. 25.4%; p = 0.037), a lower prevalence of potential sources of cardioembolism (0% vs. 16.9%; p = 0.002), and a nonsignificantly lower prevalence of potential embolic sources from extracranial arteries (9.6% vs. 20.3%; p = 0.186) than those without. Patients with distal residual flow beyond the thrombus had a lower prevalence of potential sources of cardioembolism (1.4% vs. 22.5%; p < 0.001) and smaller infarct volumes (5.0 [1.4-12.7] mL vs. 16.6 [2.4-94.6] mL; p = 0.012) than those without. CONCLUSIONS: Our study showed that HR-MRI helps clarify the pathogenesis of acute intracranial artery thrombus. The presence of peri-thrombus plaque and distal residual flow beyond the thrombus favor the stroke mechanism of atherosclerosis rather than cardioembolism.

Patterns and Implications of Intracranial Atherosclerosis in Anterior and Posterior Circulation Identified by High-Resolution Vessel Wall Imaging.

INTRODUCTION: Anterior and posterior circulation atheroscleroses differ in vascular risk factors and stroke patterns. Posterior circulation stroke has worse clinical outcomes. However, few studies described the differentiation of plaque features between anterior and posterior circulation atheroscleroses via high-resolution vessel wall imaging (HR-VWI). We aimed to compare the plaque imaging features between anterior and posterior circulations to highlight the relevance of plaque imaging features to clinical events of ischemic stroke. METHODS: Prospective data from a HR-VWI cohort of adult patients with acute ischemic stroke or transient ischemic attack were retrospectively analyzed. Quantitative and qualitative measurements of atherosclerotic plaques along the middle cerebral arteries (MCAs), the basilar artery (BA), and the vertebral arteries (VAs) were conducted on HR-VWI. Vessels with stenotic degrees over 30% were identified on the matched time-of-flight magnetic resonance angiography (TOF-MRA) and visually classified into normal, irregular, stenotic, and occluded. The sensitivity, specificity, positive and negative predictive values for TOF-MRA in detecting abnormal vessels were calculated by using quantification on the basis of HR-VWI findings as the reference standard. RESULTS: One hundred and one patients (median age, 64 years old; 62.4% males) were included in this study. A total of 292 plaques were identified, with 152 in the MCAs, 35 in the BA, and 105 in the VAs. The VAs possessed significantly higher enhancement index (EI) (median 38.37 vs. 18.40, p <0.001), more plaques with positive remodeling (76.2% vs. 57.2%, p = 0.002) and intraplaque hypo-intensity (43.8% vs. 12.5%, p <0.001) than the MCAs. The MCAs presented with more intraplaque hemorrhage (IPH) (20.4% vs. 8.6%, p = 0.014) than the VAs. The sensitivity and specificity of TOF-MRA for evaluating luminal stenosis were 89.0 (82.5-93.4) and 66.7 (24.1-94.0) in anterior circulation, respectively, and were 75.2 (66.7-82.2) and 27.3 (7.3-60.7) in posterior circulation, respectively. CONCLUSION: Our findings might elucidate the clinical events and outcomes in anterior and posterior circulation stroke. Posterior circulation atherosclerosis had higher EI and more plaques with hypo-intensity, suggesting a heavier atherosclerosis burden. Positive remodeling pattern in posterior circulation atherosclerosis might create an impression of "wider" vascular lumen, leading to possible underestimation of atherosclerosis burden of posterior circulation on TOF-MRA as compared to HR-VWI. Besides, anterior circulation atherosclerosis with IPH might be associated with plaque rupture and artery-to-artery embolism. Future studies are needed to verify these findings.

The incomplete circle of Willis is associated with vulnerable intracranial plaque features and acute ischemic stroke.

BACKGROUND: The circle of Willis (CoW) plays a significant role in intracranial atherosclerosis (ICAS). This study investigated the relationship between different types of CoW, atherosclerosis plaque features, and acute ischemic stroke (AIS). METHODS: We investigated 97 participants with AIS or transient ischemic attacks (TIA) underwent pre- and post-contrast 3T vessel wall cardiovascular magnetic resonance within 7 days of the onset of symptoms. The culprit plaque characteristics (including enhancement grade, enhancement ratio, high signal in T1, irregularity of plaque surface, and normalized wall index), and vessel remodeling (including arterial remodeling ratio and positive remodeling) for lesions were evaluated. The anatomic structures of the anterior and the posterior sections of the CoW (A-CoW and P-CoW) were also evaluated. The plaque features were compared among them. The plaque features were also compared between AIS and TIA patients. Finally, univariate and multivariate regression analysis was performed to evaluate the independent risk factors for AIS. RESULT: Patients with incomplete A-CoW showed a higher plaque enhancement ratio (P = 0.002), enhancement grade (P = 0.01), and normalized wall index (NWI) (P = 0.018) compared with the patients with complete A-CoW. A higher proportion of patients with incomplete symptomatic P-CoW demonstrated more culprit plaques with high T1 signals (HT1S) compared with those with complete P-CoW (P = 0.013). Incomplete A-CoW was associated with a higher enhancement grade of the culprit plaques [odds ratio (OR):3.84; 95% CI: 1.36-10.88, P = 0.011], after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Incomplete symptomatic P-CoW was associated with a higher probability of HT1S (OR:3.88; 95% CI: 1.12-13.47, P = 0.033), after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Furthermore, an irregularity of the plaque surface (OR: 6.24; 95% CI: 2.25-17.37, P < 0.001), and incomplete symptomatic P-CoW (OR: 8.03, 95% CI: 2.43-26.55, P = 0.001) were independently associated with AIS. CONCLUSIONS: This study demonstrated that incomplete A-CoW was associated with enhancement grade of the culprit plaque, and incomplete symptomatic side P-CoW was associated with the presence of HT1S of culprit plaque. Furthermore, an irregularity of plaque surface and incomplete symptomatic side P-CoW were associated with AIS.

Angioplasty, stenting, or both - rescue maneuvers and reperfusion after endovascular therapy for intracranial atherosclerosis-related occlusion.

PURPOSE: Data concerning reperfusion strategies of intracranial atherosclerosis-related occlusion (ICARO) and clinico-angiographic outcomes remain scarce, particularly in Caucasians. We aim to compare the reperfusion rate and functional outcome between reperfusion strategies in the setting of the ICARO. METHODS: Retrospective analysis of prospectively maintained endovascular thrombectomy (EVT) registries at three high-volume stroke centers were retrospectively analyzed for consecutive ICARO patients from January 2015 to December 2019. We defined ICARO as any fixed high-degree (> 70%) focal narrowing or stenosis of any degree with a perpetual tendency for reocclusion. We categorized reperfusion strategies into four groups: EVT [group 1], balloon angioplasty [(BAp), group 2], placement of self-expandable stents [(SES), group 3], and BAp combined with implantation of SES; or direct placement of balloon mounted stents (BMS) [(BAp-SES/BMS), group 4]. We evaluated the association with the successful reperfusion [mTICI 2b - 3] and favorable outcome [mRS 0-2] with logistic regression analysis. RESULTS: Out of 2550 EVT, 124 patients (median age, 70 (61-80) years; 76 men) with ICARO and 130 reperfusion attempts [36 EVT, 38 BAp, 17 SES, and 39 BAp + SES/BMS] were analyzed. SES implantation showed the highest frequency of post-procedural symptomatic intracranial hemorrhage [(18%, 3/17), p = .03]; however, we observed no significant differences in the mortality rate. Overall, we achieved successful reperfusion in 71% (92/130) and favorable outcomes in 42% (52/124) of the patients. BAp + SES/BMS was the only independent predictor of the final successful reperfusion [aOR, 4.488 (95% CI, 1.364-14.773); p = .01], which was significantly associated with the 90-day favorable outcome [aOR, 10.837 (95% CI, 3.609-32.541); p = < .001] after adjustment for confounding variables between the reperfusion strategies. CONCLUSION: Among patients with ICARO, the rescue angioplasty stenting effectively contributed to higher odds of successful reperfusion with no increased risk for intracranial hemorrhage.