Ferrostatin-1 inhibits ferroptosis of vascular smooth muscle cells and alleviates abdominal aortic aneurysm formation through activating the SLC7A11/GPX4 axis.

Ferroptosis, a type of iron-catalyzed necrosis, is responsible for vascular smooth muscle cell (VSMC) death and serves as a potential therapeutic target for alleviating aortic aneurysm. Here, our study explored the underlying mechanism of ferroptosis affecting VSMC functions and the resultant formation of AAA using its inhibitor Ferrostatin-1 (Fer-1). Microarray-based gene expression profiling was employed to identify differentially expressed genes related to AAA and ferroptosis. An AAA model was established by angiotensin II (Ang II) induction in apolipoprotein E-knockout (ApoE-/- ) mice, followed by injection of Fer-1 and RSL-3 (ferroptosis inducer). Then, the role of Fer-1 and RSL-3 in the ferroptosis of VSMCs and AAA formation was analyzed in Ang II-induced mice. Primary mouse VSMCs were cultured in vitro and treated with Ang II, Fer-1, sh-SLC7A11, or sh-GPX4 to assess the effect of Fer-1 via the SLC7A11/GPX axis. Bioinformatics analysis revealed that GPX4 was involved in the fibrosis formation of AAA, and there was an interaction between SLC7A11 and GPX4. In vitro assays showed that Fer-1 alleviated Ang II-induced ferroptosis of VSMCs and retard the consequent AAA formation. The mechanism was associated with activation of the SLC7A11/GPX4 pathway. Silencing of SLC7A11 or GPX4 could inhibit the ameliorating effect of Fer-1 on the ferroptosis of VSMCs. In vivo animal studies further demonstrated that Fer-1 inhibited Ang II-induced ferroptosis and vessel wall structural abnormalities in AAA mouse through activation of the SLC7A11/GPX4 pathway. Fer-1 may prevent AAA formation through activation of the SLC7A11/GPX4 pathway.

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200-2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1-20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

An extended phase graph-based framework for DANTE-SPACE simulations including physiological, temporal, and spatial variations.

PURPOSE: The delay alternating with nutation for tailored excitation (DANTE)-sampling perfection with application-optimized contrasts (SPACE) sequence facilitates 3D intracranial vessel wall imaging with simultaneous suppression of blood and CSF. However, the achieved image contrast depends closely on the selected sequence parameters, and the clinical use of the sequence is limited in vivo by observed signal variations in the vessel wall, CSF, and blood. This paper introduces a comprehensive DANTE-SPACE simulation framework, with the aim of providing a better understanding of the underlying contrast mechanisms and facilitating improved parameter selection and contrast optimization. METHODS: An extended phase graph formalism was developed for efficient spin ensemble simulation of the DANTE-SPACE sequence. Physiological processes such as pulsatile flow velocity variation, varying flow directions, intravoxel velocity variation, diffusion, and B 1 + $$ {\mathrm{B}}_1^{+} $$ effects were included in the framework to represent the mechanisms behind the achieved signal levels accurately. RESULTS: Intravoxel velocity variation improved temporal stability and robustness against small velocity changes. Time-varying pulsatile velocity variation affected CSF simulations, introducing periods of near-zero velocity and partial rephasing. Inclusion of diffusion effects was found to substantially reduce the CSF signal. Blood flow trajectory variations had minor effects, but B 1 + $$ {\mathrm{B}}_1^{+} $$ differences along the trajectory reduced DANTE efficiency in low- B 1 + $$ {\mathrm{B}}_1^{+} $$ areas. Introducing low-velocity pulsatility of both CSF and vessel wall helped explain the in vivo observed signal heterogeneity in both tissue types. CONCLUSION: The presented simulation framework facilitates a more comprehensive optimization of DANTE-SPACE sequence parameters. Furthermore, the simulation framework helps to explain observed contrasts in acquired data.

Simulation-based optimization and experimental comparison of intracranial T2-weighted DANTE-SPACE vessel wall imaging at 3T and 7T.

PURPOSE: T2-weighted DANTE-SPACE (Delay Alternating with Nutation for Tailored Excitation - Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) sequences facilitate non-invasive intracranial vessel wall imaging at 7T through simultaneous suppression of blood and CSF. However, the achieved vessel wall delineation depends closely on the selected sequence parameters, and little information is available about the performance of the sequence using more widely available 3T MRI. Therefore, in this paper a comprehensive DANTE-SPACE simulation framework is used for the optimization and quantitative comparison of T2-weighted DANTE-SPACE at both 7T and 3T. METHODS: Simulations are used to propose optimized sequence parameters at both 3T and 7T. At 7T, an additional protocol which uses a parallel transmission (pTx) shim during the DANTE preparation for improved suppression of inflowing blood is also proposed. Data at both field strengths using optimized and literature protocols are acquired and quantitatively compared in six healthy volunteers. RESULTS: At 7T, more vessel wall signal can be retained while still achieving sufficient CSF suppression by using fewer DANTE pulses than described in previous implementations. The use of a pTx shim during DANTE at 7T provides a modest further improvement to the inner vessel wall delineation. At 3T, aggressive DANTE preparation is required to achieve CSF suppression, resulting in reduced vessel wall signal. As a result, the achievable vessel wall definition at 3T is around half that of 7T. CONCLUSION: Simulation-based optimization of DANTE parameters facilitates improved T2-weighted DANTE-SPACE contrasts at 7T. The improved vessel definition of T2-weighted DANTE-SPACE at 7T makes DANTE preparation more suitable for T2-weighted VWI at 7T than at 3T.

Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification.

INTRODUCTION: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification. METHODS: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively. CONCLUSION: QSM was the most reliable MR sequence for the detection of plaque calcification.

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.

Nomogram Based on High-Resolution Vessel Wall MRI Features to Differentiate Moyamoya Disease From Atherosclerosis-Associated Moyamoya Vasculopathy.

BACKGROUND: The angiographic features of moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) are similar, but the etiology and clinical treatment strategies are different. Differentiating MMD from AS-MMV helps to choose the appropriate treatment. PURPOSE: To investigate the feasibility of a nomogram based on high-resolution vessel wall (HR-VWI) MRI features to differentiate MMD from AS-MMV. STUDY TYPE: Retrospective. SUBJECTS: One hundred and two patients with MMD (N = 52) or AS-MMV (N = 50) in the training cohort (9-72 years; 54 females) and 70 patients with MMD (N = 42) or AS-MMV (N = 28) in the validation cohort (7-69 years; 33 females). FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional time-of-flight MR angiography (3D-TOF-MRA), spin echo high-resolution 3D T1-weighted imaging (3D-T1WI), 3D T2-weighted imaging (3D-T2WI), and contrast-enhanced 3D-T1WI. ASSESSMENT: Image assessment was performed by three neuroradiologists (with 10, 15, and 18 years of experience). Demographic characteristic and image features were evaluated and compared. Independent factors of MMD were screened to construct a nomogram model in the training cohort. The validation cohort was used to validated its generality. STATISTICAL TESTS: Interclass correlation coefficient (ICC), kappa, t-test, χ2 test, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve and concordance index (C-index). A P-value <0.05 was considered statistically significant. RESULTS: Significant differences were observed between MMD and AS-MMV in terms of age, vessel outer diameter, vessel wall thickening pattern, maximum thickness, dot sign, and anterior cerebral artery (ACA) involved. Age, outer diameter, dot sign, and ACA involved were independent factors. The C-index was 0.886 in the training cohort and 0.859 in the validation cohort. The ROC demonstrated high diagnostic efficacy with an AUC of 0.884 in the training cohort and 0.857 in the validation cohort. DATA CONCLUSION: A nomogram model based on age, vessel outer diameter, dot sign and ACA involved may effectively distinguish MMD from AS-MMV with good reliability and accuracy. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Evaluating Middle Cerebral Artery Plaque Characteristics and Lenticulostriate Artery Morphology Associated With Subcortical Infarctions at 7T MRI.

BACKGROUND: Lenticulostriate artery (LSA) obstruction is a potential cause of subcortical infarcts. However, MRI LSA evaluation at 3T is challenging. PURPOSE: To investigate middle cerebral artery (MCA) plaque characteristics and LSA morphology associated with subcortical infarctions in LSA territories using 7-T vessel wall MRI (VW-MRI) and time-of-flight MR angiography (TOF-MRA). STUDY TYPE: Prospective. POPULATION: Sixty patients with 80 MCA atherosclerotic plaques (37 culprit and 43 non-culprit). FIELD STRENGTH/SEQUENCE: 7-T with 3D TOF-MRA and T1-weighted 3D sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE) sequences. ASSESSMENT: Plaque distribution (superior, inferior, ventral, or dorsal walls), LSA origin involvement, LSA morphology (numbers of stems, branches, and length), and plaque characteristics (normalized wall index, maximal wall thickness, plaque length, remodeling index, intraplaque hemorrhage, and plaque surface morphology (regular or irregular)) were assessed. STATISTICAL TESTS: Least absolute shrinkage and selection operator regression, generalized estimating equations regression, receiver operating characteristic curve, independent t-test, Mann-Whitney U test, Chi-square test, Fisher's exact test, and intra-class coefficient. A P value <0.05 was considered statistically significant. RESULTS: Plaque irregular surface, superior wall plaque, longer plaque length, LSA origin involvement, fewer LSA stems, and shorter total and average lengths of LSAs were significantly associated with culprit plaques. Multivariable logistic analysis confirmed that LSA origin involvement (OR, 28.51; 95% CI, 6.34-181.02) and plaque irregular surface (OR, 8.32; 95% CI, 1.41-64.73) were independent predictors in differentiating culprit from non-culprit plaques. A combination of LSA origin involvement and plaque irregular surface (area under curve = 0.92; [95% CI, 0.86-0.98]) showed good performance in identifying culprit plaques, with sensitivity and specificity of 86.5% and 86.0%, respectively. DATA CONCLUSION: 7-T VW-MRI and TOF-MRA can demonstrate plaque involvement with LSA origins. MCA plaque characteristics derived from 7-T VW-MRI showed good diagnostic accuracy in determining the occurrence of subcortical infarctions. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Development and Validation of a Fusion Model Based on Carotid Plaques and White Matter Lesion Burden Imaging Characteristics to Evaluate Ischemic Stroke Severity in Symptomatic Patients.

BACKGROUND: The diagnostic value of carotid plaque characteristics based on higher-resolution vessel wall MRI (HRVW-MRI) combined with white matter lesion (WML) burden for the risk of ischemic stroke is unclear. PURPOSE: To combine carotid plaque features and WML burden to construct a hybrid model for evaluating ischemic stroke severity and prognosis in patients with symptomatic carotid artery stenosis. STUDY TYPE: Retrospective. SUBJECTS: One hundred and ninty-three patients with least one confirmed carotid atherosclerotic stenosis ≥30% and cerebrovascular symptoms within the last 2 weeks (136 in the training cohort and 57 in the test cohort). FIELD STRENGTH/SEQUENCE: 3.0T, T2-weighted fluid attenuated inversion recovery (T2-FLAIR) and diffusion-weighted imaging (DWI); HRVW-MRI: 3D T1-weighted variable flip angle fast spin-echo sequences (VISTA), T2-weighted VISTA, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP), and contrast-enhanced T1-VISTA. ASSESSMENT: The following features of the plaques or vessel wall were assessed by three MRI readers independently: calcification (CA), intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), ulceration, plaque enhancement (PE), maximum vessel diameter (Max VD), maximum wall thickness (Max WT), total vessel area (TVA), lumen area (LA), plaque volume, and lumen stenosis. WMLs were graded visually and categorized as absent-to-mild WMLs (Fazekas score 0-2) or moderate-severe WMLs (Fazekas score 3-6). WML volumes were quantified using a semiautomated volumetric analysis program. Modified Rankin scores (mRS) were assessed at 90 days, following an outpatient interview, or by telephone. STATISTICAL TESTS: LASSO-logistic regression analysis was performed to construct a model. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analyses, calibration curves, decision curve analyses, and clinical imaging curves. Conditional logistic regression analysis was used to explore the associations between the hybrid model-derived score and the modified Rankin Scale (mRS) score at 90 days. RESULTS: The model was constructed using five selected features, including IPH, plaque enhancement, ulceration, NWI, and total Fazekas score in deep WMLs (DWMLs). The hybrid model yielded an area under the curve of 0.92 (95% confidence interval [CI] 0.87-0.97) in the training cohort and 0.88 (0.80-0.96) in the test cohort. Furthermore, the hybrid model-derived score (odds ratio = 1.28; 95% CI 1.06-1.53) was independently associated with the mRS score 90 days after stroke. DATA CONCLUSIONS: The hybrid model constructed using MRI plaque characteristics and WML burden has potential to be an effective noninvasive method of assessing ischemic stroke severity. The model-derived score has promising utility in judging neurological function recovery. TECHNICAL EFFICACY: Stage 2.

Wall permeability on magnetic resonance imaging is associated with intracranial aneurysm symptoms and wall enhancement.

OBJECTIVES: Wall remodeling and inflammation accompany symptomatic unruptured intracranial aneurysms (UIAs). The volume transfer constant (Ktrans) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) reflects UIA wall permeability. Aneurysmal wall enhancement (AWE) on vessel wall MRI (VWI) is associated with inflammation. We hypothesized that Ktrans is related to symptomatic UIAs and AWE. METHODS: Consecutive patients with UIAs were prospectively recruited for 3-T DCE-MRI and VWI from January 2018 to March 2023. UIAs were classified as asymptomatic and symptomatic if associated with sentinel headache or oculomotor nerve palsy. Ktrans and AWE were assessed on DCE-MRI and VWI, respectively. AWE was evaluated using the AWE pattern and wall enhancement index (WEI). Spearman's correlation coefficient and univariate and multivariate analyses were used to assess correlations between parameters. RESULTS: We enrolled 82 patients with 100 UIAs (28 symptomatic and 72 asymptomatic). The median Ktrans (2.1 versus 0.4 min-1; p < 0.001) and WEI (1.5 versus 0.4; p < 0.001) were higher for symptomatic aneurysms than for asymptomatic aneurysms. Ktrans (odds ratio [OR]: 1.60, 95% confidence interval [95% CI]: 1.01-2.52; p = 0.04) and WEI (OR: 3.31, 95% CI: 1.05-10.42; p = 0.04) were independent risk factors for symptomatic aneurysms. Ktrans was positively correlated with WEI (Spearman's coefficient of rank correlation (rs) = 0.41, p < 0.001). The combination of Ktrans and WEI achieved an area under the curve of 0.81 for differentiating symptomatic from asymptomatic aneurysms. CONCLUSIONS: Ktrans may be correlated with symptomatic aneurysms and AWE. Ktrans and WEI may provide an additional value than the PHASES score for risk stratification of UIAs. CLINICAL RELEVANCE STATEMENT: The volume transfer constant (Ktrans) from DCE-MRI perfusion is associated with symptomatic aneurysms and provides additional value above the clinical PHASES score for risk stratification of intracranial aneurysms. KEY POINTS: • The volume transfer constant is correlated with intracranial aneurysm symptoms and aneurysmal wall enhancement. • Dynamic contrast-enhanced and vessel wall MRI facilitates understanding of the pathophysiological characteristics of intracranial aneurysm walls. • The volume transfer constant and wall enhancement index perform better than the traditional PHASES score in differentiating symptomatic aneurysms.

Optimizing timing for quantification of intracranial aneurysm enhancement: a multi-phase contrast-enhanced vessel wall MRI study.

OBJECTIVES: Aneurysm wall enhancement (AWE) on high-resolution contrast-enhanced vessel wall MRI (VWMRI) is an emerging biomarker for intracranial aneurysms (IAs) stability. Quantification methods of AWE in the literature, however, are variable. We aimed to determine the optimal post-contrast timing to quantify AWE in both saccular and fusiform IAs. MATERIALS AND METHODS: Consecutive patients with unruptured IAs were prospectively recruited. VWMRI was acquired on 1 pre-contrast and 4 consecutive post-contrast phases (each phase was 9 min). Signal intensity values of cerebrospinal fluid (CSF) and aneurysm wall on pre- and 4 post-contrast phases were measured to determine the aneurysm wall enhancement index (WEI). AWE was also qualitatively analyzed on post-contrast images using previous grading criteria. The dynamic changes of AWE grade and WEI were analyzed for both saccular and fusiform IAs. RESULTS: Thirty-four patients with 42 IAs (27 saccular IAs and 15 fusiform IAs) were included. The changes in AWE grade occurred in 8 (30%) saccular IAs and 6 (40%) in fusiform IAs during the 4 post-contrast phases. The WEI of fusiform IAs decreased 22.0% over time after contrast enhancement (p = 0.009), while the WEI of saccular IAs kept constant during the 4 post-contrast phases (p > 0.05). CONCLUSIONS: When performing quantitative analysis of AWE, acquiring post-contrast VWMRI immediately after contrast injection achieves the strongest AWE for fusiform IAs. While the AWE degree is stable for 36 min after contrast injection for saccular IAs. CLINICAL RELEVANCE STATEMENT: The standardization of imaging protocols and analysis methods for AWE will be helpful for imaging surveillance and further treatment decisions of patients with unruptured IAs. KEY POINTS: Imaging protocols and measurements of intracranial aneurysm wall enhancement are reported heterogeneously. Aneurysm wall enhancement for fusiform intracranial aneurysms (IAs) is strongest immediately post-contrast, and stable for 36 min for saccular IAs. Future multi-center studies should investigate aneurysm wall enhancement as an emerging marker of aneurysm growth and rupture.

Dilated lenticulostriate artery on whole-brain vessel wall imaging differentiates pathogenesis and predicts clinical outcomes in single subcortical infarction.

OBJECTIVES: This study aimed to investigate the dilation of lenticulostriate artery (LSA) identified by whole-brain vessel wall imaging (WB-VWI) in differentiating the etiologic subtypes of single subcortical infarction (SSI) and to determine whether the appearance of dilated LSA was associated with 90-day clinical outcomes in parental atherosclerotic disease (PAD)-related SSI. METHODS: Patients with acute SSI were prospectively enrolled and categorized into PAD-related SSI and cerebral small-vessel disease (CSVD)-related SSI groups. The imaging features of LSA morphology (branches, length, dilation, and tortuosity), plaques (burden, remodeling index, enhancement degree, and hyperintense plaque), and CSVD (white matter hyperintensity, lacunes, cerebral microbleed, and enlarged perivascular space) were evaluated. The logistic regression was performed to determine the association of dilated LSA with PAD-related SSI and 90-day clinical outcomes. RESULTS: In total, 131 patients (mean age, 52.2 ± 13.2 years; 99 men) were included. The multivariate logistic regression analysis revealed that the presence of dilated LSAs (odds ratio (OR), 7.40; 95% confidence interval (CI): 1.88-29.17; p = 0.004)) was significantly associated with PAD-related SSI. Moreover, after adjusting for confounding factors, the association of poor outcomes with the total length of LSAs (OR, 0.94; 95% CI: 0.90-0.99; p = 0.011), dilated LSAs (OR, 0.001; 95% CI: 0.0001-0.08; p = 0.002), and plaque burden (OR, 1.35; 95% CI: 1.11-1.63; p = 0.002) remained statistically significant. CONCLUSION: The dilation of LSA visualized on WB-VWI could differentiate various subtypes of SSI within LSA territory and was a prognostic imaging marker for 90-day clinical outcomes for PAD-related SSI. CLINICAL RELEVANCE STATEMENT: Evaluation of LSA morphology based on WB-VWI can differentiate the pathogenesis and predict clinical outcomes in SSI, providing crucial insights into the etiologic mechanisms, risk stratification, and tailored therapies for these patients. KEY POINTS: The prognosis of SSIs within lenticulostriate territory depend on the etiology of the disease. LSA dilation on WB-VWI was associated with parental atherosclerosis and better 90-day outcomes. Accurately identifying the etiology of SSIs in lenticulostriate territory assists in treatment decision-making.

High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes.

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

Plaque features of the middle cerebral artery are associated with periprocedural complications of intracranial angioplasty and stenting.

PURPOSE: The identification of plaque features in the middle cerebral artery (MCA) may help minimize periprocedural complications and select patients suitable for percutaneous transluminal angioplasty and stenting (PTAS). However, relevant research is lacking. METHODS: We retrospectively included patients with symptomatic MCA stenosis who received PTAS. All patients underwent intracranial vessel wall MRI (VWMRI) before surgery. Periprocedural complications (PC) included ischemic and hemorrhagic stroke within 30 days. Stenosis location, MCA shape, plaque eccentricity and distribution, plaque thickness and length, and enhancement ratio were compared between patients with and without PC. RESULTS: Sixty-six patients were included in the study, of which 12.1% (8/66) had PC. Of the eight patients with PC, seven (87.5%) had superior wall plaques. In the non-PC group (n = 58), nine (17%) patients had superior wall plaques. Compared with patients without PC, those with PC had more frequent superior wall plaques (17% vs 87.5%, p < 0.001) and s-shaped MCAs (19% vs 50%, p = 0.071), different stenosis locations (p = 0.012), thicker plaques (1.58 [1.35, 2.00] vs 1.98 [1.73, 2.43], p = 0.038), and less frequent inferior wall plaques (79.2% vs 12.5%, p < 0.001). Multivariate analysis showed that only the presence of superior wall plaques (OR = 41.54 [2.31, 747.54]) was independently associated with PC. CONCLUSION: MCA plaque features were highly correlated with PC in patients with symptomatic MCA stenosis who underwent PTAS.

Does it stable? Intracranial aneurysm wall enhancement might be the warning signals: a meta-analysis of observational studies.

Magnetic resonance vessel wall imaging (MR-VWI) is an emerging imaging technology used to assess the progressive risk of unruptured intracranial aneurysms (UIAs). Unlike the standard evaluation model, MR-VWI is still debatable. This study aims to further define the potential relationship between aneurysm wall enhancement (AWE) and aneurysm stability. Using "intracranial aneurysm", "magnetic resonance", and "enhancement" as keywords, relevant studies were systematically searched in PubMed, Embase, and Cochrane, and the qualified studies were enrolled for further analysis. There were 13 case-control studies, 4 cohort studies, and 2,678 cases of intracranial aneurysms included in the meta-analysis. It was shown that AWE was correlated with intracranial aneurysm rupture (OR = 35.90, 95% CI: 15.58 to 82.75, p < 0.001), growth (OR = 6.69, 95% CI: 2.69 to 16.63, p < 0.001), and presence of symptoms (OR = 14.46, 95% CI: 9.07 to 23.05, p < 0.001). This finding had a high diagnostic value, but the correlation was probably not independent of aneurysm size. The pooled relative risks of the follow-up studies revealed that the risk of UIA progression was approximately 3.33 times higher with AWE than without AWE (RR = 3.33, 95% CI: 2.33 to 4.78, p < 0.001). In addition, the pooled results demonstrated that quantitative indices of VWI enhancement were equally linked with aneurysm stability (OR = 19.61, 95% CI: 10.63 to 36.17, p < 0.001). AWE is an effective imaging method to assess the stability of UIAs, and it can be a marker for the prophylactic treatment of small unruptured intracranial aneurysms in the future, which remains to be validated by prospective studies with large samples.

Basilar artery perforator aneurysms: a comparison with non-perforator saccular aneurysms.

BACKGROUND: Basilar artery perforator aneurysms (BAPAs) are rare. There is no systematic description of their presentation, imaging, natural history and outcomes and how these compare to conventional non-perforator aneurysms. Thus, the authors in this study aimed to compare BAPAs to non-perforator aneurysms. METHODS: Cases were identified from a prospective neurovascular database, notes and imaging retrospectively reviewed and compared to a consecutive series of patients with non-perforator aneurysms. Blood volume on CT and vessel wall imaging (VWI) were compared to controls. RESULTS: 9/739 patients with aneurysmal subarachnoid haemorrhage (aSAH) harboured BAPAs. Compared to 103 with aSAH from posterior circulation aneurysms, they were more likely to be male (6/9, p = 0.008), but of equal severity (4/9 poor grade, p = 0.736) and need of CSF drainage (5/9, p = 0.154). Blood volume was similar to controls (30.2 ml vs 26.7 ml, p = 0.716). 6/9 BAPAs were initially missed on CTA. VWI showed thick (2.9 mm ± 2.7) bright enhancement (stalk ratio 1.05 ± 0.12), similar to controls with ruptured aneurysms (0.95 ± 0.23, p = 0.551), and greater than unruptured aneurysms (0.43 ± 0.11, p < 0.001). All were initially managed conservatively. Six thrombosed spontaneously. Three grew and had difficult access with few good endovascular options and were treated through a subtemporal craniotomy without complication. None rebled. At 3 months, all presenting in poor grade were mRS 3-4 and those in good grade mRS 1-2. CONCLUSIONS: Despite their small size, BAPAs present with similar volume SAH, WFNS grade and hydrocephalus to other aneurysms. They are difficult to identify on CTA but enhance strikingly on VWI. The majority thrombosed. Initial conservative management reserving treatment for growth was associated with no rebleeds or complications.

Diagnostic value of high-resolution vessel wall imaging technique in intracranial arterial stenosis and occlusion: a comparative analysis with digital subtraction angiography.

OBJECTIVE: To analyze the diagnostic value of HR-VWI in intracranial arterial stenosis and occlusion and compare it with DSA. METHODS: A retrospective analysis of clinical data of 59 patients with intracranial arterial stenosis in our hospital was conducted to compare the diagnostic results of the two methods for different degrees of intracranial stenosis and various morphological plaques. RESULTS: The diagnosis of stenosis and occlusion by both methods showed no significant difference (p > 0.05). Comparison of plaque morphology detected by HR-VWI with pathological examination results showed no significant difference (p > 0.05); however, there was a significant difference between plaque morphology detected by DSA and pathological examination results (p < 0.05). Additionally, there was a significant difference between plaque morphology detected by HR-VWI and DSA (p < 0.05). CONCLUSION: HR-VWI technique is comparable to DSA technique in diagnosing intracranial arterial stenosis and occlusion, but it is superior to DSA in plaque morphology diagnosis.

A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.

Relationship between Gut, Blood, Aneurysm Wall and Thrombus Microbiome in Abdominal Aortic Aneurysm Patients.

Previous research confirmed gut dysbiosis and translocation of selected intestinal bacteria into the vessel wall in abdominal aortic aneurysm patients. We studied the stool, blood, thrombus and aneurysm microbiomes of 21 abdominal aortic aneurysm patients using 16S rRNA sequencing. Our goals were to determine: 1. whether the microbiome characteristic of an aneurysm differs from that of a healthy vessel, 2. whether bacteria detectable in the aneurysm are translocated from the gut through the bloodstream, 3. whether the enzymatic activity of the aneurysm microbiome can contribute to the destruction of the vessel wall. The abundance of Acinetobacter, Burkholderia, Escherichia, and Sphingobium in the aneurysm samples was significantly higher than that in the microbiome of healthy vessels, but only a part of these bacteria can come from the intestine via the blood. Environmental bacteria due to the oral cavity or skin penetration route, such as Acinetobacter, Sphingobium, Enhydrobacter, and Aquabacterium, were present in the thrombus and aneurysm with a significantly higher abundance compared to the blood. Among the enzymes of the microbiome associated with the healthy vessel wall, Iron-chelate-transporting ATPase and Polar-amino-acid-transporting ATPase have protective effects. In addition, bacterial Peptidylprolyl isomerase activity found in the aneurysm has an aggravating effect on the formation of aneurysm.

Association of systemic inflammatory response index and plaque characteristics with the severity and recurrence of cerebral ischemic events.

AIM: We aimed to investigate the relationship between systemic inflammatory response index (SIRI) and intracranial plaque features, as well as the risk factors related to the severity and recurrence of cerebral ischemic events. METHODS: We enrolled 170 patients with cerebral ischemic events. Baseline demographic characteristics and laboratory indicators were collected from all participants. All patients were assessed by high-resolution magnetic resonance vessel wall imaging for culprit plaque characteristics and intracranial atherosclerotic burden. Outpatient or telephone follow-up were conducted at 1, 3, and 6 months after discharge. RESULTS: SIRI levels were significantly associated with the enhanced plaque number (r = 0.205, p = 0.007), total plaque stenosis score (r = 0.178, p = 0.020), total plaque enhancement score (r = 0.222, p = 0.004), intraplaque hemorrhage (F = 5.630, p = 0.004), and plaque surface irregularity (F = 3.986, p = 0.021). Higher SIRI levels (OR = 1.892), total plaque enhancement score (OR = 1.392), intraplaque hemorrhage (OR = 3.370) and plaque surface irregularity (OR = 2.846) were independent risk factors for moderate-severe stroke, and these variables were significantly positively correlated with NIHSS (P < 0.05 for all). In addition, higher age (HR = 1.063, P = 0.015), higher SIRI levels (HR = 2.003, P < 0.001), and intraplaque hemorrhage (HR = 4.482, P = 0.008) were independently associated with recurrent stroke. CONCLUSIONS: Higher SIRI levels may have adverse effects on the vulnerability and burden of intracranial plaques, and links to the severity and recurrence of ischemic events. Therefore, SIRI may provide important supplementary information for evaluating intracranial plaque stability and risk stratification of patients.