Correlation of Adventitial Vasa Vasorum with Intracranial Atherosclerosis: A Postmortem Study.
ABSTRACT: BACKGROUND AND PURPOSE:Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. METHODS:We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. RESULTS:Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P<0.001), severer luminal stenosis (25%±21% vs. 12%±9%, P=0.002), higher rate of concentric lesions (79% vs. 36%, P=0.002), and denser intraplaque calcification (44% vs. 0%, P=0.003). Histologically, intracranial VA with VV had a larger diameter (3.40±0.79 mm vs. 2.34±0.58 mm, P<0.001), thicker arterial wall (0.31±0.13 mm vs. 0.23±0.06 mm, P=0.002), and a larger intima-media (0.19±0.09 mm vs. 0.13± 0.04 mm, P=0.003) than VA without VV. CONCLUSION:s Our study demonstrated the distribution of adventitial VV within brain vasculature and association between vertebral VV and progressive atherosclerotic lesions with a heavier plaque load and denser intraplaque calcification.
Project description:Autopsy studies have suggested a relationship between intraplaque hemorrhage (IPH) and vasa vasorum, which arise primarily from the adventitia. Adventitial vasa vasorum can be characterized in the carotid arteries by estimating perfusion parameters via dynamic contrast-enhanced MRI. The purpose of this investigation was to use dynamic contrast-enhanced MRI to test in vivo in a clinical population whether adventitial perfusion, indicative of vasa vasorum microstructure, is associated with IPH.Symptomatic patients with carotid plaque ipsilateral to the ischemic event underwent bilateral carotid artery MRI examination, which included multicontrast sequences for detecting IPH and a dynamic contrast-enhanced MRI sequence for characterizing adventitial perfusion. Kinetic modeling of the dynamic contrast-enhanced MRI time series was performed to estimate adventitial vp (fractional plasma volume, reflecting local blood supply) and K(trans) (transfer constant, reflecting vessel surface area, and permeability).From the 27 patients (22 men; 69 ± 10 years of age) recruited, adventitial perfusion parameters were obtained in 50 arteries. The presence of IPH was associated with a significantly higher value in adventitial K(trans) (0.142 ± 0.042 vs 0.112 ± 0.029 min(-1); P<0.001) but not in vp (0.163 ± 0.064 vs 0.149 ± 0.062; P=0.338). This relationship remained after adjusting for symptomatic status, degree of stenosis, and other confounding factors.This study demonstrated an independent pathophysiological link between the adventitia and IPH and related it to the microstructure of adventitial vasa vasorum. Adventitial perfusion imaging may be useful in studying plaque pathogenesis, but further examination through prospective studies is needed.
Project description:The aim of this multicenter study was to demonstrate the distribution pattern of atherosclerotic stenosis and its trend with aging between extracranial and intracranial arteries and its distribution between the anterior and posterior circulations in Chinese patients hospitalized with ischemic stroke. In addition, the risk factors for the distribution pattern were illustrated. From June 2015 to May 2016, 9,346 patients with ischemic stroke from 20 hospitals were enrolled. Carotid artery ultrasonography and transcranial color-coded sonography/transcranial Doppler were used to evaluate the extracranial and intracranial arteries. The distribution pattern of atherosclerotic stenosis and its trend with aging were analyzed. Logistic regression was used to analyze the risk factors for the distribution pattern. Among the 9,346 patients, 2,882 patients (30.8%) had at least one artery with a degree of stenosis ?50%. Among patients with arterial stenosis, the proportion of patients with intracranial artery stenosis was higher than those with extracranial artery stenosis (52.6% vs. 27.6%), and the proportion of anterior circulation artery stenosis was higher than that in the posterior circulation (52.2% vs.26.2%). With aging, the proportion of intracranial artery stenosis alone decreased; at the same time, the proportion of extracranial artery stenosis and extracranial plus intracranial artery stenosis increased (trend ?2=6.698, P=0.001). Hypertension (OR 1.416, P=0.008) and family history of stroke (OR 1.479, P=0.014) were risk factors for intracranial artery stenosis. Male, aging, and smoking were factors more related to extracranial artery stenosis. Aging (OR 1.022, P<0.001) and hypertension (OR 1.392, P=0.019) were related to posterior circulation artery stenosis. Intracranial arteries and anterior circulation arteries were susceptible to stenosis in Chinese patients with ischemic stroke. However, the distribution pattern of atherosclerotic stenosis was dynamic and varied with aging. Aging and different risk factors contribute to this distribution pattern.
Project description:This study used an atherosclerotic rabbit model to investigate the feasibility of quantifying adventitial vasa vasorum (VV) via contrast-enhanced ultrasound (CEUS) imaging to identify early atherosclerosis. Recent evidence has linked adventitial VV with atherosclerotic plaque progression and vulnerability. A growth in VV density has been detected preceding intimal thickening and even endothelial dysfunction. In our study, carotid atherosclerosis rabbit models were used, and animals underwent CEUS imaging at the end of the atherosclerotic induction period. Normalized maximal video-intensity enhancement (MVE) was calculated to quantify VV density. After CEUS imaging, animals were euthanized, and their carotids were processed for histopathological analysis following staining for CD31 and VEGF. Adventitial normalized MVE increased as atherosclerosis progressed (p?<?0.001), and normalized MVE also progressed, demonstrating a linear correlation with histological findings (r?=?0.634, p?<?0.001 for VEGF-positive; r?=?0.538, p?<?0.001 for CD31-positive). Thus, we histologically validated that CEUS imaging can be used to quantify the development of adventitial VV associated with atherosclerosis progression. This method can be used for monitoring the VV to detect early atherosclerosis.
Project description:This study sought to evaluate adventitial vasa vasorum (VV) in vivo with novel imaging technique of optical coherence tomography (OCT).To verify OCT methods for quantification of VV, we first studied 2 swine carotid arteries in a model of focal angiogenesis by autologous blood injection, and compared microchannel volume (MCV) by OCT and VV by m-CT, and counts of those. In OCT images, adventitial MC was identified as signal-voiding areas which were located within 1 mm from the lumen-intima border. After manually tracing microchannel areas and the boundaries of lumen-intima and media-adventitial in all slices, we reconstructed 3D images. Moreover, we performed with OCT imaging in 8 recipients referred for evaluation of cardiac allograft vasculopathy at 1 year after heart transplantation. MCV and plaque volume (PV) were assessed with 3D images in each 10-mm-segment.In the animal study, among the 16 corresponding 1-mm-segments, there were significant correlations of count and volume between both the modalities (count r(2) = 0.80, P < 0.01; volume r(2) = 0.50, P < 0.01) and a good agreement with a systemic bias toward underestimation with m-CT. In the human study, there was a significant positive correlation between MCV and PV (segment number = 24, r(2) = 0.63, P < 0.01).Our results suggest that evaluation of MCV with 3D OCT imaging might be a novel method to estimate the amount of adventitial VV in vivo, and further has the potential to provide a pathophysiological insight into a role of the VV in allograft vasculopathy.
Project description:<h4>Background</h4>Hypoxia and low pulmonary arterial (PA) blood flow stimulate the development of systemic-to-pulmonary collateral blood vessels, which can be an adverse factor when performing the Fontan operation. The aim of this study was to use optical coherence tomography (OCT) to elucidate the morphological changes in PA vasculature after creation of a bidirectional cavopulmonary connection (BCPC) in children.<h4>Methods</h4>This prospective study evaluated PA wall thickness and development of PA vasa vasorum (VV) in the distal PA of eight patients (BCPC group, 1.3 ± 0.3 years) and 20 age-matched children with normal pulmonary artery hemodynamics and morphology (Control group, 1.4 ± 0.3 years). VV development was defined by the VV area ratio, defined as the VV area divided by the adventitial area in cross-sectional images.<h4>Results</h4>There was no significant difference in PA wall thickness between the BCPC and control groups (0.12 ± 0.03 mm vs. 0.12 ± 0.02 mm, respectively). The VV area ratio was significantly greater in the BCPC group than in the Control group (14.5 ± 3.5% vs. 5.3 ± 1.6%, respectively; p<0.0001).<h4>Conclusion</h4>OCT is a promising new tool for evaluating PA pathology, including the development of VV in patients after BCPC.
Project description:BACKGROUND:It is still unknown that whether co-existing intracranial stenosis and extracranial carotid vulnerable plaques have higher predictive value for subsequent vascular events. This study aimed to determine the relationship between co-existing extracranial carotid vulnerable plaques and intracranial stenosis and subsequent vascular events utilizing cardiovascular magnetic resonance (CMR) vessel wall imaging. METHODS:Patients who had recent cerebrovascular symptoms in anterior circulation (<?2?weeks) were consecutively enrolled and underwent multi-contrast CMR vessel wall imaging for extracranial carotid arteries and 3D time-of flight CMR angiography for intracranial arteries at baseline. After baseline examination, all patients were followed-up for at least 1?year to determined recurrence of vascular events. The co-existing cerebrovascular atherosclerosis was defined as presence of both intracranial artery stenosis and at least one the following measures of extracranial artery atherosclerosis: plaque, calcification, lipid-rich necrotic core (LRNC), or intraplaque hemorrhage. Univariate and multivariate Cox regressions were used to calculate the hazard ratio (HR) and corresponding 95% confidence interval (CI) of co-existing plaques in predicting subsequent vascular events. RESULTS:In total, 150 patients (mean age: 61.8?±?11.9?years; 109 males) were recruited. During the median follow-up time of 12.1?months, 41 (27.3%) patients experienced vascular events. Co-existing intracranial artery stenosis and extracranial carotid plaque (HR, 3.57; 95% CI, 1.63-7.82; P?=?0.001) and co-existing intracranial artery stenosis and extracranial carotid LRNC (HR, 4.47; 95% CI, 2.15-9.27; P?<?0.001) were significantly associated with subsequent vascular events, respectively. After adjusted for confounding factors and carotid stenosis, these associations remained statistically significant (HR, 5.12; 95% CI, 1.36-19.24; P?=?0.016 and HR, 8.12; 95% CI, 2.41-27.31; P?=?0.001, respectively). CONCLUSIONS:The co-existing cerebrovascular atherosclerotic diseases, particularly co-existing carotid lipid-rich necrotic core and intracranial stenosis, are independent predictors for subsequent vascular events.
Project description:The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30-49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.
Project description:Background Intracranial atherosclerotic stroke is prevalent in Asians. We hypothesized that patients with the ring finger protein 213 (RNF213) variant, a susceptibility locus for moyamoya disease in Asians, have different neuroimaging characteristics in terms of the vessel wall and hemodynamics. Methods and Results We analyzed consecutive patients with ischemic events in middle cerebral artery distribution and relevant plaques of the distal internal carotid artery or proximal middle cerebral artery on high-resolution magnetic resonance imaging. Patients with carotid/cardiac sources of embolism or moyamoya disease were excluded. High-resolution magnetic resonance imaging features (eg, outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time-of-flight magnetic resonance angiography) were compared between RNF213 p.Arg4810Lys variant carriers and noncarriers. Among 144 patients included, 44 (29.9%) had the RNF213 variant. Clinical characteristics, including age, sex, body mass index, and vascular risk factors, were not significantly different between RNF213 variant carriers and noncarriers. However, the outer vessel diameter was smaller in RNF213 variant carriers than in noncarriers (P<0.0001 for middle cerebral artery of relevant stenosis [2.05-mm analysis of RNF213 gene for moyamoya disease in the Chinese HAN population 2.75 mm]; P<0.0001 for contralateral side [2.42 versus 3.00 mm] and P<0.001 for basilar artery [3.19 versus 3.53 mm]). Other high-resolution magnetic resonance imaging features, including plaque morphology and eccentricity, were not significantly different. Fractional flow was diminished in patients with smaller-diameter intracranial arteries with a similar degree of stenosis. Conclusions The RNF213 variant may be associated with vasculogenesis, but not with atherogenesis. Patients with this variant had small intracranial arteries predisposing hemodynamic compromise in the presence of intracranial atherosclerosis. In addition to antiatherosclerotic strategies, further studies are warranted to develop novel therapeutic strategies against RNF213 vasculopathy in Asians.
Project description:<b>Background and Objectives:</b> Previous studies on symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion that was refractory to medical therapy are rare. We aimed to assess the clinical features, imaging characteristics, endovascular treatment feasibility and follow-up outcomes of patients with this condition. <b>Methods:</b> Data from consecutive patients who had symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion and underwent endovascular recanalization from February 2016 to April 2020 were retrospectively collected in our prospective database. Clinical, imaging, procedural, and follow-up data were collected and analyzed. <b>Results:</b> Thirty-one patients, predominantly males, were enrolled in this study. These patients presented with recurrent/progressive stroke in the posterior circulation despite aggressive medical therapy. Angiographic analysis revealed asymmetric vertebral arteries due to unilateral hypoplasia and intracranial vertebral artery total occlusions in the dominant vertebral arteries, which were characterized by long lesion length and high clot burden. Multiple infarctions and perfusion defects in the posterior circulation were demonstrated by diffusion-weighted imaging and arterial spin labeling, respectively. Successful endovascular recanalization was achieved in 87.1% of the patients. Over a median clinical follow-up duration of 11.0 months, 74.1% of patients with successful recanalization achieved favorable clinical outcomes (mRS score ?2). <b>Conclusion:</b> Symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion attributable to hypoperfusion is characterized by recurrent/progressive ischemic events, dominant intracranial vertebral artery total occlusion, long lesion length, and high clot burden. Endovascular recanalization of the dominant intracranial vertebral artery occlusion appears to be a feasible treatment for these patients.
Project description:Vertebral artery (VA) stenosis is relevant to a high early risk of recurrent stroke and basilar artery (BA) is the most common intracranial site of atherosclerotic lesions. It is important to show predictive risk factors for transient ischemic attack (TIA) or posterior infarctions. The aim of the study is to investigate morphometry and hemodynamics in intracranial vertebral and basilar arteries of health and diseased patients to enhance the risk assessment. Based on the geometrical model reconstructed from CTA images in 343 patients, a transient three-dimensional computational model was used to determine the hemodynamics. Patients were classified in symmetric, asymmetric, hypoplastic, and stenotic groups while patients in the stenotic group were divided into unilateral, bilateral, bifurcation, and tandem stenotic sub-groups. Patients in bilateral, bifurcation, and tandem stenotic sub-groups had significantly lower basilar artery diameters than other groups. Patients in the stenotic group had significantly higher surface area ratio (SAR) of high time-averaged wall shear stress gradient (TAWSSG) and higher incidence of TIAs or posterior infarctions than other groups while patients in the tandem stenotic sub-group had the highest values (SAR-TAWSSG of 57 ± 22% and TIAs or posterior infarction incidence of 54%). The high SAR-TAWSSG is predisposed to induce TIAs or posterior infarction.