Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling to Assess Peripheral Artery Disease.

Background Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). Methods and Results The computational microvascular model was used to study skeletal calf muscle perfusion in 56 individuals (36 patients with PAD, 20 matched controls).

Comparison of Longitudinal Skeletal Thigh Muscle Findings With Magnetic Resonance Imaging in Patients With Peripheral Artery Disease With-Versus-Without Diabetes Mellitus.

The aim of this secondary analysis of ELIMIT (The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial) was to determine longitudinal changes over 24 months in skeletal thigh muscle volumes and individual muscle compartments in patients with peripheral artery disease (PAD) with and without diabetes. A total of 48 patients with available magnetic resonance imaging of the distal superficial femoral artery at baseline and 2 years were included in this analysis. Muscle volumes and superficial femoral artery wall, lumen, and total vessel volumes were quantified.

Magnetic resonance imaging based superficial femoral artery velocity measurements in peripheral artery disease.

Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. In this study, we analyzed how non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) measured velocity markers of the distal superficial femoral artery (SFA) are associated with clinical and functional characteristics of PAD. A total of 70 (27 diabetic and 43 non-diabetic) PAD patients were included in this secondary analysis of data collected from the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT).

Differential proteome profile, biological pathways, and network relationships of osteogenic proteins in calcified human aortic valves.

Calcific aortic valve disease (CAVD) is the most common heart valve disease requiring intervention. Most research on CAVD has focused on inflammation, ossification, and cellular phenotype transformation. To gain a broader picture into the wide range of cellular and molecular mechanisms involved in this disease, we compared the total protein profiles between calcified and non-calcified areas from 5 human valves resected during surgery.

Relation of Magnetic Resonance Imaging Based Arterial Signal Enhancement to Markers of Peripheral Artery Disease.

Peripheral artery disease (PAD) is associated with impaired lower extremity function. We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) based arterial signal enhancement (SE) measures are associated with markers of PAD. A total of 66 participants were enrolled, 10 were excluded due to incomplete data, resulting in 56 participants for the final analyses (36 PAD, 20 matched controls).

The Ryanodine Receptor Contributes to the Lysophosphatidylcholine-Induced Mineralization in Valvular Interstitial Cells.

Purpose: Fibrocalcific aortic valve disease (CAVD) is caused by the deposition of calcific nodules in the aortic valve leaflets, resulting in progressive loss of function that ultimately requires surgical intervention. This process is actively mediated by the resident valvular interstitial cells (VICs), which, in response to oxidized lipids, transition from a quiescent to an osteoblast-like state. The purpose of this study was to examine if the ryanodine receptor, an intracellular calcium channel, could be therapeutically targeted to prevent this phenotypic conversion.

Patient-Specific Flow Descriptors and Normalized wall index in Peripheral Artery Disease: a Preliminary Study.

Background And Aims: MRI-based hemodynamics have been applied to study the relationship between time-averaged wall shear stresses (TAWSS), oscillatory shear index (OSI) and atherosclerotic lesions in the coronary arteries, carotid artery, and human aorta. However, the role of TAWSS and OSI are poorly understood in lower extremity arteries. The aim of this work was to investigate the feasibility of hemodynamic assessment of the superficial femoral artery (SFA) in patients with peripheral artery disease (PAD) and we hypothesized that there is an association between TAWSS and OSI, respectively, and atherosclerotic burden expressed as the normalized wall index (NWI).

Magnetic Resonance Venous Volume Measurements in Peripheral Artery Disease (from ELIMIT).

The relation between the arterial and venous systems in patients with impaired lower extremity blood flow remains poorly described. The objective of this secondary analysis of the Effectiveness of Intensive Lipid Modification Medication in Preventing the Progression on Peripheral Artery Disease Trial was to determine the association between femoral vein (FV) volumes and measurements of peripheral artery disease. FV wall, lumen, and total volumes were quantified with fast spin-echo proton density-weighted magnetic resonance imaging scans in 79 patients with peripheral artery disease over 2 years.

Calf muscle perfusion as measured with magnetic resonance imaging to assess peripheral arterial disease.

We hypothesized that skeletal muscle perfusion is impaired in peripheral arterial disease (PAD) patients compared to healthy controls and that perfusion patterns exhibit marked differences across five leg muscle compartments including the anterior muscle group (AM), lateral muscle group (LM), deep posterior muscle group (DM), soleus (SM), and the gastrocnemius muscle (GM). A total of 40 individuals (26 PAD patients and 14 healthy controls) underwent contrast-enhanced magnetic resonance imaging (CE-MRI) utilizing a reactive hyperemia protocol. Muscle perfusion maps were developed for AM, LM, DM, SM, and GM.

Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues.

Background: Advanced atherosclerotic lesions are commonly characterized by the presence of calcification. Several studies indicate that extensive calcification is associated with plaque stability, yet recent studies suggest that calcification morphology and location may adversely affect the mechanical stability of atherosclerotic plaques. The underlying cause of atherosclerotic calcification and the importance of intra-plaque calcium distribution remains poorly understood.

Distribution of alkaline phosphatase, osteopontin, RANK ligand and osteoprotegerin in calcified human carotid atheroma.

Ectopic vascular calcification is a significant component of atherosclerotic disease. Osteopontin (OPN), Osteoprotegerin (OPG), Receptor Activator of NFκB Ligand (RANKL), and alkaline phosphatase (ALP) are each thought to play central roles in the calcification or demineralization of atherosclerotic lesions. Abnormalities in the balance of these proteins may lead to perturbations in bone remodeling and arterial calcification.

Postprandial effects on arterial stiffness parameters in healthy young adults.

Postprandial lipemia has been associated with acute endothelial dysfunction. Endothelial dysfunction, in turn, is associated with increased arterial stiffness. However, the relationship between postprandial lipemia and acute changes in arterial stiffness has not been extensively investigated.

Differential Aortic and Mitral Valve Interstitial Cell Mineralization and the Induction of Mineralization by Lysophosphatidylcholine .

Purpose: Calcific aortic valve disease (CAVD) is a serious condition with vast uncertainty regarding the precise mechanism leading to valve calcification. This study was undertaken to examine the role of the lipid lysophosphatidylcholine (LPC) in a comparison of aortic and mitral valve cellular mineralization.

Methods: The proportion of LPC in differentially calcified regions of diseased aortic valves was determined using thin layer chromatography (TLC).

Distribution of calcification in carotid endarterectomy tissues: comparison of micro-computed tomography imaging with histology.

Background: Calcification in atherosclerotic plaques has been viewed as a marker of plaque stability, but whether calcification accumulates in specific anatomic sites in the carotid artery is unknown. We determined the burden and distribution of calcified plaque in carotid endarterectomy (CEA) tissues.

Methods: A total of 22 CEA tissues were imaged with high-resolution micro-computed tomography (micro-CT).

The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT).

Methods: A total of 102 patients were randomized to either mono-therapy with simvastatin (40 mg daily) or triple-therapy with simvastatin (40 mg daily), extended-release niacin (1500 mg daily), and ezetimibe (10 mg daily). MRI was performed at baseline and 6, 12, and 24 months. SFA wall, lumen, and total vessel volumes were quantified.

Application of speckle-tracking in the evaluation of carotid artery function in subjects with hypertension and diabetes.

Background: Speckle-tracking enables direct tracking of carotid arterial wall motion. Timing intervals determined with carotid speckle-tracking and slopes calculated from carotid artery area versus cardiac cycle curves may provide further information on arterial function and stiffness. The proposed arterial stiffness parameters were examined in healthy controls (n = 20), nondiabetic patients with hypertension (n = 20), and patients with type 2 diabetes (n = 21).

Effect of lyso-phosphatidylcholine and Schnurri-3 on osteogenic transdifferentiation of vascular smooth muscle cells to calcifying vascular cells in 3D culture.

Background: In vitro cell culture is a widely used technique for investigating a range of processes such as stem cell behavior, regenerative medicine, tissue engineering, and drug discovery. Conventional cell culture is performed in Petri dishes or flasks where cells typically attach to a flat glass or plastic surface as a cell monolayer. However, 2D cell monolayers do not provide a satisfactory representation of in vivo conditions.

Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves.

The calcification process in aortic stenosis has garnered considerable interest but only limited investigation into selected signaling pathways. This study investigated mechanisms related to hypoxia, hyaluronan homeostasis, brown adipocytic differentiation, and ossification within calcified valves. Surgically explanted calcified aortic valves (n=14) were immunostained for markers relevant to these mechanisms and evaluated in the center (NodCtr) and edge (NodEdge) of the calcified nodule (NodCtr), tissue directly surrounding nodule (NodSurr); center and tissue surrounding small "prenodules" (PreNod, PreNodSurr); and normal fibrosa layer (CollFibr).

Detection of hydroxyapatite in calcified cardiovascular tissues.

Objective: The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues.

Methods: A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo.

Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study.

Background: On the basis of studies with limited statistical power, lipoprotein(a) [Lp(a)] is not considered a risk factor for cardiovascular disease (CVD) in blacks. We evaluated associations between Lp(a) and incident CVD events in blacks and whites in the Atherosclerosis Risk in Communities (ARIC) study.

Methods And Results: Plasma Lp(a) was measured in blacks (n=3467) and whites (n=9851).

Automatic quantification of muscle volumes in magnetic resonance imaging scans of the lower extremities.

Muscle volume measurements are essential for an array of diseases ranging from peripheral arterial disease, muscular dystrophies, neurological conditions to sport injuries and aging. In the clinical setting, muscle volume is not routinely measured due to the lack of standardized ways for its repeatable quantification. In this paper, we present magnetic resonance muscle quantification (MRMQ), a method for the automatic quantification of thigh muscle volume in magnetic resonance imaging (MRI) scans.

Real-time co-registration using novel ultrasound technology: ex vivo validation and in vivo applications.

Objective: The study objective was to evaluate whether a novel global position system (GPS)-like position-sensing technology will enable accurate co-registration of images between imaging modalities. Co-registration of images obtained by different imaging modalities will allow for comparison and fusion between imaging modalities, and therefore has significant clinical and research implications. We compared ultrasound (US) and magnetic resonance imaging (MRI) scans of carotid endarterectomy (CEA) specimens using a novel position-sensing technology that uses an electromagnetic (EM) transmitter and sensors mounted on a US transducer.

Variability and persistence of aspirin response in lower extremity peripheral arterial disease patients.

Objective: To determine the prevalence of poor response to aspirin (ASA) therapy over 12-month follow-up in patients with lower extremity peripheral arterial disease (PAD), and to compare the classification agreement among different ASA response assays.

Methods: Patients with PAD on ASA therapy at baseline were included from the ongoing Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention Trial (ELIMIT), which is a randomized trial testing whether combination treatment with ezetimibe, niacin, and a statin will halt/regress atherosclerosis compared with statin monotherapy. Patients who had baseline platelet testing and repeat testing at 6-month or 12-month follow-up were included.

Differential proteoglycan and hyaluronan distribution in calcified aortic valves.

Background: While the prevalence of calcified aortic valve disease continues to rise and no pharmacological treatments exist, little is known regarding the pathogenesis of the disease. Proteoglycans and the glycosaminoglycan hyaluronan are involved in calcification in arteriosclerosis and their characterization in calcified aortic valves may lend insight into the pathogenesis of the disease.

Methods: Fourteen calcified aortic valves removed during valve replacement surgery were immunohistochemically stained for the proteoglycans decorin, biglycan, and versican, as well as the glycosaminoglycan hyaluronan.