Molecular MR imaging of neovascular progression in the Vx2 tumor with αvß3-targeted paramagnetic nanoparticles.

PURPOSE: To assess the dependence of neovascular molecular magnetic resonance (MR) imaging on relaxivity (r1) of αvß3-targeted paramagnetic perfluorocarbon (PFC) nanoparticles and to delineate the temporal-spatial consistency of angiogenesis assessments for individual animals. MATERIALS AND METHODS: Animal protocols were approved by the Washington University Animal Studies Committee. Proton longitudinal and transverse relaxation rates of αvß3-targeted and nontargeted PFC nanoparticles incorporating gadolinium diethylenetrianime pentaacedic acid (Gd-DTPA) bisoleate (BOA) or gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA) phosphatidylethanolamine (PE) into the surfactant were measured at 3.0 T. These paramagnetic nanoparticles were compared in 30 New Zealand White rabbits (four to six rabbits per group) 14 days after implantation of a Vx2 tumor. Subsequently, serial MR (3.0 T) neovascular maps were developed 8, 14, and 16 days after tumor implantation by using αvß3-targeted Gd-DOTA-PE nanoparticles (n = 4) or nontargeted Gd-DOTA-PE nanoparticles (n = 4). Data were analyzed with analysis of variance and nonparametric statistics. RESULTS: At 3.0 T, Gd-DTPA-BOA nanoparticles had an ionic r1 of 10.3 L · mmol(-1) · sec(-1) and a particulate r1 of 927000 L · mmol(-1) · sec(-1). Gd-DOTA-PE nanoparticles had an ionic r1 of 13.3 L · mmol(-1) · sec(-1) and a particulate r1 of 1 197000 L · mmol(-1) · sec(-1). Neovascular contrast enhancement in Vx2 tumors (at 14 days) was 5.4% ± 1.06 of the surface volume with αvß3-targeted Gd-DOTA-PE nanoparticles and 3.0% ± 0.3 with αvß3-targeted Gd-DTPA-BOA nanoparticles (P = .03). MR neovascular contrast maps of tumors 8, 14, and 16 days after implantation revealed temporally consistent and progressive surface enhancement (1.0% ± 0.3, 4.5% ± 0.9, and 9.3% ± 1.4, respectively; P = .0008), with similar time-dependent changes observed among individual animals. CONCLUSION: Temporal-spatial patterns of angiogenesis for individual animals were followed to monitor longitudinal tumor progression. Neovasculature enhancement was dependent on the relaxivity of the targeted agent.

Sensitive biological detection with a soluble and stable polymeric paramagnetic nanocluster.

We describe the design, synthesis, and biological characterization of manganese oxocluster-based "single molecule magnets (SMMs)". We demonstrate that polymeric micellar nanoparticles can serve as a carrier and help to stabilize delicate SMM molecules from breaking down easily and thus prevent their property loss. Concentrating thousands of Mn-clusters per micelle provided a high ionic and per-particle relaxivity allowing sensitive MR imaging in vivo. This reports one of the earliest examples of in vivo imaging of a rationally designed polymeric micelle that features SMM.

MR molecular imaging of aortic angiogenesis.

OBJECTIVES: The objectives of this study were to use magnetic resonance (MR) molecular imaging to 1) characterize the aortic neovascular development in a rat model of atherosclerosis and 2) monitor the effects of an appetite suppressant on vascular angiogenesis progression. BACKGROUND: The James C. Russell:LA corpulent rat strain (JCR:LA-cp) is a model of metabolic syndrome characterized by obesity, insulin resistance, hyperlipidemia, and vasculopathy, although plaque neovascularity has not been reported in this strain. MR molecular imaging with alpha(nu)beta(3)-targeted nanoparticles can serially map angiogenesis in the aortic wall and monitor the progression of atherosclerosis. METHODS: Six-week old JCR:LA-cp (+/?; lean, n = 5) and JCR:LA-cp (cp/cp; obese, n = 5) rats received standard chow, and 6 obese rats were fed the appetite suppressant benfluorex over 16 weeks. Body weight and food consumption were recorded at baseline and weeks 4, 8, 12, and 16. MR molecular imaging with alpha(nu)beta(3)-targeted paramagnetic nanoparticles was performed at weeks 0, 8, and 16. Fasted plasma triglyceride, cholesterol, and glucose were measured immediately before MR scans. Plasma insulin and leptin levels were assayed at weeks 8 and 16. RESULTS: Benfluorex reduced food consumption (p < 0.05) to the same rate as lean animals, but had no effect on serum cholesterol or triglyceride levels. MR (3-T) aortic signal enhancement with alpha(nu)beta(3)-targeted nanoparticles was initially equivalent between groups, but increased (p < 0.05) in the untreated obese animals over 16 weeks. No signal change (p > 0.05) was observed in the benfluorex-treated or lean rat groups. MR differences paralleled adventitial microvessel counts, which increased (p < 0.05) among the obese rats and were equivalently low in the lean and benfluorex-treated animals (p > 0.05). Body weight, insulin, and leptin were decreased (p < 0.05) from the untreated obese animals by benfluorex, but not to the lean control levels (p < 0.05). CONCLUSIONS: Neovascular expansion is a prominent feature of the JCR:LA-cp model. MR imaging with alpha(nu)beta(3)-targeted nanoparticles provided a noninvasive assessment of angiogenesis in untreated obese rats, which was suppressed by benfluorex.

Molecular imaging of angiogenic therapy in peripheral vascular disease with alphanubeta3-integrin-targeted nanoparticles.

Noninvasive molecular imaging of angiogenesis could play a critical role in the clinical management of peripheral vascular disease patients. The alpha(nu)beta(3)-integrin, a well-established biomarker of neovascular proliferation, is an ideal target for molecular imaging of angiogenesis. This study investigates whether MR molecular imaging with alpha(nu)beta(3)-integrin-targeted perfluorocarbon nanoparticles can detect the neovascular response to angiogenic therapy. Hypercholesterolemic rabbits underwent femoral artery ligation followed by no treatment or angiogenic therapy with dietary L-arginine. MR molecular imaging performed 10 days after vessel ligation revealed increased signal enhancement in L-arginine-treated animals compared to controls. Furthermore, specifically targeted nanoparticles produced two times higher MRI signal enhancement compared to nontargeted particles, demonstrating improved identification of angiogenic vasculature with biomarker targeting. X-ray angiography performed 40 days postligation revealed that L-arginine treatment increased the development of collateral vessels. Histologic staining of muscle capillaries revealed a denser pattern of microvasculature in L-arginine-treated animals, confirming the MR and X-ray imaging results. The clinical application of noninvasive molecular imaging of angiogenesis could lead to earlier and more accurate detection of therapeutic response in peripheral vascular disease patients, enabling individualized optimization for a variety of treatment strategies.

Detecting vascular biosignatures with a colloidal, radio-opaque polymeric nanoparticle.

A synthetic methodology for developing a polymeric nanoparticle for targeted computed tomographic (CT) imaging is revealed in this manuscript. The work describes a new class of soft type, vascularly constrained, stable colloidal radio-opaque metal-entrapped polymeric nanoparticle using organically soluble radio-opaque elements encapsulated by synthetic amphiphile. This agent offers several-fold CT signal enhancement in vitro and in vivo demonstrating detection sensitivity reaching to the low nanomolar particulate concentration range.

Sensitive and efficient detection of thrombus with fibrin-specific manganese nanocolloids.

In this work, we report novel fibrin targeted "soft-type" manganese-based contrast agents for MRI with the potential to noninvasively image intravascular thrombus which could warrant aggressive medical intervention to preclude subsequent myocardial infarction or stroke.

Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging.

Contrast agents targeted to molecular markers of disease are currently being developed with the goal of identifying disease early and evaluating treatment effectiveness using noninvasive imaging modalities such as MRI. Pharmacokinetic profiling of the binding of targeted contrast agents, while theoretically possible with MRI, has thus far only been demonstrated with more sensitive imaging techniques. Paramagnetic liquid perfluorocarbon nanoparticles were formulated to target alpha(v)beta(3)-integrins associated with early atherosclerosis in cholesterol-fed rabbits to produce a measurable signal increase on magnetic resonance images after binding. In this work, we combine quantitative information of the in vivo binding of this agent over time obtained by means of MRI with blood sampling to derive pharmacokinetic parameters using simultaneous and individual fitting of the data to a three compartment model. A doubling of tissue exposure (or area under the curve) is obtained with targeted as compared to control nanoparticles, and key parameter differences are discovered that may aid in development of models for targeted drug delivery.

Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model.

Our objectives were 1) to characterize angiogenesis in the MDA-MB-435 xenograft mouse model with three-dimensional (3D) MR molecular imaging using alpha(5)beta(1)(RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2) to use MR molecular imaging to assess the antiangiogenic effectiveness of alpha(5)beta(1)(alpha(nu)beta(3))- vs. alpha(nu)beta(3)-targeted fumagillin (50 mug/kg) nanoparticles. Tumor-bearing mice were imaged with MR before and after administration of either alpha(5)beta(1)(RGD) or irrelevant RGS-paramagnetic nanoparticles. In experiment 2, mice received saline or alpha(5)beta(1)(alpha(nu)beta(3))- or alpha(nu)beta(3)-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using alpha(5)beta(1)(alpha(nu)beta(3))-targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of alpha(5)beta(1)(RGD)-signal enhancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied <2.0% tumor surface area. alpha(5)beta(1)-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. alpha(5)beta(1)(alpha(nu)beta(3))-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; alpha(nu)beta(3)-targeted fumagillin nanoparticles were less effective (P>0.05). Reduction of angiogenesis in MDA-MB-435 tumors from low to negligible levels did not decrease tumor volume. MR molecular imaging may be useful for characterizing tumors with sparse neovasculature that are unlikely to have a reduced growth response to targeted antiangiogenic therapy.

Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury.

BACKGROUND: Drug eluting stents prevent vascular restenosis but can delay endothelial healing. A rabbit femoral artery model of stenosis formation after vascular injury was used to study the effect of intramural delivery of alpha(v)beta(3)-integrin-targeted rapamycin nanoparticles on vascular stenosis and endothelial healing responses. METHODS AND RESULTS: Femoral arteries of 48 atherosclerotic rabbits underwent balloon stretch injury and were locally treated with either (1) alpha(v)beta(3)-targeted rapamycin nanoparticles, (2) alpha(v)beta(3)-targeted nanoparticles without rapamycin, (3) nontargeted rapamycin nanoparticles, or (4) saline. Intramural binding of integrin-targeted paramagnetic nanoparticles was confirmed with MR molecular imaging (1.5 T). MR angiograms were indistinguishable between targeted and control arteries at baseline, but 2 weeks later they showed qualitatively less luminal plaque in the targeted rapamycin treated segments compared with contralateral control vessels. In a first cohort of 19 animals (38 vessel segments), microscopic morphometric analysis of the rapamycin-treated segments revealed a 52% decrease in the neointima/media ratio (P<0.05) compared to control. No differences (P>0.05) were observed among balloon injured vessel segments treated with alpha(v)beta(3)-targeted nanoparticles without rapamycin, nontargeted nanoparticles with rapamycin, or saline. In a second cohort of 29 animals, endothelial healing followed a parallel pattern over 4 weeks in the vessels treated with alpha(v)beta(3)-targeted rapamycin nanoparticles and the 3 control groups. CONCLUSIONS: Local intramural delivery of alpha(v)beta(3)-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.

Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis.

OBJECTIVES: Studies were performed to develop a prolonged antiangiogenesis therapy regimen based on theranostic alpha(nu)beta(3)-targeted nanoparticles. BACKGROUND: Antiangiogenesis therapy may normalize atherosclerotic plaque vasculature and promote plaque stabilization. alpha(nu)beta(3)-targeted paramagnetic nanoparticles can quantify atherosclerotic angiogenesis and incorporate fumagillin to elicit acute antiangiogenic effects. METHODS: In the first experiment, hyperlipidemic rabbits received alpha(nu)beta(3)-targeted fumagillin nanoparticles (0, 30, or 90 microg/kg) with either a continued high fat diet or conversion to standard chow. The antiangiogenic response was followed for 4 weeks by cardiac magnetic resonance (CMR) molecular imaging with alpha(nu)beta(3)-targeted paramagnetic nanoparticles. In a second 8-week study, atherosclerotic rabbits received atorvastatin (0 or 44 mg/kg diet) alone or with alpha(nu)beta(3)-targeted fumagillin nanoparticles (only week 0 vs. weeks 0 and 4), and angiogenesis was monitored with CMR molecular imaging. Histology was performed to determine the location of bound nanoparticles and to correlate the level of CMR enhancement with the density of angiogenic vessels. RESULTS: The alpha(nu)beta(3)-targeted fumagillin nanoparticles reduced the neovascular signal by 50% to 75% at 1 week and maintained this effect for 3 weeks regardless of diet and drug dose. In the second study, atherosclerotic rabbits receiving statin alone had no antineovascular benefit over 8 weeks. The alpha(nu)beta(3)-targeted fumagillin nanoparticles decreased aortic angiogenesis for 3 weeks as in study 1, and readministration on week 4 reproduced the 3-week antineovascular response with no carry-over benefit. However, atorvastatin and 2 doses of alpha(nu)beta(3)-targeted fumagillin nanoparticles (0 and 4 weeks) achieved marked and sustainable antiangiogenesis. Microscopic studies corroborated the high correlation between CMR signal and neovessel counts and confirmed that the alpha(nu)beta(3)-targeted nanoparticles were constrained to the vasculature of the aortic adventia. CONCLUSIONS: The CMR molecular imaging with alpha(nu)beta(3)-targeted paramagnetic nanoparticles demonstrated that the acute antiangiogenic effects of alpha(nu)beta(3)-targeted fumagillin nanoparticles could be prolonged when combined with atorvastatin, representing a potential strategy to evaluate antiangiogenic treatment and plaque stability.

Efficacy and safety of right and left atrial ablations on the beating heart with irrigated bipolar radiofrequency energy: a long-term animal study.

OBJECTIVE: The Cox maze procedure is the most effective surgical treatment for atrial fibrillation; however, its complexity has limited its clinical utility. The purpose of this study was to simplify the procedure by using an irrigated bipolar radiofrequency ablation device on the beating heart without cardiopulmonary bypass. METHODS: Six domestic pigs underwent median sternotomy. The pulmonary veins were circumferentially ablated. Electrical isolation was confirmed by pacing. Eight lesions were performed epicardially, and three lesions were performed through purse-string sutures with one of the jaws of the device introduced into the right atrium. After 30 days, magnetic resonance imaging was performed to assess atrial function, pulmonary vein anatomy, and coronary artery patency. Cholinergic stimulation and burst pacing were administered to induce atrial fibrillation. Histologic assessment of the heart was performed after the animal was killed. RESULTS: A modified Cox maze procedure was successfully performed with the irrigated bipolar radiofrequency device with no deaths. In every instance, the pulmonary veins were electrically isolated. Cholinergic stimulation with burst pacing failed to produce atrial fibrillation. Imaging studies revealed tricuspid regurgitation without evidence of pulmonary vein stenosis, coronary artery stenosis, or intra-atrial thrombus. Total atrial ejection fraction was 16.9% +/- 7.5%, a significant reduction. Histologically, 99% of the lesions were transmural, and there was no evidence of coronary sinus injury. CONCLUSION: Lesions on both the right and left atria can be created successfully on the beating heart with irrigated bipolar radiofrequency. The great majority of lesions with this device were transmural. This device should not be used on valvular tissue.

Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis.

OBJECTIVE: Angiogenic expansion of the vasa vasorum is a well-known feature of progressive atherosclerosis, suggesting that antiangiogenic therapies may stabilize or regress plaques. Alpha(v)beta3 integrin-targeted paramagnetic nanoparticles were prepared for noninvasive assessment of angiogenesis in early atherosclerosis, for site-specific delivery of antiangiogenic drug, and for quantitative follow-up of response. METHODS AND RESULTS: Expression of alpha(v)beta3 integrin by vasa vasorum was imaged at 1.5 T in cholesterol-fed rabbit aortas using integrin-targeted paramagnetic nanoparticles that incorporated fumagillin at 0 microg/kg or 30 microg/kg. Both formulations produced similar MRI signal enhancement (16.7%+/-1.1%) when integrated across all aortic slices from the renal arteries to the diaphragm. Seven days after this single treatment, integrin-targeted paramagnetic nanoparticles were readministered and showed decreased MRI enhancement among fumagillin-treated rabbits (2.9%+/-1.6%) but not in untreated rabbits (18.1%+/-2.1%). In a third group of rabbits, nontargeted fumagillin nanoparticles did not alter vascular alpha(v)beta3-integrin expression (12.4%+/-0.9%; P>0.05) versus the no-drug control. In a second study focused on microscopic changes, fewer microvessels in the fumagillin-treated rabbit aorta were counted compared with control rabbits. CONCLUSIONS: This study illustrates the potential of combined molecular imaging and drug delivery with targeted nanoparticles to noninvasively define atherosclerotic burden, to deliver effective targeted drug at a fraction of previous levels, and to quantify local response to treatment.

MR tagging demonstrates quantitative differences in regional ventricular wall motion in mice, rats, and men.

Rats and genetically manipulated mouse models have played an important role in the exploration of molecular causes of cardiovascular diseases. However, it has not been fully investigated whether mice or rats and humans manifest similar patterns of ventricular wall motion. Although similarities in anatomy and myofiber architecture suggest that fundamental patterns of ventricular wall motion may be similar, the considerable differences in heart size, heart rate, and sarcomeric protein isoforms may yield quantitative differences in ventricular wall mechanics. To further our understanding of the basic mechanisms of myofiber contractile performance, we quantified regional and global indexes of ventricular wall motion in mice, rats, and men using magnetic resonance (MR) imaging. Both regular cine and tagged MR images at apical, midventricular, and basal levels were acquired from six male volunteers, six Fischer 344 rats, and seven C57BL/6 mice. Morphological parameters and ejection fraction were computed directly from cine images. Myocardial twist (rotation angle), torsion (net twist per unit length), circumferential strain, and normalized radial shortening were calculated by homogeneous strain analysis from tagged images. Our data show that ventricular twist was conserved among the three species, leading to a significantly smaller torsion, measured as net twist per unit length, in men. However, both circumferential strain and normalized radial shortening were the largest in male subjects. Although other parameters, such as circumferential-longitudinal shear strain, need to be evaluated, and the causes of these differences in contractile mechanics remain to be elucidated, the preservation of twist appears fundamental to cardiac function and should be considered in studies that extrapolate data from animals to humans.

Molecular MR imaging of melanoma angiogenesis with alphanubeta3-targeted paramagnetic nanoparticles.

Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether alpha(nu)beta(3)-targeted paramagnetic nanoparticles can detect and characterize sparse alpha(nu)beta integrin expression on neovasculature induced by nascent melanoma xenografts ( approximately 30 mm(3)) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or alpha(v)beta(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of alpha(nu)beta(3)-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.

Quantification of stenotic mitral valve area with magnetic resonance imaging and comparison with Doppler ultrasound.

OBJECTIVES: The purpose of this study was to evaluate the reliability of the pressure half-time (PHT) method for estimating mitral valve areas (MVAs) by velocity-encoded cardiovascular magnetic resonance (VE-CMR) and to compare the method with paired Doppler ultrasound. BACKGROUND: The pressure half-time Doppler echocardiography method is a practical technique for clinical evaluation of mitral stenosis. As CMR continues evolving as a routine clinical tool, its use for estimating MVA requires thorough evaluation. METHODS: Seventeen patients with mitral stenosis underwent echocardiography and CMR. Using VE-CMR, MVA was estimated by PHT method. Additionally, peak E and peak A velocities were defined. Interobserver repeatability of VE-CMR was evaluated. RESULTS: By Doppler, MVAs ranged from 0.87 to 4.49 cm2; by CMR, 0.91 to 2.70 cm2, correlating well between modalities (r = 0.86). The correlation coefficient for peak E and peak A between modalities was 0.81 and 0.89, respectively. Velocity-encoded CMR data analysis provided robust, repeatable estimates of peak E, peak A, and MVA (r = 0.99, 0.99, and 0.96, respectively). CONCLUSIONS: Velocity-encoded cardiovascular magnetic resonance can be used routinely as a robust tool to quantify MVA via mitral flow velocity analysis with PHT method.

Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles.

BACKGROUND: Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to plaque instability, however, cannot be detected directly with any current diagnostic modality. METHODS AND RESULTS: Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 80 days. alpha(v)beta3-Integrin-targeted, paramagnetic nanoparticles were injected intravenously and provided specific detection of the neovasculature within 2 hours by routine magnetic resonance imaging (MRI) at a clinically relevant field strength (1.5 T). Increased angiogenesis was detected as a 47+/-5% enhancement in MRI signal averaged throughout the abdominal aortic wall among rabbits that received alpha(v)beta3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with alpha(v)beta3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the alpha(v)beta3-targeted paramagnetic agent. MRI revealed a pattern of increased alpha(v)beta3-integrin distribution within the atherosclerotic wall that was spatially heterogeneous along both transverse and longitudinal planes of the abdominal aorta. Histology and immunohistochemistry confirmed marked proliferation of angiogenic vessels within the aortic adventitia, coincident with prominent, neointimal proliferation among cholesterol-fed, atherosclerotic rabbits in comparison with sparse incidence of neovasculature in the control animals. CONCLUSIONS: This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.

Practical value of cardiac magnetic resonance imaging for clinical quantification of aortic valve stenosis: comparison with echocardiography.

BACKGROUND: Valvular pathology can be analyzed quickly and accurately through the use of Doppler ultrasound. For aortic stenosis, the continuity equation approach with Doppler velocity-time integral (VTI) data is by far the most commonly used clinical method of quantification. In view of the emerging popularity of cardiac magnetic resonance (CMR) as a routine clinical imaging tool, the purposes of this study were to define the reliability of velocity-encoded CMR as a routine method for quantifying stenotic aortic valve area, to compare this method with the accepted standard, and to evaluate its reproducibility. METHODS AND RESULTS: Patients (n=24) with aortic stenosis (ranging from 0.5 to 1.8 cm2) were imaged with CMR and echocardiography. Velocity-encoded CMR was used to obtain velocity information in the aorta and left ventricular outflow tract. From this flow data, pressure gradients were estimated by means of the modified Bernoulli equation, and VTIs were calculated to estimate aortic valve orifice dimensions by means of the continuity equation. The correlation coefficients between modalities for pressure gradients were r=0.83 for peak and r=0.87 for mean. The measurements of VTI correlated well, leading to an overall strong correlation between modalities for the estimation of valve dimension (r=0.83, by means of the identified best approach). For 5 patients, the CMR examination was repeated using the best approach. The repeat calculations of valve size correlated well (r=0.94). CONCLUSIONS: Velocity-encoded CMR can be used as a reliable, user-friendly tool to evaluate stenotic aortic valves. The measurements of pressure gradients, VTIs, and the valve dimension correlate well with the accepted standard of Doppler ultrasound.