MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial.

AIMS: Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. METHODS AND RESULTS: In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. CONCLUSION: In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial).

BACKGROUND: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. METHODS: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. RESULTS: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). CONCLUSION: In this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00977093.

Visualization of anomalous origin and course of coronary arteries in 748 consecutive symptomatic patients by 64-slice computed tomography angiography.

BACKGROUND: Coronary artery anomalies (CAAs) are currently undergoing profound changes in understanding potentially pathophysiological mechanisms of disease. Aim of this study was to investigate the prevalence of anomalous origin and course of coronary arteries in consecutive symptomatic patients, who underwent cardiac 64-slice multidetector-row computed tomography angiography (MDCTA). METHODS: Imaging datasets of 748 consecutive symptomatic patients referred for cardiac MDCTA were analyzed and CAAs of origin and further vessel course were grouped according to a recently suggested classification scheme by Angelini et al. RESULTS: An overall of 17/748 patients (2.3%) showed CAA of origin and further vessel course. According to aforementioned classification scheme no Subgroup 1- (absent left main trunk) and Subgroup 2- (anomalous location of coronary ostium within aortic root or near proper aortic sinus of Valsalva) CAA were found. Subgroup 3 (anomalous location of coronary ostium outside normal "coronary" aortic sinuses) consisted of one patient with high anterior origin of both coronary arteries. The remaining 16 patients showed a coronary ostium at improper sinus (Subgroup 4). Latter group was subdivided into a right coronary artery arising from left anterior sinus with separate ostium (subgroup 4a; n = 7) and common ostium with left main coronary artery (subgroup 4b; n = 1). Subgroup 4c consisted of one patient with a single coronary artery arising from the right anterior sinus (RAS) without left circumflex coronary artery (LCX). In subgroup 4d, LCX arose from RAS (n = 7). CONCLUSIONS: Prevalence of CAA of origin and further vessel course in a symptomatic consecutive patient population was similar to large angiographic series, although these patients do not reflect general population. However, our study supports the use of 64-slice MDCTA for the identification and definition of CAA.

Diagnostic accuracy of quantitative cardiac MRI evaluation compared to stress single-photon-emission computed tomography.

BACKGROUND: Cardiac MRI (cMRI) perfusion is a promising non-invasive tool to assess myocardial ischemia. The accuracy of quantitative cMRI perfusion has been recently demonstrated, but to date no previous study has compared this technique with stress single-photon-emission computed tomography (SPECT). The aim of this study was to evaluate the diagnostic accuracy of myocardial perfusion reserve (MPR) based on cMRI compared with SPECT. METHODS: We examined 24 patients who underwent coronary angiography, stress SPECT and cMRI perfusion. Qualitative assessment of both SPECT and cMRI images, quantification of cMRI perfusion, and quantitative coronary angiography (QCA) were independently performed. MPR was calculated using Fermi deconvolution technique. Accuracy of quantitative and qualitative data was examined to detect > 50% diameter stenosis (DS) by QCA. RESULTS: Qualitative analysis was obtained in 198 segments and quantitative analysis was performed in 171 segments. Significant coronary artery disease (CAD) was present in 81.8% of patients. Visual cMRI assessment yielded sensitivity of 74.4% and specificity of 79.4% to predict > 50%DS, while SPECT showed sensitivity of 67.4% and specificity of 81.3%. The sensitivity for SPECT in the right coronary artery territory and apex was low compared to cMRI. Sensitivity and specificity for detection of significant CAD were 89.5% and 46.6% for MPR (cutoff 1.92). Area under the curve was 0.75 for MPR (P < 0.01). CONCLUSIONS: The diagnostic accuracy of qualitative examination of perfusion cardiac MRI and stress SPECT were comparable. The high sensitivity and low operator dependency of quantitative cMRI makes it an attractive tool to evaluate myocardial perfusion.

Safety of magnetic resonance imaging in patients with cardiovascular devices: an American Heart Association scientific statement from the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Council on Cardiovascular Radiology and Intervention: endorsed by the American College of Cardiology Foundation, the North American Society for Cardiac Imaging, and the Society for Cardiovascular Magnetic Resonance.

Advances in magnetic resonance (MR) imaging over the past 2 decades have led to MR becoming an increasingly attractive imaging modality. With the growing number of patients treated with permanent implanted or temporary cardiovascular devices, it is becoming ever more important to clarify safety issues in regard to the performance of MR examinations in patients with these devices. Extensive, although not complete, ex vivo, animal, and clinical data are available from which to generate recommendations regarding the safe performance of MR examination in patients with cardiovascular devices, as well as to ascertain caveats and contraindications regarding MR examination for such patients. Safe MR imaging involves a careful initial patient screening, accurate determination of the permanent implanted or temporary cardiovascular device and its properties, a thoughtful analysis of the risks and benefits of performing the examination at that time, and, when indicated, appropriate physician management and supervision. This scientific statement is intended to summarize and clarify issues regarding the safety of MR imaging in patients with cardiovascular devices.

Quantitative magnetic resonance perfusion imaging detects anatomic and physiologic coronary artery disease as measured by coronary angiography and fractional flow reserve.

OBJECTIVES: To evaluate the ability of quantitative perfusion cardiac magnetic resonance (CMR) to assess the hemodynamic significance of coronary artery disease (CAD) compared with well-established anatomic and physiologic techniques. BACKGROUND: Fractional flow reserve (FFR) is considered by many investigators to be a reliable stenosis-specific method to determine hemodynamically significant CAD. Quantitative perfusion CMR is a promising noninvasive approach to detect CAD but has yet to be validated against FFR. METHODS: This is a prospective study in patients with suspected CAD who underwent coronary angiography, FFR, and CMR assessments. The quantitative myocardial perfusion reserve (MPR) was calculated in 720 myocardial sectors (8 sectors/slice). The MPR was calculated from the ratio between stress and rest myocardial flow based on signal intensity time curves using deconvolution analysis. Stress was simulated with adenosine for both FFR and MPR. The MPR assessments were compared to FFR (n = 44 coronary segments) and quantitative coronary angiography (n = 108 segments) in the corresponding coronary territories. RESULTS: The MPR was 1.54 +/- 0.36 in segments with FFR < or =0.75 (n = 14) and 2.11 +/- 0.68 in those with FFR >0.75 (n = 30; p = 0.0054). An MPR cutoff of 2.04 was 92.9% (95% CI 77.9 to 100.0) sensitive and 56.7% (95% CI 32.8 to 80.6) specific in predicting a coronary segment with FFR < or =0.75. The MPR was 1.54 +/- 0.49 in coronary segments with > or =50% diameter stenosis (DS) (n = 47) and 2.13 +/- 0.80 in segments with <50% DS (n = 61; p < 0.001). An MPR cutoff of 2.04 was 85.1% (95% CI 71.1 to 99.2) sensitive and 49.2% (95% CI 33.6 to 64.8) specific in predicting CAD with > or =50% DS. CONCLUSIONS: Quantitative perfusion CMR is a safe noninvasive test that represents a stenosis-specific alternative to determine the hemodynamic significance of CAD.

Evaluation of cardiac magnetic resonance imaging parameters to detect anatomically and hemodynamically significant coronary artery disease.

BACKGROUND: Cardiac magnetic resonance (cMR) perfusion imaging is a promising technique to assess coronary artery disease (CAD). Our objective was to evaluate accuracy of various cMR imaging parameters to detect significant CAD as compared with angiography or fractional flow reserve (FFR). METHODS: We prospectively enrolled 37 patients who underwent coronary angiography, FFR, and cMR perfusion imaging. Semiquantitative assessments, namely maximum up-slope and peak-intensity indexes, were derived from time-intensity ratios between rest and stress. Myocardial perfusion reserve (MPR), calculated using Fermi deconvolution technique, was the quantitative cMR imaging parameter. Qualitative assessments were visually performed by independent analysts. Accuracy of quantitative, semiquantitative, and qualitative cMR imaging data was compared with quantitative coronary angiography in 108 segments and FFR in 44 segments. RESULTS: Sensitivity and specificity for hemodynamically significant CAD (FFR < or = 0.75) were 92.9% and 56.7%, respectively, for MPR (cutoff, 2.06). Area under the curve to detect FFR < or = 0.75 was 0.78 for MPR (P < .01), 0.63 for up-slope (P = NS), and 0.66 (P = NS) for peak intensity. Sensitivity and specificity for anatomically significant CAD (> 50% diameter stenosis [DS]) were 87.2% and 49.2%, respectively, for MPR (cutoff, 2.06). Area under the curve was 0.75 for MPR, 0.69 for up-slope, and 0.65 for peak intensity to detect > 50% DS (all P < .05). Visual assessment yielded sensitivity of 78.6% and specificity of 65.5% to predict FFR < or = 0.75 and sensitivity of 74.5% and specificity of 67.2% to predict > 50% DS. CONCLUSIONS: Myocardial perfusion reserve appears to be the most accurate index to detect anatomical and hemodynamically significant CAD. Standardization of such quantitative methods, with minimal operator dependency, would be useful for clinical and research applications.

A comparison of myocardial perfusion and rejection in cardiac transplant patients.

INTRODUCTION: Although histological evaluation of the cardiac tissue is the current gold standard for evaluation of rejection, we hypothesized that cardiac perfusion MRI is a safe non-invasive method that correlates tissue blood flow changes with biopsy proven rejection in the cardiac transplant patient. MATERIALS AND METHODS: In a retrospective study from 1984-2001, 83 patients underwent 135 MR Gd-DTPA imaging studies. In 8 patients (9%), biopsies graded 2 or higher (by ISHLT criteria) provided evidence of rejection. Patients were age and sex matched to 11 non-rejected controls for imaging analysis. Time-signal intensity curves generated for a mid-ventricle LV short axis slice during rest and adenosine stress allowed determination of myocardial blood flow (MBF, ml/min/gm). ROC curve analysis by SPSS allowed estimation of sensitivity and specificity. RESULTS: At rest, there was no difference in MBF between patients with prior rejection vs. those without (1.18 +/- 0.26 vs. 1.16 +/- 0.29). At stress there was a decrease in MBF for patients with prior rejection episodes (3.27 +/- 0.74) compared to no rejection (3.60 +/- 0.72), P = 0.067). The area under the ROC curve was 0.82, with specificity and sensitivity of 75% and 81%, respectively. CONCLUSION: This study suggests that perfusion MR imaging can be used in assessing the cardiac transplant patient for rejection related microvascular changes. The high specificity and sensitivity recorded from the ROC curve illustrates the potential utility of this diagnostic test for future studies.

Quantitative contrast enhanced magnetic resonance imaging for the evaluation of peripheral arterial disease: a comparative study versus standard digital angiography.

OBJECTIVE: The purpose of this study is to evaluate the accuracy of semiautomated analysis of contrast enhanced magnetic resonance angiography (MRA) in patients who have undergone standard angiographic evaluation for peripheral vascular disease (PVD). BACKGROUND: Magnetic resonance angiography is an important tool for evaluating PVD. Although this technique is both safe and noninvasive, the accuracy and reproducibility of quantitative measurements of disease severity using MRA in the clinical setting have not been fully investigated. METHODS: 43 lesions in 13 patients who underwent both MRA and digital subtraction angiography (DSA) of iliac and common femoral arteries within 6 months were analyzed using quantitative magnetic resonance angiography (QMRA) and quantitative vascular analysis (QVA). Analysis was repeated by a second operator and by the same operator in approximately 1 month time. RESULTS: QMRA underestimated percent diameter stenosis (%DS) compared to measurements made with QVA by 2.47%. Limits of agreement between the two methods were +/- 9.14%. Interobserver variability in measurements of %DS were +/- 12.58% for QMRA and +/- 10.04% for QVA. Intraobserver variability of %DS for QMRA was +/- 4.6% and for QVA was +/- 8.46%. CONCLUSIONS: QMRA displays a high level of agreement to QVA when used to determine stenosis severity in iliac and common femoral arteries. Similar levels of interobserver and intraobserver variability are present with each method. Overall, QMRA represents a useful method to quantify severity of PVD.

Magnetic resonance quantitative myocardial perfusion reserve demonstrates improved myocardial blood flow after angiogenic implant therapy.

PURPOSE: The purpose of this study is to follow myocardial angiogenesis temporally using quantitative magnetic resonance first pass perfusion imaging and compare this with the "gold standard" of radioactive microspheres in a random subset of animals. MATERIALS AND METHODS: Ameriod constrictors were placed around the left circumflex in 15 pigs to induce an ischemic area. Two groups were randomized to receive either a sham operation or treatment with angiogenic implants inserted into myocardium in the distribution of the left circumflex artery (LCX). These implants are designed to induce myocardial angiogenesis. Magnetic resonance first pass perfusion imaging was performed at baseline and also after treatment with either sham or implant therapy by using first pass perfusion imaging with a TurboFLASH sequence. Absolute myocardial blood flow was derived by applying a quantitative Fermi function model. Radioactive microspheres were also injected into a random subset of animals to measure myocardial blood flow. RESULTS: Angiogenic implant therapy increased absolute myocardial blood flow in the left circumflex territory relative to baseline and sham treated groups during adenosine infusion. Myocardial blood flows measured with radioactive microspheres was increased significantly in both the LCX and LAD territories during stress. Myocardial Perfusion reserve was also significantly increased in both the LCX and left anterior descending territories relative to baseline. Ejection Fraction during stress with dobutamine infusion increased significantly in the implant therapy group while that in the sham group was not affected. CONCLUSION: Quantitative MR myocardial first pass perfusion imaging can be used to track the development of angiogenesis as corroborated by radioactive microspheres. Angiogenic implant therapy is a new device based therapy that has potential to protect an ischemic region by accelerating angiogenesis although further research is necessary with this device.

Ethical considerations in CT angiography.

The rapid development and clinical deployment of CT angiography raises several important issues, including assurance of professional competence and technical quality, self-referral, the relative role of radiologists and cardiologists, appropriateness and proper indications, the detection and disposition of unexpected or incidental findings and the concern for the rapidly increasing costs of health care and imaging. These questions are properly addressed within the framework of medical ethics, including principles of beneficence, autonomy and justice.

MRI of myocardial perfusion.

An overwhelming number of myocardial perfusion studies are done by nuclear isotope imaging. Magnetic resonance imaging during the first pass of an injected, contrast bolus has some significant advantages for detection of blood flow deficits, namely higher spatial resolution, absence of ionizing radiation, and speed of the test. Previous clinical studies have demonstrated that excellent sensitivity and specificity can be achieved with MR myocardial perfusion imaging for detecting coronary artery disease, and assessment of patients with acute chest pain. Furthermore, an absolute quantification of myocardial blood flow is feasible, as was demonstrated by comparison of MR perfusion imaging, to measurements with isotope labeled microspheres in experimental models. An integrated assessment of perfusion, function, and viability, is thus feasible by MRI to answer important clinical challenges such as the identification of stunned or hibernating, but viable myocardium.

Magnetic resonance first pass perfusion imaging for detecting coronary artery disease.

Magnetic resonance first pass perfusion imaging can be used to detect abnormalities in myocardial blood flow. This technique involves imaging the first pass of gadolinium based contrast through the myocardium. Images are initially read qualitatively for areas of reduced signal intensity. Additionally, at our institution a quantitative method is applied that can aid both detection and diagnosis of perfusion defects. This method involves fitting the myocardial signal intensity curves and then calculates absolute myocardial blood flow. Our approach to first pass perfusion imaging will be reviewed. Magnetic resonance first pass perfusion imaging has a complimentary role with coronary angiography either non-invasively using CT or with catheterization. Perfusion imaging defines the physiology and angiography in the anatomy of coronary artery disease.

Cardiovascular interventional MR imaging: a new road for therapy and repair in the heart.

Over the last 5 years, interventional MR imaging has been fertile ground for research. Real-time MR imaging, combined with recent advances in other MR imaging modalities such as perfusion imaging and intravascular imaging, has opened up new paths for cardiac therapy. The recent reports on cardiac stem cell therapy guided and monitored by MR imaging suggest that we are already seeing the establishment of an important role for cardiac MR imaging in cardiac restoration. The collaborative effort from a multidisciplinary team of basic biologists, engineers, and clinicians will refine stem cell incubation and labeling for MR-guided transcatheter endomyocardial injections, and this in turn may facilitate new studies in humans. Several groups have demonstrated in animal studies the feasibility of MR-guided catheter interventions for the treatment of congenital heart disease and arrythmia therapy. Hence, applications in humans remain the challenge for the next years. Although there have been first reports of cardiac catheterizations in humans by combined use of x-ray fluoroscopy and MR imaging, there are no reports in the literature suggesting that active tracking methods by MR imaging have been applied to humans. Safety issues (namely, heating of catheters and wires) hamper clinical use, particularly in infants and children. Current reports are promising that these limitations will be overcome in the near future and will eventually reduce x-ray usage during catheterization. In its current state, cardiac MR imaging offers a unique opportunity to investigate new therapeutic strategies for the treatment of congenital and acquired heart disease.

Utility of cardiac magnetic resonance imaging in the diagnosis of hypertrophic cardiomyopathy.

BACKGROUND: Two-dimensional echocardiography is currently the standard test for the clinical diagnosis of hypertrophic cardiomyopathy (HCM). The present study was undertaken to determine whether cardiac MRI (CMR) affords greater accuracy than echocardiography in establishing the diagnosis and assessing the magnitude of left ventricular (LV) hypertrophy in HCM. METHODS AND RESULTS: Forty-eight patients (age 34+/-16 years) suspected of having HCM (or with a confirmed diagnosis) were imaged by both echocardiography and CMR to assess LV wall thickness in 8 anatomic segments (total n=384 segments) and compared in a blinded fashion. Maximum LV thickness was similar by echocardiography (21.7+/-9.1 mm) and CMR (22.5+/-9.6 mm; P=0.21). However, in 3 (6%) of the 48 patients, echocardiography did not demonstrate LV hypertrophy, and CMR identified otherwise undetected areas of wall thickening in the anterolateral LV free wall (17 to 20 mm), which resulted in a new diagnosis of HCM. In the overall study group, compared with CMR, echocardiography also underestimated the magnitude of hypertrophy in the basal anterolateral free wall (by 20+/-6%; P=0.001), as well as the presence of extreme LV wall thickness (> or =30 mm) in 10% of patients (P<0.05). CONCLUSIONS: CMR is capable of identifying regions of LV hypertrophy not readily recognized by echocardiography and was solely responsible for diagnosis of the HCM phenotype in an important minority of patients. CMR enhances the assessment of LV hypertrophy, particularly in the anterolateral LV free wall, and represents a powerful supplemental imaging test with distinct diagnostic advantages for selected HCM patients.

Recommendations of the National Heart, Lung, and Blood Institute Working Group on Future Direction in Cardiac Surgery.

New surgical procedures, imaging modalities, and medical devices have improved therapy for many patients and made treatment possible for others who have had few options in the past. In February 2004, the National Heart, Lung, and Blood Institute's (NHLBI) Advisory Council proposed that the institute evaluate the status and future directions in cardiac surgery. In response to this recommendation, the NHLBI convened a working group of cardiac surgeons on May 7 and 8, 2004, to assess the state of cardiac surgery research, identify critical gaps in current knowledge, determine areas of opportunity, and obtain specific recommendations for future research activities. The working group discussed surgical revascularization, novel surgical approaches, valvular research directions, biotechnology and cell-based therapy, heart failure, imaging modalities, and barriers to clinical research and presents its recommendations here.

Improved myocardial function after transmyocardial laser revascularization according to cine magnetic resonance in a porcine model.

OBJECTIVE: This study was undertaken to demonstrate that transmyocardial laser revascularization of hypoperfused myocardium improves regional and global myocardial function. METHODS: Cine magnetic resonance imaging was used to monitor regional wall thickening (in millimeters) and cardiac output (in milliliters per kilogram per minute). Cine magnetic resonance imaging was performed before and 8 weeks after transmyocardial laser revascularization was applied to the hypoperfused lateral wall of the left ventricle (target area) in a porcine model (n = 9, transmyocardial laser revascularization group). A second group of animals was left untreated (n = 8, control group). RESULTS: Regional wall thickening in the target area improved after transmyocardial laser revascularization (0.7 +/- 0.3 mm to 3.7 +/- 1.9 mm, P <.02) and was significantly higher (P <.01) after transmyocardial laser revascularization than in the control group, in which it did not improve (0.5 +/- 0.6 mm to 0.5 +/- 1.2 mm). Accordingly, cardiac output and microsphere-derived myocardial blood flows were significantly higher than in the control group (P <.01), and the amount of triphenyltetrazolium chloride-stained myocardium was lower (P <.01). CONCLUSION: Cine magnetic resonance imaging demonstrates improved global and regional myocardial function after transmyocardial laser revascularization in a porcine model.