Elmar Spuentrup

Noninvasive Coronary Vessel Wall and Plaque Imaging With Magnetic Resonance Imaging

Background—Conventional x-ray angiography frequently underestimates the true burden of atherosclerosis. Although intravascular ultrasound allows for imaging of coronary plaque, this invasive technique is inappropriate for screening or serial examinations. We therefore sought to develop a noninvasive free-breathing MR technique for coronary vessel wall imaging. We hypothesized that such an approach would allow for in vivo imaging of coronary atherosclerosis. Methods and Results—Ten subjects, including 5 healthy adult volunteers (aged 35±17 years, range 19 to 56 years) and 5 patients (aged 60±4 years, range 56 to 66 years) with x-ray–confirmed coronary artery disease (CAD), were studied with a T2-weighted, dual-inversion, fast spin-echo MR sequence. Multiple adjacent 5-mm cross-sectional images of the proximal right coronary artery were obtained with an in-plane resolution of 0.5×1.0 mm. A right hemidiaphragmatic navigator was used to facilitate free-breathing MR acquisition. Coronary vessel wall images were readily acquired in all subjects . Both coronary vessel wall thickness (1.5±0.2 versus 1.0±0.2 mm) and wall area (21.2±3.1 versus 13.7±4.2 mm2) were greater in patients with CAD (both P <0.02 versus healthy adults). Conclusions—In vivo free-breathing coronary vessel wall and plaque imaging with MR has been successfully implemented in humans. Coronary wall thickness and wall area were significantly greater in patients with angiographic CAD. The presented technique may have potential applications in patients with known or suspected atherosclerotic CAD or for serial evaluation after pharmacological intervention.

In Vivo Magnetic Resonance Imaging of Coronary Thrombosis Using a Fibrin-Binding Molecular Magnetic Resonance Contrast Agent

Background—The advent of fibrin-binding molecular magnetic resonance (MR) contrast agents and advances in coronary MRI techniques offers the potential for direct imaging of coronary thrombosis. We tested the feasibility of this approach using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis. Methods and Results—Ex vivo and in vivo sensitivity of coronary MR thrombus imaging was tested by use of intracoronarily delivered Gd-DTPA–labeled fibrinogen thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was induced by x-ray–guided placement of thrombogenic-coated, MR-lucent stents (n=5). After stent placement, 60 &mgr;mol of EP-2104R was injected via the left main coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and thrombus imaging were performed (1) before and after stent placement and (2) before and after EP-2104R. Thrombi were confirmed by x-ray angiography and autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled fibrinogen clots (≈250 &mgr;mol/L Gd) were visible on MRI and subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to 147 &mgr;mol/L Gd. Conclusions—We demonstrate the feasibility of MRI of coronary thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR contrast agent. Potential applications include detection of coronary in-stent thrombosis or thrombus burden in patients with acute coronary syndromes.

3D coronary vessel wall imaging utilizing a local inversion technique with spiral image acquisition

Current 2D black blood coronary vessel wall imaging suffers from a relatively limited coverage of the coronary artery tree. Hence, a 3D approach facilitating more extensive coverage would be desirable. The straightforward combination of a 3D‐acquisition technique together with a dual inversion prepulse can decrease the effectiveness of the black blood preparation. To minimize artifacts from insufficiently suppressed blood signal of the nearby blood pools, and to reduce residual respiratory motion artifacts from the chest wall, a novel local inversion technique was implemented. The combination of a nonselective inversion prepulse with a 2D selective local inversion prepulse allowed for suppression of unwanted signal outside a user‐defined region of interest. Among 10 subjects evaluated using a 3D‐spiral readout, the local inversion pulse effectively suppressed signal from ventricular blood, myocardium, and chest wall tissue in all cases. The coronary vessel wall could be visualized within the entire imaging volume. Magn Reson Med 46:848–854, 2001.

Molecular Magnetic Resonance Imaging of Coronary Thrombosis and Pulmonary Emboli With a Novel Fibrin-Targeted Contrast Agent

Background—The differential diagnosis of acute chest pain is challenging, especially in patients with normal ECG findings, and may include coronary thrombosis or pulmonary emboli. The aim of this study was to investigate the novel fibrin-specific contrast agent EP-2104R for molecular targeted MR imaging of coronary thrombosis and pulmonary emboli. Methods and Results—Fresh clots were engineered ex vivo from human blood and delivered in the lungs and coronary arteries of 7 swine. Subsequent molecular MR imaging was performed with a navigator-gated free-breathing and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence before and after systemic administration of 7.5 &mgr;mol/kg EP-2104R. Two swine served as the control group. MR images were analyzed by 2 investigators, and contrast-to-noise ratio and gadolinium concentration in the clots were assessed. Before contrast media application, no thrombi were visible. After contrast administration, all 32 pulmonary emboli, 3 emboli in the right heart, and 5 coronary thrombi were selectively visualized as white spots with a mean contrast-to-noise ratio of 32±19. The average gadolinium concentration from all 3 types of thrombi was 144±79 &mgr;mol/L. Conclusions—Molecular MR imaging with the fibrin-targeted contrast-agent EP-2104R allows selective visualization of acute coronary, cardiac, and pulmonary thrombi.

Thrombus imaging with fibrin-specific gadolinium-based MR contrast agent EP-2104R: results of a phase II clinical study of feasibility.

Purpose:To determine the feasibility of detecting thrombi using a fibrin-specific gadolinium-based magnetic resonance imaging contrast agent, EP-2104R. Methods:Subjects with confirmed thrombus in the venous system (n = 14), or in the heart, or arterial system (n = 38) were enrolled. Patients were imaged before and at various times following a 4 μmol/kg intravenous bolus injection of EP-2104R: <1 hour (N = 16), 2 to 6 hours (N = 36), and/or 20 to 36 hours (N = 33). Images were assessed by investigators at each site and by a single reader not affiliated with the sites to determine whether thrombi were visible, not visible, or further enhanced with EP-2104R. A subset of data was analyzed quantitatively by measuring a signal intensity relative to background tissue. Results:Overall, 29 thrombi were visible before contrast administration, 3 of 14 in the venous system, and 26 of 38 in the arteries and heart. Thrombi generally enhanced in signal after EP-2104R injection, and an additional 7 were visualized. After contrast, 4 of 14 thrombi were visible in the venous system, and 32 of 38 in the arteries and heart. Thrombi were more conspicuous when imaged at 2 to 6 hours post EP-2104R compared with within 1 hour, because of lower blood background. Quantitatively, the post: pre signal intensity ratio was 1.90 at 2 to 6 hours post injection (standard deviation = 1.08, N = 20, P < 0.001); and 2.04 (standard deviation = 1.29, N = 19, P < 0.0025) for the 20 to 36 hours time point. There were no serious adverse events considered related to study drug. Conclusion:EP-2104R enhanced magnetic resonance imaging detects thrombi not readily visible in precontrast screening and gives additional enhancement of thrombi that are visible in precontrast imaging.

Molecular magnetic resonance imaging of atrial clots in a swine model.

Background—The detection and differentiation of intracardiac masses is still challenging and may include neoplasms and thrombi. The aim of this study was the investigation of a targeted, fibrin-specific contrast agent (EP-2104R) for molecular targeted magnetic resonance imaging (MRI) of left atrial clots. Methods and Results—Chronic human thrombi were surgically implanted in the left atrial appendage of 5 swine. Molecular MRI was performed with a navigator-gated, free-breathing, cardiac-triggered 3D inversion-recovery, black-blood, gradient-echo sequence before and after systemic administration of 4 &mgr;mol/kg EP-2104R. MR images were analyzed by 2 investigators, and the contrast-to-noise ratio was calculated. Location of clots was confirmed by autopsy, and the gadolinium concentration in the clots was assessed. Before contrast agent administration, thrombi were not visible on black-blood MR images. After contrast administration, all atrial clots (n=5) were selectively visualized as white spots with a high contrast-to-noise ratio (clot/blood, 29.7±8.0). The gadolinium concentration in the clots averaged 74±45 &mgr;mol/L. Conclusions—The fibrin-specific MR contrast agent EP-2104R allows for selective and high-contrast visualization of left atrial clots by means of molecular targeted MRI.

Navigator-gated free-breathing three-dimensional balanced fast field echo (TrueFISP) coronary magnetic resonance angiography

Spuentrup E, Börnert P, Botnar RM, et al. Navigator-gated free-breathing 3D balanced fast field echo (trueFISP) coronary magnetic resonance angiography. Invest Radiol 2002;37: 637–642. Rationale and Objectives.Recent developments of MR imaging equipment enabled high-quality steady state-free-precession (Balanced FFE, True-FISP) MR-imaging with a substantial ‘T2 like’ contrast, resulting in a high signal intensity of the blood-pool without the application of exogenous contrast agents. It is hypothesized that Balanced-FFE may be valuable for contrast enhancement in 3D free-breathing coronary MRA. Materials and Methods.Navigator-gated free-breathing cardiac triggered coronary MRA was performed in 10 healthy adult subjects and three patients with radiograph defined coronary artery disease using a segmented k-space 3D Balanced FFE imaging sequence. Results.High contrast-to-noise ratio between the blood-pool and the myocardium (29 ± 8) and long segment visualization of both coronary arteries could be obtained in about 5 minutes during free breathing using the present navigator-gated Balanced-FFE coronary MRA approach. First patient results demonstrated successful display of coronary artery stenoses. Conclusion.Balanced FFE offers a potential alternative for endogenous contrast enhancement in navigator-gated free-breathing 3D coronary MRA. The obtained results together with the relatively short scanning time warrant further studies in larger patient collectives.

Magnetic resonance-guided placement of atrial septal closure device in animal model of patent foramen ovale

Background—Percutaneous closure of the patent foramen ovale (PFO) is usually performed under x-ray in combination with ultrasound guidance. We tested the feasibility of applying magnetic resonance (MR) guidance for percutaneous closure of PFO in an animal model, thus avoiding the disadvantage of ionizing radiation. Methods and Results—Real-time MRI with radial or spiral k-space filling (15 frames per second) on an interventional 1.5-T high-field whole-body system was exploited to examine the feasibility of MR-guided closure of the PFO in 7 piglets weighing ≈14 kg. A specially designed prototype nonmagnetic closure device was introduced via the femoral vein. The short bore of the magnet and in-room monitors allowed for visualization and steering of the catheter with the loaded occluder. Catheterization of the left atrium and, finally, correct placement of the device was possible in all animals. Deployment of the device was depicted by real-time MR, and initial misplacement, which occurred in 2 animals, was easily detected and corrected. Conclusions—Real-time MR guidance of PFO closure, without the use of ionizing radiation, is feasible in an animal model.

A feasibility study of contrast enhancement of acute myocardial infarction in multislice computed tomography: comparison with magnetic resonance imaging and gross morphology in pigs.

Introduction:Late enhancement magnetic resonance imaging (MRI) of myocardial infarction (MI) is clinically established. There are no reports on MI assessment using state-of-the-art multislice CT technology. For this reason, animal experiments were conducted to examine the applicability of contrast-enhanced ECG-gated multislice computed tomography (MSCT) for the detection of acute MI. The results were correlated with MRI and postmortem tissue staining. Material and Methods:Acute MI was induced in 14 pigs by balloon occlusion of the LAD. In 8 animals, the LAD was reperfused after 45 minutes. In 6 animals, the LAD was permanently blocked. MR imaging was performed 15 minutes after the administration of 0.2 mmol Gd-DTPA/kg/bodyweight. Subsequently, 16-slice MSCT was performed at various timepoints after injecting 120 mL of iodinated contrast medium. 2,3,5-Triphenyltetrazolin-chloride (TTC) staining was acquired for all hearts investigated. Correlation analysis was applied to compare the area of MI derived from MRI, MSCT, and TTC. The reperfused infarcts were compared with the nonreperfused infarcts using an unpaired t test. Results:Mean infarct area as measured by TTC staining was 18.3% ± 7.8% of the left ventricular area. Good correlation of the spatial extent of the infarcted area was found for TTC and MRI as well as for TTC and MSCT data obtained 5 minutes postcontrast injection. MSCT imaging demonstrated a significant difference in density (P < 0.001) between nonreperfused (47.0 ± 6.6 HU) and reperfused (116.4 ± 19.8 HU) infarction. Conclusion:In our pilot study, contrast-enhanced MSCT was feasible to assess myocardial viability in pigs. MSCT also affords differentiation of nonreperfused and reperfused acute MI. MI sizes derived from MSCT imaging correlate well to those obtained with MRI and TTC.

Three‐dimensional high‐resolution fast spin‐echo coronary magnetic resonance angiography

Due to SNR constraints, current “bright‐blood” 3D coronary MRA approaches still suffer from limited spatial resolution when compared to conventional x‐ray coronary angiography. Recent 2D fast spin‐echo black‐blood techniques maximize signal for coronary MRA at no loss in image spatial resolution. This suggests that the extension of black‐blood coronary MRA with a 3D imaging technique would allow for a further signal increase, which may be traded for an improved spatial resolution. Therefore, a dual‐inversion 3D fast spin‐echo imaging sequence and real‐time navigator technology were combined for high‐resolution free‐breathing black‐blood coronary MRA. In‐plane image resolution below 400 μm was obtained. Magn Reson Med 45:206–211, 2001.