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Warren J Manning

Publications and source records attributed to Warren J Manning.

At least 37 records · Page 2Linked to original sources

Meeting highlights of the 8th Annual Scientific Sessions of the Society For Cardiovascular Magnetic Resonance, January 21 to 23, 2005.

Parallel tracks for clinical scientists, basic scientists, and pediatric imagers was the novel approach taken for the highly successful 8th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance, held in San Francisco, California, January 21 to 23, 2005. Attendees were immersed in information on the latest scientific advances in cardiovascular magnetic resonance (CMR) from mice to man and technological advances from systems with field strengths from 0.5 T to 11.7 T. State-of-the-art applications were reviewed, spanning a wide range from molecular imaging to predicting outcome with CMR in large patient populations.

Adult↗

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 micromol/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 micromol/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.

Animals↗

Heterozygous knockout of neuregulin-1 gene in mice exacerbates doxorubicin-induced heart failure.

Neuregulins and their erbB receptors are essential for cardiac development and postulated to be cardioprotective in the presence of injury in the postnatal heart. We tested the hypothesis that the development of doxorubicin-induced cardiotoxicity in vivo is more severe in mice with heterozygous knockout of the neuregulin-1 gene (NRG-1(+/-)) compared with wild-type mice (WT). Three-month old NRG-1(+/-) and WT mice were injected with a single dose of doxorubicin (20 mg/kg ip). Survival was analyzed by the Kaplan-Meier approach. Left ventricular (LV) function and signaling pathways were analyzed 4 days after treatment. Fifteen days after treatment, survival was significantly lower in doxorubicin-treated NRG-1(+/-) mice (NRG-1(+/-)-Dox) compared with doxorubicin-treated WT mice (WT-Dox) (15% vs. 33%, P < 0.01). LV mass was significantly lower in NRG-1(+/-)-Dox but not in WT-Dox compared with nontreated animals. LV systolic pressure and LV midwall fractional shortening were significantly lower in NRG-1(+/-)-Dox compared with WT-Dox mice. LV protein levels of NRG-1, erbB2, and erbB4 receptors were similar in WT-Dox and NRG-1(+/-)-Dox mice. However, levels of phosphorylated erbB2, Akt, and ERK-1/2 were significantly decreased in NRG-1(+/-)-Dox compared with WT-Dox mice. A significant decrease in phosphorylated P70S6K levels was also observed in NRG-1(+/-)-Dox compared with nontreated NRG-1(+/-) mice. These results demonstrate that heterozygous knockout of the neuregulin-1 gene worsens survival and LV function in the presence of doxorubicin-induced cardiac injury in vivo. This is associated with the depression of activation of the erbB2 receptor as well as Akt, p70S6K, and ERK-1/2 pathways.

Animals↗

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 micromol/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 micromol/L. CONCLUSIONS: Molecular MR imaging with the fibrin-targeted contrast-agent EP-2104R allows selective visualization of acute coronary, cardiac, and pulmonary thrombi.

Angiography↗

Correction for heart rate variability improves coronary magnetic resonance angiography.

PURPOSE: To address degradation of coronary MR angiography (MRA) image quality due to heart rate variability (HRV)-associated variations in coronary artery position and motion. MATERIALS AND METHODS: Free-breathing navigator-gated and -corrected coronary MRA using subject-specific trigger delays and acquisition windows was combined with a real-time HRV correction algorithm, such as commonly used in left ventricular wall motion studies. Ten healthy adults underwent free-breathing navigator-gated and -corrected coronary MRA with and without HRV correction. Signal-to-noise (SNR), contrast-to-noise (CNR), vessel length, diameter, sharpness, and subjective image quality (on a five-point scale) were compared in a blinded fashion. RESULTS: Vessel sharpness improved significantly for both the left (LCA) and right (RCA) coronary artery systems (P = 0.016 and P = 0.015, respectively) with the use of HRV correction. Subjective image quality also improved significantly when HRV correction was used (P = 0.003). There were no significant differences with regard to SNR and CNR (P > 0.1). CONCLUSIONS: Preliminary results suggest that HRV correction improves objective and subjective image quality in coronary MRA. Continued studies in patients with known or suspected coronary artery disease are warranted to investigate the clinical impact of this technique.

Adolescent↗

Effect of raloxifene on aortic elasticity in healthy postmenopausal women.

BACKGROUND: The effect of raloxifene on aortic elasticity in healthy postmenopausal women is unknown. The purpose of the present study was to examine the effect of raloxifene on aortic elasticity and cardiovascular structure and function in healthy postmenopausal women. METHODS: A randomized, crossover, double-blind, placebo-controlled clinical trial was performed. Fourteen healthy postmenopausal women received treatment with raloxifene 60 mg daily and matching placebo for 8 weeks with an 8-week washout period in between the 2 treatment periods. Cardiovascular magnetic resonance imaging was used to assess ascending thoracic and abdominal aortic elasticity and cardiovascular structure and function (left ventricular volumes, ejection fraction, and mass and mitral annular displacement) before and at the end of each treatment period. RESULTS: Administration of raloxifene had no significant effect on either heart rate or systemic blood pressure. Raloxifene treatment was associated with a small decrease of the ascending aorta wall thickness (pretreatment 2.4 +/- 0.3 vs posttreatment 2.2 +/- 0.2 mm, P = .01). Consequently, there was an increase in the Young's elastic modulus after raloxifene treatment at the ascending thoracic aorta but not the abdominal aorta. There were no significant differences in aortic compliance or any cardiac indexes after raloxifene treatment. CONCLUSIONS: Raloxifene administration in healthy postmenopausal women over an 8-week period may decrease the aortic wall thickness but has no significant effects on aortic compliance or cardiac structure and function.

Aorta↗

Coronary magnetic resonance imaging: current state-of-the-art.

Over the past decade, coronary magnetic resonance imaging has been transformed from a scientific curiosity to a clinically useful imaging tool for patients with known or suspected anomalous coronary arteries or coronary artery aneurysms and for assessment of coronary artery bypass graft patency. Coronary magnetic resonance imaging also appears to be of clinical value for assessment of native vessel integrity in selected patients, especially those patients with suspected left main/multivessel disease. Among patients referred for X-ray angiography, a normal coronary magnetic resonance imaging strongly suggests the absence of severe multivessel disease. Technical and methodological advances in motion suppression, along with increasing clinical experience will no doubt facilitate improved visualization of the distal and branch vessel.

Blood Vessel Prosthesis Implantation↗

Comparison of 3D segmented gradient-echo and steady-state free precession coronary MRI sequences in patients with coronary artery disease.

OBJECTIVE: Our objective was to compare two state-of-the-art coronary MRI (CMRI) sequences with regard to image quality and diagnostic accuracy for the detection of coronary artery disease (CAD). SUBJECTS AND METHODS: Twenty patients with known CAD were examined with a navigator-gated and corrected free-breathing 3D segmented gradient-echo (turbo field-echo) CMRI sequence and a steady-state free precession sequence (balanced turbo field-echo). CMRI was performed in a transverse plane for the left coronary artery and a double-oblique plane for the right coronary artery system. Subjective image quality (1- to 4-point scale, with 1 indicating excellent quality) and objective image quality parameters were independently determined for both sequences. Sensitivity, specificity, and accuracy for the detection of significant (> or = 50% diameter) coronary artery stenoses were determined as defined in invasive catheter X-ray coronary angiography. RESULTS: Subjective image quality was superior for the balanced turbo field-echo approach (1.8 +/- 0.9 vs 2.3 +/- 1.0 for turbo field-echo; p < 0.001). Vessel sharpness, signal-to-noise ratio, and contrast-to-noise ratio were all superior for the balanced turbo field-echo approach (p < 0.01 for signal-to-noise ratio and contrast-to-noise ratio). Of the 103 segments, 18% of turbo field-echo segments and 9% of balanced turbo field-echo segments had to be excluded from disease evaluation because of insufficient image quality. Sensitivity, specificity, and accuracy for the detection of significant coronary artery stenoses in the evaluated segments were 92%, 67%, 85%, respectively, for turbo field-echo and 82%, 82%, 81%, respectively, for balanced turbo field-echo. CONCLUSION: Balanced turbo field-echo offers improved image quality with significantly fewer nondiagnostic segments when compared with turbo field-echo. For the detection of CAD, both sequences showed comparable accuracy for the visualized segments.

Aged↗

Computed tomography and magnetic resonance imaging of the pericardium: anatomy and pathology.

The purpose of this article is to review the characteristics of computed tomography (CT) and magnetic resonance imaging (MRI) of the pericardium and pericardial diseases. Because patients with pericardial diseases usually present with nonspecific symptoms, these diseases may not be detected until they have reached an advanced stage. It is therefore important to distinguish between normal pericardial structure and disease. Multiplanar reconstruction images of CT and MRI are useful for evaluating faint changes of the pericardium. The specific pericardial diseases described in this article include pericardial cyst, constrictive pericarditis, pericarditis with radiation pericarditis, postoperative pericardial hematoma, and cardiac tamponade due to a paracardiac mass (lymphoma).

Heart Diseases↗

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 micromol 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 (approximately 250 micromol/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 micromol/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.

Animals↗

In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent.

BACKGROUND: Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis. METHODS AND RESULTS: Fifteen male New Zealand White rabbits (weight, approximately 3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell's viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as "hot spots" after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology. CONCLUSIONS: We demonstrate the feasibility of in vivo "molecular" MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.

Acute Disease↗

Free-breathing 3D steady-state free precession coronary MR angiography with radial k-space sampling: comparison with cartesian k-space sampling and cartesian gradient-echo coronary MR angiography--pilot study.

The authors compared radial steady-state free precession (SSFP) coronary magnetic resonance (MR) angiography, cartesian k-space sampling SSFP coronary MR angiography, and gradient-echo coronary MR angiography in 16 healthy adults and four pilot study patients. Standard gradient-echo MR imaging with a T2 preparatory pulse and cartesian k-space sampling was the reference technique. Image quality was compared by using subjective motion artifact level and objective contrast-to-noise ratio and vessel sharpness. Radial SSFP, compared with cartesian SSFP and gradient-echo MR angiography, resulted in reduced motion artifacts and superior vessel sharpness. Cartesian SSFP resulted in increased motion artifacts (P <.05). Contrast-to-noise ratio with radial SSFP was lower than that with cartesian SSFP and similar to that with the reference technique. Radial SSFP coronary MR angiography appears preferable because of improved definition of vessel borders.

Adult↗