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Stefan Neubauer

Publications and source records attributed to Stefan Neubauer.

At least 73 records · Page 4Linked to original sources
PubMed2004

Effects of off-pump versus on-pump coronary surgery on reversible and irreversible myocardial injury: a randomized trial using cardiovascular magnetic resonance imaging and biochemical markers.

BACKGROUND: There is biochemical evidence that off-pump coronary artery bypass grafting (OPCABG) reduces myocardial injury compared with the use of cardiopulmonary bypass (ONCABG), but the functional significance of this is uncertain. We hypothesized that OPCABG surgery would result in reduced postoperative reversible (stunning) and irreversible myocardial injury, as assessed by cardiovascular MRI (CMRI). METHODS AND RESULTS: In a single-center randomized trial, 60 patients undergoing multivessel total arterial revascularization were randomly assigned: 30 to OPCABG and 30 to ONCABG. Patients underwent preoperative and early postoperative cine MRI for assessment of global left ventricular function, and contrast-enhanced CMRI for assessment of irreversible myocardial injury. Serial troponin I measurements were obtained perioperatively and correlated with the CMRI findings. The mean preoperative cardiac index was similar in the 2 surgical groups (2.9+/-0.7 ONCABG; 2.9+/-0.8 OPCABG; P=0.9). After surgery, the cardiac index was significantly higher in the OPCABG group (2.7+/-0.6 ONCABG; 3.2+/-0.8 OPCABG; P=0.04). New irreversible myocardial injury was similar in incidence (36% ONCABG; 44% OPCABG; P=0.8) and magnitude (6.3+/-3.6 g ONCABG; 6.8+/-4.0 g OPCABG; P=0.9) across the 2 groups. The median area-under-the-curve (AUC) troponin I values were significantly larger in the ONCABG group (182 versus 135 microg/L; P=0.02). There was a moderate correlation between the troponin I AUC values and mean mass of new myocardial hyperenhancement (r(2)=0.4; P=0.008). CONCLUSIONS: OPCABG results in significantly better left ventricular function early after surgery but does not reduce the incidence or extent of irreversible myocardial injury.

Cardiopulmonary Bypass↗
PubMed2004

Assessment of motion gating strategies for mouse magnetic resonance at high magnetic fields.

PURPOSE: To assess the performance of motion gating strategies for mouse cardiac magnetic resonance (MR) at high magnetic fields by quantifying the levels of motion artifact observed in images and spectra in vivo. MATERIALS AND METHODS: MR imaging (MRI) of the heart, diaphragm, and liver; MR angiography of the aortic arch; and slice-selective 1H-spectroscopy of the heart were performed on anesthetized C57Bl/6 mice at 11.75 T. Gating signals were derived using a custom-built physiological motion gating device, and the gating strategies considered were no gating, cardiac gating, conventional gating (i.e., blanking during respiration), automatic gating, and user-defined gating. Both automatic and user-defined modes used cardiac and respiratory gating with steady-state maintenance during respiration. Gating performance was assessed by quantifying the levels of motion artifact observed in images and the degree of amplitude and phase stability in spectra. RESULTS: User-defined gating with steady-state maintenance during respiration gave the best performance for mouse cardiac imaging, angiography, and spectroscopy, with a threefold increase in signal intensity and a sixfold reduction in noise intensity compared to cardiac gating only. CONCLUSION: Physiological gating with steady-state maintenance during respiration is essential for mouse cardiac MR at high magnetic fields.

Animals↗
PubMed2004

High-resolution, multicontrast three-dimensional-MRI characterizes atherosclerotic plaque composition in ApoE-/- mice ex vivo.

PURPOSE: To systematically investigate intrinsic MR contrast mechanisms that would facilitate plaque characterization and quantification in the aortic root and brachiocephalic artery of ApoE-/- mice ex vivo. MATERIALS AND METHODS: To establish unambiguous MR parameters for routinely analyzing atherosclerotic plaque ex vivo at 11.7 T, relaxation times of plaque components were quantitatively assessed. Magnetization transfer and lipid-proton three-dimensional MR imaging was investigated for visualization of collagen- and lipid-rich plaque regions, respectively. A three-dimensional multiecho sequence with a spatial resolution of 47 x 47 x 63 microm was implemented providing a variable degree of T2-weighting. RESULTS: Relaxation time measurements showed clear tissue heterogeneity between atherosclerotic plaque components in the T2-values, but similar T1-values at 11.7 T (T1/T2 mean +/- SD; cellular plaque component: 1.2 +/- 0.3 seconds/26.3 +/- 0.4 msec; fibrofatty plaque component: 1.1 +/- 0.2 seconds/13.7 +/- 2.0 msec). The three-dimensional multiecho sequence allowed the calculation of the intrinsic proton density and T2-maps. The sum of the multiecho data provided strong T2-weighting that facilitated quantification of various components of atherosclerotic plaque in the mouse aortic root and correlated well with histology (P < 0.0001). CONCLUSION: High-resolution MRI allows for accurate classification and quantification of atherosclerotic plaque components in the aortic root of mice.

Animals↗
PubMed2004

Human imaging of phosphorus in cortical and trabecular bone in vivo.

Phosphorus was imaged in vivo in human cortical and trabecular bone and the T(1) and T(2) (*) were measured. An ultrashort TE (UTE) pulse sequence (TE = 70 microm) was used with half pulse excitation and radial mapping of k-space from the center out. T(2) (*) was measured using multiple echo times and T(1) was measured both by saturation recovery and by a method using different RF pulse amplitudes. Seven normal subjects (32-85 years) were examined. Phosphorus was imaged, with a true in-plane resolution of 2.9 x 2.9 mm and a signal-to-noise ratio (SNR) of 19:1, in both cortical and trabecular bone. The mean T(2) (*) value was 207 +/- 12 micros, and the mean T(1) value was 8.6 +/- 3.0 sec. Images and measurements were obtained in realistic times on a clinical MR system. This may provide a new approach to characterizing disease of bone.

Adult↗
PubMed2004

Time course of 23Na signal intensity after myocardial infarction in humans.

Experimental studies demonstrated persistently increased 23Na content in nonviable myocardium post-myocardial infarction (MI). We hypothesized that nonviable myocardium in humans would show elevated 23Na content at all stages of infarct development, and therefore could be imaged with 23Na MRI. Ten patients were examined on days 4, 14, and 90 after infarction, and five of these patients participated in a 12-month follow-up. Double angulated short-axis cardiac 23Na images were obtained with the use of a 23Na surface coil and an ECG-triggered, 3D gradient-echo sequence. 1H T2-weighted imaging (N = 9) was performed on days 4, 14, and 90. Wall motion was assessed by cine MRI, and the infarct size was determined by late enhancement on day 90. The 23Na signal intensity (SI) of infarcted myocardium was expressed as the percentage increase over 23Na SI of noninfarcted myocardium. All of the patients showed an area of elevated SI on 23Na and 1H T2-weighted images that correlated with wall motion abnormalities and late enhancement. 23Na SI was highest on day 4. It then decreased until day 90, but remained elevated (39% +/- 18%, 31% +/- 17%, 28% +/- 13% on days 4, 14, and 90, respectively, P = 0.001). No further decrease was found 1 year after infarction (25% +/- 7%, P = 0.89 vs. day 90). 1H T2-weighted SI decreased between days 4 and 14, but on day 90 only six of nine patients had a residual elevated SI. Thus, 23Na SI is elevated in nonviable infarction at all time points following MI, and 23Na MRI may become a suitable technique for imaging nonviable myocardium in humans.

Adult↗
PubMed2004

In vivo cardiac 1H-MRS in the mouse.

The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero-order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 microl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/- mice. This is the first study to report the application of cardiac 1H-MRS in mice in vivo.

Animals↗
PubMed2004

Resolution of ventricular thrombus identified by contrast enhanced cardiac MRI.

A 53 year old man was referred for a contrast enhanced cardiovascular magnetic resonance (CMR) scan for assessment of anterior myocardial wall viability. An earlier coronary angiogram had shown a mid left anterior descending artery (LAD) occlusion, and echocardiography had shown mildly reduced global left ventricular function without any other abnormalities. Cine CMR images (steady state free precession sequence) showed a dilated left ventricle (LV) with reduced global systolic function [End-diastolic volume 224 mls (NR 77-195 mls); end-systolic volume 124 mis (NR 19-72 mls); ejection fraction 45%]. There was wall thinning and akinesis of the anteroapical wall and severe hypokinesis of the mid anteroseptal wall. Postgadolinium images (segmented inversion recovery turboFLASH sequence) revealed a prominent LV apical thrombus which measured 1.4 cm at greatest diameter (Figure 1). Using the late gadolinium technique there was extensive (mainly transmural) hyperenhancement (HE) involving the mid and apical septum and the apex. The patient was commenced on warfarin. A second CMR scan repeated after 4 months of warfarin therapy showed complete resolution of the thrombus in the early and late post-gadolinium images (Figures 2 and 3). CMR imaging post-contrast administration is a sensitive tool in the detection of left ventricular thrombi, and overcomes some of the near-field limitations of 2D echocardiography.

Anticoagulants↗
PubMed2004

Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging.

BACKGROUND: Delayed contrast-enhanced magnetic resonance imaging (ceMRI) has been shown to identify areas of irreversible myocardial injury due to infarction (MI) with high spatial resolution, allowing precise quantification of nonviable (hyperenhanced) myocardium. The aim of our study was to investigate the size of nonviable myocardium quantitatively as a function of time post-contrast when inversion time is held constant in patients post-myocardial infarction using two contrast agent (CA) doses. METHODS: Nine patients with chronic MI underwent two MR scans on a 1.5 Tesla system. Contrast-enhanced MRI data in two short-axis (SA) slices were continuously acquired until 40 minutes after CA injection [gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), 0.1 mmol/kg body weight = single dose] interrupted only for a complete stack of SA slices encompassing the entire left ventricle (LV) between minutes 20 and 28. Left ventricular mass showing hyperenhancement was determined. The measurement was repeated on the subsequent day with double dose CA (0.2 mmol/kg body weight). Differences of signal intensities for hyperenhanced, nonhyperenhanced myocardium, and LV cavity were calculated. RESULTS: Total mass of hyperenhancement from a complete SA stack acquired between minutes 20 and 28 was lower for single dose CA [9.0% vs. 14.2% for single and double dose, respectively (p = 0.03)]. Ten to 18 minutes after CA injection, there was no significant difference between the two doses and to an internal reference for both single and double dose. For single dose the image contrast between hyperenhancement and LV cavity was superior (minutes 10 to 16, p < 0.05) but inferior between hyperenhanced and nonhyperenhanced myocardium (minutes 6 to 16, p < 0.05). CONCLUSION: Myocardial infarct size measurements are a function of time postcontrast when inversion time is held constant regardless of the contrast agent dose. These data underscore the fact that a standardized imaging protocol that defines how the appropriate inversion time should be selected is needed for comparison of results obtained at various cMR sites.

Contrast Media↗
PubMed2004

Anteroseptal or apical myocardial infarction: a controversy addressed using delayed enhancement cardiovascular magnetic resonance imaging.

AIM: Delayed enhancement MRI (DE-MRI) of the heart has been shown to reliably identify areas of irreversible myocardial damage. We sought to determine if the term anteroseptal MI is appropriate by correlating electrocardiographic, angiographic, cine MRI and DE-MRI findings. METHODS AND RESULTS: Nineteen patients admitted to our hospital with their first acute anterior MI and whose ECG showed new Q waves in leads V1-V4 were studied. All patients underwent cardiac catheterization, cine MRI, and DE-MRI. The mean left ventricular ejection fraction was 53%+/-16%. All 19 patients had evidence of delayed hyperenhancement in one or more myocardial segments (mean number of affected segments 5.5+/-2.1). The mean mass of hyperenhanced myocardium was 14+/-8 grams, or 10%+/-6% of absolute LV mass. Nineteen (100%) and 15 (79%) patients showed evidence of delayed hyperenhancement of the apex and apical anterior segments respectively. Seven (37%) patients showed evidence of mid ventricular anteroseptal hyperenhancement and none had any hyperenhancement of basal anteroseptal segments. CONCLUSION: High resolution cardiac MRI applied in patients with acute infarction and new Q waves in leads V1-V4 demonstrates the presence of predominantly apical, but not isolated septal or anteroseptal infarction.

Coronary Angiography↗
PubMed2004

Accuracy of quantitative MR vessel wall imaging applying a semi-automated gradient detection algorithm--a validation study.

UNLABELLED: Magnetic resonance imaging (MRI) is uniquely suited to study the pathophysiology of arteriosclerosis. So far, magnetic resonance (MR) measurements of vessel dimensions have mainly been done by manual tracing of vessel wall contours. However, such data postprocessing is very time-consuming and has limited accuracy due to difficulties in precise tracing of the thin vessel wall. PURPOSE: To assess the accuracy and reproducibility of quantitative vascular MR imaging applying a data analysis method based on (1) vessel wall unwrapping, followed by (2) a gradient detection algorithm for MR data postprocessing. Vascular MR imaging studies were done both in vessel phantoms and in healthy volunteers (n=29) on a clinical 1.5 T MR scanner. A dark blood double-inversion turbo spin echo sequence with fat suppression was applied, with proton-density-weighted and breath-hold acquisition for aortic imaging and T2-weighted acquisition for carotid imaging. Intraobserver and interobserver variability were systematically evaluated by two independent observers. A repeat study within 10 days of the first MRI was performed in 10 of these subjects for assessment of interstudy reproducibility. RESULTS: The semiautomated edge detection software revealed a clear view of the inner and outer vessel wall boundaries both in the phantoms and in the volunteers studied. There was close agreement between MR-derived measurements and phantom dimensions (mean difference of 1.1+/-16.9 mm2, 8.0+/-19.9 mm2, 9.0+/-12.1 mm2 for vessel wall cross-sectional area, inner vessel area, and total vessel area, respectively). Quantification of vessel dimensions was feasible in all 29 healthy volunteers studied. Semiautomated quantification of cross-sectional vessel wall area (mean+/-SD, 253.6+/-208.4 mm2) revealed close correlation for repeated measurements by one or two observers (r=0.99 each). Both intraobserver and interobserver variability of vessel wall area MR measurements were low (mean difference 7.5+/-16.7 mm2 and 14.4+/-24.6 mm2 , respectively). In the repeat study of 10 volunteers, MRI with semiautomated postprocessing quantitation revealed a high correlation and agreement of vessel dimensions between the two scans (r=0.994, mean difference 2.6+/-25.1 mm2). CONCLUSION: Semiautomated analysis methods can provide approaches that benefit from the human understanding of the image and the computer's ability to measure precisely and rapidly. Thus, by combining the latest MRI methods and semiautomated image analysis methods, we are now able to reproducibly determine the geometric parameters of blood vessels.

Adult↗
PubMed2004

Heart rate reduction by zatebradine reduces infarct size and mortality but promotes remodeling in rats with experimental myocardial infarction.

The importance of heart rate for left ventricular remodeling and prognosis after myocardial infarction is not known. We examined the contribution of heart rate reduction by zatebradine, a direct sinus node inhibitor without negative inotropic effects on left ventricular function and dilatation, on mortality, energy metabolism, and neurohormonal changes in rats with experimental myocardial infarction (MI). Thirty minutes after left coronary artery ligation or sham operation, the rats were randomized to receive either placebo or zatebradine (100 mg x kg(-1) x day(-1) per gavage) continued for 8 wk. Mortality during 8 wk was 33.3% in the placebo and 23.0% in the zatebradine group (P < 0.05); MI size was 36 +/- 2% and 30 +/- 1% (means +/- SE, P < 0.05), respectively. Zatebradine improved stroke volume index in all treated rats but increased left ventricular volume in rats with small MI (2.43 +/- 0.10 vs. 1.81 +/- 0.10 ml/kg, P < 0.05) but not in rats with large MI (2.34 +/- 0.09 vs. 2.35 +/- 0.11 ml/kg, not significant). Zatebradine reduced left and right ventricular norepinephrine and increased left and right ventricular 3,4-dihydroxyphenyl ethylene glycol-to-norepinephrine ratio suggesting aggravation of cardiac sympathetic activation by zatebradine after MI. Creatine kinase and lactate dehydrogenase isoenzymes in rats with MI remained unchanged by zatebradine. Lowering heart rate per se reduces mortality and MI size in this model but induces adverse effects on left ventricular remodeling in rats with small MI.

Animals↗
PubMed2003

Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat.

Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 +/- 9%, ischemic region: 9 +/- 3%, P < 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 +/- 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 +/- 0.09) compared with remote (1.27 +/- 0.08) and control hearts (1.43 +/- 0.08; P < 0.05). The histological fraction of fibrosis within the ischemic region (12.8 +/- 1.4%) correlated to ATP signal reduction from remote to the ischemic region (r = 0.71, P < 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.

Animals↗
PubMed2003

Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes.

BACKGROUND: It is well known that patients with type 2 diabetes have increased risk of cardiovascular disease, but it is not known whether they have underlying abnormalities in cardiac or skeletal muscle high-energy phosphate metabolism. METHODS AND RESULTS: We studied 21 patients with type 2 diabetes with no evidence of coronary artery disease or impaired cardiac function, as determined by echocardiography, and 15 age-, sex-, and body mass index-matched control subjects. Cardiac high-energy phosphate metabolites were measured at rest using 31P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy phosphate metabolites, intracellular pH, and oxygenation were measured using 31P MRS and near infrared spectrophotometry, respectively, before, during, and after exercise. Although their cardiac morphology, mass, and function appeared to be normal, the patients with diabetes had significantly lower phosphocreatine (PCr)/ATP ratios, at 1.50+/-0.11, than the healthy volunteers, at 2.30+/-0.12. The cardiac PCr/ATP ratios correlated negatively with the fasting plasma free fatty acid concentrations. Although skeletal muscle energetics and pH were normal at rest, PCr loss and pH decrease were significantly faster during exercise in the patients with diabetes, who had lower exercise tolerance. After exercise, PCr recovery was slower in the patients with diabetes and correlated with tissue reoxygenation times. The exercise times correlated negatively with the deoxygenation rates and the hemoglobin (Hb)A1c levels and the reoxygenation times correlated positively with the HbA1c levels. CONCLUSIONS: Type 2 diabetic patients with apparently normal cardiac function have impaired myocardial and skeletal muscle energy metabolism related to changes in circulating metabolic substrates.

Adenosine Diphosphate↗
PubMed2003

The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction.

OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators may be beneficial in heart failure due to their metabolic and antihypertrophic effects, but these agents can cause oedema. We hypothesized that, on balance, the PPARgamma activator rosiglitazone would be beneficial in heart failure post-myocardial infarction. METHODS AND RESULTS: Rosiglitazone (3 mg/kg/day p.o.) given to male Wistar rats for 14 days, caused a 31% increase in left ventricular (LV) dP/dt(max) (P<0.05 vs. placebo). A separate group of rats was subjected to sham (SH) or coronary artery ligation and randomised to: untreated (UT); rosiglitazone 3 mg/kg/day (R); captopril, 2 g/l in drinking water (C); captopril+rosiglitazone (C+R). Mean LV infarct sizes were similar for all groups at 40+/-2%. After 8 weeks, echocardiographic ejection fractions were 82+/-3, 40+/-3, 50+/-2*, 49+/-2, 50+/-3% for SH, UT, R, C and C+R groups, respectively (*P<0.05 vs. UT). Captopril prevented LV dilatation, but rosiglitazone did not. In vivo hemodynamics showed that only UT had significantly elevated LV end-diastolic pressures and reduced +dP/dt(max), with R partially, and C and C+R almost completely preventing the increase in LVEDP. Captopril, but not rosiglitazone, significantly reduced LV hypertrophy [LV/bw; 1.97+/-0.09 (SH), 2.15+/-0.04 (UT), 2.10+/-0.05 (R), 1.81+/-0.04* (C), 1.88+/-0.07 (C+R); *(P<0.05 vs. UT)]. Rosiglitazone increased 8-week mortality, which was 26% for R and 19% for C+R compared with 0% for UT and C (P=0.03 vs. UT). CONCLUSIONS: Rosiglitazone did not modulate LV remodeling, but was associated with increased mortality post-myocardial infarction (MI) in rats. The mechanisms require further study, but these results caution against use of PPARgamma activators in post-MI heart failure in non-diabetics.

Angiotensin-Converting Enzyme Inhibitors↗