Thomas Pabst

Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy

BACKGROUND In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging.

Abstract. We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 ± 7), women aged under 45 (27 ± 6), men aged over 45 (59 ± 8), and women aged over 45 (57 ± 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 ± 18 and 110 ± 16 g; LV EDV, 118 ± 27 and 96 ± 21 ml; LV ESV, 40 ± 13 and 29 ± 9 ml; RV mass, 52 ± 10 and 39 ± 5 g; RV EDV, 131 ± 28 and 100 ± 23 ml; RV ESV, 53 ± 17 and 33 ± 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4 % and 5.9 % for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values.

Detection of myocardial viability by low-dose dobutamine Cine MR imaging.

The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for predicting recovery of regional myocardial contractility after revascularization. Cardiac wall motion abnormalities are due to either non-viable and/or scarred, or viable, but hibernating, myocardial tissue. Dobutamine stress leads to increased systolic wall thickening only in viable myocardium. Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress (10 microg/kg/min). Patients were re-examined at rest 3, and in case of persisting wall motion defects, 6 months after revascularization. Criterion of viability was increasing end-systolic wall thickening during stress and/or at follow-up. Akinetic regions related either to the LAD (n = 19) or to the RCA (n = 6) were judged viable if > or = 50% of the affected segments improved. MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms. Sensitivity, specificity, and positive predictive value for the prediction of myocardial viability were 61%, 90%, and 87% for the segment-related analysis, and 76%, 100%, and 100% for the patient-related analysis based on coronary artery distribution, respectively. Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity.

Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19–29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off‐resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 ± 1.2 and 5.3 ± 1.2 mmol/kg wet wt (mean ± SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed. Magn Reson Med 41:657–663, 1999.

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age‐matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two‐dimensional cine fast low‐angle shot sequence was used for the evaluation of absolute values and indices related to 1 m 2 body surface area for function, mass, and LV wall thickening. Fourteen age‐matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end‐systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year. J. Magn. Reson. Imaging 2000;12:240–246.

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. Magn Reson Med 52:545–551, 2004.

Optimization of ECG-triggered 3D 23Na MRI of the human heart

23Na MRI may allow distinction of normal and ischemically injured myocardium. The aim of this study was to optimize 23Na MRI of the human heart by improvement of spatial resolution and ECG‐triggering and to measure the signal/noise of blood and myocardium and the myocardium/blood signal ratios in a volunteer study. A spoiled gradient echo sequence was developed on a 1.5T scanner equipped with a 23Na heart surface coil. 3D short axis ECG‐triggered 23Na MRI was performed in 10 healthy subjects. The signal/noise of myocardium and blood were 8.2 ± 0.7 and 18.3 ± 1.3, respectively, signal ratio myocardium/blood was 0.44 ± 0.03. This value is in good agreement with the theoretical value of 0.45. ECG gated 3D 23Na MRI of the human heart is feasible with sufficient spatial resolution and signal/noise ratio. Magn Reson Med 45:164–166, 2001.

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans

Abstract. The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm3 each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ATP) ratio of volunteers (SD 1.72 ± 0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47 ± 0.38 (non-significant vs volunteers; p > 0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92 ± 0.73 vs 6.68 ± 0.80; patients vs volunteers; p <0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction.

Advances in human cardiac 31P-MR spectroscopy: SLOOP and clinical applications.

Phosphorus magnetic resonance spectroscopy (31P‐MRS) has revealed a lot about the biochemistry of physiological and pathological processes in the heart. Nevertheless, until today, cardiac 31P‐MRS has not had any clinical impact, albeit some pioneering studies demonstrated that 31P‐MRS can indeed provide diagnostic information. In this paper, the development of techniques for human cardiac 31P‐MRS over the past decade is reviewed, and the requirements for a reliable clinical measurement protocol are discussed. Spatial localization with optimal pointspread function (SLOOP) is a new method to achieve spatial localization and absolute quantitation. Its properties are detailed, and preliminary findings in patients with dilated cardiomyopathy or myocardial infarction are presented. J. Magn. Reson. Imaging 2001;13:521–527.

Understanding Why Contrast Enhancement in Dynamic MRI Is Not Reproducible: Illustration with a Simple Phantom

Abstract: The goal of this work was to verify in a phantom study the necessity of a calibration method for comparison in dynamic contrast‐enhanced magnetic resonance imaging (MRI) examinations. A perspex phantom with a dilution series of Gd‐DTPA was used to measure the dynamic signal enhancement of a sequence. With nine MRI scanners from Bruker (0.23, 0.5, and 2 Tesla), Philips [0.5 and 1.5 Tesla (ACS‐NT and S15)], and Siemens (0.2, 1.0, and 1.5 Tesla) one 2D FLASH and two 3D FLASH experiments were performed under identical measurement conditions. Under different measurement conditions (2D and 3D FLASH, TR, TE, FA) different characteristics in signal enhancement exist on a scanner. The same measurement conditions at different scanners (same magnetic field strength) also result in different signal enhancement. Dynamic contrast enhanced MRI examinations from different measurement conditions or scanners cannot be compared. To solve this problem a calibration is needed.