Wilfried Landschütz

Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with 31P-SLOOP magnetic resonance spectroscopy☆

OBJECTIVE The purpose of the present study was to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in normal, hypertrophied, and failing human heart. BACKGROUND Conflicting evidence exists on the extent of changes of high-energy phosphate metabolites in hypertrophied and failing human heart. Previous reports using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) have quantified metabolites in relative terms only. However, this analysis cannot detect simultaneous reductions. METHODS Four groups of subjects (n = 10 each), were studied: volunteers and patients with hypertensive heart disease (HHD), aortic stenosis, and dilated cardiomyopathy (DCM). Left ventricular (LV) function and mass were measured by cine magnetic resonance imaging. Absolute and relative concentrations of PCr and ATP were determined by (31)P-MRS with spatial localization with optimum point spread function. RESULTS Left ventricular ejection fraction remained normal in HHD and aortic stenosis, but was severely reduced to 18% in DCM; LV mass was increased by 55%, 79%, and 68% respectively. In volunteers, PCr and ATP concentrations were 8.82 +/- 1.30 mmol/kg wet weight and 5.69 +/- 1.02 mmol/kg wet weight, and the PCr/ATP ratio was 1.59 +/- 0.33. High-energy phosphate levels were unaltered in HHD. In aortic stenosis, PCr was decreased by 28%, whereas ATP remained constant. In DCM, PCr was reduced by 51%, ATP by 35%, and reduction of the PCr/ATP ratio by 25% was of borderline significance (p = 0.06). Significant correlations were observed among energetic and functional variables, with the closest relations for PCr. CONCLUSIONS In human heart failure due to DCM, both PCr and ATP are significantly reduced. Ratios of PCr to ATP underestimate changes of high-energy phosphate levels.

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.

Auto‐SENSE perfusion imaging of the whole human heart

To show the application of auto‐sensitivity encoding (SENSE)—a self‐calibrating parallel imaging technique—to first pass perfusion imaging of the whole human heart.

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.

Age and gender dependence of human cardiac phosphorus metabolites determined by SLOOP 31P MR spectroscopy.

The aim of this study was to apply 31P magnetic resonance spectroscopy (MRS) using spatial localization with optimal point spread function (SLOOP) to investigate possible age and gender dependencies of the energy metabolite concentrations in the human heart. Thirty healthy volunteers (18 males and 12 females, 21–67 years old, mean = 40.7 years) were examined with the use of 31P‐MRS on a 1.5 T scanner. Intra‐ and interobserver variability measures (determined in eight of the volunteers) were both 3.8% for phosphocreatine (PCr), and 4.7% and 8.3%, respectively, for adenosine triphosphate (ATP). High‐energy phosphate (HEP) concentrations in mmol/kg wet weight were 9.7 ± 2.4 (age < 40 years, N = 16) and 7.7 ± 2.5 (age ≥ 40 years, N = 14) for PCr, and 5.1 ± 1.0 (age < 40 years) and 4.1 ± 0.8 (age ≥ 40 years) for ATP, respectively. Separated by gender, PCr concentrations of 9.2 ± 2.4 (men, N = 18) and 8.0 ± 2.8 (women, N = 12) and ATP concentrations of 4.9 ± 1.0 (men) and 4.2 ± 0.9 (women) were measured. A significant decrease of PCr and ATP was found for volunteers older than 40 years (P < 0.05), but the differences in metabolic concentrations between both sexes were not significant. In conclusion, age has a minor but still significant impact on cardiac energy metabolism, and no significant gender differences were detected. Magn Reson Med, 2006.

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.

31P-MR Spectroscopy for the evaluation of energy metabolism in intact residual myocardium after acute myocardial infarction in humans

Objectiveexperimental studies have demonstrated that acute myocardial infarction (MI) alters energy metabolism even in non-infarcted adjacent tissue. In patients with subacute MI, the influence of the regional ischemie insult on energy metabolism of intact septal myocardium was analyzed using31P-Magnetic resonance spectroscopy (MRS).Patients and Methodsin eight patients with wall motion abnormalities in the anterior wall31P-spectra were obtained from non-infarcted adjacent scptal myocardium, as well as infarcted anterior myocardium (voxel size 25 ccm each) 29 ±8 days after MI using a 3D-CSI technique. Additionally, cardiac function was analyzed using breath-hold cine MRI. MR1 was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group.Resultsaccording to follow-up MRI 4/8 patients showed regional wall motion recovery. Here, PCr/ATP-ratios were not significantly reduced in intact septal myocardium as well as infarcted anterior myocardium compared to healthy volunteers (1.28 ±0.10 and 1.14 ±0.09 vs. 1.45 ±0.29). No recovery of regional function was detected in 4/8 patients with —therefore—non-viable anterior myocardium. PCr/ATP-ratios were significantly reduced in intact and infarcted myocardium compared with healthy volunteers as well as to patients with wall motion recovery (0.77 ±0.17 and 0.49 ±0.23;P < 0.05).Discussionthese preliminary results indicate that energy metabolism is reduced in patients with persisting wall motion abnormalities after myocardial infarction and revascularization in ischemically injured as well as in adjacent non-injured myocardium.

Assessment of myocardial viability by 31P-MR-spectroscopy and 23Na-MR imaging

An exact differentiation between viable (hibernating or stunned) and non-viable (scar) tissue is crucial for the decision whether revascularisation is required after myocardial infarction [I]. Former studies demonstrated altered energy metabolism in ischemic myocardium [2]. 3~p-MR-Spectroscopy offers the unique possibility for non-invasive study of cardiac energy metabolism. Aim of the present work was to analyze whether a reliable detection of myocardial viability is possible by 3tp-MRSpectroscopy. All examinations were performed on a 1.5 Tesla clinical MR system (Magnetom VISION, Siemens, Erlangen). 3~p-spectra were acquired using a double-resonant 3~p/~H-surface coil and a double-angulated 3D-CSI-technique (voxelsize 25 ccm). Due to the limited sensitivity for the deeper parts of the heart only patients with anterior wall infarction were included (n=20) . For each patient 3~P-spectra from the infarcted area were compared to 3~p-spectra from non-infarcted septat myocardium (internal reference). Additionally, left ventricular function was analyzed by short axis cine-MRI breath-hold sequences (slice thickness 8 mm). Both examinations were performed at study entry (3 weeks after acute myocardial infarction) and 3 months after revascularization. Improvement of regional function in MRI was used as gold standard for viability [3]. Aged-matched healthy volunteers (n = 10) served as control group. Using the AMARES software

Assessment of myocardial viability by 31 P-MR-spectroscopy and 23 Na-MR imaging

An exact differentiation between viable (hibernating or stunned) and non-viable (scar) tissue is crucial for the decision whether revascularisation is required after myocardial infarction [I]. Former studies demonstrated altered energy metabolism in ischemic myocardium [2]. 3~p-MR-Spectroscopy offers the unique possibility for non-invasive study of cardiac energy metabolism. Aim of the present work was to analyze whether a reliable detection of myocardial viability is possible by 3tp-MRSpectroscopy. All examinations were performed on a 1.5 Tesla clinical MR system (Magnetom VISION, Siemens, Erlangen). 3~p-spectra were acquired using a double-resonant 3~p/~H-surface coil and a double-angulated 3D-CSI-technique (voxelsize 25 ccm). Due to the limited sensitivity for the deeper parts of the heart only patients with anterior wall infarction were included (n=20) . For each patient 3~P-spectra from the infarcted area were compared to 3~p-spectra from non-infarcted septat myocardium (internal reference). Additionally, left ventricular function was analyzed by short axis cine-MRI breath-hold sequences (slice thickness 8 mm). Both examinations were performed at study entry (3 weeks after acute myocardial infarction) and 3 months after revascularization. Improvement of regional function in MRI was used as gold standard for viability [3]. Aged-matched healthy volunteers (n = 10) served as control group. Using the AMARES software

Concentration of human cardiac31P-metabolites determined by SLOOP31P-MRS

31p-MRS of the human heart can discriminate viable and non-viable tissue post myocardial infarction, if absolute concentrations of the high-energy phosphates can be measured [1]. The quality of this quantification depends strongly on the signal contamination from surrounding regions and the consideration of experimental parameters like local flip angles or saturation effects. SLOOP (spatial localization with optimal p_ointspread function) [2,3] minimizes the signal contamination from surrounding regions, uses all possible prior knowledge like local flip angle and sensitivity, and considers them with high spatial resolution during the reconstruction. Therefore, in combination with an external standard SLOOP is especially suited for a determination of absolute concentrations. In our study we demonstrated this ability on nine volunteers.