Michael Horn

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.

Tumour size measurement in a mouse model using high resolution MRI

BackgroundAnimal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (10−2–10−1u2009g). The aim of this study was to assess the accuracy of MRI based tumour size measurements of small tumours on mice.Methods2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7u2009T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1u2009g/cm3, using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis.ResultsStrong correlations were demonstrated between MRI- and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2u2009g) tumours were assessed for inter- and intraobserver variation. In 3D images, the voxel sizes could be increased from 1603u2009μm3 to 2403u2009μm3 without affecting the results significantly, thus reducing acquisition time substantially.Conclusions2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2u2009g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session.

Imaging of intracellular sodium with shift reagent aided 23Na CSI in isolated rat hearts

23Na chemical shift imaging (CSI) in conjunction with shift reagents was used to obtain images of intracellular (Nai) and extracellular sodium (Nae) in isolated rat hearts. It was demonstrated that the increase of Nai concentration in ischemic myocardium can be detected with this technique. 3D acquisition‐weighted 23Na CSI datasets with a nominal spatial resolution of 1.7 × 1.7 × 2.9 mm were acquired in 30 min in normoxic hearts and in globally or locally ischemic hearts. The shift reagent Tm(DOTP)5− was used to discriminate Nai and Nae signals. Nai maps could be generated in ischemic hearts, but not in normoxic hearts as the signal‐to‐noise ratio is too low. The Nai signal increased by more than 100% and the Nae signal decreased by more than 50% in myocardium of globally ischemic hearts (n = 3) compared to normoxic hearts (n = 3). In hearts with an acute occlusion of the left anterior descending coronary artery (n = 3), there was a local Nai signal increase in the anterior wall in the range of 60–110% compared to remote, normoxic tissue. Magn Reson Med 48:89–96, 2002.

31P-Nuclear Magnetic Resonance Spectroscopy of Blood: A Species Comparison

31P-nuclear magnetic resonance (NMR) spectroscopy isfrequently used as a tool in the study of organs from various animal species and humans. Because signals arising from the presence of blood are visible in in vivo 31P-NMR spectra of blood-filled organs, such as the heart, it is necessary to correct these spectra for the contribution of blood to the signal. It is unknown whether species differences in 31P signals of blood exist. 31P-containing metabolites of blood from various species were therefore quantified by means of 31P-NMR spectroscopy. Signals of 2,3-bisphosphoglycerate (2,3-DPG); phosphodiesters (PDE); and gamma-, alpha-, and beta-ATP were detected in all 31P-NMR spectra of blood. 2,3-DPG/ATP ratios were significantly higher in dogs, rats, and guinea pigs than in humans but lower in sheep. Pig and rabbit were the only animals with a 2,3-DPG/ATP ratio similar to that of humans. PDE levels varied among species but were significantly lower than in humans only in guinea pigs. The PDE/ATP ratio was relatively similar among all species compared with humans, except dog and guinea pig, where it was significantly higher and lower, respectively. We conclude that because of large species differences, species-specific 31P metabolite ratios should be applied for the correction of in vivo 31P-NMR spectra.

Untersuchungen des kardialen Energiestoffwechsels bei Herzvitien mit der 31P-MR-Spektroskopie

ZusammenfassungZielsetzung: Mit einer linksventrikulären Hypertrophie einhergehende Herzvitien führen zu Veränderungen des kardialen Energiestoffwechsels, die mit der 31P-MR-Spektroskopie nichtinvasiv erfasst werden können. Ziel der vorliegenden Studie war es, zu untersuchen, ob nach chirurgischem Klappenersatz eine Normalisierung des Energiestoffwechsels beobachtet werden kann.nn Patienten und Methode: 10 gesunde Probanden und 10 Patienten mit Aortenklappenstenose (Druckgradient >60xa0mmHg) wurden untersucht. Zur Erfassung des kardialen Energiestoffwechsels wurde eine doppelt angulierbare 3D-CSI-Technik verwendet (Voxelgröße 25 ccm). 3 Monate nach Aortenklappenersatz (AKE) erfolgte bei 5 Patienten eine Nachkontrolle. Bei den Patienten wurden zusätzlich linksventrikuläre (LV) Funktionsparameter mittels cine-MRI-Technik analysiert.nn Ergebnisse: Vor Klappenersatz war bei den Patienten das Phosphokreatin-Adenosintriphosphat(PCr-ATP)-Verhältnis mit 0,80±0,25 signifikant im Vergleich zu Gesunden (1,65±0,21; p=0,0002) erniedrigt. 3 Monate nach AKE konnte eine signifikante (p=0,04) Verringerung der LV-Masse von 238±33xa0g auf 206±47xa0g nachgewiesen werden. Die LV-Ejektionsfraktion änderte sich jedoch nicht wesentlich (von 61±11% auf 65±7%; p=0,22). Zur selben Zeit zeigte sich ein signifikanter (p=0,04) Anstieg des PCr-ATP-Verhältnis von 0,80±0,25 auf 1,28±0,22 an. Für das Phosphodiester-ATP-Verhältnis zeigte sich eine geringe, jedoch nicht signifikante Reduzierung vor AKE, mit einer Tendenz zum Wiederanstieg nach AKE.nn Schlussfolgerungen: Nach Klappenersatz ist eine Tendenz zur Normalisierung des pathologisch veränderten Energiestoffwechsels zu beobachten. Weitere Nachkontrollen sind notwendig, um zu klären, ob es zu einem späteren Zeitpunkt zu einer vollständigen Normalisierung des Energiestoffwechsels kommt.SummaryPurpose: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement.nn Patients and methods: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients >60xa0mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25xa0cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI.nn Results: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p=0.0002) reduced to 0.80±0.25 in patients compared to 1.65±0.21 in volunteers. 3 months after SVR, LV mass had significantly (p=0.04) decreased from 238±33xa0g to 206±47xa0g. At the same time a significant (p=0.04) increase of the PCr-ATP ratio from 0.80±0.25 to 1.28±0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR.nn Conclusions: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.

Non-invasive Determination of Myocardial Lipid Content in Fabry Disease by 1H-MR Spectroscopy

PURPOSEnIn Fabry disease (FD), a progressive deposition of sphingolipids is reported in different organs. The present study applied 1H magnetic resonance spectroscopy (MRS) to investigate the myocardial lipid content in FD.nnnMATERIALS AND METHODSnIn patients (PTS, n = 15) with genetically proven FD, 1H MRS of the heart was acquired in the same examination as routine cardiac cine and late enhancement MR imaging. Healthy volunteers (n = 11) without history of cardiac disease served as control (CTL). Myocardial triglycerides in vivo were quantified in 1H MRS. Left ventricular (LV) ejection fraction (EF) and late enhancement were assessed for the determination of LV systolic function, and onset or absence of myocardial fibrosis.nnnRESULTSnAll 1H MRS revealed resonances for intramyocardial triglycerides. Clinical parameters, e.g. EF (PTS 64 ± 2 % vs. CTL 61 ± 1 %) were similar in PTS and CTL or showed a non-significant trend (LV mass). Apart from a single patient with elevated myocardial triglycerides, no significant impact of Fabry disease on the triglyceride/water resonance ratio (PTS 0.47 ± 0.11 vs. CTL 0.52 ± 0.11 %) was observed in our patient cohort.nnnCONCLUSIONnA comprehensive cardiac evaluation of morphology, function as well as metabolism in Fabry PTS with suspected cardiac involvement is feasible in a single examination. No significant effect of myocardial triglyceride deposition could be observed in patients. The remarkably high myocardial triglyceride content in one patient with advanced FD warrants further studies in PTS with an extended history of the disease.

Mechanisms of the Effects of Nicorandil in the Isolated Rat Heart During Ischemia and Reperfusion: A 31P-Nuclear Magnetic Resonance Study

Nicorandil (SG75) is a potent K+-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K+-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandil-containing (100, 300, or 1000 microM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10(-3) M), nicorandil reduced ATP depletion during ischemia by 26% compared with untreated hearts. Blockade of K+ channels by glibenclamide prevented this protective effect. At all doses (10(-4) to 10(-3) M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 +/- 0.03 vs. 6.02 +/- 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K+ channels by glibenclamide. Hearts treated with nitroglycerine before ischemia also showed reduced proton accumulation. Therefore, NO release accompanied by increased coronary flow before ischemia, which is caused by the nitro moiety of nicorandil and nitroglycerine treatment, results in reduced proton accumulation. During reperfusion, a pro-arrhythmic effect was observed in hearts treated with the nonpharmacologically high dose of nicorandil (1000 microM). Thus, we conclude that the effects of nicorandil are caused by the simultaneous action of both mechanisms K+-channel activation and NO release. The activation of K+ channels prevents deterioration of ATP during ischemia, whereas NO release and increased coronary flow reduce the accumulation of protons--and thus the decrease in pH--during ischemia.

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.

965-48 Ejection Fraction and Wall Thickness Correlate with Impaired Energy Metabolism in Patients with Dilated Cardiomyopathy

Using 31P-MR spectroscopy, abnormalities of cardiac energy metabolism have been demonstrated in patients with dilated cardiomyopathy (DCM). However. a detailed analysis of the correlations among energy metabolism, cardiac hemodynamics and myocardial hypertrophy obtained from 31P-MR, right and left heart catheterization and echocardiography has not been presented, 23 patients with DCM (left ventricular (LV) EF 34xa0±xa03%; NYHA class 2.7xa0±xa00.1; SE) underwent right and left heart catheterization and echocardiographyxa0±xa03 days before/after MR spectroscopy. Coronary artery disease was ruled out by coronary angiography. ECG-triggered. localized 31 P-MR spectra from the anteroseptal myocardium were acquired at rest (prone position) during 30xa0min on a 1.5 T Philips Gyroscan MR system using ISIS localization, adiabatic pulses. and a 15 sec repetition time. Peak areas were corrected for T1 effects and for blood contamination. and were determined with Lorentzian line fits in the time domain. Linear correlations between creatine phosphate (CP)/ATP ratios and hemodynamic parameters were calculated. Download : Download high-res image (69KB) Download : Download full-size image LV pressures and diameters. cardiac output, stroke volume, pulmonary arterial pressures, right atrial pressure and pulmonary arterial oxygen saturation did not correlate with CP/ATP. Thus, our data demonstrate that in DCM, the extent of high-energy phosphate depletion is related to the extent of mechanical dysfunction as well as to LV wall thickness.