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Biomedical subjects

M von Kienlin

Publications and source records attributed to M von Kienlin.

At least 19 recordsLinked to original sources

Natural abundance 13C-NMR spectroscopy for the quantitative determination of fecal fat.

OBJECTIVE: To evaluate 13C-NMR spectroscopy as a method for fat quantitation in human feces without time consuming or unpleasant preparation steps. DESIGN AND METHODS: Stool samples of seven healthy subjects were collected for 18 days before and during oral intake of the inhibitor of gastrointestinal lipases Orlistat. Fecal lipid content was determined first using 13C-NMR, then by conventional gravimetry after homogenization and Bligh & Dyer lipid extraction. RESULTS: The correlation between gravimetry and 13C-NMR was excellent (R2 = 0.91). In repeated measurements, the mean percentage error was 2.8%. On average, 13C-NMR yielded 1.27 g less fat than gravimetry. Orlistat efficacy for fat excretion assessed by 13C-NMR and by gravimetry was 34.3% and 33.9%, respectively. CONCLUSIONS: With a total measurement time of three minutes, 13C-NMR spectroscopy of unprocessed whole stool provides an accurate alternative to gravimetry for assessing total fecal fat excretion. 13C-NMR is superior with regard to practicability and speed.

Calibration↗

High glycolytic activity in rat glioma demonstrated in vivo by correlation peak 1H magnetic resonance imaging.

High-grade brain tumors are known to have a high rate of glucose (Glc) consumption. Postmortem measurements have suggested that Glc content in experimental brain tumors is relatively low. We used magnetic resonance spectroscopy to investigate this, in vivo, in the brains of seven rats bearing intracerebral C6 gliomas. We combined the high spectral resolution allowed by two-dimensional proton nuclear magnetic resonance with spatial encoding by magnetic field gradient pulses to obtain in vivo maps of Glc, alanine, hypotaurine, aspartate, phosphoethanolamine, Glu/Gln, N-acetylaspartate (NAA), phosphocreatine/creatine (PCr/Cr), choline-containing compounds, and lactate (Lac) (some of which are involved in energy metabolism). Compared with normal brain tissue, the main differences found in the gliomas were that Glc, NAA, PCr/Cr, and aspartate concentrations were much lower, whereas concentrations of alanine, hypotaurine, phosphoethanolamine, and Lac were higher, whatever the extent of necrosis. A striking observation is the similarity of the NAA and Glc images: the concentrations of both metabolites are lower in the tumor than they are in the contralateral brain. If Glc was completely absent from the tumor tissue, and if the residual Glc level was due only to a partial volume effect like that for NAA, a neuronal marker, the ratio [Glc]tumor/[Glc]contralateral tissue, should be similar to that found for NAA. The ratio for Glc was 0.48 +/- 0.22 (+/- SD; n = 6), a ratio similar to that found for PCr/Cr (0.50 +/- 0.19) but significantly higher than that obtained for NAA (0.29 +/- 0.07). This observation indicates that a measurable Glc concentration is still present in the tumor tissue. Intense glycolysis in tumor cells may explain the increased production of Lac and alanine and decreased amount of Glc. These nuclear magnetic resonance measurements of metabolite concentrations are complementary to positron emission tomography, which measures Glc consumption.

Alanine↗

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

(23)Na MRI may allow distinction of normal and ischemically injured myocardium. The aim of this study was to optimize (23)Na 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 (23)Na heart surface coil. 3D short axis ECG-triggered (23)Na 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 (23)Na MRI of the human heart is feasible with sufficient spatial resolution and signal/noise ratio. Magn Reson Med 45:164-166, 2001.

Adult↗

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.

Heart Diseases↗

Detection of myocardial viability based on measurement of sodium content: A (23)Na-NMR study.

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content post-myocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in buffer-perfused rat hearts, infarct scar can be differentiated from intact myocardium by (23)Na-MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post-MI (N = 6-8 each), Na content was determined by (23)Na-NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083 vs. control). In Protocol 2, (23)Na-MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, (23)Na-MRI revealed a mean increase in signal intensity, to 142 +/- 6% of control values, in scar tissue. A threshold of 2 standard deviations of the image intensity allowed determination of infarct size, correlating with histologically determined infarct size (r = 0.91, P < 0.0001).

Animals↗

Accurate phosphorus metabolite images of the human heart by 3D acquisition-weighted CSI.

Fourier imaging modalities suffer from significant signal contamination between adjacent voxels, especially when the spatial resolution is comparable to the size of the anatomical structures. This contamination can be positive or negative, depending on the spatial response function and the geometry of the object. Such a situation arises in human cardiac (31)P chemical shift imaging (CSI). Acquisition-weighted CSI reduces this contamination substantially, which is demonstrated by comparing conventional CSI to Hanning-weighted 3D (31)P-CSI experiments in 13 healthy volunteers at 2 T. The nominal spatial resolution and the total number of scans were identical for both experiments. The improved spatial response function of the acquisition-weighted experiment led to a significantly (P < 0.0001) higher myocardial PCr/ATP ratio (2.05 +/- 0.31, mean +/- SD, N = 33, corrected for saturation and blood contribution) compared to the conventional CSI experiment (1.60 +/- 0.46). This is explained by the absence of negative contamination from skeletal muscle, which also resulted in an increase of the observed SNR (from 5.4 +/- 1.4 to 7.2 +/- 1.4 for ATP). With acquisition-weighted CSI, metabolic images with a nominal resolution of 16 ml could be obtained in a measurement time of 30 min. After correction for the inhomogeneous B(1) field of the surface coil, these images show uniform ATP distribution in the entire myocardium, including the posterior wall.

Adenosine Triphosphate↗

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

OBJECTIVE: Experimental 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 ischemic insult on energy metabolism of intact septal myocardium was analyzed using 31P-Magnetic resonance spectroscopy (MRS). PATIENTS AND METHODS: In eight patients with wall motion abnormalities in the anterior wall 31P-spectra were obtained from non-infarcted adjacent septal 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. MRI was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group. RESULTS: According 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). DISCUSSION: These 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.

Aged↗

Cardiac metabolism and function in patients with multiple sclerosis: a combined 31P-MR-spectroscopy and MRI study.

OBJECTIVE: Involvement of the autonomic system in multiple sclerosis (MS) may concur with dysfunction of the cardiovascular system. The introduction of potentially cardiotoxic immunosuppressive drugs like Mitoxantrone into the treatment of MS warrants proper assessment of preexisting heart disease. However, systematic analyses of functional and metabolic derangements in MS are missing. Using quantitative 31P-MR-spectroscopy (MRS) and MR-imaging (MRI) metabolic and functional parameters were analyzed in patients with MS in comparison to healthy volunteers. SUBJECTS/METHODS: 14/15 patients with MS could be included in the study, as the MRS examination of one patient had to be excluded from analysis due to movement during the examination. Using chemical shift imaging (CSI) and AMARES, phosphocreatine (PCr) to adenosine triphosphate (ATP) ratios, characterizing myocardial high-energy phosphate metabolism, were determined. Additionally, absolute concentrations of PCr and ATP were calculated by SLOOP (Spatial Localization with Optimal Pointspread Function). Analysis of functional changes was performed by Cine-MRI. 14 healthy volunteers matched for age and gender served as control. RESULTS: A significant decrease of absolute PCr concentration was observed in patients with MS compared to matched volunteers (p < 0.05), whereas ATP concentrations showed no significant changes (p = 0.27). Metabolite ratios calculated by SLOOP or AMARES showed a tendency to be reduced in patients, however, did not reach significance (p = 0.08, SLOOP; p = 0.47, AMARES). Using volunteers' mean values +/- 2 x SD as cut off value revealed PCr changes in 5 of 14 patients, whereas only 2 also had pathologic PCr/ATP ratios. Functional analysis by MRI depicted depressed left ventricular ejection fraction in 4 patients. CONCLUSIONS: The reduction in cardiac high-energy phosphates in some patients with MS points to a subclinical involvement of the heart. This may be important for treatment with potentially cardiotoxic drugs. Longitudinal studies are need to understand the clinical relevance of our findings.

Adenosine Triphosphate↗

[31P-MR spectroscopy of all regions of the human heart at 1.5 T with acquisition-weighted chemical shift imaging].

AIM: Aim of this study was to show whether or not acquisition-weighted chemical shift imaging (AW-CSI) allows the determination of PCr and ATP in the lateral and posterior wall of the human heart at 1.5 T. METHODS: 12 healthy volunteers were examined using a conventional chemical shift imaging (CSI) and an AW-CSI. The sequences differed only in the number of repetitions for each point in k space. A hanning function was used as filter function leading to 7 repetitions in the center of the k space and 0 in the corners. Thus, AW-CSI had the same resolution as the CSI sequence. The results for both sequences were analyzed using identically positioned voxels in the septal, anterior, lateral and posterior wall. RESULTS: The determined averaged AW-CSI signal to noise ratios were higher for PCr by a factor of 1.3 and for ATP by 1.4 than those of CSI. The PCr/ATP ratios were higher by a factor of 1.2 - 1.3 and showed a smaller standard deviation in all locations for AW-CSI. The mean PCr/ATP ratios determined by AW-CSI of septal, lateral and posterior wall were almost identical (1.72 - 1.76), while it was higher in the anterior wall (1.9). CONCLUSIONS: The reduced contamination in AW-CSI improves the signal to noise ratio and the determination of the PCr/ATP ratio in cardiac (31)P spectroscopy compared to CSI with the same resolution. The results in volunteers indicate that AW-CSI renders (31)P spectroscopy of the lateral and posterior wall of the human heart feasible for patient studies at 1.5 T.

Adenosine Triphosphate↗

2D-spatial/2D-spectral spectroscopic imaging of intracerebral gliomas in rat brain.

1H-MR spectroscopy in vivo is often hampered by poor spectral resolution. Spectral overlap can be avoided with two-dimensional spectroscopic techniques. Correlation peak imaging has been implemented to measure unambiguously the distribution of several metabolites in a rat brain glioma model. Acquisition-weighted spectroscopic imaging reduced the experimental time and provided excellent spatial localization. The choice of an appropriate spectral acquisition window granted good sensitivity. Spectroscopic images presenting a full two-dimensional spectrum in every image pixel were acquired in seven rats at 7 Tesla in 195 min, with a nominal voxel volume of 75 microl. Among other metabolites, the distribution of hypotaurine, phosphoethanolamine, alanine, and even glucose could be visualized both in the C6-glioma and in the unaffected brain.

Animals↗

Reduced (1)H-NMR visibility of creatine in isolated rat hearts.

The aim of this study was to measure the concentration of creatine in Langendorff perfused rat hearts, both by quantitative (1)H-MRS and by high-pressure liquid chromatography (HPLC). First, the relaxation times and other parameters affecting absolute quantification by MRS were determined. At 11.75 T, the relaxation times of myocardial creatine were T(1) = 1.1+/-0.29 sec (mean +/- SD, n = 5) and T(2) = 56.4+/-6.2 ms (n = 9). In phantom experiments the MRS measurements gave accurate values for the known relative concentrations of the detected substances. In glucose-perfused rat hearts, the creatine concentration measured by HPLC was 14.2+/-1.9 mmol/kg wet weight (n = 8), in good agreement with literature values. The (1)H-MRS measurements, however, resulted in creatine concentrations of only approximately 60% of this value. The application of CHESS-pulses for water suppression led to a further 30% reduction of the creatine MRS signal. These results indicate a reduced (1)H-NMR visibility of creatine in the myocardium, which suggests a compartmentation of myocardial creatine into various pools.

Animals↗

Three-dimensional (13)C-spectroscopic imaging in the isolated infarcted rat heart.

Acquisition weighted (13)C-spectroscopic imaging with three spatial dimensions is demonstrated in the isolated, perfused rat heart. Experiments were performed at 11.75 T with a home-built double resonant (13)C-(1)H probehead. Three-dimensional chemical shift imaging was used to obtain (1)H-decoupled (13)C-spectra in 96-microl voxels in about 58 min. Acquisition weighting significantly reduced signal contamination and improved image quality, with no penalty in sensitivity. As a first application, infarcted hearts were studied during perfusion with [2-(13)C]-sodium acetate. The extent of the incorporation of the (13)C-label into glutamate allows us to distinguish intact and infarcted myocardium. Chemical shift images show a homogeneous glutamate distribution in intact tissue, but a negligible amount in the infarction scar.

Animals↗

[Cardiac energy metabolism in heart valve diseases with 31P MR spectroscopy].

PURPOSE: 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. PATIENTS AND METHODS: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients > 60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). 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. 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 +/- 33 g to 206 +/- 47 g. 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. 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.

Adult↗

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

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.

Adenosine Triphosphate↗