Biomedical subjects

Markus von Kienlin

Publications and source records attributed to Markus von Kienlin.

7 recordsLinked to original sources

PubMed2005

Functional magnetic resonance imaging reveals similar brain activity changes in two different animal models of schizophrenia.

RATIONALE AND OBJECTIVES: In schizophrenia research, most of the functional imaging studies have been performed in psychotic patients, but little is known about brain areas involved in the expression of psychotic-like symptoms in animal models. The objective of this study was to visualize and compare brain activity abnormalities in a neurodevelopmental and a pharmacological animal model of schizophrenia. METHODS: Blood perfusion of specific brain areas, taken as indirect measure of brain activity, was investigated in adult rats following either neonatal ventral hippocampal lesion or acute administration of phencyclidine. Quantitative perfusion magnetic resonance imaging was performed on five frontal brain slices using the continuous arterial spin labeling technique. The mean perfusion was calculated in several brain structures, which were identified on anatomical images. RESULTS: Lesioned animals exhibiting deficits in prepulse inhibition of the startle reflex showed a significant blood perfusion increase in the nucleus accumbens, basolateral amygdala, ventral pallidum, entorhinal-piriform cortex, orbital prefrontal cortex, and in the bed nucleus of the stria terminalis, and a decrease of perfusion in the temporal cortex. Similar effects were seen following acute phencyclidine administration in naïve animals. CONCLUSION: Our data point out specific cortical and subcortical brain areas involved in the development of psychotic-like symptoms in two different animal models of schizophrenia. The observed brain activity abnormalities are reminiscent of classical neuroimaging findings described in schizophrenic patients.

Acoustic Stimulation↗

PubMed2005

Improved cardiac sodium MR imaging by density-weighted phase-encoding.

PURPOSE: To show that density-weighted (DW) k-space sampling improves the quality of human cardiac sodium imaging, a novel method was implemented that combines the high signal-to-noise efficiency of three-dimensional phase-encoding with the advantageous localization performance of nonuniform sampling. A simulation demonstrates substantially reduced blood contamination in the myocardium. MATERIALS AND METHODS: At 2.0 T, DW cardiac "fast" sodium images with a voxel size of 844 microL in seven minutes and "high-resolution" scans in 30 minutes with a voxel size of 570 microL were acquired. For comparison, conventional gradient-echo imaging was also performed. RESULTS: In the DW images, a myocardial signal-to-noise ratio (SNR) of 16.0 in the left ventricle and 8.5 in the septum (N = 4) was measured. With longer experimental duration (about 30 minutes; N = 3), the image quality and the SNR could be further improved (voxel size: 570 microL; SNR: blood 16.1, septum 10.6). Compared to the gradient-echo images, the image quality was substantially improved. CONCLUSION: This new method for human cardiac sodium imaging provides high image quality combined with optimal sensitivity and thus may improve the clinical applicability of 23Na cardiac MRI.

Computer Simulation↗

PubMed2005

Altered metabolic profile in the frontal cortex of PS2APP transgenic mice, monitored throughout their life span.

The transgenic mouse line PS2APP (PS2N141I x APP(swe)) develops an age-related cognitive decline associated with severe amyloidosis, mimicking the pathophysiologic processes in Alzheimer disease (AD). In the quest for biomarkers to monitor, noninvasively, the progression of the disease, we used magnetic resonance imaging and 1H-spectroscopy to characterize PS2APP mice throughout their life span. Morphometric measurements revealed only small size differences to controls. The metabolic profile, however, showed clear indicators of hypometabolism with age in the PS2APP mice: both N-acetyl-aspartate and glutamate were significantly reduced in the older animals. These spectroscopic measures in vivo correlated well with the plaque load in the frontal cortex. A diagnostic test, based on these measures, reached 92% sensitivity and 82% specificity at age 20 months. These noninvasive biomarkers can be exploited in preclinical pharmaceutical research to cope with the high variability in transgenic animal models and to enhance the power of drug efficacy studies.

Age Factors↗

PubMed2004

Quantitative body composition analysis in awake mice and rats by magnetic resonance relaxometry.

OBJECTIVE: Magnetic resonance (MR) relaxometry has recently been introduced for noninvasive body composition analysis in awake mice. The purpose of the present study was to extend the method to rats and to introduce calibration procedures that render MR relaxometry fully quantitative. RESEARCH METHODS AND PROCEDURES: Proton T(2) MR relaxometry at 4.7 Tesla was used for body composition analyses in 700 awake mice and 400 rats of different strains and conditions. Relaxograms calculated from the signal decays observed with multi-spin-echo acquisition provided well-separated contributions of tissue water and fat. Analysis of fat composition was carried out in vivo using (13)C-MR spectroscopy. Evolution of body composition in rats was assessed during drug treatment. RESULTS: MR relaxometry for noninvasive body composition analysis in laboratory rodents was implemented on a standard MR scanner, and a throughput of >30 animals per hour was achieved. Excellent linearity and reproducibility with coefficients of variance as low as 2.5% and 1.7% were obtained in mice and rats, respectively. The lean mass-to-water ratio (mice, 1.35 +/- 0.03; rats, 1.39 +/- 0.04) and the proton density of fat (mice, 8.1 +/- 0.2; rats, 8.9 +/- 0.2 g/mol) were determined from cross-sectional data. Fat composition analysis by (13)C-MR spectroscopy corroborated these findings and yielded information on the average acyl chain length (16.3 +/- 1.6) and contributions of saturated (27 +/- 3%), monounsaturated (22 +/- 2%), and polyunsaturated (51 +/- 3%) fatty acids. Longitudinal assessments in rats treated with sibutramine and dexfenfluramine showed dose-related changes in body composition. DISCUSSION: T(2) MR relaxometry backed by solid calibration provides a powerful means for rapid quantitative body composition analysis in awake mice and rats that is suitable for serial investigations in pharmaceutical research.

Animals↗

PubMed2003

Efficient k-space sampling by density-weighted phase-encoding.

Acquisition-weighting improves the localization of MRI experiments. An approach to acquisition-weighting in a purely phase-encoded experiment is presented that is based on a variation of the sampling density in k-space. In contrast to conventional imaging or to accumulation-weighting, where k-space is sampled with uniform increments, density-weighting varies the distance between neighboring sampling points Deltak to approximate a given radial weighting function. A fast, noniterative algorithm has been developed to calculate the sampling matrix in one, two, and three dimensions from a radial weighting function w(k), the desired number of scans NA(tot) and the nominal spatial resolution Deltax(nom). Density-weighted phase-encoding combines the improved shape of the spatial response function and the high SNR of acquisition-weighting with an extended field of view. The artifact energy that results from aliasing due to a small field of view is substantially reduced. The properties of density-weighting are compared to uniform and to accumulation-weighted phase-encoding in simulations and experiments. Density-weighted (31)P 3D chemical shift imaging of the human heart is shown which demonstrates the superior performance of density-weighted metabolic imaging.

Heart↗

PubMed2002

Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-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.

Adenosine Triphosphate↗

PubMed2002

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

23Na chemical shift imaging (CSI) in conjunction with shift reagents was used to obtain images of intracellular (Na(i)) and extracellular sodium (Na(e)) in isolated rat hearts. It was demonstrated that the increase of Na(i) concentration in ischemic myocardium can be detected with this technique. 3D acquisition-weighted (23)Na CSI datasets with a nominal spatial resolution of 1.7 x 1.7 x 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 Na(i) and Na(e) signals. Na(i) maps could be generated in ischemic hearts, but not in normoxic hearts as the signal-to-noise ratio is too low. The Na(i) signal increased by more than 100% and the Na(e) 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 Na(i) signal increase in the anterior wall in the range of 60-110% compared to remote, normoxic tissue.

Animals↗