Search PubMed⌕ Search

Biomedical subjects

A Heerschap

Publications and source records attributed to A Heerschap.

At least 73 records · Page 4Linked to original sources
PubMed1998

Calibration of the 1H decoupling field strength and experimental evaluation of the specific RF absorption rate in 1H-decoupled human 13C-MRS.

For patient safety in human 1H decoupled 13C-MRS, it is absolutely necessary to evaluate the specific RF absorption rate (SAR) of the tissue exposed to 1H frequency irradiation. With the use of surface coils, the local SAR at the body surface is of most concern due to the inherent RF field inhomogeneity. An empirical procedure to spatially calibrate the decoupler power level and to evaluate the local SAR at the body surface is described. For head, liver, muscle gastrocnemius, and muscle vastus lateralis, the SAR at the body surface was estimated for an 1H/13C double surface coil setup. Optimized duty cycle values obtained with this procedure show that broad-band 1H-decoupled 13C-MR spectroscopy is clinically feasible at 1.5 T for such a coil configuration within safety guidelines.

Absorption↗
PubMed1998

Heteronuclear cross polarization for enhanced sensitivity of in vivo 13C MR spectroscopy on a clinical 1.5 T MR system.

The potential of heteronuclear ¿1H-13C¿ cross polarization was studied for optimization of the signal-to-noise ratio in in vivo 13C MR spectroscopy at the clinical field strength of 1.5 T. Experiments on the human calf showed a significant chemical-shift selective signal enhancement on triglyceride signals of 3.9 by heteronuclear cross polarization, compared to a standard pulse-acquire sequence. Studies on a neonatal piglet brain showed an enhancement by cross polarization of 2.2 for the detection of 13C-1-glucose. This enhancement allowed a fourfold improvement in time resolution in dynamic 13C MR of 13C-1-glucose inflow in piglet brain. Phantom experiments demonstrated the efficiency of this technique for interleaved detection of two spectral regions. Tests with a volume coil showed the feasibility of signal enhancement by cross polarization over a large volume of interest.

Adipose Tissue↗
PubMed1998

Influence of the pharmacokinetic model on the quantification of the Gd-DTPA uptake rate in brain tumours using direct T1 measurements.

After a bolus injection of Gd-DTPA, a fast tracer uptake in rat brain tumours was already observed during the tracer bolus passage. For the quantification of the uptake rate constant, pharmacokinetic models are commonly used. For a good quantification, the changes of the plasma tracer concentration directly after the bolus injection must be incorporated into these models as prior knowledge. The aim of this paper is to investigate whether or not it is necessary to include the bolus passage into the description for the plasma tracer concentration. The result of this study indicates that the best quantification of the uptake rate constant is achieved by using only the data points after the bolus passage. Using all the data points and incorporating the bolus passage in the pharmacokinetic models results in a less accurate estimation.

Animals↗
PubMed1998

Proton magnetic resonance spectroscopy of fetal lamb brain during hypoxia.

Proton magnetic resonance spectroscopy of fetal lamb brain was performed simultaneously with repeated measurements of fetal arterial oxygen saturation during decrease of oxygen supply. Magnetic resonance spectra displayed the same metabolite peaks as detected in the human fetal brain. Cerebral lactate signals could be detected during fetal hypoxia.

Animals↗
PubMed1998

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK) mediated phosphocreatine (PCr) <==> ATP transphosphorylation in mitochondria and cytosol of skeletal muscle by knocking out the genes for the mitochondrial (ScCKmit) and the cytosolic (M-CK) CK isoforms in mice. Animals which carry single or double mutations, if kept and tested under standard laboratory conditions, have surprisingly mild changes in muscle physiology. Strenuous ex vivo conditions were necessary to reveal that MM-CK absence in single and double mutants leads to a partial loss of tetanic force output. Single ScCKmit deficiency has no noticeable effects but in combination the mutations cause slowing of the relaxation rate. Importantly, our studies revealed that there is metabolic and cytoarchitectural adaptation to CK defects in energy metabolism. The effects involve mutation type-dependent alterations in the levels of AMP, IMP, glycogen and phosphomonoesters, changes in activity of metabolic enzymes like AMP-deaminase, alterations in mitochondrial volume and contractile protein (MHC isoform) profiles, and a hyperproliferation of the terminal cysternae of the SR (in tubular aggregates). This suggests that there is a compensatory resiliency of loss-of-function and redirection of flux distributions in the metabolic network for cellular energy in our mutants.

Animals↗
PubMed1997

Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice. Contrary to expectation, the PCr level was only marginally affected, but the compound was rendered metabolically inert. Mutant muscles in vivo showed significantly impaired tetanic force output, increased relaxation times, altered mitochondrial volume and location, and conspicuous tubular aggregates of sarcoplasmic reticulum membranes, as seen in myopathies with electrolyte disturbances. In depolarized myotubes cultured in vitro, CK absence influenced both the release and sequestration of Ca2+. Our data point to a direct link between the CK-PCr system and Ca2+-flux regulation during the excitation and relaxation phases of muscle contraction.

Adenosine Triphosphate↗
PubMed1997

Proton MR spectroscopy of the normal human prostate with an endorectal coil and a double spin-echo pulse sequence.

This report describes the use of an endorectal coil and a double spin-echo pulse sequence for localized 1H MR spectroscopy of the normal prostate in volunteers. The spectra showed well-resolved signals for citrate, (phospho)choline, and creatine protons. Additional signals were assigned to taurine and myoinositol protons. J modulation of the main and outer peaks of citrate could be monitored in vivo. Apparent relaxation times T1 and T2 have been estimated for the methyl protons of cholines and creatine. An effective T1 relaxation time was estimated for the main peaks of the citrate multiplet. Ratios of the integrals of these resonances have been evaluated, and tissue contents of choline and creatine were estimated using the H2O signal as an internal reference. Spectroscopic imaging experiments revealed a lower relative citrate signal in central parts of the prostate than in peripheral parts.

Adult↗
PubMed1997

ATP content measured by 31P NMR correlates with post-ischaemic recovery of external work output in an isolated rat heart perfused with erythrocyte suspension.

The limited capacity of the heart to survive ischaemia presents a recognized problem during open-heart surgery. In order to provide a baseline for the study of cardioprotection we subjected a series of isolated rat hearts to periods of ischaemia of increasing duration, and sought correlations between phosphate metabolite levels as measured by 11P NMR and post-ischaemic recovery of external work output. A strong linear correlation was found between the fraction of ATP measured after reperfusion expressed as a ratio. RATP to the pre-ischaemic level, and the fractional recovery of external work output, RW: Rw = 1.06 (SE 0.27) RATP + 0.01 (SE 0.21) (Spearman rank correlation coefficient 0.72, two-tailed P value 0.006).

Adenosine Triphosphate↗
PubMed1997

Post-ischemic 31P NMR determination of myocardial intracellular pH in vivo using ATP peak.

31P NMR allows non-invasive measurement of intracellular pH, which drops during tissue hypoxia or ischemia. Determination is usually based on the chemical shift between the inorganic phosphate (P(i)) and phosphocreatine (PCr) peaks. During reperfusion, P(i) is taken up to form PCr and ATP, and in our model at least (an isolated, working rat heart perfused with an erythrocyte suspension), the level of P(i) reduces well below the pre-ischemic level, making pH determination difficult. The chemical shifts of the three ATP peaks also depend on pH, and the level of ATP remains high during reperfusion, so these might be used to determine pH. The results of one experiment are presented in detail, showing the time course of high energy phosphate levels before, during and after a 32 min ischemic insult, and close agreement between the pH determinations from the Pi and gamma-ATP peaks can be seen. The formula used to calculate pH from the ATP peak was: pH (ATP) = 0.59 delta 2-5.0 delta + 15.9 where delta is the shift in ppm between PCr and gamma-ATP. All pH readings by both methods from a series of seven experiments were compared and a 1:1 agreement demonstrated (correlation coefficient 0.63, p < 0.0001). Although the ATP shifts also depend on magnesium complexation which we have ignored, this appears to be justifiable within the errors of the method; the good agreement between the results of the two methods, and the ability to determine pH during reperfusion suggest that calculation of intracellular pH from the chemical shift of gamma-ATP is a useful technique.

Adenosine Triphosphate↗
PubMed1997

Coronary flow response after myocardial ischemia may predict level of functional recovery.

Is there a quantity, potentially measurable in the operating theater, which predicts rapid recovery of heart power output after surgical intervention with ischemia? We have enhanced our blood-perfused, ejecting, isolated rat heart model for use inside the magnet of an NMR spectrometer, in order to conduct fundamental research into cardioprotective techniques. To provide a baseline, we investigated the effect of normothermic ischemic insults of varying duration. Hemodynamic and metabolic data were collected, and analyzed to seek measures predictive of rapid recovery of aortic power output, which was selected as the most important measure of function. The presence of erythrocytes in the perfusate ensures that oxygen supply is sufficient to support a physiological workload, and that there is reserve coronary flow. On reperfusion, reactive hyperemia occurs: coronary flow increases to a peak, then declines to a steady value. This response was mathematically modeled, and the data for each of fifteen experiments were fitted to the model. Correlating power output recovery against time to reach peak coronary flow yielded the following equation: R = -0.45 log10tp + 1.74 where R is the ratio of power output ten minutes after reperfusion to that before the ischemic insult, and tp is the time taken to reach peak coronary flow, in seconds. The correlation is very significant (p = 0.005). In the clinic, coronary flow response on reperfusion could be used to predict the patient's need for post-operative support.

Animals↗
PubMed1997

Removal of the outer lines of the citrate multiplet in proton magnetic resonance spectra of the prostatic gland by accurate timing of a point-resolved spectroscopy pulse sequence.

Proton MR spectra of a healthy human prostatic gland show a major signal for citrate appearing as an AB-type multiplet. After application of multipulse localization sequences, the outer lines of this multiplet often appear with dispersion line shapes disturbing the baseline and interfering with proper quantification of citrate itself and other nearby resonances. Based upon analytical descriptions of the time evaluation of an AB spin system during a point resolved spectroscopy (PRESS) pulse sequence (90x-tau 1-180y-tau 2-180y-t), equations were derived representing the intensity of the absorption and dispersion line shape of the outer lines of the citrate multiplet at the top of echo t = tau 2-tau 1. From these equations, it was calculated that the outer lines of citrate can be removed almost completely using a PRESS pulse sequence with tau 1 = 11 ms and tau 2 = 60 ms. The theoretical description was confirmed by the almost complete disappearance of the two outer citrate resonances in in vitro and in vivo proton MR spectra acquired with this pulse sequence timing.

Citric Acid↗
PubMed1997

Use of gene targeting for compromising energy homeostasis in neuro-muscular tissues: the role of sarcomeric mitochondrial creatine kinase.

We have introduced a single knock-out mutation in the mitochondrial creatine kinase gene (ScCKmit) in the mouse germ line via targeted mutagenesis in mouse embryonic stem (ES) cells. Surprisingly, ScCKmit -/- muscles, unlike muscles of mice with a deficiency of cytosolic M-type creatine kinase (M-CK -/-; Van Deursen et al. (1993) Cell 74, 621-631), display no altered morphology, performance or oxidative phosphorylation capacity. Also, the levels of high energy phosphate metabolites were essentially unaltered in ScCKmit mutants. Our results challenge some of the present concepts about the strict coupling between CKmit function and aerobic respiration.

Adenosine Triphosphate↗
PubMed1997

In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice.

The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence microscopy and two-dimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from 100 microm to 300 microm. Two morphometric parameters - the percentage of intervascular distances larger than 200 microm (ivd200) and the non-perfused area fraction at a distance larger than 100 microm from a nearest perfused vessel (area100), - were deduced from these experiments and related to the P(i)/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly with the percentage of ivd200 and the area100.

Animals↗
PubMed1996

5-Fluorouracil metabolite patterns in viable and necrotic tumor areas of murine colon carcinoma determined by 19F NMR spectroscopy.

High-resolution 19F NMR spectroscopy at 9.4 T was used to study the difference in the metabolite pattern of 5-fluorouracil (5-FU) between viable and necrotic tissues of C38 murine colon tumors grown in C57BI/6 mice. Studies were performed on perchloric acid extracts of these tumor fractions after 5-FU treatment. The 19F nuclear magnetic resonance spectra exhibited resonances representing 5-FU, the catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine, as well as several fluoronucleotide anabolites. The absolute concentrations of anabolites and catabolites and the anabolite-to-catabolite ratio were significantly lower in the necrotic fraction than in the viable tumor fraction 50 min after administration of 5-FU, whereas the absolute concentration of 5-FU was the same. Therefore, in 5-FU metabolism studies with NMR spectroscopy, it is important to consider the necrotic contribution to the tumor volume.

Animals↗