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R Kreis

Publications and source records attributed to R Kreis.

At least 19 recordsLinked to original sources

Observation of intramyocellular lipids by 1H-magnetic resonance spectroscopy.

Magnetic resonance (MR) methods are increasingly being used to investigate the physiology of human muscle. Although MR imaging (MRI) reveals the morphology of muscles in great detail, for example, for determining their volume and fiber orientation, MR spectroscopy (MRS) provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the observation of high-energy phosphates (31P-MRS), glycogen (13C-MRS), or intramyocellular lipids (1H-MRS), to give only a few examples. 1H-MRS of human skeletal muscle requires special techniques because 1H nuclei in water or adipose tissue are far more concentrated than in any other metabolite of human tissue. The strong signal from water can be suppressed by special prepulses, whereas large signals from fat in adipose tissue can be reduced by carefully selecting the region of interest. Until recently, it was presumed that only a few metabolites would be visible underneath the large resonances of water and subcutaneous fat. Meanwhile, it was clear that 1H-MR spectra of human muscle reveal much metabolic and structural information. The determination of intramyocellular lipids (IMCL) by 1H-MRS was initiated by the observation of two compartments of triacylglycerols with a resonance-frequency shift of approximately 0.2 ppm. The two resonances can be attributed to CH2 protons of lipids in fat cells, and to lipids inside muscle cells (IMCL). 1H-MRS examinations are noninvasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace biopsy to follow-up IMCL levels; however, biopsy still has the advantage that other methods, such as molecular biology, can be applied to the sample. It can be shown that IMCL levels (expressed in mMol/kg wet weight and volume %) are muscle specific and vary with diet and physical activity. In addition, it has been reported that IMCL levels are correlated with insulin sensitivity. A comparison of different methods for assessing IMCL levels, including MRS, chemical analysis, and morphometry, revealed a satisfactory correlation among them and a superior correlation of MRS with the average of the three methods. The observation of IMCL levels by means of 1H-MRS is extremely promising, but several methodological limitations and pitfalls need to be considered.

Adipose Tissue↗

Non-invasive observation of acetyl-group buffering by 1H-MR spectroscopy in exercising human muscle.

The observation of a previously unidentified peak in localized 1H magnetic resonance (MR) spectra of human muscle during and after a work load is reported. Basic NMR properties of this resonance, as well as physiologic circumstances of its observation, suggest that it is due to the acetyl group of acetylcarnitine. The relatively large pool of muscular carnitine acts as a buffering system stabilizing the ratio of acetylated to free coenzyme A. Free carnitine can be acetylated to a large extent whenever a mismatch occurs between the fluxes through pyruvate dehydrogenase and the TCA cycle. Results of initial applications of 1H MR spectroscopy in several muscles and under different exercise regimens are in agreement with earlier invasive measurements of acetylcarnitine. It is demonstrated that the detailed dynamics of acetyl group formation are now likely to be observable non-invasively in humans by localized 1H magnetic resonance spectroscopy on standard MR imaging systems, and that acetylcarnitine buffering as a function of exercise type, oxygenation states, diet and pathology could thus be studied repeatedly and in various muscle groups with much improved temporal resolution.

Acetylation↗

Restoration of electrophysiological signals distorted by inductive effects of magnetic field gradients during MR sequences.

A generally applicable method for almost complete suppression of signal artifacts on electrophysiological signals caused by B0-gradient switching (gradient noise) is presented. The method is demonstrated for electrocardiograms (ECGs) but can also be used for other electrophysiological signals. It takes advantage of the fact that under certain conditions, the effect of switching the B0-field gradient upon an electrophysiological signal can be modeled as a linear time-invariant system and fully characterized by pulse response functions. It is shown how the system's pulse response functions of the X, Y, and Z gradients can be determined and how gradient noise can be eliminated efficiently. The elimination of gradient noise by the proposed method causes in the current arrangement a constant delay of 128 msec, which is acceptable for patient monitoring and magnetic resonance sequence triggering.

Artifacts↗

Methods and reproducibility of cardiac/respiratory double-triggered (1)H-MR spectroscopy of the human heart.

Localized (1)H-MR spectroscopy is sensitive to motion and has mostly been applied to the brain. For the human heart, cardiac and respiratory motion lead to displacements on the order of the localized voxel and lead to substantial variations of voxel content, lineshape, water suppression, and signal phase and amplitude. Combined respiratory and cardiac double triggering can avoid these complications to a large extent. Three methods of double triggering are evaluated, with reproducibility established in nine subjects for a method based on respiratory modulation of the ECG amplitude and a visual feedback mechanism. Quantitated with respect to water, within-subject reproducibilities for this setup were 9% for trimethylammonium compounds, 10% for creatine/phosphocreatine, and 13% for lipids. ANOVA showed significant differences between subjects which may relate to natural variability between subjects or exact location within the heart. Unresolved issues for this technique are its susceptibility to precise placement of ECG electrodes and the reasons for failure in 20% of examination. With this technique it is possible to investigate open questions in cardiac pathophysiology, such as the creatine content in chronic heart disease. Variants of this triggering method may also improve cardiovascular MRI methods relying on data acquired in several heartbeats. Magn Reson Med 42:903-910, 1999.

Adult↗

Effect of exercise on the creatine resonances in 1H MR spectra of human skeletal muscle.

1H MR spectra of human muscles were recorded before, during, and after fatiguing exercise. In contrast to expectations, it was found that the spectral contributions of creatine/phosphocreatine (Cr/PCr) were subject to change as a function of exercise. In particular, the dipolar-coupled methylene protons of Cr/PCr were found to be reduced in intensity in proportion to the co-registered PCr levels. Recovery after exercise and behavior under ischemic conditions provide further evidence to suggest that the contributions of the CH2 protons of Cr/PCr to 1H MR spectra of human muscle in vivo reflect PCr rather than Cr levels. Variation of experimental parameters showed that this effect is not due to a trivial change in relaxation times. At present it can only be speculated about why the Cr resonances have reduced NMR visibility. If temporary binding to macromolecules should be involved, the free Cr concentration-important for equilibrium calculations of the creatine kinase reaction-might be different from what was previously assumed.

Adult↗

Observation of intramyocellular lipids by means of 1H magnetic resonance spectroscopy.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.

Diet↗

Creatine supplementation--part I: performance, clinical chemistry, and muscle volume.

PURPOSE: Our purpose was to study the effects and side effects of creatine (Cr) supplementation on high-intensity, short-term muscle work, on biochemical parameters related to Cr metabolism in blood and urine, and on muscle volume of the lower limb muscles. METHODS: A cycling ergometer was used in a double-blind, cross-over study on 10 well-trained male physical education students to measure physical performance with 10 repetitive ergometer sprints (6-s duration, 30-s rest) before and after supplementation (5 d, 20 g x d(-1), washout period 61 +/- 8 d, mean +/- SEM, minimum 28 d) with Cr or placebo. Before and after supplementation, blood and urine were taken and the muscle volume of the lower limb was determined by magnetic resonance imaging (MRI). RESULTS: A significant (P << 0.05) increase in performance (+7%) at the end [4-6 s] of the later sprints (4-7 and 8-10) was observed combined with a lower production of blood lactate (-1 mmol x L(-1)) with Cr supplementation. The concentration of Cr was increased significantly in urine (P < 0.001) and serum (P = 0.005), whereas creatinine (Crn) was increased in serum (P < 0.001). Crn in urine and Crn clearance did not change significantly with Cr intake. There were no significant changes in the analyzed blood enzyme activities. A significant gain of body weight (pre-Cr 76.5 +/- 1.7 kg to 77.9 +/- 1.7 kg post-Cr) with Cr supplementation was measured, but no accompanying increase of muscle mass in a limited volume of the lower limb was observed by MRI. CONCLUSION: Cr supplementation is effective in improving short-term performance, and the methods used show no detrimental side effects with this supplementation protocol.

Adult↗

Creatine supplementation--part II: in vivo magnetic resonance spectroscopy.

PURPOSE: Our purpose was to study effects of creatine (Cr) supplementation on muscle metabolites noninvasively by means of magnetic resonance spectroscopy (MRS) before and after supplementation with Cr or placebo. METHODS: 1H-MRS was used in a comprehensive, double-blind, cross-over study in 10 volunteers to measure Cr in m. tibialis anterior and m. rectus femoris at rest. PCr/ATP was observed in m. quadriceps femoris by 31P-MRS at rest and after exercise. RESULTS: A significant increase in total Cr was observed with Cr intake in m. tibialis anterior (+9.6 +/- 1.7%, P = 0.001) and in m. rectus femoris (+18.0 +/- 1.8%, P < 0.001). PCr/ATP showed a significant increase (+23.9 +/- 2.3%, P < 0.001) in m. quadriceps femoris at rest with Cr supplementation. Post-Cr supplementation recovery rates from exercise were significantly lower (k = 0.029 s(-1), P < 0.01) compared with postplacebo consumption (k = 0.034 s(-1)) and presupplementation (k = 0.037 s(-1)). However, higher levels of PCr/ATP at rest compensate for this reduction of the recovery rate after Cr supplementation. The increase of PCr/ATP determined by 31P-MRS correlates with the increase of Cr observed by 1H-MRS (r = 0.824, P < 0.001). CONCLUSION: Noninvasive observation of Cr and PCr after Cr supplementation shows an increase in a muscle specific manner. Higher preexercise levels of PCr/ATP at rest compensate for significantly slower recovery rates of PCr/ATP after Cr supplementation.

Adenosine Triphosphate↗

Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria.

Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.

Adult↗

Effects of physiologic motion of the human brain upon quantitative 1H-MRS: analysis and correction by retro-gating.

Signal loss and absolute quantitation errors in 1H-MRS (localized proton MR spectroscopy) because of physiologic brain motion are analyzed quantitatively. Cardiac and respiratory related motion lead to substantial phase dispersion when using a standard, short echo-time STEAM sequence. The loss in signal area varies from 6-7% with TM (middle interval time in a STEAM sequence) = 13.7 ms, to 25-39% with TM = 100 ms. The variation in signal area because of motion-related phase dispersion is up to 16% for TM = 100 ms. The signal phase as a function of the position in the cardiac cycle is shown to be reproducible. Maximal differences in the signal phase are over 180 degrees for long TMs. ECG-gating reduces the phase dispersion considerably but introduces problems with variable repetition times. Using a phase calibration curve recorded with the water suppression turned off, it is possible to retrogate subsequent untriggered acquisitions with the water suppression activated, if the time points in the cardiac cycle are recorded for each acquisition. The gain in signal intensity is between 3 and 21%. For absolute quantification via brain water, this phase analysis has the important consequence that reference scans must be phased individually before co-adding, otherwise metabolite concentrations may be severely overestimated.

Brain↗

Versatile frequency domain fitting using time domain models and prior knowledge.

An iterative nonlinear least-squares fitting algorithm in the frequency domain using time domain models for quantification of complex frequency domain MR spectra is presented. The algorithm allows incorporation of prior knowledge and has both the advantage of time-domain fitting with respect to handling the problem of missing data points and truncated data sets and of frequency-domain fitting with respect to multiple frequency-selective fitting. The described algorithm can handle, in addition to Lorentzian and Gaussian lineshapes, Voigt and nonanalytic lineshapes. The program allows the user the design of his own fitting strategy to optimize the probability of reaching the global least-squares minimum. The application of the fitting program is illustrated with examples from in vivo 1H-, 31P-, and 13C-MR spectroscopy.

Algorithms↗

Tissue characterization of symptomatic and asymptomatic disc herniations by quantitative magnetic resonance imaging.

The purpose of this investigation was to determine differences in tissue composition of symptomatic and asymptomatic disc herniations as reflected in T1 and T2 relaxation times (quantitative magnetic resonance imaging). Thirty patients with sciatica severe enough to require a discectomy and 46 asymptomatic volunteers (controls) were included in this study. Both groups had a clinical examination as well as a magnetic resonance investigation of the lumbar spine. The longitudinal and transverse magnetic relaxation times (T1 and T2, respectively) were calculated from a set of 20 images obtained with five single-slice/multi-echo sequences at different repetition time values on a commercial whole-body system (1.5 T). Twenty-two symptomatic and asymptomatic disc herniations could be matched according to age, gender, disc level, and the extent of herniation (protrusion or extrusion) and were compared with regard to T1 and T2 relaxation times. Symptomatic disc herniations exhibited significantly (pT1 < 0.04 and pT2 < 0.003) shorter T1 (delta T1: -182.1 milliseconds, -15%) and T2 (delta T2: -11.0 milliseconds, -21%) relaxation times than matched asymptomatic herniations. Symptomatic disc herniations also exhibited more advanced disc degeneration as graded by Pearce's criteria (p < 0.01). These results suggest that symptomatic and morphologically matched asymptomatic disc herniations differ with regard to disc matrix composition.

Adult↗

Peak assignment in localized 1H MR spectra of human muscle based on oral creatine supplementation.

1H-MR spectra of human skeletal muscle feature peak splittings due to dipolar coupling. Quantitative difference spectroscopy in a double-blind cross-over trial testing oral creatine supplementation revealed that most of the resonances affected by dipolar coupling can be assigned to creatine and/or phosphocreatine. The assignment was performed in two different skeletal muscles and confirmed by measurements at the magic angle where dipolar splittings vanish. Numerical spectral simulations revealed that the observed spectra are consistent with partly-averaged dipolar coupling among methylene and methyl protons of (phospho)creatine. The possible nature of the molecular dynamics leading to incomplete dipolar averaging is discussed.

Administration, Oral↗

In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy.

Intra-myocellular lipids (IMCL) are stored in droplets in the cytoplasm of muscle cells and are an energy storage form readily accessed during long-term exercise. 1H-MR spectroscopy methods are presented for noninvasive determination of IMCL in human muscle. This is based on (a) the separation of two resonances in the lipid-CH2-region, with the one assigned to IMCL being independent of muscle orientation relative to the magnetic field and (b) the fact that IMCL resonances scale along with signal amplitudes of metabolites in the muscle cell (e.g., creatine) when voxel size is increased, while lipid signals of bulk fat show a disproportionate growth. Inter-individual and intra-individual reproducibility studies indicate that the error of the method is about 6% and that IMCL levels differ significantly between identical muscles in different subjects, as well as intra-individually when measured at 1 week intervals. IMCL determinations in a single subject before and after strenuous exercise indicate that lipid stores recover with a t1/2 of about 1 day.

Adult↗

Dipolar resonance frequency shifts in 1H MR spectra of skeletal muscle: confirmation in rats at 4.7 T in vivo and observation of changes postmortem.

Non-isotropic contributions to 1H MR spectra from human skeletal muscle in vivo have recently been observed in the 0- to 5-ppm region. One pair of peaks has been identified to be subject to dipolar couplings. The corresponding changes in resonance frequency are related to the orientation of muscle fibers with respect to the external magnetic field and are analogous to the behavior of small molecules dissolved in liquid crystals. Image-guided localized spectroscopy based on the STEAM method has been applied to verify these phenomena in rat skeletal muscle in vivo and to investigate the effect postmortem. Residual dipolar couplings and anisotropic contributions to 1H MR spectra of skeletal muscle have been confirmed in animals and at a higher field strength--albeit with a slightly different spectral pattern compared to the human study. The most prominent dipolar doublet due to creatine and/or phosphocreatine vanishes postmortem with a rate similar to the disappearance of phosphocreatine, and is no longer observable 2 h postmortem.

Animals↗

Hypoxic encephalopathy after near-drowning studied by quantitative 1H-magnetic resonance spectroscopy.

Early prediction of outcome after global hypoxia of the brain requires accurate determination of the nature and extent of neurological injury and is cardinal for patient management. Cerebral metabolites of gray and white matter were determined sequentially after near-drowning using quantitative 1H nuclear magnetic resonance spectroscopy (MRS) in 16 children. Significant metabolite abnormalities were demonstrated in all patients compared with their age-matched normal controls. Severity of brain damage was quantified from metabolite concentrations and ratios. Loss of N-acetylaspartate, a putative neuronal marker, from gray matter preceded that observed in white matter and was more severe. Total creatine decreased, while lactate and glutamine/glutamate concentrations increased. Changes progressed with time after injury. A spectroscopic prognosis index distinguished between good outcome (n = 5) and poor outcome (n = 11) with one false negative (bad outcome after borderline MRS result) and no false positive results (100% specificity). The distinction was made with 90% sensitivity early (after 48 h) and became 100% later (by days 3 and 4). This compared with 50-75% specificity and 70-100% sensitivity based upon single clinical criteria. MRS performed sequentially in occipital gray matter provides useful objective information which can significantly enhance the ability to establish prognosis after near-drowning.

Brain↗