Nobel Prizes for nuclear magnetic resonance imaging: 2003 and historical perspectives.
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History, 20th Century↗
Biomedical subjects
Chris Boesch
Publications and source records attributed to Chris Boesch.
Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes.
It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O-acyltransferase 1, DGAT), and beta-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor-alpha (PPAR-alpha), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects.
Adaptation, Physiological↗
Cerebral energy metabolism in phenylketonuria: findings by quantitative In vivo 31P MR spectroscopy.
Both severe impairments of brain development in untreated infants and acute reversible neurotoxic effects on brain function are clinical features of phenylketonuria (PKU). For determining whether impairments of cerebral energy metabolism play a role in the pathophysiology of PKU, quantitative in vivo 31P magnetic resonance spectroscopy (MRS) was performed in a supratentorial voxel of 11 adult PKU patients and controls. Peak areas of inorganic phosphate; phosphocreatine; alpha-, beta-, and gamma-ATP; NAD; phosphomonoesters; phosphodiesters; and a broad phospholipid signal were converted to millimolar concentrations. Mg2+, pH, ADP, the phosphorylation potential, and the relative velocity of oxidative metabolism V/Vmax were derived. Clinical evaluation included mutation analysis, neurologic investigation, intelligence testing, magnetic resonance imaging, and concurrent plasma and brain phenylalanine (Phe), the last by 1H-MRS. Phe loading was performed in five patients with an oral dose of 100 mg/kg body wt L-Phe monitored by spectral EEG analysis. Under steady-state conditions, 31P-MRS revealed normal values for ATP, phosphocreatine, NAD, phosphomonoesters, phosphodiesters, Mg2+, and pH in PKU. ADP (+11%) and the phosphorylation potential (+22%) were increased. Peak areas of inorganic phosphate (-22%) and phospholipid (-8%) were decreased. ADP correlated with concurrent plasma (r = 0.65) and brain (r = 0.55) Phe. During the Phe load, blood Phe levels increased steeply. EEG revealed slowing of background activity. The phosphorylation potential decreased, whereas ADP and V/Vmax increased. In vivo 31P-MRS demonstrated subtle abnormalities of cerebral energy metabolism in PKU in steady-state conditions that were accentuated by a Phe load, indicating a link between Phe neurotoxicity and imbalances of cerebral energy metabolism.
Adult↗
Mapping fiber orientation in human muscle by proton MR spectroscopic imaging.
Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) was used to determine muscle fiber orientations in human calf muscles. The method is based on the fact that some resonances show orientation-dependent dipolar splitting, caused by incomplete motional averaging. This leads to proton spectra that depend strongly on the angle between muscle fibers and the magnetic field B(0). The orientation-dependent dipolar splittings were mapped using a fit with a basis set of predefined coupling patterns reflecting the fiber orientation. The fitted coupling patterns were displayed as images and assigned to different muscles based on segmented MR images. They showed gross differences in fiber orientation between some muscles, including m. soleus and m. tibialis anterior, for all subjects. In addition, smaller but significant differences between subjects were detected, which could be due to localization differences or real interindividual differences. Since dipolar splitting affects metabolite intensities, it is important to take this effect into account when calculating metabolite concentrations from MR spectra in muscle tissue. Spatial maps of the MR signals of trimethyl-ammonium groups and creatine/ phosphocreatine revealed significant differences in intensity between muscles.
Creatine↗
Normal hepatic glycogen storage after fasting and feeding in children and adolescents with type 1 diabetes.
OBJECTIVE: Hypoglycemia is the most important acute complication in patients with type 1 diabetes. Liver glycogen is an important storage form of glucose and thus important for maintaining glucose homeostasis. To test the hypothesis whether abnormal storage of glycogen in the liver is contributing to the risk of hypoglycemia in type 1 diabetic children and adolescents, liver glycogen was measured. STUDY DESIGN: Hepatic glycogen concentrations were measured in 19 type 1 diabetic children and adolescents as well as in 19 age-matched controls, following overnight fasting and 4 h after two standardized meals. Hepatic glycogen was assessed by natural abundance 13C nuclear magnetic resonance spectroscopy (MRS). RESULTS: Mean (+/- SEM) fasting hepatic glycogen concentrations measured in arbitrary units (au) were similar in type 1 diabetic subjects and controls (4.98 +/- 0.36 vs. 4.48 +/- 0.33 au; p = 0.31). Both groups presented with an increase in liver glycogen concentrations 4 h after the standardized meals (diabetic subjects 5.70 +/- 0.37 au, p = 0.01; controls 5.78 +/- 0.47 au, p < 0.01). Hepatic glycogen accumulation after feeding was 19.1% in diabetic children and adolescents compared with 35.8% in controls, but this difference did not reach significance. CONCLUSION: In children and adolescents with moderately controlled type 1 diabetes, hepatic glycogen stores after fasting and feeding are comparable to those of matched controls.
Adolescent↗
Virtopsy, a new imaging horizon in forensic pathology: virtual autopsy by postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI)--a feasibility study.
Using postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI), 40 forensic cases were examined and findings were verified by subsequent autopsy. Results were classified as follows: (I) cause of death, (II) relevant traumatological and pathological findings, (III) vital reactions, (IV) reconstruction of injuries, (V) visualization. In these 40 forensic cases, 47 partly combined causes of death were diagnosed at autopsy, 26 (55%) causes of death were found independently using only radiological image data. Radiology was superior to autopsy in revealing certain cases of cranial, skeletal, or tissue trauma. Some forensic vital reactions were diagnosed equally well or better using MSCT/MRI. Radiological imaging techniques are particularly beneficial for reconstruction and visualization of forensic cases, including the opportunity to use the data for expert witness reports, teaching, quality control, and telemedical consultation. These preliminary results, based on the concept of "virtopsy," are promising enough to introduce and evaluate these radiological techniques in forensic medicine.
Adolescent↗
No evidence for individual blood-brain barrier phenylalanine transport to influence clinical outcome in typical phenylketonuria patients.
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Adult↗
Observation and identification of metabolites emerging during postmortem decomposition of brain tissue by means of in situ 1H-magnetic resonance spectroscopy.
Postmortem decomposition of brain tissue was investigated by (1)H-magnetic resonance spectroscopy (MRS) in a sheep head model and selected human cases. Aiming at the eventual estimation of postmortem intervals in forensic medicine, this study focuses on the characterization and identification of newly observed metabolites. In situ single-voxel (1)H-MRS at 1.5 T was complemented by multidimensional homo- and heteronuclear high-resolution NMR spectroscopy of an extract of sheep brain tissue. The inclusion of spectra of model solutions in the program LC Model confirmed the assignments in situ. The first postmortem phase was characterized mainly by changes in the concentrations of metabolites usually observed in vivo and by the appearance of previously reported decay products. About 3 days postmortem, new metabolites, including free trimethylammonium, propionate, butyrate, and iso-butyrate, started to appear in situ. Since the observed metabolites and the time course is comparable in sheep and human brain tissue, the model system seems to be appropriate.
Animals↗
Long-term administration of L-carnitine to humans: effect on skeletal muscle carnitine content and physical performance.
BACKGROUND: Long-term administration of high oral doses of L-carnitine on the skeletal muscle composition and the physical performance has not been studied in humans. METHODS: Eight healthy male adults were treated with 2 x 2 g of L-carnitine per day for 3 months. Muscle biopsies and exercise tests were performed before, immediately after, and 2 months after the treatment. Exercise tests were performed using a bicycle ergometer for 10 min at 20%, 40%, and 60% of the individual maximal workload (P(max)), respectively, until exhaustion. RESULTS: There were no significant differences between V(O(2)max), RER(max), and P(max) between the three time points investigated. At submaximal intensities, the only difference to the pretreatment values was a 5% increase in V(O(2)) at 20% and 40% of P(max) 2 months after the cessation of the treatment. The total carnitine content in the skeletal muscle was 4.10 +/- 0.82 micromol/g before, 4.79 +/- 1.19 micromol/g immediately after, and 4.19 +/- 0.61 micromol/g wet weight 2 months after the treatment (no significant difference). Activities of the two mitochondrial enzymes citrate synthase and cytochrome oxidase, as well as the skeletal muscle fiber composition also remained unaffected by the administration of L-carnitine. CONCLUSIONS: Long-term oral treatment of healthy adults with L-carnitine is not associated with a significant increase in the muscle carnitine content, mitochondrial proliferation, or physical performance. Beneficial effects of the long-term treatment with L-carnitine on the physical performance of healthy adults cannot be explained by an increase in the carnitine muscle stores.
Adult↗
Content of intramyocellular lipids derived by electron microscopy, biochemical assays, and (1)H-MR spectroscopy.
Three different methods to determine intramyocellular lipid (IMCL) contents in human skeletal muscle have been compared. (1)H-magnetic resonance spectroscopy (MRS) was evaluated against electron microscopic morphometry and biochemical assays of biopsy samples from m. tibialis anterior of 10 healthy subjects. The results of (1)H-MRS and morphometry were strongly correlated, proving the validity of the (1)H-MRS results for the noninvasive determination of IMCL. Biochemical assays yielded results that did not significantly correlate with the results of the other methods. When IMCL levels obtained from the three methods are expressed in common units, it was found that (1)H-MRS yielded IMCL average levels that were 1.8 times lower than those found by morphometry. Potential reasons for the discrepancy are discussed. It is expected that (1)H-MRS will be suitable to replace invasive techniques for IMCL determination, whenever noninvasiveness is crucial, e.g., for repeated investigations in studies of substrate recruitment and recovery in exercise.
Aged↗