Christoph Hans Boesch

Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy

Biochemical maturation of the brain can be studied noninvasively by 1H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short‐TE 1H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32–43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, γ‐aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo‐inositol, macromolecular contributions, N‐acetylaspartate, N‐acetylaspartylglutamate, o‐phosphoethanolamine, scyllo‐inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N‐acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight. Magn Reson Med 48:949–958, 2002.

Characterization of the macromolecule baseline in localized 1H-MR spectra of human brain

Short‐echo‐time magnetic resonance spectra of human brain contain broad contributions from macromolecules. As they are a priori of unknown shape and intensity, they pose a problem if one wants to quantitate the overlying spectral features from low‐molecular‐weight metabolites. On the other hand, the macromolecular contributions may provide relevant clinical information themselves, if properly evaluated. Several methods, based on T1, T2, or spectral shape, have previously been suggested to suppress or edit the macromolecule contributions. Here, a method is presented based on a series of saturation recovery scans and that allows for simultaneous recording of the macromolecular baseline and the fully relaxed metabolite spectrum. In comparison to an inversion recovery technique aimed at nulling signals from long‐T1 components, the saturation recovery method is less susceptible to T1 differences inherent in signals from different metabolites or introduced by pathology. The saturation recovery method was used to quantitate the macromolecular baseline in white and/or gray matter locations of the human brain in 40 subjects. It was found that the content and composition of MR visible macromolecules depends on cerebral location, as well as the age of the investigated subject, while no gender dependence could be found. Magn Reson Med 46:855–863, 2001.

Quantitative 1H-magnetic resonance spectroscopy of human brain: Influence of composition and parameterization of the basis set in linear combination model-fitting

Localized short‐echo‐time 1H‐MR spectra of human brain contain contributions of many low‐molecular‐weight metabolites and baseline contributions of macromolecules. Two approaches to model such spectra are compared and the data acquisition sequence, optimized for reproducibility, is presented. Modeling relies on prior knowledge constraints and linear combination of metabolite spectra. Investigated was what can be gained by basis parameterization, i.e., description of basis spectra as sums of parametric lineshapes. Effects of basis composition and addition of experimentally measured macromolecular baselines were investigated also. Both fitting methods yielded quantitatively similar values, model deviations, error estimates, and reproducibility in the evaluation of 64 spectra of human gray and white matter from 40 subjects. Major advantages of parameterized basis functions are the possibilities to evaluate fitting parameters separately, to treat subgroup spectra as independent moieties, and to incorporate deviations from straightforward metabolite models. It was found that most of the 22 basis metabolites used may provide meaningful data when comparing patient cohorts. In individual spectra, sums of closely related metabolites are often more meaningful. Inclusion of a macromolecular basis component leads to relatively small, but significantly different tissue content for most metabolites. It provides a means to quantitate baseline contributions that may contain crucial clinical information. Magn Reson Med 48:440–453, 2002.

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans

To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short‐term overfeeding in healthy subjects.

Forensic Application of Postmortem Diffusion-Weighted and Diffusion Tensor MR Imaging of the Human Brain in Situ

BACKGROUND AND PURPOSE: DWI and DTI of the brain have proved to be useful in many neurologic disorders and in traumatic brain injury. This prospective study aimed at the evaluation of the influence of the PMI and the cause of death on the ADC and FA for the application of DWI and DTI in forensic radiology. MATERIALS AND METHODS: DWI and DTI of the brain were performed in situ in 20 deceased subjects with mapping of the ADC and FA. Evaluation was performed in different ROIs, and the influence of PMI and cause of death was assessed. RESULTS: Postmortem ADC values of the brain were decreased by 49%–72% compared with healthy living controls. With increasing PMI, ADCs were significantly reduced when considering all ROIs together and, particularly, GM regions (all regions, P < .05; GM, P < .01), whereas there was no significant effect in WM. Concerning the cause of death, ADCs were significantly lower in mechanical and hypoxic brain injury than in brains from subjects having died from heart failure (traumatic brain injury, P < .005; hypoxia, P < .001). Postmortem FA was not significantly different from FA in living persons and showed no significant influence of PMI or cause of death. CONCLUSIONS: Performing postmortem DWI and DTI of the brain in situ can provide valuable information for application in forensic medicine. ADC could be used as an indicator of PMI and could help in the assessment of the cause of death.

Sugar- and artificially sweetened beverages and intrahepatic fat: A randomized controlled trial

To test the hypothesis that substituting artificially sweetened beverages (ASB) for sugar‐sweetened beverages (SSB) decreases intrahepatocellular lipid concentrations (IHCL) in overweight subjects with high SSB consumption.

Quantitative 1H magnetic resonance spectroscopy of myoglobin de‐ and reoxygenation in skeletal muscle: Reproducibility and effects of location and disease

1H‐magnetic resonance spectroscopy (1H‐MRS) of deoxymyoglobin (DMb) provides a means to noninvasively monitor the oxygenation state of human skeletal muscle in work and disease. As shown in this work, it also offers the opportunity to measure the absolute tissue content of DMb, the basic oxygen consumption of resting muscle, and the reperfusion characteristics after release of a pressure cuff. The methodology to determine these tissue properties simultaneously at two positions along the calf is presented. The obtained values are in agreement with invasive determinations. The reproducibility of the 1H‐MRS measurements is established for healthy controls and patients with peripheral arterial disease (PAD). A location dependence in axial direction, as well as differences between controls and patients are demonstrated for all parameters. The reoxygenation time in particular is expected to provide a means to quantitatively monitor therapies aimed at improving muscular perfusion in these patients. Magn Reson Med 46:240–248, 2001.

Image registration for triggered and non-triggered DTI of the human kidney: Reduced variability of diffusion parameter estimation

To investigate if non‐rigid image‐registration reduces motion artifacts in triggered and non‐triggered diffusion tensor imaging (DTI) of native kidneys. A secondary aim was to determine, if improvements through registration allow for omitting respiratory‐triggering.

Exercise efficiency relates with mitochondrial content and function in older adults

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty‐eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙ O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1‐h submaximal test (55% V˙ O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with 31P‐MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Diffusion tensor imaging of the human kidney: Does image registration permit scanning without respiratory triggering?

To investigate if image registration of diffusion tensor imaging (DTI) allows omitting respiratory triggering for both transplanted and native kidneys