Y. Le Fur

31P magnetic resonance spectroscopy study of phosphocreatine recovery kinetics in skeletal muscle: the issue of intersubject variability.

We have analyzed by (31)P MRS the relationship between kinetic parameters of phosphocreatine (PCr) recovery and end-of-exercise status under conditions of moderate and large acidosis induced by dynamic exercise. Thirteen healthy subjects performed muscular contractions at 0.47 Hz (low frequency, moderate exercise) and 0.85 Hz (high frequency, heavy exercise). The rate constant of PCr resynthesis (k(PCr)) varied greatly among subjects (variation coefficients: 43 vs. 57% for LF vs. HF exercises) and protocols (k(PCr) values: 1.3+/-0.5 min(-1) vs. 0.9+/-0.5 min(-1) for LF vs. HF exercises, P<0.03). The large intersubject variability can be captured into a linear relationship between k(PCr), the amount of PCr consumed ([PCr(2)]) and pH reached at the end of exercise (pH(end)) (k(PCr)=-3.3+0.7 pH(end)-0.03 [PCr(2)]; P=0.0007; r=0.61). This dual relationship illustrates that mitochondrial activity is affected by end-of-exercise metabolic status and allows reliable comparisons between control, diseased and trained muscles. In contrast to k(PCr), the initial rate of PCr recovery and the maximum oxidative capacity were always constant whatever the metabolic conditions of end-of-exercise and can then be additionally used in the identification of dysfunctions in the oxidative metabolic pathway.

Multiparametric differentiation of posterior fossa tumors in children using diffusion-weighted imaging and short echo-time 1H-MR spectroscopy.

To assess the combined value of diffusion‐weighted imaging (DWI) and proton magnetic resonance spectroscopy (1H‐MRS) in differentiating medulloblastoma, ependymoma, pilocytic astrocytoma, and infiltrating glioma in a pediatric population.

MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis

A trophy of corpus callosum (C C) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of C C are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (C ISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure C C volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/C ho) ratio, N-acetyl aspartate/total creatine (NA A/C r) ratio and C ho/C r ratio inside the C C of 46 C ISSMS patients and 24 sexand age-matched controls. No atrophy of C C was observed in the C ISSMS group. C C of patients was character ized by decreased MTR and increased MD. No change in the NA A/C r ratio was observed while the NA A/C ho ratio decreased and C ho/C r ratio increased in the splenium and the central anterio r part of C C. These abnormalities were present in patients with, but also without, macroscopic lesions inside the C C. O ur results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin patho logy, occur in the C C at the earliest stage of MS before any atrophy is detected.

Segmentation of fascias, fat and muscle from magnetic resonance images in humans: the DISPIMAG software.

Segmentation of human limb MR images into muscle, fat and fascias remains a cumbersome task. We have developed a new software (DISPIMAG) that allows automatic and highly reproducible segmentation of lower-limb MR images. Based on a pixel intensity analysis, this software does not need any previous mathematical or statistical assumptions. It displays a histogram with two main signals corresponding to fat and muscle, and permits an accurate quantification of their relative spatial distribution. To allow a systematic discrimination between muscle and fat in any subject, fixed boundaries were first determined manually in a group of 24 patients. Secondly, an entirely automatic process using these boundaries was tested by three operators on four patients and compared to the manual approach, showing a high concordance.

High cerebral scyllo-inositol: a new marker of brain metabolism disturbances induced by chronic alcoholism

Cerebral metabolic changes that concur to motor and/or cognitive disorders in actively drinking alcoholics are not well established. We tested the hypothesis that chronic alcoholics exhibit profound alterations in the cerebral metabolism of scyllo-inositol. Brain metabolism was explored in nine actively drinking and 11 recently detoxified chronic alcoholics by in vivo brain 1H-MRS and in vitro1H-MRS of blood serum and cerebrospinal fluid. The cohort was composed of individuals with acute, subacute or chronic encephalopathy or without any clinical encephalopathy. Chronic alcoholism is associated with a hitherto unrecognized accumulation of brain scyllo-inositol. Our results suggest that scyllo-inositol is produced within the central nervous system and shows a diffuse but heterogenous distribution in brain where it can persist several weeks after detoxification. Its highest levels were observed in subjects with a clinically symptomatic alcohol-related encephalopathy. When detected, brain scyllo-inositol takes part in a metabolic encephalopathy since it is associated with reduced N-acetylaspartate and increased creatine. High levels of cerebral scyllo-inositol are correlated with altered glial and neuronal metabolism. Our findings suggest that the accumulation of scyllo-inositol may precede and take part in the development of symptomatic alcoholic metabolic encephalopathy.

Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MS : A MRSI study

AbstractProton magnetic resonance spectroscopic imaging (1H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T1 gadolinium-enhancing lesions in patients at the very early stage of multiple sclerosis (MS). The spectroscopic examination was performed in the axial plane using a home-designed acquisition-weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms). Bilateral thalami and the medial occipital cortex were explored in 35 patients (15 with and 20 without T1-Gd enhancing lesions) with clinically isolated syndrome suggestive of MS and in 30 controls. The mean duration since the first presenting symptom was 9.1 (±6.7) months. The two groups of patients (with or without T1 Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T2 lesion load. The spatial contamination of surrounding WM tissues was obtained in each GM region by determining the tissue component in the ROI from GM and WM probability maps smoothed with the point spread function of the MRSI acquisition. Contribution of WM signal was important (60%) inside thalami while the region centered on the medial occipital cortex was well representative of GM metabolism (>70%). Comparisons of relative metabolite levels (ratios of each metabolite over the sum of all metabolites) between all patients and controls showed significant decrease in relative N-acetyl aspartate (NAA) levels, increase in relative choline-containing compounds (Cho) levels and no change in relative creatine/phosphocreatine levels inside the three ROIs. Decrease in relative NAA levels and increase in relative Cho levels were found in patients with inflammatory activity, while no metabolic alterations were present in patients without T1 Gd-enhancing lesions. These results suggest that abnormalities in GM metabolism observed in patients at the very early stage of MS are mainly related to neuronal dysfunction occurring during acute inflammatory processes.

1H-MRS imaging in intractable frontal lobe epilepsies characterized by depth electrode recording.

Presurgical evaluation of frontal lobe epilepsy (FLE) remains a challenging issue and frequently requires invasive depth electrode recording. In this study, we aimed at evaluating the potential usefulness of a non-invasive technique such as proton magnetic resonance spectroscopic imaging ((1)H-MRSI) in the presurgical evaluation of FLE and at investigating the potential electrophysiological correlates of the metabolic disturbances as defined by (1)H-MRSI. We compared the distribution of (1)H-MRSI abnormalities with the electrophysiological abnormalities defined by stereo-electroencephalography (SEEG) recording in 12 patients presenting with several subtypes of FLE. We also used 12 control subjects in order to obtain normative (1)H-MRSI data. We used a multilevel (1)H-MRSI protocol to better sample the principal regions of the frontal lobe. We also applied a metabolic mapping technique allowing a visual display of metabolic data. A significant decrease of both N-acetyl-aspartate/phosphocreatine-creatine and N-acetyl-aspartate/(choline-compounds + phosphocreatine-creatine) ratios was observed in regions involved in the epileptogenic zone (EZ) and/or the irritative zone (IZ) compared to regions without electrical abnormalities in the same patients (P = 0.044 and P = 0.018, respectively), and also compared to controls (P = 0.004 and P = 0.0001, respectively). No significant differences in metabolic ratios were observed between those regions involved in the EZ and those involved in the IZ only. Our results suggest a link between the relative decrease of N-acetyl-aspartate and the EZ as well as the IZ in FLE. Thus, multilevel (1)H-MRSI protocol may add pertinent information during the non-invasive presurgical evaluation of FLE.

Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans.

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used 31P‐magnetic resonance spectroscopy (31P‐MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min‐1, CVinter‐subject = 42%) as compared with PF (46 ± 20 mM min‐1, CVinter‐subject = 44%) and tended to be higher in FF (43 ± 35 mM min‐1, CVinter‐subject = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end‐exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end‐exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter‐ and intra‐individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright

Structure cristalline de la phase β-KEr2F7. Composés isotypes

Abstract Potassium erbium fluoride β-KEr 2 F 7 crystallizes in the orthorhombic system, space group Pna 2 1 , with the unit-cell dimensions a = 11.820, b = 13.333, c = 7.816A ( Z = 8). The crystal structure has been solved from single-crystal diffractometer measurements (Ag Kα ) by Patterson and Fourier syntheses and refined by a least-squares method. The final R value is 0.042 for 2374 independent observed reflections ( R W = 0.051). The four species of erbium atoms are surrounded by eight fluorine atoms. These fluorine atoms form, respectively, three quadratic antiprisms and one dodecahedron, derived from a distorted cube. Two antiprisms and the dodecahedron share two of their faces to form (Er 3 F 17 ) 8− groups. These groups are bidimensionally linked and the planes they form are joined together by the third antiprism. A three-dimensional network is then produced, in the tunnels of which potassium atoms are located. Lattice parameters of compounds which are isotypic to the new structure type of β-KEr 2 F 7 are given.

Capsiate administration results in an uncoupling protein-3 downregulation, an enhanced muscle oxidative capacity and a decreased abdominal fat content in vivo

Objectives:The involvement of skeletal muscle mitochondrial uncoupling protein-3 (UCP3) in the control of energy expenditure in skeletal muscle and at the whole-body level is still a matter of debate. We previously reported that UCP3 downregulation is linked to an enhanced mitochondrial energy metabolism in rat skeletal muscle as a result of acute capsiate treatment. Here, we aimed at investigating noninvasively the effects of chronic capsiate ingestion on metabolic changes occurring in exercising gastrocnemius muscle and at the whole-body level.Methods:We used an original experimental setup allowing a complete noninvasive investigation of gastrocnemius muscle function in situ using 31-phosphorus magnetic resonance spectroscopy. Whole-body fat composition was determined using magnetic resonance imaging and UCP3 gene expression was measured by quantitative real-time RT-PCR analysis.Results:We found that a 14-day daily administration of capsiate (100 mg kg−1 body weight) reduced UCP3 gene expression and increased phosphocreatine level at baseline and during the stimulation period in gastrocnemius muscle. During muscle stimulation, pHi showed a larger alkalosis in the capsiate group suggesting a lower glycolysis and a compensatory higher aerobic contribution to ATP production. Although the capsiate-treated rats were hyperphagic as compared to control animals, they showed a lower weight gain coupled to a decreased abdominal fat content.Conclusion:Overall, our data indicated that capsiate administration contributes to the enhancement of aerobic ATP production and the reduction of body fat content coupled to a UCP3 gene downregulation.