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International audience; ObjectiveTo quantify individual muscle volume in rat leg MR images using a fully automatic multi-atlas-based segmentation method.Materials and methodsWe optimized a multi-atlas-based segmentation method to take into account the voxel anisotropy of numbers of MRI acquisition protocols. We mainly tested an image upsampling process along Z and a constraint on the nonlinear deformation in the XY plane. We also evaluated a weighted vote procedure and an original implementation of an artificial atlas addition. Using this approach, we measured gastrocnemius and plantaris muscle volumes and compared the results with manual segmentation. The method reliability for volume quantification was evaluated using the relative overlap index.ResultsThe most accurate segmentation was obtained using a nonlinear registration constrained in the XY plane by zeroing the Z component of the displacement and a weighted vote procedure for both muscles regardless of the number of atlases. The performance of the automatic segmentation and the corresponding volume quantification outperformed the interoperator variability using a minimum of three original atlases.ConclusionWe demonstrated the reliability of a multi-atlas segmentation approach for the automatic segmentation and volume quantification of individual muscles in rat leg and found that constraining the registration in plane significantly improved the results.

Background To derive an adapted protocol at ultra high magnetic field for mouse kidney perfusion measurements using pCASL in combination with three widely available fast imaging readouts: segmented SE EPI (sSE EPI), RARE, and TrueFISP. Methods pCASL sSE EPI, pCASL RARE, and pCASL TrueFISP were used for the acquisition of mouse kidney perfusion images in the axial and coronal planes at 11.75T. Results were compared in terms of perfusion sensitivity, signal-to-noise ratio (SNR), blood flow values, intrasession and intersession repeatability, and image quality (subjectively classified into three grades: good, satisfactory, and unacceptable). Results Renal cortex perfusion measurements were performed within 2 min with pCASL RARE/pCASL TrueFISP and 4 min with pCASL sSE EPI. In an axial direction, SNR values of 6.6/5.6/2.8, perfusion sensitivity values of 16.1 ± 3.7/13.6 ± 2.4/13.4 ± 1.0 %, blood flow values of 679 ± 149/466 ± 111/572 ± 46 mL/100 g/min and in-ROI variations values of 192/161/181 mL/100 g/min were obtained with pCASL sSE EPI/pCASL RARE/pCASL TrueFISP. Highest SNR per unit of time (1.8) and highest intra/intersession reliability (92.9% and 95.1%) were obtained with pCASL RARE, which additionally presented highly reproducible satisfactory image quality. In coronal plane, significantly lower SNR, perfusion sensitivity and perfusion values were obtained for all techniques compared with that in the axial plane (P

Background We measured the functional and metabolic status of hearts submitted to normothermic ischemia before preservation through the use of an ex vivo pig heart model to assess the feasibility of donation after cardiac death (DCD) in heart transplantation. Methods Ten pigs were separated into 2 groups: control ( n = 6, brain-dead group) and DCD ( n = 4, heart donation after cardiac death). In the control group, hearts were excised 20 minutes after the brachiocephalic trunk cross-clamping and were immediately reperfused. In DCD, hearts were excised 20 minutes after exsanguination and asphyxia, stored in the Centre de Resonance Magnetique Biologique et Medicale (CRMBM) solution for 2 hours, and then were reperfused. Cardioplegic arrest was induced with the use of 1 L of CRMBM solution (4°C) and the heart was reperfused for 60 minutes through the use of an ex vivo perfusion system in Langendorff mode with normothermic autologous blood. During reperfusion, functional parameters were analyzed. Biochemical assays were performed in myocardial effluents and freeze-clamped hearts. Results No electromechanical activity was found in DCD compared with control. Creatine kinase (CK) was higher at 2 minutes of reperfusion in DCD versus control ( P = .005). Adenosine triphosphate was lower in DCD versus control ( P = .0019). Malondialdehyde, an oxidative stress index, was present only in DCD. The nitric oxide (NO) pathway was impaired in DCD versus control, with lower eNOS expression ( P P = .04). Conclusions We reported no cardiac functional and metabolic recovery in the DCD group after normothermic ischemia and reperfusion, which indicates that a single immersion of the cardiac graft during storage does not provide an optimal protection. New strategies in heart preservation are necessary for recruiting heart donation after cardiac death.

BACKGROUND: To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers. METHODS: Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure-posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1 (+) , B1 (-) , and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained. RESULTS: The combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA = 10.03 + 1.71; cCho = 1.78 ± 0.55; cCr = 7.29 ± 1.69; cmIns = 5.30 ± 2.67) and in cerebellum (cNAA = 5.28 ± 1.77; cCho = 1.60 ± 0.41; cCr = 6.95 ± 2.15; cmIns = 3.60 ± 0.74). CONCLUSION: A double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain. J. Magn. Reson. Imaging 2015;42:280-289.

We have designed and constructed an experimental set-up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high-field (11.75T). We performed high-resolution multimodal MRI (including T2 -weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1-week period to investigate the reliability of mechanical measurements and T2 changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T2 values were highly reproducible as illustrated by the low coefficient of variation (

Purpose Quantitative measure of blood flow provides important information regarding renal function, nephropathies and viability of kidney transplantation. Therefore, a method that would allow quantitative and reliable assessment of the renal microvascular perfusion would be very valuable. Arterial spin labeling Magnetic Resonance Imaging has started to be widely used for human studies. For rodents though, despite the increasing number of transgenic mouse models, renal perfusion Magnetic Resonance Imaging has been only sparsely reported. This study investigated the use of FAIR (flow-sensitive alternating inversion recovery) and pseudo-continuous arterial spin labeling (pCASL) for mouse renal blood flow measurements. Methods FAIR and pCASL were compared in terms of sensitivity, absolute quantification, reproducibility and flexibility of implementation. Multislice and coronal imaging were also investigated. Studies were performed at 11.75 T with volumic transmitter/receiver radiofrequency coils and fast imaging. Results pCASL demonstrated better experimental flexibility and higher sensitivity compared to FAIR (> +20%). Renal blood flow values in the range of 550–750 mL/100 g/min for the cortex and of 140–230 mL/100 g/min for the medulla, consistent with literature data, were measured. Conclusion pCASL was successfully applied at very high field for mouse renal blood flow measurements, demonstrating high sensitivity, flexibility and multislice imaging capability. pCASL may be considered as a method of choice for mouse kidney perfusion studies. Magn Reson Med 71:1186–1196, 2014. © 2013 Wiley Periodicals, Inc.

Background: In this study, we evaluated how adding L-arginine to Centre de Resonance Magnetique Biologique et Medicale (CRMBM) solution affected myocardial performance during post-ischemic in vivo reperfusion. Methods: Experiments were conducted using a modified Lewis–Lewis heterotopic heart transplantation model, with a total ischemic time of 3 hours followed by 1 or 24 hours of blood reperfusion. Heart grafts were arrested using intra-aortic injection of CRMBM solution, either supplemented or not supplemented with 2 mmol/liter L-arginine (n = 12 in each group). We measured systolic indexes and simultaneously performed phosphorus magnetic resonance spectroscopy (31P MRS). We quantified total endothelial nitric oxide synthase (eNOS) protein using the Western blot test of freeze-clamped hearts. Results: Contractility during early reperfusion was significantly better in grafts arrested with CRMBM solution enriched with L-arginine: mean rate pressure product, 11249 ± 1,548 vs 5,637 ± 1,118 mm Hg/min (p = 0.05), and maximal first derivative of the pressure signal (dP/dtmax), 1,721 ± 177 vs 1,214 ± 321 mm Hg/sec (p = 0.013). Conversely, during late reperfusion, contractility did not relate to the nature of the preservation solution. The presence of L-arginine in the CRMBM solution did not alter time-related variations of high-energy phosphate ratios measured using in vivo 31P MRS. The eNOS protein level decreased significantly during early compared with late reperfusion, with no effect caused by L-arginine. Conclusions: During early reperfusion, the limited myocardial stunning observed with CRMBM solution containing L-arginine does not relate to energy metabolism but to better preservation of the NO pathway.

INTRODUCTION: Endurance training elicits tremendous adaptations of the mitochondrial energetic capacity. Yet, the effects of training or physical fitness on mitochondrial efficiency during exercise are still unclear. Accordingly, the purpose of the present study was to examine in vivo the differences in mitochondrial efficiency and ATP cost of contraction during exercise in two groups of adults differing in their aerobic capacity. METHOD: We simultaneously assessed the ATP synthesis and O2 fluxes with P-magnetic resonance spectroscopy and pulmonary gas exchange measurements in seven endurance-trained (ET, V˙O2max: 67 ± 8 mL·min⁻¹·kg⁻¹) and seven recreationally active (RA, V˙O2max: 43 ± 7 mL·min⁻¹·kg⁻¹) subjects during 6 min of dynamic moderate-intensity knee extension. RESULTS: The ATP cost of dynamic contraction was not significantly different between ET and RA (P > 0.05). Similarly, end-exercise O2 consumption was not significantly different between groups (ET: 848 ± 155 mL·min⁻¹ and RA: 760 ± 131 mL·min⁻¹, P > 0.05). During the recovery period, the PCr offset time constant was significantly faster in ET compared with RA (ET: 32 ± 8 s and RA: 43 ± 10 s, P < 0.05), thus indicating an increased mitochondrial capacity for ATP synthesis in the quadriceps of ET. In contrast, the estimated mitochondrial efficiency during exercise was not significantly different (P/O, ET: 2.0 ± 1.0 and RA: 1.8 ± 0.4, P > 0.05). Consequently, the higher mitochondrial capacity for ATP synthesis in ET likely originated from an elevated mitochondrial volume density, mitochondria-specific respiratory capacity, and/or slower postexercise inactivation of oxidative phosphorylation by the parallel activation mechanism. CONCLUSION: Together, these findings reveal that 1) mitochondrial and contractile efficiencies are unaltered by several years of endurance training in young adults, and 2) the training-induced improvement in mitochondrial energetic capacity appears to be independent from changes in mitochondrial coupling.y.

Gaborit, Benedicte Kober, Frank Jacquier, Alexis Moro, Pierre Julien Flavian, Antonin Quilici, Jacques Cuisset, Thomas Simeoni, Umberto Cozzone, Patrick Alessi, Marie-Christine Clement, Karine Bernard, Monique Dutour, Anne Research Support, Non-U.S. Gov't United States Obesity (Silver Spring, Md.) Obesity (Silver Spring). 2012 Jun;20(6):1200-5. doi: 10.1038/oby.2011.283. Epub 2011 Oct 6.; Epicardial fat (EF) is an active ectopic fat depot, which has been associated with coronary atherosclerosis, and which could early influence endothelial function. We thus investigated the relationship between EF and endothelium-dependent vasoreactivity of the coronary microcirculation, in highly selected healthy volunteers. Myocardial blood flow (MBF) was determined by measuring coronary sinus flow with velocity-encoded cine magnetic resonance imaging (MRI) at 3T. We measured MBF at baseline and in response to sympathetic stimulation by cold pressor testing (CPT) in 30 healthy volunteers with normal left ventricular (LV) function (age 22 +/- 4 years, BMI = 21.3 +/- 2.8 kg/m(2)). EF volume was volumetrically assessed by manual delineation on short-axis views. CPT was applied by immersing one foot in ice water for 4 min. Mean EF volume was 56 +/- 26 ml and mean LV mass 100 +/- 28 g. CPT significantly increased heart rate (HR) by 32 +/- 19%, systolic blood pressure by 14 +/- 10%, and rate-pressure product by 45 +/- 25%, P < 0.0001. The increase in HR, reflecting sympathetic stimulation, was not influenced by sex, age or EF volume. CPT induced a decrease in coronary vascular resistance (135 +/- 72 vs. 100 +/- 42 mm Hg.ml(-1).min.g, P = 0.0006), and a significant increase in MBF (0.81 +/- 0.37 vs. 1.24 +/- 0.56 ml.min(-1).g(-1), P < 0.0001). Interestingly, we found a significant negative correlation between EF volume and DeltaMBF (r= - 0.40, P = 0.03), which remained significant after adjusting for DeltaHR. DeltaMBF was also associated with adiponectin (r = 0.41, P = 0.046), but not with waist circumference, BMI, C-reactive protein, lipid or glycemic parameters. In multivariate analysis, adiponectin and EF volume remained both independently associated with DeltaMBF. A high EF amount is associated with a lower coronary microvascular response, suggesting that EF could early influence endothelial function.

Durante, Laurence Zaaraoui, Wafaa Rico, Audrey Crespy, Lydie Wybrecht, Delphine Faivre, Anthony Reuter, Francoise Malikova, Irina Pommier, Gilbert Confort-Gouny, Sylviane Cozzone, Patrick J Ranjeva, Jean-Philippe Pelletier, Jean Boucraut, Jose Audoin, Bertrand Research Support, Non-U.S. Gov't England Multiple sclerosis (Houndmills, Basingstoke, England) Mult Scler. 2012 May;18(5):587-91. Epub 2011 Sep 30.; BACKGROUND: Previous studies have demonstrated that intrathecal synthesis of IgM is observed in multiple sclerosis (MS) and correlates with a worse disease course. These results suggest that IgM participates in the formation of MS lesions. OBJECTIVE: The aim of the present study was to assess the potential association between the level of intrathecal synthesis of IgM measured after a clinically isolated syndrome (CIS) and the subsequent formation of brain lesions. METHODS: Fifty seven patients with a CIS and a high risk developing MS were enrolled in a longitudinal study. Examination of cerebrospinal fluid was performed after the CIS and included measures of intrathecal IgM and IgG synthesis. Patients were assessed with the same 1.5 Tesla magnetic resonance imaging (MRI) system at baseline and after a mean follow-up period of 49 months (range 36-60). Spearman Rank correlation was used to assess the potential correlations between levels of intrathecal immunoglobulin synthesis and MRI data. RESULTS: The level of intrathecal IgM synthesis was correlated with the number of gadolinium-enhancing lesions at baseline (p = 0.01) and with accrual of brain lesions during the follow-up period (p = 0.02). By taking into account brain sub-regions, we demonstrated that the level of intrathecal IgM synthesis was only correlated with the increased number of lesions in the periventricular regions (p = 0.004). The level of intrathecal IgG synthesis was not correlated with any MRI data. CONCLUSION: The present longitudinal study demonstrates that the level of intrathecal IgM synthesis measured after a CIS is associated with subsequent lesion accrual during the first years of MS. This result emphasizes the involvement of IgM in plaque formation.

While muscle damage resulting from electrically-induced muscle isometric contractions has been reported in humans, animal studies have failed to illustrate similar deleterious effects and it remains to be determined whether these conflicting results are related to differences regarding experimental procedures or to species. We have investigated in vivo , in rat gastrocnemius muscles, using experimental conditions as close as possible to those used in humans (i.e., muscle length, number of contractions, stimulated muscle), the effects of a single bout of neuromuscular electrical stimulation (NMES). Maximal tetanic force was measured before, immediately after and 1h and 1, 2, 3, 7 and 14days after NMES. Magnetic resonance imaging measurements, including volume of gastrocnemius muscles and proton transverse relaxation time ( T 2 ) were performed at baseline and 3, 7, and 14days after the NMES session. Control animals did not perform any exercise and measurements were recorded at the same time points. For both groups, blood creatine kinase (CK) activity was measured within the first 3days that followed the initial evaluation. Maximal tetanic force decreased immediately after NMES whereas measurements performed 1h and the days afterwards were similar to the baseline values. CK activity, muscle volume and T 2 values were similar throughout the experimental protocol between the two groups. Under carefully controlled experimental conditions, isometric NMES per se did not induce muscle damage in rat gastrocnemius muscles on the contrary to what has been repeatedly reported in humans. Further experiments would then be warranted in order to clearly delineate these differences and to better understand the physiological events associated with muscle damage resulting from NMES-induced isometric contractions.

Development of surrogate markers is necessary to assess the potential efficacy of new therapeutics in Niemann–Pick Disease Type C (NP-C). In the present study, magnetization transfer ratio (MTR) imaging, a quantitative MRI imaging technique sensitive to subtle brain microstructural changes, was applied in two patients suffering from adult NP-C. Statistical mapping analysis was performed to compare each patient's MTR maps with those of a group of 34 healthy controls to quantify and localize the extent of brain injury of each patient. Using this method, pathological changes were evidenced in the cerebellum, the thalami and the lenticular nuclei in both patients and also in the fronto-temporal cortices in the patient with the worse functional deficit. In addition, white matter changes were located in the midbrain, the cerebellum and the fronto-temporal lobes in the patient with the higher level of disability and in only one limited periventricular white matter region in the other patient. A 6-month follow-up was performed in the patient with the lower functional deficit and evidenced significant extension of grey matter (GM) and white matter (WM) injuries during the following period (14% of increased injury for GM and 53% for WM). This study demonstrates that significant brain injury related to clinical deficit can be assessed in vivo in adult NP-C using MTR imaging. Although preliminary, these findings suggest that MTR imaging may be a relevant candidate for the development of biomarker in NP-C.

Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits "small-world" properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer's disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies.

The purpose of the present study was to assess the reliability of metabolic parameters measured using 31P magnetic resonance spectroscopy (31P MRS) during two standardized rest-exercise-recovery protocols. Twelve healthy subjects performed the standardized protocols at two different intensities; i.e., a moderate intensity (MOD) repeated over a two-month period and heavy intensity (HEAVY) repeated over a year's time. Test-retest reliability was analyzed using coefficient of variation (CV), limits of agreement (LOA), and intraclass correlation coefficients (ICC). During exercise and recovery periods, most of the metabolic parameters exhibited a good reliability. The CVs of individual concentration of phosphocreatine ([PCr]), concentration of adenosine diphosphate ([ADP]), and pH values recorded at end of the HEAVY exercise were lower than 15%. The CV calculated for the rate of PCr resynthesis and the maximal oxidative capacity were less than 13% during the HEAVY protocol. Inferred parameters such as oxidative and total adenosine triphosphate (ATP) production rates exhibited a good reliability (ICC ≈ 0.7; CV < 15% during the HEAVY protocol). Our results demonstrated that measurement error using 31P-MRS during a standardized exercise was low and that biological variability accounted for the vast majority of the measurement variability. In addition, the corresponding metabolic measurements can reliably be used for longitudinal studies performed even over a long period of time. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc.

International audience; In spinal cord injuries (SCI), tissue edema and consequent ischemia play an important role in neuronal damage. The assessment of quantitative spinal cord blood flow (SCBF) would be very valuable to help in understanding SCI pathophysiology. SCBF has previously been measured in animals with invasive techniques such as hydrogen clearance or labeled microspheres. A recent preliminary study also demonstrated the feasibility of assessing cervical SCBF by MRI with arterial spin labeling (ASL). However, due to bulk motion and field inhomogeneities, the feasibility of perfusion MRI at lower levels of the SC (thoracic, lumbar) remained an open question. In the present study, absolute SCBF measurements were carried out at both the cervical C3 and lumbar L1 levels of mouse SC using an adapted presaturated flow-sensitive alternating inversion recovery (presat-FAIR) ASL technique at 11.75T. Quantitative SCBF maps (resolution of 133 x 133 microm(2)) showed significantly lower gray matter (GM) perfusion values at the L1 level as compared to the C3 level (6% and 11% for the ventral and dorsal horns and 8% for total GM). The presat-FAIR technique was then successfully applied to a mouse model of hemisection performed at the L1 level, illustrating the potential of ASL to help in SC pathology characterization.

International audience; PURPOSE: Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. METHODS: We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. RESULTS: Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. CONCLUSION: These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the "net sum" of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective.

Although the exact mechanisms are still unclear, it is commonly acknowledged that acute eccentric exercise alters muscle performance whereas the repetition of successive bouts leads to the disappearance of the deleterious signs. In order to clarify this issue, we measured blood creatine kinase, lactate dehydrogenase activities and proton T2 relaxation time in various leg muscles 72 hours after a single and repeated bouts of exhausting downhill running sessions (-15 degrees ;1.5km/h), elapsed by either 4 or 7-days. After a single exercise bout, T2 and enzyme activities initially increased and recovered rapidly. When exercise bouts were repeated over a short time period (4-days), initial changes did not recover and endurance time throughout additional exercise sessions was significantly reduced. On the contrary, with a longer resting time between exercises (7-days), endurance time of additional running sessions was significantly longer and muscle changes (T2 increase, muscle oedema and enzyme activities changes) slowly and completely reversed. Significant correlations were found between T2 changes and enzymes activities. T2 changes in the soleus and gastrocnemius muscle heads were differently affected by lengthening contractions suggesting a muscle-specificity and indicating that muscle alterations might be linked to different anatomical properties such as fiber pennation angles, typology and/or to the exhausting nature of the downhill running sessions. We documented a "less muscle injury" effect due to the repetition of exercise bouts at a low frequency (i.e. 1 session per week), in accordance with the delayed muscle inflammation. This effect was not observed when the between-exercise resting time was shorter. Key words: eccentric, skeletal muscle, rat, lengthening, functional MR imaging.

The mechanical and structural properties of skin subjected to expansion have been widely investigated in the context of plastic surgery. To determine the actual metabolic state of skin following skin expander placement, we determined the basic biochemical parameters for various conditions of postsurgical wound healing and cutaneous growth. Studying, for the first time, comprehensive metabolic profiles ("metabolomics") of the skin in a minipig model, we found that the lactate/alanine ratios were significantly increased (p

Purpose To investigate the capacity of multimodal MR to detect endothelial hyperplasia (EH), which has been linked to the aggressiveness of gliomas and which is so far only detected by biopsy, an invasive technique that prevents repeated measurements and early detection. Materials and Methods A total of 26 patients with low-grade gliomas participated in the study. All underwent a histopathological analysis and a multimodal MR examination (spectroscopic, anatomic, diffusion, perfusion, and postcontrast imaging). Results EH was present (EH+) in 15 patients and absent (EH–) in 11. No differences were observed between EH– and EH+ groups when comparing spectroscopic and diffusion parameters. Perfusion measurements, however, allowed us to distinguish EH+ from EH–: the relative regional cerebral blood flow (rCBF) was found equal to 3.23 ± 2.05 for EH+ and 1.33 ± 0.46 for EH– (P = 0.006). Conclusion We have observed a strong correlation between the presence of EH and the increase of rCBF. Compared to conventional imaging, MR perfusion provides additional and complementary information that may be used for biopsy guidance, early detection of tumor aggressiveness, and noninvasive follow-ups. J. Magn. Reson. Imaging 2007;26:52–60. © 2007 Wiley-Liss, Inc.

International audience; PURPOSE: This study compared the metabolic and activation changes induced by electrically evoked (neuromuscular electrical stimulation (NMES)) and voluntary (VOL) contractions performed at the same submaximal intensity using P chemical shift imaging (CSI) and T2 mapping investigations. METHODS: Fifteen healthy subjects were asked to perform both NMES and VOL protocols with the knee extensors (i.e., 232 isometric contractions at 30% of maximal force) inside a 3-T scanner for two experimental sessions. During the first session, metabolic variations, i.e., phosphocreatine (PCr), inorganic phosphate (Pi), and pH, were recorded using localized P CSI. During a second session, T2 maps of the knee extensors were obtained at rest and immediately after each exercise. Voxels of interest were selected from the directly stimulated vastus lateralis and from the nondirectly stimulated rectus femoris/vastus intermedius muscles. RESULTS: PCr depletion recorded throughout the NMES session was significantly larger in the vastus lateralis as compared with the rectus femoris/vastus intermedius muscles for both conditions (VOL and NMES). A higher occurrence of Pi splitting and a greater acidosis was found during NMES as compared with VOL exercise, illustrating the heterogeneous activation of both slow and fast muscle fibers. T2 changes were greater after NMES as compared with VOL for both muscles but were not necessarily related to the localized metabolic demand. CONCLUSION: We provided direct evidence that the metabolic demand was strongly related to both the exercise modality and the site of stimulation. On the basis of the occurrence of Pi splitting, we suggested that NMES can activate fast muscle fibers even at low force levels.

We present a method for the analysis of basal ganglia (including the thalamus) for accurate detection of human spongiform encephalopathy in multisequence magnetic resonance imaging (MRI) of the brain. One common feature of most forms of prion protein diseases is the appearance of hyperintensities in the deep grey matter area of the brain in T2-weighted magnetic resonance (MR) images. We employ T1, T2, and Flair-T2 MR sequences for the detection of intensity deviations in the internal nuclei. First, the MR data are registered to a probabilistic atlas and normalized in intensity. Then smoothing is applied with edge enhancement. The segmentation of hyperintensities is performed using a model of the human visual system. For more accurate results, a priori anatomical data from a segmented atlas are employed to refine the registration and remove false positives. The results are robust over the patient data and in accordance with the clinical ground truth. Our method further allows the quantification of intensity distributions in basal ganglia. The caudate nuclei are highlighted as main areas of diagnosis of sporadic Creutzfeldt-Jakob Disease (sCJD), in agreement with the histological data. The algorithm permitted the classification of the intensities of abnormal signals in sCJD patient FLAIR images with a higher hypersignal in caudate nuclei (10/10) and putamen (6/10) than in thalami. Defining normalized MRI measures of the intensity relations between the internal grey nuclei of patients, we robustly differentiate sCJD and variant CJD (vCJD) patients, in an attempt to create an automatic classification tool of human spongiform encephalopathies.

Resume Les rhabdomyolyses suscitent de nos jours un regain d'interet. Qu'elles soient toxiques, medicamenteuses, infectieuses, associees a un effort, a un ecrasement musculaire ou a une maladie (dystrophinopathies, myopathies metaboliques) il est important de cerner le contexte physiopathologique pour circonscrire ce processus de lyse musculaire le plus rapidement possible et en eviter la recidive. Cette mise au point presente les mecanismes physiopathologiques, les differents contextes nosologiques et les modalites d'exploration des rhabdomyolyses avec un accent tout particulier sur les methodes d'exploration non invasive.

Rhabdomyolysis has sparked new interest in recent years. The causes of rhabdomyolysis include drugs and other toxic agents, infections, physical exertion, crush injury, and muscle diseases (dystrophinopathies and metabolic myopathies). Prompt identification of the pathophysiological mechanism is the key to rapid control of the acute episode and to prevention of recurrences. In this update, we discuss the pathophysiological mechanisms and nosology of rhabdomyolysis, as well as diagnostic investigations, with special emphasis on noninvasive methods.

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.

Purpose: Aerobic training of professional road cyclists is linked to tremendous aerobic capacities that have never been clearly related to what occur in skeletal muscles submitted to a specific exercise. The aim of the present study was to examine specifically metabolic recovery after an incremental cycling exercise performed until exhaustion in professional road cyclists as compared with moderately trained subjects and so using 31P- MRS. Methods: Subjects performed a progressive cycling exercise on a cycloergometer until exhaustion, then they were positioned back in the magnet (delay lower than 45 s) for recovery scanning. 31P spectra of thigh muscles were time averaged in 2-s blocks at rest and for 15 min throughout the recovery period. Results: For a significantly more intense exercise (477 ± 28 vs 334 ± 24 W in controls; P < 0.001), professional road cyclists displayed similar end-of-exercise extrapolated pH values (6.43 ± 0.16 vs 6.34 ± 0.05 in controls) and a significantly higher PCr concentration (20.1 ± 0.8 vs 13.3 ± 0.5 mM in controls, P < 0.001). The pH recovery kinetics provided the evidence of metabolic adaptations related to a specific training in professional cyclists with a significantly faster rate (P < 0.01) of pH return toward basal values (32.8 ± 18.9 vs 10.8 ± 6.7 mM·min-1). On the contrary, no significant difference was measured for the PCr recovery kinetics. At rest, PDE concentration was significantly higher in professional cyclists (2.50 ± 0.80 vs 1.76 ± 0.42 mM), likely indicating a difference regarding fiber-type composition. Discussion: The present data demonstrated for the first time that the tremendous aerobic capacity in professional cyclists is linked to faster pH recovery kinetics after a specific cycling exercise. Copyright

OBJECTIVE: Microvascular alterations in the diabetic and hypertensive heart are likely to contribute to heart failure. In this work, myocardial blood flow and left ventricular function were measured in vivo in diabetic, hypertensive, and diabetic-hypertensive rats using MRI methods. METHODS: An 8-week-duration type 1 diabetes was induced by streptozotocin (STZ) in 8 Wistar-Kyoto (WKY) rats (STZ) and in 11 spontaneously hypertensive (SHR) rats (STZ-SHR). Fourteen WKY and 12 SHR served as control and hypertensive groups. Myocardial blood flow quantification was performed using an arterial spin-labeling MRI method. Left ventricular morphology and function were assessed during the same experiment using cine-MRI. RESULTS: Respective myocardial blood flow values for each group were 6.4 +/- 1.1 (WKY), 6.0 +/- 1.9 (STZ), 5.5 +/- 1.3 (SHR), and 4.3 +/- 0.9 mL. g(-1). min(-1) (STZ-SHR). Myocardial blood flow was significantly decreased in STZ-SHR rats compared with the other groups (p \textless.05, STZ-SHR vs. all groups). Cine-MRI showed morphological alterations in all pathological groups. No alteration of the ejection fraction was observed in the pathological groups. CONCLUSION: Myocardial blood flow is altered in vivo before any sign of heart failure when rats have type 1 diabetes and hypertension simultaneously. When only one of the pathologies occurs, MBF does not vary significantly.

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.

Purpose To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). Materials and Methods We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P < 0.0001, k = 20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. Results A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. Conclusion These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease. J. Magn. Reson. Imaging 2004;20:765–771. © 2004 Wiley-Liss, Inc.

Multiple sclerosis: needs for biomarkers of neuronal injury Multiple sclerosis (MS) is a chronic disease of the CNS, representing the leading cause of neuro­ logical disability in young adults. Focal inflam­ matory and demyelinating lesions disseminated in the cerebral white matter have been considered for several decades to be the main feature of MS. However, recent histological studies have also demonstrated the presence of diffuse and progressive damage in cerebral white and gray matter, leading to neuronal injury [1–3]. While neuronal injury is known to occur progressively from the onset of MS and is thought to be a significant cause of increasing clinical disability, the mechanisms underlying neuronal injury are still poorly understood. Furthermore, the conventional MRI metrics lack the specificity required to depict this pathological process, so noninvasive and in vivo biomarkers of neuronal injury are needed. Recently, several experimental studies have highlighted the potential key role of sodium accumulation leading to the pathogenesis of neuronal injury [4–7]. It appears that occurrence of demyelination is followed by upregulation and redistribution of sodium channels along the entire demyelinated axolemna [4,8,9]. The increased number of sodium channels enhances the amount of energy required from the Na/K ATPase. Concomitantly, soluble mediators of inflammation disturb the functional integrity of mitochondria, resulting in decreased ATP production [5,10]. All of these mechanisms driven by mitochondrial energy failure result in axonal sodium accumulation, which leads to reversed activity of the Na/Ca exchanger and axonal calcium import. This calcium overload stimulates a variety of toxic calcium­dependent enzymes, causing structural and functional axonal injury [6,10]. Brain sodium MRI: a unique noninvasive tool to depict accumulation of sodium in MS Sodium (Na) MRI appears to be the unique noninvasive way to detect and quantify in vivo the sodium concentration in the brain based on the magnetic properties of the Na nucleus [11–13]. In the human brain, sodium is distributed in two compartments; the intracellular and the extracellular compartments. The concentration gradient between the two compartments is kept constant through the effect of the sodium–potassium pump. The total sodium concentration measured by sodium MRI is the average sodium concentration between the two compartments. Sodium MRI is a promising diagnostic tool since pathological processes can alter this ion gradient. This technique has already been used to investigate strokes and brain tumors [14]. However, sodium MRI remains a challenging technique due to several limitations. A major problem of sodium MRI is related to the very short transverse relaxation time (T 2 ) of Na (

Introduction. - We aimed to characterize the physical capacities of a population of professional cyclists using anthropometrical, cardiovascular, respiratory, ventilatory, and energetic measures. Synthesis of facts. - Eight professional cyclists participated in this study. They performed over 1 day, 5 exercises (progressive and constant-load test) on a cyclo-ergometer. Conclusions. - Physical and physiological results confirmed previous observations done on professional cyclists. The values of maximal power tolerated and time to exhaustion at this power are reproducible during the day thus demonstrated the excellent capability to recover of the professional cyclists.

Objective. The authors performed a multi-institutional, prospective, blind study on hearts from local donors to validate the feasibility and accuracy of the metabolic evaluation of human hearts by phosphorus-31 ( 31 P) magnetic resonance spectroscopy (MRS) before transplantation. Methods. Twenty-one hearts were separated into two groups according to a transplantation score (TS) on the basis of the current clinical and echocardiographic evaluation as follows: TS1 (n=7), grafts for United Network for Organ Sharing (UNOS) 1 patients only; and TS2 (n=14), grafts suitable for UNOS 2 patients. All hearts were cold preserved with Celsior and underwent ex situ 31 P MRS to measure ratios of various high-energy phosphate metabolites and the intracellular pH (pH i ). Results. The total duration of the MRS procedure was 32 min, thereby not unacceptably increasing the total ischemic time for the transplanted grafts. Phosphocreatine (PCr) and inorganic phosphate (P i ) was significantly different between the two groups (0.95±0.29 for TS1 and 2.05±0.74 for TS2). The difference in pH i was also significant (7.44±0.13 for TS1 and 7.64±0.19 for TS2). Conclusions. Determination of PCr-Pi and pHi as markers of ischemic injury before transplantation can be considered as an objective and accurate criterion for the decision to accept or refuse heart grafts for transplantation.

This study compared the metabolic regional alterations, characterized by proton magnetic spectroscopic imaging ((1)H-MRSI), with electrophysiological abnormalities recorded by using depth electrodes and with structural lesions, in patients with several subtypes of temporal lobe epilepsy (TLE).Twenty-five subjects were investigated, including 15 controls and 10 patients with drug-resistant unilateral TLE, nine of whom had structural abnormalities identified by MRI. All patients underwent noninvasive presurgical evaluation and then stereoelectroencephalography (SEEG). We performed an original metabolic exploration combining two (1)H-MRS imaging acquisitions associated with two single-voxel acquisitions (temporal poles) to map the most informative regions of interest (ROIs) including mesial and neocortical localizations. The N-acetyl aspartate/(choline+creatine) ratio was chosen as a metabolic index. SEEG analysis allowed the classification of each ROI as electrically normal or abnormal (i.e., involved in ictal and/or interictal discharges). Groups were compared by using a nonparametric Mann-Whitney U test.N-Acetyl aspartate/(choline+creatine) was significantly lower in all regions involved in SEEG electrophysiological epileptic abnormalities than in controls (p0.05). In contrast, the regions without any electrophysiological abnormalities were not metabolically different from those in controls (p0.05) except in one ROI. No differences between the metabolic profiles of epileptogenic and irritative zones were found. The metabolic alterations included, but also extended beyond, the lesions. The presence of metabolic abnormalities in mesial structures was not specific for the mesial subtype and generally extended outside the mesial structures.These results indicate that metabolic abnormalities are linked to ictal and interictal epileptiform activities rather than to structural alterations in TLE.

RATIONALE AND OBJECTIVES. The neurotrophic effect of Xaliproden has been followed using sequential cerebral magnetic resonance imaging (MRI) in rats with vincristine-induced brain lesion as a model of Alzheimer disease. METHODS. Nineteen rats received an intraseptal injection of vincristine on day 0, followed by a daily gavage with either the vehicle (Tween-20 1%) (n = 10) or Xaliproden (10 mg/kg) (n = 9). Eight sham-operated controls received a daily gavage with either the vehicle (n = 4) or Xaliproden (n = 4). Brain MR imaging was performed at 4.7 T on a Biospec 47/30 MR system before surgery then 3, 7, 10, and 14 days after surgery. RESULTS. At day 3 following vincristine injection, an increase in MR signal intensity in the septum was observed on T2-weighted images. This increase was maximal at day 10, and remained stable until day 14. Daily treatment with Xaliproden delayed the appearance of hypersignals until day 7 and reduced by Ca. 50% the magnitude of the increase in signal intensity from day 10. No changes were observed in the hippocampus. CONCLUSION. Quantitative MRI objectifies noninvasively the neuroprotective effect of Xaliproden on rat brain anatomy.

Object Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury. Materials and methods 3D-23Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed. Results Progressive MS patients presented higher GM-TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T2lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability. Conclusion Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.

MR spectroscopy of the posterior fossa is pitted with numerous technical difficulties. It is, however, of great clinical interest in the study of the degenerative diseases and tumors of this area. We have developed a method to perform 2D CSI of this area, by using a sagittal slice and a careful positioning of outer volume saturation. We performed this acquisition in 30 healthy volunteers to determine the normal metabolic ratios in five voxels of this area (mesencephalon, pons, medulla oblongata, vermis, cerebellar white matter). The main technical difficulty was magnetic field inhomogeneity in the lower brainstem generated by dental alloys. However, 88% of the voxels were of sufficient quality to be analyzed. The statistically significant regional variations were a higher NAA/Cr ratio in the pons than in the medulla oblongata, higher Cho/Cr in the pons than in the mesencephalon and higher Cho/Cr in the cerebellar white matter than in the vermis. We conclude that 2D CSI of the brainstem, although technically delicate can be performed in most patients.

The current applications of magnetic resonance spectroscopy (MRS) in the clinical management of epileptic patients are reviewed. A major contribution of MRS to epilepsy is its ability to determine lateralisation before surgical resection of the diseased brain region. Phosphorus-31 and proton single-voxel MRS identify abnormalities in high-energy metabolism, neuronal function and neurotransmitter levels, but information can only be obtained from restricted regions of the brain. Spectroscopic imaging techniques (also known as chemical shift imaging) provide a metabolic mapping of the whole brain. They expand the range of applications of MRS to other types of epilepsy (neocortical, frontal) than temporal lobe epilepsy, which is the most often studied. Also, spectral editing techniques in proton MRS make it possible to detect and monitor drug-induced variations of GABA in the human brain, opening new insights into patient response to drug therapy of epilepsy. MRS is playing an increasing role in the noninvasive characterisation and management of epileptic patients.

Cerebral metabolism in six children with X-linked adrenoleukodystrophy (X-ALD) was studied using 1H magnetic resonance spectroscopy (MRS), and the status of the patients was monitored for evaluating disease progression. Spectra were abnormal even in patients with no cerebral impairment. Four different metabolic patterns were identified, and a metabolic classification of the disease was proposed, from grade 0 to grade III. The evolution of the disease toward grade II appears to be systematic, but many patients did not evolve from this grade to grade III, which is the metabolic mark of severe progressive forms. Metabolic data of X-ALD were processed using discriminant analysis, which provides a classification accuracy of 95.2%. Proton cerebral MRS together with discriminant analysis may be useful during the follow-up in X-ALD for monitoring the evolution of the disease and the effects of therapy. Magn Reson Med 41:1119–1126, 1999. © 1999 Wiley-Liss, Inc.

This study examined the influence of metabolic substrates on the effects of trimetazidine on functional and metabolic aspects of the ischemic reperfused heart. Isovolumic rat hearts were submitted to a 30-minute period of global mild ischemia (coronary flow decreased by an average of 70%) and then reperfused at constant preischemic coronary flow rate. Either glucose (11 m M ) or glucose and palmitic acid (0.1 m M ) were used as metabolic substrates. Trimetazidine (6 × 10 −7 M ) markedly reduced the increase in diastolic pressure that occurred on reperfusion after the ischemic episode, whatever the exogenous substrate used. However, in those hearts that received fatty acid, the postischemic increase in diastolic pressure was abolished. Ischemia-induced increase in acyl carnitine levels—determined as indicators of fatty acid utilization by myocardial cells—was significantly decreased by trimetazidine in those hearts receiving fatty acid. Also, similar effects to those of trimetazidine on the postischemic increase in diastolic pressure and on tissue levels of acyl carnitine were obtained in the presence of dichloroacetate. Moreover, the presence of trimetazidine was associated with a reduction in the intracellular pH decrease during ischemia in those hearts receiving fatty acid. Combined with previous studies, these results suggest that an improved metabolic balance by trimetazidine may well consequently decrease the ionic imbalance after a transient period of ischemia.

La SRM cerebrale du proton detecte de maniere non invasive des pools de metabolites cellulaires. Dans les abces bacteriens, elle permet de realiser le diagnostic differentiel d'avec les tumeurs gliales malignes. Dans le sida, la SRM detecte, avant l'IRM, la presence d'une encephalopathie liee au VIH et offre une evaluation quantifiee de la reponse therapeutique. Dans les autres encephalites virales, la SRM permet de faire le bilan de la gravite et de l'extension des lesions.

Background Metabolic anomalies are known in skeletal muscles of patients with malignant hyperthermia (MH). Methods The authors used 31-phosphorus (31P) magnetic resonance spectroscopy (MRS) to compare metabolic changes of the finger flexor muscles recorded throughout two rest-exercise-recovery protocols (each including aerobic or ischemic exercise) in 26 healthy persons and in 13 MH-susceptible (MHS) persons who were unequivocally diagnosed by in vitro halothane-caffeine contracture tests on muscle biopsies. Results No abnormality was observed at rest and during recovery periods. A larger phosphocreatine decrease associated with an early drop of pH was noted during the first minute of both exercise periods for MHS patients compared with controls. The early pH decrease indicated a disorder affecting glycolytic activation, probably reflecting defects of Ca2+ cycling, and provided a sensitivity of 77% for MHS diagnosis. A diagnostic strategy based on the retrospective analysis of 19 selected MR parameters was developed. An MRS score, corresponding to the number of abnormal values among the 19 parameters, was calculated and provided sensitivity and specificity rates of 100%; that is, no false-positive or false-negative results were found. A prospective analysis of 10 new participants further confirmed these findings. Conclusions These results (1) further confirm that MH is associated with the preexistence of latent muscular disorders; (2) enhance the potential diagnostic capacity of MRS, although it should be tested prospectively on a larger group of participants; and (3) allows the characterization of several abnormal metabolic profiles, in persons with MHS, reflecting the recently described polymorphism of MH.

BACKGROUND AND PURPOSE: Pretherapeutic determination of tumor grade and genotype in grade II and III oligodendroglial tumors is clinically important but is still challenging. Tumor grade and 1p/19q status are currently the 2 most important factors in therapeutic decision making for patients with these tumors. Histopathology and cMRI studies are still limited in some cases. In the present study, we were interested in determining whether the combination of PWI, DWI, and MR spectroscopy could help distinguish oligodendroglial tumors according to their histopathologic grade and genotype. MATERIALS AND METHODS: We retrospectively reviewed 50 adult patients with grade II and III oligodendrogliomas and oligoastrocytomas who had DWI, PWI, and MR spectroscopy at short and long TE data and known 1p/19q status. Univariate analyses and multivariate random forest models were performed to determine which criteria could differentiate between grades and genotypes. RESULTS: ADC, rCBV, rCBF, and rK2 were significantly different between grade II and III oligodendroglial tumors. DWI, PWI, and MR spectroscopy showed no significant difference between tumors with and without 1p/19q loss. Separation between tumor grades and genotypes with cMRI alone showed 31% and 48% misclassification rates, respectively. Multimodal MR imaging helps to determine tumor grade and 1p/19q genotype more accurately (misclassification rates of 17% and 40%, respectively). CONCLUSIONS: Although multimodal investigation of oligodendroglial tumors has a lower contribution to 1p/19q genotyping compared with cMRI alone, it greatly improves the accuracy of grading of these neoplasms. Use of multimodal MR imaging could thus provide valuable information that may assist clinicians in patient preoperative management and treatment decision making. ABBREVIATIONS: cMRI conventional MRI; Glx complex glutamine/glutamate; K2 permeability index; WHO World Health Organization

Introduction: We investigated the functional and structural integrity of the corticospinal tract (CST) using diffusion tensor imaging (DTI) and the triple stimulation technique (TST) in patients with amyotrophic lateral sclerosis (ALS). Methods: Fourteen patients with ALS, 13 healthy controls (HCs), and 6 patients with lower motor neuron (LMN) syndrome underwent DTI and TST. Results: The mean diffusivity was higher in ALS patients than HCs (P < 0.01). The TST ratio was lower in ALS patients compared with HCs (P < 0.001) and in LMN patients compared with HCs (P < 0.05). The increase in the mean diffusivity was correlated with the decrease in the TST ratio (P < 0.01). Conclusions: Significant correlations exist between the DTI and TST results, indicating both structural and functional involvement of the CST in patients with ALS. Muscle Nerve 49:551–557, 2014

OBJECTIVE A point mutation in the mitochondrial genome has been identified as a cause of diabetes and deafness. We report two pedigrees with and A-to-G transition at nucleotide 3243 of mtDNA within the tRNALeu(UUR) gene and focus our investigations on other localizations of the anomaly, particularly muscle and retina. RESEARCH DESIGN AND METHODS Muscular localization has been studied in probands by invasive and noninvasive methods, including muscle biopsy (evaluation of the proportion of mutated mtDNA in comparison to blood cells, measurement of respiratory chain complex activities and histological and histochemical aspects) and 31P-nuclear magnetic resonance (NMR) spectroscopy. Ophthalmic and angiographic examination of retina, electroretinography, and visual evoked potentials were performed in five subjects. RESULTS This mutation, previously described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), was expressed more abundantly in muscle than in nucleated blood cells. This low expression in blood cells could hamper the diagnosis for some patients. In addition, despite poor clinical expression, muscle was found to be highly affected. Ragged red fibers and dystrophic mitochondria were observed in muscle biopsy. Histochemical assays showed decreased activity of respiratory chain complexes, and 31P-NMR in vivo data further confirmed the defect of muscle oxidative processes. Exercise-induced lactate production was increased. Finally, in both families, an atypical “salt and pepper” pigmentary retinopathy was observed without consequences on visual acuity. CONCLUSIONS In diabetes secondary to 3243 mtDNA mutation, infraclinical muscular and ocular lesions are frequent. These two locations of the disease, which are easily investigated by simple methods, can help in the diagnosis of this new type of diabetes.

Ratel, Sebastien Martin, Vincent Tonson, Anne Cozzone, Patrick J Bendahan, David Comment Letter United States Pediatric research Pediatr Res. 2012 Aug;72(2):221. doi: 10.1038/pr.2012.67.

Bun, Sok-Sithikun Kober, Frank Jacquier, Alexis Espinosa, Leon Kalifa, Jerome Bonzi, Marie-France Kopp, Francis Lalevee, Nathalie Zaffran, Stephane Deharo, Jean-Claude Cozzone, Patrick J Bernard, Monique Research Support, Non-U.S. Gov't United States Investigative radiology Invest Radiol. 2012 May;47(5):319-23. doi: 10.1097/RLI.0b013e318243e062.; OBJECTIVE: The aim of the study was to assess the value of in vivo T2 measurements to noninvasively quantify myocardial fibrosis in diabetic mice at 11.75 T. Diabetic cardiomyopathy is characterized by extracellular matrix alteration and microcirculation impairment. These conditions might provide electrical heterogeneity, which is a substrate for arrhythmogenesis. T1 mapping has been proposed to quantify diffuse myocardial fibrosis in cardiac diseases but has several limitations. T2 measurement may represent an alternative for fibrosis quantification at high magnetic field. MATERIALS AND METHODS: A magnetic resonance imaging protocol including in vivo T2 measurements at 11.75 T was performed in 9 male C57BL/6J mice after 8 weeks of streptozotocin-induced diabetes and in 9 control mice. Programmed ventricular stimulation was performed in both groups. T2 measurements were compared with histologic quantification of fibrosis using picrosirius red staining. RESULTS: Myocardial T2 was significantly lower in diabetic mice (13.8 +/- 2.8 ms) than in controls (18.9 +/- 2.3 ms, P < 0.001). There was a good correlation between T2 and fibrosis area obtained by histopathology (R = 0.947, P < 0.001). During programmed ventricular stimulation, 3 nonsustained ventricular tachycardias were induced in diabetic mice versus none in the control group. CONCLUSIONS: The in vivo T2 relaxation time strongly correlated with myocardial fibrosis area assessed with histologic staining in diabetic mice.

Zaaraoui, Wafaa Konstandin, Simon Audoin, Bertrand Nagel, Armin M Rico, Audrey Malikova, Irina Soulier, Elisabeth Viout, Patrick Confort-Gouny, Sylviane Cozzone, Patrick J Pelletier, Jean Schad, Lothar R Ranjeva, Jean-Philippe Research Support, Non-U.S. Gov't United States Radiology Radiology. 2012 Sep;264(3):859-67. doi: 10.1148/radiol.12112680. Epub 2012 Jul 17.; PURPOSE: To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration 5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed. RESULTS: TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks. CONCLUSION: TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.

Bartoli, M A Kober, F Cozzone, P Thompson, R W Alessi, M C Bernard, M England European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery Eur J Vasc Endovasc Surg. 2012 Nov;44(5):475-81. doi: 10.1016/j.ejvs.2012.08.002. Epub 2012 Aug 30.; OBJECTIVES: There are, to date, no published non-invasive or longitudinal studies performed in mice to measure aortic diameter and wall thickness in an elastase-induced abdominal aortic aneurysm. This MRI study at 11.75 T aimed at evaluating the reliability of longitudinal in vivo aortic diameter and wall thickness measurements in this particular model. METHODS: Adult male C57BL/6 mice underwent transient elastase or heat-inactivated elastase perfusion (controls). Aortic dilatation was measured before, during and immediately after elastase perfusion, and again 14 days after, with a calibrated ocular grid. MRI was performed just before initial surgery and at day 14 before harvest using an 11.75 T MR microscopy imager. RESULTS: Aortic diameter was significantly greater in elastase-perfused mice compared to controls as measured by optic grid (1.150 +/- 0.153 mm vs 0.939 +/- 0.07 mm, P = 0.038) and according to MRI measurement of the outer diameter on spin echo images (1.203 +/- 0.105 mm vs 1070 +/- 0.048 mm, P = 0.0067). Aortic wall thickness was found to be significantly increased in elastase-perfused mice at day 14. CONCLUSIONS: This study demonstrates in the mouse elastase-induced aneurysm model that characterization of aneurysm development by its inner and outer vessel diameter and vessel wall thickness can be carried out longitudinally using high resolution MRI without significant mortality.

International audience; An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.