EPFL E E-DAF EPFL-GYMN
1999 Young Investigator Award Plenary Lectureship, International Society for Neurochemistry
2011 Fellow, ESMRMB
2011 Teaching Award, Section Sciences de la Vie, EPFL
Fundamentals of biomedical imaging (Master, SPH, SSV, Mineurs) - spring semester, on moodle & filmed, since Feb. 2006
Physique générale I SV (SSV) - fall semester (moodle), since Sept. 2009
Advanced biomedical imaging methods and instrumentation (EDPY) - Fall semester, since Sept. 2006
Minor contributions to courses:
Neuroscience for engineers (SSV)- spring semester (moodle)
Molecular pahtology and therapy of neurodegenerative diseass (EDNE)
Editorial Board, Journal of Neuroscience Research (2001 present)
Editorial Board, Magma (2003 present)
Editorial Board, Neurochemical Research (2003 present)
Editorial Board, ASN Neuro
Associate Editor, Frontiers in Neuroenergetics
Deputy Editor, Magnetic Resonance in Medicine (1999-2011)
Editorial Board, NMR in Biomedicine (2003 2011)
Editorial Board, Magnetic Resonance in Medicine (2001- 2004)
Reviewing activity: Journals
Am. J. Physiol. (Metabolism and Endocrinology)
Am. J. Physiol. (Integrative and Comparative)
Am. J. Physiol. (Cell Physiology)
Brain Res. Bull.
Brain Res. Rev.
Eur. J. Pediatrics
Eur. J. Neurosci.
J. Cereb. Blood Flow Metab.
J. Magn. Reson.,
J. Neurosci. Res.
Magn. Reson. Med.,
Proc. Natl. Acad. Sci. USA,
Trends in Neuroscienes
Grant Review Boards
National Institute of Health
ad hoc member
NINDS, study section NSD-B / NSD-C ad hoc member
NIDA ad hoc member, Special Emphasis Panels
NIDDK ad hoc member, special emphasis panel
National Science bodies
Fonds National Suisse
Dutch Science Foundation
National Science Foundation (US)
Binational Science Foundation
Alzheimer Disease Foundation
Diabetes Foundation Netherlands
Juvenile Diabetes Research Foundation International
List of publications
Is provided here
Citation rates 2000-2010
Shown is number of citations per published item (articles & reviews, source ISI), amounting to 106 publications over the period 2000-2010.
Indicated in parentheses is the next best field (i.e. having a lower average citation rate) and its rank of 21 disciplines (see for comparison here )
2000: 52.0 (1. Molecular Biology)
2001: 54.7 (1. Molecular Biology)
2002: 34.2 (2. Immunology)
2003: 46.2 (1. Molecular Biology)
2004: 39.5 (1. Molecular Biology)
2005: 14.3 (8. Pharmacology)
2006: 14.9 (4. Biochemistry)
2007: 13.7 (3. Neuroscience)
2008: 6.7 (7. Clinical Medicine)
2009: 5.0 (4. Neuroscience)
2010: 0.4 (10. Physics)
Average citations/item covering the period 2000-2010 : 20.2 (3. Neuroscience)
QRED analysis : 16 publications in 2009, on average cited 4.9 times in 2010 : Q >>100%
Magnetic resonance spectroscopy
Magnetic resonance imaging
Mathematical models of metabolism
Neuroscience of hypoglycemia
In vivo kinetics
can be found on Biography tab or click link (google scholar profile)
|all papers published|
Last 5 years
A human cerebral and cerebellar 8-channel transceive RF dipole coil array at 7T
Magnetic Resonance in Medicine. 2019.
DOI : 10.1002/mrm.27476.
PURPOSE: Dipole antennas that provide high transmit field penetration with large coverage, and their use in a parallel transmit setup, may be advantageous in minimizing B 1+ -field inhomogeneities at ultra-high field, i.e 7T. We have developed and evaluated an 8-channel RF dipole coil array for imaging the entire cerebral and cerebellar regions in man. METHODS: A coil array was modeled with seven dipoles: six placed covering the occipital and temporal lobes; one covering the parietal lobe; and two loops covering the frontal lobe. Center-shortened and fractionated dipoles were simulated for the array configuration and assessed with respect to B 1+ -field at maximum specific absorption rate averaged over 10 g tissue regions in human brain. The whole-brain center-shortened dipoles with frontal loops coil array was constructed and its transmit properties were assessed with respect to MR images, B 1+ -field, and homogeneity. RESULTS: In simulations, the dipole arrays showed comparable performances to cover the whole-brain. However, for ease of construction, the center-shortened dipole was favored. High spatial resolution anatomical images of the human brain with the coil array demonstrated a full coverage of the cerebral cortex and cerebellum. CONCLUSIONS: The 8-channel center-shortened dipoles and frontal loops coil array promises remarkable efficiency in highly challenging regions as the cerebellum, and phase-only RF shimming of whole-brain could greatly benefit ultra-high field magnetic resonance imaging of the human brain at 7T.
N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis
SCHIZOPHRENIA BULLETIN. 2018.
DOI : 10.1093/schbul/sbx093.
Feasibility of in vivo measurement of glucose metabolism in the mouse hypothalamus by H-1-[C-13] MRS at 14.1T
MAGNETIC RESONANCE IN MEDICINE. 2018.
DOI : 10.1002/mrm.27129.
AN ADD-ON TRIAL WITH N-ACETYL-CYSTEINE (NAC) IN EARLY PSYCHOSIS PATIENTS: TOWARDS BIOMARKER GUIDED TREATMENT
DOI : 10.1093/schbul/sby017.575.
High-fat diet consumption alters energy metabolism in the mouse hypothalamus
International Journal of Obesity. 2018.
DOI : 10.1038/s41366-018-0224-9.
BACKGROUND/OBJECTIVES: High-fat diet consumption is known to trigger an inflammatory response in the hypothalamus, which has been characterized by an initial expression of pro-inflammatory genes followed by hypothalamic astrocytosis, microgliosis, and the appearance of neuronal injury markers. The specific effects of high-fat diet on hypothalamic energy metabolism and neurotransmission are however not yet known and have not been investigated before. SUBJECTS/METHODS: We used (1)H and (13)C magnetic resonance spectroscopy (MRS) and immunofluorescence techniques to evaluate in vivo the consequences of high-saturated fat diet administration to mice, and explored the effects on hypothalamic metabolism in three mouse cohorts at different time points for up to 4 months. RESULTS: We found that high-fat diet increases significantly the hypothalamic levels of glucose (P < 0.001), osmolytes (P < 0.001), and neurotransmitters (P < 0.05) from 2 months of diet, and alters the rates of metabolic (P < 0.05) and neurotransmission fluxes (P < 0.001), and the contribution of non-glycolytic substrates to hypothalamic metabolism (P < 0.05) after 10 weeks of high-fat feeding. CONCLUSIONS/INTERPRETATION: We report changes that reveal a high-fat diet-induced alteration of hypothalamic metabolism and neurotransmission that is quantifiable by (1)H and (13)C MRS in vivo, and present the first evidence of the extension of the inflammation pathology to a localized metabolic imbalance.
N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial
Translational Psychiatry. 2018.
DOI : 10.1038/s41398-018-0266-8.
Mechanism-based treatments for schizophrenia are needed, and increasing evidence suggests that oxidative stress may be a target. Previous research has shown that N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor almost devoid of side effects, improved negative symptoms, decreased the side effects of antipsychotics, and improved mismatch negativity and local neural synchronization in chronic schizophrenia. In a recent double-blind randomized placebo-controlled trial by Conus et al., early psychosis patients received NAC add-on therapy (2700 mg/day) for 6 months. Compared with placebo-treated controls, NAC patients showed significant improvements in neurocognition (processing speed) and a reduction of positive symptoms among patients with high peripheral oxidative status. NAC also led to a 23% increase in GSH levels in the medial prefrontal cortex (GSHmPFC) as measured by (1)H magnetic resonance spectroscopy. A subgroup of the patients in this study were also scanned with multimodal MR imaging (spectroscopy, diffusion, and structural) at baseline (prior to NAC/placebo) and after 6 months of add-on treatment. Based on prior translational research, we hypothesized that NAC would protect white matter integrity in the fornix. A group x time interaction indicated a difference in the 6-month evolution of white matter integrity (as measured by generalized fractional anisotropy, gFA) in favor of the NAC group, which showed an 11% increase. The increase in gFA correlated with an increase in GSHmPFC over the same 6-month period. In this secondary study, we suggest that NAC add-on treatment may be a safe and effective way to protect white matter integrity in early psychosis patients.
Brain metabolism during Chronic Hepatic Encephalopathy studied by in vivo 1H and 31P MRS
Lausanne, EPFL, 2018.
DOI : 10.5075/epfl-thesis-8612.
Magnetic resonance spectroscopy (MRS) is a powerful tool increasingly used in biomedical research and also in clinical practice. This thesis focused on the improvements of in vivo 31P MRS and 31P magnetization transfer methods at high magnetic field (9.4T). Then, in vivo 31P MRS was combined with 1H MRS to longitudinally study neurometabolic changes during chronic hepatic encephalopathy (CHE) in adult and developing brain using a well-recognized animal model of cholestatic chronic liver disease and HE type C â bile duct ligated (BDL) rats. CHE is neuro-psychiatric disorder caused by chronic liver disease (CLD), with not well-understood molecular mechanisms, inducing important and sometimes lethal brain changes. In a next step, potential protective treatments (probiotics and high creatine diet) were tested. To the best of our knowledge such a detailed approach was not yet published. Firstly, we showed by in vivo 1H MRS in hippocampus that adult BDL rats suffered from increase in brain glutamine, decrease in metabolites involved in osmoregulation including creatine, decrease in neurotransmitters and ascorbate and we were able to show the importance of early metabolic changes compared to late changes thanks to longitudinal measurements. 31P MRS study in larger brain volume found only mild perturbation of energy metabolism such as non-significant trend in ATP decrease in adult BDL rats. Secondly, studies in young BDL rats at two developmental stages by 1H MRS in the hippocampus revealed similar changes that the one observed in adult brain during CHE. However almost all the neurometabolic changes were more profound or appeared earlier in the evolution of the disease in young BDL rats. A new surface 1H-31P double-tuned coil was built and several optimizations and development were done to improve the spectral resolution, SNR and localization, including implementation of 1H-31P NOE enhancement and 1H decoupling in static 31P MRS, optimization of localization method and also development of an optimal protocol for 31P magnetization transfer. 31P MRS study in p21 BDL rats was performed with an improved 31P MRS protocol and revealed a decreased creatine kinase rate constant 2 weeks after BDL surgery and significant changes in metabolites involved in high-phosphate metabolism, in phospholipid metabolism and also cellular redox state 6 weeks after BDL. In the last part of this thesis, some therapeutic approaches were tested. A probiotic treatment delayed some neurometabolic changes present in CHE in adult BDL rats and improved motor activity. Based on previously shown devastating effects of decreased brain creatine during brain development, we proposed the high creatine diet as a possible treatment for young BDL rats. We demonstrated that oral administration of creatine partially restored brain creatine levels and also had a positive effect on other neurometabolic changes present in CHE. In conclusion, the work done in this thesis revealed for the first time a large spectrum of neurometabolic alterations present in adult and young BDL rats suffering from CLD and CHE, together with the time evolution of these changes during the disease progression, using in vivo longitudinal 1H MRS, improved 31P MRS and 31P magnetization transfer protocols developed herein. In addition, we brought some insight on the positive effects of two innovative treatments on the progression of CHE in adult and young BDL rats.
Nutritional Ketosis Increases NAD+/NADH Ratio in Healthy Human Brain: An in Vivo Study by 31P-MRS
Frontiers in Nutrition. 2018.
DOI : 10.3389/fnut.2018.00062.
Ketones represent an important alternative fuel for the brain under glucose hypo-metabolic conditions induced by neurological diseases or aging, however their metabolic consequences in healthy brains remain unclear. Here we report that ketones can increase the redox NAD+/NADH ratio in the resting brain of healthy young adults. As NAD is an important energetic and signaling metabolic modulator, these results provide mechanistic clues on how nutritional ketosis might contribute to the preservation of brain health.
In vivo characterization of brain metabolism by 1 H MRS, 13 C MRS and 18 FDG PET reveals significant glucose oxidation of invasively growing glioma cells
International Journal of Cancer. 2018.
DOI : 10.1002/ijc.31299.
Glioblastoma are notorious for their highly invasive growth, diffusely infiltrating adjacent brain structures that precludes complete resection, and is a major obstacle for cure. To characterize this "invisible" tumor part, we designed a high resolution multimodal imaging approach assessing in vivo the metabolism of invasively growing glioma xenografts in the mouse brain. Animals were subjected longitudinally to Magnetic Resonance Imaging (MRI) and (1) H spectroscopy (MRS) at ultra high field (14.1 Tesla) that allowed the measurement of 16 metabolic biomarkers to characterize the metabolic profiles. As expected, the neuronal functionality was progressively compromised as indicated by decreasing N-acetyl aspartate, glutamate and gamma-aminobutyric acid, and reduced neuronal TCA cycle (-58%) and neurotransmission (-50%). The dynamic metabolic changes observed, captured differences in invasive growth that was modulated by reexpression of the tumor suppressor gene WNT inhibitory factor 1 (WIF1) in the orthotopic xenografts that attenuates invasion. At late stage mice were subjected to (13) C MRS with infusion of [1,6-(13) C]glucose and (18) FDG Positron Emission Tomography (PET) to quantify cell-specific metabolic fluxes involved in glucose metabolism. Most interestingly, this provided the first in vivo evidence for significant glucose oxidation in glioma cells. This suggests that the infiltrative front of glioma does not undergo the glycolytic switch per se, but that environmental triggers may induce metabolic reprogramming of tumor cells.
Increased hepatic fatty acid polyunsaturation precedes ectopic lipid deposition in the liver in adaptation to high-fat diets in mice
Magnetic Resonance Materials in Physics, Biology and Medicine. 2018.
DOI : 10.1007/s10334-017-0654-8.
Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T
Human Brain Mapping. 2018.
DOI : 10.1002/hbm.24012.
External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI.
Feasibility of in vivo measurement of glucose metabolism in the mouse hypothalamus by (1) H-[(13) C] MRS at 14.1T
Magnetic Resonance in Medicine. 2018.
PURPOSE: Determine the feasibility of (1) H-[(13) C] MRS in the mouse hypothalamus using a 14.1T magnet. METHODS: We optimized the design of a (1) H-[(13) C] surface coil to maximize the signal-to-noise ratio of (1) H-[(13) C] MRS in the mouse hypothalamus. With enhanced signal, (13) C accumulation in glucose metabolites was measured in a 8.7 microL voxel in the hypothalamus of 5 healthy mice during the continuous administration of [1,6-(13) C2 ]glucose. RESULTS: Accumulation of (13) C label in glucose C6 and lactate C3 was visible in the hypothalamus 11 min after glucose administration. The (13) C fractional enrichment (FE) curves of lactate C3, glutamate and glutamine C4, glutamate+glutamine C3 and C2, GABA C2, C3, and C4, and aspartate C3 were measured with a time resolution of 11 min over 190 min. FE time-courses and metabolic pool sizes were averaged to fit a novel one-compartment model of brain energy metabolism that incorporates the main features of the hypothalamus. CONCLUSION: Dynamic (1) H-[(13) C] MRS is able to measure in vivo brain metabolism in small and deep areas of the mouse brain such as the hypothalamus, and it can be used to calculate metabolic fluxes, including glutamatergic and GABAergic metabolism as well as the contribution of metabolic sources other than glucose.
Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis
In vivo (1)H magnetic resonance spectroscopy ((1)H-MRS) investigations of amyotrophic lateral sclerosis (ALS) mouse brain may provide neurochemical profiles and alterations in association with ALS disease progression. We aimed to longitudinally follow neurochemical evolutions of striatum, brainstem and motor cortex of mice transgenic for G93A mutant human superoxide dismutase type-1 (G93A-SOD1), an ALS model. Region-specific neurochemical alterations were detected in asymptomatic G93A-SOD1 mice, particularly in lactate (-19%) and glutamate (+8%) of brainstem, along with gamma-amino-butyric acid (-30%), N-acetyl-aspartate (-5%) and ascorbate (+51%) of motor cortex. With disease progression towards the end-stage, increased numbers of metabolic changes of G93A-SOD1 mice were observed (e.g. glutamine levels increased in the brainstem (>+66%) and motor cortex (>+54%)). Through ALS disease progression, an overall increase of glutamine/glutamate in G93A-SOD1 mice was observed in the striatum ( p < 0.01) and even more so in two motor neuron enriched regions, the brainstem and motor cortex ( p < 0.0001). These (1)H-MRS data underscore a pattern of neurochemical alterations that are specific to brain regions and to disease stages of the G93A-SOD1 mouse model. These neurochemical changes may contribute to early diagnosis and disease monitoring in ALS patients.
Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals
Magnetic Resonance in Medicine. 2018.
DOI : 10.1002/mrm.27122.
Purpose To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Methods Droplets of mixed [1-13C]pyruvic and [1-13C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Results Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Conclusion Copolarization of two different 13C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.
In Vivo Heteronuclear Magnetic Resonance Spectroscopy
Methods in molecular biology (Clifton, N.J.); Springer, 2018. p. 169-187.
Magnetic Resonance Spectroscopy is a technique that has the capability of measuring metabolites in vivo and, in appropriate conditions, to infer its metabolic rates. The success of MRS depends a lot on its sensitivity, which limits the usage of X-nuclei MRS. However, technological developments and refinements in methods have made in vivo heteronuclear MRS possible in humans and in small animals. This chapter provides detailed descriptions of the main procedures needed to perform successful in vivo heteronuclear MRS experiments, with a particular focus on experimental setup in 13C MRS experiments in rodents.
Clinical Neuroimaging Using 7 T MRI: Challenges and Prospects
Enseignement & Phd
- Doctoral Program in Physics
- Doctoral Program in Neuroscience
- Doctoral Program in Molecular Life Sciences
- Doctoral Program in Biotechnology and Bioengineering
- Doctoral Program in Electrical Engineering
Cherix Antoine Timothée
Clément Jérémie Daniel
Flatt Emmanuelle Ines
Frank Steffen Frederic
Lê Thanh Phong Kevin
Zanella Claudia Christina
A dirigé les thèses deAuffret Matthieu Pierre ...
Balzan Riccardo ...
Bastiaansen Josefina Adriana Maria ...
Can Emine ...
Cheng Tian ...
Craveiro Mélanie ...
Dehghani Moghadam Masoumeh ...
Eggenschwiler Florent ...
Forjaco Jorge João Pedro ...
Khabipova Diana ...
Kober Tobias ...
Kunz Nicolas ...
Lai Marta ...
Lanz Bernard ...
Narsude Mayur ...
Rackayová Veronika ...
Schaller Benoît ...
Serés Roig Eulalia ...
Sonnay Sarah Catherine ...
Vinckenbosch Elise Marie Catherine ...
Waszak Maryna Volodimirivna ...
Xin Lijing ...
van Heeswijk Ruud ...
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