Leader:

Beyond the signal of ¹H₂O, in vivo NMR of 1H and low gyromagnetic nuclei (¹³C, ²H, ⁷Li, ³¹P and ²³Na) are unique tools to non-invasively investigate brain metabolites of interest for biochemistry, physiology and pharmacology, in normal or pathological conditions. My aim is to advance the methods necessary to detect, image and quantify those meaningful signals at ultra-high magnetic fields (7, 11.7 & 17 T) with unprecedented sensitivity and spatial specificity.The goal isto establish robust and efficient 1H MRS and X-MRI protocols to be incorporated within multimodal studies of psychiatric and neurologic diseases in patients as well as in animal models.

While ¹H₂O is the focus of almost all MRI studies, several other molecules and ions exist whose NMR signals are much more informative regarding the biophysical, metabolic or physiological status of those tissues. Over the past years, I used ¹H and ³¹P NMR Spectroscopy to quantify metabolites involved in neurotransmission and metabolism, such as neurotransmitters Glutamate and GABA or energy store/substrates Adenosine Tri-Phosphate and Lactate. Using dedicated fast ultra-short echo-time imaging sequences, I also investigated Sodium (²³Na) ions whose transmembrane concentration gradient is maintained at great energy cost and plays a major role in establishing the neurons’ resting potential.

One of my recent research line is Lithium-7 MRI. Lithium salts are the main treatment for bipolar disorder, yet the mechanism of action remains a mystery, and 7Li MRI is the only technique allowing lithium non- invasive mapping and quantification in the brain. Dynamic ¹³C or ²H NMR are very interesting non-irradiating alternatives to [18F]FDG-PET benefitting from their greater chemical/spectral specificities notably to discriminate and quantify aerobic vs. anaerobic energy synthesis pathways, neuronal and glial metabolism or even probe neurotransmission via the GABA and Glutamate synthesis and recycling rates. All of those weak signals benefit from the extremely high magnetic fields available at NeuroSpin enabling their investigation at better temporal and spatial resolutions.

My goal is to advance those methods and collaborate with biologists, physicians, bio-informaticians and neuroscientists to incorporate them within multimodal clinical and preclinical research protocols to better understand psychiatric and neurological diseases, their eventual treatments, and to develop novel biomarkers of disease progression or response to treatment.

In January 2024, Alfredo Lopez-Kolkovsky joined the CICLOPS group to accelerate the development of metabolic neuroimaging in particular on the 11.7T Iseult scanner.