In vivo ¹H or ³¹P MRS allow for the non-invasive detection and quantification of more than 20 biomolecules (or metabolites) involved in energy metabolism (phosphocreatine, ATP, lactate, glucose), neurotransmission (glutamate, GABA), neuronal (N-acetyl-aspartate) or glial (myo-inositol, glutamine) function/density or membrane metabolism (choline compounds, phosphoethanolamine). Thus, a metabolic profiling of the brain can be performed longitudinally to explore and follow metabolic alterations in pathological conditions. 

 

Following the administration of ¹³C-labeled energy substrates such as [¹³C]Glucose, [¹³C]Acetate or [¹³C]Lactate, detection of carbon-13 nuclei in biomolecules using dynamic ¹³C MRS allow for the direct assessment of rates of metabolic pathways. By following the incorporation of the ¹³C nuclei from these energy substrates through the intermediates of the tricarboxylic acid cycle (TCA), it is possible to estimate the rates of the neuronal (V_TCAn) and glial TCA (V_TCAg) cycles as well as the recycling rate of glutamate corresponding more or less to the rate of glutamatergic neurotransmission (V_NT). This is done by adjusting the ¹³C fractional enrichments time-courses via the numerical resolution of the differential equations derived from a metabolic model of the neuronal-glial functional unit. No other method offers the opportunity to investigate specifically the neuronal and glial compartments as well as the glutamatergic neurotransmission.

 

Sodium-23 yields the second strongest NMR signal among biologically relevant NMR-active nuclei. Yet, the average concentration of Na⁺ ions in the brain remains 1/2000 that of protons. Furthermore, only the low intracellular ²³Na concentration (ISC~15 mmol/L) is considered as an operational proof of cellular integrity and viability. As a consequence, ²³Na MRI has been proposed as a relevant imaging approach for the early detection of brain disorders such as brain tumours, ischemic stroke, Alzheimer’s disease and multiple sclerosis. A sophisticated method of multiple-quanta-filtering (MFQ) takes advantage of the differences in mobility of the Na⁺ ions in the intra- and extra-cellular compartments to filter out the signal from the extracellular space. By combining the MFQ preparation module to a fast imaging encoding schemes, maps of ISC can be obtained. The implementation of such tool at 11.7T could complement advantageously our other cerebral imaging methods to probe cellular metabolism and homeostasis.

​	​     Figure 3. 3D Twisted-projection imaging acquisition scheme (A) and prototype of a 23Na RF coil dedicated to imaging the brain of non-human primate at 7T (B). TPI encoding scheme from Riemer et al. (MAGMA 2013).

Finally, lithium salts are the leading treatment for relapse prevention in patients with bipolar disorders. However, its mechanism of action remains unknown. For years, psychiatrists have been looking for a non-invasive method to investigate the transport kinetics of lithium salts through the BBB and the subsequent spatial distribution of lithium in the brain, assuming that both aspects play a critical role in the understanding and the successful management of lithium treatment. Recently, Komorovsky et al. have demonstrated that ⁷Li MRSI could be used to study the brain of bipolar patients in a clinical setting. By harnessing the increased polarization at 7T, we are looking to improve the time and spatial resolution of such acquisitions in order to investigate in collaboration with Pr. Frank Bellivier (Inserm UMR-S1144, Centre Expert Bipolaire et Dépression Résistante de la fondation FondaMental, Hôpital Fernand Widal, Paris) the relationship between lithium brain distribution and its therapeutic response.​