Intra and Extracellular Sodium Quantification by Multi-modal Modelling
MRI is mostly used to detect signal from hydrogen nuclei in water molecules thanks to their large abundance in the body and the fact that alterations in a number of biological properties of tissue can alter this signal revealing damage. It is also possible to sensitize the acquisition to specific microstructural properties such as the Brownian motion (diffusion) of water in tissue and therefore characterize different molecular compartments. Tissue properties can be assessed also through the analysis of signal relaxation times (T2) or magnetization transfer techniques. As well as being able to image water, MRI can be sensitized to other molecules. With the appropriate hardware and software, it is possible to acquire images that quantify the amount of sodium ions (23Na) present in the tissue. This is extremely important because sodium channels are responsible for neuronal conductivity and any imbalance between intra and extracellular sodium could result (or be the result) of cellular dysfunction. Several drugs for neurological conditions acting on sodium channels are currently being tested. To date, with 3T clinical scanners, it is possible to measure total sodium content but not intra and extra cellular concentration. Total sodium quantification though has been proved to be sensitive to pathological changes in neurological and neurovascular conditions.
There is a real need now for driving sodium imaging to the next step and design a method to separate quantification in intra and extracellular compartments. If successful, the result would contribute substantially to providing a method for assessing damage but also for studying mechanisms of tissue damage and repair.
Recently, the MR Physics group @ the NMR Research Unit has invested efforts to model intra and extra cellular sodium concentrations in terms of compartments defined by microstructural models of water diffusion.
This PhD project will aim to quantify intra and extra cellular components of sodium by developing this mathematical model further, using multi-modal proton imaging for determining unknown variables, such as volume fractions of specific compartments. This development will be performed in healthy subjects to assess reproducibility of measurements and will establish a protocol that will be clinically feasible for a pilot study in multiple sclerosis.