The growing availability of ultra-high field MR scanners has heralded a revival of interest in in vivo MRI and MRS, using non-proton nuclei (X-nuclei). The intrinsic involvement of these nuclei in metabolic processes allows their use as direct metabolic markers. Images or spectra obtained from X-nuclei carry valuable information on the viability of different organisms and on emerging or progressing pathology.

The inherently low signal of X-nuclei, combined with their rapid signal decay, makes investigations of these nuclei technologically and methodologically challenging, requiring specialised signal acquisition methods and state of the art, dedicated hardware components. In cases where natural abundance and endogenous tissue concentration are low, an exogenous supply of the nucleus of interest may become necessary.

Most prominent MR active X-nuclei are sodium and phosphorous, which provide information on cellular integrity and energy metabolism, respectively. Candidates where exogenous enrichment of concentration adds information are oxygen and lithium, which can be applied to measure oxygen consumption and pharmacokinetics of lithium carrying substances. Generally, the prevalent quantitative measure used in conjunction with X-nuclei is total tissue concentration; however, more localised information is often desired ranging down to cellular level, for example, when quantifying compartmental distribution of sodium to detect apoptosis and necrosis.