MR spectroscopy and CEST imaging

Metabolites of low molecular mass (e.g. creatine and glucose), proteins, and other macromolecular structures carry weakly bound protons (¹H nuclei) at their surface which can exchange with protons in neighboring bulk water molecules. This process, named chemical exchange (CE), occurs spontaneously and depends on concentration, pH, temperature, and other properties of the solution.

Exchanging protons can resonate at different frequencies ("chemical shifts") in the ¹H NMR spectrum. Hence, they can be labeled selectively (e.g. by resonant radiofrequency irradiation) to induce equal population of the two ¹H spin states in a magnetic field – this technique is called saturation. Chemical exchange pumps this information into the water pool. Ongoing irradiation accumulates saturation in the water pool and produces the CEST effect (chemical exchange saturation transfer), i.e. a detectable reduction of the NMR signal of water protons. The amplification effect can make up several orders of magnitude. Note that in contrast to conventional NMR spectroscopy (MRS), which acquires the signal of tightly bound, hence non-exchanging nuclei (¹H, ¹³C, ¹⁹F, ³¹P...), CEST employs the water signal to indirectly detect the signal of weakly bound protons in biomolecules.

When CEST is combined with MR imaging (MRI) techniques, different entities of cellular compounds – as illustrated in the Figure – can be scanned in living tissue (in vivo) with a sensitivity comparable to conventional MRI. Since the discovery of the phenomenon in the year 2000, CEST-MRI has been applied to diagnostic imaging of various diseases (e.g. tumors, stroke, neurodegenerative disorders). These studies revealed new information about those pathologies on a molecular level.