Water, the main tissue solvent, is in contact with all tissue components, including membranes, cytoplasm, cellular metabolites, proteins, extracellular liquid, blood, etc. We are developing technology that sensitizes the MRI measurement to tissue microstructure properties using MRI pulse sequences consisting of special radiofrequency (RF) pulses and magnetic field gradient (G) pulses. Two approaches will be used:

(i) application of a noninvasive RF or G or relaxation (T2 or T2*) filter that affects only part of the MRI signal (Figure). For instance, RF can be used to magnetically label the protons of metabolites, mobile proteins, or semisolid-like structures, the magnetization of which is transferred to neighboring water protons. Gradients can be used for diffusion filters, selecting for slower-moving water components (1). T2-filters select for fast-relaxing components, generally less mobile tissue components. The affected water molecules then diffuse between cellular compartments. By performing a time dependent diffusion measurement following the filter application, we can assess tissue composition in normal tissue and changed composition in disease.
(ii) spatial encoding with gradients that affect different water components in the tissue based on the microscopic tissue anisotropy of water diffusion (2,3).
(1) Nilsson M, Lätt J, van Westen D, Brockstedt S, Lasič S, Ståhlberg F, Topgaard D. Noninvasive mapping of water diffusional exchange in the human brain using filter-exchange imaging. Magn Reson Med. 2013 Jun;69(6):1573-81.
(2) Nilsson M, Englund E, Szczepankiewicz F, van Westen D, Sundgren PC. Imaging brain tumour microstructure. Neuroimage. 2018 Nov 15;182:232-250.
(3) Szczepankiewicz F, Lasič S, van Westen D, Sundgren PC, Englund E, Westin CF, Ståhlberg F, Lätt J, Topgaard D, Nilsson M. Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: applications in healthy volunteers and in brain tumors. Neuroimage. 2015 Jan 1;104:241-52.

MRI Process Flow