Theoretical and experimental framework for encoding and analysis of restricted anisotropic diffusion and flow with magnetic resonance

We will develop MRI methods for resolving and separately characterizing restricted diffusion, anisotropy, and flow in heterogeneous porous materials.

The methods build on principles from physical chemistry and multidimensional NMR spectroscopy while the primary area of application is diagnostic radiology and noninvasive studies of brain tissue microstructure, vascularity, and heterogeneity.

The specific aims are to 1) develop a joint theoretical framework describing how the detected MRI signal is given by the interplay between complexly modulated magnetic field gradients and the distinct aspects of translational motion and establish the limits of validity of the theory with molecular dynamics simulations; 2) apply theory to design minimal sets of gradient waveforms encoding the signal with enough information to support model-free data inversion and extraction of quantitative metrics reporting on the amounts and individual diffusion properties of distinct water populations; and 3) implement methods on preclinical and clinical MRI scanners, validate methods using colloidal materials with well-defined diffusion properties, and determine normal values of the quantitative metrics for healthy brain.

With the ultimate goal of providing noninvasive methods for diagnosing pathologies and guiding treatment decisions, the methods will be applied in clinical research studies within international collaborations on brain tumors, traumatic injury, and neurodegeneration.