Standards for Spin-Based Diffusion Measurements for Quantitative MRI

Diffusion coefficients of water and small biological molecules are important biomarkers used in cancer and neurologic imaging. Diffusion in tissue may be anisotropic, non-gaussian, vary on different length scales, and complicated due to perfusion and flow. Spin-based nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) techniques are routinely used to measure and map self-diffusion. Here, we discuss standards for MRI-based diffusion measurements including the development of reference materials, phantoms, validated protocols, and the determination of uncertainties using Monte Carlo based solutions of the Bloch-Torrey equations. Uncertainties are due to NMR/MRI system imperfections (magnetic gradient nonuniformities, eddy currents, nonuniform RF spin excitation), spin dynamics/transport model inadequacy, and material complexity (multiple interreacting spin-populations). We present an examination of uncertainties in simple materials such as water, moderately complex materials such as polymer solutions, and finally in tissue. We compare uncertainties in complex spin manipulation pulse sequences, such as those used in neural MRI, to basic pulsed gradient spin echo sequences.