Magnetic Resonance in Medicine 60:439–448 (2008) A General Framework for Experiment Design in Diffusion MRI and Its Application in Measuring Direct Tissue-Microstructure Features

This article introduces a new and general framework for opti-mizing the experiment design for diffusion MRI of samples with unknown orientation. An illustration then uses the framework to study the feasibility of measuring direct features of brain-tissue microstructure in vivo. The study investigates the accuracy and precision with which we can estimate potentially important new biomarkers suchas axondensity and radius inwhitematter. Sim-ulation experiments use a simple model of white matter based on CHARMED (composite hindered and restricted model of dif-fusion). The optimization finds acquisition protocols achievable on modern human and animal systems that consist of 120 mea-surements with fixed maximum gradient strengths. Axon radii in brain tissue are typically in the range 0.25–10 µm. Simu-lations suggest that estimates of radii in the range 5–10 µm have highest precision and that a maximum gradient strength of 0.07Tm−1 is sufficient to distinguish radii of 5, 10, and 20µm. Smaller radii are more difficult to distinguish from one another but are identifiable as small. A maximum gradient strength of 0.2 Tm−1 distinguishes radii of 1 and 2µm. The simulations also suggest that axon densities and diffusivity parameters in the normal range for white matter are recoverable. The experiment-design optimization has applications well beyond the current work to optimize the protocol for fitting any model of the diffusion process. Magn Reson Med 60:439–448, 2008. © 2008 Wiley-Liss, Inc. Key words: quantitative MRI; diffusion MRI; microstructure; axon density; axon diameter; experiment design; Cramer-Rao lower bound; Rician noise; active imagin