We enable the estimation of the per-axon axial diffusivity from single encoding, strongly diffusion-weighted, pulsed gradient spin echo data. Additionally, we improve the estimation of the per-axon radial diffusivity compared to estimates based on spherical averaging. The use of strong diffusion weightings in magnetic resonance imaging (MRI) allows to approximate the signal in white matter as the sum of the contributions from axons. At the same time, spherical averaging leads to a major simplification of the modeling by removing the need to explicitly account for the unknown orientation distribution of axons. However, the spherically averaged signal acquired at strong diffusion weightings is not sensitive to the axial diffusivity, which cannot therefore be estimated. After revising existing theory, we introduce a new general method for the estimation of both axonal diffusivities at strong diffusion weightings based on zonal harmonics modeling. We additionally show how this could lead to estimates that are free from partial volume bias with, for instance, gray matter. We test the method on publicly available data from the MGH Adult Diffusion Human Connectome project dataset. We report reference values of axonal diffusivities based on 34 subjects, and derive estimates of axonal radii. We address the estimation problem also from the angle of the required data preprocessing, the presence of biases related to modeling assumptions, current limitations, and future possibilities.
Purpose: To investigate aspects of the validation of self-supervised algorithms for reconstruction of undersampled MR images: quantitative evaluation of prospective reconstructions, potential differences between prospective and retrospective reconstructions, suitability of commonly used quantitative metrics, and generalizability. Theory and Methods: Two self-supervised algorithms based on self-supervised denoising and neural network image priors were investigated. These methods are compared to a least squares fitting and a compressed sensing reconstruction using in-vivo and phantom data. Their generalizability was tested with prospectively under-sampled data from experimental conditions different to the training. Results: Prospective reconstructions can exhibit significant distortion relative to retrospective reconstructions/ground truth. Pixel-wise quantitative metrics may not capture differences in perceptual quality accurately, in contrast to a perceptual metric. All methods showed potential for generalization; generalizability is more affected by changes in anatomy/contrast than other changes. No-reference image metrics correspond well with human rating of image quality for studying generalizability. Compressed Sensing and learned denoising perform similarly well on all data. Conclusion: Self-supervised methods show promising results for accelerating image reconstruction in clinical routines. Nonetheless, more work is required to investigate standardized methods to validate reconstruction algorithms for future clinical use.