Modeling of Fiber Orientation‐Dependent R1 Relaxation in Human White Matter In Vivo Within The Framework of The Transient Hydrogen Bond Model

Purpose: Axon fiber orientation‐dependent R1 relaxation in human white matter (WM) in vivo at B0 = 1.5 T, 3 T, and 7 T was studied within the framework of the transient hydrogen bond (THB) model, which attributes MR signal relaxation to quantum magnetization interactions of water and motion‐restricted protons in hydrophilic heads of lipid bilayers forming cellular and myelinated membranes. Methods: R1 images by MP2RAGE MRI with microstructural DTI and NODDI indices by dMRI from WM were acquired. Angular R1 patterns were experimentally determined in WM with Orientation Dispersion Index (ODI) ranging from 0 to 0.2. The THB model was used to identify the biophysical parameters responsible for the R1 angular and field dependencies in quantitative terms. Results: At all B0s, non‐monotonic R1 behavior was observed with higher R1 of axons perpendicular to the B0 direction and a broad, low R1 minimum centered around 40° fiber‐to‐field angles. The THB model with the same set of biophysical parameters yielded a good fit for R1 angular patterns in axon fibers oriented between 9.5° and 90° in respect to B0 at all fields. The experimental R1 values in the fibers between the 0° and 9.5° orientations showed an additional dip consistent with their inherent microstructural features. These fibers were found in the cortico‐spinal tract with large and giant axons that would have a lower surface‐to‐volume ratio for forming THB, hence lower R1 relative to tracts with small‐diameter axons. Conclusions: The data show that the THB model provides a robust physical framework for R1 relaxation anisotropy and B0 field dependence in vivo.