On the origin of R2 orientation dependence angle offsets in white matter

Purpose to identify the origin of confounding angle offset ε in R 2 orientation dependence and to propose a novel framework for better characterizing anisotropic R 2 in brain white matter (WM). Methods Anisotropic ( ε ) rather than principal diffusivity direction (Φ) was theorized along axon fiber, with ε determined by all eigenvalues and eigenvectors from diffusion tensor. An extra parameter ε was introduced into generalized magic angle effect function to account for any offset in R 2 orientation dependence derived from T 2-weighted image ( b= 0). These dependences referenced by ε were compared to those referenced as usual by Φ at b -values of 1000 and 2000 (s/mm2) on both linear and planar tensor image voxels in WM, based on public domain ultrahigh-resolution (760 µ m[3][1]) Connectome DTI datasets of a healthy young adult brain. A Student’s t-test was used to assess the mean differences and the statistical significance was considered at P < 0.05. Results Fitted ε became zero if referenced by ε or nonzero if referenced by Φ, signifying the origin of ε . Nonzero ε relied on b -values and tensor shapes so did other model parameters, e.g., the amplitude of anisotropic R 2 (1/s) significantly increased when using a higher b -value for the linear tensor image voxels, i.e., 3.3±0.1 vs. 1.8±0.1, P < 0.01. Conclusion The origin of R 2 orientation dependence angle offsets has been identified and the combined anisotropic diffusion and transverse relaxation models have fully quantified R 2 orientational anisotropies, thus providing novel insights otherwise unattainable on microstructural alterations in WM. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-3