Toward tract-specific fractional anisotropy (TSFA) at crossing-fiber regions with clinical diffusion MRI

Purpose White matter fractional anisotropy (FA), a measure suggesting microstructure, is significantly underestimated with single diffusion tensor model at crossing-fiber regions (CFR). We propose a tract-specific FA (TSFA), corrected for the effects of crossing-fiber geometry and free water at CFR, and adapted for tract analysis with diffusion MRI (dMRI) in clinical research. Methods At CFR voxels, the proposed technique estimates free water fraction (f_iso) as a linear function of mean apparent diffusion coefficient (mADC), fits the dual tensors and estimates TSFA. Digital phantoms were designed for testing the accuracy of f_iso and fitted dual-anisotropies at CFR. The technique was applied to clinical dMRI of normal subjects and hereditary spastic paraplegia (HSP) patients to test the effectiveness of TSFA. Results Phantom simulation showed unbiased estimates of dual-tensor anisotropies at CFR and high accuracy of f_iso as a linear function of mADC. TSFA at CFR was highly consistent to the single tensor FA at non-CFR within the same tract with normal human dMRI. Additional HSP imaging biomarkers with significant correlation to clinical motor function scores could be identified with TSFA. Conclusion Results suggest the potential of the proposed technique in estimating unbiased TSFA at CFR and conducting tract analysis in clinical research. Magn Reson Med 74:1768-1779, 2015.