Strong diffusion gradients allow the separation of intra- and extra-axonal gradient-echo signals in the human brain

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2020-08, Vol.217, p.116793-116793, Article 116793
• Main Authors: Kleban, Elena, Tax, Chantal M.W., Rudrapatna, Umesh S., Jones, Derek K., Bowtell, Richard
• Format: Article
• Language: English
• Subjects: Adult; Anisotropy; Axons; Brain - diagnostic imaging; Brain research; Brownian motion; Connectome; Corpus callosum; Diffusion Magnetic Resonance Imaging - methods; Echo-Planar Imaging; Electromagnetic Fields; Evolution; Female; Humans; Image Processing, Computer-Assisted - methods; Magnetic fields; Magnetic resonance imaging; Male; Microstructure; MRI contrast mechanisms; Myelin; Nerve Fibers - ultrastructure; Neural Pathways - diagnostic imaging; Neuroimaging; NMR; Nuclear magnetic resonance; Pyramidal tracts; Pyramidal Tracts - diagnostic imaging; Substantia alba; White matter; White Matter - diagnostic imaging
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2020.116793

The quantification of brain white matter properties is a key area of application of Magnetic Resonance Imaging (MRI), with much effort focused on using MR techniques to quantify tissue microstructure. While diffusion MRI probes white matter (WM) microstructure by characterising the sensitivity of Brownian motion of water molecules to anisotropic structures, susceptibility-based techniques probe the tissue microstructure by observing the effect of interaction between the tissue and the magnetic field. Here, we unify these two complementary approaches by combining ultra-strong (300mT/m) gradients with a novel Diffusion-Filtered Asymmetric Spin Echo (D-FASE) technique. Using D-FASE we can separately assess the evolution of the intra- and extra-axonal signals under the action of susceptibility effects, revealing differences in the behaviour in different fibre tracts. We observed that the effective relaxation rate of the ASE signal in the corpus callosum decreases with increasing b-value in all subjects (from 17.1±0.7s−1 at b=0s/mm2 to 14.6±0.7s−1 at b=4800s/mm2), while this dependence on b in the corticospinal tract is less pronounced (from 12.0±1.1s−1 at b=0s/mm2 to 10.7±0.5s−1 at b=4800s/mm2). Voxelwise analysis of the signal evolution with respect to b-factor and acquisition delay using a microscopic model demonstrated differences in gradient echo signal evolution between the intra- and extra-axonal pools. •300 ​mT/m gradients used in Diffusion-Filtered Asymmetric Spin Echo (D-FASE) imaging.•D-FASE disentangles the gradient echo signals from the intra- and extra-axonal pools.•Macroscopic R2∗ decreases with increasing diffusion weighting b in white matter tracts.•Lower R2∗(b) in the corticospinal tract than in the corpus callosum and the cingulum.•Joint estimation of diffusion and susceptibility effects using a 2-parameter 2-pool model.