title: The impact of gradient strength on in vivo diffusion MRI estimates of axon diameter.
abstract: Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3T human MRI scanner with a maximum gradient strength of 300 mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293 mT/m and diffusion times encompassing short (16 and 25 ms) and long (60 and 94 ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. Electronic address: syhuang@nmr.mgh.harvard.edu.
authors.forename: Susie Y
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Aapo
authors.initials: A
authors.lastname: Nummenmaa
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Witzel
authors.affiliation: Institute of Biomedical Engineering, Ecole Polytechnique de Montreal, Montreal, QC, Canada.
authors.forename: Tanguy
authors.initials: T
authors.lastname: Duval
authors.affiliation: Institute of Biomedical Engineering, Ecole Polytechnique de Montreal, Montreal, QC, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Cohen-Adad
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States.
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Wald
authors.affiliation: Radiological Sciences Laboratory, Department of Radiology, Stanford University, Stanford, CA, United States.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McNab
mesh_terms: D001369:Axons; D003337:Corpus Callosum / Q000033:anatomy & histology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008390:Markov Chains; D015233:Models, Statistical; D009010:Monte Carlo Method