Scan-rescan repeatability of axonal imaging metrics using high-gradient diffusion MRI and statistical implications for study design

Abstract

Axon diameter mapping using diffusion MRI in the living human brain has attracted growing interests with the increasing availability of high gradient strength MRI systems. A systematic assessment of the consistency of axon diameter estimates within and between individuals is needed to gain a comprehensive understanding of how such methods extend to quantifying differences in axon diameter index between groups and facilitate the design of neurobiological studies using such measures. We examined the scan-rescan repeatability of axon diameter index estimation based on the spherical mean technique (SMT) approach using diffusion MRI data acquired with gradient strengths up to 300 mT/m on a 3T Connectom system in 7 healthy volunteers. We performed statistical power analyses using data acquired with the same protocol in a larger cohort consisting of 15 healthy adults to investigate the implications for study design. Results revealed a high degree of repeatability in voxel-wise restricted volume fraction estimates and tract-wise estimates of axon diameter index derived from high-gradient diffusion MRI data. On the region of interest (ROI) level, across white matter tracts in the whole brain, the Pearson’s correlation coefficient of the axon diameter index estimated between scan and rescan experiments was r = 0.72 with an absolute deviation of 0.18 μ m. For an anticipated 10% effect size in studies of axon diameter index, most white matter regions required a sample size of less than 15 people to observe a measurable difference between groups using an ROI-based approach. To facilitate the use of high-gradient strength diffusion MRI data for neuroscientific studies of axonal microstructure, the comprehensive multi-gradient strength, multi-diffusion time data used in this work will be made publicly available, in support of open science and increasing the accessibility of such data to the greater scientific community.

Axonal and myelin changes and their inter-relationship in the optic radiations in people with multiple sclerosis

“…The DW-MRI protocol was designed to obtain reproducible estimates of apparent axon diameter and density within an hour of scan time (total acquisition time of 51 min). 17 …”

“…The DW-MRI protocol was designed to obtain reproducible estimates of apparent axon diameter and density within an hour of scan time (total acquisition time of 51 min). 17 A multiple flip angle spoiled gradient-echo threedimensional fast low-angle shot (3D-FLASH) sequence was used to acquire macromolecular tissue volume (MTV) data for myelin quantification (1 mm isotropic resolution, TE/TR = 2.74/20 ms, flip angle = 4°-10°-20°, 15 min total acquisition time (5 min per sequence)). 18 .…”

Accuracy and reliability of diffusion imaging models

“…More complex models potentially can account for multiple diffusion compartments and thus resolve crossing fibers ( Behrens et al, 2003 ; Ferizi et al, 2014 ; Jbabdi et al, 2012 ; Jensen et al, 2005 ; Tournier et al, 2013 , 2019 ; Tuch, 2004 ; Zhang et al, 2012 ). Microstructure models using specialized imaging sequences have attempted to further probe tissue characteristics even further ( Fan et al, 2021 ; Palombo et al, 2020 ; Wang et al, 2014 , 2015 ; Zong et al, 2021 ).…”

Linear multi‐scale modeling of diffusion MRI data: A framework for characterization of oriented structures across length scales

“…This hardware limitation has been addressed through the introduction of high‐performance gradient systems for human imaging (Foo et al, 2020 ; Vachha & Huang, 2021 ; van Essen et al, 2012 ), including dedicated engineering of the Connectome MRI scanner (Fan et al, 2014 ; Fan et al, 2016 ; Huang et al, 2015 ; Jones et al, 2018 ; McNab et al, 2013 ; Setsompop et al, 2013 ), which was the first of its kind to incorporate a 300 mT/m whole‐body gradient coil into a wide‐bore 3 T scanner platform. When combined with parallel imaging acquisition and reconstruction techniques such as Simultaneous Multi‐Slice (SMS) (Feinberg et al, 2010 ; Feinberg & Setsompop, 2013 ; Setsompop, Cohen‐Adad, et al, 2012a ; Setsompop, Gagoski, et al, 2012b ) and Fast Low‐angle Excitation Echo‐planar Technique (FLEET) (Polimeni et al, 2016 ), as well as appropriate post‐processing methods (Andersson et al, 2016 ; Andersson & Sotiropoulos, 2015 ), such hardware advances have enabled the acquisition of extensive diffusion imaging datasets showing that reproducible estimation of an apparent axon diameter index is indeed feasible and requires high gradient amplitudes to sensitize the DW‐MRI signal to intra‐axonal water diffusion (Fan et al, 2021 ; Huang et al, 2015 ; Huang et al, 2020 ; Veraart et al, 2020 ).…”