Alfred Anwander^{1}, Thomas R. Knösche^{1}, Thomas Witzel^{2}, Assaf Horowitz^{3}, and Yaniv Assaf^{3}

The estimation of neural micro-structure in general and axon diameter in particular became feasible using advanced diffusion imaging frameworks such as CHARMED and AxCaliber. Recently, the AxCaliber model was extended to 3D enabling to capture the axonal properties of any fiber system in the brain. In this work we challenged the utility of using the CONNECTOM MRI, that provides a gradient strength of up to 300 mT/m, for axon diameter estimation. We found that the sensitivity of the model towards small diameter axons increases dramatically with the use of the strong gradient system increasing the validity and accuracy of AxCaliber3D.

Acquisition: Subjects were scanned on either a Siemens Magnetom CONNECTOM or a Siemens Magnetom PRISMA scanner. Diffusion weighted images were acquired with the following parameters:

CONNECTOM: TR/TE = 7500/70 ms, 86 gradient directions distributed on 5 b-value
shells with maximal b-value of 5000 s/mm^{2}, three diffusion times $$$\Delta$$$
ranging from 16 to 40 ms and $$$\delta$$$ of 9 ms, G_{max} of 259 mT/m, resolution
1.8mm isotropic EPI, 210 mm FOV, matrix size of 116, 2268 Hz/Px bandwidth, GRAPPA 2, no partial Fourier, 70 slices;

PRISMA: TR/TE = 3000/151 ms, 86 gradient directions
distributed on 5 b-value shells with maximal b-value of 3000 s/mm^{2},
three diffusion times $$$\Delta$$$ ranging from 40 to 100 ms and $$$\delta$$$ of
22ms, G_{max} of 72 mT/m, resolution 2.2 mm iso. In addition to the
multi-shell, multi diffusion time acquisition, we also acquired a HARDI dataset
with a single shell (b=1000 s/mm^{2}) and 64 gradient directions.

AxCaliber Analysis: Following motion correction and estimation of the major fiber directions using constrained spherical deconvolution of the HARDI dataset (Tournier et al., 2007), a regression model was used to fit the diffusion MRI data in each voxel. The AxCaliber 3D model was used to produce signal predictors for 4 diffusion components: a CSF component, a hindered diffusion (using a diffusion tensor model) and two axonal populations. The axonal populations were modeled using the AxCaliber pipeline as described previously using two different gamma functions to represent populations of small axons (narrow distribution centered around 1.5 mm) and large axons (broad distribution centered around 4 mm).

Fiber tracking: The HARDI dataset was used to compute streamlines representing fiber-tracts using a deterministic model with FA threshold of 0.2, maximum angle of 30°, and voxel sub-sampling of 4. Fiber-tracking was performed using ExploreDTI (Leemans et al. 2009).

Tract based analysis: Under the assumption that along a tract the diameter distribution should not change, for each tract we averaged the regression betas for the different component predictors (CSF, hindered, small axons, large axons). From these tract-based data we computed a map of the ratio between the small and large axonal populations as well as the sum of them (as a measure of axonal density).

- Assaf Y, Blumenfeld-Katzir T, Yovel Y, Basser PJ. AxCaliber: A Method for Measuring Axon Diameter Distribution from Diffusion MRI. Magnetic Resonance in Medicine. 2008;59(6):1347-1354. doi:10.1002/mrm.21577.
- Leemans A, Jeurissen B, Sijbers J, Jones DK. Proceedings of the 17th Annual Meeting of International Society for Magnetic Resonance in Medicine. Hawaii. 2009. ExploreDTI: A graphical toolbox for processing, analyzing, and visualizing diffusion MR data; p. 3537.
- Mitra, P. P., & Halperin, B. I. Effects of finite gradient-pulse widths in pulsed-field-gradient diffusion measurements. Journal of Magnetic Resonance, Series A, 1995;113(1):94-101. doi: 10.1006/jmra.1995.1060.
- Tournier JD, Calamante F, Connelly A. Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. NeuroImage. 2007;35:1459–72. doi: 10.1016/j.neuroimage.2007.02.016.

Figure 1: Prisma: Relative
fiber density and ratio of small/large fibers of the AxCaliber 3D model.The image shows a sagittal slice of the corpus callosum (top) and a sagittal slice at the level of the internal capsule of
participant 01.

Figure 2: Connectom: Relative
fiber density and ratio of small/large fibers of the AxCaliber 3D model of
participant 02.

Figure 3: Connectom: Relative fiber density and ratio of
small/large fibers of the AxCaliber 3D model of participant 03.

Figure 4: Relative
fiber density of small fibers of the AxCaliber 3D model of two participants
measured on the Prisma (top) and the Connectom (bottom).