AxTract: Toward microstructure informed tractography

Abstract

Diffusion-weighted (DW) magnetic resonance imaging (MRI) tractography has become the tool of choice to probe the human brain's white matter in vivo. However, tractography algorithms produce a large number of erroneous streamlines (false positives), largely due to complex ambiguous tissue configurations. Moreover, the relationship between the resulting streamlines and the underlying white matter microstructure characteristics remains poorly understood. In this work, we introduce a new approach to simultaneously reconstruct white matter fascicles and characterize the apparent distribution of axon diameters within fascicles. To achieve this, our method, AxTract, takes full advantage of the recent development DW-MRI microstructure acquisition, modeling, and reconstruction techniques. This enables AxTract to separate parallel fascicles with different microstructure characteristics, hence reducing ambiguities in areas of complex tissue configuration. We report a decrease in the incidence of erroneous streamlines compared to the conventional deterministic tractography algorithms on simulated data. We also report an average increase in streamline density over 15 known fascicles of the 34 healthy subjects. Our results suggest that microstructure information improves tractography in crossing areas of the white matter. Moreover, AxTract provides additional microstructure information along the fascicle that can be studied alongside other streamline-based indices. Overall, AxTract provides the means to distinguish and follow white matter fascicles using their microstructure characteristics, bringing new insights into the white matter organization. This is a step forward in microstructure informed tractography, paving the way to a new generation of algorithms able to deal with intricate configurations of white matter fibers and providing quantitative brain connectivity analysis. Hum Brain Mapp 38:5485-5500, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: ActiveAx; axon diameter index; diffusion MRI; microstructure; multi-shell acquisition; white matter tractography.

Figure 1

Simulated kissing dataset (SNR = 20). The left fascicle and right fascicle have a mean axon diameter of $6.88\hspace{0.17em}\hspace{0.17em}\mu \mathrm{m}$ and $2.44\hspace{0.17em}\hspace{0.17em}\mu \mathrm{m}$, respectively. (a) shows the ground truth directions used to generate the data with their length scaled by the axon diameter index α, (b) the estimated fiber ODFs (fODFs), (c) the fiber ODF peaks and (d) the fiber ODF peaks with their length scaled by α, (e) show VC and IC for AxTract, and (f) show VC and IC for conventional deterministic tractography (CDT). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Axon diameter index α obtained with AxTract along the arcuate fasciculus (AF) and the CST. Column 1 shows a sagittal view of the T1‐weighted image with the blue squares indicating the zooming areas for streamlines visualization. Column 2 shows fascicles colored by α estimated per segment, with the histogram in Column 3. Columns 4 and 5 show, respectively, fascicles with streamlines colored by the whole‐streamline median α and the histogram of whole‐streamline median α, for all streamlines. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Axon diameter index α obtained with AxTract along the IFOF, the SLF, and the UF. Column 1 shows a sagittal view of the T1‐weighted image with the blue squares indicating the zooming areas for streamlines visualization. Column 2 shows fascicles colored by α estimated per segment, with the histogram in Column 3. Columns 4 and 5 show, respectively, fascicles with streamlines colored by the whole‐streamline median α and the histogram of whole‐streamline median α, for all streamlines. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Axon diameter index α obtained with AxTract along the CC sub‐fascicles. Column 1 shows the areas used to split the fascicle. Column 2 shows sub‐fascicles colored by α estimated per segment, with the histogram in Column 3. Columns 4 and 5 show, respectively, fascicles with streamlines colored by the whole‐streamline median α and the histogram of whole‐streamline median α, for all streamlines. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Axon diameter index α obtained with AxTract of the CC. (a,b) Streamlines colored using α estimated per segment and the whole‐streamline median α, respectively. The top row show streamlines in lateral and inferior views and the bottom row show a sagittal cut of the streamlines going through the midsagittal slice of the CC. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 6

Occurrence mapping of AxTract selecting a different propagation direction than conventional deterministic tractography (CDT). (a) Average occurrence map of AxTract selecting a different propagation direction than CDT over the 34 subjects. Individual subject occurrence maps were co‐registered on the ICBM 152 average brain map, prior to the averaging. AxTract changed the propagation direction using the axon diameter index α in $19.0\%\pm 0.3$ of tracking steps with multiple directions available. (b,c,d) Occurrences of AxTract selecting a different propagating direction than CDT on three fascicles of one subject (yellow segments). The white ellipses highlight crossing areas where the use of the axon diameter index α modified the tractography. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 7

Fascicle property distributions of 34 healthy subjects. (a) Percentage change in the number of streamlines between AxTract and conventional deterministic tractography ( $\frac{AxTract-\text{CDT}}{\text{CDT}}\times 100$). Fascicle with significant increase or decrease in streamline count are marked with an asterisk ( ${}^{\ast }$). (b) The mean axon diameter index α, (c) the mean apparent fiber density, and (d) the mean fractional anisotropy, along streamline fascicles of 34 healthy subjects, obtained with AxTract. Results are shown for six fascicles: the arcuate fasciculus (AF), the CST, the IFOF, the SLF, the UF, and the CC. The CC is split in five sub‐fascicles using the FreeSurfer parcellation (anterior, mid‐anterior, central, mid‐posterior, posterior) and TractQuerier. Projection and association fascicles are reported for each hemisphere. The black line indicates the median, the square indicates the mean, the box extends from the first and third quartile and the whiskers are at the 5th and 95th percentile of the distribution.