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A novel diffusion registration method with the NTU-DSI-122 template to transform free water signal fraction maps to stereotaxic space. 
Benjamin T Newman1,2, Ana Untaroiu1, and T. Jason Druzgal1,2
1Department of Radiology & Medical Imaging, Division of Neuroradiology, University of Virginia Health System, University of Virginia, Charlottesville, VA, United States, 2Brain Institute, University of Virginia, Charlottesville, VA, United States

Synopsis

We propose the use of the NTU-DSI-122 template as a flexible, diffusion specific, means of registering subject images to stereotaxic MNI-space for further analysis. This allows for registration to be performed based on matching white matter fiber orientation distributions, which create within tissue contrasts, unlike voxel intensity metrics. This advantage is demonstrated by observing the increased consistency of registration versus a leading intensity-based algorithm. The range of b-values present in the NTU-DSI-122 allows for tailoring to selectively register at b-values matching those acquired in an experimental cohort, providing flexibility for both single- and multi-shell acquisitions.

Introduction

Registering subjects to a common template space is a necessary step in almost any neuroimaging study. A straightforward process for doing so aligns the brains of each acquisition in a study cohort from the acquired ‘native’ space to a ‘common’ template space. This common space is intended to achieve voxel-voxel correspondence between images and allow for comparison between subjects without interference from factors such as head orientation in the scanner or naturally occurring anatomical variation. The idea of a stereotaxic common space that could allow for images, atlases, and ROIs from different studies to be applied in a standardized manner gained attention with the definition of Talairach space-registered atlases1, and the release of stereotaxic templates such as the Colin 27 Average Brain2, and the MNI 152 linear template3.
Aligning subject brains in native space to these templates in stereotaxic space is frequently performed using intensity-based registration, which attempts to minimize voxel-voxel differences between native and template images. One of the most widely applied registration algorithms in neuroimaging, the ‘SyN’ model implemented in the program ANTs4, utilizes a diffeomorphic regularization to minimize the intensity difference between images (by maximizing a cross-correlation metric), combined with assistance from anatomical priors5. This has been demonstrated to be a highly reproducible brain image registration method5, and has performed well against other methods in open competitions6,7.
Diffusion MRI registration can be challenging due to large changes in voxel intensity between b-value shells, and different contrast at each b-value shell depending on the tissue within the voxel8. One solution to this problem has been to register the b=0 volumes collected with the diffusion images to a T2-weighted image9-11 due to the similar anatomical contrast present in both images. The voxel-wise image intensity between two white matter (WM) fiber bundles may not be greatly different at b=0 (i.e., they lack within tissue contrast), thus intensity-based algorithms may have lower sensitivity toward within tissue location. However, the orientation of those WM fiber bundles is important for tractography and reconstructing accurate connectomes. Additionally, some measures of cellular microstructure, such as free water signal fractions, have a small value range (between 0-1 in this case), making the measure sensitive to even small changes in value or introduction of noise. Symmetric diffeomorphic registration via cross-correlation of the spherical hormonic coefficients has previously been demonstrated as a means of accurately co-registering WM fiber orientation distributions (FODs) within a cohort12 but not to stereotaxic space.
The NTU-DSI-122 template is a composite template composed of 122 individual subjects registered in stereotaxic MNI space13. Rather than a single volume, the template consists of 102 individual gradient directions and 12 different b-value shells. By extracting the b-value shells corresponding to collected experimental data, then calculating the FOD using constrained spherical deconvolution14,15, it is possible to generate an FOD-based template for registering diffusion data in stereotaxic space. In this study we demonstrate that FOD-based registration from an experimental cohort leads to more consistent transforms of free water signal fraction maps compared to intensity-based registration.

Methods

We collected 5 diffusion MRIs from healthy controls using a Siemens Prisma 3T scanner with an isotropic voxel size of 1.7⨉1.7⨉1.7mm3, TE=70ms and TR=2900ms; 10 b=0 images and 64 gradient directions at both b=1500s/mm2 and b=3000s/mm2. Each image set was analyzed using MSMT-CSD14 implemented in the open source software MRtrix16. Several preprocessing steps utilized FSL17. Diffusion images were denoised18, corrected for Gibbs ringing19, susceptibility distortions20, motion21, and eddy currents22. Response functions were generated23 from both experimental data and the NTU-DSI-122 template at b=1538s/mm2 and b=3077s/mm2 and used to generate FODs14. The number of directions was sufficient to generate FODs with a harmonic order of lmax = 4, which has been suggested to be optimal for registration12. CSF-like signal fractions were calculated from the FODs24,25.
Each of the 5 diffusion MRIs were then registered from native space to MNI space using both ANTs SyN algorithm4 to register the processed b=0 images with the Colin 272 T2 template and using MRtrix16 to register the WM FODs with the NTI-DSI-122 template WM FODs12,26. Each registration was used to generate a transform that was applied to the CSF-like free water signal fraction from that subject. Because these registrations are not deterministic processes, and can produce slightly different transforms each time it is performed on the same images, this procedure was repeated independently 5 times for each subject, via each method (Figure 1). The mean squared difference was then calculated for each whole-brain image between every same-method same-subject combination to analyze which method more consistently transformed the free water signal fraction map into MNI space.

Results

The MRtrix FOD transform resulted in a significantly lower mean squared difference between repetitions compared to the ANTs SyN generated transform (pairwise T-test, T49 = 8.02, p<0.001) indicating that the FOD algorithm was able to more consistently register and transform the free water signal fraction maps (Figure 2).

Conclusion

This study demonstrates the ability of the NSU-DSI-122 template to serve as a useful means to register experimentally collected diffusion data and free water signal fraction maps in stereotaxic space. The use of FOD-based registration reduces variation between registration attempts, minimizing the introduction of noise.

Acknowledgements

No acknowledgement found.

References

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Figures

Study workflow illustrating the process of moving from native space images (three images on left), registering with the respective template for each method, applying the transform generated from that registration to the free water signal fraction map, and obtaining the free water signal fraction maps in stereotaxic MNI space (two images on right). This process was repeated 5 independent times for each of the 5 subjects.

The mean squared difference between each of the 5 independent registration attempts for each of the 5 subjects involved in analysis are presented, alongside the group mean (±SE). Grey bars represent the SyN intensity-based registration implemented in ANTs and yellow bars represent the WM-FOD based registration implemented in MRtrix.

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)
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