Sub-mm diffusion MRI on the Connectome 2.0 for reconstructing cortico-sucortical projections ex vivo
Poster No:
1310
Submission Type:
Abstract Submission
Authors:
Chiara Maffei1, Ting Gong1, Dongsuk Sung1, Gabriel Ramos Llorden1, Alina Scholz2, Mirsad Mahmutovic2, Boris Keil2, Susie Huang3, Angela Noecker4, Cameron McIntyre4, Anastasia Yendiki1
Institutions:
1Massachusetts General Hospital, Charlestown, MA, 2Mittelhessen University of Applied Sciences, Giessen, Hesse, 3Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical, Boston, MA, 4Duke University, Durham, NC
First Author:
Co-Author(s):
Susie Huang
Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical
Boston, MA
Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical
Boston, MA
Introduction:
We seek to establish a protocol for mesoscopic diffusion MRI (dMRI) on ex vivo human brains as part of the center for Large-scale Imaging of Neural Circuits (LINC). The final data will be accompanied by downstream correlative microscopy and will be made public to serve as a resource for the neuroscience community. We focus on cortico-subcortical pathways relevant to deep-brain stimulation (DBS), with the aim of building a next-generation tract atlas for DBS. To this end, we use as our reference the current gold-standard atlas for this purpose (Petersen, 2019), which was not built using dMRI tractography but based on input from expert neuroanatomists who relied on prior knowledge from tracer studies. The ideal protocol will match the fascicles in this atlas as closely as is currently possible with dMRI tractography, while augmenting the atlas by filling in currently missing projections.
Methods:
Data are collected on the Connectome 2.0, a unique 3T MRI scanner with Gmax = 500 mT/m (Huang, 2021), using a 64-channel ex vivo human brain coil (Scholz, 2023). Initial tests are performed on two whole brains (B1,B2) and one left hemisphere (B3). For specimen demographics and imaging parameters, see Fig. 1a. We use a multi-shot 3D echo-planar imaging sequence for dMRI (Miller, 2011), with 4 shots for B1/B2 and 8 shots for B3. After preprocessing to mitigate susceptibility and eddy-current distortions (Andersson, 2003; Andersson, 2016), we perform probabilistic tractography with fiber orientation distributions from multi-shell, multi-tissue constrained spherical deconvolution (Jeurissen, 2014; Dhollander, 2019) and 5 seeds per white-matter voxel. This initial evaluation focuses on three pathways from the Petersen atlas, including both large cortico-subcortical and small deep-brain bundles: the projections of the prefrontal and motor cortex through the internal capsule (IC), and pallidosubthalamic projections (Fig. 1b). The reference fibers of the Petersen atlas are in CIT168 template space (Pauli, 2018). We use symmetric normalization (Avants, 2008) to map the T1w template to the 0-th order spherical harmonic map from each ex vivo brain. We annotate the streamlines from each brain most closely matching the reference fibers using Trackvis.
Results:
Fig. 2 shows the manually annotated pathways in each ex vivo dataset as streamlines, and the corresponding reference pathways mapped from the Petersen atlas to the individual brain as a red isosurface. The compared protocols had variable success in reconstructing the prefrontal IC projections. The most successful cases (B2 and B3) matched the trajectories of the prefrontal IC bundles included in the reference atlas, and also filled in the remaining projections through the anterior limb of the IC that are missing from the atlas. The most challenging were the highly curved projections to the medial orbitofrontal cortex. The difficulty in reconstructing these in vivo is typically attributed to susceptibility distortions near the sinuses and low signal-to-noise ratio due to distance from the coil, but these factors are not present in our ex vivo acquisitions, suggesting an algorithmic limitation. Similarly, the high-curvature projections to the hand region were the most challenging of the motor fibers traveling from the IC. The 0.55mm resolution in these scans was sufficient to resolve the pallidosubthalamic fibers, a small sub-cortical bundle that would be difficult to resolve in vivo.
Conclusions:
We present the first results from ex vivo human dMRI protocol optimization for the LINC project. We are currently imaging additional specimens and exploring even higher spatial resolutions. As dMRI tractography can resolve crossing fibers but not fanning or sharply bending fibers, we do not expect to reach perfect accuracy with dMRI. We anticipate that the optical and X-ray microscopy that will be performed on these specimens after dMRI will provide the ground truth needed for benchmarking current dMRI methods and developing new ones.
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Keywords:
MRI
Sub-Cortical
Tractography
White Matter
1|2Indicates the priority used for review
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Provide references using APA citation style.
Andersson, J. L. R. (2016). An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. NeuroImage, 125, 1063–1078.
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Dhollander T. (2019). Improved white matter response function estimation for 3-tissue constrained spherical deconvolution. Proc. Intl. Soc. Mag. Res. Med., p. 555.
Huang, S. Y. (2021). Connectome 2.0: Developing the next-generation ultra-high gradient strength human MRI scanner for bridging studies of the micro-, meso- and macro-connectome. NeuroImage, 243, 118530.
Jeurissen, B. (2014). Multi-tissue constrained spherical deconvolution for improved analysis of multi-shell diffusion MRI data. NeuroImage, 103, pp. 411–426.
Miller, K. L. (2011). Diffusion imaging of whole, post-mortem human brains on a clinical MRI scanner. NeuroImage, 57(1), 167–181.
Pauli, W. (2018). J. A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei. Sci Data 5, 180063.
Petersen, M. V. (2019). Holographic Reconstruction of Axonal Pathways in the Human Brain. Neuron, 104(6), 1056–1064.e3.
Scholz, A. (2023). Design of a 64-channel ex vivo brain Rx array coil with field monitoring and temperature control for DWI at 3T, Proc. Intl. Soc. Mag. Res. Med., p. 215.