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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session A

Poster F7 - A Robust Whole-Brain Structural Assessment of White Matter Using Cortico-Cortical Path Lengths and Their Potential Role in Brain Function

Thursday, October 24, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Understanding the structural organization of the human brain is crucial for measuring the functional activity of various brain networks that give rise to cognitive processes. Nevertheless, our ability to quantify large-scale white matter (WM) organization using neuroimaging remains unclear. This knowledge is crucial for diagnosing neurodevelopmental disorders and advancing treatments for autism, schizophrenia, epilepsy, and neurodegenerative diseases like Alzheimer's and Parkinson's.

In the past decade, scientists have used diffusion MRI to map white matter connectivity patterns that support important brain networks. While diffusion MRI (dMRI) is uniquely suited to quantify local microstructure in complex tissues, its application to directly measure large-scale connections between remote areas of the brain is highly speculative. Mapping connectivity patterns with dMRI hinges on several assumptions and is sensitive to experimental factors like the diffusion gradient scheme, spatial resolution, and tractography algorithm parameters.

We propose a new method for quantifying the large-scale structure and architecture of white matter using a cortico-cortical pathlength matrix (CPM). We believe CPMs represent an accurate and reproducible tool for characterizing WM structure, on par with other brain morphometry techniques. Unlike conventional dMRI-derived connectomes, CPMs don't aim to measure connectivity but to quantify the physical distances neuronal impulses need to traverse between cortical areas, limiting action potential propagation delays and brain network function.

Our study aims to 1) measure pathlengths between pairs of cortical areas, 2) understand how tractography parameters affect CPMs, and 3) establish CPMs as quantitative measurements of white matter geometry and tensor structure, accurately approximating 3D neuronal trajectories.

Materials and

Methods:  We applied streamline tractography to a dMRI dataset acquired in a fixed brain of a Macaque monkey, a common animal model for studying brain structure and function due to its similarities to the human brain. At a spatial resolution of 200um, diffusion MRI can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei.

We parcellated the cortex using the D99 macaque monkey atlas and estimated the trajectories of white matter pathways in the brain using a deterministic algorithm for streamline tractography in MRtrix3. The algorithm sampled the local Fiber Orientation Distribution at each point, performed Newton optimization on a spherical surface to find the highest fiber density, and ensured the streamline accurately followed the path of maximum fiber density.

We seeded 500,000 streamlines with eigenvector turning angles set to 20°, 40°, 60°, and 80°, termination thresholds for fiber tracking at 0.01, 0.05, 0.1, and 0.5 and a step size of 0.5 mm. We set the maximum fiber length to 220 mm.

Using MRtrix3 we calculated each streamline's length and averaged these lengths for each pair of atlas ROIs, creating a symmetric matrix where each entry shows the average length of streamlines for the corresponding pair of cortical ROIs, also known as the CPM.

For the human dataset, the CPM was constructed using the Freesurfer anatomic segmentation scheme. We then created a whole-brain CPM representing streamlines between atlas regions (84x84).

Results, Conclusions, and Discussions: The CPMs follow a weighted format where elements of the resulting matrices signify the absence or presence of a pathway with regard to its mean length. Rows and columns are ordered such that all left hemisphere regions appear first, followed by all right hemisphere regions.

Brighter boxes in the upper-left and lower-right quadrants of the matrix represent strong intrahemispheric pathlength presence, whereas the darker-colored lower-left and upper-right quadrants represent weaker interhemispheric pathlength presence.

The cortico-cortical pathlength matrices show that a decrease in termination threshold (cutoff) introduces an increase in pathway length (Figure 1), while an increase in eigenvector angle value presents a decrease in pathway length (Figure 2). Establishing these patterns helps refine parameter optimization for streamline tractography.

Our multi-modal approach offers valuable neuropathological insights that complement brain morphometry techniques like cortical thickness and volumetric analysis. Together with standard cognitive performance measures, it could enhance our understanding and characterization of complex neurological conditions.

The continuation of this project will follow the study of control and clinical populations to establish fiber length pattern correlation.

Acknowledgements (Optional):  This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, “Connectome 2.0: Developing the next generation human MRI scanner for bridging studies of the micro-, meso- and macro-connectome”, NIH BRAIN Initiative 1U01EB026996-01 and the CNRM Neuroradiology-Neuropathology Correlation/Integration Core, 309698-4.01-65310, (CNRM-89-9921) and the Military Traumatic Brain Injury Initiative MTBI^2, 66978-313057-6.01 (HU0001-22-2-0058). This work utilized computational resources of the NIH HPC Biowulf cluster http://hpc.nih.gov. B.b. was supported by the Biomedical Engineering Summer Internship Program hosted by the BETA Center.