Abstract
The ability to dissociate axonal density in vivo from other microstructural properties is important for the diagnosis and treatment of neurologic disease, and new methods to do so are being developed. We investigated one such method—restricted diffusion imaging (RDI)—to see whether it can more accurately replicate histological axonal density patterns in the corpus callosum (CC) of adults and children compared to diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and generalized q-sampling imaging (GQI) methods. To do so, we compared known axonal density patterns defined by histology to diffusion-weighted imaging (DWI) scans of 840 healthy 20- to 40-year-old adults, and to DWI scans of 129 typically developing 7-month-old to 18-year-old children and adolescents. Contrast analyses were used to compare pattern similarities between the in vivo metric and previously published histological density models. We found that RDI was effective at mapping axonal density of small (Cohen’s d = 2.60) and large fiber sizes (Cohen’s d = 2.84) in adults. The same pattern was observed in the developing sample (Cohen’s d = 3.09 and 3.78, respectively). Other metrics, notably NODDI’s intracellular volume fraction in adults and GQI generalized fractional anisotropy in children, were also sensitive metrics. In conclusion, the study showed that the novel RDI metric is sensitive to density of small and large axons in adults and children, with both single- and multi-shell acquisition DWI data. Its effectiveness and availability to be used on standard as well as advanced DWI acquisitions makes it a promising method in clinical settings.
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Data availability
Data on adult participants were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. Data on child participants were from the Cincinnati MR Imaging of NeuroDevelopment (C-MIND) database, provided by the Pediatric Functional Neuroimaging Research Network (https://research.cchmc.org/c-mind/) and supported by a contract from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275200900018C).
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Acknowledgements
Thank you to Adam Dick for help with figures, and to both reviewers for helpful comments on the earlier version of the manuscript.
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This research was supported by NIH Grants R01MH112588 and R01DK119814 to P.G. and A.S.D.
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DG and ASD analyzed the data and wrote the initial draft. F-C Y provided advice on analyses of diffusion data and wrote the DSIStudio software. F-C Y and PG provided edits to the initial draft for the final manuscript.
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Garic, D., Yeh, FC., Graziano, P. et al. In vivo restricted diffusion imaging (RDI) is sensitive to differences in axonal density in typical children and adults. Brain Struct Funct 226, 2689–2705 (2021). https://doi.org/10.1007/s00429-021-02364-y
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DOI: https://doi.org/10.1007/s00429-021-02364-y