Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions

Abstract

Network approaches provide sensitive biomarkers for neurological conditions, such as Alzheimer's disease (AD). Mouse models can help advance our understanding of underlying pathologies, by dissecting vulnerable circuits. While the mouse brain contains less white matter compared to the human brain, axonal diameters compare relatively well (e.g., ∼0.6 µm in the mouse and ∼0.65-1.05 µm in the human corpus callosum). This makes the mouse an attractive test bed for novel diffusion models and imaging protocols. Remaining questions on the accuracy and uncertainty of connectomes have prompted us to evaluate diffusion imaging protocols with various spatial and angular resolutions. We have derived structural connectomes by extracting gradient subsets from a high-spatial, high-angular resolution diffusion acquisition (120 directions, 43-µm-size voxels). We have simulated protocols with 12, 15, 20, 30, 45, 60, 80, 100, and 120 angles and at 43, 86, or 172-µm voxel sizes. The rotational stability of these schemes increased with angular resolution. The minimum condition number was achieved for 120 directions, followed by 60 and 45 directions. The percentage of voxels containing one dyad was exceeded by those with two dyads after 45 directions, and for the highest spatial resolution protocols. For the 86-or 172-µm resolutions, these ratios converged toward 55% for one and 39% for two dyads, respectively, with <7% from voxels with three dyads. Tractography errors, estimated through dyad dispersion, decreased most with angular resolution. Spatial resolution effects became noticeable at 172 µm. Smaller tracts, e.g., the fornix, were affected more than larger ones, e.g., the fimbria. We observed an inflection point for 45 directions, and an asymptotic behavior after 60 directions, corresponding to similar projection density maps. Spatially downsampling to 86 µm, while maintaining the angular resolution, achieved a subgraph similarity of 96% relative to the reference. Using 60 directions with 86-or 172-µm voxels resulted in 94% similarity. Node similarity metrics indicated that major white matter tracts were more robust to downsampling relative to cortical regions. Our study provides guidelines for new protocols in mouse models of neurological conditions, so as to achieve similar connectomes, while increasing efficiency.

Resolution and b value dependent structural connectome in ex vivo mouse brain

“…The influences of experimental factors of dMRI associated with the tractography and connectome have been investigated in detail in primate brains, but not fully explored in rodents ( Anderson et al, 2020 ; Caiazzo et al, 2018 ). Various biophysical models have been developed to probe the tissue microstructure, but the b values may vary dramatically for different models ( Alexander et al, 2002 ; Assaf et al, 2008 ; Calamante et al, 2010 ; Edwards et al, 2017 ; Henriques et al, 2019 ; Huang et al, 2020 ; Kaden et al, 2016 ; Tournier et al, 2004 , 2011 ; Tuch et al, 2002 ; Wedeen et al, 2008 ; Zhang et al, 2011 ).…”

“…However, most of these studies focus on small areas of the white matter. Alterations due to the different acquisition parameters to the whole brain structural connectome are not fully investigated ( Anderson et al, 2020 ; Caiazzo et al, 2018 ).…”

Resolution and b value dependent Structural Connectome in ex vivo Mouse Brain

“…The influences of experimental factors of dMRI associated with the tractography and connectome have been investigated in detail in primate brains, but not fully explored in rodents (Anderson et al, 2020; Caiazzo et al, 2018). Various biophysical models have been developed to probe the tissue microstructure, but the b values may vary dramatically for different models (Alexander et al, 2002; Assaf et al, 2008; Calamante et al, 2010; Edwards et al, 2017; Henriques et al, 2019; Huang et al, 2020; Kaden et al, 2016; Tournier et al, 2004; Tournier et al, 2011; Tuch et al, 2002; Wedeen et al, 2008; Zhang et al, 2011).…”

“…The HCP scanner can achieve b values up to 20,550 s/mm 2 with maximum gradients of 300 mT/m to generate structural connectome and probe the different tissue microstructures in live human (Duval et al, 2015; Guglielmetti et al, 2016; Jensen et al, 2005; Landman et al, 2007; Palombo et al, 2020; Zhang et al, 2012). The effect of b value on tractogram has been investigated in previous studies, but remains largely unanswered for preclinical MRI (Anderson et al, 2020; Schilling et al, 2017b; Sepehrband et al, 2017; Sotiropoulos and Zalesky, 2017). A relative lower b value may be adequate for accurately quantifying the DTI metrics, such as FA and MD.…”

“…A more recently study, more than 45 DW directions were recommended to resolve the complex fibers and detect the number of fiber populations in a voxel more accurately in white matter area (Schilling et al, 2017b). In the mouse brain with 43 µm isotropic resolution, it has been also suggested that a dMRI protocol with more than 45 angular samples helped to substantially reduce the tractography errors (Anderson et al, 2020). In this study, both dice coefficient and network properties achieve plateaus when the angular resolution is higher than 50.…”