Cardiovascular effects on high-resolution 3D multi-shot diffusion MRI of the rhesus macaque brain

The monkey brain represents a key research model thanks to its strong homologies with the humans, but diffusion-MRI (dMRI) performed at millimeter-level resolution using clinical scanners and pulse-sequences cannot take full advantage of this. Cardiovascular effects on 3D multi-shot Echo-Planar Imaging (3D-msEPI) dMRI were characterized at submillimetric resolution by comparing triggered and non-triggered diffusion-weighted (DW)-images and diffusion tensor imaging (DTI) maps. We also investigated the value of 3D-msEPI with cardiovascular-triggering to achieve dMRI of the anesthetized macaque brain with high resolution previously restricted to ex-vivo brains. Eight DW-images with voxel-size = 0.5 × 0.5 × 1 mm³ and b = 1500 s/mm² were collected at 3 Tesla from two macaques using triggered and then non-triggered 3D-msEPI. Statistical analysis by mixed models was used to compare signal-to-noise ratio (SNR) and ghost-to-signal ratio (GSR) of DW-images with and without triggering. Brain DTI with isotropic-resolution of 0.4 mm and b = 1000 s/mm² was also collected in three macaques with triggered 3D-msEPI and reapplied without triggering in one. Cardiovascular pulsations induce inter-shot phase-errors with non-linear spatial dependency on DW-images, resulting in ghost-artifacts and signal loss particularly in the brainstem, thalamus, and cerebellum. Cardiovascular-triggering proved effective in addressing these, recovering SNR in white and gray matter (all p < 0.0001), and reducing GSR from 16.5 ± 10% to 4.7 ± 4.2% on DW-images (p < 0.0001). Triggered 3D-msEPI provided DTI-maps with the unprecedented spatial-resolution of 0.4 mm, enabling several substructures of the macaque brain to be discerned and thus analyzed in vivo. The value of cardiovascular-triggering in maintaining DTI-map sharpness and guaranteeing accurate tractography results in the brainstem, thalamus, and cerebellum was also demonstrated. In conclusion, this work highlights the effects of cardiovascular pulsations on brain 3D-dMRI and the value of triggered 3D-msEPI to provide high-quality diffusion-MRI of the anesthetized macaque brain. For routine studies, 3D-msEPI must be coupled with appropriate techniques to reduce acquisition duration.