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

Abstract

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.

Keywords: 3D multi-shot EPI; cardiovascular effect; diffusion MRI; high-resolution brain imaging; macaque brain; triggered diffusion MRI.

Fig. 1.

Coronal and axial views of phase-maps (A) and magnitude-maps (B) of the anesthetized macaque brain acquired with a b = 1500 s/mm² using 3D-msEPI. Non-triggered magnitude-maps suffer from significant signal loss (blue arrows) and ghosting artifacts (green arrow). The phase curves, corresponding to the red line in A, show the intershot phase-errors with nonlinear space dependence, induced by the cardiovascular pulsations only on the non-triggered images (C). The triggered to non-triggered magnitude ratio map illustrates the signal loss due to cardiovascular-pulsations (D).

Fig. 2.

Axial views of diffusion tensor maps (colored fractional anisotropy (cFA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)) of 3 anesthetized macaque brains achieved using triggered 3D multi-shot EPI at an isotropic spatial-resolution of 400 microns and with b = 1000 s/mm². Color/gray scales are indicated on the right.

Fig. 3.

Coronal views of triggered and non-triggered colored fractional anisotropy (cFA) maps of the macaque brain with a resolution of 0.4 mm. The zoomed-in triggered cFA map reveals some substructures of the brainstem, such as central gray of the midbrain (CGM), medial longitudinal fasciculus (MLF), decussation of the superior cerebellar peduncle (DSCP), anterior pretectal nucleus (ATP), pontine nuclei (Pn), and third ventricle (3rd VT), which remain difficult to delineate on the non-triggered map. The intraparietal sulcus (IPS), middle temporal gyrus (MTG), medial pulvinar (PM), lateral pulvinar (PL), and inferior pulvinar (PI) are used as landmarks to locate the same brain sections on the cFA maps and on the Neuromap atlas.

Fig. 4.

Coronal views of triggered colored fractional anisotropy (cFA) maps of the macaque brain achieved with a spatial-resolution of 0.4 mm, down-sampled up to 1.2 mm.

Fig. 5.

Axial views of triggered and non-triggered colored fractional anisotropy (cFA) maps of the macaque brain, achieved with a spatial-resolution of 0.4 mm. Arrows indicate artifacts induced by cardiac pulsations on the non-triggered FA map.

Fig. 6.

Sagittal views of triggered and non-triggered cFA (colored fractional anisotropy) maps of the macaque brain achieved with a spatial-resolution of 400 microns. A focus on the cerebellum reveals a blurring covering the complex anatomy of the cerebellum’s white matter when DTI maps are generated using non-triggered 3D multi-shot EPI.

Fig. 7.

Tractograms of the macaque middle cerebellum peduncle (MCP) and inferior cerebellum peduncle (ICP). In comparison to the triggered tractograms, the red and the pink arrows indicate the false-positives and true-negatives generated by the non-triggered data, respectively.