In vivo high-resolution diffusion tensor imaging of the mouse brain

Abstract

Diffusion tensor imaging (DTI) of the laboratory mouse brain provides important macroscopic information for anatomical characterization of mouse models in basic research. Currently, in vivo DTI of the mouse brain is often limited by the available resolution. In this study, we demonstrate in vivo high-resolution DTI of the mouse brain using a cryogenic probe and a modified diffusion-weighted gradient and spin echo (GRASE) imaging sequence at 11.7 T. Three-dimensional (3D) DTI of the entire mouse brain at 0.125 mm isotropic resolution could be obtained in approximately 2 h. The high spatial resolution, which was previously only available with ex vivo imaging, enabled non-invasive examination of small structures in the adult and neonatal mouse brains. Based on data acquired from eight adult mice, a group-averaged DTI atlas of the in vivo adult mouse brain with 60 structure segmentations was developed. Comparisons between in vivo and ex vivo mouse brain DTI data showed significant differences in brain morphology and tissue contrasts, which indicate the importance of the in vivo DTI-based mouse brain atlas.

Keywords: Brain atlas; Diffusion tensor imaging; High-resolution; In vivo; Magnetic resonance imaging; Mouse brain.

Fig. 1

In vivo 3D high-resolution DTI and tractography of a representative adult mouse brain at 0.125 mm isotropic resolution. Direction-encoded colormaps (DECs) at several coronal slices (A) and sagittal slices (B) of the mouse brain are compared to matching images from our previous ex vivo data (C) of the same resolution after rigid alignment of the two datasets. The high resolution of the in vivo data allows reconstruction of both major and small white matter tracts (D & E) in the brain. The red-green-blue color scheme used in the DEC images is: red: left-right axis; green: rostral-caudal axis; blue: superior-inferior axis. Abbreviations: ac – anterior commissure; bsc: brachium sup colliculus; cp – cerebral peduncle; opt – optical tract; fi – fimbria; ec – external capsule; f – fornix; ml: medial lemniscus; sm – stria medullaris; st – stria terminalis; fr – fasciculus retroflexus; LV – lateral ventricle; 3V – third ventricle; 4V – fourth ventricle. Scale bar = 1 mm.

Fig. 2

In vivo DTI of normal neonatal mouse brains at 0.125mm isotropic resolution. Coronal and sagittal FA and DEC images at postnatal day 7 (P7), 11 (P11), and 14 (P14). Abbreviations: cc –corpus callosum; ac – anterior commissure; cp– cerebral peduncle; opt – optical tract; fi – fimbria; sm – stria medullaris; st – stria terminalis; fr– fasciculus retroflexus. Scale bar = 1 mm.

Fig. 3

Group-averaged FA and DEC images and structural segmentations in the in vivo mouse brain DTI atlas. Average FA and DEC images from eight adult mouse brains are shown in coronal and horizontal views. Inset figures magnify complex structures from the hippocampus and cerebellum. Outlines of structural segmentations are overlaid on the DEC images.

Fig.4

Morphological differences between the in vivo (n=8) and ex vivo (n=10) mouse brains. (Top row) Color-coded Log-Jacobian maps of the transformation between the in vivo and ex vivo mouse brains superimposed on average in vivo FA maps). Only the voxels with significant changes in Log-Jacobian values (p < 0.05 after corrections for multiple comparisons) are shown. A Log-Jacobian value greater than 0 indicates expansion of the ex vivo mouse brains with respect to the in vivo mouse brains, and shrinkage otherwise. (Bottom row) Color-coded maps of estimated tissue displacement between the average ex vivo and in vivo mouse brain images superimposed on average in vivo FA maps. Cortical and hippocampal regions that show large morphological changes between the in vivo and ex vivo images are indicated by the yellow and white arrows, respectively.

Fig. 5

Morphological and diffusion properties differ between the average in vivo and ex vivo mouse brains. (a) ADC measured in the in vivo mouse brain (left) is much higher than that in the ex vivo mouse brain (right). (b) Parallel diffusivity (λ_∥) and radial diffusivity (λ_⊥) show different white matter – gray matter contrasts in the in vivo and ex vivo mouse brains. (c) Standard deviation of ADC and FA maps in the in vivo (n=8) and ex vivo (n=10) groups.