Diffusion tensor imaging of the developing mouse brain

Abstract

It is shown that diffusion tensor MR imaging (DTI) can discretely delineate the microstructure of white matter and gray matter in embryonic and early postnatal mouse brains based on the existence and orientation of ordered structures. This order was found not only in white matter but also in the cortical plate and the periventricular zone, which are precursors of the cerebral cortex. This DTI-based information could be used to accomplish the automated spatial definition of the cortical plate and various axonal tracts. The DTI studies also revealed a characteristic evolution of diffusion anisotropy in the cortex of the developing brain. This ability to detect changes in the organization of the brain during development will greatly enhance morphological studies of transgenic and knockout models of cortical dysfunction. With the advent of murine models of disease and development generated by gene engineering, a new noninvasive technique is needed to characterize 3D morphological changes appearing over time in the brain. At present, the microscopic anatomical analyses of mammalian developmental studies are almost exclusively based on the histological examination. While this technique is most effective for examining microscopic changes in developing brains, it is not particularly suitable to characterize large-scale morphology, such as the anatomy of the entire brain. Although it is possible to reconstruct a macroscopic 3D-volume dataset using serial histological sections and stereology, this is an extremely labor-intensive process (1,2). To examine global anatomy in developing mouse brains, MRI technology is especially promising (3,4) because it can provide a 3D dataset without sectioning and is free of artifacts related to brain deformation or missing tissue due to imperfect sectioning. The data are intrinsically numerical and quantification for shape and volume analyses is more straightforward. Similar to various staining techniques for histological preparations, MRI also provides a family of contrast types based on the physical properties of water. For example, mouse embryonic imaging has been performed using proton density T 1 -and T 2 -weighted images (3-6). While these imaging methods can provide clear contrast for various tissue compartments in the entire body, it is not always optimal for the differentiation of compartments within the brain because of small differences in T 1 and T 2 relaxation parameters in young brains (7,8). Moreover, even in adult brains conventional MRI methods are not suitable to differentiate various white matter tracts within the brain white matter.In this report, we apply an MRI technology called diffusion tensor imaging (DTI) (9,10) to study mouse brain development from a period starting at embryonic day 15.5 in utero to adult. This technique uses water diffusion to probe tissue microstructure. For example, in regions where axon tracts form an ordered environment, water diffusion has directionality (anisotropy). Application of this technique to the adult brain has revealed that whi...

Diffusion MR imaging characteristics of the developing primate brain

“…Changes in MR-measured anisotropy within the cortex echo the microstructural changes taking place during development, and are consistent with diffusion MR-based findings in the developing mouse brain (Mori et al, 2001;Zhang et al, 2003). At the earliest developmental stages examined here (90 days gestation), ontogenic columns are already formed and are highly structured.…”

“…Anisotropy is high early in development, with the preferred displacement direction oriented radially with respect to the cortical surface (Maas et al, 2004;Mori et al, 2001;Neil et al, 1998). This has been attributed to the orientation of radial glial fibers and the apical dendrites of pyramidal cells.…”

“…This has been attributed to the orientation of radial glial fibers and the apical dendrites of pyramidal cells. As the brain matures, the magnitude of cortical diffusion anisotropy decreases (McKinstry et al, 2002;Mori et al, 2001), reflecting a loss in orientational coherence of cortical structures that restrict diffusion. This may be due to the elaboration of pyramidal cell basal dendrites, addition of interneurons, and/or development of thalamocortical afferent fibers.…”

Mapping somatosensory connectivity in adult mice using diffusion MRI tractography and super-resolution track density imaging

“…These findings would not result from connectivity between adjacent layer IV barrels (Feldmeyer, 2012) and, although there is evidence to suggest a higher concentration of myelin within the septal area compared to barrel hollows (Barrera et al, 2012), myelin is not essential for anisotropic diffusion in nerve fibres, with evidence of minor amounts of anisotropy in rodent and piglet cortex (Hoehn-Berlage et al, 1999;Mori et al, 2001;Thornton et al, 1997). In fact, anisotropy from un-myelinated nerves in garfish (Beaulieu and Allen, 1994), rodent (Seo et al, 1999), zebrafish (Ullmann et al, 2013) and human fetal brain (Tucciarone et al, 2009) suggest the radial alignment of microstructure including cell membranes is a sufficient barrier to diffusion to result in anisotropic diffusivity.…”

Multimodal imaging of mouse development: Tools for the postgenomic era

“…Abnormalities in embryonic and postnatal neural development can be facilitated by highly sensitive methods such as diffusion tensor imaging (DTI), which makes use of water diffusion to highlight ordered structures such as axonal tracts (Mori et al, 2001). DTI imaging has been used in the quantitative analysis of conditional Bcl-x mutants showing that normal neuronal development can occur after Bcl-x deletion at 13.5 dpc, but neurons later degenerate .…”