Three-Dimensional High-Resolution Diffusion Tensor Imaging and Tractography of the Developing Rabbit Brain

Abstract

Diffusion tensor imaging (DTI) is sensitive to structural ordering in brain tissue particularly in the white matter tracts. Diffusion anisotropy changes with disease and also with neural development. We used high-resolution DTI of fixed rabbit brains to study developmental changes in regional diffusion anisotropy and white matter fiber tract development. Imaging was performed on a 4.7-tesla Bruker Biospec Avance scanner using custom-built solenoid coils and DTI was performed at various postnatal ages. Trace apparent diffusion coefficient, fractional diffusion anisotropy maps and fiber tracts were generated and compared across the ages. The brain was highly anisotropic at birth and white matter anisotropy increased with age. Regional DTI tractography of the internal capsule showed refinement in regional tract architecture with maturation. Interestingly, brains with congenital deficiencies of the callosal commissure showed selectively strikingly different fiber architecture compared to age-matched brains. There was also some evidence of subcortical to cortical fiber connectivity. DTI tractography of the anterior and posterior limbs of the internal capsule showed reproducibly coherent fiber tracts corresponding to known corticospinal and corticobulbar tract anatomy. There was some minor interanimal tract variability, but there was remarkable similarity between the tracts in all animals. Therefore, ex vivo DTI tractography is a potentially powerful tool for neuroscience investigations and may also reveal effects (such as fiber tract pruning during development) which may be important targets for in vivo human studies.

Neonatal Neurobehavior and Diffusion MRI Changes in Brain Reorganization Due to Intrauterine Growth Restriction in a Rabbit Model

“…With the purpose of detecting subtle changes we used high-resolution MRI acquisition in fixed whole brain preparations. This approach allows revealing submillimetric tissue structure differences, particularly in the GM, which are difficult to detect in vivo [21]. As a trade-off, fixation process may decrease brain water content reducing ADC absolute values, although diffusion anisotropy is preserved [51].…”

“…Notwithstanding their obvious shortcomings, animal models may overcome some limitations of human studies. Aside from the reproducibility of experimental conditions, such settings permit performing MRI on isolated whole brain preparations, which allows increasing substantially the duration of acquisition time and hence, the use of high resolution acquisition approaches [21].…”

Longitudinal Changes in Diffusion Properties in White Matter Pathways of Children With Tuberous Sclerosis Complex

“…31–35 T1-weighted magnetization-prepared rapid-acquisition gradient-echo, T2-weighted turbo spin-echo, and a 3D diffusion-weighted spin-echo echo-planar imaging were performed. Thirty diffusion-weighted measurements ( b = 1,000 sec/mm 2 ) and 5 non-diffusion-weighted measurements ( b = 0 sec/mm 2 ) were acquired from a 3T Siemens MR system with TR (repetition time) = 10 sec; TE (echo time) = 88 msec; ∂ = 12.0 msec; Δ = 24.2 msec; field of view = 22 cm; slice thickness = 2.0 mm; matrix size = 128×128; iPAT = 2.…”

Long-Term Functional Outcomes and Correlation with Regional Brain Connectivity by MRI Diffusion Tractography Metrics in a Near-Term Rabbit Model of Intrauterine Growth Restriction

“…Notwithstanding the obvious limitations, animal models provide the opportunity to conduct comprehensive studies spanning long maturational periods in homogeneous groups. Aside from the reproducibility of experimental conditions, MRI can be performed in isolated whole brain preparations allowing very long acquisition times with high-resolution [42]. The rabbit is a suitable model to reproduce IUGR [43]–[46] and it presents a human-like timing of perinatal brain WM maturation [44].…”