In vivo Diffusion Tensor Magnetic Resonance Tractography of the Sheep Brain: An Atlas of the Ovine White Matter Fiber Bundles

Abstract

Diffusion Tensor Magnetic Resonance Imaging (DTI) allows to decode the mobility of water molecules in cerebral tissue, which is highly directional along myelinated fibers. By integrating the direction of highest water diffusion through the tissue, DTI Tractography enables a non-invasive dissection of brain fiber bundles. As such, this technique is a unique probe for in vivo characterization of white matter architecture. Unraveling the principal brain texture features of preclinical models that are advantageously exploited in experimental neuroscience is crucial to correctly evaluate investigational findings and to correlate them with real clinical scenarios. Although structurally similar to the human brain, the gyrencephalic ovine model has not yet been characterized by a systematic DTI study. Here we present the first in vivo sheep (ovis aries) tractography atlas, where the course of the main white matter fiber bundles of the ovine brain has been reconstructed. In the context of the EU's Horizon EDEN2020 project, in vivo brain MRI protocol for ovine animal models was optimized on a 1.5T scanner. High resolution conventional MRI scans and DTI sequences (b-value = 1,000 s/mm2, 15 directions) were acquired on ten anesthetized sheep o. aries, in order to define the diffusion features of normal adult ovine brain tissue. Topography of the ovine cortex was studied and DTI maps were derived, to perform DTI tractography reconstruction of the corticospinal tract, corpus callosum, fornix, visual pathway, and occipitofrontal fascicle, bilaterally for all the animals. Binary masks of the tracts were then coregistered and reported in the space of a standard stereotaxic ovine reference system, to demonstrate the consistency of the fiber bundles and the minimal inter-subject variability in a unique tractography atlas. Our results determine the feasibility of a protocol to perform in vivo DTI tractography of the sheep, providing a reliable reconstruction and 3D rendering of major ovine fiber tracts underlying different neurological functions. Estimation of fiber directions and interactions would lead to a more comprehensive understanding of the sheep's brain anatomy, potentially exploitable in preclinical experiments, thus representing a precious tool for veterinaries and researchers.

Infusion Mechanisms in Brain White Matter and Their Dependence on Microstructure: An Experimental Study of Hydraulic Permeability

“…The WM matrix is composed of aligned myelinated axons and relatively soft extracellular matrix [45]. In the case of S∥, the cross sectional area of the tissue exposed to infusate pressure is composed of both axons and the relatively soft ECM, whereas in case of S⊥, the exposed cross-sectional area is predominantly composed of axons [39]. It is harder to deform axons (stiffness of a single axon reported to be e.g.…”

“…WM anisotropy, due to directionality of axons in the matrix [38], [39], makes WM hydraulic permeability directiondependent. This detail is often overlooked, and only a few theoretical studies have reported the effect of anisotropy of brain WM on the hydraulic permeability [40].…”

Diffusion Tensor Imaging Tractography of White Matter Tracts in the Equine Brain

“…As DTI tractography assesses the structural integrity of white matter, it has been widely used for prognostic and/or diagnostic purposes in various brain pathologies such as stroke (3)(4)(5)(6), neurodegenerative diseases (7)(8)(9)(10)(11), and brain tumors (12). With the increasing availability of high-field-strength MRI (1.5 and 3 T) in veterinary facilities (13)(14)(15)(16)(17), the use of this technique is now gradually growing for the description of white matter anatomy and structural connectivity of domestic mammals (dog, cat, ferret, and sheep) (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). These collected anatomical data are of particular interest as they might have applications in both veterinary medicine and experimental research.…”

The sheep brain: an interesting translational model for functional MRI studies?

“…In order to study sexual behaviour and hormonal status in the sheep brain, functional magnetic resonance imaging (fMRI) demonstrated valuable features (Ella et al, 2019). Recently, a few studies explored MRI functional possibilities in the sheep brain (Lee et al, 2015;Pieri et al, 2019) demonstrating reproducible and translatable features at clinical magnetic fields (1.5T and 3T). To the best of our knowledge, cerebral perfusion MRI has not been reported in sheep.…”