Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 µm isotropic voxels for the MRI volume and 78 µm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multilevel data integration and analysis across reference spaces.

Diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying biological tissue microarchitectures in vivo. Recently, there has been increased effort to develop quantitative dMRI methods to probe both length scale and orientation information in diffusion media. Diffusion spectrum imaging (DSI) is one such approach that aims to resolve such information on the basis of the three-dimensional diffusion propagator at each voxel. However, in practice only the orientation component of the propagator function is preserved when deriving the orientation distribution function. Here, we demonstrate how a straightforward extension of the linear spherical deconvolution (SD) model can be used to probe tissue orientation structures over a range (or “spectrum”) of length scales with minimal assumptions on the underlying microarchitecture. Using high b-value Cartesian q-space data on a fixed rat brain sample, we demonstrate how this “restriction spectrum imaging” (RSI) model allows for separating the volume fraction and orientation distribution of hindered and restricted diffusion, which we argue stems primarily from diffusion in the extra- and intra-neurite water compartment, respectively. Moreover, we demonstrate how empirical RSI estimates of the neurite orientation distribution and volume fraction capture important additional structure not afforded by traditional DSI or fixed-scale SD-like reconstructions, particularly in grey matter. We conclude that incorporating length scale information in geometric models of diffusion offers promise for advancing state-of-the-art dMRI methods beyond white matter into grey matter structures while allowing more detailed quantitative characterization of water compartmentalization and histoarchitecture of healthy and diseased tissue.

Diffusion MRI (dMRI) is widely used to measure microstructural features of brain white matter, but commonly used dMRI measures have limited capacity to resolve the orientation structure of complex fiber architectures. While several promising new approaches have been proposed, direct quantitative validation of these methods against relevant histological architectures remains missing. In this study, we quantitatively compare neuronal fiber orientation distributions (FODs) derived from ex vivo dMRI data against histological measurements of rat brain myeloarchitecture using manual recordings of individual myelin stained fiber orientations. We show that accurate FOD estimates can be obtained from dMRI data, even in regions with complex architectures of crossing fibers with an intrinsic orientation error of approximately 5–6 degrees in these regions. The reported findings have implications for both clinical and research studies based on dMRI FOD measures, and provide an important biological benchmark for improved FOD reconstruction and fiber tracking methods.

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Modern high throughput brain wide profiling techniques for cells and their morphology, connectivity, and other properties, make the use of reference atlases with 3D coordinate frameworks essential. However, anatomical location of observations made in microscopic sectional images from rodent brains is typically determined by comparison with 2D anatomical reference atlases. A major challenge in this regard is that microscopic sections often are cut with orientations deviating from the standard planes used in the reference atlases, resulting in inaccuracies and a need for tedious correction steps. Overall, efficient tools for registration of large series of section images to reference atlases are currently not widely available. Here we present QuickNII, a stand-alone software tool for semi-automated affine spatial registration of sectional image data to a 3D reference atlas coordinate framework. A key feature in the tool is the capability to generate user defined cut planes through the reference atlas, matching the orientation of the cut plane of the sectional image data. The reference atlas is transformed to match anatomical landmarks in the corresponding experimental images. In this way, the spatial relationship between experimental image and atlas is defined, without introducing distortions in the original experimental images. Following anchoring of a limited number of sections containing key landmarks, transformations are propagated across the entire series of sectional images to reduce the amount of manual steps required. By having coordinates assigned to the experimental images, further analysis of the distribution of features extracted from the images is greatly facilitated.

In the primary somatosensory cortex (SI), the body surface is mapped in a relatively continuous fashion, with adjacent body regions represented in adjacent cortical domains. In contrast, somatosensory maps found in regions of the cerebellar hemispheres, which are influenced by the SI through a monosynaptic link in the pontine nuclei, are discontinuous ("fractured") in organization. To elucidate this map transformation, the authors studied the organization of the first link in the SI-cerebellar pathway, the SI-pontine projection. After injecting anterograde axonal tracers into electrophysiologically defined parts of the SI, three-dimensional reconstruction and computer-graphic visualization techniques were used to analyze the spatial distribution of labeled fibers. Several target regions in the pontine nuclei were identified for each major body representation. The labeled axons formed sharply delineated clusters that were distributed in an inside-out, shell-like fashion. Upper lip and other perioral representations were located in a central core, whereas extremity and trunk representations were found more externally. The multiple clusters suggest that the pontine nuclei contain several representations of the SI map. Within each representation, the spatial relationships of the SI map are largely preserved. This corticopontine projection pattern is compatible with recently proposed principles for the establishment of subcortical topographic patterns during development. The largely preserved spatial relationships in the pontine somatotopic map also suggest that the transformation from an organized topography in SI to a fractured map in the cerebellum takes place primarily in the mossy fiber pontocerebellar projection.

The hippocampal region, comprising the hippocampal formation and the parahippocampal region, has been one of the most intensively studied parts of the brain for decades. Better understanding of its functional diversity and complexity has led to an increased demand for specificity in experimental procedures and manipulations. In view of the complex 3D structure of the hippocampal region, precisely positioned experimental approaches require a fine-grained architectural description that is available and readable to experimentalists lacking detailed anatomical experience. In this paper, we provide the first cyto- and chemoarchitectural description of the hippocampal formation and parahippocampal region in the rat at high resolution and in the three standard sectional planes: coronal, horizontal and sagittal. The atlas uses a series of adjacent sections stained for neurons and for a number of chemical marker substances, particularly parvalbumin and calbindin. All the borders defined in one plane have been cross-checked against their counterparts in the other two planes. The entire dataset will be made available as a web-based interactive application through the Rodent Brain WorkBench (http://www.rbwb.org) which, together with this paper, provides a unique atlas resource.

Atlases of the rat brain are widely used as reference for orientation, planning of experiments, and as tools for assigning location to experimental data. Improved quality and use of magnetic resonance imaging (MRI) and other tomographical imaging techniques in rats have allowed the development of new three-dimensional (3-D) volumetric brain atlas templates. The rat hippocampal region is a commonly used model for basic research on memory and learning, and for preclinical investigations of brain disease. The region features a complex anatomical organization with multiple subdivisions that can be identified on the basis of specific cytoarchitectonic or chemoarchitectonic criteria. We here investigate the extent to which it is possible to identify boundaries of divisions of the hippocampal region on the basis of high-resolution MRI contrast. We present the boundaries of 13 divisions, identified and delineated based on multiple types of image contrast observed in the recently published Waxholm Space MRI/DTI template for the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374-386, 2014). The new detailed delineations of the hippocampal formation and parahippocampal region (Waxholm Space atlas of the Sprague Dawley rat brain, v2.0) are shared via the INCF Software Center (http://software.incf.org/), where also the MRI/DTI reference template is available. The present update of the Waxholm Space atlas of the rat brain is intended to facilitate interpretation, analysis, and integration of experimental data from this anatomically complex region.