A road map to manual segmentation of cerebral structures.

Manual segmentation is an essential tool in the researcher's technical arsenal. It is a frequent practice necessary for image analysis in many protocols, especially in neuroimaging and comparative brain anatomy. In the framework of emergence of studies focusing on alternative animal models, manual segmentation procedures play a critical role. Nevertheless, this critical task is often assigned to students, a process that, unfortunately, tends to be time-consuming and repetitive. Well-conducted and well-described segmentation procedures can potentially guide novice and even expert operators and enhance research works' internal and external validity, making it possible to harmonize studies and facilitate data sharing. Furthermore, recent advances in neuroimaging, such as ex vivo imaging or ultra-high-field MRI, enable new acquisition modalities and the identification of minute structures that are barely visible with typical approaches. In this context of increasingly detailed and multimodal brain studies, reflecting on methodology is relevant and necessary. Because it is crucial to implement good practices in manual segmentation per se but also in the description of the segmentation procedures in research papers, we propose a general roadmap for optimizing the technique, its process and the reporting of manual segmentation. For each of them, the relevant elements of the literature have been collected and cited. The article is accompanied by a checklist that the reader can use to verify that the critical steps are being followed.

Comparative analysis of the chimpanzee and human brain superficial structural connectivities.

Diffusion MRI tractography (dMRI) has fundamentally transformed our ability to investigate white matter pathways in the human brain. While long-range connections have extensively been studied, superficial white matter bundles (SWMBs) have remained a relatively underexplored aspect of brain connectivity. This study undertakes a comprehensive examination of SWMB connectivity in both the human and chimpanzee brains, employing a novel combination of empirical and geometric methodologies to classify SWMB morphology in an objective manner. Leveraging two anatomical atlases, the Ginkgo Chauvel chimpanzee atlas and the Ginkgo Chauvel human atlas, comprising respectively 844 and 1375 superficial bundles, this research focuses on sparse representations of the morphology of SWMBs to explore the little-understood superficial connectivity of the chimpanzee brain and facilitate a deeper understanding of the variability in shape of these bundles. While similar, already well-known in human U-shape fibers were observed in both species, other shapes with more complex geometry such as 6 and J shapes were encountered. The localisation of the different bundle morphologies, putatively reflecting the brain gyrification process, was different between humans and chimpanzees using an isomap-based shape analysis approach. Ultimately, the analysis aims to uncover both commonalities and disparities in SWMBs between chimpanzees and humans, shedding light on the evolution and organization of these crucial neural structures.

ProbaStem, a pipeline towards the first high-resolution probabilistic atlas of the whole human brainstem.

The brainstem plays an essential role in many vital functions, such as autonomic control, consciousness and sleep, motricity, somatic afferent function, and cognition. Its involvement in several neurological diseases and the definition of brainstem targets for deep brain stimulation (DBS) explain the need for brainstem atlases describing its structural organization and connectivity from several modalities, from histology to ultrahigh field ex vivo MRI. Nonetheless, these atlases are often limited to a subpart of the brainstem or only include a single subject, the brainstem variability being considered low. This paper proposes a pipeline to create a high-resolution multisubject probabilistic atlas of the whole human brainstem based on four ultrahigh field ex vivo MRI datasets. The variability of the brainstem structures appears higher than usually considered, both for the volume and position of the central gray matter structures of the brainstem. This justifies the creation of atlases that capture the anatomical variability across subjects. The one we present here only included four specimens, but can easily be incremented due to its highly flexible design.

In vivo mapping of the deep and superficial white matter connectivity in the chimpanzee brain.

Mapping the chimpanzee brain connectome and comparing it to that of humans is key to our understanding of similarities and differences in primate evolution that occurred after the split from their common ancestor around 6 million years ago. In contrast to studies on macaque species' brains, fewer studies have specifically addressed the structural connectivity of the chimpanzee brain and its comparison with the human brain. Most comparative studies in the literature focus on the anatomy of the cortex and deep nuclei to evaluate how their morphology and asymmetry differ from that of the human brain, and some studies have emerged concerning the study of brain connectivity among humans, monkeys, and apes. In this work, we established a new white matter atlas of the deep and superficial white matter structural connectivity in chimpanzees. In vivo anatomical and diffusion-weighted magnetic resonance imaging (MRI) data were collected on a 3-Tesla MRI system from 39 chimpanzees. These datasets were subsequently processed using a novel fiber clustering pipeline adapted to the chimpanzee brain, enabling us to create two novel deep and superficial white matter connectivity atlases representative of the chimpanzee brain. These atlases provide the scientific community with an important and novel set of reference data for understanding the commonalities and differences in structural connectivity between the human and chimpanzee brains. We believe this study to be innovative both in its novel approach and in mapping the superficial white matter bundles in the chimpanzee brain, which will contribute to a better understanding of hominin brain evolution.

A novel male Japanese quail structural connectivity atlas using ultra-high field diffusion MRI at 11.7 T.

The structural connectivity of animal brains can be revealed using post-mortem diffusion-weighted magnetic resonance imaging (MRI). Despite the existence of several structural atlases of avian brains, few of them address the bird's structural connectivity. In this study, a novel atlas of the structural connectivity is proposed for the male Japanese quail (Coturnix japonica), aiming at investigating two lines divergent on their emotionality trait: the short tonic immobility (STI) and the long tonic immobility (LTI) lines. The STI line presents a low emotionality trait, while the LTI line expresses a high emotionality trait. 21 male Japanese quail brains from both lines were scanned post-mortem for this study, using a preclinical Bruker 11.7 T MRI scanner. Diffusion-weighted MRI was performed using a 3D segmented echo planar imaging (EPI) pulsed gradient spin-echo (PGSE) sequence with a 200 [Formula: see text]m isotropic resolution, 75 diffusion-encoding directions and a b-value fixed at 4500 s/mm2. Anatomical MRI was likewise performed using a 2D anatomical T2-weighted spin-echo (SE) sequence with a 150 [Formula: see text]m isotropic resolution. This very first anatomical connectivity atlas of the male Japanese quail reveals 34 labeled fiber tracts and the existence of structural differences between the connectivity patterns characterizing the two lines. Thus, the link between the male Japanese quail's connectivity and its underlying anatomical structures has reached a better understanding.

Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice.

Reversible detyrosination of tubulin, the building block of microtubules, is crucial for neuronal physiology. Enzymes responsible for detyrosination were recently identified as complexes of vasohibins (VASHs) one or two with small VASH-binding protein (SVBP). Here we report three consanguineous families, each containing multiple individuals with biallelic inactivation of SVBP caused by truncating variants (p.Q28* and p.K13Nfs*18). Affected individuals show brain abnormalities with microcephaly, intellectual disability and delayed gross motor and speech development. Immunoblot testing in cells with pathogenic SVBP variants demonstrated that the encoded proteins were unstable and non-functional, resulting in a complete loss of VASH detyrosination activity. Svbp knockout mice exhibit drastic accumulation of tyrosinated tubulin and a reduction of detyrosinated tubulin in brain tissue. Similar alterations in tubulin tyrosination levels were observed in cultured neurons and associated with defects in axonal differentiation and architecture. Morphological analysis of the Svbp knockout mouse brains by anatomical magnetic resonance imaging showed a broad impact of SVBP loss, with a 7% brain volume decrease, numerous structural defects and a 30% reduction of some white matter tracts. Svbp knockout mice display behavioural defects, including mild hyperactivity, lower anxiety and impaired social behaviour. They do not, however, show prominent memory defects. Thus, SVBP-deficient mice recapitulate several features observed in human patients. Altogether, our data demonstrate that deleterious variants in SVBP cause this neurodevelopmental pathology, by leading to a major change in brain tubulin tyrosination and alteration of microtubule dynamics and neuron physiology.