Preserving Derivative Information while Transforming Neuronal Curves

The international neuroscience community is building the first comprehensive atlases of brain cell types to understand how the brain functions from a higher resolution, and more integrated perspective than ever before. In order to build these atlases, subsets of neurons (e.g. serotonergic neurons, prefrontal cortical neurons etc.) are traced in individual brain samples by placing points along dendrites and axons. Then, the traces are mapped to common coordinate systems by transforming the positions of their points, which neglects how the transformation bends the line segments in between. In this work, we apply the theory of jets to describe how to preserve derivatives of neuron traces up to any order. We provide a framework to compute possible error introduced by standard mapping methods, which involves the Jacobian of the mapping transformation. We show how our first order method improves mapping accuracy in both simulated and real neuron traces under random diffeomorphisms. Our method is freely available in our open-source Python package brainlit

Lineage dynamics of murine pancreatic development at single-cell resolution.

Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types. Within the epithelium, we find a previously undescribed endocrine progenitor population, as well as an analogous population in both human fetal tissue and human embryonic stem cells differentiating toward a pancreatic beta cell fate. Further, we identify candidate transcriptional regulators along the differentiation trajectory of this population toward the alpha or beta cell lineages. This work establishes a roadmap of pancreatic development and demonstrates the broad utility of this approach for understanding lineage dynamics in developing organs

Patient Specific Dosimetry Phantoms Using Multichannel LDDMM of the Whole Body

This paper describes an automated procedure for creating detailed patient-specific pediatric dosimetry phantoms from a small set of segmented organs in a child's CT scan. The algorithm involves full body mappings from adult template to pediatric images using multichannel large deformation diffeomorphic metric mapping (MC-LDDMM). The parallel implementation and performance of MC-LDDMM for this application is studied here for a sample of 4 pediatric patients, and from 1 to 24 processors. 93.84% of computation time is parallelized, and the efficiency of parallelization remains high until more than 8 processors are used. The performance of the algorithm was validated on a set of 24 male and 18 female pediatric patients. It was found to be accurate typically to within 1-2 voxels (2–4 mm) and robust across this large and variable data set

A Guide to the Brain Initiative Cell Census Network Data Ecosystem

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain

On the Complexity of Human Neuroanatomy at the Millimeter Morphome Scale: Developing Codes and Characterizing Entropy Indexed to Spatial Scale

In this work we devise a strategy for discrete coding of anatomical form as described by a Bayesian prior model, quantifying the entropy of this representation as a function of code rate (number of bits), and its relationship geometric accuracy at clinically relevant scales. We study the shape of subcortical gray matter structures in the human brain through diffeomorphic transformations that relate them to a template, using data from the Alzheimer's Disease Neuroimaging Initiative to train a multivariate Gaussian prior model. We find that the at 1 mm accuracy all subcortical structures can be described with less than 35 bits, and at 1.5 mm error all structures can be described with less than 12 bits. This work represents a first step towards quantifying the amount of information ordering a neuroimaging study can provide about disease status

Robust Diffeomorphic Mapping via Geodesically Controlled Active Shapes

This paper presents recent advances in the use of diffeomorphic active shapes which incorporate the conservation laws of large deformation diffeomorphic metric mapping. The equations of evolution satisfying the conservation law are geodesics under the diffeomorphism metric and therefore termed geodesically controlled diffeomorphic active shapes (GDAS). Our principal application in this paper is on robust diffeomorphic mapping methods based on parameterized surface representations of subcortical template structures. Our parametrization of the GDAS evolution is via the initial momentum representation in the tangent space of the template surface. The dimension of this representation is constrained using principal component analysis generated from training samples. In this work, we seek to use template surfaces to generate segmentations of the hippocampus with three data attachment terms: surface matching, landmark matching, and inside-outside modeling from grayscale T1 MR imaging data. This is formulated as an energy minimization problem, where energy describes shape variability and data attachment accuracy, and we derive a variational solution. A gradient descent strategy is employed in the numerical optimization. For the landmark matching case, we demonstrate the robustness of this algorithm as applied to the workflow of a large neuroanatomical study by comparing to an existing diffeomorphic landmark matching algorithm

Vestibular function and cortical and sub-cortical alterations in an aging population

International audienceWhile it is well known that the vestibular system is responsible for maintaining balance, posture and coordination, there is increasing evidence that it also plays an important role in cognition. Moreover, a growing number of epidemiological studies are demonstrating a link between vestibular dysfunction and cognitive deficits in older adults; however, the exact pathways through which vestibular loss may affect cognition are unknown. In this cross-sectional study, we sought to identify relationships between vestibular function and variation in morphometry in brain structures from structural neuroimaging. We used a subset of 80 participants from the Baltimore Longitudinal Study of Aging, who had both brain MRI and vestibular physiological data acquired during the same visit. Vestibular function was evaluated through the cervical vestibular-evoked myogenic potential (cVEMP). The brain structures of interest that we analyzed were the hippocampus, amygdala, thalamus, caudate nucleus, putamen, insula, entorhinal cortex (ERC), trans-entorhinal cortex (TEC) and perirhinal cortex, as these structures comprise or are connected with the putative "vestibular cortex." We modeled the volume and shape of these structures as a function of the presence/absence of cVEMP and the cVEMP amplitude, adjusting for age and sex. We observed reduced overall volumes of the hippocampus and the ERC associated with poorer vestibular function. In addition, we also found significant relationships between the shape of the hippocampus (p ¼ 0.0008), amygdala (p ¼ 0.01), thalamus (p ¼ 0.008), caudate nucleus (p ¼ 0.002), putamen (p ¼ 0.02), and ERC-TEC complex (p ¼ 0.008) and vestibular function. These findings provide novel insight into the multiple pathways through which vestibular loss may impact brain structures that are critically involved in spatial memory, navigation and orientation