Biology subjects

Trouve, A.

Publications and source records attributed to Trouve, A..

2 recordsLinked to original sources

bioRxiv2021

Hierarchical Computational Anatomy: Unifying the Molecular to Tissue Continuum via Measure Representations of the Brain

ObjectiveThe objective of this research is to unify the molecular representations of spatial transcriptomics and cellular scale histology with the tissue scales of Computational Anatomy for brain mapping. Impact statementWe present a unified representation theory for brain mapping based on geometric measures of the micro-scale phenotypes of molecular disease simultaneously with the connectomic scales of complex interacting brain circuits. IntroductionMapping across coordinate systems in computational anatomy allows us to understand structural and functional properties of the brain at the millimeter scale. New measurement technologies in digital pathology and spatial transcriptomics allow us to measure the brain molecule by molecule and cell by cell based on protein and transcriptomic identity. We currently have no mathematical representations for integrating consistently the tissue limits with the molecular particle descriptions. The formalism derived here demonstrates the methodology for transitioning consistently from the molecular scale of quantized particles - as first introduced by Dirac as the class of generalized functions - to the continuum and fluid mechanics scales appropriate for tissue. MethodsWe introduce two methods based on notions of generalized function geometric measures and statistical mechanics. We use generalized functions expanded to include functional geometric descriptions - electrophysiology, transcriptomic, molecular histology - to represent the molecular biology scale integrated with a Boltzman like procedure to pass from the sparse particles to empirical probability laws on the functional state of the tissue. ResultsWe demonstrate a unified mapping methodology for transferring molecular information in the transcriptome and histological scales to the human atlas scales for understanding Alzheimers disease. ConclusionsWe demonstrate a unified brain mapping theory for molecular and tissue scales based on geometric measure representations.

neuroscience↗

bioRxiv2020

Reaction-Diffusion Model of Cortical Atrophy Spread during Early Stages of Alzheimer's Disease

1.This study introduces a reaction-diffusion model of atrophy spread across the rhinal cortex during early stages of Alzheimers disease. Our finite elements model of atrophy spread is motivated by histological evidence of a spatio-temporally specific pattern of neurofibrillary tau accumulation, and evidence of grey matter atrophy correlating with sites of neurofibrillary tau accumulation. The goal is to estimate disease-related parameters such as the origin of atrophy, the speed at which atrophy spreads, and the stage of the disease. We solve a constrained optimization problem using the adjoint state method and gradient descent to match modeled cortical thickness to observed cortical thickness as calculated from 3T MRI scans. Simulation testing shows that disease-related parameters can be estimated accurately with as little as 2 years of annual observations, depending on the stage of the disease. Case studies of 3 subjects suggests that we can pinpoint the origin of atrophy to the anterior transentorhinal cortex, and that the speed of atrophy spread is less than 1 mm per year. In the future, this type of modeling could be useful to stage the progression of the disease prior to the onset of clinical symptoms. 2. Author SummaryMisfolded tau proteins are associated with Alzheimers disease. They are known to accumulate and spread across the rhinal cortex, which is an area of the temporal lobe. Recent imaging studies suggest that we can detect grey matter thinning that occurs in pattern similar to tau spread. In this study, we introduce a model of disease spread to examine where thinning begins, how fast it spreads, and the stage of the disease. The results show that the origin of thinning corresponds with the earliest known location of tau accumulation, and spreads at a rate of less than 1 mm per year. Future work may focus on staging the progression of the disease using this type of model.

neuroscience↗