A novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves

TL;DR

This paper introduces a new statistical approach using spatial point process models and Sinkhorn distances to analyze and compare the complex, inhomogeneous spatial arrangements of axons in peripheral nerves, advancing neuroanatomy quantification.

Contribution

It presents a novel methodology combining spatial statistics, optimal transport metrics, and deep learning segmentation for detailed neuroanatomical analysis.

Findings

Differences observed between male and female nerve samples.

Similarities found between pelvic and abdominal vagus nerves.

A generalizable pipeline for nerve architecture analysis is proposed.

Abstract

A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial arrangement of myelinated and unmyelinated axons in peripheral nerves is random, however, in reality the axonal organization is inhomogeneous and anisotropic. Present quantitative neuroanatomy methods analyze peripheral nerves in terms of the number of axons and the morphometric characteristics of the axons, such as area and diameter. In this study, we employed spatial statistics and point process models to describe the spatial arrangement of axons and Sinkhorn distances to compute the similarities between these arrangements (in terms of first- and second-order statistics) in various vagus and pelvic nerve cross-sections. We utilized high-resolution TEM images that have been segmented using a custom-built high-throughput deep learning system based on a highly modified U-Net architecture. Our findings show a novel and innovative approach to quantifying similarities between spatial point patterns using metrics derived from the solution to the optimal transport problem. We also present a generalizable pipeline for quantitative analysis of peripheral nerve architecture. Our data demonstrate differences between male- and female-originating samples and similarities between the pelvic and abdominal vagus nerves.