Bayesian In Vivo Tracking of Synapses using Joint Poisson Deconvolution and Diffeomorphic Registration
Authors: Shashwat Kumar, Dominic M. Padova, Binish Narang, Gabrielle I. Coste, Austin R. Graves, Richard L. Huganir, Adam S. Charles, Michael I. Miller, +1 more
Organizations: Department of Biomedical Engineering, Johns Hopkins University · Department of Neuroscience, Johns Hopkins University · Kavli Neuroscience Discovery Institute, Johns Hopkins University · Data Science and AI Institute, Johns Hopkins University · Department of Applied Mathematics and Statistics, Johns Hopkins University
Abstract
Synapses are densely packed submicron structures that dynamically reorganize during learning and memory formation. Longitudinal \textit{in vivo} imaging of fluorescently tagged synaptic receptors offers a promising opportunity to study large-scale synaptic dynamics and how these processes are disrupted in neurological disease. However, in vivo imaging with 2-photon microscopy uses low laser power and therefore suffers from low signal-to-noise ratio (SNR) and high shot noise, nonlinear tissue motion between days, nonstationary fluctuations in synaptic fluorescence, and significant blur induced by the microscope point spread function (PSF). Together, these factors make it challenging to detect and track synapses, especially in regions with high synaptic density. This paper presents a novel template-based framework for modeling synapses as varying luminance point sources that move under a nonlinear tissue deformation. Taking a unified Bayesian approach, we apply this model to microscopy data by deriving a posterior that incorporates a diffeomorphic mapping for domain warping, a Gaussian point spread function for the imaging process, and a Poisson observation model for raw photon counts. The Bayesian solution simultaneously: (1) Constructs a probabilistic template of synapse locations, (2) denoises and deconvolves the image data, (3) infers fluorescence intensities, (4) performs diffeomorphic image registration to correct for tissue motion, and (5) provides confidence regions for these parameter estimates. We demonstrate the framework on both a 2D+t simulated dataset and a 3D+t longitudinal \textit{in vivo} microscopy dataset of fluorescent synapses imaged in a mouse over two weeks.
In time-lapse fluorescence imaging, single-particle-tracking is a powerful tool to monitor the dynamics of objects of interest, and extract information about biological processes. However, tracked particles can be subject to occlusion and intermittent detectability. When these phenomena persist over a few frames, tracking algorithms tend to produce multiple tracklets for the same particle. In this work, we introduce self-supervised learning of visual features to compare tracked particles, and we exploit both visual and positional distances to robustly stitch tracklets representing the same particle. We demonstrate the performance of our stitching framework on time-lapse fluorescence sequences of Hydra vulgaris neurons. Results show high stitching precision, and reduction of errors made by previous algorithms on the same data by a factor of two.
Neuron counting and segmentation in microscopy images of neuronal cultures is a routine and time-consuming task in neuroscience research, traditionally performed through manual inspection or semi-automatic tools. We present NeuroAdaptTrainer, an open-source Fiji/ImageJ plugin that integrates a YOLO instance-segmentation model directly into the microscopist's workflow. The plugin allows a user to run automatic neuron detection on a single image or a batch of images, manually correct the resulting detections from within Fiji, and use those corrections to adapt the model to new imaging conditions via transfer learning. A built-in external validation module allows the base and adapted models to be compared quantitatively on a held-out annotated set. NeuroAdaptTrainer lowers the barrier for non-specialist users to benefit from deep-learning-based segmentation while keeping expert supervision at the center of the workflow.
Many disciplines need quantitative models that synthesize experimental data across multiple instances of the same general system. For example, neuroscientists must combine data from the brains of many individual animals to understand the species' brain in general. However, typical machine learning models treat one system instance at a time. Here we introduce a machine learning framework, deep probabilistic model synthesis (DPMS), that leverages system properties auxiliary to the model to combine data across system instances. DPMS specifically uses variational inference to learn a conditional prior distribution and instance-specific posterior distributions over model parameters that respectively tie together the system instances and capture their unique structure. DPMS can synthesize a wide variety of model classes, such as those for regression, classification, and dimensionality reduction, and we demonstrate its ability to improve upon single-instance models on synthetic data and whole-brain neural activity data from larval zebrafish.
William E. Bishop, Luuk W. Hesselink, Bernhard Englitz +2