MERMAID-v1 is a prototype PET scanner designed to support biomedical research involving adult zebrafish and similar species. The current experimental setup has been characterized, and scans of various phantoms, as well as adult zebrafish have been conducted. A dedicated reconstruction software was implemented, including accurate modeling of the parallax effect. The average energy resolution was 21.6% (FWHM at 511keV), with no significant dead-time effects observed for activities up to 18MBq. The absolute sensitivity at the center of the field of view (FOV) ranged from 0.06% to 0.31%, depending on the energy window (from 450-550 to 300-600keV), reflecting the limitations of the current two-head configuration. In the central 12mm of the transaxial FOV, the averaged spatial resolution is approximately 0.77mm (FWHM) transaxially and 0.66mm axially, as evaluated using a point source. Image quality was assessed using a downscaled NEMA-inspired IQ phantom and a 3D-printed Derenzo phantom. The reconstructed images suggest a spatial resolution around 0.7mm - 0.8mm, despite the lack of depth-of-interaction information. The first ex- and in-vivo PET scans of adult zebrafish were successfully
Zebrafish embryos are a valuable model for drug discovery due to their optical transparency and genetic similarity to humans. However, current evaluations rely on manual inspection, which is costly and labor-intensive. While machine learning offers automation potential, progress is limited by the lack of comprehensive datasets. To address this, we introduce a large-scale dataset of high-resolution microscopic image sequences capturing zebrafish embryonic development under both control conditions and exposure to compounds (3,4-dichloroaniline). This dataset, with expert annotations at fine-grained temporal levels, supports two benchmarking tasks: (1) fertility classification, assessing zebrafish egg viability (130,368 images), and (2) toxicity assessment, detecting malformations induced by toxic exposure over time (55,296 images). Alongside the dataset, we present the first transformer-based baseline model that integrates spatiotemporal features to predict developmental abnormalities at early stages. Experimental results present the model's effectiveness, achieving 98% accuracy in fertility classification and 92% in toxicity assessment. These findings underscore the potential of aut
Zebrafish share a high degree of homology with human genes and are commonly used as model organism in biomedical research. For medical laboratories, counting zebrafish is a daily task. Due to the tiny size of zebrafish, manual visual counting is challenging. Existing counting methods are either not applicable to small fishes or have too many limitations. The paper proposed a zebrafish counting algorithm based on the event stream data. Firstly, an event camera is applied for data acquisition. Secondly, camera calibration and image fusion were preformed successively. Then, the trajectory information was used to improve the counting accuracy. Finally, the counting results were averaged over an empirical of period and rounded up to get the final results. To evaluate the accuracy of the algorithm, 20 zebrafish were put in a four-liter breeding tank. Among 100 counting trials, the average accuracy reached 97.95%. As compared with traditional algorithms, the proposed one offers a simpler implementation and achieves higher accuracy.
Implicit neural representations (INRs) offer continuous coordinate-based encodings for atlas registration, cross-modality resampling, sparse-view completion, and compact sharing of neuroanatomical data. Yet reproducible evaluation is lacking for high-resolution larval zebrafish microscopy, where preserving neuropil boundaries and fine neuronal processes is critical. We present a reproducible INR benchmark for the MapZebrain larval zebrafish brain atlas. Using a unified, seed-controlled protocol, we compare SIREN, Fourier features, Haar positional encoding, and a multi-resolution grid on 950 grayscale microscopy images, including atlas slices and single-neuron projections. Images are normalized with per-image (1,99) percentiles estimated from 10% of pixels in non-held-out columns, and spatial generalization is tested with a deterministic 40% column-wise hold-out along the X-axis. Haar and Fourier achieve the strongest macro-averaged reconstruction fidelity on held-out columns (about 26 dB), while the grid is moderately behind. SIREN performs worse in macro averages but remains competitive on area-weighted micro averages in the all-in-one regime. SSIM and edge-focused error further s
Biological neural circuits contain specialized substructures that support distinct computational functions, yet many bio-inspired neural networks borrow biological motifs without identifying their circuit-level origins. In this study, we investigate whether zebrafish tectal microcircuits can be attributed along two computational axes: energy-efficient information processing and robustness-preserving stabilization. We reconstruct a directed zebrafish-inspired retinotectal microcircuit graph and verify retinotectal signal propagation through dynamic simulation. A leaky integrate-and-fire spiking neural network is then used as a nonlinear perturbation testbed, where predefined subcircuits are selectively ablated and evaluated using the Energy Sensitivity Index and the Robustness Sensitivity Index.The results reveal a functional dissociation between two tectal subcircuits.The \textit{ns\_TIN} subcircuit shows a low spike footprint but a measurable influence on prediction error, suggesting a role as a spike-efficient internal information gate.In contrast, the \textit{superficial\_TIN} subcircuit produces the highest robustness sensitivity, suggesting a feedback-like role in maintaining
We demonstrate in vivo dynamic optical coherence tomography (DOCT) imaging of zebrafish development from 2 weeks to 12 months post-fertilization, integrated with polarization-sensitive OCT (PS-OCT), OCT angiography (OCTA), and histological validation. Two DOCT algorithms were utilized: logarithmic intensity variance and late OCT correlation decay speed, which characterize the occupancy of dynamic scatterers and their motion speeds, respectively. Our results show that skin stripes exhibit high DOCT signals and it varies among the pigment-cell types. Furthermore, the combination of DOCT and PS-OCT captures the maturation of these stripes. In addition, DOCT and OCTA successfully visualized the developmental progression of blood and lymphatic vessels, as well as spinal tissues.
Achieving stable in vivo locomotion is essential for using magnetically actuated microswimmers for biomedical applications; however, while existing microswimmers have excellent motion control in vitro, their motion is greatly hindered inside living organisms. Moreover, previous work had only visually demonstrated in vivo motion through gradient pulling or rolling, but not swimming. This study investigated the injection and imaging of the achiral planar microswimmers (APMs) inside a live zebrafish embryo. The APMs can be actuated under a rotating magnetic field to generate a forward thrust at low Reynolds number environment. Combined with a safe injection technique and clear in vivo imaging at high resolution, it would be possible to control the swimming motion of APMs inside the zebrafish embryo. This work shows the safe injection and the clear imaging of an APM in a transparent zebrafish model, demonstrating the possibility for follow-up in-depth studies of the swimming motion of microswimmers in vivo.
Larval zebrafish hunting provides a tractable setting to study how ecological and energetic constraints shape adaptive behavior in both biological brains and artificial agents. Here we develop a minimal agent-based model, training recurrent policies with deep reinforcement learning in a bout-based zebrafish simulator. Despite its simplicity, the model reproduces hallmark hunting behaviors -- including eye vergence-linked pursuit, speed modulation, and stereotyped approach trajectories -- that closely match real larval zebrafish. Quantitative trajectory analyses show that pursuit bouts systematically reduce prey angle by roughly half before strike, consistent with measurements. Virtual experiments and parameter sweeps vary ecological and energetic constraints, bout kinematics (coupled vs. uncoupled turns and forward motion), and environmental factors such as food density, food speed, and vergence limits. These manipulations reveal how constraints and environments shape pursuit dynamics, strike success, and abort rates, yielding falsifiable predictions for neuroscience experiments. These sweeps identify a compact set of constraints -- binocular sensing, the coupling of forward speed
Constructing mechanistic models of neural circuits is a fundamental goal of neuroscience, yet verifying such models is limited by the lack of ground truth. To rigorously test model discovery, we establish an in silico testbed using neuromechanical simulations of a larval zebrafish as a transparent ground truth. We find that LLM-based tree search autonomously discovers predictive models that significantly outperform established forecasting baselines. Conditioning on sensory drive is necessary but not sufficient for faithful system identification, as models exploit statistical shortcuts. Structural priors prove essential for enabling robust out-of-distribution generalization and recovery of interpretable mechanistic models. Our insights provide guidance for modeling real-world neural recordings and offer a broader template for AI-driven scientific discovery.
Spatial patterns arising from the collective behavior of individual agents are present across biological systems. While agent-based models offer a natural framework for uncovering unknown agent (e.g., cell) interactions, these stochastic models face significant challenges. For spatial patterns, agent-based modeling often involves manual tuning to attain qualitative consistency with multiple experiments. This process limits predictive power and raises questions about parameter identifiability and model uniqueness. Combining topological techniques and Bayesian computation, we present a multi-objective methodology for parameter inference in detailed models. We illustrate our approach by inferring parameters in an agent-based model of zebrafish patterns, achieving practical identifiability in several case studies. By introducing extended prior distributions, we then reframe parameter inference as rule inference, allowing us to search across over 80 candidate agent-based rules to identify an alternative, simpler model consistent with our data.
Zebrafish are widely used in biomedical research and developmental stages of their embryos often need to be synchronized for further analysis. We present an unsupervised approach to extract descriptive features from 3D+t point clouds of zebrafish embryos and subsequently use those features to temporally align corresponding developmental stages. An autoencoder architecture is proposed to learn a descriptive representation of the point clouds and we designed a deep regression network for their temporal alignment. We achieve a high alignment accuracy with an average mismatch of only 3.83 minutes over an experimental duration of 5.3 hours. As a fully-unsupervised approach, there is no manual labeling effort required and unlike manual analyses the method easily scales. Besides, the alignment without human annotation of the data also avoids any influence caused by subjective bias.
Data-driven benchmarks have led to significant progress in key scientific modeling domains including weather and structural biology. Here, we introduce the Zebrafish Activity Prediction Benchmark (ZAPBench) to measure progress on the problem of predicting cellular-resolution neural activity throughout an entire vertebrate brain. The benchmark is based on a novel dataset containing 4d light-sheet microscopy recordings of over 70,000 neurons in a larval zebrafish brain, along with motion stabilized and voxel-level cell segmentations of these data that facilitate development of a variety of forecasting methods. Initial results from a selection of time series and volumetric video modeling approaches achieve better performance than naive baseline methods, but also show room for further improvement. The specific brain used in the activity recording is also undergoing synaptic-level anatomical mapping, which will enable future integration of detailed structural information into forecasting methods.
Neural dynamics underlie behaviors from memory to sleep, yet identifying mechanisms for higher-order phenomena (e.g., social interaction) is experimentally challenging. Existing whole-brain models often fail to scale to single-neuron resolution, omit behavioral readouts, or rely on PCA/conv pipelines that miss long-range, non-linear interactions. We introduce a sparse-attention whole-brain foundation model (SBM) for larval zebrafish that forecasts neuron spike probabilities conditioned on sensory stimuli and links brain state to behavior. SBM factorizes attention across neurons and along time, enabling whole-brain scale and interpretability. On a held-out subject, it achieves mean absolute error <0.02 with calibrated predictions and stable autoregressive rollouts. Coupled to a permutation-invariant behavior head, SBM enables gradient-based synthesis of neural patterns that elicit target behaviors. This framework supports rapid, behavior-grounded exploration of complex neural phenomena.
The zebrafish is a valuable model organism for studying cardiac development and diseases due to its many shared aspects of genetics and anatomy with humans and ease of experimental manipulations. Computational fluid-structure interaction (FSI) simulations are an efficient and highly controllable means to study the function of cardiac valves in development and diseases. Due to their small scales, little is known about the mechanical properties of zebrafish cardiac valves, limiting existing computational studies of zebrafish valves and their interaction with blood. To circumvent these limitations, we took a largely first-principles approach called design-based elasticity that allows us to derive valve geometry, fiber orientation and material properties. In FSI simulations of an adult zebrafish aortic valve, these models produce realistic flow rates when driven by physiological pressures and demonstrate the spatiotemporal dynamics of valvular mechanical properties. These models can be used for future studies of zebrafish cardiac hemodynamics, development, and disease.
In the field of environmental toxicology, rapid and precise assessment of the inflammatory response to pollutants in biological models is critical. This study leverages the power of deep learning to enable automated assessments of zebrafish, a model organism widely used for its translational relevance to human disease pathways. We present an innovative approach to assessing inflammatory responses in zebrafish exposed to various pollutants through an end-to-end deep learning model. The model employs a Unet-based architecture to automatically process high-throughput lateral zebrafish images, segmenting specific regions and quantifying neutrophils as inflammation markers. Alongside imaging, qPCR analysis offers gene expression insights, revealing the molecular impact of exposure on inflammatory pathways. Moreover, the deep learning model was packaged as a user-friendly executable file (.exe), facilitating widespread application by enabling use on virtually any computer without the need for specialized software or training.
Zebrafish are an ideal system to study the effect(s) of chemical, genetic, and environmental perturbations on development due to their high fecundity and fast growth. Recently, single cell sequencing has emerged as a powerful tool to measure the effect of these perturbations at a whole embryo scale. These types of experiments rely on the ability to isolate nuclei from a large number of individually barcoded zebrafish embryos in parallel. Here we report a method for efficiently isolating high-quality nuclei from zebrafish embryos in a 96-well plate format by bead homogenization in a lysis buffer. Through head-to-head sciPlex-RNA-seq experiments, we demonstrate that this method represents a substantial improvement over enzymatic dissociation and that it is compatible with a wide range of developmental stages.
In this report, we introduce a novel self-supervised learning method for extracting latent embeddings from behaviors of larval zebrafish. Drawing inspiration from Masked Modeling techniquesutilized in image processing with Masked Autoencoders (MAE) \cite{he2022masked} and in natural language processing with Generative Pre-trained Transformer (GPT) \cite{radford2018improving}, we treat behavior sequences as a blend of images and language. For the skeletal sequences of swimming zebrafish, we propose a pioneering Transformer-CNN architecture, the Sequence Spatial-Temporal Transformer (SSTFormer), designed to capture the inter-frame correlation of different joints. This correlation is particularly valuable, as it reflects the coordinated movement of various parts of the fish body across adjacent frames. To handle the high frame rate, we segment the skeleton sequence into distinct time slices, analogous to "words" in a sentence, and employ self-attention transformer layers to encode the consecutive frames within each slice, capturing the spatial correlation among different joints. Furthermore, we incorporate a CNN-based attention module to enhance the representations outputted by the tr
Collective behaviour in living systems is observed across many scales, from bacteria to insects, to fish shoals. Zebrafish have emerged as a model system amenable to laboratory study. Here we report a three-dimensional study of the collective dynamics of fifty zebrafish. We observed the emergence of collective behaviour changing between \yy{ordered} to randomised, upon \yy{adaptation} to new environmental conditions. We quantify the spatial and temporal correlation functions of the fish and identify two length scales, the persistence length and the nearest neighbour distance, that capture the essence of the behavioural changes. The ratio of the two length scales correlates robustly with the polarisation of collective motion that we explain with a reductionist model of self--propelled particles with alignment interactions.
Zebrafish have been used as a model organism in many areas of biology, including the study of pattern formation. The mean-field survival model is a coupled ODE system describing the expected evolution of chromatophores coordinating to form stripes in zebrafish. This paper presents analysis of the model focusing on parameters for the number of cells, length of distant-neighbor interactions, and rates related to birth and death of chromatophores. We derive the conditions on these parameters for a Turing bifurcation to occur and show that the model predicts patterns qualitatively similar to those in nature. In addition to answering questions about this particular model, this paper also serves as a case study for Turing analysis on coupled ODE systems. The qualitative behavior of such coupled ODE models may deviate significantly from continuum limit models. The ability to analyze such systems directly avoids this concern and allows for a more accurate description of the behavior at physically relevant scales.
Quantifying cardiovascular parameters like ejection fraction in zebrafish as a host of biological investigations has been extensively studied. Since current manual monitoring techniques are time-consuming and fallible, several image processing frameworks have been proposed to automate the process. Most of these works rely on supervised deep-learning architectures. However, supervised methods tend to be overfitted on their training dataset. This means that applying the same framework to new data with different imaging setups and mutant types can severely decrease performance. We have developed a Zebrafish Automatic Cardiovascular Assessment Framework (ZACAF) to quantify the cardiac function in zebrafish. In this work, we further applied data augmentation, Transfer Learning (TL), and Test Time Augmentation (TTA) to ZACAF to improve the performance for the quantification of cardiovascular function quantification in zebrafish. This strategy can be integrated with the available frameworks to aid other researchers. We demonstrate that using TL, even with a constrained dataset, the model can be refined to accommodate a novel microscope setup, encompassing diverse mutant types and accommod