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Animal Models

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Selected Grantee Publications

Characterizing a Photoacoustic and Fluorescence Imaging Platform for Preclinical Murine Longitudinal Studies

Thompson et al., Journal of Biomedical Optics . 2023.

https://pubmed.ncbi.nlm.nih.gov/36895414/

Preclinical studies using animal models require medical imaging technology with sufficient resolution and sensitivity for anatomical, functional, and molecular assessments. Photoacoustic (PA) tomography provides high resolution and specificity, and fluorescence (FL) molecular tomography provides high sensitivity; the combination of these imaging modalities capitalizes on their strengths and mitigates disadvantages. In this publication, the authors describe TriTom, a preclinical imaging system that integrates PA and FL. They characterized the PA spatial resolution, PA sensitivity, PA spectral accuracy, optical spatial resolution, and FL sensitivity of the platform and demonstrated anatomical imaging in mice. This report demonstrates TriTom’s suitability for biomedical imaging applications. Supported by ORIP (R43OD023029) and NCI.

Gigapixel Imaging With a Novel Multi-Camera Array Microscope

Thomson et al., eLife. 2022.

https://www.doi.org/10.7554/eLife.74988

The dynamics of living organisms are organized across many spatial scales. The investigators created assembled a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution, large field-of-view recording from multiple spatial scales simultaneously, ranging from structures that approach the cellular scale to large-group behavioral dynamics. By collecting data from up to 96 cameras, they computationally generated gigapixel-scale images and movies with a field of view over hundreds of square centimeters at an optical resolution of 18 µm. This system allows the team to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales (e.g., larval zebrafish, fruit flies, slime mold). Overall, by removing the bottlenecks imposed by single-camera image acquisition systems, the MCAM provides a powerful platform for investigating detailed biological features and behavioral processes of small model organisms. Supported by ORIP (R44OD024879), NIEHS, NCI, and NIBIB.

A Novel Wireless ECG System for Prolonged Monitoring of Multiple Zebrafish for Heart Disease and Drug Screening Studies

Le et al., Biosensors and Bioelectronics. 2022.

https://pubmed.ncbi.nlm.nih.gov/34801796/

Zebrafish and their mutant lines have been extensively used in cardiovascular studies. In the current study, the novel system Zebra II is presented for prolonged electrocardiogram (ECG) acquisition and analysis for multiple zebrafish within controllable working environments. The Zebra II is composed of a perfusion system, apparatuses, sensors, and an in-house electronic system. First, the Zebra II is validated in comparison with a benchmark system, namely iWORX, through various experiments. The validation displayed comparable results in terms of data quality and ECG changes in response to drug treatment. The effects of anesthetic drugs and temperature variation on zebrafish ECG were subsequently investigated in experiments that need real-time data assessment. The Zebra II's capability of continuous anesthetic administration enabled prolonged ECG acquisition up to 1 h compared to that of 5 min in existing systems. The novel cloud-based automated analysis with data obtained from four fish further provided a useful solution for combinatorial experiments and helped save significant time and effort. The system showed robust ECG acquisition and analytics for various applications, including arrhythmia in sodium-induced sinus arrest, temperature-induced heart rate variation, and drug-induced arrhythmia in Tg(SCN5A-D1275N) mutant and wildtype fish. The multiple channel acquisition also enabled the implementation of randomized controlled trials on zebrafish models. The developed ECG system holds promise and solves current drawbacks in order to greatly accelerate drug screening applications and other cardiovascular studies using zebrafish. Supported by ORIP (R44OD024874) and NHLBI.

Functional and Ultrastructural Analysis of Reafferent Mechanosensation in Larval Zebrafish

Odstrcil et al., Current Biology. 2022.

https://www.sciencedirect.com/science/article/pii/S096098222101530X

All animals need to differentiate between exafferent stimuli (caused by the environment) and reafferent stimuli (caused by their own movement). Researchers characterized how hair cells in zebrafish larvae discriminate between reafferent and exafferent signals. Dye labeling of the lateral line nerve and functional imaging was combined with ultra-structural electron microscopy circuit reconstruction to show that cholinergic signals originating from the hindbrain transmit efference copies, and dopaminergic signals from the hypothalamus may affect threshold modulation. Findings suggest that this circuit is the core implementation of mechanosensory reafferent suppression in these young animals. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.