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Principal Investigator: Liang Gao
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $495,587
Funding agency: National Heart Lung and Blood Institute
Project Summary: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia, and it is a major risk factor for
ischemic stroke and provokes morbidity and mortality along with a significant economic burden. Although AF has
been studied in various animals, the embryonic zebrafish has been the genetically tractable and optically
transparent model to investigate electromechanical coupling during cardiac development. Like in humans, the
action potential and the consequent myocardial contraction are also key indicators of cardiac function in the
zebrafish. By virtual of its transparency, optical mapping has been a primary means to investigate the interplay
between cardiac action potential and myocardial contraction to study the mechanisms of AF.
Dysregulation of electrical and mechanical coupling is a significant factor underlying the pathogenesis and
perpetuation of AF. Optical mapping of electromechanical decoupling in zebrafish is nontrivial because it requires
simultaneous recording of fast propagating voltage waves and myocardial contraction. Particularly in a beating
heart, the rapid myocardial contraction can easily blur the image—the motion artifacts superimpose the wave
patterns appearing in the optical maps and can prohibit further analysis of the imaging data. Pharmacological
uncoupling has been widely used to suppress heart motion. However, this makes studying electromechanical
coupling impossible. Alternatively, post-acquisition synchronization approach records a z-stack of movies, each
covering at least one cardiac cycle. After the recording is completed, one 3D cardiac cycle can be reconstructed
by synchronizing the movies in time. Nonetheless, this method is inapplicable to nonperiodic movements, such
as irregular heartbeats with AF. Therefore, there is an unmet need to develop innovative optical techniques for
high-speed 3D mapping of electromechanical coupling in a rapidly and irregularly beating AF heart.
To solve this problem, we propose to develop a light-sheet light-field tomography (light-sheet LIFT) technique
for kilohertz 3D imaging of electromechanical coupling in zebrafish hearts undergoing AF. Our method has only
recently become possible due to two emerging technologies, light-field tomography (LIFT) and light-sheet
microscopy, both of which we have extensive experience with. We will integrate LIFT with light-sheet microscopy
and enable high-resolution 3D imaging with an unprecedented volumetric frame rate. The resultant system, light-
sheet LIFT, will provide enough spatiotemporal resolution to fully depict the interplay between voltage waves,
myocardial contraction, and intracardiac blood flow in a pitx2c zebrafish arrhythmia model. We expect our
method will advance the understanding of AF's fundamental mechanism from the electrical activities at a single-
cell level.
Terms: <2-dimensional><3-D><3-D Imaging><3-Dimensional><3D><3D imaging><AF9><Action Potentials><Address><Algorithms><Animals><Arrhythmia><Artifacts><Atrial><Atrial Fibrillation><Auricular Fibrillation><Blood flow><Brachydanio rerio><CAT scan><CT X Ray><CT Xray><CT imaging><CT scan><Calcium><Cardiac><Cardiac Arrhythmia><Cardiac Atrium><Cardiac development><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Clinical><Color><Columbidae><Computed Tomography><Contracting Opportunities><Contracts><Coupling><Danio rerio><Data Analyses><Data Analysis><Doves><Dysfunction><Economic Burden><Embryo><Embryonic><Emergent Technologies><Emerging Technologies><Faculty><Fluorescence><Fluorescence Light Microscopy><Fluorescence Microscopy><Functional disorder><Goals><Heart><Heart Arrhythmias><Heart Atrium><Heart Vascular><Human><Image><Intracellular Communication and Signaling><Investigators><Ischemic Stroke><Knowledge><Light><MLLT3><MLLT3 gene><Maps><Mechanics><Mediating><Medicine><Membrane><Methods><Microscope><Microscopy><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Morphologic artifacts><Motion><Movement><Myocardial><Myocardial Contraction><Myocardium><Optics><Palpitations><Palsy><Paralysed><Pathogenesis><Pattern><Performance><Phenotype><Photoradiation><Physiopathology><Pigeons><Plegia><Process><Property><Records><Reproduction><Research><Research Personnel><Researchers><Resolution><Risk Factors><Rotation><Sampling><Scanning><Signal Transduction><Signal Transduction Systems><Signaling><Speed><System><Techniques><Testing><Three-Dimensional Imaging><Time><Tomodensitometry><Ventricular><Visualization><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><Zebra Danio><Zebra Fish><Zebrafish><atrium><biological signal transduction><body movement><cardiac function><cardiac motion><cardiac muscle><cardiogenesis><catscan><circulatory system><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><data interpretation><experience><fluorophore><function of the heart><heart contraction><heart development><heart formation><heart function><heart motion><heart muscle><hemodynamics><imaging><innovate><innovation><innovative><interest><lens><lenses><mechanic><mechanical><membrane structure><mortality><movie><multiplexed imaging><non-contrast CT><noncontrast CT><noncontrast computed tomography><optic imaging><optical><optical imaging><paralysis><paralytic><pathophysiology><pharmacologic><reconstruction><resolutions><spatiotemporal><spectral image><spectral imagery><spectrograph><spectrum image><spectrum imagery><temporal measurement><temporal resolution><three dimensional><time measurement><tomography><two-dimensional><virtual><voltage>