Optoheart SIGNED

Project "Optoheart" data sheet

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 Project objective

Myocardial infarction (MI) is a key risk factor for sudden cardiac death, a leading global cause of mortality. Understanding how altered tissue architecture in MI influences cardiac electrical conduction is crucial to develop therapies which treat abnormal heart rhythms (arrhythmias) clinically. Optical measurement of transmembrane voltage in cardiac muscle is a versatile, non-invasive tool to investigate myocardial conduction. However, the current techniques of wide-field and multiphoton imaging have individual limitations restricting their ability to study key features of conduction in a 3D framework. Furthermore, optogenetics cannot be easily implemented in imaging platforms due to spectral overlap with the activation of light-gated ion channels such as channelrhodopsin. Combining all 3 techniques will provide a platform to study electrical conduction within mammalian myocardium in a 3D context and will be capable of quantifying effects introduced by tissue heterogeneity such as vasculature and scar tissue. The proposed project combines development of novel imaging technology with applied cardio-(patho)-physiology to study cardiac conduction at tissue interfaces in intact hearts with an innovative correlative approach. A new all-optical platform will be developed to simultaneously measure and stimulate cardiac activity, with the capability for real-time stimulation using custom optical patterns. Conduction will be mapped experimentally across structurally distinct regions and depths in healthy and MI hearts. This data will be correlated with underlying cytoarchitecture in the same hearts by employing tissue clearing in combination with novel light-sheet microscopy for imaging of structurally intact whole organs. This work will realise a new platform to study conduction in 3D microstructural context and deliver proof-of-concept data to address key questions concerning electrical behaviour in healthy and diseased hearts.