Simultaneous widefield voltage and interferometric dye-free optical mapping quantifies electromechanical waves in human iPSC-cardiomyocytes
Bibliographic record
Abstract
ABSTRACT Coupled electro-mechanical waves define heart’s function in health and disease. Genetic abnormalities, drug-triggered or acquired pathologies can disrupt and uncouple these waves with potentially lethal consequences. Optical mapping of electrical waves using fluorescent dyes or genetically-encoded sensors in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) offers mechanistic insights into cardiac conduction abnormalities. Interferometric dye-free/label-free wave mapping (without specific sensors) presents an alternative, likely capturing the mechanical aspects of cardiac conduction. Because of its non-invasive nature and spectral flexibility (not restricted to a specific excitation wavelength), it is an attractive chronic imaging tool in iPSC-CMs, as part of all-optical high-throughput platforms. In this study, we developed simultaneous widefield voltage and interferometric dye-free optical imaging methodology that was used: 1) to validate dye-free optical mapping for quantification of cardiac wave properties in human iPSC-CMs; 2) to demonstrate low-cost optical mapping of electromechanical waves in hiPSC-CMs using recent near-infrared (NIR) voltage sensors and orders of magnitude cheaper miniature CMOS cameras; 3) to uncover previously underexplored frequency- and space-varying parameters of cardiac electromechanical waves in hiPSC-CMs. We find similarity in the frequency-dependent responses of electrical (NIR fluorescence imaged) and mechanical (dye-free imaged) waves, with the latter being more sensitive to faster rates and showing steeper restitution and earlier appearance of wave-front tortuosity. During regular pacing, the dye-free imaged conduction velocity and the electrical wave velocity are correlated; both modalities being sensitive to pharmacological uncoupling and both dependent on gap-junctional protein (connexins) determinants of wave propagation. We uncover strong frequency-dependence of the electromechanical delay (EMD) locally and globally in hiPSC-CMs on a rigid substrate. The presented framework and results offer new means to track the functional responses of hiPSC-CM inexpensively and non-invasively for counteracting heart disease and aiding cardiotoxicity testing and drug development.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".