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Model-based temporal unmixing towards quantitative photo-switching optoacoustic tomography
Optics Express
|August 13, 2025
Summary
This study introduces a new computational method for optoacoustic imaging, improving the ability to distinguish multiple cell types in live tissues. The advanced technique enhances imaging sensitivity and accuracy for preclinical research.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Preclinical Research
Background:
- Optoacoustic (OA) imaging with photoswitchable proteins offers high-sensitivity, multiplexed imaging in live tissues.
- Existing methods face challenges in accurately unmixing signals from multiple reporter species and background noise.
Purpose of the Study:
- To develop a model-based variational framework for computationally unmixing and imaging photo-switching reporters using optoacoustic tomography.
- To improve the robustness and unmixing quality of optoacoustic imaging for complex biological samples.
Main Methods:
- A detailed mathematical model of the photo-switching mechanism, incorporating kinetic constants and light fluence.
- An iterative image-based inversion algorithm utilizing ℓ1 and total-variation regularization.
- Application to controlled phantoms and in vivo mice experiments.
Main Results:
- Successful disentanglement of multiple, spatially overlapping fluorescent labels.
- Recovery of continuous quantitative maps for different reporter species.
- Demonstrated robustness to noise and improved unmixing accuracy.
Conclusions:
- The proposed framework provides a powerful computational tool for advanced optoacoustic imaging.
- This method enables more precise multiplexed imaging of cells in preclinical research.
- The approach enhances the utility of photoswitchable proteins for in vivo molecular imaging.

