Optoacoustic imaging is a method that relies on reading out ultrasound signal generated by light. It already has the power to deliver a combination of higher penetration depth, higher resolution, and larger fields of view than other imaging technologies. However, for many research questions, optoacoustics needs tools like genetically encoded reporters and sensors. Photoswitchable label proteins can help here.

Photoswitchable label proteins can change their state upon illumination with different colors of light. The molecular mechanism acts like a tiny switch that changes the state of the protein from “on” to “off”, and with that the signal it generates. In nature, those proteins are often responsible for light dependent responses – for example of plants orienting towards the light. In Optoacoustic we use the light switchable signal to make the label blink (create a modulation) which enables the visualization of small numbers of cells against a strong background of other signals which shows a constant signal. One can imagine the effect like the blinking of a lighthouse in a stormy dark night at sea.

The ability to visualize few cells in a live organism is important because many biological phenomena, especially in the immune system, the onset of tumors or fundamental developmental biology, rely on a small number of cells.

The objectives of SWOPT are:

1. Develop a new generation of optoacoustic instrumentation, optimally implementing the photoswitching concept
2. Develop inversion algorithms that exploit the particular modulation characteristics of SWOPT to provide high resolution quantitative maps of photo-switchable contrast agent
3. Create tailored transgene photoswitching reporters and sensors as SWOPT contrast agents
4. Develop synthetic photoswitching dyes and sensors tailored to SWOPT
5. Validate SWOPT by proof-of-concept in vivo imaging of the heterogenous tumor microenvironment in renal cell carcinoma mouse models