Observing melanomas in 3D using a low-cost photoacoustic microscope

Photoacoustic imaging, also known as optoacoustic, is an emerging molecular biomedical imaging technique that allows three-dimensional images to be formed of the interior of a living organism, in a non-invasive and painless way and without the use of ionizing radiation, through illumination with pulses of light. short lasers combined with the detection of ultrasound waves that are generated by the absorption of this light in the molecules inside.

Thus, using this technique, the observation of certain substances specific to the organism or endogenous chromophores can be selected, such as hemoglobin, melanin, lipids or collagen, among others, by choosing the wavelength or color of the laser at which these molecules have a greater contrast of light absorption with respect to the surrounding tissue.

Additionally, this imaging technique can benefit from contrast agents or exogenous chromophores to improve images at greater depth. To do this, fluorophores or nanoparticles linked to molecules of the organism, such as proteins or antibodies, are used to obtain more specific images of areas of the tissue where there is a higher concentration of these molecules, and also functional images, visualizing the evolution of the different biological processes.

Researchers from the Institute of Instrumentation for Molecular Imaging (I3M), a joint center of the Higher Council for Scientific Research (CSIC) and the Polytechnic University of Valencia (UPV), all of these entities in Spain, have obtained the first three-dimensional images of a melanoma in mice in vivo with a low-cost photoacoustic microscope.

The prototype has been built by this team of scientists with the aim of obtaining images of melanomas at depths of several millimeters under the skin and at high resolution (between 50 and 75 microns). This microscope can help in the early diagnosis of dermatological diseases such as melanoma, the type of skin cancer with the worst prognosis due to its high probability of metastasis, through the bloodstream or lymphatic system.

The prototype has been created from a very low-cost microscope design, with a patent granted in early 2024, which allows the use of pulsed laser diodes (PLD) of infrared light (wavelength of 905 nanometers), as a source compact and efficient semiconductor laser, instead of lasers based on solid-state crystals, bulky and cost much higher than PLDs, which are commonly used in similar photoacoustic microscopes.

The project has been developed by the team led by Juan José García Garrigós, CSIC researcher at the Ultrasound Laboratory (UMIL) of the I3M. This group, co-directed by I3M researcher Alejandro Cebrecos, is a pioneer in Spain in the research and development of photoacoustic imaging. In addition, Professor Francisco Marco Jiménez, from the Institute of Animal Science and Technology (ICTA), of the Polytechnic University of Valencia, has collaborated in the tests, and the Institute of Biomechanics of Valencia (IBV) has participated in the design of the prototype.

It is worth highlighting the participation of Javier Navarro Calvo, who is developing his doctoral thesis on this technology at the I3M, and who recently received the Andrés Lara Award for Young Researchers at the Tecniacústica 2024 congress, held in the city of Faro (Portugal).

Tests in mice

Last July, the I3M team carried out several in vivo imaging tests on mice with this prototype photoacoustic microscope, thanks to which, for the first time, images of melanoma in mice were obtained with this low-cost technology based in pulsed laser diode. According to García Garrigós, “this technique allows us to obtain volumetric images of the tissue relatively quickly, that is, in a few minutes for approximately one cubic millimeter. All this through its laser scanning design with mirrors. Furthermore, the fidelity of the depth image is achieved thanks to the development of new processing algorithms, based on the compensation of the response to spatial impulse, pending publication in specialized academic journals.”

The I3M has obtained the first 3D images of melanoma in mice with a low-cost photoacoustic microscope. (Images: I3M / CSIC / UPV)

Currently, the I3M scientist points out, “work is being done to evolve the prototype, with a more portable design clearly aimed at facilitating its clinical practice, in addition to adding another laser source with visible wavelength, turning it into a dual photoacoustic microscope with which, in addition to the melanomas, the surrounding vascular networks will be observed with much greater sensitivity than in the current prototype, which, for example, would allow us to see possible angiogenesis associated with tumor evolution, thus improving the precision of the diagnosis. (Source: Polytechnic University of Valencia)