Newswise — Optoacoustic imaging has emerged as a powerful technique for visualizing biological tissues with high resolution and contrast. In a new study published in , a team of scientists led by Jaber Malekzadeh-Najafabadi  and Vasilis Ntziachristos explored the origins and applications of nonlinear changes in optoacoustic tomography at low light fluence.

The team identified that changes in electromagnetic permittivity, induced by thermally excited third-order nonlinear susceptibility, significantly contribute to optoacoustic signal nonlinearity at low light fluences. Using theoretical models and experimental validations, the researchers demonstrated that nonlinear variations are most prominent at high-frequency optoacoustic signals and can be harnessed as a novel imaging contrast mechanism.

The findings open the door to new imaging methodologies that improve the accuracy of tissue characterization. By mapping thermally excited nonlinear susceptibility, the researchers reconstructed the first images showcasing this unique contrast in phantoms and in vivo mouse tissues. The method also displayed potential for monitoring physiological and pathological changes in organs such as the kidney and liver, offering insights into diseases linked to tissue composition changes, including obesity and metabolic disorders.

"We were fundamentally interested in better understanding the source of non-linearity observed in optoacoustic signals" says Ntziachristos. "Our findings underscore the potential of using the non-linearity of the optoacoustic signal to offer a revolutionary new contrast mechanism in optoacoustic imaging," adds Malekzadeh-Najafabadi. "While further studies are required to corroborate our postulation on the sources of non-linearity, the new method can be widely employed in basic research and clinical translation applications” adds Ntziachristos.

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Funding Information

This work was funded by the European Union under the 7th Framework Program grant agreement no 605162 (BERTI), the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 687866 (INNODERM), and the Deutsche Forschungsgemeinschaft (DFG) as part of the CRC 1123 (Z1). JR acknowledges funding from the European Commission grant agreement No 801347 (SENSITIVE), and Spanish Ministry of Economy and Competitiveness (MINECO) Grant FIS2016-77892-R. Jaya Prakash acknowledges the Alexander von Humboldt Postdoctoral Fellowship program.

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Newswise: Nonlinearity of Optoacoustic Signals and a New Contrast Mechanism for Imaging

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Caption: (a-b) Reconstructed image of absorption coefficient at (a) low and (b) high light fluence. The entire optoacoustic data (c) was generated using a modified model-based reconstruction algorithm designed to image the thermally excited third-order nonlinear susceptibility (TETONS). This algorithm processed optoacoustic signals acquired at two different light fluences, as shown in panels a and b. By analyzing the nonlinear variations in optoacoustic pressure and reconstructing the data with the modified algorithm, the image highlights differences in tissue TETONS and reveals structures within the kidney cross-section, particularly emphasizing the high-frequency components of the signal. Arrows 1 and 2 show the skin and muscle of the abdomen, respectively. Arrows 3-6 indicate structures within the kidney (Arrow 3: Capsule, Arrow 4: Cortex, Arrow 5: Medulla, and Arrow 6: Calyx). (d) Anatomical reference for the kidney structures.

Newswise: Nonlinearity of Optoacoustic Signals and a New Contrast Mechanism for Imaging

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Caption: (a) Unmixed fat images overlaid on optoacoustic anatomical images (acquired at 800 nm) for a mouse from the CTRL group, showing fat distribution across four cross-sections: liver, kidney, spleen, and shoulder. (b) Corresponding reconstructed TETONS images for the cross-sections shown in panel (a). (c) Unmixed fat images overlaid on optoacoustic anatomical images for a mouse from the HFD group. (d) Corresponding reconstructed TETONS images for the cross-sections shown in panel (c). (e) Mean intensity indicating fat in different organs in the HFD and CTRL groups. (f) Mean TETONS intensity in different organs in the HFD and CTRL groups.

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