Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging

Abstract Optoacoustic signals behave nonlinearly at light fluences above a few mJ/cm2, which may affect the interpretation and quantification of measurements. It has been proposed that optoacoustic nonlinearity arises from the heat-induced formation of nanobubbles or changes in local thermo-physical...

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Main Authors: Jaber Malekzadeh-Najafabadi, Jaya Prakash, Daniel Razansky, Jorge Ripoll, Vipul Gujrati, Vasilis Ntziachristos
Format: Article
Language:English
Published: Nature Publishing Group 2025-03-01
Series:Light: Science & Applications
Online Access:https://doi.org/10.1038/s41377-025-01772-7
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author Jaber Malekzadeh-Najafabadi
Jaya Prakash
Daniel Razansky
Jorge Ripoll
Vipul Gujrati
Vasilis Ntziachristos
author_facet Jaber Malekzadeh-Najafabadi
Jaya Prakash
Daniel Razansky
Jorge Ripoll
Vipul Gujrati
Vasilis Ntziachristos
author_sort Jaber Malekzadeh-Najafabadi
collection DOAJ
description Abstract Optoacoustic signals behave nonlinearly at light fluences above a few mJ/cm2, which may affect the interpretation and quantification of measurements. It has been proposed that optoacoustic nonlinearity arises from the heat-induced formation of nanobubbles or changes in local thermo-physical parameters. However, such explanations are only valid at much higher fluences than typically used in biomedical optoacoustic imaging (> 20 mJ/cm2) or in the presence of materials with high absorption coefficients such as gold nanoparticles. We propose herein that electromagnetic permittivity changes in response to photon absorption are major source of optoacoustic signal nonlinearity at low fluences. We provide theoretical and experimental evidence that supports this postulation and show that optoacoustic pressure responses due to permittivity changes, which are function of thermally excited third-order nonlinear susceptibility, can explain the nonlinear behavior of the optoacoustic signal. Since different materials exhibit different thermally excited third-order nonlinear susceptibility, this property could function as a new contrast mechanism that can identify the sensitivity of a substance’s dielectric constant to photon-induced temperature changes. Consequently, we propose an imaging method based on nonlinear optoacoustic signals that exploits this newly identified contrast mechanism. These findings may have far-reaching implications for improving the accuracy of optoacoustics and utilizing the proposed new contrast mechanism would advance our understanding of cellular and tissue functionality.
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spelling doaj-art-2fd0bc1b2197420893b8ecda2a651f632025-08-20T02:10:23ZengNature Publishing GroupLight: Science & Applications2047-75382025-03-0114111310.1038/s41377-025-01772-7Nonlinearity of optoacoustic signals and a new contrast mechanism for imagingJaber Malekzadeh-Najafabadi0Jaya Prakash1Daniel Razansky2Jorge Ripoll3Vipul Gujrati4Vasilis Ntziachristos5Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of MunichChair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of MunichInstitute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of ZurichDepartment of Bioengineering and Aerospace Engineering, Universidad Carlos III de MadridChair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of MunichChair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of MunichAbstract Optoacoustic signals behave nonlinearly at light fluences above a few mJ/cm2, which may affect the interpretation and quantification of measurements. It has been proposed that optoacoustic nonlinearity arises from the heat-induced formation of nanobubbles or changes in local thermo-physical parameters. However, such explanations are only valid at much higher fluences than typically used in biomedical optoacoustic imaging (> 20 mJ/cm2) or in the presence of materials with high absorption coefficients such as gold nanoparticles. We propose herein that electromagnetic permittivity changes in response to photon absorption are major source of optoacoustic signal nonlinearity at low fluences. We provide theoretical and experimental evidence that supports this postulation and show that optoacoustic pressure responses due to permittivity changes, which are function of thermally excited third-order nonlinear susceptibility, can explain the nonlinear behavior of the optoacoustic signal. Since different materials exhibit different thermally excited third-order nonlinear susceptibility, this property could function as a new contrast mechanism that can identify the sensitivity of a substance’s dielectric constant to photon-induced temperature changes. Consequently, we propose an imaging method based on nonlinear optoacoustic signals that exploits this newly identified contrast mechanism. These findings may have far-reaching implications for improving the accuracy of optoacoustics and utilizing the proposed new contrast mechanism would advance our understanding of cellular and tissue functionality.https://doi.org/10.1038/s41377-025-01772-7
spellingShingle Jaber Malekzadeh-Najafabadi
Jaya Prakash
Daniel Razansky
Jorge Ripoll
Vipul Gujrati
Vasilis Ntziachristos
Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
Light: Science & Applications
title Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
title_full Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
title_fullStr Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
title_full_unstemmed Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
title_short Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
title_sort nonlinearity of optoacoustic signals and a new contrast mechanism for imaging
url https://doi.org/10.1038/s41377-025-01772-7
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