Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography

Pavel V. Subochev; Xosé Luís Deán-Ben; Zhenyue Chen; Maxim B. Prudnikov; Vladimir A. Vorobev; Alexey A. Kurnikov; Anna G. Orlova; Anna S. Postnikova; Alexey V. Kharitonov; Mikhail D. Proyavin; Roman I. Ovsyannikov; Anatoly G. Sanin; Mikhail Y. Kirillin; Francisco Montero de Espinosa; Ilya V. Turchin; Daniel Razansky

doi:10.1038/s41377-025-01894-y

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Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography

Original Articles

- Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography
- Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography
- LSA 2025年14卷第9期页码：2489-2502
- Affiliations：
  
  1.Institute of Applied Physics, Russian Academy of Sciences, Nizhny Novgorod, Russia
  2.Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, Zurich, Switzerland
  3.Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland
  4.Instituto de Tecnologías Físicas y de la Información—CSIC, Madrid, Spain
  5.Institute for Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany
  6.Present address: Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, China
- Author bio：
  
  Pavel V. Subochev (pavel.subochev@gmail.com)
  Daniel Razansky (daniel.razansky@uzh.ch)
- Funds：
- DOI：10.1038/s41377-025-01894-y
  中图分类号：
- 收稿日期：2024-06-16，
  
  修回日期：2025-04-15，
  
  录用日期：2025-05-16，
  
  网络出版日期：2025-07-07，
  
  纸质出版日期：2025-09-30
- Accepted：
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Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography[J]. LSA, 2025,14(9):2489-2502.

Subochev, P.V. et al. Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography. Light: Science & Applications, 14, 2489-2502 (2025).
Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography[J]. LSA, 2025,14(9):2489-2502. DOI： 10.1038/s41377-025-01894-y.

Subochev, P.V. et al. Ultrawideband high density polymer-based spherical array for real-time functional optoacoustic micro-angiography. Light: Science & Applications, 14, 2489-2502 (2025). DOI： 10.1038/s41377-025-01894-y.

摘要

Abstract

Owing to its unique ability to capture volumetric tomographic information with a single light flash

optoacoustic (OA) tomography has recently demonstrated ultrafast imaging speeds ultimately limited by the ultrasound time-of-flight. The method's scalability and the achievable spatial resolution are yet limited by the narrow bandwidth of piez

o-composite arrays currently employed for OA signal detection. Here we report on the first implementation of high-density spherical array technology based on flexible polyvinylidene difluoride films featuring ultrawideband (0.3–40 MHz) sub mm

area elements

thus enabling real-time multi-scale volumetric imaging with 22–35 µm spatial resolution

superior image fidelity and over an order of magnitude signal-to-noise enhancement compared to piezo-composite equivalents. We further demonstrate five-dimensional (spectroscopic

time-resolved

volumetric) imaging capabilities by visualizing fast stimulus-evoked cerebral oxygenation changes in mice and performing real-time functional angiography of deep human micro-vasculature. The new technology thus leverages the true potential of OA for quantitative high-resolution visualization of rapid bio-dynamics across scales.

关键词

Keywords

references

Wang, L. V. & Hu, S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335 , 1458–1462 (2012)..

Taruttis, A. & Ntziachristos, V. Advances in real-time multispectral optoacoustic imaging and its applications. Nat. Photonics 9 , 219–227 (2015)..

Beard, P. Biomedical photoacoustic imaging. Interface Focus 1 , 602–631 (2011)..

Wang, L. V. & Yao, J. J. A practical guide to photoacoustic tomographyin the life sciences. Nat. Methods 13 , 627–638 (2016)..

Deán-Ben, X. L. et al. Spiral volumetric optoacoustic tomography visualizes multi-scale dynamics in mice. Light Sci. Appl. 6 , e16247 (2017)..

Özbek, A., Deán-Ben, X. L. & Razansky, D. Optoacoustic imaging at kilohertz volumetric frame rates. Optica 5 , 857–863 (2018)..

Haltmeier, M. & Zangerl, G. Spatial resolution in photoacoustic tomography: effects of detector size and detector bandwidth. Inverse Probl. 26 , 125002 (2010)..

Yao, J. J. & Wang, L. V. Sensitivity of photoacoustic microscopy. Photoacoustics 2 , 87–101 (2014)..

Gottschalk, S. et al. Rapid volumetric optoacoustic imaging of neural dynamics across the mouse brain. Nat. Biomed. Eng. 3 , 392–401 (2019)..

Li, L. et al. Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution. Nat. Biomed. Eng. 1 , 0071 (2017)..

Rebling, J. et al. Optoacoustic characterization of broadband directivity patterns of capacitive micromachined ultrasonic transducers. J. Biomed. Opt. 22 , 041005 (2016)..

Li, Z. H., Ilkhechi, A. K. & Zemp, R. Transparent capacitive micromachined ultrasonic transducers (CMUTs) for photoacoustic applications. Opt. Express 27 , 13204–13218 (2019)..

Guggenheim, J. A. et al. Ultrasensitive plano-concave optical microresonators for ultrasound sensing. Nat. Photonics 11 , 714–719 (2017)..

Wissmeyer, G. et al. Looking at sound: optoacoustics with all-optical ultrasound detection. Light Sci. Appl. 7 , 53 (2018)..

Huynh, N. T. et al. A fast all-optical 3D photoacoustic scanner for clinical vascular imaging. Nat. Biomed. Eng . 9 , 638−655 (2024)..

Anosov, A. et al. Volumetric quantification of skin microcirculation disturbance induced by local compression. Laser Phys. Lett. 17 , 085601 (2020)..

Mishra, S. et al. Advances in piezoelectric polymer composites for energy harvesting applications: a systematic review. Macromol. Mater. Eng. 304 , 1800463 (2019)..

Kurnikov, A., Sanin, A., Ben, X. L. D., Razansky, D. & Subochev, P. Ultrawideband sub-pascal sensitivity piezopolymer detectors. Ultrasonics 141 , 107349 (2024)..

Kurnikov, A. et al. Fisheye piezo polymer detector for scanning optoacoustic angiography of experimental neoplasms. Photoacoustics 31 , 100507 (2023)..

Liu, Y. -H., Kurnikov, A., Li, W., Subochev, P. & Razansky, D. Highly sensitive miniature needle PVDF-TrFE ultrasound sensor for optoacoustic microscopy. Adv. Photonics Nexus 2 , 056006 (2023)..

Li, Q. et al. Flexible high-temperature dielectric materials from polymer nanocomposites. Nature 523 , 576–579 (2015)..

Ribeiro, C. et al. Electroactive poly (vinylidene fluoride)-based structures for advanced applications. Nat. Protoc. 13 , 681–704 (2018)..

Cox, B. T., Laufer, J. G. & Beard, P. C. The challenges for quantitative photoacoustic imaging. In Proc. SPIE 7177, Photons Plus Ultrasound: Imaging and Sensing 2009 717713 (SPIE, 2009).

Rosenthal, A., Ntziachristos, V. & Razansky, D. Acoustic inversion in optoacoustic tomography: a review. Curr. Med. Imaging 9 , 318–336 (2013)..

Orlova, A. et al. Raster-scan optoacoustic angiography of blood vessel development in colon cancer models. Photoacoustics 13 , 25–32 (2019)..

Subochev, P. et al. Raster-scan optoacoustic angiography reveals 3D microcirculatory changes during cuffed occlusion. Laser Phys. Lett. 15 , 045602 (2018)..

Wang, X. D. et al. Photoacoustic imaging with a commercial ultrasound system and a custom probe. Ultrasound Med. Biol. 37 , 484–492 (2011)..

Subochev, P. et al. Wideband linear detector arrays for optoacoustic imaging based on polyvinylidene difluoride films. J. Biomed. Opt. 23 , 091408 (2018)..

Tang, J. B. et al. Wearable 3-D photoacoustic tomography for functional brain imaging in behaving rats. Sci. Rep. 6 , 25470 (2016)..

Heijblom, M. et al. Photoacoustic image patterns of breast carcinoma and comparisons with magnetic resonance imaging and vascular stained histopathology. Sci. Rep. 5 , 11778 (2015)..

Orlova, A. et al. Noninvasive optoacoustic microangiography reveals dose and size dependency of radiation-induced deep tumor vasculature remodeling. Neoplasia 26 , 100778 (2022)..

Subochev, P. et al. Simultaneous triple-modality imaging of diffuse reflectance, optoacoustic pressure and ultrasonic scattering using an acoustic-resolution photoacoustic microscope: feasibility study. Laser Phys. Lett. 13 , 025605 (2016)..

Lin, L. et al. High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation. Nat. Commun. 12 , 882 (2021)..

Deán-Ben, X. L., López-Schier, H. & Razansky, D. Optoacoustic micro-tomography at 100 volumes per second. Sci. Rep. 7 , 6850 (2017)..

Kurnikov, A. et al. Broadband (100 kHz–100 MHz) ultrasound PVDF detectors for raster-scan optoacoustic angiography with acoustic resolution. Quantum Electron. 51 , 383 (2021)..

Perekatova, V. et al. Quantitative techniques for extraction of blood oxygenation from multispectral optoacoustic measurements. Laser Phys. Lett. 16 , 116201 (2019)..

Aguirre, J. et al. Precision assessment of label-free psoriasis biomarkers with ultra-broadband optoacoustic mesoscopy. Nat. Biomed. Eng. 1 , 0068 (2017)..

Weber, J., Beard, P. C. & Bohndiek, S. E. Contrast agents for molecular photoacoustic imaging. Nat. Methods 13 , 639–650 (2016)..

Chen, Y. S. et al. Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window. Nat. Nanotechnol. 14 , 465–472 (2019)..

Ron, A. et al. Volumetric optoacoustic imaging unveils high-resolution patterns of acute and cyclic hypoxia in a murine model of breast cancer. Cancer Res. 79 , 4767–4775 (2019)..

Bosschaart, N. et al. A literature review and novel theoretical approach on the optical properties of whole blood. Lasers Med. Sci. 29 , 453–479 (2014)..

Taylor, N. A. & Machado-Moreira, C. A. Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolyte composition in resting and exercising humans. Extrem. Physiol. Med. 2 , 4 (2013)..

Schwarz, M. et al. Optoacoustic dermoscopy of the human skin: tuning excitation energy for optimal detection bandwidth with fast and de ep imaging in vivo. IEEE Trans. Med. Imaging 36 , 1287–1296 (2017)..

Schellenberg, M. W. & Hunt, H. K. Hand-held optoacoustic imaging: a review. Photoacoustics 11 , 14–27 (2018)..

Toi, M. et al. Visualization of tumor-related blood vessels in human breast by photoacoustic imaging system with a hemispherical detector array. Sci. Rep. 7 , 41970 (2017)..

Lin, L. et al. Single-breath-hold photoacoustic computed tomography of the breast. Nat. Commun. 9 , 2352 (2018)..

Schoustra, S. M. et al. Twente photoacoustic mammoscope 2: system overview and three-dimensional vascular network images in healthy breasts. J. Biomed. Opt. 24 , 121909 (2019)..

Nagaoka, R. et al. Development of real-time 3-D photoacoustic imaging system employing spherically curved array transducer. IEEE Trans. Ultrason. Ferroelectr. Frequency Control 64 , 1223–1233 (2017)..

Deán-Ben, X. L. et al. Functional optoacoustic neuro-tomography for scalable whole-brain monitoring of calcium indicators. Light Sci. Appl. 5 , e16201 ( 2016)..

Knauer, N., Deán-Ben, X. L. & Razansky, D. Spatial compounding of volumetric data enables freehand optoacoustic angiography of large-scale vascular networks. IEEE Trans. Med. Imaging 39 , 1160–1169 (2020)..

Gottschalk, S. et al. Noninvasive real-time visualization of multiple cerebral hemodynamic parameters in whole mouse brains using five-dimensional optoacoustic tomography. J. Cereb. Blood Flow. Metab. 35 , 531–535 (2015)..

Bakker, R., Tiesinga, P. & Kötter, R. The scalable brain atlas: instant web-based access to public brain atlases and related content. Neuroinformatics 13 , 353–366 (2015)..

Ni, R. Q., Rudin, M. & Klohs, J. Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer's disease. Photoacoustics 10 , 38–47 (2018)..

Chen, Z. et al. Multi-modal noninvasive functional neurophotonic imaging of murine brain-wide sensory stimulation. Adv. Sci. 9 , 2105588 (2022)..

Shim, H. J. et al. Mouse fMRI under ketamine and xylazine anesthesia: robust contralateral somatosensory c ortex activation in response to forepaw stimulation. Neuroimage 177 , 30–44 (2018)..

Friston, K. J. et al. Statistical parametric maps in functional imaging: a general linear approach. Hum. Brain Mapp. 2 , 189–210 (1994)..

Zhang, P. F. et al. High‐resolution deep functional imaging of the whole mouse brain by photoacoustic computed tomography in vivo. J. Biophoton. 11 , e201700024 (2018)..

Upputuri, P. K. & Pramanik, M. Dynamic in vivo imaging of small animal brain using pulsed laser diode-based photoacoustic tomography system. J. Biomed. Opt. 22 , 090501 (2017)..

Liang, B. Y. et al. Impacts of the murine skull on high‐frequency transcranial photoacoustic brain imaging. J. Biophoton. 12 , e201800466 (2019)..

Estrada, H. et al. Broadband acoustic properties of a murine skull. Phys. Med. Biol. 61 , 1932–1946 (2016)..

Haltmeier, M., Kowar, R. & Nguyen, L. V. Iterative methods for photoacoustic tomography in attenuating acoustic media. Inverse Probl. 33 , 115009 (2017)..

Tian, C. et al. Spatial resolution in photoacoustic computed tomography. Rep. Prog. Phys. 84 , 036701 (2021)..

Logothetis, N. K. & Pfeuffer, J. On the nature of the BOLD fMRI contrast mechanism. Magn. Reson. Imaging 22 , 1517–1531 (2004)..

Zhao, S. Y. et al. Full activation pattern mapping by simultaneous deep brain stimulation and fMRI with graphene fiber electrodes. Nat. Commun. 11 , 1788 (2020)..

Dizeux, A. et al. Functional ultrasound imaging of the brain reveals propagation of task-related brain activity in behaving primates. Nat. Commun. 10 , 1400 (2019)..

Deffieux, T. et al. Functional ultrasound neuroimaging: a review of the preclinical and clinical state of the art. Curr. Opin. Neurobiol. 50 , 128–135 (2018)..

Mc Larney, B. et al. Monitoring of stimulus evoked murine somatosensory cortex hemodynamic activity with volumetric multi-spectral optoacoustic tomography. Front. Neurosci. 14 , 536 (2020)..

Deán-Ben, X. L., Gottschalk, S., Mc Larney, B., Shoham, S. & Razansky, D. Advanced optoacoustic methods for multiscale imaging of in vivo dynamics. Chem. Soc. Rev. 46 , 2158–2198 (2017)..

Ovsepian, S. V. et al. Visualizing cortical response to optogenetic stimulation and sensory inputs using multispectral handheld optoacoustic imaging. Photoacoustics 17 , 100153 (2020)..

Kwok, K. W., Chan, H. L. W. & Choy, C. L. Evaluation of the material parameters of piezoelectric materials by various methods. IEEE Trans. Ultrason., Ferroelectr. Frequency Control 44 , 733–742 (1997)..

Deán-Ben, X. L. & Razansky, D. Functional optoacoustic human angiography with handheld video rate three dimensional scanner. Photoacoustics 1 , 68–73 (2013)..

Needles, A. et al. Development and initial application of a fully integrated photoacoustic micro-ultrasound system. IEEE Trans. Ultrason. Ferroelectr. Frequency Control 60 , 888–897 (2013)..

Liu, S. Y. et al. Handheld photoacoustic imager for theranostics in 3D. IEEE Trans. Med. Imaging 38 , 2037–2046 (2019)..

Jaeger, M. et al. In LED-Based Photoacoustic Imaging 1st edn, Vol. 393 (Springer, 2020).

Kruger, R. A. et al. Dedicated 3D photoacoustic breast imaging. Med. Phys. 40 , 113301 (2013)..

Brecht, H. P. F. et al. Whole-body three-dimensional optoacoustic tomography system for small animals. J. Biomed. Opt. 14 , 064007 (2009)..

Yang, J. M. et al. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat. Med. 18 , 1297–1302 (2012)..

Ron, A. et al. Characterization of brown adipose tissue in a diabetic mouse model with spiral volumetric optoacoustic tomography. Mol. Imaging Biol. 21 , 620–625 (2019)..

Ivankovic, I. et al. Real-time volumetric assessment of the human carotid artery: handheld multispectral optoacoustic tomography. Radiology 291 , 45–50 (2019)..

Deán-Ben, X. L., Ozbek, A. & Razansky, D. Volumetric real-time tracking of peripheral human vasculature with GPU-accelerated three-dimensional optoacoustic tomography. IEEE Trans. Med. Imaging 32 , 2050–2055 (2013)..

Nemirova, S. et al. Scanning optoacoustic angiography for assessing structural and functional alterations in superficial vasculature of patients with post-thrombotic syndrome: a pilot study. Photoacoustics 38 , 100616 (2024)..

Deán-Ben, X. L. & Razansky, D. A practical guide for model-based reconstruction in optoacoustic imaging. Front. Phys. 10 , 1028258 (2022)..

Oruganti, T., Laufer, J. G. & Treeby, B. E. Vessel filtering of photoacoustic images. In Proc. SPIE 8581, Photons Plus Ultrasound: Imaging and Sensing 2013. 85811W (SPIE, 2013).

Jacques, S. L. Optical properties of biological tissues: a review. Phys. Med. Biol. 58 , R37–R61 (2013)..

Schweiger, M. et al. The finite element method for the propagation of light in scattering media: boundary and source conditions. Med. Phys. 22 , 1779–1792 (1995)..

Laser Institute of America. American National Standard For Safe Use Of Lasers . https://blog.ansi.org/ansi-z136-1-2022-safe-use-of-lasers/ https://blog.ansi.org/ansi-z136-1-2022-safe-use-of-lasers/ (2022)..

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