1.Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
2.Medical Device Innovation Center, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
3.Center for 3D Organ Printing and Stem Cells, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
4.Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
5.Department of Electrical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
6.Opticho Inc., Pohang, Republic of Korea
7.Engineering Research Center for Color-modulated Extra-sensory Perception Technology, Pusan National University, Busan, Republic of Korea
8.Department of Congo-Mechatronics Engineering & Optics and Mechatronics Engineering, Pusan National University, Busan, Republic of Korea
9.Department of Medical Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
10.Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, Republic of Korea
11.Graduate School of Artificial Intelligence, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
Jinah Jang (jinahjang@postech.ac.kr)
Chulhong Kim (chulhong@postech.edu)
收稿:2025-06-17,
修回:2025-10-13,
录用:2025-11-02,
网络首发:2026-01-04,
纸质出版:2026-02-28
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Eunwoo Park, Dong Gyu Hwang, Hwanyong Choi, 等. Label-free mid-infrared dichroism-sensitive photoacoustic microscopy for histostructural analysis of engineered heart tissues[J]. Light: Science & Applications, 2026,15(2):600-610.
Park, E. et al. Label-free mid-infrared dichroism-sensitive photoacoustic microscopy for histostructural analysis of engineered heart tissues. Light: Science & Applications, 15, 600-610 (2026).
Eunwoo Park, Dong Gyu Hwang, Hwanyong Choi, 等. Label-free mid-infrared dichroism-sensitive photoacoustic microscopy for histostructural analysis of engineered heart tissues[J]. Light: Science & Applications, 2026,15(2):600-610. DOI: 10.1038/s41377-025-02117-0.
Park, E. et al. Label-free mid-infrared dichroism-sensitive photoacoustic microscopy for histostructural analysis of engineered heart tissues. Light: Science & Applications, 15, 600-610 (2026). DOI: 10.1038/s41377-025-02117-0.
Many biological tissues
such as cardiac muscle
tendons
and the cornea
exhibit highly organized microstructural alignment that is critical for mechanical and physiological functions. Disruptions in this structural organization are commonly associated with pathological conditions such as fibrosis
infarction
and cancer. However
conventional histological imaging techniques rely on immunofluorescence or histochemical staining
and they evaluate tissue alignment via non-physical 2D gradient-based calculation
which is labor-intensive
antibody-dependent
and prone to variability. Here
we demonstrate label-free mid-infrared dichroism-sensitive photoacoustic microscopy (MIR-DS-PAM)
an analytical imaging system for cardiac tissue assessments. By combining molecular specificity with polarization sensitivity
this method selectively visualizes protein-rich engineered heart tissue (EHT) and quantifies the extracellular matrix (ECM) alignment without any labeling. The extracted dichroism-sensitive parameters
such as the degree of dichroism and the orientation angle
enable histostructural evaluation of tissue integrity and reveal diagnostic cues in fibrotic EHT. This technique offers a label-free analytical tool for fibrosis research and tissue engineering applications.
Kossmann, C. E. & Huxley, H. E. The contractile structure of cardiac and skeletal muscle. Circulation 24 , 328–335 (1961)..
Benjamin, M., Kaiser, E. & Milz, S. Structure-function relationships in tendons: a review. J. Anat. 212 , 211–228 (2008)..
Holmes, D. F. et al. Corneal collagen fibril structure in three dimensions: structural insights into fibril assembly, mechanical properties, and tissue organization. Proc. Natl. Acad. Sci. USA 98 , 7307–7312 (2001)..
Hwang, D. G. et al. Bioprinting-assisted tissue assembly for structural and functional modulation of engineered heart tissue mimicking left ventricular myocardial fiber orientation. Adv. Mater. 36 , 2400364 (2024)..
Ahrens, J. H. et al. Programming cellular alignment in engineered cardiac tissue via bioprinting anisotropic organ building blocks. Adv. Mater. 34 , 2200217 (2022)..
Jerosch-Herold, M. et al. Myocardial tissue characterization in cardiac magnetic resonance studies of patients recovering from COVID-19: a meta-analysis. J. Am. Heart Assoc. 12 , e027801 (2023)..
Riching, K. M. et al. 3D collagen alignment limits protrusions to enhance breast cancer cell persistence. Biophysical J. 107 , 2546–2558 (2014)..
Maffulli, N. et al. Movin and bonar scores assess the same characteristics of tendon histology. Clin. Orthop. Relat. Res. 466 , 1605–1611 (2008)..
Bose, P. et al. Effects of geometry on the mechanics and alignment of three-dimensional engineered microtissues. ACS Biomater. Sci. Eng. 5 , 3843–3855 (2019)..
Ghosh, B. & Agarwal, K. Viewing life without labels under optical microscopes. Commun. Biol. 6 , 559 (2023)..
Park, J. et al. Clinical translation of photoacoustic imaging. Nat. Rev. Bioeng. 3 , 193–212 (2025)..
Choi, W. et al. Recent advances in contrast-enhanced photoacoustic imaging: overcoming the physical and practical challenges. Chem. Rev. 123 , 7379–7419 (2023)..
Park, E. et al. A comprehensive review of high-performance photoacoustic microscopy systems. Photoacoustics 44 , 100739 (2025)..
Park, B. et al. Functional photoacoustic imaging: from nano-and micro-to macro-scale. Nano Convergence 10 , 29 (2023)..
Ahn, J. et al. In vivo photoacoustic monitoring of vasoconstriction induced by acute hyperglycemia. Photoacoustics 30 , 100485 (2023)..
Kim, J. et al. Enhanced dual-mode imaging: Superior photoacoustic and ultrasound endoscopy in live pigs using a transparent ultrasound transducer. Sci. Adv. 10 , eadq9960 (2024)..
Kim, D. et al. In vivo quantitative photoacoustic monitoring of corticosteroid-induced vasoconstriction. J. Biomed. Opt. 28 , 082805 (2023)..
Lee, H. et al. Nanosecond SRS fiber amplifier for label-free near-infrared photoacoustic microscopy of lipids. Photoacoustics 25 , 100331 (2022)..
Park, E. et al. Effective photoacoustic absorption spectrum for collagen-based tissue imaging. J. Biomed. Opt. 25 , 056002 (2020)..
Kim, D. et al. An ultraviolet-transparent ultrasound transducer enables high-resolution label-free photoacoustic histopathology. Laser Photonics Rev. 18 , 2300652 (2024)..
Yoon, C. et al. Deep learning-based virtual staining, segmentation, and classification in label-free photoacoustic histology of human specimens. Light Sci. Appl. 13 , 226 (2024)..
Visscher, M. et al. Label-free analytic histology of carotid atherosclerosis by mid-infrared optoacoustic microscopy. Photoacoustics 26 , 100354 (2022)..
Pleitez, M. A. et al. Label-free metabolic imaging by mid-infrared optoacoustic microscopy in living cells. Nat. Biotechnol. 38 , 293–296 (2020)..
Shi, J. H. et al. High-resolution, high-contrast mid-infrared imaging of fresh biological samples with ultraviolet-localized photoacoustic microscopy. Nat. Photonics 13 , 609–615 (2019)..
Park, E. et al. Unsupervised inter-domain transformation for virtually stained high-resolution mid-infrared photoacoustic microscopy using explainable deep learning. Nat. Commun. 15 , 10892 (2024)..
Hu, S. et al. Dichroism optical-resolution photoacoustic microscopy. Proceedings of SPIE 8223, Photons Plus Ultrasound: Imaging and Sensing 2012. San Francisco, California, United States: SPIE, 2012, 82233T.
Zhou, Y. Y. et al. Single-shot linear dichroism optical-resolution photoacoustic microscopy. Photoacoustics 16 , 100148 (2019)..
Zhang, Z. H. et al. Polarized photoacoustic microscopy for vectorial-absorption-based anisotropy detection. Opt. Lett. 43 , 5267–5270 (2018)..
de Boer, J. F., Hitzenberger, C. K. & Yasuno, Y. Polarization sensitive optical coherence tomography–a review [Invited ] . Biomed. Opt. Express 8 , 1838–1873 (2017)..
Villiger, M. et al. Optic axis mapping with catheter-based polarization-sensitive optical coherence tomography. Optica 5 , 1329–1337 (2018)..
Chang, S. et al. Birefringent tissue-mimicking phantom for polarization-sensitive optical coherence tomography imaging. J. Biomed. Opt. 27 , 074711 (2022)..
Zoumi, A., Yeh, A. & Tromberg, B. J. Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence. Proc. Natl. Acad. Sci. USA 99 , 11014–11019 (2022)..
James, D. S. & Campagnola, P. J. Recent advancements in optical harmonic generation microscopy: applications and perspectives. BME Front. 2021 , 3973857 (2021)..
Aghigh, A. et al. Second harmonic generation microscopy: a powerful tool for bio-imaging. Biophysical Rev. 15 , 43–70 (2023)..
Park, E. et al. Azimuth mapping of fibrous tissue in linear dichroism-sensitive photoacoustic microscopy. Photoacoustics 31 , 100510 (2023)..
Wang, T. et al. Polarized photoacoustic microscopy based on high-order harmonics for anisotropy detection. Ann. Transl. Med. 10 , 293 (2022)..
Zhang, Z. H. et al. Collagen fiber anisotropy characterization by polarized photoacoustic imaging for just-in-time quantitative evaluation of burn severity. Photonics Res. 11 , 817–828 (2023)..
Qiu, Y. et al. Collagen fibers quantification for liver fibrosis assessment using linear dichroism photoacoustic microscopy. Photoacoustics 42 , 100694 (2025)..
Kular, J. K., Basu, S. & Sharma, R. I. The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering. J. Tissue Eng. 5 , 2041731414557112 (2014)..
Ariga, R. et al. Identification of myoca rdial disarray in patients with hypertrophic cardiomyopathy and ventricular arrhythmias. J. Am. Coll. Cardiol. 73 , 2493–2502 (2019)..
Kuzmanov, U. et al. Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources. Nat. Biomed. Eng. 4 , 889–900 (2020)..
Wang, E. Y. et al. Biowire model of interstitial and focal cardiac fibrosis. ACS Cent. Sci. 5 , 1146–1158 (2019)..
Daly, A. C., Davidson, M. D. & Burdick, J. A. 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels. Nat. Commun. 12 , 753 (2021)..
Sadeghi, A. H. et al. Engineered 3D cardiac fibrotic tissue to study fibrotic remodeling. Adv. Healthc. Mater. 6 , 1601434 (2017)..
Mastikhina, O. et al. Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing. Biomaterials 233 , 119741 (2020)..
Min, S. et al. Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications. Nat. Commun. 15 , 2564 (2024)..
Lee, M. O. et al. Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells. J. Biol. Eng. 13 , 15 (2019)..
Iseoka, H. et al. Cardiac fibrosis models using human induced pluripotent stem cell-derived cardiac tissues allow anti-fibrotic drug screening in vitro. Stem Cell Res. 54 , 102420 (2021)..
Hwang, D. G. et al. Bioprinting-assisted tissue assembly to investigate endothelial cell contributions in cardiac fibrosis and focal fibrosis modeling. Adv. NanoBiomed Res. 5 , 2400148 (2025)..
Fu, P. C. et al. Breaking the diffraction limit in molecular imaging by structured illumination mid-infrared photothermal microscopy. Adv. Photonics 7 , 036003 (2025)..
Tamamitsu, M. et al. Mid-infrared wide-field nanoscopy. Nat. Photonics 18 , 738–743 (2024)..
Cao, R. et al. Optical-resolution photoacoustic microscopy with a needle-shaped beam. Nat. Photonics 17 , 89–95 (2023)..
Barulin, A. et al. Axially multifocal metalens for 3D volumetric photoacoustic imaging of neuromelanin in live brain organoid. Sci. Adv. 11 , eadr0654 (2025)..
Choi, S. et al. Advancements in photoacoustic detection techniques for biomedical imaging. npj Acoust. 1 , 1 (2025)..
Cho, S. et al. An ultrasensitive and broadband transparent ultrasound transducer for ultrasound and photoacoustic imaging in-vivo. Nat. Commun. 15 , 1444 (2024)..
Kim, H. et al. Nonlinear beamforming for intracardiac echocardiography: a comparative study. Biomed. Eng. Lett. 14 , 571–582 (2024)..
Ko, V. et al. Fast histological assessment of adipose tissue inflammation by label-free mid-infrared optoacoustic microscopy. npj Imaging 1 , 3 (2023)..
Koziol, P. et al. Macromolecular orientation in biological tissues using a four-polarization method in FT-IR imaging. Anal. Chem. 92 , 13313–13318 (2020)..
Yoon, C. et al. Label-free optical microscopy with artificial intelligence: a new paradigm in pathology. Biophotonics Discov. 2 , 020901 (2025)..
Sun, Y. et al. Synthetic polarization-sensitive optical coherence tomography by deep learning. npj Digital Med. 4 , 105 (2021)..
Le, T. D. et al. Synthetic polarization-sensitive optical coherence tomography using contrastive unpaired translation. Sci. Rep. 14 , 31366 (2024)..
Zha, L. B. et al. 3D bioprinting and label-free imaging: Bridging innovations for organoid research. Int. J. Bioprinting 11 , 55–78 (2025)..
Oh, D. et al. Photoacoustic imaging for three-dimensional bioprinted constructs. Int. J. Bioprinting 10 , 3448 (2024)..
Lee, Y. J. et al. Quantification method to objectively evaluate the fibrous structural status of tendons based on polarization-sensitive OCT. J. Biophotonics 15 , e202200065 (2022)..
Tang, P. J. et al. Polarization sensitive optical coherence tomography with single input for imaging depth-resolved collagen organiza tions. Light Sci. Appl. 10 , 237 (2021)..
Raoux, C. et al. Unveiling the lamellar structure of the human cornea over its full thickness using polarization-resolved SHG microscopy. Light Sci. Appl. 12 , 190 (2023)..
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