Research progress of photoacoustic imaging in diagnosis of limb lymphedema_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

SHEN Yijun ¹ , PAN Jiadong ² ,  WANG Xin ^1,2

1. School of Medicine, Ningbo University, Ningbo Zhejiang, 315211, P. R. China;
2. Department of Hand and Microsurgical Reconstruction, Ningbo Sixth Hospital, Ningbo Zhejiang, 315042, P. R. China;

Corresponding?author：

WANG Xin, Email: dr.wangxin@hotmail.com

Keywords：

Photoacoustic imaging; lymphedema; multimodal imaging; nanoprobes

DOI：

10.7507/1002-1892.202511035

Video：

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Objective To summarize recent advances in photoacoustic imaging (PAI) for the diagnosis of limb lymphedema. Methods Relevant domestic and international studies on PAI were reviewed to systematically summarize its imaging principles, technological development, applications in the diagnosis of limb lymphedema, and recent advances in related technologies. Results PAI combines the high contrast of optical imaging with the favorable tissue penetration of ultrasound. It has evolved from high-resolution microscopic imaging to large-field tomographic imaging, portable imaging, and molecularly targeted imaging, thereby establishing a technical foundation for the clinical translation of lymphatic imaging. Current studies have shown that PAI can visualize lymphatic vessels, accompanying veins, and dermal backflow, while also providing functional information to a certain extent. It therefore shows promising potential in the early diagnosis, preoperative localization, intraoperative assessment, postoperative follow-up, and staging of limb lymphedema. Furthermore, advances in related integrative and innovative technologies have further expanded the value of PAI in the diagnosis of lymphedema. Conclusion PAI provides a promising approach for precise diagnosis and perioperative management of limb lymphedema. However, large-scale prospective studies and standardized imaging protocols are required to validate its long-term clinical value.

Citation： SHEN Yijun, PAN Jiadong, WANG Xin. Research progress of photoacoustic imaging in diagnosis of limb lymphedema. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(6): 984-989. doi: 10.7507/1002-1892.202511035 Copy

1.	Azhar SH, Lim HY, Tan BK, et al. The unresolved pathophysiology of lymphedema. Front Physiol, 2020, 11: 137. doi: 10.3389/fphys.2020.00137.
2.	Oliver G, Kipnis J, Randolph GJ, et al. The lymphatic vasculature in the 21st century: novel functional roles in homeostasis and disease. Cell, 2020, 182(2): 270-296.
3.	Rockson SG, Rivera KK. Estimating the population burden of lymphedema. Ann N Y Acad Sci, 2008, 1131: 147-154.
4.	DiSipio T, Rye S, Newman B, et al. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol, 2013, 14(6): 500-515.
5.	Tian W, Rockson SG, Jiang X, et al. Leukotriene B4 antagonism ameliorates experimental lymphedema. Sci Transl Med, 2017, 9(389): eaal3920. doi: 10.1126/scitranslmed.aal3920.
6.	Brahma B, Yamamoto T. Breast cancer treatment-related lymphedema (BCRL): An overview of the literature and updates in microsurgery reconstructions. Eur J Surg Oncol, 2019, 45(7): 1138-1145.
7.	Aron A, Zavaleta C. Current and developing lymphatic imaging approaches for elucidation of functional mechanisms and disease progression. Mol Imaging Biol, 2024, 26(1): 1-16.
8.	Szuba A, Shin WS, Strauss HW, et al. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med, 2003, 44(1): 43-57.
9.	van Heumen S, Riksen JJM, Bramer WM, et al. Imaging of the lymphatic vessels for surgical planning: a systematic review. Ann Surg Oncol, 2023, 30(1): 462-479.
10.	Forte AJ, Huayllani MT, Boczar D, et al. Ultrasound elastography use in lower extremity lymphedema: a systematic review of the literature. Cureus, 2019, 11(9): e5578. doi: 10.7759/cureus.5578.
11.	Salehi BP, Sibley RC, Friedman R, et al. MRI of lymphedema. J Magn Reson Imaging, 2023, 57(4): 977-991.
12.	Guo J, Shen WB, Xin JF, et al. Evaluation of CT imaging in secondary lower extremity lymphedema: a prospective study. CT Theory and Applications, 2022, 31(2): 237-243.
13.	Nagy BI, Mohos B, Tzou CJ. Imaging Modalities for Evaluating Lymphedema. Medicina (Kaunas), 2023, 59(11): 2016. doi: 10.3390/medicina59112016.
14.	Van Heumen S, Riksen JJM, Singh MKA, et al. LED-based photoacoustic imaging for preoperative visualization of lymphatic vessels in patients with secondary limb lymphedema. Photoacoustics, 2022, 29: 100446. doi: 10.1016/j.pacs.2022.100446.
15.	Watanabe S, Kajita H, Suzuki Y, et al. Photoacoustic lymphangiography is a possible alternative for lymphedema staging. J Vasc Surg Venous Lymphat Disord, 2022, 10(6): 1318-1324.
16.	Kajita H, Oh A, Urano M, et al. Photoacoustic lymphangiography. J Surg Oncol, 2020, 121: 48-50.
17.	Lediju Bell MA. Photoacoustic imaging for surgical guidance: Principles, applications, and outlook. J Appl Phys, 2020, 128(6): 060904. doi: 10.1063/5.0018190.
18.	Lin L, Wang LV. Photoacoustic imaging//Optical imaging in human disease and biological research. Singapore : Springer, 2021: 147-175.
19.	Bell AG. Upon the production and reproduction of sound by light. J Soc Telegraph Eng, 1880, 9(34): 404-426.
20.	Yao JJ, Wang LV. Photoacoustic microscopy. Laser & Photonics Reviews, 2013, 7(5): 758-778.
21.	Maslov K, Zhang HF, Hu S, et al. Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries. Opt Lett, 2008, 33(9): 929-931.
22.	Zhang HF, Maslov K, Stoica G, et al. Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging. Nat Biotechnol, 2006, 24(7): 848-851.
23.	Kruger RA, Liu P, Fang YR, et al. Photoacoustic ultrasound (PAUS)—reconstruction tomography. Med Phys, 1995, 22(10): 1605-1609.
24.	Yao J, Maslov KI, Zhang Y, et al. Label-free oxygen-metabolic photoacoustic microscopy in vivo. J Biomed Opt, 2011, 16(7): 076003. doi: 10.1117/1.3594786.
25.	Yao J, Wang L, Yang JM, et al. High-speed label-free functional photoacoustic microscopy of mouse brain in action. Nat Methods, 2015, 12(5): 407-410.
26.	Forbrich A, Heinmiller A, Zemp RJ. Photoacoustic imaging of lymphatic pumping. J Biomed Opt, 2017, 22(10): 1-6.
27.	Suzuki Y, Kajita H, Imanishi N, et al. Observation of a lymphatic pump in a human by using photoacoustic imaging. Plast Reconstr Surg Glob Open, 2020, 8(6): e2914. doi: 10.1097/GOX.0000000000002914.
28.	Suzuki Y, Kajita H, Oh A, et al. Visualising lymphatic flow dynamics during complex physical therapy: A photoacoustic imaging study. JPRAS Open, 2025, 44: 348-353.
29.	Onoda S, Satake T, Hamada E. Super-microsurgery technique for lymphaticovenular anastomosis. J Vasc Surg Venous Lymphat Disord, 2023, 11(1): 177-181.
30.	何挺, 王澤文, 張濤, 等. 外科技術治療肢體淋巴水腫的研究進展. 中國修復重建外科雜志, 2025, 39(2): 230-236.
31.	Suzuki Y, Kajita H, Watanabe S, et al. Preoperative photoacoustic versus indocyanine green lymphography in lymphaticovenular anastomosis outcomes for lower extremity lymphedema: A pilot study. Microsurgery, 2024, 44(3): e31153. doi: 10.1002/micr.31153.
32.	Oh A, Kajita H, Matoba E, et al. Photoacoustic lymphangiography before and after lymphaticovenular anastomosis. Arch Plast Surg, 2021, 48(3): 323-328.
33.	Suzuki Y, Kajita H, Otaki M, et al. Evaluation of postoperative anastomotic patency in lymphaticovenular anastomosis using photoacoustic imaging. J Surg Oncol, 2025, 131(1): 42-46.
34.	Suzuki Y, Kajita H, Oh A, et al. Photoacoustic lymphangiography exhibits advantages over near-infrared fluorescence lymphangiography as a diagnostic tool in patients with lymphedema. J Vasc Surg Venous Lymphat Disord, 2022, 10(2): 454-462.
35.	歐陽靖, 羅慕晴, 張堃. 淋巴水腫影像學診斷的技術進展與臨床應用. 磁共振成像, 2025, 16(3): 216-221.
36.	Chen Z, Gezginer I, Zhou Q, et al. Multimodal optoacoustic imaging: methods and contrast materials. Chem Soc Rev, 2024, 53(12): 6068-6099.
37.	Garcia-Uribe A, Erpelding TN, Krumholz A, et al. Dual-modality photoacoustic and ultrasound imaging system for noninvasive sentinel lymph node detection in patients with breast cancer. Sci Rep, 2015, 5: 15748. doi: 10.1038/srep15748.
38.	Sivasubramanian K, Periyasamy V, Pramanik M. Hand-held clinical photoacoustic imaging system for real-time non-invasive small animal imaging. J Vis Exp, 2017(128): 56649. doi: 10.3791/56649.
39.	Kim C, Chen Z. Multimodal photoacoustic imaging: systems, applications, and agents. Biomed Eng Lett, 2018, 8(2): 137-138.
40.	Park JW, Oh DH, Yoo JH, et al. Clinical ultrasound, photoacoustic, and fluorescence image-guided lymphovenous anastomosis microsurgery via a transparent ultrasound transducer array. Nat Commun, 2025, 16(1): 9853. doi: 10.1038/s41467-025-64827-8.
41.	Li J, Zhuang Z, Jiang B, et al. Advances and perspectives in nanoprobes for noninvasive lymph node mapping. Nanomedicine (Lond), 2015, 10(6): 1019-1036.
42.	Xu R, Jiao D, Long Q, et al. Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-Ⅱ fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes. Biomaterials, 2022, 289: 121780. doi: 10.1016/j.biomaterials.2022.121780.
43.	Chen J, Chen L, Wu Y, et al. A H₂O₂-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-Ⅱ fluorescent imaging. Nat Commun, 2021, 12(1): 6870. doi: 10.1038/s41467-021-27233-4.
44.	Paul S, Lee SA, Zhao S, et al. Model-informed deep-learning photoacoustic reconstruction for low-element linear array. Photoacoustics, 2025, 44: 100732. doi: 10.1016/j.pacs.2025.100732.
45.	Yang C, Lan H, Gao F, et al. Review of deep learning for photoacoustic imaging. Photoacoustics, 2021, 21: 100215. doi: 10.1016/j.pacs.2020.100215.
46.	Lan HR, Jiang DH, Yang CC, et al. Y-Net: Hybrid deep learning image reconstruction for photoacoustic tomography in vivo. Photoacoustics, 2020, 20: 100197. doi: 10.1016/j.pacs.2020.100197.
47.	Chlis NK, Karlas A, Fasoula NA, et al. A sparse deep learning approach for automatic segmentation of human vasculature in multispectral optoacoustic tomography. Photoacoustics, 2020, 20: 100203. doi: 10.1016/j.pacs.2020.100203.
48.	Shakeri-Zadeh A, Bulte JWM. Imaging-guided precision hyperthermia with magnetic nanoparticles. Nat Rev Bioeng, 2025, 3(3): 245-260.

1. Azhar SH, Lim HY, Tan BK, et al. The unresolved pathophysiology of lymphedema. Front Physiol, 2020, 11: 137. doi: 10.3389/fphys.2020.00137.
2. Oliver G, Kipnis J, Randolph GJ, et al. The lymphatic vasculature in the 21st century: novel functional roles in homeostasis and disease. Cell, 2020, 182(2): 270-296.
3. Rockson SG, Rivera KK. Estimating the population burden of lymphedema. Ann N Y Acad Sci, 2008, 1131: 147-154.
4. DiSipio T, Rye S, Newman B, et al. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol, 2013, 14(6): 500-515.
5. Tian W, Rockson SG, Jiang X, et al. Leukotriene B4 antagonism ameliorates experimental lymphedema. Sci Transl Med, 2017, 9(389): eaal3920. doi: 10.1126/scitranslmed.aal3920.
6. Brahma B, Yamamoto T. Breast cancer treatment-related lymphedema (BCRL): An overview of the literature and updates in microsurgery reconstructions. Eur J Surg Oncol, 2019, 45(7): 1138-1145.
7. Aron A, Zavaleta C. Current and developing lymphatic imaging approaches for elucidation of functional mechanisms and disease progression. Mol Imaging Biol, 2024, 26(1): 1-16.
8. Szuba A, Shin WS, Strauss HW, et al. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med, 2003, 44(1): 43-57.
9. van Heumen S, Riksen JJM, Bramer WM, et al. Imaging of the lymphatic vessels for surgical planning: a systematic review. Ann Surg Oncol, 2023, 30(1): 462-479.
10. Forte AJ, Huayllani MT, Boczar D, et al. Ultrasound elastography use in lower extremity lymphedema: a systematic review of the literature. Cureus, 2019, 11(9): e5578. doi: 10.7759/cureus.5578.
11. Salehi BP, Sibley RC, Friedman R, et al. MRI of lymphedema. J Magn Reson Imaging, 2023, 57(4): 977-991.
12. Guo J, Shen WB, Xin JF, et al. Evaluation of CT imaging in secondary lower extremity lymphedema: a prospective study. CT Theory and Applications, 2022, 31(2): 237-243.
13. Nagy BI, Mohos B, Tzou CJ. Imaging Modalities for Evaluating Lymphedema. Medicina (Kaunas), 2023, 59(11): 2016. doi: 10.3390/medicina59112016.
14. Van Heumen S, Riksen JJM, Singh MKA, et al. LED-based photoacoustic imaging for preoperative visualization of lymphatic vessels in patients with secondary limb lymphedema. Photoacoustics, 2022, 29: 100446. doi: 10.1016/j.pacs.2022.100446.
15. Watanabe S, Kajita H, Suzuki Y, et al. Photoacoustic lymphangiography is a possible alternative for lymphedema staging. J Vasc Surg Venous Lymphat Disord, 2022, 10(6): 1318-1324.
16. Kajita H, Oh A, Urano M, et al. Photoacoustic lymphangiography. J Surg Oncol, 2020, 121: 48-50.
17. Lediju Bell MA. Photoacoustic imaging for surgical guidance: Principles, applications, and outlook. J Appl Phys, 2020, 128(6): 060904. doi: 10.1063/5.0018190.
18. Lin L, Wang LV. Photoacoustic imaging//Optical imaging in human disease and biological research. Singapore : Springer, 2021: 147-175.
19. Bell AG. Upon the production and reproduction of sound by light. J Soc Telegraph Eng, 1880, 9(34): 404-426.
20. Yao JJ, Wang LV. Photoacoustic microscopy. Laser & Photonics Reviews, 2013, 7(5): 758-778.
21. Maslov K, Zhang HF, Hu S, et al. Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries. Opt Lett, 2008, 33(9): 929-931.
22. Zhang HF, Maslov K, Stoica G, et al. Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging. Nat Biotechnol, 2006, 24(7): 848-851.
23. Kruger RA, Liu P, Fang YR, et al. Photoacoustic ultrasound (PAUS)—reconstruction tomography. Med Phys, 1995, 22(10): 1605-1609.
24. Yao J, Maslov KI, Zhang Y, et al. Label-free oxygen-metabolic photoacoustic microscopy in vivo. J Biomed Opt, 2011, 16(7): 076003. doi: 10.1117/1.3594786.
25. Yao J, Wang L, Yang JM, et al. High-speed label-free functional photoacoustic microscopy of mouse brain in action. Nat Methods, 2015, 12(5): 407-410.
26. Forbrich A, Heinmiller A, Zemp RJ. Photoacoustic imaging of lymphatic pumping. J Biomed Opt, 2017, 22(10): 1-6.
27. Suzuki Y, Kajita H, Imanishi N, et al. Observation of a lymphatic pump in a human by using photoacoustic imaging. Plast Reconstr Surg Glob Open, 2020, 8(6): e2914. doi: 10.1097/GOX.0000000000002914.
28. Suzuki Y, Kajita H, Oh A, et al. Visualising lymphatic flow dynamics during complex physical therapy: A photoacoustic imaging study. JPRAS Open, 2025, 44: 348-353.
29. Onoda S, Satake T, Hamada E. Super-microsurgery technique for lymphaticovenular anastomosis. J Vasc Surg Venous Lymphat Disord, 2023, 11(1): 177-181.
30. 何挺, 王澤文, 張濤, 等. 外科技術治療肢體淋巴水腫的研究進展. 中國修復重建外科雜志, 2025, 39(2): 230-236.
31. Suzuki Y, Kajita H, Watanabe S, et al. Preoperative photoacoustic versus indocyanine green lymphography in lymphaticovenular anastomosis outcomes for lower extremity lymphedema: A pilot study. Microsurgery, 2024, 44(3): e31153. doi: 10.1002/micr.31153.
32. Oh A, Kajita H, Matoba E, et al. Photoacoustic lymphangiography before and after lymphaticovenular anastomosis. Arch Plast Surg, 2021, 48(3): 323-328.
33. Suzuki Y, Kajita H, Otaki M, et al. Evaluation of postoperative anastomotic patency in lymphaticovenular anastomosis using photoacoustic imaging. J Surg Oncol, 2025, 131(1): 42-46.
34. Suzuki Y, Kajita H, Oh A, et al. Photoacoustic lymphangiography exhibits advantages over near-infrared fluorescence lymphangiography as a diagnostic tool in patients with lymphedema. J Vasc Surg Venous Lymphat Disord, 2022, 10(2): 454-462.
35. 歐陽靖, 羅慕晴, 張堃. 淋巴水腫影像學診斷的技術進展與臨床應用. 磁共振成像, 2025, 16(3): 216-221.
36. Chen Z, Gezginer I, Zhou Q, et al. Multimodal optoacoustic imaging: methods and contrast materials. Chem Soc Rev, 2024, 53(12): 6068-6099.
37. Garcia-Uribe A, Erpelding TN, Krumholz A, et al. Dual-modality photoacoustic and ultrasound imaging system for noninvasive sentinel lymph node detection in patients with breast cancer. Sci Rep, 2015, 5: 15748. doi: 10.1038/srep15748.
38. Sivasubramanian K, Periyasamy V, Pramanik M. Hand-held clinical photoacoustic imaging system for real-time non-invasive small animal imaging. J Vis Exp, 2017(128): 56649. doi: 10.3791/56649.
39. Kim C, Chen Z. Multimodal photoacoustic imaging: systems, applications, and agents. Biomed Eng Lett, 2018, 8(2): 137-138.
40. Park JW, Oh DH, Yoo JH, et al. Clinical ultrasound, photoacoustic, and fluorescence image-guided lymphovenous anastomosis microsurgery via a transparent ultrasound transducer array. Nat Commun, 2025, 16(1): 9853. doi: 10.1038/s41467-025-64827-8.
41. Li J, Zhuang Z, Jiang B, et al. Advances and perspectives in nanoprobes for noninvasive lymph node mapping. Nanomedicine (Lond), 2015, 10(6): 1019-1036.
42. Xu R, Jiao D, Long Q, et al. Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-Ⅱ fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes. Biomaterials, 2022, 289: 121780. doi: 10.1016/j.biomaterials.2022.121780.
43. Chen J, Chen L, Wu Y, et al. A H₂O₂-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-Ⅱ fluorescent imaging. Nat Commun, 2021, 12(1): 6870. doi: 10.1038/s41467-021-27233-4.
44. Paul S, Lee SA, Zhao S, et al. Model-informed deep-learning photoacoustic reconstruction for low-element linear array. Photoacoustics, 2025, 44: 100732. doi: 10.1016/j.pacs.2025.100732.
45. Yang C, Lan H, Gao F, et al. Review of deep learning for photoacoustic imaging. Photoacoustics, 2021, 21: 100215. doi: 10.1016/j.pacs.2020.100215.
46. Lan HR, Jiang DH, Yang CC, et al. Y-Net: Hybrid deep learning image reconstruction for photoacoustic tomography in vivo. Photoacoustics, 2020, 20: 100197. doi: 10.1016/j.pacs.2020.100197.
47. Chlis NK, Karlas A, Fasoula NA, et al. A sparse deep learning approach for automatic segmentation of human vasculature in multispectral optoacoustic tomography. Photoacoustics, 2020, 20: 100203. doi: 10.1016/j.pacs.2020.100203.
48. Shakeri-Zadeh A, Bulte JWM. Imaging-guided precision hyperthermia with magnetic nanoparticles. Nat Rev Bioeng, 2025, 3(3): 245-260.

Chinese Journal of Reparative and Reconstructive Surgery

Research progress of photoacoustic imaging in diagnosis of limb lymphedema

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