Progresses and clinical application of super‑resolution ultrasound imaging: a narrative review
Keywords:
Super-resolution ultrasound, Microcirculation, MicrobubbleAbstract
Microcirculation plays a crucial role in maintaining normal physiological functions in the human body by facilitating the exchange of materials between tissues and blood through a network of microvessels with diameters less than 100 μm. It regulates local hemodynamics and participates in important pathophysiological processes, such as inflammatory reactions and immune responses. In recent years, the monitoring of super-resolution ultrasound (SRUS) in microcirculation has significantly enhanced our understanding of microvascular structure and function, while also providing insights into the noninvasive evaluation of organ conditions at the micro-level, thereby promoting the diagnosis and treatment of related diseases. This review summarizes the development and clinical application progress of SRUS, offering valuable insights into future research directions.
References
1. Rasmussen LD, Westra J, Karim SR et al (2025) Microvascular resistance reserve: impact on health status and myocardial perfusion after revascularization in chronic coronary syndrome. Eur Heart J 46(5):424–435. https://doi.org/10.1093/eurheartj/ehae604
2. Sablik M, Sannier A, Raynaud M et al (2025) Microvascular inflammation of kidney allografts and clinical outcomes. N Engl J Med 392(8):763–776. https://doi.org/10.1056/NEJMoa2408835
3. Souza A, Troschel AS, Marquardt JP et al (2025) Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes. Eur Heart J 46(12):1112–1123. https://doi.org/10.1093/eurheartj/ehae827
4. Tang MX, Mulvana H, Gauthier T et al (2011) Quantitative contrast-enhanced ultrasound imaging: a review of sources of variability. Interface Focus 1(4):520–539. https://doi.org/10.1098/rsfs.2011.0026
5. Xia S, Zheng Y, Hua Q et al (2024) Super-resolution ultrasound and microvasculomics: a consensus statement. Eur Radiol 34(11):7503–7513. https://doi.org/10.1007/s00330-024-10796-3
6. Huang X, Zhang Y, Zhou Q, Deng Q (2024) Value of ultrasound super-resolution imaging for the assessment of renal microcirculation in patients with acute kidney injury: a preliminary study. Diagnostics (Basel) 14(11):1192. https://doi.org/10.3390/diagnostics14111192
7. Xia S, Hua Q, Song Y et al (2025) Super-resolution ultrasound imaging of intranodal lymphatic sinuses for predicting sentinel lymph node metastasis in breast cancer: a preliminary study. Eur Radiol. https://doi.org/10.1007/s00330-025-11520-5
8. Ikeda O, Sato T, Suzuki K (1979) Super-resolution imaging system using waves with a limited frequency bandwidth. J Acoust Soc Am 65:75–81. https://doi.org/10.1121/1.382270
9. Errico C, Pierre J, Pezet S et al (2015) Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature 527(7579):499–502. https://doi.org/10.1038/nature16066
10. Betzig E, Patterson GH, Sougrat R et al (2006) Imaging intracellular fluorescent proteins at nanometer resolution. Science 313(5793):1642–1645. https://doi.org/10.1126/science.1127344
11. Hess ST, Girirajan TP, Mason MD (2006) Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys J 91(11):4258–4272. https://doi.org/10.1529/biophysj.106.091116
12. Rust MJ, Bates M, Zhuang X (2006) Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat Methods 3(10):793–795. https://doi.org/10.1038/nmeth929
13. Zheng Y, Krupka T, Wu H, Wang Z, Exner AA (2009) 0079: Direct measurement of blood flow velocity in small diameter vessels using contrast-enhanced ultrasound. Ultrasound Med Biol 35(8):S16. https://doi.org/10.1016/j.ultrasmedbio.2009.06.063
14. Couture O, Besson B, Montaldo G, Fink M & Tanter M. In 2011 IEEE International Ultrasonics Symposium. 1285–1287.
15. Lowerison M, Shin Y, Song P (2024) Super-resolution ultrasound imaging: the quest for microvessels. Acoustics Today 20(3):20. https://doi.org/10.1121/AT.2024.20.3.20
16. Shang Y, Xie X, Luo Y et al (2023) Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers. Eur Radiol 33(2):988–995. https://doi.org/10.1007/s00330-022-09108-4
17. Yi HM, Lowerison MR, Song PF, Zhang W (2022) A review of clinical applications for super-resolution ultrasound localization microscopy. Curr Med Sci 42(1):1–16. https://doi.org/10.1007/s11596-021-2459-2
18. Shekhawat GS, Dravid VP (2005) Nanoscale imaging of buried structures via scanning near-field ultrasound holography. Science 310(5745):89–92. https://doi.org/10.1126/science.1117694
19. Lowerison MR, Sekaran NVC, Zhang W et al (2022) Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse. Sci Rep 12(1):619. https://doi.org/10.1038/s41598-021-04712-8
20. Huang C, Zhang W, Gong P et al (2021) Super-resolution ultrasound localization microscopy based on a high frame-rate clinical ultrasound scanner: an in-human feasibility study. Phys Med Biol. https://doi.org/10.1088/1361-6560/abef45
21. Quan B, Liu X, Zhao S et al (2023) Detecting early ocular choroidal melanoma using ultrasound localization microscopy. Bioengineering (Basel) 10(4):428. https://doi.org/10.3390/bioengineering10040428
22. Hingot V, Errico C, Tanter M, Couture O (2017) Subwavelength motion-correction for ultrafast ultrasound localization microscopy. Ultrasonics 77:17–21. https://doi.org/10.1016/j.ultras.2017.01.008
23. Lin H, Wang Z, Liao Y et al (2024) Super-resolution ultrasound imaging reveals temporal cerebrovascular changes with disease progression in female 5×FAD mouse model of Alzheimer’s disease: correlation with pathological impairments. EBioMedicine 108:105355. https://doi.org/10.1016/j.ebiom.2024.105355
24. Zheng H, Niu L, Qiu W et al (2023) The emergence of functional ultrasound for noninvasive brain-computer interface. Research 6:0200. https://doi.org/10.34133/research.0200
25. Yan J, Huang B, Tonko J et al (2024) Transthoracic ultrasound localization microscopy of myocardial vasculature in patients. Nat Biomed Eng 8(6):689–700. https://doi.org/10.1038/s41551-024-01206-6
26. Wang Y, Lowerison MR, Huang Z et al (2024) Longitudinal awake imaging of mouse deep brain microvasculature with super-resolution ultrasound localization microscopy. bioRxiv. https://doi.org/10.1101/2023.09.01.555789
27. Chabouh G, Denis L, Abioui-Mourgues M et al. An open-source platform for 3D transcranial Ultrasound Localization Microscopy in awake mice. 2024.
28. Favre H, Pernot M, Tanter M, Papadacci C (2023) Transcranial 3D ultrasound localization microscopy using a large element matrix array with a multi-lens diffracting layer: anin vitrostudy. Phys Med Biol. https://doi.org/10.1088/1361-6560/acbde3
29. Viessmann OM, Eckersley RJ, Christensen-Jeffries K, Tang MX, Dunsby C (2013) Acoustic super-resolution with ultrasound and microbubbles. Phys Med Biol 58(18):6447. https://doi.org/10.1088/0031-9155/58/18/6447
30. Desailly Y, Couture O, Fink M, Tanter M (2013) Sono-activated ultrasound localization microscopy. Appl Phys Lett. https://doi.org/10.1063/1.4826597
31. Simpson DH, Chin CT, Burns PN (1999) Pulse inversion doppler: a new method for detecting nonlinear echoes from microbubble contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 46(2):372–382. https://doi.org/10.1109/58.753026
32. Huang C, Lowerison MR, Trzasko JD et al (2020) Short acquisition time super-resolution ultrasound microvessel imaging via microbubble separation. Sci Rep 10(1):6007. https://doi.org/10.1038/s41598-020-62898-9
33. Heiles B, Chavignon A, Hingot V et al (2022) Performance benchmarking of microbubble-localization algorithms for ultrasound localization microscopy. Nat Biomed Eng 6(5):605–616. https://doi.org/10.1038/s41551-021-00824-8
34. Song P, Trzasko JD, Manduca A et al (2018) Improved super-resolution ultrasound microvessel imaging with spatiotemporal nonlocal means filtering and bipartite graph-based microbubble tracking. IEEE Trans Ultrason Ferroelectr Freq Control 65(2):149–167. https://doi.org/10.1109/tuffc.2017.2778941
35. Christensen-Jeffries K, Browning RJ, Tang MX, Dunsby C, Eckersley RJ (2015) In vivo acoustic super-resolution and super-resolved velocity mapping using microbubbles. IEEE Trans Med Imaging 34(2):433–440. https://doi.org/10.1109/tmi.2014.2359650
36. Zhao S, Hartanto J, Joseph R et al (2023) Hybrid photoacoustic and fast super-resolution ultrasound imaging. Nat Commun 14(1):2191. https://doi.org/10.1038/s41467-023-37680-w
37. Bar-Zion A, Solomon O, Tremblay-Darveau C, Adam D, Eldar YC (2018) SUSHI: sparsity-based ultrasound super-resolution hemodynamic imaging. IEEE Trans Ultrason Ferroelectr Freq Control 65(12):2365–2380. https://doi.org/10.1109/tuffc.2018.2873380
38. Harput S, Christensen-Jeffries K, Brown J et al. In 2017 IEEE International Ultrasonics Symposium (IUS). 1–4.
39. Gao F, Li B, Chen L et al (2024) Ultrasound image super-resolution reconstruction based on semi-supervised CycleGAN. Ultrasonics 137:107177. https://doi.org/10.1016/j.ultras.2023.107177
40. Liu J, Liang M, Ma J et al (2025) Microbubble tracking based on partial smoothing-based adaptive generalized labelled Multi-Bernoulli filter for super-resolution imaging. Ultrasonics 145:107455. https://doi.org/10.1016/j.ultras.2024.107455
41. Lyu Y, Jiang X, Xu Y et al (2023) ARU-GAN: U-shaped GAN based on attention and residual connection for super-resolution reconstruction. Comput Biol Med 164:107316. https://doi.org/10.1016/j.compbiomed.2023.107316
42. Desailly Y, Pierre J, Couture O, Tanter M (2015) Resolution limits of ultrafast ultrasound localization microscopy. Phys Med Biol 60(22):8723–8740. https://doi.org/10.1088/0031-9155/60/22/8723
43. Hoyt K, Sorace A, Saini R (2012) Quantitative mapping of tumor vascularity using volumetric contrast-enhanced ultrasound. Invest Radiol 47(3):167–174. https://doi.org/10.1097/RLI.0b013e318234e6bc
44. Huang SF, Chang RF, Moon WK et al (2008) Analysis of tumor vascularity using three-dimensional power doppler ultrasound images. IEEE Trans Med Imaging 27(3):320–330. https://doi.org/10.1109/TMI.2007.904665
45. Mahoney M, Sorace A, Warram J, Samuel S, Hoyt K (2014) Volumetric contrast-enhanced ultrasound imaging of renal perfusion. J Ultrasound Med 33(8):1427–1437. https://doi.org/10.7863/ultra.33.8.1427
46. Renaudin N, Demene C, Dizeux A et al (2022) Functional ultrasound localization microscopy reveals brain-wide neurovascular activity on a microscopic scale. Nat Methods 19(8):1004–1012. https://doi.org/10.1038/s41592-022-01549-5
47. Demene C, Robin J, Dizeux A et al (2021) Transcranial ultrafast ultrasound localization microscopy of brain vasculature in patients. Nat Biomed Eng 5(3):219–228. https://doi.org/10.1038/s41551-021-00697-x
48. Yan L, Bai C, Zheng Y et al (2021) Study on the application of super-resolution ultrasound for cerebral vessel imaging in rhesus monkeys. Front Neurol 12:720320. https://doi.org/10.3389/fneur.2021.720320
49. Xing P, Perrot V, Dominguez-Vargas AU et al (2025) 3D ultrasound localization microscopy of the nonhuman primate brain. EBioMedicine 111:105457. https://doi.org/10.1016/j.ebiom.2024.105457
50. Lowerison MR, Vaithiyalingam Chandra Sekaran N, Dong Z et al (2024) Super-resolution ultrasound reveals cerebrovascular impairment in a mouse model of Alzheimer’s disease. J Neurosci 44(9):e1251232024. https://doi.org/10.1523/jneurosci.1251-23.2024
51. Huang W, Hua C, Guo Y et al (2023) Super resolution imaging reconstruction reveals that gold standard methods may not correctly conclude neural/brain functional recovery. Comput Med Imaging Graph 105:102198. https://doi.org/10.1016/j.compmedimag.2023.102198
52. Zhang Z, Hwang M, Kilbaugh TJ, Sridharan A, Katz J (2022) Cerebral microcirculation mapped by echo particle tracking velocimetry quantifies the intracranial pressure and detects ischemia. Nat Commun 13(1):666. https://doi.org/10.1038/s41467-022-28298-5
53. Hingot V, Brodin C, Lebrun F et al (2020) Early ultrafast ultrasound imaging of cerebral perfusion correlates with ischemic stroke outcomes and responses to treatment in mice. Theranostics 10(17):7480–7491. https://doi.org/10.7150/thno.44233
54. Lin BZ, Fan AC, Wang Y et al (2025) Combined nanodrops imaging and ultrasound localization microscopy for detecting intracerebral hemorrhage. Ultrasound Med Biol 51(4):707–714. https://doi.org/10.1016/j.ultrasmedbio.2025.01.002
55. Dong HR, Yu JJ, Chen XY, Xu KL, Xie R (2024) Application of super-resolution and ultrafast ultrasound to reveal the characteristics of vascular blood flow changes after rat spinal cord injury at different segments. Zhonghua Yi Xue Za Zhi 104(9):690–694. https://doi.org/10.3760/cma.j.cn112137-20231020-00830
56. Zeng QQ, Liang P (2024) Super-resolution US imaging of focal nodular hyperplasia. Radiology 311(1):e233130. https://doi.org/10.1148/radiol.233130
57. Brown KG, Li J, Margolis R et al (2023) Assessment of transarterial chemoembolization using super-resolution ultrasound imaging and a rat model of hepatocellular carcinoma. Ultrasound Med Biol 49(5):1318–1326. https://doi.org/10.1016/j.ultrasmedbio.2023.01.021
58. Zhang W, Lowerison MR, Dong Z et al (2021) Super-resolution ultrasound localization microscopy on a rabbit liver VX2 tumor model: an initial feasibility study. Ultrasound Med Biol 47(8):2416–2429. https://doi.org/10.1016/j.ultrasmedbio.2021.04.012
59. Denis L, Bodard S, Hingot V et al (2023) Sensing ultrasound localization microscopy for the visualization of glomeruli in living rats and humans. EBioMedicine 91:104578. https://doi.org/10.1016/j.ebiom.2023.104578
60. Andersen SB, Taghavi I, Hoyos CAV et al (2020) Super-resolution imaging with ultrasound for visualization of the renal microvasculature in rats before and after renal ischemia: a pilot study. Diagnostics (Basel) 10(11):862. https://doi.org/10.3390/diagnostics10110862
61. Chen Q, Yu J, Rush BM et al (2020) Ultrasound super-resolution imaging provides a noninvasive assessment of renal microvasculature changes during mouse acute kidney injury. Kidney Int 98(2):355–365. https://doi.org/10.1016/j.kint.2020.02.011
62. Søgaard SB, Andersen SB, Taghavi I et al (2023) Super-resolution ultrasound imaging of renal vascular alterations in zucker diabetic fatty rats during the development of diabetic kidney disease. Diagnostics (Basel) 13(20):3197. https://doi.org/10.3390/diagnostics13203197
63. Qiu L, Zhang J, Yang Y et al (2022) In vivo assessment of hypertensive nephrosclerosis using ultrasound localization microscopy. Med Phys 49(4):2295–2308. https://doi.org/10.1002/mp.15583
64. Lowerison MR, Huang C, Lucien F, Chen S, Song P (2020) Ultrasound localization microscopy of renal tumor xenografts in chicken embryo is correlated to hypoxia. Sci Rep 10(1):2478. https://doi.org/10.1038/s41598-020-59338-z
65. Bodard S, Denis L, Hingot V et al (2023) Ultrasound localization microscopy of the human kidney allograft on a clinical ultrasound scanner. Kidney Int 103(5):930–935. https://doi.org/10.1016/j.kint.2023.01.027
66. Hysi E, Baek J, Koven A et al (2025) A first-in-human study of quantitative ultrasound to assess transplant kidney fibrosis. Nat Med 31(3):970–978. https://doi.org/10.1038/s41591-024-03417-5
67. Chabouh G, Denis L, Bodard S et al (2024) Whole organ volumetric sensing ultrasound localization microscopy for characterization of kidney structure. IEEE Trans Med Imaging 43(11):4055–4063. https://doi.org/10.1109/tmi.2024.3411669
68. Kanoulas E, Butler M, Rowley C et al (2019) Super-resolution contrast-enhanced ultrasound methodology for the identification of in vivo vascular dynamics in 2D. Invest Radiol 54(8):500–516. https://doi.org/10.1097/rli.0000000000000565
69. Wang X, Hua C, Ying T et al (2024) Super-resolution imaging of urethral vasculature in healthy pre- and post-menopausal females. iScience 27(3):109310. https://doi.org/10.1016/j.isci.2024.109310
70. Zhu J, Rowland EM, Harput S et al (2019) 3D super-resolution US imaging of rabbit lymph node vasculature in vivo by using microbubbles. Radiology 291(3):642–650. https://doi.org/10.1148/radiol.2019182593
71. Zhu J, Zhang C, Christensen-Jeffries K et al (2022) Super-resolution ultrasound localization microscopy of microvascular structure and flow for distinguishing metastatic lymph nodes - an initial human study. Ultraschall Med 43(6):592–598. https://doi.org/10.1055/a-1917-0016
72. Hou C, M-x Li, He W (2024) Carotid plaque-RADS: a novel stroke risk classification system. JACC Cardiovasc Imaging 17(2):226. https://doi.org/10.1016/j.jcmg.2023.11.007
73. Yu J, Lavery L, Kim K (2018) Super-resolution ultrasound imaging method for microvasculature in vivo with a high temporal accuracy. Sci Rep 8(1):13918. https://doi.org/10.1038/s41598-018-32235-2
74. Hou C, Xuan JQ, Zhao L et al (2024) Comparison of the diagnostic performance of contrast-enhanced ultrasound and high-resolution magnetic resonance imaging in the evaluation of histologically defined vulnerable carotid plaque: a systematic review and meta-analysis. Quant Imaging Med Surg 14(8):5814–5830. https://doi.org/10.21037/qims-24-540
75. Leroy H, Wang LZ, Jimenez A et al (2025) Assessment of microvascular flow in human atherosclerotic carotid plaques using ultrasound localization microscopy. EBioMedicine 111:105528. https://doi.org/10.1016/j.ebiom.2024.105528
76. Goudot G, Jimenez A, Mohamedi N et al (2023) Assessment of Takayasu’s arteritis activity by ultrasound localization microscopy. EBioMedicine 90:104502. https://doi.org/10.1016/j.ebiom.2023.104502
77. Lei S, Zhang C, Zhu B et al (2023) In vivo ocular microvasculature imaging in rabbits with 3D ultrasound localization microscopy. Ultrasonics 133:107022. https://doi.org/10.1016/j.ultras.2023.107022
78. Qian X, Huang C, Li R et al (2022) Super-resolution ultrasound localization microscopy for visualization of the ocular blood flow. IEEE Trans Biomed Eng 69(5):1585–1594. https://doi.org/10.1109/tbme.2021.3120368
79. Ul Banna H, Mitchell B, Chen S, Palko J (2023) Super-resolution ultrasound localization microscopy using high-frequency ultrasound to measure ocular perfusion velocity in the rat eye. Bioengineering (Basel) 10(6):689. https://doi.org/10.3390/bioengineering10060689
80. Yin J, Dong F, An J et al (2024) Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy. Theranostics 14(3):1312–1324. https://doi.org/10.7150/thno.89306
81. Zhang G, Yu J, Lei YM et al (2022) Ultrasound super-resolution imaging for the differential diagnosis of thyroid nodules: a pilot study. Front Oncol 12:978164. https://doi.org/10.3389/fonc.2022.978164
82. Zhang G, Lei YM, Li N et al (2022) Ultrasound super-resolution imaging for differential diagnosis of breast masses. Front Oncol 12:1049991. https://doi.org/10.3389/fonc.2022.1049991
83. Opacic T, Dencks S, Theek B et al (2018) Motion model ultrasound localization microscopy for preclinical and clinical multiparametric tumor characterization. Nat Commun 9(1):1527. https://doi.org/10.1038/s41467-018-03973-8
84. Ghosh D, Peng J, Brown K et al (2019) Super-resolution ultrasound imaging of skeletal muscle microvascular dysfunction in an animal model of type 2 diabetes. J Ultrasound Med 38(10):2589–2599. https://doi.org/10.1002/jum.14956
85. Zhang G, Hu X, Ren X et al (2024) In vivo ultrasound localization microscopy for high-density microbubbles. Ultrasonics 143:107410. https://doi.org/10.1016/j.ultras.2024.107410
86. Chen J, Liu B, Peng G et al (2025) Achieving high-performance transcranial ultrasound transmission through Mie and Fano resonance in flexible metamaterials. Adv Sci (Weinh). https://doi.org/10.1002/advs.202500170
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