Harnessing Ultrasound for Tumor Vascular Targeting: From Mechanistic Insights to Clinical Monitoring and Therapeutic Applications

Lingling Lei , Huai Yang , Meng Du , Youchao Chen

BIO Integration ›› 2026, Vol. 7 ›› Issue (1) : 18

PDF (6762KB)
BIO Integration ›› 2026, Vol. 7 ›› Issue (1) :18 DOI: 10.15212/bioi-2025-0117
Review
research-article
Harnessing Ultrasound for Tumor Vascular Targeting: From Mechanistic Insights to Clinical Monitoring and Therapeutic Applications
Author information +
History +
PDF (6762KB)

Abstract

The tumor vasculature, characterized by pathological angiogenesis and structural abnormalities, drives the progression of solid tumors by inducing hypoxia-acidosis microenvironments and therapeutic resistance. Targeting the tumor vasculature has emerged as a critical therapeutic strategy. Although conventional approaches such as anti-angiogenic drugs, vascular disrupting agents, and embolization have shown efficacy, their single-target focus hinders addressing tumor heterogeneity and evolving stage-specific needs. For example, rapid vascular disruption is effective for debulking advanced tumors, whereas vascular normalization enhances early- to mid-stage therapy by improving postoperative chemo-radiotherapy outcomes. Unlike single-mechanism interventions, ultrasound modulates acoustic parameters to achieve diverse effects including angiogenesis suppression, vessel disruption, and vasodilation, thus addressing multi-stage vascular needs. Ultrasound-based monitoring systems provide precise, dynamic vascular assessments to guide intervention strategies. Compared with traditional static imaging ultrasound offers real-time angiogenesis visualization and therapeutic response evaluation, thus enabling treatment optimization. This review synthesizes recent advances in ultrasound-based vascular targeting, emphasizing its dual role in spatiotemporally adaptive therapy and angiogenesis monitoring. We critically examine clinical translation challenges and future directions, highlighting how ultrasound-driven strategies, by bridging mechanistic precision with clinical scalability, might enable personalized, multi-effect therapeutic paradigms in oncology.

Keywords

Anti-angiogenesis / tumor microenvironment / tumor vasculature / ultrasound / vascular monitoring / vascular normalization

Cite this article

Download citation ▾
Lingling Lei, Huai Yang, Meng Du, Youchao Chen. Harnessing Ultrasound for Tumor Vascular Targeting: From Mechanistic Insights to Clinical Monitoring and Therapeutic Applications. BIO Integration, 2026, 7 (1) : 18 DOI:10.15212/bioi-2025-0117

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Koos B, Kamali-Moghaddam M, David L, Sobrinho-Simões M, Dimberg A, et al. Next-generation pathology——surveillance of tumor microecology. J Mol Biol 2015; 427(11): 2013-22. [PMID: 25725260 DOI: 10.1016/j.jmb.2015.02.017]

[2]

Hanahan D, Weinberg R. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74. [PMID: 21376230 DOI: 10.1016/j.cell.2011.02.013]

[3]

Huang Z. Roles of main pro- and anti-angiogenic factors in tumor angiogenesis. World J Gastroenterol 2004; 10(4): 463. [PMID: 14966899 DOI: 10.3748/wjg.v10.i4.463]

[4]

Al-Ostoot FH, Salah S, Khamees HA, Khanum SA. Tumor angiogenesis: current challenges and therapeutic opportunities. Cancer Treat Res Commun 2021; 28: 100422. [PMID: 34147821 DOI: 10.1016/j.ctarc.2021.100422]

[5]

Mazzone M, Dettori D, de Oliveira RL, Loges S, Schmidt T, et al. Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 2009; 136(5): 839-51. [PMID: 19217150 DOI: 10.1016/j.cell.2009.01.020]

[6]

De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer 2017; 17(8): 457-74. [PMID: 28706266 DOI: 10.1038/nrc.2017.51]

[7]

Giaccia AJ, Simon MC, Johnson R. The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes Dev 2004; 18(18): 2183-94. [PMID: 15371333 DOI: 10.1101/gad.1243304]

[8]

De Bock K, Cauwenberghs S, Carmeliet P. Vessel abnormalization: another hallmark of cancer? Molecular mechanisms and therapeutic implications. Curr Opin Genet Dev 2011; 21(1): 73-9. [PMID: 21106363 DOI: 10.1016/j.gde.2010.10.008]

[9]

Goel S, Duda DG, Xu L, Munn LL, Boucher Y, et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 2011; 91(3): 1071-121. [PMID: 21742796 DOI: 10.1152/physrev.00038.2010]

[10]

Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol 2013; 31(17): 2205-18. [PMID: 23669226 DOI: 10.1200/jco.2012.46.3653]

[11]

Sivakumar B, Harry LE, Paleolog EM. Modulating angiogenesis: more vs less. JAMA 2004; 292(8): 972. [PMID: 15328330 DOI: 10.1001/jama.292.8.972]

[12]

Guelfi S, Hodivala-Dilke K, Bergers G. Targeting the tumour vasculature: from vessel destruction to promotion. Nat Rev Cancer 2024; 24(10): 655-75. [PMID: 39210063 DOI: 10.1038/s41568-024-00736-0]

[13]

Jain R. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell 2014; 26(5): 605-22. [PMID: 25517747 DOI: 10.1016/j.ccell.2014.10.006]

[14]

Yang T, Xiao H, Liu X, Wang Z, Zhang Q, et al. Vascular normalization: a new window opened for cancer therapies. Front Oncol 2021; 11: 719836. [PMID: 34476218 DOI: 10.3389/fonc.2021.719836]

[15]

Hinnen P, Eskens FALM. Vascular disrupting agents in clinical development. Br J Cancer 2007; 96(8): 1159-65. [PMID: 17375046 DOI: 10.1038/sj.bjc.6603694]

[16]

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285(21): 1182-6. [PMID: 4938153 DOI: 10.1056/nejm197111182852108]

[17]

Pellow C, Jafari Sojahrood A, Zhao X, Kolios MC, Exner AA, et al. Synchronous intravital imaging and cavitation monitoring of antivascular focused ultrasound in tumor microvasculature using monodisperse low boiling point nanodroplets. ACS Nano 2023; 18(1): 410-27. [PMID: 38147452 DOI: 10.1021/acsnano.3c07711]

[18]

Ho YJ, Chu SW, Liao EC, Fan CH, Chan HL, et al. Normalization of tumor vasculature by oxygen microbubbles with ultrasound. Theranostics 2019; 9(24): 7370-83. [PMID: 31695774 DOI: 10.7150/thno.37750]

[19]

Belcik JT, Davidson BP, Xie A, Wu MD, Yadava M, et al. Augmentation of muscle blood flow by ultrasound cavitation is mediated by ATP and purinergic signaling. Circulation 2017; 135(13): 1240-52. [PMID: 28174191 DOI: 10.1161/circulationaha.116.024826]

[20]

Padilla F, Brenner J, Prada F, Klibanov AL. Theranostics in the vasculature: bioeffects of ultrasound and microbubbles to induce vascular shutdown. Theranostics 2023; 13(12): 4079-101. [PMID: 37554276 DOI: 10.7150/thno.70372]

[21]

Wang J, Lv F, Fei X, Cui Q, Wang L, et al. Study on the characteristics of contrast-enhanced ultrasound and its utility in assessing the microvessel density in ovarian tumors or tumor-like lesions. Int J Biol Sci 2011; 7(5): 600-6. [PMID: 21614152 DOI: 10.7150/ijbs.7.600]

[22]

Pysz MA, Guracar I, Foygel K, Tian L, Willmann JK. Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging. Angiogenesis 2012; 15(3): 433-42. [PMID: 22535383 DOI: 10.1007/s10456-012-9271-3]

[23]

Yin J, Dong F, An J, Guo T, Cheng H, et al. Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy. Theranostics 2024; 14(3): 1312-24. [PMID: 38323316 DOI: 10.7150/thno.89306]

[24]

Rao SR, Shelton SE, Dayton PA. The “fingerprint” of cancer extends beyond solid tumor boundaries: assessment with a novel ultrasound imaging approach. IEEE Trans Biomed Eng 2016; 63(5): 1082-6. [PMID: 26394410 DOI: 10.1109/TBME.2015.2479590]

[25]

Kaneko OF, Willmann JK. Ultrasound for molecular imaging and therapy in cancer. Quant Imaging Med Surg 2012; 2(2): 87-97. [PMID: 23061039 DOI: 10.3978/j.issn.2223-4292.2012.06.06]

[26]

Tian L, Goldstein A, Wang H, Ching Lo H, Sun Kim I, et al. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nature 2017; 544(7649): 250-4. [PMID: 28371798 DOI: 10.1038/nature21724]

[27]

Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407(6801): 249-57. [PMID: 11001068 DOI: 10.1038/35025220]

[28]

Hashizume H, Falcón BL, Kuroda T, Baluk P, Coxon A, et al. Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth. Cancer Res 2010; 70(6): 2213-23. [PMID: 20197469 DOI: 10.1158/0008-5472.can-09-1977]

[29]

Zhu D, Li Y, Zhang Z, Xue Z, Hua Z, et al. Recent advances of nanotechnology-based tumor vessel-targeting strategies. J Nanobiotechnol 2021; 19(1): 435. [PMID: 34930293 DOI: 10.1186/s12951-021-01190-y]

[30]

Cooney MM, van Heeckeren W, Bhakta S, Ortiz J, Remick SC. Drug insight: vascular disrupting agents and angiogenesis——novel approaches for drug delivery. Nat Clin Pract Oncol 2006; 3(12): 682-92. [PMID: 17139319 DOI: 10.1038/ncponc0663]

[31]

Davis GE, Senger DR. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 2005; 97(11): 1093-107. [PMID: 16306453 DOI: 10.1161/01.res.0000191547.64391.e3]

[32]

Reymond N, d’Água BB, Ridley AJ. Crossing the endothelial barrier during metastasis. Nat Rev Cancer 2013; 13(12): 858-70. [PMID: 24263189 DOI: 10.1038/nrc3628]

[33]

Munn LL, Jain RK. Vascular regulation of antitumor immunity. Science 2019; 365(6453): 544-5. [PMID: 31395771 DOI: 10.1126/science.aaw7875]

[34]

Vasudev NS, Reynolds AR. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 2014; 17(3): 471-94. [PMID: 24482243 DOI: 10.1007/s10456-014-9420-y]

[35]

Wong PP, Bodrug N, Hodivala-Dilke K. Exploring novel methods for modulating tumor blood vessels in cancer treatment. Curr Biol 2016; 26(21): R1161-6. [PMID: 27825457 DOI: 10.1016/j.cub.2016.09.043]

[36]

Wong PP, Demircioglu F, Ghazaly E, Alrawashdeh W, Stratford M, et al. Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread. Cancer Cell 2015; 27(1): 123-37. [PMID: 25584895 DOI: 10.1016/j.ccell.2014.10.015]

[37]

Tannock IF. Population kinetics of carcinoma cells, capillary endothelial cells, and fibroblasts in a transplanted mouse mammary tumor. Cancer Res 1970; 30(10): 2470-6. [PMID: 4097429]

[38]

Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953; 26(312): 638-48. [PMID: 13106296 DOI: 10.1259/0007-1285-26-312-638]

[39]

Suwa T, Kobayashi M, Nam JM, Harada H. Tumor microenvironment and radioresistance. Exp Mol Med 2021; 53(6): 1029-35. [PMID: 34135469 DOI: 10.1038/s12276-021-00640-9]

[40]

Pan Y, Liu L, Mou X, Cai Y. Nanomedicine strategies in conquering and utilizing the cancer hypoxia environment. ACS Nano 2023; 17(21): 20875-924. [PMID: 37871328 DOI: 10.1021/acsnano.3c07763]

[41]

Pinzón-Daza ML, Cuellar-Saenz Y, Nualart F, Ondo-Mendez A, Del Riesgo L, Castillo-Rivera F, et al. Oxidative stress promotes doxorubicin-induced Pgp and BCRP expression in colon cancer cells under hypoxic conditions. J Cell Biochem 2017; 118(7): 1868-78. [PMID: 28106284 DOI: 10.1002/jcb.25890]

[42]

Lv Y, Zhao S, Han J, Zheng L, Yang Z, Zhao L. Hypoxia-inducible factor-1α induces multidrug resistance protein in colon cancer. Onco Targets Ther 2015; 8: 1941- 8. [PMID: 26251616 DOI: 10.2147/OTT.S82835]

[43]

Mohammadi M, Aghanajafi C, Soltani M, Raahemifar K. Numerical investigation on the anti-angiogenic therapy-induced normalization in solid tumors. Pharmaceutics 2022; 14(2): 363. [PMID: 35214095 DOI: 10.3390/pharmaceutics14020363]

[44]

Mpekris F, Voutouri C, Baish JW, Duda DG, Munn LL, et al. Combining microenvironment normalization strategies to improve cancer immunotherapy. Proc Natl Acad Sci U S A 2020; 117(7): 3728-37. [PMID: 32015113 DOI: 10.1073/pnas.1919764117]

[45]

Viallard C, Audiger C, Popovic N, Akla N, Lanthier K, et al. BMP9 signaling promotes the normalization of tumor blood vessels. Oncogene 2020; 39(14): 2996-3014. [PMID: 32042114 DOI: 10.1038/s41388-020-1200-0]

[46]

Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR. Targeting tumor microenvironment for cancer therapy. Int J Mol Sci 2019; 20(4): 840. [PMID: 30781344 DOI: 10.3390/ijms20040840]

[47]

Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol 2018; 15(5): 325-40. [PMID: 29508855 DOI: 10.1038/nrclinonc.2018.29]

[48]

Khan KA, Kerbel RS. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat Rev Clin Oncol 2018; 15(5): 310-24. [PMID: 29434333 DOI: 10.1038/nrclinonc.2018.9]

[49]

Kashyap AS, Schmittnaegel M, Rigamonti N, Pais-Ferreira D, Mueller P, et al. Optimized antiangiogenic reprogramming of the tumor microenvironment potentiates CD40 immunotherapy. Proc Natl Acad Sci USA 2020; 117(1): 541-51. [PMID: 31889004 DOI: 10.1073/pnas.1902145116]

[50]

Ma S, Pradeep S, Hu W, Zhang D, Coleman R, et al. The role of tumor microenvironment in resistance to anti-angiogenic therapy. F1000Res 2018; 7: 326. [PMID: 29560266 DOI: 10.12688/f1000research.11771.1]

[51]

Meadows KL, Hurwitz HI. Anti-VEGF therapies in the clinic. Cold Spring Harb Perspect Med 2012; 2(10): a006577. [PMID: 23028128 DOI: 10.1101/cshperspect.a006577]

[52]

Zarrin B, Zarifi F, Vaseghi G, Javanmard SH. Acquired tumor resistance to antiangiogenic therapy: mechanisms at a glance. J Res Med Sci 2017; 22(1): 117. [PMID: 29184575 DOI: 10.4103/jrms.JRMS_182_17]

[53]

Pinto MP, Sotomayor P, Carrasco-Avino G, Corvalan AH, Owen GI. Escaping antiangiogenic therapy: strategies employed by cancer cells. Int J Mol Sci 2016; 17(9): 1489. [PMID: 27608016 DOI: 10.3390/ijms17091489]

[54]

Liu Y, Liu X, Cui Y, Yuan W. Ultrasound for microalgal cell disruption and product extraction: a review. Ultrason Sonochem 2022; 87: 106054. [PMID: 35688121 DOI: 10.1016/j.ultsonch.2022.106054]

[55]

Miller DL, Dou C. Induction of apoptosis in sonoporation and ultrasonic gene transfer. Ultrasound Med Biol 2009; 35(1): 144-54. [PMID: 18723272 DOI: 10.1016/j.ultrasmedbio.2008.06.007]

[56]

Sitta J, Howard CM . Applications of ultrasound-mediated drug delivery and gene therapy. Int J Mol Sci 2021; 22(21): 11491. [PMID: 34768922 DOI: 10.3390/ijms222111491]

[57]

Wu Y, Sun T, Tang J, Liu Y, Li F. Ultrasound-targeted microbubble destruction enhances the antitumor efficacy of doxorubicin in a mouse hepatocellular carcinoma model. Ultrasound Med Biol. 2020; 46(3): 679-89. [PMID: 31882167 DOI: 10.1016/j.ultrasmedbio.2019.09.017]

[58]

Liu H, Li X, Chen Z, Bai L, Wang Y, et al. Synergic fabrication of pembrolizumab loaded doxorubicin incorporating microbubbles delivery for ultrasound contrast agents mediated anti-proliferation and apoptosis. Drug Deliv 2021; 28(1): 1466-77. [PMID: 34259093 DOI: 10.1080/10717544.2021.1921080]

[59]

Barmin RA, Dasgupta A, Bastard C, De Laporte L, Rütten S, et al. Engineering the acoustic response and drug loading capacity of PBCA-based polymeric microbubbles with surfactants. Mol Pharm 2022; 19(9): 3256-66. [PMID: 35905480 DOI: 10.1021/acs.molpharmaceut.2c00416]

[60]

Ingram N, McVeigh LE, Abou-Saleh RH, Maynard J, Peyman SA, et al. Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues. Theranostics 2020; 10(24): 10973-92. [PMID: 33042265 DOI: 10.7150/thno.49670]

[61]

Ingram N, Abou-Saleh RH, Race AD, Loadman PM, Bushby RJ, et al. Maleimide-thiol linkages alter the biodistribution of SN38 therapeutic microbubbles compared to biotin-avidin while preserving parity in tumoral drug delivery. Pharmaceutics 2024; 16(3): 434. [PMID: 38543328 DOI: 10.3390/pharmaceutics16030434]

[62]

Huo S, Liao Z, Zhao P, Zhou Y, Göstl R, Herrmann A. Mechano-nanoswitches for ultrasound-controlled drug activation. Adv Sci 2022; 9(12): e2104696. [PMID: 35195372 DOI: 10.1002/advs.202104696]

[63]

Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003; 111(9): 1287-95. [PMID: 12727920 DOI: 10.1172/JCI17929]

[64]

Siemann DW, Bibby MC, Dark GG, Dicker AP, Eskens FA, et al. Differentiation and definition of vascular-targeted therapies. Clin Cancer Res 2005; 11(2 Pt 1): 416-20. [PMID: 15701823]

[65]

Kudo M, Han G, Finn RS, Poon RT, Blanc JF, et al. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase III trial. Hepatology 2014; 60(5): 1697-707. [PMID: 24996197 DOI: 10.1002/hep.27290]

[66]

Monk BJ, Minion LE, Coleman RL. Anti-angiogenic agents in ovarian cancer: past, present, and future. Ann Oncol 2016; 27(Suppl 1): i33-9. [PMID: 27141068 DOI: 10.1093/annonc/mdw093]

[67]

Liu Z, Zhang Y, Shen N, Sun J, Tang Z, et al. Destruction of tumor vasculature by vascular disrupting agents in overcoming the limitation of EPR effect. Adv Drug Deliv Rev 2022; 183: 114138. [PMID: 35143895 DOI: 10.1016/j.addr.2022.114138]

[68]

Lei X, Chen M, Huang M, Li X, Shi C, et al. Desacetylvinblastine monohydrazide disrupts tumor vessels by promoting VE-cadherin internalization. Theranostics 2018; 8(2): 384-98. [PMID: 29290815 DOI: 10.7150/thno.22222]

[69]

Dark GG, Hill SA, Prise VE, Tozer GM, Pettit GR, et al. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res 1997; 57(10): 1829-34. [PMID: 9157969]

[70]

Chase DM, Chaplin DJ, Monk BJ. The development and use of vascular targeted therapy in ovarian cancer. Gynecol Oncol 2017; 145(2): 393-406. [PMID: 28238563 DOI: 10.1016/j.ygyno.2017.01.031]

[71]

Zweifel M, Jayson GC, Reed NS, Osborne R, Hassan B, et al. Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer. Ann Oncol 2011; 22(9): 2036-41. [PMID: 21273348 DOI: 10.1093/annonc/mdq708]

[72]

Eskens FA, Tresca P, Tosi D, Van Doorn L, Fontaine H, et al. A phase I pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours. Br J Cancer 2014; 110(9): 2170-7. [PMID: 24714750 DOI: 10.1038/bjc.2014.137]

[73]

McKeage MJ. The potential of DMXAA (ASA404) in combination with docetaxel in advanced prostate cancer. Expert Opin Investig Drugs 2008; 17(1): 23-9. [PMID: 18095916 DOI: 10.1517/13543784.17.1.23]

[74]

Tamura K, Nakagawa K, Kurata T, Satoh T, Nogami T, et al. Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, which was administered to patients with advanced solid tumors on days 1 and 8 in 3-week courses. Cancer Chemother Pharmacol 2007; 60(2): 285-93. [PMID: 17136542 DOI: 10.1007/s00280-006-0382-7]

[75]

Ho YJ, Wang TC, Fan CH, Yeh CK. Current progress in antivascular tumor therapy. Drug Discov Today 2017; 22(10): 1503-15. [PMID: 28625610 DOI: 10.1016/j.drudis.2017.06.001]

[76]

El Kaffas A, Gangeh MJ, Farhat G, Tran WT, Hashim A, et al. Tumour vascular shutdown and cell death following ultrasound-microbubble enhanced radiation therapy. Theranostics 2018; 8(2): 314-27. [PMID: 29290810 DOI: 10.7150/thno.19010]

[77]

Gu L, Shen Z, Ji L, Ng DM, Du N, et al. High-intensity focused ultrasound alone or combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with unsuitable indications for hepatectomy and radiofrequency ablation: a phase II clinical trial. Surg Endosc 2022; 36(3): 1857-67. [PMID: 33788029 DOI: 10.1007/s00464-021-08465-3]

[78]

Lee J, Karshafian R, Papanicolau N, Giles A, Kolios MC, et al. Quantitative ultrasound for the monitoring of novel microbubble and ultrasound radiosensitization. Ultrasound Med Biol 2012; 38(7): 1212-21. [PMID: 22579547 DOI: 10.1016/j.ultrasmedbio.2012.01.028]

[79]

Zhao X, Pellow C, Goertz DE. Intravital imaging and cavitation monitoring of antivascular ultrasound in tumor microvasculature. Theranostics 2023; 13(1): 250-66. [PMID: 36593952 DOI: 10.7150/thno.79186]

[80]

Abdulkarim B, Deutsch E. Endothelial-cell apoptosis and tumour response to radiotherapy. Lancet Oncol 2004; 5(1): 9. [PMID: 14700602 DOI: 10.1016/s1470-2045(03)01317-2]

[81]

Daecher A, Stanczak M, Liu JB, Zhang J, Du S, et al. Localized microbubble cavitation-based antivascular therapy for improving HCC treatment response to radiotherapy. Cancer Lett 2017; 411: 100-5. [PMID: 28969964 DOI: 10.1016/j.canlet.2017.09.037]

[82]

Hwang JH, Brayman AA, Reidy MA, Matula TJ, Kimmey MB, et al. Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo. Ultrasound Med Biol 2005; 31(4): 553-64. [PMID: 15831334 DOI: 10.1016/j.ultrasmedbio.2004.12.014]

[83]

Jing Y, Xiu-Juan Z, Hong-Jiao C, Zhi-Kui C, Qing-Fu Q, et al. Ultrasound-targeted microbubble destruction improved the antiangiogenic effect of endostar in triple-negative breast carcinoma xenografts. J Cancer Res Clin Oncol 2019; 145(5): 1191-200. [PMID: 30805775 DOI: 10.1007/s00432-019-02866-7]

[84]

Liu Z, Gao S, Zhao Y, Li P, Liu J, et al. Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis. Ultrasound Med Biol 2012; 38(2): 253-61. [PMID: 22178162 DOI: 10.1016/j.ultrasmedbio.2011.11.007]

[85]

Tozer GM, Kanthou C, Baguley BC. Disrupting tumour blood vessels. Nat Rev Cancer 2005; 5(6): 423-35. [PMID: 15928673 DOI: 10.1038/nrc1628]

[86]

Frentzas S, Simoneau E, Bridgeman VL, Vermeulen PB, Foo S, et al. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med 2016; 22(11): 1294-302. [PMID: 27748747 DOI: 10.1038/nm.4197]

[87]

Xie H, Li W, Liu H, Chen Y, Ma M, et al. Erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle for inducing tumor thrombotic infarction by precisely damaging tumor vascular endothelium. Small 2022; 18(30): e2201933. [PMID: 35789094 DOI: 10.1002/smll.202201933]

[88]

Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, et al. A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 2003; 30(5 Suppl 16): 117-24. [PMID: 14613032 DOI: 10.1053/j.seminoncol.2003.08.013]

[89]

Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 2010; 28(19): 3191-8. [PMID: 20516443 DOI: 10.1200/JCO.2009.27.7723]

[90]

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350(23): 2335-42. [PMID: 15175435 DOI: 10.1056/NEJMoa032691]

[91]

Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7(9): 987-9. [PMID: 11533692 DOI: 10.1038/nm0901-987]

[92]

Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 2004; 6(6): 553-63. [DOI: 10.1016/j.ccr.2004.10.011]

[93]

Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004; 10(2): 145-7. [PMID: 14745444 DOI: 10.1038/nm988]

[94]

Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 2005; 23(31): 8136-9. [PMID: 16258121 DOI: 10.1200/JCO.2005.02.5635]

[95]

Mpekris F, Panagi M, Charalambous A, Voutouri C, Stylianopoulos T. Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy. Cell Rep Med 2024; 5(7): 101626. [PMID: 38944037 DOI: 10.1016/j.xcrm.2024.101626]

[96]

Trédan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst 2007; 99(19): 1441-54. [PMID: 17895480 DOI: 10.1093/jnci/djm135]

[97]

Dickson PV, Hamner JB, Sims TL, Fraga CH, Ng CY, et al. Bevacizumabinduced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res 2007; 13(13): 3942-50. [PMID: 17606728 DOI: 10.1158/1078-0432.CCR-07-0278]

[98]

McGee MC, Hamner JB, Williams RF, Rosati SF, Sims TL, et al. Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation. Int J Radiat Oncol Biol Phys 2010; 76(5): 1537-45. [PMID: 20338480 DOI: 10.1016/j.ijrobp.2009.12.010]

[99]

Van der Veldt AA, Lubberink M, Bahce I, Walraven M, de Boer MP, et al. Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs. Cancer Cell 2012; 21(1): 82-91. [PMID: 22264790 DOI: 10.1016/j.ccr.2011.11.023]

[100]

Shan Y, Ni Q, Zhang Q, Zhang M, Wei B, et al. Targeting tumor endothelial hyperglycolysis enhances immunotherapy through remodeling tumor microenvironment. Acta Pharm Sin B 2022; 12(4): 1825-39. [PMID: 35847509 DOI: 10.1016/j.apsb.2022.02.014]

[101]

Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A 2012; 109(43): 17561-6. [PMID: 23045683 DOI: 10.1073/pnas.1215397109]

[102]

Seyedmirzaei Sarraf S, Rokhsar Talabazar F, Namli I, Maleki M, Sheibani Aghdam A, et al. Fundamentals, biomedical applications and future potential of micro-scale cavitation-a review. Lab Chip 2022; 22(12): 2237-58. [DOI: 10.1039/D2LC00169A]

[103]

Belcik JT, Mott BH, Xie A, Zhao Y, Kim S, et al. Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation. Circ Cardiovasc Imaging 2015; 8(4): e002979. [PMID: 25834183 DOI: 10.1161/CIRCIMAGING.114.002979]

[104]

Li N, Tang J, Yang J, Zhu B, Wang X, et al. Tumor perfusion enhancement by ultrasound stimulated microbubbles potentiates PD-L1 blockade of MC38 colon cancer in mice. Cancer Lett 2021; 498: 121-9. [PMID: 33129956 DOI: 10.1016/j.canlet.2020.10.046]

[105]

Tang N, Tang J, Tang J, Zhu Q, Dong X, et al. Sononeoperfusion: a new therapeutic effect to enhance tumour blood perfusion using diagnostic ultrasound and microbubbles. Cancer Imaging 2023; 23(1): 29. [PMID: 36959681 DOI: 10.1186/s40644-023-00545-y]

[106]

Yang G, Li H, Yin J, Yao L, Yang J, et al. Alleviating tumor hypoxia and immunosuppression via sononeoperfusion: a new ally for potentiating anti-PD-L1 blockade of solid tumor. Ultrason Sonochem 2025; 112: 107115. [PMID: 39482116 DOI: 10.1016/j.ultsonch.2024.107115]

[107]

Miller DL. Overview of experimental studies of biological effects of medical ultrasound caused by gas body activation and inertial cavitation. Prog Biophys Mol Biol 2007; 93(1-3): 314-30. [PMID: 16989895 DOI: 10.1016/j.pbiomolbio.2006.07.027]

[108]

Gao Y, Gao S, Zhao B, Zhao Y, Hua X, et al. Vascular effects of microbubble-enhanced, pulsed, focused ultrasound on liver blood perfusion. Ultrasound Med Biol 2012; 38(1): 91-8. [PMID: 22104531 DOI: 10.1016/j.ultrasmedbio.2011.09.018]

[109]

Mason OR, Davidson BP, Sheeran P, Muller M, Hodovan JM, et al. Augmentation of tissue perfusion in patients with peripheral artery disease using microbubble cavitation. JACC Cardiovasc Imaging 2020; 13(3): 641-51. [PMID: 31422129 DOI: 10.1016/j.jcmg.2019.06.012]

[110]

Moccetti F, Belcik T, Latifi Y, Xie A, Ozawa K, et al. Flow augmentation in the myocardium by ultrasound cavitation of microbubbles: role of shear-mediated purinergic signaling. J Am Soc Echocardiogr 2020; 3(8): 1023-31.e2. [PMID: 32532642 DOI: 10.1016/j.echo.2020.03.016]

[111]

Bulner S, Prodeus A, Gariepy J, Hynynen K, Goertz DE. Enhancing checkpoint inhibitor therapy with ultrasound stimulated microbubbles. Ultrasound Med Biol 2019; 45(2): 500-12. [PMID: 30447880 DOI: 10.1016/j.ultrasmedbio.2018.10.002]

[112]

Li C, Xiao C, Zhan L, Zhang Z, Xing J, et al. Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization. Bioact Mater 2022; 18: 399-408. [PMID: 35415302 DOI: 10.1016/j.bioactmat.2022.03.027]

[113]

Liang Y, Zhang S, Wang D, Ji P, Zhang B, et al. Dual-functional nanodroplet for tumor vasculature ultrasound imaging and tumor immunosuppressive microenvironment remodeling. Adv Healthc Mater 2024; 13(31): e2401274. [PMID: 39031111 DOI: 10.1002/adhm.202401274]

[114]

Qin H, Yu H, Sheng J, Zhang D, Shen N, et al. PI3Kgamma inhibitor attenuates immunosuppressive effect of poly(l-Glutamic Acid)-combretastatin A4 conjugate in metastatic breast cancer. Adv Sci 2019; 6(12): 1900327. [PMID: 31380170 DOI: 10.1002/advs.201900327]

[115]

Zhao B, Dong Z, Liu W, Lou F, Wang Q, et al. Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma. J Nanobiotechnology 2021; 19(1): 124. [PMID: 33933077 DOI: 10.1186/s12951-021-00865-w]

[116]

Bao X, Shen N, Lou Y, Yu H, Wang Y, et al. Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101. Theranostics 2021; 11(12): 5955-69. [PMID: 33897892 DOI: 10.7150/thno.58164]

[117]

Wang B, Zhai Y, Shi J, Zhuang L, Liu W, et al. Simultaneously overcome tumor vascular endothelium and extracellular matrix barriers via a non-destructive size-controlled nanomedicine. J Control Release 2017; 268: 225-36. [PMID: 29054372 DOI: 10.1016/j.jconrel.2017.10.029]

[118]

Bellary A, Nowak C, Iwanicki I, Flores-Guzman F, Wu L, et al. Non-viral nitric oxide-based gene therapy improves perfusion and liposomal doxorubicin sonopermeation in neuroblastoma models. Theranostics 2023; 13(10): 3402-18. [PMID: 37351172 DOI: 10.7150/thno.81700]

[119]

Shirvalilou S, Tavangari Z, Parsaei MH, Sargazi S, Sheervalilou R, et al. The future opportunities and remaining challenges in the application of nanoparticle-mediated hyperthermia combined with chemo-radiotherapy in cancer. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2023; 15(6): e1922. [PMID: 37778031 DOI: 10.1002/wnan.1922]

[120]

Xia H, Zhu J, Men C, Wang A, Mao Q, et al. Light-initiated aggregation of gold nanoparticles for synergistic chemo-photothermal tumor therapy. Nanoscale Adv 2023; 5(11): 3053-62. [PMID: 37260491 DOI: 10.1039/d3na00114h]

[121]

Xiang Y, Tang L, Pang H, Xu H, He Y, et al. Ultrasound-induced thermal effect enhances the efficacy of chemotherapy and immunotherapy in tumor treatment. Int J Nanomedicine 2024; 19: 6677-92. [PMID: 38975322 DOI: 10.2147/IJN.S464830]

[122]

Gouda MA, Janku F, Wahida A, Buschhorn L, Schneeweiss A, et al. Liquid biopsy response evaluation criteria in solid tumors (LB-RECIST). Ann Oncol 2024; 35(3): 267-75. [PMID: 38145866 DOI: 10.1016/j.annonc.2023.12.007]

[123]

Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009; 6(6): 327-38. [PMID: 19483739 DOI: 10.1038/nrclinonc.2009.63]

[124]

Huang Y, Goel S, Duda DG, Fukumura D, Jain RK. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res 2013; 73(10): 2943-8. [PMID: 23440426 DOI: 10.1158/0008-5472.CAN-12-4354]

[125]

Shrestha B, Stern NB, Zhou A, Dunn A, Porter T. Current trends in the characterization and monitoring of vascular response to cancer therapy. Cancer Imaging 2024; 24(1): 143. [PMID: 39438891 DOI: 10.1186/s40644-024-00767-8]

[126]

Aziz MU, Eisenbrey JR, Deganello A, Zahid M, Sharbidre K, et al. Microvascular flow imaging: a state-of-the-art review of clinical use and promise. Radiology 2022; 305(2): 250-64.

[127]

Yang WT, Chang J, Metreweli C. Patients with breast cancer: differences in color Doppler flow and gray-scale US features of benign and malignant axillary lymph nodes. Radiology 2000; 215(2): 568-73. [PMID: 10796941 DOI: 10.1148/radiology.215.2.r00ap20568]

[128]

Liu M, Cai L, Li Q, Chen X, Gao L, et al. The expression of VEGF and CD31 in endometrial lesions and its associations with blood flow parameters of transvaginal 3D power Doppler ultrasonography: a preliminary study. Cancer Manag Res 2020; 12: 11211-8. [PMID: 33177872 DOI: 10.2147/CMAR.S277274]

[129]

Demené C, Payen T, Dizeux A, Barrois G, Gennisson JL, et al. 3-D longitudinal imaging of tumor angiogenesis in mice in vivo using ultrafast Doppler tomography. Ultrasound Med Biol 2019; 45(5): 1284-96. [PMID: 30799125 DOI: 10.1016/j.ultrasmedbio.2018.12.010]

[130]

Mace E, Montaldo G, Osmanski BF, Cohen I, Fink M, et al. Functional ultrasound imaging of the brain: theory and basic principles. IEEE Trans Ultrason Ferroelectr Freq Control 2013; 60(3): 492-506. [PMID: 23475916 DOI: 10.1109/TUFFC.2013.2592]

[131]

Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 2000; 156(4): 1363-80. [PMID: 10751361 DOI: 10.1016/S0002-9440(10)65006-7]

[132]

Rix A, Piepenbrock M, Flege B, von Stillfried S, Koczera P, et al. Effects of contrast-enhanced ultrasound treatment on neoadjuvant chemotherapy in breast cancer. Theranostics 2021; 11(19): 9557-70. [PMID: 34646386 DOI: 10.7150/thno.64767]

[133]

Schutt EG, Klein DH, Mattrey RM, Riess JG. Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals. Angew Chem Int Ed Engl 2003; 42(28): 3218-35. [PMID: 12876730 DOI: 10.1002/anie.200200550]

[134]

Leong-Poi H. Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy. Cardiovasc Res 2009; 84(2): 190-200. [PMID: 19628466 DOI: 10.1093/cvr/cvp248]

[135]

Zhang G, Ye HR, Sun Y, Guo ZZ. Ultrasound molecular imaging and its applications in cancer diagnosis and therapy. ACS Sens 2022; 7(10): 2857-64. [PMID: 36190830 DOI: 10.1021/acssensors.2c01468]

[136]

Caremani M, Benci A, Lapini L, Tacconi D, Caremani A, et al. Contrast enhanced ultrasonography (CEUS) in peripheral lung lesions: a study of 60 cases. J Ultrasound 2008; 11(3): 89-96. [PMID: 23397023 DOI: 10.1016/j.jus.2008.05.008]

[137]

Wang Y, Li L, Wang YX, Cui NY, Zou SM, et al. Time-intensity curve parameters in rectal cancer measured using endorectal ultrasonography with sterile coupling gels filling the rectum: correlations with tumor angiogenesis and clinicopathological features. Biomed Res Int 2014; 2014(1): 587806. [PMID: 24900973 DOI: 10.1155/2014/587806]

[138]

Cartana ET, Gheonea DI, Cherciu IF, Streaţa I, Uscatu CD, et al. Assessing tumor angiogenesis in colorectal cancer by quantitative contrast-enhanced endoscopic ultrasound and molecular and immunohistochemical analysis. Endosc Ultrasound 2018; 7(3): 175-83. [PMID: 28685747 DOI: 10.4103/eus.eus_7_17]

[139]

Malmstrøm ML, Săftoiu A, Riis LB, Hassan H, Klausen TW, et al. Dynamic contrast-enhanced EUS for quantification of tumor perfusion in colonic cancer: a prospective cohort study. Gastrointest Endosc 2018; 87(6): 1530-8. [PMID: 29329991 DOI: 10.1016/j.gie.2018.01.001]

[140]

Ntoulia A, Anupindi SA, Darge K, Back SJ. Applications of contrast-enhanced ultrasound in the pediatric abdomen. Abdom Radiol 2018; 43(4): 948-59. [PMID: 28980061 DOI: 10.1007/s00261-017-1315-0]

[141]

Santiesteban DY, Hallam KA, Yarmoska SK, Emelianov SY. Color-coded perfluorocarbon nanodroplets for multiplexed ultrasound and Photoacoustic imaging. Nano Res 2019; 12(4): 741-7. [PMID: 31572565 DOI: 10.1007/s12274-019-2279-x]

[142]

Laumer F, Di Vece D, Cammann VL, Würdinger M, Petkova V, et al. Assessment of artificial intelligence in echocardiography diagnostics in differentiating takotsubo syndrome from myocardial infarction. JAMA Cardiol 2022; 7(5): 494-503. [PMID: 35353118 DOI: 10.1001/jamacardio.2022.0183]

[143]

Chen ZY, Wang YX, Lin Y, Zhang JS, Yang F, et al. Advance of molecular imaging technology and targeted imaging agent in imaging and therapy. Biomed Res Int 2014; 2014(1): 819324. [PMID: 24689058 DOI: 10.1155/2014/819324]

[144]

Verger A, Grimaldi S, Ribeiro MJ, Frismand S, Guedj E. Single photon emission computed tomography/positron emission tomography molecular imaging for parkinsonism: a fast-developing field. Ann Neurol 2021; 90(5): 711-9. [PMID: 34338333 DOI: 10.1002/ana.26187]

[145]

Siddiqui S, Kadlecek S, Pourfathi M, Xin Y, Mannherz W, et al. The use of hyperpolarized carbon-13 magnetic resonance for molecular imaging. Adv Drug Deliv Rev 2017; 113: 3-23. [PMID: 27599979 DOI: 10.1016/j.addr.2016.08.011]

[146]

Zhang H, Tam S, Ingham ES, Mahakian LM, Lai CY, et al. Ultrasound molecular imaging of tumor angiogenesis with a neuropilin-1-targeted microbubble. Biomaterials 2015; 56: 104-13. [PMID: 25934284 DOI: 10.1016/j.biomaterials.2015.03.043]

[147]

Wang J, Wang Y, Zhong L, Yan F, Zheng H. Nanoscale contrast agents: a promising tool for ultrasound imaging and therapy. Adv Drug Deliv Rev 2024; 207: 115200. [PMID: 38364906 DOI: 10.1016/j.addr.2024.115200]

[148]

Seol SH, Lindner JR. A primer on the methods and applications for contrast echocardiography in clinical imaging. J Cardiovasc Ultrasound 2014; 22(3): 101-10. [PMID: 25309685 DOI: 10.4250/jcu.2014.22.3.101]

[149]

Wang S, Hossack JA, Klibanov AL. Targeting of microbubbles: contrast agents for ultrasound molecular imaging. J Drug Target 2018; 26(5-6): 420-34. [PMID: 29258335 DOI: 10.1080/1061186X.2017.1419362]

[150]

Reinhardt M, Hauff P, Briel A, Uhlendorf V, Linker RA, et al. Sensitive particle acoustic quantification (SPAQ): a new ultrasound-based approach for the quantification of ultrasound contrast media in high concentrations. Invest Radiol 2005; 40(1): 2-7. [PMID: 15597013]

[151]

El Kaffas A, Sigrist RMS, Fisher G, Bachawal S, Liau J, et al. Quantitative three-dimensional dynamic contrast-enhanced ultrasound imaging: first-in-human pilot study in patients with liver metastases. Theranostics 2017; 7(15): 3745-58. [PMID: 29109773 DOI: 10.7150/thno.20329]

[152]

Fournier L, de La Taille T, Chauvierre C. Microbubbles for human diagnosis and therapy. Biomaterials 2023; 294: 122025. [PMID: 36716588 DOI: 10.1016/j.biomaterials.2023.122025]

[153]

Smeenge M, Tranquart F, Mannaerts CK, de Reijke TM, van de Vijver MJ, et al. First-in-human ultrasound molecular imaging with a VEGFR2-specific ultrasound molecular contrast agent (BR55) in prostate cancer: a safety and feasibility pilot study. Invest Radiol 2017; 52(7): 419-27. [PMID: 28257340 DOI: 10.1097/RLI.0000000000000362]

[154]

Willmann JK, Bonomo L, Testa AC, Rinaldi P, Rindi G, et al. Ultrasound molecular imaging with BR55 in patients with breast and ovarian lesions: first-in-human results. J Clin Oncol 2017; 35(19): 2133-40. [PMID: 28291391 DOI: 10.1200/JCO.2016.70.8594]

[155]

Willmann JK, Paulmurugan R, Chen K, Gheysens O, Rodriguez-Porcel M, et al. US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology 2008; 246(2): 508-18. [PMID: 18180339 DOI: 10.1148/radiol.2462070536]

[156]

John R, Nguyen FT, Kolbeck KJ, Chaney EJ, Marjanovic M, et al. Targeted multifunctional multimodal protein-shell microspheres as cancer imaging contrast agents. Mol Imaging Biol 2012; 14(1): 17-24. [PMID: 21298354 DOI: 10.1007/s11307-011-0473-7]

[157]

Fan CH, Cheng YH, Ting CY, Ho YJ, Hsu PH, et al. Ultrasound/magnetic targeting with SPIO-DOX-microbubble complex for image-guided drug delivery in brain tumors. Theranostics 2016; 6(10): 1542-56. [PMID: 27446489 DOI: 10.7150/thno.15297]

[158]

Li X, Xing L, Zheng K, Wei P, Du L, et al. Formation of gold nanostar-coated hollow mesoporous silica for tumor multimodality imaging and photothermal therapy. ACS Appl Mater Interfaces 2017; 9(7): 5817-27. [PMID: 28118704 DOI: 10.1021/acsami.6b15185]

[159]

Zhao F, Unnikrishnan S, Herbst EB, Klibanov AL, Mauldin FW Jr, et al. A targeted molecular localization imaging method applied to tumor microvasculature. Invest Radiol 2021; 56(4): 197-206. [PMID: 32976207 DOI: 10.1097/RLI.0000000000000728]

[160]

Ilovitsh T, Ilovitsh A, Foiret J, Fite BZ, Ferrara KW. Acoustical structured illumination for super-resolution ultrasound imaging. Commun Biol 2018; 1(1): 3. [DOI: 10.1038/s42003-017-0003-5]

[161]

Christensen-Jeffries K, Couture O, Dayton PA, Eldar YC, Hynynen K, et al. Super-resolution ultrasound imaging. Ultrasound Med Biol 2020; 46(4): 865-91. [PMID: 31973952 DOI: 10.1016/j.ultrasmedbio.2019.11.013]

[162]

Couture O, Bannouf S, Montaldo G, Aubry JF, Fink M, et al. Ultrafast imaging of ultrasound contrast agents. Ultrasound Med Biol 2009; 35(11): 1908-16. [PMID: 19699026 DOI: 10.1016/j.ultrasmedbio.2009.05.020]

[163]

Couture O, Fink M, Tanter M. Ultrasound contrast plane wave imaging. IEEE Trans Ultrason Ferroelectr Freq Control 2012; 59(12): 2676-83. [PMID: 23221216 DOI: 10.1109/TUFFC.2012.2508]

[164]

Viessmann OM, Eckersley RJ, Christensen-Jeffries K, Tang MX, Dunsby C. Acoustic super-resolution with ultrasound and microbubbles. Phys Med Biol 2013; 58(18): 6447- 58. [PMID: 23999099 DOI: 10.1088/0031-9155/58/18/6447]

[165]

Ghosh D, Xiong F, Sirsi SR, Mattrey R, Brekken R, et al. Monitoring early tumor response to vascular targeted therapy using super-resolution ultrasound imaging. Washington, DC, USA: IEEE International Ultrasonics Symposium (IUS); 2017. [DOI: 10.1109/ULTSYM.2017.8092944]

[166]

Kollmann C, Jenderka KV, Moran CM, Draghi F, Jimenez Diaz JF, et al. EFSUMB clinical safety statement for diagnostic ultrasound - (2019 revision). Ultraschall Med 2020; 41(4): 387-9. [PMID: 31594007 DOI: 10.1055/a-1010-6018]

[167]

Ternifi R, Wang Y, Gu J, Polley EC, Carter JM, et al. Ultrasound high-definition microvasculature imaging with novel quantitative biomarkers improves breast cancer detection accuracy. Eur Radiol 2022; 32(11): 7448-62. [PMID: 35486168 DOI: 10.1007/s00330-022-08815-2]

[168]

Sabeti S, Ternifi R, Larson NB, Olson MC, Atwell TD, et al. Morphometric analysis of tumor microvessels for detection of hepatocellular carcinoma using contrast-free ultrasound imaging: a feasibility study. Front Oncol 2023; 13: 1121664. [PMID: 37124492 DOI: 10.3389/fonc.2023.1121664]

[169]

Adusei SA, Sabeti S, Larson NB, Dalvin LA, Fatemi M, et al. Quantitative biomarkers derived from a novel, contrast-free ultrasound, high-definition microvessel imaging for differentiating choroidal tumors. Cancers 2024; 16(2): 395. [PMID: 38254884 DOI: 10.3390/cancers16020395]

[170]

Sabeti S, Larson NB, Boughey JC, Stan DL, Solanki MH, et al. Ultrasound-based quantitative microvasculature imaging for early prediction of response to neoadjuvant chemotherapy in patients with breast cancer. Breast Cancer Res 2025; 27(1): 24. [PMID: 39962614 DOI: 10.1186/s13058-025-01978-y]

[171]

Mendiratta-Lala M, Wiggermann P, Pech M, Serres-Créixams X, White SB, et al. The #HOPE4LIVER single-arm pivotal trial for histotripsy of primary and metastatic liver tumors. Radiology 2024; 312(3): e233051. [PMID: 39225612 DOI: 10.1148/radiol.233051]

[172]

Wu F, Wang ZB, Cao YD, Chen WZ, Bai J, et al. A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer. Br J Cancer 2003; 89(12): 2227-33. [PMID: 14676799 DOI: 10.1038/sj.bjc.6601411]

[173]

Zhu XQ, Lu P, Xu ZL, Zhou Q, Zhang J, et al. Alterations in immune response profile of tumor-draining lymph nodes after high-intensity focused ultrasound ablation of breast cancer patients. Cells 2021; 10(12): 3346. [PMID: 34943854 DOI: 10.3390/cells10123346]

[174]

Lee JY, Chung HH, Kang SY, Park EJ, Park DH, et al. Portable ultrasound-guided high-intensity focused ultrasound with functions for safe and rapid ablation: prospective clinical trial for uterine fibroids-short-term and long-term results. Eur Radiol 2020; 30(3): 1554-63. [PMID: 31705252 DOI: 10.1007/s00330-019-06468-2]

[175]

Chen X, Gole J, Gore A, He Q, Lu M, et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nat Commun 2020; 11(1): 3475. [PMID: 32694610 DOI: 10.1038/s41467-020-17316-z]

[176]

Bogers HA, Sedelaar JP, Beerlage HP, de la Rosette JJ, Debruyne FM, et al. Contrast-enhanced three-dimensional power Doppler angiography of the human prostate: correlation with biopsy outcome. Urology 1999; 54(1): 97-104. [PMID: 10414734 DOI: 10.1016/s0090-4295(99)00040-0]

[177]

Görges R, Eising EG, Fotescu D, Renzing-Köhler K, Frilling A, et al. Diagnostic value of high-resolution B-mode and power-mode sonography in the follow-up of thyroid cancer. Eur J Ultrasound. 2003; 16(3): 191-206. [PMID: 12573788 DOI: 10.1016/s0929-8266(02)00073-3]

[178]

Kabil Kucur S, Temizkan O, Atis A, Gozukara I, Uludag EU, et al. Role of endometrial power Doppler ultrasound using the international endometrial tumor analysis group classification in predicting intrauterine pathology. Arch Gynecol Obstet 2013; 288(3): 649-54. [PMID: 23529686 DOI: 10.1007/s00404-013-2813-0]

[179]

Chen M, Wang WP, Jia WR, Tang L, Wang Y, et al. Three-dimensional contrast-enhanced sonography in the assessment of breast tumor angiogenesis: correlation with microvessel density and vascular endothelial growth factor expression. J Ultrasound Med 2014; 33(5): 835-46. [PMID: 24764339 DOI: 10.7863/ultra.33.5.835]

[180]

Hoyt K, Umphrey H, Lockhart M, Robbin M, Forero-Torres A. Ultrasound imaging of breast tumor perfusion and neovascular morphology. Ultrasound Med Biol 2015; 41(9): 2292-302. [PMID: 26116159 DOI: 10.1016/j.ultrasmedbio.2015.04.016]

[181]

Bezircioglu I, Baloglu A, Tarhan MO, Oziz E, Yigit S. Evaluation of endometrium by transvaginal ultrasonography and Doppler in tamoxifen-treated women with breast cancer. Eur J Gynaecol Oncol 2012; 33(3): 295-9. [PMID: 22873103 DOI: 10.12892/ejgo201203295]

[182]

Pochon S, Tardy I, Bussat P, Bettinger T, Brochot J, et al. BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol 2010; 45(2): 89-95. [PMID: 20027118 DOI: 10.1097/RLI.0b013e3181c5927c]

[183]

Baetke SC, Rix A, Tranquart F, Schneider R, Lammers T, et al. Squamous cell carcinoma xenografts: use of VEGFR2-targeted microbubbles for combined functional and molecular US to monitor antiangiogenic therapy effects. Radiology 2016; 278(2): 430-40. [PMID: 26313618 DOI: 10.1148/radiol.2015142899]

[184]

Helbert A, Von Wronski M, Colevret D, Botteron C, Padilla F, et al. Ultrasound molecular imaging with BR55, a predictive tool of antiangiogenic treatment efficacy in a chemo-induced mammary tumor model. Invest Radiol 2020; 55(10): 657-65. [PMID: 32229739 DOI: 10.1097/RLI.0000000000000661]

[185]

Qiu C, Sha T, Yin T, Zhang W, Chen X, et al. VEGFR2-targeted ultrasound molecular imaging of angiogenesis to evaluate liver allograft fibrosis. Biomater Sci 2021; 9(17): 5802-11. [PMID: 34008615 DOI: 10.1039/d1bm00100k]

PDF (6762KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/