Faculty & Staff
Xucai Chen, PhD
Research Associate Professor of Medicine, University of Pittsburgh School of Medicine
UPMC Heart and Vascular Institute
Peer Reviewed Articles
1. Chen X, Schwarz KQ, Parker KJ. Radiation pattern of a focused transducer: A numerically convergent solution. J Acoust Soc Am 1993;94(5):2979-2991.
2. Harpaz D, Chen X, Francis CW, Marder VJ, Meltzer RS. Ultrasound enhancement of fibrinolysis and reperfusion in vitro. J Am Coll Cardiol 1993;21(6):1507-1511.
3. Schwarz KQ, Bezante GP, Chen X, Mottley JG, Schlief R. Volumetric arterial flow quantification using echo contrast agent. An in vitro comparison of three ultrasonic intensity methods: radio frequency, video and Doppler. Ultrasound Med Biol 1993;19(6):447-460.
4. Schwarz KQ, Bezante GP, Chen X, Schlief R. Quantitative echo contrast measurement by Doppler sonography. Ultrasound Med Biol 1993;19(4):289-297.
5. Brayman AA, Azadniv M, Miller MW, Chen X. Bubble recycling and bubble translational velocities in a stationary exposure vessel. J Acoust Soc Am 1994;96(2):627-633.
6. Chen X, Schwarz KQ, Parker KJ. Acoustic coupling from a focused transducer to a flat plate and back to the transducer. J Acoust Soc Am 1994;95(6):3049-3054.
7. Harpaz D, Chen X, Francis CW, Meltzer RS. Ultrasound accelerates urokinase induced thrombolysis and reperfusion. Am Heart J 1994;127(5):1211-1219.
8. Schwarz KQ, Bezante GP, Chen X. When can Doppler be used in place of integrated backscatter as a measure of scattered ultrasound intensity? Ultrasound Med Biol 1995;21(2):231-242.
9. Chen X, Apfel RE. Radiation force on a spherical object in an axi-symmetric wave field and its application to the calibration of high frequency transducers. J Acoust Soc Am 1996;99(2):713-724.
10. Schwarz KQ, Bezante GP, Chen X, Phillips D, Schlief R. Hemodynamic effects of microbubble echo contrast. J Am Soc Echo 1996;9(6):795-804.
11. Schwarz KQ, Chen X, Bezante GP, Phillips D, Schlief R. The Doppler kinetics of microbubble echo contrast agents. Ultrasound Med Biol 1996;22(4):453-462.
12. Chen X, Apfel RE. Radiation force on a spherical object in the field of a focused transducer. J Acoust Soc Am 1997;101(5):2442-2447.
13. Chen X, Phillips D, Schwarz KQ, Mottley JG, Parker KJ. The measurement of backscatter coefficient from pulse-echo measurements: a new formulation. IEEE Trans Ultrason Ferroelectr Freq Control 1997;44(2):515-525. doi: 10.1109/58.585136.
14. Schwarz KQ, Chen X, Steinmetz S, Phillips D. Harmonic imaging with Levovist. J Am Soc Echo 1997;10(1):1-10.
15. Chen X, Schwarz KQ, Phillips D, Steinmetz S, Schlief R. A mathematical model for the assessment of hemodynamic parameters using quantitative contrast echocardiography. IEEE Trans Biomed Eng 1998;45(6):754-765.
16. Phillips D, Chen X, Baggs R, Rubens D, Violante M, Parker KJ. The Particle/Bubble ultrasound contrast agent. Ultrasonics 1998;36(8):883-892.
17. Schwarz KQ, Chen X, Steinmetz S. Methods for quantifying ultrasound backscatter and 2D video intensity: Implications for contrast enhanced sonography. J Am Soc Echo 1998;11(2):155-168.
18. Schwarz KQ, Bezante GB, Chen X, Villa G, Brunelli C. Contrast harmonic color Doppler left ventriculography: Machine-interpreted left ventricular ejection fraction compared with equilibrium-gated radionuclide ventriculography. J Am Soc Echo 2000;13(5):368-78.
19. Gudavalli A, Kalaria VG, Chen X, Schwarz KQ. Intrapulmonary arteriovenous shunt: Diagnosis by saline contrast bubbles in the pulmonary veins. J Am Soc Echo 2002;15:1012-4. doi: 10.1067/mje.2002.121435.
20. Yokoyama N, Schwarz KQ, Chen X, Steinmetz S, Becher H, Schimpky C, Schlief R. The effect of echo contrast agent on Doppler velocity measurements. Ultrasound Med Biol 2003;29(5):765-770.
21. Yokoyama N, Schwarz KQ, Steinmetz S, Li X, Chen X. Prognostic value of contrast stress echocardiography in patients with image quality too limited for traditional non-contrast harmonic echocardiography. J Am Soc Echo 2004;17(1):15-20. doi: 10.1016/j.echo.2003.09.008.
22. Bezante GP, Chen X, Molinari G, Valbusa A, Deferrari L, Sebastiani V, Yokoyama N, Steinmetz S, Barsotti A, Schwarz KQ. Left ventricular myocardial mass determination by contrast enhanced colour Doppler compared with magnetic resonance imaging. Heart 2005;91(1):38-43. doi: 10.1136/hrt.2003.023234.
23. Bezante GP, Rosa GM, Bruni R, Chen X, Villa G, Scopinaro A, Balbi M, Barsotti A, Schwarz KQ. Improved assessment of left ventricular volumes and ejection fraction by contrast enhanced harmonic color Doppler echocardiography. Int J Cardiovas Imaging 2005;21(6):609-616.
24. Schwarz KQ, Parikh SS, Chen X, Farrar DJ, Steinmetz S, Ramamurthi S, Hallinan W, Massey T, Chen L. Non-invasive flow measurement of a rotary pump ventricular assist device using quantitative contrast echocardiography – an in-vitro evaluation. J Am Soc Echo 2010;23(3):324-329. doi: 10.1016/j.echo.2009.12.005.
25. Carson AR, McTieman CF, Lavery L, Hodnick A, Grata M, Leng X, Wang J, Chen X, Modzelewski RA, Villanueva FS. Gene therapy of carcinoma using ultrasound-targeted microbubble destruction. Ultrasound Med Biol 2011;37(3):393-402. doi: 10.1016/j.ultrasmedbio.2010.11.011. PMID: 21256666; PMC4111473.
26. Moguillansky D, Leng X, Carson A, Lavery L, Schwartz A, Chen X, Villanueva FS. Quantification of plaque neovascularization using contrast ultrasound: a histologic validation. Eur Heart J 2011;32(5):646-653. doi: 10.1093/eurheartj/ehq197. PMID: 20581005; PMCID: PMC3046374.
27. Toma C, Fisher A, Wang J, Chen X, Grata M, Winston B, Leeman J, Kaya M, Fu H, Lavery L, Fischer D, Wagner W, Villanueva FS. Vascular endoluminal delivery of stem cells using acoustic radiation force. Tissue Eng Part A 2011;17(9-10):1457-1464. doi: 10.1089/ten.TEA.2010.0539. PMID: 21247343 PMCID: PMC3079165.
28. Kim JS, Leeman JE, Kagemann L, Yu FTH, Chen X, Pacella JJ, Schuman JS, Villanueva FS, Kim K. Volumetric quantification of in vitro sonothrombolysis with microbubbles using high-resolution optical coherence tomography. J Biomed Opt 2012;17(7):070502. doi: 10.1117/1.JBO.17.7.070502. PMID:22894458.
29. Leeman JE, Kim JS, Yu F, Chen X, Kim K, Wang J, Villanueva FS, Pacella JJ. Effect of acoustic conditions on microbubble-mediated microvascular sonothrombolysis. Ultrasound Med Biol 2012;38(9):1589-1598. doi: 10.1016/j.ultrasmedbio.2012.05.020. PMID: 22766112.
30. Kaya M, Toma C, Wang J, Grata M, Fu H, Villanueva FS, Chen X. Acoustic radiation force for vascular cell therapy: In vitro validation. Ultrasound Med Biol 2012;38(11):1989-1997. doi: 10.1016/j.ultrasmedbio.2012.07.019. PMID: 22975034; PMCID: PMC3471247.
31. Carson AR, McTiernan CF, Lavery L, Grata M, Leng X, Wang J, Chen X, Villanueva FS. Ultrasound-targeted microbubble destruction to deliver siRNA. Cancer Research 2012;72:6191-6199. doi: 10.1158/0008-5472.CAN-11-4079. PMID: 23010078; PMCID: PMC3654825.
32. Wexler O, Morgan MM, Gough MS, Steinmetz SD, Mack CM, Darling DC, Doolin KP, Apostolakos MJ, Graves BT, Frampton MW, Chen X, Pietropaoli AP. Brachial artery reactivity in patients with severe sepsis: an observational study. Crit Care 2012;16(2):R38. doi: 10.1186/cc11223. PMID: 22390813; PMCID:PMC3568781.
33. Chen X, Wang J, Versluis M, de Jong N, Villanueva FS. Ultra-fast bright-field and fluorescence imaging of the dynamics of micrometer-sized objects. Rev Sci Instrum 2013;84(6):063701. doi: 10.1063/1.4809168. PMID: 23822346; PMCID: PMC4108723.
34. Stephens D, Mahmoud A, Ding X, Lucero S, Dutta D, Yu F, Chen X, Kim K. Flexible integration of both high imaging resolution and high power arrays for ultrasound-induced thermal strain imaging (US-TSI). IEEE Trans Ultrason Ferroelectr Freq Control 2013;60(12):2645-56. doi: 10.1109/TUFFC.2013.2863. PMID: 24297029; PMCID: PMC3857565.
35. Chen X, Leeman JE, Wang J, Pacella JJ, Villanueva FS. New insights into mechanisms of sonothrombolysis using ultra high speed imaging. Ultrasound Med Biol 2014;40(1):258-62. Epub 2013 Oct 18. doi: 10.1016/j.ultrasmedbio.2013.08.021. PMID: 24139920.
36. Leng X, Wang J, Carson A, Chen X, Fu H, Ottoboni S, Wagner WR, Villanueva FS. Ultrasound detection of myocardial ischemic memory using an E-selectin targeting peptide amenable to human application. Mol Imaging 2014;13(4):1-9. doi: 10.2310/7290.2014.00006. PMID: 24824960.
37. Yu Francois, Villanueva FS, Chen X. Radial modulation contrast imaging using a 20-MHz single-element intravascular ultrasound catheter. IEEE Trans Ultrason Ferroelectr Freq Control 2014;61(5):779-791. doi: 10.1109/TUFFC.2014.2970. PMID:24803134; PMCID: PMC4094374.
38. Pacella JJ, Brands J, Schnatz F, Black JJ, Chen X, Villanueva FS. Treatment of microvascular micro-embolization using microbubbles and long-tone-burst ultrasound: an in vivo study. Ultrasound Med Biol 2015;41:456-464. Epub 2014 Dec 23. doi: 10.1016/j.ultrasmedbio.2014.09.033. PMID: 25542487.
39. Kopechek JA, Carson AR, McTiernan CF, Chen X, Hasjim B, Lavery L, Sen M, Grandis JR, Villanueva FS. Ultrasound targeted microbubble destruction-mediated delivery of a transcription factor decoy inhibits STAT3 signaling and tumor growth. Theranostics 2015;5(12):1378-1387. Epub 2014 Dec 23. doi: 10.7150/thno.12822. PMID: 25542487.
40. Helfield B, Chen X, Qin B, Villanueva FS. Individual lipid encapsulated microbubble radial oscillations: Effects of fluid viscosity. J Acoust Soc Am 2016;139(1):204-214. Epub 2016 January 11. doi: 10.1121/1.4939123. PMID: 26827018.
41. Yu FTH, Chen X, Wang J, Qin B, Panday R, Villanueva FS. Low intensity ultrasound mediated liposomal doxorubicin delivery using polymer microbubbles. Mol Pharmaceutics 2016;13(1):55-64. Epub 2015 Nov 15. doi: 10.1021/acs.molpharmaceut.5b00421. PMID: 26567985.
42. Chen X, Wang J, Pacella JJ, Villanueva FS. Dynamic behavior of microbubbles during long ultrasound tone-burst excitation: mechanistic insights into ultrasound-microbubble mediated therapeutics using high-speed imaging and cavitation detection. Ultrasound Med Biol 2016;42(2):528-538. Epub 2015 Nov 18. doi: 10.1016/j.ultrasmedbio.2015.09.017. PMID: 26603628.
43. Helfield B, Black JJ, Qin B, Pacella J, Chen X, Villanueva FS. Fluid viscosity affects the fragmentation and inertial cavitation threshold of lipid encapsulated microbubbles. Ultrasound Med Biol 2016;42(3):782-794. Epub 2015 Dec 7. doi: 10.1016/j.ultrasmedbio.2015.10.023. PMID: 26674676.
44. Kopechek JA, Carson AR, McTiernan CF, Chen X, Klein EC, Villanueva FS. Cardiac gene expression knockdown using small inhibitory RNA-loaded microbubbles and ultrasound. PLoS ONE 2016;11(7):e0159751. doi: 10.1371/journal.pone.0159751. PMID: 27471848.
45. Black JJ, Yu FTH, Schnatz RG, Chen X, Villanueva FS, Pacella JJ. Effect of thrombus composition and viscosity on sonoreperfusion efficacy in a model of microvascular obstruction. Ultrasound Med Biol 2016;42(9):2220-2231. Epub 2016 May 17. doi: 10.1016/j.ultrasmedbio.2016.04.004. PMID: 27207018.
46. Helfield B, Chen X, Watkins S, Villanueva FS. Biophysical insight into mechanisms of sonoporation. Proc Natl Acad Sci USA 2016;113(36):9983-9988. EPub 2016 August 22. doi: 10.1073/pnas.1606915113. PMID: 27551081.
47. Roos ST, Yu FT, Kamp O, Chen X, Villanueva FS, Pacella JJ. Sonoreperfusion therapy kinetics in whole blood using ultrasound, microbubbles and tPA. Ultrasound Med Biol 2016;42(12):3001-3009. Epub 2016 Sep 26. doi: 10.1016/j.ultrasmedbio.2016.08.013. PMID: 27687734.
48. Yu J, Chen X, Villanueva FS, Kim K. Vaporization and recondensation dynamics of indocyanine green-loaded perfluoropentane droplets irradiated by a short pulse laser. Appl Phys Lett 2016;109(24):243701. Epub 2016 Dec 16. doi: 10.1063/1.4972184.
49. Wang J, Qin B, Chen X, Wagner WR, Villanueva FS. Ultrasound molecular imaging of angiogenesis using vascular endothelial growth factor-conjugated microbubbles. Mol Pharmaceutics 2017;14(3):781–790. Epub 2017 Feb 6. doi: 10.1021/acs.molpharmaceut.6b01033.
50. Goyal A, Yu FTH, Tenwalde MG, Chen X, Althouse A, Villanueva FS, Pacella JJ. Inertial cavitation ultrasound with microbubbles improves reperfusion efficacy when combined with tPA in an in vitro model of microvascular obstruction. Ultrasound Med Biol 2017;43(7):1391-1400. Epub 2017 Apr 7. doi: 10.1016/j.ultrasmedbio.2017.02.013.
51. Kooiman K, van Rooij T, Qin B, Mastik F, Vos HJ, Versluis M, Klibanov AL, de Jong N, Villanueva FS, Chen X. Focal areas of increased lipid concentration on the coating of microbubbles during short tone-burst ultrasound insonification. PLoS One 2017;12(7):e0180747. doi: 10.1371/journal.pone.0180747.
52. Yu FTH, Chen X, Straub A, Pacella JJ. The role of nitric oxide during sonoreperfusion of microvascular obstruction. Theranostics 2017;7(14):3527-3538. Epub 2017 Aug 18. doi: 10.7150/thno.19422.
53. Helfield B, Chen X, Qin B, Watkins SC, Villanueva FS.Mechanistic insight into sonoporation with ultrasound-stimulated polymer microbubbles. Ultrasound Med Biol 2017;43(11):2678-2689. Epub 2017 Aug 25. doi: 10.1016/j.ultrasmedbio.2017.07.017.
54. Kopechek JK, McTiernan CF, Chen X, Zhu J, Mburu M, Feroze R, Whitehurst DA, Lavery L, Cyriac J, Villanueva FS. Ultrasound and microbubble-targeted delivery of a microRNA inhibitor to the heart suppresses cardiac hypertrophy and preserves cardiac function. Theranostics 2019;9(23):7088-7098. doi: 10.7150/thno.34895. eCollection 2019. PMID: 31660088; PMCID: PMC6815962.
55. Yu GZ, Istvanic F, Chen X, Nouraie M, Shiva S, Straub AC, Pacella JJ. Ultrasound-targeted microbubble cavitation with sodium nitrite synergistically enhances nitric oxide production and microvascular perfusion. Ultrasound Med Biol 2020;46(3):667-678. Epub 2019 Dec 3. doi: 10.1016/j.ultrasmedbio.2019.10.012. PMID: 31810801; PMCID: PMC7010556.
56. Istvanic F, Yu G, Yu FTH, Chen X, Pacella JJ. Sonoreperfusion therapy for microvascular obstruction: A step toward clinical translation. Ultrasound Med Biol 2020;46(3):712-720. Epub 2020 Jan 7. doi: 10.1016/j.ultrasmedbio.2019.11.011. PMID: 31924423; PMCID: PMC7010545.
57. Helfield B, Chen X, Watkins SC, Villanueva FS. Transendothelial perforations and the sphere of influence of single-site sonoporation. Ultrasound Med Biol 2020;46(7):1686-1697. Epub 2020 May 10. doi: 10.1016/j.ultrasmedbio.2020.02.017. PMID: 32402675; PMCID: PMC7293920.
58. Ramasamy T, Chen X, Qin B, Johnson DE, Grandis JR, Villanueva FS. STAT3 decoy oligonucleotide-carrying microbubbles with pulsed ultrasound for enhanced therapeutic effect in head and neck tumors. PLoS One 2020 Nov 18;15(11):e0242264. doi: 10.1371/journal.pone.0242264. eCollection 2020. PMID: 33206698; PMCID: PMC7673576.
59. Khalid WB, Chen X, Kim K. Multifous thermal strain imaging using a curved linear array transducer for identification of lipids in tissue. Ultrasound Med Biol 2021;47(7):1711-1724. doi: 10.1016/j.ultrasmedbio.2021.03.005.
60. Yu GZ, Ramasamy T, Fazzari M, Chen X, Freeman B, Pacella JJ. Lipid nitroalkene nanoparticles for the focal treatment of ischemia reperfusion. Nanotheranostics 2022;6(2):215–229. doi: 10.7150/ntno.62351. PMID: 34976596; PMCID: PMC8671954.
61. van Wamel A, Mühlenpfordt M, Hansen R, Healey A, Villanueva FS, Kotopoulis S, Davies CL, Chen X. Ultrafast microscopy imaging of Acoustic Cluster Therapy bubbles: activation and oscillation. Ultrasound Med Biol 2022 Sep;48(9):1840-1857. Epub 2022 Jun 27. doi: 10.1016/j.ultrasmedbio.2022.05.009. PMID: 35773079.
62. Zeng P, Chen C, Lof J, Stolze E, Li S, Chen X, Pacella JJ, Villanueva FS, Matsunaga T, Everbach EC, Xie F, Porter T. Acoustic detection of retained perfluoropropane droplets within the developing myocardial infarct zone. Ultrasound Med Biol 2022 Nov;48(11):2322-2334. Epub 2022 August 30. doi: 10.1016/j.ultrasmedbio.2022.07.005.
63. Yu FTH, Amjad MW, Mohammed SA, Yu GZ, Chen X, Pacella JJ. The effect of ultrasound pulse length on sonoreperfusion therapy. Ultrasound Med Biol 2023 Jan;49(1):152-164. doi: 10.1016/j.ultrasmedbio.2022.08.009. Epub 2022 Oct 15. PMID: 36253230.
64. Chen X, Chen X, Yu FTH, Villanueva FS, Pacella JJ. Dynamic behavior of polymer microbubbles during long ultrasound tone-burst excitation and its application for sonoreperfusion therapy. Ultrasound Med Biol (in press). doi: 10.1016/j.ultrasmedbio.2022.12.013.
Book Chapters, Editorials, and Review Articles
1. Schwarz KQ, Chen X, Bezante GP. Quantitative Doppler Intensitometry, in Advances in Echo Imaging Using Contrast Enhancement (eds. Nanda NC, Schlief R, and Goldberg BB), Kluwer Academic Publishers, Netherlands. 1993;pp. 187-206.
2. Phillips D, Chen X, Baggs R, Rubens D, Violante M, Parker KJ. The Particle/Bubble Ultrasound Contrast Agent, in Ultrasound Contrast Agents (ed. Goldberg BB), Martin Dunitz Publishers, London. 1996;pp. 149-158.
3. Villanueva FS, Chen X. Complex Highways on the Translational Roadmap for Therapeutic Ultrasound-Targeted Microbubble Cavitation: Where Are We Now? JACC Cardiovasc Imaging 2020 Mar;13(3):652-654. Epub 2019 Oct 11. doi: 10.1016/j.jcmg.2019.08.010. PMID: 31607657.
4. Istvanic F, Yu G, Chen X, Pacella JJ. Sonoreperfusion Therapy for Microvascular Obstruction: A Review. J Clin Cardiol 2021;2(4):81-87.
Patents
1. Toma C, Villanueva FS, Wagner WR, Lee JS, Wang J, Chen X, Fischer A. Directed cell-based therapy using microbubble tagged cells. US Patent 8,460,269 issued June 11, 2013.
2. Wang J, Villanueva FS, Chen X, Fisher A, Wagner WR. Intracellular microbubble for imaging an anatomical site. US Patent 8,940,277 issued January 27, 2015.
3. Chen X, Yu F, Villanueva FS. Method and device for contrast assisted intravascular ultrasound imaging. US Patent 9,603,582 issued March 28, 2017.
4. Chen X, Wang J, Pacella J, Villanueva FS. Method and device for ultrasound contrast assisted therapy. US Patent 10,413,278 issued September 17, 2019.
