Faculty & Staff

Faculty & Staff

Flordeliza S. Villanueva, MD

Director, Center for Ultrasound Molecular Imaging and Therapeutics

Director, Non-Invasive Cardiac Imaging, UPMC Heart and Vascular Institute

Professor of Medicine, University of Pittsburgh School of Medicine

Faculty Member

Peer Reviewed Articles

* = First author was mentored by Dr. Villanueva

1. Villanueva FS, Heinsimer JA, Burkman MH, Fananapzir L, Halvorsen RA, Chen JR.  Echocardiographic detection of perforation of the cardiac ventricular septum by a permanent pacemaker lead.  Am J Cardiol 1987;59:370-71.

2. Villanueva FS, Murali S, Uretsky BF, Reddy PS, Griffith BP, Hardesty RL, Kormos RL.  Resolution of severe pulmonary hypertension after heterotopic cardiac transplantation.  J Am Coll Cardiol 1989;14:1239-43.

3. Villanueva FS, Kaul S, Glasheen WP, Broccoli A, Spotnitz WD.  Intraoperative assessment of the distribution of retrograde cardioplegia using myocardial contrast echocardiography.  Surg Forum 1990;XLI:252-54.

4.Villanueva FS, Kaul S, Smith WH, Watson DD, Varma SK, Beller GA. Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease. Am J Cardiol 1990;66:1324-28.

5. Villanueva FS, Kaul S, Jayaweera AR, Sklenar J, Dent JM, Gimple LW, Wyatt D, Spotnitz WD.  On-line quantitation of myocardial perfusion pre- and post-coronary artery bypass grafting using myocardial contrast echocardiography.  Surg Forum 1991;XLII:208-210.

6. Villanueva FS, Smith W, Watson DD, Beller GA.  ST segment depression during dipyridamole infusion:  clinical, scintigraphic and hemodynamic correlates.  Am J Cardiol 1992;69:445-48.

7. Villanueva FS, Sabia P, Afrookteh A, Pollock SG, Hwang LJ, Kaul S.  Value and limitations of current methods of evaluating patients presenting to the emergency room with cardiac-related symptoms for determining long-term outcome.  Am J Cardiol 1992;69:746-50.

8. Villanueva FS, Glasheen WD, Sklenar J, Jayaweera AR, Kaul S.  Successful and reproducible myocardial opacification during two-dimensional echocardiography from right heart injection of contrast.  Circulation 1992;85:1557-64.

9. Villanueva FS, Spotnitz WD, Jayaweera AR, Gimple LW, Dent JM, Kaul S.  Myocardial contrast echocardiography in humans:  On-line intraoperative quantitation of regional myocardial perfusion during coronary artery bypass graft operations.  J Thorac Cardiovasc Surg 1992;104:1529-31.

10. Dent JM, Jayaweera AR, Glasheen WP, Nolan SP, Spotnitz WD, Villanueva FS, Kaul S. A mathematical model for the quantitation of mitral regurgitation:  Experimental validation in the canine model using contrast echocardiography.  Circulation 1992;86:553-62.

11. Kaul S, Jayaweera AR, Glasheen WP, Villanueva FS, Gutgessel HP, Spotnitz WD.  Myocardial contrast echocardiography and the transmural distribution of flow:  A critical appraisal during myocardial ischemia not associated with infarction.  J Am Coll Cardiol 1992;20:1005-16.

12. Villanueva, FS, Glasheen WP, Dent JM, Kaul S, Spotnitz WD.  Discrepancy between capillary perfusion and myocardial cooling during retrograde cardioplegia:  Comparison with antegrade cardioplegia.  Surg Forum 1992;43:213-15.

13. Galanti G, Jayaweera AR, Villanueva FS, Glasheen WP, Kaul S.  Transpulmonary transit of microbubbles during contrast echocardiography:  implications for estimating cardiac output and pulmonary blood volume.  J Am Soc Echo 1993;6:272-78.

14. Villanueva FS, Glasheen WP, Sklenar J, Kaul S.  Assessment of risk area during coronary occlusion and infarct size after reperfusion with myocardial contrast echocardiography using left and right atrial injections of contrast. Circulation 1993;88:596-604.

15. Villanueva FS, Glasheen WP, Sklenar J, Kaul S. Characterization of spatial patterns of flow within the reperfused myocardium using myocardial contrast echocardiography: implications in determining extent of myocardial salvage. Circulation 1993;88:2596-2606.

16. Jayaweera AR, Edwards N, Glasheen WP, Villanueva FS, Abbott RD, Kaul S.  In-vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography: comparison with radiolabeled red blood cells.  Circ Res 1994;74:1157-1165.

17. Sklenar J, Ismail S, Villanueva FS, Goodman NC, Glasheen WP, Kaul S. Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion:  An experimental evaluation.  Circulation 1994;90:1502-1512.

18. Villanueva, FS, Kaul S.  Assessment of myocardial perfusion in coronary artery disease using myocardial contrast echocardiography.   Coronary Artery Disease 1995;6:18-28.

19. Villanueva FS, Spotnitz WD, Glasheen WP, Watson DD, Jayaweera AR, Kaul S.  New insights into the physiology of retrograde cardioplegia delivery.  Am J Physiol 1995;268(4 Pt 2):H1555-H1566.

20. Villanueva FS, Camarano G, Ismail S, Goodman NC, Sklenar J, Kaul S.  Coronary reserve abnormalities in the infarcted myocardium:  Assessment of myocardial viability immediately versus late after reflow by contrast echocardiography. Circulation 1996;94:748-754.

21. McNamara DM, Rosenblum WD, Kanosko KM, Trost MK, Villanueva FS, Demetris AJ, Murali S, Feldman AM. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation 1997;95:2476-2479.

22.*  Wu C, Feldman MD, Mills JD, Fischer D, Jafar MZ, Villanueva FS.  Myocardial contrast echocardiography can be used to quantify intramyocardial blood volume:  new insights into structural mechanisms of coronary autoregulation.  Circulation 1997;96:1004-1011 (with Editorial Comment).

23. Villanueva FS, Jankowski RJ, Manaugh C, Wagner WR.  Albumin microbubble adherence to human coronary endothelium:  implications for the assessment of endothelial function using myocardial contrast echocardiography.  J Am Coll Cardiol 1997;30:689-694.

24. Villanueva FS, Jankowski RJ, Klibanov S, Pina ML, Alber SM, Watkins SC, Brandenburger GH, Wagner WR. Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells: a novel approach to assessing endothelial function using myocardial contrast echocardiography. Circulation 1998;98:1-5.

25. Villanueva FS.  Use of myocardial contrast echocardiography in clinical evaluation after myocardial infarction.  Coronary Artery Disease 2000;11:235-244.

26. Bozkurt B, Villanueva FS, Tokarcyzyk T, Holubkov R, Alvarez RJ, MacGowan G, Murali S, Rosenblum WD, Feldman AM, McNamara DM.  Intravenous immune globulin in the therapy of peripartum cardiomyopathy.  J Am Coll Cardiol 1999;34:177-180.

27. Lindner JR, Villanueva FS, Dent JM.  Assessment of resting perfusion with myocardial contrast echocardiography:  theoretical and practical considerations.  Am Heart J  2000;139:231-240.

28. Mulvagh SL, DeMaria AN, Feinstein SB, Burns PN, Kaul S, Miller JG, Monaghan M, Porter TR, Shaw LJ, Villanueva FS.  Contrast echocardiography:  current and future applications.  American Society of Echocardiography Task Force on Standards and Guidelines for the Use of Ultrasonic Contrast in Echocardiography.  J Am Soc Echo 2000;13:331-342.

29.* Mills JD, Fischer D, Villanueva FS.  Coronary collateral development during chronic ischemia:  serial assessment using harmonic myocardial contrast echocardiography.  J Am Coll Cardiol 2000;36:618-624.

30. Villanueva FS, Gertz EW, Csikari M, Pulido G, Fisher D, Sklenar J.  Detection of coronary artery stenosis using power Doppler imaging.  Circulation 2001;103:2624-2630.

31. Villanueva FS, Abraham JA, Schreiner GF, Csikari MM, Fischer D, Mills JD, Schellenberger U, Koci BJ, Lee JS. Myocardial contrast echocardiography can be used to assess the microvascular response to vascular endothelial growth factor-121.  Circulation 2002;105:759-765.

32. Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, Kornblit CA, Angelilli A, Villanueva FS, McNamara DM, London B. Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation 2002;105:707-713.

33.  Villanueva FS, Klibanov A, Wagner W. Microbubble-endothelial cell interactions as a basis for assessing endothelial function.  Echocardiography 2002;19:427-38.

34.* Weller G, Villanueva FS, Klibanov AL, Wagner WR. Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium.  Ann Biomed Eng 2002;30:1012-1019.

35. Villanueva FS.  Myocardial contrast echocardiography in acute myocardial infarction.  Am J Cardiol 2002;90(suppl):38J-47J.

36. Wei  K, Crouse L, Weiss J, Villanueva FS, Schiller NB, Naqvi TZ, Siegel R, Monaghan M, Goldman J, Aggarwal P, Feigenbaum H, DeMaria A.  Comparison of usefulness of dipyridamole stress myocardial contrast echocardiography to technetium-99m sestamibi single-photon emission computed tomography for detection of coronary artery disease (PB127 multicenter phase 2 trial results).  Am J Cardiol 2003;91:1293-1298.

37.* Lu E, Wagner WR, Schellenberger U, Abraham JA, Klibanov, AL, Woulfe SR, Csikari MM, Fischer D, Schreiner GF, Brandenburger GH, Villanueva FS.  Targeted in vivo labeling of receptors for vascular endothelial growth factor:  approach to identification of ischemic tissue.  Circulation 2003;108:97-103.

38.* Weller GER, Lu E, Csikari MM, Klibanov AL, Fischer D, Wagner WR, Villanueva FS.  Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1.  Circulation 2003;108:218-224.

39. Raisinghani A, Wei KS, Crouse L, Villanueva FS, Feigenbaum H, Schiller NB, Weiss J, Naqvi TZ, Siegel R, Monaghan M, Goldman JH, DeMaria A. Myocardial contrast echocardiography (MCE) with triggered ultrasound does not cause premature ventricular complexes: evidence from PB127 MCE studies. Myocardial contrast echocardiography with triggered ultrasound does not cause ventricular premature beats: evidence from PB127 studies. J Am Soc Echo 2003;16:1037-1042.

40. Villanueva FS.  Targeted imaging using microbubbles.  Cardiol Clin 2004;22:283-298.

41. Senior R, Villanueva FS, Vannan MA.  Myocardial contrast echocardiography in acute coronary syndromes.  Cardiol Clin 2004;22:253-268.

42. Kaul S, Senior R, Firschke C, Wang W, Lindner J, Villanueva FS, Firoza S, Kontos MC, Taylor A, Nixon IJ, Watson DD, Harrell FE.  Incremental value of cardiac imaging in patients presenting to the emergency department with chest pain and without ST segment elevation:  a multicenter study.  Am Heart J 2004;148:129-136.

43.* Weller GER, Wong MKK, Modzelewski RA, Lu E, Klibanov AL, Wagner WR, Villanueva FS.  Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide RRL.  Cancer Res 2005;65:533-539.

44.* Weller GE, Villanueva FS, Tom EM, Wagner WR. Targeted ultrasound contrast agents: in vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewisx  Biotechnol Bioeng 2005;92:780-788.

45.*Pacella JJ, Kameneva MV, Lu E, Csikari M, Fischer D, Villanueva FS. Effect of drag reducing polymers on myocardial perfusion during coronary stenosis. Eur Heart J 2006;27:2362-2369 (with Editorial Comment).

46.* Pacella JJ, Villanueva FS.  Effect of coronary stenosis on adjacent bed flow reserve:  assessment of microvascular mechanisms using myocardial contrast echocardiography.  Circulation 2006:114:1940-1947.

47. Villanueva FS, Lu E, Bowry S, Kilic S, Tom E, Wang J, Gretton J, Pacella JJ, Wagner WR.  Myocardial ischemic memory imaging using molecular echocardiography. Circulation 2007;115:345-352 (with Editorial Comment) PMID: 17210843.

48.*Deglau TE, Johnson JD, Villanueva FS, Wagner WR. Targeting microspheres and cells to PEG-modified biological surfaces.  J Biomed Mater Res Part A 2007;81:578-585. PMID: 17177289; PMCID: PMC2873022.

49. Villanueva FS, Wagner WR. Ultrasound molecular imaging of cardiovascular disease. Nature Clin Prac Cardiovasc Med 2008;5(suppl 2):s26-32. PMID: 18641604; PMCID: PMC4111455.

50. Villanueva FS. Molecular imaging of cardiovascular disease using ultrasound. J Nucl Cardiol 2008 Jul-Aug;15(4):576-86. PMID: 18674725; PMCID: PMC3491978.

51.* Toma C, Wagner WR, Bowry S, Schwartz A, Villanueva FS.  Fate of culture-expanded  mesenchymal stem cells in the microvasculature.  In vivo observations of cell kinetcs. Circ Res 2009;104:398-402. PMID: 19096027; PMCID: PMC3700384.

52.* Pacella JJ, Kameneva MV, Lavery LL, Bowry S, Schwartz A, Fisher AR, Villanueva FS.  A novel hydrodynamic method for microvascular flow enhancement.  Biorrheology 2009;46:293-308. PMID: 19721191.

53.* Pacella JJ, Kameneva MV, Villanueva FS.  Drag reducing polymers improve coronary flow reserve through modulation of capillary resistance.  Biorheology 2009;46;365-378. PMID: 19940353.

54.* Simon MA, Girod JP, Kliner DE, Moguillansky D, Villanueva FS, Pacella JJ.  Detection of elevated right atrial pressure using a simple bedside ultrasound measure.  Am Heart J 2010;159:421-427. PMID: 20211304.

55.* Maul TM, Dudgeon DD, Beste MT, Hammer DA, Lazo JS, Villanueva FS, Wagner WR.  Optimization of contrast ultrasound agents with computational models to improve selection of ligands and binding strength.  Biotechnol Bioeng 2010;107;854-864. PMID: 20665479; PMCID: PMC3225194.

56.* Carson AE, McTiernan 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; PMCID: PMC4111473.

57.* 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;32:646-653. doi: 10.1093/eurheartj/ehq197. PMID: 20581005; PMCID: PMC3046374.

58.* Toma C, Fisher A, Wang J, Chen X, Grata M, Leeman J, Winston B, Kaya M, Fu H, Lavery L, Fischer D, Wagner WR, Villanueva FS.  Vascular endoluminal delivery of mesenchymal stem cells using acoustic radiation force. Tissue Eng J Part A 2011;17(9-10):1457-1464. doi: 10.1089/ten.TEA.2010.0539. PMID: 21247343; PMCID: PMC3079165.

59.* Deglau T, Villanueva FS, Wagner WR.  In vivo peg-modification of vascular surfaces for targeted delivery.  J Vasc Surg 2012;55:1087-1095. DOI: 10.1016/j.jvs.2011.09.081. PMCID: PMC3319259.

60.* Carson AR, McTiernan CF, Lavery L, Grata M, Leng X, Wang J, Chen X, Villanueva FS.  Therapy of carcinoma using small inhibitory RNA against epidermal growth factor receptor and ultrasound targeted microbubble destruction.  Cancer Res 2012; 72(23):6191-9. doi: 10.1158/0008-5472.CAN-11-4079. PMID: 23010078; PMCID: PMC3654825.

61.* Leeman JE, Kim JS, Yu F, Chen X, Kim K, Villanueva FS, Pacella JJ.  Effect of acoustic conditions on  microbubble-mediated microvascular sonothrombolysis.  Ultrasound Med Biol 2012;38:1589-1598.  doi: 10.1016/j.ultrasmedbio.2012.05.020. PMID: 22766112.

62*. Pacella JJ, Kameneva MV, Brands J, Lopowsky HH, Vink H, Lavery L, Villanueva FS.  Modulation of pre-capillary arteriolar pressure with drag reducing polymers:  A novel method for enhancing microvascular perfusion.  Microcirculation 2012;19(7):580-585. doi:  10.1111/j.1549-8719.2012.00190.x. PMID: 22578102.

63.* Kim JS, Leeman JE, Kagemann MS, Yu F, 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 Optics 2012;17(7):070502. doi: 10.1117/1.JBO.17.7.070502. PMID: 22894458.

64.* Kaya M, Toma C, Wang J, Grata M, Fu H, Villanueva FS, Chen X.  Acoustic radiation force for vascular cell therapy:  Theory and in vitro validation.  Ultrasound Med Biol 2012;38(11):1989-1997. doi: 10.1016/j.ultrasmedbio.2012.07.019.   PMID: 22975034;  PMCID: PMC3471247.

65. Weiss RJ, Ahmad M, Villanueva FS, Schmitz S, Bhat G, Hibberd MG, Main ML; CaRES Investigators.  CaRES (Contrast Echocardiography Registry for Safety Surveillance):  A prospective multicenter study to evaluate the safety of the ultrasound contrast agent Definity in clinical practice.  J Am Soc Echo 2012;25:790-705. doi: 10.1016/j.echo.2012.04.002. PMID: 22560734.

66. Chen X, Wang J, Versluis M, de Jong N, Villanueva FS.  Ultra-fast brightfield and fluorescence imaging of the dynamics of micrometer sized objects.  Rev Sci Instrum 2013;84(6):063701;1-13. doi: 10.1063/1.4809168. PMID: 23822346; PMCID: PMC4108723.

67.* Mahmoud AM, Dutta D, Lavery L, Stephens DN, Villanueva FS, Kim K.  Noninvasive detection of lipids in atherosclerotic plaque using ultrasound thermal strain imaging:  in vivo animal study.  J Am Coll Cardiol 2013;62:1804-1809. doi: 10.1016/j.jacc.2013.07.013. PMID: 23916926; PMCID: PMC3815971.

68.*     Brands J, Kliner D, Kameneva MV, Villanueva FS, Pacella JJ.  New insights into the microvascular mechanisms of drag reducing polymers:  effect on the cell free layer.  PLoS One 2013;8(10):e77252. doi: 10.1371/journal.pone.0077252 PMID:24124610; PMCID: PMC3790673.

69.*  Yu FTH, Villanueva FS, Chen X.  Radial modulation contrast imaging using a 20-MHz single element intravascular ultrasound catheter.  IEEE Trans Ultrason Ferroelect Freq Control 2014;61(5):779-791. doi: 10.1109/TUFFC.2014.2970. PMID: 24803134; PMCID: PMC4094374.

70.* 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.  J Molecular Imaging 2014;13(4):1-9. doi: 10.2310/7290.2014.00006. PMID:24742373; PMCID: PMC4083464.

71. 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):258-262. Epub 2013 October 18. doi: 10.1016/j.ultrasmedbio.2013.08.021. PMID: 24139920.

72. 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. doi: 10.1016/j.ultrasmedbio.2014.09.033. PMID: 25542487.

73. Zanetti A, Grata M, Etling E, Panday R, Villanueva FS, Toma C. Suspension-expansion of bone marrow results in small mesenchymal stem cells exhibiting increased transpulmonary passage following intravenous administration. Tissue Eng Part C Methods 2015;21(7):683-92. doi: 10.1089/ten.TEC.2014.0344. PMID: 25567723.

74.* 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. doi: 10.7150/thno.12822. PMID: 25542487.

75. 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.

76.* 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.

77.* 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.

78.* 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.

79.* 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):2220-31. Epub 2016 May 17. doi: 10.1016/j.ultrasmedbio.2016.04.004. PMID: 27207018.

80.* 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.

81.* Helfield B, Chen X, Watkins S, Villanueva FS. Biophysical insight into mechanisms of sonoporation. PNAS 2016; 113(36):9983-9988. EPub 2016 August 22. doi: 10.1073/pnas.1606915113. PMID: 27551081.

82.* 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 Sep26. doi: 10.1016/j.ultrasmedbio.2016.08.013. PMID: 27687734.

83. 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.

84.* 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.

85.* 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.

86.* 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.

87.* 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.

88*. 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.

89*. 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.

90*. 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.

91*. 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.

92. 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;(accepted for publication).




1. Kaul S, Villanueva FS.  Dipyridamole thallium-201 imaging:  How safe is it?  When should it be used?  J Nucl Med 1991;32:2115-2117.

2. Kaul S, Villanueva FS.  Is the determination of myocardial perfusion necessary to evaluate the success of reperfusion when the infarct-related artery is open?  Circulation 1992;85:1942-1944.

3. Villanueva FS.  Molecular images of neovascularization:  Art for art's sake or form with a function?  Circulation 2005;111:3188-3191.

4. Villanueva FS.  Ultrasound mediated destruction of DNA-loaded microbubbles for enhancement of cell-based therapies:  New promise amidst a confluence of uncertainties?  J Am Coll Cardiol Img 2009;2:880-882.

5. Villanueva FS.  Myocardial Perfusion Imaging Using Ultrasound Contrast Agents: Now or Never?  J Am Coll Cardiol Img 2010;3:944-946.

6. Villanueva FS.  Getting Good Vibes:  The Therapeutic Power of Microbubbles and Ultrasound.  J Am Coll Cardiol Img 2012;5:1263-1266.

7. 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.



Reviews, invited published papers, conference and symposia proceedings, monographs, and book chapters (selected)

1. Kaul S, Villanueva FS, Spotnitz WD.  Value of myocardial contrast echocardiography in patients undergoing coronary artery bypass graft surgery. In Pezzano A, Faletra F, Gullace G, Scarpini S (ed.): Ecocardiografia '93. Centro Scientifico Editore, 1993;pp 125-33.

2. Villanueva FS, Spotnitz WD, Kaul S.  The selection of anterograde versus retrograde cardioplegia delivery:  Relevant anatomic and physiologic considerations, In Mohl W (ed.): Coronary Sinus Interventions in Cardiac Surgery.  Medical Intelligence Unit, RG Landes Publishers, Austin, TX, 1994;pp59-66.

3. Villanueva FS. Assessment of endothelial function using myocardial contrast echocardiography.  In “Perfusion Imaging Today:  Symposium on Contrast Echocardiography,” June 1998.

4. Klibanov AL, Hughes MS, Villanueva FS, Jankowski RJ, Pina ML, Wagner WR, Wojdyla JK, Wible JH, Brandenburger GH.  Targeting and ultrasound imaging of microbubble-based contrast agents. MAGMA (Magnetic resonance materials in physics, biology and medicine) 1999;8:177-194.

5. Klibanov AL, Wojdyla JK, Wible JH, Kim DH, Needham D, Villanueva FS , Brandenburger GH. Attachment of ligands to gas-filled microbubbles via PEG spacer and lipid residues anchored at the interface.  Proceed Intl Symp Control Rel Bioact Mater 1999;26:124.

6. Villanueva FS.  Local control of the coronary circulation and adenosine, in Coronary Circulation and Myocardial Ischemia,  eds Pinsky MR, Artigas A, Dhainaut JF, Springer, Verlag, Heidelberg, Germany, 2000;pg. 3-10.

7. Villanueva FS. Book review of “Echocardiography and cardiovascular function:  tools for the next decade,”  Kluwer Academic Publishers, MA  1997.  In J Nucl Cardiol 1999;6(6):688-689 .

8. Villanueva FS, Wagner WR, Klibanov AL.  Targeted ultrasound contrast agents:  identification of endothelial function, In Goldberg BB, Raichlen JS, Forsberg F (ed.):  Ultrasound Contrast Agents:  Basic Principles and Clinical Applications.  Martin Dunitz Publishers, London, 2001.

9. Villanueva FS.  Part 1:  Recent advances in myocardial contrast echocardiography: An overview Echocardiography. 2002;19:227-28.

10. Proceedings from Lake Tahoe Invitational Conference. Panel 4: Angiogenesis Imaging.  Co-Chairs:  Leppo J, Sinusas AJ. Panelists: Hendel R, Simons M, Udelson J, Villanueva FSJ Nuc Cardiol 2003;10:223-257.

11. Villanueva FS. Echocardiographic imaging of myocardial inflammation (Chapter 33).  In Textbook of Cardiovascular Molecular Imaging.  Eds Sinusas A, Glover D, Taegtmeyer H 2007.

12. Villanueva FS. Molecular imaging of cardiovascular disease using ultrasound.  Bench to Bedside series.  J Nuc Cardiol 2008;l5;576-586.

13. Sinusas AJ, Bengel F, Nahrendorf M, Epstein FH, Wu JC, Villanueva FS, Fayad ZA, Gropler RJ.  Multimodality cardiovascular molecular imaging, Part I.  Circulation: Cardiovasc Imaging  2008;1:244-256.

14. Gropler RJ, Beanlands RS, Dilsizian V, Lewandowski ED, Villanueva FS, Ziadi MC.  Imaging myocardial metabolic remodeling.  J Nuc Med 2010;51(suppl 1):88S-101S.

15. Yu F, Villanueva FS, Chen X. The selection of the low frequency for radial modulation imaging at 20 MHz. Proceedings of the 2010 IEEE International Ultrasonics Symposium 2010;908-911.

16. Villanueva FS . Ultrasound Cell Labeling Methods.  Chapter 19.  In Stem Cell Labeling for Delivery and Tracking Using Non-Invasive Imaging.  Eds Kraitchman D, Wu J.  Taylor & Francis/CRC Press , 2011.

17. Yu F, Villanueva FS, Chen X. Intravascular ultrasound contrast imaging at 25 MHz using radial modulation: a promising approach for coronary vasa vasorum imaging. Proceedings of the 2011 IEEE International Ultrasonics Symposium (IUS) 2011;168-171.

18. Kaya M, Toma C, Wang J, Grata M, Fu H, Villanueva FS, Chen X. Acoustic radiation force for vascular stem cell therapy: an in vitro validation. Proceedings of the 2011 IEEE International Ultrasonics Symposium (IUS) 2011;1886-1889.

19. Chen X, Wang J, Villanueva FS. Ultra fast brightfield and fluorescence imaging of micron size objects for research in microbubble-ultrasound mediated therapeutics. American Heart Association Scientific Sessions. Circulation 2011;124:A17437.

20. Fu H, Wang J, Chen X, Leng X, Thorne S, Villanueva FS. Long Term in vivo Stem Cell Tracking Using Contrast Ultrasound. American Heart Association Scientific Sessions. Circulation 2011;124:A16631.

21. Pellikka PA, Douglas P, Miller U, Abraham TP, Baumann R, Buxton DB, Byrd BF, Chen P, Cook NL, Gardin JM, Hansen G, Moule Husson S, Kaul S, Klein AL, Lang RM, Leong Poi H, Lopez H, Mahmoud TM, Maslak S, Pibarot P, Picard M, Porter TR, Prater D, Sinusas A, Slosky JJ, Sugeng L, Tatpati A, Villanueva FS, von Ramm OT, Weissman NJ, Zamani S.  American Society of Echocardiography Cardiovascular Technology and Research Summit:  A roadmap for 2020.  J Am Soc Echocardiodgr 2013;26:325-38.

22. Kopechek JA, Carson AR, Chen X, McTiernan CF, Hasjim B, Sen M, Grandis JR, Villanueva FS. Effect of cavitation on ultrasound and microbubble-mediated gene knockdown in squamous cell carcinoma. 2014 IEEE International Ultrasonics Symposium (IUS) 2014;Abstract 2A-2.

23. Kooiman K, Villanueva FS, Qin B, Rooij TV, Mastik F, Klibanov AL, de Jong N, Chen X. Unraveling lipid-coating movements of oscillating microbubbles - a fluorescence high-speed optical study. 2014 IEEE International Ultrasonics Symposium (IUS) 2014;Abstract 1E-1.

24. Yu F, Chen X, Wang J, Qin B, Panday R, Villanueva FS. Release, uptake and cytotoxicity of doxorubicin loaded lipopolyplexes exposed to low intensity ultrasound. 2014 IEEE International Ultrasonics Symposium (IUS) 2014;Abstract P1C10-1.

25. Black J, Schnatz R, Yu F, Chen X, Villanueva FS, Pacella JJ. Sonoreperfusion efficacy is greater with venous thrombi compared to arterial thrombi in an in vitro model of arteriolar microvascular obstruction. 2014 IEEE International Ultrasonics Symposium (IUS) 2014;Abstract P1C11-6.

26. Helfield B, Chen X, Qin B, Villanueva FS. Ultrafast frame rate microscopy of microbubble oscillations: current studies employing the UPMC-Cam. J Acoust Soc Am 2015;137(4 Pt 2):2252:2aBA2.

27. Chen X, Wang W, Pacella J, Villanueva FS. Microbubble behavior during long tone-burst ultrasound excitation. J Acoust Soc Am 2015;137(4 Pt 2):2253:2aBA8.

28. Black J, Schnatz F, Yu FT, Chen X, Brands B, Villanueva FS, Pacella J. Effect of blood viscosity and thrombus composition on sonoreperfusion efficacy. J Acoust Soc Am 2015;137(4 Pt 2):2254:2aBA10.

29. Villanueva FS. Molecular imaging using ultrasound and microbubbles. J Acoust Soc Am 2015;137(4 Pt 2):2397:4pBAa1.

30. Villanueva FS. Insights into mechanisms of sonothrombolysis using high speed imaging. J Acoust Soc Am 2015;138(3 Pt 2):1989:3aBAa2.

31. Kopechek KA, Carson AR, McTiernan CF, Chen X, Feroze R, Lavery L, Hasjim B, Villanueva FS.  Targeted delivery of an anti-miR to cardiomyocytes using ultrasound and microbubbles suppresses hypertrophy. Circulation 2015;132:A14662.

32. Helfield B, Qin B, Chen X, Villanueva FS.  Ultrasound-stimulated microbubbles for drug/gene delivery: microbubble-generated shear stress induces pores in cellular membranes. Orlando, FL. Circulation 2015;132:A14619.




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.