1. Ultrasound imaging. (1) Ultrasound molecular imaging of angiogenesis using vascular endothelial growth factor-conjugated microbubbles and ischemic memory imaging with targeted microbubbles. (2) Novel intravascular ultrasound system (IVUS) for contrast enhanced imaging of coronary vasa vasorum for quantification of plaque neovascularization during atherosclerosis progression. (3) Stem cell imaging with ultrasound to track the trafficking of mesenchymal stem cells by uptake of the microbubbles.
2. Ultrasound mediated therapy. (1) Ultrasound assisted gene and drug delivery and therapy for cancer and cardiovascular diseases such as hypertrophic cardiomyopathy. (2) Sonoreperfusion and microvascular reperfusion therapy by using ultrasound and microbubbles to resolve microvascular obstruction post percutaneous coronary intervention of acute myocardial infarction (AMI).
3. Ultra-high-speed digital microscopy. A High-speed Digital Microscopy Laboratory has been developed to support the functions of the Pittsburgh Center for Ultrasound Molecular Imaging and Therapeutics. The Center houses the fasted multi-frame digital microscopy laboratory (UPMC Cam, 25 million frames per second, 128 frames) in North America dedicated to biomedical research. When combined with the Acoustics Laboratory, we are able to observe microbubble oscillations when exposed to ultrasound energy and their interactions with biological cells at very high temporal resolutions. This system is used to investigate mechanisms of ultrasound mediated bioeffects, such as sonoporation for drug delivery and gene transfection for cancer therapy, sonothrombolysis for reperfusion therapy for microvascular obstruction, and the phase transition phenomena for photoacoustic imaging and contrast ultrasound imaging.
- BEng, China University of Mining and Technology, 1982
- PhD, Yale University, 1991
- Postdoctoral Fellow, Electrical & Computer Eng. and Cardiology, University of Rochester, 1993
Education & Training
Brayman, A. A., Azadniv, M., Miller, M. W., Chen, X. Bubble recycling and bubble translational velocities in a stationary exposure vessel. Journal of the Acoustical Society of America. 1994; 96(2): 627-633.
Chen, X., Apfel, R. E. Radiation force on a spherical object in an axi-symmetric wave field and its application to the calibration of high frequency transducers. Journal of the Acoustical Society of America. 1996; 99: 713-724.
Chen, X., Phillips, D., Schwarz, K. Q., Mottley, J. G., Parker, K. J. The measurement of backscatter coefficient from pulse-echo measurements: a new formulation. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency. 1997; 44(2): 515-525.
Kaya, M., Toma, C., Wang, J., Grata, M., Fu, H., Villanueva, F. S., Chen, X. Acoustic radiation force for vascular cell therapy: In vitro validation. Ultrasound in Medicine & Biology. 2012; 38(11): 1189-1997.
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. Review of Scientific Instruments. 2013; 84(6): 063701.
Chen, X., Leeman, J. E., Wang, J., Pacella, J. J., Villanueva, F. S. New insights into mechanisms of sonothrombolysis using ultra high speed imaging. Ultrasound in Medicine & Biology. 2014; 40: 258-262.
Yu, F., Villanueva, F. S., Chen, X. Radial modulation contrast imaging using a 20-MHz single element intravascular ultrasound catheter. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency. 2014; 61: 779-791.
Pacella, J. J., Brands, J., Schnatz, F., Black, J. J., Chen, X., Villanueva, F. S. Treatment of microvascular micro-embolization using microbubbles and long -tone-burst ultrasound: an in vivo study. Ultrasound in Medicine & Biology. 2015; 41(2): 456-464.
Chen, X., Wang, J., Pacella, J. J., Villanueva, F. S. 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 in Medicine & Biology. 2016; 42(2): 528–538.
- Toma C, Villanueva FS, Wagner WR, Lee JS, Wang J, Chen X, Fischer A. Patent 8,460,269 "Directed cell-based therapy using microbubble tagged cells.", 2013
- Wang J, Villanueva FS, Chen X, Fisher A, Wagner WR. Patent 8,940,277 "Intracellular microbubble for imaging an anatomical site.", 2015
Title: Ultrasound Targeted Microbubble Cavitation to Treat Coronary Microvascular Obstruction
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL157497
Start Year: 2021
End Year: 2026
