The research in my group encompasses the use of ultrasound in both clinical/pre-clinical imaging and to effect localized drug delivery.
1. Mouse Heart Imaging
The mouse species has a unique role in basic research aimed at understanding the evolution of heart disease and the efficacy of proposed therapies. In particular, specialized genetic strains are used to examine the roles of specific genes on the evolution of heart disease and therapy. Our primary focus involves developing quantitative methods for assessing left ventricular (LV) function at various time points post myocardial infarction. In particular, we observe that complex dyssynchrony in the LV early after myoinfarction is predictive of the long term evolution of the LV's response. Specifically, a large infarct results in greater dyssynchrony that evolves into increased left ventricular remodeling and reduced ejection fraction (a measure of the LV's pumping efficiency).
2. Molecular Imaging
Microbubbles are gas filled bubbles in the 1-4 micron diameter range that normally act as a tracer for blood flow. Because the microbubbles have a density and compressibility very different from soft tissue, ultrasound is able to detect single microbubbles. In microbubble-based molecular imaging, the surface of the microbubble is modified by attaching a molecule specific (e.g. VCAM-1) ligand that will cause the microbubble to attach to matching molecular receptors present on the blood vessel wall. Using this approach, it is possible to detect the earliest stage of a vascular wall related disease months or years prior to any detectable anatomic or physiological change. In our laboratory, we are exploring new ultrasound signal processing schemes to uniquely identify attached microbubbles. In our case, the primary application is to develop a method for very early detection of stroke risk. Stroke is the leading cause of morbidity in the US and the third leading cause of death (after heart disease and cancer).
3. Microbubbles for localized drug delivery
In this work, microbubbles are most frequently modified to carry a drug payload in their shell. It is also possible to coinject microbubbles and drug if the drug is not suitable for incorporation in the microbubble shell. We are developing multi-function intravascular ultrasound catheters that are capable of imaging the microbubbles as they are dispensed in a vessel. Thereafter, a high intensity ultrasound burst is used to oscillated the microbubbles to induce transient cell membrane permeabilization. In this way, localized drug delivery is effected. We also use ultrasound radiation force to improve the translation of dispensed microbubbles from the catheter to the vessel wall. A component of this work involves developing microfluidic devices, placed inside the catheter, to produce upon demand a stream of precisely dimensioned microbubbles wherein the microbubble diameter is a function of device aperture size, liquid flow rate and gas pressure. We have also initiated work to develop optical-based catheter using a single glass fiber and side-fire tip to allow for optical detection of drug deposition when the drug is labeled with a fluorophore.
4. Bone surface imaging
X-ray based methods are normally used to assess bone surfaces for cracks and dislocation. However, ultrasound possesses many advantages over X-ray that make it attractive for imaging bony anatomy. Unfortunately, current ultrasound technology generally images bone poorly. Our team is working to combine the benefits of X-ray and ultrasound by designing specialized transducers and processing methods that can be used to develop inexpensive, handheld, intrinsically safe ultrasound devices for diagnostic imaging of bone in 3D. Applications of the technology include spinal anesthesia guidance, sports medicine, and orthopedics.
Our laboratory also explores various aspects of transducer design and ultrasound signal processing to support each of these areas of interest. We are also expanding our interest at the intersection of ultrasound and optical methods - in particular in the area of photoacoustic imaging. Our research involves collaboration from a number of colleagues within BME, and additional faculty members in the School of Engineering and Applied Science and the School of Medicine. The research is primarily supported by the National Institutes of Health, Virginia state funding and Coulter Research Partnership grants.