DAYTON LAB

(Left to right: Huy Nguyen, Esra Talu, Paul Dayton, Shukui Zhao)

Molecular imaging has the potential for detection of molecular changes before phenotypic  changes become apparent, and therefore holds promise for highly sensitive detection of disease.   Key components of molecular imaging with ultrasound include the development of targeted contrast agents specific for biochemical markers and the development of methods to detect the agents at the target site.  Targeted microbubbles, liposomes, and nanoparticles have been developed through conjugation of a peptide, antibody, or other ligand to the contrast agent shell.  Since ultrasound contrast agents are blood pool agents, these biomarkers are generally located on endothelial or blood cells available to targeted agents.  Detection of inflammation, heart transplant rejection, thrombus, and angiogenesis (rapid new blood vessel development associated with tumor growth) have been reported using ultrasonic molecular imaging.
 
Microscopy images of targeted contrast agents adhering to angiogenic cells.

Oscillating bubbles can be eight orders of magnitude more efficient than purely passive scatters in terms of active sound emission, and encapsulation by a lipid shell further increases their stability and provides opportunity for incorporation of targeting ligands.  Single microbubbles can be detected in the bloodstream with various ultrasound signal processing techniques, and these agents provide spatial resolution on the order of hundreds of microns.      
Although initial studies have been promising, some major challenges remain in ultrasonic molecular imaging.  Our research encompasses three main areas related to molecular (targeted) imaging with the goal of improving sensitivity and specificity.  These areas include improvements in signal processing for contrast agent detection, improvements in contrast agent delivery, and improvements in the contrast agents themselves.  Additionally, we are working on new vehicles for ultrasound-mediated therapeutics. 
Research methods in the lab include high-speed video microscopy, fluorescence microscopy, ultrasonic testing with custom and clinical systems, signal acquisition and analysis using MATLAB and LabView, small animal imaging, bioMEMS, and microfluidics.

Small-animal ultrasound imaging to detect angiogenesis.

Microscopy for analysis of new contrast agents.

Working in the clean room to fabricate microfluidic devices.

DAYTON LAB NEWS

Paul Dayton selected as finalist for 2007 Academic Federation Award for Excellence in Research

Scientist Paul Dayton (http://daytonlab.bme.ucdavis.edu), an Associate Research Engineer in the Biomedical Engineering Department, was recently selected as a finalist for the 2007 Academic Federation Award for Excellence in Research.  There are only three finalists chosen university-wide for this prestigious research award.  Dr. Dayton is working to develop new technologies for molecular imaging with ultrasound in collaboration with Katherine Ferrara (BME) and Marjorie Longo (Chemical Engineering).

NIH ROADMAP GRANT AWARDED TO BME SCIENTIST Paul Dayton has been awarded a NIH Roadmap grant for $1,451,200.00 to study the Development of High Resolution Probes for Cellular Imaging. His research title: “High-Sensitivity Molecular Imaging with Ultrasound (RMI).” Recently, the development of targeted contrast agents for molecular imaging has caught the attention of the medical and scientific community. Targeted ultrasound contrast agents, microbubbles which bear adhesion ligands to specific molecular targets expressed in areas such as angiogenesis, inflammation, or thrombus have the potential to make a significant impact in the detection, assessment, and localization of pathologies otherwise undetectable with medical imaging. Because of the convenience and availability of ultrasound as an imaging technology, targeted contrast agents for use with ultrasound have the potential to rapidly transform this modality into an even more powerful clinical tool. Unfortunately, recent studies with targeted ultrasound contrast agents have failed to illustrate the sensitivity hoped for to make this technique revolutionary. In this proposal, we present a plan to increase the sensitivity of ultrasound to targeted contrast agents over an order of magnitude. Our model target for these studies is angiogenesis (the formation of new blood vessels), which is required for tumor growth beyond 1-2 mm in diameter. The integrin alpha(v)beta(3) is over-expressed in regions of angiogenesis, and has been shown to correlate with tumor grade. These properties make the alpha (v)beta(3) integrin an ideal target for site-directed contrast agents. This proposal describes a three-part method to achieve the desired substantial increase in sensitivity by combining a completely new contrast agent with a novel contrast agent delivery technique, and we package these improvements with the substantially improved detection strategies only possible due to the improvements in the agent and the delivery. The combined tools and experience of the Departments of Biomedical and Chemical Engineering, the School of Veterinary Medicine, and the Cancer Center at the University of California, Davis, provide a unique and qualified research group for implementing this new system for molecular imaging with ultrasound.

Contact Information:
Paul Dayton, Ph.D.
padayton(at)ncsu.edu