Nearly all humans have atherosclerotic plaque, but only a subset of us will experience its most perilous effects-a heart attack or stroke. Atherosclerosis accounts for thirty percent of worldwide deaths and brings a financial burden greater than all cancers combined an estimated $300 billion per year in the United States. The key to lessening the burden and limiting the vast number of deaths is to determine which of us are at risk so they can be medically treated to prevent heart attack, stroke, and death. Doctors rely on information gained from imaging studies such as magnetic resonance imaging (MRI) to make treatment decisions aimed at improving patient quality of life and lifespan. With this project, we aim to create a contrast agent for MRI that more effectively detects the most dangerous plaques that cause heart attacks and strokes. The studies proposed here are aimed at filling the void in our clinical ability to assess patient risk for heart attack and stroke by creating a contrast agent capable of functionally determining plaque severity with an 'on-switch'triggered by a critical process in atherosclerosis known as oxidative stress. The contrast agent becomes visible on the MR image at the disease site when superoxides present during oxidative stress disassemble the polymer coating that up until the point had masked the contrast agent. First, we will create and evaluate a nanoparticle comprised of a contrast agent shielded within a polymer coating. The polymer coating makes the contrast agent invisible to MR, as is desired in our design until such time as the agent reaches the disease site. Second, we will evaluate whether the polymer coating disintegrates in the presence of superoxide molecules (similar to those present in atherosclerosis) in a way that allows the contrast agent to become visible to MRI. Third, we will evaluate whether the nanoparticles exhibit the same superoxide-triggered contrast in the presence of superoxides produced by human cells. We will also evaluate the levels of toxicity of the nanoparticle to human cells. With these steps, we expect to move the field towards: more accurate assessment of plaque severity via a functionally-based contrast mechanism, better informed clinical decisions, and ultimately improved patient health.

Public Health Relevance

Atherosclerosis is a complex disease that causes heart attacks and strokes, and the disease accounts for thirty percent of worldwide deaths. Information gained from imaging studies helps identify patients at risk for heart attacks and strokes and is used to determine the appropriate treatment. With this project, we aim to improve patient lifespan and quality of life by creating a contrast agent that more effectively detects the dangerous plaques and allows doctors to make the right patient care decisions critical to patient outcome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB017504-02
Application #
8675234
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Liu, Christina
Project Start
2013-06-15
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$179,812
Indirect Cost
$27,994
Name
State University of NY, Binghamton
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
090189965
City
Binghamton
State
NY
Country
United States
Zip Code
13902