Our goal is to facilitate unprecedented levels of imaging breakthroughs in diagnostic capability and anatomic resolution to provide enhanced risk assessment for the detection and treatment of atherosclerotic disease. This multifaceted proposal seeks to define for practicing clinicians' new diagnostic imaging standards that will facilitate the noninvasive detection and treatment of cardiovascular disease. Accordingly, a multidisciplinary investigative team comprising faculty of the Ohio State University College of Medicine and Public Health in the Departments of Internal Medicine/Cardiology, Radiology, and Surgery has been assembled. The commitment of the Ohio State University has been demonstrated through its funding with the selective investment program to develop cardiovascular bioengineering, and the support of General Electric (GE) medical systems has been established with the installation of state-of-the-art cardiovascular imaging technology. With the support of the state of Ohio through the biomedical research technology transfer trust fund, we will have a transparent environment in which investigators from many different branches of academia and industry work together to address the adverse health consequences of tobacco on the leading cause of morbidity and mortality to the citizens of Ohio, namely, heart disease.
PROJECT 1: Early detection of coronary artery disease.
VISION
The central goal of Node 1 is to perform clinical studies with the most advanced cardiovascular imaging technologies including magnetic resonance imaging (MRI), multislice computed tomography (CT), digital flat panel x-ray imaging (XR), and optical coherence tomography with the central focus of identifying and characterizing atherosclerotic plaque. These technologies show promise in improving diagnosis and therapy in cardiovascular disease; appropriate implementation requires design and analysis by both the engineers on the technical side as well as the clinicians who understand the challenges in cardiovascular medicine.
The overall structure of Node 1 is three-fold:
1: implement state-of-the-art MRI' CT, and XR solutions in a cohort of patients with newly diagnosed coronary artery disease;
2: develop contrast agents specifically designed to facilitate imaging of atherosclerotic plaque and the components which make it more likely to cause clinical events; and
3: investigate the feasibility of optical imaging in the operating room to immediately identify the success of coronary artery bypass surgery.
The spectrum from 1.1 to 1.3 includes technologies that are immediately available as well as those which are in development, underscoring the need for continuous interaction between the individual projects. This ensures that clinical insights gained in lA help direct developments in 1.2 and 1.3, and also that advances in 1.2 and 1.3 lead to improvements in the techniques deployed in l.1. As an example, there may be characteristics (e.g.: inflammation) identified in a coronary plaque that are determinants of short-term failure or success of surgical bypass intervention. Development of these imaging technologies has the strong potential to aid in determining the appropriate therapeutic intervention for the coronary disease identified. The same degree of interaction outlined within Node 1 will occur between Node 1 and the Node 2 components of the Cardiovascular Bioengineering Enterprise, namely the Basic Science and Nanotechnology focus.
The work of Node 2 will identify the fundamental mechanisms involved in atherosclerotic plaque development and rupture. Key signaling pathways and mediators can then be identified and targeted with nanotechnology vehicle-based contrast agents that identify atherosclerotic plaques with adverse molecular characteristics. To fully realize nanotech's potential for diagnosis as well as therapy requires communication between the nodes of the CBE. Ultimately, novel contrast agents for identification and therapy of atherosclerosis will be available for clinical use in Node 1 where the utility in the care of individuals with cardiovascular disease can be rigorously assessed.
BACKGROUND
Since its development in the 1960s, invasive cardiac catheterization has become the gold standard for identifying and defining the extent of atherosclerosis, or hardening of the arteries, in patients suspected of having coronary artery disease (CAD). This population is vast, ranging from those who present with chest pain to an emergency department to asymptomatic individuals concerned about their future risk of having a heart attack. Noninvasive detection of ischemia (abnormal blood supply to heart muscle) with stress testing has been relied upon to provide inferences about the presence of coronary artery disease, but currently does not directly provide information about the coronary arteries themselves. Furthermore, stress testing cannot reliably detect atherosclerosis in the absence of significant luminal narrowing which typically occurs only after years of disease progression. An ideal noninvasive test would produce detailed information about the presence and extent of atherosclerosis at its earliest stages, since coronary artery disease may be present at levels insufficient to cause ischemia using standard stress testing but sufficient to cause an acute coronary syndrome without warning. At the Ohio State University we are actively developing such technologies using multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) through the collaborative efforts of physicians, biomedical engineers, and industry partners in cardiovascular imaging. Cardiac imaging and assessment of coronary artery stenosis is a challenging problem due to the dynamic nature of the heart and the limited rotation speed of the gantry. MDCT technology has enabled the development of sophisticated cardiac reconstruction algorithms by offering wider area of axial coverage, increased rotation speed, and higher spatial resolution compared to the previous generation CT technology. MRI offers the advantage of requiring no ionizing radiation compared to X-ray technology, only a precisely controlled magnetic field to generate exceptional images of the beating heart and blood vessels. Much preliminary work has been done to describe gross plaque morphology with MRI; we plan to build upon these efforts by taking advantage of novel pulse sequences and contrast agents specifically designed to characterize atherosclerotic plaque.
PROJECT 2: Assessment of contrast agents, mechanisms and pathways for crosssectional imaging of atherosclerotic disease and its cardiovascular effects.
VISION
In collaboration with the leading pharmaceutical manufacturer of imaging contrast agents (Berlex/Schering), clinical studies will be conducted to assess new approaches and uses of contrast agents to image and characterize atherosclerotic disease This will be accomplished by
1) assessing improved and new contrast agent applications in all the imaging modalities: X-ray, CT, MR, ultrasound and radionuclide techniques;
2) establishing and assessing the corresponding new image processing and visualization techniques;
3) evaluation of new imaging pathways such as targeted agents and;
4) establishing new imaging pathways as molecular imaging methodologies can be integrated.
BACKGROUND
Imaging technologies require contrast agents to visualize morphologic and molecular features of the cardiovascular system. Contrast agents are used already in all cardiovascular imaging technologies such as x-ray angiography, computed tomography, magnetic resonance, ultrasound and radionuclide studies. Current modalities, especially the cross-sectional, non-invasive procedures, have not reached the quality of resolution and specificity of findings needed to advance cardiovascular disease management, diagnosis, prevention and therapeutic intervention. Recent developments in contrast media have led to new characteristics of imaging agents that hold great promise for cardiovascular imaging. Higher concentration agents such as Gd-BT-DO3A promise to advance non-invasive imaging. |
