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Detection of Recent Ischemia by Targeted Ultrasound Imaging with P-selectin-targeted Microbubbles

 

OHSU # 1102

Summary:

This technology, combined with OHSU Technology 1184, includes methods and reagents to target microbubbles to specific cardiovascular disease indications and provide a non-invasive diagnostic imaging tool for diseases with some of the highest rates of incidence in the general population. The inventions presented here are targeted to imaging and diagnosing “vulnerable” atherosclerotic lesions that identify a patient at high risk for stroke, as well as cardiovascular disease, caused by restricted or blocked blood flow. Microbubbles are small (typically 3 µm in diameter) gas filled bubbles that are usually injected intravenously. Microbubbles increase the sensitivity for echocardiograms -- one of the most common non-invasive, bedside, clinical imaging techniques. The targeting of microbubbles to a variety of cardiovascular diseases and disorders has the potential to enhance diagnostic algorithms that are currently used to evaluate the millions of patients who present yearly to emergency departments with chest pain. Development of this technology will provide a faster, more specific and definitive technique to enhance or replace diagnostic cardiac catheterization or cardiac-specific troponin assays.

Detailed description:Targeted molecular and cellular imaging has the potential to improve patient care by detecting diseases at an early stage, guiding treatment strategy, and rapidly evaluating response to therapy. The technology represents a novel contrast-enhanced ultrasound (CEU) molecular imaging method that targets specific ligands in the vasculature which indicate thrombus build-up, inflammation or ischemic injury. CEU has been shown to be well-suited for molecular and cellular imaging, and involves the conjugation of several thousand targeting ligands per square micron via a long, molecular polyethyleneglycol tether on the microbubble surface. Gas-filled microbubbles provide a safe, non-toxic method to detect specific regions of interest within the vasculature. Microbubbles are prepared with ligands targeted to markers of inflammation (P-Selectin and VCAM-1) and thrombosis (VWF). P-Selectin and VCAM-1 targeted microbubbles have been prepared, tested in an in vitro flow chamber model and administered in vivo to rodents, resulting in the detection of micorobubble adherence to sites of inflammation with high levels of sensitivity and specificity. Currently, work is underway to develop VWF-targeted microbubbles in order to detect vascular thrombi and atherosclerotic lesions that would indicate high risk for complications and rupture. Work is currently beginning on the use of this technology in a primate model.

Inventor Profiles: Dr. Jonathan Lindner is an international leader in the field of molecular imaging for the diagnosis of cardiac diseases. Dr. Lindner’s non-invasive cardiac imaging group has pioneered methods for molecular imaging with CEU that rely on the conjugation of specific monoclonal antibodies or other ligands to a lipid microbubble surface. Dr. Owen McCarty is a specialist in the area of platelet biology and has utilized engineering principles to understand the critical steps that regulate thrombus formation under physiological levels of shear flow in the vasculature.

Market size: This technology could be developed to compete with the 1.2-1.4 million diagnostic cardiac catheterizations performed annually in the U.S. alone (data from the American Heart Association, for the years 1995-2005). In addition, this method would be effective in the detection of left atrial thrombus formation that occurs in approximately 15% of patients with atrial fibrillation (prevalence >2% of U.S. population over the age of 60).

Value Proposition: This technology offers the prospect of using a non-invasive, highly sensitive, bedside imaging technique to diagnose a variety of cardiovascular diseases. The best-recognized advantages of CEU are the widespread availability of ultrasound systems, the convenience and portability of ultrasound imaging equipment, and the ability to perform targeted imaging protocols in less than 15 min. Clinical need is prompting development of this novel strategy for the non-invasive, safer detection of cardiac muscle suffering from restricted blood supply, providing faster and more specific results than what is offered by current clinical practices. Development of this invention also offers the potential of a diagnostic for patients at high risk of stroke, where no such diagnostic is currently in practice. This diagnostic procedure would help direct therapy to prevent cardiovascular events that lead to some of the most debilitating medical conditions.

See also OHSU Technology #1184.

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For more information, contact:

Trina Voss
Technology Development Manager
503-494-9839