Magnetic Particle Detection Test for Vulnerable Carotid Plaque

Project SummaryIschemic stroke is the leading cause of long term disability and is responsible for an estimatedof deaths worldwidewith an estimatedof incidences attributed to thromboembolism emanating from vulnerable carotid artery plaquesCarotid plaque risk is stratified based on luminal narrowingstenosismeasured by ultrasoundbut stenosis does not directly inform plaque stabilityStenosis based grading results in carotid revascularizations performed on patients with stable plaquewhile opportunities for intervention are missed on patients bearing vulnerable plaque but sub threshold stenosisThustechnology to accurately characterize plaque compositioni efibrin contentis sorely needed to impact the risk benefit of revascularizationPlaque vulnerability is heightened by prior ruptureintraplaque hemorrhageor plaque erosionall of which are associated with the presence of fibrinDirect non invasive detection of fibrin could provide powerful information about plaque composition and stability that is currently lacking in standard practiceFibrin is a specific target for carotid disease because it is only present in advancedvulnerable Stage VI plaques or in thrombusbut is not present in stable plaquesnormal vessel wall or circulating bloodMolecular imaging of fibrin using fibrin specific probes has been achieved in human clinical trials using magnetic resonance imagingMRIpositron emission tomographyPETand single photon emission computed tomographySPECTHowever these are all expensive techniquesnot well suited for screeningNewly emergent magnetic particle detection technology represents a low costportableand easy to operate alterativeMagnetic particle detection uses low costshelf stable superparamagnetic iron oxide nanoparticlesSPIONswhich can be detected at picomolar sensitivity with little to no background signalThis Phase I SBIR proposal combines fibrin binding peptide technology owned by Collagen Medical with new magnetic particle detector technology being developed at Massachusetts General Hospital to generate initial proof of concept data for a low costportableand easy to operate magnetic particle detection test for vulnerable carotid plaqueWe will conjugate our proprietary fibrin specific peptides to SPIONs to create fibrin targeted nanoparticles and then quantify their fibrin affinitydetection sensitivityand stability in vitroConcurrently we will develop a prototype magnetic particle detector designed for use in human carotid artery diseaseWe will select a lead candidate with high fibrin affinity and stability and use it to quantify the detection sensitivity of the magnetic particle detectorWe will then demonstrate the ability and sensitivity to detect decreasing concentrations of magnetic particles in fibrin gels using an anthropomorphic phantom that simulates a fibrin presenting carotid artery plaque Project Narrative An estimatedof ischemic stroke derive from unstable carotid artery plaque yet no clinical methods to noninvasively and accurately detect vulnerable plaques existIn this project we propose to couple fibrin targeted superparamagnetic iron oxide nanoparticlesSPIONsand magnetic particle detection technology as a low costportableand easy to operate diagnostic test for high risk plaques