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Characterizing Thrombus Age and Molecular Organization Using Magnetic Nanoparticle Spectroscopy

J Weaver1,3,4*, H Khurshid2 , Y Shi3 , B Berwin4 , D Schartz4 , B Friedman1 , W Wells1 , C Eskey1 , (1) Dartmouth-Hitchcock Medical Center, Lebanon, NH, (2) University of Sharjah, Sharjah, Sharjah, (3) Dartmouth College, Hanover, NH, (4) Geisel School of Medicine, Hanover, NH


(Sunday, 7/29/2018) 4:00 PM - 6:00 PM

Room: Davidson Ballroom B

Purpose: The most common cause of massive stroke is a thrombus, i.e. a clot, breaking off from the heart or carotid arteries and blocking a major cerebral artery. The use of interventional radiology procedures to mechanically extract the thrombus through a catheter has revolutionized treatment of this type of stroke dramatically reducing both morbidity and mortality. We intended to noninvasively characterize the age and organization of thrombi providing interventional radiologists information to predict how to best remove or lyse a thrombus.

Methods: We studied the binding of nanoparticles to thrombi of different ages using magnetic spectroscopy of Brownian motion. The ability of a magnetic nanoparticle’s magnetization to follow an alternating magnetic field allows us to measure the nanoparticle’s bound state. The magnetization can be measured at depth in the body using low frequency magnetic fields: 400 Hz to 1400 Hz. Thrombi formed for a fixed period between 15 and 100 min. A fixed size clot was then added to a solution of nanoparticles targeted for thrombin. The magnetic spectrum was measured after binding. The relaxation and number of nanoparticles bound to the thrombus was estimated.

Results: The number of nanoparticles bound to the oldest (100 min old) thrombi was only a third of what bound the youngest (15 min old) thrombi reflecting fewer thrombin molecules on the more highly organized fibrin mesh characterizing more mature thrombi. The relaxation time of nanoparticles bound to oldest clots was a third lower than that of the youngest clots. More thrombin on young clots produce multiple bonds to each nanoparticle and increased porosity in younger clots allow the nanoparticles greater penetration into the fibrin mesh both contributing to higher relaxation.

Conclusion: The magnetic spectra of nanoparticles targeted for thrombin can be used to characterize the age and molecular organization of thrombi.

Funding Support, Disclosures, and Conflict of Interest: NIH R21EB021456


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