Abstract 16590: Sensitive, Concentration-dependent Entropy Metrics for Quantitative Ultrasound Molecular Imaging of Thrombi
Introduction: Ligand-targeted liquid perfluorocarbon nanoparticles (PFC NP: ~200 nm) were the first described contrast agents for ultrasound molecular imaging demonstrated over 20 years ago for tissue factor imaging in atherosclerotic plaques using conventional processing of signal energy. Recently we have developed alternative analytical (entropy) approaches using information-theoretic detectors (ITD) that provide enhanced detectability for PFC NP beacons that can penetrate into targeted tissues well beyond the range of conventional microbubbles. Here we assess the relationship between targeted PFC NP accumulation and signal intensity over time with selected entropy metrics to illustrate the concentration dependence of the method for ultrasound molecular imaging.
Methods: Human plasma clots were created in vitro and exposed to a dilute suspension of fibrin-targeted PFC NP incorporating an anti-fibrin mAb ligand. Clots were scanned every 10-min for 1 hr with a 25-MHz acoustic microscope.
Results: A monotonic increase in clot reflectivity was observed for both conventional (energy) and ITD metrics, consistent with increasing amounts of NP targeting to fibrin. An exponential recovery model fit to the data (r2=0.999) yielded asymptotic values for enhancement. Shannon entropy and its continuous analog (Hc) exhibited greater initial sensitivity to NP deposition than conventional energy-based metrics as determined by slope of noise-normalized signal change (mLogE=0.146 vs. mHs=0.161, mHc=0.158).
Conclusions: The monotonic rise in signal emanating from targeted substrates reflects the accumulation of PFC NP rapidly “filling in” gaps in a naturally poorly reflective clot surface to produce a progressively brighter scattering interface created by PFC NP, demonstrating the concentration dependence of the technique for imaging sparse epitopes. The early detectability of signal enhancement with ITD attests to its sensitivity at these frequencies.
Author Disclosures: J.N. Marsh: None. J.E. McCarthy: None. S.A. Wickline: None.
- © 2016 by American Heart Association, Inc.