High-resolution vascular tissue characterization in mice using 55MHz ultrasound hybrid imaging

► A high-resolution (⩽40μm) ultrasound-based tissue characterization technique based on hybrid imaging was described. ► Novel ultrasonic parameters for tissue characterization were presented and compared with previously described parameters. ► Ultrasound hybrid imaging characterized vascular tissue in control and atherosclerotic mouse models in vitro and in vivo. ► The technique quantitatively assessed atherosclerosis progression in vessels and results compared well with histology. ► This technique was able to characterize different plaque components including calcification, fibrosis, and lipid pool. Ultrasound and Duplex ultrasonography in particular are routinely used to diagnose cardiovascular disease (CVD), which is the leading cause of morbidity and mortality worldwide. However, these techniques may not be able to characterize vascular tissue compositional changes due to CVD. This work describes an ultrasound-based hybrid imaging technique that can be used for vascular tissue characterization and the diagnosis of atherosclerosis. Ultrasound radiofrequency (RF) data were acquired and processed in time, frequency, and wavelet domains to extract six parameters including time integrated backscatter (TIB), time variance (Tvar), time entropy (TE), frequency integrated backscatter (FIB), wavelet root mean square value (Wrms), and wavelet integrated backscatter (WIB). Each parameter was used to reconstruct an image co-registered to morphological B-scan. The combined set of hybrid images were used to characterize vascular tissue in vitro and in vivo using three mouse models including control (C57BL/6), and atherosclerotic apolipoprotein E-knockout (APOE-KO) and APOE/A1 adenosine receptor double knockout (DKO) mice. The technique was tested using high-frequency ultrasound including single-element (center frequency=55MHz) and commercial array (center frequency=40MHz) systems providing superior spatial resolutions of 24μm and 40μm, respectively. Atherosclerotic vascular lesions in the APOE-KO mouse exhibited the highest values (contrast) of −10.11±1.92dB, −12.13±2.13dB, −7.54±1.45dB, −5.10±1.06dB, −5.25±0.94dB, and −10.23±2.12dB in TIB, Tvar, TE, FIB, Wrms, WIB hybrid images (n=10, p