For over a decade, the application of acoustic radiation force (ARF) has been proposed as a mechanism to increase ultrasonic molecular imaging (MI) sensitivity in vivo. Presented herein is the first noninvasive in vivo validation of ARF-enhanced MI with an unmodified clinical system. First, an in vitro optical-acoustical setup was used to optimize system parameters and ensure sufficient microbubble translation when exposed to ARF. 3D ARF-enhanced MI was then performed on 7 rat fibrosarcoma tumors using microbubbles targeted to αvβ3 and non-targeted microbubbles. Low-amplitude (< 25 kPa) 3D ARF pulse sequences were tested and compared to passive targeting studies in the same animal. Our results demonstrate that a 78% increase in image intensity from targeted microbubbles can be achieved when using ARF relative to the passive targeting studies. Furthermore, ARF did not significantly increase image contrast when applied to non-targeted agents, suggesting that ARF did not increase non-specific adhesion.

Over the years, several polymers have been developed for use in prosthetic heart valves as alternatives to xenografts. However, most of these materials are beset with a variety of issues, including low material strength, biodegradation, high dynamic creep, calcification, and poor hemocompatibility. We studied the mechanical, surface, and flow-mediated thrombogenic response of poly(Styrene-coblock-4-vinylbenzocyclobutene)-polyIsoButylene-poly(Styrene-coblock-4-vinylbenzocylcobutene) (xSIBS), a thermoset version of the thermoplastic elastomeric polyolefin poly(Styrene-block-IsoButylene-block-Styrene) (SIBS), which has been shown to be resistant to in vivo hydrolysis, oxidation, and enzymolysis. Uniaxial tensile testing yielded an ultimate tensile strength of 35 MPa, 24.5 times greater than for SIBS. Surface analysis yielded a mean contact angle of 82.05° and surface roughness of 144 nm, which was greater than for poly(ε-caprolactone) (PCL) and poly(methyl methacrylate) (PMMA). However, the change in platelet activation state, a predictor of thrombogenicity, was not significantly different from PCL and PMMA after fluid exposure to 1 dyne/cm2 and 20 dyne/cm2. In addition, the number of adherent platelets after 10 dyne/cm2 flow exposure was on the same order of magnitude as PCL and PMMA. The mechanical strength and low thrombogenicity of xSIBS therefore suggest it as a viable polymeric substrate for fabrication of prosthetic heart valves, and other cardiovascular devices.

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IntroductionWe describe initial validation of a new system for digital to analog conversion (DAC) and reconstruction of 12-lead ECGs. The system utilizes an open and optimized software format with a commensurately optimized DAC hardware configuration to accurately reproduce, from digital files, the original analog electrocardiographic signals of previously instrumented patients. By doing so, the system also ultimately allows for transmission of data collected on one manufacturer's 12-lead ECG hardware/software into that of any other.Materials and MethodsTo initially validate the system, we compared original and post-DAC re-digitized 12-lead ECG data files (∼5-minutes long) in two types of validation studies in 10 patients. The first type quantitatively compared the total waveform voltage differences between the original and re-digitized data while the second type qualitatively compared the automated electrocardiographic diagnostic statements generated by the original versus re-digitized data.ResultsThe grand-averaged difference in root mean squared voltage between the original and re-digitized data was 20.8 µV per channel when re-digitization involved the same manufacturer's analog to digital converter (ADC) as the original digitization, and 28.4 µV per channel when it involved a different manufacturer's ADC. Automated diagnostic statements generated by the original versus reconstructed data did not differ when using the diagnostic algorithm from the same manufacturer on whose device the original data were collected, and differed only slightly for just 1 of 10 patients when using a third-party diagnostic algorithm throughout.ConclusionOriginal analog 12-lead ECG signals can be reconstructed from digital data files with accuracy sufficient for clinical use. Such reconstructions can readily enable automated second opinions for difficult-to-interpret 12-lead ECGs, either locally or remotely through the use of dedicated or cloud-based servers.

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