@article{kim_bautista_deruiter_goel_jiang_xu_dayton_2022, title={An Analysis of Sonothrombolysis and Cavitation for Retracted and Unretracted Clots Using Microbubbles Versus Low-Boiling-Point Nanodroplets}, volume={69}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2021.3137125}, abstractNote={The thrombolysis potential of low-boiling-point (−2 °C) perfluorocarbon phase-change nanodroplets (NDs) has previously been demonstrated on aged clots, and we hypothesized that this efficacy would extend to retracted clots. We tested this hypothesis by comparing sonothrombolysis of both unretracted and retracted clots using ND-mediated ultrasound (US+ND) and microbubble-mediated ultrasound (US+MB), respectively. Assessment data included clot mass reduction, cavitation detection, and cavitation cloud imaging in vitro. Acoustic parameters included a 7.9-MPa peak negative pressure and 180-cycle bursts with 5-Hz repetition (the corresponding duty cycle and time-averaged intensity of 0.09% and 1.87 W/cm2, respectively) based on prior studies. With these parameters, we observed a significantly reduced efficacy of US+MB in the retracted versus unretracted model (the averaged mass reduction rate from 1.83%/min to 0.54%/min). Unlike US+MB, US+ND exhibited less reduction of efficacy in the retracted model (from 2.15%/min to 1.04%/min on average). The cavitation detection results correlate with the sonothrombolysis efficacy results showing that both stable and inertial cavitation generated in a retracted clot by US+ND is higher than that by US+MB. We observed that ND-mediated cavitation shows a tendency to occur inside a clot, whereas MB-mediated cavitation occurs near the surface of a retracted clot, and this difference is more significant with retracted clots compared to unretracted clots. We conclude that ND-mediated sonothrombolysis outperforms MB-mediated therapy regardless of clot retraction, and this advantage of ND-mediated cavitation is emphasized for retracted clots. The primary mechanisms are hypothesized to be sustained cavitation level and cavitation clouds in the proximity of a retracted clot by US+ND.}, number={2}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Kim, Jinwook and Bautista, Kathlyne Jayne B. and Deruiter, Ryan M. and Goel, Leela and Jiang, Xiaoning and Xu, Zhen and Dayton, Paul A.}, year={2022}, month={Feb}, pages={711–719} }
 @article{chandrasekaran_santibanez_tripathi_deruiter_bruegge_pinton_2022, title={In situ ultrasound imaging of shear shock waves in the porcine brain}, volume={134}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2021.110913}, abstractNote={Direct measurement of brain motion at high spatio-temporal resolutions during impacts has been a persistent challenge in brain biomechanics. Using high frame-rate ultrasound and high sensitivity motion tracking, we recently showed shear waves sent to the ex vivo porcine brain developing into shear shock waves with destructive local accelerations inside the brain, which may be a key mechanism behind deep traumatic brain injuries. Here we present the ultrasound observation of shear shock waves in the acoustically challenging environment of the in situ porcine brain during a single-shot impact with sinusoidal and haversine time profiles. The brain was impacted to generate surface amplitudes of 25-33g, and to propagate a 40-50 Hz shear waves into the brain. Simultaneously, images of the moving brain were acquired at 2193 images/s, using a custom sequence with 8 interleaved ultrasound propagation events. For a long field-of-view, wide-beam emissions were designed using time-reversal ultrasound simulations and no compounding was used to avoid motion blurring. For a 40 Hz, 25g sinusoidal impact, a shock-front acceleration of 102g was measured 7.1 mm deep inside the brain. Using a haversine pulse that models a realistic impact more closely, a shock acceleration of 113g was observed 3.0 mm inside the brain, from a 50 Hz, 33g excitation. The experimental velocity, acceleration, and strain-rate waveforms in brain for the monochromatic impact are shown to be in excellent agreement with theoretical predictions from a custom higher-order finite volume method hence demonstrating the capabilities to measure rapid brain motion despite strong acoustical reverberations from the porcine skull.}, journal={JOURNAL OF BIOMECHANICS}, author={Chandrasekaran, Sandhya and Santibanez, Francisco and Tripathi, Bharat B. and DeRuiter, Ryan and Bruegge, Ruth Vorder and Pinton, Gianmarco}, year={2022}, month={Mar} }
 @article{kim_deruiter_goel_xu_jiang_dayton_2020, title={A COMPARISON OF SONOTHROMBOLYSIS IN AGED CLOTS BETWEEN LOWBOILING-POINT PHASE-CHANGE NANODROPLETS AND MICROBUBBLES OF THE SAME COMPOSITION}, volume={46}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2020.07.008}, abstractNote={We present enhanced cavitation erosion of blood clots exposed to low-boiling-point (−2°C) perfluorocarbon phase-change nanodroplets and pulsed ultrasound, as well as microbubbles with the same formulation under the same conditions. Given prior success with microbubbles as a sonothrombolysis agent, we considered that perfluorocarbon phase-change nanodroplets could enhance clot disruption further beyond that achieved with microbubbles. It has been hypothesized that owing to their small size and ability to penetrate into a clot, nanodroplets could enhance cavitation inside a blood clot and increase sonothrombolysis efficacy. The thrombolytic effects of lipid-shell-decafluorobutane nanodroplets were evaluated and compared with those of microbubbles with the same formulation, in an aged bovine blood clot flow model. Seven different pulsing schemes, with an acoustic intensity (ISPTA) range of 0.021–34.8 W/cm2 were applied in three different therapy scenarios: ultrasound only, ultrasound with microbubbles and ultrasound with nanodroplets (n = 5). Data indicated that pulsing schemes with 0.35 W/cm2 and 5.22 W/cm2 produced a significant difference (p < 0.05) in nanodroplet sonothrombolysis performance compared with compositionally identical microbubbles. With these excitation conditions, nanodroplet-mediated treatment achieved a 140% average thrombolysis rate over the microbubble-mediated case. We observed distinctive internal erosion in the middle of bovine clot samples from nanodroplet-mediated ultrasound, whereas the microbubble-mediated case generated surface erosion. This erosion pattern was supported by ultrasound imaging during sonothrombolysis, which revealed that nanodroplets generated cavitation clouds throughout a clot, whereas microbubble cavitation formed larger cavitation clouds only outside a clot sample.}, number={11}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Kim, Jinwook and DeRuiter, Ryan M. and Goel, Leela and Xu, Zhen and Jiang, Xiaoning and Dayton, Paul A.}, year={2020}, month={Nov}, pages={3059–3068} }
 @article{espindola_deruiter_santibanez_dayton_pinton_2020, title={Quantitative sub-resolution blood velocity estimation using ultrasound localization microscopy ex-vivo and in-vivo}, volume={6}, ISSN={["2057-1976"]}, DOI={10.1088/2057-1976/ab7f26}, abstractNote={Super-resolution ultrasound imaging relies on the sub-wavelength localization of microbubble contrast agents. By tracking individual microbubbles, the velocity and flow within microvessels can be estimated. It has been shown that the average flow velocity, within a microvessel ranging from tens to hundreds of microns in diameter, can be measured. However, a 2D super-resolution image can only localize bubbles with sub-wavelength resolution in the imaging plane whereas the resolution in the elevation plane is limited by conventional beamwidth physics. Since ultrasound imaging integrates echoes over the elevation dimension, velocity estimates at a single location in the imaging plane include information throughout the imaging slice thickness. This slice thickness is typically a few orders or magnitude larger than the super-resolution limit. It is shown here that in order to estimate the velocity, a spatial integration over the elevation direction must be considered. This operation yields a multiplicative correction factor that compensates for the elevation integration. A correlation-based velocity estimation technique is then presented. Calibrated microtube phantom experiments are used to validate the proposed velocity estimation method and the proposed elevation integration correction factor. It is shown that velocity measurements are in excellent agreement with theoretical predictions within the considered range of flow rates (10 to 90 μl/min) in a microtube with a diameter of 200 μm. Then, the proposed technique is applied to two in-vivo mouse tail experiments imaged with a low frequency human clinical transducer (ATL L7-4) with human clinical concentrations of microbubbles. In the first experiment, a vein was visible with a diameter of 140 μm and a peak flow velocity of 0.8 mm s−1. In the second experiment, a vein was observed in the super-resolved image with a diameter of 120 μm and with maximum local velocity of ≈4.4 mm s−1. It is shown that the parabolic flow profiles within these micro-vessels are resolvable.}, number={3}, journal={BIOMEDICAL PHYSICS & ENGINEERING EXPRESS}, author={Espindola, David and DeRuiter, Ryan M. and Santibanez, Francisco and Dayton, Paul A. and Pinton, Gianmarco}, year={2020}, month={Apr} }
 @article{deruiter_markley_rojas_pinton_dayton_2020, title={Transient acoustic vaporization signatures unique to low boiling point phase change contrast agents enable super-resolution ultrasound imaging without spatiotemporal filtering}, volume={10}, ISSN={["2158-3226"]}, DOI={10.1063/5.0029207}, abstractNote={The unique activation signal of phase-change contrast agents (PCCAs or droplets) can be separated from the tissue signal and localized to generate super-resolution (SR) ultrasound (US) images. Lipid-shelled, perfluorocarbon PCCAs can be stochastically vaporized (activated) by a plane wave US transmission thereby enabling them to be used as separable targets for ultrasound localization microscopy. The unique signature of droplet vaporization imaging and the transient inherent nature of this signature increases signal contrast and therefore localization confidence, while the poor resolution of the low-frequency vaporization signal is overcome by the super-resolution result. Furthermore, our proposed PCCA SR technique does not require the use of user-dependent and flow-dependent spatio-temporal filtering via singular-value decomposition. Rather, matched filters selected by Fourier-domain analysis are able to identify and localize PCCA activations. Droplet SR was demonstrated in a crossed-microtube water phantom by localizing the activation signals of octafluoropropane nanodroplets (OFP, C3F8, −37 °C boiling point) to resolve 100 µm diameter fluorinated ethylene propylene tubes, which are ordinarily 35% smaller than the native diffraction-limited resolution of the imaging system utilized.}, number={10}, journal={AIP ADVANCES}, author={DeRuiter, R. M. and Markley, E. N. and Rojas, J. D. and Pinton, G. F. and Dayton, P. A.}, year={2020}, month={Oct} }