Sonothrombolysis: the contribution of stable and inertial cavitation to clot lysis.

Microbubble-mediated sonothrombolysis (STL) is a remarkable approach to vascular occlusion therapy. However, STL remains a complex process with multiple interactions between clot, ultrasound (US), microbubbles (MB) and thrombolytic drug. The aim of this study was to evaluate the ability of combining US and MB to degrade fibrin and, more specifically, to assess the roles of both stable (SC) and inertial (IC) cavitation. Human blood clots containing radiolabeled fibrin were exposed to different combinations of recombinant tissue plasminogen activator (rtPA), US (1 MHz) and phospholipid MB. Three acoustic pressures were tested: 200, 350 and 1,300 kPa (peak-negative pressure). Clot lysis was assessed by diameter loss and release of radioactive fibrin degradation products. The combination rtPA + US + MB clearly revealed that IC (1,300 kPa) was able to enhance fibrin degradation significantly (66.3 ± 1.8%) compared with rtPA alone (51.7 ± 2.0%, p < 0.001). However, SC failed to enhance fibrin degradation at an acoustic pressure of 200 kPa. At 350 kPa, a synergistic effect between rtPA and US + MB was observed with an absolute increase of 6% compared to rtPA alone (p < 0.001). Conversely, without rtPA, the combination of US + MB was unable to degrade the fibrin network (0.3 ± 0.1%, p > 0.05 vs. control), but induced a distinct loss of red blood cells throughout the entire thickness of the clot, implying that MB were able to penetrate and cavitate inside the clot.

Perfusion quantification in contrast-enhanced ultrasound (CEUS)--ready for research projects and routine clinical use.

With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers.

Nonlinear contrast imaging with an array-based micro-ultrasound system.

The main goal of this study was to determine the optimal strategy for a real-time nonlinear contrast mode for small-animal imaging at high frequencies, on a new array-based micro-ultrasound system. Previously reported contrast imaging at frequencies above 15 MHz has primarily relied on subtraction schemes involving B-mode image data. These approaches provide insufficient contrast to tissue ratios under many imaging conditions. In this work, pulse inversion, amplitude modulation and combinations of these were systematically investigated for the detection of nonlinear fundamental and subharmonic signal components to maximize contrast-to-tissue ratio (CTR) in the 18-24 MHz range. From in vitro and in vivo measurements, nonlinear fundamental detection with amplitude modulation provided optimal results, allowing an improvement in CTR of 13 dB compared with fundamental imaging. Based on this detection scheme, in vivo parametric images of murine kidneys were generated using sequences of nonlinear contrast images after intravenous bolus injections of microbubble suspensions. Initial parametric images of peak enhancement (PE), wash-in rate (WiR) and rise time (RT) are presented. The parametric images are indicative of blood perfusion kinetics, which, in the context of preclinical imaging with small animals, are anticipated to provide valuable insights into the progression of human disease models, where blood perfusion plays a critical role in either the diagnosis or treatment of the disease.