RESUMEN
Ultrasound localization microscopy is becoming well established in preclinical applications. For its translation into clinical practice, the localization precision achievable with commercial ultrasound scanners is crucial - especially with volume imaging, which is essential for dealing with out-of-plane motion. Here, we propose an easy-to-perform method to estimate the localization precision of 3D ultrasound scanners. With this method, we evaluated imaging sequences of the Philips Epiq 7 ultrasound device using the X5-1 and the XL14-3 matrix transducers, and also tested different localization methods. For the X5-1 transducer, the best lateral, elevational, and axial precision was 109 µm, 95 µm, and 55 µm for one contrast mode, and 29 µm, 22 µm, and 19 µm for the other. The higher frequency XL14-3 transducer yielded precisions of 17 µm, 38 µm, and 6 µm using the harmonic imaging mode. Although the center of mass was the most robust localization method also often providing the best precision, the localization method has only minor influence on the localization precision compared to the impact by the imaging sequence and transducer. The results show that with one of the imaging modes of the X5-1 transducer, precisions comparable to the XL14-3 transducer can be achieved. However, due to localization precisions worse than 10 µm, reconstruction of the microvasculature at the capillary level will not be possible. These results show the importance to evaluate the localization precision of imaging sequences from different ultrasound transducers or scanners in all directions before using them for in vivo measurements.
RESUMEN
Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US-enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features. This study here shows that manipulating the polymer chemistry of poly(butyl cyanoacrylate) (PBCA) MB via temporarily mixing the monomer with the monomer-mimetic butyl cyanoacetate (BCC) during the polymerization process improves the drug loading capacity of PBCA MB by more than twofold, and the in vitro and in vivo acoustic responses of PBCA MB by more than tenfold. Computer simulations and physisorption experiments show that BCC manipulates the growth of PBCA polymer chains and creates nanocavities in the MB shell, endowing PBCA MB with greater drug entrapment capability and stronger acoustic properties. Notably, because BCC can be readily and completely removed during MB purification, the resulting formulation does not include any residual reagent beyond the ones already present in current PBCA-based MB products, facilitating the potential translation of next-generation PBCA MB.
RESUMEN
With the widespread interest and uptake of super-resolution ultrasound (SRUS) through localization and tracking of microbubbles, also known as ultrasound localization microscopy (ULM), many localization and tracking algorithms have been developed. ULM can image many centimeters into tissue in-vivo and track microvascular flow non-invasively with sub-diffraction resolution. In a significant community effort, we organized a challenge, Ultrasound Localization and TRacking Algorithms for Super-Resolution (ULTRA-SR). The aims of this paper are threefold: to describe the challenge organization, data generation, and winning algorithms; to present the metrics and methods for evaluating challenge entrants; and to report results and findings of the evaluation. Realistic ultrasound datasets containing microvascular flow for different clinical ultrasound frequencies were simulated, using vascular flow physics, acoustic field simulation and nonlinear bubble dynamics simulation. Based on these datasets, 38 submissions from 24 research groups were evaluated against ground truth using an evaluation framework with six metrics, three for localization and three for tracking. In-vivo mouse brain and human lymph node data were also provided, and performance assessed by an expert panel. Winning algorithms are described and discussed. The publicly available data with ground truth and the defined metrics for both localization and tracking present a valuable resource for researchers to benchmark algorithms and software, identify optimized methods/software for their data, and provide insight into the current limits of the field. In conclusion, Ultra-SR challenge has provided benchmarking data and tools as well as direct comparison and insights for a number of the state-of-the art localization and tracking algorithms.