Technologies enabling in vivo range verification during proton therapy are actively sought as a means to reduce the clinical safety margins currently adopted to avoid tumor underdosage. In this contribution, we applied the semi-empirical theory of radiation-induced vaporization of superheated liquids to coated nanodroplets. Nanodroplets are injectable phase-change contrast agents that can vaporize into highly echogenic microbubbles to provide contrast in ultrasound images. We exposed nanodroplet dispersions in aqueous phantoms to monoenergetic proton beams of varying energies and doses. Ultrasound imaging of the phantoms revealed that radiation-induced droplet vaporization occurred in regions proximal to the proton Bragg peak. A statistically significant increase in contrast was observed in irradiated regions for doses as low as 2 Gy and found to be proportional to the proton fluence. The absence of enhanced response in the vicinity of the Bragg peak, combined with theoretical considerations, suggest that droplet vaporization is induced by high linear energy transfer (LET) recoil ions produced by nuclear reactions with incoming protons. Vaporization profiles were compared to non-elastic cross sections and LET characteristics of oxygen recoils. Shifts between the ultrasound image contrast drop and the expected proton range showed a sub-millimeter reproducibility. These early findings confirm the potential of superheated nanodroplets as a novel tool for proton range verification.

Purpose: Despite the physical benefits of protons over conventional photon radiation in cancer treatment, range uncertainties impede the ability to harness the full potential of proton therapy. While monitoring the proton range in vivo could reduce the currently adopted safety margins, a routinely applicable range verification technique is still lacking. Recently, phase-change nanodroplets were proposed for proton range verification, demonstrating a reproducible relationship between the proton range and generated ultrasound contrast after radiation-induced vaporization at 25°C. In this study, previous findings are extended with proton irradiations at different temperatures, including the physiological temperature of 37°C, for a novel nanodroplet formulation. Moreover, the potential to modulate the linear energy transfer (LET) threshold for vaporization by varying the degree of superheat is investigated, where the aim is to demonstrate vaporization of nanodroplets directly by primary protons. Methods: Perfluorobutane nanodroplets with a shell made of polyvinyl alcohol (PVA-PFB) or 10,12-pentacosadyinoic acid (PCDA-PFB) were dispersed in polyacrylamide hydrogels and irradiated with 62 MeV passively scattered protons at temperatures of 37°C and 50°C. Nanodroplet transition into echogenic microbubbles was assessed using ultrasound imaging (gray value and attenuation analysis) and optical images. The proton range was measured independently and compared to the generated contrast. Results: Nanodroplet design proved crucial to ensure thermal stability, as PVA-shelled nanodroplets dramatically outperformed their PCDA-shelled counterpart. At body temperature, a uniform radiation response proximal to the Bragg peak is attributed to nuclear reaction products interacting with PVA-PFB nanodroplets, with the 50% drop in ultrasound contrast being 0.17 mm AE 0.20 mm 1983

In vitro cardiovascular simulators (namely mock circulatory loops (MCLs)) refer to fully physical systems which can be connected or used with medical devices (MDs). They usually adopt their design from a lumped parameters model dedicated to the simulation of the hemodynamics of the human cardiovascular system. 1,2

Abstract-This paper investigates the consistency in phased array element performance by extracting information from the Full Matrix Capture (FMC) of a reflection from a planar interface. The purpose of this work is to generate a robust methodology for tracking phased array performance over time, therefore, ensuring the reliability of measured data. To achieve this, a calibration method has been developed that quantifies the pulse length, sensitivity, bandwidth and phase error for each element in the array. This paper will highlight the variation across individual array elements and the experimental variation across FMC replicates. Finally, to illustrate the impact of the element performance variation, the phase error is included within the Total Focussing Method imaging algorithm, resulting in an 8% increase in ultrasonic image resolution.

In this paper, ultrasonic phased arrays are deployed as an imaging tool for industrial process analysis. Such arrays are typically used for sonar, medical diagnosis and non-destructive testing, however, they have not yet been applied to industrial process analysis. The precise positioning of array elements and high frequencies possible with this technology mean that highly focused images can be generated that cannot currently be achieved using ultrasound tomography. This paper aims to highlight the potential of this technology for measurement of bubble size distribution (BSD) and to demonstrate its application to both intrusive and non-invasive process measurement. Ultrasound images of bubble reflectors are generated using the total focusing method deployed using a 32 element, 5 MHz linear phased array and an image processing algorithm for BSD determination is presented and evaluated under stationary and dynamic acquisition conditions. It is found that the sizing accuracy is within 10% for stationary reflectors larger than 4λ in diameter and that the algorithm is stable across the expected spatial variation of reflectors. The phased array is coupled to a six-axis robotic arm to scan a solid sample containing bubble reflectors at velocities up to 500 mms −1. The sizing accuracy is within 45% for bubbles larger than 4λ in diameter and at velocities up to 300 mms −1. However, above this velocity the algorithm breaks down for reflectors smaller than 9λ in diameter. The ultrasound system is applied to a stream of air bubbles rising through water that is verified via photographic analysis. Images were generated both intrusive and non-invasive, via a 10 mm Perspex barrier, to the process stream. The high bubble density in the process stream introduced scattering, limiting the measurement repeatability and the sample size in the measured distribution. Notwithstanding, this result demonstrates the potential of this technology to size bubbles for intrusive and non-invasive process analysis.