Phase-change ultrasound contrast agents for proton range verification: towards anapplication.

In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility.

A Preliminary Investigation of Radiation-Sensitive Ultrasound Contrast Agents for Photon Dosimetry.

Radiotherapy treatment plans have become highly conformal, posing additional constraints on the accuracy of treatment delivery. Here, we explore the use of radiation-sensitive ultrasound contrast agents (superheated phase-change nanodroplets) as dosimetric radiation sensors. In a series of experiments, we irradiated perfluorobutane nanodroplets dispersed in gel phantoms at various temperatures and assessed the radiation-induced nanodroplet vaporization events using offline or online ultrasound imaging.

Analytic prediction of droplet vaporization events to estimate the precision of ultrasound-based proton range verification.

Background: The safety and efficacy of proton therapy is currently hampered by range uncertainties. The combination of ultrasound imaging with injectable radiation-sensitive superheated nanodroplets was recently proposed for in vivo range verification. The proton range can be estimated from the distribution of nanodroplet vaporization events, which is stochastically related to the stopping distribution of protons, as nanodroplets are vaporized by protons reaching their maximal LET at the end of their range.

On the Identification of Orthotropic Elastic Stiffness Using 3D Guided Wavefield Data.

Scanning laser Doppler vibrometry is a widely adopted method to measure the full-field out-of-plane vibrational response of materials in view of detecting defects or estimating stiffness parameters. Recent technological developments have led to performant 3D scanning laser Doppler vibrometers, which give access to both out-of-plane and in-plane vibrational velocity components. In the present study, the effect of using (i) the in-plane component; (ii) the out-of-plane component; and (iii) both the in-plane and out-of-plane components of the recorded vibration velocity on the inverse determination of the stiffness parameters is studied.

Ultrasound-assisted carbon ion dosimetry and range measurement using injectable polymer-shelled phase-change nanodroplets: in vitro study.

Methods allowing for in situ dosimetry and range verification are essential in radiotherapy to reduce the safety margins required to account for uncertainties introduced in the entire treatment workflow. This study suggests a non-invasive dosimetry concept for carbon ion radiotherapy based on phase-change ultrasound contrast agents. Injectable nanodroplets made of a metastable perfluorobutane (PFB) liquid core, stabilized with a crosslinked poly(vinylalcohol) shell, are vaporized at physiological temperature when exposed to carbon ion radiation (C-ions), converting them into echogenic microbubbles.

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature.

Superheated nanodroplet (ND) vaporization by proton radiation was recently demonstrated, opening the door to ultrasound-based in vivo proton range verification. However, at body temperature and physiological pressures, perfluorobutane nanodroplets (PFB-NDs), which offer a good compromise between stability and radiation sensitivity, are not directly sensitive to primary protons. Instead, they are vaporized by infrequent secondary particles, which limits the precision for range verification.

Spatiotemporal Distribution of Nanodroplet Vaporization in a Proton Beam Using Real-Time Ultrasound Imaging for Range Verification.

The potential of proton therapy to improve the conformity of the delivered dose to the tumor volume is currently limited by range uncertainties. Injectable superheated nanodroplets have recently been proposed for ultrasound-based in vivo range verification, as these vaporize into echogenic microbubbles on proton irradiation. In previous studies, offline ultrasound images of phantoms with dispersed nanodroplets were acquired after irradiation, relating the induced vaporization profiles to the proton range.

Ultrasound-assisted investigation of photon triggered vaporization of poly(vinylalcohol) phase-change nanodroplets: A preliminary concept study with dosimetry perspective.

Purpose: We investigate the vaporization of phase-change ultrasound contrast agents using photon radiation for dosimetry perspectives in radiotherapy.

Methods: We studied superheated perfluorobutane nanodroplets with a crosslinked poly(vinylalcohol) shell. The nanodroplets' physico-chemical properties, and their acoustic transition have been assessed firstly.

Modeling lamb wave propagation in visco-elastic composite plates using a fifth-order plate theory.

A new extension of the shear deformation theory to fifth order in order to calculate the spectrum of Lamb waves in orthotropic media over a wide frequency range is developed and analyzed. The aspiration of the proposed method is to create an alternative framework to exhaustive 3D elasticity based solutions by increasing computational efficiency without losing accuracy, nor robustness. A new computational framework is introduced which allows to estimate the dispersion curves for the first nine symmetric and nine anti-symmetric Lamb modes.

Effect of a Radiotherapeutic Megavoltage Beam on Ultrasound Contrast Agents.

Collateral damage to healthy surrounding tissue during conventional radiotherapy increases when deviations from the treatment plan occur. Ultrasound contrast agents (UCAs) are a possible candidate for radiation dose monitoring. This study investigated the size distribution and acoustic response of two commercial formulations, SonoVue/Lumason and Definity/Luminity, as a function of dose on clinical megavoltage photon beam exposure (24 Gy).

Optimal Design Parameters for a Phased-Array-Based Ultrasonic Polar Scan.

In the context of designing a next-generation ultrasonic polar scan (UPS) measurement system for viscoelastic material characterization, a novel approach is proposed, which draws on a set of cylindrically focused emitters in conjunction with a circular phased array (C-PA) receiver in order to create a portable measurement system while improving the data quality and ease the data interpretation. To explore the potential of the new approach and determine its optimal design parameters, a 3-D analytical model is presented to numerically simulate UPS experiments with the proposed system. Furthermore, a postprocessing procedure is worked out to treat the acquired raw data with the aim to deal with the integrating effect of finite size transducers and directly reconstruct the angle-dependent plane wave reflection coefficients of the sample under study.

Modulating ultrasound contrast generation from injectable nanodroplets for proton range verification by varying the degree of superheat.

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.

Proton range verification with ultrasound imaging using injectable radiation sensitive nanodroplets: a feasibility study.

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.

Numerical Study of a Phased Array-Based Ultrasonic Polar Scan to Determine Plane-Wave Reflection Coefficients of Plates.

Numerical finite-element (FE) simulations and postprocessing analysis methods are presented for ultrasonic polar scan (UPS) measurements involving a circular phased array (C-PA) to determine the plane-wave reflection coefficient of plates. Apodization weights for the C-PA elements are determined to assure the generation of a quasi-plane wave upon excitation at the plate surface and to mitigate bounded beam effects on the assessed reflection coefficient. In addition, postprocessing of the reflection signals is performed via the synthetic plane-wave technique to further filter out any bounded beam effects.

Phase Change Ultrasound Contrast Agents with a Photopolymerized Diacetylene Shell.

Phase change contrast agents for ultrasound (US) imaging consist of nanodroplets (NDs) with a perfluorocarbon (PFC) liquid core stabilized with a lipid or a polymer shell. Liquid ↔ gas transition, occurring in the core, can be triggered by US to produce acoustically active microbubbles (MBs) in a process named acoustic droplet vaporization (ADV). MB shells containing polymerized diacetylene moiety were considered as a good trade off between the lipid MBs, showing optimal attenuation, and the polymeric ones, displaying enhanced stability.

The study of wood knots using acoustic nondestructive testing methods.

In the process of wood grading with the focus on detecting wood knots, nondestructive testing methods based on sound transmission can assist the traditional characterization methods to achieve a higher efficiency and better results. In this paper, we use two independent methods based on resonance and sound speed measurements to evaluate the elastic modulus of wood beams containing different knots. The results show that the method based on sound speed measurements offers a fast procedure to evaluate whether the knot is in the middle of the cross-section of the beam or not.

Attenuation estimation by repeatedly solving the forward scattering problem.

Estimation of the attenuation is important in medical ultrasound not only for correct time-gain compensation but also for tissue characterization. In this paper, the feasibility of a new method for attenuation estimation is tested. The proposed method estimates the attenuation by repeatedly solving the forward wave propagation problem and matching the simulated signals to the measured ones.

Temperature dependence of speed of sound and attenuation of porcine left ventricular myocardium.

The temperature dependence of soft tissue acoustic properties is relevant for monitoring tissue hyperthermia. In the current work, the propagation speed and attenuation of healthy porcine left ventricular myocardium (N=5) was investigated in a frequency range relevant for clinical diagnostic imaging, i.e.

Linear and Nonlinear Guided Wave Imaging of Impact Damage in CFRP Using a Probabilistic Approach.

The amount and variety of composite structures that need to be inspected for the presence of impact damage has grown significantly in the last few decades. In this paper, an application of a probabilistic ultrasonic guided wave imaging technique for impact damage detection in carbon fiber-reinforced polymers (CFRP) is presented. On the one hand, a linear, baseline-dependent, technique utilizing the well-known correlation-based RAPID method and an array of piezoelectric transducers is applied to detect impact-induced damage in plate-like composite structures.

Two dimensional modeling of elastic wave propagation in solids containing cracks with rough surfaces and friction - Part II: Numerical implementation.

Our study aims at the creation of a numerical toolbox that describes wave propagation in samples containing internal contacts (e.g. cracks, delaminations, debondings, imperfect intergranular joints) of known geometry with postulated contact interaction laws including friction.

Two dimensional modeling of elastic wave propagation in solids containing cracks with rough surfaces and friction - Part I: Theoretical background.

Our study aims at the creation of a numerical toolbox that describes wave propagation in samples containing internal contacts (e.g. cracks, delaminations, debondings, imperfect intergranular joints) of known geometry with postulated contact interaction laws including friction.

A protocol for sustained reduction of Total Parenteral Nutrition and cost savings by improvement of nutritional care in hospitals.

Background And Aims: Malnutrition and the use of Total Parenteral Nutrition (TPN) contribute considerably to hospital costs. Recently, we reported on the introduction of malnutrition screening and monitoring of TPN use in our hospital, which resulted in a large (40%) reduction in TPN and improved quality of nutritional care in two years (2011/12). Here, we aimed to assure continuation of improved care by developing a detailed malnutrition screening and TPN use protocol involving instruction tools for hospital staff, while monitoring the results in the following two years (2013/14).

Extension of the angular spectrum method to model the pressure field of a cylindrically curved array transducer.

An extension to the angular spectrum approach for modelling pressure fields of a cylindrically curved array transducer is described in this paper. The proposed technique is based on representing the curved transducer surface as a set of planar elements whose contributions are combined at a selected intermediate plane from which the field is further propagated using the conventional angular spectrum approach. The accuracy of the proposed technique is validated through comparison with Field II simulations.

Modeling the dose dependence of the vis-absorption spectrum of EBT3 GafChromic™ films.

Purpose: The aim of this work was to model the dose dependence of the darkening of GafChromic™ EBT3 films by combining the optical properties of the polydiacetylene polymer phases, and a modified version of the single-hit model, which will take the stick-like shape of the monomer microcrystals into account. Second, a comparison is made between the quantification of the film darkening by flatbed scanning and by UV-vis absorption spectroscopy.

Method: GafChromic EBT3 films were irradiated with a 6 MV photon beam at dose levels between 0 and 50 Gy.

Isothermal Crystallization Behavior of Cocoa Butter at 17 and 20 °C with and without Limonene.

Differential scanning calorimetry and real-time X-ray diffraction using synchrotron radiation were used to elucidate isothermal cocoa butter crystallization at 17 and 20 °C in the absence and presence of different limonene concentrations. At 17 °C, a three-step crystallization process was visible for pure cocoa butter, whereby first an unknown structure with long spacings between a 2L and 3L structure was formed that rapidly transformed into the more stable α structure, which in turn was converted into more stable β' crystals. At 20 °C, an α-mediated β' crystallization was observed.