Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature

Heymans, Sophie V.; Collado-Lara, Gonzalo; Rovituso, Marta; Vos, Hendrik J.; D'hooge, Jan; Jong, Nico de; Abeele, Koen Van Den

doi:10.1109/tuffc.2022.3164805

Cited by 5 publications

(7 citation statements)

References 58 publications

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“…Furthermore, the use of external physical forcing, such as ultrasound which causes the local pressure to decrease as the rarefaction portion of the wave traverses the droplet location, can reduce the laser fluence threshold for droplet vaporization. 25,26 Similar results were observed in our ultrasound study, where droplet vaporization was achieved at a laser fluence of 25 mJ/cm 2 .…”

Section: ■ Results and Discussionsupporting

confidence: 86%

Photoacoustic Vaporization of Endoskeletal Droplets Loaded with Zinc Naphthalocyanine

et al. 2022

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Vaporizable endoskeletal droplets are solid hydrocarbons in liquid fluorocarbon droplets in which melting of the hydrocarbon phase leads to the vaporization of the fluorocarbon phase. In prior work, vaporization of the endoskeletal droplets was achieved thermally by heating the surrounding aqueous medium. In this work, we introduce a near-infrared (NIR) optically absorbing naphthalocyanine dye (zinc 2,11,20,29-tetra-tert-butyl-2,3-naphthalocynanine) into the solid hydrocarbon (eicosane, n-C 20 H 42 ) core of liquid fluorocarbon (C 5 F 12 ) drops suspended in an aqueous medium. Droplets with a uniform diameter of 11.7 ± 0.7 μm were formed using a flow-focusing microfluidic device. The solid hydrocarbon formed a crumpled spherical structure within the liquid fluorocarbon droplet. The photoactivation behavior of these dye-containing endoskeletal droplets was investigated using NIR laser irradiation. When exposed to a pulsed laser of 720 nm wavelength, the dyecontaining droplets vaporized at an average laser fluence of 65 mJ/cm 2 , whereas blank droplets without the dye did not vaporize at any fluence up to 100 mJ/cm 2 . Furthermore, dye-loaded droplets with a smaller, polydisperse size distribution were prepared using a simple shaking method and studied in a flow phantom for their photoacoustic signal and ultrasound contrast imaging. These results demonstrate that dye-containing endoskeletal droplets can be made to vaporize by externally applied optical energy. Such droplets may be useful for a variety of photoacoustic applications for sensing, imaging, and therapy.

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Section: ■ Results and Discussionsupporting

confidence: 86%

Photoacoustic Vaporization of Endoskeletal Droplets Loaded with Zinc Naphthalocyanine

et al. 2022

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“…Nanodroplet preparation: NDs with a perfluorobutane core and a polyvinyl alcohol shell (PVA-PFB NDs) were prepared two days before the proton experiment following the protocol described in [16], [33]. Briefly, a PVA solution was obtained by dissolving 1g of PVA powder (Sigma Aldrich) in 50 mL of milli-Q water at 80°C (2% w/v), followed by the addition of 90 mg of sodium metaperiodate (NaIO4, Sigma Aldrich).…”

Section: Experimental Methods and Data Analysismentioning

confidence: 99%

“…However, the applicability of P-ULM does not depend on the type of charged particle that induces ND vaporization. In addition, sensitivity to protons at body temperature could be obtained through the use of acoustic modulation [16] or by replacing the decafluorobutane liquid core of the NDs by a liquid with a lower boiling point, such as octafluoropropane.…”

Section: Phantommentioning

confidence: 99%

“…At low degrees of superheat, NDs are only vaporized by high-LET secondary particles, generated by rare nuclear reactions [11], [12]. At higher degrees of superheat, primary protons (which have a lower LET) can also vaporize NDs [12], [16]. In both cases, the proton range can be estimated by relating the distribution of vaporization events with the distribution of charged particles.…”

Section: Introductionmentioning

confidence: 99%

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Passive Ultrasound Localization Microscopy of Nanodroplet Vaporizations During Proton Irradiation

Heymans

Collado-Lara

Rovituso³

et al. 2022

IEEE Open J. Ultrason., Ferroelect., Freq. Contr.

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Superheated nanodroplets (NDs) were recently proposed for in vivo proton range verification, owing to their ability to vaporize into echogenic microbubbles (MBs) upon exposure to ionizing radiation. In a previous publication, vaporization events were detected with 2D Ultrasound Localization Microscopy (ULM) based on a pulse-echo method. Here, we introduce P-ULM, a passive version of ULM, based on the detection of acoustic signatures emitted by vaporizing NDs, without actively transmitting ultrasound. Due to the lack of a time reference for the trigger of the ND vaporization, the time differences of arrival to each transducer element are used to retrieve the position of vaporizing NDs. P-ULM, compared to ULM, can continuously detect and super-localize sparse radiation-induced vaporization events with inherent specificity against already existing microbubbles, which otherwise would hinder range verification in the presence of vascular flow. We evaluated the localization performances of both methods theoretically and experimentally, by interleaving active and passive acquisitions on ND-phantoms irradiated with protons. P-ULM offered a higher sensitivity to vaporizations, as it detected twice as many events as ULM. Both methods retrieved, in the acoustic lateral direction, the proton range and range dispersion with sub-millimeter accuracy. In the acoustic axial direction, despite a degraded theoretical resolution limit, P-ULM retrieved the proton spot size with an accuracy similar to ULM. Importantly, P-ULM detected vaporization events with high specificity in the presence of flowing MBs, which makes the technique a candidate for in vivo proton range verification in the presence of flow.

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“…Since the radiation-induced vaporization behavior has been shown to be equivalent for different halocarbons with the same degree of superheat, 19 clinical translation could be achieved through the use of droplet formulations with a similar degree of superheat at 37 • C, either by changing the liquid core to a lower boiling point, 56 or by acoustically modulating the degree of superheat. 51 Another important aspect regarding clinical translation is the droplet diameter. Here, droplets with diameters > 1 µm were used to allow their characterization with a Coulter counter.…”

Section: Clinical Translationmentioning

confidence: 99%

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

Collado-Lara

Heymans

Rovituso³

et al. 2023

Medical Physics

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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. Purpose: Here, we aim to estimate the range estimation precision of this technique. As for any stochastic measurement, the precision will increase with the sample size, that is, the number of detected vaporizations. Thus, we first develop and validate a model to predict the number of vaporizations, which is then applied to estimate the range verification precision for a set of conditions (droplet size, droplet concentration, and proton beam parameters). Methods: Starting from the thermal spike theory, we derived a model that predicts the expected number of droplet vaporizations in an irradiated sample as a function of the droplet size, concentration, and number of protons. The model was validated by irradiating phantoms consisting of size-sorted perfluorobutane droplets dispersed in an aqueous matrix. The number of protons was counted with an ionization chamber, and the droplet vaporizations were recorded and counted individually using high frame rate ultrasound imaging. After validation, the range estimate precision was determined for different conditions using a Monte Carlo algorithm. Results: A good agreement between theory and experiments was observed for the number of vaporizations, especially for large (5.8 ± 2.2 µm) and medium (3.5 ± 1.1 µm) sized droplets. The number of events was lower than expected in phantoms with small droplets (2.0 ± 0.7 µm), but still within the same order of magnitude. The inter-phantom variability was considerably larger (up to 30x) than predicted by the model. The validated model was then combined with Monte Carlo simulations, which predicted a theoretical range retrieval precision improving with the square-root of the number of vaporizations, and degrading at high beam energies due to range straggling. For single pencil beams withThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature

Cited by 5 publications

References 58 publications

Photoacoustic Vaporization of Endoskeletal Droplets Loaded with Zinc Naphthalocyanine

Photoacoustic Vaporization of Endoskeletal Droplets Loaded with Zinc Naphthalocyanine

Passive Ultrasound Localization Microscopy of Nanodroplet Vaporizations During Proton Irradiation

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

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