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

Toumia, Yosra; Miceli, R; Domenici, Fabio; Heymans, Sophie V.; Carlier, Bram; Cociorb, Madalina; Oddo, Letizia; Rossi, Piero; D'Angellilo, Rolando Maria; Sterpin, Edmond; D’Agostino, Emiliano; Abeele, Koen Van Den; D'hooge, Jan; Paradossi, Gaio

doi:10.1016/j.ejmp.2021.08.006

Cited by 7 publications

(15 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both pellets were then recombined and redispersed in 5 ml of Milli-Q water, yielding a droplet concentration in the range 5-50 mM (PFB in water concentration measured with Nuclear Magnetic Resonance spectroscopy). The radiation sensitivity of this nanodroplet formulation has been demonstrated in previous studies [12], [13], [42]. The intensity-weighted mean diameter of this nanodroplet formulation, measured by Dynamic Light Scattering, is 799 nm ± 25 nm, with a polydispersity index of 0.3 [12] (Fig.…”

Section: A Nanodroplet Formulationsupporting

confidence: 67%

See 1 more Smart Citation

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature

Heymans

Collado-Lara

Rovituso³

et al. 2022

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

Self Cite

View full text Add to dashboard Cite

Superheated nanodroplet 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. The radiation-induced vaporization threshold (i.e. sensitization threshold) can be reduced by lowering the pressure in the droplet such that nanodroplet vaporization by primary protons can occur. Here, we propose to use an acoustic field to modulate the pressure, intermittently lowering the proton sensitization threshold of PFB-NDs during the rarefactional phase of the ultrasound wave. Simultaneous proton irradiation and sonication with a 1.1 MHz focused transducer, using increasing peak negative pressures (PNPs), were applied on a dilution of PFB-NDs flowing in a tube, while vaporization was acoustically monitored with a linear array. Sensitization to primary protons was achieved at temperatures between 29 and 40°C using acoustic PNPs of relatively low amplitude (from 800 kPa to 200 kPa, respectively), while sonication alone did not lead to ND vaporization at those PNPs. Sensitization was also measured at the clinically relevant body temperature (i.e., 37°C) using a PNP of 400 kPa. These findings confirm that acoustic modulation lowers the sensitization threshold of superheated nanodroplets, enabling a direct proton response at body temperature.

show abstract

Section: A Nanodroplet Formulationsupporting

confidence: 67%

“…Perfluorobutane nanodroplets with a polyvinyl alcohol shell (PVA-PFB) were prepared according to the protocol detailed in [42]. Briefly, an empty glass vial sealed with a rubber cap was immersed in liquid nitrogen, and gaseous PFB was injected into the vial.…”

Section: A Nanodroplet Formulationmentioning

confidence: 99%

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature

Heymans

Collado-Lara

Rovituso³

et al. 2022

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, the aqueous suspensions of PVA/PFB NDs, prepared by pre-condensation of PFB (b.p. − 2 °C) followed by its encapsulation with a crosslinked PVA shell (see Methods) in a sonication-mediated process, have consistently proven to exhibit an exceptional shelf-life and thermal stability even at temperatures highly exceeding 37 °C 26 , 27 , 49 . The additional Laplace pressure exerted by the shell’s surface tension keeps the core in its metastable liquid state in the absence of external stimuli necessary to reach the vaporization conditions (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The PVA shelled PFB NDs were prepared as described elsewhere 26 , 27 . Typically, an aqueous solution of fully hydrolyzed PVA (Mn = 30 ± 5 kg/mol; Merck, Milan, Italy) at a concentration of 2% (w/v) is first prepared by dissolving the polymer at 80 °C.…”

Section: Methodsmentioning

confidence: 99%

“…In recent publications, we have successfully demonstrated the use of superheated perfluorocarbon (PFC) nanodroplets (i.e. with PFCs being in the liquid phase above their boiling point), with an average size of a few hundred nanometers 22 – 24 , as a novel concept for radiation dosimetry assisted by ultrasound imaging 25 – 27 . In particular, perfluorobutane (C 4 F 10 ) nanodroplets (PFB NDs, b.p.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Toumia

Pullia

Domenici

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

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. Nanodroplets, embedded in tissue-mimicking phantoms, are exposed at 37 °C to a 312 MeV/u clinical C-ions beam at different doses between 0.1 and 4 Gy. The evaluation of the contrast enhancement from ultrasound imaging of the phantoms, pre- and post-irradiation, reveals a significant radiation-triggered nanodroplets vaporization occurring at the C-ions Bragg peak with sub-millimeter shift reproducibility and dose dependency. The specific response of the nanodroplets to C-ions is further confirmed by varying the phantom position, the beam range, and by performing spread-out Bragg peak irradiation. The nanodroplets’ response to C-ions is influenced by their concentration and is dose rate independent. These early findings show the ground-breaking potential of polymer-shelled PFB nanodroplets to enable in vivo carbon ion dosimetry and range verification.

show abstract

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 7 publications

References 54 publications

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature

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

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

Contact Info

Product

Resources

About