Repetitive optical coherence elastography measurements with blinking nanobombs

Boerner, P.; Nevozhay, Dmitry; Hatamimoslehabadi, Maryam; Chawla, Harshdeep Singh; Zvietcovich, Fernando; Aglyamov, Salavat R.; Larin, Kirill V.; Sokolov, Konstantin

doi:10.1364/boe.401734

Cited by 8 publications

(11 citation statements)

References 68 publications

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“…Five PNCA formulations with different PFC cores (100% C5 [C6‐0]; 75% C5 and 25% C6 [C6‐25]; 50% C5 and C6 [C6‐50]; 25% C5 and 75% C6 [C6‐75]; and 100% C6 [C6‐100]) were prepared according to previous work, 15–18 with PFC mixtures being mixed on a per‐particle level. Briefly, a lipid cake composed of 18.0 mg 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC, 94.3% by molarity), 1.7 mg 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐methoxy‐polyethyleneglycol‐2000 (DSPE‐PEG‐2000, 2.5%), and 0.3 mg cholesterol (3.2%; all from Avanti Polar Lipids, Inc., Alabaster, AL) was formed and then rehydrated in 2 ml deionized (DI) water for each of these preparations.…”

Section: Methodsmentioning

confidence: 99%

“…We address this problem by investigating high-frequency (i.e., 12.3 MHz) activation and imaging of PNCAs with varying HBP PFC cores and two distinct lipid shells to achieve a stable formulation that can be reliably activated and imaged with high contrast using diagnostic US. [15][16][17][18] with PFC mixtures being mixed on a perparticle level. Briefly, a lipid cake composed of 18.0 mg 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC, 94.3% by molarity), 1.7 mg 1,2-distearoyl-sn-glycero-3phosphoethanolamine-N-methoxy-polyethyleneglycol-2000 (DSPE-PEG-2000, 2.5%), and 0.3 mg cholesterol (3.2%; all from Avanti Polar Lipids, Inc., Alabaster, AL) was formed and then rehydrated in 2 ml deionized (DI) water for each of these preparations.…”

Section: Introductionmentioning

confidence: 99%

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Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

et al. 2022

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Background: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase-changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US. Purpose: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high-frequency US suitable for clinical imaging. Methods: PNCAs with varied core compositions (i.e., mixtures of perfluoropentane [C5] and/or perfluorohexane [C6]) and two coating formulations (i.e., with and without cholesterol) were characterized and investigated for thermal/temporal stability and postactivation, nonlinear US contrast in phantom and in vivo environments. Through hydrophone measurements and nonlinear numerical modeling, MI was estimated for pulse sequences used for PNCA activation. Results: All PNCA compositions were characterized to have similar diameters (249-267 nm) and polydispersity (0.151-0.185) following fabrication. While PNCAs with majority C5 core composition showed higher levels of spontaneous signal (i.e., not due to US activation) in phantoms than C6-majority PNCAs, all compositions were stable during imaging experiments. When activating PNCAs with a 12.3-MHz US pulse (MI = 1.1), C6-core particles with cholesterol-free coatings (i.e., CF-C6-100 particles) generated a median contrast of 3.1, which was significantly higher (p < 0.001) than other formulations. Further, CF-C6-100 particles were activated in a murine model, generating US contrast ≥3.4. Conclusion: C6-core PNCAs can provide high-contrast US imaging with minimal nonspecific activation in phantom and in vivo environments.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

et al. 2022

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“…For the synthesis of MaMAs, 1.97 mg of lipids and 0.4 mg of IONPs (based on the iron content measured by ICP-MS) were taken for a typical batch. The exact ratio of lipids is outlined in Table and consisted of PEGylated DSPE phospholipids that are commonly used in various biomedical applications − including clinical lipid formulations. − Specifically, 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-1000] (DSPE-PEG-1000), 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG-2000), and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[azido(polyethylene glycol)-2000] (DSPE-PEG-2k-Azide) were mixed at the molar ratios of 60%:20%:20%, respectively.…”

Section: Resultsmentioning

confidence: 99%

One-Pot, One-Step Synthesis of Drug-Loaded Magnetic Multimicelle Aggregates

et al. 2022

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Lipid-based formulations provide a nanotechnology platform that is widely used in a variety of biomedical applications because it has several advantageous properties including biocompatibility, reduced toxicity, relative ease of surface modifications, and the possibility for efficient loading of drugs, biologics, and nanoparticles. A combination of lipid-based formulations with magnetic nanoparticles such as iron oxide was shown to be highly advantageous in a growing number of applications including magnet-mediated drug delivery and image-guided therapy. Currently, lipid-based formulations are prepared by multistep protocols. Simplification of the current multistep procedures can lead to a number of important technological advantages including significantly decreased processing time, higher reaction yield, better product reproducibility, and improved quality. Here, we introduce a one-pot, single-step synthesis of drug-loaded magnetic multimicelle aggregates (MaMAs), which is based on controlled flow infusion of an iron oxide nanoparticle/lipid mixture into an aqueous drug solution under ultrasonication. Furthermore, we prepared molecular-targeted MaMAs by directional antibody conjugation through an Fc moiety using Cu-free click chemistry. Fluorescence imaging and quantification confirmed that antibody-conjugated MaMAs showed high cell-specific targeting that was enhanced by magnetic delivery.

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“…When the surface of an elastic medium is excited with force/displacement perpendicular to such surface (axial motion in figure 3(b)), LSWs are generated and travel towards depth with interesting properties for OCE: they have a longitudinal (axial) component of motion detectable by OCT, and they travel at the shear wave speed (not being guided by the sample's surface as in SAW). In recent years, this type of waves have been leveraged by OCE for the characterization of tissue-mimicking phantoms and biological tissues ex vivo [76][77][78][79][80][81][82].…”

Section: Lswsmentioning

confidence: 99%

“…Laser-pulse stimulation has been applied in the elastography of cornea [112], skin [113], and liver [111] for the non-contact generation of large bandwidth SAWs and Lamb waves. Moreover, laser stimulation in conjunction with photo-absorbers [114], and dye-loaded perfluorocarbon nanodroplets (also named as 'nanobombs') [79][80][81][82] inside tissues allows the localized generation of shear and LSWs of great importance in the transverse elastic characterization of tissues. Finally, the dependence of optical absorption coefficient in tissues with the laser energy fluence needed to produce detectable displacements are in the same range and, in some cases, surpasses the permissible safety levels.…”

Section: Laser-pulse Stimulationmentioning

confidence: 99%

Wave-based optical coherence elastography: the 10-year perspective

Zvietcovich

Larin

2022

Prog. Biomed. Eng.

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After ten years of progress and innovation, optical coherence elastography (OCE) based on the propagation of mechanical waves has become one of the major and, perhaps, one of the most studied OCE branches, producing a fundamental impact in the quantitative and nondestructive biomechanical characterization of tissues. Preceding previous progress made in ultrasound and magnetic resonance elastography; wave-based OCE has pushed to the limit the advance of three major pillars: (1) implementation of novel wave excitation methods in tissues, (2) understanding new types of mechanical waves in complex boundary conditions by proposing advance analytical and numerical models, and (3) the development of novel estimators capable of retrieving quantitative 2D/3D biomechanical information of tissues. This remarkable progress promoted a major advance in answering basic science questions and improving medical disease diagnosis and treatment monitoring in several types of tissues leading, ultimately, to the first attempts of clinical trials and translational research. This paper summarizes the fundamental up-to-date principles and categories of wave-based OCE, revises the timeline and the state-of-the-art techniques and applications lying in those categories, and concludes with a discussion of current challenges and future directions, including clinical translation research.

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Repetitive optical coherence elastography measurements with blinking nanobombs

Cited by 8 publications

References 68 publications

Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

One-Pot, One-Step Synthesis of Drug-Loaded Magnetic Multimicelle Aggregates

Wave-based optical coherence elastography: the 10-year perspective

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