Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated Nanodroplets

Luke, Geoffrey P.; Hannah, Andrew; Emelianov, Stanislav

doi:10.1021/acs.nanolett.6b00108

Cited by 104 publications

(131 citation statements)

References 19 publications

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“…While perfluoropentane (PFP, T b = 29°C) is a more common nanodroplet internal phase due its lower vaporization threshold, we found that PFH droplets were not only more stable but also provided a greater variation of acoustic signal over a smaller range of incident intensities. 26 This combination of stability and control over vaporization has led to the increasing use of PFH nanodroplets for in vitro and in vivo applications, including conventional ultrasound theranostics, 27,28 and photoacoustic imaging 29 and therapy. 30 Here, the variation of acoustic responses of droplets with varying monolayer compositions was correlated to the phase behavior on the droplet.…”

Section: Introductionmentioning

confidence: 99%

Phase behavior of mixed lipid monolayers on perfluorocarbon nanoemulsions and its effect on acoustic contrast

et al. 2016

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Lipid-stabilized nanoemulsions containing a volatile liquid perfluorocarbon core have been studied as ultrasound contrast agents owing to their ability to transform into high-contrast microbubbles when subjected to high intensity focused ultrasound (HIFU). However, while there have been several studies on the effect of acoustic parameters on contrast, the effect of the droplet’s stabilizing shell has not been studied as extensively. Inspired by previous studies showing lateral phase separation in microbubbles and vesicles, nanodroplets were formulated with a perfluorohexane core and a shell composed of varying amounts of saturated (DPPC) phospholipids, unsaturated (DOPC) phospholipids, and cholesterol, which were fractionated to obtain nanodroplets of mean diameter 300–400 nm and were stable over one week. When the DOPC content was increased to 40 mol%, ultrasound contrast increased by about one order of magnitude over DPPC-only droplets. Based on fluorescence microscopy results of lateral lipid phase separation on the droplet surface, the various combinations of DPPC, DOPC, and cholesterol were assigned to three regimes on the ternary phase diagram: solid-liquid ordered (low contrast), liquid ordered-liquid disordered (medium contrast), and solid-liquid disordered (high contrast). These regimes were confirmed by TEM analysis of nanoscale droplets. Droplets containing mixed lipid monolayers were also found to produce a significantly greater yield than single-component droplets. The discovery of the dependence of acoustic response on lipid phase separation will help to understand the formulation, behavior, and vaporization mechanism of acoustically-responsive nanoemulsions.

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Section: Introductionmentioning

confidence: 99%

Phase behavior of mixed lipid monolayers on perfluorocarbon nanoemulsions and its effect on acoustic contrast

et al. 2016

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“…Moreover, the PFH-based agent serves as a good diagnostic SPA imaging probe because the bulk boiling point of PFH is above body temperature but below water (T PFH boiling = 56°C). Because PFH has a boiling point between these limits, the droplet will recondense back into its liquid phase after activation 26,27,29,33,34 . Furthermore, because these agents can also be synthesized at diameters well less than 200 nm with the ouzo method, they should be able, when additionally functionalized, to accumulate in tumors.…”

mentioning

confidence: 99%

Polypyrrole-Coated Perfluorocarbon Nanoemulsions as a Sono-Photoacoustic Contrast Agent

Yoon

Pelivanov

et al. 2017

Nano Lett.

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A new contrast agent for combined photoacoustic and ultrasound imaging is presented. It has a liquid perfluorocarbon (PFC) core of about 250 nm diameter coated by a 30 nm thin polypyrrole (PPy) doped polymer shell emulsion which represents a broadband absorber covering the visible and near-infrared ranges (peak optical extinction at 1050 nm). When exposed to a sufficiently high intensity optical or acoustic pulse, the droplets vaporize to form microbubbles providing a strong increase in imaging sensitivity and specificity. The threshold for contrast agent activation can further drastically be reduced by up to two orders of magnitude if simultaneously exposing them with optical and acoustic pulses. The selection of PFC core liquids with low boiling points (i.e. perfluorohexane (56°C), perfluoropentane (29°C) and perfluorobutane (−2°C)) facilitates activation and reduces the activation threshold of PPy coated emulsion contrast agents to levels well within clinical safety limits (as low as 0.2 MPa at 1 mJ/cm2). Finally, the potential use of these nanoemulsions as a contrast agent is demonstrated in a series of phantom imaging studies.

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“…Conventional ultrasound is a low-cost and non-invasive technique [25], but has a low resolution and specificity [26], making it insufficient for BC diagnosis, especially for small tumors. PAI provides better spatial resolution than conventional ultrasound [27].…”

Section: Discussionmentioning

confidence: 99%

Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study

Peng

Shang

Guo

et al. 2018

Molecular Cancer Therapeutics

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Bladder cancer (BC) is a common human malignancy. Conventional ultrasound and white light cystoscopy are often used for BC diagnosis and resection, but insufficient specificity results in a high BC recurrence rate. New strategy for the diagnosis and resection of BC are needed. In this study, we developed a highly specific peptide-based probe for BC photoacoustic imaging (PAI) diagnosis and near-infrared (NIR)-imaging-guided resection post-instillation. A BC-specific peptide (PLSWT7) was selected by in vivo phage display technology and labeled with IRDye800CW to synthesize a BC-specific dual-modality imaging (DMI) probe (PLSWT7-DMI). The feasibility of PLSWT7-DMI-based dual-modality PAI-NIR imaging was assessed in vitro, in mouse models, and ex vivo human bladders. An air-pouch BC (APBC) model suitable for probe instillation was established to evaluate the probe-based BC PAI diagnosis and NIR-imaging-guided resection. Human bladders were used to assess whether PLSWT7-DMI-based DMI strategy is a translatable approach for BC detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo. Post-instillation of the probe, tumors <3 mm were detectable by PAI, and NIR-imaging-guided tumor resection decreased the BC recurrence rate by 90% and increased the survival in the mouse model. Additionally, ex vivo NIR imaging of human bladders indicated that PLSWT7-DMI-based imaging would potentially allowed precise resection of BC in clinical settings. This PLSWT7-DMI-based DMI strategy was a translatable approach for BC diagnosis and resection and could potentially lower the BC recurrence rate.

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Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated Nanodroplets

Cited by 104 publications

References 19 publications

Phase behavior of mixed lipid monolayers on perfluorocarbon nanoemulsions and its effect on acoustic contrast

Phase behavior of mixed lipid monolayers on perfluorocarbon nanoemulsions and its effect on acoustic contrast

Polypyrrole-Coated Perfluorocarbon Nanoemulsions as a Sono-Photoacoustic Contrast Agent

Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study

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