Volumetric Passive Acoustic Mapping and Cavitation Detection of Nanobubbles under Low-Frequency Insonation.

Gas bubbles, commonly used in medical ultrasound (US), witness advancements with nanobubbles (NB), providing improved capabilities over microbubbles (MB). NBs offer enhanced penetration into capillaries and the ability to extravasate into tumors following systemic injection, alongside prolonged circulation and persistent acoustic contrast. Low-frequency insonation (<1 MHz) with NBs holds great potential in inducing significant bioeffects, making the monitoring of their acoustic response critical to achieving therapeutic goals.

Rationally designed acoustic holograms for uniform nanodroplet-mediated tissue ablation.

Nanodroplets are phase-changing agents that have shown great potential for ultrasound applications. When ultrasound is applied, nanodroplets can undergo a phase transition into gas bubbles, enabling cavitation that can be used to reduce the pressure threshold required for mechanical ablation of tissues. Effective tissue fractionation depends on precise vaporization to achieve uniform and predictable bubble formation.

Versatile Ultrasound-Compatible Microfluidic Platform for In Vitro Microvasculature Flow Research and Imaging Optimization.

Ultrasound localization microscopy (ULM) enables the creation of super-resolved images and velocity maps by localizing and tracking microbubble contrast agents through a vascular network over thousands of frames of ultrafast plane wave images. However, a significant challenge lies in developing ultrasound-compatible microvasculature phantoms to investigate microbubble flow and distribution in controlled environments. In this study, we introduce a new class of gelatin-based microfluidic-inspired phantoms uniquely tailored for ULM studies.

Nanobubble-mediated cancer cell sonoporation using low-frequency ultrasound.

Ultrasound insonation of microbubbles can form transient pores in cell membranes that enable the delivery of non-permeable extracellular molecules to the cells. Reducing the size of microbubble contrast agents to the nanometer range could facilitate cancer sonoporation. This size reduction can enhance the extravasation of nanobubbles into tumors after an intravenous injection, thus providing a noninvasive sonoporation platform.

Nonlinear Frequency Mixing Ultrasound Imaging of Nanoscale Contrast Agents.

Objective: Nanoscale ultrasound contrast agents show promise as alternatives for diagnostics and therapies due to their enhanced stability and ability to traverse blood vessels. Nonetheless, their reduced size limits echogenicity. This study introduces an enhanced nanobubble frequency mixing ultrasound imaging method, by capitalizing on their nonlinear acoustic response to dual-frequency excitation.

Dense speed-of-sound shift imaging for ultrasonic thermometry.

. Develop a dense algorithm for calculating the speed-of-sound shift between consecutive acoustic acquisitions as a noninvasive means to evaluating temperature change during thermal ablation..

Diameter-dependent assessment of microvascular leakage following ultrasound-mediated blood-brain barrier opening.

Blood brain barrier disruption (BBBD) using focused ultrasound (FUS) and microbubbles (MB) is an effective tool for therapeutic delivery to the brain. BBBD depends to a great extent on MB oscillations. Because the brain vasculature is heterogenic in diameter, reduced MB oscillations in smaller blood vessels, together with a lower number of MBs in capillaries, can lead to variations in BBBD.

Ratiometric Fluorescent Detection of Ultrasound-Regulated ATP Release: An Ultrasound-Resistant Cu,N-Doped Carbon Nanosphere.

Focused ultrasound, as a protocol of cancer therapy, might induce extracellular adenosine triphosphate (ATP) release, which could enhance cancer immunotherapy and be monitored as a therapeutic marker. To achieve an ATP-detecting probe resistant to ultrasound irradiation, we constructed a Cu/N-doped carbon nanosphere (CNS), which has two fluorescence (FL) emissions at 438 and 578 nm to detect ultrasound-regulated ATP release. The addition of ATP to Cu/N-doped CNS was conducted to recover the FL intensity at 438 nm, where ATP enhanced the FL intensity probably via intramolecular charge transfer (ICT) primarily and hydrogen-bond-induced emission (HBIE) secondarily.

Deep Learning-Based Ultrasound Beam Shaping for Spatiotemporal Acoustic Holograms Generation.

Acoustical hologram generation can be achieved via controlled beam shaping by engineering the transmitted phases to create a desired pattern. Optically inspired phase retrieval algorithms and standard beam shaping methods assume continuous wave (CW) insonation, which successfully generate acoustic holograms for therapeutic applications that involve long burst transmissions. However, a phase engineering technique designed for single-cycle transmission and capable of achieving spatiotemporal interference of the transmitted pulses is needed for imaging applications.

Dual ligand-capped gold nanoclusters for the smart detection of specific reactive oxygen species.

Quantitative detection of different types of reactive oxygen species (ROS) is vital for understanding the crucial roles of them in biological processes. However, few researches achieved the detection of multiple types of ROS with one probe until now. Given this, we designed and prepared fluorescent gold nanoclusters capped by dual ligand bovine serum albumin and lysozyme (BSA-LYS-AuNCs), which could detect 3 specific types of ROS based on its different fluorescent responses to HO, •OH and ClO, respectively.

Development of an ultrasound guided focused ultrasound system for 3D volumetric low energy nanodroplet-mediated histotripsy.

Low pressure histotripsy is likely to facilitate current treatments that require extremely high pressures. An ultrasound guided focused ultrasound system was designed to accommodate a rotating imaging transducer within a low frequency therapeutic transducer that operates at a center frequency of 105 kHz. The implementation of this integrated system provides real-time therapeutic and volumetric imaging functions, that are used here for low-cost, low-energy 3D volumetric ultrasound histotripsy using nanodroplets.

On-demand regulation and enhancement of the nucleation in acoustic droplet vaporization using dual-frequency focused ultrasound.

Acoustic droplet vaporization (ADV) plays an important role in focused ultrasound theranostics. Better understanding of the relationship between the ultrasound parameters and the ADV nucleation could provide an on-demand regulation and enhancement of ADV for improved treatment outcome. In this work, ADV nucleation was performed in a dual-frequency focused ultrasound configuration that consisted of a continuous low-frequency ultrasound and a short high-frequency pulse.

Efficacy optimization of low frequency microbubble-mediated sonoporation as a drug delivery platform to cancer cells.

Ultrasound insonation of microbubbles can be used to form pores in cell membranes and facilitate the local trans-membrane transport of drugs and genes. An important factor in efficient delivery is the size of the delivered target compared to the generated membrane pores. Large molecule delivery remains a challenge, and can affect the resulting therapeutic outcomes.

Low frequency nanobubble-enhanced ultrasound mechanotherapy for noninvasive cancer surgery.

Scaling down the size of microbubble contrast agents to the nanometer level holds the promise for noninvasive cancer therapy. However, the small size of nanobubbles limits the obtained bioeffects as a result of ultrasound cavitation, when operating near the nanobubble resonance frequency. Here we show that coupled with low energy insonation at a frequency of 80 kHz, well below the resonance frequency of these agents, nanobubbles serve as noninvasive therapeutic warheads that trigger potent mechanical effects in tumors following a systemic injection.

Optimized Simultaneous Axial Multifocal Imaging via Frequency Multiplexed Focusing.

Simultaneous axial multifocal imaging (SAMI) using a single acoustical transmission was developed to enhance the depth of field. This technique transmits a superposition of axial multifoci waveforms in a single transmission, thus increasing the frame rate. However, since all the waveforms are transmitted at a constant center frequency, there is a tradeoff between attenuation and lateral resolution when choosing a constant frequency for all the axial depths.

Ultrasound Frequency Mixing for Enhanced Contrast Harmonic Imaging of Microbubbles.

Microbubbles (MBs) serve as contrast agents in diagnostic ultrasound (US) imaging. Contrast harmonic imaging (CHI) of MBs takes advantage of their nonlinear properties that generate additional harmonic frequencies in the received spectrum. However, CHI suffers from limitations in terms of contrast, the signal-to-noise ratio, and artifacts.

Nanodroplet-Mediated Low-Energy Mechanical Ultrasound Surgery.

Mechanical ultrasound surgery methods use short, high-intensity pulses to fractionate tissues. This study reports the development of a two-step technology for low-energy mechanical ultrasound surgery of tissues using nanodroplets to reduce the pressure threshold. Step 1 consists of vaporizing the nanodroplets into gaseous microbubbles via megahertz ultrasound excitation.

Enhanced HIFU Theranostics with Dual-Frequency-Ring Focused Ultrasound and Activatable Perfluoropentane-Loaded Polymer Nanoparticles.

High-intensity focused ultrasound (HIFU) has been widely used in tumor ablation in clinical settings. Meanwhile, there is great potential to increase the therapeutic efficiency of temporary cavitation due to enhanced thermal effects and combined mechanical effects from nonlinear vibration and collapse of the microbubbles. In this study, dual-frequency (1.

Acoustically Detonated Microbubbles Coupled with Low Frequency Insonation: Multiparameter Evaluation of Low Energy Mechanical Ablation.

Noninvasive ultrasound surgery can be achieved using focused ultrasound to locally affect the targeted site without damaging intervening tissues. Mechanical ablation and histotripsy use short and intense acoustic pulses to destroy the tissue via a purely mechanical effect. Here, we show that coupled with low-frequency excitation, targeted microbubbles can serve as mechanical therapeutic warheads that trigger potent mechanical effects in tumors using focused ultrasound.

Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer.

High intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer underwent ablation with a parameter set designed to achieve mechanical disruption with minimal thermal dose or a protocol in which tumor temperature reached 65 °C.

Multiplexed ultrasound beam summation for side lobe reduction.

Two-way focusing, which relies on sweeping a focused beam across a field of view, is the conventional method for performing high-quality ultrasound imaging. Side lobes resulting from diffraction reduce the image contrast, thus degrade the image quality. In this paper, we present a new method for beam shaping the transmitted ultrasound waveform in order to reduce side lobes and improve image quality.

Acoustic radiation force imaging using a single-shot spiral readout.

The purpose of this study is to develop and validate rapid magnetic resonance acoustic radiation force imaging (MR-ARFI) using a single shot spiral readout for focused ultrasound (FUS) guidance and for local tissue displacement measurements. A magnetic resonance guided FUS system was used to focus a 3 MHz ultrasound beam to a predetermined position. MR-ARFI was performed with a Bruker 7 T MRI using a modified single-shot spiral readout, with additional motion encoding gradients that convert local displacement into the phase image.