Whole-Body Human Ultrasound Tomography.

Ultrasonography is a vital component of modern clinical care, with handheld probes routinely used for a variety of applications. However, handheld ultrasound imaging is limited by factors such as the partial-body field of view, operator dependency, contact-induced distortion, and lack of transmission contrast. Here, we demonstrate a new system enabling whole-body ultrasound tomography of humans in reflection and transmission modes.

The Targeted Degradation of BRAF V600E Reveals the Mechanisms of Resistance to BRAF-Targeted Treatments in Colorectal Cancer Cells.

The V600E mutation is frequently found in cancer. It activates the MAPK pathway and promotes cancer cell proliferation, making BRAF an excellent target for anti-cancer therapy. While BRAF-targeted therapy is highly effective for melanoma, it is often ineffective against other cancers harboring the mutation.

Single-shot 3D photoacoustic computed tomography with a densely packed array for transcranial functional imaging.

Photoacoustic computed tomography (PACT) is emerging as a new technique for functional brain imaging, primarily due to its capabilities in label-free hemodynamic imaging. Despite its potential, the transcranial application of PACT has encountered hurdles, such as acoustic attenuations and distortions by the skull and limited light penetration through the skull. To overcome these challenges, we have engineered a PACT system that features a densely packed hemispherical ultrasonic transducer array with 3072 channels, operating at a central frequency of 1 MHz.

Identification of Lethal Inhibitors and Inhibitor Combinations for Mono-Driver versus Multi-Driver Triple-Negative Breast Cancer Cells.

There are no signaling-based targeted therapies for triple-negative breast cancer. The development of targeted cancer therapy relies on identifying oncogenic signaling drivers, understanding their contributions to oncogenesis and developing inhibitors to block such drivers. In this study, we determine that DU-4475 is a mono-driver cancer cell line relying on BRAF and the mitogen-activated protein kinase pathway for viability and proliferation.

Induction of antitumor immunity in mice by the combination of nanoparticle-based photothermolysis and anti-PD-1 checkpoint inhibition.

Generation of durable tumor-specific immune response without isolation and expansion of dendritic cells or T cells ex vivo remains a challenge. In this study, we investigated the impact of nanoparticle-mediated photothermolysis in combination with checkpoint inhibition on the induction of systemic antitumor immunity. Photothermolysis based on near-infrared light-absorbing copper sulfide nanoparticles and 15-ns laser pulses combined with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) increased tumor infiltration by antigen-presenting cells and CD8-positive T lymphocytes in the B16-OVA mouse model.

Spatial and Temporal Confined Photothermolysis of Cancer Cells Mediated by Hollow Gold Nanospheres Targeted to Epidermal Growth Factor Receptors.

To date, a few studies have investigated the potential use of a short-pulsed laser in selective tumor cell destruction or its mechanism of cell killing. Computer simulation of the spatial and temporal profiles of temperature elevation after pulsed laser irradiation on an infinitesimal point source estimated that the temperature reached its highest point at ∼35 ns after a single 15 ns laser pulse. Moreover, temperature elevation was confined to a radius of sub-micrometer and returned to baseline within 100 ns.

Laser streaming: Turning a laser beam into a flow of liquid.

Transforming a laser beam into a mass flow has been a challenge both scientifically and technologically. We report the discovery of a new optofluidic principle and demonstrate the generation of a steady-state water flow by a pulsed laser beam through a glass window. To generate a flow or stream in the same path as the refracted laser beam in pure water from an arbitrary spot on the window, we first fill a glass cuvette with an aqueous solution of Au nanoparticles.

CuS-labeled nanoparticles: a new sentinel-lymph-node-mapping agent for PET-CT and photoacoustic tomography.

Determining sentinel lymph node (SLN) status is critical to cancer staging and treatment decisions. Currently, in clinical practice, Tc-radiocolloid-mediated planar scintigraphy and single-photon emission computed tomography (SPECT) are used to guide the biopsy and resection of SLNs. Recently, an emerging technique that combines positron emission tomography (PET) and photoacoustic tomography (PAT; PET-PAT) may offer accurate information in detecting SLNs.

Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model.

Here, we report that polyethylene glycol (PEG)-coated copper(II) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time.

[The design of all solid-state tunable pulsed Ti:sapphire laser system].

This paper presented a design of broadly all solid-state tunable pulsed Ti:sapphire laser with high power and stable performance. The laser was pumped by custom-made Nd:YAG laser which had water cooling system and amplified by two stage amplifier. The method accomplished tunable output of all solid-state tunable pulsed Ti:sapphire laser by modifying the reflection angle of the back mirror.

Apoptosis imaging probe predicts early chemotherapy response in preclinical models: A comparative study with 18F-FDG PET.

Unlabelled: Previously, we reported a small-molecular-weight peptide, single amino acid chelae((99m)Tc)-conjugated phosphatidylserine-binding peptide (SAAC((99m)Tc)-PSBP-6), with high binding affinity to phosphatidylserine on the surface of apoptotic cells. The purpose of this study was to determine the effectiveness of SAAC((99m)Tc)-PSBP-6 in detecting apoptosis induced by chemotherapy.

Methods: B16/F10 melanoma and 38C13 lymphoma tumor models were used in this study.

Copper sulfide nanoparticles as a new class of photoacoustic contrast agent for deep tissue imaging at 1064 nm.

Photoacoustic tomography (PAT) is an emerging molecular imaging modality. Here, we demonstrate use of semiconductor copper sulfide nanoparticles (CuS NPs) for PAT with an Nd:YAG laser at a wavelength of 1064 nm. CuS NPs allowed visualization of mouse brain after intracranial injection, rat lymph nodes 12 mm below the skin after interstitial injection, and CuS NP-containing agarose gel embedded in chicken breast muscle at a depth of ~5 cm.

Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma.

Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma.

Small-animal PET of tumor damage induced by photothermal ablation with 64Cu-bis-DOTA-hypericin.

Unlabelled: The purpose of this study was to investigate the potential application of small-molecular-weight (64)Cu-labeled bis-DOTA-hypericin in the noninvasive assessment of response to photothermal ablation therapy.

Methods: Bis-DOTA-hypericin was labeled with (64)Cu with high efficiency (>95% without purification). Nine mice bearing subcutaneous human mammary BT474 tumors were used.

Photoacoustic microscopy with 2-microm transverse resolution.

We present a new-generation optical-resolution confocal photoacoustic microscope, consisting of a 0.25-numerical aperture optical microscope objective and a 75-MHz center-frequency spherically focused ultrasonic transducer. Experiments verified that this microscope has a transverse resolution of 2 microm, which is the highest to our knowledge among all photoacoustic imaging systems.

Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres.

Photoacoustic tomography (PAT) also referred to as optoacoustic tomography (OAT) is a hybrid imaging modality that employs nonionizing optical radiation and ultrasonic detection. Here, we describe the application of a new class of optical contrast agents based on mesoscopic hollow gold nanospheres (HAuNS) to PAT. HAuNS are approximately 40 nm in diameter with a hollow interior and consist of a thin gold wall.

Three-dimensional combined photoacoustic and optical coherence microscopy for in vivo microcirculation studies.

Photoacoustic microscopy is predominantly sensitive to optical absorption, while optical coherence tomography relies on optical backscattering. Integrating their complementary contrasts can provide comprehensive information about biological tissue. We have developed a dual-modality microscope that combines the two for studying microcirculation.

Tangential resolution improvement in thermoacoustic and photoacoustic tomography using a negative acoustic lens.

We developed a novel concept of using a negative acoustic lens to increase the acceptance angle of an unfocused large-area ultrasonic transducer (detector), leading to more than twofold improvement of the tangential resolution in both thermoacoustic and photoacoustic tomography. In both thermoacoustic and photoacoustic tomography, for a given transducer bandwidth, the aperture size of the detector affects the tangential resolution greatly when the object of interest is near the detector surface. We were able to overcome such tangential resolution deterioration by attaching an acoustic concave lens, made of acrylic in front of the flat detector surface.

Adaptive and robust methods of reconstruction (ARMOR) for thermoacoustic tomography.

In this paper, we present new adaptive and robust methods of reconstruction (ARMOR) for thermoacoustic tomography (TAT), and study their performances for breast cancer detection. TAT is an emerging medical imaging technique that combines the merits of high contrast due to electromagnetic or laser stimulation and high resolution offered by thermal acoustic imaging. The current image reconstruction methods used for TAT, such as the delay-and-sum (DAS) approach, are data-independent and suffer from low-resolution, high sidelobe levels, and poor interference rejection capabilities.

Negative lens concept for photoacoustic tomography.

Although a small point ultrasound transducer has a wide acceptance angle, its small active area leads to a high thermal-noise-induced electric voltage in the transducer, thus the sensitivity is low. By contrast, a finite-size flat transducer has high sensitivity, but the acceptance angle is small, which limits its application in reconstruction-based photoacoustic tomography (PAT). Here, we propose a negative lens concept to increase the acceptance angle of a flat transducer without losing sensitivity.

Design and evaluation of a novel breast cancer detection system combining both thermoacoustic (TA) and photoacoustic (PA) tomography.

We have developed a novel scanner for breast cancer detection, integrating both thermoacoustic and photoacoustic techniques to achieve dual contrast (microwave and light absorption) imaging. This scanner is nonionizing, low cost, and can potentially provide high-resolution, dual modality three-dimensional images of the breast. The scanner uses front instead of side breast compression and dry instead of gel ultrasonic coupling.

Image distortion in thermoacoustic tomography caused by microwave diffraction.

We report an intrinsic image distortion in microwave-induced thermoacoustic tomography. The distortion, due to microwave diffraction in the object to be imaged, leads to nonuniform excitation of acoustic pressure during microwave illumination. Both numerical simulations and phantom experiments demonstrate this phenomenon.

Combined photoacoustic and molecular fluorescence imaging in vivo.

Because of the overwhelming scattering of light in biological tissues, the spatial resolution and imaging depth of conventional fluorescent imaging is unsatisfactory. Therefore, we present a dual modality imaging technique by combining fluorescence imaging with high-resolution noninvasive photoacoustic tomography (PAT) for the study of an animal tumor model. PAT provides high-resolution structural images of tumor angiogenesis, and fluorescence imaging offers high sensitivity to molecular probes for tumor detection.

High-resolution ultrasound-aided biophotonic imaging.

Optical contrast is sensitive to functional parameters, including the oxygen saturation and total concentration of hemoglobin, in biological tissues. However, due to the overwhelming scattering encountered by light in tissues, traditional optical modalities cannot provide satisfactory spatial resolution beyond the ballistic (a few hundred microns) and quasiballistic (1-2 mm) regimes. Photoacoustic tomography is based on the high optical contrast yet utilizing the high ultrasonic resolution.

Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography.

Simultaneous transcranial imaging of two functional parameters, the total concentration of hemoglobin and the hemoglobin oxygen saturation, in the rat brain in vivo is realized noninvasively using laser-based photoacoustic tomography (PAT). As in optical diffusion spectroscopy, PAT can assess the optical absorption of endogenous chromophores, e.g.