Joint segmentation and image reconstruction with error prediction in photoacoustic imaging using deep learning.

Deep learning has been used to improve photoacoustic (PA) image reconstruction. One major challenge is that errors cannot be quantified to validate predictions when ground truth is unknown. Validation is key to quantitative applications, especially using limited-bandwidth ultrasonic linear detector arrays.

Multiplex Ultrasound Imaging of Perfluorocarbon Nanodroplets Enabled by Decomposition of Postvaporization Dynamics.

Despite the real-time, nonionizing, and cost-effective nature of ultrasound imaging, there is a dearth of methods to visualize two or more populations of contrast agents simultaneously─a technique known as multiplex imaging. Here, we present a new approach to multiplex ultrasound imaging using perfluorocarbon (PFC) nanodroplets. The nanodroplets, which undergo a liquid-to-gas phase transition in response to an acoustic trigger, act as activatable contrast agents.

Dual-drug loaded ultrasound-responsive nanodroplets for on-demand combination chemotherapy.

Phase-changing nanodroplets are nanometric sized constructs that can be vaporized via external stimuli, such as focused ultrasound, to generate gaseous bubbles that are visible in ultrasound. Their activation can also be leveraged to release their payload, creating a method for ultrasound-modulated localized drug delivery. Here, we develop a perfluoropentane core nanodroplet that can simultaneously load paclitaxel and doxorubicin, and release them in response to an acoustic trigger.

Approximating the uncertainty of deep learning reconstruction predictions in single-pixel imaging.

Single-pixel imaging (SPI) has the advantages of high-speed acquisition over a broad wavelength range and system compactness. Deep learning (DL) is a powerful tool that can achieve higher image quality than conventional reconstruction approaches. Here, we propose a Bayesian convolutional neural network (BCNN) to approximate the uncertainty of the DL predictions in SPI.

EGFR-Targeted Perfluorohexane Nanodroplets for Molecular Ultrasound Imaging.

Perfluorocarbon nanodroplets offer an alternative to gaseous microbubbles as contrast agents for ultrasound imaging. They can be acoustically activated to induce a liquid-to-gas phase transition and provide contrast in ultrasound images. In this study, we demonstrate a new strategy to synthesize antibody-conjugated perfluorohexane nanodroplet (PFHnD-Ab) ultrasound contrast agents that target cells overexpressing the epidermal growth factor receptor (EGFR).

Fluorescent Phase-Changing Perfluorocarbon Nanodroplets as Activatable Near-Infrared Probes.

The sensitivity of fluorescence imaging is limited by the high optical scattering of tissue. One approach to improve sensitivity to small signals is to use a contrast agent with a signal that can be externally modulated. In this work, we present a new phase-changing perfluorocarbon nanodroplet contrast agent loaded with DiR dye.

Focused ultrasound stimulation of an ex-vivo Aplysia abdominal ganglion preparation.

Background: A growing body of research demonstrates that focused ultrasound stimulates activity in human and other mammalian nervous systems. However, there is no consensus on which sonication parameters are optimal. Furthermore, the mechanism of action behind ultrasound neurostimulation remains poorly understood.

Sparsity-Based Recovery of Three-Dimensional Photoacoustic Images from Compressed Single-Shot Optical Detection.

Photoacoustic (PA) imaging combines optical excitation with ultrasonic detection to achieve high-resolution imaging of biological samples. A high-energy pulsed laser is often used for imaging at multi-centimeter depths in tissue. These lasers typically have a low pulse repetition rate, so to acquire images in real-time, only one pulse of the laser can be used per image.

Repeated Acoustic Vaporization of Perfluorohexane Nanodroplets for Contrast-Enhanced Ultrasound Imaging.

Superheated perfluorocarbon nanodroplets are emerging ultrasound imaging contrast agents that boast biocompatible components, unique phase-change dynamics, and therapeutic loading capabilities. Upon exposure to a sufficiently high-intensity pulse of acoustic energy, the nanodroplet's perfluorocarbon core undergoes a liquid-to-gas phase change and becomes an echogenic microbubble, providing ultrasound contrast. The controllable activation leads to high-contrast images, while the small size of the nanodroplets promotes longer circulation times and better in vivo stability.

Two-step training deep learning framework for computational imaging without physics priors.

Deep learning (DL) is a powerful tool in computational imaging for many applications. A common strategy is to use a preprocessor to reconstruct a preliminary image as the input to a neural network to achieve an optimized image. Usually, the preprocessor incorporates knowledge of the physics priors in the imaging model.

Compressed ultrafast tomographic imaging by passive spatiotemporal projections.

Existing streak-camera-based two-dimensional (2D) ultrafast imaging techniques are limited by long acquisition time, the trade-off between spatial and temporal resolutions, and a reduced field of view. They also require additional components, customization, or active illumination. Here we develop compressed ultrafast tomographic imaging (CUTI), which passively records 2D transient events with a standard streak camera.

Antibody-Conjugated Barium Titanate Nanoparticles for Cell-Specific Targeting.

Barium titanate nanoparticles (BTNPs) are gaining popularity in biomedical research because of their piezoelectricity, nonlinear optical properties, and high biocompatibility. However, the potential of BTNPs is limited by the ability to create stable nanoparticle dispersions in water and physiological media. In this work, we report a method of surface modification of BTNPs based on surface hydroxylation followed by covalent attachment of hydrophilic poly(ethylene glycol) (PEG) polymers.

Imaging of singlet oxygen feedback delayed fluorescence and lysosome permeabilization in tumor in vivo during photodynamic therapy with aluminum phthalocyanine.

Singlet oxygen is a key cytotoxic agent in photodynamic therapy (PDT). As such, its imaging is highly desirable, but existing direct imaging methods are still limited by the exceptionally low yield of the luminescence signal. Singlet oxygen feedback delayed fluorescence (SOFDF) of the photosensitizer is a higher yield alternative for indirect measurement of this signal.

Sparsity-based photoacoustic image reconstruction with a linear array transducer and direct measurement of the forward model.

Photoacoustic (PA) imaging is an emerging imaging technique for many clinical applications. One of the challenges posed by clinical translation is that imaging systems often rely on a finite-aperture transducer rather than a full tomography system. This results in imaging artifacts arising from an underdetermined reconstruction of the initial pressure distribution (IPD).

Impact of depth-dependent optical attenuation on wavelength selection for spectroscopic photoacoustic imaging.

An optical wavelength selection method based on the stability of the absorption cross-section matrix to improve spectroscopic photoacoustic (sPA) imaging was recently introduced. However, spatially-varying chromophore concentrations cause the wavelength- and depth-dependent variations of the optical fluence, which degrades the accuracy of quantitative sPA imaging. This study introduces a depth-optimized method that determines an optimal wavelength set minimizing an inverse of the multiplication of absorption cross-section matrix and fluence matrix to minimize the errors in concentration estimation.

Spectroscopic Photoacoustic Imaging of Gold Nanorods.

Photoacoustic imaging is a rapidly developing tool capable of achieving high-resolution images with optical contrast at imaging depths up to a few centimeters. When combined with targeted nanoparticle contrast agents, sensitive detection of molecular signatures is possible. In this chapter, we discuss the achievements and future directions of nanoparticle-augmented photoacoustic imaging.

Blinking Phase-Change Nanocapsules Enable Background-Free Ultrasound Imaging.

Microbubbles are widely used as contrast agents to improve the diagnostic capability of conventional, highly speckled, low-contrast ultrasound imaging. However, while microbubbles can be used for molecular imaging, these agents are limited to the vascular space due to their large size (> 1 μm). Smaller microbubbles are desired but their ultrasound visualization is limited due to lower echogenicity or higher resonant frequencies.

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

We have developed a method for super-resolution ultrasound imaging, which relies on a new class of blinking nanometer-size contrast agents: laser-activated nanodroplets (LANDs). The LANDs can be repeatedly optically triggered to undergo vaporization; the resulting spatially stationary, temporally transient microbubbles provide high ultrasound contrast for several to hundreds of milliseconds before recondensing to their native liquid nanodroplet state. By capturing high frame rate ultrasound images of blinking LANDs, we demonstrate the ability to detect individual recondensation events.

Label-free Detection of Lymph Node Metastases with US-guided Functional Photoacoustic Imaging.

Purpose: To determine the ability of ultrasonography (US)-guided spectroscopic photoacoustic (sPA) imaging to depict changes in blood oxygen saturation (SO2) in metastatic lymph nodes of a mouse model of oral cancer.

Materials And Methods: All studies were performed by following protocols approved by the institutional animal care and use committee at the University of Texas at Austin. Coregistered US and photoacoustic images were acquired spanning volumes containing a total of 31 lymph nodes in 17 female nu/nu mice.

Sentinel lymph node biopsy revisited: ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors.

Metastases rather than primary tumors are responsible for killing most patients with cancer. Cancer cells often invade regional lymph nodes (LN) before colonizing other parts of the body. However, due to the low sensitivity and specificity of current imaging methods to detect localized nodal spread, an invasive surgical procedure--sentinel LN biopsy--is generally used to identify metastatic cancer cells.

In-vivo ultrasound and photoacoustic image- guided photothermal cancer therapy using silica-coated gold nanorods.

In nanoparticle-augmented photothermal therapy, evaluating the delivery and spatial distribution of nanoparticles, followed by remote temperature mapping and monitoring, is essential to ensure the optimal therapeutic outcome. The utility of ultrasound and photoacoustic imaging to assist photothermal therapy has been previously demonstrated. Here, using a mouse xenograft tumor model, it is demonstrated in vivo that ultrasound-guided photoacoustic imaging can be used to plan the treatment and to guide the therapy.

Optimization of in vivo spectroscopic photoacoustic imaging by smart optical wavelength selection.

Spectroscopic photoacoustic (sPA) imaging is an emerging biomedical imaging modality which can be used to simultaneously identify multiple optical absorbers in tissue. With current technology, the image acquisition time is limited primarily by the laser repetition rate, and sPA image acquisition can take seconds to minutes, depending on the system and imaging volume. We have developed an algorithm that can be used to eliminate extraneous wavelengths and decrease image acquisition time while maintaining image quality.

Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging.

A biopsy of the first lymph node to which a tumor drains-the sentinel lymph node (SLN)-is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs).

Optical wavelength selection for improved spectroscopic photoacoustic imaging.

Spectroscopic photoacoustic imaging has the potential to become a powerful tool that can estimate distributions of optically absorbing chromophores in the body. We have developed an algorithm to select imaging wavelengths for spectroscopic photoacoustics given the spectra of expected chromophores. The algorithm uses the smallest singular value of a matrix constructed from the absorption spectra as a criterion to remove extraneous wavelengths.