Significance: Photoacoustic (PA) tomography has demonstrated versatile biomedical applications. However, an array-based PA computed tomography (PACT) system is complex and expensive, whereas a single-element detector-based scanning PA system is too slow to detect some fast biological dynamics in vivo. New PA imaging methods are sought after.
Aim: To overcome these limitations, we developed photoacoustic topography through an ergodic relay (PATER), a novel high-speed imaging system with a single-element detector.
Approach: PATER images widefield PA signals encoded by the acoustic ergodic relay with a single-laser shot.
Results: We applied PATER in vivo to monitor changes in oxygen saturation in a mouse brain and also to demonstrate high-speed matching of vascular patterns for biometric authentication.
Conclusions: PATER has achieved a high-speed temporal resolution over a large field of view. Our results suggest that PATER is a promising and economical alternative to PACT for fast imaging.
Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention.
Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs.
Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans.
Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression.
Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma.
An estimated ~250,000 new cases of both invasive and non-invasive breast cancer were diagnosed in US women almost every year. To reduce the local recurrence rate, the breast conserving surgery (BCS) is widely used as the initial therapy, which is to excise the tumor with a rim of normal surrounding tissue such that no cancer cells remain at the cut margin, Patients with positive margin commonly require a second surgical procedure to obtain clear margins. To this end, optical-resolution photoacoustic microscopy (OR-PAM) with ultraviolet (UV) laser illumination (OR-UV-PAM) has been developed for providing label-free, high-resolution, and histology like imaging of fixed, unprocessed breast tissue. To further improve the performance of OR-UV-PAM, here, we introduce dual-view UV-PAM (DV-UV-PAM) to significantly improve the axial resolution, achieving three-dimensional (3D) resolution isotropy. We first use 0.5 μm polystyrene beads and carbon fibers to validate the resolution isotropy improvement. Imaging of mouse brain slices further demonstrates the improved resolution isotropy, revealing the 3D structure of cell nuclei in detail, which facilitates quantitative cell nuclear analysis.
Ultraviolet photoacoustic microscopy (UV-PAM) is a promising intraoperative tool for surgical margin assessment (SMA), one that can provide label-free histology-like images with high resolution. In this study, using a microlens array and a one-dimensional (1-D) array ultrasonic transducer, we developed a high-throughput multifocal UV-PAM (MF-UV-PAM). Our new system achieved a 1.6 ± 0.2 μm lateral resolution and produced images 40 times faster than the previously developed point-by-point scanning UV-PAM. MF-UV-PAM provided a readily comprehensible photoacoustic image of a mouse brain slice with specific absorption contrast in ∼16 min, highlighting cell nuclei. Individual cell nuclei could be clearly resolved, showing its practical potential for intraoperative SMA.
Based on the photoacoustic (PA) effect, PA tomography directly measures specific optical absorption, i.e., absorbed optical energy per unit volume. We recently developed a full-ring ultrasonic transducer array-based photoacoustic computed tomography (PACT) system for small-animal whole-body imaging. The system has a full-view detection angle and high in-plane resolution (∼100 μm). However, due to the bandpass frequency response of the piezoelectric transducer elements and the limited elevational detection coverage of the full-ring transducer array, the reconstructed images present bipolar (i.e., both positive and negative) pixel values, which cause ambiguities in image interpretation for physicians and biologists. We propose a multiview Hilbert transformation method to recover the unipolar initial pressure for full-ring PACT. The effectiveness of the proposed algorithm was first validated by numerical simulations and then demonstrated with ex vivo mouse brain structural imaging and in vivo mouse whole-body imaging.
The brain has been likened to a great stretch of unknown territory consisting of a number of unexplored continents. Small animal brain imaging plays an important role charting that territory. By using 1064 nm illumination from the side, we imaged the full coronal depth of rat brains in vivo. The experiment was performed using a real-time full-ring-array photoacoustic computed tomography (PACT) imaging system, which achieved an imaging depth of 11 mm and a 100 μm radial resolution.
Because of the fast imaging speed of the full-ring-array PACT system, no animal motion artifact was induced. The frame rate of the system was limited by the laser repetition rate (50 Hz). In addition to anatomical imaging of the blood vessels in the brain, we continuously monitored correlations between the two brain hemispheres in one of the coronal planes. The resting states in the coronal plane were measured before and after stroke ligation surgery at a neck artery.
Imaging of small animals, especially rodents provides physiological, pathological, and phenotypical insights into the most relevant milieu—an intact, living system. Currently, non-optical small-animal wholebody imaging approaches lack either spatiotemporal resolution or functional contrasts, whereas pure optical imaging suffers from either shallow penetration (up to ~1 mm) or a poor resolution-to-depth ratio (~1/3). Here, we present a standalone system that breaks all the above limitations. Our system features high spatiotemporal resolution and deep penetration, and can capture anatomical and functional contrasts. We imaged mouse wholebody dynamics in real time with clear sub-organ anatomical and functional details.
We have enhanced photoacoustic computed tomography with dry acoustic coupling that eliminates water immersion anxiety and wrinkling of the animal and facilitates incorporating complementary modalities and procedures. The dry acoustic coupler is made of a tubular elastic membrane enclosed by a closed transparent water tank. The tubular membrane ensures water-free contact with the animal, and the closed water tank allows pressurization for animal stabilization. The dry coupler was tested using a whole-body small-animal ring-shaped photoacoustic computed tomography system. Dry coupling was found to provide image quality comparable to that of conventional water coupling.
We present single-shot real-time video recording of light scattering dynamics by second-generation compressed ultrafast photography (G2-CUP). Using G2-CUP at 100 billion frames per second, in a single camera exposure, we experimentally captured the evolution of the light intensity distribution in an engineered thin scattering plate assembly. G2-CUP, which implements a new reconstruction paradigm and a more efficient hardware design than its predecessors, markedly improves the reconstructed image quality. The ultrafast imaging reveals the instantaneous light scattering pattern as a photonic Mach cone. We envision that our technology will find a diverse range of applications in biomedical imaging, materials science, and physics.
Photoacoustic tomography (PAT) exploits optical contrast and ultrasonic detection principles to form images of absorbed optical energy density within tissue. Based on the photoacoustic effect, PAT directly and quantitatively measures specific optical absorption. A full-ring ultrasonic transducer array based photoacoustic computed tomography (PACT) system was recently developed for small animal whole-body imaging with a full-view detection angle and high in-plane resolution (100 µm). However, due to the band-pass frequency response of the piezoelectric transducer elements, the reconstructed images present bipolar (both positive and negative) pixel values, which is artificial and counterintuitive for physicians and biologists seeking to interpret the image. Moreover, bipolar pixel values hinder quantification of physiological parameters, such as oxygen saturation and blood flow speed. Unipolar images can be obtained by deconvolving the raw channel data with the transducer’s electrical impulse response and applying non-negativity during iteration, but this process requires complex transducer modeling and time-consuming computation.
Here, we present a multi-view Hilbert transformation method to recover the unipolar initial pressure for full-ring PACT. Multi-view Hilbert transformation along the acoustic wave propagation direction minimizes reconstruction artifacts during envelope extraction and maintains the signal-to-noise ratio of the reconstructed images. The in-plane isotropic spatial resolution of this method was quantified to 168 μm within a 20 × 20 mm2 field of view. The effectiveness of the proposed algorithm was first validated by numerical simulations and then demonstrated with ex-vivo mouse brain structural imaging and in-vivo mouse wholebody imaging.
KEYWORDS: Melanoma, In vivo imaging, Photoacoustic spectroscopy, Transducers, Microscopes, Ultrasonics, Diagnostics, Tumors, Acquisition tracking and pointing, Biopsy, Imaging systems
We applied a linear-array-based photoacoustic probe to detect the tumor depth and volume of melanin-containing melanoma in nude mice in vivo. We demonstrated the ability of this linear-array-based system to measure both the depth and volume of melanoma through phantom, ex vivo, and in vivo experiments. The volume detection ability also enables us to accurately calculate the rate of growth of the tumor, which is important in quantifying tumor activity. Our results show that this system can be used for clinical melanoma diagnosis and treatment at the bedside.
The single-shot compressed ultrafast photography (CUP) camera is the fastest receive-only camera in the world. In this work, we introduce an external CCD camera and a space- and intensity-constrained (SIC) reconstruction algorithm to improve the image quality of CUP. The CCD camera takes a time-unsheared image of the dynamic scene. Unlike the previously used unconstrained algorithm, the proposed algorithm incorporates both spatial and intensity constraints, based on the additional prior information provided by the external CCD camera. First, a spatial mask is extracted from the time-unsheared image to define the zone of action. Second, an intensity threshold constraint is determined based on the similarity between the temporally projected image of the reconstructed datacube and the time-unsheared image taken by the external CCD. Both simulation and experimental studies showed that the SIC reconstruction improves the spatial resolution, contrast, and general quality of the reconstructed image.
Due to their low cost, hand-held convenience, wide selection of bandwidths, and ultrasound imaging capability, linear ultrasonic transducer arrays have been widely studied for photoacoustic computed tomography (PACT). As linear-array PACT suffers from a limited view, full-view imaging requires either the transducer or the object to be rotated. So far, both the central frequencies and bandwidth of linear transducer arrays applied in full-view PACT are low, limiting the spatial resolutions of the reconstructed images. Here, we present a multiview high-frequency PACT imaging system implemented with a commercial 40-MHz central frequency linear transducer array. By rotating the object through multiple angles with respect to the linear transducer array, we acquired full-view photoacoustic pressure measurements. Further, to quantify the unipolar initial pressures and overcome the limitations of the single-view Hilbert transformation, we developed a multiview Hilbert transformation method. The in-plane spatial resolution of this full-view linear-array PACT was quantified to be isotropically 60 μm within a 10×10 mm2 field of view. The system was demonstrated by imaging both a leaf skeleton and a zebrafish in vivo.
Conventional photoacoustic computed tomography (PACT) image reconstruction methods assume that the object and surrounding medium are described by a constant speed-of-sound (SOS) value. In order to accurately recover fine structures, SOS heterogeneities should be quantified and compensated for during PACT reconstruction. To address this problem, several groups have proposed hybrid systems that combine PACT with ultrasound computed tomography (USCT). In such systems, a SOS map is reconstructed first via USCT. Consequently, this SOS map is employed to inform the PACT reconstruction method. Additionally, the SOS map can provide structural information regarding tissue, which is complementary to the functional information from the PACT image. We propose a paradigm shift in the way that images are reconstructed in hybrid PACT-USCT imaging. Inspired by our observation that information about the SOS distribution is encoded in PACT measurements, we propose to jointly reconstruct the absorbed optical energy density and SOS distributions from a combined set of USCT and PACT measurements, thereby reducing the two reconstruction problems into one. This innovative approach has several advantages over conventional approaches in which PACT and USCT images are reconstructed independently: (1) Variations in the SOS will automatically be accounted for, optimizing PACT image quality; (2) The reconstructed PACT and USCT images will possess minimal systematic artifacts because errors in the imaging models will be optimally balanced during the joint reconstruction; (3) Due to the exploitation of information regarding the SOS distribution in the full-view PACT data, our approach will permit high-resolution reconstruction of the SOS distribution from sparse array data.
We present a photoacoustic microscopy (PAM) technique with an optical sectioning capability. By combining crossoptical- beam illumination with nonlinear PAM, an axial resolution of 8.7 μm was measured, demonstrating a fourfold improvement over the acoustically determined value. Compared to methods relying on high-frequency ultrasound transducers to improve the axial resolution, our approach offers a greater working distance and a higher signal-to-noise ratio.
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