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A computational and experimental study is conducted to examine how directivity associated with a finite aperture sensor affects photoacoustic tomography (PAT) image reconstruction. Acoustic signals for the simulation work were computed using a discrete particle approach from three numerical phantoms including a vasculature. The theoretical framework and a Monte Carlo approach for construction of a tissue configuration are discussed in detail. While simulating forward data, the directivity of the sensor was taken into account. The image reconstruction was accomplished using system matrix based methods like l₂ norm Tikhonov regularization, l₁ norm regularization and total variation (TV) minimization. Accordingly, two different system matrices were constructed- (i) assuming transducer as a point detector (PD) and (ii) retaining properties of a finite detector with directivity (FDWD). Image reconstruction was also performed utilizing experimentally measured PA signals. Both the computational and experimental results demonstrate that blur-free PAT imaging can be achieved with the FDWD method. Additionally, TV minimization provides marginally better image reconstruction compared to the other schemes.

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional information of tissues with high resolution. Although NIR-PAI is promising, its widespread use is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represents an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agents with tunable size down to 230 nm and direct functionalization with targeting moieties. The ICG-JA platform has a detectable PA signal in vitro that is two times stronger than whole blood and high photostability. The targeting ability of ICG-JA was measured in vitro using HeLa cells. The ICG-JA platform was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 min post-injection with a contrast-to-noise ratio of 2.42.

Exogenous contrast agents in photoacoustic imaging help improve spatial resolution and penetration depth and enable targeted molecular imaging. To screen efficient photoacoustic signaling materials as contrast agents, we propose a light absorption-weighted figure of merit (FOM) that can be calculated using material data from the literature and numerically simulated light absorption cross-sections. The calculated light absorption-weighted FOM shows that a Ti nanodisc has a photoacoustic conversion performance similar to that of an Au nanodisc and better than that of a Pt nanodisc. The photoacoustic imaging results of Ti, Au, and Pt nanodiscs, which are physically synthesized with identical shapes and dimensions, experimentally demonstrated that the Ti nanodisc could be a highly efficient contrast agent.

Abstract Significant effort focused on developing photoactivatable theranostics for localized image guided therapy of cancer by thermal ablation. In this context iron complexes were recently identified as photoactivatable theranostic agents with adequate biocompatibility and body clearance. Herein, a series of FeII complexes bearing polypyridine or N-heterocyclic carbenes is reported that rely on rational complex engineering to red-shift their MLCT based excited-state deactivation via a straightforward approach. The non-radiative decay of their MLCT upon irradiation is exploited for theranostic purposes by combining both tracking in photoacoustic imaging (PA) and photothermal therapy (PTT). The influence of structural modifications introduced herein on the solubility and stability of the complexes in biorelevant aqueous media is discussed. The relationship between complexes’ design, production of contrast in photoacoustic and photothermal efficiency are explored to develop tailored PA/PTT theranostic agents.

Two-dimensional matrix transducer arrays are the most appropriate imaging probes for acquiring dual-modal 3D photoacoustic (PA)/ultrasound (US) images. However, they have small footprints which limit the field-of-view (FOV) to less than 10 mm × 10 mm and degrade the spatial resolution. In this study, we demonstrate a dual-modal PA and US imaging system (using a 2D matrix transducer array and a motorized 2D scanning system) to enlarge the FOV of volumetric images. Multiple PA volumes were merged to form a wide-field image of approximately 45 mm × 45 mm. In vivo imaging was demonstrated using rat sentinel lymph nodes (SLNs) and bladders stained with methylene blue. We believe that this volumetric PA/US imaging technique with a 2D matrix transducer array can be a useful tool for narrow-field real-time monitoring and wide-field imaging of various preclinical and clinical studies.

Optoacoustic (photoacoustic) imaging has gained tremendous attention in research and in clinical practice as a point-of-care system for noninvasive, fast, and safe tests. The first optoacoustic (OA) tomograph has recently passed the Food and Drug Administration (FDA) approval stage for clinical applications aimed at early breast cancer diagnostics. Furthermore, a broad application of OA imaging for Biomedical and Materials Science fields requires a proper tool to test the equipment and verify the quality of the measurements on a daily basis. In the present work, we propose fibers based on single-walled carbon nanotubes (SWCNTs) as a material for designing a stable and reliable calibration grid. The main advantage of the developed test system is the broad optical absorption of SWCNT-based fibers, ranging from visible to mid-infrared regions. Inspired by stringed instruments, we elaborate a grid to calibrate and verify spatial resolution in three projections and sensitivity of OA imaging systems. Thus, the real calibration grid parameters, such as fiber length and diameter, could be translated to the OA signal measurements. This proof-of-the-concept study evaluates the geometry of fibers, that is, the length/diameter and design of fibers, such as free-standing/twisted, and shows the fabrication procedure of the calibration grid prototype toward the successful validation of the OA imaging system, including raster-scanning optoacoustic mesoscopy (RSOM) at one wavelength and tomography at several wavelengths, which have grand prospects in preclinical and clinical practices. Besides, the more advanced geometry based on double-twisted fibers, or twistrons, applied here provided us with a chance to reach the lower resolution limit for RSOM because of the difference in diameter between the thin and thick parts in the morphology is verified by scanning electron microscopy.

Hotothermal therapy (PTT) is an alternative to surgery, which is commonly used to treat tumors in intracavitary organs. PTT involves heating the diseased tissue with radiation energy, resulting in tumor necrosis. In order to improve the safety and effectiveness of PT, it is necessary to monitor the tissue temperature in real time and regulate the laser power during PTT. Photoacoustic imaging (PAI) is a non-invasive and non-ionizing imaging method with high resolution and high accuracy. Due to the dependence of the thermal expansion coefficient on temperature, the Grüneisen parameter is linearly proportional to temperature, and the variation of the amplitude of the photoacoustic signal is related to the variation of the Grüneisen parameter. In this study, we propose a system for laser dose regulation with photoacoustic signal temperature feedback based on PID algorithm. The pulsed laser is irradiated on the sample surface, the ultrasonic probe receives the photoacoustic signal generated by the sample, and the photoacoustic signal is collected by the oscilloscope and transmitted to the computer, which generates the corresponding command to the heating laser according to the signal and changes the output power of the heating laser. The experimental results show that this method can effectively control the photothermal damage range.

Diffuse optical tomography (DOT) use near-infrared light for imaging optical properties of biological tissues. Time-domain (TD) DOT systems use pulsed lasers and measure time-varying temporal point spread function (TPSF), carrying information from both superficial and deep layers of imaged target. In this work, feasibility of nanosecond scale light pulses as sources for TD-DOT is studied. Nanosecond sources enable using relatively robust measurement setups with standard analogue-to-digital converter waveform digitizers, such as digital oscilloscopes. However, this type of systems have some properties, such as variations in source pulses and limited temporal sampling, that could limit their usage. In this work, these different aspects and possible limitations were studied with simulations and experiments. Simulations showed that information carried by TD data of diffuse medium is on low frequencies. This enables usage of relatively slow response time measurement electronics, and image processing using Fourier-transformed TD data. Furthermore, the temporal sampling in measurements needs to be high enough to capture the TPSF, but this rate can be achieved with standard digital oscilloscopes. It was shown that, although variations in light pulses of nanosecond lasers are larger than those of picosecond sources, these variations do not affect significantly on image quality. Overall, the simulations demonstrated the capability of nanosecond sources to be utilised in TD-DOT in diffuse medium. In this work, a prototype TD-DOT experimental system utilising a high-energy nanosecond laser was constructed. The system is relatively robust consisting of a nanosecond Nd:YAG laser combined with optical parametric oscillator for light input and optical fibres for guiding the light, and avalanche photodetector and high-bandwidth oscilloscope for TPSF measurements. The system was used in both absolute and difference imaging of two phantoms. The experiments verified that both absorbing and scattering objects can be reconstructed with good accuracy with TD-DOT using a nanosecond laser.

Photoacoustic tomography (PAT) is an imaging modality that utilizes the photoacoustic effect. In PAT, a photoacoustic image is computed from measured data by modeling ultrasound propagation in the imaged domain and solving an inverse problem utilizing a discrete forward operator. However, in realistic measurement geometries with several ultrasound transducers and relatively large imaging volume, an explicit formation and use of the forward operator can be computationally prohibitively expensive. In this work, we propose a transformation-based approach for efficient modeling of photoacoustic signals and reconstruction of photoacoustic images. In the approach, the forward operator is constructed for a reference ultrasound transducer and expanded into a general measurement geometry using transformations that map the formulated forward operator in local coordinates to the global coordinates of the measurement geometry. The inverse problem is solved using a Bayesian framework. The approach is evaluated with numerical simulations and experimental data. The results show that the proposed approach produces accurate 3-D photoacoustic images with a significantly reduced computational cost both in memory requirements and time. In the studied cases, depending on the computational factors, such as discretization, over the 30-fold reduction in memory consumption was achieved without a reduction in image quality compared to a conventional approach.

Surface sensitivity of lanthanide-doped nanocrystals has a great utility in controlling their optical properties. Surface sensitivity can be principally promoted by energy migration. Herein, we demonstrate that cross-relaxation between lanthanides makes nanocrystals less sensitive to environmental changes. We show that by codoping ytterbium ions (Yb³⁺) and neodymium ions (Nd³⁺) in hexagonal-phase sodium yttrium fluorides, surface sensitivity can be manipulated by energy transfer from Yb³⁺ to Nd³⁺. These findings enhance our understanding of surface quenching of nanocrystals and offer new opportunities in developing highly luminous nanoprobes for molecular sensing and biomedical applications.