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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.

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.

The generation, control and transfer of triplet excitons in molecular and hybrid systems is of great interest owing to their long lifetime and diffusion length in both solid-state and solution phase systems, and to their applications in light emission1, optoelectronics, photon frequency conversion and photocatalysis. Molecular triplet excitons (bound electron–hole pairs) are ‘dark states’ because of the forbidden nature of the direct optical transition between the spin-zero ground state and the spin-one triplet levels. Hence, triplet dynamics are conventionally controlled through heavy-metal-based spin–orbit coupling or tuning of the singlet–triplet energy splitting via molecular design. Both these methods place constraints on the range of properties that can be modified and the molecular structures that can be used. Here we demonstrate that it is possible to control triplet dynamics by coupling organic molecules to lanthanide-doped inorganic insulating nanoparticles. This allows the classically forbidden transitions from the ground-state singlet to excited-state triplets to gain oscillator strength, enabling triplets to be directly generated on molecules via photon absorption. Photogenerated singlet excitons can be converted to triplet excitons on sub-10-picosecond timescales with unity efficiency by intersystem crossing. Triplet exciton states of the molecules can undergo energy transfer to the lanthanide ions with unity efficiency, which allows us to achieve luminescent harvesting of the dark triplet excitons. Furthermore, we demonstrate that the triplet excitons generated in the lanthanide nanoparticle–molecule hybrid systems by near-infrared photoexcitation can undergo efficient upconversion via a lanthanide–triplet excitation fusion process: this process enables endothermic upconversion and allows efficient upconversion from near-infrared to visible frequencies in the solid state. These results provide a new way to control triplet excitons, which is essential for many fields of optoelectronic and biomedical research.

Multimodal imaging with photoacoustic microscopy (PAM) and optical coherence tomography (OCT) can be an effective method to evaluate the choroidal and retinal microvasculature. To improve the efficiency for visualizing capillaries, colloidal gold nanoparticles (AuNPs) have been applied as a multimodal contrast agent for both OCT and PAM imaging by taking advantage of the strong optical scattering and the strong optical absorption of AuNPs due to their surface plasmon resonance. Ultra-pure AuNPs were fabricated by femtosecond laser ablation, capped with polyethylene glycol (PEG), and administered to 13 New Zealand white rabbits and 3 Dutch Belted pigmented rabbits. The synthesized PEG-AuNPs (20.0 ± 1.5 nm) were demonstrated to be excellent contrast agents for PAM and OCT, and do not demonstrate cytotoxicity to bovine retinal endothelial cells in cell studies. The image signal from the retinal and choroidal vessels in living rabbits was enhanced by up to 82% for PAM and up to 45% for OCT, respectively, by the administered PEG-AuNPs, which enables detection of individual blood vessels by both imaging modalities. The biodistribution study demonstrated the AuNP accumulated primarily in the liver and spleen. Histology and TUNEL staining did not indicate cell injury or death in the lung, liver, kidney, spleen, heart, or eyes up to seven days after AuNP administration. PEG-AuNPs offer an efficient and safe contrast agent for multimodal ocular imaging to achieve improved characterization of microvasculature.