High-contrast Photoacoustic Imaging Research Articles

Coupling Gold Nanospheres into Nanochain Constructs for High-Contrast, Longitudinal Photoacoustic Imaging.

Structural parameters play a crucial role in determining the electromagnetic and thermal responses of gold nanoconstructs (GNCs) at near-infrared (NIR) wavelengths. Therefore, developing GNCs for reliable, high-contrast photoacoustic imaging has been focused on adjusting structural parameters to achieve robust NIR light absorption with photostability. In this study, we introduce an efficient photoacoustic imaging contrast agent: gold sphere chains (GSCs) consisting of plasmonically coupled gold nanospheres. The chain geometry results in enhanced photoacoustic signal generation originating from outstanding photothermal characteristics compared to traditional gold contrast agents, such as gold nanorods. Furthermore, the GSCs produce consistent photoacoustic signals at laser fluences within the limits set by the American National Standards Institute. The exceptional photoacoustic response of GSCs allows for high-contrast photoacoustic imaging over multiple imaging sessions. Finally, we demonstrate the utility of our GSCs for molecular photoacoustic cancer imaging, both in vitro and in vivo, through the integration of a tumor-targeting moiety.

Quantification and characterization of an ultrasound-induced polarization wavefront aberration in the phase space.

Light propagation wavefront and photon composition variations occur when the beam encounters acoustic waves, bringing mechanical and chemical inhomogeneity-induced light-intensity modulation, while phase variations, which carry more information about the acoustic-optical coupling in the medium, are often overlooked. This paper investigates the coupling of the light beam with the propagating ultrasound and the polarization aberration of the optical wave induced by the ultrasound. A model was developed to express the variation of the ultrasound-induced polarization aberration (UIPA). The ultrasound-induced refractive index variation of the sample was observed in both the simulation and experiments. The phase differences in various ultrasound states (valley dominant state, peak dominant state) are characterized in detail. The UIPA expressed in the phase space provides a way to quantify multidimensional polarization information of the ultrasound-tagged optical waves and allows refraction-sensitive polarization parametric imaging, which may be exploited for directional high-contrast photoacoustic imaging with ultrasound tagging.

High-Contrast Photoacoustic Imaging of Localized Cysteine in Orthotopic Breast Cancer Enabled by A Totally-Caged Methylene Blue Probe.

High-contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue-based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical "OFF-to-ON" absorption transition for high-contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue-based probe for cysteine (MB-Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π-conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130-fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high-contrast manner. Therefore, this work established an up-to-date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo.

D-A-D structured selenadiazolesbenzothiadiazole-based near-infrared dye for enhanced photoacoustic imaging and photothermal cancer therapy

Near-infrared (NIR) small molecular organic dyes as photothermal agents for cancer photothermal therapy (PTT) have attracted considerable research attention. Herein, two donor-acceptor-donor (D-A-D) structured NIR dyes, BBTT and SeBTT, are rationally designed, where the only difference is one heteroatom within the acceptor unit varying from sulfur to selenium (Se). More importantly, SeBTT NPs exhibit stronger NIR absorbance and higher photothermal conversion efficiency (PTCE ≈ 65.3%). In vivo experiments illustrate that SeBTT NPs can be utilized as a high contrast photoacoustic imaging (PAI) agent, and succeed in tumor suppression without noticeable damage to main organs under NIR photoirradiation. This study presents an effective molecular heteroatom surgery strategy to regulate the photothermal properties of NIR small molecules for enhanced PAI and PTT.

Thinking outside the macrocycle: Potential biomedical roles for nanostructured porphyrins and phthalocyanines — a SPP/JPP Young Investigator Award paper

Porphyrins and phthalocyanines feature strong light absorption, capacity for metal chelation, and a track record of use in human therapeutic applications. Various conjugates and formulations of these macrocycles have shown potential to forge new applications in the biomedical sciences. Our lab has explored several such approaches including porphyrin polymer hydrogels, porphyrin-lipid nanovesicles, and surfactant-stripped micelles. These all feature in common a high density of tetrapyrroles, as well as unique functional properties. Porphyrin polymer hydrogels with high porphyrin density and bright fluorescence emission were demonstrated for use as a new class of implantable biosensors. Porphyrin-lipid nanovesicles hold potential for phototherapy, imaging, and also drug and vaccine delivery. Surfactant-stripped micelles have been developed for high-contrast photoacoustic imaging. In this ICPP Young Investigator Award brief perspective, we discuss our own efforts on these fronts. Taken together, the results show that tetrapyrroles enable new approaches for tackling biomedical problems and also confirm what was already well-known to members of the Society of Porphyrins and Phthalocyanines: that these molecules are remarkably versatile and enable research to flow in unexpected directions.

Broadband and Ultrasensitive Graphene-Based Mechanical Wave Detector with Nanosecond Response Used for Biological Photoacoustic Imaging.

Achieving broadband and sensitive mechanical wave detection with fast time response remains a great challenge. Here, we exploited the polarization-sensitive absorption characteristics and ultrafast photoelectric response of graphene to construct a broadband and ultrasensitive detector with a nanosecond response for mechanical wave detection. The unprecedented performance of the graphene-based detector allowed us to detect high-frequency mechanical waves over 100 MHz with a detection limit of 0.18 kPa. Moreover, we applied the detector in high-contrast photoacoustic imaging of human hairs and a mouse hindlimb to demonstrate its capability in detection of photoacoustic waves. This device could also find application in other areas such as THz detection and modulation.

High-contrast photoacoustic imaging through scattering media using correlation detection of adaptive time window

Photoacoustic imaging has the advantages of high contrast and deep imaging depth. However, with the increasing of imaging depth, the signal-to-noise ratio (SNR) of the detected signal decreases, due to the light scattering that seriously affects the recovery image quality. In this paper, we experimentally demonstrated that higher contrast photoacoustic imaging was achieved using photoacoustic wavefront shaping technology in the presence of light scattering and low SNR signals. The imaging contrast is improved from 1.51 to 5.30. More importantly, we propose a dynamic time window method for the photoacoustic signal extraction algorithm, named correlation detection of adaptive time window, which further improves the contrast of photoacoustic imaging to 9.57. Our method effectively improves the contrast of photoacoustic imaging through scattering media.

Surfactant-Stripped Micelles for NIR-II Photoacoustic Imaging through 12 cm of Breast Tissue and Whole Human Breasts.

Surfactant-stripped micelles are formed from a commercially available cyanine fluoroalkylphosphate (CyFaP) salt dye and used for high contrast photoacoustic imaging (PAI) in the second near-infrared window (NIR-II). The co-loading of Coenzyme Q10 into surfactant-stripped CyFaP (ss-CyFaP) micelles improves yield, storage stability, and results in a peak absorption wavelength in the NIR-II window close to the 1064 nm output of Nd-YAG lasers used for PAI. Aqueous ss-CyFaP dispersions exhibit intense NIR-II optical absorption, calculated to be greater than 500 at 1064 nm. ss-CyFaP is detected through 12 cm of chicken breast tissue with PAI. In preclinical animal models, ss-CyFaP is visualized in draining lymph nodes of rats through 3.1 cm of overlaid chicken breast tissue. Following intravenous administration, ss-CyFaP accumulates in neoplastic tissues of mice and rats bearing orthotopic mammary tumors without observation of acute toxic side effects. ss-CyFaP is imaged through whole compressed human breasts in three female volunteers at depths of 2.6-5.1 cm. Taken together, these data show that ss-CyFaP is an accessible contrast agent for deep tissue PAI in the NIR-II window.

Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles

The exciting applications of molecular motion are still limited and are in urgent pursuit, although some fascinating concepts such as molecular motors and molecular machines have been proposed for years. Utilizing molecular motion in a nanoplatform for practical application has been scarcely explored due to some unconquered challenges such as how to achieve effective molecular motion in the aggregate state within nanoparticles. Here, we introduce a class of near infrared-absorbing organic molecules with intramolecular motion-induced photothermy inside nanoparticles, which enables most absorbed light energy to dissipate as heat. Such a property makes the nanoparticles a superior photoacoustic imaging agent compared to widely used methylene blue and semiconducting polymer nanoparticles and allow them for high-contrast photoacoustic imaging of tumours in live mice. This study not only provides a strategy for developing advanced photothermal/photoacoustic imaging nanoagents, but also enables molecular motion in a nanoplatform to find a way for practical application.

Engineering an NIR rhodol derivative with spirocyclic ring-opening activation for high-contrast photoacoustic imaging.

Molecular probes that enable high-contrast photoacoustic (PA) imaging of cellular processes are valuable tools for in vivo studies. Design of activatable PA probes with high contrast remains elusive. We develop a new NIR rhodol derivative, Rhodol-NIR, with a large extinction coefficient, low quantum yield and structural switching from a 'ring-open' form to a 'closed' spirolactone upon esterification. This structural transition, together with the ideal photophysical properties, enables the development of activatable probes for high-contrast PA imaging via a target-specific de-esterification reaction. This strategy is demonstrated using a PA probe designed for a tumor biomarker, human NAD(P)H: quinone oxidoreductase isozyme 1 (hNQO1), which affords high contrast and excellent sensitivity for PA detection and imaging of hNQO1 in living cells and animals. The strategy can provide a new paradigm for engineering activatable PA probes for high-contrast imaging.

Feasibility of photoacoustic evaluations on dual-thermal treatment of ex vivo bladder tumors.

A variety of thermal therapeutic methods have been investigated to treat bladder tumors but often cause bowel injury and bladder wall perforation due to high treatment dosage and limited clinical margins. The objective of the current study is to develop a dual-thermal modality to deeply coagulate the bladder tumors at low thermal dosage and to evaluate therapeutic outcomes with high contrast photoacoustic imaging (PAI). High intensity focused ultrasound (HIFU) is combined with 532nm laser light to enhance therapeutic depth during thermal treatments on artificial tumor-injected bladder tissue ex vivo. PAI is employed to identify the margins of the tumors pre- and post-treatments. The dual-thermal modality achieves 3- and 1.8-fold higher transient temperature changes and 2.2- and 1.5-fold deeper tissue denaturation than laser and HIFU, respectively. PAI vividly identifies the position of the injected tumor and entails approximately 7.9 times higher image contrast from the coagulated tumor as that from the untreated tumor. Spectroscopic analysis exhibits that both 740nm and 760nm attains the maximum photoacoustic amplitudes from the treated areas. The proposed PAI-guided dual-thermal treatments (laser and HIFU) treatments can be a feasible therapeutic modality to treat bladder tumors in a controlled and efficient manner.

Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging

A targeted gold nanoparticle has been developed as a contrast agent for photoacoustic medical imaging. We have studied cancer cell targeting by antibody conjugated gold nanorods for high contrast photoacoustic imaging. By changing the aspect ratio of the elongated “rod” shape of the gold nanoparticle, its plasmon peak absorption wavelength can be tuned to the near IR (700–900nm) for an increased penetration depth into biological tissue. Effective cell targeting and sensitive photoacoustic detection of a single layer of cells are demonstrated. Combining ultrasound with contrast agent based photoacoustic imaging is proposed as a visual tool to compound molecular and structural information for early stage prostate cancer detection.

Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy

Dual-wavelength reflection-mode photoacoustic microscopy is used to noninvasively obtain three-dimensional (3-D) images of subcutaneous melanomas and their surrounding vasculature in nude mice in vivo. The absorption coefficients of blood and melanin-pigmented melanomas vary greatly relative to each other at these two optical wavelengths (764 and 584 nm). Using high-resolution and high-contrast photoacoustic imaging in vivo with a near-infrared (764-nm) light source, the 3-D melanin distribution inside the skin is imaged, and the maximum thickness of the melanoma (approximately 0.5 mm) is measured. The vascular system surrounding the melanoma is also imaged with visible light (584 nm) and the tumor-feeding vessels found. This technique can potentially be used for melanoma diagnosis, prognosis, and treatment planning.