Contrast Agent For Photoacoustic Imaging Research Articles

In Vivo Quantitative Photoacoustic Diagnosis of Gastric and Intestinal Dysfunctions with a Broad pH-Responsive Sensor

Gastrointestinal diseases affect many people in the world and significantly impair life quality and burden the healthcare system. The functional parameters of the gastrointestinal tract such as motility and pH can effectively reflect the changes of gastrointestinal activity in physiological and pathological conditions. Thus, a noninvasive method for real-time and quantitative measurement of gastrointestinal functional parameters in vivo is highly desired. At present, there are many strategies widely used for the diagnosis of gastrointestinal diseases in clinic, including X-ray barium meal examination, ultrasound imaging, radionuclide examination, endoscopy, etc. However, these methods are limited in determining the gastrointestinal status and cannot provide comprehensive quantitative information. Photoacoustic imaging (PAI) is a rapid noninvasive real-time imaging technique in which multiple types of functional and quantitative information can be simultaneously obtained. Unfortunately, very few ratiometric PAI contrast agents have been reported for quantification of gastrointestinal functional parameters in vivo. In this work, a broad, pH-responsive ratiometric sensor based on polyaniline and Au triangular nanoplates was developed. Utilizing the sensor as a contrast agent, PAI served as an all-in-one technique, accurately measuring the gastrointestinal functional parameters in a single test. Notably, this sensor was examined to be ultrasensitive with pH responses as fast as 0.6 s and durability as long as 24 h, and was repeatable and reversible for longitudinal monitoring. The quantitative results demonstrated a significant disorder in motility and decrease in pH for gastric and duodenal ulcers. Collectively, the combination of PAI and this broad pH-responsive sensor might be a promising candidate for quantitative diagnosis of gastrointestinal diseases.

Gold Nanotetrapods with Unique Topological Structure and Ultranarrow Plasmonic Band as Multifunctional Therapeutic Agents.

Owing to their excellent surface plasmonic properties, Au nanobranches have drawn increasing attention in various bioapplications, such as contrast agents for photoacoustic imaging, nanomedicines for photothermal therapy, and carriers for drug delivery. The monodispersity and plasmonic bandwidth of Au nanobranches are of great importance for the efficacy of those bioapplications. However, it is still a challenge to accurately synthesize size- and shape-controlled Au nanobranches. Here we report a facile seed-mediated growth method to synthesize monodisperse Au nanotetrapods (NTPs) with tunable and ultranarrow plasmonic bands. The NTPs have a novel D2d symmetry with four arms elongated in four ⟨110⟩ directions. The growth mechanism of NTPs relies on the delicate kinetic control of deposition and diffusion rates of adatoms. Upon laser irradiation, the PEGylated NTPs possess remarkable photothermal conversion efficiencies and photoacoustic imaging properties. The NTPs can be applied as a multifunctional theranostic agent for both photoacoustic imaging and image-guided photothermal therapy.

Molecular photoacoustic imaging with ultra-small gold nanoparticles.

Gold nanoparticles (AuNPs) below 10 nm in size can undergo renal clearance, which could facilitate their clinical translation. However, due to non-linear, direct relationship between their absorption and size, use of such "ultra-small" AuNPs as contrast agents for photoacoustic imaging (PAI) is challenging. This problem is complicated by the tendency of absorption for ultra-small AuNPs to be below the NIR range, which is optimal for in vivo imaging. Herein, we present 5-nm molecularly activated plasmonic nanosensors (MAPS) that produce a strong photoacoustic signal in labeled cancer cells in the NIR, demonstrating the feasibility of sensitive PAI with ultra-small AuNPs.

Design and Synthesis of an Activatable Photoacoustic Probe for Hypochlorous Acid

Photoacoustic (PA) imaging is a novel imaging modality that combines the high contrast of optical imaging and the deep tissue penetration of ultrasound. PA imaging contrast agents targeting various biological phenomena have been reported, but the development of activatable PA probes, which show a PA signal only in the presence of target molecules, remains challenging in spite of their potential usefulness for real-time PA imaging of specific biomolecules in vivo. To establish a simple design strategy for activatable PA probes, we first designed and synthesized a silicon-rhodamine based near-infrared nonfluorescent dye, wsSiNQ660 (water-soluble SiNQ660), as a scaffold and demonstrated that it offers a high conversion efficiency from light to ultrasound compared to typical near-infrared fluorescent dyes. Importantly, absorption off/on strategies previously established for rhodamine-based fluorescent probes are also applicable to this nonfluorescent dye scaffold. We validated this approach by synthesizing an activatable PA probe for hypochlorous acid (HOCl) and confirmed that it enables three-dimensional imaging of HOCl in mouse subcutis.

Correction to Acidity/Reducibility Dual-Responsive Hollow Mesoporous Organosilica Nanoplatforms for Tumor-Specific Self-Assembly and Synergistic Therapy.

Featured with a large surface area, uniform interpenetrating mesopores, diverse organic framework hybridization, and well-defined surface properties, the hollow mesoporous organosilica nanoparticle (HMON) represents a promising paradigm in drug delivery systems with excellent biocompatibility. However, effective tumor accumulation and precise cancer theranostics of the HMON still remain a challenge. In this study, an “ammonia-assisted hot water etching” method is applied for the successful construction of sub-50 nm thioether/phenylene dual-hybridized HMON with low hemolytic effect. Particularly, the surface modification with Mo(VI)-based polyoxometalate (POM) clusters drives the self-assembly of HMON in the mild acidic tumor microenvironment (TME) to achieve enhanced tumor retention and accumulation. More importantly, the reducibility-activated Mo(VI)-to-Mo(V) conversion within POM not only endows the POM-anchored HMON with outstanding TME-responsive photoacoustic (PA) imaging contrast and photothermal th...

PEGylated liposomal photosensitizers as theranostic agents for dual-modal photoacoustic and fluorescence imaging-guided photodynamic therapy

The photosensitizer (PS) as photodynamic therapy (PDT) agent, can also serve as the contrast agent for dual-modal fluorescence imaging (FLI) and photoacoustic imaging (PAI) for precise cancer theranostics. In this study, the PAI capability of commercial PS, benzoporphyrin derivative monoacid ring-A (BPD) were examined and compared with that from the other PSs and dyes such as TPPS4, Cy5 dye and ICG. We discovered that BPD exhibited its advantage as contrast agent for PAI. Meanwhile, BPD can also serve as the contrast agent for enhanced FLI. In particular, the PEGylated nanoliposome (PNL) encapsulated BPD (LBPD) was produced for contrast enhanced dual-modal FLI and PAI and imaging-guided high-efficiency PDT. Enhanced FLI and PAI results demonstrated the significant accumulation of LBPD both within and among individual tumor during 24[Formula: see text]h monitoring for in vivo experiment tests. In-vitro and in-vivo PDT tests were also performed, which showed that LBPD have higher PDT efficiency and can easily break the blood vessel of tumor tissues as compared to that from BPD. It was discovered that LBPD has great potentials as a diagnosis and treatment agent for dual-modal FLI and PAI-guided PDT of cancer.

Editorial

Journal of Innovative Optical Health SciencesVol. 12, No. 03, 1902001 (2019) Open AccessEditorialZhen Yuan and Changfeng WuZhen YuanCancer Center, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China and Changfeng WuDepartment of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. Chinahttps://doi.org/10.1142/S1793545819020012Cited by:0 Next AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Librarian ShareShare onFacebookTwitterLinked InRedditEmail Cancer including lung cancer, rectal and prostate cancer, colon cancer and breast cancer remains the leading cause of morbidity and mortality worldwide. The use of noninvasive imaging technique to detect cancers at an early stage and achieve image-guided cancer therapy provides better opportunities for patients to obtain effective treatment with fewer side effects. To date, photoacoustic (PA) imaging (PAI) is the fastest-growing area of biomedical imaging technology because PAI enables anatomical, functional and metabolic imaging of tumors with high resolution, high contrast and satisfactory penetration depth. However, the sensitivity of PAI to visualize tumors is determined by its endogenous contrast. By contrast, multifunctional nanoprobes have exhibited their potentials as theranostic agents for PAI-guided cancer theranostics.Interestingly, different multifunctional nanoprobes including inorganic and organic nanoparticles have been developed to improve PAI contrast and enhance cancer efficacy. The inorganic nanoprobes consist of the metal nanoparticles such as the Au and Pd, transition metal dichalcogenides such as the MoS2, WS2 nanosheets and CuS2 nanoparticles, and carbon nanomaterials such as graphene and carbon nanotubes. In addition to inorganic nanoprobes, organic nanoparticles such as BDT-IID based conjugated polymer dots (Pdots) can also serve as multifunctional nanoprobes for enhanced PAI-guided cancer theranostics.This special issue highlights the latest development of inorganic and organic nanoparticles that range from design of multifunctional nanoparticles to PAI and PAI-guided cancer theranostics. The topics for this special issue include but are not limited to:(1)Development of multifunctional nanoparticles for PAI and PA-based multimodal imaging for cancer detection.(2)Development of organic/inorganic nanoprobes for PAI-guided cancer treatment such as phototherapy and immunotherapy.(3)Development of multifunctional nanoprobes for PAI-guided drug/gene delivery and tumor microenvironments monitoring.It is expected that the selected original and review works from this issue can promote the development of multifunctional PA probes for cancer detection and treatment.AcknowledgmentsWe want to take this opportunity to thank the authors and reviewers for their contributions to this special issue. FiguresReferencesRelatedDetails Recommended Vol. 12, No. 03 Metrics History Received 27 May 2019 Accepted 27 May 2019 Published: 30 May 2019 Information© The Author(s)This is an Open Access article published by World Scientific Publishing Company. It is distributed under the terms of the Creative Commons Attribution 4.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited.PDF download

Photoacoustic molecular imaging using combined acupuncture and gold nanorods as a composite contrast agent

In this study, we developed a novel photoacoustic imaging technique based on poly (ethyleneglycol)-coated (PEGylated) gold nanorods (PEG-GNRs) (as the contrast agent) combined with traditional Chinese medicine (TCM) acupuncture (as the auxiliary method) for quantitatively monitoring contrast enhancement in the vasculature of a mouse brain in vivo. This study takes advantage of the strong near-infrared absorption (peak at [Formula: see text][Formula: see text]nm) of GNRs and the ability to adjust the hemodynamics of acupuncture. Experimental results show that photoacoustic tomography (PAT) successfully reveals the optical absorption variation of the vasculature of the mouse brain in response to intravenous administration of GNRs and acupuncture at the Zusanli acupoint (ST36) both individually and combined. The quantitative measurement of contrast enhancement indicates that the composite contrast agents (integration of acupuncture and GNRs) would greatly enhance the photoacoustic imaging contrast. The quantitative results also have the potential to estimate the local concentration of GNRs and even the real-time effects of acupuncture.

De-noising of photoacoustic sensing and imaging based on combined empirical mode decomposition and independent component analysis.

Photoacoustic (PA) imaging breaks the diffusion limit of conventional optical imaging by listening to the PA wave. As a new kind of functional imaging method, it has experienced tremendous growth in research community with wide range of applications. However, it is still an open and fundamental challenge that the conversion efficiency from light to sound based on PA effect is extremely low. The consequence is the poor signal-to-noise ratio (SNR) of PA signal especially in scenarios of low laser power and deep penetration. Conventional approach to enhance the SNR of PA signal in these noisy scenarios is data averaging, which is quite time-consuming. To improve the signal fidelity and imaging speed, an algorithm of using empirical mode decomposition and independent component analysis de-noising methods in PA imaging is proposed. The simulation and in vivo experimental results show obvious SNR enhancement of the PA signal and image contrast. The proposed method provides the potential to develop real-time low-cost PA imaging system with low-power laser source.

Photoacoustic imaging in the second near-infrared window: a review.

.Photoacoustic (PA) imaging is an emerging medical imaging modality that combines optical excitation and ultrasound detection. Because ultrasound scatters much less than light in biological tissues, PA generates high-resolution images at centimeters depth. In recent years, wavelengths in the second near-infrared (NIR-II) window (1000 to 1700 nm) have been increasingly explored due to its potential for preclinical and clinical applications. In contrast to the conventional PA imaging in the visible (400 to 700 nm) and the first NIR-I (700 to 1000 nm) window, PA imaging in the NIR-II window offers numerous advantages, including high spatial resolution, deeper penetration depth, reduced optical absorption, and tissue scattering. Moreover, the second window allows a fivefold higher light excitation energy density compared to the visible window for enhancing the imaging depth significantly. We highlight the importance of the second window for PA imaging and discuss the various NIR-II PA imaging systems and contrast agents with strong absorption in the NIR-II spectral region. Numerous applications of NIR-II PA imaging, including whole-body animal imaging and human imaging, are also discussed.

Cryodesiccation-driven crystallization preparation approach for zinc(II)-phthalocyanine nanodots in cancer photodynamic therapy and photoacoustic imaging.

Multifunctional nanodots represent an emerging platform for overcoming the delivery challenges of poorly water-soluble drugs for use in the diagnosis and treatment of cancer. The authors describe the preparation of nanocrystallites composed of the water-insoluble photosensitizer zinc(II)-phthalocyanine in the form of nanodots by applying a cryodesiccation-driven crystallization approach. Modification of the surface of the nanodots with Pluronic F127 and folic acid endows them with excellent water solubility and stealth properties in blood. Under near-infrared (NIR) photoexcitation at 808nm, the nanodots are shown to produce singlet oxygen, which is widely used in photodynamic therapy of cancer. The nanodots exhibit strong NIR absorbance at 808nm and can be used as a non-toxic contrast agent for photoacoustic imaging of tissue. Graphical abstract Schematic presentation of the preparation of ZnPcNDs by droplet-confined/cryodesiccation-driven crystallization.

Nanomaterials for photoacoustic imaging in the second near-infrared window.

Photoacoustic imaging (PAI) is a rapidly developing imaging technique for both fundamental research and clinical applications. Recent studies revealed that PAI in the second near-infrared (NIR-II) region exhibits enhanced deep-tissue imaging capability, which benefits from reduced photon scattering, minimized background noise and increased applicable power in comparison to PAI in the first near-infrared (NIR-I) region. This review focuses on the latest achievements on PAI in the NIR-II region. The advantages of shifting PAI from NIR-I to NIR-II is first compared, followed by discussions on nanomaterials as contrast agents for NIR-II PAI. In the end, the challenges and perspectives of PAI in the NIR-II region are also elaborated.

Current concepts in nanostructured contrast media development for in vivo photoacoustic imaging.

Photoacoustic (PA) imaging is indeed one of the most promising bioimaging techniques for theranostics applications in humans, allowing for the visualization of blood vessels and melanomas with high spatial resolution. However, in order to overcome the endogenous contrast arising from interfering endogenous species such as haemoglobin and melanin, specific contrast agents need to be developed, allowing PAI to successfully identify targeted contrast in the range of wavelengths in which interference from the biomatrix is minimized. This has been first performed by small molecule dyes, which, however, suffer from some important limitations such as low hydrophilicity and short circulation times. For this reason, scientific research has recently directed its efforts towards the development of nanostructured contrast agents capable of providing efficient PA contrast at low concentrations with low toxicity and high biocompatibility. The principal nanostructures are based on (1) metal and semiconducting nanoparticles, amongst which variously shaped nano-gold plays the main role, (2) carbon nanomaterials, such as carbon nanotubes and graphene, and (3) conjugated polymer nanoparticles. In this review, the principal characteristics of this class of materials are reported and greater focus is directed towards in vivo studies. A detailed analysis is performed on various physical-chemical parameters that define the PA response of reported contrast agents, like absorption coefficients and photoacoustic efficiencies. By comparing the experimental data, this review provides a comprehensive tool for the evaluation of new nanostructured contrast agents for PA imaging.

A 1064 nm excitable semiconducting polymer nanoparticle for photoacoustic imaging of gliomas.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window (especially at 1064 nm) has the benefits of low background signal, high spatial resolution and deep tissue penetration. Here we report a semiconducting polymer nanoparticle (PDPPTBZ NP) and demonstrate its potential as a contrast agent for PA imaging of orthotopic brain tumors, using a 1064 nm pulsed laser as a light source. PDPPTBZ NPs have maximum absorption at 1064 nm with a mass extinction coefficient of 43 mL mg-1 cm-1, which is the highest value reported so far in this region. The high photothermal conversion efficiency (67%) and near non-fluorescence impart PDPPTBZ NPs with excellent PA properties. We used PDPPTBZ NP-containing agar gel phantoms even at a low concentration (50 μg mL-1) to successfully image to a depth of 4 cm (of chicken-breast tissue), with an ultralow power fluence (4 mJ cm-2). Furthermore, we could clearly visualize a glioma tumor in a mouse at a depth of 3.8 mm below the skull. This study demonstrates that PDPPTBZ NPs display great potential as a NIR-II PA contrast agent for high quality deep tissue imaging.

The theranostic nanoagent Mo2C for multi-modal imaging-guided cancer synergistic phototherapy.

Multifunctional theranostic platforms, especially single component-based platforms, enable both cancer treatment and real-time imaging as well as enhance the efficiency of treatment. In this study, 50 nm Mo2C nanospheres were explored as a "one-for-all" theranostic agent. The light-harvesting of Mo2C covered the entire near infrared region, and NIR irradiation concurrently triggered hyperthermia and reactive oxygen species (ROS) production; thus, synergistic outcomes of photothermal and photodynamic therapy could be realized. Both in vitro and in vivo experiments have confirmed the superiority of the synergistic phototherapy in killing cancer cells and removing solid tumors; moreover, Mo2C proposed herein has been proven to be applicable as a photoacoustic imaging and CT imaging contrast agent for in vivo tumor depiction; furthermore, Mo2C demonstrates excellent biocompatibility, showing minimal hematotoxicity and tissue toxicity. A theoretical simulation performed by density functional theory revealed that the metallic character and the interband/intraband transition of Mo2C accounted for its broad photoabsorption. The antitumor mechanism of Mo2C was investigated on a solid tumor by B-mode ultrasonography (US) and magnetic resonance imaging (MRI), revealing a typical liquefactive necrosis process; hence, herein, the dual-imaging guided phototherapy was efficiently mediated by Mo2C.

Developing gold nanotubes as photoacoustic contrast agents

Photoacoustic imaging (PAI) combines the spectral selectivity of laser excitation with the high resolution of ultrasound imaging, representing a noninvasive modality that holds remarkable potential for clinical translation. In particular, multispectral optoacoustic tomography has emerged has an innovative PAI technology, which enables high detection specificity by resolving multiple spectral signatures through tissues and accurately decomposing the biodistribution of relevant molecules from non-specific background contributions. Key criteria for developing PAI contrast agents include strong absorbance in the near-infrared (NIR) tissue transparent region and low toxicity. In this study, we have fabricated gold nanotubes (Au NTs) with controlled length and NIR absorption for the application as in vivo MSOT contrast agents. The length control relies on the synthesis of silver nanorod template under certain growth conditions. The Au NTs were coated with a layer of biocompatible polymer, poly(sodium 4-styrenesulfonate) (PSS), to ensure colloidal stability and low cytotoxicity. The PSS-Au NTs have shown excellent MSOT signal enhancement on tissue-mimicking phantom and in vivo, demonstrating the potential for further development towards a theranostic nanoplatform integrating PAI capability and therapeutic functions.

Surface-engineered vanadium nitride nanosheets for an imaging-guided photothermal/photodynamic platform of cancer treatment.

Of the many strategies for precise tumor treatment, near-infrared (NIR) light-activated "one-for-all" theranostic modality with real-time diagnosis and therapy has attracted extensive attention from researchers. Herein, a brand-new theranostic nanoplatform was established on versatile vanadium nitride (VN) nanosheets, which show significant NIR optical absorption, and resultant photothermal effect and reactive oxygen species activity under NIR excitation, thereby realizing the synergistic action of photothermal/photodynamic co-therapy. As expected, systematic in vitro and in vivo antitumor evaluations demonstrated efficient cancer cell killing and solid tumor removal without recurrence. Meanwhile, the surface modification of VN nanosheets with poly(allylamine hydrochloride) and bovine serum albumin enhanced the biocompatibility of VN and made it more suitable for in vivo delivery. Moreover, VN has been ascertained as a potential photoacoustic imaging contrast for in vivo tumor depiction. Thus, this work highlights the potential of VN nanosheets as a single-component theranostic nanoplatform.

Surfactant-Stripped Pheophytin Micelles for Multimodal Tumor Imaging and Photodynamic Therapy.

Porphyrin-based nanomaterials can inherently integrate multiple contrast imaging functionalities with phototherapeutic capabilities. We dispersed pheophytin (Pheo) into Pluronic F127 and carried out low-temperature surfactant-stripping to remove the bulk surfactant. Surfactant-stripped Pheo (ss-Pheo) micelles exhibited a similar size, but higher near-infrared fluorescence, compared to two other nanomaterials also with high porphyrin density (surfactant-stripped chlorophyll micelles and porphysomes). Singlet oxygen generation, which was higher for ss-Pheo, enabled photodynamic therapy (PDT). ss-Pheo provided contrast for photoacoustic and fluorescence imaging, and following seamless labeling with 64Cu, was used for positron emission tomography. ss-Pheo had a long blood circulation and favorable accumulation in an orthotopic murine mammary tumor model. Trimodal tumor imaging was demonstrated, and PDT resulted in delayed tumor growth.

Exosome-like Nanozyme Vesicles for H2O2-Responsive Catalytic Photoacoustic Imaging of Xenograft Nasopharyngeal Carcinoma.

Photoacoustic imaging (PAI) is an attractive imaging modality, which is promising for clinical cancer diagnosis due to its advantages on deep tissue penetration and fine spatial resolution. However, few tumor catalytic/responsive PAI strategies are developed. Here, we design an exosome-like nanozyme vesicle for in vivo H2O2-responsive PAI of nasopharyngeal carcinoma (NPC). The intrinsic peroxidase-like activity of graphene quantum dot nanozyme (GQDzyme) effectively converts the 2,2'-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form in the presence of H2O2. The oxidized ABTS exhibits strong near-infrared (NIR) absorbance, rendering it to be an ideal contrast agent for PAI. Thus, GQDzyme/ABTS nanoparticle is a novel type of catalytic PAI contrast agent, which is sensitive to H2O2 produced from NPC cells. Furthermore, we develop an approach to construct exosome-like nanozyme vesicle via biomimetic functionalization of GQDzyme/ABTS nanoparticle with natural erythrocyte membrane modified with folate acid. In vivo animal experiments demonstrated that this exosome-like nanozyme vesicle effectively accumulated in NPC and selectively triggered catalytic PAI for NPC. In addition, our nanozyme vesicle exhibits excellent biocompatibility and stealth ability for long blood circulation. Together, we demonstrate that GQDzyme/ABTS based exosome-like nanozyme vesicle is an ideal nanoplatform for developing deep-tissue tumor-targeted catalytic PAI in vivo.

Hybrid multi-wavelength nonlinear photoacoustic sensing and imaging.

Multi-wavelength photoacoustic (PA) imaging has been studied extensively to explore the spectroscopic absorption contrast of biological tissues. To generate strong PA signals, a high-power wavelength tunable pulsed laser source has to be employed, which is bulky and quite expensive. In this Letter, we propose a hybrid multi-wavelength PA imaging (hPAI) method based on the combination of a single-wavelength pulsed laser source and multi-wavelength continuous-wave (CW) laser sources. By carefully controlling the laser illumination sequence (pulse-CW-pulse) and extracting the PA signal difference before and after the heating of CW lasers, the optical absorption property of multi-wavelength light illumination could be obtained. Compared with conventional PA imaging, the proposed hPAI shows a much lower system cost due to the usage of single-wavelength pulsed lasers and multiple inexpensive CW lasers. As the preliminary results show in this Letter, hPAI imaging has the potential to provide another pathway for high spectroscopic optical absorption contrast in PA imaging.