Utility of biodegradable plasmonic nanoclusters in photoacoustic imaging

Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast agents because of their resonant optical absorption properties in the visible and near-IR regions. However, the nanoparticles could accumulate and result in long-term toxicity in vivo, because they are generally not biodegradable. Recently, biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold nanoparticles and biodegradable polymer stabilizer, were introduced. In this Letter, we demonstrate the feasibility of biodegradable nanoclusters as a photoacoustic contrast agent. We performed photoacoustic and ultrasound imaging of a tissue-mimicking phantom with inclusions containing nanoclusters at various concentrations. The results indicate that the biodegradable gold nanoclusters can be used as effective contrast agents in photoacoustic imaging.     

Shell thickness determination of polymer-shelled microbubbles using transmission electron microscopy

Intravenously injected microbubbles (MBs) can be utilized as ultrasound contrast agent (CA) resulting in enhanced image quality. A novel CA, consisting of air filled MBs stabilized with a shell of polyvinyl alcohol (PVA) has been developed. These spherical MBs have been decorated with superparamagnetic iron oxide nanoparticles (SPIONs) in order to serve as both ultrasound and magnetic resonance imaging (MRI) CA. In this study, a mathematical model was introduced that determined the shell thickness of two types of SPIONs decorated MBs (Type A and Type B). The shell thickness of MBs is important to determine, as it affects the acoustical properties. In order to investigate the shell thickness, thin sections of plastic embedded MBs were prepared and imaged using transmission electron microscopy (TEM). However, the sections were cut at random distances from the MB center, which affected the observed shell thickness. Hence, the model determined the average shell thickness of the MBs from corrected mean values of the outer and inner radii observed in the TEM sections. The model was validated using simulated slices of MBs with known shell thickness and radius. The average shell thickness of Type A and Type B MBs were 651 nm and 637 nm, respectively.     

Cobalt Phosphide Nanoparticles Applied as a Theranostic Agent for Multimodal Imaging and Anticancer Photothermal Therapy

Biocompatible single‐component theranostic nanoagents instinctly affording multiple imaging modalities with satisfying therapeutic functions are highly desirable for anticancer treatments. Although cobalt‐based phosphides are well‐recognized as competent electrocatalysts, their potentials for biomedical applications remain unexplored. In this work, cobalt phosphide nanoparticles (CoP NPs) are developed to be a powerful theranostic agent for multimodal imaging and anticancer photothermal therapy. The uniform CoP NPs in a size of ≈21 nm are synthesized via a facile thermal decomposition method, followed by surface modification. The resultant CoP NPs exhibit excellent compatibility and stability in water as well as various physiological solutions. Supported by the good biocompatibility, strong near‐infrared absorption, and high photothermal conversion property, significant photothermal effect of the NPs is demonstrated, realizing efficient hyperthermia ablation on cancer cells. Importantly, the CoP NPs have shown considerable capabilities on high‐contrast in vitro and in vivo triple‐modal imaging, including infrared thermal (IRT), photoacoustic (PA), and T₂‐weighted magnetic resonance (MR) imaging. This work has unraveled the promising potentials of CoP‐based nanoagent for precise diagnosis and efficient therapy.     

Copper Sulfide Nanodisks and Nanoprisms for Photoacoustic Ovarian Tumor Imaging

Transvaginal ultrasound is widely used for ovarian cancer screening but has a high false‐positive rate. Photoacoustic imaging provides additional optical contrast to supplement ultrasound and might be able to improve the accuracy of screening. Two copper sulfide (CuS) nanoparticle types (nanodisks and triangular nanoprisms) are reported as photoacoustic contrast agents for imaging ovarian cancer. Both CuS nanoprisms and nanodisks are ≈6 nm thick and ≈26 nm wide and are coated with poly(ethylene glycol) to make them colloidally stable in phosphate‐buffered saline for at least two weeks. The CuS nanodisks and nanoprisms reveal strong localized surface plasmon resonances with peak maxima at 1145 and 1098 nm, respectively. Both nanoparticle types have strong and stable photoacoustic intensity with detection limits below 120 pm . The circular CuS nanodisk remains in the circulation of nude mice (n = 4) and xenograft 2008 ovarian tumors (n = 4) 17.9‐fold and 1.8‐fold more than the triangular nanoprisms, respectively. Finally, the photoacoustic intensity of the tumors from the mice (n = 3) treated with CuS nanodisks is threefold higher than the baseline. The tumors treated with nanodisks have a characteristic peak at 920 nm in their spectrum to potentially differentiate the tumor from adjacent tissues.     

Monte Carlo light transport-based blood vessel quantification using linear array photoacoustic tomography

Photoacoustic tomography is a noninvasive and nonionized biomedical imaging modality but it cannot reveal the inner structure and sideward boundary information of blood vessels in the linear array detection mode.In contrast,Monte Carlo(MC) light transport could provide the optical fluence distribution around the entire vascular area.This research explores the combination of linear array transducer-based photoacoustic tomography and MC light transport in the blood vessel quantification.Simulation,phantom,and in vivo experiments are in good correlation with the ultrasound imaging,validating this approach can clearly visualize the internal region of blood vessels from background tissue.     

Noninvasive photoacoustic angiography of animal brains in vivo with near-infrared light and an optical contrast agent

Optical contrast agents have been widely applied to enhance the sensitivity and specificity of optical imaging with near-infrared (NIR) light. However, because of the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. Here, for the first time to our knowledge, we present noninvasive photoacoustic angiography of animal brains in vivo with NIR light and an optical contrast agent. When indocyanine green polyethylene glycol, a novel absorption dye with prolonged clearance, is injected into the circulatory system of a rat, it obviously enhances the absorption contrast between the blood vessels and the background tissues. Because NIR light can penetrate deep into the brain tissues through the skin and skull, we are able to successfully reconstruct the vascular distribution in the rat brain from the photoacoustic signals. On the basis of differential optical absorption with and without contrast enhancement, a photoacoustic angiograph of a rat brain is acquired that matches the anatomical photograph well and exhibits high spatial resolution and a much-reduced background. This new technology demonstrates the potential for dynamic and molecular biomedical imaging.     

In Vivo Targeted Cancer Theranostics by Core/Shell‐Structured Multifunctional Prussian Blue/PLGA “Nanococktails”

The construction of high‐performance nanotheranostic agent with Food and Drug Administration (FDA)‐approved materials for efficient treatment of breast cancer is still of great challenge. This work reports, for the first time, on the elaborate integration of two FDA‐approved materials together to construct a multifunctional core/shell‐structured “nanococktail” for cancer theranostics. The biocompatible Prussian blue nanoparticles with high photothermal‐conversion performance are coated by poly(lactic‐co‐glycolic acid) followed by further surface targeting engineering (folic acid conjugation). The anticancer drug paclitaxel is concurrently encapsulated into the nanocarrier with high efficiency and capacity. Especially, these “nanococktails” act as the desirable contrast agents for photoacoustic/magnetic resonance imaging dual‐mode diagnostic imaging, providing the potential for guidance and monitoring during the therapeutic process, which has been systematically demonstrated both in vitro and in vivo. Importantly, these “nanococktails” have demonstrated their high performance in synergistic in vivo photothermal therapy and chemotherapy against breast cancer tumor xenograft. This work not only provides a high‐performance theranostic “nanococktail” platform for efficient theranostic treatment of cancer but also paves a new way for the integration of various functional moieties together for realizing the specific diagnostic imaging‐guided and synergistic cancer therapy.     

Noninvasive detection of intimal xanthoma using combined ultrasound, strain rate and photoacoustic imaging

Background and motivation

The structure, composition and mechanics of carotid artery are good indicators of early progressive atherosclerotic lesions. The combination of three imaging modalities (ultrasound, strain rate and photoacoustic imaging) which could provide corroborative information about the named arterial properties could enhance the characterization of intimal xanthoma.

Methods

The experiments were performed using a New Zealand white rabbit model of atherosclerosis. The aorta excised from an atherosclerotic rabbit was scanned ex vivo using the three imaging techniques: (1) ultrasound imaging of the longitudinal section: standard ultrasound B-mode (74 Hz frame rate); (2) strain rate imaging: the artery was flushed with blood and a 1.5 Hz physiologic pulsation was induced, while the ultrasound data were recorded at higher frame rate (296 Hz); (3) photoacoustic imaging: the artery was irradiated with nanosecond pulsed laser light of low fluence in the 1210-1230 nm wavelength range and the photoacoustic data was recorded at 10 Hz frame rate. Post processing algorithms based on cross-correlation and optical absorption variation were implemented to derive strain rate and spectroscopic photoacoustic images, respectively.

Results

Based on the spatio-temporal variation in displacement of different regions within the arterial wall, strain rate imaging reveals differences in tissue mechanical properties. Additionally, spectroscopic photoacoustic imaging can spatially resolve the optical absorption properties of arterial tissue and identify the location of lipid pools.

Conclusions

The study demonstrates that ultrasound, strain rate and photoacoustic imaging can be used to simultaneously evaluate the structure, the mechanics and the composition of atherosclerotic lesions to improve the assessment of plaque vulnerability.     

High-contrast imaging based on wavefront shaping to improve low signal-to-noise ratio photoacoustic signals using superpixel method

Photoacoustic(PA) imaging has drawn tremendous research interest for various applications in biomedicine and experienced exponential growth over the past decade. Since the scattering effect of biological tissue on ultrasound is two-to three-orders magnitude weaker than that of light, photoacoustic imaging can effectively improve the imaging depth.However, as the depth of imaging further increases, the incident light is seriously affected by scattering that the generated photoacoustic signal is very weak and the signal-to-noise ratio(SNR) is quite low. Low SNR signals can reduce imaging quality and even cause imaging failure. In this paper, we proposed a new wavefront shaping and imaging method of low SNR photoacoustic signal using digital micromirror device(DMD) based superpixel method. We combined the superpixel method with DMD to modulate the phase and amplitude of the incident light, and the genetic algorithm(GA) was used as the wavefront shaping algorithm. The enhancement of the photoacoustic signal reached 10.46. Then we performed scanning imaging by moving the absorber with the translation stage. A clear image with contrast of 8.57 was obtained while imaging with original photoacoustic signals could not be achieved. The proposed method opens new perspectives for imaging with weak photoacoustic signals.     

Synergistic Effect of Thermo‐Radiotherapy Using Au@FeS Core–Shell Nanoparticles as Multifunctional Therapeutic Nanoagents

Imaging guided combined therapy has attracted great attention in recent years. This study develops core–shell Au@FeS nanoparticles with polyethylene glycol (PEG) coating as multifunctional nanotheranostic agent for tumor imaging and combined photothermal therapy (PTT) and radiotherapy (RT). In this Au@FeS nanostructure, the gold core can act as a radiosensitizer for enhanced RT, while FeS shell offers contrast for T2‐weighted magnetic resonance imaging and endows the nanoparticles with strong high near‐infrared (NIR) for photoacoustic imaging and PTT. As demonstrated by both in vitro and in vivo experiments, Au@FeS‐PEG can act as excellent therapeutic agent for cancer synergistic treatment. More importantly, mild PTT boosts the blood flow into tumor and increases oxygenation to overcome the tumor hypoxia microenvironment, further enhancing the efficacy of RT. Moreover, Au@FeS‐PEG induces on obvious toxicity at a high dose (20 mg kg^?1) to the treated mice as evidenced by blood biochemistry. Therefore, this study brings an excellent strategy for cancer enhanced RT through NIR‐triggered mild PTT to overcome hypoxia‐associated radioresistance.     

Feasibility of photoacoustic tomography for ophthalmology

For the eyeball composed of membrane and liquid, the contrast of ultrasound imaging is not high due to its small variance in acoustic impedance. As a new imaging modality, photoacoustic tomography combines the advantages of pure optical and ultrasonic imaging together and can provide high resolution, high contrast images. In this paper, the feasibility of photoacoustic tomography for ophthalmology is studied experimentally. A Q-switched Nd:YAG pulsed laser with 7-ns pulse width is used to generate photoacoustic signal of a porcine eyeball in vitro. The two-dimensional (2D) optical absorption image of the entire eyeball is reconstructed by time-domain spherical back projection algorithm. The imaging results agree well with the histological structure of the eyeball and show a high imaging contrast.     

多模态光声分子成像进展*

现代的各种医学影像术,如射线成像、CT、正电子发射(PET)、磁共振(MR)、超声(US)、荧光(FL)等都各具特色,并成功地应用于多种疾病的诊疗。但每种影像术都不能对生物组织做出完整的描述。由若干个成像技术组成的多模态成像技术,是获得组织更多信息的有效途径。光声(PA)成像是能提供组织的成分和功能信息的新成像技术。它不仅灵敏,可以对较深层的组织进行实时、快速、安全的成像,而且可以利用光声光热造影剂实施非侵入的光热靶向治疗。因此,与光声成像相结合的多模态分子成像是实现精准诊疗的重要技术途径。该文以手持US-PA探头的双模态成像系统,直径为1 mm的血管內窥镜US-PA成像系统,可同时用于术前和术中的US-PA-FL三模态成像系统,以及采用外磁场可操控的磁共振-光声光热分子造影剂、进行MR-PA成像引导的光热治疗技术为例,对多模态光声分子成像系统在医学诊断、手术和光热治疗方面的进展做简单介绍。     

改进的同步迭代算法在光声血管成像中的应用

光声成像结合了光学成像和声学成像的优点，是一种高分辨率，高对比度的无损伤医学成像技术.一种改进的同步迭代算法应用于光声图像重建.仿真和模拟结果表明，与传统的代数迭代算法相比，在90°，135°，180°的有限场光声成像中，此算法对测量误差的校正和迭代次数的收敛上具有较大的优势，图像重建的速度和成像质量都有了明显的提高.实验中，一种圆形扫描结构的光声成像装置，用于180°的有限场扫描，利用改进的同步迭代算法，重建出了高对比度和高分辨率（60μm）的鸡胚胎光声血管图像.实验证明，这种算法的应用，大幅度减少了数据采集时间，为光声成像技术运用于实时监测血流灌注和肿瘤光动力治疗的血管损伤效应提供了潜在的应用价值. 关键词： 光声成像 有限角度 代数迭代算法 光声血管成像     

Hydrophilic Cu3BiS3 Nanoparticles for Computed Tomography Imaging and Photothermal Therapy

Hydrophilic Cu₃BiS₃ nanoparticles (NPs) have been prepared using the thermal decomposition of precursor complexes in oily‐mixed solvent followed by coating the produced Cu₃BiS₃ NPs with polyvinylpyrrolidone (PVP). The resulting Cu₃BiS₃/PVP NPs remain stable in aqueous solutions over a long period of time, and meanwhile, they show low in vitro cytotoxicity and negligible toxicity to mice in vivo. Cu₃BiS₃/PVP NPs could operate as an efficient dual‐modal contrast agent to simultaneously enhance X‐ray computed tomography imaging and photothermal imaging of tumor model in vivo. Moreover, highly efficient ablation of cancer cells both in vitro and in vivo has been successfully achieved by combining Cu₃BiS₃/PVP NPs with near‐infrared (NIR) laser irradiation. All of the positive results in this study highlight that Cu₃BiS₃/PVP NPs could serve as a promising platform for cancer diagnosis and therapy.     

Multifunctional Hybrids Based on 2D Fluorinated Graphene Oxide and Superparamagnetic Iron Oxide Nanoparticles

Carbon‐based nanomaterials have garnered a lot of attention in the research of yesteryear. Here this study reports a composite based on fluorinated graphene oxide—a multifunctional subsidiary of graphene; and iron oxide nanoparticles as a contrast agent for magnetic resonance imaging (MRI). Extensive structural and functional characterization is carried out to understand composite behavior toward biotoxicity and its performance as a contrast agent. The electron withdrawing fluorine group decreases the charge transfer to iron oxide increasing the magnetic saturation of the composite thus enhancing the contrast. The interaction of paramagnetic and superparamagnetic systems yields a superior contrast agent for MRI and fluorescent imaging.     

Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the presence of luminal blood

Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.     

Multifocal optical-resolution photoacoustic microscopy in vivo

Although ultrasound arrays have been exploited in photoacoustic imaging to improve imaging speed, ultrasound-array-based optical-resolution photoacoustic microscopy (OR-PAM) has never been achieved previously to our knowledge. Here we present our development of multifocal OR-PAM using a microlens array for optical illumination and an ultrasound array for photoacoustic detection. Our system is capable of imaging hemoglobin concentration and oxygenation in individual microvessels in vivo at high speed. Compared with a single focus, multiple foci reduce the scanning load and increase the imaging speed significantly. The current multifocal system can acquire 1000 × 500 × 200 voxels at ~10 μm lateral resolution within 4 min.     

基于多元线性阵列探测器的快速光声层析成像

报道了一种基于相控聚焦的多元线性阵列探测器进行快速光声层析成像的方法和装置,并实现了模拟组织的光声层析成像。实验中采用波长为532nm脉宽为7ns的倍频Q-YAG激光器作为激发光源。多元线性阵列探测器由320个振元组成,采用相控聚焦的方法成像,每次由11个振群的探测器接受信号并合并1路,一幅图像由64路这样的信号组成。实验结果能够正确反映样品中的光学吸收分布。与现有的方法比较,本系统具有快速方便的特点,它有望成为一种组织功能在体成像的新方法,发展成为一种低成本的实用的临床诊断装置。     

Contrast enhanced vascular three-dimensional ultrasound imaging

In other imaging modalities three-dimensional (3D) data displays are well established; not so in ultrasound. Due to the real-time requirements of ultrasound the time available to compute 3D displays is limited, particularly when flow data is acquired with Doppler techniques. Consequently, it is only recently that improvements in computer processing power have resulted in useful vascular 3D ultrasound scans. Many manufacturers have now implemented free-hand 3D power Doppler capabilities on their scanners. However, to obtain flow signals from smaller vessels associated e.g., with tumor neovascularity, may very well require the introduction of a microbubble based ultrasound contrast agent into the blood stream. Given the up to 30 dB enhancement of Doppler signals produced by the contrast microbubbles quite spectacular vascular 3D images are feasible. Moreover, new contrast imaging techniques, such as harmonic imaging, have now permitted 3D vascular information to be acquired and displayed in grayscale with the associated improvement in resolution. In this paper we will review different aspects of contrast enhanced vascular 3D ultrasound imaging including implementation, contrast specific techniques and in vivo imaging.     

Ultrasound mediated destruction of multifunctional microbubbles for image guided delivery of oxygen and drugs

We synthesized multifunctional activatible microbubbles (MAMs) for ultrasound mediated delivery of oxygen and drugs with both ultrasound and fluorescence imaging guidance. Oxygen enriched perfluorocarbon (PFC) compound was encapsulated in liposome microbubbles (MBs) by a modified emulsification process. DiI dye was loaded as a model drug. The ultrasound targeted microbubble destruction (UTMD) process was guided by both ultrasonography and fluorescence imaging modalities. The process was validated in both a dialysis membrane tube model and a porcine carotid artery model. Our experiment results show that the UTMD process effectively facilitates the controlled delivery of oxygen and drug at the disease site and that the MAM agent enables ultrasound and fluorescence imaging guidance of the UTMD process. The proposed MAM agent can be potentially used for UTMD-mediated combination therapy in hypoxic ovarian cancer.