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。     

Energy relaxation time in a gas mixture measured by a photothermal probe beam deflection technique

The deflection of a cw probe laser beam, which occurs in a gas mixture after the absorption of a short laser pump pulse, was experimentally studied inside the irradiated region in order to characterize the generation of photothermal and photoacoustic effects. The time varying component of the probe deflection was detected, and the results are presented as functions of pumping fluences, laser wavelengths and gas pressures. Numerical modelling of the thermo-acoustic dynamics leads to the definition of an effective energy relaxation time for SF₆/Ar gas mixtures. An interesting nonlinear behaviour of this energy relaxation time is reported.     

纳秒脉冲激光特性对金纳米球光声响应的影响

由于局部表面等离激元共振现象,金纳米颗粒具有显著的光热效应,而近年来随着人们对精准医疗和非介入性组织成像的需要,作为纳米颗粒光热衍生效应的金纳米颗粒光声效应得到了人们的广泛关注.金纳米颗粒自身特性对其光声效应的影响目前已经得到一定的研究,而对于脉冲激光特性对其光声效应的影响尚缺乏深入探讨,因此,本文对金纳米球在不同脉冲...     

Photoacoustic and related photothermal techniques

We review the theory and applications of the photoacoustic and related methods belonging to the general area of photothermal measurement techniques. This essay is intended for researchers especially unfamiliar with the basic ideas and potentialities of this rapidly developing field. The applications of photothermal techniques include spectroscopic applications, such as infrared and microwave spectroscopies, monitoring of non-radiative deexcitation processes, biological applications, and measurements of thermal properties.     

Tantalum Nitride Nanosheets for Photoacoustic Imaging-Guided Photothermal Cancer Therapy

In this study, the synthesis of TaN nanosheets and their application in theranostic agents is reported. After coating polyethylene glycol (PEG) on the TaN nanosheets, the as-synthesized PEG-modified TaN nanosheets (TaN-PEG) show good stability and biocompatibility. Because of their high absorbance in the near-IR region, TaN-PEG can be utilized as photoacoustic imaging contrast agents for tumor imaging. Moreover, TaN-PEG has significant photothermal conversion performance, exhibiting effective laser-induced tumor ablation capability. The TaN-PEG possessing excellent photoacoustic contrast effect and photothermal properties thus have great promise in theranostic applications, especially imaging-guided cancer treatment.     

Theoretical and experimental investigation of the photoacoustic effect in solids with residual stresses

Modern experiment and theory in the field of residual stress detection by the photoacoustic method are summarized and analyzed. A multimode approach based on the simultaneous application of several photothermal and photoacoustic methods is proposed for the study of thermal and thermoelastic effects in solids with residual stress. Some experimental results obtained within the framework of this approach for Vickers indentation zones in ceramics are presented. The effect of annealing on the photoacoustic, piezoelectric signal for ceramics and the influence of the given external loading on the behavior of the photoacoustic signal near the radial crack tips is investigated. It is experimentally shown that both compressive and shear stresses contribute to the photoacoustic signal near the radial crack tips. The model of the photoacoustic, thermoelastic effect in solids with residual stress is proposed. It is based on the modified Murnaghan model of non-linear elastic bodies, which takes into account a possible dependence of the thermoelastic constant on stress. This model is further developed to explain the photoacoustic signal behavior near the radial crack tips. It is demonstrated that this model of the photoacoustic effect agrees qualitatively with the available experimental data.     

Double resonance 1-D photonic crystal cavities for single-molecule mid-infrared photothermal spectroscopy: theory and design

We propose and theoretically examine a novel mid-infrared (mid-IR) photothermal spectroscopic sensing technique capable of detecting a single small molecule. Our conceptual design attains such high sensitivity by leveraging dramatically amplified photothermal effects in an optical nanocavity doubly resonant at both mid-IR pump and near-IR probe wavelengths. Unlike conventional mid-IR spectroscopy, the technique eliminates the need for cryogenically cooled mid-IR photodetectors, as optical detection is performed solely at the near-IR probe wavelength. A device design based on nested one-dimensional nanobeam photonic crystal cavities is numerically analyzed to demonstrate the technique's potential for single small gas molecule detection.     

A DESCRIPTION OF THE THERMO-ELASTIC RESPONSE OF LAYERED MEDIA BY A MATRIX FORMALISM

A matrix formalism is introduced here for the analytical calculation of the thermo-elastic response of one-dimensional optically inhomogeneous layered structures exposed to the periodic laser heating. The multilayer structure consists of thermally and mechanically homogeneous solid layers which can be interleaved by liquid ot galore interlayers. The method enables the modelling of photoacoustic and photothermal measurements in a variety of engineering applications.     

An improved photothermal gas analyser: Monitoring of simultaneous thermal diffusivity and thermal effusivity

In this paper we describe a new, simple and fast photothermal method for characterizing simultaneously the thermal diffusivity and thermal effusivity. The improved PTGA essentially combines a photoacoustic cell and a thermal wave pyroelectric cell enclosed in a single compact gas analyzer. The photo- acoustic cell is kept filled with nitrogen and sealed. The pyroelectric cell is also filled with nitrogen and after some warm up time, the nitrogen is exchanged to the gas of interest. It is shown that the analysis of the transient and saturation signals of both photoacoustic and pyroelectric cells are capable of measuring the thermal properties with an accuracy of 5%. The measurements were performed for hydrocarbons as ethane and propane, which are combustible gases. Knowing thermal diffusivity and effusivity, others important properties can be determinate: the thermal conductivity and the volumetric thermal capacity.     

光声内窥镜系统在人体直肠癌离体组织中的实验研究

研制了基于4阵列传感器的光声内窥镜探头,并基于此搭建了光声内窥镜成像系统,开展了仿体实验成像研究,通过内窥镜探头4个阵元位置激光吸收强度的变化情况来分析仿体中吸收体的位置,论证了其定位能力,利用光声内窥镜系统对人体离体的正常组织、直肠癌早期组织进行成像研究;通过对不同阵元位置的光吸收强度分布进行统计分析,证明了光声内窥镜对早期直肠癌组织和正常组织的辨别能力,此项技术有望提高直肠癌早期诊断的准确率,具有潜在的临床应用前景。     

In vivo flow speed measurement of capillaries by photoacoustic correlation spectroscopy

We recently proposed photoacoustic correlation spectroscopy (PACS) and demonstrated a proof-of-concept experiment. Here we use the technique for in vivo flow speed measurement in capillaries in a chick embryo model. The photoacoustic microscopy system is used to render high spatial resolution and high sensitivity, enabling sufficient signals from single red blood cells. The probe beam size is calibrated by a blood-mimicking phantom. The results indicate the feasibility of using PACS to study flow speeds in capillaries.     

Simulation of light delivery for photoacoustic breast imaging using the handheld probe

The photoacoustic tomography by using the handheld probe has a great potential in clinical breast imag- ing. However, tile shape of the probe limits the choice of light delivery in this setup. In this letter, we study two commonly used illumination types for handheld probe： bright-field illumination and dark-field illumination. Our results demonstrate several parameters have important impact on the photon fluence in deep breast tissue. The results will help to optimize the design of the photoaeoustie breast imaging system with a handheld probe.     

Thermo‐plasmonics: using metallic nanostructures as nano‐sources of heat

Recent years have seen a growing interest in using metal nanostructures to control temperature on the nanoscale. Under illumination at its plasmonic resonance, a metal nanoparticle features enhanced light absorption, turning it into an ideal nano‐source of heat, remotely controllable using light. Such a powerful and flexible photothermal scheme is the basis of thermo‐plasmonics. Here, the recent progress of this emerging and fast‐growing field is reviewed. First, the physics of heat generation in metal nanoparticles is described, under both continuous and pulsed illumination. The second part is dedicated to numerical and experimental methods that have been developed to further understand and engineer plasmonic‐assisted heating processes on the nanoscale. Finally, some of the most recent applications based on the heat generated by gold nanoparticles are surveyed, namely photothermal cancer therapy, nano‐surgery, drug delivery, photothermal imaging, protein tracking, photoacoustic imaging, nano‐chemistry and optofluidics.     

基于探测超声的新型生物组织光声层析成像

利用一束单频探测超声穿过由脉冲激光照射产生的光声激发区域，使之与光致声场产生相互作用，光声信号将耦合到探测束上，再解调探测超声来重建光吸收区域的图像，可以得到丰富的组织信息.该信息不仅反映了组织中光吸收的特性，也反映了组织的声学特性.实验中，通过旋转超声探测器进行数据采集，并利用滤波反投影算法重建图像，可得到高信噪比的光声层析图像.由于激光的窄光谱线宽，其吸收是特征分子选择性的，所以此方法既是一种无损伤的结构层析成像方法，也可用于组织的功能成像.     

多参量光声成像及其在生物医学领域的应用

光声成像兼具声学成像和光学成像两者的优点, 因而成为近十年来发展最迅速的生物医学成像技术之一. 本文介绍了光声成像的特点及其相对于广泛应用的光学成像技术和声学成像技术的优点; 其次, 解释了光声成像的成像原理, 在此基础上介绍了光声断层成像和光声显微镜这两种典型的光声成像方案, 并介绍了它们的技术特点; 然后, 介绍了光声成像对生物组织的生化特性、组织力学特性、血液流速分布、温度分布参数、微结构特性等多信息参量的提取能力, 及其在生物系统的结构成像、功能成像、代谢成像、分子成像、基因成像等多领域的应用; 最后, 展望了光声成像在生物医学领域的应用潜力并讨论了其局限性.     

基于声学扫描振镜的超声/光声双模态成像技术

超声/光声双模态成像技术因其同时兼具超声的高分辨率结构成像和光声的高对比度功能成像优势,极大地推动了光声成像技术的临床应用推广.传统超声/光声双模态成像技术多基于超声成像所用阵列探头同时收集光声信号,系统结构紧凑且无需图像配准,操作便捷.但该类设备使用阵列探头和多通道数据采集,使得其成本较高;且成像结果易受通道一致性差异影响.本文提出了一种基于声学扫描振镜的超声/光声双模态成像技术,该技术采用单个超声换能器结合一维声学扫描振镜进行快速声束扫描,实现超声/光声双模态成像,是一种小型化、低成本的双模态快速成像技术.本文开展了系列仿体和活体成像研究,实验结果表明:系统有效成像范围为15.6 mm,超声和光声成像B扫描速度分别为1.0 s^–1和0.1 s^–1 (光声成像速度主要受制于脉冲激光器重复频率).基于本文所提技术研究,有助于进一步推动超声/光声双模态成像技术的临床转化和普及;也为基于超声信号检测的多模态成像技术提供了一种低成本、小型化和快速声信号检测的参考方案.     

Effective thermal conductivity of condensed polymeric nanofluids (nanosolids) controlled by diffusion and interfacial scattering

Thermal properties of polymeric nanosolids, obtained by condensing the corresponding nanofluids, are investigated using photothermal techniques. The heat transport properties of two sets of polyvinyl alcohol (PVA) based nanosolids, TiO₂/PVA and Cu/PVA, prepared by condensing the respective nanofluids, which are prepared by dispersing nanoparticles of TiO₂ and metallic copper in liquid PVA, are reported. Two photothermal techniques, the photoacoustic and the photopyroelectric techniques, have been employed for measuring thermal diffusivity, thermal conductivity and specific heat capacity of these nanosolids. The experimental results indicate that thermal conduction in these polymer composites is controlled by heat diffusion through the embedded particles and interfacial scattering at matrix–particle boundaries. These two mechanisms are combined to arrive at an expression for their effective thermal conductivity. Analysis of the results reveals the possibility to tune the thermal conductivity of such nanosolids over a wide range using the right types of nanoparticles and right concentration.     

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.     

Photothermal deflection microscopy for imaging sub-micronic defects in optical materials

Photothermal deflection is widely used to study defects in optical coatings and role of these defects in laser damage. Because defects responsible for laser damage are assumed to be nanometer-sized and lowly absorbing, both high spatial resolution and high sensitivity are required to detect them. In this work we theoretically and experimentally explore the capability of collinear photothermal deflection to give micronic resolution by reduction of the pump beam diameter. Thanks to a model describing temperature distribution and photothermal deflection, we have studied the effects of pump beam focusing on photothermal deflection. Then, we have developed a high resolution, high sensitivity microscope based on the photothermal deflection of a transmitted probe beam. The setup is characterized and the theoretical predictions are checked. We present a test of lateral spatial resolution obtained on specially prepared absorbing resolution targets and show that a lateral spatial resolution of 1 μm is reached on non-isolated defects. In case of single defects, we expect that 10 nm sized defects could be detected.     

IR spectral depth profiling using fourier transform photothermal beam deflection

FTIR photothermal beam-deflection spectroscopy (PBDS) was used to make spectral depth-profiling measurements with synthetic bilayer samples of polyethylene/nitrocellulose, with a commercial plastic having surface printing and with a single human hair. A Digilab interferometer modified to operate at several scan speeds was used to record the spectra, without the cell-resonance problems found with photoacoustic spectroscopy (PAS). The utility of spectral depth profiling is discussed; significant S/N improvements seem to be needed and, with either PBDS or PAS, a wider range of modulation frequencies is required for the methods to be useful.