Novel imaging system for positioning of the indocyanine green (ICG) target;visible projection of the near-infrared fluorescence image

Background: Even though NIR fluorescence imaging has many advantages in SLN mapping and cancer detection, NIR fluorescence imaging shows a serious drawback that NIR cannot be detected by the naked eye without any detectors. This limitation further disturbs accurate SLN detection and adequate tumor resection resulting in the presence of cancerous cells near the boundaries of surgically removed tissues. Materials and methods: To overcome the drawback of the conventional NIR imaging method, we suggest a novel NIR imaging system which can make the NIR fluorescence image visible to the naked eye as NIR fluorescence image detected by a video camera is processed by a computer and then projected back onto the NIR fluorescence excitation position with a projector using conspicuous color light. Image processing techniques were used for projection onto the exact position of the NIR fluorescence image. Also, we implemented a phantom experiment to evaluate the performance of the developed NIR fluorescence projection system by use of the ICG. Results: The developed NIR fluorescence projection system was applied in normal mouse model to confirm the usefulness of the system in the clinical field. A BALB/c nude mouse was prepared to be applied in normal mouse model and 0.25 mg/ml stock solution of the ICG was injected through a tail vein of the mouse. From the application in normal mouse model, we could confirm that the injected ICG stayed in the liver of the mouse and verify that the projection system projected the ICG fluorescence image at the exact location of the ICG by performing laparotomy of the mouse. Conclusions: From the application in normal mouse model, we could verify that the ICG fluorescence image was precisely projected back on the site where ICG fluorescence generated. It can be demonstrated that the NIR fluorescence projection system can make it possible to visualize the invisible NIR fluorescence image and to realize that SLN mapping and cancer detection in clinical surgery.

Near-Infrared Absorption Imaging and Processing Technologies Based on Gold Nanorods

Noble metal nanoparticles with localized surface plasmon resonance （LSPR） properties are widely used as optical sensors in biochemical detection and medical diagnosis. In this paper, we propose an effective determination method to measure the LSPR absorption intensity of gold nanorods （GNRs）. A near-infrared （NIR） imaging system is established, and an NIR absorption image of the multiple samples of the colloidal GNRs is captured. Then, the LSPR absorption intensities of these samples are obtained by calculating the average grayscale of the target areas based on the NIR image processing technology. By using this method, the LSPR absorption intensities of the multiple samples are determined all at once, and their accuracy is as high as that obtained by using spectrophotometry. These results suggest that this method is an efficient multi-channel determination technique with high-throughput sensing applications.

Rational design of biodegradable semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photodynamic therapy

Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of SPNs.In this study,we rationally designed a biodegradable SPN(BSPN50)for NIR-II fluorescence imaging-guided photodynamic therapy(PDT).BSPN50 is prepared by encapsulating a biodegradable SP(BSP50)with an amphiphilic copolymer F-127.BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole(DPP)segment and degradable poly(phenylenevinylene)(PPV)segment with the ratio of 50/50.BSPN50 has both satisfactory degradability under myeloperoxidase(MPO)/hydrogen peroxide(H_(2)O_(2))and NIR-II fluorescence emission upon 808 nm laser excitation.Furthermore,BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation.BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo.In addition,BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT.Thus,our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.

Preclinical characterization and validation of a dual-labeled trastuzumab-based imaging agent for diagnosing breast cancer

Objective： The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was to synthesize and optimize a dual-labeled trastuzumab-based imaging agent that can be used to validate an optical imaging agent with potential use in identifying tumor metastases in human epidermal growth factor receptor 2 （HER2） positive breast cancer patients. Methods： [111In]-DTPA-trastuzumab-IRDye 800 was synthesized by a three-step procedure. Purity, stability, immunoreactivity, internalization and biodistribution were explored in HER2＋ SKBR-3 cells. Biodistribution of [111In]-DTPA-trastuzumab-IRDye 800 was performed in a SKBR-3 xenograft model. Results： [111In]-DTPA-trastuzumab-IRDye 800 demonstrated high purity by both chemical and fluorometric determinations. Both flow cytometry and the Lindmo assay demonstrated a high binding affinity of [111In]-DTPA-trastuzumab-IRDye 800 to HER2-overexpressing cells. The dual-labeled conjugate was stable in PBS, but not in serum after 24 h at 37 ℃. Larger molecules （〉150 kD） were seen after a 24 h-incubation in human serum. Biodistribution studies revealed tumor-specific accumulation of [111In]-DTPA- trastuzumab-IRDye 800 in SKBR-3 tumors, and tumor uptakes at 24 and 48 h were （12.42±1.72）% and （9.96±1.05） %, respectively, following intravenous administration. The tumor-to-muscle ratio was 9.13±1.68 at 24 h, and increased to 12.79±2.13 at 48 h. Liver and kidney showed marked uptake of the dual-labeled imaging agent. Conclusions： [111In]-DTPA-trastuzumab-IRDye 800 is an effective diagnostic biomarker that can be used to validate dual-labeled, molecularly targeted imaging agents and can allow these agents to be translated into clinical practice for identifying HER2＋ lesions.

Applications of smartphone-based near-infrared(NIR)imaging,measurement,and spectroscopy technologies to point-of-care(POC)diagnostics

The role of point-of-care(POC)diagnostics is important in public health.With the support of smartphones,POC diagnostic technologies can be greatly improved.This opportunity has arisen from not only the large number and fast spread of cell-phones across the world but also their improved imaging/diagnostic functions.As a tool,the smartphone is regarded as part of a compact,portable,and low-cost system for real-time POC,even in areas with few resources.By combining near-infrared(NIR)imaging,measurement,and spectroscopy techniques,pathogens can be detected with high sensitivity.The whole process is rapid,accurate,and low-cost,and will set the future trend for POC diagnostics.In this review,the development of smartphone-based NIR fluorescent imaging technology was described,and the quality and potential of POC applications were discussed.

Hierarchically self-assembled fluorescent nanoparticles for near-infrared lysosome-targeted imaging

Manipulating emitting properties of fluorescent dyes plays a critical role in various fields such as light emitting materials, living cell imaging, and phototheranostics [1]. In particular, supramolecular strategies, such as complexation-induced quenching, aggregation-induced emission, have attracted ever-growing attention[2]. Near-infrared (NIR) probes have been demonstrated to possess

纤维红外吸收特性及其在皮棉杂质检测中的应用

皮棉异性纤维杂质检测技术是近几年来国内外研究的难点。为有效检测皮棉中与棉纤维外观极其相似的异性纤维杂质,提出了一种显微近红外成像方法用于检测皮棉中异性纤维。该方法将棉纤维与异性纤维在特定红外波段的吸收特性差别,转化为近红外光谱成像系统中两者的灰度、形态图像特征差别,通过显微光路对图像特征差别放大,利用图像分割技术将异性纤维目标分割出来。试验结果表明,采用显微近红外成像方法捕获的图像中,异性纤维灰度、形态特征明显,其检测结果与实际相符,此方法可有效识别皮棉中异性纤维杂质。

基于近红外波长成像的异物检测新方法(英文)

为有效检测出与背景形态、颜色极其相似的异物,根据异物与背景近红外吸收特性的差别,提出近红外光谱成像检测异物的方法.该方法分析近红外波段中异物与背景吸收特性差异随波长变化的规律,确定了区分背景与多种异物的最佳检测波段范围,建立近红外光谱成像系统,将近红外吸收特性差别转化为近红外图像中异物与背景的图像特征差别,利用自适应图像增强和二值化图像处理从背景中提取异物.实验结果表明,该方法获取的异物图像特征明显,检测结果与实际相符,此方法可有效检测与背景特征相似的异物.

Silica shell-assisted synthetic route for mono-disperse persistent nanophosphors with enhanced in vivo recharged near-infrared persistent luminescence

Near-infrared （NIR） persistent-luminescence nanoparticles have emerged as a new class of background-free contrast agents that are promising for in vivo imaging. The next key roadblock is to establish a robust and controllable method for synthesizing monodisperse nanoparticles with high luminescence brightness and long persistent duration. Herein, we report a synthesis strategy involving the coating/etching of the SiO2 shell to obtain a new class of small NIR highly persistent luminescent ZnGa2O4：Cr^3＋,Sn^4＋（ZGOCS） nanoparticles. The optimized ZGOCS nanoparticles have an excellent size distribution of -15 nm without any agglomeration and an NIR persistent luminescence that is enhanced by a factor of 13.5, owing to the key role of the SiO2 shell in preventing nanoparticle agglomeration after annealing. The ZGOCS nanoparticles have a signal-to-noise ratio -3 times higher than that of previously reported ZnGa204：Cr^3＋ （ZGC-1） nanoparticles as an NIR persistent-luminescence probe for in vivo bioimaging. Moreover, the persistent-luminescence signal from the ZGOCS nanoparticles can be repeatedly re-charged in situ with external excitation by a white light- emitting diode; thus, the nanopartides are suitable for long-term in vivo imaging applications. Our study suggests an improved strategy for fabricating novel high-performance optical nanoparticles with good biocompatibility.

A pinacol boronate caged NIAD-4 derivative as a near-infrared fluorescent probe for fast and selective detection of hypochlorous acid

Hypochlorous acid （HOCI） is one of highly reactive oxygen species （ROS）. It is involved in both immune defense against invading microbes and the progression of many diseases including cardiovascular disease and neurodegeneration disorders. It is generated from hydrogen peroxide （H2O2） and chloride ions in the presence of myeloperoxidase in activated neutrophils. To illustrate HOCI＇s biological functions, fluorescent probes, particularly those fluorescence emissions are in the near-infrared range, are highly needed for in vivo applications. Herein, we reported the design of a pinacol boronate caged near-infrared （NIR） fluorescent probe I derived from an Aft binding fluorophore NIAD-4 for fast and selective detection of HOC1/C10 over other ROS. Upon exposure to HOCI/CIO-, the pinacol boronate caging group of the probe 1 was quickly converted to electron-donating hydroxyl group, which increased intramolecular charge transfer OCT） in the excited state and resulted in the red-shift and intensity enhancement of fluorescence emission. The probe bears several unique features： （1） It could be used as either a ratiomatic or turn-on fluorescent probe; （2） Reaction of the caging group boronate with HOCI is very fast and finishes within seconds, which provides the selectivity over H2O2; （3） The NIAD-4 fluorophore provides additional selectivity for detection of HOCl over peroxynitrite. Moreover, the utility of the probe in imaging HOCllClO- was demonstrated in in vitro phantom imaging studies using mouse brain homogenate as biological relevant media.

In vivo tumor ultrasound-switchable fluorescence imaging via intravenous injections of size-controlled thermosensitive nanoparticles

Near-infrared fluorescence imaging has emerged as a noninvasive,inexpensive,and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy.In particular,ultrasound switchable fluorescence(USF)imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues.This study achieved the size control of polymer-based and indocyanine green(ICG)encapsulated USF contrast agents,capable of accumulating in the tumor after intravenous injections.These nanoprobes varied in size from 58 to 321 nm.The bioimaging profiles demonstrated that the proposed nanoparticles can efficiently eliminate the background light from normal tissue and show a tumor-specific fluorescence enhancement in the BxPC-3 tumor-bearing mice models possibly via the enhanced permeability and retention effect.In vivo tumor USF imaging further demonstrated that these nanoprobes can effectively be switched“ON”with enhanced fluorescence in response to a focused ultrasound stimulation in the tumor microenvironment,contributing to the high-resolution USF images.Therefore,our findings suggest that ICG-encapsulated nanoparticles are good candidates for USF imaging of tumors in live animals,indicating their great potential in optical tumor imaging in deep tissue.

NON-INVASIVE MEASUREMENT OF DEEP TISSUE TEMPERATURE CHANGES CAUSED BY APOPTOSIS DURING BREAST CANCER NEOADJUVANT CHEMOTHERAPY:A CASE STUDY

Treatment-induced apoptosis of cancer cells is one goal of cancer therapy.Interestingly,more heat is generated by mitochondria during apoptosis,especially the uncoupled apoptotic state,^(1,2) compared to the resting state.In this case study,we explore these thermal effects by longitudinally measuring temperature variations in a breast lesion of a pathological complete responder during neoadjuvant chemotherapy(NAC).Diffuse Optical Spectroscopic Imaging(DOSI)was employed to derive absolute deep tissue temperature using subtle spectral features of the water peak at 975 nm.^(3)A significant temperature increase was observed in time windows during the anthracycline and cyclophosphamide(AC)regimen but not in the paclitaxel and bevacizumab regimen.Hemoglobin concentration changes generally did not follow temperature,suggesting the measured temperature increases were likely due to mitochondrial uncoupling rather than a direct vascular effect.A simultaneous increase of tissue oxygen saturation with temperature was observed,suggesting that oxidative stress also contributes to apoptosis.Although preliminary,this study indicates longitudinal DOSI tissue temperature monitoring provides information that can improve our understanding of the mechanisms of tissue response during NAC.

具有NIR-Ⅱ吸收的碳包覆磁铁矿纳米团簇用于成像引导的光热-化学动力学协同治疗

化学动力学疗法(CDT)是基于磁铁矿纳米酶治疗癌症的新兴治疗方式.但是,它的低催化能力和单模治疗限制了其治疗功效.本工作中,我们开发了一种在第二近红外(NIR-Ⅱ)窗口中具有高吸光度的碳涂覆的磁铁矿纳米团簇(CCMNCs),用于NIR-Ⅱ光热增强的化学动力抗癌疗法.这种尺寸约58 nm的CCMNCs通过使用二茂铁作为单一前体的一步溶剂热法合成.CCMNCs不仅用作肿瘤靶向磁共振成像的造影剂,而且还吸收并将NIR-Ⅱ辐射转化为局部热量,用于高温杀死癌细胞.CCMNCs在酸溶液中产生的亚铁离子和铁离子催化Fenton反应生成CDT的羟基自由基(·OH),并减少作为自由基清除剂的细胞内谷胱甘肽.本文报道的CCMNCs通过组合的化学动力学光热处理的协同效应显示出优异的治疗功效.

Tumor microenvironment-responsive modular integrated nanocomposites for magnetically targeted and photothermal enhanced catalytic therapy

Achieving efficient integration of cancer diagnosis and therapy is of great significance to human health,but the construction of a multifunctional intelligent therapy system still faces great challenges.In this study,we report an integrated multifunctional nanocomposite constructed by a simple modular assembly technology.The nanocomposites are composed of three different nanomaterials:Fe_(3)O_(4),Au,and NaErF_(4):0.5%Tm@NaYF_(4)upconversion nanoparticles(UCNPs).In this design,Fe_(3)O_(4)nanoparticles have nanozyme effect of peroxidase-like activity,which can react with H_(2)O_(2)in the tumor microenvironment to generate hydroxyl radicals.Because of its magnetic properties,it can help the nanocomposites to aggregate under the induction of magnetic fields.Au nanoparticles exhibit nanozyme effect of glucose oxidase-like activity.It can catalyze the conversion of glucose to gluconic acid and H_(2)O_(2).Ingeniously,the generated H_(2)O_(2)provides a source of reactants for the reaction of the Fe_(3)O_(4)nanozyme.In addition,the photothermal effect of Au nanoparticles under 808 nm irradiation further enhanced the nanozyme activity of Fe_(3)O_(4)and Au nanoparticles.Besides,UCNPs can emit near-infrared(NIR)-II fluorescence under 808 nm irradiation,which can provide imaging-guided during cancer treatment.Then,the nanocomposites were further modified by poly(vinylpyrrolidone)(PVP)to obtain UCNPs/Au/Fe_(3)O_(4)-PVP with good biocompatibility and high-efficiency cancer treatment ability.

Engineering the inter-island plasmonic coupling in homometallic Au-Au_(n)core-satellite structures

We show that through strong ligand mediated interfacial energy control between Au seeds and the deposited Au,the non-wetting growth of Au on Au seeds led to the formation homometallic core-satellite nanostructures.To modulate the intraparticle plasmonic coupling between the core and the satellites,the number and size of the Au satellites,and their inter-island distances were continuously tuned by varying the growth kinetics.As a result of the precise structural control,the plasmonic absorptions of the core-satellite nanostructures were tuned from visible to near-infrared(NIR)spectral range,and the extent of spectral modulation(500-1300 nm)is among the best of the literature methods.This synthetic advance enriches the toolbox for nanosynthesis and points to a new direction in the exploration of sophisticated functional designs.