Peptide-conjugated polymeric micellar nanoparticles for Dual SPECT and optical imaging of EphB4 receptors in prostate cancer xenografts

EphB4, a member of the largest family of receptor tyrosine kinases, is overexpressed in numerous tumors. In this study, we developed a new class of multimodal nanoplatform for dual single photon emission computed tomography (SPECT) and near-infrared fluorescence imaging of EphB4. EphB4-binding peptide TNYL-FSPNGPIARAW (TNYL-RAW) was conjugated to polyethylene glycol-coated, core-crosslinked polymeric micelles (CCPM) dually labeled with near-infrared fluorescence fluorophores (Cy7) and a radioisotope (indium 111). In vitro, TNYL-RAW-CCPM selectively bound to EphB4-positive PC-3M prostate cancer cells, but not to EphB4-negative A549 lung cancer cells. In vivo, PC-3M tumors were clearly visualized by both SPECT and near-infrared fluorescence tomography after intravenous administration of (111)In-labeled TNYL-RAW-CCPM. In contrast, there was little signal in A549 tumors of mice injected with (111)In-labeled TNYL-RAW-CCPM or in PC-3M tumors of mice injected with (111)In-labeled CCPM. The high accumulation of (111)In-labeled TNYL-RAW-CCPM in PC-3M tumor could be significantly reduced after co-injection with an excess amount of TNYL-RAW peptide. Immunohistochemical analysis showed that fluorescence signal from the nanoparticles correlated with their radioactivity count, and co-localized with the EphB4 expressing region. (111)In-labeled TNYL-RAW-CCPM allowed visualization of cancer cells overexpressing EphB4 by both nuclear and optical techniques. The complementary information acquired with multiple imaging techniques should be advantageous in early detection of cancer.     

应用于生物组织的光学成像技术及国内可实施技术探讨

本文介绍了应用近红外或远红外光对高散射介质及生物组织中物体（肿瘤）进行光学成像的原理和目前主要采用的研究技术。对几种主要光学成像技术,时间分辨法、光学相干层析、应用光折变晶体的相干层析等技术的实验原理和设备进行分析比较,进一步探讨低成本可实施技术及可开展的有关研究。     

Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer

We have investigated the application of near-infrared (NIR) fiber-optic spectroscopy for the diagnosis of pancreatic cancer. Cluster analysis of the Fourier transformed near-infrared (FTNIR) fiber-optic spectra of surgically resected pancreatic tumor tissues allowed discrimination of tumor from normal tissue with high sensitivity and specificity. The sensitivity of the method using spectral information of the CH stretching first overtone region (5951-5608 cm(-1)) was 83.3% with a specificity of 83.3%. Based on the CH stretching second overtone region (8605-7938 cm(-1)) we could achieve a sensitivity of 88.9% and specificity of 72.2%. These findings suggest that NIR spectroscopy offers the potential for minimally invasive in-vivo diagnosis of pancreatic cancer.     

超声显像技术对乳腺癌新辅助化疗后病理反应性的预测作用

探讨不同超声显像技术在预测乳腺癌新辅助化疗(neoadjuvant chemotherapy,NAC)病理反应性方面的研究进展。目前用于预测NAC病理反应性的超声技术有二维灰阶超声、多普勒超声、超声造影、弹性成像、近红外光谱及光散射成像。超声可通过上述不同的技术模式从肿物形态、血流、硬度、及氧含量等不同方面对乳腺癌的生物学特性进行评估,进而对NAC后病理反应性进行预测,其在该领域应用前景广阔。     

A spectroscopic approach to imaging and quantification of cartilage lesions in human knee joints

We have previously described a technology based on diffuse reflectance of broadband light for measuring joint articular cartilage thickness, utilizing that optical absorption is different in cartilage and subchondral bone. This study is the first evaluation of the technology in human material. We also investigated the prospects of cartilage lesion imaging, with the specific aim of arthroscopic integration. Cartilage thickness was studied ex vivo in a number of sites (n = 87) on human knee joint condyles, removed from nine patients during total knee replacement surgery. A reflectance spectrum was taken at each site and the cartilage thickness was estimated using the blue, green, red and near-infrared regions of the spectrum, respectively. Estimated values were compared with reference cartilage thickness values (taken after sample slicing) using an exponential model. Two-dimensional Monte Carlo simulations were performed in a theoretical analysis of the experimental results. The reference cartilage thickness of the investigated sites was 1.60 ± 1.30 mm (mean ± SD) in the range 0-4.2 mm. Highest correlation coefficients were seen for the calculations based on the near-infrared region after normalization to the red region (r = 0.86) and for the green region (r = 0.80).     

Removing the heart from the brain: Compensation for the pulse artifact in the photon migration signal

Various factors, including variations in the concentration of hemoglobin, determine changes in the transparency of living tissue to near-infrared light. Hence, optical measures have been proposed as a noninvasive method for investigating regional changes in brain activity. However, the amount of near-infrared light traversing a region of the head is also influenced by the periodic changes in blood pressure that occur during the cardiac cycle (pulse). These large changes may obscure smaller, localized events associated with brain activity. We developed a least-squares regression algorithm for compensating for the artifact introduced by the pulse. This procedure takes into account beat-to-beat variability in heart rate and differences in the shape of the pulse among subjects and among recording conditions.     

The development of terahertz sources and their applications

The terahertz region of the electromagnetic spectrum spans the frequency range between the mid-infrared and the millimetre/microwave. This region has not been exploited fully to date owing to the limited number of suitable (in particular, coherent) radiation sources and detectors. Recent demonstrations, using pulsed near-infrared femtosecond laser systems, of the viability of THz medical imaging and spectroscopy have sparked international interest; yet much research still needs to be undertaken to optimize both the power and bandwidth in such THz systems. In this paper, we review how femtosecond near-infrared laser pulses can be converted into broad band THz radiation using semiconductor crystals, and discuss in depth the optimization of one specific generation mechanism based on ultra-fast transport of electrons and holes at a semiconductor surface. We also outline a few of the opportunities for a technology that can address a diverse range of challenges spanning the physical and biological sciences, and note the continuing need for the development of solid state, continuous wave, THz sources which operate at room temperature.     

硫化铅量子点辅助近红外二区荧光成像技术在活体应用中的研究进展

近红外二区（NIR-Ⅱ, 900～1 700 nm）的光相较于传统可见光（400～700 nm）和近红外一区（NIR-Ⅰ, 700～900 nm）的光,波长更长,生物组织内传播时散射更小。因此,NIR-II荧光成像技术在活体生物组织内具有深层穿透能力和高时空分辨率成像等优点。发射NIR-II荧光的纳米探针备受研究者们的关注,其中硫化铅（PbS）量子点凭借尺寸可调、波段可调、易被修饰和量子产率高等优势成为生物医学活体成像的研究热点,如心脑血管和肿瘤等多种疾病的动物造影实验。本文介绍PbS量子点的荧光特性和合成方法,概述NIR-II窗口下PbS量子点基于多种物质的修饰,在胃肠道、血管、肿瘤、淋巴结等生物活体组织内荧光成像的应用,为探索该成像模式下未来发展潜力做铺垫。     

Near-infrared autofluorescence for the detection of parathyroid glands

A major challenge in endocrine surgery is the intraoperative detection of parathyroid glands during both thyroidectomies and parathyroidectomies. Current localization techniques such as ultrasound and sestamibi scan are mostly preoperative and rely on an abnormal parathyroid for its detection. In this paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real-time, automated in vivo method for the detection of the parathyroid gland. A pilot in vivo study was conducted to assess the ability of NIR fluorescence to identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence measurements at 785 nm excitation were obtained intra-operatively from the different tissues exposed in the neck region in 21 patients undergoing endocrine surgery. The fluorescence intensity of the parathyroid gland was found to be consistently greater than that of the thyroid and all other tissues in the neck of all patients. In particular, parathyroid fluorescence was two to eleven times higher than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm. These results indicate that NIR fluorescence has the potential to be an excellent optical tool to locate parathyroid tissue during surgery.     

A multimodal nano agent for image-guided cancer surgery

Intraoperative imaging technologies including computed tomography and fluorescence optical imaging are becoming routine tools in the cancer surgery operating room. They constitute an enabling platform for high performance surgical resections that assure local control while minimizing morbidity. New contrast agents that can increase the sensitivity and visualization power of existing intraoperative imaging techniques will further enhance their clinical benefit. We report here the development, detection and visualization of a dual-modality computed tomography and near-infrared fluorescence nano liposomal agent (CF800) in multiple preclinical animal models of cancer. We describe the successful application of this agent for combined preoperative computed tomography based three-dimensional surgical planning and intraoperative target mapping (>200 Hounsfield Units enhancement), as well as near-infrared fluorescence guided resection (>5-fold tumor-to-background ratio). These results strongly support the clinical advancement of this agent for image-guided surgery with potential to improve lesion localization, margin delineation and metastatic lymph node detection.     

Transillumination imaging performance: spatial resolution simulation studies

Monte Carlo calculations were used to simulate the propagation of visible and near-infrared light through homogenous tissue in order to quantitate the potential spatial resolution performance for transillumination imaging. Specifically, the relative effectiveness of coaxial collimation and time of flight (TOF) detection for improving spatial resolution was investigated. The results demonstrate that significant improvements in spatial resolution can be achieved through these techniques, with TOF methods offering superior performance for a given level of detected signal intensity.     

Recent advances in diffuse optical imaging

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.     

Gd3+ complex-modified NaLuF4-based upconversion nanophosphors for trimodality imaging of NIR-to-NIR upconversion luminescence, X-Ray computed tomography and magnetic resonance

Multimodality molecular imaging has recently attracted much attention, because it can take advantage of individual imaging modalities by fusing together information from several molecular imaging techniques. Herein, we report a multifunctional lanthanide-based nanoparticle for near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence (UCL), X-ray computed tomography (CT) and T(1)-enhanced magnetic resonance (MR) trimodality in-vivo imaging. By careful selection of the lanthanide elements, core-shell structured lanthanide-based nanoparticles, NaLuF(4):Yb(3+),Tm(3+)@SiO(2)-GdDTPA nanoparticles (UCNP@SiO(2)-GdDTPA) have been designed and synthesized. We also prove that the application of UCNP@SiO(2)-GdDTPA for NIR-to-NIR UCL, CT and MRI multi-modality in-vivo imaging can be established successfully. In addition, the biological toxicity of UCNP@SiO(2)-GdDTPA is evaluated by the methyl thiazolyl tetrazolium (MTT) assay and histological analysis of viscera sections.     

基于粒子群和反向传播神经网络的近红外光无创血糖检测方法研究EI北大核心CSCD

现有的近红外无创血糖检测模型研究大多数关注的是近红外吸光度与血糖浓度之间的关系,但没有考虑人体生理状态对血糖浓度的影响。为了提升血糖预测模型性能,本文采用了粒子群优化算法(PSO)对反向传播(BP)神经网络的结构参数进行训练,并引入了收缩压、脉率、体温以及1550 nm吸光度作为血糖浓度预测模型的输入变量,采用BP神经网络作为预测模型。为解决传统BP神经网络容易陷入局部最优的问题,本文提出了一种基于PSO-BP的混合模型。结果表明,训练得到的PSO-BP模型预测效果优于传统的BP神经网络。十折交叉验证预测均方根误差和相关系数分别为0.95 mmol/L和0.74;克拉克误差网格分析结果表明,模型预测结果落入A区域的比例为84.39%,落入B区域的比例为15.61%,均满足临床要求。该模型可以快速地测量血糖浓度,且具相对较高的精度。     

Imagerie médicale: les techniques photoniques

Optical techniques are a new, non invasive method which provides an efficient means of vizualizing soft tissue. They are gradually being integrated into clinical practice, and have the advantage of being simple to use and also allowing any number of investigations to be made without risk. Unlike X-ray, optical techniques are not harmful to the organism. There are three basic ways in which these new techniques can be utilized: i) transillumination imaging, principally used for near-infrared mammography; ii) fluorescence imaging, which can be used for the early detection of tumors, since endogenous or exogenous fluorophores are tissue-specific; and iii) optical coherence tomography (OCT), which provides microscopic tomographic section imaging of biological tissue and subsurface imaging with high spatial 3-D resolution. However, due to its high absorption by biological tissue this method cannot on its own replace existing techniques. It is thus considered as a useful complement to current imaging methods.     

Refractive index of carcinogen-induced rat mammary tumours

Near-infrared optical techniques for clinical breast cancer screening in humans are rapidly advancing. Based on the computational inversion of the photon diffusion process through the breast, these techniques rely on optical tissue models for accurate image reconstruction. Recent interest has surfaced regarding the effect of refractive index variations on these reconstructions. Although many data exist regarding the scattering and absorption properties of normal and diseased tissue, no measurements of refractive index appear in the literature. In this paper, we present near-infrared refractive index data acquired from N-methyl-N-nitrosourea-induced rat mammary tumours, which are similar in pathology and disease progression to human ductal carcinoma. Eight animals, including one control, were employed in this study, yielding data from 32 tumours as well as adjacent adipose and connective tissues.     

Localization of fluorescence spots with space-space MUSIC for mammographylike measurement systems

Breast cancer diagnosis may be improved by optical fluorescence imaging techniques in the near-infrared wavelength range. We have shown that the recently proposed space-space MUSIC (multiple signal classification) algorithm allows the 3-D localization of focal fluorophore-tagged lesions in a turbid medium from 2-D fluorescence data obtained from laser excitations at different positions. The data are assumed to be measured with two parallel planar sensor arrays on the top and bottom of the medium. The laser sources are integrated at different positions in one of the planes. The space-space data are arranged into an MxN matrix (M, number of sensors; N, number of excitation sources). A singular-value decomposition (SVD) of this matrix yields the detectable number of spot regions with linearly independent behavior with respect to the laser excitation positions and thus allows definition of a signal subspace. Matches between this signal subspace and data from model spots are tested at scanned points in a model medium viewed as the breast region under study. The locations of best matches are then considered the centers of gravity of focal lesions. The optical model used was unbounded and optically homogeneous. Nevertheless, simulated spots in bounded, inhomogeneous media modeling the breast could be localized accurately.     

量子点探针辅助的近红外荧光成像技术在肿瘤显影中的应用

肿瘤早期检测是精准并高效诊疗癌症的关键因素。荧光成像技术凭借其高灵敏度、高时空分辨率、无电离辐射和无创实时成像等优点,在生物医学领域,尤其在肿瘤检测方面展现出了广泛的应用前景。近红外光穿过生物组织时,受到的吸收和散射较少,因此在生物成像方面体现了高信噪比和强组织穿透能力。在众多荧光探针中,近红外发光的量子点探针因其量子产率高、抗光漂白性强、发射光可调和稳定性良好等特点在荧光成像方面显示出突出的优势。本文基于量子点探针的近红外荧光成像技术在肿瘤显影中的应用,介绍了量子点优异的光学性能,并重点讨论了硫化铅（PbS）和硫化银（Ag2S）近红外发光量子点探针在肿瘤成像方面的研究进展,并对近红外发光量子点探针的应用前景进行了展望。     

In vivo manipulation of fluorescently labeled organelles in living cells by multiphoton excitation

Femtosecond laser pulses in the near-infrared region have potential applications in the imaging and manipulation of intracellular organelles. We report on the manipulation of intracellular organelles by two-photon excitation. The dynamics of green fluorescent protein (GFP)-histone are investigated by two-photon fluorescence recovery after photobleaching (FRAP). Intracellular ablation of fluorescently labeled organelles in living cells is performed by focusing femtosecond laser pulses. We report on the selective marking of individual organelles by using two-photon conversion of a photoconvertible fluorescent protein.     

用于疼痛感知与评估的功能性近红外光谱成像研究进展

疼痛是一种涉及感觉、运动和认知的复杂体验。传统的疼痛评估方法有主观偏倚性较强的特点,但激发了人们对客观疼痛评估成像技术的兴趣。研究表明,在体时大脑痛觉可被定量评估,其中的功能性近红外光谱(fNIRS)技术,因其具有时间分辨率高、成本低、便携等特点,及其可在复杂临床环境中可实时观测疼痛的优势,已被疼痛研究所关注。为了进一步揭示疼痛在临床环境中的潜在皮质作用机制,以构建优化的实验范式设计为基础,综述了与疼痛相关的脑部区域、fNIRS探针定位和数据处理算法的研究进展,特别是现有fNIRS技术在疼痛研究中的主要发现;探讨fNIRS成像与人工智能算法相结合用于疼痛研究和客观评估的相关进展,并对未来发展方向和尚待优化的问题提出建议。