A novel paramagnetic substrate for detecting myeloperoxidase activity in vivo.

PubMed

Shazeeb, Mohammed S; Xie, Yang; Gupta, Suresh; Bogdanov, Alexei A

2012-01-01

Bis-phenylamides and bis-hydroxyindolamides of diethylenetriaminepentaacetic acid-gadolinium (DTPA(Gd)) are paramagnetic reducing substrates of peroxidases that enable molecular imaging of peroxidase activity in vivo. Specifically, gadolinium chelates of bis-5-hydroxytryptamide-DTPA (bis-5HT-DTPA(Gd)) have been used to image localized inflammation in animal models by detecting neutrophil-derived myeloperoxidase (MPO) activity at the inflammation site. However, in other preclinical disease models, bis-5HT-DTPA(Gd) presents technical challenges due to its limited solubility in vivo. Here we report a novel MPO-sensing probe obtained by replacing the reducing substrate serotonin (5-HT) with 5-hydroxytryptophan (HTrp). Characterization of the resulting probe (bis-HTrp-DTPA(Gd)) in vitro using nuclear magnetic resonance spectroscopy and enzyme kinetic analysis showed that bis-HTrp-DTPA(Gd) (1) improves solubility in water; (2) acts as a substrate for both horseradish peroxidase and MPO enzymes; (3) induces cross-linking of proteins in the presence of MPO; (4) produces oxidation products, which bind to plasma proteins; and (5) unlike bis-5HT-DTPA(Gd), does not follow first-order reaction kinetics. In vivo magnetic resonance imaging (MRI) in mice demonstrated that bis-HTrp-DTPA(Gd) was retained for up to 5 days in MPO-containing sites and cleared faster than bis-5HT-DTPA(Gd) from MPO-negative sites. Bis-HTrp-DTPA(Gd) should offer improvements for MRI of MPO-mediated inflammation in vivo, especially in high-field MRI, which requires a higher dose of contrast agent.

Targeted Endoscopic Imaging

PubMed Central

Li, Meng; Wang, Thomas D

2011-01-01

Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

Flash trajectory imaging of target 3D motion

NASA Astrophysics Data System (ADS)

Wang, Xinwei; Zhou, Yan; Fan, Songtao; He, Jun; Liu, Yuliang

2011-03-01

We present a flash trajectory imaging technique which can directly obtain target trajectory and realize non-contact measurement of motion parameters by range-gated imaging and time delay integration. Range-gated imaging gives the range of targets and realizes silhouette detection which can directly extract targets from complex background and decrease the complexity of moving target image processing. Time delay integration increases information of one single frame of image so that one can directly gain the moving trajectory. In this paper, we have studied the algorithm about flash trajectory imaging and performed initial experiments which successfully obtained the trajectory of a falling badminton. Our research demonstrates that flash trajectory imaging is an effective approach to imaging target trajectory and can give motion parameters of moving targets.

A Sensitive TLRH Targeted Imaging Technique for Ultrasonic Molecular Imaging

PubMed Central

Hu, Xiaowen; Zheng, Hairong; Kruse, Dustin E.; Sutcliffe, Patrick; Stephens, Douglas N.; Ferrara, Katherine W.

2010-01-01

The primary goals of ultrasound molecular imaging are the detection and imaging of ultrasound contrast agents (microbubbles), which are bound to specific vascular surface receptors. Imaging methods that can sensitively and selectively detect and distinguish bound microbubbles from freely circulating microbubbles (free microbubbles) and surrounding tissue are critically important for the practical application of ultrasound contrast molecular imaging. Microbubbles excited by low frequency acoustic pulses emit wide-band echoes with a bandwidth extending beyond 20 MHz; we refer to this technique as TLRH (transmission at a low frequency and reception at a high frequency). Using this wideband, transient echo, we have developed and implemented a targeted imaging technique incorporating a multi-frequency co-linear array and the Siemens Antares® imaging system. The multi-frequency co-linear array integrates a center 5.4 MHz array, used to receive echoes and produce radiation force, and two outer 1.5 MHz arrays used to transmit low frequency incident pulses. The targeted imaging technique makes use of an acoustic radiation force sub-sequence to enhance accumulation and a TLRH imaging sub-sequence to detect bound microbubbles. The radiofrequency (RF) data obtained from the TLRH imaging sub-sequence are processsed to separate echo signatures between tissue, free microbubbles, and bound microbubbles. By imaging biotin-coated microbubbles targeted to avidin-coated cellulose tubes, we demonstrate that the proposed method has a high contrast-to-tissue ratio (up to 34 dB) and a high sensitivity to bound microbubbles (with the ratio of echoes from bound microbubbles versus free microbubbles extending up to 23 dB). The effects of the imaging pulse acoustic pressure, the radiation force sub-sequence and the use of various slow-time filters on the targeted imaging quality are studied. The TLRH targeted imaging method is demonstrated in this study to provide sensitive and selective

Target detection method by airborne and spaceborne images fusion based on past images

NASA Astrophysics Data System (ADS)

Chen, Shanjing; Kang, Qing; Wang, Zhenggang; Shen, ZhiQiang; Pu, Huan; Han, Hao; Gu, Zhongzheng

2017-11-01

To solve the problem that remote sensing target detection method has low utilization rate of past remote sensing data on target area, and can not recognize camouflage target accurately, a target detection method by airborne and spaceborne images fusion based on past images is proposed in this paper. The target area's past of space remote sensing image is taken as background. The airborne and spaceborne remote sensing data is fused and target feature is extracted by the means of airborne and spaceborne images registration, target change feature extraction, background noise suppression and artificial target feature extraction based on real-time aerial optical remote sensing image. Finally, the support vector machine is used to detect and recognize the target on feature fusion data. The experimental results have established that the proposed method combines the target area change feature of airborne and spaceborne remote sensing images with target detection algorithm, and obtains fine detection and recognition effect on camouflage and non-camouflage targets.

Leptin protects vital organ functions after sepsis through recovering tissue myeloperoxidase activity: an anti-inflammatory role resonating with indomethacin.

PubMed

Lin, Ji; Yan, Guang-Tao; Xue, Hui; Hao, Xiu-Hua; Zhang, Kai; Wang, Lu-Huan

2007-08-01

In this research, the role of leptin on sepsis-induced organ dysfunction was evaluated. Making use of a mice sepsis model, changes of alanine transaminase and uric acid in serum, myeloperoxidase activity, leptin levels and histological alterations in heart, lung, liver and kidney were determined. Results showed that sepsis induced significantly higher levels of serum alanine transaminase and uric acid, decreased tissue myeloperoxidase activity and leptin levels, and triggered distinct histological alterations. However, leptin and indomethacin injections reversed those impairments at 6h and/or 12h after injury. These data reveal a protective role of both leptin and indomethacin on vital organ functions after sepsis by recovering tissue myeloperoxidase activity.

Fluorescent imaging of cancerous tissues for targeted surgery

PubMed Central

Bu, Lihong; Shen, Baozhong; Cheng, Zhen

2014-01-01

To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

Targeted Nuclear Imaging Probes for Cardiac Amyloidosis.

PubMed

Bravo, Paco E; Dorbala, Sharmila

2017-07-01

The aim of the present manuscript is to review the latest advancements of radionuclide molecular imaging in the diagnosis and prognosis of individuals with cardiac amyloidosis. 99m Technetium labeled bone tracer scintigraphy had been known to image cardiac amyloidosis, since the 1980s; over the past decade, bone scintigraphy has been revived specifically to diagnose transthyretin cardiac amyloidosis. 18 F labeled and 11 C labeled amyloid binding radiotracers developed for imaging Alzheimer's disease, have been repurposed since 2013, to image light chain and transthyretin cardiac amyloidosis. 99m Technetium bone scintigraphy for transthyretin cardiac amyloidosis, and amyloid binding targeted PET imaging for light chain and transthyretin cardiac amyloidosis, are emerging as highly accurate methods. Targeted radionuclide imaging may soon replace endomyocardial biopsy in the evaluation of patients with suspected cardiac amyloidosis. Further research is warranted on the role of targeted imaging to quantify cardiac amyloidosis and to guide therapy.

Clean image synthesis and target numerical marching for optical imaging with backscattering light

PubMed Central

Pu, Yang; Wang, Wubao

2011-01-01

Scanning backscattering imaging and independent component analysis (ICA) are used to probe targets hidden in the subsurface of a turbid medium. A new correction procedure is proposed and used to synthesize a “clean” image of a homogeneous host medium numerically from a set of raster-scanned “dirty” backscattering images of the medium with embedded targets. The independent intensity distributions on the surface of the medium corresponding to individual targets are then unmixed using ICA of the difference between the set of dirty images and the clean image. The target positions are localized by a novel analytical method, which marches the target to the surface of the turbid medium until a match with the retrieved independent component is accomplished. The unknown surface property of the turbid medium is automatically accounted for by this method. Employing clean image synthesis and target numerical marching, three-dimensional (3D) localization of objects embedded inside a turbid medium using independent component analysis in a backscattering geometry is demonstrated for the first time, using as an example, imaging a small piece of cancerous prostate tissue embedded in a host consisting of normal prostate tissue. PMID:21483608

Effects of Resolution, Range, and Image Contrast on Target Acquisition Performance.

PubMed

Hollands, Justin G; Terhaar, Phil; Pavlovic, Nada J

2018-05-01

We sought to determine the joint influence of resolution, target range, and image contrast on the detection and identification of targets in simulated naturalistic scenes. Resolution requirements for target acquisition have been developed based on threshold values obtained using imaging systems, when target range was fixed, and image characteristics were determined by the system. Subsequent work has examined the influence of factors like target range and image contrast on target acquisition. We varied the resolution and contrast of static images in two experiments. Participants (soldiers) decided whether a human target was located in the scene (detection task) or whether a target was friendly or hostile (identification task). Target range was also varied (50-400 m). In Experiment 1, 30 participants saw color images with a single target exemplar. In Experiment 2, another 30 participants saw monochrome images containing different target exemplars. The effects of target range and image contrast were qualitatively different above and below 6 pixels per meter of target for both tasks in both experiments. Target detection and identification performance were a joint function of image resolution, range, and contrast for both color and monochrome images. The beneficial effects of increasing resolution for target acquisition performance are greater for closer (larger) targets.

Biosynthesis of human myeloperoxidase.

PubMed

Nauseef, William M

2018-03-15

Members of Chordata peroxidase subfamily [1] expressed in mammals, including myeloperoxidase (MPO), eosinophil peroxidase (EPO), lactoperoxidase (LPO), and thyroid peroxidase (TPO), express conserved motifs around the heme prosthetic group essential for their activity, a calcium-binding site, and at least two covalent bonds linking the heme group to the protein backbone. Although most studies of the biosynthesis of these peroxidases have focused on MPO, many of the features described occur during biosynthesis of other members of the protein subfamily. Whereas MPO biosynthesis includes events typical for proteins generated in the secretory pathway, the importance and consequences of heme insertion are events uniquely associated with peroxidases. This Review summarizes decades of work elucidating specific steps in the biosynthetic pathway of human MPO. Discussion includes cotranslational glycosylation and subsequent modifications of the N-linked carbohydrate sidechains, contributions by molecular chaperones in the endoplasmic reticulum, cleavage of the propeptide from proMPO, and proteolytic processing of protomers and dimerization to yield mature MPO. Parallels between the biosynthesis of MPO and TPO as well as the impact of inherited mutations in the MPO gene on normal biosynthesis will be summarized. Lastly, specific gaps in our knowledge revealed by this review of our current understanding will be highlighted. Copyright © 2018 Elsevier Inc. All rights reserved.

Space-based infrared sensors of space target imaging effect analysis

NASA Astrophysics Data System (ADS)

Dai, Huayu; Zhang, Yasheng; Zhou, Haijun; Zhao, Shuang

2018-02-01

Target identification problem is one of the core problem of ballistic missile defense system, infrared imaging simulation is an important means of target detection and recognition. This paper first established the space-based infrared sensors ballistic target imaging model of point source on the planet's atmosphere; then from two aspects of space-based sensors camera parameters and target characteristics simulated atmosphere ballistic target of infrared imaging effect, analyzed the camera line of sight jitter, camera system noise and different imaging effects of wave on the target.

Imaging of polarized target in underwater environment

NASA Astrophysics Data System (ADS)

Carrizo, Carlos; Foster, Robert; El-Habashi, Ahmed; Gray, Deric; Gilerson, Alex

2017-10-01

Imaging of underwater targets is challenging because of the significant attenuation of the propagating light field due to the absorption and scattering by water and suspended/dissolved matter. Some living and manmade objects in water have surfaces which partially polarize the light, whose properties can be used to camouflage or, conversely, to detect such objects. The attenuation of light by the intervening water (so-called veiling light) changes both the intensity and polarization characteristics at each pixel of the image, but does not contain any information about the target and contributes to image degradation and blurring. Its properties need to be understood in order to isolate the true optical signature of the target. The main goal of this study is to retrieve the polarization characteristics of the target from the image in different water environmental and illumination conditions by taking into account coincidentally measured inherent water optical properties (IOPs) during recent field campaigns outside the Chesapeake Bay and in New York Bight. Data, in the form of images and videos, were acquired using a green-band full-Stokes polarimetric video camera. Analysis of the acquired images show reasonable agreement in Stokes vector components with the measurements by the underwater polarimeter and modeled polarized signals. In addition, Stokes vector components of the veiling light were also estimated and compared with the models. Finally, retrieval of the attenuation coefficient for the light from the target is attempted from the measurements and compared with the results of the independent measurements of IOPs.

Audible sonar images generated with proprioception for target analysis.

PubMed

Kuc, Roman B

2017-05-01

Some blind humans have demonstrated the ability to detect and classify objects with echolocation using palatal clicks. An audible-sonar robot mimics human click emissions, binaural hearing, and head movements to extract interaural time and level differences from target echoes. Targets of various complexity are examined by transverse displacements of the sonar and by target pose rotations that model movements performed by the blind. Controlled sonar movements executed by the robot provide data that model proprioception information available to blind humans for examining targets from various aspects. The audible sonar uses this sonar location and orientation information to form two-dimensional target images that are similar to medical diagnostic ultrasound tomograms. Simple targets, such as single round and square posts, produce distinguishable and recognizable images. More complex targets configured with several simple objects generate diffraction effects and multiple reflections that produce image artifacts. The presentation illustrates the capabilities and limitations of target classification from audible sonar images.

Target identification by image analysis.

PubMed

Fetz, V; Prochnow, H; Brönstrup, M; Sasse, F

2016-05-04

Covering: 1997 to the end of 2015Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches.

Stroma Targeting Nuclear Imaging and Radiopharmaceuticals

PubMed Central

Shetty, Dinesh; Jeong, Jae-Min; Shim, Hyunsuk

2012-01-01

Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [18F]fluorodeoxyglucose ([18F]FDG)-PET is particularly useful. However, [18F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy. PMID:22685650

[Cytochemical parameters of myeloperoxidase activity and catecholamine level in blood of postpartum women living in areas near the Semipalatinsk nuclear test site].

PubMed

Kokabaeva, A E; Bazeliuk, L T

2002-01-01

The activity of neitrophil myeloperoxidase and content of blood etyrhrocyte cathecholamines in the blood of women in early postpartum period in dependence on distance of their living area from Semipalatinsk nuclear testing were studied. It was found that women who live closer to Semipalatinsk were characterised by significantly lower neitrophil myeloperoxidase activity and content of cathecholamines in erythrocytes than in control.

Improved target detection by IR dual-band image fusion

NASA Astrophysics Data System (ADS)

Adomeit, U.; Ebert, R.

2009-09-01

Dual-band thermal imagers acquire information simultaneously in both the 8-12 μm (long-wave infrared, LWIR) and the 3-5 μm (mid-wave infrared, MWIR) spectral range. Compared to single-band thermal imagers they are expected to have several advantages in military applications. These advantages include the opportunity to use the best band for given atmospheric conditions (e. g. cold climate: LWIR, hot and humid climate: MWIR), the potential to better detect camouflaged targets and an improved discrimination between targets and decoys. Most of these advantages have not yet been verified and/or quantified. It is expected that image fusion allows better exploitation of the information content available with dual-band imagers especially with respect to detection of targets. We have developed a method for dual-band image fusion based on the apparent temperature differences in the two bands. This method showed promising results in laboratory tests. In order to evaluate its performance under operational conditions we conducted a field trial in an area with high thermal clutter. In such areas, targets are hardly to detect in single-band images because they vanish in the clutter structure. The image data collected in this field trial was used for a perception experiment. This perception experiment showed an enhanced target detection range and reduced false alarm rate for the fused images compared to the single-band images.

Synthetic aperture radar target detection, feature extraction, and image formation techniques

NASA Technical Reports Server (NTRS)

Li, Jian

1994-01-01

This report presents new algorithms for target detection, feature extraction, and image formation with the synthetic aperture radar (SAR) technology. For target detection, we consider target detection with SAR and coherent subtraction. We also study how the image false alarm rates are related to the target template false alarm rates when target templates are used for target detection. For feature extraction from SAR images, we present a computationally efficient eigenstructure-based 2D-MODE algorithm for two-dimensional frequency estimation. For SAR image formation, we present a robust parametric data model for estimating high resolution range signatures of radar targets and for forming high resolution SAR images.

Radar Imaging for Moving Targets

DTIC Science & Technology

2009-06-01

MOVING TARGETS by Teo Beng Koon William June 2009 Thesis Advisor: Brett H. Borden Second Reader: Donald L. Walters THIS PAGE...Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project...TITLE AND SUBTITLE Radar Imaging for Moving Targets 6. AUTHOR(S) Teo Beng Koon William 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S

Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

PubMed Central

Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

2015-01-01

Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

NASA Astrophysics Data System (ADS)

Healey, A. J.; Bendiksen, R.; Attramadal, T.; Bjerke, R.; Waagene, S.; Hvoslef, A. M.; Johannesen, E.

2008-02-01

Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

Target recognition in passive terahertz image of human body

NASA Astrophysics Data System (ADS)

Zhao, Ran; Zhao, Yuan-meng; Deng, Chao; Zhang, Cun-lin; Li, Yue

2014-11-01

THz radiation can penetrate through many nonpolar dielectric materials and can be used for nondestructive/noninvasive sensing and imaging of targets under nonpolar, nonmetallic covers or containers. Thus using THz systems to "see through" concealing barriers (i.e. packaging, corrugated cardboard, clothing) has been proposed as a new security screening method. Objects that can be detected by THz include concealed weapons, explosives, and chemical agents under clothing. Passive THz imaging system can detect THz wave from human body without transmit any electromagnetic wave, and the suspicious objects will become visible because the THz wave is blocked by this items. We can find out whether or not someone is carrying dangerous objects through this image. In this paper, the THz image enhancement, segmentation and contour extraction algorithms were studied to achieve effective target image detection. First, the terahertz images are enhanced and their grayscales are stretched. Then we apply global threshold segmentation to extract the target, and finally the targets are marked on the image. Experimental results showed that the algorithm proposed in this paper can extract and mark targets effectively, so that people can identify suspicious objects under clothing quickly. The algorithm can significantly improve the usefulness of the terahertz security apparatus.

Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging.

PubMed

Wang, Chung-Hsin; Huang, Yu-Fen; Yeh, Chih-Kuang

2011-06-07

Targeted ultrasound contrast agents can be prepared by some specific bioconjugation techniques. The biotin-avidin complex is an extremely useful noncovalent binding system, but the system might induce immunogenic side effects in human bodies. Previous proposed covalently conjugated systems suffered from low conjugation efficiency and complex procedures. In this study, we propose a covalently conjugated nanobubble coupling with nucleic acid ligands, aptamers, for providing a higher specific affinity for ultrasound targeting studies. The sgc8c aptamer was linked with nanobubbles through thiol-maleimide coupling chemistry for specific targeting to CCRF-CEM cells. Further improvements to reduce the required time and avoid the degradation of nanobubbles during conjugation procedures were also made. Several investigations were used to discuss the performance and consistency of the prepared nanobubbles, such as size distribution, conjugation efficiency analysis, and flow cytometry assay. Further, we applied our conjugated nanobubbles to ex vivo ultrasound targeted imaging and compared the resulting images with optical images. The results indicated the availability of aptamer-conjugated nanobubbles in targeted ultrasound imaging and the practicability of using a highly sensitive ultrasound system in noninvasive biological research.

Targeted Single-Shot Methods for Diffusion-Weighted Imaging in the Kidneys

PubMed Central

Jin, Ning; Deng, Jie; Zhang, Longjiang; Zhang, Zhuoli; Lu, Guangming; Omary, Reed A.; Larson, Andrew C.

2011-01-01

Purpose To investigate the feasibility of combining the inner-volume-imaging (IVI) technique with single-shot diffusion-weighted (DW) spin-echo echo-planar imaging (SE-EPI) and DW-SPLICE (split acquisition of fast spin-echo) sequences for renal DW imaging. Materials and Methods Renal DW imaging was performed in 10 healthy volunteers using single-shot DW-SE-EPI, DW-SPLICE, targeted-DW-SE-EPI and targeted-DW-SPLICE. We compared the quantitative diffusion measurement accuracy and image quality of these targeted-DW-SE-EPI and targeted DW-SPLICE methods with conventional full FOV DW-SE-EPI and DW-SPLICE measurements in phantoms and normal volunteers. Results Compared with full FOV DW-SE-EPI and DW-SPLICE methods, targeted-DW-SE-EPI and targeted-DW-SPLICE approaches produced images of superior overall quality with fewer artifacts, less distortion and reduced spatial blurring in both phantom and volunteer studies. The ADC values measured with each of the four methods were similar and in agreement with previously published data. There were no statistically significant differences between the ADC values and intra-voxel incoherent motion (IVIM) measurements in the kidney cortex and medulla using single-shot DW-SE-EPI, targeted-DW-EPI and targeted-DW-SPLICE (p > 0.05). Conclusion Compared with full-FOV DW imaging methods, targeted-DW-SE-EPI and targeted-DW-SPLICE techniques reduced image distortion and artifacts observed in the single-shot DW-SE-EPI images, reduced blurring in DW-SPLICE images and produced comparable quantitative DW and IVIM measurements to those produced with conventional full-FOV approaches. PMID:21591023

Camouflage target detection via hyperspectral imaging plus information divergence measurement

NASA Astrophysics Data System (ADS)

Chen, Yuheng; Chen, Xinhua; Zhou, Jiankang; Ji, Yiqun; Shen, Weimin

2016-01-01

Target detection is one of most important applications in remote sensing. Nowadays accurate camouflage target distinction is often resorted to spectral imaging technique due to its high-resolution spectral/spatial information acquisition ability as well as plenty of data processing methods. In this paper, hyper-spectral imaging technique together with spectral information divergence measure method is used to solve camouflage target detection problem. A self-developed visual-band hyper-spectral imaging device is adopted to collect data cubes of certain experimental scene before spectral information divergences are worked out so as to discriminate target camouflage and anomaly. Full-band information divergences are measured to evaluate target detection effect visually and quantitatively. Information divergence measurement is proved to be a low-cost and effective tool for target detection task and can be further developed to other target detection applications beyond spectral imaging technique.

Geometric shapes inversion method of space targets by ISAR image segmentation

NASA Astrophysics Data System (ADS)

Huo, Chao-ying; Xing, Xiao-yu; Yin, Hong-cheng; Li, Chen-guang; Zeng, Xiang-yun; Xu, Gao-gui

2017-11-01

The geometric shape of target is an effective characteristic in the process of space targets recognition. This paper proposed a method of shape inversion of space target based on components segmentation from ISAR image. The Radon transformation, Hough transformation, K-means clustering, triangulation will be introduced into ISAR image processing. Firstly, we use Radon transformation and edge detection to extract space target's main body spindle and solar panel spindle from ISAR image. Then the targets' main body, solar panel, rectangular and circular antenna are segmented from ISAR image based on image detection theory. Finally, the sizes of every structural component are computed. The effectiveness of this method is verified using typical targets' simulation data.

Impact of 4D image quality on the accuracy of target definition.

PubMed

Nielsen, Tine Bjørn; Hansen, Christian Rønn; Westberg, Jonas; Hansen, Olfred; Brink, Carsten

2016-03-01

Delineation accuracy of target shape and position depends on the image quality. This study investigates whether the image quality on standard 4D systems has an influence comparable to the overall delineation uncertainty. A moving lung target was imaged using a dynamic thorax phantom on three different 4D computed tomography (CT) systems and a 4D cone beam CT (CBCT) system using pre-defined clinical scanning protocols. Peak-to-peak motion and target volume were registered using rigid registration and automatic delineation, respectively. A spatial distribution of the imaging uncertainty was calculated as the distance deviation between the imaged target and the true target shape. The measured motions were smaller than actual motions. There were volume differences of the imaged target between respiration phases. Imaging uncertainties of >0.4 cm were measured in the motion direction which showed that there was a large distortion of the imaged target shape. Imaging uncertainties of standard 4D systems are of similar size as typical GTV-CTV expansions (0.5-1 cm) and contribute considerably to the target definition uncertainty. Optimising and validating 4D systems is recommended in order to obtain the most optimal imaged target shape.

Feature-aided multiple target tracking in the image plane

NASA Astrophysics Data System (ADS)

Brown, Andrew P.; Sullivan, Kevin J.; Miller, David J.

2006-05-01

Vast quantities of EO and IR data are collected on airborne platforms (manned and unmanned) and terrestrial platforms (including fixed installations, e.g., at street intersections), and can be exploited to aid in the global war on terrorism. However, intelligent preprocessing is required to enable operator efficiency and to provide commanders with actionable target information. To this end, we have developed an image plane tracker which automatically detects and tracks multiple targets in image sequences using both motion and feature information. The effects of platform and camera motion are compensated via image registration, and a novel change detection algorithm is applied for accurate moving target detection. The contiguous pixel blob on each moving target is segmented for use in target feature extraction and model learning. Feature-based target location measurements are used for tracking through move-stop-move maneuvers, close target spacing, and occlusion. Effective clutter suppression is achieved using joint probabilistic data association (JPDA), and confirmed target tracks are indicated for further processing or operator review. In this paper we describe the algorithms implemented in the image plane tracker and present performance results obtained with video clips from the DARPA VIVID program data collection and from a miniature unmanned aerial vehicle (UAV) flight.

Calibration Target as Seen by Mars Hand Lens Imager

NASA Image and Video Library

2012-02-07

During pre-flight testing, the Mars Hand Lens Imager MAHLI camera on NASA Mars rover Curiosity took this image of the MAHLI calibration target from a distance of 3.94 inches 10 centimeters away from the target.

Assessment of myeloperoxidase activity in renal tissue after ischemia/reperfusion.

PubMed

Laight, D W; Lad, N; Woodward, B; Waterfall, J F

1994-11-01

We have shown that a photometric assay of myeloperoxidase derived from rat blood polymorphonucleocytes employing 3,3',5,5'-tetramethylbenzidine as substrate is more sensitive than an established assay employing o-dianisidine. We went on to demonstrate that rat renal tissue is capable of inhibiting peroxidase activity. This activity approached 100% when the rat renal supernate was incubated at 60 degree C for 2 h and the assay was conducted in the presence of a 10-fold higher concentration of hydrogen peroxide (H2O2). Rat kidneys undergoing 45 min ischaemia and 1,3 and 6 h reperfusion in vivo, exhibited significant increases in myeloperoxidase activity, indicating tissue polymorphonucleocyte accumulation. Monoclonal antibodies against rat intercellular adhesion molecule 1 (ICAM-1) and CD18 of beta 2-integrins administered both 5 min before a period of 45 min renal ischaemia (20 micrograms/kg i.v.) and at the commencement of 1 h reperfusion (20 micrograms/kg i.v.) reduced renal tissue polymorphonucleocyte accumulation. However, similar treatment with the parent murine antibody immunoglobulin G1 (IgG1) and an unrelated murine antibody, IgG2a, also significantly reduced renal tissue polymorphonucleocyte accumulation. In conclusion, we demonstrate that the rat renal suppression of peroxidase activity can be overcome by a combination of heat inactivation and the provision of excess assay H2O2. In addition, the available evidence suggests that murine monoclonal antibodies against rat adhesion molecules may exert non-specific actions in our model of renal ischaemia/reperfusion in vivo.

Myeloperoxidase-hydrogen peroxide-chloride antimicrobial system: effect of exogenous amines on antibacterial action against Escherichia coli.

PubMed

Thomas, E L

1979-07-01

Exogenous ammonium ions (NH(4) (+)) and amine compounds had a profound influence on the antibacterial activity of the myeloperoxidase-hydrogen peroxide-chloride system against Escherichia coli. The rate of killing increased in the presence of NH(4) (+) and certain guanidino compounds and decreased in the presence of alpha-amino acids, polylysine, taurine, or tris (hydroxymethyl) aminomethane. Myeloperoxidase catalyzed the oxidation of chloride to hypochlorous acid, which reacted either with bacterial amine or amide components or both or with the exogenous compounds to yield chloramine or chloramide derivatives or both. These nitrogen-chlorine derivatives could oxidize bacterial components. Killing was correlated with oxidation of bacterial components. The rate of oxidation of bacterial sulfhydryls increased in the presence of the compounds that increased the rate of killing and decreased in the presence of the other compounds. The reaction of HOCl with NH(4) (+) yielded monochloramine (NH(2)Cl), which could be extracted into organic solvents. The N-Cl derivatives of bacterial components or of polylysine, taurine, or tris(hydroxymethyl)aminomethane could not be extracted. The effect of NH(4) (+) on killing is attributed to the ability of NH(2)Cl to penetrate the hydrophobic cell membrane and thus to oxidize intracellular components. Polylysine, taurine, and tris(hydroxymethyl)aminomethane formed high-molecular-weight, charged, or polar N-Cl derivatives that would be unable to penetrate the cell membrane. These results suggest an important role for leukocyte amine components in myeloperoxidase-catalyzed antimicrobial activity in vivo.

PEGylated Peptide-Based Imaging Agents for Targeted Molecular Imaging.

PubMed

Wu, Huizi; Huang, Jiaguo

2016-01-01

Molecular imaging is able to directly visualize targets and characterize cellular pathways with a high signal/background ratio, which requires a sufficient amount of agents to uptake and accumulate in the imaging area. The design and development of peptide based agents for imaging and diagnosis as a hot and promising research topic that is booming in the field of molecular imaging. To date, selected peptides have been increasingly developed as agents by coupling with different imaging moieties (such as radiometals and fluorophore) with the help of sophisticated chemical techniques. Although a few successes have been achieved, most of them have failed mainly caused by their fast renal clearance and therefore low tumor uptakes, which may limit the effectively tumor retention effect. Besides, several peptide agents based on nanoparticles have also been developed for medical diagnostics. However, a great majority of those agents shown long circulation times and accumulation over time into the reticuloendothelial system (RES; including spleen, liver, lymph nodes and bone marrow) after systematic administration, such long-term severe accumulation probably results in the possible likelihood of toxicity and potentially induces health hazards. Recently reported design criteria have been proposed not only to enhance binding affinity in tumor region with long retention, but also to improve clearance from the body in a reasonable amount of time. PEGylation has been considered as one of the most successful modification methods to prolong tumor retention and improve the pharmacokinetic and pharmacodynamic properties for peptide-based imaging agents. This review summarizes an overview of PEGylated peptides imaging agents based on different imaging moieties including radioisotopes, fluorophores, and nanoparticles. The unique concepts and applications of various PEGylated peptide-based imaging agents are introduced for each of several imaging moieties. Effects of PEGylation on

Incoherent imaging of radar targets

NASA Astrophysics Data System (ADS)

van Ommen, A.; van der Spek, G. A.

1986-05-01

Theory suggests that, if a target can be modeled as a rigid constellation of point scatterers, the RCS pattern over a certain aspect change can be used to produce a one-dimensional image. The results for actual measured RCS patterns, however, are not promising. This is illustrated by processing on 4 s of echo data obtained from a Boeing 737 in straight flight, during which its aspect change is 2 deg. The conclusion might be that, for the application considered, aircraft cannot be modeled as a rigid constellation of point scatterers; this is partly due to the treatment of a three-dimensional target as a line target.

Targeting Apoptosis for Optical Imaging of Infection

PubMed Central

Thakur, Mathew L.; Zhang, Kaijun; Paudyal, Bishnuhari; Devakumar, Devadhas; Covarrubias, Maria Y.; Cheng, Changpo; Gray, Brian D.; Wickstrom, Eric; Pak, Koon Y.

2018-01-01

Purpose Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging. Methods Bacterial infection and sterile inflammation were induced in separate groups (n=5) of mice. PS was targeted with a NIR fluorophore, PSVue®794 (2.7 pmol). Imaging was performed (ex=730 nm, em=830 nm) using Kodak Multispectral FX-Pro system. The contralateral normal thigh served as an individualized control. Confocal microscopy of normal and apoptotic neutrophils and bacteria confirmed PS specificity. Results Lesions, with a 10-s image acquisition, were unequivocally visible at 5 min post-injection. At 3 h post-injection, the lesion to background intensity ratios in the foci of infection (6.6±0.2) were greater than those in inflammation (3.2±0.5). Image fusions confirmed anatomical locations of the lesions. Confocal microscopy determined the fluorophore specificity for PS. Conclusions Targeting PS presented on the outer leaflet of apoptotic or necrotic neutrophils as well as gram-positive microorganism with PS-specific NIR fluorophore provides a sensitive means of imaging infection. Literature indicates that NIR fluorophores can be detected 7-14 cm deep in tissue. This observation together with the excellent results and the continued development of versatile imaging devices could make optical imaging a simple, specific, and rapid modality for imaging infection. PMID:21538153

A review of NIR dyes in cancer targeting and imaging.

PubMed

Luo, Shenglin; Zhang, Erlong; Su, Yongping; Cheng, Tianmin; Shi, Chunmeng

2011-10-01

The development of multifunctional agents for simultaneous tumor targeting and near infrared (NIR) fluorescence imaging is expected to have significant impact on future personalized oncology owing to the very low tissue autofluorescence and high tissue penetration depth in the NIR spectrum window. Cancer NIR molecular imaging relies greatly on the development of stable, highly specific and sensitive molecular probes. Organic dyes have shown promising clinical implications as non-targeting agents for optical imaging in which indocyanine green has long been implemented in clinical use. Recently, significant progress has been made on the development of unique NIR dyes with tumor targeting properties. Current ongoing design strategies have overcome some of the limitations of conventional NIR organic dyes, such as poor hydrophilicity and photostability, low quantum yield, insufficient stability in biological system, low detection sensitivity, etc. This potential is further realized with the use of these NIR dyes or NIR dye-encapsulated nanoparticles by conjugation with tumor specific ligands (such as small molecules, peptides, proteins and antibodies) for tumor targeted imaging. Very recently, natively multifunctional NIR dyes that can preferentially accumulate in tumor cells without the need of chemical conjugation to tumor targeting ligands have been developed and these dyes have shown unique optical and pharmaceutical properties for biomedical imaging with superior signal-to-background contrast index. The main focus of this article is to provide a concise overview of newly developed NIR dyes and their potential applications in cancer targeting and imaging. The development of future multifunctional agents by combining targeting, imaging and even therapeutic routes will also be discussed. We believe these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis

Influence of polarization characteristic of targets on synthetic aperture imaging ladar

NASA Astrophysics Data System (ADS)

Xu, Qian; Sun, Jianfeng; Lu, Zhiyong; Wang, Lijuan; Hou, Peipei; Lu, Wei; Liu, Liren

2017-09-01

Synthetic aperture imaging ladar (SAIL) is one of the most possible optical active imaging methods to break the diffraction limit and achieve super-resolution in a long distance. Nevertheless, two-dimensional reconstructed images of the natural targets have not been achieved. Polarization state change of the backscattered light, which is always determined by the interaction of the light and the materials on the target plane, will affect the imaging of SAIL. The Mueller matrices can describe the complex polarization features of the target reflection and treat this interaction. In this paper, a measurement of the Mueller matrices for different target materials will be designed, and the influences of polarization characteristic of targets on resolution element imaging in side-looking and down-looking SAILs will be theoretically analyzed.

Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives.

PubMed

Khan, Amjad A; Alsahli, Mohammed A; Rahmani, Arshad H

2018-04-18

Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications, such as the removal of introns and signal peptides, and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing inactive proMPO by the insertion of a heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into the extracellular fluid after oxidative stress and different inflammatory responses. Myeloperoxidase is the only type of peroxidase that uses H₂O₂ to oxidize several halides and pseudohalides to form different hypohalous acids. So, the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and the pathogenesis of several other major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants. Thus, the enhanced level of MPO activity is one of the best diagnostic tools of inflammatory and oxidative stress biomarkers among these commonly-occurring diseases.

Non-Cooperative Target Imaging and Parameter Estimation with Narrowband Radar Echoes.

PubMed

Yeh, Chun-mao; Zhou, Wei; Lu, Yao-bing; Yang, Jian

2016-01-20

This study focuses on the rotating target imaging and parameter estimation with narrowband radar echoes, which is essential for radar target recognition. First, a two-dimensional (2D) imaging model with narrowband echoes is established in this paper, and two images of the target are formed on the velocity-acceleration plane at two neighboring coherent processing intervals (CPIs). Then, the rotating velocity (RV) is proposed to be estimated by utilizing the relationship between the positions of the scattering centers among two images. Finally, the target image is rescaled to the range-cross-range plane with the estimated rotational parameter. The validity of the proposed approach is confirmed using numerical simulations.

Developing Targeted Hybrid Imaging Probes by Chelator Scaffolding

PubMed Central

2017-01-01

Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore, the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin αVβ3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labeled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalization, and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG αVβ3- and A431-CCK2R expressing tumor xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumor uptake accompanied by slow blood clearance and retention in nontargeted tissues (spleen, liver, and kidneys) leading to visualization of tumors at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine-tune pharmacokinetics are needed to translate this into a clinical setting. PMID:28462989

Infrared moving small target detection based on saliency extraction and image sparse representation

NASA Astrophysics Data System (ADS)

Zhang, Xiaomin; Ren, Kan; Gao, Jin; Li, Chaowei; Gu, Guohua; Wan, Minjie

2016-10-01

Moving small target detection in infrared image is a crucial technique of infrared search and tracking system. This paper present a novel small target detection technique based on frequency-domain saliency extraction and image sparse representation. First, we exploit the features of Fourier spectrum image and magnitude spectrum of Fourier transform to make a rough extract of saliency regions and use a threshold segmentation system to classify the regions which look salient from the background, which gives us a binary image as result. Second, a new patch-image model and over-complete dictionary were introduced to the detection system, then the infrared small target detection was converted into a problem solving and optimization process of patch-image information reconstruction based on sparse representation. More specifically, the test image and binary image can be decomposed into some image patches follow certain rules. We select the target potential area according to the binary patch-image which contains salient region information, then exploit the over-complete infrared small target dictionary to reconstruct the test image blocks which may contain targets. The coefficients of target image patch satisfy sparse features. Finally, for image sequence, Euclidean distance was used to reduce false alarm ratio and increase the detection accuracy of moving small targets in infrared images due to the target position correlation between frames.

Phase calibration target for quantitative phase imaging with ptychography.

PubMed

Godden, T M; Muñiz-Piniella, A; Claverley, J D; Yacoot, A; Humphry, M J

2016-04-04

Quantitative phase imaging (QPI) utilizes refractive index and thickness variations that lead to optical phase shifts. This gives contrast to images of transparent objects. In quantitative biology, phase images are used to accurately segment cells and calculate properties such as dry mass, volume and proliferation rate. The fidelity of the measured phase shifts is of critical importance in this field. However to date, there has been no standardized method for characterizing the performance of phase imaging systems. Consequently, there is an increasing need for protocols to test the performance of phase imaging systems using well-defined phase calibration and resolution targets. In this work, we present a candidate for a standardized phase resolution target, and measurement protocol for the determination of the transfer of spatial frequencies, and sensitivity of a phase imaging system. The target has been carefully designed to contain well-defined depth variations over a broadband range of spatial frequencies. In order to demonstrate the utility of the target, we measure quantitative phase images on a ptychographic microscope, and compare the measured optical phase shifts with Atomic Force Microscopy (AFM) topography maps and surface profile measurements from coherence scanning interferometry. The results show that ptychography has fully quantitative nanometer sensitivity in optical path differences over a broadband range of spatial frequencies for feature sizes ranging from micrometers to hundreds of micrometers.

Adaptive Microwave Staring Correlated Imaging for Targets Appearing in Discrete Clusters.

PubMed

Tian, Chao; Jiang, Zheng; Chen, Weidong; Wang, Dongjin

2017-10-21

Microwave staring correlated imaging (MSCI) can achieve ultra-high resolution in real aperture staring radar imaging using the correlated imaging process (CIP) under all-weather and all-day circumstances. The CIP must combine the received echo signal with the temporal-spatial stochastic radiation field. However, a precondition of the CIP is that the continuous imaging region must be discretized to a fine grid, and the measurement matrix should be accurately computed, which makes the imaging process highly complex when the MSCI system observes a wide area. This paper proposes an adaptive imaging approach for the targets in discrete clusters to reduce the complexity of the CIP. The approach is divided into two main stages. First, as discrete clustered targets are distributed in different range strips in the imaging region, the transmitters of the MSCI emit narrow-pulse waveforms to separate the echoes of the targets in different strips in the time domain; using spectral entropy, a modified method robust against noise is put forward to detect the echoes of the discrete clustered targets, based on which the strips with targets can be adaptively located. Second, in a strip with targets, the matched filter reconstruction algorithm is used to locate the regions with targets, and only the regions of interest are discretized to a fine grid; sparse recovery is used, and the band exclusion is used to maintain the non-correlation of the dictionary. Simulation results are presented to demonstrate that the proposed approach can accurately and adaptively locate the regions with targets and obtain high-quality reconstructed images.

Rheumatoid arthritis antigens homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2, 3 and 4 in rheumatoid nodule and synovial tissue.

PubMed

Turunen, Sanna; Huhtakangas, Johanna; Nousiainen, Tomi; Valkealahti, Maarit; Melkko, Jukka; Risteli, Juha; Lehenkari, Petri

2016-10-20

Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and homocitrulline contents using HPLC. The location of citrulline- and homocitrulline-containing proteins, PAD 2, 3, 4 and myeloperoxidase were shown by immunostaining. Myeloperoxidase and citrulline- or homocitrulline-containing proteins were stained on Western blot. Overall, necrosis was frequent in metatarsals of seropositive RA and absent in seronegative RA and osteoarthritis patients. In histological analysis, there was a significant local patterning and variation in the citrulline and homocitrulline content and it was highest in metatarsal synovial tissues of seropositive RA patients. We found peptidyl arginine deiminase 2, 3 and 4 in the lining and sublining layers of intact synovial tissue. Myeloperoxidase was found locally around necrotic areas. The tissues with necrosis contained the highest levels of citrulline and homocitrulline. Rheumatoid nodules and synovia contain significant amount of PAD2, 3 and 4 and myeloperoxidase enzymes. These enzymes could explain the levels of citrulline and homocitrulline in seropositive RA synovial and rheumatoid nodule tissues especially around necrotic tissue.

Specialized Color Targets for Spectral Reflectance Reconstruction of Magnified Images

NASA Astrophysics Data System (ADS)

Kruschwitz, Jennifer D. T.

Digital images are used almost exclusively instead of film to capture visual information across many scientific fields. The colorimetric color representation within these digital images can be relayed from the digital counts produced by the camera with the use of a known color target. In image capture of magnified images, there is currently no reliable color target that can be used at multiple magnifications and give the user a solid understanding of the color ground truth within those images. The first part of this dissertation included the design, fabrication, and testing of a color target produced with optical interference coated microlenses for use in an off-axis illumination, compound microscope. An ideal target was designed to increase the color gamut for colorimetric imaging and provide the necessary "Block Dye" spectral reflectance profiles across the visible spectrum to reduce the number of color patches necessary for multiple filter imaging systems that rely on statistical models for spectral reflectance reconstruction. There are other scientific disciplines that can benefit from a specialized color target to determine the color ground truth in their magnified images and perform spectral estimation. Not every discipline has the luxury of having a multi-filter imaging system. The second part of this dissertation developed two unique ways of using an interference coated color mirror target: one that relies on multiple light-source angles, and one that leverages a dynamic color change with time. The source multi-angle technique would be used for the microelectronic discipline where the reconstructed spectral reflectance would be used to determine a dielectric film thickness on a silicon substrate, and the time varying technique would be used for a biomedical example to determine the thickness of human tear film.

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential

PubMed Central

Wang, Lulu; Habib, Amyn A.; Mintz, Akiva; Li, King C.; Zhao, Dawen

2017-01-01

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood–brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors. PMID:28654387

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential.

PubMed

Wang, Lulu; Habib, Amyn A; Mintz, Akiva; Li, King C; Zhao, Dawen

2017-01-01

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood-brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.

Passive synthetic aperture radar imaging of ground moving targets

NASA Astrophysics Data System (ADS)

Wacks, Steven; Yazici, Birsen

2012-05-01

In this paper we present a method for imaging ground moving targets using passive synthetic aperture radar. A passive radar imaging system uses small, mobile receivers that do not radiate any energy. For these reasons, passive imaging systems result in signicant cost, manufacturing, and stealth advantages. The received signals are obtained by multiple airborne receivers collecting scattered waves due to illuminating sources of opportunity such as commercial television, radio, and cell phone towers. We describe a novel forward model and a corresponding ltered-backprojection type image reconstruction method combined with entropy optimization. Our method determines the location and velocity of multiple targets moving at dierent velocities. Furthermore, it can accommodate arbitrary imaging geometries. we present numerical simulations to verify the imaging method.

Target recognition and phase acquisition by using incoherent digital holographic imaging

NASA Astrophysics Data System (ADS)

Lee, Munseob; Lee, Byung-Tak

2017-05-01

In this study, we proposed the Incoherent Digital Holographic Imaging (IDHI) for recognition and phase information of dedicated target. Although recent development of a number of target recognition techniques such as LIDAR, there have limited success in target discrimination, in part due to low-resolution, low scanning speed, and computation power. In the paper, the proposed system consists of the incoherent light source, such as LED, Michelson interferometer, and digital CCD for acquisition of four phase shifting image. First of all, to compare with relative coherence, we used a source as laser and LED, respectively. Through numerical reconstruction by using the four phase shifting method and Fresnel diffraction method, we recovered the intensity and phase image of USAF resolution target apart from about 1.0m distance. In this experiment, we show 1.2 times improvement in resolution compared to conventional imaging. Finally, to confirm the recognition result of camouflaged targets with the same color from background, we carry out to test holographic imaging in incoherent light. In this result, we showed the possibility of a target detection and recognition that used three dimensional shape and size signatures, numerical distance from phase information of obtained holographic image.

Astatine-211 imaging by a Compton camera for targeted radiotherapy.

PubMed

Nagao, Yuto; Yamaguchi, Mitsutaka; Watanabe, Shigeki; Ishioka, Noriko S; Kawachi, Naoki; Watabe, Hiroshi

2018-05-24

Astatine-211 is a promising radionuclide for targeted radiotherapy. It is required to image the distribution of targeted radiotherapeutic agents in a patient's body for optimization of treatment strategies. We proposed to image 211 At with high-energy photons to overcome some problems in conventional planar or single-photon emission computed tomography imaging. We performed an imaging experiment of a point-like 211 At source using a Compton camera, and demonstrated the capability of imaging 211 At with the high-energy photons for the first time. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

Robust through-the-wall radar image classification using a target-model alignment procedure.

PubMed

Smith, Graeme E; Mobasseri, Bijan G

2012-02-01

A through-the-wall radar image (TWRI) bears little resemblance to the equivalent optical image, making it difficult to interpret. To maximize the intelligence that may be obtained, it is desirable to automate the classification of targets in the image to support human operators. This paper presents a technique for classifying stationary targets based on the high-range resolution profile (HRRP) extracted from 3-D TWRIs. The dependence of the image on the target location is discussed using a system point spread function (PSF) approach. It is shown that the position dependence will cause a classifier to fail, unless the image to be classified is aligned to a classifier-training location. A target image alignment technique based on deconvolution of the image with the system PSF is proposed. Comparison of the aligned target images with measured images shows the alignment process introducing normalized mean squared error (NMSE) ≤ 9%. The HRRP extracted from aligned target images are classified using a naive Bayesian classifier supported by principal component analysis. The classifier is tested using a real TWRI of canonical targets behind a concrete wall and shown to obtain correct classification rates ≥ 97%. © 2011 IEEE

OPTICAL correlation identification technology applied in underwater laser imaging target identification

NASA Astrophysics Data System (ADS)

Yao, Guang-tao; Zhang, Xiao-hui; Ge, Wei-long

2012-01-01

The underwater laser imaging detection is an effective method of detecting short distance target underwater as an important complement of sonar detection. With the development of underwater laser imaging technology and underwater vehicle technology, the underwater automatic target identification has gotten more and more attention, and is a research difficulty in the area of underwater optical imaging information processing. Today, underwater automatic target identification based on optical imaging is usually realized with the method of digital circuit software programming. The algorithm realization and control of this method is very flexible. However, the optical imaging information is 2D image even 3D image, the amount of imaging processing information is abundant, so the electronic hardware with pure digital algorithm will need long identification time and is hard to meet the demands of real-time identification. If adopt computer parallel processing, the identification speed can be improved, but it will increase complexity, size and power consumption. This paper attempts to apply optical correlation identification technology to realize underwater automatic target identification. The optics correlation identification technology utilizes the Fourier transform characteristic of Fourier lens which can accomplish Fourier transform of image information in the level of nanosecond, and optical space interconnection calculation has the features of parallel, high speed, large capacity and high resolution, combines the flexibility of calculation and control of digital circuit method to realize optoelectronic hybrid identification mode. We reduce theoretical formulation of correlation identification and analyze the principle of optical correlation identification, and write MATLAB simulation program. We adopt single frame image obtained in underwater range gating laser imaging to identify, and through identifying and locating the different positions of target, we can improve

Breaking camouflage and detecting targets require optic flow and image structure information.

PubMed

Pan, Jing Samantha; Bingham, Ned; Chen, Chang; Bingham, Geoffrey P

2017-08-01

Use of motion to break camouflage extends back to the Cambrian [In the Blink of an Eye: How Vision Sparked the Big Bang of Evolution (New York Basic Books, 2003)]. We investigated the ability to break camouflage and continue to see camouflaged targets after motion stops. This is crucial for the survival of hunting predators. With camouflage, visual targets and distracters cannot be distinguished using only static image structure (i.e., appearance). Motion generates another source of optical information, optic flow, which breaks camouflage and specifies target locations. Optic flow calibrates image structure with respect to spatial relations among targets and distracters, and calibrated image structure makes previously camouflaged targets perceptible in a temporally stable fashion after motion stops. We investigated this proposal using laboratory experiments and compared how many camouflaged targets were identified either with optic flow information alone or with combined optic flow and image structure information. Our results show that the combination of motion-generated optic flow and target-projected image structure information yielded efficient and stable perception of camouflaged targets.

Clearance Pathways and Tumor Targeting of Imaging Nanoparticles

PubMed Central

Yu, Mengxiao; Zheng, Jie

2016-01-01

A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID:26149184

Multispectral image fusion for target detection

NASA Astrophysics Data System (ADS)

Leviner, Marom; Maltz, Masha

2009-09-01

Various different methods to perform multi-spectral image fusion have been suggested, mostly on the pixel level. However, the jury is still out on the benefits of a fused image compared to its source images. We present here a new multi-spectral image fusion method, multi-spectral segmentation fusion (MSSF), which uses a feature level processing paradigm. To test our method, we compared human observer performance in an experiment using MSSF against two established methods: Averaging and Principle Components Analysis (PCA), and against its two source bands, visible and infrared. The task that we studied was: target detection in the cluttered environment. MSSF proved superior to the other fusion methods. Based on these findings, current speculation about the circumstances in which multi-spectral image fusion in general and specific fusion methods in particular would be superior to using the original image sources can be further addressed.

Deep kernel learning method for SAR image target recognition

NASA Astrophysics Data System (ADS)

Chen, Xiuyuan; Peng, Xiyuan; Duan, Ran; Li, Junbao

2017-10-01

With the development of deep learning, research on image target recognition has made great progress in recent years. Remote sensing detection urgently requires target recognition for military, geographic, and other scientific research. This paper aims to solve the synthetic aperture radar image target recognition problem by combining deep and kernel learning. The model, which has a multilayer multiple kernel structure, is optimized layer by layer with the parameters of Support Vector Machine and a gradient descent algorithm. This new deep kernel learning method improves accuracy and achieves competitive recognition results compared with other learning methods.

Remote sensing image ship target detection method based on visual attention model

NASA Astrophysics Data System (ADS)

Sun, Yuejiao; Lei, Wuhu; Ren, Xiaodong

2017-11-01

The traditional methods of detecting ship targets in remote sensing images mostly use sliding window to search the whole image comprehensively. However, the target usually occupies only a small fraction of the image. This method has high computational complexity for large format visible image data. The bottom-up selective attention mechanism can selectively allocate computing resources according to visual stimuli, thus improving the computational efficiency and reducing the difficulty of analysis. Considering of that, a method of ship target detection in remote sensing images based on visual attention model was proposed in this paper. The experimental results show that the proposed method can reduce the computational complexity while improving the detection accuracy, and improve the detection efficiency of ship targets in remote sensing images.

Myeloperoxidase-induced Genomic DNA-centered Radicals*

PubMed Central

Gomez-Mejiba, Sandra E.; Zhai, Zili; Gimenez, Maria S.; Ashby, Michael T.; Chilakapati, Jaya; Kitchin, Kirk; Mason, Ronald P.; Ramirez, Dario C.

2010-01-01

Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis. PMID:20406811

Receptor-Targeted Nanoparticles for In Vivo Imaging of Breast Cancer

PubMed Central

Yang, Lily; Peng, Xiang-Hong; Wang, Y. Andrew; Wang, Xiaoxia; Cao, Zehong; Ni, Chunchun; Karna, Prasanthi; Zhang, Xinjian; Wood, William C.; Gao, Xiaohu; Nie, Shuming; Mao, Hui

2009-01-01

Purpose Cell surface receptor-targeted magnetic iron oxide (IO) nanoparticles provide molecular magnetic resonance imaging (MRI) contrast agents for improving specificity of the detection of human cancer. Experimental design The present study reports the development of a novel targeted IO nanoparticle using a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator conjugated to IO nanoparticles (ATF-IO). This nanoparticle targets urokinase plasminogen activator receptor (uPAR), which is overexpressed in breast cancer tissues. Results ATF-IO nanoparticles are able to specifically bind to and be internalized by uPAR-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing subcutaneous and intraperitoneal mammary tumors leads to the accumulation of the particles in tumors, generating a strong MRI contrast detectable by a clinical MRI scanner at a field strength of 3 Tesla. Target specificity of ATF-IO nanoparticles demonstrated by in vivo MRI is further confirmed by near infrared (NIR) fluorescence imaging of the mammary tumors using NIR dye-labeled ATF peptides conjugated to IO nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared to those receiving non-targeted IO nanoparticles. Conclusions Our results suggest that uPAR-targeted ATF-IO nanoparticles have potential as molecularly-targeted, dual modality imaging agents for in vivo imaging of breast cancer. PMID:19584158

Camouflage target reconnaissance based on hyperspectral imaging technology

NASA Astrophysics Data System (ADS)

Hua, Wenshen; Guo, Tong; Liu, Xun

2015-08-01

Efficient camouflaged target reconnaissance technology makes great influence on modern warfare. Hyperspectral images can provide large spectral range and high spectral resolution, which are invaluable in discriminating between camouflaged targets and backgrounds. Hyperspectral target detection and classification technology are utilized to achieve single class and multi-class camouflaged targets reconnaissance respectively. Constrained energy minimization (CEM), a widely used algorithm in hyperspectral target detection, is employed to achieve one class camouflage target reconnaissance. Then, support vector machine (SVM), a classification method, is proposed to achieve multi-class camouflage target reconnaissance. Experiments have been conducted to demonstrate the efficiency of the proposed method.

Relationship between the lipophilicity of gallic acid n-alquil esters' derivatives and both myeloperoxidase activity and HOCl scavenging.

PubMed

Rosso, Rober; Vieira, Tiago O; Leal, Paulo C; Nunes, Ricardo J; Yunes, Rosendo A; Creczynski-Pasa, Tânia B

2006-09-15

The gallic acid and several n-alkyl gallates, with the same number of hydroxyl substituents, varying only in the side carbonic chain length, with respective lipophilicity defined through the C log P, were studied. It evidenced the structure-activity relationship of the myeloperoxidase activity inhibition and the hypochlorous acid scavenger property, as well as its low toxicity in rat hepatic tissue. The gallates with C log P below 3.0 (compounds 2-7) were more active against the enzyme activity, what means that the addition of 1-6 carbons (C log P between 0.92 and 2.92) at the side chain increased approximately 50% the gallic acid effect. However, a relationship between the HOCl scavenging capability and the lipophilicity was not observed. With these results it is possible to suggest that the gallates protect the HOCl targets through two mechanisms: inhibiting its production by the enzyme and scavenging the reactive specie.

Evidence that a formyl-substituted iron porphyrin is the prosthetic group of myeloperoxidase: magnetic circular dichroism similarity of the peroxidase to Spirographis heme-reconstituted myoglobin.

PubMed Central

Sono, M; Bracete, A M; Huff, A M; Ikeda-Saito, M; Dawson, J H

1991-01-01

To probe the identity of the active site heme-type prosthetic group of myeloperoxidase, whose structure has not been established unambiguously [proposed structures are (i) a chlorin (dihydroporphyrin) or (ii) a formyl-substituted porphyrin such as present in heme a], Spirographis heme (2-formyl-4-vinyldeuteroheme IX) has been incorporated into apo-myoglobin as a possible iron porphyrin model. Comparison of parallel derivatives of these two green proteins with magnetic circular dichroism spectroscopy reveals considerable similarities between several derivatives of these proteins, including the pyridine hemochromogen, the native ferric, ferrous-oxy, and ferrous-CO forms. In contrast, the magnetic circular dichroism spectra of available iron chlorin (octaethylchlorin) model complexes in analogous ligation and oxidation states do not show any significant spectral similarities to myeloperoxidase. This finding provides important evidence in favor of a formyl-substituted porphyrin as the structure of the prosthetic group macrocycle of myeloperoxidase. PMID:1662385

Image-algebraic design of multispectral target recognition algorithms

NASA Astrophysics Data System (ADS)

Schmalz, Mark S.; Ritter, Gerhard X.

1994-06-01

In this paper, we discuss methods for multispectral ATR (Automated Target Recognition) of small targets that are sensed under suboptimal conditions, such as haze, smoke, and low light levels. In particular, we discuss our ongoing development of algorithms and software that effect intelligent object recognition by selecting ATR filter parameters according to ambient conditions. Our algorithms are expressed in terms of IA (image algebra), a concise, rigorous notation that unifies linear and nonlinear mathematics in the image processing domain. IA has been implemented on a variety of parallel computers, with preprocessors available for the Ada and FORTRAN languages. An image algebra C++ class library has recently been made available. Thus, our algorithms are both feasible implementationally and portable to numerous machines. Analyses emphasize the aspects of image algebra that aid the design of multispectral vision algorithms, such as parameterized templates that facilitate the flexible specification of ATR filters.

Hand-held optical imager (Gen-2): improved instrumentation and target detectability

PubMed Central

Gonzalez, Jean; DeCerce, Joseph; Erickson, Sarah J.; Martinez, Sergio L.; Nunez, Annie; Roman, Manuela; Traub, Barbara; Flores, Cecilia A.; Roberts, Seigbeh M.; Hernandez, Estrella; Aguirre, Wenceslao; Kiszonas, Richard

2012-01-01

Abstract. Hand-held optical imagers are developed by various researchers towards reflectance-based spectroscopic imaging of breast cancer. Recently, a Gen-1 handheld optical imager was developed with capabilities to perform two-dimensional (2-D) spectroscopic as well as three-dimensional (3-D) tomographic imaging studies. However, the imager was bulky with poor surface contact (∼30%) along curved tissues, and limited sensitivity to detect targets consistently. Herein, a Gen-2 hand-held optical imager that overcame the above limitations of the Gen-1 imager has been developed and the instrumentation described. The Gen-2 hand-held imager is less bulky, portable, and has improved surface contact (∼86%) on curved tissues. Additionally, the forked probe head design is capable of simultaneous bilateral reflectance imaging of both breast tissues, and also transillumination imaging of a single breast tissue. Experimental studies were performed on tissue phantoms to demonstrate the improved sensitivity in detecting targets using the Gen-2 imager. The improved instrumentation of the Gen-2 imager allowed detection of targets independent of their location with respect to the illumination points, unlike in Gen-1 imager. The developed imager has potential for future clinical breast imaging with enhanced sensitivity, via both reflectance and transillumination imaging. PMID:23224163

Time-reversal MUSIC imaging of extended targets.

PubMed

Marengo, Edwin A; Gruber, Fred K; Simonetti, Francesco

2007-08-01

This paper develops, within a general framework that is applicable to rather arbitrary electromagnetic and acoustic remote sensing systems, a theory of time-reversal "MUltiple Signal Classification" (MUSIC)-based imaging of extended (nonpoint-like) scatterers (targets). The general analysis applies to arbitrary remote sensing geometry and sheds light onto how the singular system of the scattering matrix relates to the geometrical and propagation characteristics of the entire transmitter-target-receiver system and how to use this effect for imaging. All the developments are derived within exact scattering theory which includes multiple scattering effects. The derived time-reversal MUSIC methods include both interior sampling, as well as exterior sampling (or enclosure) approaches. For presentation simplicity, particular attention is given to the time-harmonic case where the informational wave modes employed for target interrogation are purely spatial, but the corresponding generalization to broadband fields is also given. This paper includes computer simulations illustrating the derived theory and algorithms.

Slant path range gated imaging of static and moving targets

NASA Astrophysics Data System (ADS)

Steinvall, Ove; Elmqvist, Magnus; Karlsson, Kjell; Gustafsson, Ove; Chevalier, Tomas

2012-06-01

This paper will report experiments and analysis of slant path imaging using 1.5 μm and 0.8 μm gated imaging. The investigation is a follow up on the measurement reported last year at the laser radar conference at SPIE Orlando. The sensor, a SWIR camera was collecting both passive and active images along a 2 km long path over an airfield. The sensor was elevated by a lift in steps from 1.6-13.5 meters. Targets were resolution charts and also human targets. The human target was holding various items and also performing certain tasks some of high of relevance in defence and security. One of the main purposes with this investigation was to compare the recognition of these human targets and their activities with the resolution information obtained from conventional resolution charts. The data collection of human targets was also made from out roof top laboratory at about 13 m height above ground. The turbulence was measured along the path with anemometers and scintillometers. The camera was collecting both passive and active images in the SWIR region. We also included the Obzerv camera working at 0.8 μm in some tests. The paper will present images for both passive and active modes obtained at different elevations and discuss the results from both technical and system perspectives.

Target Detection Using an AOTF Hyperspectral Imager

NASA Technical Reports Server (NTRS)

Cheng, L-J.; Mahoney, J.; Reyes, F.; Suiter, H.

1994-01-01

This paper reports results of a recent field experiment using a prototype system to evaluate the acousto-optic tunable filter polarimetric hyperspectral imaging technology for target detection applications.

Seismoelectric imaging of shallow targets

USGS Publications Warehouse

Haines, S.S.; Pride, S.R.; Klemperer, S.L.; Biondi, B.

2007-01-01

We have undertaken a series of controlled field experiments to develop seismoelectric experimental methods for near-surface applications and to improve our understanding of seismoelectric phenomena. In a set of off-line geometry surveys (source separated from the receiver line), we place seismic sources and electrode array receivers on opposite sides of a man-made target (two sand-filled trenches) to record separately two previously documented seismoelectric modes: (1) the electromagnetic interface response signal created at the target and (2) the coseismic electric fields located within a compressional seismic wave. With the seismic source point in the center of a linear electrode array, we identify the previously undocumented seismoelectric direct field, and the Lorentz field of the metal hammer plate moving in the earth's magnetic field. We place the seismic source in the center of a circular array of electrodes (radial and circumferential orientations) to analyze the source-related direct and Lorentz fields and to establish that these fields can be understood in terms of simple analytical models. Using an off-line geometry, we create a multifold, 2D image of our trenches as dipping layers, and we also produce a complementary synthetic image through numerical modeling. These images demonstrate that off-line geometry (e.g., crosswell) surveys offer a particularly promising application of the seismoelectric method because they effectively separate the interface response signal from the (generally much stronger) coseismic and source-related fields. ?? 2007 Society of Exploration Geophysicists.

SAR Image Simulation of Ship Targets Based on Multi-Path Scattering

NASA Astrophysics Data System (ADS)

Guo, Y.; Wang, H.; Ma, H.; Li, K.; Xia, Z.; Hao, Y.; Guo, H.; Shi, H.; Liao, X.; Yue, H.

2018-04-01

Synthetic Aperture Radar (SAR) plays an important role in the classification and recognition of ship targets because of its all-weather working ability and fine resolution. In SAR images, besides the sea clutter, the influence of the sea surface on the radar echo is also known as the so-called multipath effect. These multipath effects will generate some extra "pseudo images", which may cause the distortion of the target image and affect the estimation of the characteristic parameters. In this paper,the multipath effect of rough sea surface and its influence on the estimation of ship characteristic parameters are studied. The imaging of the first and the secondary reflection of sea surface is presented . The artifacts not only overlap with the image of the target itself, but may also appear in the sea near the target area. It is difficult to distinguish them, and this artifact has an effect on the length and width of the ship.

A long-term target detection approach in infrared image sequence

NASA Astrophysics Data System (ADS)

Li, Hang; Zhang, Qi; Wang, Xin; Hu, Chao

2016-10-01

An automatic target detection method used in long term infrared (IR) image sequence from a moving platform is proposed. Firstly, based on POME(the principle of maximum entropy), target candidates are iteratively segmented. Then the real target is captured via two different selection approaches. At the beginning of image sequence, the genuine target with litter texture is discriminated from other candidates by using contrast-based confidence measure. On the other hand, when the target becomes larger, we apply online EM method to estimate and update the distributions of target's size and position based on the prior detection results, and then recognize the genuine one which satisfies both the constraints of size and position. Experimental results demonstrate that the presented method is accurate, robust and efficient.

PIRATE: pediatric imaging response assessment and targeting environment

NASA Astrophysics Data System (ADS)

Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho

2010-02-01

By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

Target-Oriented High-Resolution SAR Image Formation via Semantic Information Guided Regularizations

NASA Astrophysics Data System (ADS)

Hou, Biao; Wen, Zaidao; Jiao, Licheng; Wu, Qian

2018-04-01

Sparsity-regularized synthetic aperture radar (SAR) imaging framework has shown its remarkable performance to generate a feature enhanced high resolution image, in which a sparsity-inducing regularizer is involved by exploiting the sparsity priors of some visual features in the underlying image. However, since the simple prior of low level features are insufficient to describe different semantic contents in the image, this type of regularizer will be incapable of distinguishing between the target of interest and unconcerned background clutters. As a consequence, the features belonging to the target and clutters are simultaneously affected in the generated image without concerning their underlying semantic labels. To address this problem, we propose a novel semantic information guided framework for target oriented SAR image formation, which aims at enhancing the interested target scatters while suppressing the background clutters. Firstly, we develop a new semantics-specific regularizer for image formation by exploiting the statistical properties of different semantic categories in a target scene SAR image. In order to infer the semantic label for each pixel in an unsupervised way, we moreover induce a novel high-level prior-driven regularizer and some semantic causal rules from the prior knowledge. Finally, our regularized framework for image formation is further derived as a simple iteratively reweighted $\\ell_1$ minimization problem which can be conveniently solved by many off-the-shelf solvers. Experimental results demonstrate the effectiveness and superiority of our framework for SAR image formation in terms of target enhancement and clutters suppression, compared with the state of the arts. Additionally, the proposed framework opens a new direction of devoting some machine learning strategies to image formation, which can benefit the subsequent decision making tasks.

A targeted molecular probe for colorectal cancer imaging

NASA Astrophysics Data System (ADS)

Attramadal, T.; Bjerke, R.; Indrevoll, B.; Moestue, S.; Rogstad, A.; Bendiksen, R.; Healey, A.; Johannesen, E.

2008-02-01

Colorectal cancer is a major cause of cancer death. Morbidity, mortality and healthcare costs can be reduced if the disease can be detected at an early stage. Screening is a viable approach as there is a clear link to risk factors such as age. We have developed a fluorescent contrast agent for use during colonoscopy. The agent is administered intravenously and is targeted to an early stage molecular marker for colorectal cancer. The agent consists of a targeting section comprising a peptide, and a fluorescent reporter molecule. Clinical imaging of the agent is to be performed with a far red fluorescence imaging channel (635 nm excitation/660-700 nm emission) as an adjunct to white light colonoscopy. Preclinical proof of mechanism results are presented. The compound has a K d of ~3nM. Two human xenograft tumour models were used. Tumour cells were implanted and grown subcutaneously in nude mice. Imaging using a fluorescence reflectance imaging system and quantitative biodistribution studies were performed. Substances tested include the targeted agent, and a scrambled sequence of the peptide (no binding) used as a negative control. Competition studies were also performed by co-administration of 180 times excess unlabelled peptide. Positive imaging contrast was shown in the tumours, with a clear relationship to expression levels (confirmed with quantitative biodistribution data). There was a significant difference between the positive and negative control substances, and a significant reduction in contrast in the competition experiment.

Target engagement imaging of PARP inhibitors in small-cell lung cancer.

PubMed

Carney, Brandon; Kossatz, Susanne; Lok, Benjamin H; Schneeberger, Valentina; Gangangari, Kishore K; Pillarsetty, Naga Vara Kishore; Weber, Wolfgang A; Rudin, Charles M; Poirier, John T; Reiner, Thomas

2018-01-12

Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition over time to calculate effective doses for individual drugs. Using patient-derived xenografts, we demonstrate that different therapeutics achieve similar integrated inhibition efficiencies under different dosing regimens. This imaging approach to non-invasive, quantitative assessment of dynamic intratumoral target inhibition may improve patient care through real-time monitoring of drug delivery.

Preparation of a Versatile Bifunctional Zeolite for Targeted Imaging Applications

PubMed Central

Ndiege, Nicholas; Raidoo, Renugan; Schultz, Michael K.; Larsen, Sarah

2011-01-01

Bifunctional zeolite Y was prepared for use in targeted in vivo molecular imaging applications. The strategy involved functionalization of the external surface of zeolite Y with chloropropyltriethoxysilane followed by reaction with sodium azide to form azide-functionalized NaY, which is amenable to copper(1) catalyzed click chemistry. In this study, a model alkyne (4-pentyn-1-ol) was attached to the azide-terminated surface via click chemistry to demonstrate feasibility for attachment of molecular targeting vectors (e.g., peptides, aptamers) to the zeolite surface. The modified particle efficiently incorporates the imaging radioisotope gallium-68 (68Ga) into the pores of the azide-functionalized NaY zeolite to form a stable bifunctional molecular targeting vector. The result is a versatile “clickable” zeolite platform that can be tailored for future in vivo molecular targeting and imaging modalities. PMID:21306141

Adaptive ISAR Imaging of Maneuvering Targets Based on a Modified Fourier Transform.

PubMed

Wang, Binbin; Xu, Shiyou; Wu, Wenzhen; Hu, Pengjiang; Chen, Zengping

2018-04-27

Focusing on the inverse synthetic aperture radar (ISAR) imaging of maneuvering targets, this paper presents a new imaging method which works well when the target's maneuvering is not too severe. After translational motion compensation, we describe the equivalent rotation of maneuvering targets by two variables-the relative chirp rate of the linear frequency modulated (LFM) signal and the Doppler focus shift. The first variable indicates the target's motion status, and the second one represents the possible residual error of the translational motion compensation. With them, a modified Fourier transform matrix is constructed and then used for cross-range compression. Consequently, the imaging of maneuvering is converted into a two-dimensional parameter optimization problem in which a stable and clear ISAR image is guaranteed. A gradient descent optimization scheme is employed to obtain the accurate relative chirp rate and Doppler focus shift. Moreover, we designed an efficient and robust initialization process for the gradient descent method, thus, the well-focused ISAR images of maneuvering targets can be achieved adaptively. Human intervention is not needed, and it is quite convenient for practical ISAR imaging systems. Compared to precedent imaging methods, the new method achieves better imaging quality under reasonable computational cost. Simulation results are provided to validate the effectiveness and advantages of the proposed method.

How Imaging Can Impact Clinical Trial Design: Molecular Imaging as a Biomarker for Targeted Cancer Therapy.

PubMed

Mankoff, David A; Farwell, Michael D; Clark, Amy S; Pryma, Daniel A

2015-01-01

The ability to measure biochemical and molecular processes to guide cancer treatment represents a potentially powerful tool for trials of targeted cancer therapy. These assays have traditionally been performed by analysis of tissue samples. However, more recently, functional and molecular imaging has been developed that is capable of in vivo assays of cancer biochemistry and molecular biology and is highly complementary to tissue-based assays. Cancer imaging biomarkers can play a key role in increasing the efficacy and efficiency of therapeutic clinical trials and also provide insight into the biologic mechanisms that bring about a therapeutic response. Future progress will depend on close collaboration between imaging scientists and cancer physicians and on public and commercial sponsors, to take full advantage of what imaging has to offer for clinical trials of targeted cancer therapy. This review will provide examples of how molecular imaging can inform targeted cancer clinical trials and clinical decision making by (1) measuring regional expression of the therapeutic target, (2) assessing early (pharmacodynamic) response to treatment, and (3) predicting therapeutic outcome. The review includes a discussion of basic principles of molecular imaging biomarkers in cancer, with an emphasis on those methods that have been tested in patients. We then review clinical trials designed to evaluate imaging tests as integrated markers embedded in a therapeutic clinical trial with the goal of validating the imaging tests as integral markers that can aid patient selection and direct response-adapted treatment strategies. Examples of recently completed multicenter trials using imaging biomarkers are highlighted.

A novel rotational invariants target recognition method for rotating motion blurred images

NASA Astrophysics Data System (ADS)

Lan, Jinhui; Gong, Meiling; Dong, Mingwei; Zeng, Yiliang; Zhang, Yuzhen

2017-11-01

The imaging of the image sensor is blurred due to the rotational motion of the carrier and reducing the target recognition rate greatly. Although the traditional mode that restores the image first and then identifies the target can improve the recognition rate, it takes a long time to recognize. In order to solve this problem, a rotating fuzzy invariants extracted model was constructed that recognizes target directly. The model includes three metric layers. The object description capability of metric algorithms that contain gray value statistical algorithm, improved round projection transformation algorithm and rotation-convolution moment invariants in the three metric layers ranges from low to high, and the metric layer with the lowest description ability among them is as the input which can eliminate non pixel points of target region from degenerate image gradually. Experimental results show that the proposed model can improve the correct target recognition rate of blurred image and optimum allocation between the computational complexity and function of region.

Molecular imaging with targeted contrast ultrasound.

PubMed

Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

2009-01-01

Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation. Copyright 2009 S. Karger AG, Basel.

Genetic variation in the myeloperoxidase gene and cognitive impairment in Multiple Sclerosis

PubMed Central

Manna, I; Valentino, P; La Russa, A; Condino, F; Nisticò, R; Liguori, M; Clodomiro, A; Andreoli, V; Pirritano, D; Cittadella, R; Quattrone, A

2006-01-01

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS. PMID:16504169

The research of multi-frame target recognition based on laser active imaging

NASA Astrophysics Data System (ADS)

Wang, Can-jin; Sun, Tao; Wang, Tin-feng; Chen, Juan

2013-09-01

Laser active imaging is fit to conditions such as no difference in temperature between target and background, pitch-black night, bad visibility. Also it can be used to detect a faint target in long range or small target in deep space, which has advantage of high definition and good contrast. In one word, it is immune to environment. However, due to the affect of long distance, limited laser energy and atmospheric backscatter, it is impossible to illuminate the whole scene at the same time. It means that the target in every single frame is unevenly or partly illuminated, which make the recognition more difficult. At the same time the speckle noise which is common in laser active imaging blurs the images . In this paper we do some research on laser active imaging and propose a new target recognition method based on multi-frame images . Firstly, multi pulses of laser is used to obtain sub-images for different parts of scene. A denoising method combined homomorphic filter with wavelet domain SURE is used to suppress speckle noise. And blind deconvolution is introduced to obtain low-noise and clear sub-images. Then these sub-images are registered and stitched to combine a completely and uniformly illuminated scene image. After that, a new target recognition method based on contour moments is proposed. Firstly, canny operator is used to obtain contours. For each contour, seven invariant Hu moments are calculated to generate the feature vectors. At last the feature vectors are input into double hidden layers BP neural network for classification . Experiments results indicate that the proposed algorithm could achieve a high recognition rate and satisfactory real-time performance for laser active imaging.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy

NASA Astrophysics Data System (ADS)

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-08-01

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

PubMed Central

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

Validation of the Electromagnetic Code FACETS for Numerical Simulation of Radar Target Images

DTIC Science & Technology

2009-12-01

Validation of the electromagnetic code FACETS for numerical simulation of radar target images S. Wong...Validation of the electromagnetic code FACETS for numerical simulation of radar target images S. Wong DRDC Ottawa...for simulating radar images of a target is obtained, through direct simulation-to-measurement comparisons. A 3-dimensional computer-aided design

Robust autofocus algorithm for ISAR imaging of moving targets

NASA Astrophysics Data System (ADS)

Li, Jian; Wu, Renbiao; Chen, Victor C.

2000-08-01

A robust autofocus approach, referred to as AUTOCLEAN (AUTOfocus via CLEAN), is proposed for the motion compensation in ISAR (inverse synthetic aperture radar) imaging of moving targets. It is a parametric algorithm based on a very flexible data model which takes into account arbitrary range migration and arbitrary phase errors across the synthetic aperture that may be induced by unwanted radial motion of the target as well as propagation or system instability. AUTOCLEAN can be classified as a multiple scatterer algorithm (MSA), but it differs considerably from other existing MSAs in several aspects: (1) dominant scatterers are selected automatically in the two-dimensional (2-D) image domain; (2) scatterers may not be well-isolated or very dominant; (3) phase and RCS (radar cross section) information from each selected scatterer are combined in an optimal way; (4) the troublesome phase unwrapping step is avoided. AUTOCLEAN is computationally efficient and involves only a sequence of FFTs (fast Fourier Transforms). Another good feature associated with AUTOCLEAN is that its performance can be progressively improved by assuming a larger number of dominant scatterers for the target. Hence it can be easily configured for real-time applications including, for example, ATR (automatic target recognition) of non-cooperative moving targets, and for some other applications where the image quality is of the major concern but not the computational time including, for example, for the development and maintenance of low observable aircrafts. Numerical and experimental results have shown that AUTOCLEAN is a very robust autofocus tool for ISAR imaging.

Tensor Fukunaga-Koontz transform for small target detection in infrared images

NASA Astrophysics Data System (ADS)

Liu, Ruiming; Wang, Jingzhuo; Yang, Huizhen; Gong, Chenglong; Zhou, Yuanshen; Liu, Lipeng; Zhang, Zhen; Shen, Shuli

2016-09-01

Infrared small targets detection plays a crucial role in warning and tracking systems. Some novel methods based on pattern recognition technology catch much attention from researchers. However, those classic methods must reshape images into vectors with the high dimensionality. Moreover, vectorizing breaks the natural structure and correlations in the image data. Image representation based on tensor treats images as matrices and can hold the natural structure and correlation information. So tensor algorithms have better classification performance than vector algorithms. Fukunaga-Koontz transform is one of classification algorithms and it is a vector version method with the disadvantage of all vector algorithms. In this paper, we first extended the Fukunaga-Koontz transform into its tensor version, tensor Fukunaga-Koontz transform. Then we designed a method based on tensor Fukunaga-Koontz transform for detecting targets and used it to detect small targets in infrared images. The experimental results, comparison through signal-to-clutter, signal-to-clutter gain and background suppression factor, have validated the advantage of the target detection based on the tensor Fukunaga-Koontz transform over that based on the Fukunaga-Koontz transform.

Target recognition of ladar range images using even-order Zernike moments.

PubMed

Liu, Zheng-Jun; Li, Qi; Xia, Zhi-Wei; Wang, Qi

2012-11-01

Ladar range images have attracted considerable attention in automatic target recognition fields. In this paper, Zernike moments (ZMs) are applied to classify the target of the range image from an arbitrary azimuth angle. However, ZMs suffer from high computational costs. To improve the performance of target recognition based on small samples, even-order ZMs with serial-parallel backpropagation neural networks (BPNNs) are applied to recognize the target of the range image. It is found that the rotation invariance and classified performance of the even-order ZMs are both better than for odd-order moments and for moments compressed by principal component analysis. The experimental results demonstrate that combining the even-order ZMs with serial-parallel BPNNs can significantly improve the recognition rate for small samples.

A long-term target detection approach in infrared image sequence

NASA Astrophysics Data System (ADS)

Li, Hang; Zhang, Qi; Li, Yuanyuan; Wang, Liqiang

2015-12-01

An automatic target detection method used in long term infrared (IR) image sequence from a moving platform is proposed. Firstly, based on non-linear histogram equalization, target candidates are coarse-to-fine segmented by using two self-adapt thresholds generated in the intensity space. Then the real target is captured via two different selection approaches. At the beginning of image sequence, the genuine target with litter texture is discriminated from other candidates by using contrast-based confidence measure. On the other hand, when the target becomes larger, we apply online EM method to iteratively estimate and update the distributions of target's size and position based on the prior detection results, and then recognize the genuine one which satisfies both the constraints of size and position. Experimental results demonstrate that the presented method is accurate, robust and efficient.

Photoacoustic imaging of tumor targeting with biotin conjugated nanostructured phthalocyanine assemblies

NASA Astrophysics Data System (ADS)

Lee, Seunghyun; Li, Xingshu; Lee, Dayoung; Yoon, Juyoung; Kim, Chulhong

2018-02-01

Visualizing biological markers and delivering bioactive agents to living organisms are important to biological research. In recent decades, photoacoustic imaging (PAI) has been significantly improved in the area of molecular imaging, which provides high-resolution volume imaging with high optical absorption contrast. To demonstrate the ability of nanoprobes to target tumors using PAI, we synthesize convertible nanostructured agents with strong photothermal and photoacoustic properties and linked the nanoprobe with biotin to target tumors in small animal model. Interestingly, these nanoprobes allow partial to disassemble in the presence of targeted proteins that switchable photoactivity, thus the nanoprobes provides a fluorescent-cancer imaging with high signal-to-background ratios. The proposed nanoprobe produce a much stronger PA signal compared to the same concentration of methylene blue (MB), which is widely used in clinical study and contrast agent for PAI. The biotin conjugated nanoprobe has high selectivity for biotin receptor positive cancer cells such as A549 (human lung cancer). Then we subsequently examined the PA properties of the nanoprobe that are inherently suitable for in vivo PAI. After injecting of the nanoprobe via intravenous method, we observed the mice's whole body by PA imaging and acquired the PA signal near the cancer. The PA signal increased linearly with time after injection and the fluorescence signal near the cancer was confirmed by fluorescence imaging. The ability to target a specific cancer of the nanoprobe was well verified by PA imaging. This study provides valuable perspective on the advancement of clinical translations and in the design of tumor-targeting phototheranostic agents that could act as new nanomedicines.

Simulation of target interpretation based on infrared image features and psychology principle

NASA Astrophysics Data System (ADS)

Lin, Wei; Chen, Yu-hua; Gao, Hong-sheng; Wang, Zhan-feng; Wang, Ji-jun; Su, Rong-hua; Huang, Yan-ping

2009-07-01

It's an important and complicated process in target interpretation that target features extraction and identification, which effect psychosensorial quantity of interpretation person to target infrared image directly, and decide target viability finally. Using statistical decision theory and psychology principle, designing four psychophysical experiment, the interpretation model of the infrared target is established. The model can get target detection probability by calculating four features similarity degree between target region and background region, which were plotted out on the infrared image. With the verification of a great deal target interpretation in practice, the model can simulate target interpretation and detection process effectively, get the result of target interpretation impersonality, which can provide technique support for target extraction, identification and decision-making.

Heterobivalent Imaging Agents Targeting Prostate Cancer Training

DTIC Science & Technology

2011-06-01

has been implicated as a salient player in the pathobiology of cancers of epithelial origin, e.g. prostate, cervix , ovarian, colon and...ANSI Std. Z39.18 W81XWH-10-1-0481 Heterobivalent Imaging Agents Targeting Prostate Cancer Training Aaron LeBeau University of California, San...Francisco San Francisco, CA 94103 Annual Summary 31 MAY 2010 - 1JUN 201101-06-2011 To determine the utility of imaging MT-SP1 in cancer , xenografts of

Image Analyzed by Mars Rover for Selection of Target

NASA Image and Video Library

2010-03-23

NASA Opportunity used newly developed and uploaded software called AEGIS, to analyze images to identify features that best matched criteria for selecting an observation target; the criteria in this image -- rocks that are larger and darker than others.

Small target detection using bilateral filter and temporal cross product in infrared images

NASA Astrophysics Data System (ADS)

Bae, Tae-Wuk

2011-09-01

We introduce a spatial and temporal target detection method using spatial bilateral filter (BF) and temporal cross product (TCP) of temporal pixels in infrared (IR) image sequences. At first, the TCP is presented to extract the characteristics of temporal pixels by using temporal profile in respective spatial coordinates of pixels. The TCP represents the cross product values by the gray level distance vector of a current temporal pixel and the adjacent temporal pixel, as well as the horizontal distance vector of the current temporal pixel and a temporal pixel corresponding to potential target center. The summation of TCP values of temporal pixels in spatial coordinates makes the temporal target image (TTI), which represents the temporal target information of temporal pixels in spatial coordinates. And then the proposed BF filter is used to extract the spatial target information. In order to predict background without targets, the proposed BF filter uses standard deviations obtained by an exponential mapping of the TCP value corresponding to the coordinate of a pixel processed spatially. The spatial target image (STI) is made by subtracting the predicted image from the original image. Thus, the spatial and temporal target image (STTI) is achieved by multiplying the STI and the TTI, and then targets finally are detected in STTI. In experimental result, the receiver operating characteristics (ROC) curves were computed experimentally to compare the objective performance. From the results, the proposed algorithm shows better discrimination of target and clutters and lower false alarm rates than the existing target detection methods.

Research on the underwater target imaging based on the streak tube laser lidar

NASA Astrophysics Data System (ADS)

Cui, Zihao; Tian, Zhaoshuo; Zhang, Yanchao; Bi, Zongjie; Yang, Gang; Gu, Erdan

2018-03-01

A high frame rate streak tube imaging lidar (STIL) for real-time 3D imaging of underwater targets is presented in this paper. The system uses 532nm pulse laser as the light source, the maximum repetition rate is 120Hz, and the pulse width is 8ns. LabVIEW platform is used in the system, the system control, synchronous image acquisition, 3D data processing and display are realized through PC. 3D imaging experiment of underwater target is carried out in a flume with attenuation coefficient of 0.2, and the images of different depth and different material targets are obtained, the imaging frame rate is 100Hz, and the maximum detection depth is 31m. For an underwater target with a distance of 22m, the high resolution 3D image real-time acquisition is realized with range resolution of 1cm and space resolution of 0.3cm, the spatial relationship of the targets can be clearly identified by the image. The experimental results show that STIL has a good application prospect in underwater terrain detection, underwater search and rescue, and other fields.

Neutrophils differentially attenuate immune response to Aspergillus infection through complement receptor 3 and induction of myeloperoxidase.

PubMed

Goh, Jessamine G; Ravikumar, Sharada; Win, Mar Soe; Cao, Qiong; Tan, Ai Ling; Lim, Joan H J; Leong, Winnie; Herbrecht, Raoul; Troke, Peter F; Kullberg, Bart Jan; Netea, Mihai G; Chng, Wee Joo; Dan, Yock Young; Chai, Louis Y A

2018-03-01

Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus. © 2017 John Wiley & Sons Ltd.

Snapshot spectral and polarimetric imaging; target identification with multispectral video

NASA Astrophysics Data System (ADS)

Bartlett, Brent D.; Rodriguez, Mikel D.

2013-05-01

As the number of pixels continue to grow in consumer and scientific imaging devices, it has become feasible to collect the incident light field. In this paper, an imaging device developed around light field imaging is used to collect multispectral and polarimetric imagery in a snapshot fashion. The sensor is described and a video data set is shown highlighting the advantage of snapshot spectral imaging. Several novel computer vision approaches are applied to the video cubes to perform scene characterization and target identification. It is shown how the addition of spectral and polarimetric data to the video stream allows for multi-target identification and tracking not possible with traditional RGB video collection.

Elevated levels of protein-bound p-hydroxyphenylacetaldehyde, an amino-acid-derived aldehyde generated by myeloperoxidase, are present in human fatty streaks, intermediate lesions and advanced atherosclerotic lesions.

PubMed Central

Hazen, S L; Gaut, J P; Crowley, J R; Hsu, F F; Heinecke, J W

2000-01-01

Reactive aldehydes might have a pivotal role in the pathogenesis of atherosclerosis by covalently modifying low-density lipoprotein (LDL). However, the identities of the aldehyde adducts that form on LDL in vivo are not yet clearly established. We previously demonstrated that the haem protein myeloperoxidase oxidizes proteins in the human artery wall. We also have shown that p-hydroxyphenylacetaldehyde (pHA), the aldehyde that forms when myeloperoxidase oxidizes L-tyrosine, covalently modifies the N(epsilon)-lysine residues of proteins. The resulting Schiff base can be quantified as N(epsilon)-[2-(p-hydroxyphenyl)ethyl]lysine (pHA-lysine) after reduction with NaCNBH(3). Here we demonstrate that pHA-lysine is a marker for LDL that has been modified by myeloperoxidase, and that water-soluble, but not lipid-soluble, antioxidants inhibit the modification of LDL protein. To determine whether myeloperoxidase-generated aldehydes might modify LDL in vivo, we used a combination of isotope-dilution GC-MS to quantify pHA-lysine in aortic tissues at various stages of lesion evolution. We also analysed LDL isolated from atherosclerotic aortic tissue. Comparison of normal and atherosclerotic aortic tissue demonstrated a significant elevation (more than 10-fold) of the reduced Schiff base adduct in fatty streaks, intermediate lesions and advanced lesions compared with normal aortic tissue. Moreover, the level of pHA-lysine in LDL recovered from atherosclerotic aortic intima was 200-fold that in plasma LDL of healthy donors. These results indicate that pHA-lysine, a specific covalent modification of LDL, is generated in human atherosclerotic vascular tissue. They also raise the possibility that reactive aldehydes generated by myeloperoxidase have a role in converting LDL into an atherogenic lipoprotein. PMID:11104675

Target recognition of log-polar ladar range images using moment invariants

NASA Astrophysics Data System (ADS)

Xia, Wenze; Han, Shaokun; Cao, Jie; Yu, Haoyong

2017-01-01

The ladar range image has received considerable attentions in the automatic target recognition field. However, previous research does not cover target recognition using log-polar ladar range images. Therefore, we construct a target recognition system based on log-polar ladar range images in this paper. In this system combined moment invariants and backpropagation neural network are selected as shape descriptor and shape classifier, respectively. In order to fully analyze the effect of log-polar sampling pattern on recognition result, several comparative experiments based on simulated and real range images are carried out. Eventually, several important conclusions are drawn: (i) if combined moments are computed directly by log-polar range images, translation, rotation and scaling invariant properties of combined moments will be invalid (ii) when object is located in the center of field of view, recognition rate of log-polar range images is less sensitive to the changing of field of view (iii) as object position changes from center to edge of field of view, recognition performance of log-polar range images will decline dramatically (iv) log-polar range images has a better noise robustness than Cartesian range images. Finally, we give a suggestion that it is better to divide field of view into recognition area and searching area in the real application.

Image-guided ex-vivo targeting accuracy using a laparoscopic tissue localization system

NASA Astrophysics Data System (ADS)

Bieszczad, Jerry; Friets, Eric; Knaus, Darin; Rauth, Thomas; Herline, Alan; Miga, Michael; Galloway, Robert; Kynor, David

2007-03-01

In image-guided surgery, discrete fiducials are used to determine a spatial registration between the location of surgical tools in the operating theater and the location of targeted subsurface lesions and critical anatomic features depicted in preoperative tomographic image data. However, the lack of readily localized anatomic landmarks has greatly hindered the use of image-guided surgery in minimally invasive abdominal procedures. To address these needs, we have previously described a laser-based system for localization of internal surface anatomy using conventional laparoscopes. During a procedure, this system generates a digitized, three-dimensional representation of visible anatomic surfaces in the abdominal cavity. This paper presents the results of an experiment utilizing an ex-vivo bovine liver to assess subsurface targeting accuracy achieved using our system. During the experiment, several radiopaque targets were inserted into the liver parenchyma. The location of each target was recorded using an optically-tracked insertion probe. The liver surface was digitized using our system, and registered with the liver surface extracted from post-procedure CT images. This surface-based registration was then used to transform the position of the inserted targets into the CT image volume. The target registration error (TRE) achieved using our surface-based registration (given a suitable registration algorithm initialization) was 2.4 mm +/- 1.0 mm. A comparable TRE (2.6 mm +/- 1.7 mm) was obtained using a registration based on traditional fiducial markers placed on the surface of the same liver. These results indicate the potential of fiducial-free, surface-to-surface registration for image-guided lesion targeting in minimally invasive abdominal surgery.

Effects of Scene Modulation Image Blur and Noise Upon Human Target Acquisition Performance.

DTIC Science & Technology

1997-06-01

AFRL-HE-WP-TR-1998-0012 UNITED STATES AIR FORCE RESEARCH LABORATORY EFFECTS OF SCENE MODULATION IMAGE BLUR AND NOISE UPON HUMAN TARGET...COVERED INTERIM (July 1996 - August 1996) TITLE AND SUBTITLE Effects of Scene Modulation Image Blur and Noise Upon Human Target Acquisition...dilemma in image transmission and display is that we must compromise between die conflicting constraints of dynamic range and noise . Three target

Robust Small Target Co-Detection from Airborne Infrared Image Sequences.

PubMed

Gao, Jingli; Wen, Chenglin; Liu, Meiqin

2017-09-29

In this paper, a novel infrared target co-detection model combining the self-correlation features of backgrounds and the commonality features of targets in the spatio-temporal domain is proposed to detect small targets in a sequence of infrared images with complex backgrounds. Firstly, a dense target extraction model based on nonlinear weights is proposed, which can better suppress background of images and enhance small targets than weights of singular values. Secondly, a sparse target extraction model based on entry-wise weighted robust principal component analysis is proposed. The entry-wise weight adaptively incorporates structural prior in terms of local weighted entropy, thus, it can extract real targets accurately and suppress background clutters efficiently. Finally, the commonality of targets in the spatio-temporal domain are used to construct target refinement model for false alarms suppression and target confirmation. Since real targets could appear in both of the dense and sparse reconstruction maps of a single frame, and form trajectories after tracklet association of consecutive frames, the location correlation of the dense and sparse reconstruction maps for a single frame and tracklet association of the location correlation maps for successive frames have strong ability to discriminate between small targets and background clutters. Experimental results demonstrate that the proposed small target co-detection method can not only suppress background clutters effectively, but also detect targets accurately even if with target-like interference.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

PubMed

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-09-21

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

Dual-Responsive Molecular Probe for Tumor Targeted Imaging and Photodynamic Therapy

PubMed Central

Meng, Xiaoqing; Yang, Yueting; Zhou, Lihua; Zhang, li; Lv, Yalin; Li, Sanpeng; Wu, Yayun; Zheng, Mingbin; Li, Wenjun; Gao, Guanhui; Deng, Guanjun; Jiang, Tao; Ni, Dapeng; Gong, Ping; Cai, Lintao

2017-01-01

The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5′-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols. Furthermore, RhoSSCy shows superb tumor targeted dual-modal imaging via near-infrared fluorescence (NIRF) and photoacoustic (PA). Importantly, RhoSSCy also induces strongly reactive oxygen species for tumor photodynamic therapy (PDT) with robust antitumor activity both in vitro and in vivo. Such versatile small-molecule theranostic probe may be promising for tumor targeted imaging and precision therapy. PMID:28638467

A Plane Target Detection Algorithm in Remote Sensing Images based on Deep Learning Network Technology

NASA Astrophysics Data System (ADS)

Shuxin, Li; Zhilong, Zhang; Biao, Li

2018-01-01

Plane is an important target category in remote sensing targets and it is of great value to detect the plane targets automatically. As remote imaging technology developing continuously, the resolution of the remote sensing image has been very high and we can get more detailed information for detecting the remote sensing targets automatically. Deep learning network technology is the most advanced technology in image target detection and recognition, which provided great performance improvement in the field of target detection and recognition in the everyday scenes. We combined the technology with the application in the remote sensing target detection and proposed an algorithm with end to end deep network, which can learn from the remote sensing images to detect the targets in the new images automatically and robustly. Our experiments shows that the algorithm can capture the feature information of the plane target and has better performance in target detection with the old methods.

64Cu-Labeled multifunctional dendrimers for targeted tumor PET imaging.

PubMed

Ma, Wenhui; Fu, Fanfan; Zhu, Jingyi; Huang, Rui; Zhu, Yizhou; Liu, Zhenwei; Wang, Jing; Conti, Peter S; Shi, Xiangyang; Chen, Kai

2018-03-29

We report the use of multifunctional folic acid (FA)-modified dendrimers as a platform to radiolabel with 64Cu for PET imaging of folate receptor (FR)-expressing tumors. In this study, amine-terminated generation 5 (G5) poly(amidoamine) dendrimers were sequentially modified with fluorescein isothiocyanate (FI), FA, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), followed by acetylation of the remaining dendrimer terminal amines. The as-formed multifunctional DOTA-FA-FI-G5·NHAc dendrimers were then radiolabeled with 64Cu via the DOTA chelation. We show that the FA modification renders the dendrimers with targeting specificity to cancer cells overexpressing FR in vitro. Importantly, the radiolabeled 64Cu-DOTA-FA-FI-G5·NHAc dendrimers can be used as a nanoprobe for specific targeting of FR-overexpressing cancer cells in vitro and targeted microPET imaging of the FR-expressing xenografted tumor model in vivo. The developed 64Cu-labeled multifunctional dendrimeric nanoprobe may hold great promise to be used for targeted PET imaging of different types of FR-expressing cancer.

Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

PubMed

Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

2014-11-21

In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

Imaging near surface mineral targets with ambient seismic noise

NASA Astrophysics Data System (ADS)

Dales, P.; Audet, P.; Olivier, G.

2017-12-01

To keep up with global metal and mineral demand, new ore-deposits have to be discovered on a regular basis. This task is becoming increasingly difficult, since easily accessible deposits have been exhausted to a large degree. The typical procedure for mineral exploration begins with geophysical surveys followed by a drilling program to investigate potential targets. Since the retrieved drill core samples are one-dimensional observations, the many holes needed to interpolate and interpret potential deposits can lead to very high costs. To reduce the amount of drilling, active seismic imaging is sometimes used as an intermediary, however the active sources (e.g. large vibrating trucks or explosive shots) are expensive and unsuitable for operation in remote or environmentally sensitive areas. In recent years, passive seismic imaging using ambient noise has emerged as a novel, low-cost and environmentally sensitive approach for exploring the sub-surface. This technique dispels with active seismic sources and instead uses ambient seismic noise such as ocean waves, traffic or minor earthquakes. Unfortunately at this point, passive surveys are not capable of reaching the required resolution to image the vast majority of the ore-bodies that are being explored. In this presentation, we will show the results of an experiment where ambient seismic noise recorded on 60 seismic stations was used to image a near-mine target. The target consists of a known ore-body that has been partially exhausted by mining efforts roughly 100 years ago. The experiment examined whether ambient seismic noise interferometry can be used to image the intact and exhausted ore deposit. A drilling campaign was also conducted near the target which offers the opportunity to compare the two methods. If the accuracy and resolution of passive seismic imaging can be improved to that of active surveys (and beyond), this method could become an inexpensive intermediary step in the exploration process and result

Subpixel target detection and enhancement in hyperspectral images

NASA Astrophysics Data System (ADS)

Tiwari, K. C.; Arora, M.; Singh, D.

2011-06-01

Hyperspectral data due to its higher information content afforded by higher spectral resolution is increasingly being used for various remote sensing applications including information extraction at subpixel level. There is however usually a lack of matching fine spatial resolution data particularly for target detection applications. Thus, there always exists a tradeoff between the spectral and spatial resolutions due to considerations of type of application, its cost and other associated analytical and computational complexities. Typically whenever an object, either manmade, natural or any ground cover class (called target, endmembers, components or class) gets spectrally resolved but not spatially, mixed pixels in the image result. Thus, numerous manmade and/or natural disparate substances may occur inside such mixed pixels giving rise to mixed pixel classification or subpixel target detection problems. Various spectral unmixing models such as Linear Mixture Modeling (LMM) are in vogue to recover components of a mixed pixel. Spectral unmixing outputs both the endmember spectrum and their corresponding abundance fractions inside the pixel. It, however, does not provide spatial distribution of these abundance fractions within a pixel. This limits the applicability of hyperspectral data for subpixel target detection. In this paper, a new inverse Euclidean distance based super-resolution mapping method has been presented that achieves subpixel target detection in hyperspectral images by adjusting spatial distribution of abundance fraction within a pixel. Results obtained at different resolutions indicate that super-resolution mapping may effectively aid subpixel target detection.

Phosphatidylserine-targeted liposome for enhanced glioma-selective imaging.

PubMed

Zhang, Liang; Habib, Amyn A; Zhao, Dawen

2016-06-21

Phosphatidylserine (PS), which is normally intracellular, becomes exposed on the outer surface of viable endothelial cells (ECs) of tumor vasculature. Utilizing a PS-targeting antibody, we have recently established a PS-targeted liposomal (PS-L) nanoplatform that has demonstrated to be highly tumor-selective. Because of the vascular lumen-exposed PS that is immediately accessible without a need to penetrate the intact blood brain barrier (BBB), we hypothesize that the systemically administered PS-L binds specifically to tumor vascular ECs, becomes subsequently internalized into the cells and then enables its cargos to be efficiently delivered to glioma parenchyma. To test this, we exploited the dual MRI/optical imaging contrast agents-loaded PS-L and injected it intravenously into mice bearing intracranial U87 glioma. At 24 h, both in vivo optical imaging and MRI depicted enhanced tumor contrast, distinct from the surrounding normal brain. Intriguingly, longitudinal MRI revealed temporal and spatial intratumoral distribution of the PS-L by following MRI contrast changes, which appeared punctate in tumor periphery at an earlier time point (4 h), but became clustering and disseminated throughout the tumor at 24 h post injection. Importantly, glioma-targeting specificity of the PS-L was antigen specific, since a control probe of irrelevant specificity showed minimal accumulation in the glioma. Together, these results indicate that the PS-L nanoplatform enables the enhanced, glioma-targeted delivery of imaging contrast agents by crossing the tumor BBB efficiently, which may also serve as a useful nanoplatform for anti-glioma drugs.

Synthetic aperture radar image formation for the moving-target and near-field bistatic cases

NASA Astrophysics Data System (ADS)

Ding, Yu

This dissertation addresses topics in two areas of synthetic aperture radar (SAR) image formation: time-frequency based SAR imaging of moving targets and a fast backprojection (BP) algorithm for near-field bistatic SAR imaging. SAR imaging of a moving target is a challenging task due to unknown motion of the target. We approach this problem in a theoretical way, by analyzing the Wigner-Ville distribution (WVD) based SAR imaging technique. We derive approximate closed-form expressions for the point-target response of the SAR imaging system, which quantify the image resolution, and show how the blurring in conventional SAR imaging can be eliminated, while the target shift still remains. Our analyses lead to accurate prediction of the target position in the reconstructed images. The derived expressions also enable us to further study additional aspects of WVD-based SAR imaging. Bistatic SAR imaging is more involved than the monostatic SAR case, because of the separation of the transmitter and the receiver, and possibly the changing bistatic geometry. For near-field bistatic SAR imaging, we develop a novel fast BP algorithm, motivated by a newly proposed fast BP algorithm in computer tomography. First we show that the BP algorithm is the spatial-domain counterpart of the benchmark o -- k algorithm in bistatic SAR imaging, yet it avoids the frequency-domain interpolation in the o -- k algorithm, which may cause artifacts in the reconstructed image. We then derive the band-limited property for BP methods in both monostatic and bistatic SAR imaging, which is the basis for developing the fast BP algorithm. We compare our algorithm with other frequency-domain based algorithms, and show that it achieves better reconstructed image quality, while having the same computational complexity as that of the frequency-domain based algorithms.

Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

NASA Astrophysics Data System (ADS)

Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

2015-11-01

Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

Optical Imaging of Targeted β-Galactosidase in Brain Tumors to Detect EGFR Levels

PubMed Central

Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

2015-01-01

A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging. PMID:25775241

Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.

PubMed

Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

2015-04-15

A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.

Multishot Targeted PROPELLER Magnetic Resonance Imaging: Description of the Technique and Initial Applications

PubMed Central

Deng, Jie; Larson, Andrew C.

2010-01-01

Objectives To test the feasibility of combining inner-volume imaging (IVI) techniques with conventional multishot periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) techniques for targeted-PROPELLER magnetic resonance imaging. Materials and Methods Perpendicular section-selective gradients for spatially selective excitation and refocusing RF pulses were applied to limit the refocused field-of-view (FOV) along the phase-encoding direction for each rectangular blade image. We performed comparison studies in phantoms and normal volunteers by using targeted-PROPELLER methods for a wide range of imaging applications that commonly use turbo-spin-echo (TSE) approaches (brain, abdominal, vessel wall, cardiac). Results In these initial studies, we demonstrated the feasibility of using targeted-PROPELLER approaches to limit the imaging FOV thereby reducing the number of blades or permitting increased spatial resolution without commensurate increases in scan time. Both phantom and in vivo motion studies demonstrated the potential for more robust regional self-navigated motion correction compared with conventional full FOV PROPELLER methods. Conclusion We demonstrated that the reduced FOV targeted-PROPELLER technique offers the potential for reducing imaging time, increasing spatial resolution, and targeting specific areas for robust regional motion correction. PMID:19465860

A targeted illumination optical fiber probe for high resolution fluorescence imaging and optical switching

NASA Astrophysics Data System (ADS)

Shinde, Anant; Perinchery, Sandeep Menon; Murukeshan, Vadakke Matham

2017-04-01

An optical imaging probe with targeted multispectral and spatiotemporal illumination features has applications in many diagnostic biomedical studies. However, these systems are mostly adapted in conventional microscopes, limiting their use for in vitro applications. We present a variable resolution imaging probe using a digital micromirror device (DMD) with an achievable maximum lateral resolution of 2.7 μm and an axial resolution of 5.5 μm, along with precise shape selective targeted illumination ability. We have demonstrated switching of different wavelengths to image multiple regions in the field of view. Moreover, the targeted illumination feature allows enhanced image contrast by time averaged imaging of selected regions with different optical exposure. The region specific multidirectional scanning feature of this probe has facilitated high speed targeted confocal imaging.

Immune evasion by a staphylococcal inhibitor of myeloperoxidase

PubMed Central

de Jong, Nienke W. M.; Ramyar, Kasra X.; Guerra, Fermin E.; Fevre, Cindy; Voyich, Jovanka M.; McCarthy, Alex J.; Garcia, Brandon L.; van Kessel, Kok P. M.; van Strijp, Jos A. G.; Geisbrecht, Brian V.; Haas, Pieter-Jan A.

2017-01-01

Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein “staphylococcal peroxidase inhibitor” (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of human MPO at 2.4-Å resolution. This structure reveals that SPIN acts as a molecular plug that prevents H2O2 substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that S. aureus secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing. PMID:28808028

Immune evasion by a staphylococcal inhibitor of myeloperoxidase

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Jong, Nienke W. M.; Ramyar, Kasra X.; Guerra, Fermin E.

Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein “staphylococcal peroxidase inhibitor” (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of humanmore » MPO at 2.4-Å resolution. This structure reveals that SPIN acts as a molecular plug that prevents H2O2 substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that S. aureus secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing.« less

Imaging Metastasis Using an Integrin-Targeting Chain-Shaped Nanoparticle

PubMed Central

Peiris, Pubudu M.; Toy, Randall; Doolittle, Elizabeth; Pansky, Jenna; Abramowski, Aaron; Tam, Morgan; Vicente, Peter; Tran, Emily; Hayden, Elliott; Camann, Andrew; Mayer, Aaron; Erokwu, Bernadette O.; Berman, Zachary; Wilson, David; Baskaran, Harihara; Flask, Chris A.; Keri, Ruth A.; Karathanasis, Efstathios

2012-01-01

While the enhanced permeability and retention effect may promote the preferential accumulation of nanoparticles into well-vascularized primary tumors, it is ineffective in the case of metastases hidden within a large population of normal cells. Due to their small size, high dispersion to organs, and low vascularization, metastatic tumors are less accessible to targeted nanoparticles. To tackle these challenges, we designed a nanoparticle for vascular targeting based on an αvβ3 integrin-targeted nanochain particle composed of four iron oxide nanospheres chemically linked in a linear assembly. The chain-shaped nanoparticles enabled enhanced ‘sensing’ of the tumor-associated remodeling of the vascular bed offering increased likelihood of specific recognition of metastatic tumors. Compared to spherical nanoparticles, the chain-shaped nanoparticles resulted in superior targeting of αvβ3 integrin due to geometrically enhanced multivalent docking. We performed multimodal in vivo imaging (Fluorescence Molecular Tomography and Magnetic Resonance Imaging) in a non-invasive and quantitative manner, which showed that the nanoparticles targeted metastases in the liver and lungs with high specificity in a highly aggressive breast tumor model in mice. PMID:23005348

SAR image dataset of military ground targets with multiple poses for ATR

NASA Astrophysics Data System (ADS)

Belloni, Carole; Balleri, Alessio; Aouf, Nabil; Merlet, Thomas; Le Caillec, Jean-Marc

2017-10-01

Automatic Target Recognition (ATR) is the task of automatically detecting and classifying targets. Recognition using Synthetic Aperture Radar (SAR) images is interesting because SAR images can be acquired at night and under any weather conditions, whereas optical sensors operating in the visible band do not have this capability. Existing SAR ATR algorithms have mostly been evaluated using the MSTAR dataset.1 The problem with the MSTAR is that some of the proposed ATR methods have shown good classification performance even when targets were hidden,2 suggesting the presence of a bias in the dataset. Evaluations of SAR ATR techniques are currently challenging due to the lack of publicly available data in the SAR domain. In this paper, we present a high resolution SAR dataset consisting of images of a set of ground military target models taken at various aspect angles, The dataset can be used for a fair evaluation and comparison of SAR ATR algorithms. We applied the Inverse Synthetic Aperture Radar (ISAR) technique to echoes from targets rotating on a turntable and illuminated with a stepped frequency waveform. The targets in the database consist of four variants of two 1.7m-long models of T-64 and T-72 tanks. The gun, the turret position and the depression angle are varied to form 26 different sequences of images. The emitted signal spanned the frequency range from 13 GHz to 18 GHz to achieve a bandwidth of 5 GHz sampled with 4001 frequency points. The resolution obtained with respect to the size of the model targets is comparable to typical values obtained using SAR airborne systems. Single polarized images (Horizontal-Horizontal) are generated using the backprojection algorithm.3 A total of 1480 images are produced using a 20° integration angle. The images in the dataset are organized in a suggested training and testing set to facilitate a standard evaluation of SAR ATR algorithms.

Autoantibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity toward cultured endothelial cells.

PubMed Central

Savage, C. O.; Pottinger, B. E.; Gaskin, G.; Pusey, C. D.; Pearson, J. D.

1992-01-01

The ability of vasculitis-associated anti-neutrophil cytoplasm antibodies (ANCA) to activate neutrophils and mediate release of radiolabel from 111Indium-labeled cultured human umbilical vein endothelial cells (HUVEC) was determined as a measure of the potential cytotoxicity of ANCA-activated neutrophils against vascular endothelium. Priming of neutrophils with low doses of phorbol 12-myristate 13-acetate (PMA) (1 ng/ml) and ionomycin (0.1 mumol/1) was required, together with pretreatment of endothelial cells with BCNU (1,3-bis-[2-chloroethyl]-1-nitrosourea; 0.26 mmol/l). Under these conditions and using a 4-hour serum-free assay system, mouse monoclonal antibodies (MAb) to the target autoantigens proteinase-3 (Pr-3) and myeloperoxidase (MPO) mediated enhanced release of 111Indium from HUVEC compared with control MAb. Human IgG Fab2 C-ANCA (recognizing Pr-3) and P-ANCA (recognizing MPO) did likewise. Preactivation of HUVEC with TNF (50 U/ml, 4 hr) enhanced the release of 111Indium from HUVEC generated by neutrophils activated with anti-Pr-3 and anti-MPO MAb. These data support the suggestion that activation of neutrophils by ANCA within the vascular lumen may contribute to endothelial cell injury. PMID:1323218

Molecular Imaging of Vasa Vasorum Neovascularization via DEspR-targeted Contrast-enhanced Ultrasound Micro-imaging in Transgenic Atherosclerosis Rat Model

PubMed Central

Decano, Julius L.; Moran, Anne Marie; Ruiz-Opazo, Nelson; Herrera, Victoria L. M.

2011-01-01

Purpose Given that carotid vasa vasorum neovascularization is associated with increased risk for stroke and cardiac events, the present in vivo study was designed to investigate molecular imaging of carotid artery vasa vasorum neovascularization via target-specific contrast-enhanced ultrasound (CEU) micro-imaging. Procedures Molecular imaging was performed in male transgenic rats with carotid artery disease and non-transgenic controls using dual endothelin1/VEGFsp receptor (DEspR)-targeted microbubbles (MBD) and the Vevo770 micro-imaging system and CEU imaging software. Results DEspR-targeted CEU-positive imaging exhibited significantly higher contrast intensity signal (CIS)-levels and pre-/post-destruction CIS-differences in seven of 13 transgenic rats, in contrast to significantly lower CIS-levels and differences in control isotype-targeted microbubble (MBC)-CEU imaging (n =8) and in MBD CEU-imaging of five non-transgenic control rats (P<0.0001). Ex vivo immunofluorescence analysis demonstrated binding of MBD to DEspR-positive endothelial cells; and association of DEspR-targeted increased contrast intensity signals with DEspR expression in vasa vasorum neovessel and intimal lesions. In vitro analysis demonstrated dose-dependent binding of MBD to DEspR-positive human endothelial cells with increasing %cells bound and number of MBD per cell, in contrast to MBC or non-labeled microbubbles (P<0.0001). Conclusion In vivo DEspR-targeted molecular imaging detected increased DEspR-expression in carotid artery lesions and in expanded vasa vasorum neovessels in transgenic rats with carotid artery disease. Future studies are needed to determine predictive value for stroke or heart disease in this transgenic atherosclerosis rat model and translational applications. PMID:20972637

Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

PubMed Central

Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

2012-01-01

Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

NASA Astrophysics Data System (ADS)

Ballard, John R.; Casper, Andrew J.; Liu, Dalong; Haritonova, Alyona; Shehata, Islam A.; Troutman, Mitchell; Ebbini, Emad S.

2012-11-01

A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for

Astrophysical targets of the Fresnel diffractive imager

NASA Astrophysics Data System (ADS)

Koechlin, L.; Deba, P.; Raksasataya, T.

2017-11-01

The Fresnel Diffractive imager is an innovative concept of distributed space telescope, for high resolution (milli arc-seconds) spectro-imaging in the IR, visible and UV domains. This paper presents its optical principle and the science that can be done on potential astrophysical targets. The novelty lies in the primary optics: a binary Fresnel array, akin to a binary Fresnel zone plate. The main interest of this approach is the relaxed manufacturing and positioning constraints. While having the resolution and imaging capabilities of lens or mirrors of equivalent size, no optical material is involved in the focusing process: just vacuum. A Fresnel array consists of millions void subapertures punched into a large and thin opaque membrane, that focus light by diffraction into a compact and highly contrasted image. The positioning law of the aperture edges drives the image quality and contrast. This optical concept allows larger and lighter apertures than solid state optics, aiming to high angular resolution and high dynamic range imaging, in particular for UV applications. Diffraction focusing implies very long focal distances, up to dozens of kilometers, which requires at least a two-vessel formation flying in space. The first spacecraft, "the Fresnel Array spacecraft", holds the large punched foil: the Fresnel Array. The second, the "Receiver spacecraft" holds the field optics and focal instrumentation. A chromatism correction feature enables moderately large (20%) relative wavebands, and fields of a few to a dozen arc seconds. This Fresnel imager is adapted to high contrast stellar environments: dust disks, close companions and (we hope) exoplanets. Specific to the particular grid-like pattern of the primary focusing zone plate, is the very high dynamic range achieved in the images, in the case of compact objects. Large stellar photospheres may also be mapped with Fresnel arrays of a few meters opertaing in the UV. Larger and more complex fields can be imaged with

Application of passive imaging polarimetry in the discrimination and detection of different color targets of identical shapes using color-blind imaging sensors

NASA Astrophysics Data System (ADS)

El-Saba, A. M.; Alam, M. S.; Surpanani, A.

2006-05-01

Important aspects of automatic pattern recognition systems are their ability to efficiently discriminate and detect proper targets with low false alarms. In this paper we extend the applications of passive imaging polarimetry to effectively discriminate and detect different color targets of identical shapes using color-blind imaging sensor. For this case of study we demonstrate that traditional color-blind polarization-insensitive imaging sensors that rely only on the spatial distribution of targets suffer from high false detection rates, especially in scenarios where multiple identical shape targets are present. On the other hand we show that color-blind polarization-sensitive imaging sensors can successfully and efficiently discriminate and detect true targets based on their color only. We highlight the main advantages of using our proposed polarization-encoded imaging sensor.

Urate as a Physiological Substrate for Myeloperoxidase

PubMed Central

Meotti, Flavia C.; Jameson, Guy N. L.; Turner, Rufus; Harwood, D. Tim; Stockwell, Samantha; Rees, Martin D.; Thomas, Shane R.; Kettle, Anthony J.

2011-01-01

Urate and myeloperoxidase (MPO) are associated with adverse outcomes in cardiovascular disease. In this study, we assessed whether urate is a likely physiological substrate for MPO and if the products of their interaction have the potential to exacerbate inflammation. Urate was readily oxidized by MPO and hydrogen peroxide to 5-hydroxyisourate, which decayed to predominantly allantoin. The redox intermediates of MPO were reduced by urate with rate constants of 4.6 × 105 m−1 s−1 for compound I and 1.7 × 104 m−1 s−1 for compound II. Urate competed with chloride for oxidation by MPO and at hyperuricemic levels is expected to be a substantive substrate for the enzyme. Oxidation of urate promoted super-stoichiometric consumption of glutathione, which indicates that it is converted to a free radical intermediate. In combination with superoxide and hydrogen peroxide, MPO oxidized urate to a reactive hydroperoxide. This would form by addition of superoxide to the urate radical. Urate also enhanced MPO-dependent consumption of nitric oxide. In human plasma, stimulated neutrophils produced allantoin in a reaction dependent on the NADPH oxidase, MPO and superoxide. We propose that urate is a physiological substrate for MPO that is oxidized to the urate radical. The reactions of this radical with superoxide and nitric oxide provide a plausible link between urate and MPO in cardiovascular disease. PMID:21266577

Highly selective luminescent nanostructures for mitochondrial imaging and targeting

NASA Astrophysics Data System (ADS)

Fanizza, E.; Iacobazzi, R. M.; Laquintana, V.; Valente, G.; Caliandro, G.; Striccoli, M.; Agostiano, A.; Cutrignelli, A.; Lopedota, A.; Curri, M. L.; Franco, M.; Depalo, N.; Denora, N.

2016-02-01

Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents.Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino

Ultrasonic backscatter imaging by shear-wave-induced echo phase encoding of target locations.

PubMed

McAleavey, Stephen

2011-01-01

We present a novel method for ultrasound backscatter image formation wherein lateral resolution of the target is obtained by using traveling shear waves to encode the lateral position of targets in the phase of the received echo. We demonstrate that the phase modulation as a function of shear wavenumber can be expressed in terms of a Fourier transform of the lateral component of the target echogenicity. The inverse transform, obtained by measurements of the phase modulation over a range of shear wave spatial frequencies, yields the lateral scatterer distribution. Range data are recovered from time of flight as in conventional ultrasound, yielding a B-mode-like image. In contrast to conventional ultrasound imaging, where mechanical or electronic focusing is used and lateral resolution is determined by aperture size and wavelength, we demonstrate that lateral resolution using the proposed method is independent of the properties of the aperture. Lateral resolution of the target is achieved using a stationary, unfocused, single-element transducer. We present simulated images of targets of uniform and non-uniform shear modulus. Compounding for speckle reduction is demonstrated. Finally, we demonstrate image formation with an unfocused transducer in gelatin phantoms of uniform shear modulus.

Infrared and visible image fusion with the target marked based on multi-resolution visual attention mechanisms

NASA Astrophysics Data System (ADS)

Huang, Yadong; Gao, Kun; Gong, Chen; Han, Lu; Guo, Yue

2016-03-01

During traditional multi-resolution infrared and visible image fusion processing, the low contrast ratio target may be weakened and become inconspicuous because of the opposite DN values in the source images. So a novel target pseudo-color enhanced image fusion algorithm based on the modified attention model and fast discrete curvelet transformation is proposed. The interesting target regions are extracted from source images by introducing the motion features gained from the modified attention model, and source images are performed the gray fusion via the rules based on physical characteristics of sensors in curvelet domain. The final fusion image is obtained by mapping extracted targets into the gray result with the proper pseudo-color instead. The experiments show that the algorithm can highlight dim targets effectively and improve SNR of fusion image.

Preliminary Quantification of Image Color Gradient on Genesis Concentrator Silicon Carbine Target 60001

NASA Technical Reports Server (NTRS)

Allton, J. H.; Calaway, M. J.; Rodriquez, M. C.

2008-01-01

The Genesis spacecraft concentrator was a device to focus solar wind ions onto a 6-cm diameter target area, thus concentrating the solar wind by 20X [1]. The target area was comprised of 4 quadrants held in place by a gold-coated stainless steel "cross" (Fig. 1). To date, two SiC and one chemical vapor deposited (CVD) quadrants have been imaged at 5X using a Leica DM-6000M in autoscan mode. Complete imaging of SiC sample 60001 required 1036 images. The mosaic of images is shown in Fig. 2 and position of analyzed areas in Fig. 3. This mosaic imaging is part of the curatorial documentation of surface condition and mapping of contamination. Higher magnification (50X) images of selected areas of the target and individual contaminant particles are compiled into reports which may be requested from the Genesis Curator [2].

RGD peptide-targeted polyethylenimine-entrapped gold nanoparticles for targeted CT imaging of an orthotopic model of human hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Zhou, Benqing; Wang, Meng; Zhou, Feifan; Song, Jun; Qu, Junle; Chen, Wei R.

2018-02-01

We report the synthesis and characterization of arginine-glycine-aspartic acid (RGD) peptide-targeted polyethylenimine (PEI)-entrapped gold nanoparticles (RGD-Au PENPs) for targeted CT imaging of hepatic carcinomas in situ. In this work, PEI sequentially modified with polyethylene glycol (PEG), and RGD linked-PEG was used as a nanoplatform to prepare AuNPs, followed by complete acetylation of PEI surface amines. We showed that the designed RGD-Au PENPs were colloidally stable and biocompatible in the given concentration range, and could be specifically taken up by αvβ3 integrin-overexpressing liver cancer cells in vitro. Furthermore, in vivo CT imaging results revealed that the particles displayed a great contrast enhancement of hepatic carcinomas region, and could target to hepatic carcinomas region in situ. With the proven biodistribution and histological examinations in vivo, the synthesized RGD-Au PENPs show a great formulation to be used as a contrast agent for targeted CT imaging of different αvβ3 integrin receptoroverexpressing tumors.

Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging.

PubMed

Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Tu, Zhui; Li, Lang; Tong, Haipeng; Xu, Yang; Li, Rui; Fang, Kejing

2015-01-01

To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles.

EGFR Targeted Theranostic Nanoemulsion For Image-Guided Ovarian Cancer Therapy

PubMed Central

Ganta, Srinivas; Singh, Amit; Kulkarni, Praveen; Keeler, Amanda W.; Piroyan, Aleksandr; Sawant, Rupa R.; Patel, Niravkumar R.; Davis, Barbara; Ferris, Craig; O’Neal, Sara; Zamboni, William; Amiji, Mansoor M.; Coleman, Timothy P.

2015-01-01

Purpose Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide. Methods The surface of the nanoemulsion is annotated with an endothelial growth factor receptor (EGFR) binding peptide to improve targeting ability and gadolinium to provide diagnostic capability for image-guided therapy of EGFR overexpressing ovarian cancers. A high shear microfludization process was employed to produce the formulation with particle size below 150 nm. Results Pharmacokinetic study showed a prolonged blood platinum and gadolinium levels with nanoemulsions in nu/nu mice. The theranostic nanoemulsions also exhibited less toxicity and enhanced the survival time of mice as compared to an equivalent cisplatin treatment. Conclusions Magnetic resonance imaging (MRI) studies indicate the theranostic nanoemulsions were effective contrast agents and could be used to track accumulation in a tumor. The MRI study additionally indicate that significantly more EGFR-targeted theranostic nanoemulsion accumulated in a tumor than non-targeted nanoemulsuion providing the feasibility of using a targeted theranostic agent in conjunction with MRI to image disease loci and quantify the disease progression. PMID:25732960

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

PubMed

Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

2016-05-05

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

Hapten-derivatized nanoparticle targeting and imaging of gene expression by multimodality imaging systems.

PubMed

Cheng, C-M; Chu, P-Y; Chuang, K-H; Roffler, S R; Kao, C-H; Tseng, W-L; Shiea, J; Chang, W-D; Su, Y-C; Chen, B-M; Wang, Y-M; Cheng, T-L

2009-01-01

Non-invasive gene monitoring is important for most gene therapy applications to ensure selective gene transfer to specific cells or tissues. We developed a non-invasive imaging system to assess the location and persistence of gene expression by anchoring an anti-dansyl (DNS) single-chain antibody (DNS receptor) on the cell surface to trap DNS-derivatized imaging probes. DNS hapten was covalently attached to cross-linked iron oxide (CLIO) to form a 39+/-0.5 nm DNS-CLIO nanoparticle imaging probe. DNS-CLIO specifically bound to DNS receptors but not to a control single-chain antibody receptor. DNS-CLIO (100 microM Fe) was non-toxic to both B16/DNS (DNS receptor positive) and B16/phOx (control receptor positive) cells. Magnetic resonance (MR) imaging could detect as few as 10% B16/DNS cells in a mixture in vitro. Importantly, DNS-CLIO specifically bound to a B16/DNS tumor, which markedly reduced signal intensity. Similar results were also shown with DNS quantum dots, which specifically targeted CT26/DNS cells but not control CT26/phOx cells both in vitro and in vivo. These results demonstrate that DNS nanoparticles can systemically monitor the expression of DNS receptor in vivo by feasible imaging systems. This targeting strategy may provide a valuable tool to estimate the efficacy and specificity of different gene delivery systems and optimize gene therapy protocols in the clinic.

Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles.

PubMed

Blanco, Víctor M; Chu, Zhengtao; LaSance, Kathleen; Gray, Brian D; Pak, Koon Yan; Rider, Therese; Greis, Kenneth D; Qi, Xiaoyang

2016-05-31

Multimodal tumor imaging with targeted nanoparticles potentially offers both enhanced specificity and sensitivity, leading to more precise cancer diagnosis and monitoring. We describe the synthesis and characterization of phenol-substituted, lipophilic orange and far-red fluorescent dyes and a simple radioiodination procedure to generate a dual (optical and nuclear) imaging probe. MALDI-ToF analyses revealed high iodination efficiency of the lipophilic reporters, achieved by electrophilic aromatic substitution using the chloramide 1,3,4,6-tetrachloro-3α,6α-diphenyl glycoluril (Iodogen) as the oxidizing agent in an organic/aqueous co-solvent mixture. Upon conjugation of iodine-127 or iodine-124-labeled reporters to tumor-targeting SapC-DOPS nanovesicles, optical (fluorescent) and PET imaging was performed in mice bearing intracranial glioblastomas. In addition, tumor vs non-tumor (normal brain) uptake was compared using iodine-125. These data provide proof-of-principle for the potential value of SapC-DOPS for multimodal imaging of glioblastoma, the most aggressive primary brain tumor.

Inhibitive Effects of Quercetin on Myeloperoxidase-Dependent Hypochlorous Acid Formation and Vascular Endothelial Injury.

PubMed

Lu, Naihao; Sui, Yinhua; Tian, Rong; Peng, Yi-Yuan

2018-05-16

Myeloperoxidase (MPO) from activated neutrophils plays important roles in multiple human inflammatory diseases by catalyzing the formation of powerful oxidant hypochlorous acid (HOCl). As a major flavonoid in the human diet, quercetin has been suggested to act as antioxidant and anti-inflammatory agent in vitro and in vivo. In this study, we showed that quercetin inhibited MPO-mediated HOCl formation (75.0 ± 6.2% for 10 μM quercetin versus 100 ± 5.2% for control group, P < 0.01) and cytotoxicity to endothelial cells in vitro, while this flavonoid was nontoxic to endothelial cell cultures ( P > 0.05, all cases). Moreover, quercetin inhibited HOCl generation by stimulated neutrophils (a rich source of MPO) and protected endothelial cells from neutrophils-induced injury. Furthermore, quercetin could inhibit HOCl-induced endothelial dysfunction such as loss of cell viability, and decrease of nitric oxide formation in endothelial cells ( P < 0.05, all cases). Consistent with these in vitro data, quercetin attenuated lipopolysaccharide-induced endothelial dysfunction and increase of MPO activity in mouse aortas, while this flavonoid could protect against HOCl-mediated endothelial dysfunction in isolated aortas ( P < 0.05). Therefore, it was proposed that quercetin attenuated endothelial injury in inflammatory vasculature via inhibition of vascular-bound MPO-mediated HOCl formation or scavenging of HOCl. These data indicate that quercetin is a nontoxic inhibitor of MPO activity and MPO/neutrophils-induced cytotoxicity in endothelial cells and may be useful for targeting MPO-dependent vascular disease and inflammation.

Immunomagnetic separation of human myeloperoxidase using an antibody-mimicking peptide identified by phage display.

PubMed

Yun, Soi; Ryu, Hyunmin; Lee, E K

2017-09-10

Phage display biopanning is a powerful in vitro selection process for screening and identifying peptides that bind to a target protein of interest. With the aim of replacing antibodies in immuno-diagnostic applications, we identified peptides whose binding characteristics mimicked those of anti-human myeloperoxidase (hMPO), a biomarker for acute cardiac diseases. Based on ELISA results from four phage clones, we selected and chemically synthesized a 12-mer peptide (SYIEPPERHRHR). Quartz crystal microbalance and surface plasmon resonance analyses revealed that the molar binding equilibrium ratio of the synthesized peptide was 0.023, approximately 43-fold lower than that of the anti-hMPO antibody. The dissociation constant (K d ) was 57nM, which was comparable to that of the native antibody (83nM). Next, we biotinylated the peptide at its N-terminus and attached the biotinylated peptide to the surface of streptavidin-coated magnetic particles to assess its ability to selectively capture hMPO. The binding equilibrium data were similar to the previous analyses; specifically, around 0.021mol peptide bound to 1mol of hMPO. Antigen capture was found to be selective and to be relatively little influenced by the presence of human serum albumin (HSA), an abundant constituent of serum. Our work demonstrates the potential of immunomagnetic isolation to achieve selective capture of a low-concentration antigen from complex solutions such as serum. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoacoustic imaging of hepatocellular carcinoma targeting gold nanoshells (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhou, Quan; Chen, Yan; Li, Zhao; Zhou, Juan; Duan, Xiyu; Wang, Thomas D.

2017-02-01

Plasmonic gold nanoshell (GNS) probe penetrates into tumors for deep imaging, enables superior photoacoustic contrast. Glypican-3 (GPC3) specific peptide (Kd = 71 nM) conjugated gold nanoshell (λabs=770nm) was used to detect HCC xenograft tumors in mice with photoacoustic imaging. This targeting probe demonstrated tumor uptake after 1 hr and cleared in 12 hrs. Images at a mean (±SD) depth of 9.7±1.4 mm from 0 to 2.1 cm beneath the skin revealed increased PA signal from tumors. Highest tumor uptake and tumor to normal tissue ratio occurred at 2 hrs post injection (T/B = 4.45±0.22, n = 8). Molecular targeting GNS showed potential as a simple, effective and rapid technique for noninvasive in vivo monitoring HCC tumor growth and GPC3 expression.

Target coverage in image-guided stereotactic body radiotherapy of liver tumors.

PubMed

Wunderink, Wouter; Méndez Romero, Alejandra; Vásquez Osorio, Eliana M; de Boer, Hans C J; Brandwijk, René P; Levendag, Peter C; Heijmen, Ben J M

2007-05-01

To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV(+)) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV(+), derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full (> or = 99%) ITV(+) coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small (< or = 2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal imaging.

Acoustical imaging of high-frequency elastic responses of targets

NASA Astrophysics Data System (ADS)

Morse, Scot F.; Hefner, Brian T.; Marston, Philip L.

2002-05-01

Acoustical imaging was used to investigate high-frequency elastic responses to sound of two targets in water. The backscattering of broadband bipolar acoustic pulses by a truncated cylindrical shell was recorded over a wide range of tilt angles [S. F. Morse and P. L. Marston, ``Backscattering of transients by tilted truncated cylindrical shells: time-frequency identification of ray contributions from measurements,'' J. Acoust. Soc. Am. (in press)]. This data set was used to form synthetic aperture images of the target based on the data within different angular apertures. Over a range of viewing angles, the visibility of the cylinder's closest rear corner was significantly enhanced by the meridional flexural wave contribution to the backscattering. In another experiment, the time evolution of acoustic holographic images was used to explore the response of tilted elastic circular disks to tone bursts having frequencies of 250 and 300 kHz. For different tilt angles, specific responses that enhance the backscattering were identified from the time evolution of the images [B. T. Hefner and P. L. Marston, Acoust. Res. Lett. Online 2, 55-60 (2001)]. [Work supported by ONR.

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

PubMed Central

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R.; Dogra, Prashant; Melancon, Marites P.; Stafford, R. Jason; Miyazono, Kohei; Gelovani, Juri G.; Kataoka, Kazunori; Brinker, C. Jeffrey; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

2016-01-01

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

PubMed

Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-16

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase

PubMed Central

1978-01-01

Ethylene formation from the thioethers, beta-methylthiopropionaldehyde (methional) and 2-keto-4-thiomethylbutyric acid by phagocytosing polymorphonuclear leukocytes (PMNs) was found to be largely dependent on myeloperoxidase (MPO). Conversion was less than 10% of normal when MPO-deficient PMNs were employed; formation by normal PMNs was inhibited by the peroxidase inhibitors, azide, and cyanide, and a model system consisting of MPO, H2O2, chloride (or bromide) and EDTA was found which shared many of the properties of the predominant PMN system. MPO-independent mechanisms of ethylene formation were also identified. Ethylene formation from methional by phagocytosing eosinophils and by H2O2 in the presence or absence of catalase was stimulated by azide. The presence of MPO-independent, azide-stimulable systems in the PMN preparations was suggested by the azide stimulation of ethylene formation from methional when MPO-deficient leukocytes were employed. Ethylene formation by dye-sensitized photooxidation was also demonstrated and evidence obtained for the involvement of singlet oxygen (1O2). These findings are discussed in relation to the participation of H2O2, hydroxyl radicals, the superoxide anion and 1O2 in the formation of ethylene by PMNs and by the MPO model system. PMID:212502

A novel neural network based image reconstruction model with scale and rotation invariance for target identification and classification for Active millimetre wave imaging

NASA Astrophysics Data System (ADS)

Agarwal, Smriti; Bisht, Amit Singh; Singh, Dharmendra; Pathak, Nagendra Prasad

2014-12-01

Millimetre wave imaging (MMW) is gaining tremendous interest among researchers, which has potential applications for security check, standoff personal screening, automotive collision-avoidance, and lot more. Current state-of-art imaging techniques viz. microwave and X-ray imaging suffers from lower resolution and harmful ionizing radiation, respectively. In contrast, MMW imaging operates at lower power and is non-ionizing, hence, medically safe. Despite these favourable attributes, MMW imaging encounters various challenges as; still it is very less explored area and lacks suitable imaging methodology for extracting complete target information. Keeping in view of these challenges, a MMW active imaging radar system at 60 GHz was designed for standoff imaging application. A C-scan (horizontal and vertical scanning) methodology was developed that provides cross-range resolution of 8.59 mm. The paper further details a suitable target identification and classification methodology. For identification of regular shape targets: mean-standard deviation based segmentation technique was formulated and further validated using a different target shape. For classification: probability density function based target material discrimination methodology was proposed and further validated on different dataset. Lastly, a novel artificial neural network based scale and rotation invariant, image reconstruction methodology has been proposed to counter the distortions in the image caused due to noise, rotation or scale variations. The designed neural network once trained with sample images, automatically takes care of these deformations and successfully reconstructs the corrected image for the test targets. Techniques developed in this paper are tested and validated using four different regular shapes viz. rectangle, square, triangle and circle.

Gaussian mixture models-based ship target recognition algorithm in remote sensing infrared images

NASA Astrophysics Data System (ADS)

Yao, Shoukui; Qin, Xiaojuan

2018-02-01

Since the resolution of remote sensing infrared images is low, the features of ship targets become unstable. The issue of how to recognize ships with fuzzy features is an open problem. In this paper, we propose a novel ship target recognition algorithm based on Gaussian mixture models (GMMs). In the proposed algorithm, there are mainly two steps. At the first step, the Hu moments of these ship target images are calculated, and the GMMs are trained on the moment features of ships. At the second step, the moment feature of each ship image is assigned to the trained GMMs for recognition. Because of the scale, rotation, translation invariance property of Hu moments and the power feature-space description ability of GMMs, the GMMs-based ship target recognition algorithm can recognize ship reliably. Experimental results of a large simulating image set show that our approach is effective in distinguishing different ship types, and obtains a satisfactory ship recognition performance.

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

NASA Astrophysics Data System (ADS)

Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G.; Yun, Dong Soo; Belcher, Angela M.; Kelly, Kimberly A.

2012-10-01

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer.

PubMed

Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G; Yun, Dong Soo; Belcher, Angela M; Kelly, Kimberly A

2012-10-01

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

Target-cancer cell specific activatable fluorescence imaging Probes: Rational Design and in vivo Applications

PubMed Central

Kobayashi, Hisataka; Choyke, Peter L.

2010-01-01

CONSPECTUS Conventional imaging methods, such as angiography, computed tomography, magnetic resonance imaging and radionuclide imaging, rely on contrast agents (iodine, gadolinium, radioisotopes) that are “always on”. While these agents have proven clinically useful, they are not sufficiently sensitive because of the inadequate target to background ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, i.e. only “turned on” under certain conditions. These probes can be designed to emit signal only after binding a target tissue, greatly increasing sensitivity and specificity in the detection of disease. There are two basic types of activatable fluorescence probes; 1) conventional enzymatically activatable probes, which exist in the quenched state until activated by enzymatic cleavage mostly outside of the cells, and 2) newly designed target-cell specific activatable probes, which are quenched until activated in targeted cells by endolysosomal processing that results when the probe binds specific cell-surface receptors and is subsequently internalized. Herein, we present a review of the rational design and in vivo applications of target-cell specific activatable probes. Designing these probes based on their photo-chemical (e.g. activation strategy), pharmacological (e.g. biodistribution), and biological (e.g. target specificity) properties has recently allowed the rational design and synthesis of target-cell specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photo-chemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include: self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation and photon-induced electron transfer (PeT). In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal

Targeted flyby images of propellers in Saturn's A ring

NASA Astrophysics Data System (ADS)

Tiscareno, Matthew S.; Baker, Emily J.; the Cassini ISS Team

2017-06-01

As part of its two-part end-of-mission maneuvers, the Cassini has targeted three "propeller moons" for close-range flybys, obtaining images that greatly improve on all previous images in terms of resolution and detailed structure. Propeller moons are ~1 km in size and are embedded in the disk of Saturn's A ring (Tiscareno et al. 2010, ApJL). Unlike the moons Pan and Daphnis, propeller moons have insufficient mass to carve out a fully circumferential gap; instead, we see a propeller-shaped disturbance around the moon (which itself is unseen) as the moon's attempted gap is filled back in, due to the dynamical viscosity of the ring particles.The Cassini Imaging Science Subsystem (ISS) has obtained images of the propeller moon "Santos-Dumont" on both the lit and unlit sides of the rings, and of "Earhart" on the lit side. As of this writing, a final targeted flyby of "Bleriot" on the unlit side of the rings has yet to take place. The resolution of these images is at least 3x to 4x better than those of nearly all previous propeller images, and at least 2x better than those of a small handful of the best previous propeller images.We will present maps of of the propeller structures, with enhanced ability to convert brightness to optical depth and surface density due to information from both the lit and unlit sides of the rings. The images contain more complex structure than is predicted by simple models, which we will describe, and for which we will comment on likely explanations. The central moonlet of each propeller (which has never been seen) should be a couple of pixels across, but we cannot confirm whether they are seen in these images or whether they are obscured by stirred-up ring material.

Target-oriented imaging of hydraulic fractures by applying the staining algorithm for downhole microseismic migration

NASA Astrophysics Data System (ADS)

Lin, Ye; Zhang, Haijiang; Jia, Xiaofeng

2018-03-01

For microseismic monitoring of hydraulic fracturing, microseismic migration can be used to image the fracture network with scattered microseismic waves. Compared with conventional microseismic location-based fracture characterization methods, microseismic migration can better constrain the stimulated reservoir volume regardless of the completeness of detected and located microseismic sources. However, the imaging results from microseismic migration may suffer from the contamination of other structures and thus the target fracture zones may not be illuminated properly. To solve this issue, in this study we propose a target-oriented staining algorithm for microseismic reverse-time migration. In the staining algorithm, the target area is first stained by constructing an imaginary velocity field and then a synchronized source wavefield only concerning the target structure is produced. As a result, a synchronized image from imaging with the synchronized source wavefield mainly contains the target structures. Synthetic tests based on a downhole microseismic monitoring system show that the target-oriented microseismic reverse-time migration method improves the illumination of target areas.

Targeting of deep-brain structures in nonhuman primates using MR and CT Images

NASA Astrophysics Data System (ADS)

Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

2015-03-01

In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.

Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging

PubMed Central

Guo, Yanli; Tu, Zhui; Li, Lang; Tong, Haipeng; Xu, Yang; Li, Rui; Fang, Kejing

2015-01-01

To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The “targeted” nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles. PMID:26111008

Total variation-based method for radar coincidence imaging with model mismatch for extended target

NASA Astrophysics Data System (ADS)

Cao, Kaicheng; Zhou, Xiaoli; Cheng, Yongqiang; Fan, Bo; Qin, Yuliang

2017-11-01

Originating from traditional optical coincidence imaging, radar coincidence imaging (RCI) is a staring/forward-looking imaging technique. In RCI, the reference matrix must be computed precisely to reconstruct the image as preferred; unfortunately, such precision is almost impossible due to the existence of model mismatch in practical applications. Although some conventional sparse recovery algorithms are proposed to solve the model-mismatch problem, they are inapplicable to nonsparse targets. We therefore sought to derive the signal model of RCI with model mismatch by replacing the sparsity constraint item with total variation (TV) regularization in the sparse total least squares optimization problem; in this manner, we obtain the objective function of RCI with model mismatch for an extended target. A more robust and efficient algorithm called TV-TLS is proposed, in which the objective function is divided into two parts and the perturbation matrix and scattering coefficients are updated alternately. Moreover, due to the ability of TV regularization to recover sparse signal or image with sparse gradient, TV-TLS method is also applicable to sparse recovering. Results of numerical experiments demonstrate that, for uniform extended targets, sparse targets, and real extended targets, the algorithm can achieve preferred imaging performance both in suppressing noise and in adapting to model mismatch.

Megavoltage planar and cone-beam imaging with low-Z targets: dependence of image quality improvement on beam energy and patient separation.

PubMed

Robar, James L; Connell, Tanner; Huang, Weihong; Kelly, Robin G

2009-09-01

The purpose of this study is to investigate the improvement of megavoltage planar and cone-beam CT (CBCT) image quality with the use of low atomic number (Z) external targets in the linear accelerator. In this investigation, two experimental megavoltage imaging beams were generated by using either 3.5 or 7.0 MeV electrons incident on aluminum targets installed above the level of the carousel in a linear accelerator (2100EX, Varian Medical, Inc., Palo Alto, CA). Images were acquired using an amorphous silicon detector panel. Contrast-to-noise ratio (CNR) in planar and CBCT images was measured as a function of dose and a comparison was made between the imaging beams and the standard 6 MV therapy beam. Phantoms of variable diameter were used to examine the loss of contrast due to beam hardening. Porcine imaging was conducted to examine qualitatively the advantages of the low-Z target approach in CBCT. In CBCT imaging CNR increases by factors as high as 2.4 and 4.3 for the 7.0 and 3.5 MeV/Al beams, respectively, compared to images acquired with 6 MV. Similar factors of improvement are observed in planar imaging. For the imaging beams, beam hardening causes a significant loss of the contrast advantage with increasing phantom diameter; however, for the 3.5 MeV/Al beam and a phantom diameter of 25 cm, a contrast advantage remains, with increases of contrast by factors of 1.5 and 3.4 over 6 MV for bone and lung inhale regions, respectively. The spatial resolution is improved slightly in CBCT images for the imaging beams. CBCT images of a porcine cranium demonstrate qualitatively the advantages of the low-Z target approach, showing greater contrast between tissues and improved visibility of fine detail. The use of low-Z external targets in the linear accelerator improves megavoltage planar and CBCT image quality significantly. CNR may be increased by a factor of 4 or greater. Improvement of the spatial resolution is also apparent.

Advances in target imaging of deep Earth structure

NASA Astrophysics Data System (ADS)

Masson, Y.; Romanowicz, B. A.; Clouzet, P.

2015-12-01

A new generation of global tomographic models (Lekić and Romanowicz, 2011; French et al, 2013, 2014) has emerged with the development of accurate numerical wavefield computations in a 3D earth combined with access to enhanced HPC capabilities. These models have sharpened up mantle images and unveiled relatively small scale structures that were blurred out in previous generation models. Fingerlike structures have been found at the base of the oceanic asthenosphere, and vertically oriented broad low velocity plume conduits extend throughout the lower mantle beneath those major hotspots that are located within the perimeter of the deep mantle large low shear velocity provinces (LLSVPs). While providing new insights into our understanding of mantle dynamics, the detailed morphology of these features, requires further efforts to obtain higher resolution images. The focus of our ongoing effort is to develop advanced tomographic methods to image remote regions of the Earth at fine scales. We have developed an approach in which distant sources (located outside of the target region) are replaced by an equivalent set of local sources located at the border of the computational domain (Masson et al., 2014). A limited number of global simulations in a reference 3D earth model is then required. These simulations are computed prior to the regional inversion, while iterations of the model need to be performed only within the region of interest, potentially allowing us to include shorter periods at limited additional computational cost. Until now, the application was limited to a distribution of receivers inside the target region. This is particularly suitable for studies of upper mantle structure in regions with dense arrays (e.g. see our companion presentation Clouzet et al., this Fall AGU). Here we present our latest development that now can include teleseismic data recorded outside the imaged region. This allows us to perform regional waveform tomography in the situation where

Radar correlated imaging for extended target by the combination of negative exponential restraint and total variation

NASA Astrophysics Data System (ADS)

Qian, Tingting; Wang, Lianlian; Lu, Guanghua

2017-07-01

Radar correlated imaging (RCI) introduces the optical correlated imaging technology to traditional microwave imaging, which has raised widespread concern recently. Conventional RCI methods neglect the structural information of complex extended target, which makes the quality of recovery result not really perfect, thus a novel combination of negative exponential restraint and total variation (NER-TV) algorithm for extended target imaging is proposed in this paper. The sparsity is measured by a sequential order one negative exponential function, then the 2D total variation technique is introduced to design a novel optimization problem for extended target imaging. And the proven alternating direction method of multipliers is applied to solve the new problem. Experimental results show that the proposed algorithm could realize high resolution imaging efficiently for extended target.

Multifunctional magnetic nanoparticles for targeted imaging and therapy

PubMed Central

McCarthy, Jason R.; Weissleder, Ralph

2008-01-01

Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials. PMID:18508157

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

PubMed Central

Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G.; Yun, Dong Soo; Belcher, Angela M.; Kelly, Kimberly A.

2014-01-01

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment1. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression2. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand3,4,5 and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells6. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection. PMID:22983492

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

DOE PAGES

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; ...

2016-02-02

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

Preparation of Monoclonal Antibodies and a Simple Myeloperoxidase-Immunosorbent Assay for Detecting Human Myeloperoxidase.

PubMed

Bian, Zhi-Ping; Li, Xiong-Zhi; Wu, Heng-Fang; Xu, Jin-Dan; Gu, Chun-Rong; Chen, Xiang-Jian; Yang, Di

2016-04-01

Myeloperoxidase (MPO), a leukocyte hemoprotein released from neutrophils, is thought to be a potential participant in plaque formation and plaque rupture. Therefore, MPO is regarded as an early marker predicting the risk for atherosclerosis, especially for coronary artery disease and acute coronary syndrome. We generated hybridoma clones 1E3 and 3E8 secreting monoclonal antibodies (mAbs) specific to human MPO. BALB/c mice were immunized with MPO protein purified from human neutrophils. Splenocytes from these mice were fused with the mouse myeloma cell line SP2/0. Based on isotyping of the mAbs, both clones 1E3 and 3E8 were referred to the IgG1 subclass. The specificities of 1E3 and 3E8 were assessed by enzyme-linked immunosorbent assay (ELISA), and only 3E8 was confirmed by western blot. We developed a simple MPO-immunosorbent assay (MPO-ISA) on microplate based on both the immune activity and peroxidase activity of MPO. The mAb secreted by clone 3E8 was chosen as coating antibody to capture the plasma MPO without interfering with the peroxidase activity of MPO. Then, tetramethylbenzidine substrate was added to the microwell directly, catalyzed by captured MPO, and a colored product was formed. The simple MPO-ISA test has a sensitivity of 3.68 ng/mL. The linear concentration of MPO-ISA for commercial MPO standard ranged to 250 ng/mL. The average recovery rate is 101.02%. The imprecision within-day was <10% at three different MPO levels. The imprecision between-day was <10% at low and middle MPO levels and varied to 14.61% at the high MPO level. We found that the established MPO-ISA can detect the plasma MPO from human and cavy, but not from mouse and rat. Compared with the commercial human MPO ELISA assay, the MPO-ISA can be used to detect the natural human MPO protein, but not recombinant MPO polypeptides. The generated mAbs and MPO-ISA test may be useful tools to assess risk for inflammation and cardiac events.

Detecting ship targets in spaceborne infrared image based on modeling radiation anomalies

NASA Astrophysics Data System (ADS)

Wang, Haibo; Zou, Zhengxia; Shi, Zhenwei; Li, Bo

2017-09-01

Using infrared imaging sensors to detect ship target in the ocean environment has many advantages compared to other sensor modalities, such as better thermal sensitivity and all-weather detection capability. We propose a new ship detection method by modeling radiation anomalies for spaceborne infrared image. The proposed method can be decomposed into two stages, where in the first stage, a test infrared image is densely divided into a set of image patches and the radiation anomaly of each patch is estimated by a Gaussian Mixture Model (GMM), and thereby target candidates are obtained from anomaly image patches. In the second stage, target candidates are further checked by a more discriminative criterion to obtain the final detection result. The main innovation of the proposed method is inspired by the biological mechanism that human eyes are sensitive to the unusual and anomalous patches among complex background. The experimental result on short wavelength infrared band (1.560 - 2.300 μm) and long wavelength infrared band (10.30 - 12.50 μm) of Landsat-8 satellite shows the proposed method achieves a desired ship detection accuracy with higher recall than other classical ship detection methods.

PET imaging of T cells: Target identification and feasibility assessment.

PubMed

Auberson, Yves P; Briard, Emmanuelle; Rudolph, Bettina; Kaupmann, Klemen; Smith, Paul; Oberhauser, Berndt

2018-06-01

Imaging T cells using positron emission tomography (PET) would be highly useful for diagnosis and monitoring in immunology and oncology patients. There are however no obvious targets that can be used to develop imaging agents for this purpose. We evaluated several potential target proteins with selective expression in T cells, and for which lead molecules were available: PKC , Lck, ZAP70 and Itk. Ultimately, we focused on Itk (interleukin-2-inducible T cell kinase) and identified a tool molecule with properties suitable for in vivo imaging of T cells, (5aR)-5,5-difluoro-5a-methyl-N-(1-((S)-3-(methylsulfonyl)-phenyl)(tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1,4,4a,5,5a,6-hexahydro-cyclopropa[f]-indazole-3-carboxamide (23). While not having the optimal profile for clinical use, this molecule indicates that it might be possible to develop Itk-selective PET ligands for imaging the distribution of T cells in patients. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Research on spatial-variant property of bistatic ISAR imaging plane of space target

NASA Astrophysics Data System (ADS)

Guo, Bao-Feng; Wang, Jun-Ling; Gao, Mei-Guo

2015-04-01

The imaging plane of inverse synthetic aperture radar (ISAR) is the projection plane of the target. When taking an image using the range-Doppler theory, the imaging plane may have a spatial-variant property, which causes the change of scatter’s projection position and results in migration through resolution cells. In this study, we focus on the spatial-variant property of the imaging plane of a three-axis-stabilized space target. The innovative contributions are as follows. 1) The target motion model in orbit is provided based on a two-body model. 2) The instantaneous imaging plane is determined by the method of vector analysis. 3) Three Euler angles are introduced to describe the spatial-variant property of the imaging plane, and the image quality is analyzed. The simulation results confirm the analysis of the spatial-variant property. The research in this study is significant for the selection of the imaging segment, and provides the evidence for the following data processing and compensation algorithm. Project supported by the National Natural Science Foundation of China (Grant No. 61401024), the Shanghai Aerospace Science and Technology Innovation Foundation, China (Grant No. SAST201240), and the Basic Research Foundation of Beijing Institute of Technology (Grant No. 20140542001).

Myeloperoxidase potentiates nitric oxide-mediated nitrosation.

PubMed

Lakshmi, Vijaya M; Nauseef, William M; Zenser, Terry V

2005-01-21

Nitrosation is an important reaction elicited by nitric oxide (NO). To better understand how nitrosation occurs in biological systems, we assessed the effect of myeloperoxidase (MPO), a mediator of inflammation, on nitrosation observed during NO autoxidation. Nitrosation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; 10 mum) to 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ) was monitored by HPLC. Using the NO donor spermine NONOate at pH 7.4, MPO potentiated N-NO-IQ formation. The minimum effective quantity of necessary components was 8.5 nm MPO, 0.25 mum H(2)O(2)/min, and 0.024 mum NO/min. Autoxidation was only detected at >/=1.2 mum NO/min. MPO potentiation was not affected by a 40-fold excess flux of H(2)O(2) over NO or less than a 2.4-fold excess flux of NO over H(2)O(2). Potentiation was due to an 8.8-fold increased affinity of MPO-derived nitrosating species for IQ. Autoxidation was inhibited by azide, suggesting involvement of the nitrosonium ion, NO(+). MPO potentiation was inhibited by NADH, but not azide, suggesting oxidative nitrosylation with NO(2)(.) or an NO(2)(.)-like species. MPO nonnitrosative oxidation of IQ with 0.3 mm NO(2)(-) at pH 5.5 was inhibited by azide, but not NADH, demonstrating differences between MPO oxidation of IQ with NO compared with NO(2)(-). Using phorbol ester-stimulated human neutrophils, N-NO-IQ formation was increased with superoxide dismutase and inhibited by catalase and NADH, but not NaN(3). This is consistent with nitrosation potentiation by MPO, not peroxynitrite. Increased N-NO-IQ formation was not detected with polymorphonuclear neutrophils from two unrelated MPO-deficient patients. Results suggest that the highly diffusible stable gas NO could initiate nitrosation at sites of neutrophil infiltration.

Study of image matching algorithm and sub-pixel fitting algorithm in target tracking

NASA Astrophysics Data System (ADS)

Yang, Ming-dong; Jia, Jianjun; Qiang, Jia; Wang, Jian-yu

2015-03-01

Image correlation matching is a tracking method that searched a region most approximate to the target template based on the correlation measure between two images. Because there is no need to segment the image, and the computation of this method is little. Image correlation matching is a basic method of target tracking. This paper mainly studies the image matching algorithm of gray scale image, which precision is at sub-pixel level. The matching algorithm used in this paper is SAD (Sum of Absolute Difference) method. This method excels in real-time systems because of its low computation complexity. The SAD method is introduced firstly and the most frequently used sub-pixel fitting algorithms are introduced at the meantime. These fitting algorithms can't be used in real-time systems because they are too complex. However, target tracking often requires high real-time performance, we put forward a fitting algorithm named paraboloidal fitting algorithm based on the consideration above, this algorithm is simple and realized easily in real-time system. The result of this algorithm is compared with that of surface fitting algorithm through image matching simulation. By comparison, the precision difference between these two algorithms is little, it's less than 0.01pixel. In order to research the influence of target rotation on precision of image matching, the experiment of camera rotation was carried on. The detector used in the camera is a CMOS detector. It is fixed to an arc pendulum table, take pictures when the camera rotated different angles. Choose a subarea in the original picture as the template, and search the best matching spot using image matching algorithm mentioned above. The result shows that the matching error is bigger when the target rotation angle is larger. It's an approximate linear relation. Finally, the influence of noise on matching precision was researched. Gaussian noise and pepper and salt noise were added in the image respectively, and the image

Oxidative stress and myeloperoxidase levels in saliva of patients with recurrent aphthous stomatitis.

PubMed

Cağlayan, F; Miloglu, O; Altun, O; Erel, O; Yilmaz, A B

2008-11-01

Recurrent aphthous stomatitis (RAS) is the most common oral ulcerative condition affecting 5-25% of the general population. The aim of this study was to evaluate the oxidative stress parameters in saliva of patients with RAS and to investigate the relationship among these parameters in either group. The study involved 50 patients with RAS of whom 24 were male and 26 were female, and 25 healthy controls of whom 13 were male and 12 were female. There was no statistically significant difference in the salivary total antioxidant capacity, total oxidant status, oxidative stress index levels, and myeloperoxidase activity between patients with RAS and those in the control group. The results show that reactive oxygen species may not play a role in the etiology of RAS.

The Efficacy of Multiparametric Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Risk Classification for Patients with Prostate Cancer on Active Surveillance.

PubMed

Recabal, Pedro; Assel, Melissa; Sjoberg, Daniel D; Lee, Daniel; Laudone, Vincent P; Touijer, Karim; Eastham, James A; Vargas, Hebert A; Coleman, Jonathan; Ehdaie, Behfar

2016-08-01

We determined whether multiparametric magnetic resonance imaging targeted biopsies may replace systematic biopsies to detect higher grade prostate cancer (Gleason score 7 or greater) and whether biopsy may be avoided based on multiparametric magnetic resonance imaging among men with Gleason 3+3 prostate cancer on active surveillance. We identified men with previously diagnosed Gleason score 3+3 prostate cancer on active surveillance who underwent multiparametric magnetic resonance imaging and a followup prostate biopsy. Suspicion for higher grade cancer was scored on a standardized 5-point scale. All patients underwent a systematic biopsy. Patients with multiparametric magnetic resonance imaging regions of interest also underwent magnetic resonance imaging targeted biopsy. The detection rate of higher grade cancer was estimated for different multiparametric magnetic resonance imaging scores with the 3 biopsy strategies of systematic, magnetic resonance imaging targeted and combined. Of 206 consecutive men on active surveillance 135 (66%) had a multiparametric magnetic resonance imaging region of interest. Overall, higher grade cancer was detected in 72 (35%) men. A higher multiparametric magnetic resonance imaging score was associated with an increased probability of detecting higher grade cancer (Wilcoxon-type trend test p <0.0001). Magnetic resonance imaging targeted biopsy detected higher grade cancer in 23% of men. Magnetic resonance imaging targeted biopsy alone missed higher grade cancers in 17%, 12% and 10% of patients with multiparametric magnetic resonance imaging scores of 3, 4 and 5, respectively. Magnetic resonance imaging targeted biopsies increased the detection of higher grade cancer among men on active surveillance compared to systematic biopsy alone. However, a clinically relevant proportion of higher grade cancer was detected using only systematic biopsy. Despite the improved detection of disease progression using magnetic resonance imaging

First Image from a Mars Rover Choosing a Target

NASA Image and Video Library

2010-03-23

This true-color image is the result of the first observation of a target selected autonomously by NASA Mars Exploration Rover Opportunity using newly developed and uploaded software named Autonomous Exploration for Gathering Increased Science, or AEGIS.

Single-domain antibody bioconjugated near-IR quantum dots for targeted cellular imaging of pancreatic cancer.

PubMed

Zaman, Md Badruz; Baral, Toya Nath; Jakubek, Zygmunt J; Zhang, Jianbing; Wu, Xiaohua; Lai, Edward; Whitfield, Dennis; Yu, Kui

2011-05-01

Successful targeted imaging of BxPC3 human pancreatic cancer cells is feasible with near-IR CdTeSe/CdS quantum dots (QDs) functionalized with single-domain antibody (sdAb) 2A3. For specific targeting, sdAbs are superior to conventional antibodies, especially in terms of stability, aggregation, and production cost. The bright CdTeSe/CdS QDs were synthesized to emit in the diagnostic window of 650-900 nm with a narrow emission band. 2A3 was derived from llama and is small in size of 13 kDa, but with fully-functional recognition to the target carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a possible biomarker as a therapeutic target of pancreatic cancer. For compelling imaging, optical may be the most sensible among the various imaging modalities, regarding the sensitivity and cost. This first report on sdAb-conjugated near-IR QDs with high signal to background sensitivity for targeted cellular imaging brings insights into the development of optical molecular imaging for early stage cancer diagnosis.

Use of PET and Other Functional Imaging to Guide Target Delineation in Radiation Oncology.

PubMed

Verma, Vivek; Choi, J Isabelle; Sawant, Amit; Gullapalli, Rao P; Chen, Wengen; Alavi, Abass; Simone, Charles B

2018-06-01

Molecular and functional imaging is increasingly being used to guide radiotherapy (RT) management and target delineation. This review summarizes existing data in several disease sites of various functional imaging modalities, chiefly positron emission tomography/computed tomography (PET/CT), with respect to RT target definition and management. For gliomas, differentiation between postoperative changes and viable tumor is discussed, as well as focal dose escalation and reirradiation. Head and neck neoplasms may also benefit from precise PET/CT-based target delineation, especially for cancers of unknown primary; focal dose escalation is also described. In lung cancer, PET/CT can influence coverage of tumor volumes, dose escalation, and adaptive management. For cervical cancer, PET/CT as an adjunct to magnetic resonance imaging planning is discussed, as are dose escalation and delineation of avoidance targets such as the bone marrow. The emerging role of choline-based PET for prostate cancer and its impact on dose escalation is also described. Lastly, given the essential role of PET/CT for target definition in lymphoma, phase III trials of PET-directed management are reviewed, along with novel imaging modalities. Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Copyright © 2018 Elsevier Inc. All rights reserved.

Artifacts in Radar Imaging of Moving Targets

DTIC Science & Technology

2012-09-01

CA, USA, 2007. [11] B. Borden, Radar imaging of airborne targets: A primer for Applied mathematicians and Physicists . New York, NY: Taylor and... Project (0704–0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE 21 September 2012 3. REPORT TYPE AND DATES COVERED...CW Continuous Wave DAC Digital to Analog Convertor DFT Discrete Fourier Transform FBP Filtered Back Projection FFT Fast Fourier Transform GPS

Target-cancer-cell-specific activatable fluorescence imaging probes: rational design and in vivo applications.

PubMed

Kobayashi, Hisataka; Choyke, Peter L

2011-02-15

Conventional imaging methods, such as angiography, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide imaging, rely on contrast agents (iodine, gadolinium, and radioisotopes, for example) that are "always on." Although these indicators have proven clinically useful, their sensitivity is lacking because of inadequate target-to-background signal ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, that is, only "turned on" under certain conditions. These probes are engineered to emit signal only after binding a target tissue; this design greatly increases sensitivity and specificity in the detection of disease. Current research focuses on two basic types of activatable fluorescence probes. The first developed were conventional enzymatically activatable probes. These fluorescent molecules exist in the quenched state until activated by enzymatic cleavage, which occurs mostly outside of the cells. However, more recently, researchers have begun designing target-cell-specific activatable probes. These fluorophores exist in the quenched state until activated within targeted cells by endolysosomal processing, which results when the probe binds specific receptors on the cell surface and is subsequently internalized. In this Account, we present a review of the rational design and in vivo applications of target-cell-specific activatable probes. In engineering these probes, researchers have asserted control over a variety of factors, including photochemistry, pharmacological profile, and biological properties. Their progress has recently allowed the rational design and synthesis of target-cell-specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photochemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include self-quenching, homo- and hetero-fluorescence resonance

Optoacoustic imaging of gold nanoparticles targeted to breast cancer cells

NASA Astrophysics Data System (ADS)

Eghtedari, Mohammad; Motamedi, Massoud; Popov, Vsevolod L.; Kotov, Nicholas A.; Oraevsky, Alexander A.

2004-07-01

Optoacoustic Tomography (OAT) is a rapidly growing technology that enables noninvasive deep imaging of biological tissues based on their light absorption. In OAT, the interaction of a pulsed laser with tissue increases the temperature of the absorbing components in a confined volume of tissue. Rapid perturbation of the temperature (<1°C) deep within tissue produces weak acoustic waves that easily travel to the surface of the tissue with minor attenuation. Abnormal angiogenesis in a malignant tumor, that increases its blood content, makes a native contrast for optoacoustic imaging; however, the application of OAT for early detection of malignant tumors requires the enhancement of optoacoustic signals originated from tumor by using an exogenous contrast agent. Due to their strong absorption, we have used gold nanoparticles (NP) as a contrast agent. 40nm spherical gold nanoparticles were attached to monoclonal antibody to target cell surface of breast cancer cells. The targeted cancer cells were implanted at depth of 5-6cm within a gelatinous object that optically resembles human breast. Experimental sensitivity measurements along with theoretical analysis showed that our optoacoustic imaging system is capable of detecting a phantom breast tumor with the volume of 0.15ml, which is composed of 25 million NP-targeted cancer cells, at a depth of 5 centimeters in vitro.

Structural and functional imaging for vascular targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Li, Buhong; Gu, Ying; Wilson, Brian C.

2017-02-01

Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

SU-E-J-252: A Motion Algorithm to Extract Physical and Motion Parameters of a Mobile Target in Cone-Beam Computed Tomographic Imaging Retrospective to Image Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, I; Ahmad, S; Alsbou, N

Purpose: A motion algorithm was developed to extract actual length, CT-numbers and motion amplitude of a mobile target imaged with cone-beam-CT (CBCT) retrospective to image-reconstruction. Methods: The motion model considered a mobile target moving with a sinusoidal motion and employed three measurable parameters: apparent length, CT number level and gradient of a mobile target obtained from CBCT images to extract information about the actual length and CT number value of the stationary target and motion amplitude. The algorithm was verified experimentally with a mobile phantom setup that has three targets with different sizes manufactured from homogenous tissue-equivalent gel material embeddedmore » into a thorax phantom. The phantom moved sinusoidal in one-direction using eight amplitudes (0–20mm) and a frequency of 15-cycles-per-minute. The model required imaging parameters such as slice thickness, imaging time. Results: This motion algorithm extracted three unknown parameters: length of the target, CT-number-level, motion amplitude for a mobile target retrospective to CBCT image reconstruction. The algorithm relates three unknown parameters to measurable apparent length, CT-number-level and gradient for well-defined mobile targets obtained from CBCT images. The motion model agreed with measured apparent lengths which were dependent on actual length of the target and motion amplitude. The cumulative CT-number for a mobile target was dependent on CT-number-level of the stationary target and motion amplitude. The gradient of the CT-distribution of mobile target is dependent on the stationary CT-number-level, actual target length along the direction of motion, and motion amplitude. Motion frequency and phase did not affect the elongation and CT-number distributions of mobile targets when imaging time included several motion cycles. Conclusion: The motion algorithm developed in this study has potential applications in diagnostic CT imaging and radiotherapy to

Gastric cancer target detection using near-infrared hyperspectral imaging with chemometrics

NASA Astrophysics Data System (ADS)

Yi, Weisong; Zhang, Jian; Jiang, Houmin; Zhang, Niya

2014-09-01

Gastric cancer is one of the leading causes of cancer death in the world due to its high morbidity and mortality. Hyperspectral imaging (HSI) is an emerging, non-destructive, cutting edge analytical technology that combines conventional imaging and spectroscopy in one single system. The manuscript has investigated the application of near-infrared hyperspectral imaging (900-1700 nm) (NIR-HSI) for gastric cancer detection with algorithms. Major spectral differences were observed in three regions (950-1050, 1150-1250, and 1400-1500 nm). By inspecting cancerous mean spectrum three major absorption bands were observed around 975, 1215 and 1450 nm. Furthermore, the cancer target detection results are consistent and conformed with histopathological examination results. These results suggest that NIR-HSI is a simple, feasible and sensitive optical diagnostic technology for gastric cancer target detection with chemometrics.

Multiple functionalized carbon quantum dots for targeting glioma and tissue imaging

NASA Astrophysics Data System (ADS)

Gao, Lipeng; Zhao, Xiao; Wang, Jing; Wang, Yiting; Yu, Lei; Peng, Hui; Zhu, Jianzhong

2018-01-01

Carbon quantum dots (CQDs) was successfully functionalized with Mal-PEG-NHS linked RGERPPR. They exhibit double functions of both tissue imaging and targeting to brain gliomas. The mean size of the functionalized CQDs about 9.0 ± 2.0 nm. The maximum absorption wavelength of the functionalized CQDs appear at 230 nm. The peak of the fluorescence spectra for the functionalized CQDs is at 460 nm, red shifted by 20 nm comparing with the unmodified CQDs. This may be due to the increased particle size. The functionalized CQDs were successfully applied to imaging and targeting gliomas.

Targeted systemic gene therapy and molecular imaging of cancer contribution of the vascular-targeted AAVP vector.

PubMed

Hajitou, Amin

2010-01-01

Gene therapy and molecular-genetic imaging have faced a major problem: the lack of an efficient systemic gene delivery vector. Unquestionably, eukaryotic viruses have been the vectors of choice for gene delivery to mammalian cells; however, they have had limited success in systemic gene therapy. This is mainly due to undesired uptake by the liver and reticuloendothelial system, broad tropism for mammalian cells causing toxicity, and their immunogenicity. On the other hand, prokaryotic viruses such as bacteriophage (phage) have no tropism for mammalian cells, but can be engineered to deliver genes to these cells. However, phage-based vectors have inherently been considered poor vectors for mammalian cells. We have reported a new generation of vascular-targeted systemic hybrid prokaryotic-eukaryotic vectors as chimeras between an adeno-associated virus (AAV) and targeted bacteriophage (termed AAV/phage; AAVP). In this hybrid vector, the targeted bacteriophage serves as a shuttle to deliver the AAV transgene cassette inserted in an intergenomic region of the phage DNA genome. As a proof of concept, we assessed the in vivo efficacy of vector in animal models of cancer by displaying on the phage capsid the cyclic Arg-Gly-Asp (RGD-4C) ligand that binds to alphav integrin receptors specifically expressed on the angiogenic blood vessels of tumors. The ligand-directed vector was able to specifically deliver imaging and therapeutic transgenes to tumors in mice, rats, and dogs while sparing the normal organs. This chapter reviews some gene transfer strategies and the potential of the vascular-targeted AAVP vector for enhancing the effectiveness of existing systemic gene delivery and genetic-imaging technologies. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Enabling automated magnetic resonance imaging-based targeting assessment during dipole field navigation

NASA Astrophysics Data System (ADS)

Latulippe, Maxime; Felfoul, Ouajdi; Dupont, Pierre E.; Martel, Sylvain

2016-02-01

The magnetic navigation of drugs in the vascular network promises to increase the efficacy and reduce the secondary toxicity of cancer treatments by targeting tumors directly. Recently, dipole field navigation (DFN) was proposed as the first method achieving both high field and high navigation gradient strengths for whole-body interventions in deep tissues. This is achieved by introducing large ferromagnetic cores around the patient inside a magnetic resonance imaging (MRI) scanner. However, doing so distorts the static field inside the scanner, which prevents imaging during the intervention. This limitation constrains DFN to open-loop navigation, thus exposing the risk of a harmful toxicity in case of a navigation failure. Here, we are interested in periodically assessing drug targeting efficiency using MRI even in the presence of a core. We demonstrate, using a clinical scanner, that it is in fact possible to acquire, in specific regions around a core, images of sufficient quality to perform this task. We show that the core can be moved inside the scanner to a position minimizing the distortion effect in the region of interest for imaging. Moving the core can be done automatically using the gradient coils of the scanner, which then also enables the core to be repositioned to perform navigation to additional targets. The feasibility and potential of the approach are validated in an in vitro experiment demonstrating navigation and assessment at two targets.

Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PubMed

Lee, Daniel J; Recabal, Pedro; Sjoberg, Daniel D; Thong, Alan; Lee, Justin K; Eastham, James A; Scardino, Peter T; Vargas, Hebert Alberto; Coleman, Jonathan; Ehdaie, Behfar

2016-09-01

We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance

Performance evaluation of the multiple-image optical compression and encryption method by increasing the number of target images

NASA Astrophysics Data System (ADS)

Aldossari, M.; Alfalou, A.; Brosseau, C.

2017-08-01

In an earlier study [Opt. Express 22, 22349-22368 (2014)], a compression and encryption method that simultaneous compress and encrypt closely resembling images was proposed and validated. This multiple-image optical compression and encryption (MIOCE) method is based on a special fusion of the different target images spectra in the spectral domain. Now for the purpose of assessing the capacity of the MIOCE method, we would like to evaluate and determine the influence of the number of target images. This analysis allows us to evaluate the performance limitation of this method. To achieve this goal, we use a criterion based on the root-mean-square (RMS) [Opt. Lett. 35, 1914-1916 (2010)] and compression ratio to determine the spectral plane area. Then, the different spectral areas are merged in a single spectrum plane. By choosing specific areas, we can compress together 38 images instead of 26 using the classical MIOCE method. The quality of the reconstructed image is evaluated by making use of the mean-square-error criterion (MSE).

Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: an early experience.

PubMed

Shoji, Sunao; Hiraiwa, Shinichiro; Endo, Jun; Hashida, Kazunobu; Tomonaga, Tetsuro; Nakano, Mayura; Sugiyama, Tomoko; Tajiri, Takuma; Terachi, Toshiro; Uchida, Toyoaki

2015-02-01

To report our early experience with manually controlled targeted biopsy with real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion images for the diagnosis of prostate cancer. A total of 20 consecutive patients suspicious of prostate cancer at the multiparametric magnetic resonance imaging scan were recruited prospectively. Targeted biopsies were carried out for each cancer-suspicious lesion, and 12 systematic biopsies using the BioJet system. Pathological findings of targeted and systematic biopsies were analyzed. The median age of the patients was 70 years (range 52-83 years). The median preoperative prostate-specific antigen value was 7.4 ng/mL (range 3.54-19.9 ng/mL). Median preoperative prostate volume was 38 mL (range 24-68 mL). The number of cancer-detected cases was 14 (70%). The median Gleason score was 6.5 (range 6-8). Cancer-detected rates of the systematic and targeted biopsy cores were 6.7 and 31.8%, respectively (P < 0.0001). In six patients who underwent radical prostatectomy, the geographic locations and pathological grades of clinically significant cancers and index lesions corresponded to the pathological results of the targeted biopsies. Prostate cancers detected by targeted biopsies with manually controlled targeted biopsy using real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion imaging have significantly higher grades and longer length compared with those detected by systematic biopsies. Further studies and comparison with the pathological findings of whole-gland specimens have the potential to determine the role of this biopsy methodology in patients selected for focal therapy and those under active surveillance. © 2014 The Japanese Urological Association.

Buried Target Imaging: A Comparative Study

NASA Astrophysics Data System (ADS)

Ghaderi Aram, Morteza; Dehmollaian, Mojtaba; Khaleghi, Ali

2017-12-01

A wide variety of qualitative methods have been proposed for microwave imaging. It is difficult to select only one of these methods based on a priori information and measurement equipment to achieve a reliable reconstruction. Various arrangements for antennas to be used in, for instance, have been proposed which have direct impacts on the complexity of inverse methods as well as the quality of output images. In this study, four qualitative methods of the linear sampling method (LSM), time reversal (TR), diffraction tomography (DT), and back-projection (BP) have been reviewed in a 2D scenario; the performance of the methods is compared within the same framework of a multi-static configuration. The goal is to compare their resolutions and determine their advantages and drawbacks. It is shown that LSM provides the best azimuth resolution but the worst range resolution. It is almost invariant to dielectric contrast and is appropriate for a wide range of dielectric contrasts and relatively large objects. It is also shown that at relatively low dielectric contrasts, TR images are most similar to the true object, show fewer artifacts, and offer high immunity to noise. While suffering from more artifacts due to the presence of some ghost images, DT offers the best range resolution. The results also show that BP has the worst azimuth resolution when reconstructing deeply-buried targets, although its implementation is straightforward and not computationally complex.

A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

PubMed

Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

2014-04-01

The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging

PubMed Central

2008-01-01

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications. PMID:18512972

Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ying; Li, Zhaohui; Liu, Misha

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeledmore » single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.« less

[Advances in nanoparticle-targeting tumor associated macrophages for cancer imaging and therapy].

PubMed

Fengliang, Guo; Guping, Tang; Qinglian, H U

2017-03-25

Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor associated macrophages (TAMs) as an important component in tumor microenvironment, play fundamental roles in tumor progression, metastasis and microenvironment regulation. Recently, studies have found that nanotechnology, as an emerging platform, provides unique potential for cancer imaging and therapy. With the nanotechnology, TAMs imaging presents direct evidence for cancer development, progression, and the effectiveness of cancer treatments; it also can regulate the immunosuppression of tumor microenvironment and improve therapeutic efficiency through TAMs targeted killing or phenotypic transformation. In this article, we illustrate the function of TAMs and review the latest development in nano-carriers and their applications in tumor associated macrophage targeting cancer imaging and therapy.

How reliable an indicator of inflammation is myeloperoxidase activity?

PubMed

Faith, Minnie; Sukumaran, Abitha; Pulimood, Anna B; Jacob, Molly

2008-10-01

Myeloperoxidase (MPO) and interleukin-6 (IL-6) are often used as markers of inflammation. The aim of this study was to ascertain whether MPO activity is as reliable as IL-6 as an indicator of inflammation. Inflammation was induced in mice, using either turpentine or indomethacin. Duodenal tissue was removed from these animals at various time periods ranging from 6 h to 7 days later. Concentrations of IL-6 and MPO activity were estimated in the tissue. Histopathological examination was also carried out at some of the time periods to determine the presence of neutrophil infiltration in turpentine-treated mice. Concentrations of IL-6 and MPO activity were significantly higher in tissue that had been treated with the agents used, at all the time periods studied, when compared with corresponding control tissue. Fold-increases in MPO activity were higher than fold-increases in IL-6. Concentrations of the 2 parameters showed significant positive correlation. Histopathological examination did not show significantly higher numbers of neutrophils infiltrating the tissue in response to turpentine, at the time periods studied. Estimation of MPO activity is a reliable indicator of inflammation, being more sensitive than histopathological examination of tissue and as good as measurement of IL-6 concentrations.

In vitro activation of dibromoacetonitrile to cyanide by myeloperoxidase.

PubMed

Al-Abbasi, Fahad A

2016-08-01

Dibromoacetonitrile (DBAN) is a disinfection by-product classified as a potential human and animal carcinogen. This study aimed at investigating the ability of myeloperoxidase (MPO) to oxidize DBAN to cyanide (CN - ) in vitro Detection of CN - served as a marker for the possible generation of free radical intermediates implicated in DBAN-induced toxicity. Optimum conditions for the oxidation of DBAN to CN - were characterized with respect to pH, temperature, and time of incubation as well as DBAN, MPO, potassium chloride, and hydrogen peroxide (H 2 O 2 ) concentrations in incubation mixtures. Maximum reaction velocity and Michaelis-Menten constant were assessed. Addition of sodium hypochlorite to the reaction mixtures significantly enhanced the rate of the reaction. Addition of the MPO inhibitors, sodium azide, 4-amino benzoic acid hydrazine, or indomethacin to the reaction mixtures significantly decreased the rate of DBAN oxidation. Inclusion of the antioxidant enzyme superoxide dismutase in the incubation mixtures significantly decreased the rate of reaction. Inclusion of the sulfhydryl compounds as reduced glutathione, N-acetylcysteine, d-penicillamine, or l-cysteine enhanced the rate of DBAN oxidation. These results demonstrate the ability of MPO/H 2 O 2 /chloride ion system to oxidize DBAN to CN - and provide insight for the elucidation of DBAN chronic toxicity. © The Author(s) 2015.

Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer

PubMed Central

Kalmuk, James; Folaron, Margaret; Buchinger, Julian; Pili, Roberto; Seshadri, Mukund

2015-01-01

The high mortality rate associated with castration-resistant prostate cancer (CRPC) underscores the need for improving therapeutic options for this patient population. The purpose of this study was to examine the potential of vascular targeting in prostate cancer. Experimental studies were carried out in subcutaneous and orthotopic Myc-CaP prostate tumors implanted into male FVB mice to examine the efficacy of a novel microtubule targeted vascular disrupting agent (VDA), EPC2407 (Crolibulin™). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to guide preclinical trial design and monitor tumor response to therapy. Imaging results were correlated with histopathologic assessment, tumor growth and survival analysis. Contrast-enhanced MRI revealed potent antivascular activity of EPC2407 against subcutaneous and orthotopic Myc-CaP tumors. Longitudinal BLI of Myc-CaP tumors expressing luciferase under the androgen response element (Myc-CaP/ARE-luc) revealed changes in AR signaling and reduction in intratumoral delivery of luciferin substrate following castration suggestive of reduced blood flow. This reduction in blood flow was validated by US and MRI. Combination treatment resulted in sustained vascular suppression, inhibition of tumor regrowth and conferred a survival benefit in both models. These results demonstrate the therapeutic potential of vascular targeting in combination with androgen deprivation against prostate cancer. PMID:26203773

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe.

PubMed

Zheng, Linfeng; Li, Kangan; Han, Yuedong; Wei, Wei; Zheng, Sujuan; Zhang, Guixiang

2014-11-01

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Opti-acoustic stereo imaging: on system calibration and 3-D target reconstruction.

PubMed

Negahdaripour, Shahriar; Sekkati, Hicham; Pirsiavash, Hamed

2009-06-01

Utilization of an acoustic camera for range measurements is a key advantage for 3-D shape recovery of underwater targets by opti-acoustic stereo imaging, where the associated epipolar geometry of optical and acoustic image correspondences can be described in terms of conic sections. In this paper, we propose methods for system calibration and 3-D scene reconstruction by maximum likelihood estimation from noisy image measurements. The recursive 3-D reconstruction method utilized as initial condition a closed-form solution that integrates the advantages of two other closed-form solutions, referred to as the range and azimuth solutions. Synthetic data tests are given to provide insight into the merits of the new target imaging and 3-D reconstruction paradigm, while experiments with real data confirm the findings based on computer simulations, and demonstrate the merits of this novel 3-D reconstruction paradigm.

New Radiotracers for Imaging of Vascular Targets in Angiogenesis-related Diseases

PubMed Central

Hong, Hao; Chen, Feng; Zhang, Yin; Cai, Weibo

2014-01-01

Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients. PMID:25086372

Object recognition of real targets using modelled SAR images

NASA Astrophysics Data System (ADS)

Zherdev, D. A.

2017-12-01

In this work the problem of recognition is studied using SAR images. The algorithm of recognition is based on the computation of conjugation indices with vectors of class. The support subspaces for each class are constructed by exception of the most and the less correlated vectors in a class. In the study we examine the ability of a significant feature vector size reduce that leads to recognition time decrease. The images of targets form the feature vectors that are transformed using pre-trained convolutional neural network (CNN).

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

PubMed Central

Wachsmann, Jason; Peng, Fangyu

2016-01-01

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

A system for the real-time display of radar and video images of targets

NASA Technical Reports Server (NTRS)

Allen, W. W.; Burnside, W. D.

1990-01-01

Described here is a software and hardware system for the real-time display of radar and video images for use in a measurement range. The main purpose is to give the reader a clear idea of the software and hardware design and its functions. This system is designed around a Tektronix XD88-30 graphics workstation, used to display radar images superimposed on video images of the actual target. The system's purpose is to provide a platform for tha analysis and documentation of radar images and their associated targets in a menu-driven, user oriented environment.

Modeling the target acquisition performance of active imaging systems

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Jacobs, Eddie L.; Halford, Carl E.; Vollmerhausen, Richard; Tofsted, David H.

2007-04-01

Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

Modeling the target acquisition performance of active imaging systems.

PubMed

Espinola, Richard L; Jacobs, Eddie L; Halford, Carl E; Vollmerhausen, Richard; Tofsted, David H

2007-04-02

Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

Background suppression of infrared small target image based on inter-frame registration

NASA Astrophysics Data System (ADS)

Ye, Xiubo; Xue, Bindang

2018-04-01

We propose a multi-frame background suppression method for remote infrared small target detection. Inter-frame information is necessary when the heavy background clutters make it difficult to distinguish real targets and false alarms. A registration procedure based on points matching in image patches is used to compensate the local deformation of background. Then the target can be separated by background subtraction. Experiments show our method serves as an effective preliminary of target detection.

Target 3-D reconstruction of streak tube imaging lidar based on Gaussian fitting

NASA Astrophysics Data System (ADS)

Yuan, Qingyu; Niu, Lihong; Hu, Cuichun; Wu, Lei; Yang, Hongru; Yu, Bing

2018-02-01

Streak images obtained by the streak tube imaging lidar (STIL) contain the distance-azimuth-intensity information of a scanned target, and a 3-D reconstruction of the target can be carried out through extracting the characteristic data of multiple streak images. Significant errors will be caused in the reconstruction result by the peak detection method due to noise and other factors. So as to get a more precise 3-D reconstruction, a peak detection method based on Gaussian fitting of trust region is proposed in this work. Gaussian modeling is performed on the returned wave of single time channel of each frame, then the modeling result which can effectively reduce the noise interference and possesses a unique peak could be taken as the new returned waveform, lastly extracting its feature data through peak detection. The experimental data of aerial target is for verifying this method. This work shows that the peak detection method based on Gaussian fitting reduces the extraction error of the feature data to less than 10%; utilizing this method to extract the feature data and reconstruct the target make it possible to realize the spatial resolution with a minimum 30 cm in the depth direction, and improve the 3-D imaging accuracy of the STIL concurrently.

External calibration of polarimetric radar images using distributed targets

NASA Technical Reports Server (NTRS)

Yueh, Simon H.; Nghiem, S. V.; Kwok, R.

1992-01-01

A new technique is presented for calibrating polarimetric synthetic aperture radar (SAR) images using only the responses from natural distributed targets. The model for polarimetric radars is assumed to be X = cRST where X is the measured scattering matrix corresponding to the target scattering matrix S distorted by the system matrices T and R (in general T does not equal R(sup t)). To allow for the polarimetric calibration using only distributed targets and corner reflectors, van Zyl assumed a reciprocal polarimetric radar model with T = R(sup t); when applied for JPL SAR data, a heuristic symmetrization procedure is used by POLCAL to compensate the phase difference between the measured HV and VH responses and then take the average of both. This heuristic approach causes some non-removable cross-polarization responses for corner reflectors, which can be avoided by a rigorous symmetrization method based on reciprocity. After the radar is made reciprocal, a new algorithm based on the responses from distributed targets with reflection symmetry is developed to estimate the cross-talk parameters. The new algorithm never experiences problems in convergence and is also found to converge faster than the existing routines implemented for POLCAL. When the new technique is implemented for the JPL polarimetric data, symmetrization and cross-talk removal are performed on a line-by-line (azimuth) basis. After the cross-talks are removed from the entire image, phase and amplitude calibrations are carried out by selecting distributed targets either with azimuthal symmetry along the looking direction or with some well-known volume and surface scattering mechanisms to estimate the relative phases and amplitude responses of the horizontal and vertical channels.

Optimized computational imaging methods for small-target sensing in lens-free holographic microscopy

NASA Astrophysics Data System (ADS)

Xiong, Zhen; Engle, Isaiah; Garan, Jacob; Melzer, Jeffrey E.; McLeod, Euan

2018-02-01

Lens-free holographic microscopy is a promising diagnostic approach because it is cost-effective, compact, and suitable for point-of-care applications, while providing high resolution together with an ultra-large field-of-view. It has been applied to biomedical sensing, where larger targets like eukaryotic cells, bacteria, or viruses can be directly imaged without labels, and smaller targets like proteins or DNA strands can be detected via scattering labels like micro- or nano-spheres. Automated image processing routines can count objects and infer target concentrations. In these sensing applications, sensitivity and specificity are critically affected by image resolution and signal-to-noise ratio (SNR). Pixel super-resolution approaches have been shown to boost resolution and SNR by synthesizing a high-resolution image from multiple, partially redundant, low-resolution images. However, there are several computational methods that can be used to synthesize the high-resolution image, and previously, it has been unclear which methods work best for the particular case of small-particle sensing. Here, we quantify the SNR achieved in small-particle sensing using regularized gradient-descent optimization method, where the regularization is based on cardinal-neighbor differences, Bayer-pattern noise reduction, or sparsity in the image. In particular, we find that gradient-descent with sparsity-based regularization works best for small-particle sensing. These computational approaches were evaluated on images acquired using a lens-free microscope that we assembled from an off-the-shelf LED array and color image sensor. Compared to other lens-free imaging systems, our hardware integration, calibration, and sample preparation are particularly simple. We believe our results will help to enable the best performance in lens-free holographic sensing.

Rare-earth doped nanocomposites enable multiscale targeted short-wave infrared imaging of metastatic breast cancer

NASA Astrophysics Data System (ADS)

Pierce, Mark C.; Higgins, Laura M.; Ganapathy, Vidya; Kantamneni, Harini; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.

2017-02-01

We are investigating the ability of targeted rare earth (RE) doped nanocomposites to detect and track micrometastatic breast cancer lesions to distant sites in pre-clinical in vivo models. Functionalizing RE nanocomposites with AMD3100 promotes targeting to CXCR4, a recognized marker for highly metastatic disease. Mice were inoculated with SCP-28 (CXCR4 positive) and 4175 (CXCR4 negative) cell lines. Whole animal in vivo SWIR fluorescence imaging was performed after bioluminescence imaging confirmed tumor burden in the lungs. Line-scanning confocal fluorescence microscopy provided high-resolution imaging of RE nanocomposite uptake and native tissue autofluorescence in ex vivo lung specimens. Co-registered optical coherence tomography imaging allowed assessment of tissue microarchitecture. In conclusion, multiscale optical molecular imaging can be performed in pre-clinical models of metastatic breast cancer, using targeted RE-doped nanocomposites.

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

PubMed

Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

2015-01-01

Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy

Use of polyclonal anti-myeloperoxidase antibody in myeloid lineage determination.

PubMed

Karnik, M P; Nair, C N; Zingde, S M; Gothoskar, B P; Zachariah, L; Barbhaya, S; Advani, S H

1994-12-01

This study reports the production of a rabbit polyclonal antibody to myeloperoxidase (MPO) and its use in ascertaining the myeloid lineage of blasts in leukaemia. Comparison of the immunocytochemical stain using the anti-MPO antibody with the routine cytochemical methodology showed that the former was more sensitive. In all subtypes of acute myeloid leukaemia (AML; 72 patients, M1-M6) greater number of MPO positive blast cells were observed by immunocytochemistry, the highest being in the promyelocytic leukaemia. It was also extremely specific for cells of the myeloid lineage as it did not react with blasts from acute lymphoblastic (50 patients) and megakaryoblastic leukaemias (1 patient). In addition, it proved most useful for the lineage determination of blasts from patients with undifferentiated acute leukaemias (AUL) and those with chronic myeloid leukaemia in blast crisis (CML-BC). Out of 8 patients of AULs, 6 were classified as acute myeloblastic leukaemia due to their reactivity to the anti-MPO antibody. Similarly, out of 12 patients of chronic myeloid leukaemia in blast crisis, blasts from 8 showed reactivity to this antibody and thus could be identified as belonging to the myeloid lineage and/or of the mixed blast crisis type.

Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

NASA Astrophysics Data System (ADS)

Rangarajan, Janaki Raman; Vande Velde, Greetje; van Gent, Friso; de Vloo, Philippe; Dresselaers, Tom; Depypere, Maarten; van Kuyck, Kris; Nuttin, Bart; Himmelreich, Uwe; Maes, Frederik

2016-11-01

Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.

Target-oriented retrieval of subsurface wave fields - Pushing the resolution limits in seismic imaging

NASA Astrophysics Data System (ADS)

Vasconcelos, Ivan; Ozmen, Neslihan; van der Neut, Joost; Cui, Tianci

2017-04-01

Travelling wide-bandwidth seismic waves have long been used as a primary tool in exploration seismology because they can probe the subsurface over large distances, while retaining relatively high spatial resolution. The well-known Born resolution limit often seems to be the lower bound on spatial imaging resolution in real life examples. In practice, data acquisition cost, time constraints and other factors can worsen the resolution achieved by wavefield imaging. Could we obtain images whose resolution beats the Born limits? Would it be practical to achieve it, and what are we missing today to achieve this? In this talk, we will cover aspects of linear and nonlinear seismic imaging to understand elements that play a role in obtaining "super-resolved" seismic images. New redatuming techniques, such as the Marchenko method, enable the retrieval of subsurface fields that include multiple scattering interactions, while requiring relatively little knowledge of model parameters. Together with new concepts in imaging, such as Target-Enclosing Extended Images, these new redatuming methods enable new targeted imaging frameworks. We will make a case as to why target-oriented approaches to reconstructing subsurface-domain wavefields from surface data may help in increasing the resolving power of seismic imaging, and in pushing the limits on parameter estimation. We will illustrate this using a field data example. Finally, we will draw connections between seismic and other imaging modalities, and discuss how this framework could be put to use in other applications

Video-rate volumetric neuronal imaging using 3D targeted illumination.

PubMed

Xiao, Sheng; Tseng, Hua-An; Gritton, Howard; Han, Xue; Mertz, Jerome

2018-05-21

Fast volumetric microscopy is required to monitor large-scale neural ensembles with high spatio-temporal resolution. Widefield fluorescence microscopy can image large 2D fields of view at high resolution and speed while remaining simple and costeffective. A focal sweep add-on can further extend the capacity of widefield microscopy by enabling extended-depth-of-field (EDOF) imaging, but suffers from an inability to reject out-of-focus fluorescence background. Here, by using a digital micromirror device to target only in-focus sample features, we perform EDOF imaging with greatly enhanced contrast and signal-to-noise ratio, while reducing the light dosage delivered to the sample. Image quality is further improved by the application of a robust deconvolution algorithm. We demonstrate the advantages of our technique for in vivo calcium imaging in the mouse brain.

Real Time Target Tracking in a Phantom Using Ultrasonic Imaging

NASA Astrophysics Data System (ADS)

Xiao, X.; Corner, G.; Huang, Z.

In this paper we present a real-time ultrasound image guidance method suitable for tracking the motion of tumors. A 2D ultrasound based motion tracking system was evaluated. A robot was used to control the focused ultrasound and position it at the target that has been segmented from a real-time ultrasound video. Tracking accuracy and precision were investigated using a lesion mimicking phantom. Experiments have been conducted and results show sufficient efficiency of the image guidance algorithm. This work could be developed as the foundation for combining the real time ultrasound imaging tracking and MRI thermometry monitoring non-invasive surgery.

Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice

PubMed Central

Majmudar, Maulik D.; Keliher, Edmund J.; Heidt, Timo; Leuschner, Florian; Truelove, Jessica; Sena, Brena F.; Gorbatov, Rostic; Iwamoto, Yoshiko; Dutta, Partha; Wojtkiewicz, Gregory; Courties, Gabriel; Sebas, Matt; Borodovsky, Anna; Fitzgerald, Kevin; Nolte, Marc W.; Dickneite, Gerhard; Chen, John W.; Anderson, Daniel G.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

2013-01-01

Background Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. We here employed nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6Chigh monocyte subset traffic, to reduce infarct inflammation in apoE−/− mice after MI. We used dual target PET/MRI of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset-targeted RNAi altered infarct inflammation and healing. Methods and Results Flow cytometry, gene expression analysis and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE−/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix crosslinking non-invasively, we developed a fluorine-18 labeled PET agent (18F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged using a molecular MRI sensor of MPO activity (MPO-Gd). PET/MRI detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal, p<0.05) while 18F-FXIII PET reflected unimpeded matrix crosslinking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29 to 35% (p<0.05). Conclusion CCR2 targeted RNAi reduced recruitment of Ly-6Chigh monocytes, attenuated infarct inflammation and curbed post-MI left ventricular remodeling. PMID:23616627

Target recognition of ladar range images using slice image: comparison of four improved algorithms

NASA Astrophysics Data System (ADS)

Xia, Wenze; Han, Shaokun; Cao, Jingya; Wang, Liang; Zhai, Yu; Cheng, Yang

2017-07-01

Compared with traditional 3-D shape data, ladar range images possess properties of strong noise, shape degeneracy, and sparsity, which make feature extraction and representation difficult. The slice image is an effective feature descriptor to resolve this problem. We propose four improved algorithms on target recognition of ladar range images using slice image. In order to improve resolution invariance of the slice image, mean value detection instead of maximum value detection is applied in these four improved algorithms. In order to improve rotation invariance of the slice image, three new improved feature descriptors-which are feature slice image, slice-Zernike moments, and slice-Fourier moments-are applied to the last three improved algorithms, respectively. Backpropagation neural networks are used as feature classifiers in the last two improved algorithms. The performance of these four improved recognition systems is analyzed comprehensively in the aspects of the three invariances, recognition rate, and execution time. The final experiment results show that the improvements for these four algorithms reach the desired effect, the three invariances of feature descriptors are not directly related to the final recognition performance of recognition systems, and these four improved recognition systems have different performances under different conditions.

Active imaging system performance model for target acquisition

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Teaney, Brian; Nguyen, Quang; Jacobs, Eddie L.; Halford, Carl E.; Tofsted, David H.

2007-04-01

The U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate has developed a laser-range-gated imaging system performance model for the detection, recognition, and identification of vehicle targets. The model is based on the established US Army RDECOM CERDEC NVESD sensor performance models of the human system response through an imaging system. The Java-based model, called NVLRG, accounts for the effect of active illumination, atmospheric attenuation, and turbulence effects relevant to LRG imagers, such as speckle and scintillation, and for the critical sensor and display components. This model can be used to assess the performance of recently proposed active SWIR systems through various trade studies. This paper will describe the NVLRG model in detail, discuss the validation of recent model components, present initial trade study results, and outline plans to validate and calibrate the end-to-end model with field data through human perception testing.

Quantitative imaging of protein targets in the human brain with PET

NASA Astrophysics Data System (ADS)

Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

2015-11-01

PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

A New SAR Image Segmentation Algorithm for the Detection of Target and Shadow Regions

PubMed Central

Huang, Shiqi; Huang, Wenzhun; Zhang, Ting

2016-01-01

The most distinctive characteristic of synthetic aperture radar (SAR) is that it can acquire data under all weather conditions and at all times. However, its coherent imaging mechanism introduces a great deal of speckle noise into SAR images, which makes the segmentation of target and shadow regions in SAR images very difficult. This paper proposes a new SAR image segmentation method based on wavelet decomposition and a constant false alarm rate (WD-CFAR). The WD-CFAR algorithm not only is insensitive to the speckle noise in SAR images but also can segment target and shadow regions simultaneously, and it is also able to effectively segment SAR images with a low signal-to-clutter ratio (SCR). Experiments were performed to assess the performance of the new algorithm on various SAR images. The experimental results show that the proposed method is effective and feasible and possesses good characteristics for general application. PMID:27924935

A New SAR Image Segmentation Algorithm for the Detection of Target and Shadow Regions.

PubMed

Huang, Shiqi; Huang, Wenzhun; Zhang, Ting

2016-12-07

The most distinctive characteristic of synthetic aperture radar (SAR) is that it can acquire data under all weather conditions and at all times. However, its coherent imaging mechanism introduces a great deal of speckle noise into SAR images, which makes the segmentation of target and shadow regions in SAR images very difficult. This paper proposes a new SAR image segmentation method based on wavelet decomposition and a constant false alarm rate (WD-CFAR). The WD-CFAR algorithm not only is insensitive to the speckle noise in SAR images but also can segment target and shadow regions simultaneously, and it is also able to effectively segment SAR images with a low signal-to-clutter ratio (SCR). Experiments were performed to assess the performance of the new algorithm on various SAR images. The experimental results show that the proposed method is effective and feasible and possesses good characteristics for general application.

Targets Mask U-Net for Wind Turbines Detection in Remote Sensing Images

NASA Astrophysics Data System (ADS)

Han, M.; Wang, H.; Wang, G.; Liu, Y.

2018-04-01

To detect wind turbines precisely and quickly in very high resolution remote sensing images (VHRRSI) we propose target mask U-Net. This convolution neural network (CNN), which is carefully designed to be a wide-field detector, models the pixel class assignment to wind turbines and their context information. The shadow, which is the context information of the target in this study, has been regarded as part of a wind turbine instance. We have trained the target mask U-Net on training dataset, which is composed of down sampled image blocks and instance mask blocks. Some post-processes have been integrated to eliminate wrong spots and produce bounding boxes of wind turbine instances. The evaluation metrics prove the reliability and effectiveness of our method for the average F1-score of our detection method is up to 0.97. The comparison of detection accuracy and time consuming with the weakly supervised targets detection method based on CNN illustrates the superiority of our method.

Enhanced detection of myeloperoxidase activity in deep tissues through luminescent excitation of near-infrared nanoparticles.

PubMed

Zhang, Ning; Francis, Kevin P; Prakash, Arun; Ansaldi, Daniel

2013-04-01

A previous study reported the use of luminol for the detection of myeloperoxidase (MPO) activity using optical imaging in infiltrating neutrophils under inflammatory disease conditions. The detection is based on a photon-emitting reaction between luminol and an MPO metabolite. Because of tissue absorption and scattering, however, luminol-emitted blue light can be efficiently detected from superficial inflammatory foci only. In this study we report a chemiluminescence resonance energy transfer (CRET) methodology in which luminol-generated blue light excites nanoparticles to emit light in the near-infrared spectral range, resulting in remarkable improvement of MPO detectability in vivo. CRET caused a 37-fold increase in luminescence emission over luminol alone in detecting MPO activity in lung tissues after lipopolysaccharide challenge. We demonstrated a dependence of the chemiluminescent signal on MPO activity using MPO-deficient mice. In addition, co-administration of 4-aminobenzoic acid hydrazide (4-ABAH), an irreversible inhibitor of MPO, significantly attenuated luminescent emission from inflamed lungs. Inhibition of nitric oxide synthase with a nonspecific inhibitor, L-NAME, had no effect on luminol-mediated chemiluminescence production. Pretreatment of mice with MLN120B, a selective inhibitor of IKK-2, resulted in suppression of neutrophil infiltration to the lung tissues and reduction of MPO activity. We also demonstrated that CRET can effectively detect MPO activity at deep tissue tumor foci due to tumor development-associated neutrophil infiltration. We developed a sensitive MPO detection methodology that provides a means for visualizing and quantifying oxidative stress in deep tissue. This method is amenable to rapid evaluation of anti-inflammatory agents in animal models.

Distributed MIMO Radar for Imaging and High Resolution Target Localization

DTIC Science & Technology

2012-02-02

Reduction in Distributed MIMO Radar with Multi-Carrier OFDM Signals Carl Georgeson 11/23/2010 Approved 17 • 10-019 Algorithms for Target Location and...28-2012 Final Report 04/15/2009 - 11/30/2011 Distributed MIMO Radar for Imaging and High Resolution Target Localization FA9550-09-1-0303 Alexander M...error for the general case of MIMO radar with multiple waveforms with non-coherent and coherent observations; (b) finds a closed-form solution for the

Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and imaging in cancer.

PubMed

Jin, Hyo-Eon; Farr, Rebecca; Lee, Seung-Wuk

2014-11-01

Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases. Published by Elsevier Ltd.

Restoration of longitudinal laser tomography target image from inhomogeneous medium degradation under common conditions.

PubMed

Yi, WenJun; Wang, Ping; Fu, MeiCheng; Tan, JiChun; Zhu, Jubo; Li, XiuJian

2017-07-10

In order to overcome the shortages of the target image restoration method for longitudinal laser tomography using self-calibration, a more general restoration method through backscattering medium images associated with prior parameters is developed for common conditions. The system parameters are extracted from pre-calibration, and the LIDAR ratio is estimated according to the medium types. Assisted by these prior parameters, the degradation caused by inhomogeneous turbid media can be established with the backscattering medium images, which can further be used for removal of the interferences of turbid media. The results of simulations and experiments demonstrate that the proposed image restoration method can effectively eliminate the inhomogeneous interferences of turbid media and achieve exactly the reflectivity distribution of targets behind inhomogeneous turbid media. Furthermore, the restoration method can work beyond the limitation of the previous method that only works well under the conditions of localized turbid attenuations and some types of targets with fairly uniform reflectivity distributions.

Gold-manganese nanoparticles for targeted diagnostic and imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murph, Simona Hunyadi

Imagine the possibility of non-invasive, non-radiation based Magnetic resonance imaging (MRI) in combating cardiac disease. Researchers at the Savannah River National Laboratory (SRNL) are developing a process that would use nanotechnology in a novel, targeted approach that would allow MRIs to be more descriptive and brighter, and to target specific organs. Researchers at SRNL have discovered a way to use multifunctional metallic gold-manganese nanoparticles to create a unique, targeted positive contrast agent. SRNL Senior Scientist Dr. Simona Hunyadi Murph says she first thought of using the nanoparticles for cardiac disease applications after learning that people who survive an infarct exhibitmore » up to 15 times higher rate of developing chronic heart failure, arrhythmias and/or sudden death compared to the general population. Without question, nanotechnology will revolutionize the future of technology. The development of functional nanomaterials with multi-detection modalities opens up new avenues for creating multi-purpose technologies for biomedical applications.« less

Targeted in-vivo computed tomography (CT) imaging of tissue ACE using concentrated lisinopril-capped gold nanoparticle solutions

NASA Astrophysics Data System (ADS)

Daniel, Marie-Christine; Aras, Omer; Smith, Mark F.; Nan, Anjan; Fleiter, Thorsten

2010-04-01

The development of cardiac and pulmonary fibrosis have been associated with overexpression of angiotensin-converting enzyme (ACE). Moreover, ACE inhibitors, such as lisinopril, have shown a benificial effect for patients diagnosed with heart failure or systemic hypertension. Thus targeted imaging of the ACE is of crucial importance for monitoring of the tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-capped gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. Concentrated solutions of these modified gold nanoparticles, with a diameter around 16 nm, showed high contrast in CT imaging. These new targeted imaging agents were thus used for in vivo imaging on rat models.

Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents.

PubMed

Gao, Yong; Hernandez, Christopher; Yuan, Hai-Xia; Lilly, Jacob; Kota, Pavan; Zhou, Haoyan; Wu, Hanping; Exner, Agata A

2017-10-01

Ultrasound is frequently utilized in diagnosis of gynecologic malignancies such as ovarian cancer. Because epithelial ovarian cancer (EOC) is often characterized by overexpression of cancer antigen 125 (CA-125), ultrasound contrast agents able to target this molecular signature could be a promising complementary strategy. In this work, we demonstrate application of CA-125-targeted echogenic lipid and surfactant-stabilized nanobubbles imaged with standard clinical contrast harmonic ultrasound for imaging of CA-125 positive OVCAR-3 tumors in mice. Surface functionalization of the nanobubbles with a CA-125 antibody achieved rapid significantly (P < 0.05) enhanced tumor accumulation, higher peak ultrasound signal intensity and slower wash out rates in OVCAR-3 tumors compared to CA-125 negative SKOV-3 tumors. Targeted nanobubbles also exhibited increased tumor retention and prolonged echogenicity compared to untargeted nanobubbles. Data suggest that ultrasound molecular imaging using CA-125 antibody-conjugated nanobubbles may contribute to improved diagnosis of EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

Tracking single membrane targets of human autoantibodies using single nanoparticle imaging.

PubMed

Jézéquel, Julie; Dupuis, Julien P; Maingret, François; Groc, Laurent

2018-04-21

Over the past decade, an increasing number of neurological and neuropsychiatric diseases have been associated with the expression of autoantibodies directed against neuronal targets, including neurotransmitter receptors. Although cell-based assays are routinely used in clinics to detect the presence of immunoglobulins, such tests often provide heterogeneous outcomes due to their limited sensitivity, especially at low titers. Thus, there is an urging need for new methods allowing the detection of autoantibodies in seropositive patients that cannot always be clinically distinguished from seronegative ones. Here we make a case for single nanoparticle imaging approaches as a highly sensitive antibody detection assay. Through high-affinity interactions between functionalized nanoparticles and autoantibodies that recognize extracellular domains of membrane neuronal targets, single nanoparticle imaging allows a live surface staining of transmembrane proteins and gives access to their surface dynamics. We show here that this method is well-suited to detect low titers of purified immunoglobulin G (IgG) from first-episode psychotic patients and demonstrate that these IgG target glutamatergic N-Methyl-d-Aspartate receptors (NMDAR) in live hippocampal neurons. The molecular behaviors of targeted membrane receptors were indistinguishable from those of endogenous GluN1 NMDAR subunit and were virtually independent of the IgG concentration present in the sample contrary to classical cell-based assays. Single nanoparticle imaging emerges as a real-time sensitive method to detect IgG directed against neuronal surface proteins, which could be used as an additional step to rule out ambiguous seropositivity diagnoses. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2 probe

NASA Astrophysics Data System (ADS)

Uddin, Md. Jashim; Crews, Brenda C.; Ghebreselasie, Kebreab; Daniel, Cristina K.; Kingsley, Philip J.; Xu, Shu; Marnett, Lawrence J.

2015-05-01

Cyclooxygenase-2 (COX-2) is a promising target for the imaging of cancer in a range of diagnostic and therapeutic settings. We report a near-infrared COX-2-targeted probe, fluorocoxib C (FC), for visualization of solid tumors by optical imaging. FC exhibits selective and potent COX-2 inhibition in both purified protein and human cancer cell lines. In vivo optical imaging shows selective accumulation of FC in COX-2-overexpressing human tumor xenografts [1483 head and neck squamous cell carcinoma (HNSCC)] implanted in nude mice, while minimal uptake is detectable in COX-2-negative tumor xenografts (HCT116) or 1483 HNSCC xenografts preblocked with the COX-2-selective inhibitor celecoxib. Time course imaging studies conducted from 3 h to 7-day post-FC injection revealed a marked reduction in nonspecific fluorescent signals with retention of fluorescence in 1483 HNSCC tumors. Thus, use of FC in a delayed imaging protocol offers an approach to improve imaging signal-to-noise that should improve cancer detection in multiple preclinical and clinical settings.

Synthesizing and binding dual-mode poly (lactic-co-glycolic acid) (PLGA) nanobubbles for cancer targeting and imaging.

PubMed

Xu, Jeff S; Huang, Jiwei; Qin, Ruogu; Hinkle, George H; Povoski, Stephen P; Martin, Edward W; Xu, Ronald X

2010-03-01

Accurate assessment of tumor boundaries and recognition of occult disease are important oncologic principles in cancer surgeries. However, existing imaging modalities are not optimized for intraoperative cancer imaging applications. We developed a nanobubble (NB) contrast agent for cancer targeting and dual-mode imaging using optical and ultrasound (US) modalities. The contrast agent was fabricated by encapsulating the Texas Red dye in poly (lactic-co-glycolic acid) (PLGA) NBs and conjugating NBs with cancer-targeting ligands. Both one-step and three-step cancer-targeting strategies were tested on the LS174T human colon cancer cell line. For the one-step process, NBs were conjugated with the humanized HuCC49 Delta C(H)2 antibody to target the over-expressed TAG-72 antigen. For the three-step process, cancer cells were targeted by successive application of the biotinylated HuCC49 Delta C(H)2 antibody, streptavidin, and the biotinylated NBs. Both one-step and three-step processes successfully targeted the cancer cells with high binding affinity. NB-assisted dual-mode imaging was demonstrated on a gelatin phantom that embedded multiple tumor simulators at different NB concentrations. Simultaneous fluorescence and US images were acquired for these tumor simulators and linear correlations were observed between the fluorescence/US intensities and the NB concentrations. Our research demonstrated the technical feasibility of using the dual-mode NB contrast agent for cancer targeting and simultaneous fluorescence/US imaging. (c) 2009 Elsevier Ltd. All rights reserved.

A motion algorithm to extract physical and motion parameters of mobile targets from cone-beam computed tomographic images.

PubMed

Alsbou, Nesreen; Ahmad, Salahuddin; Ali, Imad

2016-05-17

A motion algorithm has been developed to extract length, CT number level and motion amplitude of a mobile target from cone-beam CT (CBCT) images. The algorithm uses three measurable parameters: Apparent length and blurred CT number distribution of a mobile target obtained from CBCT images to determine length, CT-number value of the stationary target, and motion amplitude. The predictions of this algorithm are tested with mobile targets having different well-known sizes that are made from tissue-equivalent gel which is inserted into a thorax phantom. The phantom moves sinusoidally in one-direction to simulate respiratory motion using eight amplitudes ranging 0-20 mm. Using this motion algorithm, three unknown parameters are extracted that include: Length of the target, CT number level, speed or motion amplitude for the mobile targets from CBCT images. The motion algorithm solves for the three unknown parameters using measured length, CT number level and gradient for a well-defined mobile target obtained from CBCT images. The motion model agrees with the measured lengths which are dependent on the target length and motion amplitude. The gradient of the CT number distribution of the mobile target is dependent on the stationary CT number level, the target length and motion amplitude. Motion frequency and phase do not affect the elongation and CT number distribution of the mobile target and could not be determined. A motion algorithm has been developed to extract three parameters that include length, CT number level and motion amplitude or speed of mobile targets directly from reconstructed CBCT images without prior knowledge of the stationary target parameters. This algorithm provides alternative to 4D-CBCT without requirement of motion tracking and sorting of the images into different breathing phases. The motion model developed here works well for tumors that have simple shapes, high contrast relative to surrounding tissues and move nearly in regular motion pattern

Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

PubMed Central

2015-01-01

We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection. PMID:25615011

Myeloperoxidase-Mediated Iodination by Granulocytes INTRACELLULAR SITE OF OPERATION AND SOME REGULATING FACTORS

PubMed Central

Root, Richard K.; Stossel, Thomas P.

1974-01-01

The intracellular site of operation of the myeloperoxidase-H2O2-halide antibacterial system of granulocytes has been determined by utilizing measurements of the fixation of iodide to trichloracetic acid (TCA) precipitates of subcellular fractions, including intact phagocytic vesicles. Na125I was added to suspensions of guinea pig granulocytes in Krebs-Ringer phosphate buffer, and they were then permitted to phagocytize different particles. Phagocytic vesicles were formed by allowing cells to ingest a paraffin oil emulsion (POE) and collected by flotation on sucrose after homogenization. Measurement of 125I bound to TCA precipitates of the different fractions and the homogenates disclosed that the lysosome-rich fraction obtained by centrifugation from control (nonphagocytizing) cells accounted for a mean 93.1% of the total cellular activity. With phagocytosis of POE, TCA-precipitable iodination increased two- to sevenfold, and the lysosomal contribution fell to a mean 36.9% of the total. The appearance of activity within phagocytic vesicles accounted for almost the entire increase seen with phagocytosis (a mean 75.7%), and iodide was bound within these structures with high specific activity. More iodide was taken up by cells than fixed, regardless of iodide concentration, and was distributed widely throughout the cell rather than selectively trapped within the vesicles. The amount of iodide taken up and fixed varied considerably with the phagocytic particle employed. Yeast particles were found to stimulate iodination to a far greater degree than the ingestion of POE or latex. Such observations are consistent with the concept that the ingested particle is a major recipient of the iodination process. Measurements of metabolic activities related to the formation and utilization of peroxide by cells phagocytizing different particles were made and correlated with iodination. The findings suggest that mechanisms must exist within granulocytes to collect or perhaps even

Prostate-specific membrane antigen as a target for cancer imaging and therapy

PubMed Central

KIESS, A. P.; BANERJEE, S. R.; MEASE, R. C.; ROWE, S. P.; RAO, A.; FOSS, C. A.; CHEN, Y.; YANG, X.; CHO, S. Y.; NIMMAGADDA, S.; POMPER, M. G.

2016-01-01

The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers. PMID:26213140

Inhibition of myeloperoxidase and antioxidative activity of Gentiana lutea extracts.

PubMed

Nastasijević, Branislav; Lazarević-Pašti, Tamara; Dimitrijević-Branković, Suzana; Pašti, Igor; Vujačić, Ana; Joksić, Gordana; Vasić, Vesna

2012-07-01

The aim of this study was to investigate the inhibitory activity of Gentiana lutea extracts on the enzyme myeloperoxidase (MPO), as well as the antioxidant activity of these extracts and their correlation with the total polyphenol content. Extracts were prepared using methanol (100%), water and ethanol aqueous solutions (96, 75, 50 and 25%v/v) as solvents for extraction. Also, isovitexin, amarogentin and gentiopicroside, pharmacologically active constituents of G. lutea were tested as potential inhibitors of MPO. Antioxidant activity of extracts was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging test and also using cyclic voltammetry (CV). Among all extracts, the antioxidant capacity of 50% ethanol aqueous extract was the highest, both when measured using the DPPH test, with IC(50)=20.6 μg/ml, and when using CV. Also, 50% ethanol extract, showed the best inhibition of MPO activity in comparison with other extracts. In the group of the selected G. lutea constituents, gentiopicroside has proved to be the strongest inhibitor of MPO, with IC(50)=0.8 μg/ml. Also, the concentration of G. lutea constituents were determined in all extracts, using Ultra Performance Liquid Chromatography (UPLC). Copyright © 2012 Elsevier B.V. All rights reserved.

Polydopamine-based functional composite particles for tumor cell targeting and dual-mode cellular imaging.

PubMed

Zhou, Yalei; Zhou, Jie; Wang, Feng; Yang, Haifeng

2018-05-01

Particles which bear tumor cell targeting and multimode imaging capabilities are promising in tumor diagnosis and cancer therapy. A simple and versatile method to fabricate gold/polydopamine-Methylene Blue@Bovine Serum Albumin-glutaraldehyde-Transferrin composite particles (Au/PDA-MB@BSA-GA-Tf NPs) for tumor cell targeting and fluorescence (FL) / surface-enhanced Raman scattering (SERS) dual-modal imaging were reported in this work. Polydopamine (PDA) spheres played an important role in gold ion reduction, gold nanoparticle (Au NPs) binding and methylene blue (MB) adsorption, MB were employed as both fluorescence label and Raman reporter. In addition, glutaraldehyde (GA) crosslinked bovine serum albumin (BSA) in the outer layer of Au/PDA-MB nanoparticles can prevent MB from dissociation and leakage. The composite nanoparticles were further conjugated with transferrin (Tf) to target transferrin receptor (TfR)-overexpressed cancer cells. The targeting ability as well as the intracellular location of the probe was investigated through SERS mapping and fluorescence imaging. Their excellent biocompatibility was demonstrated by low cytotoxicity against breast cancer cell (4T1 cell). Copyright © 2018 Elsevier B.V. All rights reserved.

Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung.

PubMed

Oh, Phil; Borgström, Per; Witkiewicz, Halina; Li, Yan; Borgström, Bengt J; Chrastina, Adrian; Iwata, Koji; Zinn, Kurt R; Baldwin, Richard; Testa, Jacqueline E; Schnitzer, Jan E

2007-03-01

How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body gamma-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola.

Electromagnetic image guidance in gynecology: prospective study of a new laparoscopic imaging and targeting technique for the treatment of symptomatic uterine fibroids.

PubMed

Galen, Donald I

2015-10-15

Uterine fibroids occur singly or as multiple benign tumors originating in the myometrium. Because they vary in size and location, the approach and technique for their identification and surgical management vary. Reference images, such as ultrasound images, magnetic resonance images, and sonohystograms, do not provide real-time intraoperative findings. Electromagnetic image guidance, as incorporated in the Acessa Guidance System, has been cleared by the FDA to facilitate targeting and ablation of uterine fibroids during laparoscopic surgery. This is the first feasibility study to verify the features and usefulness of the guidance system in targeting symptomatic uterine fibroids-particularly hard-to-reach intramural fibroids and those abutting the endometrium. One gynecologic surgeon, who had extensive prior experience in laparoscopic ultrasound-guided identification of fibroids, treated five women with symptomatic uterine fibroids using the Acessa Guidance System. The surgeon evaluated the system and its features in terms of responses to prescribed statements; the responses were analyzed prospectively. The surgeon strongly agreed (96 %) or agreed (4 %) with statements describing the helpfulness of the transducer and handpiece's dynamic animation in targeting each fibroid, reaching the fibroid quickly, visualizing the positions of the transducer and handpiece within the pelvic cavity, and providing the surgeon with confidence when targeting the fibroid even during "out-of-plane" positioning of the handpiece. The surgeon's positive user experience was evident in the guidance system's facilitation of accurate handpiece tip placement during targeting and ablation of uterine fibroids. Continued study of electromagnetic image guidance in the laparoscopic identification and treatment of fibroids is warranted. ClinicalTrials.gov Identifier: NCT01842789.

Sequential Superresolution Imaging of Multiple Targets Using a Single Fluorophore

PubMed Central

Lidke, Diane S.; Lidke, Keith A.

2015-01-01

Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides nanometer scale detail of cellular structures and allows for imaging of biological processes at the molecular level. Specific SR imaging methods, such as localization-based imaging, rely on stochastic transitions between on (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular structures using multi-color imaging is complicated and limited by the differing properties of various organic dyes including their fluorescent state duty cycle, photons per switching event, number of fluorescent cycles before irreversible photobleaching, and overall sensitivity to buffer conditions. In addition, multiple color imaging requires consideration of multiple optical paths or chromatic aberration that can lead to differential aberrations that are important at the nanometer scale. Here, we report a method for sequential labeling and imaging that allows for SR imaging of multiple targets using a single fluorophore with negligible cross-talk between images. Using brightfield image correlation to register and overlay multiple image acquisitions with ~10 nm overlay precision in the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647 for dSTORM to image four distinct cellular proteins. We also visualize the changes in co-localization of the epidermal growth factor (EGF) receptor and clathrin upon EGF addition that are consistent with clathrin-mediated endocytosis. These results are the first to demonstrate sequential SR (s-SR) imaging using direct stochastic reconstruction microscopy (dSTORM), and this method for sequential imaging can be applied to any superresolution technique. PMID:25860558

The Inextricable Axis Of Targeted Diagnostic Imaging And Therapy: An Immunological Natural History Approach

PubMed Central

Cope, FO; Abbruzzese, B; Sanders, J; Metz, W; Sturms, K; Ralph, D; Blue, M; Zhang, J; Bracci, P; Bshara, W; Behr, S; Maurer, T; Beverly, A; Blay, B; Damughatla, A; Larsen, M; Mountain, C; Neylon, E; Parcel, K; Raghuraman, K; Ricks, K; Rose, L; Sivakumar, A; Streck, N; Wang, B; Wasco, C; Williams, A; McGrath, M

2016-01-01

Summary In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. 99mTc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10−11 M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 minutes to bind more tilmanocept (acting as intracellular “drug compilers” of tilmanocept into non-degraded vesicles), give serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate 99mTc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for

The inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach.

PubMed

Cope, Frederick O; Abbruzzese, Bonnie; Sanders, James; Metz, Wendy; Sturms, Kristyn; Ralph, David; Blue, Michael; Zhang, Jane; Bracci, Paige; Bshara, Wiam; Behr, Spencer; Maurer, Toby; Williams, Kenneth; Walker, Joshua; Beverly, Allison; Blay, Brooke; Damughatla, Anirudh; Larsen, Mark; Mountain, Courtney; Neylon, Erin; Parcel, Kaeli; Raghuraman, Kapil; Ricks, Kevin; Rose, Lucas; Sivakumar, Akhilesh; Streck, Nicholas; Wang, Bryan; Wasco, Christopher; Williams, Amifred; McGrath, Michael

2016-03-01

In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. (99m)Tc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10(-11)M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), that the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 min to bind more tilmanocept (acting as intracellular "drug compilers" of tilmanocept into non-degraded vesicles), gives serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate (99m)Tc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for imaging

HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

NASA Astrophysics Data System (ADS)

Wang, Can; Bao, Chenchen; Liang, Shujing; Zhang, Lingxia; Fu, Hualin; Wang, Yutian; Wang, Kan; Li, Chao; Deng, Min; Liao, Qiande; Ni, Jian; Cui, Daxiang

2014-05-01

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future.

[Morphological characteristics of inflammation in HIV-associated pulmonary tuberculosis with regard to the expression of myeloperoxidase].

PubMed

Bykhalov, L S; Smirnov, A V

2015-01-01

to characterize the morphological features of inflammation and the degree of myeloperoxidase expression in the lung of patients who died from HIV-associated tuberculosis (TB). Autopsy lung tissue specimens from 229 patients with HIV-associated TB were examined. A comparison group consisted of dead TB mono-infected patients (n = 30). Dead HIV/TB co-infected patients were divided into subgroups: 1) 50 patients with Stage 4A-4B and a CD4(+)-lymphocyte count of more than 200 cells/µl; 2) 54 with Stage 4B-4C and a CD4(+)-lymphocyte count of 100 to 200 cells/µl; 3) 125 with Stage 4C-5 and a CD4(+)-lymphocyte count of less than 100 cells/µl. Histological and immunohistochemical examinations of lung slices were performed using antibodies to myeloperoxidase (MPO). The predominant types of an inflammatory response were revealed according to the level of CD4+ lymphocytes. The lungs in Subgroup 1 showed a predominant typical granulomatous response (82%). Subgroup 2 exhibited an exudative-productive inflammatory response (57.4%) while Subgroup 3 displayed an alterative necrotic type (92.8%). Subgroup 3 showed the most marked reduction in lymphocyte numbers in the areas of inflammation, which was accompanied by a significant increase in the relative density and other morphometric parameters of MPO-positive macrophages and granulocytes in the inflammatory infiltration zones and alveolar walls. The identified changes in the lungs suggest that there is a decline in the magnitude of a delayed type hypersensitivity reaction, a progression of alterative necrotic processes as CD4(+) lymphocytes decrease in the systemic blood flow, and an increase in the proportion of functionally immature macrophages in the areas of inflammation, which reflects a substantially impaired local immune response to the persistence of M. tuberculosis in HIV infection.

Assessment of α-fetoprotein targeted HSV1-tk expression in hepatocellular carcinoma with in vivo imaging.

PubMed

Park, Ju Hui; Kim, Kwang Il; Lee, Kyo Chul; Lee, Yong Jin; Lee, Tae Sup; Chung, Wee Sup; Lim, Sang Moo; Kang, Joo Hyun

2015-02-01

Tumor-specific enhancer/promoter is applicable for targeting gene expression in tumors and helpful for tumor-targeting imaging and therapy. We aimed to acquire α-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) specific images using adenovirus containing HSV1-tk gene controlled by AFP enhancer/promoter and evaluate in vivo ganciclovir (GCV)-medicated therapeutic effects on AFP-targeted HSV1-tk expression with (18)F-FDG positron emission tomography (PET). Recombinant adenovirus expressing HSV1-tk under AFP enhancer/promoter was produced (AdAFP-TK) and the expression levels were evaluated by RT-PCR and (125)I-IVDU uptake. GCV-mediated HSV1-tk cytotoxicity was determined by MTT assay. After the mixture of AdAFP-fLuc and AdAFP-TK was administrated, bioluminescent images (BLIs) and (18)F-FHBG PET images were obtained in tumor-bearing mice. In vivo therapeutic effects of AdAFP-TK and GCV in the HuH-7 xenograft model were monitored by (18)F-FDG PET. When infected with AdAFP-TK, cell viability in HuH-7 was reduced, but those in HT-29 and SK-Hep-1 were not significantly decreased at any GCV concentration less than 100 μM. AFP-targeted fLuc and HSV1-tk expression were clearly visualized by BLI and (18)F-FHBG PET images in AFP-producing HCC, respectively. In vivo GCV-mediated tumor growth inhibition by AFP-targeted HSV1-tk expression was monitored by (18)F-FDG PET. Recombinant AdAFP-TK could be applied for AFP-targeted HCC gene therapy and imaging in AFP-producing HCC.

[Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124].

PubMed

Zhu, H; Wang, F; Guo, X Y; Li, L Q; Duan, D B; Liu, Z B; Yang, Z

2018-04-18

To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application. 124 Te (p,n) 124 I nuclide reaction was used for the 124 I production. Firstly, the target material, 124 TeO 2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124 I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124 I.After 740 kBq 124 I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124 I's metabolism in the mice. It was been successfully applied for 200 mg 124 TeO 2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124 Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 μA current on HM-20 cyclotron. Then 370-1 110 MBq 124 I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification. 124 I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124 I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124 I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge

Myeloperoxidase Antineutrophil Cytoplasmic Antibody (MPO-ANCA) Associated Crescentic and Necrotizing Glomerulonephritis (GN) with Membranoproliferative GN Features.

PubMed

Koda, Ryo; Nagahori, Katsuhiro; Kitazawa, Atsushi; Imanishi, Yuji; Yoshino, Atsunori; Kawamoto, Shinya; Ueda, Yoshihiko; Takeda, Tetsuro

2016-01-01

A 77-year-old man presented with a fever, non-productive cough, and edema formation. A laboratory analysis showed an elevated creatinine level (2.5 mg/dL), a high titer of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (99 U/mL), positive reaction for antinuclear antibody (×320), hematuria, and massive proteinuria (3.33 g/day). A renal biopsy revealed crescentic and necrotizing glomerulonephritis (GN) with membranoproliferative GN features [double contour appearance of the glomerular basement membrane, granular deposition of immunoglobulin (Ig) G, IgM, and C3 along the capillary wall, subendothelial and subepithelial deposits with mesangial interposition]. A potential relationship between MPO-ANCA associated GN and membranoproliferative GN is discussed.

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

PubMed

Arsenault, Frédéric; Beauregard, Jean-Mathieu; Pouliot, Frédéric

2018-06-22

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact management impacts of PSMA-targeted molecules are urgently needed.

First Image from a Mars Rover Choosing a Target, False Color

NASA Image and Video Library

2010-03-23

This image is the result of the first observation of a target selected autonomously by NASA Opportunity using newly developed and uploaded software called AEGIS. The false color makes some differences between materials easier to see.

Sulphoxidation reaction catalysed by myeloperoxidase from human leucocytes.

PubMed Central

Capeillère-Blandin, C; Martin, C; Gaggero, N; Pasta, P; Carrea, G; Colonna, S

1998-01-01

The oxidation of alkyl aryl sulphides by myeloperoxidase (MPO) at the expense of hydrogen peroxide was investigated under steady-state conditions. The sulphide concentration effect was studied under saturating H2O2 concentrations at pH 5.0 and 20 degreesC. The kinetic constants, kcat and Km, of the different substrates were determined and the values were in the 1-10 s-1 range and around 43+/-26 microM respectively, whatever the sulphide considered. In the case of p-substituted thioanisoles, the oxidation rate was dependent upon the substituent effect. The correlation of log(kcat) with the substituent constants (sigma+ values) (Hammett equation) could be explained by a reaction mechanism involving the enzyme compound II and a sulphenium radical cation. This conclusion was also supported by spectrophotometric analysis of catalytic intermediates of the enzyme, showing the accumulation of compound II. Moreover, chiral HPLC analyses showed that MPO oxidation of alkyl aryl sulphides produced the corresponding (R)-sulphoxides with a low enantioselectivity (4-8%). Chloride ion effects on the MPO-catalysed oxygenation of sulphides were also studied. Chloride acted as a substrate for MPO and as an activator in MPO-catalysed sulphoxidation. Inhibition occurred at chloride concentrations above 120 mM, whereas below 120 mM, chloride increased the reaction rate when using p-tolyl methyl sulphide as the substrate. In the presence of 100 mM chloride the catalytic efficiency (kcat/Km) of MPO increased 3-4-fold, whatever the sulphide considered, but racemic products were obtained. These data have been interpreted in the light of known structural information on the accessibility of the distal haem cavity. PMID:9742209

Sulphoxidation reaction catalysed by myeloperoxidase from human leucocytes.

PubMed

Capeillère-Blandin, C; Martin, C; Gaggero, N; Pasta, P; Carrea, G; Colonna, S

1998-10-01

The oxidation of alkyl aryl sulphides by myeloperoxidase (MPO) at the expense of hydrogen peroxide was investigated under steady-state conditions. The sulphide concentration effect was studied under saturating H2O2 concentrations at pH 5.0 and 20 degreesC. The kinetic constants, kcat and Km, of the different substrates were determined and the values were in the 1-10 s-1 range and around 43+/-26 microM respectively, whatever the sulphide considered. In the case of p-substituted thioanisoles, the oxidation rate was dependent upon the substituent effect. The correlation of log(kcat) with the substituent constants (sigma+ values) (Hammett equation) could be explained by a reaction mechanism involving the enzyme compound II and a sulphenium radical cation. This conclusion was also supported by spectrophotometric analysis of catalytic intermediates of the enzyme, showing the accumulation of compound II. Moreover, chiral HPLC analyses showed that MPO oxidation of alkyl aryl sulphides produced the corresponding (R)-sulphoxides with a low enantioselectivity (4-8%). Chloride ion effects on the MPO-catalysed oxygenation of sulphides were also studied. Chloride acted as a substrate for MPO and as an activator in MPO-catalysed sulphoxidation. Inhibition occurred at chloride concentrations above 120 mM, whereas below 120 mM, chloride increased the reaction rate when using p-tolyl methyl sulphide as the substrate. In the presence of 100 mM chloride the catalytic efficiency (kcat/Km) of MPO increased 3-4-fold, whatever the sulphide considered, but racemic products were obtained. These data have been interpreted in the light of known structural information on the accessibility of the distal haem cavity.

The myeloperoxidase-derived oxidant HOSCN inhibits protein tyrosine phosphatases and modulates cell signalling via the mitogen-activated protein kinase (MAPK) pathway in macrophages

PubMed Central

Lane, Amanda E.; Tan, Joanne T. M.; Hawkins, Clare L.; Heather, Alison K.; Davies, Michael J.

2010-01-01

MPO (myeloperoxidase) catalyses the oxidation of chloride, bromide and thiocyanate by hydrogen peroxide to HOCl (hypochlorous acid), HOBr (hypobromous acid) and HOSCN (hypothiocyanous acid) respectively. Specificity constants indicate that SCN− is a major substrate for MPO. HOSCN is also a major oxidant generated by other peroxidases including salivary, gastric and eosinophil peroxidases. While HOCl and HOBr are powerful oxidizing agents, HOSCN is a less reactive, but more specific, oxidant which targets thiols and especially low pKa species. In the present study we show that HOSCN targets cysteine residues present in PTPs (protein tyrosine phosphatases) with this resulting in a loss of PTP activity for the isolated enzyme, in cell lysates and intact J774A.1 macrophage-like cells. Inhibition also occurs with MPO-generated HOCl and HOBr, but is more marked with MPO-generated HOSCN, particularly at longer incubation times. This inhibition is reversed by dithiothreitol, particularly at early time points, consistent with the reversible oxidation of the active site cysteine residue to give either a cysteine–SCN adduct or a sulfenic acid. Inhibition of PTP activity is associated with increased phosphorylation of p38a and ERK2 (extracellular-signal-regulated kinase 2) as detected by Western blot analysis and phosphoprotein arrays, and results in altered MAPK (mitogen-activated protein kinase) signalling. These data indicate that the highly selective targeting of some protein thiols by HOSCN can result in perturbation of cellular phosphorylation and altered cell signalling. These changes occur with (patho)physiological concentrations of SCN− ions, and implicate HOSCN as an important mediator of inflammation-induced oxidative damage, particularly in smokers who have elevated plasma levels of SCN−. PMID:20528774

An automatic target recognition system based on SAR image

NASA Astrophysics Data System (ADS)

Li, Qinfu; Wang, Jinquan; Zhao, Bo; Luo, Furen; Xu, Xiaojian

2009-10-01

In this paper, an automatic target recognition (ATR) system based on synthetic aperture radar (SAR) is proposed. This ATR system can play an important role in the simulation of up-to-data battlefield environment and be used in ATR research. To establish an integral and available system, the processing of SAR image was divided into four main stages which are de-noise, detection, cluster-discrimination and segment-recognition, respectively. The first three stages are used for searching region of interest (ROI). Once the ROIs are extracted, the recognition stage will be taken to compute the similarity between the ROIs and the templates in the electromagnetic simulation software National Electromagnetic Scattering Code (NESC). Due to the lack of the SAR raw data, the electromagnetic simulated images are added to the measured SAR background to simulate the battlefield environment8. The purpose of the system is to find the ROIs which can be the artificial military targets such as tanks, armored cars and so on and to categorize the ROIs into the right classes according to the existing templates. From the results we can see that the proposed system achieves a satisfactory result.

Autoradiography imaging in targeted alpha therapy with Timepix detector.

PubMed

A L Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

2015-01-01

There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

PubMed Central

AL Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

2015-01-01

There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy. PMID:25688285

Myeloperoxidase scavenges peroxynitrite: A novel anti-inflammatory action of the heme enzyme

PubMed Central

Koyani, Chintan N.; Flemmig, Joerg; Malle, Ernst; Arnhold, Juergen

2015-01-01

Peroxynitrite, a potent pro-inflammatory and cytotoxic species, interacts with a variety of heme containing proteins. We addressed the question whether (i) the interaction of myeloperoxidase (MPO, an enzyme generating hypochlorous acid from hydrogen peroxide and chloride ions) with peroxynitrite affects the clearance of peroxynitrite, and (ii) if peroxynitrite could modulate the chlorinating activity of MPO. Our results show that this interaction promotes the decomposition of the highly reactive pro-inflammatory oxidant, whereby MPO Compound II (but not Compound I) is formed. The efficiency of MPO to remove peroxynitrite was enhanced by l-tyrosine, nitrite and (−)-epicatechin, substances known to reduce Compound II with high reaction rate. Next, peroxynitrite (added as reagent) diminished the chlorinating activity of MPO in the presence of hydrogen peroxide. Alternatively, SIN-1, a peroxynitrite donor, reduced hypochlorous acid formation by MPO, as measured by aminophenyl fluorescein oxidation (time kinetics) and taurine chloramine formation (end point measurement). At inflammatory loci, scavenging of peroxynitrite by MPO may overcome the uncontrolled peroxynitrite decomposition and formation of reactive species, which lead to cell/tissue damage. PMID:25731855

Supervised target detection in hyperspectral images using one-class Fukunaga-Koontz Transform

NASA Astrophysics Data System (ADS)

Binol, Hamidullah; Bal, Abdullah

2016-05-01

A novel hyperspectral target detection technique based on Fukunaga-Koontz transform (FKT) is presented. FKT offers significant properties for feature selection and ordering. However, it can only be used to solve multi-pattern classification problems. Target detection may be considered as a two-class classification problem, i.e., target versus background clutter. Nevertheless, background clutter typically contains different types of materials. That's why; target detection techniques are different than classification methods by way of modeling clutter. To avoid the modeling of the background clutter, we have improved one-class FKT (OC-FKT) for target detection. The statistical properties of target training samples are used to define tunnel-like boundary of the target class. Non-target samples are then created synthetically as to be outside of the boundary. Thus, only limited target samples become adequate for training of FKT. The hyperspectral image experiments confirm that the proposed OC-FKT technique provides an effective means for target detection.

Minimal resin embedding of multicellular specimens for targeted FIB-SEM imaging.

PubMed

Schieber, Nicole L; Machado, Pedro; Markert, Sebastian M; Stigloher, Christian; Schwab, Yannick; Steyer, Anna M

2017-01-01

Correlative light and electron microscopy (CLEM) is a powerful tool to perform ultrastructural analysis of targeted tissues or cells. The large field of view of the light microscope (LM) enables quick and efficient surveys of the whole specimen. It is also compatible with live imaging, giving access to functional assays. CLEM protocols take advantage of the features to efficiently retrace the position of targeted sites when switching from one modality to the other. They more often rely on anatomical cues that are visible both by light and electron microscopy. We present here a simple workflow where multicellular specimens are embedded in minimal amounts of resin, exposing their surface topology that can be imaged by scanning electron microscopy (SEM). LM and SEM both benefit from a large field of view that can cover whole model organisms. As a result, targeting specific anatomic locations by focused ion beam-SEM (FIB-SEM) tomography becomes straightforward. We illustrate this application on three different model organisms, used in our laboratory: the zebrafish embryo Danio rerio, the marine worm Platynereis dumerilii, and the dauer larva of the nematode Caenorhabditis elegans. Here we focus on the experimental steps to reduce the amount of resin covering the samples and to image the specimens inside an FIB-SEM. We expect this approach to have widespread applications for volume electron microscopy on multiple model organisms. Copyright © 2017 Elsevier Inc. All rights reserved.

3D range-gated super-resolution imaging based on stereo matching for moving platforms and targets

NASA Astrophysics Data System (ADS)

Sun, Liang; Wang, Xinwei; Zhou, Yan

2017-11-01

3D range-gated superresolution imaging is a novel 3D reconstruction technique for target detection and recognition with good real-time performance. However, for moving targets or platforms such as airborne, shipborne, remote operated vehicle and autonomous vehicle, 3D reconstruction has a large error or failure. In order to overcome this drawback, we propose a method of stereo matching for 3D range-gated superresolution reconstruction algorithm. In experiment, the target is a doll of Mario with a height of 38cm at the location of 34m, and we obtain two successive frame images of the Mario. To confirm our method is effective, we transform the original images with translation, rotation, scale and perspective, respectively. The experimental result shows that our method has a good result of 3D reconstruction for moving targets or platforms.

Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications

NASA Astrophysics Data System (ADS)

Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi

2014-07-01

Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a

Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms

PubMed Central

Kwon, Yong-Soo; Cho, Young-Seok; Yoon, Tae-Jong; Kim, Ho-Shik; Choi, Myung-Gyu

2012-01-01

Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer. PMID:22442742

Multimodality Imaging with Silica-Based Targeted Nanoparticle Platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jason S. Lewis

2012-04-09

Objectives: To synthesize and characterize a C-Dot silica-based nanoparticle containing 'clickable' groups for the subsequent attachment of targeting moieties (e.g., peptides) and multiple contrast agents (e.g., radionuclides with high specific activity) [1,2]. These new constructs will be tested in suitable tumor models in vitro and in vivo to ensure maintenance of target-specificity and high specific activity. Methods: Cy5 dye molecules are cross-linked to a silica precursor which is reacted to form a dye-rich core particle. This core is then encapsulated in a layer of pure silica to create the core-shell C-Dot (Figure 1) [2]. A 'click' chemistry approach has beenmore » used to functionalize the silica shell with radionuclides conferring high contrast and specific activity (e.g. 64Cu and 89Zr) and peptides for tumor targeting (e.g. cRGD and octreotate) [3]. Based on the selective Diels-Alder reaction between tetrazine and norbornene, the reaction is bioorthogonal, highyielding, rapid, and water-compatible. This radiolabeling approach has already been employed successfully with both short peptides (e.g. octreotate) and antibodies (e.g. trastuzumab) as model systems for the ultimate labeling of the nanoparticles [1]. Results: PEGylated C-Dots with a Cy5 core and labeled with tetrazine have been synthesized (d = 55 nm, zeta potential = -3 mV) reliably and reproducibly and have been shown to be stable under physiological conditions for up to 1 month. Characterization of the nanoparticles revealed that the immobilized Cy5 dye within the C-Dots exhibited fluorescence intensities over twice that of the fluorophore alone. The nanoparticles were successfully radiolabeled with Cu-64. Efforts toward the conjugation of targeting peptides (e.g. cRGD) are underway. In vitro stability, specificity, and uptake studies as well as in vivo imaging and biodistribution investigations will be presented. Conclusions: C-Dot silica-based nanoparticles offer a robust, versatile, and

Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery across Biological Barriers

PubMed Central

Kievit, Forrest M.; Zhang, Miqin

2012-01-01

Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge that requires targeted therapy to treat effectively. Targeted therapy can be achieved with appropriate designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of materials commonly used to synthesize nanotheranostic particles and their use in imaging. We then discuss biological barriers that these nanoparticles encounter and must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells using nanoparticles, adult stem cells, and T cells in immunotherapy. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy. PMID:21842473

Performance of target detection algorithm in compressive sensing miniature ultraspectral imaging compressed sensing system

NASA Astrophysics Data System (ADS)

Gedalin, Daniel; Oiknine, Yaniv; August, Isaac; Blumberg, Dan G.; Rotman, Stanley R.; Stern, Adrian

2017-04-01

Compressive sensing theory was proposed to deal with the high quantity of measurements demanded by traditional hyperspectral systems. Recently, a compressive spectral imaging technique dubbed compressive sensing miniature ultraspectral imaging (CS-MUSI) was presented. This system uses a voltage controlled liquid crystal device to create multiplexed hyperspectral cubes. We evaluate the utility of the data captured using the CS-MUSI system for the task of target detection. Specifically, we compare the performance of the matched filter target detection algorithm in traditional hyperspectral systems and in CS-MUSI multiplexed hyperspectral cubes. We found that the target detection algorithm performs similarly in both cases, despite the fact that the CS-MUSI data is up to an order of magnitude less than that in conventional hyperspectral cubes. Moreover, the target detection is approximately an order of magnitude faster in CS-MUSI data.

Imaging cellularity in benign and malignant peripheral nerve sheath tumors: Utility of the "target sign" by diffusion weighted imaging.

PubMed

Ahlawat, Shivani; Fayad, Laura M

2018-05-01

To determine the utility of "target sign" on diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping for peripheral nerve sheath tumor (PNST) characterization. This IRB-approved, HIPAA-compliant study retrospectively reviewed the MR imaging (comprised of T2- FS, DWI (b-values 50, 400, 800 s/mm 2 and ADC mapping), and static contrast-enhanced (CE) T1-W imaging) of 42 patients (mean age: 40 years (range 8-68 years), 48% (20/42) females) with 15 malignant PNSTs (MPNSTs) and 33 benign PNSTs (BPNSTs). MPNSTs were histologically confirmed while BPNSTs were histologically-proven or with stable clinical and imaging appearance for at least 12 months. Two radiologists assessed imaging characteristics (size, signal intensity, heterogeneity, perilesional edema or enhancement) and the presence or absence of "target sign," on each sequence. A "target sign" was defined as a biphasic pattern of peripheral hyperintensity and homogeneous central hypointensity. Descriptive statistics are reported. Cohen's κ statistic or interclass correlation coefficient (ICC) were used to evaluate interobserver agreement between two observers. Univariate and multiple logistic regression analysis were performed to identify MRI features with predictive values. MPNSTs were larger than BPNSTs (6.3 ± 2.5 cm vs 3.5 ± -2.1 cm, p = 0.0002), had perilesional edema (87%(13/15) vs 18%(6/33), p < 0.0001), heterogeneous enhancement (71%(10/14) vs 13%(4/31), p = 0.0001) and perilesional enhancement (79%(11/14) vs 18%(6/31), p = 0.0001), respectively. The "target sign" was present in: 24%(8/33) BPNSTs vs 0/15 MPNST on T2-FS (p = 0.26); 39%(13/33) BPNSTs vs 20%(3/15) MPNST on DWI using b-value = 50 s/mm 2 (p = 0.5); 55%(18/33) BPNSTs vs 6%(1/15) MPNST on DWI using b-value = 400 s/mm 2 (p = 0.002); 48%(16/33) BPNSTs vs 6%(1/15) MPNST on DWI using b-value = 800 s/mm 2 (p = 0.005) and 64%(21/33) benign vs 0/15 MPNST on ADC

Multifunctional quantum dot-polypeptide hybrid nanogel for targeted imaging and drug delivery

NASA Astrophysics Data System (ADS)

Yang, Jie; Yao, Ming-Hao; Wen, Lang; Song, Ji-Tao; Zhang, Ming-Zhen; Zhao, Yuan-Di; Liu, Bo

2014-09-01

A new type of multifunctional quantum dot (QD)-polypeptide hybrid nanogel with targeted imaging and drug delivery properties has been developed by metal-affinity driven self-assembly between artificial polypeptides and CdSe-ZnS core-shell QDs. On the surface of QDs, a tunable sandwich-like microstructure consisting of two hydrophobic layers and one hydrophilic layer between them was verified by capillary electrophoresis, transmission electron microscopy, and dynamic light scattering measurements. Hydrophobic and hydrophilic drugs can be simultaneously loaded in a QD-polypeptide nanogel. In vitro drug release of drug-loaded QD-polypeptide nanogels varies strongly with temperature, pH, and competitors. A drug-loaded QD-polypeptide nanogel with an arginine-glycine-aspartic acid (RGD) motif exhibited efficient receptor-mediated endocytosis in αvβ3 overexpressing HeLa cells but not in the control MCF-7 cells as analyzed by confocal microscopy and flow cytometry. In contrast, non-targeted QD-polypeptide nanogels revealed minimal binding and uptake in HeLa cells. Compared with the original QDs, the QD-polypeptide nanogels showed lower in vitro cytotoxicity for both HeLa cells and NIH 3T3 cells. Furthermore, the cytotoxicity of the targeted QD-polypeptide nanogel was lower for normal NIH 3T3 cells than that for HeLa cancer cells. These results demonstrate that the integration of imaging and drug delivery functions in a single QD-polypeptide nanogel has the potential for application in cancer diagnosis, imaging, and therapy.A new type of multifunctional quantum dot (QD)-polypeptide hybrid nanogel with targeted imaging and drug delivery properties has been developed by metal-affinity driven self-assembly between artificial polypeptides and CdSe-ZnS core-shell QDs. On the surface of QDs, a tunable sandwich-like microstructure consisting of two hydrophobic layers and one hydrophilic layer between them was verified by capillary electrophoresis, transmission electron

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

PubMed Central

Molenaar, Ger; de Waard, Vivian; Lutgens, Esther; van Eck-Smit, Berthe L. F.; de Bruin, Kora; Piek, Jan J.; Eersels, Jos L. H.; Booij, Jan; Verberne, Hein J.; Windhorst, Albert D.

2017-01-01

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice. PMID:29190653

Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

PubMed Central

Balasundaram, Ghayathri; Ho, Chris Jun Hui; Li, Kai; Driessen, Wouter; Dinish, US; Wong, Chi Lok; Ntziachristos, Vasilis; Liu, Bin; Olivo, Malini

2015-01-01

Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications. PMID:25609951

A computational imaging target specific detectivity metric

NASA Astrophysics Data System (ADS)

Preece, Bradley L.; Nehmetallah, George

2017-05-01

Due to the large quantity of low-cost, high-speed computational processing available today, computational imaging (CI) systems are expected to have a major role for next generation multifunctional cameras. The purpose of this work is to quantify the performance of theses CI systems in a standardized manner. Due to the diversity of CI system designs that are available today or proposed in the near future, significant challenges in modeling and calculating a standardized detection signal-to-noise ratio (SNR) to measure the performance of these systems. In this paper, we developed a path forward for a standardized detectivity metric for CI systems. The detectivity metric is designed to evaluate the performance of a CI system searching for a specific known target or signal of interest, and is defined as the optimal linear matched filter SNR, similar to the Hotelling SNR, calculated in computational space with special considerations for standardization. Therefore, the detectivity metric is designed to be flexible, in order to handle various types of CI systems and specific targets, while keeping the complexity and assumptions of the systems to a minimum.

Distinct gene alterations with a high percentage of myeloperoxidase-positive leukemic blasts in de novo acute myeloid leukemia.

PubMed

Kamijo, Rena; Itonaga, Hidehiro; Kihara, Rika; Nagata, Yasunobu; Hata, Tomoko; Asou, Norio; Ohtake, Shigeki; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ogawa, Seishi; Naoe, Tomoki; Kiyoi, Hitoshi; Miyazaki, Yasushi

2018-02-01

The myeloperoxidase (MPO)-positivity of blasts in bone marrow smears is an important marker for not only the diagnosis, but also the prognosis of acute myeloid leukemia (AML). To investigate the relationship between genetic alterations and MPO-positivity, we performed targeted sequencing for 51 genes and 10 chimeric gene transcripts in 164 newly diagnosed de novo AML patients; 107 and 57 patients were classified as AML with >50% MPO-positive blasts (MPO-high group) and ≤50% MPO-positive blasts, (MPO-low group), respectively. The univariate analysis revealed that RUNX1-RUNX1T1 (P < 0.001), the KIT mutation (P < 0.001), and CEBPA double mutation (P = 0.001) were more likely to be found in the MPO-high group, while the DNMT3A mutation (P = 0.001), FLT3 tyrosine kinase domain mutation (P = 0.004), and TP53 mutation (P = 0.020) were more likely to be present in the MPO-low group. Mutations in genes related to DNA hypermethylation signatures (IDH1, IDH2, TET2, and WT1 genes) were more frequent in the MPO-high group (P = 0.001) when patients with fusion genes of core-binding factors were excluded from the analysis. Our results suggest that MPO-positivity of blasts was related with the distinct gene mutation patterns among de novo AML patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imaging-guided preclinical trials of vascular targeting in prostate cancer

NASA Astrophysics Data System (ADS)

Kalmuk, James

Purpose: Prostate cancer is the most common non-cutaneous malignancy in American men and is characterized by dependence on androgens (Testosterone/Dihydrotestosterone) for growth and survival. Although reduction of serum testosterone levels by surgical or chemical castration transiently inhibits neoplastic growth, tumor adaptation to castrate levels of androgens results in the generation of castration-resistant prostate cancer (CRPC). Progression to CRPC following androgen deprivation therapy (ADT) has been associated with changes in vascular morphology and increased angiogenesis. Based on this knowledge, we hypothesized that targeting tumor vasculature in combination with ADT would result in enhanced therapeutic efficacy against prostate cancer. Methods: To test this hypothesis, we examined the therapeutic activity of a tumor-vascular disrupting agent (tumor-VDA), EPC2407 (Crolibulin(TM)), alone and in combination with ADT in a murine model of prostate cancer (Myc-CaP). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to characterize tumor response to therapy and to guide preclinical trial design. Imaging results were correlated with histopathologic (H&E) and immunohistochemical (CD31) assessment as well as tumor growth inhibition and survival analyses. Results: Our imaging techniques were able to capture an acute reduction (within 24 hours) in tumor perfusion following castration and VDA monotherapy. BLI revealed onset of recurrent disease 5-7 days post castration prior to visible tumor regrowth suggestive of vascular recovery. Administration of VDA beginning 1 week post castration for 3 weeks resulted in sustained vascular suppression, inhibition of tumor regrowth, and conferred a more pronounced survival benefit compared to either monotherapy. Conclusion: The high mortality rate associated with CRPC underscores the need for investigating novel treatment

Fluorescence imaging with multifunctional polyglycerol sulfates: novel polymeric near-IR probes targeting inflammation.

PubMed

Licha, Kai; Welker, Pia; Weinhart, Marie; Wegner, Nicole; Kern, Sylvia; Reichert, Stefanie; Gemeinhardt, Ines; Weissbach, Carmen; Ebert, Bernd; Haag, Rainer; Schirner, Michael

2011-12-21

We present a highly selective approach for the targeting of inflammation with a multivalent polymeric probe. Dendritic polyglycerol was employed to synthesize a polyanionic macromolecular conjugate with a near-infrared fluorescent dye related to Indocyanine Green (ICG). On the basis of the dense assembly of sulfate groups which were generated from the polyol core, the resulting polyglycerol sulfate (molecular weight 12 kD with ~70 sulfate groups) targets factors of inflammation (IC(50) of 3-6 nM for inhibition of L-selectin binding) and is specifically transported into inflammatory cells. The in vivo accumulation studied by near-IR fluorescence imaging in an animal model of rheumatoid arthritis demonstrated fast and selective uptake which enabled the differentiation of diseased joints (score 1-3) with a 3.5-fold higher fluorescence level and a signal maximum at 60 min post injection. Localization in tissues using fluorescence histology showed that the conjugates are deposited in the inflammatory infiltrate in the synovial membrane, whereas nonsulfated control was not detected in association with disease. Hence, this type of polymeric imaging probe is an alternative to current bioconjugates and provides future options for targeted imaging and drug delivery.

Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

PubMed Central

Wang, Xinning; Huang, Steve S.; Heston, Warren D.W.; Guo, Hong; Wang, Bing-Cheng; Basilion, James P.

2015-01-01

Prostate cancer is the most common noncutaneous malignancy affecting men in North America. Radical prostatectomy remains a definitive treatment for prostate cancer. However, prostate surgeries are still performed “blindly” with the extent of tumor infiltration past the margins of the surgery only being determined postoperatively. An imaging modality that can be used during surgery is needed to help define the tumor margins. With its abundant expression in prostate cancer, prostate-specific membrane antigen (PSMA) is an ideal target for detection of prostate cancer. The purpose of this study was to develop PSMA-targeted near-infrared (NIR) optical imaging probes for intraoperative visualization of prostate cancer. We synthesized a high-affinity PSMA ligand (PSMA-1) with low molecular weight and further labeled it with commercially available NIR dyes IRDy800 and Cy5.5. PSMA-1 and PSMA-1–NIR conjugates had binding affinities better than the parent ligand Cys-CO-Glu. Selective binding was measured for each of the probes in both in vitro and in vivo studies using competitive binding and uptake studies. Interestingly, the results indicated that the pharmacokinetics of the probes was dependent of the fluorophore conjugated to the PSMA-1 ligand and varied widely. These data suggest that PSMA-targeted probes have the potential to be further developed as contrast agents for clinical intraoperative fluorescence-guided surgery. PMID:25239933

Comparison of conventional ultrasonography and ultrasonography-computed tomography fusion imaging for target identification using digital/real hybrid phantoms: a preliminary study.

PubMed

Soyama, Takeshi; Sakuhara, Yusuke; Kudo, Kohsuke; Abo, Daisuke; Wang, Jeff; Ito, Yoichi M; Hasegawa, Yu; Shirato, Hiroki

2016-07-01

This preliminary study compared ultrasonography-computed tomography (US-CT) fusion imaging and conventional ultrasonography (US) for accuracy and time required for target identification using a combination of real phantoms and sets of digitally modified computed tomography (CT) images (digital/real hybrid phantoms). In this randomized prospective study, 27 spheres visible on B-mode US were placed at depths of 3.5, 8.5, and 13.5 cm (nine spheres each). All 27 spheres were digitally erased from the CT images, and a radiopaque sphere was digitally placed at each of the 27 locations to create 27 different sets of CT images. Twenty clinicians were instructed to identify the sphere target using US alone and fusion imaging. The accuracy of target identification of the two methods was compared using McNemar's test. The mean time required for target identification and error distances were compared using paired t tests. At all three depths, target identification was more accurate and the mean time required for target identification was significantly less with US-CT fusion imaging than with US alone, and the mean error distances were also shorter with US-CT fusion imaging. US-CT fusion imaging was superior to US alone in terms of accurate and rapid identification of target lesions.

Oxidant-induced DNA damage of target cells.

PubMed Central

Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

1988-01-01

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

High-resolution inverse synthetic aperture radar imaging for large rotation angle targets based on segmented processing algorithm

NASA Astrophysics Data System (ADS)

Chen, Hao; Zhang, Xinggan; Bai, Yechao; Tang, Lan

2017-01-01

In inverse synthetic aperture radar (ISAR) imaging, the migration through resolution cells (MTRCs) will occur when the rotation angle of the moving target is large, thereby degrading image resolution. To solve this problem, an ISAR imaging method based on segmented preprocessing is proposed. In this method, the echoes of large rotating target are divided into several small segments, and every segment can generate a low-resolution image without MTRCs. Then, each low-resolution image is rotated back to the original position. After image registration and phase compensation, a high-resolution image can be obtained. Simulation and real experiments show that the proposed algorithm can deal with the radar system with different range and cross-range resolutions and significantly compensate the MTRCs.

[The significances of peripheral neutrophils CD(55) and myeloperoxidase expression in patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody associated vasculitis].

PubMed

Zhou, X L; Zheng, M J; Shuai, Z W; Zhang, L; Zhang, M M; Chen, S Y

2017-06-01

Objective: To investigate the expression of CD(55) and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation. Methods: Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study. The CD(55) on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry. Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA. The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3). The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis. Results: (1)The mean fluorescence intensity(MFI) of CD(55) expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9, P =0.033]. Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L, P <0.001; 35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L, P <0.001], respectively. However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0, P =0.003) . (2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO( r =-0.710, P <0.001) and Ba ( r =-0.589, P =0.001). Moreover, serum MPO was positively associated with serum Ba( r =0.691, P <0.001). Membrane intensity of CD(55) on neutrophils was positively correlated with patient age ( r =0.514, P =0.001), C reactive protein ( r =0.376, P =0.018), peripheral neutrophils count ( r =0.485, P =0.001) and BVAS-V3 ( r =0.484, P =0.002), whereas negative correlation between membrane CD(55) and disease duration was seen ( r =-0.403, P =0.01). (3) The result of multiple

Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

PubMed

Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

2015-06-15

Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. ©2015 American Association for Cancer Research.

Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy.

PubMed

Chen, Dan; Li, Bowen; Cai, Songhua; Wang, Peng; Peng, Shuwen; Sheng, Yuanzhi; He, Yuanyuan; Gu, Yueqing; Chen, Haiyan

2016-09-01

Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to αvβ3integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

PubMed Central

Lee, J. J.; Poirier, M.; Little, D. J.; Prince, L. K.; Baker, T. P.; Edison, J. D.; Abbott, K. C.

2017-01-01

Background The subclinical pathophysiology of proliferative lupus nephritis (PLN) has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with PLN, but prediagnostic levels have not been reported. Methods We performed a retrospective case-control Department of Defense Serum Repository (DoDSR) study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN) patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab). Results A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p < 0.001; 57% versus 5%, p < 0.001, resp.). In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p = 0.007) and 1–4 years (87% versus 38%, p = 0.009) prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL) occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p = 0.003). Conclusions Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity. PMID:29435367

Advances in image compression and automatic target recognition; Proceedings of the Meeting, Orlando, FL, Mar. 30, 31, 1989

NASA Technical Reports Server (NTRS)

Tescher, Andrew G. (Editor)

1989-01-01

Various papers on image compression and automatic target recognition are presented. Individual topics addressed include: target cluster detection in cluttered SAR imagery, model-based target recognition using laser radar imagery, Smart Sensor front-end processor for feature extraction of images, object attitude estimation and tracking from a single video sensor, symmetry detection in human vision, analysis of high resolution aerial images for object detection, obscured object recognition for an ATR application, neural networks for adaptive shape tracking, statistical mechanics and pattern recognition, detection of cylinders in aerial range images, moving object tracking using local windows, new transform method for image data compression, quad-tree product vector quantization of images, predictive trellis encoding of imagery, reduced generalized chain code for contour description, compact architecture for a real-time vision system, use of human visibility functions in segmentation coding, color texture analysis and synthesis using Gibbs random fields.

Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On-Demand Release.

PubMed

Guldris, Noelia; Gallo, Juan; García-Hevia, Lorena; Rivas, José; Bañobre-López, Manuel; Salonen, Laura M

2018-04-12

A versatile iron oxide nanoparticle platform is reported that can be orthogonally functionalized to obtain highly derivatized nanomaterials required for a wide variety of applications, such as drug delivery, targeted therapy, or imaging. Facile functionalization of the nanoparticles with two ligands containing isocyanate moieties allows for high coverage of the surface with maleimide and alkyne groups. As a proof-of-principle, the nanoparticles were subsequently functionalized with a fluorophore as a drug model and with biotin as a targeting ligand towards tumor cells through Diels-Alder and azide-alkyne cycloaddition reactions, respectively. The thermoreversibility of the Diels-Alder product was exploited to induce the on-demand release of the loaded molecules by magnetic hyperthermia. Additionally, the nanoparticles were shown to target cancer cells through in vitro experiments, as analyzed by magnetic resonance imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Mathematical Model for Storage and Recall of Images using Targeted Synchronization of Coupled Maps.

PubMed

Palaniyandi, P; Rangarajan, Govindan

2017-08-21

We propose a mathematical model for storage and recall of images using coupled maps. We start by theoretically investigating targeted synchronization in coupled map systems wherein only a desired (partial) subset of the maps is made to synchronize. A simple method is introduced to specify coupling coefficients such that targeted synchronization is ensured. The principle of this method is extended to storage/recall of images using coupled Rulkov maps. The process of adjusting coupling coefficients between Rulkov maps (often used to model neurons) for the purpose of storing a desired image mimics the process of adjusting synaptic strengths between neurons to store memories. Our method uses both synchronisation and synaptic weight modification, as the human brain is thought to do. The stored image can be recalled by providing an initial random pattern to the dynamical system. The storage and recall of the standard image of Lena is explicitly demonstrated.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

NASA Astrophysics Data System (ADS)

Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, Daegab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2016-03-01

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

PubMed Central

Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2016-01-01

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

Noninvasive Imaging of Early Venous Thrombosis by 19F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions.

PubMed

Temme, Sebastian; Grapentin, Christoph; Quast, Christine; Jacoby, Christoph; Grandoch, Maria; Ding, Zhaoping; Owenier, Christoph; Mayenfels, Friederike; Fischer, Jens W; Schubert, Rolf; Schrader, Jürgen; Flögel, Ulrich

2015-04-21

Noninvasive detection of deep venous thrombi and subsequent pulmonary thromboembolism is a serious medical challenge, since both incidences are difficult to identify by conventional ultrasound techniques. Here, we report a novel technique for the sensitive and specific identification of developing thrombi using background-free 19F magnetic resonance imaging, together with α2-antiplasmin peptide (α2AP)-targeted perfluorocarbon nanoemulsions (PFCs) as contrast agent, which is cross-linked to fibrin by active factor XIII. Ligand functionality was ensured by mild coupling conditions using the sterol-based postinsertion technique. Developing thrombi with a diameter<0.8 mm could be visualized unequivocally in the murine inferior vena cava as hot spots in vivo by simultaneous acquisition of anatomic matching 1H and 19F magnetic resonance images at 9.4 T with both excellent signal-to-noise and contrast-to-noise ratios (71±22 and 17±5, respectively). Furthermore, α2AP-PFCs could be successfully applied for the diagnosis of experimentally induced pulmonary thromboembolism. In line with the reported half-life of factor XIIIa, application of α2AP-PFCs>60 minutes after thrombus induction no longer resulted in detectable 19F magnetic resonance imaging signals. Corresponding results were obtained in ex vivo generated human clots. Thus, α2AP-PFCs can visualize freshly developed thrombi that might still be susceptible to pharmacological intervention. Our results demonstrate that 1H/19F magnetic resonance imaging, together with α2AP-PFCs, is a sensitive, noninvasive technique for the diagnosis of acute deep venous thrombi and pulmonary thromboemboli. Furthermore, ligand coupling by the sterol-based postinsertion technique represents a unique platform for the specific targeting of PFCs for in vivo 19F magnetic resonance imaging. © 2015 American Heart Association, Inc.

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma

PubMed Central

Salloum, Darin; Carney, Brandon; Brand, Christian; Kossatz, Susanne; Sadique, Ahmad; Lewis, Jason S.; Weber, Wolfgang A.; Wendel, Hans-Guido; Reiner, Thomas

2017-01-01

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [18F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL. PMID:28827325

Arginine-glycine-aspartic acid-conjugated dendrimer-modified quantum dots for targeting and imaging melanoma.

PubMed

Li, Zhiming; Huang, Peng; Lin, Jing; He, Rong; Liu, Bing; Zhang, Xiaomin; Yang, Sen; Xi, Peng; Zhang, Xuejun; Ren, Qiushi; Cui, Daxiang

2010-08-01

Angiogenesis is essential for the development of malignant tumors and provides important targets for tumor diagnosis and therapy. Quantum dots have been broadly investigated for their potential application in cancer molecular imaging. In present work, CdSe quantum dots were synthesized, polyamidoamine dendrimers were used to modify surface of quantum dots and improve their solubility in water solution. Then, dendrimer-modified CdSe quantum dots were conjugated with arginine-glycine-aspartic acid (RGD) peptides. These prepared nanoprobes were injected into nude mice loaded with melanoma (A375) tumor xenografts via tail vessels, IVIS imaging system was used to image the targeting and bio-distribution of as-prepared nanoprobes. The dendrimer-modified quantum dots exhibit water-soluble, high quantum yield, and good biocompatibility. RGD-conjugated quantum dots can specifically target human umbilical vein endothelial cells (HUVEC) and A375 melanoma cells, as well as nude mice loaded with A735 melanoma cells. High-performance RGD-conjugated dendrimers modified quantum dot-based nanoprobes have great potential in application such as tumor diagnosis and therapy.

Kit formulated asialoglycoprotein receptor targeting tracer based on copolymer for liver SPECT imaging.

PubMed

Liu, Chang; Guo, Zhide; Zhang, Pu; Song, Manli; Zhao, Zuoquan; Wu, Xiaowei; Zhang, Xianzhong

2014-08-01

Specific targeting of galactose-carrying molecule to ASGP-R in normal hepatocytes has been demonstrated before. In this study, galactosyl polystyrene was synthesized from controllable ratio of functional monomers and radio-labelled with (99m)Tc by formulated kit for SPECT imaging of hepatic function. p(VLA-co-VNI)(46:54) was synthesized by free-radical copolymerization initiated by AIBN, purified by dialysis, lyophilized to kit with Tricine and TPPTS as co-ligands for (99m)Tc labeling. Radiotracer (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was prepared and evaluated by in vitro stability, in vivo metabolism, ex vivo biodistribution and microSPECT/CT imaging in normal KM mice. MicroSPECT/CT and microMRI imaging were also performed in C57BL/b6 mice with xenograft hepatic carcinoma for hepatic function evaluation. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was obtained in high radio chemical purity (RCP) (>99%) by using instant kit without further purification and excellent in vitro and in vivo stability. The result of biodistribution showed that liver had high uptake (90.49±10.68 ID%/g) at 30 min after injection and was blocked significantly by cold copolymer. MicroSPECT imaging in normal KM mice at 1h and 4h after injection showed good liver retention and targeting properties. Significant defect of activity was observed in the tumor site which was confirmed by MRI imaging. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) with lower ratio of targeting moiety has no observable effect on the specific binding affinity and liver uptake. This makes it possible to introduce more imaging units for multi-modality imaging. Furthermore, the instant kit preparation of (99m)Tc-labeling provides great potential for the evaluation of hepatocyte function in clinical application. Copyright © 2014 Elsevier Inc. All rights reserved.

Four-arm variable-resolution x-ray detector for CT target imaging

NASA Astrophysics Data System (ADS)

DiBianca, Frank A.; Gulabani, Daya; Jordan, Lawrence M.; Vangala, Sravanthi; Rendon, David; Laughter, Joseph S.; Melnyk, Roman; Gaber, M. W.; Keyes, Gary S.

2005-04-01

The basic VRX technique boosts spatial resolution of a CT scanner in the scan plane by two or more orders of magnitude by reducing the angle of incidence of the x-ray beam with respect to the detector surface. A four-arm Variable-Resolution X-ray (VRX) detector has been developed for CT scanning. The detector allows for "target imaging" in which an area of interest is scanned at higher resolution than the remainder of the subject, yielding even higher resolution for the focal area than that obtained from the basic VRX technique. The new VRX-CT detector comprises four quasi-identical arms each containing six 24-cell modules (576 cells total). The modules are made of individual custom CdWO4 scintillators optically-coupled to custom photodiode arrays. The maximum scan field is 40 cm for a magnification of 1.4. A significant advantage of the four-arm geometry is that it can transform quickly to the two-arm, or even the single-arm geometry, for comparison studies. These simpler geometries have already been shown experimentally to yield in-plane CT detector resolution exceeding 60 cy/mm (<8μ) for small fields of view. Geometrical size and resolution limits of the target VRX field are calculated. Two-arm VRX-CT data are used to simulate and establish the feasibility of VRX CT target imaging. A prototype target VRX-CT scanner has been built and is undergoing initial testing.

Emerging preclinical pharmacological targets for Parkinson's disease

PubMed Central

More, Sandeep Vasant; Choi, Dong-Kug

2016-01-01

Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms. PMID:26988916

Smart Cancer Cell Targeting Imaging and Drug Delivery System by Systematically Engineering Periodic Mesoporous Organosilica Nanoparticles.

PubMed

Lu, Nan; Tian, Ying; Tian, Wei; Huang, Peng; Liu, Ying; Tang, Yuxia; Wang, Chunyan; Wang, Shouju; Su, Yunyan; Zhang, Yunlei; Pan, Jing; Teng, Zhaogang; Lu, Guangming

2016-02-10

The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we first present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near-infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8% in 10 mM of GSH solution within 24 h, which is more than 2-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6% at pH 5 and 31.7% at pH 7.4 within 24 h. Confocal laser scanning microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a novel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug release, and high tumor cell targeting ability.

Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

2013-03-01

Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

Aptamer-conjugated Magnetic Nanoparticles as Targeted Magnetic Resonance Imaging Contrast Agent for Breast Cancer.

PubMed

Keshtkar, Mohammad; Shahbazi-Gahrouei, Daryoush; Khoshfetrat, Seyyed Mehdi; Mehrgardi, Masoud A; Aghaei, Mahmoud

2016-01-01

Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe 3 O 4 @Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells. The ability of the synthesized nanoprobe to target specifically the nucleolin overexpressed cells was assessed with the MRI technique. Results show that the synthesized nanoprobe produced strongly darkened T 2 -weighted magnetic resonance (MR) images with 4T1 cells, whereas the MR images of HFFF-PI6 cells incubated with the nanoprobe are brighter, showing small changes compared to water. The results demonstrate that in a Fe concentration of 45 μg/mL, the nanoprobe reduced by 90% MR image intensity in 4T1 cells compared with the 27% reduction in HFFF-PI6 cells. Analysis of MR signal intensity showed statistically significant signal intensity difference between 4T1 and HFFF-PI6 cells treated with the nanoprobe. MRI experiments demonstrate the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of nucleolin-expressing breast cancer cells.

Enzymatic single-chain antibody tagging: a universal approach to targeted molecular imaging and cell homing in cardiovascular disease.

PubMed

Ta, H T; Prabhu, S; Leitner, E; Jia, F; von Elverfeldt, D; Jackson, Katherine E; Heidt, T; Nair, A K N; Pearce, H; von Zur Muhlen, C; Wang, X; Peter, K; Hagemeyer, C E

2011-08-05

Antibody-targeted delivery of imaging agents can enhance the sensitivity and accuracy of current imaging techniques. Similarly, homing of effector cells to disease sites increases the efficacy of regenerative cell therapy while reducing the number of cells required. Currently, targeting can be achieved via chemical conjugation to specific antibodies, which typically results in the loss of antibody functionality and in severe cell damage. An ideal conjugation technique should ensure retention of antigen-binding activity and functionality of the targeted biological component. To develop a biochemically robust, highly reproducible, and site-specific coupling method using the Staphylococcus aureus sortase A enzyme for the conjugation of a single-chain antibody (scFv) to nanoparticles and cells for molecular imaging and cell homing in cardiovascular diseases. This scFv specifically binds to activated platelets, which play a pivotal role in thrombosis, atherosclerosis, and inflammation. The conjugation procedure involves chemical and enzyme-mediated coupling steps. The scFv was successfully conjugated to iron oxide particles (contrast agents for magnetic resonance imaging) and to model cells. Conjugation efficiency ranged between 50% and 70%, and bioactivity of the scFv after coupling was preserved. The targeting of scFv-coupled cells and nanoparticles to activated platelets was strong and specific as demonstrated in in vitro static adhesion assays, in a flow chamber system, in mouse intravital microscopy, and in in vivo magnetic resonance imaging of mouse carotid arteries. This unique biotechnological approach provides a versatile and broadly applicable tool for procuring targeted regenerative cell therapy and targeted molecular imaging in cardiovascular and inflammatory diseases and beyond.

Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

PubMed Central

Harpel, Kaitlin; Baker, Robert Dawson; Amirsolaimani, Babak; Mehravar, Soroush; Vagner, Josef; Matsunaga, Terry O.; Banerjee, Bhaskar; Kieu, Khanh

2016-01-01

The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained and ultrasound gel may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate, label-free imaging of tissues and cells with high resolution and contrast. We have recently determined a novel application of MPM to be used for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders. PMID:27446711

Radionuclide 131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors

NASA Astrophysics Data System (ADS)

Zhu, Jingyi; Zhao, Lingzhou; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Shen, Mingwu; Zhao, Jinhua; Shi, Xiangyang

2015-10-01

We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and

Multifunctional nanoparticle-EpCAM aptamer bioconjugates: a paradigm for targeted drug delivery and imaging in cancer therapy.

PubMed

Das, Manasi; Duan, Wei; Sahoo, Sanjeeb K

2015-02-01

The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and imaging agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-imaging modality both in 2D monolayer culture and tumor spheroid model. Our result suggests that, these aptamer-guided multifunctional NPs may act as indispensable nanotheranostic approach toward cancer therapy. This study investigated the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. It was concluded that the studied multifunctional targeted nanoparticle may become a viable and efficient approach in cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Imaging Tiny Hepatic Tumor Xenografts via Endoglin-Targeted Paramagnetic/Optical Nanoprobe.

PubMed

Yan, Huihui; Gao, Xihui; Zhang, Yunfei; Chang, Wenju; Li, Jianhui; Li, Xinwei; Du, Qin; Li, Cong

2018-05-23

Surgery is the mainstay for treating hepatocellular carcinoma (HCC). However, it is a great challenge for surgeons to identify HCC in its early developmental stage. The diagnostic sensitivity for a tiny HCC with a diameter less than 1.0 cm is usually as low as 10-33% for computed tomography (CT) and 29-43% for magnetic resonance imaging (MRI). Although MRI is the preferred imaging modality for detecting HCC, with its unparalleled spatial resolution for soft tissue, the commercially available contrast agent, such as Gd 3+ -DTPA, cannot accurately define HCC because of its short circulation lifetime and lack of tumor-targeting specificity. Endoglin (CD105), a type I membrane glycoprotein, is highly expressed both in HCC cells and in the endothelial cells of neovasculature, which are abundant at the tumor periphery. In this work, a novel single-stranded DNA oligonucleotide-based aptamer was screened by systematic evolution of ligands in an exponential enrichment assay and showed a high binding affinity ( K D = 98 pmol/L) to endoglin. Conjugating the aptamers and imaging reporters on a G5 dendrimer created an HCC-targeting nanoprobe that allowed the successful visualization of orthotopic HCC xenografts with diameters as small as 1-4 mm. Significantly, the invasive tumor margin was clearly delineated, with a tumor to normal ratio of 2.7 by near-infrared (NIR) fluorescence imaging and 2.1 by T 1 -weighted MRI. This multimodal nanoprobe holds promise not only for noninvasively defining tiny HCC by preoperative MRI but also for guiding tumor excision via intraoperative NIR fluorescence imaging, which will probably gain benefit for the patient's therapeutic response and improve the survival rate.

Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis

PubMed Central

Kluza, Ewelina; Van Tilborg, Geralda A. F.; van der Schaft, Daisy W. J.; Griffioen, Arjan W.; Mulder, Willem J. M.; Nicolay, Klaas

2010-01-01

Angiogenesis is essential for tumor growth and metastatic potential and for that reason considered an important target for tumor treatment. Noninvasive imaging technologies, capable of visualizing tumor angiogenesis and evaluating the efficacy of angiostatic therapies, are therefore becoming increasingly important. Among the various imaging modalities, magnetic resonance imaging (MRI) is characterized by a superb spatial resolution and anatomical soft-tissue contrast. Revolutionary advances in contrast agent chemistry have delivered versatile angiogenesis-specific molecular MRI contrast agents. In this paper, we review recent advances in the preclinical application of paramagnetic and fluorescent liposomes for noninvasive visualization of the molecular processes involved in tumor angiogenesis. This liposomal contrast agent platform can be prepared with a high payload of contrast generating material, thereby facilitating its detection, and is equipped with one or more types of targeting ligands for binding to specific molecules expressed at the angiogenic site. Multimodal liposomes endowed with contrast material for complementary imaging technologies, e.g., MRI and optical, can be exploited to gain important preclinical insights into the mechanisms of binding and accumulation at angiogenic vascular endothelium and to corroborate the in vivo findings. Interestingly, liposomes can be designed to contain angiostatic therapeutics, allowing for image-supervised drug delivery and subsequent monitoring of therapeutic efficacy. PMID:20390447

Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy.

PubMed

Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E

2017-12-11

Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.

Beyond the Sparsity-Based Target Detector: A Hybrid Sparsity and Statistics Based Detector for Hyperspectral Images.

PubMed

Du, Bo; Zhang, Yuxiang; Zhang, Liangpei; Tao, Dacheng

2016-08-18

Hyperspectral images provide great potential for target detection, however, new challenges are also introduced for hyperspectral target detection, resulting that hyperspectral target detection should be treated as a new problem and modeled differently. Many classical detectors are proposed based on the linear mixing model and the sparsity model. However, the former type of model cannot deal well with spectral variability in limited endmembers, and the latter type of model usually treats the target detection as a simple classification problem and pays less attention to the low target probability. In this case, can we find an efficient way to utilize both the high-dimension features behind hyperspectral images and the limited target information to extract small targets? This paper proposes a novel sparsitybased detector named the hybrid sparsity and statistics detector (HSSD) for target detection in hyperspectral imagery, which can effectively deal with the above two problems. The proposed algorithm designs a hypothesis-specific dictionary based on the prior hypotheses for the test pixel, which can avoid the imbalanced number of training samples for a class-specific dictionary. Then, a purification process is employed for the background training samples in order to construct an effective competition between the two hypotheses. Next, a sparse representation based binary hypothesis model merged with additive Gaussian noise is proposed to represent the image. Finally, a generalized likelihood ratio test is performed to obtain a more robust detection decision than the reconstruction residual based detection methods. Extensive experimental results with three hyperspectral datasets confirm that the proposed HSSD algorithm clearly outperforms the stateof- the-art target detectors.

Moving target detection in flash mode against stroboscopic mode by active range-gated laser imaging

NASA Astrophysics Data System (ADS)

Zhang, Xuanyu; Wang, Xinwei; Sun, Liang; Fan, Songtao; Lei, Pingshun; Zhou, Yan; Liu, Yuliang

2018-01-01

Moving target detection is important for the application of target tracking and remote surveillance in active range-gated laser imaging. This technique has two operation modes based on the difference of the number of pulses per frame: stroboscopic mode with the accumulation of multiple laser pulses per frame and flash mode with a single shot of laser pulse per frame. In this paper, we have established a range-gated laser imaging system. In the system, two types of lasers with different frequency were chosen for the two modes. Electric fan and horizontal sliding track were selected as the moving targets to compare the moving blurring between two modes. Consequently, the system working in flash mode shows more excellent performance in motion blurring against stroboscopic mode. Furthermore, based on experiments and theoretical analysis, we presented the higher signal-to-noise ratio of image acquired by stroboscopic mode than flash mode in indoor and underwater environment.

Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

PubMed

Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

2015-01-01

Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel receptor-targeted contrast agents for optical imaging of tumors

NASA Astrophysics Data System (ADS)

Becker, Andreas; Hessenius, Carsten; Bhargava, Sarah; Ebert, Bernd; Sukowski, Uwe; Rinneberg, Herbert H.; Wiedenmann, Bertram; Semmler, Wolfhard; Licha, Kai

2000-04-01

Many gastroenteropancreatic tumors express receptors for somatostatin (SST) and/or vasoactive intestinal peptide (VIP). These receptors can be used as molecular targets for the delivery of contrast agents for tumor diagnostics. We have synthesized conjugates consisting of a cyanine dye and an SST analogue or VIP for use as contrast agents in optical imaging. Receptor binding and internalization of these compounds were examined with optical methods in transfected RIN38 tumor cells expressing the SST2 receptor or a GFP- labeled VIP (VPAC1) receptor. Furthermore, biodistribution of the conjugates was examined by laser-induced fluorescence imaging in nude mice bearing SST2 or VPAC1 receptor- expressing tumors. After incubation of RIN38 SSTR2 cells in the presence of 100 nM indotricarbocyanine-SST analogue, cell-associated fluorescence increased, whereas no increase was observed when receptor-medicated endocytosis was inhibited. Indodicarbocyanine-VIP accumulated in RIN38 VPAC1 cells and co-localization with the GFP-labeled VPAC1 receptor was observed. After injection of indotricarbocyanine-SST analogue into tumor-bearing nude mice, SST2 receptor-positive tumors could be visualized for a time period from 10 min to at least 48 h. After application of indodicarbocyanine-VIP, a fluorescence signal in VIP1 receptor-expressing tumors was only detected during the first hour. We conclude that cyanine dye-labeled VIP and SST analogue are novel, targeted contrast agents for the optical imaging of tumors expressing the relevant receptor.

Arthritis imaging using a near-infrared fluorescence folate-targeted probe

PubMed Central

Chen, Wei-Tsung; Mahmood, Umar; Weissleder, Ralph; Tung, Ching-Hsuan

2005-01-01

A recently developed near-infrared fluorescence-labeled folate probe (NIR2-folate) was tested for in vivo imaging of arthritis using a lipopolysaccharide intra-articular injection model and a KRN transgenic mice serum induction mouse model. In the lipopolysaccharide injection model, the fluorescence signal intensity of NIR2-folate (n = 12) and of free NIR2 (n = 5) was compared between lipopolysaccharide-treated and control joints. The fluorescence signal intensity of the NIR2-folate probe at the inflammatory joints was found to be significantly higher than the control normal joints (up to 2.3-fold, P < 0.001). The NIR2-free dye injection group showed a persistent lower enhancement ratio than the NIR2-folate probe injection group. Excessive folic acid was also given to demonstrate a competitive effect with the NIR2-folate. In the KRN serum transfer model (n = 4), NIR2-folate was applied at different time points after serum transfer, and the inflamed joints could be detected as early as 30 hours after arthritogenic antibody transfer (1.8-fold increase in signal intensity). Fluorescence microscopy, histology, and immunohistochemistry validated the optical imaging results. We conclude that in vivo arthritis detection was feasible using a folate-targeted near-infrared fluorescence probe. This receptor-targeted imaging method may facilitate improved arthritis diagnosis and early assessment of the disease progress by providing an in vivo characterization of active macrophage status in inflammatory joint diseases. PMID:15743478

Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy.

PubMed

Cheng, Liang; Yang, Kai; Li, Yonggang; Zeng, Xiao; Shao, Mingwang; Lee, Shuit-Tong; Liu, Zhuang

2012-03-01

Theranostics, the combination of diagnostics and therapies, has become a new concept in the battles with various major diseases such as cancer. Herein, we develop multifunctional nanoparticles (MFNPs) with highly integrated functionalities including upconversion luminescence, superparamagnetism, and strong optical absorption in the near-infrared (NIR) region with high photostability. In vivo dual modal optical/magnetic resonance imaging of mice uncovers that by placing a magnet nearby the tumor, MFNPs tend to migrate toward the tumor after intravenous injection and show high tumor accumulation, which is ~8 folds higher than that without magnetic targeting. NIR laser irradiation is then applied to the tumors grown on MFNP-injected mice under magnetic tumor-targeting, obtaining an outstanding photothermal therapeutic efficacy with 100% of tumor elimination in a murine breast cancer model. We present here a strategy for multimodal imaging-guided, magnetically targeted physical cancer therapy and highlight the promise of using multifunctional nanostructures for cancer theranostics. Copyright © 2011 Elsevier Ltd. All rights reserved.

2-Thioxanthines Are Mechanism-based Inactivators of Myeloperoxidase That Block Oxidative Stress during Inflammation*

PubMed Central

Tidén, Anna-Karin; Sjögren, Tove; Svensson, Mats; Bernlind, Alexandra; Senthilmohan, Revathy; Auchère, Francoise; Norman, Henrietta; Markgren, Per-Olof; Gustavsson, Susanne; Schmidt, Staffan; Lundquist, Stefan; Forbes, Louisa V.; Magon, Nicholas J.; Paton, Louise N.; Jameson, Guy N. L.; Eriksson, Håkan; Kettle, Anthony J.

2011-01-01

Myeloperoxidase (MPO) is a prime candidate for promoting oxidative stress during inflammation. This abundant enzyme of neutrophils uses hydrogen peroxide to oxidize chloride to highly reactive and toxic chlorine bleach. We have identified 2-thioxanthines as potent mechanism-based inactivators of MPO. Mass spectrometry and x-ray crystal structures revealed that these inhibitors become covalently attached to the heme prosthetic groups of the enzyme. We propose a mechanism whereby 2-thioxanthines are oxidized, and their incipient free radicals react with the heme groups of the enzyme before they can exit the active site. 2-Thioxanthines inhibited MPO in plasma and decreased protein chlorination in a mouse model of peritonitis. They slowed but did not prevent neutrophils from killing bacteria and were poor inhibitors of thyroid peroxidase. Our study shows that MPO is susceptible to the free radicals it generates, and this Achilles' heel of the enzyme can be exploited to block oxidative stress during inflammation. PMID:21880720

Time-reversal imaging for classification of submerged elastic targets via Gibbs sampling and the Relevance Vector Machine.

PubMed

Dasgupta, Nilanjan; Carin, Lawrence

2005-04-01

Time-reversal imaging (TRI) is analogous to matched-field processing, although TRI is typically very wideband and is appropriate for subsequent target classification (in addition to localization). Time-reversal techniques, as applied to acoustic target classification, are highly sensitive to channel mismatch. Hence, it is crucial to estimate the channel parameters before time-reversal imaging is performed. The channel-parameter statistics are estimated here by applying a geoacoustic inversion technique based on Gibbs sampling. The maximum a posteriori (MAP) estimate of the channel parameters are then used to perform time-reversal imaging. Time-reversal implementation requires a fast forward model, implemented here by a normal-mode framework. In addition to imaging, extraction of features from the time-reversed images is explored, with these applied to subsequent target classification. The classification of time-reversed signatures is performed by the relevance vector machine (RVM). The efficacy of the technique is analyzed on simulated in-channel data generated by a free-field finite element method (FEM) code, in conjunction with a channel propagation model, wherein the final classification performance is demonstrated to be relatively insensitive to the associated channel parameters. The underlying theory of Gibbs sampling and TRI are presented along with the feature extraction and target classification via the RVM.

Independent trafficking of flavocytochrome b558 and myeloperoxidase to phagosomes during phagocytosis visualised by energy-filtering and energy-dispersive spectroscopy-scanning transmission electron microscopy.

PubMed

Moriguchi, Keiichi

2018-03-01

When polymorphonuclear leukocytes (PMNs) phagocytose opsonised zymosan particles (OPZ), free radicals and reactive oxygen species (ROS) are formed in the phagosomes. ROS production is mediated by NADPH oxidase (Nox), which transfers electrons in converting oxygen to superoxide (O 2 - ). Nox-generated O 2 - is rapidly converted to other ROS. Free radical-forming secretory vesicles containing the Nox redox center flavocytochrome b558, a membrane protein, and azurophil granules with packaged myeloperoxidase (MPO) have been described. Presuming the probable fusion of these vesicular and granular organelles with phagosomes, the translation process of the enzymes was investigated using energy-filtering and energy-dispersive spectroscopy-scanning transmission electron microscopy. In this work, the primary method for imaging cerium (Ce) ions demonstrated the localisation of H 2 O 2 generated by phagocytosing PMNs. The MPO activity of the same PMNs was continuously monitored using 0.1% 3,3'-diaminobenzidine-tetrahydrochloride (DAB) and 0.01% H 2 O 2 . A detailed view of these vesicular and granular structures was created by overlaying each electron micrograph with pseudocolors: blue for Ce and green for nitrogen (N). © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Cellular myeloperoxidase activity in human monocytes stimulated by hyposialylated immunoglobulins and rheumatoid factors.

PubMed Central

Dodon, M D; Gazzolo, L; Quash, G A

1984-01-01

When hyposialylated , immunoglobulins become immunogenic and tend to form aggregates. In pursuit of the possibility that hyposialylated immunoglobulins (hs-Ig) can trigger human mononuclear phagocytic cells, we have investigated the effects of such hs-Ig on the myeloperoxidase (MPO) activity of these cells. The incubation of human monocytes with aggregated hs-Ig leads to the decrease of intracellular MPO activity. This decrease is dependent on the incubation time, on the amount of hs-Ig added, and on the degree of aggregation. Incubation with unaggregated hs-Ig has a similar effect, thus providing evidence that the loss of sialic acid residues per se is enough to render these molecules capable of decreasing the MPO content of phagocytic cells. Furthermore, human rheumatoid factors, isolated from the sera of rheumatoid arthritis patients, and previously characterized as hyposailylated Ig, interact in the same way with monocytes in triggering the MPO decrease. These observations imply that hs-Ig may be considered as active stimuli in the induction of inflammatory processes, through the initiation of oxidative reactions. PMID:6329948

Instrumentation of Molecular Imaging on Site-Specific Targeting Fluorescent Peptide for Early Detection of Breast Cancer

NASA Astrophysics Data System (ADS)

Yu, Ping; Ma, Lixin

2012-02-01

In this work we developed two biomedical imaging techniques for early detection of breast cancer. Both image modalities provide molecular imaging capability to probe site-specific targeting dyes. The first technique, heterodyne CCD fluorescence mediated tomography, is a non-invasive biomedical imaging that uses fluorescent photons from the targeted dye on the tumor cells inside human breast tissue. The technique detects a large volume of tissue (20 cm) with a moderate resolution (1 mm) and provides the high sensitivity. The second technique, dual-band spectral-domain optical coherence tomography, is a high-resolution tissue imaging modality. It uses a low coherence interferometer to detect coherent photons hidden in the incoherent background. Due to the coherence detection, a high resolution (20 microns) is possible. We have finished prototype imaging systems for the development of both image modalities and performed imaging experiments on tumor tissues. The spectroscopic/tomographic images show contrasts of dense tumor tissues and tumor necrotic regions. In order to correlate the findings from our results, a diffusion-weighted magnetic resonance imaging (MRI) of the tumors was performed using a small animal 7-Telsa MRI and demonstrated excellent agreement.

Direct Imaging Of Long Period Radial Velocity Targets With NICI

NASA Astrophysics Data System (ADS)

Salter, Graeme S.; Tinney, Chris G.; Wittenmyer, Robert A.; Jenkins, James S.; Jones, Hugh R. A.; O'Toole, Simon J.

2014-01-01

We are finally entering an era where radial velocity and direct imaging parameter spaces are starting to overlap. Radial velocity measurements provide us with a minimum mass for an orbiting companion (the mass as a function of the inclination of the system). By following up these long period radial velocity detections with direct imaging we can determine whether a trend seen is due to an orbiting planet at low inclination or an orbiting brown dwarf at high inclination. In the event of a non-detection we are still able to put a limit on the maximum mass of the orbiting body. The Anglo-Australian Planet Search is one of the longest baseline radial velocity planet searches in existence, amongst its targets are many that show long period trends in the data. Here we present our direct imaging survey of these objects with our results to date. ADI Observations have been made using NICI (Near Infrared Coronagraphic Imager) on Gemini South and analysed using an in house, LOCI-like, post processing.

Effect of inherent location uncertainty on detection of stationary targets in noisy image sequences.

PubMed

Manjeshwar, R M; Wilson, D L

2001-01-01

The effect of inherent location uncertainty on the detection of stationary targets was determined in noisy image sequences. Targets were thick and thin projected cylinders mimicking arteries, catheters, and guide wires in medical imaging x-ray fluoroscopy. With the use of an adaptive forced-choice method, detection contrast sensitivity (the inverse of contrast) was measured both with and without marker cues that directed the attention of observers to the target location. With the probability correct clamped at 80%, contrast sensitivity increased an average of 77% when the marker was added to the thin-cylinder target. There was an insignificant effect on the thick cylinder. The large enhancement with the thin cylinder was obtained even though the target was located exactly in the center of a small panel, giving observers the impression that it was well localized. Psychometric functions consisting of d' plotted as a function of the square root of the signal-energy-to-noise-ratio gave a positive x intercept for the case of the thin cylinder without a marker. This x intercept, characteristic of uncertainty in other types of detection experiments, disappeared when the marker was added or when the thick cylinder was used. Inherent location uncertainty was further characterized by using four different markers with varying proximity to the target. Visual detection by human observers increased monotonically as the markers better localized the target. Human performance was modeled as a matched-filter detector with an uncertainty in the placement of the template. The removal of a location cue was modeled by introducing a location uncertainty of approximately equals 0.4 mm on the display device or only 7 microm on the retina, a size on the order of a single photoreceptor field. We conclude that detection is affected by target location uncertainty on the order of cellular dimensions, an observation with important implications for detection mechanisms in humans. In medical

Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer.

PubMed

Du, Jing; Li, Xiao-Yu; Hu, He; Xu, Li; Yang, Shi-Ping; Li, Feng-Hua

2018-03-01

Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C 3 F 8 )-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro, single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo, US imaging signal in the murine breast cancer model was significantly higher (P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo. This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.

Near-infrared optical imaging in glioblastoma xenograft with ligand targeting α3 integrin

PubMed Central

Xiao, Wenwu; Yao, Nianhuan; Peng, Li; Liu, Ruiwu; Lam, Kit S

2010-01-01

Purpose Patients with glioblastoma usually have a very poor prognosis. Even with a combination of radiotherapy plus temozolomide, the median survival of these patients is only 14.6 months. New treatment approaches to this cancer are needed. Our purpose is to develop new cell-surface binding ligands for glioblastoma cells, and use them as targeted imaging and therapeutic agents for this deadly disease. Methods One-bead one-compound combinatorial cyclic peptide libraries were screened with live human glioblastoma U-87MG cells. The binding affinity and targeting specificity of peptides identified were tested with in vitro experiments on cells and in vivo, and ex vivo experiments on U-87MG xegnograft mouse model. Results A cyclic peptide, LXY1, was identified and shown to be binding to the α3 integrin of U-87MG cells with moderately high affinity (Kd = 0.5+/−0.1 μM) and high specificity. Biotinylated LXY1, when complexed with streptavidin-Cy5.5 (SA-Cy5.5) conjugate, targeted both subcutaneous and orthotopic U-87MG xenograft implants in nude mice. The in vivo targeting specificity was further verified by strong inhibition of tumor uptake of LXY1-biotin-SA-Cy5.5 complex when intravenously injecting the animals with anti-α3 integrin antibody or excess unlabeled LXY1 prior to administrating the imaging probe. The smaller univalent LXY1-Cy5.5 conjugate (2279 Da) was found to have a faster accumulation in the U-87MG tumor and shorter retention time compared with the larger tetravalent LXY1-biotin-SA-Cy5.5 complex (~ 64 KDa). Conclusions Collectively, the data reveals that LXY1 has the potential to be developed into an effective imaging and therapeutic targeting agent for human glioblastoma. PMID:18712382

Trans-rectal ultrasound visibility of prostate lesions identified by magnetic resonance imaging increases accuracy of image-fusion targeted biopsies.

PubMed

Ukimura, Osamu; Marien, Arnaud; Palmer, Suzanne; Villers, Arnauld; Aron, Manju; de Castro Abreu, Andre Luis; Leslie, Scott; Shoji, Sunao; Matsugasumi, Toru; Gross, Mitchell; Dasgupta, Prokar; Gill, Inderbir S

2015-11-01

To compare the diagnostic yield of targeted prostate biopsy using image-fusion of multi-parametric magnetic resonance (mp-MR) with real-time trans-rectal ultrasound (TRUS) for clinically significant lesions that are suspicious only on mp-MR versus lesions that are suspicious on both mp-MR and TRUS. Pre-biopsy MRI and TRUS were each scaled on a 3-point score: highly suspicious, likely, and unlikely for clinically significant cancer (sPCa). Using an MR-TRUS elastic image-fusion system (Koelis), a 127 consecutive patients with a suspicious clinically significant index lesion on pre-biopsy mp-MR underwent systematic biopsies and MR/US-fusion targeted biopsies (01/2010-09/2013). Biopsy histological outcomes were retrospectively compared with MR suspicion level and TRUS-visibility of the MR-suspicious lesion. sPCa was defined as biopsy Gleason score ≥7 and/or maximum cancer core length ≥5 mm. Targeted biopsies outperformed systematic biopsies in overall cancer detection rate (61 vs. 41 %; p = 0.007), sPCa detection rate (43 vs. 23 %; p = 0.0013), cancer core length (7.5 vs. 3.9 mm; p = 0.0002), and cancer rate per core (56 vs. 12 %; p < 0.0001), respectively. Highly suspicious lesions on mp-MR correlated with higher positive biopsy rate (p < 0.0001), higher Gleason score (p = 0.018), and greater cancer core length (p < 0.0001). Highly suspicious lesions on TRUS in corresponding to MR-suspicious lesion had a higher biopsy yield (p < 0.0001) and higher sPCa detection rate (p < 0.0001). Since majority of MR-suspicious lesions were also suspicious on TRUS, TRUS-visibility allowed selection of the specific MR-visible lesion which should be targeted from among the multiple TRUS suspicious lesions in each prostate. MR-TRUS fusion-image-guided biopsies outperformed systematic biopsies. TRUS-visibility of a MR-suspicious lesion facilitates image-guided biopsies, resulting in higher detection of significant cancer.

Multimodal Hierarchical Imaging of Serial Sections for Finding Specific Cellular Targets within Large Volumes

PubMed Central

Wacker, Irene U.; Veith, Lisa; Spomer, Waldemar; Hofmann, Andreas; Thaler, Marlene; Hillmer, Stefan; Gengenbach, Ulrich; Schröder, Rasmus R.

2018-01-01

Targeting specific cells at ultrastructural resolution within a mixed cell population or a tissue can be achieved by hierarchical imaging using a combination of light and electron microscopy. Samples embedded in resin are sectioned into arrays consisting of ribbons of hundreds of ultrathin sections and deposited on pieces of silicon wafer or conductively coated coverslips. Arrays are imaged at low resolution using a digital consumer like smartphone camera or light microscope (LM) for a rapid large area overview, or a wide field fluorescence microscope (fluorescence light microscopy (FLM)) after labeling with fluorophores. After post-staining with heavy metals, arrays are imaged in a scanning electron microscope (SEM). Selection of targets is possible from 3D reconstructions generated by FLM or from 3D reconstructions made from the SEM image stacks at intermediate resolution if no fluorescent markers are available. For ultrastructural analysis, selected targets are finally recorded in the SEM at high-resolution (a few nanometer image pixels). A ribbon-handling tool that can be retrofitted to any ultramicrotome is demonstrated. It helps with array production and substrate removal from the sectioning knife boat. A software platform that allows automated imaging of arrays in the SEM is discussed. Compared to other methods generating large volume EM data, such as serial block-face SEM (SBF-SEM) or focused ion beam SEM (FIB-SEM), this approach has two major advantages: (1) The resin-embedded sample is conserved, albeit in a sliced-up version. It can be stained in different ways and imaged with different resolutions. (2) As the sections can be post-stained, it is not necessary to use samples strongly block-stained with heavy metals to introduce contrast for SEM imaging or render the tissue blocks conductive. This makes the method applicable to a wide variety of materials and biological questions. Particularly prefixed materials e.g., from biopsy banks and pathology labs

Long-range and depth-selective imaging of macroscopic targets using low-coherence and wide-field interferometry (Conference Presentation)

NASA Astrophysics Data System (ADS)

Woo, Sungsoo; Kang, Sungsam; Yoon, Changhyeong; Choi, Wonshik

2016-03-01

With the advancement of 3D display technology, 3D imaging of macroscopic objects has drawn much attention as they provide the contents to display. The most widely used imaging methods include a depth camera, which measures time of flight for the depth discrimination, and various structured illumination techniques. However, these existing methods have poor depth resolution, which makes imaging complicated structures a difficult task. In order to resolve this issue, we propose an imaging system based upon low-coherence interferometry and off-axis digital holographic imaging. By using light source with coherence length of 200 micro, we achieved the depth resolution of 100 micro. In order to map the macroscopic objects with this high axial resolution, we installed a pair of prisms in the reference beam path for the long-range scanning of the optical path length. Specifically, one prism was fixed in position, and the other prism was mounted on a translation stage and translated in parallel to the first prism. Due to the multiple internal reflections between the two prisms, the overall path length was elongated by a factor of 50. In this way, we could cover a depth range more than 1 meter. In addition, we employed multiple speckle illuminations and incoherent averaging of the acquired holographic images for reducing the specular reflections from the target surface. Using this newly developed system, we performed imaging targets with multiple different layers and demonstrated imaging targets hidden behind the scattering layers. The method was also applied to imaging targets located around the corner.

Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles

PubMed Central

Kim, Jeong-Yeon; Ryu, Ju Hee; Schellingerhout, Dawid; Sun, In-Cheol; Lee, Su-Kyoung; Jeon, Sangmin; Kim, Jiwon; Kwon, Ick Chan; Nahrendorf, Matthias; Ahn, Cheol-Hee; Kim, Kwangmeyung; Kim, Dong-Eog

2015-01-01

Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP. This targeted imaging agent and non-targeted control agent were characterized in vitro and in vivo in C57Bl/6 mice (n = 107) with FeCl3-induced carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt detection and quantification of cerebral thrombi, and monitoring of tPA-mediated thrombolytic effect, which reflected histological stroke outcome. Furthermore, recurrent thrombosis could be diagnosed by mCT without further nanoparticle administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus imaging greatly enhance the value and information obtainable by regular CT, has multiple uses in basic / translational vascular research, and will likely allow personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match thrombus burden, b) enabling the rational triage of patients to more radical therapies such as endovascular clot-retrieval, and c) potentially serving as a theranostic platform for targeted delivery of concurrent thrombolysis. PMID:26199648

Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions.

PubMed

Neesse, Albrecht; Hahnenkamp, Anke; Griesmann, Heidi; Buchholz, Malte; Hahn, Stefan A; Maghnouj, Abdelouahid; Fendrich, Volker; Ring, Janine; Sipos, Bence; Tuveson, David A; Bremer, Christoph; Gress, Thomas M; Michl, Patrick

2013-07-01

Novel imaging methods based on specific molecular targets to detect both established neoplasms and their precursor lesions are highly desirable in cancer medicine. Previously, we identified claudin-4, an integral constituent of tight junctions, as highly expressed in various gastrointestinal tumours including pancreatic cancer. Here, we investigate the potential of targeting claudin-4 with a naturally occurring ligand to visualise pancreatic cancer and its precursor lesions in vitro and in vivo by near-infrared imaging approaches. A non-toxic C-terminal fragment of the claudin-4 ligand Clostridium perfringens enterotoxin (C-CPE) was labelled with a cyanine dye (Cy5.5). Binding of the optical tracer was analysed on claudin-4 positive and negative cells in vitro, and tumour xenografts in vivo. In addition, two genetically engineered mouse models for pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancer were used for in vivo validation. Optical imaging studies were conducted using 2D planar fluorescence reflectance imaging (FRI) technology and 3D fluorescence-mediated tomography (FMT). In vitro, the peptide-dye conjugate showed high binding affinity to claudin-4 positive CAPAN1 cells, while claudin-4 negative HT1080 cells revealed little or no fluorescence. In vivo, claudin-4 positive tumour xenografts, endogenous pancreatic tumours, hepatic metastases, as well as preinvasive PanIN lesions, were visualised by FRI and FMT up to 48 h after injection showing a significantly higher average of fluorochrome concentration as compared with claudin-4 negative xenografts and normal pancreatic tissue. C-CPE-Cy5.5 combined with novel optical imaging methods enables non-invasive visualisation of claudin-4 positive murine pancreatic tumours and their precursor lesions, representing a promising modality for early diagnostic imaging.

Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic Molecular Imaging of Human Bladder Cancer.

PubMed

Wang, Jiaqi; Fang, Ruizhe; Wang, Lu; Chen, Guang; Wang, Hongzhi; Wang, Zhichao; Zhao, Danfeng; Pavlov, Valentin N; Kabirov, Ildar; Wang, Ziqi; Guo, Pengyu; Peng, Li; Xu, Wanhai

2018-06-27

Emerging novel optical imaging techniques with cancer-specific molecular imaging agents offer a powerful and promising platform for cancer detection and resection. White-light cystoscopy and random bladder biopsies remain the most appropriate but nonetheless suboptimal diagnostic technique for bladder cancer, which is associated with high morbidity and recurrence. However, white-light cystoscopy has intrinsic shortcomings. Although current optical imaging technologies hold great potential for improved diagnostic accuracy, there are few imaging agents for specific molecular targeting. Carbonic anhydrase IX (CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential value as an imaging target. Here, we investigated the feasibility of CAIX as a target and validated the diagnostic performance and significance of CAIX as an imaging agent. We first analyzed the data from The Cancer Genome Atlas (TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue were collected. All tissue samples were used for real-time PCR and immunohistochemistry to compare CAIX expression in normal and cancer tissue. Using blue-light cystoscopy, we observed the optical distribution of fluorescently labeled CAIX antibody in freshly excised human bladders and obtained random bladder biopsies to assess sensitivity and specificity. The TCGA data revealed that CAIX expression was significantly higher in bladder cancer specimens than in normal tissue. The outcome was similar in quantitative real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens classified in four pathological subtypes presented a variety of positive staining intensities, whereas no benign specimens showed CAIX staining. Using blue-light cystoscopy, we distinguished bladder cancers that were mainly papillary, some variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue, despite the presence of suspicious-appearing mucosa. The sensitivity and

Effect of g.9476869G>A myeloperoxidase (MPO) gene polymorphism on the antioxidant activity of milk from Polish Holstein-Friesian cows of the Black-and-White variety (HO).

PubMed

Pokorska, Joanna; Poskart, Karolina; Kułaj, Dominika; Ochrem, Andrzej; Dusza, Magdalena; Gil, Zygmunt; Świętek, Ewa; Makulska, Joanna

2017-05-01

Myeloperoxidase (MPO) is an important enzyme, which is one of the components of the antibacterial system in neutrophils and monocytes. MPO participates in the inflammatory response in multiple locations in the body, including the mammary glands. As a result of the activity of MPO, many oxidising compounds as well as reactive oxygen species are generated. It seems that myeloperoxidase may be a marker linking inflammation processes and oxidative stress. So far, there are no literature data on the association between the MPO gene polymorphism and the antioxidant properties of milk. The aim of the study was to analyse the effect of g.9476869G > A polymorphism of myeloperoxidase (MPO) gene and age of cows on the antioxidant activity of milk and other milk traits in Polish Holstein-Friesian cows. Polymorphism of MPO gene was identified by the PCR-RFLP method using the HphI endonuclease. The total antioxidant capacity of milk samples was measured by the Trolox Equivalent Antioxidant Capacity (TEAC) method. It was found that the GG genotype was the most frequent (0·606). The genotype at the tested MPO locus and the age of the animals affected the antioxidant activity of milk. Milk from cows with the GA genotype was characterised by a significantly higher antioxidant activity than milk from cows with the GG genotype (P < 0·0001). The analysis of interaction showed that cows with the GA genotype and older than 6·5 years produced milk with a significantly higher antioxidant activity compared with younger cows with the same genotype (P < 0·0001), as well as cows with the GG genotype of all ages (P < 0·0001).

Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging.

PubMed

Vinegoni, Claudio; Fumene Feruglio, Paolo; Brand, Christian; Lee, Sungon; Nibbs, Antoinette E; Stapleton, Shawn; Shah, Sunil; Gryczynski, Ignacy; Reiner, Thomas; Mazitschek, Ralph; Weissleder, Ralph

2017-07-01

The ability to directly image and quantify drug-target engagement and drug distribution with subcellular resolution in live cells and whole organisms is a prerequisite to establishing accurate models of the kinetics and dynamics of drug action. Such methods would thus have far-reaching applications in drug development and molecular pharmacology. We recently presented one such technique based on fluorescence anisotropy, a spectroscopic method based on polarization light analysis and capable of measuring the binding interaction between molecules. Our technique allows the direct characterization of target engagement of fluorescently labeled drugs, using fluorophores with a fluorescence lifetime larger than the rotational correlation of the bound complex. Here we describe an optimized protocol for simultaneous dual-channel two-photon fluorescence anisotropy microscopy acquisition to perform drug-target measurements. We also provide the necessary software to implement stream processing to visualize images and to calculate quantitative parameters. The assembly and characterization part of the protocol can be implemented in 1 d. Sample preparation, characterization and imaging of drug binding can be completed in 2 d. Although currently adapted to an Olympus FV1000MPE microscope, the protocol can be extended to other commercial or custom-built microscopes.

Structural colour printing from a reusable generic nanosubstrate masked for the target image

NASA Astrophysics Data System (ADS)

Rezaei, M.; Jiang, H.; Kaminska, B.

2016-02-01

Structural colour printing has advantages over traditional pigment-based colour printing. However, the high fabrication cost has hindered its applications in printing large-area images because each image requires patterning structural pixels in nanoscale resolution. In this work, we present a novel strategy to print structural colour images from a pixelated substrate which is called a nanosubstrate. The nanosubstrate is fabricated only once using nanofabrication tools and can be reused for printing a large quantity of structural colour images. It contains closely packed arrays of nanostructures from which red, green, blue and infrared structural pixels can be imprinted. To print a target colour image, the nanosubstrate is first covered with a mask layer to block all the structural pixels. The mask layer is subsequently patterned according to the target colour image to make apertures of controllable sizes on top of the wanted primary colour pixels. The masked nanosubstrate is then used as a stamp to imprint the colour image onto a separate substrate surface using nanoimprint lithography. Different visual colours are achieved by properly mixing the red, green and blue primary colours into appropriate ratios controlled by the aperture sizes on the patterned mask layer. Such a strategy significantly reduces the cost and complexity of printing a structural colour image from lengthy nanoscale patterning into high throughput micro-patterning and makes it possible to apply structural colour printing in personalized security features and data storage. In this paper, nanocone array grating pixels were used as the structural pixels and the nanosubstrate contains structures to imprint the nanocone arrays. Laser lithography was implemented to pattern the mask layer with submicron resolution. The optical properties of the nanocone array gratings are studied in detail. Multiple printed structural colour images with embedded covert information are demonstrated.

Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.

PubMed

Verjans, Johan W; Osborn, Eric A; Ughi, Giovanni J; Calfon Press, Marcella A; Hamidi, Ehsan; Antoniadis, Antonios P; Papafaklis, Michail I; Conrad, Mark F; Libby, Peter; Stone, Peter H; Cambria, Richard P; Tearney, Guillermo J; Jaffer, Farouc A

2016-09-01

This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and

Evaluation of bone marrow specimens with acute myelogenous leukemia for CD34, CD15, CD117, and myeloperoxidase.

PubMed

Dunphy, C H; Polski, J M; Evans, H L; Gardner, L J

2001-08-01

Immunophenotyping of bone marrow (BM) specimens with acute myelogenous leukemia (AML) may be performed by flow cytometric (FC) or immunohistochemical (IH) techniques. Some markers (CD34, CD15, and CD117) are available for both techniques. Myeloperoxidase (MPO) analysis may be performed by enzyme cytochemical (EC) or IH techniques. To determine the reliability of these markers and MPO by these techniques, we designed a study to compare the results of analyses of these markers and MPO by FC (CD34, CD15, and CD117), EC (MPO), and IH (CD34, CD15, CD117, and MPO) techniques. Twenty-nine AMLs formed the basis of the study. These AMLs all had been immunophenotyped previously by FC analysis; 27 also had had EC analysis performed. Of the AMLs, 29 had BM core biopsies and 26 had BM clots that could be evaluated. The paraffin blocks of the 29 BM core biopsies and 26 BM clots were stained for CD34, CD117, MPO, and CD15. These results were compared with results by FC analysis (CD34, CD15, and CD117) and EC analysis (MPO). Immunodetection of CD34 expression in AML had a similar sensitivity by FC and IH techniques. Immunodetection of CD15 and CD117 had a higher sensitivity by FC analysis than by IH analysis. Detection of MPO by IH analysis was more sensitive than by EC analysis. There was no correlation of French-American-British (FAB) subtype of AML with CD34 or CD117 expression. Expression of CD15 was associated with AMLs with a monocytic component. Myeloperoxidase reactivity by IH analysis was observed in AMLs originally FAB subtyped as M0. CD34 can be equally detected by FC and IH techniques. CD15 and CD117 are better detected by FC analysis and MPO is better detected by IH analysis.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

PubMed

Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

2016-07-21

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

PubMed Central

Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

2016-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene’s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual-modal targeted imaging and chemotherapy.

PubMed

Chiu, Sheng-Hui; Gedda, Gangaraju; Girma, Wubshet Mekonnen; Chen, Jem-Kun; Ling, Yong-Chien; Ghule, Anil V; Ou, Keng-Liang; Chang, Jia-Yaw

2016-12-01

Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of FA-GdNS@CQDs. FA-GdNS@CQDs enhanced the MR response as compared to that for commercial Gd-DTPA. The targeting capabilities of FA-GdNS@CQDs were confirmed in HeLa and HepG2 cells using in vitro fluorescence and MR dual modality imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the FA-GdNS@CQDs forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. Importantly, the prepared FA-GdNS@CQDs-DOX showed a high quantity of doxorubicin loading capacity (about 80%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the FA-GdNS@CQDs were observed by confocal laser scanning microscopy. We also successfully demonstrated in vivo fluorescence bio imaging of the FA-GdNS@CQDs, using zebrafish as an animal model. In this manuscript, we reported a facial, rapid, and environmental friendly method to fabricate hetero atoms including gadolinium, nitrogen, and sulfur doped multi-functional magnetofluorescent carbon quantum dots (GdNS@CQDs) nanocomposite. These multifunctional GdNS@CQDs were conjugated with a folic acid for targeting dual modal fluorescence/magnetic resonance imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the nanocomposite forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. We have developed GdNS@CQDs with integrated functions for simultaneous in

SU-E-J-115: Correlation of Displacement Vector Fields Calculated by Deformable Image Registration Algorithms with Motion Parameters of CT Images with Well-Defined Targets and Controlled-Motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaskowiak, J; Ahmad, S; Ali, I

Purpose: To investigate correlation of displacement vector fields (DVF) calculated by deformable image registration algorithms with motion parameters in helical axial and cone-beam CT images with motion artifacts. Methods: A mobile thorax phantom with well-known targets with different sizes that were made from water-equivalent material and inserted in foam to simulate lung lesions. The thorax phantom was imaged with helical, axial and cone-beam CT. The phantom was moved with a cyclic motion with different motion amplitudes and frequencies along the superior-inferior direction. Different deformable image registration algorithms including demons, fast demons, Horn-Shunck and iterative-optical-flow from the DIRART software were usedmore » to deform CT images for the phantom with different motion patterns. The CT images of the mobile phantom were deformed to CT images of the stationary phantom. Results: The values of displacement vectors calculated by deformable image registration algorithm correlated strongly with motion amplitude where large displacement vectors were calculated for CT images with large motion amplitudes. For example, the maximal displacement vectors were nearly equal to the motion amplitudes (5mm, 10mm or 20mm) at interfaces between the mobile targets lung tissue, while the minimal displacement vectors were nearly equal to negative the motion amplitudes. The maximal and minimal displacement vectors matched with edges of the blurred targets along the Z-axis (motion-direction), while DVF’s were small in the other directions. This indicates that the blurred edges by phantom motion were shifted largely to match with the actual target edge. These shifts were nearly equal to the motion amplitude. Conclusions: The DVF from deformable-image registration algorithms correlated well with motion amplitude of well-defined mobile targets. This can be used to extract motion parameters such as amplitude. However, as motion amplitudes increased, image artifacts

Target discrimination method for SAR images based on semisupervised co-training

NASA Astrophysics Data System (ADS)

Wang, Yan; Du, Lan; Dai, Hui

2018-01-01

Synthetic aperture radar (SAR) target discrimination is usually performed in a supervised manner. However, supervised methods for SAR target discrimination may need lots of labeled training samples, whose acquirement is costly, time consuming, and sometimes impossible. This paper proposes an SAR target discrimination method based on semisupervised co-training, which utilizes a limited number of labeled samples and an abundant number of unlabeled samples. First, Lincoln features, widely used in SAR target discrimination, are extracted from the training samples and partitioned into two sets according to their physical meanings. Second, two support vector machine classifiers are iteratively co-trained with the extracted two feature sets based on the co-training algorithm. Finally, the trained classifiers are exploited to classify the test data. The experimental results on real SAR images data not only validate the effectiveness of the proposed method compared with the traditional supervised methods, but also demonstrate the superiority of co-training over self-training, which only uses one feature set.

Myeloperoxidase-catalyzed incorporation of amines into proteins: role of hypochlorous acid and dichloramines.

PubMed

Thomas, E L; Jefferson, M M; Grisham, M B

1982-11-23

Myeloperoxidase-catalyzed oxidation of chloride (Cl-) to hypochlorous acid (HOCl) resulted in formation of mono- and dichloramine derivatives (RNHCl and RNCl2) of primary amines. The RNCl2 derivatives could undergo a reaction that resulted in incorporation of the R moiety into proteins. The probable mechanism was attack of RNCl2 or an intermediate formed in the decomposition of RNCl2 on histidine, tyrosine, and cystine residues and on lysine residues at high pH. Incorporation of radioactivity from labeled amines into stable, high molecular weight derivatives of proteins was measured by acid or acetone precipitation and by gel chromatography and electrophoresis. Whereas formation of RNCl2 was favored at low pH, the subsequent incorporation reaction was favored at high pH. Up to several hours were required for the maximum amount of incorporation, which was less than 10% of the label in RNCl2. For the amines tested, incorporation was in the order histamine greater than 1,2-diaminoethane greater than putrescine greater than taurine greater than lysine greater than glucosamine greater than leucine greater than methylamine. Initiation of the reaction required HOCl, and oxidized forms of bromide, iodide, or thiocyanate did not substitute. Inhibitors of incorporation fell into three classes. First, ammonia or amines competed with the labeled amine for reaction with HOCl, so that larger amounts of HOCl were required. Second, readily oxidized substances such as sulfhydryl or diketo compounds or thioethers (methionine) reduced RNCl2. Third, certain compounds competed with protein as the acceptor for the incorporation reaction. The amount required to block incorporation into protein depended on protein concentration. Among these inhibitors were imidazole compounds (histidine), phenols (tyrosine), and disulfides (glutathione disulfide, GSSG). Low yields of derivatives of histidine, tyrosine, and GSSG were detected by thin-layer chromatography. Acid-precipitable derivatives were

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging

PubMed Central

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-01-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane–modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

PubMed

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-04-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

In Vivo Tumor Targeting and Image-Guided Drug Delivery with Antibody-Conjugated, Radiolabeled Mesoporous Silica Nanoparticles

PubMed Central

Chen, Feng; Hong, Hao; Zhang, Yin; Valdovinos, Hector F.; Shi, Sixiang; Kwon, Glen S.; Theuer, Charles P.; Barnhart, Todd E.; Cai, Weibo

2013-01-01

Since the first use of biocompatible mesoporous silica (mSiO2) nanoparticles as drug delivery vehicles, in vivo tumor targeted imaging and enhanced anti-cancer drug delivery has remained a major challenge. In this work, we describe the development of functionalized mSiO2 nanoparticles for actively targeted positron emission tomography (PET) imaging and drug delivery in 4T1 murine breast tumor-bearing mice. Our structural design involves the synthesis, surface functionalization with thiol groups, PEGylation, TRC105 antibody (specific for CD105/endoglin) conjugation, and 64Cu-labeling of uniform 80 nm sized mSiO2 nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that 64Cu-NOTA-mSiO2-PEG-TRC105 could accumulate prominently at the 4T1 tumor site via both the enhanced permeability and retention effect and TRC105-mediated binding to tumor vasculature CD105. As a proof-of-concept, we also demonstrated successful enhanced tumor targeted delivery of doxorubicin (DOX) in 4T1 tumor-bearing mice after intravenous injection of DOX-loaded NOTA-mSiO2-PEG-TRC105, which holds great potential for future image-guided drug delivery and targeted cancer therapy. PMID:24083623

Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells.

PubMed

Yogalingam, Gouri; Lee, Amanda R; Mackenzie, Donald S; Maures, Travis J; Rafalko, Agnes; Prill, Heather; Berguig, Geoffrey Y; Hague, Chuck; Christianson, Terri; Bell, Sean M; LeBowitz, Jonathan H

2017-03-10

Neutrophil myeloperoxidase (MPO) catalyzes the H 2 O 2 -dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N -retinylidene- N -retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N -retinylidene- N -retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells*

PubMed Central

Yogalingam, Gouri; Lee, Amanda R.; Mackenzie, Donald S.; Maures, Travis J.; Rafalko, Agnes; Prill, Heather; Berguig, Geoffrey Y.; Hague, Chuck; Christianson, Terri; Bell, Sean M.; LeBowitz, Jonathan H.

2017-01-01

Neutrophil myeloperoxidase (MPO) catalyzes the H2O2-dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N-retinylidene-N-retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N-retinylidene-N-retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death. PMID:28115520

SU-E-I-81: Targeting of HER2-Expressing Tumors with Dual PET-MR Imaging Probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, P; Peng, Y; Sun, M

2015-06-15

Purpose: The detection of human epidermal growth factor receptor type 2 (HER2) expression in malignant tumors provides important information influencing patient management. Radionuclide in vivo imaging of HER2 may permit the detection of HER2 in both primary tumors and metastases by a single noninvasive procedure. Trastuzumab, effective in about 15 % of women with breast cancer, downregulates signalling through the Akt/PI3K and MAPK pathways.These pathways modulate metabolism which can be monitored by positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: The relationship between response of HER2 overexpressing tumours and changes in imaging PET or SPECT and MRI willmore » be examined by a integrated bimodal imaging probe.Small (7 kDa) high-affinity anti-HER2 Affibody molecules and KCCYSL targeting peptide may be suitable tracers for visualization of HER2-expressing tumors. Peptide-conjugated iron oxide nanoparticles (Fe3O4 NPs) as MRI imaging and CB-TE2A as PET imaging are integrated into a single synthetic molecule in the HER2 positive cancer. Results: One of targeted contrast bimodal imaging probe agents was synthesized and evaluated to target HER2-expressing tumors in a HER2 positive rat model. We will report the newest results regarding the development of bimodal imaging probes. Conclusion: The preliminary results of the bimodal imaging probe presents high correlation of MRI signal and PET imaging intensity in vivo. This unique feature can hardly be obtained by single model contrast agents. It is envisioned that this bimodal agents can hold great potential for accurate detection of HER2-expressing tumors which are critical for clinical management of the disease.« less

Non-negative infrared patch-image model: Robust target-background separation via partial sum minimization of singular values

NASA Astrophysics Data System (ADS)

Dai, Yimian; Wu, Yiquan; Song, Yu; Guo, Jun

2017-03-01

To further enhance the small targets and suppress the heavy clutters simultaneously, a robust non-negative infrared patch-image model via partial sum minimization of singular values is proposed. First, the intrinsic reason behind the undesirable performance of the state-of-the-art infrared patch-image (IPI) model when facing extremely complex backgrounds is analyzed. We point out that it lies in the mismatching of IPI model's implicit assumption of a large number of observations with the reality of deficient observations of strong edges. To fix this problem, instead of the nuclear norm, we adopt the partial sum of singular values to constrain the low-rank background patch-image, which could provide a more accurate background estimation and almost eliminate all the salient residuals in the decomposed target image. In addition, considering the fact that the infrared small target is always brighter than its adjacent background, we propose an additional non-negative constraint to the sparse target patch-image, which could not only wipe off more undesirable components ulteriorly but also accelerate the convergence rate. Finally, an algorithm based on inexact augmented Lagrange multiplier method is developed to solve the proposed model. A large number of experiments are conducted demonstrating that the proposed model has a significant improvement over the other nine competitive methods in terms of both clutter suppressing performance and convergence rate.

Exploration of target molecules for molecular imaging of inflammatory bowel disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu

2011-07-08

Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternativemore » probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

PubMed

Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

2014-05-28

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

Photoacoustic imaging with an acoustic lens detects prostate cancer cells labeled with PSMA-targeting near-infrared dye-conjugates

NASA Astrophysics Data System (ADS)

Dogra, Vikram; Chinni, Bhargava; Singh, Shalini; Schmitthenner, Hans; Rao, Navalgund; Krolewski, John J.; Nastiuk, Kent L.

2016-06-01

There is an urgent need for sensitive and specific tools to accurately image early stage, organ-confined human prostate cancers to facilitate active surveillance and reduce unnecessary treatment. Recently, we developed an acoustic lens that enhances the sensitivity of photoacoustic imaging. Here, we report the use of this device in conjunction with two molecular imaging agents that specifically target the prostate-specific membrane antigen (PSMA) expressed on the tumor cell surface of most prostate cancers. We demonstrate successful imaging of phantoms containing cancer cells labeled with either of two different PSMA-targeting agents, the ribonucleic acid aptamer A10-3.2 and a urea-based peptidomimetic inhibitor, each linked to the near-infrared dye IRDye800CW. By specifically targeting cells with these agents linked to a dye chosen for optimal signal, we are able to discriminate prostate cancer cells that express PSMA.

Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes

PubMed Central

Ghosh, Debadyuti; Bagley, Alexander F.; Na, Young Jeong; Birrer, Michael J.; Bhatia, Sangeeta N.; Belcher, Angela M.

2014-01-01

Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950–1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery. PMID:25214538

Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes.

PubMed

Ghosh, Debadyuti; Bagley, Alexander F; Na, Young Jeong; Birrer, Michael J; Bhatia, Sangeeta N; Belcher, Angela M

2014-09-23

Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950-1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery.

Location of planar targets in three space from monocular images

NASA Technical Reports Server (NTRS)

Cornils, Karin; Goode, Plesent W.

1987-01-01

Many pieces of existing and proposed space hardware that would be targets of interest for a telerobot can be represented as planar or near-planar surfaces. Examples include the biostack modules on the Long Duration Exposure Facility, the panels on Solar Max, large diameter struts, and refueling receptacles. Robust and temporally efficient methods for locating such objects with sufficient accuracy are therefore worth developing. Two techniques that derive the orientation and location of an object from its monocular image are discussed and the results of experiments performed to determine translational and rotational accuracy are presented. Both the quadrangle projection and elastic matching techniques extract three-space information using a minimum of four identifiable target points and the principles of the perspective transformation. The selected points must describe a convex polygon whose geometric characteristics are prespecified in a data base. The rotational and translational accuracy of both techniques was tested at various ranges. This experiment is representative of the sensing requirements involved in a typical telerobot target acquisition task. Both techniques determined target location to an accuracy sufficient for consistent and efficient acquisition by the telerobot.

RGD-functionalized ultrasmall iron oxide nanoparticles for targeted T1-weighted MR imaging of gliomas

NASA Astrophysics Data System (ADS)

Luo, Yu; Yang, Jia; Yan, Yu; Li, Jingchao; Shen, Mingwu; Zhang, Guixiang; Mignani, Serge; Shi, Xiangyang

2015-08-01

We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing αvβ3 integrin in vitro. With the relatively high r1 relaxivity (r1 = 1.4 mM-1 s-1), the Fe3O4-PEG-RGD particles can be used as an efficient nanoprobe for targeted T1-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe3O4 NPs may hold great promise to be used as a nanoprobe for targeted T1-weighted MR imaging of different αvβ3 integrin-overexpressing cancer cells or biological systems.We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration

Development of anti-HER2 conjugated ICG-loaded polymeric nanoparticles for targeted optical imaging of ovarian cancer

NASA Astrophysics Data System (ADS)

Bahmani, Baharak; Vullev, Valentine; Anvari, Bahman

2012-03-01

Targeted delivery of therapeutic and imaging agents using surface modified nanovectors has been explored immensely in recent years. The growing demand for site-specific and efficient delivery of nanovectors entails stable surface conjugation of targeting moieties. We have developed a polymeric nanocapsule doped with Indocyanine green (ICG) with potential for targeted and deep tissue optical imaging and phototherapy. Our ICG-loaded nanocapsules (ICG-NCs) have potential for covalent coupling of various targeting moieties and materials due to presence of amine groups on the surface. Here, we covalently bioconjugate polyethylene glycol(PEG)-coated ICG-NCs with monoclonal antibody against HER2 through reductive amination-mediated procedures. The irreversible and stable bonds are formed between anti- EGFR and aldehyde termini of PEG chains on the surface of ICG-NCs. We confirm the uptake of conjugated ICG-NCs by ovarian cancer cells over-expressing HER2 using fluorescent confocal microscopy. The proposed process for covalent attachment of anti-HER2 to PEGylated ICG-NCs can be used as a methodology for bioconjugation of various antibodies to such nano-constrcuts, and provides the capability to use these optically active nano-probes for targeted optical imaging of ovarian and other cancer types.

In vivo targeting and imaging of tumor vasculature with radiolabeled, antibody-conjugated nanographene.

PubMed

Hong, Hao; Yang, Kai; Zhang, Yin; Engle, Jonathan W; Feng, Liangzhu; Yang, Yunan; Nayak, Tapas R; Goel, Shreya; Bean, Jero; Theuer, Charles P; Barnhart, Todd E; Liu, Zhuang; Cai, Weibo

2012-03-27

Herein we demonstrate that nanographene can be specifically directed to the tumor neovasculature in vivo through targeting of CD105 (i.e., endoglin), a vascular marker for tumor angiogenesis. The covalently functionalized nanographene oxide (GO) exhibited excellent stability and target specificity. Pharmacokinetics and tumor targeting efficacy of the GO conjugates were investigated with serial noninvasive positron emission tomography imaging and biodistribution studies, which were validated by in vitro, in vivo, and ex vivo experiments. The incorporation of an active targeting ligand (TRC105, a monoclonal antibody that binds to CD105) led to significantly improved tumor uptake of functionalized GO, which was specific for the neovasculature with little extravasation, warranting future investigation of these GO conjugates for cancer-targeted drug delivery and/or photothermal therapy to enhance therapeutic efficacy. Since poor extravasation is a major hurdle for nanomaterial-based tumor targeting in vivo, this study also establishes CD105 as a promising vascular target for future cancer nanomedicine. © 2012 American Chemical Society

Image registration via optimization over disjoint image regions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pitts, Todd; Hathaway, Simon; Karelitz, David B.

Technologies pertaining to registering a target image with a base image are described. In a general embodiment, the base image is selected from a set of images, and the target image is an image in the set of images that is to be registered to the base image. A set of disjoint regions of the target image is selected, and a transform to be applied to the target image is computed based on the optimization of a metric over the selected set of disjoint regions. The transform is applied to the target image so as to register the target imagemore » with the base image.« less

Targeted Molecular Imaging of Cancer Cells Using MS2-Based 129 Xe NMR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Keunhong; Netirojjanakul, Chawita; Munch, Henrik K.

Targeted, selective, and highly sensitive 129Xe NMR nanoscale biosensors have been synthesized using a spherical MS2 viral capsid, Cryptophane A molecules, and DNA aptamers. The biosensors showed strong binding specificity toward targeted lymphoma cells (Ramos line). Hyperpolarized 129Xe NMR signal contrast and hyper-CEST 129Xe MRI image contrast indicated its promise as highly sensitive hyperpolarized 129Xe NMR nanoscale biosensor for future applications in cancer detection in vivo.

Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton imaging

NASA Astrophysics Data System (ADS)

Cromey, Benjamin; McDaniel, Ashley; Matsunaga, Terry; Vagner, Josef; Kieu, Khanh Quoc; Banerjee, Bhaskar

2018-04-01

Surgical resection of pancreatic cancer represents the only chance of cure and long-term survival in this common disease. Unfortunately, determination of a cancer-free margin at surgery is based on one or two tiny frozen section biopsies, which is far from ideal. Not surprisingly, cancer is usually left behind and is responsible for metastatic disease. We demonstrate a method of receptor-targeted imaging using peptide ligands, lipid microbubbles, and multiphoton microscopy that could lead to a fast and accurate way of examining the entire cut surface during surgery. Using a plectin-targeted microbubble, we performed a blinded in-vitro study to demonstrate avid binding of targeted microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further work should lead to a much-needed point-of-care diagnostic test for determining clean margins in oncologic surgery.

Tomographic diffractive microscopy with agile illuminations for imaging targets in a noisy background.

PubMed

Zhang, T; Godavarthi, C; Chaumet, P C; Maire, G; Giovannini, H; Talneau, A; Prada, C; Sentenac, A; Belkebir, K

2015-02-15

Tomographic diffractive microscopy is a marker-free optical digital imaging technique in which three-dimensional samples are reconstructed from a set of holograms recorded under different angles of incidence. We show experimentally that, by processing the holograms with singular value decomposition, it is possible to image objects in a noisy background that are invisible with classical wide-field microscopy and conventional tomographic reconstruction procedure. The targets can be further characterized with a selective quantitative inversion.

Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

PubMed Central

Lavenant, Gwendoline Thiery; Zavalin, Andrey I.; Caprioli, Richard M.

2013-01-01

Targeted multiplex Imaging Mass Spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This manuscript describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet. PMID:23397138

Residual translation compensations in radar target narrowband imaging based on trajectory information

NASA Astrophysics Data System (ADS)

Yue, Wenjue; Peng, Bo; Wei, Xizhang; Li, Xiang; Liao, Dongping

2018-05-01

High velocity translation will result in defocusing scattering centers in radar imaging. In this paper, we propose a Residual Translation Compensations (RTC) method based on target trajectory information to eliminate the translation effects in radar imaging. Translation could not be simply regarded as a uniformly accelerated motion in reality. So the prior knowledge of the target trajectory is introduced to enhance compensation precision. First we use the two-body orbit model to figure out the radial distance. Then, stepwise compensations are applied to eliminate residual propagation delay based on conjugate multiplication method. Finally, tomography is used to confirm the validity of the method. Compare with translation parameters estimation method based on the spectral peak of the conjugate multiplied signal, RTC method in this paper enjoys a better tomography result. When the Signal Noise Ratio (SNR) of the radar echo signal is 4dB, the scattering centers can also be extracted clearly.

Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

NASA Astrophysics Data System (ADS)

Thiery-Lavenant, Gwendoline; Zavalin, Andre I.; Caprioli, Richard M.

2013-04-01

Targeted multiplex imaging mass spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This article describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet.

Optimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment.

PubMed

Bjurlin, Marc A; Meng, Xiaosong; Le Nobin, Julien; Wysock, James S; Lepor, Herbert; Rosenkrantz, Andrew B; Taneja, Samir S

2014-09-01

Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy, including false-negative rates, incorrect risk stratification, detection of clinically insignificant disease and the need for repeat biopsy. Magnetic resonance imaging is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of biopsy, and thereby enhances clinical risk assessment and improves the ability to appropriately counsel patients regarding therapy. In this review we 1) summarize the various sequences that comprise a prostate multiparametric magnetic resonance imaging examination along with its performance characteristics in cancer detection, localization and reporting standards; 2) evaluate potential applications of magnetic resonance imaging targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy and those with low stage cancer; and 3) describe the techniques of magnetic resonance imaging targeted biopsy and comparative study outcomes. A bibliographic search covering the period up to October 2013 was conducted using MEDLINE®/PubMed®. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Multiparametric magnetic resonance imaging consists of anatomical T2-weighted imaging coupled with at least 2 functional imaging techniques. It has demonstrated improved prostate cancer detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A prostate cancer magnetic resonance imaging suspicion score has been developed, and is depicted using the Likert or PI-RADS (Prostate Imaging Reporting and Data System) scale for better standardization of magnetic resonance imaging interpretation and reporting. Among men with no previous biopsy, magnetic resonance imaging increases the frequency of significant cancer detection to 50

Accurate Analysis of Target Characteristic in Bistatic SAR Images: A Dihedral Corner Reflectors Case.

PubMed

Ao, Dongyang; Li, Yuanhao; Hu, Cheng; Tian, Weiming

2017-12-22

The dihedral corner reflectors are the basic geometric structure of many targets and are the main contributions of radar cross section (RCS) in the synthetic aperture radar (SAR) images. In stealth technologies, the elaborate design of the dihedral corners with different opening angles is a useful approach to reduce the high RCS generated by multiple reflections. As bistatic synthetic aperture sensors have flexible geometric configurations and are sensitive to the dihedral corners with different opening angles, they specially fit for the stealth target detections. In this paper, the scattering characteristic of dihedral corner reflectors is accurately analyzed in bistatic synthetic aperture images. The variation of RCS with the changing opening angle is formulated and the method to design a proper bistatic radar for maximizing the detection capability is provided. Both the results of the theoretical analysis and the experiments show the bistatic SAR could detect the dihedral corners, under a certain bistatic angle which is related to the geometry of target structures.

Accurate Analysis of Target Characteristic in Bistatic SAR Images: A Dihedral Corner Reflectors Case

PubMed Central

Ao, Dongyang; Hu, Cheng; Tian, Weiming

2017-01-01

The dihedral corner reflectors are the basic geometric structure of many targets and are the main contributions of radar cross section (RCS) in the synthetic aperture radar (SAR) images. In stealth technologies, the elaborate design of the dihedral corners with different opening angles is a useful approach to reduce the high RCS generated by multiple reflections. As bistatic synthetic aperture sensors have flexible geometric configurations and are sensitive to the dihedral corners with different opening angles, they specially fit for the stealth target detections. In this paper, the scattering characteristic of dihedral corner reflectors is accurately analyzed in bistatic synthetic aperture images. The variation of RCS with the changing opening angle is formulated and the method to design a proper bistatic radar for maximizing the detection capability is provided. Both the results of the theoretical analysis and the experiments show the bistatic SAR could detect the dihedral corners, under a certain bistatic angle which is related to the geometry of target structures. PMID:29271917

Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro.

PubMed

Ma, Jing; Shen, Ming; Xu, Chang Song; Sun, Ying; Duan, You Rong; Du, Lian Fang

2016-11-29

A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.

Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

DTIC Science & Technology

2008-08-01

AD_________________ Award Number: W81XWH-04-1-0697 TITLE: Alpha -v Integrin Targeted PET Imaging of...SUBTITLE 5a. CONTRACT NUMBER Alpha -v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low- Dose Metronomic Anti-Angiogenic...Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide-paclitaxel conjugate in mice with breast cancer” was published in Eur J Nucl

Generalized Wideband Harmonic Imaging of Nonlinearly Loaded Scatterers: Theory, Analysis, and Application for Forward-Looking Radar Target Detection

DTIC Science & Technology

2014-09-01

signal) operations; it is general enough so that it can accommodate high - power (large-signal) sensing as well—which may be needed to detect targets... Generalized Wideband Harmonic Imaging of Nonlinearly Loaded Scatterers: Theory, Analysis, and Application for Forward-Looking Radar Target...Research Laboratory Adelphi, MD 20783-1138 ARL-TR-7121 September 2014 Generalized Wideband Harmonic Imaging of Nonlinearly Loaded

Random Access Memories: A New Paradigm for Target Detection in High Resolution Aerial Remote Sensing Images.

PubMed

Zou, Zhengxia; Shi, Zhenwei

2018-03-01

We propose a new paradigm for target detection in high resolution aerial remote sensing images under small target priors. Previous remote sensing target detection methods frame the detection as learning of detection model + inference of class-label and bounding-box coordinates. Instead, we formulate it from a Bayesian view that at inference stage, the detection model is adaptively updated to maximize its posterior that is determined by both training and observation. We call this paradigm "random access memories (RAM)." In this paradigm, "Memories" can be interpreted as any model distribution learned from training data and "random access" means accessing memories and randomly adjusting the model at detection phase to obtain better adaptivity to any unseen distribution of test data. By leveraging some latest detection techniques e.g., deep Convolutional Neural Networks and multi-scale anchors, experimental results on a public remote sensing target detection data set show our method outperforms several other state of the art methods. We also introduce a new data set "LEarning, VIsion and Remote sensing laboratory (LEVIR)", which is one order of magnitude larger than other data sets of this field. LEVIR consists of a large set of Google Earth images, with over 22 k images and 10 k independently labeled targets. RAM gives noticeable upgrade of accuracy (an mean average precision improvement of 1% ~ 4%) of our baseline detectors with acceptable computational overhead.

Red blood cells serve as intravascular carriers of myeloperoxidase.

PubMed

Adam, Matti; Gajdova, Silvie; Kolarova, Hana; Kubala, Lukas; Lau, Denise; Geisler, Anne; Ravekes, Thorben; Rudolph, Volker; Tsao, Philip S; Blankenberg, Stefan; Baldus, Stephan; Klinke, Anna

2014-09-01

Myeloperoxidase (MPO) is a heme enzyme abundantly expressed in polymorphonuclear neutrophils. MPO is enzymatically capable of catalyzing the generation of reactive oxygen species (ROS) and the consumption of nitric oxide (NO). Thus MPO has both potent microbicidal and, upon binding to the vessel wall, pro-inflammatory properties. Interestingly, MPO - a highly cationic protein - has been shown to bind to both endothelial cells and leukocyte membranes. Given the anionic surface charge of red blood cells, we investigated binding of MPO to erythrocytes. Red blood cells (RBCs) derived from patients with elevated MPO plasma levels showed significantly higher amounts of MPO by flow cytometry and ELISA than healthy controls. Heparin-induced MPO-release from patient-derived RBCs was significantly increased compared to controls. Ex vivo experiments revealed dose and time dependency for MPO-RBC binding, and immunofluorescence staining as well as confocal microscopy localized MPO-RBC interaction to the erythrocyte plasma membrane. NO-consumption by RBC-membrane fragments (erythrocyte "ghosts") increased with incrementally greater concentrations of MPO during incubation, indicating preserved catalytic MPO activity. In vivo infusion of MPO-loaded RBCs into C57BL/6J mice increased local MPO tissue concentrations in liver, spleen, lung, and heart tissue as well as within the cardiac vasculature. Further, NO-dependent relaxation of aortic rings was altered by RBC bound-MPO and systemic vascular resistance significantly increased after infusion of MPO-loaded RBCs into mice. In summary, we find that MPO binds to RBC membranes in vitro and in vivo, is transported by RBCs to remote sites in mice, and affects endothelial function as well as systemic vascular resistance. RBCs may avidly bind circulating MPO, and act as carriers of this leukocyte-derived enzyme. Copyright © 2014 Elsevier Ltd. All rights reserved.