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Sample records for cetuximab-based imaging probe

  1. Multispectral imaging probe

    SciTech Connect

    Sandison, David R.; Platzbecker, Mark R.; Descour, Michael R.; Armour, David L.; Craig, Marcus J.; Richards-Kortum, Rebecca

    1999-01-01

    A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector.

  2. Multispectral imaging probe

    DOEpatents

    Sandison, D.R.; Platzbecker, M.R.; Descour, M.R.; Armour, D.L.; Craig, M.J.; Richards-Kortum, R.

    1999-07-27

    A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector. 8 figs.

  3. Molecular probes for cardiovascular imaging.

    PubMed

    Liang, Grace; Nguyen, Patricia K

    2016-08-01

    Molecular probes provide imaging signal and contrast for the visualization, characterization, and measurement of biological processes at the molecular level. These probes can be designed to target the cell or tissue of interest and must be retained at the imaging site until they can be detected by the appropriate imaging modality. In this article, we will discuss the basic design of molecular probes, differences among the various types of probes, and general strategies for their evaluation of cardiovascular disease. PMID:27189171

  4. Samara Probe For Remote Imaging

    NASA Technical Reports Server (NTRS)

    Burke, James D.

    1989-01-01

    Imaging probe descends through atmosphere of planet, obtaining images of ground surface as it travels. Released from aircraft over Earth or from spacecraft over another planet. Body and single wing shaped like samara - winged seed like those of maple trees. Rotates as descends, providing panoramic view of terrain below. Radio image obtained by video camera to aircraft or spacecraft overhead.

  5. Activatable Molecular Probes for Cancer Imaging

    PubMed Central

    Lee, Seulki; Xie, Jin; Chen, Xiaoyuan

    2013-01-01

    The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging. PMID:20388112

  6. Design and Development of Molecular Imaging Probes

    PubMed Central

    Chen, Kai; Chen, Xiaoyuan

    2013-01-01

    Molecular imaging, the visualization, characterization and measurement of biological processes at the cellular, subcellular level, or even molecular level in living subjects, has rapidly gained importance in the dawning era of personalized medicine. Molecular imaging takes advantage of the traditional diagnostic imaging techniques and introduces molecular imaging probes to determine the expression of indicative molecular markers at different stages of diseases and disorders. As a key component of molecular imaging, molecular imaging probe must be able to specifically reach the target of interest in vivo while retaining long enough to be detected. A desirable molecular imaging probe with clinical translation potential is expected to have unique characteristics. Therefore, design and development of molecular imaging probe is frequently a challenging endeavor for medicinal chemists. This review summarizes the general principles of molecular imaging probe design and some fundamental strategies of molecular imaging probe development with a number of illustrative examples. PMID:20388106

  7. Discrete Bimodal Probes for Thrombus Imaging

    PubMed Central

    Uppal, Ritika; Ciesienski, Kate L.; Chonde, Daniel B.; Loving, Galen S.; Caravan, Peter

    2012-01-01

    Here we report a generalizable solid/solution phase strategy for the synthesis of discrete bimodal fibrin-targeted imaging probes. A fibrin-specific peptide was conjugated with two distinct imaging reporters at the C- and N-terminus. In vitro studies demonstrated retention of fibrin affinity and specificity. Imaging studies showed that these probes could detect fibrin over a wide range of probe concentrations by optical, magnetic resonance, and positron emission tomography imaging. PMID:22698259

  8. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  9. Further capacitive imaging experiments using modified probes

    NASA Astrophysics Data System (ADS)

    Yin, Xiaokang; Li, Zhen; Yan, An; Li, Wei; Chen, Guoming; Hutchins, David A.

    2016-02-01

    In recent years, capacitive imaging (CI) is growing in popularity within the NDE communities, as it has the potential to test materials and structures for defects that are not easily tested by other techniques. In previous work, The CI technique has been successfully used on a various types of materials, including concrete, glass/carbon fibre composite, steel, etc. In such CI experiments, the probes are normally with symmetric or concentric electrodes etched onto PCBs. In addition to these conventional coplanar PCB probes, modified geometries can be made and they can lead to different applications. A brief overview of these modified probes, including high resolution surface imaging probe, combined CI/eddy current probe, and CI probe using an oscilloscope probe as the sensing electrode, is presented in this work. The potential applications brought by these probes are also discussed.

  10. Multifunctional imaging probe based on gadofulleride nanoplatform

    NASA Astrophysics Data System (ADS)

    Zheng, Jun-Peng; Liu, Qiao-Ling; Zhen, Ming-Ming; Jiang, Feng; Shu, Chun-Ying; Jin, Chan; Yang, Yongji; Alhadlaq, Hisham A.; Wang, Chun-Ru

    2012-05-01

    A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity.A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity. Electronic supplementary information (ESI) available: Materials, instruments and methods, synthesis details, XPS characterization for estimation of average molecular formula, evaluation of conjugated FA and FITC ratio, zeta potential and fluorescent images. See DOI: 10.1039/c2nr30836c

  11. Developing MR probes for molecular imaging.

    PubMed

    McMahon, Michael T; Chan, Kannie W Y

    2014-01-01

    Molecular imaging plays an important role in the era of personalized medicine, especially with recent advances in magnetic resonance (MR) probes. While the first generation of these probes focused on maximizing contrast enhancement, a second generation of probes has been developed to improve the accumulation within specific tissues or pathologies, and the newest generation of agents is also designed to report on changes in physiological status and has been termed "smart" agents. This represents a paradigm switch from the previously commercialized gadolinium and iron oxide probes to probes with new capabilities, and leads to new challenges as scanner hardware needs to be adapted for detecting these probes. In this chapter, we highlight the unique features for all five different categories of MR probes, including the emerging chemical exchange saturation transfer, (19)F, and hyperpolarized probes, and describe the key physical properties and features motivating their design. As part of this comparison, the strengths and weaknesses of each category are discussed. PMID:25287693

  12. Molecular Imaging Probe Development using Microfluidics

    PubMed Central

    Liu, Kan; Wang, Ming-Wei; Lin, Wei-Yu; Phung, Duy Linh; Girgis, Mark D.; Wu, Anna M.; Tomlinson, James S.; Shen, Clifton K.-F.

    2012-01-01

    In this manuscript, we review the latest advancement of microfluidics in molecular imaging probe development. Due to increasing needs for medical imaging, high demand for many types of molecular imaging probes will have to be met by exploiting novel chemistry/radiochemistry and engineering technologies to improve the production and development of suitable probes. The microfluidic-based probe synthesis is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional systems. Numerous chemical reactions have been successfully performed in micro-reactors and the results convincingly demonstrate with great benefits to aid synthetic procedures, such as purer products, higher yields, shorter reaction times compared to the corresponding batch/macroscale reactions, and more benign reaction conditions. Several ‘proof-of-principle’ examples of molecular imaging probe syntheses using microfluidics, along with basics of device architecture and operation, and their potential limitations are discussed here. PMID:22977436

  13. Recent Progress in Fluorescent Imaging Probes.

    PubMed

    Pak, Yen Leng; Swamy, K M K; Yoon, Juyoung

    2015-01-01

    Due to the simplicity and low detection limit, especially the bioimaging ability for cells, fluorescence probes serve as unique detection methods. With the aid of molecular recognition and specific organic reactions, research on fluorescent imaging probes has blossomed during the last decade. Especially, reaction based fluorescent probes have been proven to be highly selective for specific analytes. This review highlights our recent progress on fluorescent imaging probes for biologically important species, such as biothiols, reactive oxygen species, reactive nitrogen species, metal ions including Zn(2+), Hg(2+), Cu(2+) and Au(3+), and anions including cyanide and adenosine triphosphate (ATP). PMID:26402684

  14. Recent Progress in Fluorescent Imaging Probes

    PubMed Central

    Pak, Yen Leng; Swamy, K. M. K.; Yoon, Juyoung

    2015-01-01

    Due to the simplicity and low detection limit, especially the bioimaging ability for cells, fluorescence probes serve as unique detection methods. With the aid of molecular recognition and specific organic reactions, research on fluorescent imaging probes has blossomed during the last decade. Especially, reaction based fluorescent probes have been proven to be highly selective for specific analytes. This review highlights our recent progress on fluorescent imaging probes for biologically important species, such as biothiols, reactive oxygen species, reactive nitrogen species, metal ions including Zn2+, Hg2+, Cu2+ and Au3+, and anions including cyanide and adenosine triphosphate (ATP). PMID:26402684

  15. Protein-based tumor molecular imaging probes

    PubMed Central

    Lin, Xin; Xie, Jin

    2013-01-01

    Molecular imaging is an emerging discipline which plays critical roles in diagnosis and therapeutics. It visualizes and quantifies markers that are aberrantly expressed during the disease origin and development. Protein molecules remain to be one major class of imaging probes, and the option has been widely diversified due to the recent advances in protein engineering techniques. Antibodies are part of the immunosystem which interact with target antigens with high specificity and affinity. They have long been investigated as imaging probes and were coupled with imaging motifs such as radioisotopes for that purpose. However, the relatively large size of antibodies leads to a half-life that is too long for common imaging purposes. Besides, it may also cause a poor tissue penetration rate and thus compromise some medical applications. It is under this context that various engineered protein probes, essentially antibody fragments, protein scaffolds, and natural ligands have been developed. Compared to intact antibodies, they possess more compact size, shorter clearance time, and better tumor penetration. One major challenge of using protein probes in molecular imaging is the affected biological activity resulted from random labeling. Site-specific modification, however, allows conjugation happening in a stoichiometric fashion with little perturbation of protein activity. The present review will discuss protein-based probes with focus on their application and related site-specific conjugation strategies in tumor imaging. PMID:20232092

  16. First-line cetuximab-based chemotherapies for patients with advanced or metastatic KRAS wild-type colorectal cancer

    PubMed Central

    Uemura, Mamoru; Kim, Ho Min; Hata, Tsuyoshi; Sakata, Kazuya; Okuyama, Masaki; Takemoto, Hiroyoshi; Fujii, Hitoshi; Fukuzaki, Takayuki; Morita, Tetsushi; Hata, Taishi; Takemasa, Ichiro; Satoh, Taroh; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Maski

    2016-01-01

    Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. A burgeoning number of studies have demonstrated that the addition of cetuximab to another standard first-line regimen markedly improves the outcome of CRC treatment. However, at present, the efficacy and safety of cetuximab-based combination chemotherapy has not been well described in Japan. The aim of the present study was to evaluate the efficacy and safety of first-line chemotherapies that included cetuximab for patients with advanced or metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type CRC in Japan. This prospective multicenter observational study was conducted at 13 affiliated medical institutions. A total of 64 patients were enrolled between 2010 and 2013. The patients met the following criteria for eligibility: i) histologically confirmed, advanced or metastatic KRAS wild-type CRC; and ii) cetuximab-based chemotherapies administered as a first-line treatment. First-line cetuximab-based treatments were administered as follows: 29 patients (45.3%) received a combination of infusional fluorouracil, leucovorin and oxaliplatin; 14 patients (21.9%) received a combination of capecitabine and oxaliplatin; and 10 patients (15.6%) received a combination of infusional fluorouracil, leucovorin and irinotecan. The overall response rate (including complete plus partial responses) was 50% (32/64 patients). Initially, 48 lesions were diagnosed as unresectable. Among those, 13 lesions (27.1%) were converted to a resectable status following cetuximab-based combination chemotherapy treatments. The median overall survival time and the progression-free survival time were 1,189 and 359 days, respectively. The most frequent grade 3/4 adverse event was neutropenia, which occurred in 20.3% of the patients. The incidence of grade 3/4 skin toxicity was 17.2% (11/64 patients). Cetuximab-based therapies may represent a promising first-line regimen for patients with advanced or

  17. Scanning probe image wizard: A toolbox for automated scanning probe microscopy data analysis

    NASA Astrophysics Data System (ADS)

    Stirling, Julian; Woolley, Richard A. J.; Moriarty, Philip

    2013-11-01

    We describe SPIW (scanning probe image wizard), a new image processing toolbox for SPM (scanning probe microscope) images. SPIW can be used to automate many aspects of SPM data analysis, even for images with surface contamination and step edges present. Specialised routines are available for images with atomic or molecular resolution to improve image visualisation and generate statistical data on surface structure.

  18. Molecular imaging probe development: a chemistry perspective

    PubMed Central

    Nolting, Donald D; Nickels, Michael L; Guo, Ning; Pham, Wellington

    2012-01-01

    Molecular imaging is an attractive modality that has been widely employed in many aspects of biomedical research; especially those aimed at the early detection of diseases such as cancer, inflammation and neurodegenerative disorders. The field emerged in response to a new research paradigm in healthcare that seeks to integrate detection capabilities for the prediction and prevention of diseases. This approach made a distinct impact in biomedical research as it enabled researchers to leverage the capabilities of molecular imaging probes to visualize a targeted molecular event non-invasively, repeatedly and continuously in a living system. In addition, since such probes are inherently compact, robust, and amenable to high-throughput production, these probes could potentially facilitate screening of preclinical drug discovery, therapeutic assessment and validation of disease biomarkers. They could also be useful in drug discovery and safety evaluations. In this review, major trends in the chemical synthesis and development of positron emission tomography (PET), optical and magnetic resonance imaging (MRI) probes are discussed. PMID:22943038

  19. An image registration based ultrasound probe calibration

    NASA Astrophysics Data System (ADS)

    Li, Xin; Kumar, Dinesh; Sarkar, Saradwata; Narayanan, Ram

    2012-02-01

    Reconstructed 3D ultrasound of prostate gland finds application in several medical areas such as image guided biopsy, therapy planning and dose delivery. In our application, we use an end-fire probe rotated about its axis to acquire a sequence of rotational slices to reconstruct 3D TRUS (Transrectal Ultrasound) image. The image acquisition system consists of an ultrasound transducer situated on a cradle directly attached to a rotational sensor. However, due to system tolerances, axis of probe does not align exactly with the designed axis of rotation resulting in artifacts in the 3D reconstructed ultrasound volume. We present a rigid registration based automatic probe calibration approach. The method uses a sequence of phantom images, each pair acquired at angular separation of 180 degrees and registers corresponding image pairs to compute the deviation from designed axis. A modified shadow removal algorithm is applied for preprocessing. An attribute vector is constructed from image intensity and a speckle-insensitive information-theoretic feature. We compare registration between the presented method and expert-corrected images in 16 prostate phantom scans. Images were acquired at multiple resolutions, and different misalignment settings from two ultrasound machines. Screenshots from 3D reconstruction are shown before and after misalignment correction. Registration parameters from automatic and manual correction were found to be in good agreement. Average absolute differences of translation and rotation between automatic and manual methods were 0.27 mm and 0.65 degree, respectively. The registration parameters also showed lower variability for automatic registration (pooled standard deviation σtranslation = 0.50 mm, σrotation = 0.52 degree) compared to the manual approach (pooled standard deviation σtranslation = 0.62 mm, σrotation = 0.78 degree).

  20. Molecular probes for malignant melanoma imaging.

    PubMed

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  1. Molecular Probes for Fluorescence Lifetime Imaging

    PubMed Central

    Sarder, Pinaki; Maji, Dolonchampa; Achilefu, Samuel

    2015-01-01

    Visualization of biological processes and pathologic conditions at the cellular and tissue levels largely rely on the use of fluorescence intensity signals from fluorophores or their bioconjugates. To overcome the concentration dependency of intensity measurements, evaluate subtle molecular interactions, and determine biochemical status of intracellular or extracellular microenvironments, fluorescence lifetime (FLT) imaging has emerged as a reliable imaging method complementary to intensity measurements. Driven by a wide variety of dyes exhibiting stable or environment-responsive FLTs, information multiplexing can be readily accomplished without the need for ratiometric spectral imaging. With knowledge of the fluorescent states of the molecules, it is entirely possible to predict the functional status of biomolecules or microevironment of cells. Whereas the use of FLT spectroscopy and microscopy in biological studies is now well established, in vivo imaging of biological processes based on FLT imaging techniques is still evolving. This review summarizes recent advances in the application of the FLT of molecular probes for imaging cells and small animal models of human diseases. It also highlights some challenges that continue to limit the full realization of the potential of using FLT molecular probes to address diverse biological problems, and outlines areas of potential high impact in the future. PMID:25961514

  2. Fluorescent nanoparticle probes for imaging of cancer.

    PubMed

    Santra, Swadeshmukul; Malhotra, Astha

    2011-01-01

    Fluorescent nanoparticles (FNPs) have received immense popularity in cancer imaging in recent years because of their attractive optical properties. In comparison to traditional organic-based fluorescent dyes and fluorescent proteins, FNPs offer much improved sensitivity and photostability. FNPs in certain size range have a strong tendency to enter and retain in solid tumor tissue with abnormal (leaky) vasculature--a phenomenon known as Enhanced Permeation and Retention (EPR) effect, advancing their use for in vivo tumor imaging. Furthermore, large surface area of FNPs and their usual core-shell structure offer a platform for designing and fabricating multimodal/multifunctional nanoparticles (MMNPs). For effective cancer imaging, often the optical imaging modality is integrated with other nonoptical-based imaging modalities such as MRI, X-ray, and PET, thus creating multimodal nanoparticle (NP)-based imaging probes. Such multimodal NP probes can be further integrated with therapeutic drug as well as cancer targeting agent leading to multifunctional NPs. Biocompatibility of FNPs is an important criterion that must be seriously considered during FNP design. NP composition, size, and surface chemistry must be carefully selected to minimize potential toxicological consequences both in vitro and in vivo. In this article, we will mainly focus on three different types of FNPs: dye-loaded NPs, quantum dots (Qdots), and phosphores; briefly highlighting their potential use in translational research. PMID:21480546

  3. The Imaging Probe Development Center and the Production of Molecular Imaging Probes

    PubMed Central

    Griffiths, Gary L

    2008-01-01

    The Imaging Probe Development Center (IPDC), part of the NIH Roadmap for Medical Research Initiative (http://nihroadmap.nih.gov/) recently became fully operational at its newly refurbished laboratories in Rockville, MD. The IPDC (http://nihroadmap.nih.gov/molecularlibraries/ipdc/) is dedicated to the production of known and novel molecular imaging probes, with its services currently being used by the NIH intramural community, although in the future it is intended that the extramural community will also benefit from the IPDC’s resources. The Center has been set up with the belief that molecular imaging, and the probe chemistry that underpins it, will constitute key technologies going forward. As part of the larger molecular libraries and imaging initiative, it is planned that the IPDC will work closely with scientists from the molecular libraries effort. Probes produced at the IPDC include optical, radionuclide and magnetic resonance agents and may encompass any type of contrast agent. As IPDC is a trans-NIH resource it can serve each of the 27 Institutes and Centers that comprise NIH so its influence can be expected to impact widely different subjects and disease conditions spanning biological research. IPDC is expected to play a key part in interdisciplinary collaborative imaging projects and to support translational R&D from basic research through clinical development, for all of the imaging modalities. Examples of probes already prepared or under preparation are outlined to illustrate the breadth of the chemistries undertaken together with a reference outline of the diverse biological applications for which the various probes are intended. PMID:20161829

  4. Progesterone-Targeted Magnetic Resonance Imaging Probes

    PubMed Central

    2015-01-01

    Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo. PMID:25019183

  5. Multimode-Optical-Fiber Imaging Probe

    NASA Technical Reports Server (NTRS)

    Jackson, Deborah

    1999-01-01

    Currently, endoscopic surgery uses single-mode fiber-bundles to obtain in vivo image information inside the orifices of the body. This limits their use to the larger natural orifices and to surgical procedures where there is plenty of room for manipulation. The knee joint, for example, can be easily viewed with a fiber optic viewer, but joints in the finger cannot. However, there are a host of smaller orifices where fiber endoscopy would play an important role if a cost effective fiber probe were developed with small enough dimensions (less than or equal to 250 microns). Examples of beneficiaries of micro-endoscopes are the treatment of the Eustatian tube of the middle ear, the breast ducts, tear ducts, coronary arteries, fallopian tubes, as well as the treatment of salivary duct parotid disease, and the neuro endoscopy of the ventricles and spinal canal. This work describes an approach for recovering images from tightly confined spaces using multimode. The concept draws upon earlier works that concentrated on image recovery after two-way transmission through a multimode fiber as well as work that demonstrated the recovery of images after one-way transmission through a multimode fiber. Both relied on generating a phase conjugated wavefront, which was predistorted with the characteristics of the fiber. The approach described here also relies on generating a phase conjugated wavefront, but utilizes two fibers to capture the image at some intermediate point (accessible by the fibers, but which is otherwise visually inaccessible).

  6. Full tip imaging in atom probe tomography.

    PubMed

    Du, Sichao; Burgess, Timothy; Loi, Shyeh Tjing; Gault, Baptiste; Gao, Qiang; Bao, Peite; Li, Li; Cui, Xiangyuan; Kong Yeoh, Wai; Tan, Hark Hoe; Jagadish, Chennupati; Ringer, Simon P; Zheng, Rongkun

    2013-01-01

    Atom probe tomography (APT) is capable of simultaneously revealing the chemical identities and three dimensional positions of individual atoms within a needle-shaped specimen, but suffers from a limited field-of-view (FOV), i.e., only the core of the specimen is effectively detected. Therefore, the capacity to analyze the full tip is crucial and much desired in cases that the shell of the specimen is also the region of interest. In this paper, we demonstrate that, in the analysis of III-V nanowires epitaxially grown from a substrate, the presence of the flat substrate positioned only micrometers away from the analyzed tip apex alters the field distribution and ion trajectories, which provides extra image compression that allows for the analysis of the entire specimen. An array of experimental results, including field desorption maps, elemental distributions, and crystallographic features clearly demonstrate the fact that the whole tip has been imaged, which is confirmed by electrostatic simulations. PMID:23142750

  7. Optical brush: Imaging through permuted probes

    PubMed Central

    Heshmat, Barmak; Lee, Ik Hyun; Raskar, Ramesh

    2016-01-01

    The combination of computational techniques and ultrafast imaging have enabled sensing through unconventional settings such as around corners, and through diffusive media. We exploit time of flight (ToF) measurements to enable a flexible interface for imaging through permuted set of fibers. The fibers are randomly distributed in the scene and are packed on the camera end, thus making a brush-like structure. The scene is illuminated by two off-axis optical pulses. Temporal signatures of fiber tips in the scene are used to localize each fiber. Finally, by combining the position and measured intensity of each fiber, the original input is reconstructed. Unlike conventional fiber bundles with packed set of fibers that are limited by a narrow field of view (FOV), lack of flexibility, and extended coaxial precalibration, the proposed optical brush is flexible and uses off-axis calibration method based on ToF. The enabled brush form can couple to other types of ToF imaging systems. This can impact probe-based applications such as, endoscopy, tomography, and industrial imaging and sensing. PMID:26868954

  8. Optical brush: Imaging through permuted probes

    NASA Astrophysics Data System (ADS)

    Heshmat, Barmak; Lee, Ik Hyun; Raskar, Ramesh

    2016-02-01

    The combination of computational techniques and ultrafast imaging have enabled sensing through unconventional settings such as around corners, and through diffusive media. We exploit time of flight (ToF) measurements to enable a flexible interface for imaging through permuted set of fibers. The fibers are randomly distributed in the scene and are packed on the camera end, thus making a brush-like structure. The scene is illuminated by two off-axis optical pulses. Temporal signatures of fiber tips in the scene are used to localize each fiber. Finally, by combining the position and measured intensity of each fiber, the original input is reconstructed. Unlike conventional fiber bundles with packed set of fibers that are limited by a narrow field of view (FOV), lack of flexibility, and extended coaxial precalibration, the proposed optical brush is flexible and uses off-axis calibration method based on ToF. The enabled brush form can couple to other types of ToF imaging systems. This can impact probe-based applications such as, endoscopy, tomography, and industrial imaging and sensing.

  9. Biomedical applications of a new portable Raman imaging probe

    NASA Astrophysics Data System (ADS)

    Sato, Hidetoshi; Tanaka, Takeyuki; Ikeda, Teruki; Wada, Satoshi; Tashiro, Hideo; Ozaki, Yukihiro

    2001-10-01

    This article reports the outline of a new portable Raman imaging probe and its applications. This probe may be the smallest and lightest Raman imaging probe in the world. It is equipped with an interchangeable long-working distance microscope objective lens. The irradiation area is about 45 and 90 μm and the spatial resolution is 1 μm. In the present study, the Raman imaging probe was used to obtain a Raman image of diamond particles and a Raman mapping of carotenoid in Euglena.

  10. Multimode-Optical-Fiber Imaging Probe

    NASA Technical Reports Server (NTRS)

    Jackson, Deborah

    2000-01-01

    Currently, endoscopic surgery uses single-mode fiber-bundles to obtain in vivo image information inside orifices of the body. This limits their use to the larger natural bodily orifices and to surgical procedures where there is plenty of room for manipulation. The knee joint, for example can be easily viewed with a fiber optic viewer, but joints in the finger cannot. However, there are a host of smaller orifices where fiber endoscopy would play an important role if a cost effective fiber probe were developed with small enough dimensions (< 250 microns). Examples of beneficiaries of micro-endoscopes are the treatment of the Eustatian tube of the middle ear, the breast ducts, tear ducts, coronary arteries, fallopian tubes, as well as the treatment of salivary duct parotid disease, and the neuro endoscopy of the ventricles and spinal canal. To solve this problem, this work describes an approach for recovering images from. tightly confined spaces using multimode fibers and analytically demonstrates that the concept is sound. The proof of concept draws upon earlier works that concentrated on image recovery after two-way transmission through a multimode fiber as well as work that demonstrated the recovery of images after one-way transmission through a multimode fiber. Both relied on generating a phase conjugated wavefront which was predistorted with the characteristics of the fiber. The described approach also relies on generating a phase conjugated wavefront, but utilizes two fibers to capture the image at some intermediate point (accessible by the fibers, but which is otherwise visually unaccessible).

  11. Imaging probe for breast cancer localization

    NASA Astrophysics Data System (ADS)

    Soluri, A.; Scafè, R.; Capoccetti, F.; Burgio, N.; Schiaratura, A.; Pani, R.; Pellegrini, R.; Cinti, M. N.; Mechella, M.; Amanti, A.; David, V.; Scopinaro, F.

    2003-01-01

    High spatial resolution, small Field Of View (FOV), fully portable scintillation cameras are lower cost and obviously lower weight than large FOV, not transportable Anger gamma cameras. Portable cameras allow easy transfer of the detector, thus of radioisotope imaging, where the bioptical procedure takes place. In this paper we describe a preliminary experience on radionuclide Breast Cancer (BC) imaging with a 22.8×22.8 mm 2 FOV minicamera, already used by our group for sentinel node detection with the name of Imaging Probe (IP). In this work IP BC detection was performed with the aim of guiding biopsy, in particular open biopsy, or to help or modify fine needle or needle addressing when main driving method was echography or digital radiography. The IP prototype weight was about 1 kg. This small scintillation camera is based on the compact Position Sensitive Photomultiplier Tube Hamamatsu R7600-00-C8, coupled to a CsI(Tl) scintillation array 2.6×2.6×5.0 mm 3 crystal-pixel size. Spatial resolution of the IP was 2.5 mm Full-Width at Half-Maximum at laboratory tests. IP was provided with acquisition software allowing quick change of pixels number on the computer acquisition frame and an on-line image-smoothing program. Both these programs were developed in order to allow nuclear physicians to quickly get target source when the patient was anesthetized in the operator room, with sterile conditions. 99mTc Sestamibi (MIBI) was injected at the dose of 740 MBq 1 h before imaging and biopsy to 14 patients with suspicious or known BC. Scintigraphic images were acquired before and after biopsy in each patient. Operator was allowed to take into account scintigraphic images as well as previously performed X-ray mammograms and echographies. High-resolution IP images were able to guide biopsy toward cancer or washout zones of the cancer, that are thought to be chemoresistant in 7 patients out of 10. Four patients, in whom IP and MIBI were not able to guide biopsy, did not show

  12. A miniature forward-imaging optical coherence tomography (OCT) probe

    NASA Astrophysics Data System (ADS)

    Joos, Karen M.; Shen, Jin-Hui

    2012-03-01

    Optical coherence tomography (OCT) has had a tremendous global health impact upon the current ability to diagnose, treat, and monitor multiple eye diseases. We propose that a miniature forward-imaging OCT probe can be developed for real-time ocular imaging. A miniature 25-gauge forward-imaging probe was designed and developed to use with an 850 nm spectral-domain optical coherence tomography (SDOCT) system (Bioptigen, Inc. Durham, NC). Imaging parameters were determined. Ocular tissues were examined with the miniature OCT probe. A miniature SDOCT probe was developed with the scanning driver within the hand piece. The SDOCT fiber-scanning probe maximally transmitted power of 800 μW. The scanning range was 3 mm when the probe tip was held 3 to 5 mm from the tissue surface. The axial resolution was 6 μm and the lateral resolution was 30-35 μm. The 25-gauge forward-imaging probe was used to image cellophane tape, eyelid skin, cornea, conjunctiva, sclera, iris, anterior lens, anterior chamber angle, retina, retinal tear, retinal detachment, optic nerve head, and optic nerve sheath. Images obtained from the miniature probe appeared similar to images from a 3 mm scanning range of a commercial large handheld OCT probe (Bioptigen, Inc. Durham, NC).

  13. Imaging bacterial peptidoglycan with near-infrared fluorogenic azide probes

    PubMed Central

    Shieh, Peyton; Siegrist, M. Sloan; Cullen, Andrew J.; Bertozzi, Carolyn R.

    2014-01-01

    Fluorescent probes designed for activation by bioorthogonal chemistry have enabled the visualization of biomolecules in living systems. Such activatable probes with near-infrared (NIR) emission would be ideal for in vivo imaging but have proven difficult to engineer. We present the development of NIR fluorogenic azide probes based on the Si-rhodamine scaffold that undergo a fluorescence enhancement of up to 48-fold upon reaction with terminal or strained alkynes. We used the probes for mammalian cell surface imaging and, in conjunction with a new class of cyclooctyne d-amino acids, for visualization of bacterial peptidoglycan without the need to wash away unreacted probe. PMID:24706769

  14. Analysis of scanning probe microscope images using wavelets.

    PubMed

    Gackenheimer, C; Cayon, L; Reifenberger, R

    2006-03-01

    The utility of wavelet transforms for analysis of scanning probe images is investigated. Simulated scanning probe images are analyzed using wavelet transforms and compared to a parallel analysis using more conventional Fourier transform techniques. The wavelet method introduced in this paper is particularly useful as an image recognition algorithm to enhance nanoscale objects of a specific scale that may be present in scanning probe images. In its present form, the applied wavelet is optimal for detecting objects with rotational symmetry. The wavelet scheme is applied to the analysis of scanning probe data to better illustrate the advantages that this new analysis tool offers. The wavelet algorithm developed for analysis of scanning probe microscope (SPM) images has been incorporated into the WSxM software which is a versatile freeware SPM analysis package. PMID:16439061

  15. Efficacy of continued cetuximab for unresectable metastatic colorectal cancer after disease progression during first-line cetuximab-based chemotherapy: a retrospective cohort study

    PubMed Central

    Yu, Yiyi; Ye, Qinghai; Ding, Jianyong; Chen, Jingwen; Chang, Wenju; Zhong, Yunshi; Zhu, Dexiang; Lin, Qi; Yang, Liangliang; Qin, Xinyu; Xu, Jianmin

    2016-01-01

    This study assessed second-line continued use of cetuximab for treatment of unresectable metastatic colorectal cancer (mCRC) after disease progression during first-line cetuximab-based therapy. Consecutive patients with wild-type KRAS exon 2 and unresectable mCRC were retrospectively enrolled after disease progression during first-line cetuximab-based chemotherapy. Second-line continued cetuximab plus changed chemotherapy (cetuximab continuation group, n = 102) was compared with changed chemotherapy only (chemotherapy only group, n = 96) with respect to treatment efficacy and safety endpoints. NRAS and other KRAS genotypes were also detected as a post hoc analysis. The cetuximab continuation group showed better progression-free survival (median, 6.3 vs. 4.5 months, P = 0.004), overall survival (median, 17.3 vs. 14.0 months, P < 0.001) and disease control rate (70.6% vs. 53.1%, P = 0.011), and a potentially better overall response rate (18.6% vs. 9.4%, P = 0.062) than the chemotherapy only group. These benefits were seen mainly in patients with all RAS wild-type and exhibiting first-line early tumor shrinkage (ETS). For patients with other RAS mutations or who did not achieve first-line ETS, there was no difference between the two groups. These findings suggest that for patients with all RAS wild-type and unresectable mCRC who had disease progression during first-line cetuximab-based treatment, second-line continued cetuximab is effective. Moreover, ETS during first-line cetuximab-based treatment may be predictive of the efficacy of second-line continued cetuximab. PMID:26863631

  16. Versatile robotic probe calibration for position tracking in ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Eirik Bø, Lars; Fagertun Hofstad, Erlend; Lindseth, Frank; Hernes, Toril A. N.

    2015-05-01

    Within the field of ultrasound-guided procedures, there are a number of methods for ultrasound probe calibration. While these methods are usually developed for a specific probe, they are in principle easily adapted to other probes. In practice, however, the adaptation often proves tedious and this is impractical in a research setting, where new probes are tested regularly. Therefore, we developed a method which can be applied to a large variety of probes without adaptation. The method used a robot arm to move a plastic sphere submerged in water through the ultrasound image plane, providing a slow and precise movement. The sphere was then segmented from the recorded ultrasound images using a MATLAB programme and the calibration matrix was computed based on this segmentation in combination with tracking information. The method was tested on three very different probes demonstrating both great versatility and high accuracy.

  17. Indirect comparison of the efficacy and safety of gefitinib and cetuximab-based therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    TANG, JIFENG; ZHANG, HENA; YAN, JIANZHOU; SHAO, RONG

    2015-01-01

    The aim of this study was to systematically evaluate the efficacy and safety of gefitinib and cetuximab-based therapies in patients with advanced non-small-cell lung cancer (NSCLC). The studies to be used for the comparisons were selected from the available literature on gefitinib and cetuximab-based therapies compared to conventional chemotherapy in patients with advanced NSCLC. The meta-analysis was performed with RevMan 5.0 software and the Bucher approach was applied to conduct the indirect comparisons. A total of 4 studies, including 935 patients, on gefitinib therapy vs. conventional chemotherapy and 4 studies, including 1,015 patients, on cetuximab-based therapy vs. conventional chemotherapy, were used for indirect comparisons. As regards efficacy, the risk ratio (RR) of objective response rate and 1-year survival rate between gefitinib and cetuximab-based therapies in patients with advanced NSCLC were 0.99 [95% confidence interval (CI): 0.75–1.32; P=0.9584] and 0.85 (95% CI: 0.71–1.01; P=0.0696), respectively, and the mean difference of progression-free survival and overall survival (OS) were −0.15 (95% CI: −0.90 to 0.60; P=0.6946) and −1.84 (95% CI: −3.53 to −0.15; P=0.0331), respectively. As regards safety, the RR of grade 3/4 adverse events (AEs) was 0.29 (95% CI: 0.19–0.44; P=0.0001). The results demonstrated that cetuximab-based therapy was superior to gefitinib therapy in terms of OS and inferior to gefitinib therapy in terms of AEs, whereas there were no significant differences in terms of efficacy and safety between the two therapies on other endpoints adopted for advanced NSCLC. However, further well-designed randomized controlled trials and continuous studies are required to confirm our findings. PMID:25469285

  18. Variable resolution imaging fiber probe using digital spatial light modulator

    NASA Astrophysics Data System (ADS)

    Shinde, Anant; Perinchery, Sandeep M.; Vadakke Matham, Murukeshan

    2015-07-01

    Flexible fiber optic imaging systems including fiber optic confocal probes have found tremendous significance in the recent past for its applications in high resolution imaging. However, motorized stage is required for scanning the sample or tip of the fiber in fiber based confocal probes. In this context, we propose a fiber probe confocal system using digital spatial light modulator devoid of using a mechanical scanning stage. Each fiberlet in the image fiber acts not only as a light conduit but also as a confocal pinhole. The paper also introduces the variation in the contrast by varying the number of illuminated fiberlets which effectively implies variation in the effective pinhole size. This approach has enabled the probe to act as an imaging unit with resolution that can be controlled and varied from a wide-field to a confocal.

  19. Carbon nanotube scanning probe for imaging in aqueous environment

    NASA Technical Reports Server (NTRS)

    Stevens, Ramsey M.; Nguyen, Cattien V.; Meyyappan, M.

    2004-01-01

    Carbon nanotubes (CNTs) used as a probe for scanning probe microscopy has become one of the many potential usages of CNTs that is finding real applications in scientific research and industrial communities. It has been proposed that the unique mechanical buckling properties of the CNT would lessen the imaging force exerted on the sample and, thus, make CNT scanning probes ideal for imaging soft materials, including biological samples in liquid environments. The hydrophobic nature of the CNT graphitic sidewall is clearly chemically incompatible with the aqueous solution requirements in some biological imaging applications. In this paper, we present electron micrograph results demonstrating the instability of CNT scanning probes when submerged in aqueous solution. Moreover, we also introduce a novel approach to resolve this chemical incompatibility problem. By coating the CNT probe with ethylenediamine, thus rendering the CNT probe less hydrophobic, we demonstrate the liquid imaging capability of treated CNT probes. Experimental data for imaging in aqueous solutions are presented, which include an ultrathin Ir film and DNA molecules on a mica surface.

  20. Probe and object function reconstruction in incoherent stem imaging

    SciTech Connect

    Nellist, P.D.; Pennycook, S.J.

    1996-09-01

    Using the phase-object approximation it is shown how an annular dark- field (ADF) detector in a scanning transmission electron microscope (STEM) leads to an image which can be described by an incoherent model. The point spread function is found to be simply the illuminating probe intensity. An important consequence of this is that there is no phase problem in the imaging process, which allows various image processing methods to be applied directly to the image intensity data. Using an image of a GaAs<110>, the probe intensity profile is reconstructed, confirming the existence of a 1.3 {Angstrom} probe in a 300kV STEM. It is shown that simply deconvolving this reconstructed probe from the image data does not improve its interpretability because the dominant effects of the imaging process arise simply from the restricted resolution of the microscope. However, use of the reconstructed probe in a maximum entropy reconstruction is demonstrated, which allows information beyond the resolution limit to be restored and does allow improved image interpretation.

  1. Image-guided surgery using multimodality strategy and molecular probes.

    PubMed

    Xi, Lei; Jiang, Hubei

    2016-01-01

    The ultimate goal of cancer surgery is to maximize the excision of tumorous tissue with minimal damage to the collateral normal tissues, reduce the postoperative recurrence, and improve the survival rate of patients. In order to locate tumor lesions, highlight tumor margins, visualize residual disease in the surgical wound, and map potential lymph node metastasis, various imaging techniques and molecular probes have been investigated to assist surgeons to perform more complete tumor resection. Combining imaging techniques with molecular probes is particularly promising as a new approach for image-guided surgery. Considering inherent limitations of different imaging techniques and insufficient sensitivity of nonspecific molecular probes, image-guided surgery with multimodality strategy and specific molecular probes appears to be an optimal choice. In this article, we briefly describe typical imaging techniques and molecular probes followed by a focused review on the current progress of multimodal image-guided surgery with specific molecular navigation. We also discuss optimal strategy that covers all stages of image-guided surgery including preoperative scanning of tumors, intraoperative inspection of surgical bed and postoperative care of patients. PMID:26053199

  2. Infrared hollow optical fiber probes for reflectance spectral imaging.

    PubMed

    Huang, Chenhui; Kino, Saiko; Katagiri, Takashi; Matsuura, Yuji

    2015-05-10

    Systems for infrared reflectance imaging are built with an FT-IR spectrometer, hollow optical fibers, and a high-speed infrared camera. To obtain reflectance images of biological samples, an optical fiber probe equipped with a light source at the distal end and a hybrid fiber probe composed of fibers for beam radiation and ones for image detection have been developed. By using these systems, reflectance spectral images of lipid painted on biomedical hard tissue, which provides reflectance of around 4%, are successfully acquired. PMID:25967522

  3. Shielding of Piezoelectric Ultrasonic Probes in Hall Effect Imaging

    PubMed Central

    Wen, Han; Bennett, Eric; Wiesler, David G.

    2010-01-01

    This paper addresses significant sources of electromagnetic noise in Hall effect imaging. Hall effect imaging employs large electrical pulses for signal generation and high sensitivity ultrasonic probes for signal reception. Coherent noise arises through various coupling mechanisms between the excitation pulse and the probe. In this paper, the coupling mechanisms are experimentally isolated and theoretically analyzed. Several methods of shielding the probe from electromagnetic interference are devised and tested. These methods are able to reduce the noise to levels below the random thermal noise, thereby improving the signal-to-noise ratio in HEI by two orders of magnitude. PMID:9921620

  4. Fluorogenic Probes for Multicolor Imaging in Living Cells.

    PubMed

    Lukinavičius, Gražvydas; Reymond, Luc; Umezawa, Keitaro; Sallin, Olivier; D'Este, Elisa; Göttfert, Fabian; Ta, Haisen; Hell, Stefan W; Urano, Yasuteru; Johnsson, Kai

    2016-08-01

    Here we present a far-red, silicon-rhodamine-based fluorophore (SiR700) for live-cell multicolor imaging. SiR700 has excitation and emission maxima at 690 and 715 nm, respectively. SiR700-based probes for F-actin, microtubules, lysosomes, and SNAP-tag are fluorogenic, cell-permeable, and compatible with superresolution microscopy. In conjunction with probes based on the previously introduced carboxy-SiR650, SiR700-based probes permit multicolor live-cell superresolution microscopy in the far-red, thus significantly expanding our capacity for imaging living cells. PMID:27420907

  5. Spatial-scanning hyperspectral imaging probe for bio-imaging applications

    NASA Astrophysics Data System (ADS)

    Lim, Hoong-Ta; Murukeshan, Vadakke Matham

    2016-03-01

    The three common methods to perform hyperspectral imaging are the spatial-scanning, spectral-scanning, and snapshot methods. However, only the spectral-scanning and snapshot methods have been configured to a hyperspectral imaging probe as of today. This paper presents a spatial-scanning (pushbroom) hyperspectral imaging probe, which is realized by integrating a pushbroom hyperspectral imager with an imaging probe. The proposed hyperspectral imaging probe can also function as an endoscopic probe by integrating a custom fabricated image fiber bundle unit. The imaging probe is configured by incorporating a gradient-index lens at the end face of an image fiber bundle that consists of about 50 000 individual fiberlets. The necessary simulations, methodology, and detailed instrumentation aspects that are carried out are explained followed by assessing the developed probe's performance. Resolution test targets such as United States Air Force chart as well as bio-samples such as chicken breast tissue with blood clot are used as test samples for resolution analysis and for performance validation. This system is built on a pushbroom hyperspectral imaging system with a video camera and has the advantage of acquiring information from a large number of spectral bands with selectable region of interest. The advantages of this spatial-scanning hyperspectral imaging probe can be extended to test samples or tissues residing in regions that are difficult to access with potential diagnostic bio-imaging applications.

  6. Imaging resolution of AFM with probes modified with FIB.

    PubMed

    Skibinski, J; Rebis, J; Wejrzanowski, T; Rozniatowski, K; Pressard, K; Kurzydlowski, K J

    2014-11-01

    This study concerns imaging of the structure of materials using AFM tapping (TM) and phase imaging (PI) mode, using probes modified with focused ion beam (FIB). Three kinds of modifications were applied - thinning of the cantilever, sharpening of the tip and combination of these two modifications. Probes shaped in that way were used for AFM investigations with Bruker AFM Nanoscope 8. As a testing material, titanium roughness standard supplied by Bruker was used. The results show that performed modifications influence the oscillation of the probes. In particular thinning of the cantilever enables one to acquire higher self-resonant frequencies, which can be advantageous for improving the quality of imaging in PI mode. It was found that sharpening the tip improves imaging resolution in tapping mode, which is consistent with existing knowledge, but lowered the quality of high frequency topography images. In this paper the Finite Element Method (FEM) was used to explain the results obtained experimentally. PMID:25080273

  7. Time of flight diffraction imaging for double-probe technique.

    PubMed

    Chang, Young-Fo; Hsieh, Cheng-I

    2002-06-01

    Due to rapid progress in microelectronics and computer technologies, the system evolving from analog to digital, and a programmable and flexible synthetic aperture focusing technique (SAFT) for the single-probe pulse-echo imaging technique of ultrasonic nondestructive testing (NDT) becomes feasible. The double-probe reflection technique usually is used to detect the nonhorizontal flaws in the ultrasonic NDT. Because there is an offset between the transmitter and receiver, the position and size of the flaw cannot be directly read from the image. Therefore, a digital signal processing (DSP) imaging method is proposed to process the ultrasonic image obtained by double-probe reflection technique. In the imaging, the signal is redistributed on an ellipsoid with the transmitter and receiver positions as focuses, and the traveltime sum for the echo from the ellipsoid to the focuses as the traveltime of signal. After redistributing all the signals, the useful signals can be constructively added in some point in which the reflected point is; otherwise, the signals will be destructively added. Therefore, the image resolution of the flaw can be improved and the position and size of the flaw can be estimated directly from the processed image. Based on the experimental results, the steep flaw (45 degrees) cannot be detected by the pulse echo technique but can be detected by the double-probe method, and the double-probe B-scan image of 30 degrees tilted crack is clearer than the pulse echo B-scan image. However, the flaw image departs from its true position greatly. After processing, the steep flaw image can be moved to its true position. When the flaws are not greater than the probe largely, the sizes of the flaws are difficult to be discriminated in both pulse echo and double-probe B-scan images. In the processed double-probe B-scan image, the size of the flaws can be estimated successfully, and the images of the flaws are close to their true shape. PMID:12075969

  8. Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy

    PubMed Central

    Nemecek, Radim; Berkovcova, Jitka; Radova, Lenka; Kazda, Tomas; Mlcochova, Jitka; Vychytilova-Faltejskova, Petra; Slaby, Ondrej; Svoboda, Marek

    2016-01-01

    Purpose Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%–45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single-institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions. Patients and methods Twenty-four paired primary and corresponding metastatic tissue samples from eight nonresponding and four responding metastatic colorectal cancer patients treated with cetuximab-based therapy were sequenced using a next-generation sequencing panel of 26 genes involved in EGFR signaling pathway and colorectal carcinogenesis. Results Mutational status of primary tumors and metastatic lesions was highly concordant in TP53, APC, CTNNB1, KRAS, PIK3CA, PTEN, and FBXW7 genes. Metastatic samples harbor significantly more mutations than primary tumors. Potentially negative predictive value of FBXW7 mutations in relationship to anti-EGFR treatment outcomes was confirmed. Finally, new occurrences of activating KRAS mutations were identified in a group of patients initially determined as wild-type RAS by routinely used qPCR-based RAS mutational tests. All newly detected activating KRAS mutations most likely led to cetuximab treatment failure. Conclusion The results of the present study suggest a need of careful consideration of previously published results of anti-EGFR-targeted therapy with regard to potentially inaccurate diagnostic tools used in the past. Based on our findings, we recommend more extensive use of next-generation sequencing testing in daily

  9. Intracellular probes for imaging oxygen concentration: how good are they?

    NASA Astrophysics Data System (ADS)

    Dmitriev, Ruslan I.; Papkovsky, Dmitri B.

    2015-09-01

    In the last decade a number of cell-permeable phosphorescence based probes for imaging of (intra)cellular oxygen (icO2) have been described. These small molecule, supramolecular and nanoparticle structures, although allowing analysis of hypoxia, local gradients and fluctuations in O2, responses to stimulation and drug treatment at sub-cellular level with high spatial and temporal resolution, differ significantly in their operational performance and applicability to different cell and tissue models. Here we discuss and compare these probes with respect to their staining efficiency, brightness, photostability, toxicity, cell specificity, compatibility with different cell and tissue models, and analytical performance. Merits and limitations of particular probes are highlighted and strategies for development of new high-performance O2 imaging probes defined. Key application areas in hypoxia research, stem cells, cancer biology and tissue physiology are also discussed.

  10. Monte Carlo modeling of ultrasound probes for image guided radiotherapy

    SciTech Connect

    Bazalova-Carter, Magdalena; Schlosser, Jeffrey; Chen, Josephine; Hristov, Dimitre

    2015-10-15

    Purpose: To build Monte Carlo (MC) models of two ultrasound (US) probes and to quantify the effect of beam attenuation due to the US probes for radiation therapy delivered under real-time US image guidance. Methods: MC models of two Philips US probes, an X6-1 matrix-array transducer and a C5-2 curved-array transducer, were built based on their megavoltage (MV) CT images acquired in a Tomotherapy machine with a 3.5 MV beam in the EGSnrc, BEAMnrc, and DOSXYZnrc codes. Mass densities in the probes were assigned based on an electron density calibration phantom consisting of cylinders with mass densities between 0.2 and 8.0 g/cm{sup 3}. Beam attenuation due to the US probes in horizontal (for both probes) and vertical (for the X6-1 probe) orientation was measured in a solid water phantom for 6 and 15 MV (15 × 15) cm{sup 2} beams with a 2D ionization chamber array and radiographic films at 5 cm depth. The MC models of the US probes were validated by comparison of the measured dose distributions and dose distributions predicted by MC. Attenuation of depth dose in the (15 × 15) cm{sup 2} beams and small circular beams due to the presence of the probes was assessed by means of MC simulations. Results: The 3.5 MV CT number to mass density calibration curve was found to be linear with R{sup 2} > 0.99. The maximum mass densities in the X6-1 and C5-2 probes were found to be 4.8 and 5.2 g/cm{sup 3}, respectively. Dose profile differences between MC simulations and measurements of less than 3% for US probes in horizontal orientation were found, with the exception of the penumbra region. The largest 6% dose difference was observed in dose profiles of the X6-1 probe placed in vertical orientation, which was attributed to inadequate modeling of the probe cable. Gamma analysis of the simulated and measured doses showed that over 96% of measurement points passed the 3%/3 mm criteria for both probes placed in horizontal orientation and for the X6-1 probe in vertical orientation. The

  11. Atomic Resolution Imaging with a sub-50 pm Electron Probe

    SciTech Connect

    Erni, Rolf P.; Rossell, Marta D.; Kisielowski, Christian; Dahmen, Ulrich

    2009-03-02

    Using a highly coherent focused electron probe in a 5th order aberration-corrected transmission electron microscope, we report on resolving a crystal spacing less than 50 pm. Based on the geometrical source size and residual coherent and incoherent axial lens aberrations, an electron probe is calculated, which is theoretically capable of resolving an ideal 47 pm spacing with 29percent contrast. Our experimental data show the 47 pm spacing of a Ge 114 crystal imaged with 11-18percent contrast at a 60-95percent confidence level, providing the first direct evidence for sub 50-pm resolution in ADF STEM imaging.

  12. Free-radical probes for functional in vivo EPR imaging

    NASA Astrophysics Data System (ADS)

    Subramanian, S.; Krishna, M. C.

    2007-02-01

    Electron paramagnetic resonance imaging (EPRI) is one of the recent functional imaging modalities that can provide valuable in vivo physiological information on its own merit and aids as a complimentary imaging technique to MRI and PET of tissues especially with respect to in vivo pO II (oxygen partial pressure), redox status and pharmacology. EPR imaging mainly deals with the measurement of distribution and in vivo dynamics and redox changes using special nontoxic paramagnetic spin probes that can be infused into the object of investigation. These spin probes should be characterized by simple EPR spectra, preferably with narrow EPR lines. The line width should be reversibly sensitive to the concentration of in vivo pO II with a linear dependence. Several non-toxic paramagnetic probes, some particulate and insoluble and others water-soluble and infusible (by intravenous or intramuscular injection) have been developed which can be effectively used to quantitatively assess tissue redox status, and tumor hypoxia. Quantitative assessment of the redox status of tissue in vivo is important in investigating oxidative stress, and that of tissue pO II is very important in radiation oncology. Other areas in which EPR imaging and oxymetry may help are in the investigation of tumorangiogenesis, wound healing, oxygenation of tumor tissue by the ingestion of oxygen-rich gases, etc. The correct choice of the spin probe will depend on the modality of measurement (whether by CW or time-domain EPR imaging) and the particular physiology interrogated. Examples of the available spin probes and some EPR imaging applications employing them are presented.

  13. Dual-function fluorescent probe for cancer imaging and therapy.

    PubMed

    Cui, Hongjing; Wang, Ran; Zhou, Ying; Shu, Chang; Song, Fengjuan; Zhong, Wenying

    2016-05-01

    To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual-function quantum dot (QD) fluorescent probes with dual-targeting action and a therapeutic effect are rare. Here, a dual-targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin-glycyrrhetinic acid conjugate and arginine-glycine-aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as-prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26387677

  14. Radioactive smart probe for potential corrected matrix metalloproteinase imaging.

    PubMed

    Huang, Chiun-Wei; Li, Zibo; Conti, Peter S

    2012-11-21

    Although various activatable optical probes have been developed to visualize metalloproteinase (MMP) activities in vivo, precise quantification of the enzyme activity is limited due to the inherent scattering and attenuation (limited depth penetration) properties of optical imaging. In this investigation, a novel activatable peptide probe (64)Cu-BBQ650-PLGVR-K(Cy5.5)-E-K(DOTA)-OH was constructed to detect tumor MMP activity in vivo. This agent is optically quenched in its native form, but releases strong fluorescence upon cleavage by selected enzymes. MMP specificity was confirmed both in vitro and in vivo by fluorescent imaging studies. The use of a single modality to image biomarkers/processes may lead to erroneous interpretation of imaging data. The introduction of a quantitative imaging modality, such as PET, would make it feasible to correct the enzyme activity determined from optical imaging. In this proof of principle report, we demonstrated the feasibility of correcting the activatable optical imaging data through the PET signal. This approach provides an attractive new strategy for accurate imaging of MMP activity, which may also be applied for other protease imaging. PMID:23025637

  15. The Wide-Field Imager for Solar Probe Plus (WISPR)

    NASA Astrophysics Data System (ADS)

    Vourlidas, Angelos; Howard, Russell A.; Plunkett, Simon P.; Korendyke, Clarence M.; Thernisien, Arnaud F. R.; Wang, Dennis; Rich, Nathan; Carter, Michael T.; Chua, Damien H.; Socker, Dennis G.; Linton, Mark G.; Morrill, Jeff S.; Lynch, Sean; Thurn, Adam; Van Duyne, Peter; Hagood, Robert; Clifford, Greg; Grey, Phares J.; Velli, Marco; Liewer, Paulett C.; Hall, Jeffrey R.; DeJong, Eric M.; Mikic, Zoran; Rochus, Pierre; Mazy, Emanuel; Bothmer, Volker; Rodmann, Jens

    2015-02-01

    The Wide-field Imager for Solar PRobe Plus (WISPR) is the sole imager aboard the Solar Probe Plus (SPP) mission scheduled for launch in 2018. SPP will be a unique mission designed to orbit as close as 7 million km (9.86 solar radii) from Sun center. WISPR employs a 95∘ radial by 58∘ transverse field of view to image the fine-scale structure of the solar corona, derive the 3D structure of the large-scale corona, and determine whether a dust-free zone exists near the Sun. WISPR is the smallest heliospheric imager to date yet it comprises two nested wide-field telescopes with large-format (2 K × 2 K) APS CMOS detectors to optimize the performance for their respective fields of view and to minimize the risk of dust damage, which may be considerable close to the Sun. The WISPR electronics are very flexible allowing the collection of individual images at cadences up to 1 second at perihelion or the summing of multiple images to increase the signal-to-noise when the spacecraft is further from the Sun. The dependency of the Thomson scattering emission of the corona on the imaging geometry dictates that WISPR will be very sensitive to the emission from plasma close to the spacecraft in contrast to the situation for imaging from Earth orbit. WISPR will be the first `local' imager providing a crucial link between the large-scale corona and the in-situ measurements.

  16. Molecular imaging probes derived from natural peptides.

    PubMed

    Charron, C L; Hickey, J L; Nsiama, T K; Cruickshank, D R; Turnbull, W L; Luyt, L G

    2016-06-01

    Covering: up to the end of 2015.Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploited as diagnostic and therapeutic agents due to the unique target specificity for their endogenous receptors. This review discusses a variety of natural peptides highlighting their discovery, endogenous receptors, as well as their derivatization to create molecular imaging agents, with an emphasis on the design of radiolabelled peptides. This review also highlights methods for discovering new and novel peptides when knowledge of specific targets and endogenous ligands are not available. PMID:26911790

  17. Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems

    PubMed Central

    Lebedev, Artem Y.; Cheprakov, Andrei V.; Sakadžić, Sava; Boas, David A.; Wilson, David F.; Vinogradov, Sergei A.

    2009-01-01

    Oxygen levels in biological systems can be measured by the phosphorescence quenching method using probes with controllable quenching parameters and defined biodistributions. We describe a general approach to the construction of phosphorescent nanosensors with tunable spectral characteristics, variable degrees of quenching, and a high selectivity for oxygen. The probes are based on bright phosphorescent Pt and Pd complexes of porphyrins and symmetrically π-extended porphyrins (tetrabenzoporphyrins and tetranaphthoporphyrins). π-Extension of the core macrocycle allows tuning of the spectral parameters of the probes in order to meet the requirements of a particular imaging application (e.g., oxygen tomography versus planar microscopic imaging). Metalloporphyrins are encapsulated into poly(arylglycine) dendrimers, which fold in aqueous environments and create diffusion barriers for oxygen, making it possible to regulate the sensitivity and the dynamic range of the method. The periphery of the dendrimers is modified with poly(ethylene glycol) residues, which enhance the probe’s solubility, diminish toxicity, and help prevent interactions of the probes with the biological environment. The probe’s parameters were measured under physiological conditions and shown to be unaffected by the presence of biomacromolecules. The performance of the probes was demonstrated in applications, including in vivo microscopy of vascular pO2 in the rat brain. PMID:20072726

  18. Using image processing techniques on proximity probe signals in rotordynamics

    NASA Astrophysics Data System (ADS)

    Diamond, Dawie; Heyns, Stephan; Oberholster, Abrie

    2016-06-01

    This paper proposes a new approach to process proximity probe signals in rotordynamic applications. It is argued that the signal be interpreted as a one dimensional image. Existing image processing techniques can then be used to gain information about the object being measured. Some results from one application is presented. Rotor blade tip deflections can be calculated through localizing phase information in this one dimensional image. It is experimentally shown that the newly proposed method performs more accurately than standard techniques, especially where the sampling rate of the data acquisition system is inadequate by conventional standards.

  19. Chemiluminescent Probes for Imaging H2S in Living Animals†

    PubMed Central

    Cao, J.; Lopez, R.; Thacker, J.M.; Moon, J.Y.; Jiang, C.; Morris, S.N.S.; Bauer, J.H.; Tao, P.; Mason, R.P.

    2015-01-01

    Hydrogen sulphide (H2S) is an endogenous mediator of human health and disease, but precise measurement in living cells and animals remains a considerable challenge. We report the total chemical synthesis and characterization of three 1,2-dioxetane chemiluminescent reaction-based H2S probes, CHS-1, CHS-2, and CHS-3. Upon treatment with H2S at physiological pH, these probes display instantaneous light emission that is sustained for over an hour with high selectivity against other reactive sulphur, oxygen, and nitrogen species. Analysis of the phenol/phenolate equilibrium and atomic charges has provided a generally applicable predictive model to design improved chemiluminescent probes. The utility of these chemiluminescent reagents was demonstrated by applying CHS-3 to detect cellularly generated H2S using a multi-well plate reader and to image H2S in living mice using CCD camera technology. PMID:25709805

  20. Ultraviolet Imaging Probe for the Pan-STARRS-1 Telescope

    NASA Astrophysics Data System (ADS)

    Hodapp, K.; Chambers, K.

    This paper describes the scientific rationale, the design, and the expected data products of the u-band Imaging Probe (UIP) for Pan-STARRS. The Pan-STARRS photometric survey itself will be conducted in the g, r, i, z, and y bands and cover the 3/4 of the sky accessible from Haleakala. In parallel to the survey conducted with the PS1 1.8m telescope, an Imaging Sky Probe (ISP, Granett et. al., these proceedings) will monitor the sky conditions, variations in transparency across the 3° field of view, provide a characterization of the astronomical diffuse sky brightness, and extend the dynamic range of PS1 stellar photometry to the brightest stars. The u-band Imaging Probe is an additional small wide-field camera to extend this bright star photometric survey to the shortest wavelengths accessible from ground-based observatories. It will thereby establish a well characterized photometric system at these wavelengths with a dense sample of stars covering 3/4 of the entire sky, including the galactic plane. The UIP will continuously make dedicated u-band measurements, and the large number of these independent measurements together with substantial overlapping fields of view and repeated visits to standard star fields as part of the PS1 mission, has the potential of substantially improving u-band calibration and photometry across the sky over all previous u-band imaging and catalog surveys. For specific future observations with larger telescopes, this system of stars will serve as secondary calibration stars to tie these deeper observations into the photometric system established in this way. The UIP is currently in the early design stages. The UIP will be operated as an extension of the PS1 Imaging Sky Probe (ISP), and the data will be processed through the same data reduction pipeline and be made available as part of the photometric survey.

  1. Integrated ultrasound and gamma imaging probe for medical diagnosis

    NASA Astrophysics Data System (ADS)

    Pani, R.; Pellegrini, R.; Cinti, M. N.; Polito, C.; Orlandi, C.; Fabbri, A.; De Vincentis, G.

    2016-03-01

    In the last few years, integrated multi-modality systems have been developed, aimed at improving the accuracy of medical diagnosis correlating information from different imaging techniques. In this contest, a novel dual modality probe is proposed, based on an ultrasound detector integrated with a small field of view single photon emission gamma camera. The probe, dedicated to visualize small organs or tissues located at short depths, performs dual modality images and permits to correlate morphological and functional information. The small field of view gamma camera consists of a continuous NaI:Tl scintillation crystal coupled with two multi-anode photomultiplier tubes. Both detectors were characterized in terms of position linearity and spatial resolution performances in order to guarantee the spatial correspondence between the ultrasound and the gamma images. Finally, dual-modality images of custom phantoms are obtained highlighting the good co-registration between ultrasound and gamma images, in terms of geometry and image processing, as a consequence of calibration procedures.

  2. Characterization of a Fluorescent Probe for Imaging Nitric Oxide

    PubMed Central

    Ghebremariam, Yohannes T; Huang, Ngan F; Kambhampati, Swetha; Volz, Katharina S; Joshi, Gururaj G; Anslyn, Eric V; Cooke, John P

    2014-01-01

    Background Nitric Oxide (NO), a potent vasodilator and anti-atherogenic molecule, is synthesized in various cell types including vascular endothelial cells (ECs). The biological importance of NO enforces the need to develop and characterize specific and sensitive probes. To date, several fluorophores, chromophores and colorimetric techniques have been developed to detect NO or its metabolites (NO2 and NO3) in biological fluids, viable cells or cell lysates. Methods Recently, a novel probe (NO550) has been developed and reported to detect NO in solution and in primary astrocytes and neuronal cells with a fluorescence signal arising from a non-fluorescent background. Results Here, we report further characterization of this probe by optimizing conditions for the detection and imaging of NO products in primary vascular endothelial cells, fibroblasts, embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)- derived endothelial cells (ESC-ECs. and iPSC-ECs respectively) in the absence and presence of pharmacological agents that modulate NO levels. In addition, we studied the stability of this probe in cells over time and evaluated its compartmentalization in reference to organelle-labeling dyes. Finally, we synthesized an inherently fluorescent diazo ring compound (AZO550) that is expected to form when the non-fluorescent NO550 reacts with cellular NO and compared its cellular distribution with that of NO550. Conclusion NO550 is a promising agent for imaging NO at baseline and in response to pharmacological agents that modulate its levels. PMID:24335468

  3. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    NASA Astrophysics Data System (ADS)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  4. Low-Temperature Scanning Capacitance Probe for Imaging Electron Motion

    NASA Astrophysics Data System (ADS)

    Bhandari, S.; Westervelt, R. M.

    2014-12-01

    Novel techniques to probe electronic properties at the nanoscale can shed light on the physics of nanoscale devices. In particular, studying the scattering of electrons from edges and apertures at the nanoscale and imaging the electron profile in a quantum dot, have been of interest [1]. In this paper, we present the design and implementation of a cooled scanning capacitance probe that operates at liquid He temperatures to image electron waves in nanodevices. The conducting tip of a scanned probe microscope is held above the nanoscale structure, and an applied sample-to-tip voltage creates an image charge that is measured by a cooled charge amplifier [2] adjacent to the tip. The circuit is based on a low-capacitance, high- electron-mobility transistor (Fujitsu FHX35X). The input is a capacitance bridge formed by a low capacitance pinched-off HEMT transistor and tip-sample capacitance. We have achieved low noise level (0.13 e/VHz) and high spatial resolution (100 nm) for this technique, which promises to be a useful tool to study electronic behavior in nanoscale devices.

  5. Imaging energy landscapes with concentrated diffusing colloidal probes

    NASA Astrophysics Data System (ADS)

    Bahukudumbi, Pradipkumar; Bevan, Michael A.

    2007-06-01

    The ability to locally interrogate interactions between particles and energetically patterned surfaces provides essential information to design, control, and optimize template directed self-assembly processes. Although numerous techniques are capable of characterizing local physicochemical surface properties, no current method resolves interactions between colloids and patterned surfaces on the order of the thermal energy kT, which is the inherent energy scale of equilibrium self-assembly processes. Here, the authors describe video microscopy measurements and an inverse Monte Carlo analysis of diffusing colloidal probes as a means to image three dimensional free energy and potential energy landscapes due to physically patterned surfaces. In addition, they also develop a consistent analysis of self-diffusion in inhomogeneous fluids of concentrated diffusing probes on energy landscapes, which is important to the temporal imaging process and to self-assembly kinetics. Extension of the concepts developed in this work suggests a general strategy to image multidimensional and multiscale physical, chemical, and biological surfaces using a variety of diffusing probes (i.e., molecules, macromolecules, nanoparticles, and colloids).

  6. Photoacoustic imaging of fluorophores using pump-probe excitation

    PubMed Central

    Märk, Julia; Schmitt, Franz-Josef; Theiss, Christoph; Dortay, Hakan; Friedrich, Thomas; Laufer, Jan

    2015-01-01

    A pump-probe technique for the detection of fluorophores in tomographic PA images is introduced. It is based on inducing stimulated emission in fluorescent molecules, which in turn modulates the amount of thermalized energy, and hence the PA signal amplitude. A theoretical model of the PA signal generation in fluorophores is presented and experimentally validated on cuvette measurements made in solutions of Rhodamine 6G, a fluorophore of known optical and molecular properties. The application of this technique to deep tissue tomographic PA imaging is demonstrated by determining the spatial distribution of a near-infrared fluorophore in a tissue phantom. PMID:26203378

  7. Imaging targeted-agent binding in vivo with two probes

    NASA Astrophysics Data System (ADS)

    Pogue, Brian W.; Samkoe, Kimberley S.; Hextrum, Shannon; O'Hara, Julia A.; Jermyn, Michael; Srinivasan, Subhadra; Hasan, Tayyaba

    2010-05-01

    An approach to quantitatively image targeted-agent binding rate in vivo is demonstrated with dual-probe injection of both targeted and nontargeted fluorescent dyes. Images of a binding rate constant are created that reveal lower than expected uptake of epidermal growth factor in an orthotopic xenograft pancreas tumor (2.3×10-5 s-1), as compared to the normal pancreas (3.4×10-5 s-1). This approach allows noninvasive assessment of tumor receptor targeting in vivo to determine the expected contrast, spatial localization, and efficacy in therapeutic agent delivery.

  8. Integrated transrectal probe for translational ultrasound-photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Bell, Kevan L.; Harrison, Tyler; Usmani, Nawaid; Zemp, Roger J.

    2016-03-01

    A compact photoacoustic transrectal probe is constructed for improved imaging in brachytherapy treatment. A 192 element 5 MHz linear transducer array is mounted inside a small 3D printed casing along with an array of optical fibers. The device is fed by a pump laser and tunable NIR-optical parametric oscillator with data collected by a Verasonics ultrasound platform. This assembly demonstrates improved imaging of brachytherapy seeds in phantoms with depths up to 5 cm. The tuneable excitation in combination with standard US integration provides adjustable contrast between the brachytherapy seeds, blood filled tubes and background tissue.

  9. In vivo imaging of light-emitting probes

    NASA Astrophysics Data System (ADS)

    Rice, Bradley W.; Cable, Michael D.; Nelson, Michael B.

    2001-10-01

    In vivo imaging of cells tagged with light-emitting probes, such as firefly luciferase or fluorescent proteins, is a powerful technology that enables a wide range of biological studies in small research animals. Reporters with emission in the red to infrared (> 600 nm) are preferred due to the low absorption in tissue at these wavelengths. Modeling of photon diffusion through tissue indicates that bioluminescent cell counts as low as a few hundred can be detected subcutaneously, while approximately106 cells are required to detect signals at approximately 2 cm depth in tissue. Signal-to- noise estimates show that cooled back-thinned integrating charge coupled devices (CCDs) are preferred to image-intensified CCDs for this application, mainly due to their high quantum efficiency (approximately 85%) at wavelengths > 600 nm where tissue absorption is low. Instrumentation for in vivo imaging developed at Xenogen is described and several examples of images of mice with bioluminescent cells are presented.

  10. Probes for intracellular RNA imaging in live cells.

    PubMed

    Santangelo, Philip J; Alonas, Eric; Jung, Jeenah; Lifland, Aaron W; Zurla, Chiara

    2012-01-01

    RNA localization, dynamics, and regulation are becoming increasingly important to our basic understanding of gene expression and RNA virus pathogenesis. An improved understanding of these processes will be necessary in order to identify new drug targets, as well as to create models of gene expression networks. Much of this new understanding will likely come from imaging studies of RNA, which can generate the spatiotemporal information necessary to characterize RNA within the cellular milieu. Ideally, this would be performed imaging native, nonengineered RNAs, but the approaches for performing these experiments are still evolving. In order for them to reach their potential, it is critical that they have characteristics that allow for the tracking of RNA throughout their life cycle. This chapter presents an overview of RNA imaging methodologies, and focuses on a single RNA sensitive method, employing exogenous probes, for imaging, native, nonengineered RNA in live cells. PMID:22289464

  11. KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Erben, Philipp; Stroebel, Philipp; Horisberger, Karoline; Popa, Juliana; Bohn, Beatrice; Hanfstein, Benjamin; Kaehler, Georg; Kienle, Peter; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2011-11-15

    Purpose: Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. Methods and Materials: We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. Results: A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. Conclusions: In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

  12. Molecular probes for nonlinear optical imaging of biological membranes

    NASA Astrophysics Data System (ADS)

    Blanchard-Desce, Mireille H.; Ventelon, Lionel; Charier, Sandrine; Moreaux, Laurent; Mertz, Jerome

    2001-12-01

    Second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) are nonlinear optical (NLO) phenomena that scale with excitation intensity squared, and hence give rise to an intrinsic 3-dimensional resolution when used in microscopic imaging. TPEF microscopy has gained widespread popularity in the biology community whereas SHG microscopy promises to be a powerful tool because of its sensitivity to local asymmetry. We have implemented an approach toward the design of NLO-probes specifically adapted for SHG and/or TPEF imaging of biological membranes. Our strategy is based on the design of nanoscale amphiphilic NLO-phores. We have prepared symmetrical bolaamphiphilic fluorophores combining very high two-photon absorption (TPA) cross-sections in the visible red region and affinity for cellular membranes. Their incorporation and orientation in lipid membranes can be monitored via TPEF anisotropy. We have also prepared amphiphilic push-pull chromophores exhibiting both large TPA cross-sections and very large first hyperpolarizabilities in the near-IR region. These NLO-probes have proved to be particularly useful for imaging of biological membranes by simultaneous SHG and TPEF microscopy and offer attractive prospects for real-time imaging of fundamental biological processes such as adhesion, fusion or reporting of membrane potentials.

  13. Photonic Doppler velocimetry lens array probe incorporating stereo imaging

    DOEpatents

    Malone, Robert M.; Kaufman, Morris I.

    2015-09-01

    A probe including a multiple lens array is disclosed to measure velocity distribution of a moving surface along many lines of sight. Laser light, directed to the moving surface is reflected back from the surface and is Doppler shifted, collected into the array, and then directed to detection equipment through optic fibers. The received light is mixed with reference laser light and using photonic Doppler velocimetry, a continuous time record of the surface movement is obtained. An array of single-mode optical fibers provides an optic signal to the multiple lens array. Numerous fibers in a fiber array project numerous rays to establish many measurement points at numerous different locations. One or more lens groups may be replaced with imaging lenses so a stereo image of the moving surface can be recorded. Imaging a portion of the surface during initial travel can determine whether the surface is breaking up.

  14. Band Excitation in Scanning Probe Microscopy: Recognition and Functional Imaging

    SciTech Connect

    Jesse, Stephen; Vasudevan, Dr. Rama; Collins, Liam; Strelcov, Evgheni; Okatan, Mahmut B; Belianinov, Alex; Baddorf, Arthur P; Proksch, Roger; Kalinin, Sergei V

    2014-01-01

    Field confinement at the junction between a biased scanning probe microscope s (SPM) tip and solid surface enables local probing of various bias-induced transformations such as polarization switching, ionic motion, or electrochemical reactions to name a few. The nanoscale size of the biased region is smaller or comparable to features like grain boundaries and dislocations, potentially allows for the study of kinetics and thermodynamics at the level of a single defect. In contrast to classical statistically averaged approaches, this allows one to link structure to functionality and deterministically decipher associated mesoscopic and atomistic mechanisms. Furthermore, this type of information can serve as a fingerprint of local material functionality, allowing for local recognition imaging. Here, current progress in multidimensional SPM techniques based on band-excitation time and voltage spectroscopies is illustrated, including discussions on data acquisition, dimensionality reduction, and visualization along with future challenges and opportunities for the field.

  15. Fluorescent carbonaceous nanospheres as biological probe for noninvasive brain imaging.

    PubMed

    Qian, Jun; Ruan, Shaobo; Cao, Xi; Cun, Xingli; Chen, Jiantao; Shen, Shun; Jiang, Xinguo; He, Qin; Zhu, Jianhua; Gao, Huile

    2014-12-15

    Fluorescent carbonaceous nanospheres (CDs) have generated much excitement in bioimaging because of their impressive fluorescent properties and good biocompatibility. In this study, we evaluated the potential application of CDs in noninvasive brain imaging. A new kind of CDs was prepared by a heat treating method using glutamic acid and glucose as the precursors. The hydrated diameter and zeta potential of CDs were 101.1 nm (PDI=0.110) and -22.4 mV respectively. Palpable emission spectrum could be observed from 400 nm to 600 nm when excited at corresponding wavelength, suggesting CDs could be used as a noninvasive bio-probe for in vivo imaging. Additionally, several experiments indicated that CDs possess good serum stability and hemocompatibility with low cytotoxicity. In vitro, the CDs could be efficiently taken up by bEnd.3 cells in a concentration- and time-dependent manner. In vivo, CDs could be used for noninvasive brain imaging due to its high accumulation in brain region, which was demonstrated by in vivo imaging and ex vivo tissue imaging. Moreover, the fluorescent distribution in tissue slice showed CDs accumulated in brain with high intensity. In conclusion, CDs were prepared using a simple one-step method with unique optical and good biological properties and could be used for noninvasive brain imaging. PMID:25278360

  16. Near-infrared dyes for molecular probes and imaging

    NASA Astrophysics Data System (ADS)

    Patonay, Gabor; Beckford, Garfield; Strekowski, Lucjan; Henary, Maged; Kim, Jun Seok; Crow, Sidney

    2009-02-01

    Near-Infrared (NIR) fluorescence has been used both as an analytical tool as molecular probes and in in vitro or in vivo imaging of individual cells and organs. The NIR region (700-1100 nm) is ideal with regard to these applications due to the inherently lower background interference and the high molar absorptivities of NIR chromophores. NIR dyes are also useful in studying binding characteristics of large biomolecules, such as proteins. Throughout these studies, different NIR dyes have been evaluated to determine factors that control binding to biomolecules, including serum albumins. Hydrophobic character of NIR dyes were increased by introducing alkyl and aryl groups, and hydrophilic moieties e.g., polyethylene glycols (PEG) were used to increase aqueous solubility. Recently, our research group introduced bis-cyanines as innovative NIR probes. Depending on their microenvironment, bis-cyanines can exist as an intramolecular dimer with the two cyanines either in a stacked form, or in a linear conformation in which the two subunits do not interact with each other. In this intramolecular H-aggregate, the chromophore has a low extinction coefficient and low fluorescence quantum yield. Upon addition of biomolecules, the H-and D- bands are decreased and the monomeric band is increased, with concomitant increase in fluorescence intensity. Introduction of specific moieties into the NIR dye molecules allows for the development of physiological molecular probes to detect pH, metal ions and other parameters. Examples of these applications include imaging and biomolecule characterizations. Water soluble dyes are expected to be excellent candidates for both in vitro and in vivo imaging of cells and organs.

  17. Nondestructive millimeter wave imaging and spectroscopy using dielectric focusing probes

    NASA Astrophysics Data System (ADS)

    Hejase, Jose A.; Shane, Steven S.; Park, Kyoung Y.; Chahal, Premjeet

    2014-02-01

    A tool for interrogating objects over a wide band of frequencies with subwavelength resolution at small standoff distances (near field region) in the transmission mode using a single source and detector measurement setup in the millimeter wave band is presented. The design utilizes optics like principles for guiding electromagnetic millimeter waves from large cross-sectional areas to considerably smaller sub-wavelength areas. While plano-convex lenses can be used to focus waves to a fine resolution, they usually require a large stand-off distance thus resulting in alignment and spacing issues. The design procedure and simulation analysis of the focusing probes are presented in this study along with experimental verification of performance and imaging and spectroscopy examples. Nondestructive evaluation will find benefit from such an apparatus including biological tissue imaging, electronic package integrity testing, composite dielectric structure evaluation for defects and microfluidic sensing.

  18. Nondestructive millimeter wave imaging and spectroscopy using dielectric focusing probes

    SciTech Connect

    Hejase, Jose A.; Shane, Steven S.; Park, Kyoung Y.; Chahal, Premjeet

    2014-02-18

    A tool for interrogating objects over a wide band of frequencies with subwavelength resolution at small standoff distances (near field region) in the transmission mode using a single source and detector measurement setup in the millimeter wave band is presented. The design utilizes optics like principles for guiding electromagnetic millimeter waves from large cross-sectional areas to considerably smaller sub-wavelength areas. While plano-convex lenses can be used to focus waves to a fine resolution, they usually require a large stand-off distance thus resulting in alignment and spacing issues. The design procedure and simulation analysis of the focusing probes are presented in this study along with experimental verification of performance and imaging and spectroscopy examples. Nondestructive evaluation will find benefit from such an apparatus including biological tissue imaging, electronic package integrity testing, composite dielectric structure evaluation for defects and microfluidic sensing.

  19. Artist: Ken Hodges Composite image explaining Objective and Motivation for Galileo Probe Heat Loads:

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Artist: Ken Hodges Composite image explaining Objective and Motivation for Galileo Probe Heat Loads: Galileo Probe descending into Jupiters Atmosphere shows heat shield separation with parachute deployed. (Ref. JPL P-19180)

  20. Model Mismatch Paradigm for Probe based Nanoscale Imaging

    NASA Astrophysics Data System (ADS)

    Agarwal, Pranav

    Scanning Probe Microscopes (SPMs) are widely used for investigation of material properties and manipulation of matter at the nanoscale. These instruments are considered critical enablers of nanotechnology by providing the only technique for direct observation of dynamics at the nanoscale and affecting it with sub Angstrom resolution. Current SPMs are limited by low throughput and lack of quantitative measurements of material properties. Various applications like the high density data storage, sub-20 nm lithography, fault detection and functional probing of semiconductor circuits, direct observation of dynamical processes involved in biological samples viz. motor proteins and transport phenomena in various materials demand high throughput operation. Researchers involved in material characterization at nanoscale are interested in getting quantitative measurements of stiffness and dissipative properties of various materials in a least invasive manner. In this thesis, system theoretic concepts are used to address these limitations. The central tenet of the thesis is to model, the known information about the system and then focus on perturbations of these known dynamics or model, to sense the effects due to changes in the environment such as changes in material properties or surface topography. Thus a model mismatch paradigm for probe based nanoscale imaging is developed. The topic is developed by presenting physics based modeling of a particular mode of operation of SPMs called the dynamic mode operation. This mode is modeled as a forced Lure system where a linear time invariant system is in feedback with an unknown static memoryless nonlinearity. Tools from averaging theory are used to tame this complex nonlinear system by approximating it as a linear system with time varying parameters. Material properties are thus transformed from being parameters of unknown nonlinear functions to being unknown coefficients of a linear plant. The first contribution of this thesis

  1. Microfluidics for Positron Emission Tomography (PET) Imaging Probe Development

    PubMed Central

    Wang, Ming-Wei; Lin, Wei-Yu; Liu, Kan; Masterman-Smith, Michael; Shen, Clifton Kwang-Fu

    2012-01-01

    Due to increased needs for Positron Emission Tomography (PET) scanning, high demands for a wide variety of radiolabeled compounds will have to be met by exploiting novel radiochemistry and engineering technologies to improve the production and development of PET probes. The application of microfluidic reactors to perform radiosyntheses is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional labeling systems. Microfluidic-based radiochemistry can lead to the use of smaller quantities of precursors, accelerated reaction rates and easier purification processes with greater yield and higher specific activity of desired probes. Several ‘proof-of-principle’ examples, along with basics of device architecture and operation, and potential limitations of each design are discussed here. Along with the concept of radioisotope distribution from centralized cyclotron facilities to individual imaging centers and laboratories (“decentralized model”), an easy-to-use, standalone, flexible, fully-automated radiochemical microfluidic platform can open up to simpler and more cost-effective procedures for molecular imaging using PET. PMID:20643021

  2. Imaging and force probing RNA by atomic force microscopy.

    PubMed

    Schön, Peter

    2016-07-01

    In the past 30years, the atomic force microscope (AFM) has become a true enabling platform in the life sciences opening entire novel avenues for structural and dynamic studies of biological systems. It enables visualization, probing and manipulation across the length scales, from single molecules to living cells in buffer solution under physiological conditions without the need for labeling or staining of the specimen. In particular, for structural studies of nucleic acids and assemblies thereof, the AFM has matured into a routinely used tool providing nanometer spatial resolution. This includes ssRNA, dsRNA and nucleoprotein complexes thereof, as well as RNA aggregates and 2D RNA assemblies. By AFM unique information can be obtained on RNA based assemblies which are becoming increasingly important as novel unique building blocks in the emerging field of RNA nanotechnology. In addition, the AFM is of fundamental relevance to study biological relevant RNA interactions and dynamics. In this short review first the basic functioning principles of commonly used AFM modes including AFM based force spectroscopy will be briefly described. Next a brief overview will be given on structural studies that have been done related to AFM topographic imaging of RNA, RNA assemblies and aggregates. Finally, an overview on AFM beyond imaging will be provided. This includes force spectroscopy of RNA under physiological conditions in aqueous buffer to probe RNA interaction with proteins and ligands as well as other AFM tip based RNA probing. The main intention of this short review to give the reader a flavor of what AFM contributes to RNA research and engineering. PMID:27222101

  3. Evaluation of improvement of diffuse optical imaging of brain function by high-density probe arrangements and imaging algorithms

    NASA Astrophysics Data System (ADS)

    Sakakibara, Yusuke; Kurihara, Kazuki; Okada, Eiji

    2016-04-01

    Diffuse optical imaging has been applied to measure the localized hemodynamic responses to brain activation. One of the serious problems with diffuse optical imaging is the limitation of the spatial resolution caused by the sparse probe arrangement and broadened spatial sensitivity profile for each probe pair. High-density probe arrangements and an image reconstruction algorithm considering the broadening of the spatial sensitivity can improve the spatial resolution of the image. In this study, the diffuse optical imaging of the absorption change in the brain is simulated to evaluate the effect of the high-density probe arrangements and imaging methods. The localization error, equivalent full-width half maximum and circularity of the absorption change in the image obtained by the mapping and reconstruction methods from the data measured by five probe arrangements are compared to quantitatively evaluate the imaging methods and probe arrangements. The simple mapping method is sufficient for the density of the measurement points up to the double-density probe arrangement. The image reconstruction method considering the broadening of the spatial sensitivity of the probe pairs can effectively improve the spatial resolution of the image obtained from the probe arrangements higher than the quadruple density, in which the distance between the neighboring measurement points is 10.6 mm.

  4. 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

  5. X-ray diffraction topography image materials by molecular probe

    NASA Astrophysics Data System (ADS)

    Hentschel, Manfred P.; Lange, Axel; Schors, Joerg; Wald, Oliver

    2005-05-01

    Crystallinity, composition, homogeneity and anisotropy determine the mechanical properties of materials significantly, but the performance of most non-destructive techniques is too poor for measuring these micro structures as they are optimized for finding individual flaws/defects. X-ray (wide angle) Diffraction Topography by single beam scanning images molecular information at a spatial resolution of several ten micrometers even in three dimensions. Especially for the non-destructive characterization of composite materials, they provide additional capabilities by crystallographic contrast by the molecular/atomic probe. The different material phases of compounds and their molecular orientation can be imaged e.g. fibers or polymer chain orientation in composites: A sample is scanned or rotated, while only part of the scattering pattern is pointing at an X-ray detector area. Three different methods have been developed: i) planar X-ray Scanning Topography at one or more pre-selected scattering angles provides high contrast of different phases of components. ii) X-Ray Rotation Topography reveals the texture angle of composite fibers and chain polymers. iii) X-ray Diffraction Microscopy images the texture and phase distribution of transversal sections of the material. The principles of Wide Angle X-Ray Diffraction Topography are explained and examples of investigations will be presented. They combine the advantages of radiographic imaging and crystal structure information. The applied X-ray energies are much lower than in NDT radiography, which recommends preferably the application to light weight materials.

  6. Efficacy of cetuximab-based chemotherapy in metastatic colorectal cancer according to RAS and BRAF mutation subgroups: A meta-analysis

    PubMed Central

    LIN, LI; CHEN, LU-LU; WANG, YOU; MENG, XIANG-YU; LIANG, CHEN; ZHOU, FU-XIANG

    2016-01-01

    The epidermal growth factor receptor (EGFR)-targeting monoclonal antibody, cetuximab, has been added to standard chemotherapy regimens for treating metastatic colorectal cancer (mCRC). However, the efficacy of adding cetuximab to chemotherapy regimens for patients of differing genetic backgrounds remains controversial. The present study aimed to investigate the efficacy of adding cetuximab to chemotherapeutic regimens in subgroups of patients defined according to the RAS and BRAF mutation status in the first-line treatment of patients with mCRC. A systematic literature search was performed in databases (including PubMed, Embase, the Cochrane library, the American Society of Clinical Oncology and the European Society For Medical Oncology) up to August 2015. Randomized controlled trials analyzing overall survival (OS) and progression-free survival (PFS) in mCRC treated with cetuximab, and grouped by RAS and BRAF mutation status, were identified. The major outcome measures were hazard ratios (HRs). Pooled HRs were calculated using fixed- or random-effects models, according to the magnitude of the heterogeneity. A total of nine studies met the inclusion criteria. Use of cetuximab was significantly associated with longer OS in KRAS exon 2 wild-type tumors [HR=0.87, 95% confidence interval (CI)=0.79–0.96, Z=2.91, P=0.004] and wild-type KRAS/RAS (in exons 2, 3 and 4 of KRAS and exons 2, 3 and 4 of an associated gene, NRAS; HR=0.72, 95% CI=0.60–0.85, Z=3.74, P=0.0002). No significant differences in OS and PFS were identified between KRAS exon 2 mutations and tumors with the other RAS mutations (in exons 3 and 4 of KRAS and exons 2, 3 and 4 of an associated gene, NRAS). The meta-analysis demonstrated that cetuximab-based chemotherapeutic regimens led to a marked improvement in OS in patients with mCRC who lacked any RAS mutations (either KRAS exon 2 or any other RAS mutation). By contrast, the subgroup analyses revealed no evident PFS or OS benefit in using cetuximab

  7. Positrons as imaging agents and probes in nanotechnology

    NASA Astrophysics Data System (ADS)

    Smith, Suzanne V.

    2009-09-01

    Positron emission tomography (PET) tracks a positron emitting radiopharmaceutical injected into the body and generates a 3-dimensional image of its location. Introduced in the early 70s, it has now developed into a powerful medical diagnostic tool for routine clinical use as well as in drug development. Unrivalled as a highly sensitive, specific and non-invasive imaging tool, PET unfortunately lacks the resolution of Computer Tomography (CT) and Magnetic Resonance Imaging (MRI). As the resolution of PET depends significantly on the energy of the positron incorporated in the radiopharmaceutical and its interaction with its surrounding tissue, there is growing interest in expanding our understanding of how positrons interact at the atomic and molecular level. A better understanding of these interactions will contribute to improving the resolution of PET and assist in the design of better imaging agents. Positrons are also used in Positron Annihilation Lifetime Spectroscopy (PALS) to determine electron density and or presence and incidence of micro- and mesopores (0.1 to 10 nm) in materials. The control of porosity in engineered materials is crucial for applications such as controlled release or air and water resistant films. Equally important to the design of nano and microtechnologies, is our understanding of the microenvironments within these pores and on surfaces. Hence as radiopharmaceuticals are designed to track disease, nuclear probes (radioactive molecules) are synthesized to investigate the chemical properties within these pores. This article will give a brief overview of the present role of positrons in imaging as well as explore its potential to contribute in the engineering of new materials to the marketplace.

  8. Red Fluorescent Carbon Nanoparticle-Based Cell Imaging Probe.

    PubMed

    Ali, Haydar; Bhunia, Susanta Kumar; Dalal, Chumki; Jana, Nikhil R

    2016-04-13

    Fluorescent carbon nanoparticle-based probes with tunable visible emission are biocompatible, environment friendly and most suitable for various biomedical applications. However, synthesis of red fluorescent carbon nanoparticles and their transformation into functional nanoparticles are very challenging. Here we report red fluorescent carbon nanoparticle-based nanobioconjugates of <25 nm hydrodynamic size and their application as fluorescent cell labels. Hydrophobic carbon nanoparticles are synthesized via high temperature colloid-chemical approach and transformed into water-soluble functional nanoparticles via coating with amphiphilic polymer followed by covalent linking with desired biomolecules. Following this approach, carbon nanoparticles are functionalized with polyethylene glycol, primary amine, glucose, arginine, histidine, biotin and folic acid. These functional nanoparticles can be excited with blue/green light (i.e., 400-550 nm) to capture their emission spanning from 550 to 750 nm. Arginine and folic acid functionalized nanoparticles have been demonstrated as fluorescent cell labels where blue and green excitation has been used for imaging of labeled cells. The presented method can be extended for the development of carbon nanoparticle-based other bioimaging probes. PMID:27011336

  9. Nanotechnology in medical imaging: probe design and applications

    PubMed Central

    Cormode, David P.; Skajaa, Torjus; Fayad, Zahi A.; Mulder, Willem J. M.

    2010-01-01

    Nanoparticles have become more and more prevalent in reports of novel contrast agents, especially for molecular imaging, the detection of cellular processes. The advantages of nanoparticles include their potency to generate contrast, the ease of integrating multiple properties, lengthy circulation times and the possibility to include high payloads. As the chemistry of nanoparticles has improved over the past years more sophisticated examples of nano-sized contrast agents have been reported, such as paramagnetic, macrophage targeted quantum dots or αvβ3-targeted, MRI visible microemulsions that also carry a drug to suppress angiogenesis. The use of these particles is producing greater knowledge of disease processes and the effects of therapy. Along with their excellent properties, nanoparticles may produce significant toxicity, which must be minimized for (clinical) application. In this review we discuss the different factors that are considered when designing a nanoparticle probe and highlight some of the most advanced examples. PMID:19057023

  10. Miniature forward-viewing common-path OCT probe for imaging the renal pelvis

    PubMed Central

    Fu, Xiaoyong; Patel, Dhruti; Zhu, Hui; MacLennan, Gregory; Wang, Yves T; Jenkins, Michael W; Rollins, Andrew M

    2015-01-01

    We demonstrate an ultrathin flexible cone-scanning forward-viewing OCT probe which can fit through the working channel of a flexible ureteroscope for renal pelvis imaging. The probe is fabricated by splicing a 200 µm section of core-less fiber and a 150 µm section of gradient-index (GRIN) fiber to the end of a single mode (SM) fiber. The probe is designed for common-path OCT imaging where the back-reflection of the GRIN fiber/air interface is used as the reference signal. Optimum sensitivity was achieved with a 2 degree polished probe tip. A correlation algorithm was used to correct image distortion caused by non-uniform rotation of the probe. The probe is demonstrated by imaging human skin in vivo and porcine renal pelvis ex vivo and is suitable for imaging the renal pelvis in vivo for cancer staging. PMID:25909002

  11. Imaging and manipulation of nanoscale materials with coaxial and triaxial AFM probes

    NASA Astrophysics Data System (ADS)

    Brown, Keith A.; Westervelt, R. M.

    2011-03-01

    We present coaxial and triaxial Atomic Force Microscope (AFM) probes and demonstrate their applications to imaging and manipulating nanoscale materials. A coaxial probe with concentric electrodes at its tip creates a highly confined electric field that decays as a dipole field, making the coaxial probe useful for near field imaging of electrical properties. We show nearly an order of magnitude improvement in the step resolution of Kelvin probe force microscopy with coaxial probes. We further demonstrate that coaxial probes can image dielectric materials with the dielectrophoretic force. In addition to imaging, the capacitive structure that makes up the cantilever of a coaxial probe is used to locally mechanically drive the probe, making them self-driving probes. Finally, coaxial probes can create strong forces with dielectrophoresis (DEP) which we combine with the nanometer precision of the AFM to create a nanometer scale pick-and-place tool. We demonstrate 3D assembly of micrometer scale objects with coaxial probes using positive DEP and discuss the assembly of nanometer scale objects with triaxial probes using negative DEP.

  12. Atomic Force Microscope Controlled Topographical Imaging and Proximal Probe Thermal Desorption/Ionization Mass Spectrometry Imaging

    SciTech Connect

    Ovchinnikova, Olga S; Kjoller, Kevin; Hurst, Gregory {Greg} B; Pelletier, Dale A; Van Berkel, Gary J

    2014-01-01

    This paper reports on the development of a hybrid atmospheric pressure atomic force microscopy/mass spectrometry imaging system utilizing nano-thermal analysis probes for thermal desorption surface sampling with subsequent atmospheric pressure chemical ionization and mass analysis. The basic instrumental setup and the general operation of the system were discussed and optimized performance metrics were presented. The ability to correlate topographic images of a surface with atomic force microscopy and a mass spectral chemical image of the same surface, utilizing the same probe without moving the sample from the system, was demonstrated. Co-registered mass spectral chemical images and atomic force microscopy topographical images were obtained from inked patterns on paper as well as from a living bacterial colony on an agar gel. Spatial resolution of the topography images based on pixel size (0.2 m x 0.8 m) was better than the resolution of the mass spectral images (2.5 m x 2.0 m), which were limited by current mass spectral data acquisition rate and system detection levels.

  13. A Dream of a Mission: Stellar Imager and Seismic Probe

    NASA Technical Reports Server (NTRS)

    Carpenter, Kenneth G.; Schrijver, Carolus J.; Fisher, Richard R. (Technical Monitor)

    2000-01-01

    The Stellar Imager and Seismic Probe (SISP) is a mission to understand the various effects of magnetic fields of stars, the dynamos that generate them, and the internal structure and dynamics of the stars in which they exist. The ultimate goal is to achieve the best-possible forecasting of solar activity on times scales ranging up to decades, and an understanding of the impact of stellar magnetic activity on astrobiology and life in the Universe. The road to that goal will revolutionize our understanding of stars and stellar systems, the building blocks of the Universe. SISP will zoom in on what today - with few exceptions - we only know as point sources, revealing processes never before seen, thus providing a tool to astrophysics as fundamental as the microscope is to the study of life on Earth. SISP is an ultraviolet aperture-synthesis imager with 8-10 telescopes with meter-class apertures, and a central hub with focal-plane instrumentation that allows spectrophotometry in passbands as narrow as a few Angstroms up to hundreds of Angstroms. SISP will image stars and binaries with one hundred to one thousand resolution elements on their surface, and sound their interiors through asteroseismology to image internal structure, differential rotation, and large-scale circulations; this will provide accurate knowledge of stellar structure and evolution and complex transport processes, and will impact numerous branches of (astro)physics ranging from the Big Bang to the future of the Universe. Fitting naturally within the NASA long-term time line, SISP complements defined missions, and with them will show us entire other solar systems, from the central star to their orbiting planets.

  14. Optofluidic needle probe integrating targeted delivery of fluid with optical coherence tomography imaging.

    PubMed

    Quirk, Bryden C; McLaughlin, Robert A; Pagnozzi, Alex M; Kennedy, Brendan F; Noble, Peter B; Sampson, David D

    2014-05-15

    We present an optofluidic optical coherence tomography (OCT) needle probe capable of modifying the local optical properties of tissue to improve needle-probe imaging performance. The side-viewing probe comprises an all-fiber-optic design encased in a hypodermic needle (outer diameter 720 μm) and integrates a coaxial fluid-filled channel, terminated by an outlet adjacent to the imaging window, allowing focal injection of fluid to a target tissue. This is the first fully integrated OCT needle probe design to incorporate fluid injection into the imaging mechanism. The utility of this probe is demonstrated in air-filled sheep lungs, where injection of small quantities of saline is shown, by local refractive index matching, to greatly improve image penetration through multiple layers of alveoli. 3D OCT images are correlated against histology, showing improvement in the capability to image lung structures such as bronchioles and blood vessels. PMID:24978229

  15. Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes

    PubMed Central

    Shim, Sang-Hee; Xia, Chenglong; Zhong, Guisheng; Babcock, Hazen P.; Vaughan, Joshua C.; Huang, Bo; Wang, Xun; Xu, Cheng; Bi, Guo-Qiang; Zhuang, Xiaowei

    2012-01-01

    Imaging membranes in live cells with nanometer-scale resolution promises to reveal ultrastructural dynamics of organelles that are essential for cellular functions. In this work, we identified photoswitchable membrane probes and obtained super-resolution fluorescence images of cellular membranes. We demonstrated the photoswitching capabilities of eight commonly used membrane probes, each specific to the plasma membrane, mitochondria, the endoplasmic recticulum (ER) or lysosomes. These small-molecule probes readily label live cells with high probe densities. Using these probes, we achieved dynamic imaging of specific membrane structures in living cells with 30–60 nm spatial resolution at temporal resolutions down to 1–2 s. Moreover, by using spectrally distinguishable probes, we obtained two-color super-resolution images of mitochondria and the ER. We observed previously obscured details of morphological dynamics of mitochondrial fusion/fission and ER remodeling, as well as heterogeneous membrane diffusivity on neuronal processes. PMID:22891300

  16. Evanescent Microwave Probes Using Coplanar Waveguide and Stripline for Super-Resolution Imaging of Materials

    NASA Technical Reports Server (NTRS)

    Ponchak, G. E.; Akinwande, D.; Ciocan, R.; LeClair, S. R.; Tabib-Azar, M.

    2000-01-01

    An evanescent field microwave imaging probe based on half-wavelength, microwave transmission line resonators is described. Optimization of the probe tip design, the coupling gap, and the data analysis has resulted in images of metal lines on semiconductor substrates with 2.6 microns spatial resolution and a minimum detectable line width of 0.4 microns at 1 GHz.

  17. Compact probing system using remote imaging for industrial plant maintenance

    NASA Astrophysics Data System (ADS)

    Ito, F.; Nishimura, A.

    2014-03-01

    Laser induced breakdown spectroscopy (LIBS) and endoscope observation were combined to design a remote probing device. We use this probing device to inspect a crack of the inner wall of the heat exchanger. Crack inspection requires speed at first, and then it requires accuracy. Once Eddy Current Testing (ECT) finds a crack with a certain signal level, another method should confirm it visually. We are proposing Magnetic particle Testing (MT) using specially fabricated the Magnetic Particle Micro Capsule (MPMC). For LIBS, a multichannel spectrometer and a Q-switch YAG laser were used. Irradiation area is 270 μm, and the pulse energy was 2 mJ. This pulse energy corresponds to 5-2.2 MW/cm2. A composite-type optical fiber was used to deliver both laser energy and optical image. Samples were prepared to heat a zirconium alloy plate by underwater arc welding in order to demonstrate severe accidents of nuclear power plants. A black oxide layer covered the weld surface and white particles floated on water surface. Laser induced breakdown plasma emission was taken into the spectroscope using this optical fiber combined with telescopic optics. As a result, we were able to simultaneously perform spectroscopic measurement and observation. For MT, the MPMC which gathered in the defective area is observed with this fiber. The MPMC emits light by the illumination of UV light from this optical fiber. The size of a defect is estimated with this amount of emission. Such technology will be useful for inspection repair of reactor pipe.

  18. In situ imaging of lung alveoli with an optical coherence tomography needle probe

    NASA Astrophysics Data System (ADS)

    Quirk, Bryden C.; McLaughlin, Robert A.; Curatolo, Andrea; Kirk, Rodney W.; Noble, Peter B.; Sampson, David D.

    2011-03-01

    In situ imaging of alveoli and the smaller airways with optical coherence tomography (OCT) has significant potential in the assessment of lung disease. We present a minimally invasive imaging technique utilizing an OCT needle probe. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within a 23-gauge needle. 3D-OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. The probe was used to image an intact, fresh (not fixed) sheep lung filled with normal saline, and the results validated against a histological gold standard. We present the first published images of alveoli acquired with an OCT needle probe and demonstrate the potential of this technique to visualize other anatomical features such as bifurcations of the bronchioles.

  19. Dedicated mobile high resolution prostate PET imager with an insertable transrectal probe

    DOEpatents

    Majewski, Stanislaw; Proffitt, James

    2010-12-28

    A dedicated mobile PET imaging system to image the prostate and surrounding organs. The imaging system includes an outside high resolution PET imager placed close to the patient's torso and an insertable and compact transrectal probe that is placed in close proximity to the prostate and operates in conjunction with the outside imager. The two detector systems are spatially co-registered to each other. The outside imager is mounted on an open rotating gantry to provide torso-wide 3D images of the prostate and surrounding tissue and organs. The insertable probe provides closer imaging, high sensitivity, and very high resolution predominately 2D view of the prostate and immediate surroundings. The probe is operated in conjunction with the outside imager and a fast data acquisition system to provide very high resolution reconstruction of the prostate and surrounding tissue and organs.

  20. High speed 3D endoscopic optical frequency domain imaging probe for lung cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Li, Jianan; Feroldi, Fabio; Mo, Jianhua; Helderman, Frank; de Groot, Mattijs; de Boer, Johannes F.

    2013-06-01

    We present a miniature motorized endoscopic probe for Optical Frequency Domain Imaging with an outer diameter of 1.65 mm and a rotation speed of 3,000 - 12,500 rpm. The probe has a motorized distal end which provides a significant advantage over proximally driven probes since it does not require a drive shaft to transfer the rotational torque to the distal end of the probe and functions without a fiber rotary junction. The probe has a focal Full Width at Half Maximum of 9.6 μm and a working distance of 0.47 mm. We analyzed the non-uniform rotation distortion and found a location fluctuation of only 1.87° in repeated measurements of the same object. The probe was integrated in a high-speed Optical Frequency Domain Imaging setup at 1310 nm. We demonstrated its performance with imaging ex vivo pig bronchial and in vivo goat lung.

  1. Magnetic nanoparticles as both imaging probes and therapeutic agents.

    PubMed

    Lacroix, Lise-Marie; Ho, Don; Sun, Shouheng

    2010-01-01

    Magnetic nanoparticles (MNPs) have been explored extensively as contrast agents for magnetic resonance imaging (MRI) or as heating agents for magnetic fluid hyperthermia (MFH) [1]. To achieve optimum operation conditions in MRI and MFH, these NPs should have well-controlled magnetic properties and biological functionalities. Although numerous efforts have been dedicated to the investigations on MNPs for biomedical applications [2-5], the NP optimizations for early diagnostics and efficient therapeutics are still far from reached. Recent efforts in NP syntheses have led to some promising MNP systems for sensitive MRI and efficient MFH applications. This review summarizes these advances in the synthesis of monodisperse MNPs as both contrast probes in MRI and as therapeutic agents via MFH. It will first introduce the nanomagnetism and elucidate the critical parameters to optimize the superparamagnetic NPs for MRI and ferromagnetic NPs for MFH. It will further outline the new chemistry developed for making monodisperse MNPs with controlled magnetic properties. The review will finally highlight the NP functionalization with biocompatible molecules and biological targeting agents for tumor diagnosis and therapy. PMID:20388109

  2. Design of Environmentally Responsive Fluorescent Polymer Probes for Cellular Imaging.

    PubMed

    Yamada, Arisa; Hiruta, Yuki; Wang, Jian; Ayano, Eri; Kanazawa, Hideko

    2015-08-10

    We report the development of environmentally responsive fluorescent polymers. The reversible temperature-induced phase transition of copolymers composed of N-isopropylacrylamide and a fluorescent monomer based on the fluorescein (FL), coumarin (CO), rhodamine (RH), or dansyl (DA) skeleton was used as a molecular switch to control the fluorescence intensity. The poly(N-isopropylacrylamide) (PNIPAAm) chain showed an expanded coil conformation below the lower critical solution temperature (LCST) due to hydration, but it changed to a globular form above the LCST due to dehydration. Through the combination of a polarity-sensitive fluorophore with PNIPAAm, the synthetic fluorescent polymer displayed a response to external temperature, with the fluorescence strength dramatically changing close to the LCST. Additionally, the P(NIPAAm-co-FL) and P(NIPAAm-co-CO) polymers, containing fluorescein and coumarin groups, respectively, exhibited pH responsiveness. The environmental responsiveness of the reported polymers is derived directly from the PNIPAAm and fluorophore structures, thus allowing for the cellular uptake of the fluorescence copolymer by RAW264.7 cells to be temperature-controlled. Cellular uptake was suppressed below the LCST but enhanced above the LCST. Furthermore, the cellular uptake of both P(NIPAAm-co-CO) and P(NIPAAm-co-RH) conjugated with a fusogenic lipid, namely, l-α-phosphatidylethanolamine, dioleoyl (DOPE), was enhanced. Such lipid-conjugated fluorescence probes are expected to be useful as physiological indicators for intracellular imaging. PMID:26121103

  3. A single probe for imaging photons, electrons and physical forces

    NASA Astrophysics Data System (ADS)

    Pilet, Nicolas; Lisunova, Yuliya; Lamattina, Fabio; Stevenson, Stephanie E.; Pigozzi, Giancarlo; Paruch, Patrycja; Fink, Rainer H.; Hug, Hans J.; Quitmann, Christoph; Raabe, Joerg

    2016-06-01

    The combination of complementary measurement techniques has become a frequent approach to improve scientific knowledge. Pairing of the high lateral resolution scanning force microscopy (SFM) with the spectroscopic information accessible through scanning transmission soft x-ray microscopy (STXM) permits assessing physical and chemical material properties with high spatial resolution. We present progress from the NanoXAS instrument towards using an SFM probe as an x-ray detector for STXM measurements. Just by the variation of one parameter, the SFM probe can be utilised to detect either sample photo-emitted electrons or transmitted photons. This allows the use of a single probe to detect electrons, photons and physical forces of interest. We also show recent progress and demonstrate the current limitations of using a high aspect ratio coaxial SFM probe to detect photo-emitted electrons with very high lateral resolution. Novel probe designs are proposed to further progress in using an SFM probe as a STXM detector.

  4. A single probe for imaging photons, electrons and physical forces.

    PubMed

    Pilet, Nicolas; Lisunova, Yuliya; Lamattina, Fabio; Stevenson, Stephanie E; Pigozzi, Giancarlo; Paruch, Patrycja; Fink, Rainer H; Hug, Hans J; Quitmann, Christoph; Raabe, Joerg

    2016-06-10

    The combination of complementary measurement techniques has become a frequent approach to improve scientific knowledge. Pairing of the high lateral resolution scanning force microscopy (SFM) with the spectroscopic information accessible through scanning transmission soft x-ray microscopy (STXM) permits assessing physical and chemical material properties with high spatial resolution. We present progress from the NanoXAS instrument towards using an SFM probe as an x-ray detector for STXM measurements. Just by the variation of one parameter, the SFM probe can be utilised to detect either sample photo-emitted electrons or transmitted photons. This allows the use of a single probe to detect electrons, photons and physical forces of interest. We also show recent progress and demonstrate the current limitations of using a high aspect ratio coaxial SFM probe to detect photo-emitted electrons with very high lateral resolution. Novel probe designs are proposed to further progress in using an SFM probe as a STXM detector. PMID:27146329

  5. Optical imaging of reporter gene expression using a positron-emission-tomography probe

    NASA Astrophysics Data System (ADS)

    Liu, Hongguang; Ren, Gang; Liu, Shuanglong; Zhang, Xiaofen; Chen, Luxi; Han, Peizhen; Cheng, Zhen

    2010-11-01

    Reporter gene/reporter probe technology is one of the most important techniques in molecular imaging. Lately, many reporter gene/reporter probe systems have been coupled to different imaging modalities such as positron emission tomography (PET) and optical imaging (OI). It has been recently found that OI techniques could be used to monitor radioactive tracers in vitro and in living subjects. In this study, we further demonstrate that a reporter gene/nuclear reporter probe system [herpes simplex virus type-1 thymidine kinase (HSV1-tk) and 9-(4-18F-fluoro-3-[hydroxymethyl] butyl) guanine ([18F]FHBG)] could be successfully imaged by OI in vitro and in vivo. OI with radioactive reporter probes will facilitate and broaden the applications of reporter gene/reporter probe techniques in medical research.

  6. Fluorogenic Probe for the Human Ether-a-Go-Go-Related Gene Potassium Channel Imaging

    PubMed Central

    2016-01-01

    The first small-molecule fluorogenic probe A1 for imaging the human Ether-a-go-go-Related Gene (hERG) potassium channel based on the photoinduced electron transfer (PET) off–on mechanism was described herein. After careful biological evaluation, this probe had the potential of detecting and imaging the hERG channel at the molecular and cellular level. Moreover, the competitive binding mechanism of this probe would presumably minimize the effects on the electrophysiological properties of the hERG channel. Therefore, this probe may serve as a powerful toolkit to the hERG-associated study. PMID:25665091

  7. Sparse sampling and reconstruction for electron and scanning probe microscope imaging

    SciTech Connect

    Anderson, Hyrum; Helms, Jovana; Wheeler, Jason W.; Larson, Kurt W.; Rohrer, Brandon R.

    2015-07-28

    Systems and methods for conducting electron or scanning probe microscopy are provided herein. In a general embodiment, the systems and methods for conducting electron or scanning probe microscopy with an undersampled data set include: driving an electron beam or probe to scan across a sample and visit a subset of pixel locations of the sample that are randomly or pseudo-randomly designated; determining actual pixel locations on the sample that are visited by the electron beam or probe; and processing data collected by detectors from the visits of the electron beam or probe at the actual pixel locations and recovering a reconstructed image of the sample.

  8. Portable LED-induced autofluorescence imager with a probe of L shape for oral cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Huang, Ting-Wei; Lee, Yu-Cheng; Cheng, Nai-Lun; Yan, Yung-Jhe; Chiang, Hou-Chi; Chiou, Jin-Chern; Mang, Ou-Yang

    2015-08-01

    The difference of spectral distribution between lesions of epithelial cells and normal cells after excited fluorescence is one of methods for the cancer diagnosis. In our previous work, we developed a portable LED Induced autofluorescence (LIAF) imager contained the multiple wavelength of LED excitation light and multiple filters to capture ex-vivo oral tissue autofluorescence images. Our portable system for detection of oral cancer has a probe in front of the lens for fixing the object distance. The shape of the probe is cone, and it is not convenient for doctor to capture the oral image under an appropriate view angle in front of the probe. Therefore, a probe of L shape containing a mirror is proposed for doctors to capture the images with the right angles, and the subjects do not need to open their mouse constrainedly. Besides, a glass plate is placed in probe to prevent the liquid entering in the body, but the light reflected from the glass plate directly causes the light spots inside the images. We set the glass plate in front of LED to avoiding the light spots. When the distance between the glasses plate and the LED model plane is less than the critical value, then we can prevent the light spots caused from the glasses plate. The experiments show that the image captured with the new probe that the glasses plate placed in the back-end of the probe has no light spots inside the image.

  9. Transillumination and reflectance probes for in vivo near-IR imaging of dental caries

    PubMed Central

    Simon, Jacob C.; Lucas, Seth A.; Staninec, Michal; Tom, Henry; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-01-01

    Previous studies have demonstrated the utility of near infrared (NIR) imaging for caries detection employing transillumination and reflectance imaging geometries. Three intra-oral NIR imaging probes were fabricated for the acquisition of in vivo, real time videos using a high definition InGaAs SWIR camera and near-IR broadband light sources. Two transillumination probes provide occlusal and interproximal images using 1300-nm light where water absorption is low and enamel manifests the highest transparency. A third reflectance probe utilizes cross polarization and operates at >1500-nm, where water absorption is higher which reduces the reflectivity of sound tissues, significantly increasing lesion contrast. These probes are being used in an ongoing clinical study to assess the diagnostic performance of NIR imaging for the detection of caries lesions in teeth scheduled for extraction for orthodontic reasons. PMID:24817803

  10. Transillumination and reflectance probes for in vivo near-IR imaging of dental caries

    NASA Astrophysics Data System (ADS)

    Simon, Jacob C.; Lucas, Seth A.; Staninec, Michal; Tom, Henry; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-02-01

    Previous studies have demonstrated the utility of near infrared (NIR) imaging for caries detection employing transillumination and reflectance imaging geometries. Three intra-oral NIR imaging probes were fabricated for the acquisition of in vivo, real time videos using a high definition InGaAs SWIR camera and near-IR broadband light sources. Two transillumination probes provide occlusal and interproximal images using 1300-nm light where water absorption is low and enamel manifests the highest transparency. A third reflectance probe utilizes cross polarization and operates at >1500-nm, where water absorption is higher which reduces the reflectivity of sound tissues, significantly increasing lesion contrast. These probes are being used in an ongoing clinical study to assess the diagnostic performance of NIR imaging for the detection of caries lesions in teeth scheduled for extraction for orthodontic reasons.

  11. Miniature real-time intraoperative forward-imaging optical coherence tomography probe

    PubMed Central

    Joos, Karen M.; Shen, Jin-Hui

    2013-01-01

    Optical coherence tomography (OCT) has a tremendous global impact upon the ability to diagnose, treat, and monitor eye diseases. A miniature 25-gauge forward-imaging OCT probe with a disposable tip was developed for real-time intraoperative ocular imaging of posterior pole and peripheral structures to improve vitreoretinal surgery. The scanning range was 2 mm when the probe tip was held 3-4 mm from the tissue surface. The axial resolution was 4-6 µm and the lateral resolution was 25-35 µm. The probe was used to image cellophane tape and multiple ocular structures. PMID:24009997

  12. Probing neutral atmospheric collision complexes with anion photoelectron imaging

    NASA Astrophysics Data System (ADS)

    Jarrold, Caroline

    Photodetachment of anionic precursors of neutral collision complexes offers a way to probe the effects of symmetry-breaking collision events on the electronic structure of normally transparent molecules. We have measured the anion photoelectron imaging (PEI) spectra of a series of O2- X complexes, where X is a volatile organic molecule with atmospheric relevance, to determine how the electronic properties of various X molecules affect the low-lying electronic structure of neutral O2 undergoing O2 - X collisons. The study was motivated by the catalog of vibrational and electronic absorption lines induced by O2 - O2, O2 - N2, and other collisions. The energies of electronic features observed in the anion PEI spectra of O2- X (X = hexane, hexene, isoprene and benzene) relative to O2- PEI spectroscopic features indicate that photodetachment of the anion does indeed access a repulsive part of the O2 - X potential. In addition, the spectra of the various complexes show an interesting variation in the intensities of transitions to the excited O2(1Δg) . X and O2(1Σg+) . X states relative to the ground O2(3Σg-) . X state. With X = non-polar species such as hexane, the relative intensities of transitions to the triplet and singlet states of O2 . X are very similar to those of isolated O2, while the relative intensity of the singlet band decreases and becomes lower in energy relative to the triplet band for X = polar molecules. A significant enhancement in the intensities of the singlet bands is observed for complexes with X = isoprene and benzene, both of which have low-lying triplet states. The role of the triplet states in isoprene and benzene, and the implications for induced electronic absorption in O2 undergoing collisions with these molecules, are explored. National Science Foundation NSF CHE 1265991.

  13. Seeing the corona with the solar probe plus mission: the wide-field imager for solar probe+ (WISPR)

    NASA Astrophysics Data System (ADS)

    Vourlidas, Angelos; Howard, Russell A.; Plunkett, Simon P.; Korendyke, Clarence M.; Carter, Michael T.; Thernisien, Arnaud F. R.; Chua, Damien H.; Van Duyne, Peter; Socker, Dennis G.; Linton, Mark G.; Liewer, Paulett C.; Hall, Jeffrey R.; Morrill, Jeff S.; DeJong, Eric M.; Mikic, Zoran; Rochus, Pierre L. P. M.; Bothmer, Volker; Rodman, Jens; Lamy, Philippe

    2013-09-01

    The Solar Probe Plus (SPP) mission scheduled for launch in 2018, will orbit between the Sun and Venus with diminishing perihelia reaching as close as 7 million km (9.86 solar radii) from Sun center. In addition to a suite of in-situ probes for the magnetic field, plasma, and energetic particles, SPP will be equipped with an imager. The Wide-field Imager for the Solar PRobe+ (WISPR), with a 95° radial by 58° transverse field of view, will image the fine-scale coronal structure of the corona, derive the 3D structure of the large-scale corona, and determine whether a dust-free zone exists near the Sun. Given the tight mass constrains of the mission, WISPR incorporates an efficient design of two widefield telescopes and their associated focal plane arrays based on novel large-format (2kx2k) APS CMOS detectors into the smallest heliospheric imaging package to date. The flexible control electronics allow WISPR to collect individual images at cadences up to 1 second at perihelion or sum several of them to increase the signal-to-noise during the outbound part of the orbit. The use of two telescopes minimizes the risk of dust damage which may be considerable close to the Sun. The dependency of the Thomson scattering emission of the corona on the imaging geometry dictates that WISPR will be very sensitive to the emission from plasma close to the spacecraft in contrast to the situation for imaging from Earth orbit. WISPR will be the first `local' imager providing a crucial link between the large scale corona and the in-situ measurements.

  14. High-throughput fiber-array transvaginal ultrasound/photoacoustic probe for ovarian cancer imaging

    NASA Astrophysics Data System (ADS)

    Salehi, Hassan S.; Kumavor, Patrick D.; Alqasemi, Umar; Li, Hai; Wang, Tianheng; Zhu, Quing

    2014-03-01

    A high-throughput ultrasound/photoacoustic probe for delivering high contrast and signal-to-noise ratio images was designed, constructed, and tested. The probe consists of a transvaginal ultrasound array integrated with four 1mm-core optical fibers and a sheath. The sheath encases transducer and is lined with highly reflecting aluminum for high intensity light output and uniformity while at the same time remaining below the maximum permissible exposure (MPE) recommended by the American National Standards Institute (ANSI). The probe design was optimized by simulating the light fluence distribution in Zemax. The performance of the probe was evaluated by experimental measurements of the fluence and real-time imaging of polyethylene-tubing filled with blood. These results suggest that our probe has great potential for in vivo imaging and characterization of ovarian cancer.

  15. Imaging of oxygenation in 3D tissue models with multi-modal phosphorescent probes

    NASA Astrophysics Data System (ADS)

    Papkovsky, Dmitri B.; Dmitriev, Ruslan I.; Borisov, Sergei

    2015-03-01

    Cell-penetrating phosphorescence based probes allow real-time, high-resolution imaging of O2 concentration in respiring cells and 3D tissue models. We have developed a panel of such probes, small molecule and nanoparticle structures, which have different spectral characteristics, cell penetrating and tissue staining behavior. The probes are compatible with conventional live cell imaging platforms and can be used in different detection modalities, including ratiometric intensity and PLIM (Phosphorescence Lifetime IMaging) under one- or two-photon excitation. Analytical performance of these probes and utility of the O2 imaging method have been demonstrated with different types of samples: 2D cell cultures, multi-cellular spheroids from cancer cell lines and primary neurons, excised slices from mouse brain, colon and bladder tissue, and live animals. They are particularly useful for hypoxia research, ex-vivo studies of tissue physiology, cell metabolism, cancer, inflammation, and multiplexing with many conventional fluorophors and markers of cellular function.

  16. Synthesis of a Targeted Biarsenical Cy3-Cy5 Affinity Probe for Superresolution Fluorescence Imaging

    SciTech Connect

    Fu, Na; Xiong, Yijia; Squier, Thomas C.

    2012-11-01

    Photoswitchable fluorescent probes capable of the targeted labeling of tagged proteins are of significant interest due to their ability to enable in situ imaging of protein complexes within native biomolecular assemblies. Here we describe the synthesis of a fluorescent probe (AsCy3Cy5), and demonstrate the targeted labeling and super-resolution imaging of a tagged protein within a supramolecular protein complex.

  17. X-ray phase computed tomography for nanoparticulated imaging probes and therapeutics: preliminary feasibility study

    NASA Astrophysics Data System (ADS)

    Tang, Xiangyang; Yang, Yi; Tang, Shaojie

    2011-03-01

    With the scientific progress in cancer biology, pharmacology and biomedical engineering, the nano-biotechnology based imaging probes and therapeutical agents (namely probes/agents) - a form of theranostics - are among the strategic solutions bearing the hope for the cure of cancer. The key feature distinguishing the nanoparticulated probes/agents from their conventional counterparts is their targeting capability. A large surface-to-volume ratio in nanoparticulated probes/agents enables the accommodation of multiple targeting, imaging and therapeutic components to cope with the intra- and inter-tumor heterogeneity. Most nanoparticulated probes/agents are synthesized with low atomic number materials and thus their x-ray attenuation are very similar to biological tissues. However, their microscopic structures are very different, which may result in significant differences in their refractive properties. Recently, the investigation in the x-ray grating-based differential phase contrast (DPC) CT has demonstrated its advantages in differentiating low-atomic materials over the conventional attenuation-based CT. We believe that a synergy of x-ray grating-based DPC CT and nanoparticulated imaging probes and therapeutic agents may play a significant role in extensive preclinical and clinical applications, or even become a modality for molecular imaging. Hence, we propose to image the refractive property of nanoparticulated imaging probes and therapeutical agents using x-ray grating-based DPC CT. In this work, we conduct a preliminary feasibility study with a focus to characterize the contrast-to-noise ratio (CNR) and contrast-detail behavior of the x-ray grating-based DPC CT. The obtained data may be instructive to the architecture design and performance optimization of the x-ray grating-based DPC CT for imaging biomarker-targeted imaging probes and therapeutic agents, and even informative to the translation of preclinical research in theranostics into clinical applications.

  18. A colorimetric and fluorescent dual probe for palladium in aqueous medium and live cell imaging.

    PubMed

    Yan, Jin-Wu; Wang, Xiao-Lin; Tan, Qi-Feng; Yao, Pei-Fen; Tan, Jia-Heng; Zhang, Lei

    2016-04-21

    A colorimetric and fluorescent dual probe for palladium species was rationally developed by combining the resorufin fluorophore with allyl chloroformate. The probe enables the visual detection of palladium based on its vivid color change from pale yellow to pink and its fluorescence off-on response to palladium in PBS solution. The detection limit was calculated to be as low as 2.1 nM. The live cell imaging results showed that this probe could be used as an effective fluorescent probe for detecting intracellular palladium species. All these results featured its promising application prospects in the palladium analytical field. PMID:26990285

  19. Fluoromodule-based reporter/probes designed for in vivo fluorescence imaging

    PubMed Central

    Zhang, Ming; Chakraborty, Subhasish K.; Sampath, Padma; Rojas, Juan J.; Hou, Weizhou; Saurabh, Saumya; Thorne, Steve H.; Bruchez, Marcel P.; Waggoner, Alan S.

    2015-01-01

    Optical imaging of whole, living animals has proven to be a powerful tool in multiple areas of preclinical research and has allowed noninvasive monitoring of immune responses, tumor and pathogen growth, and treatment responses in longitudinal studies. However, fluorescence-based studies in animals are challenging because tissue absorbs and autofluoresces strongly in the visible light spectrum. These optical properties drive development and use of fluorescent labels that absorb and emit at longer wavelengths. Here, we present a far-red absorbing fluoromodule–based reporter/probe system and show that this system can be used for imaging in living mice. The probe we developed is a fluorogenic dye called SC1 that is dark in solution but highly fluorescent when bound to its cognate reporter, Mars1. The reporter/probe complex, or fluoromodule, produced peak emission near 730 nm. Mars1 was able to bind a variety of structurally similar probes that differ in color and membrane permeability. We demonstrated that a tool kit of multiple probes can be used to label extracellular and intracellular reporter–tagged receptor pools with 2 colors. Imaging studies may benefit from this far-red excited reporter/probe system, which features tight coupling between probe fluorescence and reporter binding and offers the option of using an expandable family of fluorogenic probes with a single reporter gene. PMID:26348895

  20. A resonant scanning dipole-antenna probe for enhanced nanoscale imaging.

    PubMed

    Neumann, Lars; van 't Oever, Jorick; van Hulst, Niek F

    2013-11-13

    We present a scanning antenna probe that provides 35 nm optical hotspots with a 16-fold excitation enhancement. A resonant optical antenna, tuned to operation in the visible, is carved into the aluminum-coated scanning probe. The antenna resonances, field localization, excitation, and polarization response are probed in the near-field by scanning over single fluorescent nanobeads. At the same time, the distance-dependent coupling of the emission to the antenna mode is mapped. Good agreement with theory is obtained. The presented scanning antenna approach is useful for both nanoscale plasmonic mode imaging and (bio)imaging. PMID:24124987

  1. Chemical-contrast imaging with pulse-shaping based pump-probe spectroscopy

    NASA Astrophysics Data System (ADS)

    Flynn, Daniel C.; Bhagwat, Amar R.; Ogilvie, Jennifer P.

    2013-02-01

    Ultrafast pump-probe spectroscopy and pulse-shaping techniques are providing new modes of contrast for the field of multiphoton microscopy. Endogenous species such as heme proteins show rich nonlinear spectroscopic signatures of excited state absorption, stimulated emission and ground-state bleaching. Commercially available octave-spanning Ti:sapphire oscillators offer new opportunities for imaging based on pump-probe contrast. Spatial light modulators take advantage of this large bandwidth, shaping pulses of light to selectively excite molecular structures with similar spectral properties. We present two-color pump-probe imaging of heme proteins solutions and red blood cells.

  2. Swept-source common-path optical coherence tomography with a MEMS endoscopic imaging probe

    NASA Astrophysics Data System (ADS)

    Duan, Can; Wang, Donglin; Zhou, Zhengwei; Liang, Peng; Samuelson, Sean; Pozzi, Antonio; Xie, Huikai

    2014-03-01

    A MEMS-based common-path endoscopic imaging probe for 3D swept-source optical coherence tomography (SSOCT) has been developed. The common path is achieved by setting the reference plane at the rear surface of the GRIN lens inside the probe. MEMS devices have the advantages of low cost, small size and fast speed, which are suitable for miniaturizing endoscopic probes. The aperture size of the two-axis MEMS mirror employed in this endoscopic probe is 1 mm by 1 mm and the footprint of the MEMS chip is 1.55 mm by 1.7 mm. The MEMS mirror achieves large two dimensional optical scan angles up to 34° at 4.0 V. The endoscopic probe using the MEMS mirror as the scan engine is only 4.0 mm in diameter. Additionally, an optimum length of the GRIN lens is established to remove the artifacts in the SSOCT images generated from the multiple interfaces inside the endoscopic imaging probe. The MEMS based commonpath probe demonstrates real time 3D OCT images of human finger with 10.6 μm axial resolution, 17.5 μm lateral resolution and 1.0 mm depth range at a frame rate of 50 frames per second.

  3. Scanning thermal microscopy probe capable of simultaneous electrical imaging and the addition of diamond tip

    NASA Astrophysics Data System (ADS)

    Brown, E.; Hao, L.; Cox, D. C.; Gallop, J. C.

    2008-03-01

    Scanning Thermal Microscopy (SThM) is a scanning probe technique that allows the mapping of the thermal properties and/or temperature of a substrate. Developments in this scanning probe technique are of great importance to further the study of thermal transport at the micron and at the nano scale, for instance to better the understanding of heat transport in nano-electronic devices or energy transfer in biological systems. Here we describe: 1) the scanning technique developed to acquire simultaneous images of the topography, the thermal and electrical properties of the substrate using a commercially available Veeco SThM probe; 2) how the SThM probe was modified by mounting a micron-sized diamond pyramid on its tip in order to improve the probe's lateral resolution and the topography resolution tests on the performance of the modified probe.

  4. Strained cyclooctyne as a molecular platform for construction of multimodal imaging probes.

    PubMed

    Sun, Yao; Ma, Xiaowei; Cheng, Kai; Wu, Biying; Duan, Jianli; Chen, Hao; Bu, Lihong; Zhang, Ruiping; Hu, Xianming; Deng, Zixin; Xing, Lei; Hong, Xuechuan; Cheng, Zhen

    2015-05-11

    Small-molecule-based multimodal and multifunctional imaging probes play prominent roles in biomedical research and have high clinical translation ability. A novel multimodal imaging platform using base-catalyzed double addition of thiols to a strained internal alkyne such as bicyclo[6.1.0]nonyne has been established in this study, thus allowing highly selective assembly of various functional units in a protecting-group-free manner. Using this molecular platform, novel dual-modality (PET and NIRF) uPAR-targeted imaging probe: (64)Cu-CHS1 was prepared and evaluated in U87MG cells and tumor-bearing mice models. The excellent PET/NIRF imaging characteristics such as good tumor uptake (3.69%ID/g at 2 h post-injection), high tumor contrast, and specificity were achieved in the small-animal models. These attractive imaging properties make (64)Cu-CHS1 a promising probe for clinical use. PMID:25800807

  5. Local collective motion analysis for multi-probe dynamic imaging and microrheology.

    PubMed

    Khan, Manas; Mason, Thomas G

    2016-08-01

    Dynamical artifacts, such as mechanical drift, advection, and hydrodynamic flow, can adversely affect multi-probe dynamic imaging and passive particle-tracking microrheology experiments. Alternatively, active driving by molecular motors can cause interesting non-Brownian motion of probes in local regions. Existing drift-correction techniques, which require large ensembles of probes or fast temporal sampling, are inadequate for handling complex spatio-temporal drifts and non-Brownian motion of localized domains containing relatively few probes. Here, we report an analytical method based on local collective motion (LCM) analysis of as few as two probes for detecting the presence of non-Brownian motion and for accurately eliminating it to reveal the underlying Brownian motion. By calculating an ensemble-average, time-dependent, LCM mean square displacement (MSD) of two or more localized probes and comparing this MSD to constituent single-probe MSDs, we can identify temporal regimes during which either thermal or athermal motion dominates. Single-probe motion, when referenced relative to the moving frame attached to the multi-probe LCM trajectory, provides a true Brownian MSD after scaling by an appropriate correction factor that depends on the number of probes used in LCM analysis. We show that LCM analysis can be used to correct many different dynamical artifacts, including spatially varying drifts, gradient flows, cell motion, time-dependent drift, and temporally varying oscillatory advection, thereby offering a significant improvement over existing approaches. PMID:27269299

  6. Local collective motion analysis for multi-probe dynamic imaging and microrheology

    NASA Astrophysics Data System (ADS)

    Khan, Manas; Mason, Thomas G.

    2016-08-01

    Dynamical artifacts, such as mechanical drift, advection, and hydrodynamic flow, can adversely affect multi-probe dynamic imaging and passive particle-tracking microrheology experiments. Alternatively, active driving by molecular motors can cause interesting non-Brownian motion of probes in local regions. Existing drift-correction techniques, which require large ensembles of probes or fast temporal sampling, are inadequate for handling complex spatio-temporal drifts and non-Brownian motion of localized domains containing relatively few probes. Here, we report an analytical method based on local collective motion (LCM) analysis of as few as two probes for detecting the presence of non-Brownian motion and for accurately eliminating it to reveal the underlying Brownian motion. By calculating an ensemble-average, time-dependent, LCM mean square displacement (MSD) of two or more localized probes and comparing this MSD to constituent single-probe MSDs, we can identify temporal regimes during which either thermal or athermal motion dominates. Single-probe motion, when referenced relative to the moving frame attached to the multi-probe LCM trajectory, provides a true Brownian MSD after scaling by an appropriate correction factor that depends on the number of probes used in LCM analysis. We show that LCM analysis can be used to correct many different dynamical artifacts, including spatially varying drifts, gradient flows, cell motion, time-dependent drift, and temporally varying oscillatory advection, thereby offering a significant improvement over existing approaches.

  7. Feasibility study on the development of a fiber-optic gamma imaging probe

    NASA Astrophysics Data System (ADS)

    Hong, Seunghan; Yoo, Wook Jae; Shin, Sang Hun; Jeon, Hyesu; Jang, Jae Seok; Kwon, Guwon; Lee, Dong Eun; Jang, Kyoung Won; Lee, Bongsoo

    2015-07-01

    In this research, we fabricated a fiber-optic gamma imaging probe that could measure the scintillation image induced by gamma-rays. For evaluating the spatial resolution of the optical and the scintillation images measured by using the proposed gamma imaging probe, first, we obtained the light intensity distributions across the sharp edge from the optical and the scintillation images by using a USAF 1951 resolution target and an X-ray beam and then analyzed each modulation transfer function (MTF) curve. Next, we measured the scintillation images with information regarding the distribution by the gamma-rays emitted from Cs-137 sources with four different radioactivities. Finally, we evaluated the intensity variation of the scintillating light from the region of interest (ROI) in the scintillation image according to the radioactivity of Cs-137.

  8. Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

    PubMed Central

    Yi, Xiaomin; Wang, Fuli; Qin, Weijun; Yang, Xiaojian; Yuan, Jianlin

    2014-01-01

    Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized. PMID:24648733

  9. Enhanced Fluorescence Imaging of Live Cells by Effective Cytosolic Delivery of Probes

    PubMed Central

    Massignani, Marzia; Canton, Irene; Sun, Tao; Hearnden, Vanessa; MacNeil, Sheila; Blanazs, Adam; Armes, Steven P.; Lewis, Andrew; Battaglia, Giuseppe

    2010-01-01

    Background Microscopic techniques enable real-space imaging of complex biological events and processes. They have become an essential tool to confirm and complement hypotheses made by biomedical scientists and also allow the re-examination of existing models, hence influencing future investigations. Particularly imaging live cells is crucial for an improved understanding of dynamic biological processes, however hitherto live cell imaging has been limited by the necessity to introduce probes within a cell without altering its physiological and structural integrity. We demonstrate herein that this hurdle can be overcome by effective cytosolic delivery. Principal Findings We show the delivery within several types of mammalian cells using nanometre-sized biomimetic polymer vesicles (a.k.a. polymersomes) that offer both highly efficient cellular uptake and endolysomal escape capability without any effect on the cellular metabolic activity. Such biocompatible polymersomes can encapsulate various types of probes including cell membrane probes and nucleic acid probes as well as labelled nucleic acids, antibodies and quantum dots. Significance We show the delivery of sufficient quantities of probes to the cytosol, allowing sustained functional imaging of live cells over time periods of days to weeks. Finally the combination of such effective staining with three-dimensional imaging by confocal laser scanning microscopy allows cell imaging in complex three-dimensional environments under both mono-culture and co-culture conditions. Thus cell migration and proliferation can be studied in models that are much closer to the in vivo situation. PMID:20454666

  10. Molecular Surface Sampling and Chemical Imaging using Proximal Probe Thermal Desorption/Secondary Ionization Mass Spectrometry

    SciTech Connect

    Ovchinnikova, Olga S; Kertesz, Vilmos; Van Berkel, Gary J

    2011-01-01

    Proximal probe thermal desorption/secondary ionization mass spectrometry was studied and applied to molecular surface sampling and chemical imaging using printed patterns on photopaper as test substrates. With the use of a circular cross section proximal probe with a tip diameter of 50 m and fixed temperature (350 C), the influence of probe-to-surface distance, lane scan spacing, and surface scan speed on signal quality and spatial resolution were studied and optimized. As a compromise between signal amplitude, signal reproducibility, and data acquisition time, a surface scan speed of 100 m/s, probe-to-paper surface distance of 5 m, and lane spacing of 10 m were used for imaging. Under those conditions the proximal probe thermal desorption/secondary ionization mass spectrometry method was able to achieve a spatial resolution of about 50 m as determined by the ability to distinguish surface patterns of known dimensions that were printed on the paper substrate. It is expected that spatial resolution and chemical image quality could be further improved by using probes of smaller cross section size and by incorporating a means to maintain a fixed optimal probe-to-surface distance real time, continuously adapting to the changing topography of the surface during a lane scan.

  11. High speed miniature motorized endoscopic probe for 3D optical frequency domain imaging

    NASA Astrophysics Data System (ADS)

    Li, Jianan; Feroldi, Fabio; Mo, Jianhua; Helderman, Frank; de Groot, Mattijs; de Boer, Johannes F.

    2013-03-01

    We present a miniature motorized endoscopic probe for Optical Frequency Domain Imaging with an outer diameter of 1.65 mm and a rotation speed of 3,000 - 12,500 rpm. This is the smallest motorized high speed OCT probe to our knowledge. The probe has a motorized distal end which provides a significant advantage over proximally driven probes since it does not require a drive shaft to transfer the rotational torque to the distal end of the probe and functions without a fiber rotary junction. The probe has a focal Full Width at Half Maximum of 9.6 μm and a working distance of 0.47 mm. We analyzed the non-uniform rotation distortion and found a location fluctuation of only 1.87° in repeated measurements of the same object. The probe was integrated in a high-speed Optical Frequency Domain Imaging setup at 1310 nm We demonstrated its performance with imaging ex vivo pig bronchial and in vivo goat lung.

  12. Portable oral cancer detection using a miniature confocal imaging probe with a large field of view

    NASA Astrophysics Data System (ADS)

    Wang, Youmin; Raj, Milan; McGuff, H. Stan; Bhave, Gauri; Yang, Bin; Shen, Ting; Zhang, Xiaojing

    2012-06-01

    We demonstrate a MEMS micromirror enabled handheld confocal imaging probe for portable oral cancer detection, where a comparatively large field of view (FOV) was generated through the programmable Lissajous scanning pattern of the MEMS micromirror. Miniaturized handheld MEMS confocal imaging probe was developed, and further compared with the desktop confocal prototype under clinical setting. For the handheld confocal imaging system, optical design simulations using CODE VR® shows the lateral and axial resolution to be 0.98 µm and 4.2 µm, where experimental values were determined to be 3 µm and 5.8 µm, respectively, with a FOV of 280 µm×300 µm. Fast Lissajous imaging speed up to 2 fps was realized with improved Labview and Java based real-time imaging software. Properties such as 3D imaging through autofocusing and mosaic imaging for extended lateral view (6 mm × 8 mm) were examined for carcinoma real-time pathology. Neoplastic lesion tissues of giant cell fibroma and peripheral ossifying fibroma, the fibroma inside the paraffin box and ex vivo gross tissues were imaged by the bench-top and handheld imaging modalities, and further compared with commercial microscope imaging results. The MEMS scanner-based handheld confocal imaging probe shows great promise as a potential clinical tool for oral cancer diagnosis and treatment.

  13. NEAR-INFRARED DYES: Probe Development and Applications in Optical Molecular Imaging

    PubMed Central

    Nolting, Donald D.; Gore, John C.; Pham, Wellington

    2010-01-01

    The recent emergence of optical imaging has brought forth a unique challenge for chemists: development of new biocompatible dyes that fluoresce in the near-infrared (NIR) region for optimal use in biomedical applications. This review describes the synthesis of NIR dyes and the design of probes capable of noninvasively imaging molecular events in small animal models. PMID:21822405

  14. Genetically Anchored Fluorescent Probes for Subcellular Specific Imaging of Hydrogen Sulfide

    PubMed Central

    Jiang, Xiqian; Sizovs, Antons; Wang, Meng C.; Provost, Christopher R.; Huang, Jia

    2016-01-01

    Imaging hydrogen sulfide (H2S) at the subcellular resolution will greatly improve the understanding of functions of this signaling molecule. Taking advantage of the protein labeling technologies, we report a general strategy for the development of organelle specific H2S probes, which enables sub-cellular H2S imaging essentially in any organelles of interest. PMID:26806071

  15. Wavelength-Dependent Differential Interference Contrast Microscopy: Selectively Imaging Nanoparticle Probes in Live Cells

    SciTech Connect

    Sun, Wei; Wang, Gufeng; Fang, Ning; and Yeung, Edward S.

    2009-11-15

    Gold and silver nanoparticles display extraordinarily large apparent refractive indices near their plasmon resonance (PR) wavelengths. These nanoparticles show good contrast in a narrow spectral band but are poorly resolved at other wavelengths in differential interference contrast (DIC) microscopy. The wavelength dependence of DIC contrast of gold/silver nanoparticles is interpreted in terms of Mie's theory and DIC working principles. We further exploit this wavelength dependence by modifying a DIC microscope to enable simultaneous imaging at two wavelengths. We demonstrate that gold/silver nanoparticles immobilized on the same glass slides through hybridization can be differentiated and imaged separately. High-contrast, video-rate images of living cells can be recorded both with and without illuminating the gold nanoparticle probes, providing definitive probe identification. Dual-wavelength DIC microscopy thus presents a new approach to the simultaneous detection of multiple probes of interest for high-speed live-cell imaging.

  16. Semiconducting Polymer Nanoparticles as Photoacoustic Molecular Imaging Probes in Living Mice

    PubMed Central

    Pu, Kanyi; Shuhendler, Adam J.; Jokerst, Jesse V.; Mei, Jianguo; Gambhir, Sanjiv S.; Bao, Zhenan; Rao, Jianghong

    2014-01-01

    Photoacoustic (PA) imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, PA molecular imaging probes have to be developed. Herein we introduce near infrared (NIR) light absorbing semiconducting polymer nanoparticles (SPNs) as a new class of contrast agents for PA molecular imaging. SPNs can produce stronger signal than commonly used single-wall carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph node PA mapping in living mice at a low systematic injection mass. Furthermore, SPNs possess high structural flexibility, narrow PA spectral profiles, and strong resistance to photodegradation and oxidation, which enables development of the first NIR ratiometric PA probe for in vivo real-time imaging of reactive oxygen species—vital chemical mediators of many diseases. These results demonstrate SPNs an ideal nanoplatform for developing PA molecular probes. PMID:24463363

  17. Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

    PubMed Central

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping; Peterson, Todd E.; Crews, Brenda C.; Marnett, Larry; Gore, John C.; Pham, Wellington

    2013-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and

  18. Probing the improbable: imaging carbon atoms in alumina

    SciTech Connect

    Marquis, E A; Yahia, Noor; Larson, David J.; Miller, Michael K; Todd, Richard

    2010-01-01

    Atom-probe tomography has proven very powerful to analyze the detailed structure and chemistry of metallic alloys and semiconductor structures while ceramic materials have remained outside its standard purview. In the current work, we demonstrate that bulk alumina can be quantitatively analyzed and microstructural features observed. The analysis of grain boundary carbon segregation - barely achievable by electron microscopy - opens the possibility of understanding the mechanistic effects of dopants on mechanical properties, fracture and wear properties of bulk oxides.

  19. Water-soluble BODIPY-based fluorescent probe for mitochondrial imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Sui, Binglin; Tang, Simon; Woodward, Adam W.; Kim, Bosung; Belfield, Kevin D.

    2016-03-01

    A new mitochondrial targeting fluorescent probe is designed, synthesized, characterized, and investigated. The probe is composed of three moieties, a BODIPY platform working as the fluorophore, two triphenylphosphonium (TPP) groups serving as mitochondrial targeting moiety, and two long highly hydrophilic polyethylene glycol (PEG) chains to increase its water solubility and reduce its cytotoxicity. As a mitochondria-selective fluorescent probe, the probe exhibits a series of desirable advantages compared with other reported fluorescent mitochondrial probes. It is readily soluble in aqueous media and emits very strong fluorescence. Photophysical determination experiments show that the photophysical properties of the probe are independent of solvent polarity and it has high quantum yield in various solvents examined. The probe also has good photostability and pH insensitivity over a broad pH range. Results obtained from cell viability tests indicate that the cytotoxicity of the probe is very low. Confocal fluorescence microscopy colocalization experiments reveal that this probe possesses excellent mitochondrial targeting ability and it is suitable for imaging mitochondria in living cells.

  20. Two-photon fluorescent probe derived from naphthalimide for cysteine detection and imaging in living cells.

    PubMed

    Liu, Yanbin; Liu, Yuwen; Liu, Wei; Liang, Shucai

    2015-02-25

    A maleimide coupling naphthalimide was reported as new two-photon fluorescent (TPF) probe for cysteine (Cys). The probe was weakly fluorescent itself due to the donor-excited photoinduced electron transfer (d-PET). After reaction with Cys, d-PET process was blocked and fluorescence enhancement of the probe was observed at 470 nm. The d-PET principle was rationalized by theoretical calculations with density functional theory and time-dependent density functional theory. Thiol-maleimide addition between the probe and Cys was confirmed by (1)H NMR and mass spectrum measurements. TPF analysis demonstrated a 24.7-fold emission increase of the probe induced by Cys upon excitation at 760 nm. The two-photon action cross-section of probe-Cys adduct at 760 nm reached 42 GM compared to 1.7 GM for free probe. The probe showed high sensitivity and selectivity to Cys over other potential interferences; especially it had the capability to discriminate Cys from glutathione and homocysteine. Through TPF imaging, the probe was successfully applied in the detection of Cys in living cells. PMID:25240143

  1. Two-photon fluorescent probe derived from naphthalimide for cysteine detection and imaging in living cells

    NASA Astrophysics Data System (ADS)

    Liu, Yanbin; Liu, Yuwen; Liu, Wei; Liang, Shucai

    2015-02-01

    A maleimide coupling naphthalimide was reported as new two-photon fluorescent (TPF) probe for cysteine (Cys). The probe was weakly fluorescent itself due to the donor-excited photoinduced electron transfer (d-PET). After reaction with Cys, d-PET process was blocked and fluorescence enhancement of the probe was observed at 470 nm. The d-PET principle was rationalized by theoretical calculations with density functional theory and time-dependent density functional theory. Thiol-maleimide addition between the probe and Cys was confirmed by 1H NMR and mass spectrum measurements. TPF analysis demonstrated a 24.7-fold emission increase of the probe induced by Cys upon excitation at 760 nm. The two-photon action cross-section of probe-Cys adduct at 760 nm reached 42 GM compared to 1.7 GM for free probe. The probe showed high sensitivity and selectivity to Cys over other potential interferences; especially it had the capability to discriminate Cys from glutathione and homocysteine. Through TPF imaging, the probe was successfully applied in the detection of Cys in living cells.

  2. Detection and Imaging of Superoxide in Roots by an Electron Spin Resonance Spin-Probe Method

    PubMed Central

    Warwar, Nasim; Mor, Avishai; Fluhr, Robert; Pandian, Ramasamy P.; Kuppusamy, Periannan; Blank, Aharon

    2011-01-01

    The detection, quantification, and imaging of short-lived reactive oxygen species, such as superoxide, in live biological specimens have always been challenging and controversial. Fluorescence-based methods are nonspecific, and electron spin resonance (ESR) spin-trapping methods require high probe concentrations and lack the capability for sufficient image resolution. In this work, a novel (to our knowledge), sensitive, small ESR imaging resonator was used together with a stable spin probe that specifically reacts with superoxide with a high reaction rate constant. This ESR spin-probe-based methodology was used to examine superoxide generated in a plant root as a result of an apical leaf injury. The results show that the spin probe rapidly permeated the plant's extracellular space. Upon injury of the plant tissue, superoxide was produced and the ESR signal decreased rapidly in the injured parts as well as in the distal part of the root. This is attributed to superoxide production and thus provides a means of quantifying the level of superoxide in the plant. The spin probe's narrow single-line ESR spectrum, together with the sensitive imaging resonator, facilitates the quantitative measurement of superoxide in small biological samples, such as the plant's root, as well as one-dimensional imaging along the length of the root. This type of methodology can be used to resolve many questions involving the production of apoplastic superoxide in plant biology. PMID:21943435

  3. Electromechanical Imaging of Biomaterials by Scanning Probe Microscopy

    SciTech Connect

    Rodriguez, Brian J; Kalinin, Sergei V; Shin, Junsoo; Jesse, Stephen; Grichko, V.; Thundat, Thomas George; Baddorf, Arthur P; Gruverman, A.

    2006-01-01

    The majority of calcified and connective tissues possess complex hierarchical structure spanning the length scales from nanometers to millimeters. Understanding the biological functionality of these materials requires reliable methods for structural imaging on the nanoscale. Here, we demonstrate an approach for electromechanical imaging of the structure of biological samples on the length scales from tens of microns to nanometers using piezoresponse force microscopy (PFM), which utilizes the intrinsic piezoelectricity of biopolymers such as proteins and polysaccharides as the basis for high-resolution imaging. Nanostructural imaging of a variety of protein-based materials, including tooth, antler, and cartilage, is demonstrated. Visualization of protein fibrils with sub-10 nm spatial resolution in a human tooth is achieved. Given the near-ubiquitous presence of piezoelectricity in biological systems, PFM is suggested as a versatile tool for micro- and nanostructural imaging in both connective and calcified tissues.

  4. Integrated flexible handheld probe for imaging and evaluation of iridocorneal angle

    NASA Astrophysics Data System (ADS)

    Shinoj, Vengalathunadakal K.; Murukeshan, Vadakke Matham; Baskaran, Mani; Aung, Tin

    2015-01-01

    An imaging probe is designed and developed by integrating a miniaturized charge-coupled diode camera and light-emitting diode light source, which enables evaluation of the iridocorneal region inside the eye. The efficiency of the prototype probe instrument is illustrated initially by using not only eye models, but also samples such as pig eye. The proposed methodology and developed scheme are expected to find potential application in iridocorneal angle documentation, glaucoma diagnosis, and follow-up management procedures.

  5. Asteroid (4179) Toutatis size determination via optical images observed by the Chang'e-2 probe

    NASA Astrophysics Data System (ADS)

    Liu, P.; Huang, J.; Zhao, W.; Wang, X.; Meng, L.; Tang, X.

    2014-07-01

    This work is a physical and statistical study of the asteroid (4179) Toutatis using the optical images obtained by a solar panel monitor of the Chang'e-2 probe on Dec. 13, 2012 [1]. In the imaging strategy, the camera is focused at infinity. This is specially designed for the probe with its solar panels monitor's principle axis pointing to the relative velocity direction of the probe and Toutatis. The imaging strategy provides a dedicated way to resolve the size by multi-frame optical images. The inherent features of the data are: (1) almost no rotation was recorded because of the 5.41-7.35 Earth-day rotation period and the small amount of elapsed imaging time, only minutes, make the object stay in the images in a fixed position and orientation; (2) the sharpness of the upper left boundary and the vagueness of lower right boundary resulting from the direction of SAP (Sun-Asteroid-Probe angle) cause a varying accuracy in locating points at different parts of Toutatis. A common view is that direct, accurate measurements of asteroid shapes, sizes, and pole positions are now possible for larger asteroids that can be spatially resolved using the Hubble Space Telescope or large ground-based telescopes equipped with adaptive optics. For a quite complex planetary/asteroid probe study, these measurements certainly need continuous validation via a variety of ways [2]. Based on engineering parameters of the probe during the fly-by, the target spatial resolving and measuring procedures are described in the paper. Results estimated are optical perceptible size on the flyby epoch under the solar phase angles during the imaging. It is found that the perceptible size measured using the optical observations and the size derived from the radar observations by Ostro et al.~in 1995 [3], are close to one another.

  6. Dual-illumination mode, wide-field probe imaging scheme for imaging irido-corneal angle region inside eye

    NASA Astrophysics Data System (ADS)

    Shinoj, V. K.; Murukeshan, V. M.; Hong, Jesmond; Baskaran, M.; Aung, Tin

    2015-07-01

    Noninvasive medical imaging techniques have generated great interest and high potential in the research and development of ocular imaging and follow up procedures. It is well known that angle closure glaucoma is one of the major ocular diseases/ conditions that causes blindness. The identification and treatment of this disease are related primarily to angle assessment techniques. In this paper, we illustrate a probe-based imaging approach to obtain the images of the angle region in eye. The proposed probe consists of a micro CCD camera and LED/NIR laser light sources and they are configured at the distal end to enable imaging of iridocorneal region inside eye. With this proposed dualmodal probe, imaging is performed in light (white visible LED ON) and dark (NIR laser light source alone) conditions and the angle region is noticeable in both cases. The imaging using NIR sources have major significance in anterior chamber imaging since it evades pupil constriction due to the bright light and thereby the artificial altering of anterior chamber angle. The proposed methodology and developed scheme are expected to find potential application in glaucoma disease detection and diagnosis.

  7. Ultrafast nanoscale imaging of surface charges by scanning resistive probe microscopy.

    SciTech Connect

    Ko, H.; Ryu, K.; Park, H.; Park, C.; Jeon, D.; Kim, Y. K.; Jung, J.; Min, D-K.; Kim, Y.; Lee, H. N.; Park, Y.; Shin, H.; Hong, S.

    2011-01-01

    Nanoscale manipulation of surface charges and their imaging are essential for understanding local electronic behaviors of polar materials and advanced electronic devices. Electrostatic force microscopy and Kelvin probe force microscopy have been extensively used to probe and image local surface charges responsible for electrodynamics and transport phenomena. However, they rely on the weak electric force modulation of cantilever that limits both spatial and temporal resolutions. Here we present a field effect transistor embedded probe that can directly image surface charges on a length scale of 25 nm and a time scale of less than 125 {mu}s. On the basis of the calculation of net surface charges in a 25 nm diameter ferroelectric domain, we could estimate the charge density resolution to be as low as 0.08 {mu}C/cm{sup 2}, which is equivalent to 1/20 electron per nanometer square at room temperature.

  8. Single-body lensed-fiber scanning probe actuated by magnetic force for optical imaging.

    PubMed

    Min, Eun Jung; Na, Jihoon; Ryu, Seon Young; Lee, Byeong Ha

    2009-06-15

    We propose a fiber-based hand-held scanning probe suitable for the sample arm of an optical imaging system including optical coherence tomography. To achieve compactness, a single-body lensed-fiber and a solenoid actuator were utilized. The focusing lens of the probe was directly formed onto the distal end of a fiber, which eliminated the need for additional optical components and optical alignment. A ferromagnetic iron bead was glued onto the middle of the fiber to enable actuation by magnetic force, which allowed easy fabrication and good practicality. The fiber piece having the built-in fiber lens was forced to oscillate in its resonant frequency. With the implemented probe, optical coherence tomography images of a human fingertip and a pearl were obtained at an imaging speed of 30 frames/s over a scanning range of 4 mm. PMID:19529740

  9. A Bridge Not Too Far: Linking Disciplines Through Molecular Imaging Probes.

    PubMed

    Valliant, John F

    2016-09-01

    The field of nuclear medicine will rely increasingly on the discovery, proper evaluation, and clinical use of molecular imaging probes and on collaborations. Collaborations will include new initiatives among experts already involved in the field and with researchers, technologists, and clinicians from different areas of science and medicine. This article serves to highlight some of the opportunities in which molecular imaging and nuclear medicine in conjunction with probe development, new imaging technologies, and multidisciplinary collaborations can have a significant impact on health care and basic science from the perspective of a person involved in probe development. The article emphasizes breast cancer, but the concepts are readily applied to other areas of medicine and medical research. PMID:27601414

  10. High Resolution Tissue Imaging Using the Single-probe Mass Spectrometry under Ambient Conditions

    NASA Astrophysics Data System (ADS)

    Rao, Wei; Pan, Ning; Yang, Zhibo

    2015-06-01

    Ambient mass spectrometry imaging (MSI) is an emerging field with great potential for the detailed spatial analysis of biological samples with minimal pretreatment. We have developed a miniaturized sampling and ionization device, the Single-probe, which uses in-situ surface micro-extraction to achieve high detection sensitivity and spatial resolution during MSI experiments. The Single-probe was coupled to a Thermo LTQ Orbitrap XL mass spectrometer and was able to create high spatial and high mass resolution MS images at 8 ± 2 and 8.5 μm on flat polycarbonate microscope slides and mouse kidney sections, respectively, which are among the highest resolutions available for ambient MSI techniques. Our proof-of-principle experiments indicate that the Single-probe MSI technique has the potential to obtain ambient MS images with very high spatial resolutions with minimal sample preparation, which opens the possibility for subcellular ambient tissue MSI to be performed in the future.

  11. Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review

    PubMed Central

    Kepe, Vladimir; Moghbel, Mateen C.; Långström, Bengt; Zaidi, Habib; Vinters, Harry V.; Huang, Sung-Cheng; Satyamurthy, Nagichettiar; Doudet, Doris; Mishani, Eyal; Cohen, Robert M.; Høilund-Carlsen, Poul F.; Alavi, Abass; Barrio, Jorge R.

    2013-01-01

    The rapidly rising prevalence and cost of Alzheimer’s disease (AD) in recent decades has made the imaging of amyloid-β (Aβ) deposits the focus of intense research. Several amyloid imaging probes with purported specificity for Aβ plaques are currently at various stages of FDA approval. However, a number of factors appear to preclude these probes from clinical utilization. As the available “amyloid specific” PET imaging probes have failed to demonstrate diagnostic value and have shown limited utility for monitoring therapeutic interventions in humans, a debate on their significance has emerged. The aim of this review is to identify and discuss critically the scientific issues contributing to the extensive inconsistencies reported in the literature on their purported in vivo amyloid specificity and potential utilization in patients. PMID:23648516

  12. Novel PET/SPECT Probes for Imaging of Tau in Alzheimer's Disease

    PubMed Central

    Ono, Masahiro

    2015-01-01

    As the world's population ages, the number of patients with Alzheimer's disease (AD) is predicted to increase rapidly. The presence of neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau protein, is one of the neuropathological hallmarks of AD brain. Since the presence of NFTs is well correlated with neurodegeneration and cognitive decline in AD, imaging of tau using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is useful for presymptomatic diagnosis and monitoring of the progression of AD. Therefore, novel PET/SPECT probes for the imaging of tau have been developed. More recently, several probes were tested clinically and evaluated for their utility. This paper reviews the current state of research on the development and evaluation of PET/SPECT probes for the imaging of tau in AD brain. PMID:25879047

  13. Turn-on trivalent cation selective chemodosimetric probe to image native cellular iron pools.

    PubMed

    Venkateswarulu, M; Mukherjee, Trinetra; Mukherjee, Subhrakanti; Koner, Rik Rani

    2014-04-14

    A new turn-on cell permeable chemodosimetric probe has been developed and its application in the selective detection of trivalent cations (Fe(3+)/Cr(3+)/Al(3+)) at a sub-nanomolar level has been demonstrated. The selectivity of over a broad spectrum of mono- and divalent metal ions was established using fluorescence spectroscopy. Moreover, the changes in the absorption spectra of in the presence of trivalent cations enabled the most bio-relevant metal ion Fe(3+) over Cr(3+)/Al(3+) to be distinguished. The probe was found to be successful in the fluorescence imaging of native cellular iron pools. The fluorescence imaging of the native iron pools of banana pith further supported the high sensitivity of towards Fe(3+) present in living systems. To the best of our knowledge, this is the first example of a turn-on chemodosimetric probe to image native cellular Fe(3+) pools. PMID:24534800

  14. Automatic guidance of an ultrasound probe by visual servoing based on B-mode image moments.

    PubMed

    Mebarki, Rafik; Krupa, Alexandre; Collewet, Christophe

    2008-01-01

    We propose a new visual servo approach to automatically control in real-time the full motion of a 2D ultrasound (US) probe held by a medical robot in order to reach a desired image of motionless soft tissue object in B-mode ultrasound imaging. Combinations of image moments of the observed object cross-section are used as feedback information in the visual control scheme. These visual features are extracted in real-time from the US image thanks to a fast image segmentation method. Simulations performed with a static US volume containing an egg-shaped object, and ex-vivo experiments using a robotized US probe that interacts with a motionless rabbit heart immersed in water, show the validity of this new approach and its robustness to different perturbations. This method shows promise for a variety of US-guided medical interventions that require real-time servoing. PMID:18982623

  15. 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.

  16. Aminopeptidase N/CD13 targeting fluorescent probes: synthesis and application to tumor cell imaging.

    PubMed

    Zhang, Zhouen; Harada, Hiroshi; Tanabe, Kazuhito; Hatta, Hiroshi; Hiraoka, Masahiro; Nishimoto, Sei-ichi

    2005-11-01

    A family of fluorescein-peptide conjugates (CNP1-3) for aminopeptidase N (APN/CD13) targeting fluorescent probes were designed and synthesized. Among the three conjugates, CNP1 bearing tumor-homing cyclic peptide CNGRC, could selectively label APN/CD13 over-expressing on the surface of tumor cells of HT-1080, as identified by means of fluorescent microscopic cell imaging. CNP1 was shown to be a promising fluorescent probe applicable to tumor-targeting molecular imaging. PMID:15885853

  17. Probing Nearby Planetary Systems by Debris Disk Imaging

    NASA Technical Reports Server (NTRS)

    Stapelfeldt, Karl

    2011-01-01

    Many main-sequence stars possess tenuous circumstellar dust clouds believed to trace extrasolar analogs of the Sun's asteroidand Kuiper Belts. While most of these "debris disks" are known only from far-infrared photometry, a growing number of them are now spatially resolved. In this talk, I'll review what is currently known about the structure of debris disks. Using images from the Hubble, Spitzer, and Herschel Space Telescopes, I will show how modeling of these resolved systems can place strong constraints on dust particle properties in the disks. Some of the disks show disturbed structures suggestive of planetary perturbations: specific cases will be discussed where directly-imaged exoplanets are clearly affecting debris disk structure. I'll conclude with thoughts on the future of high contrast exoplanet imaging.

  18. In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe

    PubMed Central

    Zhang, Shaojuan; Shao, Pin; Ling, Xiaoxi; Yang, Ling; Hou, Weizhou; Thorne, Steve H; Beaino, Wissam; Anderson, Carolyn J; Ding, Ying; Bai, Mingfeng

    2015-01-01

    Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe. Herein, we report the first in vivo CB2R-targeted NIR inflammation imaging study using a synthetic fluorescent probe developed in our laboratory, NIR760-mbc94. In vitro binding assay and fluorescence microscopy study indicate NIR760-mbc94 specifically binds towards CB2R in mouse RAW264.7 macrophage cells. Furthermore, in vivo imaging was performed using a Complete Freund’s Adjuvant (CFA)-induced inflammation mouse model. NIR760-mbc94 successfully identified inflamed tissues and the probe uptake was blocked by a CB2R ligand, SR144528. Additionally, immunofluorescence staining in cryosectioned tissues validated the NIR760-mbc94 uptake in inflamed tissues. In conclusion, this study reports the first in vivo CB2R-targeted inflammation imaging using an NIR fluorescent probe. Specific targeting of NIR760-mbc94 has been demonstrated in macrophage cells, as well as a CFA-induced inflammation mouse model. The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases. PMID:26069858

  19. The development and evaluation of head probes for optical imaging of the infant head

    NASA Astrophysics Data System (ADS)

    Branco, Gilberto

    The objective of this thesis was to develop and evaluate optical imaging probes for mapping oxygenation and haemodynamic changes in the newborn infant brain. Two imaging approaches are being developed at University College London (UCL): optical topography (surface mapping of the cortex) and optical tomography (volume imaging). Both have the potential to provide information about the function of the normal brain and about a variety of neurophysiologies! abnormalities. Both techniques require an array of optical fibres/fibre bundles to be held in contact with the head, for periods of time from tens of seconds to an hour or more. The design of suitable probes must ensure the comfort and safety of the subject, and provide measurements minimally sensitive to external sources of light and patient motion. A series of prototype adaptable helmets were developed for optical tomography of the premature infant brain using the UCL 32-channel time-resolved system. They were required to attach 32 optical fibre bundles over the infant scalp, and were designed to accommodate infants with a variety of head shapes and sizes, aged between 24-weeks gestational age and term. Continual improvements to the helmet design were introduced following the evaluation of each prototype on infants in the hospital. Data were acquired to generate images revealing the concentration and oxygenation of blood in the brain, and the response of the brain to sensory stimulation. This part of the project also involved designing and testing new methods of acquiring calibration data using reference phantoms. The second focus of the project was the development of probes for use with the UCL frequency-multiplexed near-infrared topography system. This is being used to image functional activation in the infant cortex. A series of probes were developed and experiments were conducted to evaluate their sensitivity to patient motion and to compression of the probe. The probes have been used for a variety of

  20. Advances of molecular imaging probes for the diagnosis of Alzheimer's disease.

    PubMed

    Zhou, Ming; Wang, Xiaobo; Liu, Zhiguo; Yu, Lun; Hu, Shuo; Chen, Lizhang; Zeng, Wenbin

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains and it becomes the most common cause of dementia in the elderly. There is an urgent need for the early diagnosis and treatment of AD to ease caregiver burden and medical costs, as well as improve patients' living activities associated with the dramatic increasing number of affected individuals. Molecular imaging with target-specific probes is contributing to identify the underlying biology in AD, which benefits to the early diagnosis of AD and the evaluation of anti-AD therapy. Molecular imaging probes, such as (11)C-PIB, (11)C-MP4A, (18)F-AV-45, and (11)F-FDG, can selectively bind to special bimolecular of AD or accurately accumulate at the location of damage areas, thus become an edge tool for a better management of the diseases in the clinical practice and new drug development. In the past decades, a large variety of probes is being developed and tested to be useful for the early and accurate diagnosis of Alzheimer's disease, patient selection for disease-modifying therapeutic trials and monitoring the effect of anti-amyloid therapy. Since imaging probes may also help to guide physicians to identify those patients that could best benefit from a given therapeutic regimen, dose, or duration of drug, this paper is to present a perspective of the available imaging probes for AD, classified on different modalities. Meanwhile, recent advances of those probes that have been selected for clinical trials and are at the different stages of the US Food and Drugs Administration (FDA) approval are outlined. Additionally, future directions and specific application of imaging strategies designed for both diagnosis and treatment for AD are discussed. PMID:24484277

  1. Design and Synthesis of Near-infrared Fluorescent Probes for Imaging of Biological Nitroxyl.

    PubMed

    Tan, Yi; Liu, Ruochuan; Zhang, Huatang; Peltier, Raoul; Lam, Yun-Wah; Zhu, Qing; Hu, Yi; Sun, Hongyan

    2015-01-01

    Nitroxyl (HNO), the reduced and protonated form of nitric oxide (NO), has recently been identified as an interesting and important signaling molecule in biological systems. However, research on its biosynthesis and bioactivities are hampered by the lack of versatile HNO detection methods applicable to living cells. In this report, two new near-infrared (NIR) probes were designed and synthesized for HNO imaging in living cells. One of the probes was found to display high sensitivity towards HNO, with up to 67-fold of fluorescence increment after reaction with HNO. The detection limit was determined to be as low as 0.043 μM. The probe displayed high selectivity towards HNO over other biologically related species including metal ions, reactive oxygen species, reactive nitrogen species and reactive sulfur species. Furthermore, the probe was shown to be suitable for imaging of exogenous and endogenous HNO in living cells. Interestingly, the probe was found to be mainly localized in lysosomes. We envision that the new NIR probe described here will serve as a useful tool for further elucidation of the intricate roles of HNO in living cells. PMID:26584764

  2. Design and Synthesis of Near-infrared Fluorescent Probes for Imaging of Biological Nitroxyl

    PubMed Central

    Tan, Yi; Liu, Ruochuan; Zhang, Huatang; Peltier, Raoul; Lam, Yun-Wah; Zhu, Qing; Hu, Yi; Sun, Hongyan

    2015-01-01

    Nitroxyl (HNO), the reduced and protonated form of nitric oxide (NO), has recently been identified as an interesting and important signaling molecule in biological systems. However, research on its biosynthesis and bioactivities are hampered by the lack of versatile HNO detection methods applicable to living cells. In this report, two new near-infrared (NIR) probes were designed and synthesized for HNO imaging in living cells. One of the probes was found to display high sensitivity towards HNO, with up to 67-fold of fluorescence increment after reaction with HNO. The detection limit was determined to be as low as 0.043 μM. The probe displayed high selectivity towards HNO over other biologically related species including metal ions, reactive oxygen species, reactive nitrogen species and reactive sulfur species. Furthermore, the probe was shown to be suitable for imaging of exogenous and endogenous HNO in living cells. Interestingly, the probe was found to be mainly localized in lysosomes. We envision that the new NIR probe described here will serve as a useful tool for further elucidation of the intricate roles of HNO in living cells. PMID:26584764

  3. Investigation of a MMP-2 Activity-Dependent Anchoring Probe for Nuclear Imaging of Cancer

    PubMed Central

    Temma, Takashi; Hanaoka, Hirofumi; Yonezawa, Aki; Kondo, Naoya; Sano, Kohei; Sakamoto, Takeharu; Seiki, Motoharu; Ono, Masahiro; Saji, Hideo

    2014-01-01

    Purpose Since matrix metalloproteinase-2 (MMP-2) is an important marker of tumor malignancy, we developed an original drug design strategy, MMP-2 activity dependent anchoring probes (MDAP), for use in MMP-2 activity imaging, and evaluated the usefulness of this probe in in vitro and in vivo experiments. Methods We designed and synthesized MDAP1000, MDAP3000, and MDAP5000, which consist of 4 independent moieties: RI unit (111In hydrophilic chelate), MMP-2 substrate unit (short peptide), anchoring unit (alkyl chain), and anchoring inhibition unit (polyethylene glycol (PEGn; where n represents the approximate molecular weight, n = 1000, 3000, and 5000). Probe cleavage was evaluated by chromatography after MMP-2 treatment. Cellular uptake of the probes was then measured. Radioactivity accumulation in tumor xenografts was evaluated after intravenous injection of the probes, and probe cleavage was evaluated in tumor homogenates. Results MDAP1000, MDAP3000, and MDAP5000 were cleaved by MMP-2 in a concentration-dependent manner. MDAP3000 pretreated with MMP-2 showed higher accumulation in tumor cells, and was completely blocked by additional treatment with an MMP inhibitor. MDAP3000 exhibited rapid blood clearance and a high tumor accumulation after intravenous injection in a rodent model. Furthermore, pharmacokinetic analysis revealed that MDAP3000 exhibited a considerably slow washout rate from tumors to blood. A certain fraction of cleaved MDAP3000 existed in tumor xenografts in vivo. Conclusions The results indicate the possible usefulness of our MDAP strategy for tumor imaging. PMID:25010662

  4. Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging.

    PubMed

    Chen, Xu; Xu, Xiaoyun; McCormick, Daniel T; Wong, Kelvin; Wong, Stephen T C

    2015-07-01

    We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery. PMID:26203361

  5. Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging

    PubMed Central

    Chen, Xu; Xu, Xiaoyun; McCormick, Daniel T.; Wong, Kelvin; Wong, Stephen T.C.

    2015-01-01

    We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery. PMID:26203361

  6. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    PubMed Central

    Meng, Qingqing; Li, Zheng

    2013-01-01

    Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained. PMID:23533377

  7. Imaging via complete cantilever dynamic detection: general dynamic mode imaging and spectroscopy in scanning probe microscopy.

    PubMed

    Somnath, Suhas; Collins, Liam; Matheson, Michael A; Sukumar, Sreenivas R; Kalinin, Sergei V; Jesse, Stephen

    2016-10-14

    We develop and implement a multifrequency spectroscopy and spectroscopic imaging mode, referred to as general dynamic mode (GDM), that captures the complete spatially- and stimulus dependent information on nonlinear cantilever dynamics in scanning probe microscopy (SPM). GDM acquires the cantilever response including harmonics and mode mixing products across the entire broadband cantilever spectrum as a function of excitation frequency. GDM spectra substitute the classical measurements in SPM, e.g. amplitude and phase in lock-in detection. Here, GDM is used to investigate the response of a purely capacitively driven cantilever. We use information theory techniques to mine the data and verify the findings with governing equations and classical lock-in based approaches. We explore the dependence of the cantilever dynamics on the tip-sample distance, AC and DC driving bias. This approach can be applied to investigate the dynamic behavior of other systems within and beyond dynamic SPM. GDM is expected to be useful for separating the contribution of different physical phenomena in the cantilever response and understanding the role of cantilever dynamics in dynamic AFM techniques. PMID:27607339

  8. Imaging via complete cantilever dynamic detection: General dynamic mode imaging and spectroscopy in scanning probe microscopy

    DOE PAGESBeta

    Somnath, Suhas; Collins, Liam; Matheson, Michael A.; Sukumar, Sreenivas R.; Kalinin, Sergei V.; Jesse, Stephen

    2016-09-08

    We develop and implement a multifrequency spectroscopy and spectroscopic imaging mode, referred to as general dynamic mode (GDM), that captures the complete spatially- and stimulus dependent information on nonlinear cantilever dynamics in scanning probe microscopy (SPM). GDM acquires the cantilever response including harmonics and mode mixing products across the entire broadband cantilever spectrum as a function of excitation frequency. GDM spectra substitute the classical measurements in SPM, e.g. amplitude and phase in lock-in detection. Here, GDM is used to investigate the response of a purely capacitively driven cantilever. We use information theory techniques to mine the data and verify themore » findings with governing equations and classical lock-in based approaches. We explore the dependence of the cantilever dynamics on the tip–sample distance, AC and DC driving bias. This approach can be applied to investigate the dynamic behavior of other systems within and beyond dynamic SPM. In conclusion, GDM is expected to be useful for separating the contribution of different physical phenomena in the cantilever response and understanding the role of cantilever dynamics in dynamic AFM techniques.« less

  9. Benzothiadiazole Derivatives as Fluorescence Imaging Probes: Beyond Classical Scaffolds.

    PubMed

    Neto, Brenno A D; Carvalho, Pedro H P R; Correa, Jose R

    2015-06-16

    This Account describes the origins, features, importance, and trends of the use of fluorescent small-molecule 2,1,3-benzothiadiazole (BTD) derivatives as a new class of bioprobes applied to bioimaging analyses of several (live and fixed) cell types. BTDs have been successfully used as probes for a plethora of biological analyses for only a few years, and the impressive responses obtained by using this important class of heterocycle are fostering the development of new fluorescent BTDs and expanding the biological applications of such derivatives. The first use of a fluorescent small-molecule BTD derivative as a selective cellular probe dates back to 2010, and since then impressive advances have been described by us and others. The well-known limitations of classical scaffolds urged the development of new classes of bioprobes. Although great developments have been achieved by using classical scaffolds such as coumarins, BODIPYs, fluoresceins, rhodamines, cyanines, and phenoxazines, there is still much to be done, and BTDs aim to succeed where these dyes have shown their limitations. Important organelles and cell components such as nuclear DNA, mitochondria, lipid droplets, and others have already been successfully labeled by fluorescent small-molecule BTD derivatives. New technological systems that use BTDs as the fluorophores for bioimaging experiments have been described in recent scientific literature. The successful application of BTDs as selective bioprobes has led some groups to explore their potential for use in studying membrane pores or tumor cells under hypoxic conditions. Finally, BTDs have also been used as fluorescent tags to investigate the action mechanism of some antitumor compounds. The attractive photophysical data typically observed for π-extended BTD derivatives is fostering interest in the use of this new class of bioprobes. Large Stokes shifts, large molar extinction coefficients, high quantum yields, high stability when stored in solution or

  10. Optimization of a gamma imaging probe for axillary sentinel lymph mapping

    NASA Astrophysics Data System (ADS)

    Georgiou, M.; Loudos, G.; Stratos, D.; Papadimitroulas, P.; Liakou, P.; Georgoulias, P.

    2012-09-01

    Sentinel lymph node (SLN) mapping is a technique for assessing whether early-stage invasive breast cancer has metastasized, thus determining prognosis and treatment options. SLN identification is achieved using the blue-dye and radioactive colloids techniques, which are sometimes combined with lymphoscintigraphy. Furthermore, intra-operative gamma acoustic probes, as well as gamma imaging probes are used during surgery. The purpose of this study is the construction of a gamma probe for sentinel lymph node imaging and its optimization in terms of sensitivity with respect to spatial resolution. The reference probe has small field of view (2.5 × 2.5 cm2) and is based on a position sensitive photomultiplier tube (PSPMT) coupled to a pixellated CsI(Tl) scintillator. Following experimental validation, we simulated the system using the GATE Monte Carlo toolkit (GATE v6.1) and modeled various collimator geometries, in order to evaluate their performance and propose the optimal configuration. The constraints of the proposed gamma imaging probe are i) sensitivity close to 2 cps/kBq and ii) spatial resolution equal to 6 mm at 2 cm source-to-collimator distance and ~ 10 mm at 5 cm. An integrated structure that achieves those requirements is a tungsten collimator with 2 × 2 mm2square holes, 16 mm thickness, 0.15 mm septa, where each CsI(Tl) 2 × 2 × 5 mm3 crystal pixel is placed inside the collimator.

  11. Continuously zoom imaging probe for the multi-resolution foveated laparoscope.

    PubMed

    Qin, Yi; Hua, Hong

    2016-04-01

    In modern minimally invasive surgeries (MIS), standard laparoscopes suffer from the tradeoff between the spatial resolution and field of view (FOV). The inability of simultaneously acquiring high-resolution images for accurate operation and wide-angle overviews for situational awareness limits the efficiency and outcome of the MIS. A dual view multi-resolution foveated laparoscope (MRFL) which can simultaneously provide the surgeon with a high-resolution view as well as a wide-angle overview was proposed and demonstrated to have great potential for improving the MIS. Although experiment results demonstrated the high-magnification probe has an adequate magnification for viewing surgical details, the dual-view MRFL is limited to two fixed levels of magnifications. A fine adjustment of the magnification is highly desired for obtaining high resolution images with desired field coverage. In this paper, a high magnification probe with continuous zooming capability without any mechanical moving parts is demonstrated. By taking the advantages of two electrically tunable lenses, one for optical zoom and the other for image focus compensation, the optical magnification of the high-magnification probe varies from 2 × to 3 × compared with that of the wide-angle probe, while the focused object position stays the same as the wide-angle probe. The optical design and the tunable lens analysis are presented, followed by prototype demonstration. PMID:27446645

  12. Continuously zoom imaging probe for the multi-resolution foveated laparoscope

    PubMed Central

    Qin, Yi; Hua, Hong

    2016-01-01

    In modern minimally invasive surgeries (MIS), standard laparoscopes suffer from the tradeoff between the spatial resolution and field of view (FOV). The inability of simultaneously acquiring high-resolution images for accurate operation and wide-angle overviews for situational awareness limits the efficiency and outcome of the MIS. A dual view multi-resolution foveated laparoscope (MRFL) which can simultaneously provide the surgeon with a high-resolution view as well as a wide-angle overview was proposed and demonstrated to have great potential for improving the MIS. Although experiment results demonstrated the high-magnification probe has an adequate magnification for viewing surgical details, the dual-view MRFL is limited to two fixed levels of magnifications. A fine adjustment of the magnification is highly desired for obtaining high resolution images with desired field coverage. In this paper, a high magnification probe with continuous zooming capability without any mechanical moving parts is demonstrated. By taking the advantages of two electrically tunable lenses, one for optical zoom and the other for image focus compensation, the optical magnification of the high-magnification probe varies from 2 × to 3 × compared with that of the wide-angle probe, while the focused object position stays the same as the wide-angle probe. The optical design and the tunable lens analysis are presented, followed by prototype demonstration. PMID:27446645

  13. Note: Seesaw actuation of atomic force microscope probes for improved imaging bandwidth and displacement range

    SciTech Connect

    Torun, H.; Torello, D.; Degertekin, F. L.

    2011-08-15

    The authors describe a method of actuation for atomic force microscope (AFM) probes to improve imaging speed and displacement range simultaneously. Unlike conventional piezoelectric tube actuation, the proposed method involves a lever and fulcrum ''seesaw'' like actuation mechanism that uses a small, fast piezoelectric transducer. The lever arm of the seesaw mechanism increases the apparent displacement range by an adjustable gain factor, overcoming the standard tradeoff between imaging speed and displacement range. Experimental characterization of a cantilever holder implementing the method is provided together with comparative line scans obtained with contact mode imaging. An imaging bandwidth of 30 kHz in air with the current setup was demonstrated.

  14. Design, fabrication, and characterization of thermoplastic microlenses for fiber-optic probe imaging.

    PubMed

    Shinoj, V K; Murukeshan, V M; Tor, S B; Loh, N H; Lye, S W

    2014-02-20

    Microlens-ended fibers could find great usefulness in future biomedical applications, particularly in endoscopic imaging applications. In this context, this paper focuses on microlens-attached specialty optical fibers such as imaging fiber that can be used for probe imaging applications. Stand-alone self-aligned polymer microlenses have been fabricated by microcompression molding. The fabrication parameters have been optimized for different materials, such as poly(methyl methacrylate) (PMMA), polycarbonate (PC Lexan 123R), Zeonor 1060R (ZNR), and Topas COC. A comparison study of the focusing and spatial resolution of the fabricated lenses is performed prior to employing them for fiber-optic fluorescence imaging applications. PMID:24663305

  15. Etchable plasmonic nanoparticle probes to image and quantify cellular internalization

    PubMed Central

    Braun, Gary B.; Friman, Tomas; Pang, Hong-Bo; Pallaoro, Alessia; de Mendoza, Tatiana Hurtado; Willmore, Anne-Mari A.; Kotamraju, Venkata Ramana; Mann, Aman P.; She, Zhi-Gang; Sugahara, Kazuki N.; Reich, Norbert O.; Teesalu, Tambet; Ruoslahti, Erkki

    2014-01-01

    There is considerable interest in using nanoparticles as labels or to deliver drugs and other bioactive compounds to cells in vitro and in vivo. Fluorescent imaging, commonly used to study internalization and subcellular localization of nanoparticles, does not allow unequivocal distinction between cell surface-bound and internalized particles, since there is no methodology to turn particles ‘off.’ We have developed a simple technique to rapidly remove silver nanoparticles outside living cells leaving only the internalized pool for imaging or quantification. The silver nanoparticle (AgNP) etching is based on the sensitivity of Ag to a hexacyanoferrate/thiosulfate redox-based destain solution. In demonstration of the technique we present a new class of multicolored plasmonic nanoprobes comprising dye-labeled AgNPs that are exceptionally bright and photostable, carry peptides as model targeting ligands, can be etched rapidly and with minimal toxicity in mice and that show tumour uptake in vivo. PMID:24907927

  16. Superresolution Imaging of Amyloid Fibrils with Binding-Activated Probes

    PubMed Central

    2013-01-01

    Protein misfolding into amyloid-like aggregates underlies many neurodegenerative diseases. Thus, insights into the structure and function of these amyloids will provide valuable information on the pathological mechanisms involved and aid in the design of improved drugs for treating amyloid-based disorders. However, determining the structure of endogenous amyloids at high resolution has been difficult. Here we employ binding-activated localization microscopy (BALM) to acquire superresolution images of α-synuclein amyloid fibrils with unprecedented optical resolution. We propose that BALM imaging can be extended to study the structure of other amyloids, for differential diagnosis of amyloid-related diseases and for discovery of drugs that perturb amyloid structure for therapy. PMID:23594172

  17. Cross-talk artefacts in Kelvin probe force microscopy imaging: A comprehensive study

    NASA Astrophysics Data System (ADS)

    Barbet, S.; Popoff, M.; Diesinger, H.; Deresmes, D.; Théron, D.; Mélin, T.

    2014-04-01

    We provide in this article a comprehensive study of the role of ac cross-talk effects in Kelvin Probe Force Microscopy (KPFM), and their consequences onto KPFM imaging. The dependence of KPFM signals upon internal parameters such as the cantilever excitation frequency and the projection angle of the KPFM feedback loop is reviewed, and compared with an analytical model. We show that ac cross-talks affect the measured KPFM signals as a function of the tip-substrate distance, and thus hamper the measurement of three-dimensional KPFM signals. The influence of ac cross-talks is also demonstrated onto KPFM images, in the form of topography footprints onto KPFM images, especially in the constant distance (lift) imaging mode. Our analysis is applied to unambiguously probe charging effects in tobacco mosaic viruses (TMVs) in ambient air. TMVs are demonstrated to be electrically neutral when deposited on silicon dioxide surfaces, but inhomogeneously negatively charged when deposited on a gold surface.

  18. Near-infrared fluorescent probes for imaging of amyloid plaques in Alzheimer׳s disease.

    PubMed

    Tong, Hongjuan; Lou, Kaiyan; Wang, Wei

    2015-01-01

    One of the early pathological hallmarks of Alzheimer׳s disease (AD) is the deposition of amyloid-β (Aβ) plaques in the brain. There has been a tremendous interest in the development of Aβ plaques imaging probes for early diagnosis of AD in the past decades. Optical imaging, particularly near-infrared fluorescence (NIRF) imaging, has emerged as a safe, low cost, real-time, and widely available technique, providing an attractive approach for in vivo detection of Aβ plaques among many different imaging techniques. In this review, we provide a brief overview of the state-of-the-art development of NIRF Aβ probes and their in vitro and in vivo applications with special focus on design strategies and optical, binding, and brain-kinetic properties. PMID:26579421

  19. A simple and non-contact optical imaging probe for evaluation of corneal diseases

    NASA Astrophysics Data System (ADS)

    Hong, Xun Jie Jeesmond; Shinoj, V. K.; Murukeshan, V. M.; Baskaran, M.; Aung, T.

    2015-09-01

    Non-contact imaging techniques are preferred in ophthalmology. Corneal disease is one of the leading causes of blindness worldwide, and a possible way of detection is by analyzing the shape and optical quality of the cornea. Here, a simple and cost-effective, non-contact optical probe system is proposed and illustrated. The probe possesses high spatial resolutions and is non-dependent on coupling medium, which are significant for a clinician and patient friendly investigation. These parameters are crucial, when considering an imaging system for the objective diagnosis and management of corneal diseases. The imaging of the cornea is performed on ex vivo porcine samples and subsequently on small laboratory animals, in vivo. The clinical significance of the proposed study is validated by performing imaging of the New Zealand white rabbit's cornea infected with Pseudomonas.

  20. Cyanine-based probe\\tag-peptide pair fluorescence protein imaging and fluorescence protein imaging methods

    DOEpatents

    Mayer-Cumblidge, M. Uljana; Cao, Haishi

    2013-01-15

    A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl.sub.3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

  1. All-optical pulse-echo ultrasound probe for intravascular imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Colchester, Richard J.; Noimark, Sacha; Mosse, Charles A.; Zhang, Edward Z.; Beard, Paul C.; Parkin, Ivan P.; Papakonstantinou, Ioannis; Desjardins, Adrien E.

    2016-02-01

    High frequency ultrasound probes such as intravascular ultrasound (IVUS) and intracardiac echocardiography (ICE) catheters can be invaluable for guiding minimally invasive medical procedures in cardiology such as coronary stent placement and ablation. With current-generation ultrasound probes, ultrasound is generated and received electrically. The complexities involved with fabricating these electrical probes can result in high costs that limit their clinical applicability. Additionally, it can be challenging to achieve wide transmission bandwidths and adequate wideband reception sensitivity with small piezoelectric elements. Optical methods for transmitting and receiving ultrasound are emerging as alternatives to their electrical counterparts. They offer several distinguishing advantages, including the potential to generate and detect the broadband ultrasound fields (tens of MHz) required for high resolution imaging. In this study, we developed a miniature, side-looking, pulse-echo ultrasound probe for intravascular imaging, with fibre-optic transmission and reception. The axial resolution was better than 70 microns, and the imaging depth in tissue was greater than 1 cm. Ultrasound transmission was performed by photoacoustic excitation of a carbon nanotube/polydimethylsiloxane composite material; ultrasound reception, with a fibre-optic Fabry-Perot cavity. Ex vivo tissue studies, which included healthy swine tissue and diseased human tissue, demonstrated the strong potential of this technique. To our knowledge, this is the first study to achieve an all-optical pulse-echo ultrasound probe for intravascular imaging. The potential for performing all-optical B-mode imaging (2D and 3D) with virtual arrays of transmit/receive elements, and hybrid imaging with pulse-echo ultrasound and photoacoustic sensing are discussed.

  2. Pre-Assembly of Near-Infrared Fluorescent Multivalent Molecular Probes for Biological Imaging.

    PubMed

    Peck, Evan M; Battles, Paul M; Rice, Douglas R; Roland, Felicia M; Norquest, Kathryn A; Smith, Bradley D

    2016-05-18

    A programmable pre-assembly method is described and shown to produce near-infrared fluorescent molecular probes with tunable multivalent binding properties. The modular assembly process threads one or two copies of a tetralactam macrocycle onto a fluorescent PEGylated squaraine scaffold containing a complementary number of docking stations. Appended to the macrocycle periphery are multiple copies of a ligand that is known to target a biomarker. The structure and high purity of each threaded complex was determined by independent spectrometric methods and also by gel electrophoresis. Especially helpful were diagnostic red-shift and energy transfer features in the absorption and fluorescence spectra. The threaded complexes were found to be effective multivalent molecular probes for fluorescence microscopy and in vivo fluorescence imaging of living subjects. Two multivalent probes were prepared and tested for targeting of bone in mice. A pre-assembled probe with 12 bone-targeting iminodiacetate ligands produced more bone accumulation than an analogous pre-assembled probe with six iminodiacetate ligands. Notably, there was no loss in probe fluorescence at the bone target site after 24 h in the living animal, indicating that the pre-assembled fluorescent probe maintained very high mechanical and chemical stability on the skeletal surface. The study shows how this versatile pre-assembly method can be used in a parallel combinatorial manner to produce libraries of near-infrared fluorescent multivalent molecular probes for different types of imaging and diagnostic applications, with incremental structural changes in the number of targeting groups, linker lengths, linker flexibility, and degree of PEGylation. PMID:27088305

  3. Broadband miniature optical ultrasound probe for high resolution vascular tissue imaging

    PubMed Central

    Colchester, Richard J.; Zhang, Edward Z.; Mosse, Charles A.; Beard, Paul C.; Papakonstantinou, Ioannis; Desjardins, Adrien E.

    2015-01-01

    An all-optical ultrasound probe for vascular tissue imaging was developed. Ultrasound was generated by pulsed laser illumination of a functionalized carbon nanotube composite coating on the end face of an optical fiber. Ultrasound was detected with a Fabry-Pérot (FP) cavity on the end face of an adjacent optical fiber. The probe diameter was < 0.84 mm and had an ultrasound bandwidth of ~20 MHz. The probe was translated across the tissue sample to create a virtual linear array of ultrasound transmit/receive elements. At a depth of 3.5 mm, the axial resolution was 64 µm and the lateral resolution was 88 µm, as measured with a carbon fiber target. Vascular tissues from swine were imaged ex vivo and good correspondence to histology was observed. PMID:25909031

  4. Probing Ultrafast Nuclear Dynamics in Halomethanes by Time-Resolved Electron and Ion Imaging

    NASA Astrophysics Data System (ADS)

    Ziaee, F.; Rudenko, A.; Rolles, D.; Savelyev, E.; Bomme, C.; Boll, R.; Manschwetus, B.; Erk, B.; Trippel, S.; Wiese, J.; Kuepper, J.; Amini, K.; Lee, J.; Brouard, M.; Brausse, F.; Rouzee, A.; Olshin, P.; Mereshchenko, A.; Lahl, J.; Johnsson, P.; Simon, M.; Marchenko, T.; Holland, D.; Underwood, J.

    2016-05-01

    Femtosecond pump-probe experiments provide opportunities to investigate photochemical reaction dynamics and the resulting changes in molecular structure in detail. Here, we present a study of the UV-induced photodissociation of gas-phase halomethane molecules (CH3 I, CH2 IBr, ...) in a pump-probe arrangement using two complementary probe schemes, either using a femtosecond near-infrared laser or the FLASH free-electron laser. We measured electrons and ions produced during the interaction using a double-sided velocity map imaging spectrometer equipped with a CCD camera for electron detection and with the Pixel Imaging Mass Spectrometry (PImMS) camera for ions, which can record the arrival time for up to four ions per pixel. This project is supported by the DOE, Office of Science, BES, Division of Chemical, Geological, and Biological Sciences.

  5. Broadband miniature optical ultrasound probe for high resolution vascular tissue imaging.

    PubMed

    Colchester, Richard J; Zhang, Edward Z; Mosse, Charles A; Beard, Paul C; Papakonstantinou, Ioannis; Desjardins, Adrien E

    2015-04-01

    An all-optical ultrasound probe for vascular tissue imaging was developed. Ultrasound was generated by pulsed laser illumination of a functionalized carbon nanotube composite coating on the end face of an optical fiber. Ultrasound was detected with a Fabry-Pérot (FP) cavity on the end face of an adjacent optical fiber. The probe diameter was < 0.84 mm and had an ultrasound bandwidth of ~20 MHz. The probe was translated across the tissue sample to create a virtual linear array of ultrasound transmit/receive elements. At a depth of 3.5 mm, the axial resolution was 64 µm and the lateral resolution was 88 µm, as measured with a carbon fiber target. Vascular tissues from swine were imaged ex vivo and good correspondence to histology was observed. PMID:25909031

  6. Comparison of imaging and probe measurements in a linear plasma column

    NASA Astrophysics Data System (ADS)

    Light, A. D.; Thakur, S. C.; Brandt, C.; Sechrest, Y.; Tynan, G. R.; Munsat, T.

    2014-10-01

    The advent of fast imaging diagnostics, which provide two-dimensional measurements on relevant plasma time scales, has proven invaluable for interpreting plasma dynamics in laboratory devices. Despite its success, imaging remains a qualitative aid for many studies, because intensity cannot often be mapped onto a single physical variable for use in a theoretical model. This study explores the relationship between visible-light and electrostatic probe measurements in the Controlled Shear Decorrelation Experiment (CSDX). CSDX is a well-characterized linear machine producing dense plasmas relevant to the tokamak edge (Te ~ 3 eV, ne ~1013 /cc). Visible light from ArI and ArII line emission is collected at high frame rates using a fast digital camera. Floating potential and ion-saturation current are measured by an array of electrostatic probe tips. We construct a detailed comparison between imaging and probe measurements of fluctuations, including temporal, spatial, and spectral properties. In addition, we combine probe and imaging techniques to identify modes in a multi-instability regime. Supported by the Center for Momentum Transport and Flow Organization.

  7. Curcumin analogues as selective fluorescence imaging probes for brown adipose tissue and monitoring browning.

    PubMed

    Zhang, Xueli; Tian, Yanli; Zhang, Hongbin; Kavishwar, Amol; Lynes, Matthew; Brownell, Anna-Liisa; Sun, Hongbin; Tseng, Yu-Hua; Moore, Anna; Ran, Chongzhao

    2015-01-01

    Manipulation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can be promising new approaches to counter metabolic disorder diseases in humans. Imaging probes that could consistently monitor BAT mass and browning of WAT are highly desirable. In the course of our imaging probe screening, we found that BAT could be imaged with curcumin analogues in mice. However, the poor BAT selectivity over WAT and short emissions of the lead probes promoted further lead optimization. Limited uptake mechanism studies suggested that CD36/FAT (fatty acid transporter) probably contributed to the facilitated uptake of the probes. By increasing the stereo-hindrance of the lead compound, we designed CRANAD-29 to extend the emission and increase the facilitated uptake, thus increasing its BAT selectivity. Our data demonstrated that CRANAD-29 had significantly improved selectivity for BAT over WAT, and could be used for imaging BAT mass change in a streptozotocin-induced diabetic mouse model, as well as for monitoring BAT activation under cold exposure. In addition, CRANAD-29 could be used for monitoring the browning of subcutaneous WAT (sWAT) induced by β3-adrenoceptor agonist CL-316, 243. PMID:26269357

  8. Non-invasive Imaging of Idiopathic Pulmonary Fibrosis Using Cathepsin Protease Probes

    PubMed Central

    Withana, Nimali P.; Ma, Xiaowei; McGuire, Helen M.; Verdoes, Martijn; van der Linden, Wouter A.; Ofori, Leslie O.; Zhang, Ruiping; Li, Hao; Sanman, Laura E.; Wei, Ke; Yao, Shaobo; Wu, Peilin; Li, Fang; Huang, Hui; Xu, Zuojun; Wolters, Paul J.; Rosen, Glenn D.; Collard, Harold R.; Zhu, Zhaohui; Cheng, Zhen; Bogyo, Matthew

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal, chronic, progressive disease characterized by formation of scar tissue within the lungs. Because it is a disease of unknown etiology, it is difficult to diagnose, to predict disease course and to devise treatment strategies. Recent evidence suggests that activated macrophages play key roles in the pathology of IPF. Therefore, imaging probes that specifically recognize these pools of activated immune cells could provide valuable information about how these cells contribute to the pathobiology of the disease. Here we demonstrate that cysteine cathepsin-targeted imaging probes can be used to monitor the contribution of macrophages to fibrotic disease progression in the bleomycin-induced murine model of pulmonary fibrosis. Furthermore, we show that the probes highlight regions of macrophage involvement in fibrosis in human biopsy tissues from IPF patients. Finally, we present first-in-human results demonstrating non-invasive imaging of active cathepsins in fibrotic lesions of patients with IPF. Together, our findings validate small molecule cysteine cathepsin probes for clinical PET imaging and suggest that they have the potential to be used to generate mechanistically-informative molecular information regarding cellular drivers of IPF disease severity and progression. PMID:26797565

  9. Dinuclear ruthenium(II) polypyridyl complexes as single and two-photon luminescence cellular imaging probes.

    PubMed

    Xu, Wenchao; Zuo, Jiarui; Wang, Lili; Ji, Liangnian; Chao, Hui

    2014-02-28

    A new series of dinuclear ruthenium(II) polypyridyl complexes, which possess larger π-conjugated systems, good water solubility and pH resistance, and high photostability, were developed to act as single and two-photon luminescence cellular imaging probes. PMID:24418839

  10. Curcumin analogues as selective fluorescence imaging probes for brown adipose tissue and monitoring browning

    PubMed Central

    Zhang, Xueli; Tian, Yanli; Zhang, Hongbin; Kavishwar, Amol; Lynes, Matthew; Brownell, Anna-Liisa; Sun, Hongbin; Tseng, Yu-Hua; Moore, Anna; Ran, Chongzhao

    2015-01-01

    Manipulation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can be promising new approaches to counter metabolic disorder diseases in humans. Imaging probes that could consistently monitor BAT mass and browning of WAT are highly desirable. In the course of our imaging probe screening, we found that BAT could be imaged with curcumin analogues in mice. However, the poor BAT selectivity over WAT and short emissions of the lead probes promoted further lead optimization. Limited uptake mechanism studies suggested that CD36/FAT (fatty acid transporter) probably contributed to the facilitated uptake of the probes. By increasing the stereo-hindrance of the lead compound, we designed CRANAD-29 to extend the emission and increase the facilitated uptake, thus increasing its BAT selectivity. Our data demonstrated that CRANAD-29 had significantly improved selectivity for BAT over WAT, and could be used for imaging BAT mass change in a streptozotocin-induced diabetic mouse model, as well as for monitoring BAT activation under cold exposure. In addition, CRANAD-29 could be used for monitoring the browning of subcutaneous WAT (sWAT) induced by β3-adrenoceptor agonist CL-316, 243. PMID:26269357

  11. A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy

    PubMed Central

    Liu, Yang; Ashton, Jeffrey R.; Moding, Everett J.; Yuan, Hsiangkuo; Register, Janna K.; Fales, Andrew M.; Choi, Jaeyeon; Whitley, Melodi J.; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Kirsch, David G.; Badea, Cristian T.; Vo-Dinh, Tuan

    2015-01-01

    Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy. PMID:26155311

  12. Exoplanet Direct Imaging: Coronagraph Probe Mission Study EXO-C

    NASA Technical Reports Server (NTRS)

    Stapelfeldt, Karl R.

    2013-01-01

    Flagship mission for spectroscopy of ExoEarths is a long-term priority for space astrophysics (Astro2010). Requires 10(exp 10) contrast at 3 lambda/D separation, ( (is) greater than 10,000 times beyond HST performance) and large telescope (is) greater than 4m aperture. Big step. Mission for spectroscopy of giant planets and imaging of disks requires 10(exp 9) contrast at 3 lambda/D (already demonstrated in lab) and (is) approximately 1.5m telescope. Should be much more affordable, good intermediate step.Various PIs have proposed many versions of the latter mission 17 times since 1999; no unified approach.

  13. Design of “smart” probes for optical imaging of apoptosis

    PubMed Central

    Huang, Xinglu; Lee, Seulki; Chen, Xiaoyuan

    2011-01-01

    Apoptosis is a mode of programmed cell death in multicellular organisms and plays a central role in controlling embryonic development, growth and differentiation and monitoring the induction of tumor cell death through anticancer therapy. Since the most effective chemotherapeutics rely on apoptosis, imaging apoptotic processes can be an invaluable tool to monitor therapeutic intervention and discover new drugs modulating apoptosis. The most attractive target for developing specific apoptosis imaging probes is caspases, crucial mediators of apoptosis. Up to now, various optical imaging strategies for apoptosis have been developed as an easy and economical modality. However, current optical applications are limited by poor sensitivity and specificity. A subset of molecular imaging contrast agents known as “activatable” or “smart” molecular probes allow for very high signal-to-background ratios compared to conventional targeted contrast agents and open up the possibility of imaging intracellular targets. In this review, we will discuss the unique design strategies and applications of activatable probes recently developed for fluorescence and bioluminescence imaging of caspase activity. PMID:22514789

  14. Probing Endoplasmic Reticulum Dynamics using Fluorescence Imaging and Photobleaching Techniques

    PubMed Central

    Costantini, Lindsey; Snapp, Erik

    2013-01-01

    This UNIT describes approaches and tools for studying the dynamics and organization of endoplasmic reticulum (ER) membranes and proteins in living cells using commercially available widefield and confocal laser scanning microscopes (CLSM). It has been long appreciated that the ER plays a number of key roles in secretory protein biogenesis, calcium regulation, and lipid synthesis. However, study of these processes has been often restricted to biochemical assays that average the behaviors of millions of lysed cells or to imaging static fixed cells. Now, with new fluorescent protein reporter tools, highly sensitive commercial microscopes, and photobleaching techniques, it is possible to interrogate the behaviors of ER proteins, membranes, and stress pathways in single cells with exquisite spatial and temporal resolution. The ER presents a unique set of imaging challenges including the high mobility of ER membranes, a diverse range of dynamic ER structures, and the influence of post-translational modifications on fluorescent protein reporters. Solutions to these challenges are described and considerations for performing photobleaching assays, especially Fluorescence Recovery after Photobleaching (FRAP) and Fluorescence Loss in Photobleaching (FLIP) for ER proteins will be discussed. In addition, ER reporters and ER-specific pharmacologic compounds are presented with a focus on misfolded secretory protein stress and the Unfolded Protein Response (UPR). PMID:24510787

  15. Ptychographic coherent diffractive imaging with orthogonal probe relaxation.

    PubMed

    Odstrcil, M; Baksh, P; Boden, S A; Card, R; Chad, J E; Frey, J G; Brocklesby, W S

    2016-04-18

    Ptychography is a scanning coherent diffractive imaging (CDI) technique that relies upon a high level of stability of the illumination during the course of an experiment. This is particularly an issue for coherent short wavelength sources, where the beam intensity is usually tightly focused on the sample in order to maximize the photon flux density on the illuminated region of the sample and thus a small change in the beam position results in a significant change in illumination of the sample. We present an improved ptychographic method that allows for limited stability of the illumination wavefront and thus significantly improve the reconstruction quality without additional prior knowledge. We have tested our reconstruction method in a proof of concept experiment, where the beam instability of a visible light source was emulated using a piezo driven mirror, and also in a short wavelength microscopy CDI setup using a high harmonic generation source in the extreme ultraviolet range. Our work shows a natural extension of the ptychography method that paves the way to use ptychographic imaging with any limited pointing stability coherent source such as free electron or soft X-ray lasers and improve reconstruction quality of long duration synchrotron experiments. PMID:27137273

  16. The Vitamin E Radical Probed by Anion Photoelectron Imaging.

    PubMed

    Anstöter, Cate S; West, Christopher W; Bull, James N; Verlet, Jan R R

    2016-07-28

    The biological antioxidant activity of vitamin E has been related to the stability of the tocopheroxyl radical. Using anion photoelectron imaging and electronic structure calculations, the four tocopheroxyl components of vitamin E have been studied in the gas phase and have yielded the adiabatic electron affinity of the α-, β/γ-, and δ-tocopheroxyl radicals. Using these values, the bond dissociation enthalpy of the O-H bond of tocopherol has been estimated and is consistent with previous studies and with the trends in biological activity. Differences in the photoelectron angular distributions have been interpreted to result from changes in the symmetry of the molecular orbitals from which the electron was detached. PMID:27367260

  17. Background-free in-vivo Imaging of Vitamin C using Time-gateable Responsive Probe

    PubMed Central

    Song, Bo; Ye, Zhiqing; Yang, Yajie; Ma, Hua; Zheng, Xianlin; Jin, Dayong; Yuan, Jingli

    2015-01-01

    Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its “off” state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background-free monitoring of cellular uptake or endogenous production of vitamin C, and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules. PMID:26373894

  18. Background-free in-vivo Imaging of Vitamin C using Time-gateable Responsive Probe.

    PubMed

    Song, Bo; Ye, Zhiqing; Yang, Yajie; Ma, Hua; Zheng, Xianlin; Jin, Dayong; Yuan, Jingli

    2015-01-01

    Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its "off" state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background-free monitoring of cellular uptake or endogenous production of vitamin C, and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules. PMID:26373894

  19. Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

    NASA Astrophysics Data System (ADS)

    Kujala, Naresh Gandhi

    Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The

  20. Validating a new methodology for optical probe design and image registration in fNIRS studies

    PubMed Central

    Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin; Boas, David A.; Magnotta, Vincent A.

    2015-01-01

    Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing. PMID:25705757

  1. Development of background-free tame fluorescent probes for intracellular live cell imaging

    PubMed Central

    Alamudi, Samira Husen; Satapathy, Rudrakanta; Kim, Jihyo; Su, Dongdong; Ren, Haiyan; Das, Rajkumar; Hu, Lingna; Alvarado-Martínez, Enrique; Lee, Jung Yeol; Hoppmann, Christian; Peña-Cabrera, Eduardo; Ha, Hyung-Ho; Park, Hee-Sung; Wang, Lei; Chang, Young-Tae

    2016-01-01

    Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky. Here we report the first predictive model for cell permeable background-free probe development through optimized lipophilicity, water solubility and charged van der Waals surface area. The model was developed by utilizing high-throughput screening in combination with cheminformatics. We demonstrate its reliability by developing CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, which specifically label intracellular target organelles and engineered proteins with minimum background. The results provide an efficient strategy for development of background-free probes, referred to as ‘tame' probes, and novel tools for live cell intracellular imaging. PMID:27321135

  2. Development of background-free tame fluorescent probes for intracellular live cell imaging.

    PubMed

    Alamudi, Samira Husen; Satapathy, Rudrakanta; Kim, Jihyo; Su, Dongdong; Ren, Haiyan; Das, Rajkumar; Hu, Lingna; Alvarado-Martínez, Enrique; Lee, Jung Yeol; Hoppmann, Christian; Peña-Cabrera, Eduardo; Ha, Hyung-Ho; Park, Hee-Sung; Wang, Lei; Chang, Young-Tae

    2016-01-01

    Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky. Here we report the first predictive model for cell permeable background-free probe development through optimized lipophilicity, water solubility and charged van der Waals surface area. The model was developed by utilizing high-throughput screening in combination with cheminformatics. We demonstrate its reliability by developing CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, which specifically label intracellular target organelles and engineered proteins with minimum background. The results provide an efficient strategy for development of background-free probes, referred to as 'tame' probes, and novel tools for live cell intracellular imaging. PMID:27321135

  3. Simulating and interpreting Kelvin probe force microscopy images on dielectrics with boundary integral equations

    NASA Astrophysics Data System (ADS)

    Shen, Yongxing; Barnett, David M.; Pinsky, Peter M.

    2008-02-01

    Kelvin probe force microscopy (KPFM) is designed for measuring the tip-sample contact potential differences by probing the sample surface, measuring the electrostatic interaction, and adjusting a feedback circuit. However, for the case of a dielectric (insulating) sample, the contact potential difference may be ill defined, and the KPFM probe may be sensing electrostatic interactions with a certain distribution of sample trapped charges or dipoles, leading to difficulty in interpreting the images. We have proposed a general framework based on boundary integral equations for simulating the KPFM image based on the knowledge about the sample charge distributions (forward problem) and a deconvolution algorithm solving for the trapped charges on the surface from an image (inverse problem). The forward problem is a classical potential problem, which can be efficiently solved using the boundary element method. Nevertheless, the inverse problem is ill posed due to data incompleteness. For some special cases, we have developed deconvolution algorithms based on the forward problem solution. As an example, this algorithm is applied to process the KPFM image of a gadolinia-doped ceria thin film to solve for its surface charge density, which is a more relevant quantity for samples of this kind than the contact potential difference (normally only defined for conductive samples) values contained in the raw image.

  4. In vivo pump-probe optical coherence tomography imaging in Xenopus laevis.

    PubMed

    Carrasco-Zevallos, Oscar; Shelton, Ryan L; Kim, Wihan; Pearson, Jeremy; Applegate, Brian E

    2015-01-01

    Currently, optical coherence tomography (OCT), is not capable of obtaining molecular information often crucial for identification of disease. To enable molecular imaging with OCT, we have further developed a technique that harnesses transient changes in light absorption in the sample to garner molecular information. A Fourier-domain Pump-Probe OCT (PPOCT) system utilizing a 532 nm pump and 830 nm probe has been developed for imaging hemoglobin. Methylene blue, a biological dye with well-know photophysics, was used to characterize the system before investigating the origin of the hemoglobin PPOCT signal. The first in vivo PPOCT images were recorded of the vasculature in Xenopus laevis. The technique was shown to work equally well in flowing and nonflowing vessels. Furthermore, PPOCT was compared with other OCT extensions which require flow, such as Doppler OCT and phase-variance OCT. PPOCT was shown to better delineate tortuous vessels, where nodes often restrict Doppler and phase-variance reconstruction. PMID:24282110

  5. Functional probe for annulus fibrosus-targeted intervertebral disc degeneration imaging

    PubMed Central

    Kim, Hye-Yeong; Mcclincy, Michael; Vo, Nam V.; Sowa, Gwendolyn A.; Kang, James D.

    2013-01-01

    Abstract. Intervertebral disc degeneration (IDD) is closely associated with low back pain. Typically nonsurgical treatment of IDD is the most effective when detected early. As such, establishing reliable imaging methods for the early diagnosis of disc degeneration is critical. The cellular and tissue localization of a facile functional fluorescent probe, HYK52, that labels disc annulus fibrosus is reported. HYK52 was synthesized with high yield and purity via a two-step chemical reaction. Rabbit disc cell studies and ex vivo tissue staining images indicated intracellular localization and intervertebral disc (IVD) tissue binding of HYK52 with negligible cytotoxicity. Moreover, HYK52 is purposefully designed with a functional terminal carboxyl group to allow for coupling with various signaling molecules for multimodal imaging applications. These results suggest that this IVD-targeted probe may have great potential in early diagnosis of IDD. PMID:23839314

  6. Functional probe for annulus fibrosus-targeted intervertebral disc degeneration imaging.

    PubMed

    Kim, Hye-Yeong; Mcclincy, Michael; Vo, Nam V; Sowa, Gwendolyn A; Kang, James D; Bai, Mingfeng

    2013-10-01

    Intervertebral disc degeneration (IDD) is closely associated with low back pain. Typically nonsurgical treatment of IDD is the most effective when detected early. As such, establishing reliable imaging methods for the early diagnosis of disc degeneration is critical. The cellular and tissue localization of a facile functional fluorescent probe, HYK52, that labels disc annulus fibrosus is reported. HYK52 was synthesized with high yield and purity via a two-step chemical reaction. Rabbit disc cell studies and ex vivo tissue staining images indicated intracellular localization and intervertebral disc (IVD) tissue binding of HYK52 with negligible cytotoxicity. Moreover, HYK52 is purposefully designed with a functional terminal carboxyl group to allow for coupling with various signaling molecules for multimodal imaging applications. These results suggest that this IVD-targeted probe may have great potential in early diagnosis of IDD. PMID:23839314

  7. Multi-Functionalized Carbon Nano-onions as Imaging Probes for Cancer Cells.

    PubMed

    Frasconi, Marco; Marotta, Roberto; Markey, Lyn; Flavin, Kevin; Spampinato, Valentina; Ceccone, Giacomo; Echegoyen, Luis; Scanlan, Eoin M; Giordani, Silvia

    2015-12-21

    Carbon-based nanomaterials have attracted much interest during the last decade for biomedical applications. Multimodal imaging probes based on carbon nano-onions (CNOs) have emerged as a platform for bioimaging because of their cell-penetration properties and minimal systemic toxicity. Here, we describe the covalent functionalization of CNOs with fluorescein and folic acid moieties for both imaging and targeting cancer cells. The modified CNOs display high brightness and photostability in aqueous solutions and their selective and rapid uptake in two different cancer cell lines without significant cytotoxicity was demonstrated. The localization of the functionalized CNOs in late-endosomes cell compartments was revealed by a correlative approach with confocal and transmission electron microscopy. Understanding the biological response of functionalized CNOs with the capability to target cancer cells and localize the nanoparticles in the cellular environment, will pave the way for the development of a new generation of imaging probes for future biomedical studies. PMID:26577582

  8. Near-field fluorescence imaging with 32 nm resolution based on microfabricated cantilevered probes

    NASA Astrophysics Data System (ADS)

    Eckert, Rolf; Freyland, J. Moritz; Gersen, Henkjan; Heinzelmann, Harry; Schürmann, Gregor; Noell, Wilfried; Staufer, Urs; de Rooij, Nico F.

    2000-12-01

    High-resolution near-field optical imaging with microfabricated probes is demonstrated. The probes are made from solid quartz tips fabricated at the end of silicon cantilevers and covered with a 60-nm-thick aluminum film. Transmission electron micrographs indicate a continuous aluminum layer at the tip apex. A specially designed instrument combines the advantages of near-field optical and beam-deflection force microscopy. Near-field optical data of latex bead projection patterns in transmission and of single fluorophores have been obtained in constant-height imaging mode. An artifact-free optical resolution of 31.7±3.6 nm has been deduced from full width at half maximum values of single molecule images.

  9. Nanoscale thermal imaging using a scanning spin probe

    NASA Astrophysics Data System (ADS)

    Laraoui, Abdelghani; Aycock-Rizzo, Halley; Gao, Yang; Riedo, Elisa; Meriles, Carlos

    We use a 30-nm diamond-nanocrystal-hosted nitrogen-vacancy (NV) center attached to the apex of a silicon tip as a local temperature sensor. First, we apply an electrical current to heat up the tip to a predefined operating temperature and rely on the NV to monitor the small thermal changes the tip experiences as it is brought into contact with surfaces of varying thermal conductivity. With the aid of a combined AFM/confocal setup, we image engineered microstructures with nanoscale resolution, and attain excellent agreement between the thermal conductivity and topographic maps. Given the small mass of the NV-hosting diamond nanoparticle, our technique shows a fast time response of order hundred microseconds, limited by the heat dissipation time of the tip. In a second approach, we heat nanostructured gold deposited on glass substrate by injecting a direct current. By monitoring the frequency shift of NV spin transitions upon scanning the AFM tip we reconstruct nanometer-resolved temperature maps. Our technique promises multiple applications ranging from the investigation of phonon dynamics in nanostructures to the characterization of heterogeneous phase transitions in various solid-state systems.

  10. In vivo imaging of brain metabolism activity using a phosphorescent oxygen-sensitive probe

    PubMed Central

    Tsytsarev, Vassiliy; Arakawa, Hiroyuki; Borisov, Sergei; Pumbo, Elena; Erzurumlu, Reha S.; Papkovsky, Dmitri B.

    2013-01-01

    Several approaches have been adopted for real-time imaging of neural activity in vivo. We tested a new cell-penetrating phosphorescent oxygen-sensitive probe, NanO2-IR, to monitor temporal and spatial dynamics of oxygen metabolism in the neocortex following peripheral sensory stimulation. Probe solution was applied to the surface of anesthetized mouse brain; optical imaging was performed using a MiCAM-02 system. Trains of whisker stimuli were delivered and associated changes in phosphorescent signal were recorded in the contralateral somatosensory (“barrel”) cortex. Sensory stimulation led to changes in oxygenation of activated areas of the barrel cortex. The oxygen imaging results were compared to those produced by the voltage-sensitive dye RH-1691. While the signals emitted by the two probes differed in shape and amplitude, they both faithfully indicated specific whisker evoked cortical activity. Thus, NanO2-IR probe can be used as a tool in visualization and realtime analysis of sensory- evoked neural activity in vivo. PMID:23624034

  11. A wireless handheld probe with spectrally constrained evolution strategies for diffuse optical imaging of tissue

    PubMed Central

    Flexman, M. L.; Kim, H. K.; Stoll, R.; Khalil, M. A.; Fong, C. J.; Hielscher, A. H.

    2012-01-01

    We present a low-cost, portable, wireless diffuse optical imaging device. The handheld device is fast, portable, and can be applied to a wide range of both static and dynamic imaging applications including breast cancer, functional brain imaging, and peripheral artery disease. The continuous-wave probe has four near-infrared wavelengths and uses digital detection techniques to perform measurements at 2.3 Hz. Using a multispectral evolution algorithm for chromophore reconstruction, we can measure absolute oxygenated and deoxygenated hemoglobin concentration as well as scattering in tissue. Performance of the device is demonstrated using a series of liquid phantoms comprised of Intralipid®, ink, and dye. PMID:22462907

  12. A ratiometric two-photon fluorescent probe for fluoride ion imaging in living cells and zebrafish.

    PubMed

    Hu, Wei; Zeng, Lingyu; Wang, Yanying; Liu, Zhihong; Ye, Xiaoxue; Li, Chunya

    2016-09-21

    Using 6-hydroxyl-quinoline-2-benzothiazole (HQB) as a two-photon fluorophore and tert-butyldiphenylsilyl as a recognition domain for F(-), a ratiometric two-photon fluorescent fluoride probe, QF, was synthesized and fully characterized. QF displays both one- and two-photon ratiometric responses towards fluoride ions in aqueous solution. QF was enabled to detect exogenous fluoride ions in living cells by a ratiometric method. Two-photon microscopic imaging of fluoride ions in living HeLa cells and zebrafish has also been achieved. QF has been demonstrated to be an excellent fluorescent probe with high selectivity, low cytotoxicity and good photostability. PMID:27353376

  13. In vivo imaging and biochemical characterization of protease function using fluorescent activity-based probes

    PubMed Central

    Edgington, Laura E.; Bogyo, Matthew

    2013-01-01

    Activity-based probes (ABPs) are reactive small molecules that covalently bind to active enzymes. When tagged with a fluorophore, ABPs serve as powerful tools to investigate enzymatic activity across a wide variety of applications. In this article, we will provide detailed protocols for using fluorescent ABPs to biochemically characterize the activity of proteases in vitro. Furthermore, we will describe how these probes can be applied to image protease activity in live animals and tissues along with subsequent analysis by histology, flow cytometry, and SDS-PAGE. PMID:23788323

  14. Imaging pigment chemistry in melanocytic conjunctival lesions with pump-probe microscopy

    NASA Astrophysics Data System (ADS)

    Wilson, Jesse W.; Vajzovic, Lejla; Robles, Francisco E.; Cummings, Thomas J.; Mruthyunjaya, Prithvi; Warren, Warren S.

    2013-03-01

    We extend nonlinear pump-probe microscopy, recently demonstrated to image the microscopic distribution of eumelanin and pheomelanin in unstained skin biopsy sections, to the case of melanocytic conjunctival lesions. The microscopic distribution of pigmentation chemistry serves as a functional indicator of melanocyte activity. In these conjunctival specimens (benign nevi, primary acquired melanoses, and conjunctival melanoma), we have observed pump-probe spectroscopic signatures of eumelanin, pheomelanin, hemoglobin, and surgical ink, in addition to important structural features that differentiate benign from malignant lesions. We will also discuss prospects for an in vivo `optical biopsy' to provide additional information before having to perform invasive procedures.

  15. Histotripsy Lesion Formation using an Ultrasound Imaging Probe Enabled by a Low-Frequency Pump Transducer

    PubMed Central

    Lin, Kuang-Wei; Hall, Timothy L.; Xu, Zhen; Cain, Charles A.

    2015-01-01

    When applying histotripsy pulses shorter than 2 cycles, the formation of a dense bubble cloud only relies on the applied peak negative pressure (p-) exceeding the “intrinsic threshold” of the medium (absolute value of 26 – 30 MPa in most soft tissue). A previous study conducted by our research group showed that a sub-threshold high-frequency probe pulse (3 MHz) can be enabled by a sub-threshold low-frequency pump pulse (500 kHz) where the sum exceeds the intrinsic threshold, thus generating lesion-producing dense bubble clouds (“dual-beam histotripsy”). This paper investigates the feasibility of using an imaging transducer to provide the high-frequency probe pulse in the dual-beam histotripsy approach. More specifically, an ATL L7–4 imaging transducer, pulsed by a Verasonics V-1 Data Acquisition System, was used to generate the high-frequency probe pulses. The low-frequency pump pulses were generated by a 20-element 345 kHz array transducer, driven by a custom high voltage pulser. These dual-beam histotripsy pulses were applied to red-blood-cell (RBC) tissue-mimicking phantoms at a pulse repetition frequency of 1 Hz, and optical imaging was used to visualize bubble clouds and lesions generated in the RBC phantoms. The results showed that dense bubble clouds (and resulting lesions) were generated when the p- of the sub-threshold pump and probe pulses combined constructively to exceed the intrinsic threshold. The average size of the smallest reproducible lesions using the imaging probe pulse enabled by the sub-threshold pump pulse was 0.7 × 1.7 mm while that using the supra-threshold pump pulse alone was 1.4 × 3.7 mm. When the imaging transducer was steered laterally, bubble clouds and lesions were steered correspondingly until the combined p- no longer exceeded the intrinsic threshold. These results were also validated with ex vivo porcine liver experiments. Using an imaging transducer for dual-beam histotripsy can have two advantages, 1) lesion

  16. Histotripsy Lesion Formation Using an Ultrasound Imaging Probe Enabled by a Low-Frequency Pump Transducer.

    PubMed

    Lin, Kuang-Wei; Hall, Timothy L; Xu, Zhen; Cain, Charles A

    2015-08-01

    When histotripsy pulses shorter than 2 cycles are applied, the formation of a dense bubble cloud relies only on the applied peak negative pressure (p-) exceeding the "intrinsic threshold" of the medium (absolute value of 26-30 MPa in most soft tissues). It has been found that a sub-threshold high-frequency probe pulse (3 MHz) can be enabled by a sub-threshold low-frequency pump pulse (500 kHz) where the sum exceeds the intrinsic threshold, thus generating lesion-producing dense bubble clouds ("dual-beam histotripsy"). Here, the feasibility of using an imaging transducer to provide the high-frequency probe pulse in the dual-beam histotripsy approach is investigated. More specifically, an ATL L7-4 imaging transducer (Philips Healthcare, Andover, MA, USA), pulsed by a V-1 Data Acquisition System (Verasonics, Redmond, WA, USA), was used to generate the high-frequency probe pulses. The low-frequency pump pulses were generated by a 20-element 345-kHz array transducer, driven by a custom high-voltage pulser. These dual-beam histotripsy pulses were applied to red blood cell tissue-mimicking phantoms at a pulse repetition frequency of 1 Hz, and optical imaging was used to visualize bubble clouds and lesions generated in the red blood cell phantoms. The results indicated that dense bubble clouds (and resulting lesions) were generated when the p- of the sub-threshold pump and probe pulses combined constructively to exceed the intrinsic threshold. The average size of the smallest reproducible lesions using the imaging probe pulse enabled by the sub-threshold pump pulse was 0.7 × 1.7 mm, whereas that using the supra-threshold pump pulse alone was 1.4 × 3.7 mm. When the imaging transducer was steered laterally, bubble clouds and lesions were steered correspondingly until the combined p- no longer exceeded the intrinsic threshold. These results were also validated with ex vivo porcine liver experiments. Using an imaging transducer for dual-beam histotripsy can have two

  17. Development of laser optoacoustic and ultrasonic imaging system for breast cancer utilizing handheld array probes

    NASA Astrophysics Data System (ADS)

    Ermilov, Sergey A.; Fronheiser, Matthew P.; Brecht, Hans-Peter; Su, Richard; Conjusteau, André; Mehta, Ketan; Otto, Pamela; Oraevsky, Alexander A.

    2009-02-01

    We describe two laser optoacoustic imaging systems for breast cancer detection based on arrays of acoustic detectors operated manually in a way similar to standard ultrasonic breast imaging. The systems have the advantages of standard light illumination (regardless of the interrogated part of the breast), the ability to visualize any part of the breast, and convenience in operation. The first system could work in both ultrasonic and optoacoustic mode, and was developed based on a linear ultrasonic breast imaging probe with two parallel rectangular optical bundles. We used it in a pilot clinical study to provide for the first time demonstration that the boundaries of the tumors visualized on the optoacoustic and ultrasonic images matched. Such correlation of coregistered images proves that the objects on both images represented indeed the same tumor. In the optoacoustic mode we were also able to visualize blood vessels located in the neighborhood of the tumor. The second system was proposed as a circular array of acoustic transducers with an axisymmetric laser beam in the center. It was capable of 3D optoacoustic imaging with minimized optoacoustic artifacts caused by the distribution of the absorbed optical energy within the breast tissue. The distribution of optical energy absorbed in the bulk tissue of the breast was removed from the image by implementing the principal component analysis on the measured signals. The computer models for optoacoustic imaging using these two handheld probes were developed. The models included three steps: (1) Monte Carlo simulations of the light distribution within the breast tissue, (2) generation of optoacoustic signals by convolving N-shaped pressure signals from spherical voxels with the shape of individual transducers, and (3) back-projecting processed optoacoustic signals onto spherical surfaces for image reconstruction. Using the developed models we demonstrated the importance of the included spatial impulse response of the

  18. Novel Strategy for Preparing Dual-Modality Optical/PET Imaging Probes via Photo-Click Chemistry.

    PubMed

    Sun, Lingyi; Ding, Jiule; Xing, Wei; Gai, Yongkang; Sheng, Jing; Zeng, Dexing

    2016-05-18

    Preparation of small molecule based dual-modality probes remains a challenging task due to the complicated synthetic procedure. In this study, a novel concise and generic strategy for preparing dual-modality optical/PET imaging probes via photo-click chemistry was developed, in which the diazole photo-click linker functioned not only as a bridge between the targeting-ligand and the PET imaging moiety, but also as the fluorophore for optical imaging. A dual-modality AE105 peptidic probe was successfully generated via this strategy and subsequently applied in the fluorescent staining of U87MG cells and the (68)Ga based PET imaging of mice bearing U87MG xenograft. In addition, dual-modality monoclonal antibody cetuximab has also been generated via this strategy and labeled with (64)Cu for PET imaging studies, broadening the application of this strategy to include the preparation of macromolecule based imaging probes. PMID:27098544

  19. Multi-scale Imaging of Cellular and Sub-cellular Structures using Scanning Probe Recognition Microscopy.

    NASA Astrophysics Data System (ADS)

    Chen, Q.; Rice, A. F.

    2005-03-01

    Scanning Probe Recognition Microscopy is a new scanning probe capability under development within our group to reliably return to and directly interact with a specific nanobiological feature of interest. In previous work, we have successfully recognized and classified tubular versus globular biological objects from experimental atomic force microscope images using a method based on normalized central moments [ref. 1]. In this paper we extend this work to include recognition schemes appropriate for cellular and sub-cellular structures. Globular cells containing tubular actin filaments are under investigation. Thus there are differences in external/internal shapes and scales. Continuous Wavelet Transform with a differential Gaussian mother wavelet is employed for multi- scale analysis. [ref. 1] Q. Chen, V. Ayres and L. Udpa, ``Biological Investigation Using Scanning Probe Recognition Microscopy,'' Proceedings 3rd IEEE Conference on Nanotechnology, vol. 2, p 863-865 (2003).

  20. Design of a rectal probe for diffuse optical spectroscopy imaging for chemotherapy and radiotherapy monitoring

    NASA Astrophysics Data System (ADS)

    van de Giessen, Martijn; Santoro, Ylenia; Mirzaei Zarandi, Soroush; Pigazzi, Alessio; Cerussi, Albert E.; Tromberg, Bruce J.

    2014-03-01

    Diffuse optical spectroscopy imaging (DOSI) has shown great potential for the early detection of non-responding tumors during neoadjuvant chemotherapy in breast cancer, already one day after therapy starts. Patients with rectal cancer receive similar chemotherapy treatment. The rectum geometry and tissue properties of healthy and tumor tissue in the rectum and the requirement of surface contact impose constraints on the probe design. In this work we present the design of a DOSI probe with the aim of early chemotherapy/radiotherapy effectiveness detection in rectal tumors. We show using Monte Carlo simulations and phantom measurements that the colon tissue can be characterized reliably using a source-detector separation in the order of 10 mm. We present a design and rapid prototype of a probe for DOSI measurements that can be mounted on a standard laparoscope and that fits through a standard rectoscope. Using predominantly clinically approved components we aim at fast clinical translation.

  1. Biocompatible Flavone-Based Fluorogenic Probes for Quick Wash-Free Mitochondrial Imaging in Living Cells

    PubMed Central

    2015-01-01

    Mitochondria, vital organelles existing in almost all eukaryotic cells, play a crucial role in energy metabolism and apoptosis of aerobic organisms. In this work, we report two new flavone-based fluorescent probes, MC-Mito1 and MC-Mito2, for monitoring mitochondria in living cells. These two probes exhibit remarkably low toxicity, good cell permeability, and high specificity; these probes complement the existing library of mitochondrial imaging agents. The new dyes give nearly no background fluorescence, and their application does not require tedious postwashing after cell staining. The appreciable tolerance of MC-Mito2 encourages a broader range of biological applications for understanding the cell degeneration and apoptosis mechanism. PMID:25382851

  2. Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice

    NASA Astrophysics Data System (ADS)

    Pu, Kanyi; Shuhendler, Adam J.; Jokerst, Jesse V.; Mei, Jianguo; Gambhir, Sanjiv S.; Bao, Zhenan; Rao, Jianghong

    2014-03-01

    Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species--vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes.

  3. Alzheimer’s disease imaging with a novel Tau targeted near infrared ratiometric probe

    PubMed Central

    Kim, Hye-Yeong; Sengupta, Urmi; Shao, Pin; Guerrero-Muñoz, Marcos J; Kayed, Rakez; Bai, Mingfeng

    2013-01-01

    Neurofibrillary tangles (NFTs) have long been recognized as one of the pathological hallmarks in Alzheimer’s disease (AD). Recent studies, however, showed that soluble aggregated Tau species, especially hyperphosphorylated Tau oligomers, which are formed at early stage of AD prior to the formation of NFT, disrupted neural system integration. Unfortunately, little is known about Tau aggregates, and few Tau targeted imaging probe has been reported. Successful development of new imaging methods that can visualize early stages of Tau aggregation specifically will obviously be important for AD imaging, as well as understanding Tau-associated neuropathology of AD. Here, we report the first NIR ratiometric probe, CyDPA2, that targets Tau aggregates. The specificity of CyPDA2 to aggregated Tau was evaluated with in vitro hyperphosphorylated Tau proteins (pTau), as well as ex vivo Tau samples from AD human brain samples and the tauopathy transgenic mouse model, P301L. The characteristic enhancements of absorption ratio and fluorescence intensity in CyDPA2 were observed in a pTau concentration-dependent manner. In addition, fluorescence microscopy and gel staining studies demonstrated CyDPA2-labeled Tau aggregates. These data indicate that CyDPA2 is a promising imaging probe for studying Tau pathology and diagnosing AD at an early stage. PMID:23526074

  4. Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice.

    PubMed

    Pu, Kanyi; Shuhendler, Adam J; Jokerst, Jesse V; Mei, Jianguo; Gambhir, Sanjiv S; Bao, Zhenan; Rao, Jianghong

    2014-03-01

    Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species--vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes. PMID:24463363

  5. Nanoparticles for Cardiovascular Imaging and Therapeutic Delivery, Part 2: Radiolabeled Probes

    PubMed Central

    Stendahl, John C.; Sinusas, Albert J.

    2016-01-01

    Nanoparticulate imaging agents and therapeutics have proven to be valuable tools in preclinical cardiovascular disease research. Because of their distinct properties and significant functional versatility, nanoparticulate imaging agents afford certain capabilities that are typically not provided by traditional small molecule agents. This review is the second in a two-part series covering nanoparticulate imaging agents and theranostics. It highlights current examples of radiolabeled nanoparticulate probes in preclinical cardiovascular research and demonstrates their utility in applications such as blood pool imaging and molecular imaging of ischemia, angiogenesis, atherosclerosis, and inflammation. These agents provide valuable insight into the molecular and cellular mechanisms of cardiovascular disease and illustrate both the limitations and the significant potential of nanoparticles in diagnostic and therapeutic applications. Further technologic development to improve performance, address safety concerns, and fulfil regulatory obligations is required for clinical translation of these emergent technologies. PMID:26294304

  6. Interventional multispectral photoacoustic imaging with a clinical linear array ultrasound probe for guiding nerve blocks

    NASA Astrophysics Data System (ADS)

    Xia, Wenfeng; West, Simeon J.; Nikitichev, Daniil I.; Ourselin, Sebastien; Beard, Paul C.; Desjardins, Adrien E.

    2016-03-01

    Accurate identification of tissue structures such as nerves and blood vessels is critically important for interventional procedures such as nerve blocks. Ultrasound imaging is widely used as a guidance modality to visualize anatomical structures in real-time. However, identification of nerves and small blood vessels can be very challenging, and accidental intra-neural or intra-vascular injections can result in significant complications. Multi-spectral photoacoustic imaging can provide high sensitivity and specificity for discriminating hemoglobin- and lipid-rich tissues. However, conventional surface-illumination-based photoacoustic systems suffer from limited sensitivity at large depths. In this study, for the first time, an interventional multispectral photoacoustic imaging (IMPA) system was used to image nerves in a swine model in vivo. Pulsed excitation light with wavelengths in the ranges of 750 - 900 nm and 1150 - 1300 nm was delivered inside the body through an optical fiber positioned within the cannula of an injection needle. Ultrasound waves were received at the tissue surface using a clinical linear array imaging probe. Co-registered B-mode ultrasound images were acquired using the same imaging probe. Nerve identification was performed using a combination of B-mode ultrasound imaging and electrical stimulation. Using a linear model, spectral-unmixing of the photoacoustic data was performed to provide image contrast for oxygenated and de-oxygenated hemoglobin, water and lipids. Good correspondence between a known nerve location and a lipid-rich region in the photoacoustic images was observed. The results indicate that IMPA is a promising modality for guiding nerve blocks and other interventional procedures. Challenges involved with clinical translation are discussed.

  7. Silica micro/nanospheres for theranostics: from bimodal MRI and fluorescent imaging probes to cancer therapy

    PubMed Central

    Walia, Shanka

    2015-01-01

    Summary Nano-theranostics offer remarkable potential for future biomedical technology with simultaneous applications for diagnosis and therapy of disease sites. Through smart and careful chemical modifications of the nanoparticle surface, these can be converted to multifunctional tiny objects which in turn can be used as vehicle for delivering multimodal imaging agents and therapeutic material to specific target sites in vivo. In this sense, bimodal imaging probes that simultaneously enable magnetic resonance imaging and fluorescence imaging have gained tremendous attention because disease sites can be characterized quick and precisely through synergistic multimodal imaging. But such hybrid nanocomposite materials have limitations such as low chemical stability (magnetic component) and harsh cytotoxic effects (fluorescent component) and, hence, require a biocompatible protecting agent. Silica micro/nanospheres have shown promise as protecting agent due to the high stability and low toxicity. This review will cover a full description of MRI-active and fluorescent multifunctional silica micro/nanospheres including the design of the probe, different characterization methods and their application in imaging and treatment in cancer. PMID:25821696

  8. Multimodal imaging probe for targeting cancer cells using uMUC-1 aptamer.

    PubMed

    Kang, Won Jun; Lee, Jonghwan; Lee, Yong Seung; Cho, Sujeong; Ali, Bahy A; Al-Khedhairy, Abdulaziz A; Heo, Hyejung; Kim, Soonhag

    2015-12-01

    For adequate cancer therapy, newer imaging modalities with more specific ligands for unique targets are crucial. Underglycosylated mucin-1 (uMUC-1) antigen is an early marker of tumor development and is widely overexpressed on most tumors. A combination of nanotechnology with optical, radionuclide, and magnetic resonance (MR) imaging has great potential to improve cancer diagnosis and therapy. In this study, a multimodal nanoparticle imaging system was developed that can be used for optical, MR and positron emission tomography (PET) imaging. Cobalt ferrite magnetic nanoparticles surrounded by fluorescent rhodamine (designated MF) within a silica shell matrix were conjugated with an aptamer targeting uMUC-1 (designated MF-uMUC-1) and further labeled by (68)Ga (designated MFR-uMUC-1) with the help of a p-SCN-bn-NOTA chelating agent, resulting in single multimodal nanoparticles. The resultant nanoparticles are spherical and monodispersed, as revealed by transmission electron microscopy. The MFR-uMUC-1 nanoparticle showed specific and dose-dependent fluorescent, radioisotope and MR signals targeting BT-20 cells expressing uMUC-1. In vivo targeting and multimodal imaging in tumor-bearing nude mice also showed great specificity for targeting cancers with MFR-uMUC-1. The MFR-uMUC-1 probe could be used as a single multimodal probe to visualize cancer cells by means of optical, radionuclide and MR imaging. PMID:26387066

  9. Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging

    PubMed Central

    Han, Jae-Ho; Lee, Junghoon; Kang, Jin U.

    2010-01-01

    A method of eliminating pixelization effect from en face optical coherence tomography (OCT) image when a fiber bundle is used as an OCT imaging probe is presented. We have demonstrated that applying a histogram equalization process before performing a weighted-averaged Gaussian smoothing filter to the original lower gray level intensity based image not only removes the structural artifact of the bundle but also enhances the image quality with minimum blurring of object’s image features. The measured contrast-to-noise ratio (CNR) for an image of the US Air Force test target was 14.7dB (4.9dB), after (before) image processing. In addition, by performing the spatial frequency analysis based on two-dimensional discrete Fourier transform (2-D DFT), we were able to observe that the periodic intensity peaks induced by the regularly arrayed structure of the fiber bundle can be efficiently suppressed by 41.0dB for the first nearby side lobe as well as to obtain the precise physical spacing information of the fiber grid. The proposed combined method can also be used as a straight forward image processing tool for any imaging system utilizing fiber bundle as a high-resolution imager. PMID:20389766

  10. Fluorescence imaging of siRNA delivery by peptide nucleic acid-based probe.

    PubMed

    Sato, Takaya; Sato, Yusuke; Iwai, Kenta; Kuge, Shusuke; Teramae, Norio; Nishizawa, Seiichi

    2015-01-01

    We report on the use of a peptide nucleic acid (PNA)-based fluorescent probe for the analysis of siRNA delivery to living cells. The probe, Py-AA-TO, possesses thiazole orange (TO) and pyrene moieties in the C- and N-termini of PNA, and can function as a light-up probe capable of selective binding to 3'-overhanging nucleotides of target siRNAs. The affinity-labeling of the siRNAs with Py-AA-TO facilitates fluorescence imaging of cellular uptake of polymer-based carriers encapsulating the siRNAs (polyplexes) through endocytosis and subsequent sequestration into lysosome. In addition, flow cytometric measurements reveal that the monitoring of Py-AA-TO fluorescence inside the cells is successfully applicable to the analysis of the polyplex disassembly. These promising functions of Py-AA-TO are presented and discussed as a basis for the design of molecular probes for fluorescent imaging and quantitative analysis of the siRNA delivery process. PMID:25864675

  11. Immobilization of human papillomavirus DNA probe for surface plasmon resonance imaging

    NASA Astrophysics Data System (ADS)

    Chong, Xinyuan; Ji, Yanhong; Ma, Suihua; Liu, Le; Liu, Zhiyi; Li, Yao; He, Yonghong; Guo, Jihua

    2009-08-01

    Human papillomavirus (HPV) is a kind of double-stranded DNA virus whose subspecies have diversity. Near 40 kinds of subspecies can invade reproductive organ and cause some high risk disease, such as cervical carcinoma. In order to detect the type of the subspecies of the HPV DNA, we used the parallel scan spectral surface plasmon resonance (SPR) imaging technique, which is a novel type of two- dimensional bio-sensing method based on surface plasmon resonance and is proposed in our previous work, to study the immobilization of the HPV DNA probes on the gold film. In the experiment, four kinds of the subspecies of the HPV DNA (HPV16, HPV18, HPV31, HPV58) probes are fixed on one gold film, and incubate in the constant temperature condition to get a HPV DNA probe microarray. We use the parallel scan spectral SPR imaging system to detect the reflective indices of the HPV DNA subspecies probes. The benefits of this new approach are high sensitive, label-free, strong specificity and high through-put.

  12. Two photon fluorescence imaging of lipid membrane domains and potentials using advanced fluorescent probes

    NASA Astrophysics Data System (ADS)

    Kilin, Vasyl; Darwich, Zeinab; Richert, Ludovic; Didier, Pascal; Klymchenko, Andrey; Mély, Yves

    2013-02-01

    Biomembranes are ordered and dynamic nanoscale structures critical for cell functions. The biological functions of the membranes strongly depend on their physicochemical properties, such as electrostatics, phase state, viscosity, polarity and hydration. These properties are essential for the membrane structure and the proper folding and function of membrane proteins. To monitor these properties, fluorescence techniques and notably, two-photon microscopy appear highly suited due to their exquisite sensitivity and their capability to operate in complex biological systems, such as living cells and tissues. In this context, we have developed multiparametric environment-sensitive fluorescent probes tailored for precise location in the membrane bilayer. We notably developed probes of the 3-hydroxychromone family, characterized by an excited state intramolecular proton transfer reaction, which generates two tautomeric emissive species with well-separated emission bands. As a consequence, the response of these probes to changes in their environment could be monitored through changes in the ratios of the two bands, as well as through changes in the fluorescence lifetimes. Using two-photon ratiometric imaging and FLIM, these probes were used to monitor the surface membrane potential, and were applied to detect apoptotic cells and image membrane domains.

  13. VCAM-1-targeting gold nanoshell probe for photoacoustic imaging of atherosclerotic plaque in mice.

    PubMed

    Rouleau, Leonie; Berti, Romain; Ng, Vanessa W K; Matteau-Pelletier, Carl; Lam, Tina; Saboural, Pierre; Kakkar, Ashok K; Lesage, Frédéric; Rhéaume, Eric; Tardif, Jean-Claude

    2013-01-01

    The development of molecular probes and novel imaging modalities, allowing better resolution and specificity, is associated with an increased potential for molecular imaging of atherosclerotic plaques especially in basic and pre-clinical research applications. In that context, a photoacoustic molecular probe based on gold nanoshells targeting VCAM-1 in mice (immunonanoshells) was designed. The molecular probe was validated in vitro and in vivo, showing no noticeable acute toxic effects. We performed the conjugation of gold nanoshells displaying near-infrared absorption properties with VCAM-1 antibody molecules and PEG to increase their biocompatibility. The resulting immunonanoshells obtained under different conditions of conjugation were then assessed for specificity and sensitivity. Photoacoustic tomography was performed to determine the ability to distinguish gold nanoshells from blood both in phantoms and in vivo. Ex vivo optical projection tomography of hearts and aortas from atherosclerotic and control mice confirmed the selective accumulation of the immunonanoshells in atherosclerotic-prone regions in mice, thus validating the utility of the probe in vivo in small animals for pre-clinical research. These immunonanoshells represent an adequate mean to target atherosclerotic plaques in small animals, leading to new tools to follow the effect of therapies on the progression or regression of the disease. PMID:23109390

  14. Ultrasonic imaging of hidden defects using dry-coupled ultrasonic probes

    NASA Astrophysics Data System (ADS)

    Komsky, Igor N.

    2006-03-01

    Safety criteria of aircraft industry require careful inspection of aircraft components for structural integrity since airworthiness of aging aircraft can be significantly affected by combination of corrosion and fatigue damage. Surface defects can be efficiently detected by visual or other surface inspection techniques. Detection of hidden defects, on the other hand, is still a challenging task. Therefore, it is essential to develop non-destructive methods that can inspect different layers of the aircraft structures for internal defects before they become a safety concern. Ultrasonic probes with the dry-coupled substrates are highly efficient for all modalities of ultrasonic techniques including pulse-echo, pitch-catch, or through-transmission modes. The probes can be deployed in conjunction with portable ultrasonic instruments for B- and C-scanning. The dry-coupled probes have already been tested on a number of aircraft for rapid inspections of the aircraft structures from the outside without any disassembly. However, adequate inspection for small pitting corrosion and incipient fatigue cracks in metallic structures or delaminations in composite panels may require superior sensitivity and resolution of the applied ultrasonic technique. Several novel configurations of the dry-coupled probes with increased sensitivity and resolution will be presented. Ultrasonic imaging with single- or double-element dry-coupled probes will be demonstrated on the specimens with heavy pitting corrosion, machined planar and volumetric defects, and embedded internal flaws.

  15. Highly sensitive cell imaging "Off-On" fluorescent probe for mitochondria and ATP.

    PubMed

    Srivastava, Priyanka; Razi, Syed S; Ali, Rashid; Srivastav, Saurabh; Patnaik, Satyakam; Srikrishna, Saripella; Misra, Arvind

    2015-07-15

    A smart Off-On molecular scaffold/fluorescent probe 1 has been designed and synthesized. The probe has shown considerable photostability, cell permeability, organelle specificity and selectivity for ATP. The multicolor live cell imaging experiments in HeLa cells showed high selectivity of probe 1 for mitochondria with fluorescence "turn-on" response. As a proof of concept and promising prospects for application in biological sciences probe 1 has been utilized to detect ATP sensitively in a partial aqueous medium and intracellularly in HeLa cells. The favorable interaction between triphosphate unit of ATP and piperazine N atoms of probe 1 is attributed to synergistic effects of H-bonding and electrostatic interactions that encouraged the CH-π and π→π stacking between anthracene and purine rings. Consequently, the observed enhanced "turn-on" emission and a naked-eye sensitive blue-green color in the medium is attributable to arrest in photoinduced electron transfer (PET) process. PMID:25727034

  16. A Nature-Inspired Betalainic Probe for Live-Cell Imaging of Plasmodium-Infected Erythrocytes

    PubMed Central

    Gonçalves, Letícia Christina Pires; Tonelli, Renata Rosito; Bagnaresi, Piero; Mortara, Renato Arruda; Ferreira, Antonio Gilberto; Bastos, Erick Leite

    2013-01-01

    A model betalainic dye was semisynthesized from betanin, the magenta pigment of the red beet, and was effective for live-cell imaging of Plasmodium-infected red blood cells. This water-soluble fluorescent probe is photostable, excitable in the visible region and cell membrane-permeable, and its photophysical properties are not notably pH-sensitive. Fluorescence imaging microscopy of erythrocytes infected with Plasmodium falciparum, a causative agent of malaria in humans, showed that only the parasite was stained. Z-stacking analysis suggested that the probe accumulates proximal to the nucleus of the parasite. Indicaxanthin, one of the natural fluorescent betalains found in the petals of certain flowers, did not stain the parasite or the red blood cell. PMID:23342028

  17. A Simple BODIPY-Based Viscosity Probe for Imaging of Cellular Viscosity in Live Cells.

    PubMed

    Su, Dongdong; Teoh, Chai Lean; Gao, Nengyue; Xu, Qing-Hua; Chang, Young-Tae

    2016-01-01

    Intracellular viscosity is a fundamental physical parameter that indicates the functioning of cells. In this work, we developed a simple boron-dipyrromethene (BODIPY)-based probe, BTV, for cellular mitochondria viscosity imaging by coupling a simple BODIPY rotor with a mitochondria-targeting unit. The BTV exhibited a significant fluorescence intensity enhancement of more than 100-fold as the solvent viscosity increased. Also, the probe showed a direct linear relationship between the fluorescence lifetime and the media viscosity, which makes it possible to trace the change of the medium viscosity. Furthermore, it was demonstrated that BTV could achieve practical applicability in the monitoring of mitochondrial viscosity changes in live cells through fluorescence lifetime imaging microscopy (FLIM). PMID:27589762

  18. A nature-inspired betalainic probe for live-cell imaging of Plasmodium-infected erythrocytes.

    PubMed

    Gonçalves, Letícia Christina Pires; Tonelli, Renata Rosito; Bagnaresi, Piero; Mortara, Renato Arruda; Ferreira, Antonio Gilberto; Bastos, Erick Leite

    2013-01-01

    A model betalainic dye was semisynthesized from betanin, the magenta pigment of the red beet, and was effective for live-cell imaging of Plasmodium-infected red blood cells. This water-soluble fluorescent probe is photostable, excitable in the visible region and cell membrane-permeable, and its photophysical properties are not notably pH-sensitive. Fluorescence imaging microscopy of erythrocytes infected with Plasmodium falciparum, a causative agent of malaria in humans, showed that only the parasite was stained. Z-stacking analysis suggested that the probe accumulates proximal to the nucleus of the parasite. Indicaxanthin, one of the natural fluorescent betalains found in the petals of certain flowers, did not stain the parasite or the red blood cell. PMID:23342028

  19. Imaging individual proteins and nanodomains on intact cell membranes with a probe-based optical antenna.

    PubMed

    van Zanten, Thomas S; Lopez-Bosque, Maria J; Garcia-Parajo, Maria F

    2010-01-01

    Optical antennas that confine and enhance electromagnetic fields in a nanometric region hold great potential for nanobioimaging and biosensing. Probe-based monopole optical antennas are fabricated to enhance fields localized to <30 nm near the antenna apex in aqueous conditions. These probes are used under appropriate excitation antenna conditions to image individual antibodies with an unprecedented resolution of 26 +/- 4 nm and virtually no surrounding background. On intact cell membranes in physiological conditions, the obtained resolution is 30 +/- 6 nm. Importantly, the method allows individual proteins to be distinguished from nanodomains and the degree of clustering to be quantified by directly measuring physical size and intensity of individual fluorescent spots. Improved antenna geometries should lead to true live cell imaging below 10-nm resolution with position accuracy in the subnanometric range. PMID:19943247

  20. Low cost FPGA based data acquisition system for a gamma imaging probe

    NASA Astrophysics Data System (ADS)

    Fysikopoulos, E.; Georgiou, M.; Loudos, G.; Matsopoulos, G.

    2013-11-01

    We present the development of a low cost field programmable gate arrays (FPGA) based data acquisition system for a gamma imaging probe proposed for sentinel lymph node (SLN) mapping. Radioguided surgery using a gamma probe is an established practice and has been widely introduced in SLN biopsies. For such applications, imaging systems require compact readout electronics and flexibility. Embedded systems implemented in the FPGA technology offer new possibilities in data acquisition for nuclear medicine imagers. FPGAs are inexpensive compared to application specific integrated circuits (ASICs), usually used for the readout electronics of dedicated gamma cameras and their size is rather small. In this study, cost effective analog to digital converters (ADCs) were used and signal processing algorithms were implemented in the FPGA to extract the energy and position information. The analog front-end electronics were carefully designed taking into account the low sampling rate of the ADCs. The reference gamma probe has a small field of view (2.5 cm × 2.5 cm) and is based on the R8900U-00-C12 position sensitive photomultiplier tube (PSPMT) coupled to a pixellated CsI(Na) scintillator with 1 mm × 1 mm × 5 mm crystal element size. Measurements were carried out using a general purpose collimator and 99mTc sources emitted at 140 keV. Performance parameters for the imaging gamma probe were compared with those obtained when data were acquired using the standard NIM (Nuclear Instrumentation Modules) electronics and found to be in very good agreement, which demonstrates the efficiency of the proposed implementation.

  1. Live-Cell Bioorthogonal Chemical Imaging: Stimulated Raman Scattering Microscopy of Vibrational Probes.

    PubMed

    Wei, Lu; Hu, Fanghao; Chen, Zhixing; Shen, Yihui; Zhang, Luyuan; Min, Wei

    2016-08-16

    Innovations in light microscopy have tremendously revolutionized the way researchers study biological systems with subcellular resolution. In particular, fluorescence microscopy with the expanding choices of fluorescent probes has provided a comprehensive toolkit to tag and visualize various molecules of interest with exquisite specificity and high sensitivity. Although fluorescence microscopy is currently the method of choice for cellular imaging, it faces fundamental limitations for studying the vast number of small biomolecules. This is because common fluorescent labels, which are relatively bulky, could introduce considerable perturbation to or even completely alter the native functions of vital small biomolecules. Hence, despite their immense functional importance, these small biomolecules remain largely undetectable by fluorescence microscopy. To address this challenge, a bioorthogonal chemical imaging platform has recently been introduced. By coupling stimulated Raman scattering (SRS) microscopy, an emerging nonlinear Raman microscopy technique, with tiny and Raman-active vibrational probes (e.g., alkynes and stable isotopes), bioorthogonal chemical imaging exhibits superb sensitivity, specificity, and biocompatibility for imaging small biomolecules in live systems. In this Account, we review recent technical achievements for visualizing a broad spectrum of small biomolecules, including ribonucleosides and deoxyribonucleosides, amino acids, fatty acids, choline, glucose, cholesterol, and small-molecule drugs in live biological systems ranging from individual cells to animal tissues and model organisms. Importantly, this platform is compatible with live-cell biology, thus allowing real-time imaging of small-molecule dynamics. Moreover, we discuss further chemical and spectroscopic strategies for multicolor bioorthogonal chemical imaging, a valuable technique in the era of "omics". As a unique tool for biological discovery, this platform has been applied to

  2. Sunscope: a video-guided intubation system through a detachable imaging probe.

    PubMed

    Yeh, Jia-Rong; Shieh, Jiann-Shing; Lin, Chih-Peng; Sun, Wei-Zen

    2008-06-01

    We have designed a novel apparatus, the Sunscope, which integrates a semiconductor image sensor into a compact video-guided intubation system. This device consists of three separate modules: viewer, console and visual tube. The 4-inch LCD viewer panel displays the real-time video image with optimal view angle. The console is designed with respect to ergonomics allowing comfortable manipulation and internally accommodating the power supply, image processing components and connector platform for both viewer and probe. The distal end of the detachable probe is packaged with a high resolution lens, CMOS sensor, and four LEDs. The proximal end is a 6-pin connector which can be readily removed and attached on demand. The probe is detachable and disposable with length and diameter adaptable to the size of the endotracheal tube. In our preliminary test, the video-guided apparatus helped inexperienced performers to identify the vocal cords correctly and improve the success rate of intubation on the simulation model. With further improvements on the miniature design, all captured images could be transmitted to remote devices through standard wireless transmission and could thus be stored in a specific database station. The wireless technique enables image sharing on multiple devices while a powerful database can provide valuable resources for training, data mining and serial case studies. We demonstrate that the CMOS image sensor combined with advanced reduced instruction set computer machine can serve as a visual aid for tracheal intubation. The disposable station will become a revolutionary technology both in clinical practice and medical education. PMID:18593652

  3. Imaging of biological samples by a collection-mode photon scanning tunneling microscope with an apertured probe

    NASA Astrophysics Data System (ADS)

    Naya, Masayuki; Mononobe, Shuji; Uma Maheswari, R.; Saiki, Tosiharu; Ohtsu, Motoichi

    1996-02-01

    We report on high resolution imaging by a collection-mode photon scanning tunneling microscope (c-mode PSTM). In our PSTM system, we have used a novel probe with a nanometric protrusion formed from a metal coated sharpened fiber. By using this probe, flagellar filaments of salmonella of diameter 25 nm could be imaged to have a full width at half maximum of 50 nm. Obtained images strongly depended on the separation of the sample to the probe, the diameter of the aperture, and polarization of the irradiated light. Comments on the origins of these dependencies are given.

  4. Metal-based optical probes for live cell imaging of nitroxyl (HNO).

    PubMed

    Rivera-Fuentes, Pablo; Lippard, Stephen J

    2015-11-17

    Nitroxyl (HNO) is a biological signaling agent that displays distinctive reactivity compared to nitric oxide (NO). As a consequence, these two reactive nitrogen species trigger different physiological responses. Selective detection of HNO over NO has been a challenge for chemists, and several fluorogenic molecular probes have been recently developed with that goal in mind. Common constructs take advantage of the HNO-induced reduction of Cu(II) to Cu(I). The sensing mechanism of such probes relies on the ability of the unpaired electron in a d orbital of the Cu(II) center to quench the fluorescence of a photoemissive ligand by either an electron or energy transfer mechanism. Experimental and theoretical mechanistic studies suggest that proton-coupled electron transfer mediates this process, and careful tuning of the copper coordination environment has led to sensors with optimized selectivity and kinetics. The current optical probes cover the visible and near-infrared regions of the spectrum. This palette of sensors comprises structurally and functionally diverse fluorophores such as coumarin (blue/green emission), boron dipyrromethane (BODIPY, green emission), benzoresorufin (red emission), and dihydroxanthenes (near-infrared emission). Many of these sensors have been successfully applied to detect HNO production in live cells. For example, copper-based optical probes have been used to detect HNO production in live mammalian cells that have been treated with H2S and various nitrosating agents. These studies have established a link between HSNO, the smallest S-nitrosothiol, and HNO. In addition, a near-infrared HNO sensor has been used to perform multicolor/multianalyte microscopy, revealing that exogenously applied HNO elevates the concentration of intracellular mobile zinc. This mobilization of zinc ions is presumably a consequence of nitrosation of cysteine residues in zinc-chelating proteins such as metallothionein. Future challenges for the optical imaging of

  5. Feasibility studies of an EMCCD-based beta imaging probe for radioguided thyroid surgery

    NASA Astrophysics Data System (ADS)

    Shestakova, Irina; Nagarkar, Vivek V.; Gaysinskiy, Valeriy; Entine, Gerald; Stack, Brendan C.; Miller, Brian

    2006-08-01

    We are developing a probe for image-guided surgery of cancer to be used in conjunction with traditional beta emitting radiopharmaceuticals such as I 131 and F 18-FDG. This device is based on a combination of two novel technologies, a microcolumnar film scintillator, CsI(Tl) and low-noise high sensitivity Electron-Multiplying CCD (EMCCD). The former allows high spatial resolution nuclear imaging and the latter facilitates detection of signal with significantly higher SNR than conventional CCDs by the virtue of internal signal gain built into its readout register. CsI(Tl) is bonded to the EMCCD via a flexible coherent fiberopic cable for easy handling. Due to its high sensitivity the probe is capable of functioning in real time providing high spatial resolution nuclear images for precise detection, delineation and excision of tumors. The evaluation of the probe using standard clinical phantoms as well as the operational data obtained on swine models and in clinical surgery will be presented.

  6. Bioengineered Probes for Molecular Magnetic Resonance Imaging in the Nervous System

    PubMed Central

    2012-01-01

    The development of molecular imaging probes has changed the nature of neurobiological research. Some of the most notable successes have involved the use of biological engineering techniques for the creation of fluorescent protein derivatives for optical imaging, but recent work has also led to a number of bioengineered probes for magnetic resonance imaging (MRI), the preeminent technique for noninvasive investigation of brain structure and function. Molecular MRI agents are beginning to be applied for experiments in the nervous system, where they have the potential to bridge from molecular to systems or organismic levels of analysis. Compared with canonical synthetic small molecule agents, biomolecular or semibiosynthetic MRI contrast agents offer special advantages due to their amenability to molecular engineering approaches, their properties in some cases as catalysts, and their specificity in targeting and ligand binding. Here, we discuss an expanding list of instances where biological engineering techniques have aided in the design of MRI contrast agents and reporter systems, examining both advantages and limitations of these types of probes for studies in the central nervous system. PMID:22896803

  7. Dual tracer imaging of SPECT and PET probes in living mice using a sequential protocol

    PubMed Central

    Chapman, Sarah E; Diener, Justin M; Sasser, Todd A; Correcher, Carlos; González, Antonio J; Avermaete, Tony Van; Leevy, W Matthew

    2012-01-01

    Over the past 20 years, multimodal imaging strategies have motivated the fusion of Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) scans with an X-ray computed tomography (CT) image to provide anatomical information, as well as a framework with which molecular and functional images may be co-registered. Recently, pre-clinical nuclear imaging technology has evolved to capture multiple SPECT or multiple PET tracers to further enhance the information content gathered within an imaging experiment. However, the use of SPECT and PET probes together, in the same animal, has remained a challenge. Here we describe a straightforward method using an integrated trimodal imaging system and a sequential dosing/acquisition protocol to achieve dual tracer imaging with 99mTc and 18F isotopes, along with anatomical CT, on an individual specimen. Dosing and imaging is completed so that minimal animal manipulations are required, full trimodal fusion is conserved, and tracer crosstalk including down-scatter of the PET tracer in SPECT mode is avoided. This technique will enhance the ability of preclinical researchers to detect multiple disease targets and perform functional, molecular, and anatomical imaging on individual specimens to increase the information content gathered within longitudinal in vivo studies. PMID:23145357

  8. Principal Component Analysis of Spectroscopic Imaging Data in Scanning Probe Microscopy

    SciTech Connect

    Jesse, Stephen; Kalinin, Sergei V

    2009-01-01

    The approach for data analysis in band excitation family of scanning probe microscopies based on principal component analysis (PCA) is explored. PCA utilizes the similarity between spectra within the image to select the relevant response components. For small signal variations within the image, the PCA components coincide with the results of deconvolution using simple harmonic oscillator model. For strong signal variations, the PCA allows effective approach to rapidly process, de-noise and compress the data. The extension of PCA for correlation function analysis is demonstrated. The prospects of PCA as a universal tool for data analysis and representation in multidimensional SPMs are discussed.

  9. Dual Frequency Band Annular Probe for Volumetric Pulse-echo Optoacoustic Imaging

    NASA Astrophysics Data System (ADS)

    Kalkhoran, Mohammad Azizian; Varray, François; Vray, Didier

    Optoacoustic (OA) pulse echo (PE) imaging is a hybridized modality that is capable of providing physiological information on the basis of anatomical structure. In this work, we propose a dual frequency band annular probe for backward mode volumetric PE/OA imaging. The performance of this design is evaluated based on the spatio-temporal impulse response, three dimensional steerability of the transducer and point spread function. Optimum settings for number of elements in each ring and maximum steering are suggested. The transducer design and synthetic array beamforming simulation are presented. The resolution performance and reconstruction capabilities are shown with the in-silico measurements.

  10. Molecular probes for two-photon excited fluorescence and second harmonic generation imaging of biological membranes

    NASA Astrophysics Data System (ADS)

    Porres, Laurent; Mongin, Olivier; Bhatthula, Bharath K. G.; Blanchard-Desce, Mireille H.; Ventelon, Lionel; Moreaux, Laurent; Pons, T.; Mertz, Jerome

    2002-11-01

    Novel microscopies based on nonlinear optical (NLO) phenomena are attracting increasing interest in the biology community owing to their potentialities in the area of real-time, non-damaging imaging of biological systems. In particular, second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) are NLO phenomena that scale with excitation intensity squared, and thus give rise to an intrinsic 3-dimensional resolution when used in microscopic imaging. In this perspective, we have implemented a molecular engineering approach toward NLO-probes specifically designed for SHG and/or TPEF imaging of cellular membranes. We have designed nanoscale rod-like fluorophores showing very large TPEF cross-sections in the visible red, outperforming standard fluorophores such as fluorescein by up to two orders of magnitude. Bolaamphiphilic derivatives combining high TPEF cross-sections and affinity for cellular membranes were prepared. Their incorporation into model or cell membranes can be monitored by TPEF microscopy. Amphiphilic push-pull chromophores showing both high TPA and SHG cross-sections in the near-IR region were designed as NLO-probes for imaging of biological membranes by simultaneous SHG and TPEF microscopy. These NLO-phores offer intriguing potentialities for imaging of fundamental biological processes such as adhesion, fusion or for reporting of membrane electrical potentials.

  11. Imaging on a Shoestring: Cost-Effective Technologies for Probing Vadose Zone Transport Processes

    NASA Astrophysics Data System (ADS)

    Corkhill, C.; Bridge, J. W.; Barns, G.; Fraser, R.; Romero-Gonzalez, M.; Wilson, R.; Banwart, S.

    2010-12-01

    Key barriers to the widespread uptake of imaging technology for high spatial resolution monitoring of porous media systems are cost and accessibility. X-ray tomography, magnetic resonance imaging (MRI), gamma and neutron radiography require highly specialised equipment, controlled laboratory environments and/or access to large synchrotron facilities. Here we present results from visible light, fluorescence and autoradiographic imaging techniques developed at low cost and applied in standard analytical laboratories, adapted where necessary at minimal capital expense. UV-visible time lapse fluorescence imaging (UV-vis TLFI) in a transparent thin bed chamber enabled microspheres labelled with fluorescent dye and a conservative fluorophore solute (disodium fluorescein) to be measured simultaneously in saturated, partially-saturated and actively draining quartz sand to elucidate empirical values for colloid transport and deposition parameters distributed throughout the flow field, independently of theoretical approximations. Key results include the first experimental quantification of the effects of ionic strength and air-water interfacial area on colloid deposition above a capillary fringe, and the first direct observations of particle mobilisation and redeposition by moving saturation gradients during drainage. UV-vis imaging was also used to study biodegradation and reactive transport in a variety of saturated conditions, applying fluorescence as a probe for oxygen and nitrate concentration gradients, pH, solute transport parameters, reduction of uranium, and mapping of two-dimensional flow fields around a model dipole flow borehole system to validate numerical models. Costs are low: LED excitation sources (< US 50), flow chambers (US 200) and detectors (although a complete scientific-grade CCD set-up costs around US$ 8000, robust datasets can be obtained using a commercial digital SLR camera) mean that set-ups can be flexible to meet changing experimental

  12. Nanoscale probing of image-dipole interactions in a metallic nanostructure

    PubMed Central

    Ropp, Chad; Cummins, Zachary; Nah, Sanghee; Fourkas, John T.; Shapiro, Benjamin; Waks, Edo

    2015-01-01

    An emitter near a surface induces an image dipole that can modify the observed emission intensity and radiation pattern. These image-dipole effects are generally not taken into account in single-emitter tracking and super-resolved imaging applications. Here we show that the interference between an emitter and its image dipole induces a strong polarization anisotropy and a large spatial displacement of the observed emission pattern. We demonstrate these effects by tracking the emission of a single quantum dot along two orthogonal polarizations as it is deterministically positioned near a silver nanowire. The two orthogonally polarized diffraction spots can be displaced by up to 50 nm, which arises from a Young’s interference effect between the quantum dot and its induced image dipole. We show that the observed spatially varying interference fringe provides a useful measure for correcting image-dipole-induced distortions. These results provide a pathway towards probing and correcting image-dipole effects in near-field imaging applications. PMID:25790228

  13. A highly sensitive ratiometric fluorescent probe with a large emission shift for imaging endogenous cysteine in living cells.

    PubMed

    Zhu, Baocun; Guo, Bingpeng; Zhao, Yunzhou; Zhang, Bing; Du, Bin

    2014-05-15

    A new design strategy for the construction of ratiometric fluorescent probe with a large emission shift was developed. Based on this strategy, a highly selective and sensitive colorimetric and ratiometic fluorescent probe for cysteine (Cys) with a 117 nm red-shifted emission was synthesized and applied to the ratiometric imaging of endogenous Cys in living cells. PMID:24362081

  14. A novel ratiometric two-photon fluorescent probe for imaging of Pd(2+) ions in living cells and tissues.

    PubMed

    Zhou, Liyi; Hu, Shunqin; Wang, Haifei; Sun, Hongyan; Zhang, Xiaobing

    2016-09-01

    Ratiometric two-photon fluorescent probes can not only eliminate interferences from environmental factors but also achieve deep-tissue imaging with improved spatial localization. To quantitatively track Pd(2+) in biosystems, herein, we reported a ratiometric two-photon fluorescent probe, termed as Np-Pd, which based on a D-π-A-structure two-photon fluorophore of the naphthalimide derivative and deprotection of aryl propargyl ethers by palladium species. The probe Np-Pd displayed a more than 25-fold enhancement towards palladium species with high sensitivity and selectivity. Additionally, the probe Np-Pd was further used for fluorescence imaging of Pd(2+) ions in living cells and tissues under two-photon excitation (820nm), which showed large tissue-imaging depth (19.6-184.6μm), and a high resolution for ratiometric imaging. PMID:27203231

  15. A novel ratiometric two-photon fluorescent probe for imaging of Pd2 + ions in living cells and tissues

    NASA Astrophysics Data System (ADS)

    Zhou, Liyi; Hu, Shunqin; Wang, Haifei; Sun, Hongyan; Zhang, Xiaobing

    2016-09-01

    Ratiometric two-photon fluorescent probes can not only eliminate interferences from environmental factors but also achieve deep-tissue imaging with improved spatial localization. To quantitatively track Pd2 + in biosystems, herein, we reported a ratiometric two-photon fluorescent probe, termed as Np-Pd, which based on a D-π-A-structure two-photon fluorophore of the naphthalimide derivative and deprotection of aryl propargyl ethers by palladium species. The probe Np-Pd displayed a more than 25-fold enhancement towards palladium species with high sensitivity and selectivity. Additionally, the probe Np-Pd was further used for fluorescence imaging of Pd2 + ions in living cells and tissues under two-photon excitation (820 nm), which showed large tissue-imaging depth (19.6-184.6 μm), and a high resolution for ratiometric imaging.

  16. A scanning Hall probe microscope for high resolution magnetic imaging down to 300 mK

    NASA Astrophysics Data System (ADS)

    Khotkevych, V. V.; Milošević, M. V.; Bending, S. J.

    2008-12-01

    We present the design, construction, and performance of a low-temperature scanning Hall probe microscope with submicron lateral resolution and a large scanning range. The detachable microscope head is mounted on the cold flange of a commercial H3e-refrigerator (Oxford Instruments, Heliox VT-50) and operates between room temperature and 300 mK. It is fitted with a three-axis slip-stick nanopositioner that enables precise in situ adjustment of the probe location within a 6×6×7 mm3 space. The local magnetic induction at the sample surface is mapped with an easily changeable microfabricated Hall probe [typically GsAs/AlGaAs or AlGaAs/InGaAs/GaAs Hall sensors with integrated scanning tunnel microscopy (STM) tunneling tips] and can achieve minimum detectable fields ⩾10 mG/Hz1/2. The Hall probe is brought into very close proximity to the sample surface by sensing and controlling tunnel currents at the integrated STM tip. The instrument is capable of simultaneous tunneling and Hall signal acquisition in surface-tracking mode. We illustrate the potential of the system with images of superconducting vortices at the surface of a Nb thin film down to 372 mK, and also of labyrinth magnetic-domain patterns of an yttrium iron garnet film captured at room temperature.

  17. A scanning Hall probe microscope for high resolution magnetic imaging down to 300 mK

    SciTech Connect

    Khotkevych, V. V.; Bending, S. J.; Milosevic, M. V.

    2008-12-15

    We present the design, construction, and performance of a low-temperature scanning Hall probe microscope with submicron lateral resolution and a large scanning range. The detachable microscope head is mounted on the cold flange of a commercial {sup 3}He-refrigerator (Oxford Instruments, Heliox VT-50) and operates between room temperature and 300 mK. It is fitted with a three-axis slip-stick nanopositioner that enables precise in situ adjustment of the probe location within a 6x6x7 mm{sup 3} space. The local magnetic induction at the sample surface is mapped with an easily changeable microfabricated Hall probe [typically GsAs/AlGaAs or AlGaAs/InGaAs/GaAs Hall sensors with integrated scanning tunnel microscopy (STM) tunneling tips] and can achieve minimum detectable fields {>=}10 mG/Hz{sup 1/2}. The Hall probe is brought into very close proximity to the sample surface by sensing and controlling tunnel currents at the integrated STM tip. The instrument is capable of simultaneous tunneling and Hall signal acquisition in surface-tracking mode. We illustrate the potential of the system with images of superconducting vortices at the surface of a Nb thin film down to 372 mK, and also of labyrinth magnetic-domain patterns of an yttrium iron garnet film captured at room temperature.

  18. Dual-Modal Magnetic Resonance/Fluorescent Zinc Probes for Pancreatic β-Cell Mass Imaging

    PubMed Central

    Stasiuk, Graeme J; Minuzzi, Florencia; Sae-Heng, Myra; Rivas, Charlotte; Juretschke, Hans-Paul; Piemonti, Lorenzo; Allegrini, Peter R; Laurent, Didier; Duckworth, Andrew R; Beeby, Andrew; Rutter, Guy A; Long, Nicholas J

    2015-01-01

    Despite the contribution of changes in pancreatic β-cell mass to the development of all forms of diabetes mellitus, few robust approaches currently exist to monitor these changes prospectively in vivo. Although magnetic-resonance imaging (MRI) provides a potentially useful technique, targeting MRI-active probes to the β cell has proved challenging. Zinc ions are highly concentrated in the secretory granule, but they are relatively less abundant in the exocrine pancreas and in other tissues. We have therefore developed functional dual-modal probes based on transition-metal chelates capable of binding zinc. The first of these, Gd⋅1, binds ZnII directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from λem=410 to 500 nm with an increase in relaxivity from r1=4.2 up to 4.9 mM−1 s−1. The probe is efficiently accumulated into secretory granules in β-cell-derived lines and isolated islets, but more poorly by non-endocrine cells, and leads to a reduction in T1 in human islets. In vivo murine studies of Gd⋅1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes. PMID:25736590

  19. Cetuximab-based therapy is effective in chemotherapy-naïve patients with advanced and metastatic non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

    PubMed

    Ibrahim, Ezzeldin M; Abouelkhair, Khaled M; Al-Masri, Osama A; Chaudry, Najeeb C; Kazkaz, Ghieth A

    2011-06-01

    Randomized controlled trails (RCTs) where cetuximab added to first-line platinum-based chemotherapy for patients with advanced/metastatic non-small-cell lung cancer (NSCLC) have yielded conflicting results. This meta-analysis intended to evaluate the efficacy and safety of cetuximab-based therapy (CBT) in that setting. We analyzed four eligible RCTs that included 1,003 and 1,015 patients randomized to CBT and control intervention, respectively. As compared with the noncetuximab group, CBT demonstrated an 9% reduction in the risk of disease progression [hazard ratio (HR) = 0.91; (CI = 0.83-1.00); p = 0.06], a 13% reduction in the risk of death [HR = 0.87; (CI = 0.78-0.96); p = 0.005], and an approximately 50% increase in objective response rate [odds ratio (OR) = 1.48; (CI = 1.22-1.80); p < 0.0001]. CBT-related adverse events were similar across comparisons except for toxicities known to be associated with anti-EGFR therapy. CBT produced significant clinical benefit with acceptable toxicity as a first-line strategy in patients with advanced/metastatic NSCLC. Further research is needed to identify markers predictive of cetuximab benefit in that disease. PMID:21424607

  20. Hard real-time beam scheduler enables adaptive images in multi-probe systems

    NASA Astrophysics Data System (ADS)

    Tobias, Richard J.

    2014-03-01

    Real-time embedded-system concepts were adapted to allow an imaging system to responsively control the firing of multiple probes. Large-volume, operator-independent (LVOI) imaging would increase the diagnostic utility of ultrasound. An obstacle to this innovation is the inability of current systems to drive multiple transducers dynamically. Commercial systems schedule scanning with static lists of beams to be fired and processed; here we allow an imager to adapt to changing beam schedule demands, as an intelligent response to incoming image data. An example of scheduling changes is demonstrated with a flexible duplex mode two-transducer application mimicking LVOI imaging. Embedded-system concepts allow an imager to responsively control the firing of multiple probes. Operating systems use powerful dynamic scheduling algorithms, such as fixed priority preemptive scheduling. Even real-time operating systems lack the timing constraints required for ultrasound. Particularly for Doppler modes, events must be scheduled with sub-nanosecond precision, and acquired data is useless without this requirement. A successful scheduler needs unique characteristics. To get close to what would be needed in LVOI imaging, we show two transducers scanning different parts of a subjects leg. When one transducer notices flow in a region where their scans overlap, the system reschedules the other transducer to start flow mode and alter its beams to get a view of the observed vessel and produce a flow measurement. The second transducer does this in a focused region only. This demonstrates key attributes of a successful LVOI system, such as robustness against obstructions and adaptive self-correction.

  1. In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy.

    PubMed

    Murugesan, R; Cook, J A; Devasahayam, N; Afeworki, M; Subramanian, S; Tschudin, R; Larsen, J A; Mitchell, J B; Russo, A; Krishna, M C

    1997-09-01

    Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 microsecond, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10-50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency. Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications. FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques. PMID:9339442

  2. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe

    PubMed Central

    Phillips, Evan; Penate-Medina, Oula; Zanzonico, Pat B.; Carvajal, Richard D.; Mohan, Pauliah; Ye, Yunpeng; Humm, John; Gönen, Mithat; Kalaigian, Hovanes; Schöder, Heiko; Strauss, H. William; Larson, Steven M.; Wiesner, Ulrich; Bradbury, Michelle S.

    2015-01-01

    A first-in-human clinical trial of ultrasmall inorganic hybrid nanoparticles, “C dots” (Cornell dots), in patients with metastatic melanoma is described for the imaging of cancer. These renally excreted silica particles were labeled with 124I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. 124I-cRGDY–PEG–C dot particles are inherently fluorescent, containing the dye, Cy5, so they may be used as hybrid PET-optical imaging agents for lesion detection, cancer staging, and treatment management in humans. However, the clinical translation of nanoparticle probes, including quantum dots, has not kept pace with the accelerated growth in minimally invasive surgical tools that rely on optical imaging agents. The safety, pharmacokinetics, clearance properties, and radiation dosimetry of 124I-cRGDY–PEG–C dots were assessed by serial PET and computerized tomography after intravenous administration in patients. Metabolic profiles and laboratory tests of blood and urine specimens, obtained before and after particle injection, were monitored over a 2-week interval. Findings are consistent with a well-tolerated inorganic particle tracer exhibiting in vivo stability and distinct, reproducible pharmacokinetic signatures defined by renal excretion. No toxic or adverse events attributable to the particles were observed. Coupled with preferential uptake and localization of the probe at sites of disease, these first-in-human results suggest safe use of these particles in human cancer diagnostics. PMID:25355699

  3. GLP-1 receptor antagonist as a potential probe for pancreatic {beta}-cell imaging

    SciTech Connect

    Mukai, Eri; Toyoda, Kentaro; Kimura, Hiroyuki; Kawashima, Hidekazu; Fujimoto, Hiroyuki; Ueda, Masashi; Temma, Takashi; Hirao, Konomu; Nagakawa, Kenji; Saji, Hideo; Inagaki, Nobuya

    2009-11-20

    We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic {beta}-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [{sup 125}I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [{sup 125}I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120 min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [{sup 125}I]BH-exendin(9-39) injection into transgenic mice with pancreatic {beta}-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic {beta}-cell imaging.

  4. Development of Follicle-Stimulating Hormone Receptor Binding Probes to Image Ovarian Xenografts

    PubMed Central

    Lee, Chung-Wein; Guo, Lili; Matei, Daniela; Stantz, Keith

    2015-01-01

    The Follicle-Stimulating Hormone Receptor (FSHR) is used as an imaging biomarker for the detection of ovarian cancer (OC). FSHR is highly expressed on ovarian tumors and involved with cancer development and metastatic signaling pathways. A decapeptide specific to the FSHR extracellular domain is synthesized and conjugated to fluorescent dyes to image OC cells in vitro and tumors xenograft model in vivo. The in vitro binding curve and the average number of FSHR per cell are obtained for OVCAR-3 cells by a high resolution flow cytometer. For the decapeptide, the measured EC50 was 160 μM and the average number of receptors per cell was 1.7 × 107. The decapeptide molecular imaging probe reached a maximum tumor to muscle ratio five hours after intravenous injection and a dose-dependent plateau after 24–48 hours. These results indicate the potential application of a small molecular weight imaging probe specific to ovarian cancer through binding to FSHR. Based on these results, multimeric constructs are being developed to optimize binding to ovarian cells and tumors. PMID:26779384

  5. Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes.

    PubMed

    Zhao, Ping; Yang, Xiaoyang; Qi, Shibo; Liu, Hongguang; Jiang, Han; Hoppmann, Susan; Cao, Qizhen; Chua, Mei-Sze; So, Samuel K; Cheng, Zhen

    2013-01-01

    Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%-20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR) has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET) or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo. PMID:23710458

  6. Volumetric synthetic aperture imaging with a piezoelectric 2D row-column probe

    NASA Astrophysics Data System (ADS)

    Bouzari, Hamed; Engholm, Mathias; Christiansen, Thomas Lehrmann; Beers, Christopher; Lei, Anders; Stuart, Matthias Bo; Nikolov, Svetoslav Ivanov; Thomsen, Erik Vilain; Jensen, Jørgen Arendt

    2016-04-01

    The synthetic aperture (SA) technique can be used for achieving real-time volumetric ultrasound imaging using 2-D row-column addressed transducers. This paper investigates SA volumetric imaging performance of an in-house prototyped 3 MHz λ/2-pitch 62+62 element piezoelectric 2-D row-column addressed transducer array. Utilizing single element transmit events, a volume rate of 90 Hz down to 14 cm deep is achieved. Data are obtained using the experimental ultrasound scanner SARUS with a 70 MHz sampling frequency and beamformed using a delay-and-sum (DAS) approach. A signal-to-noise ratio of up to 32 dB is measured on the beamformed images of a tissue mimicking phantom with attenuation of 0.5 dB cm-1 MHz-1, from the surface of the probe to the penetration depth of 300λ. Measured lateral resolution as Full-Width-at-Half-Maximum (FWHM) is between 4λ and 10λ for 18% to 65% of the penetration depth from the surface of the probe. The averaged contrast is 13 dB for the same range. The imaging performance assessment results may represent a reference guide for possible applications of such an array in different medical fields.

  7. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe.

    PubMed

    Phillips, Evan; Penate-Medina, Oula; Zanzonico, Pat B; Carvajal, Richard D; Mohan, Pauliah; Ye, Yunpeng; Humm, John; Gönen, Mithat; Kalaigian, Hovanes; Schöder, Heiko; Strauss, H William; Larson, Steven M; Wiesner, Ulrich; Bradbury, Michelle S

    2014-10-29

    A first-in-human clinical trial of ultrasmall inorganic hybrid nanoparticles, "C dots" (Cornell dots), in patients with metastatic melanoma is described for the imaging of cancer. These renally excreted silica particles were labeled with (124)I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. (124)I-cRGDY-PEG-C dot particles are inherently fluorescent, containing the dye, Cy5, so they may be used as hybrid PET-optical imaging agents for lesion detection, cancer staging, and treatment management in humans. However, the clinical translation of nanoparticle probes, including quantum dots, has not kept pace with the accelerated growth in minimally invasive surgical tools that rely on optical imaging agents. The safety, pharmacokinetics, clearance properties, and radiation dosimetry of (124)I-cRGDY-PEG-C dots were assessed by serial PET and computerized tomography after intravenous administration in patients. Metabolic profiles and laboratory tests of blood and urine specimens, obtained before and after particle injection, were monitored over a 2-week interval. Findings are consistent with a well-tolerated inorganic particle tracer exhibiting in vivo stability and distinct, reproducible pharmacokinetic signatures defined by renal excretion. No toxic or adverse events attributable to the particles were observed. Coupled with preferential uptake and localization of the probe at sites of disease, these first-in-human results suggest safe use of these particles in human cancer diagnostics. PMID:25355699

  8. Photoacoustic Imaging with a Commercial Ultrasound System and a Custom Probe

    PubMed Central

    Wang, Xueding; Fowlkes, J. Brian; Cannata, Jonathan M.; Hu, Changhong; Carson, Paul L.

    2010-01-01

    Building photoacoustic imaging (PAI) systems by using stand-alone ultrasound (US) units makes it convenient to take advantage of the state-of-the-art ultrasonic technologies. However, the sometimes limited receiving sensitivity and the comparatively narrow bandwidth of commercial US probes may not be sufficient to acquire high quality photoacoustic images. In this work, a high-speed PAI system has been developed using a commercial US unit and a custom built 128-element piezoelectric-polymer array (PPA) probe using a P(VDF-TrFE) film and flexible circuit to define the elements. Since the US unit supports simultaneous signal acquisition from 64 parallel receive channels, PAI data for synthetic image formation from a 64 or 128 element array aperture can be acquired after a single or dual laser firing, respectively. Therefore, 2D B-scan imaging can be achieved with a maximum frame rate up to 10 Hz, limited only by the laser repetition rate. The uniquely properties of P(VDF-TrFE) facilitated a wide -6 dB receiving bandwidth of over 120 % for the array. A specially designed 128-channel preamplifier board made the connection between the array and the system cable which not only enabled element electrical impedance matching but also further elevated the signal-to-noise ratio (SNR) to further enhance the detection of weak photoacoustic signals. Through the experiments on phantoms and rabbit ears, the good performance of this PAI system was demonstrated. PMID:21276653

  9. Magnetic resonance imaging compatibility testing of intracranial pressure probes. Technical note.

    PubMed

    Williams, E J; Bunch, C S; Carpenter, T A; Downey, S P; Kendall, I V; Czosnyka, M; Pickard, J D; Martin, J; Menon, D K

    1999-10-01

    There is increasing recognition that magnetic resonance (MR) imaging and spectroscopy may provide important information in the assessment of patients with acute brain injury. However, optimum care of the acutely head injured patient requires monitoring of intracranial pressure (ICP). Although many monitoring modalities have been integrated into commercially available MR-compatible systems, there have been no reports of commonly used intraparenchymal ICP sensors in an MR environment. The authors describe the use of an ICP micromanometer probe in an MR environment, with a fiberoptic connection that interfaces the probe with a commercially available MR-compatible monitoring system. Phantom studies were performed to demonstrate the safety and compatibility of the modified MR system at 0.5 tesla. The safety of the device was assessed in relation to its interaction with the static, gradient, and radiofrequency fields used in MR imaging. The MR compatibility was documented by demonstrating that its performance was unaffected by the operation of imaging sequences and by showing that there was no degradation of the diagnostic quality of imaging data obtained during ICP monitoring. PMID:10507397

  10. Optimized multimodal functional magnetic resonance imaging/near-infrared spectroscopy probe for ultrahigh-resolution mapping.

    PubMed

    Hocke, Lia Maria; Cayetano, Kenroy; Tong, Yunjie; Frederick, Blaise

    2015-10-01

    Functional near-infrared spectroscopy (fNIRS) is an increasingly important noninvasive method in neuroscience due to its high temporal resolution and ability to independently measure oxy- and deoxy-hemoglobin. However, the relatively low spatial resolution of fNIRS makes it difficult to relate this signal to underlying anatomy. Simultaneous functional magnetic resonance imaging (fMRI) can complement fNIRS with superior spatial resolution and the ability to image the entire brain, providing additional information to improve fNIRS localization. However, current simultaneous fMRI/fNIRS acquisition methods are not optimal, due to the poor physical compatibility of existing MR coils and fNIRS optodes. Here, we present a technique to manufacture a true multimodal fMRI/fNIRS probe in which both modalities can be used with maximal sensitivity. To achieve this, we designed custom MR coils with integral fNIRS optodes using three-dimensional printing. This multimodal probe can be used to optimize spatial ([Formula: see text]) and temporal resolution (2.5 Hz) of fMRI, and it provides maximal MRI sensitivity, while allowing for high flexibility in the location and density of fNIRS optodes within the area of interest. Phantom and human data are shown to confirm the improvement in sensitivity in both modalities. This probe shows promise for addressing fundamental questions of the relation of fNIRS to physiology. PMID:26668816

  11. Nanoparticle-based luminescent probes for intracellular sensing and imaging of pH.

    PubMed

    Schäferling, Michael

    2016-05-01

    Fluorescence imaging microscopy is an essential tool in biomedical research. Meanwhile, various fluorescent probes are available for the staining of cells, cell membranes, and organelles. Though, to monitor intracellular processes and dysfunctions, probes that respond to ubiquitous chemical parameters determining the cellular function such as pH, pO2 , and Ca(2+) are required. This review is focused on the progress in the design, fabrication, and application of photoluminescent nanoprobes for sensing and imaging of pH in living cells. The advantages of using nanoprobes carrying fluorescent pH indicators compared to single molecule probes are discussed as well as their limitations due to the mostly lysosomal uptake by cells. Particular attention is paid to ratiometric dual wavelength nanosensors that enable intrinsic referenced measurements. Referencing and proper calibration procedures are basic prerequisites to carry out reliable quantitative pH determinations in complex samples such as living cells. A variety of examples will be presented that highlight the diverseness of nanocarrier materials (polymers, micelles, silica, quantum dots, carbon dots, gold, photon upconversion nanocrystals, or bacteriophages), fluorescent pH indicators for the weak acidic range, and referenced sensing mechanisms, that have been applied intracellularly up to now. WIREs Nanomed Nanobiotechnol 2016, 8:378-413. doi: 10.1002/wnan.1366 For further resources related to this article, please visit the WIREs website. PMID:26395962

  12. Non-invasive Imaging of Staphylococcus aureus Infections with a Nuclease-Activated Probe

    PubMed Central

    Hernandez, Frank J.; Huang, Lingyan; Olson, Michael E.; Powers, Kristy M.; Hernandez, Luiza I.; Meyerholz, David K.; Thedens, Daniel R.; Behlke, Mark A.; Horswill, Alexander R.; McNamara, James O.

    2013-01-01

    Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, non-invasive detection of S. aureus based on the activity of its secreted nuclease, micrococcal nuclease (MN). Several short, synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications, flanked with a fluorophore and quencher, were activated upon degradation by recombinant MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing bioluminescent S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This novel bacterial imaging approach has potential clinical applicability for S. aureus and several other medically significant pathogens. PMID:24487433

  13. Dual PET and Near-Infrared Fluorescence Imaging Probes as Tools for Imaging in Oncology

    PubMed Central

    An, Fei-Fei; Chan, Mark; Kommidi, Harikrishna; Ting, Richard

    2016-01-01

    OBJECTIVE The purpose of this article is to summarize advances in PET fluorescence resolution, agent design, and preclinical imaging that make a growing case for clinical PET fluorescence imaging. CONCLUSION Existing SPECT, PET, fluorescence, and MRI contrast imaging techniques are already deeply integrated into the management of cancer, from initial diagnosis to the observation and management of metastases. Combined positron-emitting fluorescent contrast agents can convey new or substantial benefits that improve on these proven clinical contrast agents. PMID:27223168

  14. Synthetic White-light Imagery for the Wide-field Imager for Solar Probe Plus (WISPR)

    NASA Astrophysics Data System (ADS)

    Liewer, P. C.; Thernisien, A. F.; Vourlidas, A.; Howard, R.; DeForest, C. E.; DeJong, E.; Desai, A.

    2015-12-01

    The Solar Probe Plus trajectory, approaching within 10 solar radii, will enable the white light imager, WISPR, to fly through corona features now only imaged remotely. The dependency of the Thomson scattering on the imaging geometry (distance and angle from the Sun) dictates that the outer WISPR telescope will be sensitive to the emission from plasma close to the spacecraft, in contrast to the situation for imaging from Earth orbit. Thus WISPR will be the first 'local' imager providing a crucial link between the large-scale corona and SPP's in-situ measurements. The high speed at perihelion will provide tomographic-like views of coronal structures at ≤1° resolution. As SPP approaches perihelion, WISPR, with a 95° radial by 58° transverse field of view, will resolve the fine-scale structure with high spatial resolution. To prepare for this unprecedented viewing of the structure of the inner corona, we are creating synthetic white light images and animations from the WISPR viewpoint using the white-light ray-tracing package developed at NRL (available through SolarSoft). We will present simulated observations of multi-strand models of coronal streamers and flux ropes of various size and make comparisons with views from Earth, Solar Orbiter and SPP. Analysis techniques for WISPR images will also be discussed.

  15. Synthetic White-light Imagery for the Wide-field Imager for Solar Probe Plus (WISPR)

    NASA Astrophysics Data System (ADS)

    Liewer, P. C.; Su, Y.; Vourlidas, A.; Thernisien, A. F.; Howard, R.; Hall, J. R.; DeJong, E.

    2014-12-01

    The Solar Probe Plus trajectory, approaching within 10 solar radii, will allow the white light imager, WISPR, to view the inner corona with unprecedented spatial resolution. WISPR, with a 95° radial by 58° transverse field of view, will image the fine-scale structure with arcminute-scale resolution. The dependency of the Thomson scattering on the imaging geometry (distance and angle from the Sun) dictates that WISPR will be very sensitive to the emission from plasma close to the spacecraft, in contrast to the situation for imaging from Earth orbit. Thus WISPR will be the first 'local' imager providing a crucial link between the large-scale corona and SPP's in-situ measurements. The high speed at perihelion will provide tomographic-like views of coronal structures. To prepare for this unprecedented viewing of the structure of the inner corona, we are creating synthetic white light images and animations from the WISPR viewpoint using the white-light ray-tracing package developed at NRL (available through SolarSoft). We will present results from multi-strand models of coronal streamers and currents sheets as well as images of coronal mass ejections as seen simultaneously from Earth, Solar Orbiter and SPP.

  16. Fourier domain Pump-Probe Optical Coherence Tomography imaging of melanin.

    PubMed

    Jacob, Desmond; Shelton, Ryan L; Applegate, Brian E

    2010-06-01

    We report the development of a two-color Fourier domain Pump-Probe Optical Coherence Tomography (PPOCT) system. Tissue phantom experiments to characterize the system performance demonstrated imaging depths in excess of 725 microm, nearly comparable to the base Optical Coherence Tomography system. PPOCT A-line rates were also demonstrated in excess of 1 kHz. The physical origin of the PPOCT signal was investigated with a series of experiments which revealed that the signal is a mixture of short and long lifetime component signals. The short lifetime component was attributed to transient absorption while the long lifetime component may be due to a mixture of transient absorption and thermal effects. Ex vivo images of porcine iris demonstrated the potential for imaging melanin in the eye, where cancer of the melanocytes is the most common form of eye cancer in adults. PMID:20588366

  17. Scanned probe imaging of nanoscale magnetism at cryogenic temperatures with a single-spin quantum sensor

    NASA Astrophysics Data System (ADS)

    Pelliccione, Matthew; Jenkins, Alec; Ovartchaiyapong, Preeti; Reetz, Christopher; Emmanuelidu, Eve; Ni, Ni; Bleszynski Jayich, Ania

    The nitrogen vacancy (NV) defect in diamond has emerged as a promising candidate for high resolution magnetic imaging based on its atomic size and quantum-limited sensing capabilities afforded by long spin coherence times. Although the NV center has been successfully implemented as a nanoscale scanning magnetic probe at room temperature, it has remained an outstanding challenge to extend this capability to cryogenic temperatures, where many solid-state systems exhibit non-trivial magnetic order. In this talk, we present NV magnetic imaging at T = 6 K, first benchmarking the technique with a magnetic hard disk sample, then utilizing the technique to image vortices in the iron pnictide superconductor BaFe2(As0.7P0.3)2 with Tc = 30 K. In addition, we discuss other candidate solid-state systems that can benefit from the high spatial resolution and field sensitivity of the scanning NV magnetometer.

  18. Two-dimensional imaging with a single-sided NMR probe.

    PubMed

    Casanova, F; Blümich, B

    2003-07-01

    A new low field unilateral NMR sensor equipped with a two-dimensional gradient coil system was built. A new NMR-MOUSE concept using a simple bar magnet instead of the classical U-shaped geometry was used to produce magnetic field profiles comparatively homogeneous in extended lateral planes defining a suitable field of view for 2D spatial localization. Slice selection along the depth direction is obtained by means of the highly constant static magnetic field gradient produced by this magnet geometry. Implementing a two-dimensional phase-encoding imaging method 2D cross sections of objects were obtained with high spatial resolution. By retuning the probe it was possible to change the depth of the selected slice obtaining a 3D imaging method. The details of the construction of the new device are presented together with imaging tests to show the quality of space encoding. PMID:12852905

  19. Characterization of a New Series of Fluorescent Probes for Imaging Membrane Order

    PubMed Central

    Abu-Siniyeh, Ahmed; Yan, Ping; Loew, Leslie M.; Gaus, Katharina

    2013-01-01

    Visualization and quantification of lipid order is an important tool in membrane biophysics and cell biology, but the availability of environmentally sensitive fluorescent membrane probes is limited. Here, we present the characterization of the novel fluorescent dyes PY3304, PY3174 and PY3184, whose fluorescence properties are sensitive to membrane lipid order. In artificial bilayers, the fluorescence emission spectra are red-shifted between the liquid-ordered and liquid-disordered phases. Using ratiometric imaging we demonstrate that the degree of membrane order can be quantitatively determined in artificial liposomes as well as live cells and intact, live zebrafish embryos. Finally, we show that the fluorescence lifetime of the dyes is also dependent on bilayer order. These probes expand the current palate of lipid order-sensing fluorophores affording greater flexibility in the excitation/emission wavelengths and possibly new opportunities in membrane biology. PMID:23390489

  20. A turn-on fluorescent probe for tumor hypoxia imaging in living cells.

    PubMed

    Cai, Qi; Yu, Tao; Zhu, Weiping; Xu, Yufang; Qian, Xuhong

    2015-10-11

    A novel "turn-on" fluorescent probe HP for hypoxia imaging was designed and synthesized based on rhodamine B and a naphthalimide fluorophore. The fluorescence of HP is very weak owing to the FRET effect from rhodamine B to the azo-naphthalimide unit. Under hypoxia conditions, the azo-bond is reduced and the fluorescence at 581 nm enhances dramatically as a result of disintegration of the quencher structure. Verified by the cyclic voltammetry reduction potential and proposed product HPN, the probe HP could undergo the chemical and cytochrome P450 enzymatic reduction quickly. When cultured with HeLa cells, HP showed remarkable fluorescence differences at various oxygen concentrations, and the ratio of fluorescence intensity between hypoxic and normoxic cells could reach 9 fold. PMID:26295073

  1. Bis-pyridinium quadrupolar derivatives. High Stokes shift selective probes for bio-imaging

    NASA Astrophysics Data System (ADS)

    Salice, Patrizio; Versari, Silvia; Bradamante, Silvia; Meinardi, Francesco; Macchi, Giorgio; Pagani, Giorgio A.; Beverina, Luca

    2013-11-01

    We describe the design, synthesis and characterization of five high Stokes shift quadrupolar heteroaryl compounds suitable as fluorescent probes in bio-imaging. In particular, we characterize the photophysical properties and the intracellular localization in Human Umbilical Vein Endothelial Cells (HUVEC) and Human Mesenchymal Stem Cells (HMSCs) for each dye. We show that, amongst all of the investigated derivatives, the 2,5-bis[1-(4-N-methylpyridinium)ethen-2-yl)]- N-methylpyrrole salt is the best candidates as selective mitochondrial tracker. Finally, we recorded the full emission spectrum of the most performing - exclusively mitochondrial selective - fluorescent probe directly from HUVEC stained cells. The emission spectrum collected from the stained mitochondria shows a remarkably more pronounced vibronic structure with respect to the emission of the free fluorophore in solution.

  2. Development of a c-scan photoacoutsic imaging probe for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Valluru, Keerthi S.; Chinni, Bhargava K.; Rao, Navalgund A.; Bhatt, Shweta; Dogra, Vikram S.

    2011-03-01

    Prostate cancer is the second leading cause of death in American men after lung cancer. The current screening procedures include Digital Rectal Exam (DRE) and Prostate Specific Antigen (PSA) test, along with Transrectal Ultrasound (TRUS). All suffer from low sensitivity and specificity in detecting prostate cancer in early stages. There is a desperate need for a new imaging modality. We are developing a prototype transrectal photoacoustic imaging probe to detect prostate malignancies in vivo that promises high sensitivity and specificity. To generate photoacoustic (PA) signals, the probe utilizes a high energy 1064 nm laser that delivers light pulses onto the prostate at 10Hz with 10ns duration through a fiber optic cable. The designed system will generate focused C-scan planar images using acoustic lens technology. A 5 MHz custom fabricated ultrasound sensor array located in the image plane acquires the focused PA signals, eliminating the need for any synthetic aperture focusing. The lens and sensor array design was optimized towards this objective. For fast acquisition times, a custom built 16 channel simultaneous backend electronics PCB has been developed. It consists of a low-noise variable gain amplifier and a 16 channel ADC. Due to the unavailability of 2d ultrasound arrays, in the current implementation several B-scan (depth-resolved) data is first acquired by scanning a 1d array, which is then processed to reconstruct either 3d volumetric images or several C-scan planar images. Experimental results on excised tissue using a in-vitro prototype of this technology are presented to demonstrate the system capability in terms of resolution and sensitivity.

  3. Articulated dual modality photoacoustic and optical coherence tomography probe for preclinical and clinical imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Liu, Mengyang; Zabihian, Behrooz; Weingast, Jessika; Hermann, Boris; Chen, Zhe; Zhang, Edward Z.; Beard, Paul C.; Pehamberger, Hubert; Drexler, Wolfgang

    2016-03-01

    The combination of photoacoustic tomography (PAT) with optical coherence tomography (OCT) has seen steady progress over the past few years. With the benchtop and semi-benchtop configurations, preclinical and clinical results have been demonstrated, paving the way for wider applications using dual modality PAT/OCT systems. However, as for the most updated semi-benchtop PAT/OCT system which employs a Fabry-Perot polymer film sensor, it is restricted to only human palm imaging due to the limited flexibility of the probe. The passband limit of the polymer film sensor further restricts the OCT source selection and reduces the sensitivity of the combined OCT system. To tackle these issues, we developed an articulated PAT/OCT probe for both preclinical and clinical applications. In the probe design, the sample arm of OCT sub-system and the interrogation part of the PAT sub-system are integrated into one compact unit. The polymer film sensor has a quick release function so that before each OCT scan, the sensor can be taken off to avoid the sensitivity drop and artefacts in OCT. The holding mechanism of the sensor is also more compact compared to previous designs, permitting access to uneven surfaces of the subjects. With the help of the articulated probe and a patient chair, we are able to perform co-registered imaging on human subjects on both upper and lower extremities while they are at rest positions. An increase in performance characteristics is also achieved. Patients with skin diseases are currently being recruited to test its clinical feasibility.

  4. Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions

    PubMed Central

    Rao, Wei; Pan, Ning; Yang, Zhibo

    2016-01-01

    Mass spectrometry imaging (MSI) and in-situ single cell mass spectrometry (SCMS) analysis under ambient conditions are two emerging fields with great potential for the detailed mass spectrometry (MS) analysis of biomolecules from biological samples. The single-probe, a miniaturized device with integrated sampling and ionization capabilities, is capable of performing both ambient MSI and in-situ SCMS analysis. For ambient MSI, the single-probe uses surface micro-extraction to continually conduct MS analysis of the sample, and this technique allows the creation of MS images with high spatial resolution (8.5 µm) from biological samples such as mouse brain and kidney sections. Ambient MSI has the advantage that little to no sample preparation is needed before the analysis, which reduces the amount of potential artifacts present in data acquisition and allows a more representative analysis of the sample to be acquired. For in-situ SCMS, the single-probe tip can be directly inserted into live eukaryotic cells such as HeLa cells, due to the small sampling tip size (< 10 µm), and this technique is capable of detecting a wide range of metabolites inside individual cells at near real-time. SCMS enables a greater sensitivity and accuracy of chemical information to be acquired at the single cell level, which could improve our understanding of biological processes at a more fundamental level than previously possible. The single-probe device can be potentially coupled with a variety of mass spectrometers for broad ranges of MSI and SCMS studies. PMID:27341402

  5. Programmable oligonucleotide probes design and applications for in situ and in vivo RNA imaging in cells

    NASA Astrophysics Data System (ADS)

    Cheglakov, Zoya

    Unequal spreading of mRNA is a frequent experience observed in varied cell lines. The study of cellular processes dynamics and precise localization of mRNAs offers a vital toolbox to target specific proteins in precise cytoplasmic areas and provides a convenient instrument to uncover their mechanisms and functions. Latest methodological innovations have allowed imaging of a single mRNA molecule in situ and in vivo. Today, Fluorescent In Situ Hybridization (FISH) methods allow the studying of mRNA expression and offer a vital toolbox for accurate biological models. Studies enable analysis of the dynamics of an individual mRNA, have uncovered the multiplex RNA transport systems. With all current approaches, a single mRNA tracking in the mammalian cells is still challenging. This thesis describes mRNA detection methods based on programmable fluorophore-labeled DNA structures complimentary to native targets providing an accurate mRNA imaging in mammalian cells. First method represents beta-actin (ACTB) transcripts in situ detection in human cells, the technique strategy is based on programmable DNA probes, amplified by rolling circle amplification (RCA). The method reports precise localization of molecule of interest with an accuracy of a single-cell. Visualization and localization of specific endogenous mRNA molecules in real-time in vivo has the promising to innovate cellular biology studies, medical analysis and to provide a vital toolbox in drugs invention area. Second method described in this thesis represents miR-21 miRNA detection within a single live-cell resolution. The method using fluorophore-labeled short synthetic DNAs probes forming a stem-loop shape and generating Fluorescent Resonance Energy Transfer (FRET) as a result of target-probes hybridization. Catalytic nucleic acid (DNAzymes) probes are cooperative tool for precise detection of different mRNA targets. With assistance of a complementary fluorophore-quencher labeled substrate, the DNAzymes provide

  6. Tension promoted circular probe for highly selective microRNA detection and imaging.

    PubMed

    Tang, Yaqin; Wang, Tingting; Chen, Ming; He, Xiao; Qu, Xiaohuan; Feng, Xuli

    2016-11-15

    The crucial role of miRNA in cell regulation and its connection with diverse human cancers as a tumor suppressor or an oncogenic fragment poses great demand for an accurate and rapid approach for highly efficient miRNA detection and imaging in live cells. However, the ability to selectively detect and image miRNA remains a significant challenge in biomedical fields. Herein, a sealed circular probe (CP) has been prepared with copper free click ligation. The big tension force of the ring structure greatly increases the sequence recognition specificity. Toehold initiated strand displacement of CP further amplify the selectivity for miRNA determination. Impressively, the different site of single base mismatch could even be discriminated. More importantly, CP was successfully applied for imaging endogenous miRNA expression in live cells. We believe that this new probe would find wide application in profiling of endogenous miRNA and be potential candidate method for helping us diagnosing miRNA related diseases. PMID:27162146

  7. Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

    NASA Astrophysics Data System (ADS)

    Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

    2016-03-01

    Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

  8. 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. PMID:22092336

  9. In vivo three-dimensional photoacoustic imaging based on a clinical matrix array ultrasound probe

    NASA Astrophysics Data System (ADS)

    Wang, Yu; Erpelding, Todd N.; Jankovic, Ladislav; Guo, Zijian; Robert, Jean-Luc; David, Guillaume; Wang, Lihong V.

    2012-06-01

    We present an integrated photoacoustic and ultrasonic three-dimensional (3-D) volumetric imaging system based on a two-dimensional (2-D) matrix array ultrasound probe. A wavelength-tunable dye laser pumped by a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2-D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3-D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.69, 0.90 and 0.84 mm for photoacoustic imaging. In vivo 3-D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model using methylene blue dye. These results highlight the clinical potential of 3-D PA imaging for identification of sentinel lymph nodes for cancer staging in humans.

  10. Forward-viewing photoacoustic imaging probe with bundled ultra-thin hollow optical fibers

    NASA Astrophysics Data System (ADS)

    Seki, A.; Iwai, K.; Katagiri, T.; Matsuura, Y.

    2016-07-01

    A photoacoustic imaging system composed of a flexible bundle of thin hollow-optical fibers is proposed for endoscopic diagnosis. In this system, a bundle of 127 hollow-optical fibers with an inner diameter of 100 μm was fabricated. The total diameter of the bundle was 2.1 mm, and the minimum bending radius was around 10 mm. Owing to the small numerical aperture of hollow optical fibers, a high resolution image was obtained without using a lens array at the distal end. In the imaging system, the hollow fibers in the bundle were aligned at the input end, so the hollow fibers were sequentially excited by linearly scanning the laser beam at the input end. Photoacoustic imaging systems consisting of the bundled fibers for excitation of acoustic wave and piezoelectric probes for detection of photoacoustic signals were built. By using the systems, photoacoustic images of blood vessels in the ovarian membrane of fish were taken to test the feasibility of the system. As a result, photoacoustic images of the vessel were successfully obtained with a laser fluence of around 6.6 mJ cm‑2.

  11. Imaging of radiation damage using complementary field ion microscopy and atom probe tomography.

    PubMed

    Dagan, Michal; Hanna, Luke R; Xu, Alan; Roberts, Steve G; Smith, George D W; Gault, Baptiste; Edmondson, Philip D; Bagot, Paul A J; Moody, Michael P

    2015-12-01

    Radiation damage in tungsten and a tungsten-tantalum alloy, both of relevance to nuclear fusion research, has been characterized using a combination of field ion microscopy (FIM) imaging and atom probe tomography (APT). While APT provides 3D analytical imaging with sub-nanometer resolution, FIM is capable of imaging the arrangements of single atoms on a crystal lattice and has the potential to provide insights into radiation induced crystal damage, all the way down to its smallest manifestation--a single vacancy. This paper demonstrates the strength of combining these characterization techniques. In ion implanted tungsten, it was found that atomic scale lattice damage is best imaged using FIM. In certain cases, APT reveals an identifiable imprint in the data via the segregation of solute and impurities and trajectory aberrations. In a W-5at%Ta alloy, a combined APT-FIM study was able to determine the atomic distribution of tantalum inside the tungsten matrix. An indirect method was implemented to identify tantalum atoms inside the tungsten matrix in FIM images. By tracing irregularities in the evaporation sequence of atoms imaged with FIM, this method enables the benefit of FIM's atomic resolution in chemical distinction between the two species. PMID:25794822

  12. 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.

  13. In vivo three-dimensional photoacoustic imaging based on a clinical matrix array ultrasound probe.

    PubMed

    Wang, Yu; Erpelding, Todd N; Jankovic, Ladislav; Guo, Zijian; Robert, Jean-Luc; David, Guillaume; Wang, Lihong V

    2012-06-01

    We present an integrated photoacoustic and ultrasonic three-dimensional (3-D) volumetric imaging system based on a two-dimensional (2-D) matrix array ultrasound probe. A wavelength-tunable dye laser pumped by a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2-D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3-D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.69, 0.90 and 0.84 mm for photoacoustic imaging. In vivo 3-D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model using methylene blue dye. These results highlight the clinical potential of 3-D PA imaging for identification of sentinel lymph nodes for cancer staging in humans. PMID:22734738

  14. Detection probe-tip configuration optimization for photopyroelectric thermal-wave imaging instrument using finite-element-method analysis

    NASA Astrophysics Data System (ADS)

    Yarai, Atsushi; Yokoyama, Yasuhiro; Nakanishi, Takuji

    1995-03-01

    This paper describes detection probe-tip configuration optimization for a photopyroelectric thermal-wave imaging instrument. In order to obtain reconstructed thermal-wave tomographic images with high fidelity, it is necessary to obtain the optimum conditions of the detection probe-tip configuration. These conditions were obtained by analyzing the electric fields around a capacitive-coupled detection probe-tip using finite-element-method (FEM) analysis. Experimental results are also shown, verifying the FEM analysis results. It was also confirmed that the equivalent probe-tip diameter determined from our previous experimental work agreed almost perfectly with that obtained using FEM analysis. As a result, high-fidelity thermal-wave tomographic images were obtained.

  15. Synthetic aperture microwave imaging with active probing for fusion plasma diagnostics

    NASA Astrophysics Data System (ADS)

    Shevchenko, Vladimir F.; Freethy, Simon J.; Huang, Billy K.; Vann, Roddy G. L.

    2014-08-01

    A Synthetic Aperture Microwave Imaging (SAMI) system has been designed and built to obtain 2-D images at several frequencies from fusion plasmas. SAMI uses a phased array of linearly polarised antennas. The array configuration has been optimised to achieve maximum synthetic aperture beam efficiency. The signals received by antennas are down-converted to the intermediate frequency range and then recorded in a full vector form. Full vector signals allow beam focusing and image reconstruction in both real time and a post-processing mode. SAMI can scan over 16 pre-programmed frequencies in the range of 10-35GHz with a switching time of 300ns. The system operates in 2 different modes simultaneously: both a 'passive' imaging of plasma emission and also an 'active' imaging of the back-scattered signal of the radiation launched by one of the antennas from the same array. This second mode is similar to so-called Doppler backscattering (DBS) reflectometry with 2-D resolution of the propagation velocity of turbulent structures. Both modes of operation show good performance in fusion plasma experiments on Mega Amp Spherical Tokamak (MAST). We have obtained the first ever 2-D images of BXO mode conversion windows. With active probing, first ever turbulence velocity maps have been obtained. We present an overview of the diagnostic and discuss recent results. In contrast to quasi-optical microwave imaging systems SAMI requires neither big aperture viewing ports nor large 2-D detector arrays to achieve the desired imaging resolution. The number of effective 'pixels' of the synthesized image is proportional to the number of receiving antennas squared. Thus only a small number of optimised antennas is sufficient for the majority of applications. Possible implementation of SAMI on ITERand DEMO is discussed.

  16. Synthetic aperture microwave imaging with active probing for fusion plasma diagnostics

    SciTech Connect

    Shevchenko, Vladimir F.; Freethy, Simon J.; Huang, Billy K.

    2014-08-21

    A Synthetic Aperture Microwave Imaging (SAMI) system has been designed and built to obtain 2-D images at several frequencies from fusion plasmas. SAMI uses a phased array of linearly polarised antennas. The array configuration has been optimised to achieve maximum synthetic aperture beam efficiency. The signals received by antennas are down-converted to the intermediate frequency range and then recorded in a full vector form. Full vector signals allow beam focusing and image reconstruction in both real time and a post-processing mode. SAMI can scan over 16 pre-programmed frequencies in the range of 10-35GHz with a switching time of 300ns. The system operates in 2 different modes simultaneously: both a 'passive' imaging of plasma emission and also an 'active' imaging of the back-scattered signal of the radiation launched by one of the antennas from the same array. This second mode is similar to so-called Doppler backscattering (DBS) reflectometry with 2-D resolution of the propagation velocity of turbulent structures. Both modes of operation show good performance in fusion plasma experiments on Mega Amp Spherical Tokamak (MAST). We have obtained the first ever 2-D images of BXO mode conversion windows. With active probing, first ever turbulence velocity maps have been obtained. We present an overview of the diagnostic and discuss recent results. In contrast to quasi-optical microwave imaging systems SAMI requires neither big aperture viewing ports nor large 2-D detector arrays to achieve the desired imaging resolution. The number of effective 'pixels' of the synthesized image is proportional to the number of receiving antennas squared. Thus only a small number of optimised antennas is sufficient for the majority of applications. Possible implementation of SAMI on ITERand DEMO is discussed.

  17. Imaging of a soft, weakly adsorbing, living cell with a colloid probe tapping atomic force microscope technique.

    PubMed

    McNamee, Cathy E; Pyo, Nayoung; Tanaka, Saaya; Kanda, Yoichi; Higashitani, Ko

    2006-01-15

    Here, we propose a new method to improve the atomic force microscopy (AFM) image resolution of soft samples, such as cells, in liquid. Attaching a colloid probe to a cantilever was seen improve the image resolution of a living cell in a physiological buffer solution, obtained by the normal tapping mode, when compared to an image obtained using a regular cantilever tip. This may be due to the averaging out of the cantilever tip swinging caused by the visco-elasticity of the cell. The resolution was best, when silica spheres with a 3.3 microm diameter were attached. Although larger spheres gave a resolution better than a bare cantilever tip, their resolution was less than that obtained for the 3.3 microm diameter silica colloid. This dependency of the image resolution on the colloid probe size may be a result of the increased macroscopic van der Waals attraction between the cell and probe, the decreased repulsive force dependence on the cantilever probe radius, and the decrease in resolution due to the increased probe size. The size of the colloid probe, which should be attached to the cantilever to give the best image resolution, would be the one that optimises the combined result of these facts. PMID:16406494

  18. Pump-probe imaging of laser-induced periodic surface structures after ultrafast irradiation of Si

    SciTech Connect

    Murphy, Ryan D.; Torralva, Ben; Adams, David P.; Yalisove, Steven M.

    2013-09-30

    Ultrafast pump-probe microscopy has been used to investigate laser-induced periodic surface structure (LIPSS) formation on polished Si surfaces. A crater forms on the surface after irradiation by a 150 fs laser pulse, and a second, subsequent pulse forms LIPSS within the crater. Sequentially delayed images show that LIPSS with a periodicity slightly less than the fundamental laser wavelength of 780 nm appear on Si surfaces ∼50 ps after arrival of the second pump laser pulse, well after the onset of melting. LIPSS are observed on the same timescale as material removal, suggesting that their formation involves material ejection.

  19. Multimodality imaging probe for positron emission tomography and fluorescence imaging studies.

    PubMed

    Pandey, Suresh K; Kaur, Jasmeet; Easwaramoorthy, Balu; Shah, Ankur; Coleman, Robert; Mukherjee, Jogeshwar

    2014-01-01

    Our goal is to develop multimodality imaging agents for use in cell tracking studies by positron emission tomography (PET) and optical imaging (OI). For this purpose, bovine serum albumin (BSA) was complexed with biotin (histologic studies), 5(6)-carboxyfluorescein, succinimidyl ester (FAM SE) (OI studies), and diethylenetriamine pentaacetic acid (DTPA) for chelating gallium 68 (PET studies). For synthesis of BSA-biotin-FAM-DTPA, BSA was coupled to (+)-biotin N-hydroxysuccinimide ester (biotin-NHSI). BSA-biotin was treated with DTPA-anhydride and biotin-BSA-DTPA was reacted with FAM. The biotin-BSA-DTPA-FAM was reacted with gallium chloride 3 to 5 mCi eluted from the generator using 0.1 N HCl and was passed through basic resin (AG 11 A8) and 150 μCi (100 μL, pH 7-8) was incubated with 0.1 mg of FAM conjugate (100 μL) at room temperature for 15 minutes to give 68Ga-BSA-biotin-DTPA-FAM. A shaved C57 black mouse was injected with FAM conjugate (50 μL) at one flank and FAM-68Ga (50 μL, 30 μCi) at the other. Immediately after injection, the mouse was placed in a fluorescence imaging system (Kodak In-Vivo F, Bruker Biospin Co., Woodbridge, CT) and imaged (λex: 465 nm, λem: 535 nm, time: 8 seconds, Xenon Light Source, Kodak). The same mouse was then placed under an Inveon microPET scanner (Siemens Medical Solutions, Knoxville, TN) injected (intravenously) with 25 μCi of 18F and after a half-hour (to allow sufficient bone uptake) was imaged for 30 minutes. Molecular weight determined using matrix-associated laser desorption ionization (MALDI) for the BSA sample was 66,485 Da and for biotin-BSA was 67,116 Da, indicating two biotin moieties per BSA molecule; for biotin-BSA-DTPA was 81,584 Da, indicating an average of 30 DTPA moieties per BSA molecule; and for FAM conjugate was 82,383 Da, indicating an average of 1.7 fluorescent moieties per BSA molecule. Fluorescence imaging clearly showed localization of FAM conjugate and FAM-68Ga at respective flanks of the mouse

  20. Ultrafast dynamics in helium nanodroplets probed by femtosecond time-resolved EUV photoelectron imaging

    SciTech Connect

    Kornilov, Oleg; Wang, Chia C.; Buenermann, Oliver; Healy, Andrew T.; Leonard, Mathew; Peng, Chunte; Leone, Stephen R.; Neumark, Daniel M.; Gessner, Oliver

    2010-07-09

    The dynamics of electronically excited helium nanodroplets are studied by femtosecond time-resolved photoelectron imaging. EUV excitation into a broad absorption band centered around 23.8 eV leads to an indirect photoemission process that generates ultraslow photoelectrons. A 1.58 eV probe pulse transiently depletes the indirect photoemission signal for pump-probe time delays <200 fs and enhances the signal beyond this delay. The depletion is due to suppression of the indirect ionization process by the probe photon, which generates a broad, isotropically emitted photoelectron band. Similar time scales in the decay of the high energy photoelectron signal and the enhancement of the indirect photoemission signal suggest an internal relaxation process that populates states in the range of a lower energy droplet absorption band located just below the droplet ionization potential (IP {approx} 23.0 eV). A nearly 70% enhancement of the ultraslow photoelectron signal indicates that interband relaxation plays a more dominant role for the droplet de-excitation mechanism than photoemission.

  1. Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential

    PubMed Central

    Robles, Francisco E.; Deb, Sanghamitra; Wilson, Jesse W.; Gainey, Christina S.; Selim, M. Angelica; Mosca, Paul J.; Tyler, Douglas S.; Fischer, Martin C.; Warren, Warren S.

    2015-01-01

    Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pump-probe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct “dusty” quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas. PMID:26417529

  2. Miniaturized CARS microendoscope probe design for label-free intraoperative imaging

    NASA Astrophysics Data System (ADS)

    Chen, Xu; Wang, Xi; Xu, Xiaoyun; Cheng, Jie; Liu, Zhengfan; Weng, Sheng; Thrall, Michael J.; Goh, Alvin C.; McCormick, Daniel T.; Wong, Kelvin; Wong, Stephen T. C.

    2014-03-01

    A Coherent Anti-Stokes Raman Scattering (CARS) microendoscope probe for early stage label-free prostate cancer diagnosis at single cell resolution is presented. The handheld CARS microendoscope probe includes a customized micro-electromechanical systems (MEMS) scanning mirror as well as miniature optical and mechanical components. In our design, the excitation laser (pump and stokes beams) from the fiber is collimated, reflected by the reflecting mirror, and transmitted via a 2D MEMS scanning mirror and a micro-objective system onto the sample; emission in the epi-direction is returned through the micro-objective lens, MEMS and reflecting mirror, and collimation system, and finally the emission signal is collected by a photomultiplier tube (PMT). The exit pupil diameter of the collimator system is designed to match the diameter of the MEMS mirror and the entrance pupil diameter of the micro-objective system. The back aperture diameter of the micro-objective system is designed according to the largest MEMS scanning angle and the distance between the MEMS mirror and the back aperture. To increase the numerical aperture (NA) of the micro-objective system in order to enhance the signal collection efficiency, the back aperture diameter of the micro-objective system is enlarged with an upfront achromatic wide angle Keplerian telescope beam expander. The integration of a miniaturized micro-optics probe with optical fiber CARS microscopy opens up the possibility of in vivo molecular imaging for cancer diagnosis and surgical intervention.

  3. Synthesis and Characterization of a Promising Novel FFAR1/GPR40 Targeting Fluorescent Probe for β-Cell Imaging.

    PubMed

    Bertrand, Romain; Wolf, Andrea; Ivashchenko, Yuri; Löhn, Matthias; Schäfer, Matthias; Brönstrup, Mark; Gotthardt, Martin; Derdau, Volker; Plettenburg, Oliver

    2016-06-17

    Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of β-cells bears the potential to contribute to an improved understanding, diagnosis, and development of new treatment options for diabetes. Here, we describe the first small molecule fluorescent probe targeting the free fatty acid receptor 1 (FFAR1/GPR40). This receptor is highly expressed on β-cells, and was up to now unexplored for imaging purposes. We designed a novel probe by facile modification of the selective and potent FFAR1 agonist TAK-875. Effective and specific binding of the probe was demonstrated using FFAR1 overexpressing cells. We also successfully labeled FFAR1 on MIN6 and INS1E cells, two widely used β-cell models, by applying an effective amplification protocol. Finally, we showed that the probe is capable of inducing insulin secretion in a glucose-dependent manner, thus demonstrating that functional activity of the probe was maintained. These results suggest that our probe represents a first important step to successful β-cell imaging by targeting FFAR1. The developed probe may prove to be particularly useful for in vitro and ex vivo studies of diabetic cellular and animal models to gain new insights into disease pathogenesis. PMID:27115176

  4. Superparamagnetic iron oxide nanoparticles as a dual imaging probe for targeting hepatocytes in vivo.

    PubMed

    Lee, Chang-Moon; Jeong, Hwan-Jeong; Kim, Eun-Mi; Kim, Dong Wook; Lim, Seok Tae; Kim, Hyoung Tae; Park, In-Kyu; Jeong, Yong Yeon; Kim, Jin Woong; Sohn, Myung-Hee

    2009-12-01

    Hepatocyte-specific targeting agents are useful for evaluation of the hepatocytic function and the monitoring of disease progress. Superparamagnetic iron oxide nanoparticles (SPION) bearing terminal galactose groups exhibit a high affinity for the asialoglycoprotein receptor on the hepatocyte surface. In this study, we synthesized and characterized the dual probe SPION detectable by both nuclear and MR imaging modality for specifically targeting hepatocytes in vivo. SPION with 12-nm diameter were functionalized with dopamine. Surface modification of the SPION was performed to target asialoglycoprotein receptor on hepatocytes, using lactobionic acid. Transmission electron microscope images demonstrated that SPION displayed highly uniform characteristics in terms of both particle size and shape. The X-ray diffraction pattern of SPION revealed a nanocrystal structure of magnetite. To radiolabel the magnetite with (99m)Tc, diethylenetriaminepentaacetic acid was conjugated to unreacted functional groups of dopamine. (99m)Tc-labeled lactobionic acid-SPION showed high accumulation in liver, with 38.43 +/- 6.45% injected dose per gram. In MR imaging, the reduction of the T(2) signal in the liver by lactobionic acid-SPION was approximately 50.8 +/- 7.3%. Competition studies and transmission electron microscope images of liver tissues demonstrated that the lactobionic acid-SPION were localized in hepatocytes. Therefore, the lactobionic acid-SPION may be used as a hepatocyte-targeted dual contrast agent for both nuclear and MR imaging. PMID:19859969

  5. Progress and prospects for small-molecule probes of bacterial imaging.

    PubMed

    Kocaoglu, Ozden; Carlson, Erin E

    2016-06-17

    Fluorescence microscopy is an essential tool for the exploration of cell growth, division, transcription and translation in eukaryotes and prokaryotes alike. Despite the rapid development of techniques to study bacteria, the size of these organisms (1-10 μm) and their robust and largely impenetrable cell envelope present major challenges in imaging experiments. Fusion-based strategies, such as attachment of the protein of interest to a fluorescent protein or epitope tag, are by far the most common means for examining protein localization and expression in prokaryotes. While valuable, the use of genetically encoded tags can result in mislocalization or altered activity of the desired protein, does not provide a readout of the catalytic state of enzymes and cannot enable visualization of many other important cellular components, such as peptidoglycan, lipids, nucleic acids or glycans. Here, we highlight the use of biomolecule-specific small-molecule probes for imaging in bacteria. PMID:27315537

  6. Mn-doped near-infrared quantum dots as multimodal targeted probes for pancreatic cancer imaging

    NASA Astrophysics Data System (ADS)

    Yong, Ken-Tye

    2009-01-01

    This work presents a novel approach to producing manganese (Mn)-doped quantum dots (Mnd-QDs) emitting in the near-infrared (NIR). Surface functionalization of Mnd-QDs with lysine makes them stably disperse in aqueous media and able to conjugate with targeting molecules. The nanoparticles were structurally and compositionally characterized and maintained a high photoluminescence quantum yield and displayed paramagnetism in water. The receptor-mediated delivery of bioconjugated Mnd-QDs into pancreatic cancer cells was demonstrated using the confocal microscopy technique. Cytotoxicity of Mnd-QDs on live cells has been evaluated. The NIR-emitting characteristic of the QDs has been exploited to acquire whole animal body imaging with high contrast signals. In addition, histological and blood analysis of mice have revealed that no long-term toxic effects arise from MnD-QDs. These studies suggest multimodal Mnd-QDs have the potentials as probes for early pancreatic cancer imaging and detection.

  7. Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes

    NASA Astrophysics Data System (ADS)

    Löser, Reik; Pietzsch, Jens

    2015-06-01

    Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging. After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge towards their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes.

  8. Imaging and therapeutic applications of zinc(ii)-dipicolylamine molecular probes for anionic biomembranes.

    PubMed

    Rice, Douglas R; Clear, Kasey J; Smith, Bradley D

    2016-07-01

    This feature article describes the development of synthetic zinc(ii)-dipicolylamine (ZnDPA) receptors as selective targeting agents for anionic membranes in cell culture and living subjects. There is a strong connection between anionic cell surface charge and disease, and ZnDPA probes have been employed extensively for molecular imaging and targeted therapeutics. Fluorescence and nuclear imaging applications include detection of diseases such as cancer, neurodegeneration, arthritis, and microbial infection, and also quantification of cell death caused by therapy. Therapeutic applications include selective targeting of cytotoxic agents and drug delivery systems, photodynamic inactivation, and modulation of the immune system. The article concludes with a summary of expected future directions. PMID:27302091

  9. Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes

    PubMed Central

    Löser, Reik; Pietzsch, Jens

    2015-01-01

    Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging. After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge toward their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes. PMID:26157794

  10. Simultaneous imaging and restoration of cell function using cell permeable peptide probe.

    PubMed

    Suh, Jin Sook; Lee, Jue Yeon; Lee, Gene; Chung, Chong Pyoung; Park, Yoon Jeong

    2014-08-01

    Targeting tissues/cells using probing materials to detect diseases such as cancer and inflammatory disease has been attempted with some success. Most of the molecular targets used in diagnosis and therapy were identified through the discovery of intracellular signaling pathways. Among intracellular signaling processes, the ubiquitination of proteins, and thereby their proteasomal degradation, is important because it plays a role in most diseases involving alterations to a component of the ubiquitination system, particularly E3 ligases, which have selective target-binding affinity and are key to the success of regulating the disorder. The regulation and monitoring of E3 ligases can be achieved using peptides containing protein-protein binding motifs. We generated a human protein-derived peptide that could target Smurf1, a member of the E3 ligase family, by competitively binding to osteo-Smads. To effectively deliver it into cells, the peptide was further modified with a cell-penetrating peptide. The peptide contains two fluorescent dyes: fluorescein isothiocyanate (FITC; absorbance/emission wavelengths: 495/519 nm) as a fluorophore and black hole quencher-1 (BHQ-1) as a fluorescence quencher. When the target Smurf1 combined with complementary sequences in the peptide probe, the distance between the fluorophore and BHQ-1 increased via a conformational change, resulting in the recovery of the fluorescence signal. Simultaneously, the degradation of Smad1/5/8 was blocked by the binding of the peptide probe to Smurf1, leading to the potentiation of the osteogenic pathway, which was reflected by an increase in the expression of osteoinductive genes, such as alkaline phosphatase and osteocalcin. Possible future applications of the peptide probe include its integration into imaging tools for the diagnosis of Smurf1-overexpressing diseases. PMID:24831974

  11. Ultrasensitive near-infrared fluorescence-enhanced probe for in vivo nitroreductase imaging.

    PubMed

    Li, Yuhao; Sun, Yun; Li, Jiachang; Su, Qianqian; Yuan, Wei; Dai, Yu; Han, Chunmiao; Wang, Qiuhong; Feng, Wei; Li, Fuyou

    2015-05-20

    Nitroreductase (NTR) can be overexpressed in hypoxic tumors, thus the selective and efficient detection of NTR is of great importance. To date, although a few optical methods have been reported for the detection of NTR in solution, an effective optical probe for NTR monitoring in vivo is still lacking. Therefore, it is necessary to develop a near-infrared (NIR) fluorescent detection probe for NTR. In this study, five NIR cyanine dyes with fluorescence reporting structure decorated with different nitro aromatic groups, Cy7-1-5, have been designed and explored for possible rapid detection of NTR. Our experimental results presented that only a para-nitro benzoate group modified cyanine probe (Cy7-1) could serve as a rapid NIR fluorescence-enhanced probe for monitoring and bioimaging of NTR. The structure-function relationship has been revealed by theoretical study. The linker connecting the detecting and fluorescence reporting groups and the nitro group position is a key factor for the formation of hydrogen bonds and spatial structure match, inducing the NTR catalytic ability enhancement. The in vitro response and mechanism of the enzyme-catalyzed reduction of Cy7-1 have been investigated through kinetic optical studies and other methods. The results have indicated that an electro-withdrawing group induced electron-transfer process becomes blocked when Cy7-1 is catalytically reduced to Cy7-NH2 by NTR, which is manifested in enhanced fluorescence intensity during the detection process. Confocal fluorescence imaging of hypoxic A549 cells has confirmed the NTR detection ability of Cy7-1 at the cellular level. Importantly, Cy7-1 can detect tumor hypoxia in a murine hypoxic tumor model, showing a rapid and significant enhancement of its NIR fluorescence characteristics suitable for fluorescence bioimaging. This method may potentially be used for tumor hypoxia diagnosis. PMID:25923361

  12. Reaction-Based Probes for Imaging Mobile Zinc in Live Cells and Tissues

    PubMed Central

    2015-01-01

    Chelatable, or mobile, forms of zinc play critical signaling roles in numerous biological processes. Elucidating the action of mobile Zn(II) in complex biological environments requires sensitive tools for visualizing, tracking, and manipulating Zn(II) ions. A large toolbox of synthetic photoinduced electron transfer (PET)-based fluorescent Zn(II) sensors are available, but the applicability of many of these probes is limited by poor zinc sensitivity and low dynamic ranges owing to proton interference. We present here a general approach for acetylating PET-based probes containing a variety of fluorophores and zinc-binding units. The new sensors provide substantially improved zinc sensitivity and allow for incubation of live cells and tissue slices with nM probe concentrations, a significant improvement compared to the μM concentrations that are typically required for a measurable fluorescence signal. Acetylation effectively reduces or completely quenches background fluorescence in the metal-free sensor. Binding of Zn(II) selectively and quickly mediates hydrolytic cleavage of the acetyl groups, providing a large fluorescence response. An acetylated blue coumarin-based sensor was used to carry out detailed analyses of metal binding and metal-promoted acetyl hydrolysis. Acetylated benzoresorufin-based red-emitting probes with different zinc-binding sites are effective for sensing Zn(II) ions in live cells when applied at low concentrations (∼50–100 nM). We used green diacetylated Zinpyr1 (DA-ZP1) to image endogenous mobile Zn(II) in the molecular layer of mouse dorsal cochlear nucleus (DCN), confirming that acetylation is a suitable approach for preparing sensors that are highly specific and sensitive to mobile zinc in biological systems. PMID:26878065

  13. Imaging of enzyme activity by scanning electrochemical microscope equipped with a feedback control for substrate-probe distance.

    PubMed

    Oyamatsu, Daisuke; Hirano, Yu; Kanaya, Norihiro; Mase, Yoshiaki; Nishizawa, Matsuhiko; Matsue, Tomokazu

    2003-08-01

    The enzymatic activity of diaphorase (Dp) immobilized on a solid substrate was characterized using a scanning electrochemical microscope (SECM) with shear force feedback to control the substrate-probe distance. The shear force between the substrate and the probe was monitored with a tuning fork-type quartz crystal and used as the feedback control to set the microelectrode probe close to the substrate surface. The sensitivity and the contrast of the SECM image were improved in the constant distance mode (distance, 50 nm) with the shear force feedback compared to the image in the constant height mode without the feedback. By using this system, the SECM and topographic images of the immobilized diaphorase were simultaneously measured. The microelectrode tip used in this study was ground aslant like a syringe needle in order to obtain the shaper topographic images. This shape was also effective for avoiding the interference during the diffusion of the enzyme substrates. PMID:12893317

  14. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

    PubMed

    Kim, Woosuk; Le, Thuc M; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T; Abt, Evan R; Capri, Joseph R; Austin, Wayne R; Van Valkenburgh, Juno S; Steele, Dalton; Gipson, Raymond M; Slavik, Roger; Cabebe, Anthony E; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S; Lee, Jason T; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F; Witte, Owen N; Donahue, Timothy R; Phelps, Michael E; Herschman, Harvey R; Herrmann, Ken; Czernin, Johannes; Radu, Caius G

    2016-04-12

    Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring. PMID:27035974

  15. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.

    PubMed

    Sun, Yao; Ma, Xiaowei; Zhang, Zhe; Sun, Ziyan; Loft, Mathias; Ding, Bingbing; Liu, Changhao; Xu, Liying; Yang, Meng; Jiang, Yuxin; Liu, Jianfeng; Xiao, Yuling; Cheng, Zhen; Hong, Xuechuan

    2016-08-17

    Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients. PMID:27399868

  16. Probing for Exoplanets Hiding in Dusty Debris Disks: Inner (<10 AU) Disk Imaging, Characterization, and Exploration

    NASA Astrophysics Data System (ADS)

    Schneider, Glenn; HST GO 12228 Team

    2011-01-01

    We are obtaining HST/STIS observations of a well-selected sample of eleven circumstellar (CS) debris disks, all with HST pedigree, using PSF-subtracted multi-roll coronagraphic imaging. Our observations are probing the interior CS regions of these debris systems (inner working distances < approximately 8 AU for half the sample), corresponding to the giant planet and Kuiper belt regions within our own solar system. These images will enable us to: (a) directly inter-compare the architectures of these exoplanetary debris systems in the context of our own Solar System, (b) characterize the material in these regions at high spatial resolution and, (c) look for sub-structures within the disks that are sign posts of planetary formation and evolution; in particular, asymmetries and non-uniform debris structures signaling the presence of co-orbiting perturbing planets. All of our objects were previously observed at longer wavelengths (with lower spatial resolution and imaging efficacy) with NICMOS, but with an inner working angle comparable to STIS multi-roll coronagraphy. The combination of new optical and existing near-IR imaging will strongly constrain the dust properties enabling an assessment of grain processing and planetesimal populations. These results will directly inform upon the posited planet formation mechanisms that occur after the approximately 10 My epoch of gas depletion (a time in our solar system when giant planets were migrating and the terrestrial planets were forming) and directly test theoretical models of these processes. The outer reaches (only) of most of these systems were previously observed with a much larger ( 6x on average), spatially limiting, effective inner working angle of the ACS coronagraph and do not reveal the inner structures of these CS disks. Our investigation will uniquely probe into the interior regions of these systems for the first time with spatial resolution comparable to ACS and with augmenting NICMOS near-IR disk photometry

  17. A novel indocyanine green nanoparticle probe for non invasive fluorescence imaging in vivo

    NASA Astrophysics Data System (ADS)

    Navarro, Fabrice P.; Berger, Michel; Goutayer, Mathieu; Guillermet, Stéphanie; Josserand, Véronique; Rizo, Philippe; Vinet, Françoise; Texier, Isabelle

    2009-02-01

    Fluorescence imaging (FLI) allows the in vivo monitoring of biological events associated with disease and represents a new promising tool for drug discovery. In particular, it speeds up the development and assessment of new therapies in oncology, helps in diagnosis, and improves surgery by fluorescence-guided tumor resection. This technique is highly sensitive, non-ionizing, easy to use and relatively inexpensive. Nevertheless, the main limitation of FLI lies in the optical properties of biological tissues. Mainly because of haemoglobin and water absorption, only near-infrared (NIR) light is adapted to image tissues in depth. Using a contrasting agent absorbing and emitting in the NIR region is therefore necessary to improve the background signal ratio, and thus the image contrast. Among many commercially available NIR optical contrast agents, only indocyanine green (ICG), has been approved by the United State Food and Drug Administration (FDA) for various medical applications. However, its instability (photo-degradation, thermal-degradation and low aqueous solubility) limits its applications as a fluorescent probe for imaging purposes. In order to improve the effectiveness of ICG, we engineered ICG-doped lipid nanoparticles (LNP). In this communication, we will report the design of these novel fluorescent nanoparticle probes. These low cost nanocarriers have numerous advantages, including their high chemical stability and biocompatibility. The characterization of the optical properties of the nanoparticles entrapping ICG will also be discussed. Finally, the biodistribution in mice of ICG when delivered through nanoparticles in comparison to free ICG in solution is presented. It demonstrates the efficient accumulation of ICG-doped nanoparticles in the tumor site.

  18. Analysis of abdominal wounds made by surgical trocars using functional luminal imaging probe (FLIP) technology.

    PubMed

    McMahon, Barry P; O'Donovan, Deidre; Liao, Donghua; Zhao, Jingbo; Schiretz, Rich; Heninrich, Russell; Gregersen, Hans

    2008-09-01

    The aim was to use a novel functional luminal imaging probe for evaluation of wound defects and tissue damage resulting from the use of trocars. Following general anesthesia of 4 adult pigs, 6 different trocars were randomly inserted at preselected locations in the porcine abdominal wall. The functional luminal imaging probe was used to profile the trocar holes during bag distension from 8 axial cross-sectional area measurements. The cross-sectional areas and pressure in the bag were recorded and exported to Matlab for analysis and data display. Geometric profiles were generated, and the minimum cross-sectional area and hole length (abdominal wall thickness) were used as endpoints. Successful distensions were made in all cases. The slope of the contours increased away from the narrowest point of the hole. The slope increased more rapidly toward the inner abdominal wall than toward the outer wall. The slope of the linear trend lines for the cross-sectional area-pressure relation represents the compliance at the narrowest point in the wall. The hole length (abdominal wall thickness) could be obtained at different cross-sectional area cutoff points. A cutoff point of 300 mm(2) gave good results when compared to the length of the hole measured after the tissue was excised. This technique represents a new and straightforward way to evaluate the effects of trocars on the abdominal wall. It may also prove useful in comparing techniques and technology from different manufacturers. PMID:18757380

  19. Near-field microwave scanning probe imaging of conductivity inhomogeneities in CVD graphene.

    PubMed

    Tselev, Alexander; Lavrik, Nickolay V; Vlassiouk, Ivan; Briggs, Dayrl P; Rutgers, Maarten; Proksch, Roger; Kalinin, Sergei V

    2012-09-28

    We have performed near-field scanning microwave microscopy (SMM) of graphene grown by chemical vapor deposition. Due to the use of probe-sample capacitive coupling and a relatively high ac frequency of a few GHz, this scanning probe method allows mapping of local conductivity without a dedicated counter electrode, with a spatial resolution of about 50 nm. Here, the coupling was enabled by atomic layer deposition of alumina on top of graphene, which in turn enabled imaging both large-area films, as well as micron-sized islands, with a dynamic range covering a low sheet resistance of a metal film and a high resistance of highly disordered graphene. The structures of graphene grown on Ni films and Cu foils are explored, and the effects of growth conditions are elucidated. We present a simple general scheme for interpretation of the contrast in the SMM images of our graphene samples and other two-dimensional conductors, which is supported by extensive numerical finite-element modeling. We further demonstrate that combination of the SMM and numerical modeling allows quantitative information about the sheet resistance of graphene to be obtained, paving the pathway for characterization of graphene conductivity with a sub-100 nm special resolution. PMID:22948033

  20. Near-field Microwave Scanning Probe Imaging of Conductivity Inhomogeneities in CVD Graphene

    SciTech Connect

    Tselev, Alexander; Lavrik, Nickolay V; Vlassiouk, Ivan V; Briggs, Dayrl P; Rutgers, Maarten; Proksch, Roger; Kalinin, Sergei V

    2012-01-01

    We have performed near-field scanning microwave microscopy (SMM) of graphene grown by chemical vapor deposition. Due to the use of probe-sample capacitive coupling and a relatively high ac frequency of a few GHz, this scanning probe method allows mapping of local conductivity without a dedicated counter electrode, with a spatial resolution of about 50 nm. Here, the coupling was enabled by atomic layer deposition of alumina on top of graphene, which in turn enabled imaging both large-area films, as well as micron-sized islands, with a dynamic range covering a low sheet resistance of a metal film and a high resistance of highly disordered graphene. The structures of graphene grown on Ni films and Cu foils are explored, and the effects of growth conditions are elucidated. We present a simple general scheme for interpretation of the contrast in the SMM images of our graphene samples and other two-dimensional conductors, which is supported by extensive numerical finite-element modeling. We further demonstrate that combination of the SMM and numerical modeling allows quantitative information about the sheet resistance of graphene to be obtained, paving the pathway for characterization of graphene conductivity with a sub-100 nm special resolution.

  1. Proton-Electron Double-Resonance Imaging of pH using phosphonated trityl probe

    PubMed Central

    Takahashi, Wataru; Bobko, Andrey A.; Dhimitruka, Ilirian; Hirata, Hiroshi; Zweier, Jay L.; Samouilov, Alexandre

    2014-01-01

    Variable Radio Frequency Proton-Electron Double-Resonance Imaging (VRF PEDRI) enables extracting a functional map from a limited number of images acquired at pre-selected EPR frequencies using specifically designed paramagnetic probes with high quality spatial resolution and short acquisition times. In this work we explored potential of VRF PEDRI for pH mapping of aqueous samples using recently synthesized pH-sensitive phosphonated trityl radical, pTR. The ratio of Overhauser enhancements measured at each pixel at two different excitation frequencies corresponding to the resonances of protonated and deprotonated forms of pTR probe allows for a pH map extraction. Long relaxation times of pTR allow for pH mapping at EPR irradiation power as low as 1.25 W during 130 s acquisition time with spatial resolution of about 1 mm. This is particularly important for in vivo applications enabling one to avoid sample overheating by reducing RF power deposition. PMID:25530673

  2. Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging

    PubMed Central

    Xiao, J.; Tian, X. M.; Yang, C.; Liu, P.; Luo, N. Q.; Liang, Y.; Li, H. B.; Chen, D. H.; Wang, C. X.; Li, L.; Yang, G. W.

    2013-01-01

    Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic resonance imaging due to the impressive contrast ability. However, the reported Mn-based NPs possess low relaxivity and there are no immunotoxicity data regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh relaxivity of water protons of 8.26 mM−1s−1 from the Mn3O4 NPs synthesized by a simple and green technique, which is twice higher than that of commercial gadolinium (Gd)-based contrast agents (4.11 mM−1s−1) and the highest value reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4 NPs biocompatibilities both in vitro and in vivo are satisfactory based on systematical studies of the intrinsic toxicity including cell viability of human nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in cells and in vivo immunotoxicity. These findings pave the way for the practical clinical diagnosis of Mn based NPs as safe probes for in vivo imaging. PMID:24305731

  3. Photophysics of Fluorescence Probes for Single Molecule Biophysics and Super-Resolution Imaging

    PubMed Central

    Ha, Taekjip; Tinnefeld, Philip

    2013-01-01

    Single-molecule fluorescence spectroscopy and super-resolution microscopy are important elements of the ongoing technical revolution to reveal biochemical and cellular processes in unprecedented clarity and precision. Demands placed on the photophysical properties of the fluorophores are stringent and drive the choice of appropriate probes. Such fluorophores are not simple light bulbs of certain color and brightness but instead have their own ‘personalities’ regarding spectroscopic parameters, redox properties, size and water solubility, photostability and several more. Here, we review the photophysics of fluorescent probes, both organic fluorophores and fluorescent proteins, used in applications such as particle tracking, single molecule FRET, stoichiometry determination, and super-resolution imaging. Of particular interest is the thiol-induced blinking of Cy5, a curse for single molecule biophysical studies which was later overcome using Trolox through reducing/oxidizing system, but a boon for super-resolution imaging due to the controllable photoswitching. Understanding photophysics is critical in design and interpreting single molecule experiments. PMID:22404588

  4. Flexible micro-OCT endobronchial probe for imaging of mucociliary transport (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Cui, Dongyao; Chu, Kengyeh K.; Unglert, Carolin I.; Ford, Tim N.; Carruth, Robert W.; Hyun, Daryl; Singh, Kanwarpal; Birket, Susan E.; Solomon, George M.; Rowe, Steve M.; Tearney, Guillermo J.

    2016-03-01

    Mucociliary clearance (MCC) plays a significant role in maintaining the health of human respiratory system by eliminating foreign particles trapped within mucus. Failure of this mechanism in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD) leads to airway blockage and lung infection, causing morbidity and mortality. The volume of airway mucus and the periciliary liquid encapsulating the cilia, in addition to ciliary beat frequency and velocity of mucociliary transport, are vital parameters of airway health. However, the diagnosis of disease pathogenesis and advances of novel therapeutics are hindered by the lack of tools for visualization of ciliary function in vivo. Our laboratory has previously developed a 1-µm resolution optical coherence tomography method, termed Micro-OCT, which is capable of visualizing mucociliary transport and quantitatively capturing epithelial functional metrics. We have also miniaturized Micro-OCT optics in a first-generation rigid 4mm Micro-OCT endoscope utilizing a common-path design and an apodizing prism configuration to produce an annular profile sample beam, and reported the first in vivo visualization of mucociliary transport in swine. We now demonstrate a flexible 2.5 mm Micro-OCT probe that can be inserted through the instrument channel of standard flexible bronchoscopes, allowing bronchoscopic navigation to smaller airways and greatly improving clinical utility. Longitudinal scanning over a field of view of more than 400 µm at a frame rate of 40 Hz was accomplished with a driveshaft transduced by a piezo-electric stack motor. We present characterization and imaging results from the flexible micro-OCT probe and progress towards clinical translation. The ability of the bronchoscope-compatible micro-OCT probe to image mucus clearance and epithelial function will enable studies of cystic fibrosis pathogenesis in small airways, provide diagnosis of mucociliary clearance disorders, and allow

  5. Scanning mass spectrometry probe: a scanning probe electrospray ion source for imaging mass spectrometry of submerged interfaces and transient events in solution.

    PubMed

    Kottke, Peter A; Degertekin, F Levent; Fedorov, Andrei G

    2010-01-01

    The scanning mass spectrometry (SMS) probe is a new electrospray ion source. Motivated by the need for untargeted chemical imaging of dynamic events in solution, we have exploited an approach to electrospray ionization (ESI) that allows continuous sampling from a highly localized volume (approximately picoliters) in a liquid environment, softly ionizes molecules in the sample to render them amenable for mass spectrometric analysis, and sends the ions to the mass spectrometer. The key underlying concepts for our approach are (1) treating the electrospray capillary inlet as a chemical scanning probe and (2) locating the electrospray point as close as possible to the sampling point, thus providing the shortest response time possible. This approach enables chemical monitoring or imaging of submerged interfaces, providing access to details of spatial heterogeneity and temporal changes within liquid samples. It also permits direct access to liquid/ liquid interfaces for ESI-MS analysis. In this letter we report the first demonstrations of these capabilities of the SMS probe and describe some of the probe's basic characteristics. PMID:19904914

  6. In vivo reproducibility of robotic probe placement for an integrated US-CT image-guided radiation therapy system

    NASA Astrophysics Data System (ADS)

    Lediju Bell, Muyinatu A.; Sen, H. Tutkun; Iordachita, Iulian; Kazanzides, Peter; Wong, John

    2014-03-01

    Radiation therapy is used to treat cancer by delivering high-dose radiation to a pre-defined target volume. Ultrasound (US) has the potential to provide real-time, image-guidance of radiation therapy to identify when a target moves outside of the treatment volume (e.g. due to breathing), but the associated probe-induced tissue deformation causes local anatomical deviations from the treatment plan. If the US probe is placed to achieve similar tissue deformations in the CT images required for treatment planning, its presence causes streak artifacts that will interfere with treatment planning calculations. To overcome these challenges, we propose robot-assisted placement of a real ultrasound probe, followed by probe removal and replacement with a geometrically-identical, CT-compatible model probe. This work is the first to investigate in vivo deformation reproducibility with the proposed approach. A dog's prostate, liver, and pancreas were each implanted with three 2.38-mm spherical metallic markers, and the US probe was placed to visualize the implanted markers in each organ. The real and model probes were automatically removed and returned to the same position (i.e. position control), and CT images were acquired with each probe placement. The model probe was also removed and returned with the same normal force measured with the real US probe (i.e. force control). Marker positions in CT images were analyzed to determine reproducibility, and a corollary reproducibility study was performed on ex vivo tissue. In vivo results indicate that tissue deformations with the real probe were repeatable under position control for the prostate, liver, and pancreas, with median 3D reproducibility of 0.3 mm, 0.3 mm, and 1.6 mm, respectively, compared to 0.6 mm for the ex vivo tissue. For the prostate, the mean 3D tissue displacement errors between the real and model probes were 0.2 mm under position control and 0.6 mm under force control, which are both within acceptable

  7. SU-E-J-205: Monte Carlo Modeling of Ultrasound Probes for Real-Time Ultrasound Image-Guided Radiotherapy

    SciTech Connect

    Hristov, D; Schlosser, J; Bazalova, M; Chen, J

    2014-06-01

    Purpose: To quantify the effect of ultrasound (US) probe beam attenuation for radiation therapy delivered under real-time US image guidance by means of Monte Carlo (MC) simulations. Methods: MC models of two Philips US probes, an X6-1 matrix-array transducer and a C5-2 curved-array transducer, were built based on their CT images in the EGSnrc BEAMnrc and DOSXYZnrc codes. Due to the metal parts, the probes were scanned in a Tomotherapy machine with a 3.5 MV beam. Mass densities in the probes were assigned based on an electron density calibration phantom consisting of cylinders with mass densities between 0.2–8.0 g/cm{sup 3}. Beam attenuation due to the probes was measured in a solid water phantom for a 6 MV and 15 MV 15x15 cm{sup 2} beam delivered on a Varian Trilogy linear accelerator. The dose was measured with the PTW-729 ionization chamber array at two depths and compared to MC simulations. The extreme case beam attenuation expected in robotic US image guided radiotherapy for probes in upright position was quantified by means of MC simulations. Results: The 3.5 MV CT number to mass density calibration curve was found to be linear with R{sup 2} > 0.99. The maximum mass densities were 4.6 and 4.2 g/cm{sup 3} in the C5-2 and X6-1 probe, respectively. Gamma analysis of the simulated and measured doses revealed that over 98% of measurement points passed the 3%/3mm criteria for both probes and measurement depths. The extreme attenuation for probes in upright position was found to be 25% and 31% for the C5-2 and X6-1 probe, respectively, for both 6 and 15 MV beams at 10 cm depth. Conclusion: MC models of two US probes used for real-time image guidance during radiotherapy have been built. As a Result, radiotherapy treatment planning with the imaging probes in place can now be performed. J Schlosser is an employee of SoniTrack Systems, Inc. D Hristov has financial interest in SoniTrack Systems, Inc.

  8. mRNA Expression of Platelet-Derived Growth Factor Receptor-{beta} and C-KIT: Correlation With Pathologic Response to Cetuximab-Based Chemoradiotherapy in Patients With Rectal Cancer

    SciTech Connect

    Erben, Philipp Horisberger, Karoline; Muessle, Benjamin; Mueller, Martin Christian; Treschl, Anne; Ernst, Thomas; Kaehler, Georg; Stroebel, Philipp; Wenz, Frederik; Kienle, Peter; Post, Stefan; Hochhaus, Andreas; Willeke, Frank; Hofheinz, Ralf-Dieter

    2008-12-01

    Purpose: Deviant expression of platelet-derived growth factor receptor-{beta} (PDGFR{beta}) and c-kit was shown in patients with colorectal cancer. In the present study, mRNA expression of PDGFR{beta} and c-kit in 33 patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy with cetuximab/capecitabine/irinotecan in correlation with the tumor regression rate was investigated. Methods and Materials: Pretherapeutic biopsy cores and tumor material from the resected specimens were collected in parallel with normal rectal mucosa. The expression levels of PDGFR{beta} and c-kit were measured by quantitative polymerase chain reaction. Tumors were classified as good responders (tumor regression grade [TRG], 2-3) or poor responders (TRG, 0-1). Results: The TRG evaluation of the resected specimen was TRG 0-1 in 11 and TRG 2-3 in 22. The median normalized ratios in the pretreatment mucosa vs. tumor biopsy cores was as follows: PDGFR{beta} ratio of 15.2 vs. 49.5 (p <0.0001) and c-kit ratio of 0.94 vs. 0.67 (p = 0.014). The same tendency was observed for the median PDGFR{beta} ratios after chemoradiotherapy completion: 34.2 vs. 170.0 (p <0.0001). The PDGFR{beta} and c-kit mRNA expression values in the pretreatment tumor biopsy cores were lower than the values in the resected specimens: PDGFR{beta} ratio 49.5 vs. 170.0 (p = 0.0002) and c-kit ratio 0.67 vs. 1.1 (p = 0.0003). Nevertheless, no correlation was seen between the pretherapeutic PDGFR{beta} and c-kit mRNA expression and the pathologic regression rate. Conclusion: Cetuximab-based chemoradiotherapy increased PDGFR{beta} levels even further compared with the pretreatment samples and deserves further investigation.

  9. Hand-held optoacoustic probe for three-dimensional imaging of human morphology and function

    NASA Astrophysics Data System (ADS)

    Deán-Ben, X. Luís.; Razansky, Daniel

    2014-03-01

    We report on a hand-held imaging probe for real-time optoacoustic visualization of deep tissues in three dimensions. The proposed solution incorporates a two-dimensional array of ultrasonic sensors densely distributed on a spherical surface, whereas illumination is performed coaxially through a cylindrical cavity in the array. Visualization of three-dimensional tomographic data at a frame rate of 10 images per second is enabled by parallel recording of 256 time-resolved signals for each individual laser pulse along with a highly efficient GPUbased real-time reconstruction. A liquid coupling medium (water), enclosed in a transparent membrane, is used to guarantee transmission of the optoacoustically generated waves to the ultrasonic detectors. Excitation at multiple wavelengths further allows imaging spectrally distinctive tissue chromophores such as oxygenated and deoxygenated haemoglobin. The performance is showcased by video-rate tracking of deep tissue vasculature and three-dimensional measurements of blood oxygenenation in a healthy human volunteer. The flexibility provided by the hand-held hardware design, combined with the real-time operation, makes the developed platform highly usable for both small animal research and clinical imaging in multiple indications, including cancer, inflammation, skin and cardiovascular diseases, diagnostics of lymphatic system and breast

  10. Starspots and relativity: Applied Doppler imaging for the Gravity Probe B mission

    NASA Astrophysics Data System (ADS)

    Marsden, S. C.; Berdyugina, S. V.; Donati, J.-F.; Eaton, J. A.; Williamson, M. H.

    2007-12-01

    We present Doppler images and surface differential rotation measurements for the primary of the RS CVn binary IM Pegasi, the guide star for the Gravity Probe B experiment. The data used is a subset of that taken during optical support of the mission and was obtained almost nightly over a near three year period from the Automatic Spectroscopic Telescope operated by Tennessee State University. Using the technique of least-squares deconvolution to increase the signal-to-noise ratio of the data, we have reconstructed 31 maximum entropy Doppler images of the star. The images show that the spot features are relatively stable for over a year (and possibly longer) with both a polar spot and lower latitude features. The most intense features are located on the side facing the secondary. In addition, we have incorporated a solar-like differential rotation law into the imaging process to determine the level of surface differential rotation for IM Peg for 22 epochs. A weighted least-squares average of the measurements gives a surface shear of 0.0142 ± 0.0007 rad/d, meaning that the equator takes ˜440 ± 20 days to lap the poles. Although the level of surface differential rotation was shown to vary over the period of the observations, this may indicate an underestimate in the errors of the method rather than any temporal evolution in the differential rotation. Movies are available via http://www.aip.de/AN/movies

  11. Scanned probe imaging of nanoscale magnetism at cryogenic temperatures with a single-spin quantum sensor

    NASA Astrophysics Data System (ADS)

    Pelliccione, Matthew; Jenkins, Alec; Ovartchaiyapong, Preeti; Reetz, Christopher; Emmanouilidou, Eve; Ni, Ni; Bleszynski Jayich, Ania C.

    2016-08-01

    High-spatial-resolution magnetic imaging has driven important developments in fields ranging from materials science to biology. However, to uncover finer details approaching the nanoscale with greater sensitivity requires the development of a radically new sensor technology. The nitrogen–vacancy (NV) defect in diamond has emerged as a promising candidate for such a sensor on the basis of its atomic size and quantum-limited sensing capabilities. It has remained an outstanding challenge to implement the NV centre as a nanoscale scanning magnetic probe at cryogenic temperatures, however, where many solid-state systems exhibit non-trivial magnetic order. Here, we present NV magnetic imaging down to 6 K with 3 μT Hz–1/2 field sensitivity, and use the technique to image vortices in the iron pnictide superconductor BaFe2(As0.7P0.3)2 with critical temperature Tc = 30 K. The expansion of NV-based magnetic imaging to cryogenic temperatures will enable future studies of previously inaccessible nanoscale magnetism in condensed-matter systems.

  12. Scanned probe imaging of nanoscale magnetism at cryogenic temperatures with a single-spin quantum sensor.

    PubMed

    Pelliccione, Matthew; Jenkins, Alec; Ovartchaiyapong, Preeti; Reetz, Christopher; Emmanouilidou, Eve; Ni, Ni; Bleszynski Jayich, Ania C

    2016-08-01

    High-spatial-resolution magnetic imaging has driven important developments in fields ranging from materials science to biology. However, to uncover finer details approaching the nanoscale with greater sensitivity requires the development of a radically new sensor technology. The nitrogen-vacancy (NV) defect in diamond has emerged as a promising candidate for such a sensor on the basis of its atomic size and quantum-limited sensing capabilities. It has remained an outstanding challenge to implement the NV centre as a nanoscale scanning magnetic probe at cryogenic temperatures, however, where many solid-state systems exhibit non-trivial magnetic order. Here, we present NV magnetic imaging down to 6 K with 3 μT Hz(-1/2) field sensitivity, and use the technique to image vortices in the iron pnictide superconductor BaFe2(As0.7P0.3)2 with critical temperature Tc = 30 K. The expansion of NV-based magnetic imaging to cryogenic temperatures will enable future studies of previously inaccessible nanoscale magnetism in condensed-matter systems. PMID:27136130

  13. Probing for Exoplanets Hiding in Dusty Debris Disks: Inner {<10 AU} Disk Imaging, Characterization, and Exploration

    NASA Astrophysics Data System (ADS)

    Schneider, Glenn

    2010-09-01

    We propose new visible-light observations of a well-selected sample of circumstellar {CS} debris disks, all with HST pedigree, using STIS PSF-subtracted multi-roll coronagraphic imaging. Our new observations will probe the interior CS regions of these debris systems {with inner working distances of < approximately 8 AU for half the stars in this sample}, corresponding to the giant planet and Kuiper belt regions within our own solar system. These new images will enable us to directly inter-compare the architectures of these exoplanetary debris systems in the context of our own Solar System. These observations will also permit us, for the first time, to characterize the material in these regions at high spatial resolution and to look for sub-structures within the disks that are the sign posts of planetary formation and evolution; in particular, asymmetries and non-uniform debris structures signal the presence of co-orbiting perturbing planets. Additionally, all of our objects have been observed previously at longer wavelengths {but much lower spatial resolution and imaging efficacy} with NICMOS, but with an inner working angle comparable to STIS multi-roll coronagraphy. The combination of new optical and existing near-IR imaging will strongly constrain the dust properties, thus enabling an assessment of grain processing and planetesimal populations. These results will directly inform upon the posited planet formation mechanisms that occur after the 10 My epoch of gas depletion, at a time in our solar system when giant planets were migrating and the terrestrial planets were forming, and directly test theoretical models of these processes. The outer reaches {only} of most of these systems were previously observed with a much larger { 6x on average}, spatially limiting, effective inner working angle of the ACS coronagraph. The previous ACS images are therefore completely inadequate to address our science goals of imaging the inner structures of these CS disks. Our

  14. High-resolution apertureless near-field optical imaging using gold nanosphere probes.

    PubMed

    Kim, Zee Hwan; Leone, Stephen R

    2006-10-12

    An apertureless near-field scanning optical microscope (ANSOM) that utilizes the enhanced field around a gold nanosphere, which is attached to the end of an atomic force microscope (AFM) tip, is used to image the local dielectric constant of the patterned metallic surfaces and local electric field around plasmonic nanosphere samples. A colloidal gold nanosphere (approximately 50 nm diameter) is linked to the extremity of the conventional etched-silicon probe. The scattering of laser radiation (633 or 532 nm) is modulated by the oscillating nanosphere-functionalized silicon tip, and the scattered radiation is detected. The approach curve (scattering intensity as a function of the tip-sample distance), the polarization dependence (scattering intensity as a function of the excitation polarization direction), and ANSOM image contrast confirm that the spherical nanosphere attached to the silicon tip acts as a point dipole that interacts with the sample surface via a dipole-dipole coupling, in which the dipole created by the field at the tip interacts with its own image dipole in the sample. The image obtained with the nanoparticle functionalized tip provides a dielectric map of the sample surface with a spatial resolution better than 80 nm. In addition, we show that the functionalized tip is capable of imaging the local electric field distribution above the plasmonic nanosphere samples. Overall, the result shows that high-resolution ANSOM is possible without the aid of the lightning-rod effect. With an improved tip-fabrication method, we believe that the method can provide a versatile high-resolution chemical imaging that is not available from usual forms of ANSOM. PMID:17020365

  15. An optical biopsy system with miniaturized Raman and spectral imaging probes; in vivo animal and ex vivo clinical application studies

    NASA Astrophysics Data System (ADS)

    Sato, Hidetoshi; Suzuki, Toshiaki; Andriana, Bibin B.; Morita, Shin'ichi; Maruyama, Atsushi; Shinzawa, Hideyuki; Komachi, Yuichi; Kanai, Gen'ichi; Ura, Nobuo; Masutani, Koji; Matsuura, Yuji; Toi, Masakazu; Shimosegawa, Toru; Ozaki, Yukihiro

    2009-02-01

    An optical biopsy system which equips miniaturized Raman probes, a miniaturized endoscope and a fluorescent image probe has been developed for in vivo studies of live experimental animals. The present report describes basic optical properties of the system and its application studies for in vivo cancer model animals and ex vivo human cancer tissues. It was developed two types of miniaturized Raman probes, micro Raman probe (MRP) made of optical fibers and ball lens hollow optical fiber Raman probe (BHRP) made of single hollow optical fiber (HOF) with a ball lens. The former has rather large working distance (WD), up to one millimeter. The latter has small WD (~300μm) which depends on the focal length of the ball lens. Use of multiple probes with different WD allows one to obtain detailed information of subsurface tissues in the totally noninvasive manner. The probe is enough narrow to be inserted into a biopsy needle (~19G), for observations of the lesion at deeper inside bodies. The miniaturized endoscope has been applied to observe progression of a stomach cancer in the same rat lesion. It was succeeded to visualize structure of non-stained cancer tissue in live model animals by the fluorescent image technique. The system was also applied to ex vivo studies of human breast and stomach cancers.

  16. Near-Infrared Fluorogenic Probes with Polarity-Sensitive Emission for in Vivo Imaging of an Ovarian Cancer Biomarker.

    PubMed

    Yao, Defan; Lin, Zhi; Wu, Junchen

    2016-03-01

    Lysophosphatidic acid (LPA, cutoff values ≥ 1.5 μM) is an effective biomarker for early stage ovarian cancer. The development of selective probes for LPA detection is therefore critical for early clinical diagnosis. Although current methods have been developed for the detection of LPA in solution, they cannot be used for tracking LPA in vivo. Here, we report a near-infrared (NIR) fluorescent probe that can selectively respond to LPA based on polarity-sensitive emission at a very low detection limit of 0.5 μM in situ. This probe exhibits a marked increase of fluorescence at 720 nm upon binding to LPA, allowing the direct visualization of LPA in vitro and in vivo without interference from other biomolecules. Moreover, the probe containing two arginine-glycine-aspartic acid units can be efficiently taken up by cancer cells based on an αvβ3 integrin receptor targeting mechanism. It also exhibits excellent biocompatibility and high pH stability in live cells and in vivo. Confocal laser scanning microscopy and flow cytometric imaging of SKOV-3 cells have confirmed that our probe can be used to image LPA in live cells. In particular, its NIR turn-on fluorescence can be used to effectively monitor LPA imaging in a SKOV-3 tumor-bearing mouse model. Our probe may pave the way for the detection of cancer-related biomarkers and even for early stage cancer diagnosis. PMID:26910257

  17. Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

    PubMed Central

    Zhang, Qilei; Gladden, Lynn F.; Avalle, Paolo; Zeitler, J. Axel; Mantle, Michael D.

    2013-01-01

    Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescol® XL) when stored under accelerated conditions (40 °C/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescol® XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor f1 and a “similarity” factor f2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance. PMID:24300564

  18. Transvaginal photoacoustic imaging probe and system based on a multiport fiber-optic beamsplitter and a real time imager for ovarian cancer detection

    NASA Astrophysics Data System (ADS)

    Kumavor, Patrick D.; Alqasemi, Umar; Tavakoli, Behnoosh; Li, Hai; Yang, Yi; Zhu, Quing

    2013-03-01

    This paper presents a real-time transvaginal photoacoustic imaging probe for imaging human ovaries in vivo. The probe consists of a high-throughput (up to 80%) fiber-optic 1 x 19 beamsplitters, a commercial array ultrasound transducer, and a fiber protective sheath. The beamsplitter has a 940-micron core diameter input fiber and 240-micron core diameter output fibers numbering 36. The 36 small-core output fibers surround the ultrasound transducer and delivers light to the tissue during imaging. A protective sheath, modeled in the form of the transducer using a 3-D printer, encloses the transducer with array of fibers. A real-time image acquisition system collects and processes the photoacoustic RF signals from the transducer, and displays the images formed on a monitor in real time. Additionally, the system is capable of coregistered pulse-echo ultrasound imaging. In this way, we obtain both morphological and functional information from the ovarian tissue. Photoacousitc images of malignant human ovaries taken ex vivo with the probe revealed blood vascular and networks that was distinguishable from normal ovaries, making the probe potential useful for characterizing ovarian tissue.

  19. Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals

    PubMed Central

    Kim, Jun Ki; Lee, Woei Ming; Kim, Pilhan; Choi, Myunghwan; Jung, Keehoon; Kim, Seonghoon; Yun, Seok Hyun

    2013-01-01

    Intravital fluorescence microscopy has emerged as a powerful technique to visualize cellular processes in vivo. However, the size of the objective lenses has limited physical accessibility to various tissue sites in the internal organs of small animals. The use of small-diameter probes using graded-index (GRIN) lenses expands the capabilities of conventional intravital microscopes into minimally invasive internal organs imaging. In this protocol, we describe the detailed steps for the fabrication of front- and side-view GRIN probes and the integration and operation of the probes in a confocal microscope for visualizing fluorescent cells and microvasculature in various murine organs. We further present longitudinal imaging of immune cells in renal allografts and the tumor development in the colon. The fabrication and integration can be completed in 5–7 hours, and a typical in vivo imaging session takes 1–2 hours. PMID:22767088

  20. Functional imaging of proteases: recent advances in the design and application of substrate-based and activity-based probes.

    PubMed

    Edgington, Laura E; Verdoes, Martijn; Bogyo, Matthew

    2011-12-01

    Proteases are enzymes that cleave peptide bonds in protein substrates. This process can be important for regulated turnover of a target protein but it can also produce protein fragments that then perform other functions. Because the last few decades of protease research have confirmed that proteolysis is an essential regulatory process in both normal physiology and in multiple disease-associated conditions, there has been an increasing interest in developing methods to image protease activity. Proteases are also considered to be one of the few 'druggable' classes of proteins and therefore a large number of small molecule based inhibitors of proteases have been reported. These compounds serve as a starting point for the design of probes that can be used to target active proteases for imaging applications. Currently, several classes of fluorescent probes have been developed to visualize protease activity in live cells and even whole organisms. The two primary classes of protease probes make use of either peptide/protein substrates or covalent inhibitors that produce a fluorescent signal when bound to an active protease target. This review outlines some of the most recent advances in the design of imaging probes for proteases. In particular, it highlights the strengths and weaknesses of both substrate-based and activity-based probes and their applications for imaging cysteine proteases that are important biomarkers for multiple human diseases. PMID:22098719

  1. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

    PubMed

    Whitley, Melodi Javid; Cardona, Diana M; Lazarides, Alexander L; Spasojevic, Ivan; Ferrer, Jorge M; Cahill, Joan; Lee, Chang-Lung; Snuderl, Matija; Blazer, Dan G; Hwang, E Shelley; Greenup, Rachel A; Mosca, Paul J; Mito, Jeffrey K; Cuneo, Kyle C; Larrier, Nicole A; O'Reilly, Erin K; Riedel, Richard F; Eward, William C; Strasfeld, David B; Fukumura, Dai; Jain, Rakesh K; Lee, W David; Griffith, Linda G; Bawendi, Moungi G; Kirsch, David G; Brigman, Brian E

    2016-01-01

    Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes. PMID:26738797

  2. High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe

    PubMed Central

    Huang, Ruimin; Harmsen, Stefan; Samii, Jason M.; Karabeber, Hazem; Pitter, Kenneth L.; Holland, Eric C.; Kircher, Moritz F.

    2016-01-01

    The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non-targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD-SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2-3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors. PMID:27279902

  3. Photoacoustic Imaging: Semiconducting Oligomer Nanoparticles as an Activatable Photoacoustic Probe with Amplified Brightness for In Vivo Imaging of pH (Adv. Mater. 19/2016).

    PubMed

    Miao, Qingqing; Lyu, Yan; Ding, Dan; Pu, Kanyi

    2016-05-01

    Despite the great potential of photoacoustic imaging in the life sciences, the development of smart activatable photoacoustic probes remains elusive. On page 3662, K. Pu and co-workers report a facile nanoengineering approach based on semiconducting oligomer nano-particles to develop ratiometric photoacoustic probes with amplified brightness and enhanced sensing capability for accurate photoacoustic mapping of pH in the tumors of living mice. PMID:27167028

  4. A rapid and automated relocation method of an AFM probe for high-resolution imaging.

    PubMed

    Zhou, Peilin; Yu, Haibo; Shi, Jialin; Jiao, Niandong; Wang, Zhidong; Wang, Yuechao; Liu, Lianqing

    2016-09-30

    The atomic force microscope (AFM) is one of the most powerful tools for high-resolution imaging and high-precision positioning for nanomanipulation. The selection of the scanning area of the AFM depends on the use of the optical microscope. However, the resolution of an optical microscope is generally no larger than 200 nm owing to wavelength limitations of visible light. Taking into consideration the two determinants of relocation-relative angular rotation and positional offset between the AFM probe and nano target-it is therefore extremely challenging to precisely relocate the AFM probe to the initial scan/manipulation area for the same nano target after the AFM probe has been replaced, or after the sample has been moved. In this paper, we investigate a rapid automated relocation method for the nano target of an AFM using a coordinate transformation. The relocation process is both simple and rapid; moreover, multiple nano targets can be relocated by only identifying a pair of reference points. It possesses a centimeter-scale location range and nano-scale precision. The main advantages of this method are that it overcomes the limitations associated with the resolution of optical microscopes, and that it is label-free on the target areas, which means that it does not require the use of special artificial markers on the target sample areas. Relocation experiments using nanospheres, DNA, SWCNTs, and nano patterns amply demonstrate the practicality and efficiency of the proposed method, which provides technical support for mass nanomanipulation and detection based on AFM for multiple nano targets that are widely distributed in a large area. PMID:27559679

  5. Advanced Magnetic Resonance Imaging techniques to probe muscle structure and function

    NASA Astrophysics Data System (ADS)

    Malis, Vadim

    aging, strain rate during isometric contraction was significantly reduced in the seniors; presumably from decrease in muscle slack and increase in stiffness with age. Other parameters of interest from this study that allow inferences on the ECM and lateral transmission are the asymmetry of deformation in the fiber cross section as well as the angle between the SR and muscle fiber. The last part of thesis, which is a 'work-in-progress', is the extension to 3D SR tensor mapping using a 3D spatial, 3D velocity encoded imaging sequence. This is combined with Diffusion Tensor Imaging to obtain the lead eigenvector (muscle fiber direction) at each voxel. The 3D SR is then rotated to the basis of the DTI to obtain a 'Fiber Aligned Strain rate: FASR'. The off diagonal elements of FASR are shear strain terms. Detailed analysis of the shear strain will provide a unique non-invasive method to probe lateral transmission.

  6. Near-infrared molecular imaging probes based on chlorin-bacteriochlorin dyads

    NASA Astrophysics Data System (ADS)

    Ptaszek, Marcin; Kee, Hooi Ling; Muthiah, Chinnasamy; Nothdurft, Ralph; Akers, Walter; Achilefu, Samuel; Culver, Joseph P.; Holten, Dewey

    2010-02-01

    Chlorin-bacteriochlorin dyads as a new class of near-infrared fluorophores were synthesized and spectroscopically characterized. Each dyad is comprised of a chlorin macrocycle (free base or zinc chelate) as an energy donor (and absorber) and a free base bacteriochlorin as an energy acceptor (and emitter). Excitation of the chlorin (λ= 650 nm, zinc chelate; 675 nm, free base) results in fast (5 ps) and nearly quantitative (>99%) energy transfer to the adjacent bacteriochlorin moiety, and consequently bacteriochlorin fluorescence (λ= 760 nm). Thus, each chlorinbacteriochlorin dyad behaves as a single chromophore, with a large effective Stokes shift (85 or 110 nm), a significant fluorescence quantum yield (Φf = 0.19), long excited-state lifetime (τ = 5.4 ns), narrow excitation and emission bands (<20 nm), and high chemical stability. Imaging experiments performed using phantoms show that the chlorin-bacteriochlorin dyads exhibit a range of superior properties compare with commercially available imaging dyes. While the latter are six-fold brighter (comparing ɛ•Φf values), the chlorin-bacteriochlorin dyads exhibit narrower excitation and emission bands and larger Stokes shift, therefore allowing more efficient and selective excitation and detection of fluorescence. The high selectivity is further demonstrated with in vivo imaging studies using mice. This selectivity together with the tunability of absorption and emission wavelengths using substituent effects under synthetic control make the chlorin-bacteriochlorin dyads ideal candidates for multicolor imaging applications. In addition, the long fluorescence lifetimes make those probes suitable for lifetime-imaging applications.

  7. Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Ning, Xinghai; Lee, Seungjun; Wang, Zhirui; Kim, Dongin; Stubblefield, Bryan; Gilbert, Eric; Murthy, Niren

    2011-08-01

    The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo, and cannot distinguish infections from other pathologies such as cancer and inflammation. Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway, endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 105 colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria.

  8. Investigation of a vitamin B12 conjugate as a PET imaging probe.

    PubMed

    Ikotun, Oluwatayo F; Marquez, Bernadette V; Fazen, Christopher H; Kahkoska, Anna R; Doyle, Robert P; Lapi, Suzanne E

    2014-06-01

    Nutrient demand is a fundamental characteristic of rapidly proliferating cells. Vitamin B12 is vital for cell proliferation; thus neoplastic cells have an increased demand for this essential nutrient. In this study we exploited the vitamin B12 uptake pathway to probe the nutritional demand of proliferating cells with a radiolabeled B12 derivative in various preclinical tumor models. We describe the synthesis and biological evaluations of copper-64-labeled B12 -ethylenediamine-benzyl-1,4,7-triazacyclononane-N,N',N''-triacetic acid (B12 -en-Bn-NOTA-(64) Cu), the first example of a B12 derivative for positron emission tomography (PET) imaging. Small-animal imaging and pharmacological evaluation show high tumor uptake ranging from 2.20 to 4.84% ID g(-1) at 6 h post-administration. Competition studies with excess native B12 resulted in a 95% decrease in tumor accumulation, indicating the specificity of this radiopharmaceutical for B12 endocytotic transport proteins. These results show that a vitamin B12 PET radiopharmaceutical has potential utility for non-invasive imaging of enhanced nutrient demand in proliferating cells. PMID:24753453

  9. Differentiation of individual human mesenchymal stem cells probed by FTIR microscopic imaging.

    PubMed

    Krafft, Christoph; Salzer, Reiner; Seitz, Sebastian; Ern, Christina; Schieker, Matthias

    2007-07-01

    Objective of this study is the novel application of Fourier transform infrared (FTIR) microscopic imaging to identify the differentiation state of individual human mesenchymal stem cells with or without osteogenic stimulation. IR spectra of several hundred single cells with lateral resolution of 5-10 microm were recorded using a FTIR imaging spectrometer coupled to a microscope with a focal plane array detector. A classification model based on linear discriminant analysis was trained to distinguish four cell types by their IR spectroscopic fingerprint. Without stimulation two cell types dominated, showing low or high levels of glycogen accumulation at the cell periphery. After stimulation, the protein composition in the cells changed and some cells started expressing calcium phosphate salts such as octacalciumphosphate, a precursor of the bone constituent hydroxyapatite. Few cells were identified which remained in their non-stimulated state. This study demonstrated for the first time that FTIR microscopic imaging can probe stem cell differentiation at the single cell level rapidly, non-destructively and with minimal preparation. PMID:17592583

  10. Biomarkers and Molecular Probes for Cell Death Imaging and Targeted Therapeutics

    PubMed Central

    Smith, Bryan A.; Smith, Bradley D.

    2012-01-01

    Cell death is a critically important biological process. Disruption of homeostasis, either by excessive or deficient cell death, is a hallmark of many pathological conditions. Recent research advances have greatly increased our molecular understanding of cell death and its role in a range of diseases and therapeutic treatments. Central to these ongoing research and clinical efforts is the need for imaging technologies that can locate and identify cell death in a wide array of in vitro and in vivo biomedical samples with varied spatiotemporal requirements. This review article summarizes community efforts over the past five years to identify useful biomarkers for dead and dying cells, and to develop molecular probes that target these biomarkers for optical, radionuclear, or magnetic resonance imaging. Apoptosis biomarkers are classified as either intracellular (caspase enzymes, mitochondrial membrane potential, cytosolic proteins) or extracellular (plasma membrane phospholipids, membrane potential, surface exposed histones). Necrosis, autophagy, and senescence biomarkers are described, as well as unexplored cell death biomarkers. The article discusses possible chemotherapeutic and theranostic strategies, and concludes with a summary of current challenges and expected eventual rewards of clinical cell death imaging. PMID:22989049

  11. 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

  12. Cathepsin Activity-Based Probes and Inhibitor for Preclinical Atherosclerosis Imaging and Macrophage Depletion

    PubMed Central

    Abd-Elrahman, Ihab; Kosuge, Hisanori; Wises Sadan, Tommy; Ben-Nun, Yael; Meir, Karen; Rubinstein, Chen; Bogyo, Matthew; McConnell, Michael V.

    2016-01-01

    Background and Purpose Cardiovascular disease is the leading cause of death worldwide, mainly due to an increasing prevalence of atherosclerosis characterized by inflammatory plaques. Plaques with high levels of macrophage infiltration are considered “vulnerable” while those that do not have significant inflammation are considered stable; cathepsin protease activity is highly elevated in macrophages of vulnerable plaques and contributes to plaque instability. Establishing novel tools for non-invasive molecular imaging of macrophages in plaques could aid in preclinical studies and evaluation of therapeutics. Furthermore, compounds that reduce the macrophage content within plaques should ultimately impact care for this disease. Methods We have applied quenched fluorescent cathepsin activity-based probes (ABPs) to a murine atherosclerosis model and evaluated their use for in vivo imaging using fluorescent molecular tomography (FMT), as well as ex vivo fluorescence imaging and fluorescent microscopy. Additionally, freshly dissected human carotid plaques were treated with our potent cathepsin inhibitor and macrophage apoptosis was evaluated by fluorescent microscopy. Results We demonstrate that our ABPs accurately detect murine atherosclerotic plaques non-invasively, identifying cathepsin activity within plaque macrophages. In addition, our cathepsin inhibitor selectively induced cell apoptosis of 55%±10% of the macrophage within excised human atherosclerotic plaques. Conclusions Cathepsin ABPs present a rapid diagnostic tool for macrophage detection in atherosclerotic plaque. Our inhibitor confirms cathepsin-targeting as a promising approach to treat atherosclerotic plaque inflammation. PMID:27532109

  13. Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes

    PubMed Central

    Sun, Minjie; Sun, Bin; Liu, Yun; Shen, Qun-Dong; Jiang, Shaojun

    2016-01-01

    Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application. PMID:26931282

  14. HER2- and EGFR-specific affiprobes: novel recombinant optical probes for cell imaging.

    PubMed

    Lyakhov, Ilya; Zielinski, Rafal; Kuban, Monika; Kramer-Marek, Gabriela; Fisher, Robert; Chertov, Oleg; Bindu, Lakshman; Capala, Jacek

    2010-02-15

    The human epidermal growth factor receptors, EGFR and HER2, are members of the EGFR family of cell-surface receptors/tyrosine kinases. EGFR- and HER2-positive cancers represent a more aggressive disease with greater likelihood of recurrence, poorer prognosis, and decreased survival rate, compared to EGFR- or HER2-negative cancers. The details of HER2 proto-oncogenic functions are not deeply understood, partially because of a restricted availability of tools for EGFR and HER2 detection (A. Sorkin and L. K. Goh, Exp. Cell Res. 2009, 315, 683-696). We have created photostable and relatively simple-to-produce imaging probes for in vitro staining of EGFR and HER2. These new reagents, called affiprobes, consist of a targeting moiety, a HER2- or EGFR-specific Affibody molecule, and a fluorescent moiety, mCherry (red) or EGFP (green). Our flow cytometry and confocal microscopy experiments demonstrated high specificity and signal/background ratio of affiprobes. Affiprobes are able to stain both live cells and frozen tumor xenograph sections. This type of optical probe can easily be extended for targeting other cell-surface antigens/ receptors. PMID:20052708

  15. Nanomechanical and topographical imaging of living cells by atomic force microscopy with colloidal probes

    NASA Astrophysics Data System (ADS)

    Puricelli, Luca; Galluzzi, Massimiliano; Schulte, Carsten; Podestà, Alessandro; Milani, Paolo

    2015-03-01

    Atomic Force Microscopy (AFM) has a great potential as a tool to characterize mechanical and morphological properties of living cells; these properties have been shown to correlate with cells' fate and patho-physiological state in view of the development of novel early-diagnostic strategies. Although several reports have described experimental and technical approaches for the characterization of cellular elasticity by means of AFM, a robust and commonly accepted methodology is still lacking. Here, we show that micrometric spherical probes (also known as colloidal probes) are well suited for performing a combined topographic and mechanical analysis of living cells, with spatial resolution suitable for a complete and accurate mapping of cell morphological and elastic properties, and superior reliability and accuracy in the mechanical measurements with respect to conventional and widely used sharp AFM tips. We address a number of issues concerning the nanomechanical analysis, including the applicability of contact mechanical models and the impact of a constrained contact geometry on the measured Young's modulus (the finite-thickness effect). We have tested our protocol by imaging living PC12 and MDA-MB-231 cells, in order to demonstrate the importance of the correction of the finite-thickness effect and the change in Young's modulus induced by the action of a cytoskeleton-targeting drug.

  16. Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes.

    PubMed

    Sun, Minjie; Sun, Bin; Liu, Yun; Shen, Qun-Dong; Jiang, Shaojun

    2016-01-01

    Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application. PMID:26931282

  17. Advanced slow-magic angle spinning probe for magnetic resonance imaging and spectroscopy

    DOEpatents

    Wind, Robert A.; Hu, Jian Zhi; Minard, Kevin R.; Rommereim, Donald N.

    2006-01-24

    The present invention relates to a probe and processes useful for magnetic resonance imaging and spectroscopy instruments. More particularly, the invention relates to a MR probe and processes for obtaining resolution enhancements of fluid objects, including live specimens, using an ultra-slow (magic angle) spinning (MAS) of the specimen combined with a modified phase-corrected magic angle turning (PHORMAT) pulse sequence. Proton NMR spectra were measured of the torso and the top part of the belly of a female BALBc mouse in a 2T field, while spinning the animal at a speed of 1.5 Hz. Results show that even in this relatively low field with PHORMAT, an isotropic spectrum is obtained with line widths that are a factor 4.6 smaller than those obtained in a stationary mouse. Resolution of 1H NMR metabolite spectra are thus significantly enhanced. Results indicate that PHORMAT has the potential to significantly increase the utility of 1H NMR spectroscopy for in vivo biochemical, biomedical and/or medical applications involving large-sized biological objects such as mice, rats and even humans within a hospital setting. For small-sized objects, including biological objects, such as excised tissues, organs, live bacterial cells, and biofilms, use of PASS at a spinning rate of 30 Hz and above is preferred.

  18. Nanomechanical and topographical imaging of living cells by atomic force microscopy with colloidal probes

    SciTech Connect

    Puricelli, Luca; Galluzzi, Massimiliano; Schulte, Carsten; Podestà, Alessandro Milani, Paolo

    2015-03-15

    Atomic Force Microscopy (AFM) has a great potential as a tool to characterize mechanical and morphological properties of living cells; these properties have been shown to correlate with cells’ fate and patho-physiological state in view of the development of novel early-diagnostic strategies. Although several reports have described experimental and technical approaches for the characterization of cellular elasticity by means of AFM, a robust and commonly accepted methodology is still lacking. Here, we show that micrometric spherical probes (also known as colloidal probes) are well suited for performing a combined topographic and mechanical analysis of living cells, with spatial resolution suitable for a complete and accurate mapping of cell morphological and elastic properties, and superior reliability and accuracy in the mechanical measurements with respect to conventional and widely used sharp AFM tips. We address a number of issues concerning the nanomechanical analysis, including the applicability of contact mechanical models and the impact of a constrained contact geometry on the measured Young’s modulus (the finite-thickness effect). We have tested our protocol by imaging living PC12 and MDA-MB-231 cells, in order to demonstrate the importance of the correction of the finite-thickness effect and the change in Young’s modulus induced by the action of a cytoskeleton-targeting drug.

  19. SU-E-I-81: Targeting of HER2-Expressing Tumors with Dual PET-MR Imaging Probes

    SciTech Connect

    Xu, P; Peng, Y; Sun, M; Yang, X

    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 will 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.

  20. High-resolution imaging with two-axis orthogonal magneto-resistive sensor based eddy current probe

    NASA Astrophysics Data System (ADS)

    Wincheski, Buzz; Simpson, John; Seebo, Jeffery P.; Powell, Jessica

    2012-05-01

    A two-channel magneto-resistive sensor with an embedded, single-strand eddy current inducer has been fabricated and tested for applications including sensory material characterization and the analysis of intermittent contact along compression boundaries and fatigue cracks. A rapid scanning technique has also been implemented to enable high-resolution imaging of relatively large areas in modest times. Applications of the probe for high-resolution imaging of calibration artifacts and sensory materials are presented. Finite element modeling of the probe is also presented and compared with experimental measurements with good agreement.

  1. Facile Probe Design: Fluorescent Amphiphilic Nucleic Acid Probes without Quencher Providing Telomerase Activity Imaging Inside Living Cells.

    PubMed

    Jia, Yongmei; Gao, Pengcheng; Zhuang, Yuan; Miao, Mao; Lou, Xiaoding; Xia, Fan

    2016-06-21

    Nowadays, the probe with fluorophore but no quencher is promising for its simple preparation, environmental friendliness, and wide application scope. This study designs a new amphiphilic nucleic acid probe (ANAP) based on aggregation-caused quenching (ACQ) effect without any quencher. Upon binding with targets, the dispersion of hydrophobic part (conjugated fluorene, CF) in ANAP is enhanced as a signal-on model for proteins, nucleic acids, and small molecules detection or the aggregation of CF is enhanced as a signal-off model for ion detection. Meanwhile, because of the high specificity of ANAP, a one-step method is developed powerfully for monitoring the telomerase activity not only from the cell extracts but also from 50 clinic urine samples (positive results from 45 patients with bladder cancer and negative results from 5 healthy people). ANAPs can also readily enter into cells and exhibit a good performance for distinguishing natural tumor cells from the tumor cells pretreated by telomerase-related drugs or normal cells. In contrast to our previous results ( Anal. Chem. 2015 , 87 , 3890 - 3894 ), the present CF is a monomer which is just the structure unit of the previous fluorescent polymer. Since the accurate molecular structure and high DNA/CF ratio of the present CF, these advanced experiments obtain an easier preparation of probes, an improved sensitivity and specificity, and broader detectable targets. PMID:27223599

  2. An intraoperative probe combining positron detection and OCT imaging for ovarian cancer detection and characterization

    NASA Astrophysics Data System (ADS)

    Yang, Yi; Wang, Tianheng; Biswal, Nrusingh; Kumavor, Patrick; Wang, Xiaohong; Karimeddini, Mozafareddin; Vento, John; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2012-01-01

    In this paper, we report an intraoperative approach by combining optical coherence tomography (OCT) and position detection to detect and characterize ovarian cancers. A total of 18 ovaries were studied ex vivo. Based on histopathology result, they were classified into normal and malignant groups, respectively. On average positron count rate of 8.0-fold higher was found between malignant and normal ovaries. OCT imaging of ovaries revealed many detailed morphologic features that could be potentially valuable for detecting early malignant changes in ovarian tissue. Optical scattering coefficients of these ovaries were estimated from OCT A-lines. Normal ovarian tissue showed higher scattering coefficient than that of malignant ovarian tissue. Using a threshold of 2.00 mm-1 for all ovaries, a sensitivity of 100% and a specificity of 100% were achieved. This initial data shows our intraoperative probe based on OCT and positron detection has a great potential for ovarian cancer detection and characterization.

  3. Synthesis of [{sup 125}I]iodoDPA-713: A new probe for imaging inflammation

    SciTech Connect

    Wang, Haofan; Pullambhatla, Mrudula; Guilarte, Tomas R.; Mease, Ronnie C.; Pomper, Martin G.

    2009-11-06

    [{sup 125}I]IodoDPA-713 [{sup 125}I]1, which targets the translocator protein (TSPO, 18 kDa), was synthesized in seven steps from methyl-4-methoxybenzoate as a tool for quantification of inflammation in preclinical models. Preliminary in vitro autoradiography and in vivo small animal imaging were performed using [{sup 125}I]1 in a neurotoxicant-treated rat and in a murine model of lung inflammation, respectively. The radiochemical yield of [{sup 125}I]1 was 44 {+-} 6% with a specific radioactivity of 51.8 GBq/{mu}mol (1400 mCi/{mu}mol) and >99% radiochemical purity. Preliminary studies showed that [{sup 125}I]1 demonstrated increased specific binding to TSPO in a neurotoxicant-treated rat and increased radiopharmaceutical uptake in the lungs of an experimental inflammation model of lung inflammation. Compound [{sup 125}I]1 is a new, convenient probe for preclinical studies of TSPO activity.

  4. Molecular imaging of hemoglobin using ground state recovery pump-probe optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Applegate, Brian E.; Izatt, Joseph A.

    2007-02-01

    We have undertaken an effort to further develop ground state recovery Pump-Probe Optical Coherence Tomograpy (gsrPPOCT) to specifically target and measure 3-D images of hemoglobin concentration with the goals of mapping tissue vasculature, total hemoglobin, and hemoglobin oxygen saturation. As a first step toward those goals we have measured the gsrPPOCT signal from the hemoglobin in the filament arteries of a zebra danio fish. We have further processed the resulting signal to extract a qualitative map of the hemoglobin concentration. We have also demonstrated the potential to use ground state recovery times to differentiate between two chromophores which may prove to be an effective tool for differentiating between oxy and deoxy hemoglobin.

  5. Probing Tissue Microstructure with Restriction Spectrum Imaging: Histological and Theoretical Validation

    PubMed Central

    White, Nathan S.; Leergaard, Trygve B.; D’Arceuil, Helen; Bjaalie, Jan G.; Dale, Anders M.

    2012-01-01

    Diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying biological tissue microarchitectures in vivo. Recently, there has been increased effort to develop quantitative dMRI methods to probe both length scale and orientation information in diffusion media. Diffusion spectrum imaging (DSI) is one such approach that aims to resolve such information on the basis of the three-dimensional diffusion propagator at each voxel. However, in practice only the orientation component of the propagator function is preserved when deriving the orientation distribution function. Here, we demonstrate how a straightforward extension of the linear spherical deconvolution (SD) model can be used to probe tissue orientation structures over a range (or “spectrum”) of length scales with minimal assumptions on the underlying microarchitecture. Using high b-value Cartesian q-space data on a fixed rat brain sample, we demonstrate how this “restriction spectrum imaging” (RSI) model allows for separating the volume fraction and orientation distribution of hindered and restricted diffusion, which we argue stems primarily from diffusion in the extra- and intra-neurite water compartment, respectively. Moreover, we demonstrate how empirical RSI estimates of the neurite orientation distribution and volume fraction capture important additional structure not afforded by traditional DSI or fixed-scale SD-like reconstructions, particularly in grey matter. We conclude that incorporating length scale information in geometric models of diffusion offers promise for advancing state-of-the-art dMRI methods beyond white matter into grey matter structures while allowing more detailed quantitative characterization of water compartmentalization and histoarchitecture of healthy and diseased tissue. PMID:23169482

  6. A two-photon fluorescent probe for bio-imaging of formaldehyde in living cells and tissues.

    PubMed

    Li, Jun-Bin; Wang, Qian-Qian; Yuan, Lin; Wu, Yong-Xiang; Hu, Xiao-Xiao; Zhang, Xiao-Bing; Tan, Weihong

    2016-05-23

    Formaldehyde (FA) plays an important role in living systems as a reactive carbonyl species (RCS). An abnormal degree of FA is known to induce neurodegeneration, cognitive decrease and memory loss owing to the formation of strong cross-link DNA and protein and other molecules. The development of efficient methods for biological FA detection is of great biomedical importance. Although a few one-photon FA fluorescent probes have been reported for imaging in living cells, probes excited by two photons are more suitable for bio-imaging due to their low background fluorescence, less photobleaching, and deep penetration depth. In this study, a two-photon fluorescent probe for FA detection and bio-imaging in living cells and tissues was reported. The detection is based on the 2-aza-Cope sigmatropic rearrangement followed by elimination to release the fluorophore, resulting in both one- and two-photon excited fluorescence increase. The probe showed a high sensitivity to FA with a detection limit of 0.2 μM. Moreover, enabled the two-photon bio-imaging of FA in live HEK-293 cells and tissues with tissue-imaging depths of 40-170 μm. Furthermore, could be applied for the monitoring of endogenous FA in live MCF-7 cells, presaging its practical applications in biological systems. PMID:27137921

  7. Development of a ruthenium(II) complex based luminescent probe for imaging nitric oxide production in living cells.

    PubMed

    Zhang, Run; Ye, Zhiqiang; Wang, Guilan; Zhang, Wenzhu; Yuan, Jingli

    2010-06-18

    A unique ruthenium(II) complex, bis(2,2'-bipyridine)(4-(3,4-diaminophenoxy)-2,2'-bipyridine)ruthenium(II) hexafluorophosphate ([(Ru(bpy)(2)(dabpy)][PF(6)](2)), has been designed and synthesized as a highly sensitive and selective luminescence probe for the imaging of nitric oxide (NO) production in living cells. The complex can specifically react with NO in aqueous buffers under aerobic conditions to yield its triazole derivative with a high reaction rate constant at the 10(10) M(-1) s(-1) level; this reaction is accompanied by a remarkable increase of the luminescence quantum yield from 0.13 to 2.2 %. Compared with organic probes, the new Ru(II) complex probe shows the advantages of a large Stokes shift (>150 nm), water solubility, and a wide pH-availability range (pH independent at pH>5). In addition, it was found that the new probe could be easily transferred into both living animal cells and plant cells by the coincubation method, whereas the triazole derivative was cell-membrane impermeable. The probe was successfully used for luminescence-imaging detection of the exogenous NO in mouse macrophage cells and endogenous NO in gardenia cells. The results demonstrated the efficacy and advantages of the new probe for NO detection in living cells. PMID:20458707

  8. Diversity oriented fluorescence library approach (DOFLA) for live cell imaging probe development.

    PubMed

    Yun, Seong-Wook; Kang, Nam-Young; Park, Sung-Jin; Ha, Hyung-Ho; Kim, Yun Kyung; Lee, Jun-Seok; Chang, Young-Tae

    2014-04-15

    A cell is the smallest functional unit of life. All forms of life rely on cellular processes to maintain normal functions, and changes in cell function induced by metabolic disturbances, physicochemical damage, infection, or abnormal gene expression may cause disease. To understand basic biology and to develop therapeutics for diseases, researchers need to study live cells. Along with advances in fluorescence microscopy and in vitro cell culture, live-cell imaging has become an essential tool in modern biology for the study of molecular and cellular events. Although researchers have often used fluorescent proteins to visualize cell-type-specific markers, this method requires genetic manipulations, which may not be appropriate in nontransgenic cells. Immunodetection of cellular markers requires the use of xenogenic antibodies, which may not detect intracellular markers in live cells. One option for overcoming these problems is the use of fluorescent small molecules targeted to specific cell types, which can enter live cells and interact with molecules of interest. We have used combinatorial chemistry to develop a large number of fluorescent small molecules as new imaging probes even without prior information about the probes' binding targets and mechanism, a strategy that we call the diversity oriented fluorescence library approach (DOFLA). We have used DOFLA to produce novel sensors and probes that detect a variety of biological and chemical molecules in vivo as well as in vitro. In this Account, we describe a series of fluorescent small molecules developed using DOFLA that bind specifically to particular cell types. These molecules provide new ways to detect and isolate these cells. The fluorescent probes CDy1, CDg4, and CDb8 tag embryonic stem cells and induced pluripotent stem cells but not fibroblasts or germ-line cells. CDr3 binds to an intracellular neural stem cell marker, fatty acid binding protein 7, which allows researchers to separate neural stem cells

  9. In vivo intra-operative breast tumor margin detection using a portable OCT system with a handheld surgical imaging probe

    NASA Astrophysics Data System (ADS)

    Erickson-Bhatt, Sarah J.; Nolan, Ryan; Shemonski, Nathan D.; Adie, Steven G.; Putney, Jeffrey; Darga, Donald; McCormick, Daniel T.; Cittadine, Andrew; Marjanovic, Marina; Chaney, Eric J.; Monroy, Guillermo L.; South, Fredrick; Carney, P. Scott; Cradock, Kimberly A.; Liu, Z. George; Ray, Partha S.; Boppart, Stephen A.

    2014-02-01

    Breast-conserving surgery is a frequent option for women with stage I and II breast cancer, and with radiation treatment, can be as effective as a mastectomy. However, adequate margin detection remains a challenge, and too often additional surgeries are required. Optical coherence tomography (OCT) provides a potential method for real-time, high-resolution imaging of breast tissue during surgery. Intra-operative OCT imaging of excised breast tissues has been previously demonstrated by several groups. In this study, a novel handheld surgical probe-based OCT system is introduced, which was used by the surgeon to image in vivo, within the tumor cavity, and immediately following tumor removal in order to detect the presence of any remaining cancer. Following resection, study investigators imaged the excised tissue with the same probe for comparison. We present OCT images obtained from over 15 patients during lumpectomy and mastectomy surgeries. Images were compared to post-operative histopathology for diagnosis. OCT images with micron scale resolution show areas of heterogeneity and disorganized features indicative of malignancy, compared to more uniform regions of normal tissue. Video-rate acquisition shows the inside of the tumor cavity as the surgeon sweeps the probe along the walls of the surgical cavity. This demonstrates the potential of OCT for real-time assessment of surgical tumor margins and for reducing the unacceptably high re-operation rate for breast cancer patients.

  10. Fluorenyl benzothiadiazole and benzoselenadiazole near-IR fluorescent probes for two-photon fluorescence imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Belfield, Kevin D.; Yao, Sheng; Kim, Bosung; Yue, Xiling

    2016-03-01

    Imaging biological samples with two-photon fluorescence (2PF) microscopy has the unique advantage of resulting high contrast 3D resolution subcellular image that can reach up to several millimeters depth. 2PF probes that absorb and emit at near IR region need to be developed. Two-photon excitation (2PE) wavelengths are less concerned as 2PE uses wavelengths doubles the absorption wavelength of the probe, which means 2PE wavelengths for probes even with absorption at visible wavelength will fall into NIR region. Therefore, probes that fluoresce at near IR region with high quantum yields are needed. A series of dyes based on 5-thienyl-2, 1, 3-benzothiadiazole and 5-thienyl-2, 1, 3-benzoselenadiazole core were synthesized as near infrared two-photon fluorophores. Fluorescence maxima wavelengths as long as 714 nm and fluorescence quantum yields as high as 0.67 were achieved. The fluorescence quantum yields of the dyes were nearly constant, regardless of solvents polarity. These diazoles exhibited large Stokes shift (<114nm), high two-photon absorption cross sections (up to 2,800 GM), and high two-photon fluorescence figure of merit (FM , 1.04×10-2 GM). Cells incubated on a 3D scaffold with one of the new probes (encapsulated in Pluronic micelles) exhibited bright fluorescence, enabling 3D two-photon fluorescence imaging to a depth of 100 µm.

  11. Dual-Labeled Near-Infrared/99mTc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells

    PubMed Central

    Yamaguchi, Haruka; Tsuchimochi, Makoto; Hayama, Kazuhide; Kawase, Tomoyuki; Tsubokawa, Norio

    2016-01-01

    We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m (99mTc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with 99mTc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner. PMID:27399687

  12. Dual-Labeled Near-Infrared/(99m)Tc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells.

    PubMed

    Yamaguchi, Haruka; Tsuchimochi, Makoto; Hayama, Kazuhide; Kawase, Tomoyuki; Tsubokawa, Norio

    2016-01-01

    We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner. PMID:27399687

  13. A Ratiometric Fluorescent Probe Based on a Through-Bond Energy Transfer (TBET) System for Imaging HOCl in Living Cells.

    PubMed

    Zhang, Yan-Ru; Meng, Ning; Miao, Jun-Ying; Zhao, Bao-Xiang

    2015-12-21

    A simple ratiometric probe (Naph-Rh) has been designed and synthesized based on a through-bond energy transfer (TBET) system for sensing HOCl. In this probe, rhodamine thiohydrazide and naphthalene formyl were connected by simple synthesis methods to construct a structure of monothio-bishydrazide. Free probe Naph-Rh showed only the emission of naphthalene. When probe Naph-Rh reacted with HOCl, monothio-bishydrazide could be converted into 1,2,4-oxadiazole, which not only ensured that the donor and the acceptor were connected with electronically conjugated bonds, but also resulted in the spiro-ring opening and the emission of rhodamine. Therefore, a typical TBET process took place. The probe possessed high-energy transfer efficiency and large pseudo-Stokes shifts. As the first TBET probe for HOCl, Naph-Rh showed excellent selectivity and sensitivity toward HOCl over other reactive oxygen species (ROS)/reactive nitrogen species (RNS), and could respond fast to a low concentration of HOCl in the real sample. In addition, the probe was suitable for imaging HOCl in living cells due to its real-time response, excellent resolution, and reduced cytotoxicity. PMID:26568524

  14. Bioorthogonal Turn-On Probe Based on Aggregation-Induced Emission Characteristics for Cancer Cell Imaging and Ablation.

    PubMed

    Yuan, Youyong; Xu, Shidang; Cheng, Xiamin; Cai, Xiaolei; Liu, Bin

    2016-05-23

    Bioorthogonal turn-on probes have been widely utilized in visualizing various biological processes. Most of the currently available bioorthogonal turn-on probes are blue or green emissive fluorophores with azide or tetrazine as functional groups. Herein, we present an alternative strategy of designing bioorthogonal turn-on probes based on red-emissive fluorogens with aggregation-induced emission characteristics (AIEgens). The probe is water soluble and non-fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide-functionalized glycans on cancer cell surface. The fluorescence turn-on is ascribed to the restriction of molecular motion of AIEgen, which populates the radiative decay channel. Moreover, the AIEgen can generate reactive oxygen species (ROS) upon visible light (λ=400-700 nm) irradiation, demonstrating its dual role as an imaging and phototherapeutic agent. PMID:27079297

  15. Imaging deep skeletal muscle structure using a high-sensitivity ultrathin side-viewing optical coherence tomography needle probe

    PubMed Central

    Yang, Xiaojie; Lorenser, Dirk; McLaughlin, Robert A.; Kirk, Rodney W.; Edmond, Matthew; Simpson, M. Cather; Grounds, Miranda D.; Sampson, David D.

    2013-01-01

    We have developed an extremely miniaturized optical coherence tomography (OCT) needle probe (outer diameter 310 µm) with high sensitivity (108 dB) to enable minimally invasive imaging of cellular structure deep within skeletal muscle. Three-dimensional volumetric images were acquired from ex vivo mouse tissue, examining both healthy and pathological dystrophic muscle. Individual myofibers were visualized as striations in the images. Degradation of cellular structure in necrotic regions was seen as a loss of these striations. Tendon and connective tissue were also visualized. The observed structures were validated against co-registered hematoxylin and eosin (H&E) histology sections. These images of internal cellular structure of skeletal muscle acquired with an OCT needle probe demonstrate the potential of this technique to visualize structure at the microscopic level deep in biological tissue in situ. PMID:24466482

  16. Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals

    PubMed Central

    Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.

    2012-01-01

    In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references). PMID:21607237

  17. Sets of RNA Repeated Tags and Hybridization-Sensitive Fluorescent Probes for Distinct Images of RNA in a Living Cell

    PubMed Central

    Kubota, Takeshi; Ikeda, Shuji; Yanagisawa, Hiroyuki; Yuki, Mizue; Okamoto, Akimitsu

    2010-01-01

    Background Imaging the behavior of RNA in a living cell is a powerful means for understanding RNA functions and acquiring spatiotemporal information in a single cell. For more distinct RNA imaging in a living cell, a more effective chemical method to fluorescently label RNA is now required. In addition, development of the technology labeling with different colors for different RNA would make it easier to analyze plural RNA strands expressing in a cell. Methodology/Principal Findings Tag technology for RNA imaging in a living cell has been developed based on the unique chemical functions of exciton-controlled hybridization-sensitive oligonucleotide (ECHO) probes. Repetitions of selected 18-nucleotide RNA tags were incorporated into the mRNA 3′-UTR. Pairs with complementary ECHO probes exhibited hybridization-sensitive fluorescence emission for the mRNA expressed in a living cell. The mRNA in a nucleus was detected clearly as fluorescent puncta, and the images of the expression of two mRNAs were obtained independently and simultaneously with two orthogonal tag–probe pairs. Conclusions/Significance A compact and repeated label has been developed for RNA imaging in a living cell, based on the photochemistry of ECHO probes. The pairs of an 18-nt RNA tag and the complementary ECHO probes are highly thermostable, sequence-specifically emissive, and orthogonal to each other. The nucleotide length necessary for one tag sequence is much shorter compared with conventional tag technologies, resulting in easy preparation of the tag sequences with a larger number of repeats for more distinct RNA imaging. PMID:20885944

  18. Combination probe for optically assisted ultrasonic velocity-change imaging aimed at detecting unstable blood vessel plaque

    NASA Astrophysics Data System (ADS)

    Tanigawa, Shohei; Mano, Kazune; Wada, Kenji; Matsunaka, Toshiyuki; Horinaka, Hiromichi

    2016-04-01

    Blood vessel plaque with a large lipid core is at risk of becoming thrombus and is likely to induce acute heart disease. To prevent this, it is necessary to determine not only the plaque's size but also its chemical composition. We, therefore, made the prototype of a combination probe to diagnose carotid artery plaque. It is used to differentiate propagation characteristics between light spectra and ultrasonic images. By propagating light and ultrasound along a common direction, it is possible to effectively warm the diagnosis domain. Moreover, the probe is thought to be compact and be easy to use for diagnosing human carotid artery plaque. We applied the combination probe to a carotid artery phantom with a lipid area and obtained an image of the ultrasonic velocity change in the fatty area.

  19. Cancer cell-targeted two-photon fluorescence probe for the real-time ratiometric imaging of DNA damage.

    PubMed

    Zhang, Hua; Wang, Kui; Xuan, Xiaopeng; Lv, Qingzhang; Nie, Yamin; Guo, Haiming

    2016-05-01

    Real-time imaging of DNA damage in cancer cells could provide valuable information on the formation and development of cancer. Herein, a two-photon fluorescence probe was discovered. Through sequential ICT processes, it allows successful in vivo visualization of DNA damage in cancer cells by one/two-photon microscopic imaging or by the unaided eye and a hand-held ultraviolet lamp. PMID:27087314

  20. A hot tip: imaging phenomena using in situ multi-stimulus probes at high temperatures.

    PubMed

    Nonnenmann, Stephen S

    2016-02-14

    Accurate high temperature characterization of materials remains a critical challenge to the continued advancement of various important energy, nuclear, electronic, and aerospace applications. Future experimental studies must assist these communities to progress past empiricism and derive deliberate, predictable designs of material classes functioning within active, extreme environments. Successful realization of systems ranging from fuel cells and batteries to electromechanical nanogenerators and turbines requires a dynamic understanding of the excitation, surface-mediated, and charge transfer phenomena which occur at heterophase interfaces (i.e. vapor-solid, liquid-solid, solid-solid) and impact overall performance. Advancing these frontiers therefore necessitates in situ (operando) characterization methods capable of resolving, both spatially and functionally, the coherence between these complex, collective excitations, and their respective response dynamics, through studies within the operating regime. This review highlights recent developments in scanning probe microscopy in performing in situ imaging at high elevated temperatures. The influence of and evolution from vacuum-based electron and tunneling microscopy are briefly summarized and discussed. The scope includes the use of high temperature imaging to directly observe critical phase transition, electronic, and electrochemical behavior under dynamic temperature settings, thus providing key physical parameters. Finally, both challenges and directions in combined instrumentation are proposed and discussed towards the end. PMID:26795921

  1. Applied Doppler Imaging: Can The Magnetic Activity Of IM Pegasi Affect The Gravity Probe B Mission?

    NASA Astrophysics Data System (ADS)

    Marsden, S. C.; Berdyugina, S. V.

    2006-08-01

    IM Pegasi is a single-lined spectroscopic RS CVn binary, with the primary being a rapidly-rotating (vsini = 27 km/s) early-K giant. Magnetic activity of the primary is evident as dark spot features covering 15% or more of the stellar surface. Since the system is bright in both optical and radio bands, IM Pegasi was chosen as a guide star for the Gravity Probe B (GP-B) satellite mission. The mission is designed to verify two predictions of Einstein's theory of general relativity, the geodetic effect and "frame-dragging", based on measurements of mean gyroscope drift with respect to the optical centroid of IM Pegasi. The requested standard error of 0.5 milliarcseconds/year implies that even small contributions to the shift of the optical centroid of IM Pegasi due to surface magnetic activity must be determined. In support of the GP-B mission we are undertaking an intensive Doppler imaging survey of the primary component of IM Pegasi to determine the effect of spot features on the optical centroid of IM Pegasi. We present an overview of our role in GP-B and report initial results from this support project, including the first magnetic maps of the IM Pegasi primary, created using Least-Squares Deconvolution and Zeeman Doppler Imaging.

  2. Applied Doppler Imaging: Can Magnetic Activity of IM Pegasi Affect the Gravity Probe B Mission?

    NASA Astrophysics Data System (ADS)

    Berdyugina, S. V.; Marsden, S. C.

    2006-12-01

    IM Peg is a single-lined, spectroscopic RS CVn binary, with a rapidly rotating (v sin i=27 km/s), early K-type, giant primary. Magnetic activity of the primary is indicated by dark spots covering > 15% of the surface. The system is bright in both optical and radio, and was chosen as a guide star for the Gravity Probe B (GP-B) satellite mission. The goal of GP-B is to verify two predictions of Einstein's theory of general relativity (geodetic effect and ``frame dragging''), based on measurements of mean gyroscopic drift with respect to the optical centroid of IM Peg. The requested precision of 0.5×10-3 arcsec/yr implies that even small shifts of the optical centroid of IM Peg due to surface magnetic activity must be determined. In support of the GP-B mission, we are undertaking an intensive Doppler imaging survey of the primary component of IM Peg, to determine the effect of spot features on its optical centroid. We present an overview of our work for GP-B, and report initial results from this support project, including the first magnetic maps of the IM~Peg primary, created using Least-Squares Deconvolution and Zeeman Doppler Imaging.

  3. A hot tip: imaging phenomena using in situ multi-stimulus probes at high temperatures

    NASA Astrophysics Data System (ADS)

    Nonnenmann, Stephen S.

    2016-02-01

    Accurate high temperature characterization of materials remains a critical challenge to the continued advancement of various important energy, nuclear, electronic, and aerospace applications. Future experimental studies must assist these communities to progress past empiricism and derive deliberate, predictable designs of material classes functioning within active, extreme environments. Successful realization of systems ranging from fuel cells and batteries to electromechanical nanogenerators and turbines requires a dynamic understanding of the excitation, surface-mediated, and charge transfer phenomena which occur at heterophase interfaces (i.e. vapor-solid, liquid-solid, solid-solid) and impact overall performance. Advancing these frontiers therefore necessitates in situ (operando) characterization methods capable of resolving, both spatially and functionally, the coherence between these complex, collective excitations, and their respective response dynamics, through studies within the operating regime. This review highlights recent developments in scanning probe microscopy in performing in situ imaging at high elevated temperatures. The influence of and evolution from vacuum-based electron and tunneling microscopy are briefly summarized and discussed. The scope includes the use of high temperature imaging to directly observe critical phase transition, electronic, and electrochemical behavior under dynamic temperature settings, thus providing key physical parameters. Finally, both challenges and directions in combined instrumentation are proposed and discussed towards the end.

  4. Two-Photon Lifetime Imaging of Voltage Indicating Proteins as a Probe of Absolute Membrane Voltage.

    PubMed

    Brinks, Daan; Klein, Aaron J; Cohen, Adam E

    2015-09-01

    Genetically encoded voltage indicators (GEVIs) can report cellular electrophysiology with high resolution in space and time. Two-photon (2P) fluorescence has been explored as a means to image voltage in tissue. Here, we used the 2P electronic excited-state lifetime to probe absolute membrane voltage in a manner that is insensitive to the protein expression level, illumination intensity, or photon detection efficiency. First, we tested several GEVIs for 2P brightness, response speed, and voltage sensitivity. ASAP1 and a previously described citrine-Arch electrochromic Förster resonance energy transfer sensor (dubbed CAESR) showed the best characteristics. We then characterized the voltage-dependent lifetime of ASAP1, CAESR, and ArcLight under voltage-clamp conditions. ASAP1 and CAESR showed voltage-dependent lifetimes, whereas ArcLight did not. These results establish 2P fluorescence lifetime imaging as a viable means of measuring absolute membrane voltage. We discuss the prospects and improvements necessary for applications in tissue. PMID:26331249

  5. Depth-sensitive subsurface imaging of polymer nanocomposites using second harmonic Kelvin probe force microscopy.

    PubMed

    Castañeda-Uribe, Octavio Alejandro; Reifenberger, Ronald; Raman, Arvind; Avila, Alba

    2015-03-24

    We study the depth sensitivity and spatial resolution of subsurface imaging of polymer nanocomposites using second harmonic mapping in Kelvin Probe Force Microscopy (KPFM). This method allows the visualization of the clustering and percolation of buried Single Walled Carbon Nanotubes (SWCNTs) via capacitance gradient (∂C/∂z) maps. We develop a multilayered sample where thin layers of neat Polyimide (PI) (∼80 nm per layer) are sequentially spin-coated on well-dispersed SWCNT/Polyimide (PI) nanocomposite films. The multilayer nanocomposite system allows the acquisition of ∂C/∂z images of three-dimensional percolating networks of SWCNTs at different depths in the same region of the sample. We detect CNTs at a depth of ∼430 nm, and notice that the spatial resolution progressively deteriorates with increasing depth of the buried CNTs. Computational trends of ∂C/∂z vs CNT depth correlate the sensitivity and depth resolution with field penetration and spreading, and enable a possible approach to three-dimensional subsurface structure reconstruction. The results open the door to nondestructive, three-dimensional tomography and nanometrology techniques for nanocomposite applications. PMID:25591106

  6. Probing the spin of the central black hole in the Galactic Centre with secondary images

    NASA Astrophysics Data System (ADS)

    Jørgensen, Jonas Helboe; Bjælde, Ole Eggers; Hannestad, Steen

    2016-06-01

    This paper explores the possibility of determining the spin of the supermassive black hole (SMBH) in Sgr A* by using secondary images of stars orbiting the SMBH. The photons propagate close to the SMBH and their trajectories probe the space-time in a region where the spin of the SMBH is important. We find the appearance of spikes in the secondary image, which depends on the angular momentum and spin axis of the SMBH and study the specific case of the star S2 in detail. The spikes have a magnitude of ˜29 in the K band and the required angular resolution is of the order of 15-20 μas. The combination of these two requirements poses an extreme observational challenge, but might be possible with interferometric observations in the sub-mm regime. The next possible time frame for observing this effect on the star S2 is in the late 2017 and then it repeats with the period of the star.

  7. Atomic force microscopy deep trench and sidewall imaging with an optical fiber probe

    SciTech Connect

    Xie, Hui Hussain, Danish; Yang, Feng; Sun, Lining

    2014-12-15

    We report a method to measure critical dimensions of micro- and nanostructures using the atomic force microscope (AFM) with an optical fiber probe (OFP). This method is capable of scanning narrow and deep trenches due to the long and thin OFP tip, as well as imaging of steep sidewalls with unique profiling possibilities by laterally tilting the OFP without any modifications of the optical lever. A switch control scheme is developed to measure the sidewall angle by flexibly transferring feedback control between the Z- and Y-axis, for a serial scan of the horizontal surface (raster scan on XY-plane) and sidewall (raster scan on the YZ-plane), respectively. In experiments, a deep trench with tapered walls (243.5 μm deep) and a microhole (about 14.9 μm deep) have been imaged with the orthogonally aligned OFP, as well as a silicon sidewall (fabricated by deep reactive ion etching) has been characterized with the tilted OFP. Moreover, the sidewall angle of TGZ3 (AFM calibration grating) was accurately measured using the switchable scan method.

  8. Validation of break-apart and fusion MYC probes using a digital fluorescence in situ hybridization capture and imaging system

    PubMed Central

    Liew, Michael; Rowe, Leslie; Clement, Parker W.; Miles, Rodney R.; Salama, Mohamed E.

    2016-01-01

    Introduction: Detection of MYC translocations using fluorescence in situ hybridization (FISH) is important in the evaluation of lymphomas, in particular, Burkitt lymphoma and diffuse large B-cell lymphoma. Our aim was to validate a digital FISH capture and imaging system for the detection of MYC 8q24 translocations using LSI-MYC (a break-apart probe) and MYC 8;14 translocation using IGH-MYC (a fusion probe). Materials and Methods: LSI-MYC probe was evaluated using tissue sections from 35 patients. IGH-MYC probe was evaluated using tissue sections from forty patients. Sections were processed for FISH and analyzed using traditional methods. FISH slides were then analyzed using the GenASIs capture and analysis system. Results: Results for LSI-MYC had a high degree of correlation between traditional method of FISH analysis and digital FISH analysis. Results for IGH-MYC had a 100% concordance between traditional method of FISH analysis and digital FISH analysis. Conclusion: Annotated whole slide images of H and E and FISH sections can be digitally aligned, so that areas of tumor within a section can be matched and evaluated with a greater degree of accuracy. Images can be archived permanently, providing a means for examining the results retrospectively. Digital FISH imaging of the MYC translocations provides a better diagnostic tool compared to traditional methods for evaluating lymphomas. PMID:27217970

  9. Radiolabeled nanoceria probes may reduce oxidative damages and risk of cancer: a hypothesis for radioisotope-based imaging procedures.

    PubMed

    Bakht, Mohamadreza K; Hosseini, Vahid; Honarpisheh, Hamid

    2013-12-01

    Low-dose ionizing radiations are commonly utilized in medical centers for diagnostic imaging procedures. Unfortunately, the absorption of ionizing radiation generates reactive chemical species that could damage cells. In diagnostic radioisotope-based imaging procedures, the radiological exposures by gamma emitter imaging probes such as radioactive technetium ((99m)Tc) could express low risk of cancer. Recently, many studies have documented cell protective, neuro-protective, anti-inflammatory and cardio-protective properties of cerium oxide nanoparticles (nanoceria) as a result of their antioxidant and free radical scavenger properties. Since there is no safe level of ionizing radiations, then we hypothesize that radiolabeled nanoceria might be an interesting probe to reduce cancer risk and other related oxidative stresses. We also provide a synthetic scheme of nanoceria functionalization with fluorine radiolabeled ligands as an exemplary approach. In conclusion, using nanoceria to combine radioisotope-based imaging probes with antioxidant activity might open new way to protect patient against radioactive emission of radioisotopes and ionizing radiations in several radioisotope-based imaging applications, in particular for patients who need frequent imaging procedures and children who are more susceptible to radiation. PMID:24210631

  10. An EGFR Targeted PET Imaging Probe for the Detection of Colonic Adenocarcinomas in the Setting of Colitis

    PubMed Central

    Turker, N. Selcan; Heidari, Pedram; Kucherlapati, Raju; Kucherlapati, Melanie; Mahmood, Umar

    2014-01-01

    Colorectal cancer is a serious complication associated with inflammatory bowel disease, often indistinguishable by screening with conventional FDG PET probes. We have developed an alternative EGFR-targeted PET imaging probe that may be used to overcome this difficulty, and successfully assessed its utility for neoplastic lesion detection in preclinical models. Cetuximab F(ab′)2 fragments were enzymatically generated, purified, and DOTA-conjugated. Radiolabeling was performed with 67Ga for cell based studies and 64Cu for in vivo imaging. Competitive binding studies were performed on CT26 cells to assess affinity (KD) and receptors per cell (Bmax). In vivo imaging using the EGFR targeted PET probe and 18F FDG was performed on CT26 tumor bearing mice in both control and dextran sodium sulfate (DSS) induced colitis settings. Spontaneous adenomas in genetically engineered mouse (GEM) models of colon cancer were additionally imaged. The EGFR imaging agent was generated with high purity (> 98%), with a labeling efficiency of 60 ± 5% and ≥99% radiochemical purity. The KD was 6.6 ± 0.7 nM and the Bmax for CT26 cells was 3.3 ± 0.1 × 106 receptors/cell. Target to background ratios (TBR) for CT26 tumors compared to colonic uptake demonstrated high values for both 18F-FDG (3.95 ± 0.13) and the developed 64Cu-DOTA-cetuximab-F(ab′)2 probe (4.42 ± 0.11) in control mice. The TBR for the EGFR targeted probe remained high (3.78 ± 0.06) in the setting of colitis, while for 18F FDG, this was markedly reduced (1.54 ± 0.08). Assessment of the EGFR targeted probe in the GEM models demonstrated a correlation between radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex vivo. A clinically translatable PET imaging probe was successfully developed to assess EGFR. The imaging agent can detect colonic tumors with a high TBR for detection of in situ lesions in the setting of colitis, and opens the possibility for a new approach for screening high

  11. Probing the functions of contextual modulation by adapting images rather than observers

    PubMed Central

    Webster, Michael A.

    2014-01-01

    Countless visual aftereffects have illustrated how visual sensitivity and perception can be biased by adaptation to the recent temporal context. This contextual modulation has been proposed to serve a variety of functions, but the actual benefits of adaptation remain uncertain. We describe an approach we have recently developed for exploring these benefits by adapting images instead of observers, to simulate how images should appear under theoretically optimal states of adaptation. This allows the long-term consequences of adaptation to be evaluated in ways that are difficult to probe by adapting observers, and provides a common framework for understanding how visual coding changes when the environment or the observer changes, or for evaluating how the effects of temporal context depend on different models of visual coding or the adaptation processes. The approach is illustrated for the specific case of adaptation to color, for which the initial neural coding and adaptation processes are relatively well understood, but can in principle be applied to examine the consequences of adaptation for any stimulus dimension. A simple calibration that adjusts each neuron’s sensitivity according to the stimulus level it is exposed to is sufficient to normalize visual coding and generate a host of benefits, from increased efficiency to perceptual constancy to enhanced discrimination. This temporal normalization may also provide an important precursor for the effective operation of contextual mechanisms operating across space or feature dimensions. To the extent that the effects of adaptation can be predicted, images from new environments could be “pre-adapted” to match them to the observer, eliminating the need for observers to adapt. PMID:25281412

  12. Fluorescence Lifetime Imaging of Membrane Lipid Order with a Ratiometric Fluorescent Probe

    PubMed Central

    Kilin, Vasyl; Glushonkov, Oleksandr; Herdly, Lucas; Klymchenko, Andrey; Richert, Ludovic; Mely, Yves

    2015-01-01

    To monitor the lateral segregation of lipids into liquid-ordered (Lo) and -disordered (Ld) phases in lipid membranes, environment-sensitive dyes that partition in both phases but stain them differently have been developed. Of particular interest is the dual-color F2N12S probe, which can discriminate the two phases through the ratio of its two emission bands. These bands are associated with the normal (N∗) and tautomer (T∗) excited-state species that result from an excited-state intramolecular proton transfer. In this work, we investigated the potency of the time-resolved fluorescence parameters of F2N12S to discriminate lipid phases in model and cell membranes. Both the long and mean lifetime values of the T∗ form of F2N12S were found to differ by twofold between Ld and Lo phases as a result of the restriction in the relative motions of the two aromatic moieties of F2N12S imposed by the highly packed Lo phase. This differed from the changes in the ratio of the two emission bands between the two phases, which mainly resulted from the decreased hydration of the N∗ form in the Lo phase. Importantly, the strong difference in lifetimes between the two phases was preserved when cholesterol was added to the Ld phase. The two phases could be imaged with high contrast by fluorescence lifetime imaging microscopy (FLIM) on giant unilamellar vesicles. FLIM images of F2N12S-labeled live HeLa cells confirmed that the plasma membrane was mainly in the Lo-like phase. Furthermore, the two phases were found to be homogeneously distributed all over the plasma membrane, indicating that they are highly mixed at the spatiotemporal resolution of the FLIM setup. Finally, FLIM could also be used to sensitively monitor the change in lipid phase upon cholesterol depletion and apoptosis. PMID:25992730

  13. Probing the functions of contextual modulation by adapting images rather than observers.

    PubMed

    Webster, Michael A

    2014-11-01

    Countless visual aftereffects have illustrated how visual sensitivity and perception can be biased by adaptation to the recent temporal context. This contextual modulation has been proposed to serve a variety of functions, but the actual benefits of adaptation remain uncertain. We describe an approach we have recently developed for exploring these benefits by adapting images instead of observers, to simulate how images should appear under theoretically optimal states of adaptation. This allows the long-term consequences of adaptation to be evaluated in ways that are difficult to probe by adapting observers, and provides a common framework for understanding how visual coding changes when the environment or the observer changes, or for evaluating how the effects of temporal context depend on different models of visual coding or the adaptation processes. The approach is illustrated for the specific case of adaptation to color, for which the initial neural coding and adaptation processes are relatively well understood, but can in principle be applied to examine the consequences of adaptation for any stimulus dimension. A simple calibration that adjusts each neuron's sensitivity according to the stimulus level it is exposed to is sufficient to normalize visual coding and generate a host of benefits, from increased efficiency to perceptual constancy to enhanced discrimination. This temporal normalization may also provide an important precursor for the effective operation of contextual mechanisms operating across space or feature dimensions. To the extent that the effects of adaptation can be predicted, images from new environments could be "pre-adapted" to match them to the observer, eliminating the need for observers to adapt. PMID:25281412

  14. Regional Variation of Distal Esophagus Distensibility Assessed Using the Functional Luminal Imaging Probe (FLIP)

    PubMed Central

    Lin, Zhiyue; Nicodème, Frédéric; Boris, Lubomyr; Lin, Chen-Yuan; Kahrilas, Peter J; Pandolfino, John E

    2013-01-01

    Background This study aimed to evaluate the spatial variation of esophageal distensibility in normal subjects using a novel multichannel functional luminal imaging probe (FLIP). Methods Ten healthy subjects (4 male, age 21–49 years) were evaluated during endoscopy with a high-resolution impedance planimetry probe (FLIP) positioned through the esophagogastric junction (EGJ) and distal 10cm of the esophageal body. Stepwise bag distensions using 5 ml increments from 0 to 60 mL were conducted and simultaneous measurements of cross-sectional area (CSA) and the associated intrabag pressure from each subject were analyzed using a customized MATLAB™ program. The distensibility along the esophagus was determined and compared between the EGJ and interval locations at 2–5 cm and 6–10 cm above the EGJ. Results The pressure-CSA relationship was nearly linear among sites at lower pressures (0 to 7.5 mmHg) and reached a distension plateau at pressures ranging from 8 to 24 mmHg. The location of greatest distensibility was 4 cm above the EGJ. Although the CSAs of individual recording loci were not significantly different, there was a significant difference between the mean CSAs when comparing the region 2 to 5 cm proximal to EGJ to that 6 to 10 cm proximal to the EGJ. Conclusions There were significant regional differences in distensibility along the distal esophagus with lower values in the proximal part compared to more distal part. The greatest distensibility was noted to occur at about 4 cm above the EGJ in close proximity to the location of the contractile deceleration point and phrenic ampulla. PMID:23965159

  15. Radioisotope guided surgery with imaging probe, a hand-held high-resolution gamma camera

    NASA Astrophysics Data System (ADS)

    Soluri, A.; Trotta, C.; Scopinaro, F.; Tofani, A.; D'Alessandria, C.; Pasta, V.; Stella, S.; Massari, R.

    2007-12-01

    Since 1997, our group of Physics together with Nuclear Physicians studies imaging probes (IP), hand-held, high-resolution gamma cameras for radio-guided surgery (RGS). Present work is aimed to verify the usefulness of two updated IP in different surgical operations. Forty patients scheduled for breast cancer sentinel node (SN) biopsy, five patients with nodal recurrence of thyroid cancer, seven patients with parathyroid adenomas, five patients with neuroendocrine tumours (NET), were operated under the guide of IP. We used two different IP with field of view of 1 and 4 in. 2, respectively and intrinsic spatial resolution of about 2 mm. Radioisotopes were 99mTc, 123I and 111In. The 1 in. 2 IP detected SN in all the 40 patients and more than one node in 24, whereas anger camera (AC) failed locating SN in four patients and detected true positive second nodes in only nine patients. The 4 in. 2 IP was used for RGS of thyroid, parathyroid and NETs. It detected eight latero-cervical nodes. In the same patients, AC detected five invaded nodes. Parathyroid adenomas detected by IP were 10 in 7 patients, NET five in five patients. One and 4 in. 2 IPs showed usefulness in all operations. Initial studies on SN biopsy were carried out on small series of patients to validate IP and to demonstrate the effectiveness and usefulness of IP alone or against conventional probes. We propose the use of the IP as control method for legal documentation and surgeon strategy guide before and after lesion(s) removal.

  16. Imaging the distribution of photoswitchable probes with temporally-unmixed multispectral optoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Deán-Ben, X. Luís.; Stiel, Andre C.; Jiang, Yuanyuan; Ntziachristos, Vasilis; Westmeyer, Gil G.; Razansky, Daniel

    2016-03-01

    Synthetic and genetically encoded chromo- and fluorophores have become indispensable tools for biomedical research enabling a myriad of applications in imaging modalities based on biomedical optics. The versatility offered by the optoacoustic (photoacoustic) contrast mechanism enables to detect signals from any substance absorbing light, and hence these probes can be used as optoacoustic contrast agents. While contrast versatility generally represents an advantage of optoacoustics, the strong background signal generated by light absorption in endogeneous chromophores hampers the optoacoustic capacity to detect a photo-absorbing agent of interest. Increasing the optoacoustic sensitivity is then determined by the capability to differentiate specific features of such agent. For example, multispectral optoacoustic tomography (MSOT) exploits illuminating the tissue at multiple optical wavelengths to spectrally resolve (unmix) the contribution of different chromophores. Herein, we present an alternative approach to enhance the sensitivity and specificity in the detection of optoacoustic contrast agents. This is achieved with photoswitchable probes that change optical absorption upon illumination with specific optical wavelengths. Thereby, temporally unmixed MSOT (tuMSOT) is based on photoswitching the compounds according to defined schedules to elicit specific time-varying optoacoustic signals, and then use temporal unmixing algorithms to locate the contrast agent based on their particular temporal profile. The photoswitching kinetics is further affected by light intensity, so that tuMSOT can be employed to estimate the light fluence distribution in a biological sample. The performance of the method is demonstrated herein with the reversibly switchable fluorescent protein Dronpa and its fast-switching fatigue resistant variant Dronpa-M159T.

  17. From hand-rotated multiplane transesophageal to fast-rotating parasternal probes for cardiac imaging

    NASA Astrophysics Data System (ADS)

    Bom, Nicolaas; Lancee, Charles T.; de Jong, Nico; van der Steen, Anton F. W.; Roelandt, J. R.

    1999-06-01

    Trans-Esophageal Echocardiographic probes were introduced around 1982. The development ranges over the years from single plane, phased array transducers at low frequency to today's multiplane probes with a large number of elements. Further miniaturization and higher frequencies allow paediatric applications. Recent development includes a probe with 48 elements at 7 MHz with a shaft diameter of only 5 mm.

  18. A Miniature Forward-imaging B-scan Optical Coherence Tomography Probe to Guide Real-time Laser Ablation

    PubMed Central

    Li, Zhuoyan; Shen, Jin H.; Kozub, John A.; Prasad, Ratna; Lu, Pengcheng; Joos, Karen M.

    2014-01-01

    Background and Objective Investigations have shown that pulsed lasers tuned to 6.1 μm in wavelength are capable of ablating ocular and neural tissue with minimal collateral damage. This study investigated whether a miniature B-scan forward-imaging optical coherence tomography (OCT) probe can be combined with the laser to provide real-time visual feedback during laser incisions. Study Design/Methods and Materials A miniature 25-gauge B-scan forward-imaging OCT probe was developed and combined with a 250 μm hollow-glass waveguide to permit delivery of 6.1 μm laser energy. A gelatin mixture and both porcine corneal and retinal tissues were simultaneously imaged and lased (6.1 μm, 10 Hz, 0.4-0.7 mJ) through air. The ablation studies were observed and recorded in real time. The crater dimensions were measured using OCT imaging software (Bioptigen, Durham, NC). Histological analysis was performed on the ocular tissues. Results The combined miniature forward-imaging OCT and mid-infrared laser-delivery probe successfully imaged real-time tissue ablation in gelatin, corneal tissue, and retinal tissue. Application of a constant number of 60 pulses at 0.5 mJ/pulse to the gelatin resulted in a mean crater depth of 123 ± 15 μm. For the corneal tissue, there was a significant correlation between the number of pulses used and depth of the lased hole (Pearson correlation coefficient = 0.82; P = 0.0002). Histological analysis of the cornea and retina tissues showed discrete holes with minimal thermal damage. Conclusions A combined miniature OCT and laser -delivery probe can monitor real-time tissue laser ablation. With additional testing and improvements, this novel instrument has the future possibility of effectively guiding surgeries by simultaneously imaging and ablating tissue. PMID:24648326

  19. Transmission Geometry Laser Ablation into a Non-Contact Liquid Vortex Capture Probe for Mass Spectrometry Imaging

    SciTech Connect

    Ovchinnikova, Olga S; Bhandari, Deepak; Lorenz, Matthias; Van Berkel, Gary J

    2014-01-01

    RATIONALE: Capture of material from a laser ablation plume into a continuous flow stream of solvent provides the means for uninterrupted sampling, transport and ionization of collected material for coupling with mass spectral analysis. Reported here is the use of vertically aligned transmission geometry laser ablation in combination with a new non-contact liquid vortex capture probe coupled with electrospray ionization for spot sampling and chemical imaging with mass spectrometry. Methods: A vertically aligned continuous flow liquid vortex capture probe was positioned directly underneath a sample surface in a transmission geometry laser ablation (355 nm, 10 Hz, 7 ns pulse width) setup to capture into solution the ablated material. The outlet of the vortex probe was coupled to the Turbo V ion source of an AB SCIEX TripleTOF 5600+ mass spectrometer. System operation and performance metrics were tested using inked patterns and thin tissue sections. Glass slides and slides designed especially for laser capture microdissection, viz., DIRECTOR slides and PEN 1.0 (polyethylene naphthalate) membrane slides, were used as sample substrates. Results: The estimated capture efficiency of laser ablated material was 24%, which was enabled by the use of a probe with large liquid surface area (~ 2.8 mm2) and with gravity to help direct ablated material vertically down towards the probe. The swirling vortex action of the liquid surface potentially enhanced capture and dissolution of not only particulates, but also gaseous products of the laser ablation. The use of DIRECTOR slides and PEN 1.0 (polyethylene naphthalate) membrane slides as sample substrates enabled effective ablation of a wide range of sample types (basic blue 7, polypropylene glycol, insulin and cyctochrome c) without photodamage using a UV laser. Imaging resolution of about 6 m was demonstrated for stamped ink on DIRECTOR slides based on the ability to distinguish features present both in the optical and in the

  20. Multi-parametric imaging of tumor spheroids with ultra-bright and tunable nanoparticle O2 probes

    NASA Astrophysics Data System (ADS)

    Dmitriev, Ruslan I.; Borisov, Sergey M.; Jenkins, James; Papkovsky, Dmitri B.

    2015-03-01

    Multi-modal probes allow for flexible choice of imaging equipment when performing quenched-phosphorescence O2 measurements: one- or two-photon, PLIM or intensity-based ratiometric read-outs. Spectral and temporal (e.g. FLIMPLIM) discrimination can be used to image O2 together with pH, Ca2+, mitochondrial membrane potential, cell death markers or cell/organelle specific markers. However, the main challenge of existing nanoparticle probes is their limited diffusion across thick (> 20-50 μm) 3D cell models such as tumor spheroids. Here, we present new class of polymeric nanoparticle probes having tunable size, charge, cell-penetrating ability, and reporter dyes. Being spectrally similar to the recently described MM2, PA2 and other O2 probes, they are 5-10 times brighter, demonstrate improved ratiometric response and their surface chemistry can be easily modified. With cultures of 2D and 3D cell models (fibroblasts, PC12 aggregates, HCT116 human colon cancer spheroids) we found cell-specific staining by these probes. However, the efficient staining of model of interest can be tuned by changing number of positive and negative surface groups at nanoparticle, to allow most efficient loading. We also demonstrate how real-time monitoring of oxygenation can be used to select optimal spheroid production with low variability in size and high cell viability.

  1. Fluorescence in vivo imaging of live tumor cells with pH-activatable targeted probes via receptor-mediated endocytosis

    NASA Astrophysics Data System (ADS)

    Asanuma, Daisuke; Urano, Yasuteru; Nagano, Tetsuo; Hama, Yukihiro; Koyama, Yoshinori; Kobayashi, Hisataka

    2009-02-01

    One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background. Here, we achieve specific in vivo tumor visualization with a newly-designed "activatable" targeted fluorescence probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the BODIPY fluorophore were synthesized, and then conjugated to a cancer-targeting monoclonal antibody, Trastuzumab, or galactosyl serum albumin (GSA). As proof of concept, ex and in vivo imaging of two different tumor mouse models was performed: HER2-overexpressed lung metastasis tumor with Trastuzumab-pH probe conjugates and lectin-overexpressed i.p. disseminated tumor with GSA-pH probe conjugates. These pH-activatable targeted probes were highly specific for tumors with minimal background signal. Because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. Furthermore, this strategy was also applied to fluorescence endoscopy in tumor mouse models, resulting in specific visualization of tumors as small as submillimeter in size that could hardly detected by naked eyes because of their poor contrast against normal tissues. The design concept can be widely adapted to cancer-specific cell-surface-targeting molecules that result in cellular internalization.

  2. Wide-field time-gated photoluminescence microscopy for fast ultrahigh-sensitivity imaging of photoluminescent probes.

    PubMed

    Razali, Wan A W; Sreenivasan, Varun K A; Bradac, Carlo; Connor, Mark; Goldys, Ewa M; Zvyagin, Andrei V

    2016-08-01

    Fluorescence microscopy is a fundamental technique for the life sciences, where biocompatible and photostable photoluminescence probes in combination with fast and sensitive imaging systems are continually transforming this field. A wide-field time-gated photoluminescence microscopy system customised for ultrasensitive imaging of unique nanoruby probes with long photoluminescence lifetime is described. The detection sensitivity derived from the long photoluminescence lifetime of the nanoruby makes it possible to discriminate signals from unwanted autofluorescence background and laser backscatter by employing a time-gated image acquisition mode. This mode enabled several-fold improvement of the photoluminescence imaging contrast of discrete nanorubies dispersed on a coverslip. It enabled recovery of the photoluminescence signal emanating from discrete nanorubies when covered by a layer of an organic fluorescent dye, which were otherwise invisible without the use of spectral filtering approaches. Time-gated imaging also facilitated high sensitivity detection of nanorubies in a biological environment of cultured cells. Finally, we monitor the binding kinetics of nanorubies to a functionalised substrate, which exemplified a real-time assay in biological fluids. 3D-pseudo colour images of nanorubies immersed in a highly fluorescent dye solution. Nanoruby photoluminescence is subdued by that of the dye in continuous excitation/imaging (left), however it can be recovered by time-gated imaging (right). At the bottom is schematic diagram of nanoruby assay in a biological fluid. PMID:27264934

  3. A new Schiff base fluorescent probe for imaging Cu2+ in living cells

    NASA Astrophysics Data System (ADS)

    Ye, Hui; Ge, Fei; Zhou, Yi-Ming; Liu, Jin-Ting; Zhao, Bao-Xiang

    2013-08-01

    A novel probe based on ferrocenyl-1,3,4-thiadiazol-containing Schiff base was synthesized by the reaction of 5-ferrocenyl-1,3,4-thiadiazol-2-amine and 4-(diethylamino)salicylaldehyde, and characterized by IR, NMR, HRMS and X-ray analysis. UV-vis spectral and fluorescence property of the probe were investigated. The probe can be used to colorimetric sensitive and selective fluorescent recognition of Cu2+ in buffer solution. Moreover, the probe can detect Cu2+ by electrochemical method. Additionally, the Schiff base was successfully used as a selective and sensitive fluorescent probe for monitoring Cu2+ ions in living cells.

  4. Ex-vivo endoscopic laryngeal cancer imaging using two forward-looking fiber optic scanning endoscope probes

    NASA Astrophysics Data System (ADS)

    Cernat, R.; Tatla, T.; Pang, J.-Y.; Tadrous, P. J.; Gelikonov, G.; Gelikonov, V.; Zhang, Y. Y.; Bradu, A.; Li, X. D.; Podoleanu, A. G.

    2012-12-01

    Larynx cancer is one of the most common primary head and neck cancers. For early-stage laryngeal cancer, both surgery and radiotherapy are effective treatment modalities, offering a high rate of local control and cure. Optical coherence tomography (OCT) is an established non-invasive optical biopsy method, capable of imaging ranges of 2- 3 mm into tissue. By using the principles of low coherence light interferometry, OCT can be used to distinguish normal from unhealthy laryngeal mucosa in patients. Two forward-looking endoscope OCT probes of different sizes in a sweeping frequency OCT (SS-OCT) configuration were compared in terms of their performances for ex-vivo laryngeal cancer imaging. The setup configuration of the first OCT probe unit was designed and constructed at the Institute of Applied Physics RAS, Russia (diameter of 1.9 mm and the rigid part at the distal end is 13 mm long). The second OCT endoscope probe was constructed at the Department of Biomedical Engineering at Johns Hopkins University, USA, using a tubular piezoelectric actuator with quartered electrodes in combination with a resonant fiber cantilever (diameter of 2.4 mm, and rigid part of 45 mm). Cross-sectional images of laryngeal lesions using the two OCT configurations were aquired and compared with OCT images obtained in a 1310 nm SS-OCT classical non-endoscopic system. The work presented here is an intermediate step in our research towards in-vivo endoscopic laryngeal cancer imaging.

  5. Thrombin-mediated ratiometric two-photon fluorescent probe for selective imaging of endogenous ultratrace glutathione in platelet.

    PubMed

    Zhang, Hua; Wang, Caixia; Wang, Ge; Wang, Kui; Jiang, Kai

    2016-04-15

    Ultratrace change of reduced glutathione (GSH) can weaken coagulation function of platelet (PLT). Thus, rapid and sensitive imaging of GSH specific in PLT is beneficial for monitoring coagulation function of PLT. Many fluorescent probes for GSH have been reported, but ratio fluorescent probe with excellent two-photon property for screening PLT from peripheral blood and quantitative imaging of GSH are scarce. In this work, a thrombin-mediated two-photon GSH-specific fluorescent probe (IQDC-L) was reported. Sulfuric diamide, a key group as linker, was introduced into IQDC-L, which resulted in not only specific selectivity for GSH, but also FRET occurring in probe. When IQDC-L encountered GSH, "S-N" in sulfonamide group was cut off, and FRET was inhibited. Furthermore, fluorescence intensities at 520 and 595 nm presented linear change on ratio mode in the range of GSH (2.0-65 nM). The lowest detection for GSH was as low as 0.083 nM. Intriguingly, IQDC-L under thrombin-mediated was able to screen PLT from peripheral blood without any interference. Thus, IQDC-L could be used to screen PLT from peripheral blood, and simultaneously, to in situ image ultratrace GSH. PMID:26649492

  6. In Vivo Optical Imaging of Acute Cell Death Using a Near-Infrared Fluorescent Zinc-Dipicolylamine Probe

    PubMed Central

    Smith, Bryan A.; Gammon, Seth T.; Xiao, Shuzhang; Wang, Wei; Chapman, Sarah; McDermott, Ryan; Suckow, Mark A.; Johnson, James R.; Piwnica-Worms, David; Gokel, George W.; Smith, Bradley D.; Leevy, W. Matthew

    2013-01-01

    Cell death is a fundamental biological process that is present in numerous disease pathologies. Fluorescent probes that detect cell death have been developed for a myriad of research applications ranging from microscopy to in vivo imaging. Here we describe a synthetic near infrared conjugate of zinc(II)-dipicolylamine (Zn2+-DPA) for in vivo imaging of cell death. Chemically induced in vivo models of myopathy were established using an ionphore, ethanol, or ketamine as chemical cytotoxins. The Zn2+-DPA fluorescent probe or corresponding control was subsequently injected and whole animal fluorescence imaging demonstrated probe uptake at the site of muscle damage, which was confirmed by ex vivo and histological analyses. Further, a comparative study with a near-infrared fluorescent conjugate Annexin V showed less intense uptake at the site of muscle damage and high accumulation in the bladder. The results indicate that the fluorescent Zn2+-DPA conjugate is an effective probe for in vivo cell death detection and in some cases may be an appropriate alternative to fluorescent Annexin V conjugates. PMID:21323375

  7. Erythrocyte-derived nano-probes functionalized with antibodies for targeted near infrared fluorescence imaging of cancer cells

    PubMed Central

    Mac, Jenny T.; Nuñez, Vicente; Burns, Joshua M.; Guerrero, Yadir A.; Vullev, Valentine I.; Anvari, Bahman

    2016-01-01

    Constructs derived from mammalian cells are emerging as a new generation of nano-scale platforms for clinical imaging applications. Herein, we report successful engineering of hybrid nano-structures composed of erythrocyte-derived membranes doped with FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG), and surface-functionalized with antibodies to achieve molecular targeting. We demonstrate that these constructs can be used for targeted imaging of cancer cells in vitro. These erythrocyte-derived optical nano-probes may provide a potential platform for clinical translation, and enable molecular imaging of cancer biomarkers. PMID:27446657

  8. Cyanine-based probe\\tag-peptide pair for fluorescence protein imaging and fluorescence protein imaging methods

    DOEpatents

    Mayer-Cumblidge, M. Uljana; Cao, Haishi

    2010-08-17

    A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl.sub.3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

  9. Correcting nonlinear drift distortion of scanning probe and scanning transmission electron microscopies from image pairs with orthogonal scan directions.

    PubMed

    Ophus, Colin; Ciston, Jim; Nelson, Chris T

    2016-03-01

    Unwanted motion of the probe with respect to the sample is a ubiquitous problem in scanning probe and scanning transmission electron microscopies, causing both linear and nonlinear artifacts in experimental images. We have designed a procedure to correct these artifacts by using orthogonal scan pairs to align each measurement line-by-line along the slow scan direction, by fitting contrast variation along the lines. We demonstrate the accuracy of our algorithm on both synthetic and experimental data and provide an implementation of our method. PMID:26716724

  10. Bright and photostable fluorescent probe with aggregation-induced emission characteristics for specific lysosome imaging and tracking.

    PubMed

    Ouyang, Jiang; Zang, Qiguang; Chen, Wansong; Wang, Liqiang; Li, Shuo; Liu, Ren-Yu; Deng, Yuanyuan; Liu, Zhao-Qian; Li, Juan; Deng, Liu; Liu, You-Nian

    2016-10-01

    We develop a new lysosome-targeting AIE fluorescent probe tetraphenylethene-morpholine (TPE-MPL), by incorporating a typical lysosome-targeting moiety of morpholine into a stable tetraphenylethene skeleton. Due to both the AIE and antenna effects, TPE-MPL possesses superior photostability, appreciable tolerance to microenvironment change and high lysosome targeting ability. Our findings confirm that TPE-MPL is a well-suited imaging agent for targeting lysosome and tracking dynamic movement of lysosome. Moreover, due to its synthetic accessibility, TPE-MPL could be further modified as a dual-functional probe for lysosome, thereby gain further insight into the role of lysosome in biomedical applications. PMID:27474306

  11. Non-invasive Detection of Breast Cancer Lymph Node Metastasis using Carbonic Anhydrases IX and XII Targeted Imaging Probes

    PubMed Central

    Tafreshi, Narges K.; Bui, Marilyn M.; Bishop, Kellsey; Lloyd, Mark C.; Enkemann, Steven A.; Lopez, Alexis S.; Abrahams, Dominique; Carter, Bradford W.; Vagner, Josef; Grobmyer, Stephen R.; Gillies, Robert J.; Morse, David L.

    2014-01-01

    Purpose To develop targeted molecular imaging probes for the non-invasive detection of breast cancer lymph node metastasis. Methods Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry (IHC) of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX and CAXII specific monoclonal antibodies (mAbs) to a near-infrared fluorescent dye. Results Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice bearing mammary fat pad tumors of marker expressing cells, and non-expressing cells or by pre-injection of unlabeled antibody. Imaging of LN metastases showed that peritumorally-injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX and CAXII expressing cells into the axillary LNs. Conclusion These imaging probes have potential for non-invasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities. PMID:22016510

  12. Probing Pluto’s Upper Atmosphere: a 2011 Occultation Graze in Visible Images and Infrared Spectra

    NASA Astrophysics Data System (ADS)

    Gulbis, Amanda A. S.; Emery, J. P.; Person, M. J.; Bosh, A. S.; Zuluaga, C. A.; Pasachoff, J. M.; Babcock, B. A.

    2012-10-01

    On 2011 June 23, a 14.43 UCAC2 magnitude star was occulted by Pluto as observed from multiple sites. Observations made at NASA’s 3-m Infrared Telescope Facility (IRTF) on Mauna Kea, Hawaii, detected a full occultation of the star by Charon followed by an atmospheric graze by Pluto. Data were taken simultaneously with MORIS (the MIT Optical Rapid Imaging System; Gulbis et al. 2011, PASP, 123, 461) and SpeX (Rayner et al. 2003, PASP, 115, 362). MORIS recorded visible images of a 1 arcmin by 1 arcmin field of view, with an effective central wavelength of 0.74 microns, at a cadence of 0.3 seconds and negligible deadtime. Low-resolution spectral IR data of the occultation star and a comparison were taken with SpeX, using the 1.6 arcsec slit, over the range of 0.9-2.5 microns, at a cadence of 1.5 seconds including approximately 0.75 seconds deadtime. Pluto’s lower atmosphere has been evolving since the first definitive detection in 1988 (e.g., Elliot et al. 2007, AJ, 134,1; Young et al. 2008, AJ, 136, 1757). Possibilities for explaining the lower atmospheric structure include a steep thermal gradient and/or extinction, the latter of which can be characterized as a dependence between occultation flux and wavelength. This graze reached a minimum normalized flux level of roughly 0.35, serving primarily as a probe of Pluto’s upper atmosphere. However, there appears to be a slight dependence of flux with wavelength in the minimum portion of the graze. We will present the IRTF lightcurves and an analysis of the wavelength-resolved data. Funding for this work was provided in part by the South African National Research Foundation and NASA grants NNX08AO50G & NNH11ZDA001N (Williams), NNX10AB27G (MIT), and NNX10AB23G (UT).

  13. Imaging thermal conductivity with nanoscale resolution using a scanning spin probe.

    PubMed

    Laraoui, Abdelghani; Aycock-Rizzo, Halley; Gao, Yang; Lu, Xi; Riedo, Elisa; Meriles, Carlos A

    2015-01-01

    The ability to probe nanoscale heat flow in a material is often limited by lack of spatial resolution. Here, we use a diamond-nanocrystal-hosted nitrogen-vacancy centre attached to the apex of a silicon thermal tip as a local temperature sensor. We apply an electrical current to heat up the tip and rely on the nitrogen vacancy to monitor the thermal changes the tip experiences as it is brought into contact with surfaces of varying thermal conductivity. By combining atomic force and confocal microscopy, we image phantom microstructures with nanoscale resolution, and attain excellent agreement between the thermal conductivity and topographic maps. The small mass and high thermal conductivity of the diamond host make the time response of our technique short, which we demonstrate by monitoring the tip temperature upon application of a heat pulse. Our approach promises multiple applications, from the investigation of phonon dynamics in nanostructures to the characterization of heterogeneous phase transitions and chemical reactions in various solid-state systems. PMID:26584676

  14. DNA-templated Ag nanoclusters as fluorescent probes for sensing and intracellular imaging of hydroxyl radicals.

    PubMed

    Zhang, Li; Liang, Ru-Ping; Xiao, Sai-Jin; Bai, Jian-Mei; Zheng, Lin-Ling; Zhan, Lei; Zhao, Xi-Juan; Qiu, Jian-Ding; Huang, Cheng-Zhi

    2014-01-01

    We have developed a simple, rapid and label-free sensor for the essential biological OH radicals based on the fluorescence quenching of DNA-templated Ag nanoclusters (DNA-Ag NCs). The OH radicals generated from the Fenton reagent attack and cleave the DNA template, which disturbs the microenvironments around Ag NCs, resulting in spontaneous aggregation due to the lack of stabilization and further the quenching of the Ag NCs fluorescence. These changes in fluorescence intensity allow sensing of OH radicals with good sensitivity and selectivity under optimal conditions. The sensor can be also applied for quantifying the radical scavenging action of antioxidants. Various characterizations including absorption spectra, fluorescence lifetimes, light scattering (LS) spectra, transmission electron microscopy (TEM), dark field light scattering imaging, and circular dichroism (CD) spectrometry have been employed to illustrate the proposed sensing mechanism. Further investigations demonstrate that the fluorescent probe could penetrate into intact cell membranes to selectively detect intracellular OH radicals induced by the phorbol myristate acetate (PMA) stimulation. These advantageous characteristics make the fluorescent DNA-Ag NCs potentially useful as a new candidate to monitor OH in broad biosystems. PMID:24274306

  15. Inner Magnetosphere Imager (IMI) solar terrestrial probe class mission preliminary design study report

    NASA Technical Reports Server (NTRS)

    Hermann, M.; Johnson, L.

    1994-01-01

    For three decades, magnetospheric field and plasma measurements have been made by diverse instruments flown on spacecraft in many different orbits, widely separated in space and time, and under various solar and magnetospheric conditions. Scientists have used this information to piece together an intricate, yet incomplete view of the magnetosphere. A simultaneous global view, using various light wavelengths and energetic neutral atoms, could reveal exciting new data and help explain complex magnetospheric processes, thus providing us with a clear picture of this region of space. The George C. Marshall Space Flight Center (MSFC) is responsible for defining the IMI mission which will study this region of space. NASA's Space Physics Division of the Office of Space Science placed the IMI third in its queue of Solar Terrestrial Probe missions for launch in the 1990's. A core instrument complement of three images (with the potential addition of one or more mission enhancing instruments) will fly in an elliptical, polar earth orbit with an apogee of 44,600 km and a perigee of 4,800 km. This paper will address the mission objectives, spacecraft design consideration, interim results of the MSFC concept definition study, and future plans.

  16. Distensibility of the Esophagogastric Junction Assessed with the Functional Lumen Imaging Probe (FLIP™) in Achalasia Patients

    PubMed Central

    Pandolfino, John E.; de Ruigh, Annemijn; Nicodème, Frédéric; Xiao, Yinglian; Boris, Lubomyr; Kahrilas, Peter J.

    2013-01-01

    Background The functional lumen imaging probe (FLIP), measures esophagogastric junction (EGJ) distensibility (cross sectional area/luminal pressure) during volume-controlled distension. The aim of this study was to apply this tool to the assessment of the EGJ in untreated and treated achalasia patients and to compare EGJ distensibility with other diagnostic tools utilized in managing achalasia. Methods Findings from FLIP, high-resolution manometry (HRM), timed barium esophagram, and symptom assessment by Eckardt Score (ES) were compared in 54 achalasia patients (23 untreated, 31 treated). Twenty healthy volunteers underwent FLIP as a comparator group. The EGJ distensibility index (EGJ-DI) was defined at the ‘waist’ of the FLIP bag during volumetric distension, expressed in mm2/mmHg. The ES was used to gauge treatment outcome: good response < 3 or poor response ≥ 3. Key Results Of the 31 treated patients, 17 had good and 14 poor treatment response. The EGJ-DI was significantly different among groups, greatest in the control subjects and least in the untreated patients; patients with good treatment response had significantly greater EGJ-DI than untreated or patients with poor response. The correlations between EGJ-DI and ES and integrated relaxation pressure on HRM were significant. Conclusion The FLIP provided a useful measure of EGJ distensibility in achalasia patients that correlated with symptom severity. The measurement of EGJ distensibility was complementary to existing tests suggesting a potentially important role in the clinical management of achalasia. PMID:23413801

  17. Imaging thermal conductivity with nanoscale resolution using a scanning spin probe

    SciTech Connect

    Laraoui, Abdelghani; Aycock-Rizzo, Halley; Gao, Yang; Lu, Xi; Riedo, Elisa; Meriles, Carlos A.

    2015-11-20

    The ability to probe nanoscale heat flow in a material is often limited by lack of spatial resolution. Here, we use a diamond-nanocrystal-hosted nitrogen-vacancy centre attached to the apex of a silicon thermal tip as a local temperature sensor. We apply an electrical current to heat up the tip and rely on the nitrogen vacancy to monitor the thermal changes the tip experiences as it is brought into contact with surfaces of varying thermal conductivity. By combining atomic force and confocal microscopy, we image phantom microstructures with nanoscale resolution, and attain excellent agreement between the thermal conductivity and topographic maps. The small mass and high thermal conductivity of the diamond host make the time response of our technique short, which we demonstrate by monitoring the tip temperature upon application of a heat pulse. Our approach promises multiple applications, from the investigation of phonon dynamics in nanostructures to the characterization of heterogeneous phase transitions and chemical reactions in various solid-state systems.

  18. Imaging thermal conductivity with nanoscale resolution using a scanning spin probe

    DOE PAGESBeta

    Laraoui, Abdelghani; Aycock-Rizzo, Halley; Gao, Yang; Lu, Xi; Riedo, Elisa; Meriles, Carlos A.

    2015-11-20

    The ability to probe nanoscale heat flow in a material is often limited by lack of spatial resolution. Here, we use a diamond-nanocrystal-hosted nitrogen-vacancy centre attached to the apex of a silicon thermal tip as a local temperature sensor. We apply an electrical current to heat up the tip and rely on the nitrogen vacancy to monitor the thermal changes the tip experiences as it is brought into contact with surfaces of varying thermal conductivity. By combining atomic force and confocal microscopy, we image phantom microstructures with nanoscale resolution, and attain excellent agreement between the thermal conductivity and topographic maps.more » The small mass and high thermal conductivity of the diamond host make the time response of our technique short, which we demonstrate by monitoring the tip temperature upon application of a heat pulse. Our approach promises multiple applications, from the investigation of phonon dynamics in nanostructures to the characterization of heterogeneous phase transitions and chemical reactions in various solid-state systems.« less

  19. A Molecular Imaging Approach to Mercury Sensing Based on Hyperpolarized (129)Xe Molecular Clamp Probe.

    PubMed

    Guo, Qianni; Zeng, Qingbin; Jiang, Weiping; Zhang, Xiaoxiao; Luo, Qing; Zhang, Xu; Bouchard, Louis-S; Liu, Maili; Zhou, Xin

    2016-03-14

    Mercury pollution, in the form of mercury ions (Hg(2+)), is a major health and environmental hazard. Commonly used sensors are invasive and limited to point measurements. Fluorescence-based sensors do not provide depth resolution needed to image spatial distributions. Herein we report a novel sensor capable of yielding spatial distributions by MRI using hyperpolarized (129)Xe. A molecular clamp probe was developed consisting of dipyrrolylquinoxaline (DPQ) derivatives and twocryptophane-A cages. The DPQ derivatives act as cation receptors whereas cryptophane-A acts as a suitable host molecule for xenon. When the DPQ moiety interacts with mercury ions, the molecular clamp closes on the ion. Due to overlap of the electron clouds of the two cryptophane-A cages, the shielding effect on the encapsulated Xe becomes important. This leads to an upfield change of the chemical shift of the encapsulated Xe. This sensor exhibits good selectivity and sensitivity toward the mercury ion. This mercury-activated hyperpolarized (129)Xe-based chemosensor is a new concept method for monitoring Hg(2+) ion distributions by MRI. PMID:26792102

  20. Probing articular cartilage damage and disease by quantitative magnetic resonance imaging

    PubMed Central

    Chan, Deva D.; Neu, Corey P.

    2013-01-01

    Osteoarthritis (OA) is a debilitating disease that reflects a complex interplay of biochemical, biomechanical, metabolic and genetic factors, which are often triggered by injury, and mediated by inflammation, catabolic cytokines and enzymes. An unmet clinical need is the lack of reliable methods that are able to probe the pathogenesis of early OA when disease-rectifying therapies may be most effective. Non-invasive quantitative magnetic resonance imaging (qMRI) techniques have shown potential for characterizing the structural, biochemical and mechanical changes that occur with cartilage degeneration. In this paper, we review the background in articular cartilage and OA as it pertains to conventional MRI and qMRI techniques. We then discuss how conventional MRI and qMRI techniques are used in clinical and research environments to evaluate biochemical and mechanical changes associated with degeneration. Some qMRI techniques allow for the use of relaxometry values as indirect biomarkers for cartilage components. Direct characterization of mechanical behaviour of cartilage is possible via other specialized qMRI techniques. The combination of these qMRI techniques has the potential to fully characterize the biochemical and biomechanical states that represent the initial changes associated with cartilage degeneration. Additionally, knowledge of in vivo cartilage biochemistry and mechanical behaviour in healthy subjects and across a spectrum of osteoarthritic patients could lead to improvements in the detection, management and treatment of OA. PMID:23135247

  1. Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe.

    PubMed

    Cui, Mengchao; Ono, Masahiro; Kimura, Hiroyuki; Liu, Bo Li; Saji, Hideo

    2011-02-01

    A series of chaclone derivatives containing an indole moiety were evaluated in competitive binding assays with Aβ(1-42) aggregates versus [(125)I]IMPY. The affinity of these compounds ranged from 4.46 to >1008 nM, depending on the substitution on the phenyl ring. Fluorescent staining in vitro showed that one compound with a N,N-dimethylamino group intensely stained Aβ plaques within brain sections of AD transgenic mice. The radioiodinated probe [(125)I]-(E)-3-(1H-indol-5-yl)-1-(4-iodophenyl)prop-2-en-1-one, [(125)I]4, was prepared and autoradiography in sections of brain tissue from an animal model of AD showed that it labeled Aβ plaques specifically. However, experiments with normal mice indicated that [(125)I]4 exhibited a low uptake into the brain in vivo (0.41% ID/g at 2 min). Additional chemical modifications of this indole-chalcone structure may lead to more useful imaging agents for detecting β-amyloid plaques in the brains of AD patients. PMID:21216142

  2. Imaging thermal conductivity with nanoscale resolution using a scanning spin probe

    PubMed Central

    Laraoui, Abdelghani; Aycock-Rizzo, Halley; Gao, Yang; Lu, Xi; Riedo, Elisa; Meriles, Carlos A.

    2015-01-01

    The ability to probe nanoscale heat flow in a material is often limited by lack of spatial resolution. Here, we use a diamond-nanocrystal-hosted nitrogen-vacancy centre attached to the apex of a silicon thermal tip as a local temperature sensor. We apply an electrical current to heat up the tip and rely on the nitrogen vacancy to monitor the thermal changes the tip experiences as it is brought into contact with surfaces of varying thermal conductivity. By combining atomic force and confocal microscopy, we image phantom microstructures with nanoscale resolution, and attain excellent agreement between the thermal conductivity and topographic maps. The small mass and high thermal conductivity of the diamond host make the time response of our technique short, which we demonstrate by monitoring the tip temperature upon application of a heat pulse. Our approach promises multiple applications, from the investigation of phonon dynamics in nanostructures to the characterization of heterogeneous phase transitions and chemical reactions in various solid-state systems. PMID:26584676

  3. DISR imaging and the geometry of the descent of the Huygens probe within Titan's atmosphere

    NASA Astrophysics Data System (ADS)

    Karkoschka, Erich; Tomasko, Martin G.; Doose, Lyn R.; See, Chuck; McFarlane, Elisabeth A.; Schröder, Stefan E.; Rizk, Bashar

    2007-11-01

    The Descent Imager/Spectral Radiometer (DISR) provided 376 images during the descent to Titan and 224 images after landing. Images of the surface had scales between 150 m/pixel and 0.4 mm/pixel, all of which we assembled into a mosaic. The analysis of the surface and haze features in these images and of other data gave tight constraints on the geometry of the descent, particularly the trajectory, the tip and tilt, and the rotation of the Huygens probe. Huygens moved on average in the direction of 2∘ north of east from 145 to 50 km altitude, turning to 5∘ south of east between 30 and 20 km altitude, before turning back to east. At 6.5 km altitude, it reversed to WNW, before reversing back to SE at 0.7 km altitude. At first, Huygens was tilting slowly by up to 15∘ as expected for a descent through layers of changing wind speeds. As the winds calmed, tilts decreased. Tilts were approximately retrieved throughout the main-parachute phase, but only for 160 specific times afterwards. Average swing rates were 5∘/s at high and low altitudes, but 13∘/s between 110 and 30 km altitude. Maximum swing rates were often above 40∘/s, far above the design limit of 6∘/s, but they caused problems only for a single component of DISR, the Sun Sensor. The excitation of such high swing rates on the stabilizer parachute is not fully understood. Before the parachute exchange, the rotational rate of Huygens smoothly approached the expected equilibrium value of 3 rotations per vertical kilometer, although clockwise instead of counterclockwise. Starting at 40 s after the parachute exchange until landing, Huygens rotated erratically. Long-term averages of the rotational rate varied between 2.0 and 4.5 rotations/km. On time scales shorter than a minute, some 100 strong rotational accelerations or decelerations created azimuthal irregularities of up to 180∘, which caused DISR to take most exposures at random azimuths instead of pre-selected azimuths. Nevertheless, we

  4. RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vascular imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Belfield, Kevin D.; Yue, Xiling; Morales, Alma R.; Githaiga, Grace W.; Woodward, Adam W.; Tang, Simon; Sawada, Junko; Komatsu, Masanobu; Liu, Xuan

    2016-03-01

    Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue vasculature imaging, probes that can be excited via two-photon absorption (2PA) in the near-infrared (NIR) and subsequently emit in the NIR are essential. In this study, the enhancement of tissue image quality with RGD conjugates was investigated with new NIR-emitting pyranyl fluorophore derivatives in two-photon fluorescence microscopy. Linear and nonlinear photophysical properties of the new probes were comprehensively characterized; significantly the probes exhibited good 2PA over a broad spectral range from 700-1100 nm. Cell and tissue images were then acquired and examined, revealing deep penetration and high contrast with the new pyranyl RGD-conjugates up to 350 μm in tumor tissue.

  5. Ultrasensitive fluorescent ratio imaging probe for the detection of glutathione ultratrace change in mitochondria of cancer cells.

    PubMed

    Zhang, Hua; Wang, Caixia; Wang, Kui; Xuan, Xiaopeng; Lv, Qingzhang; Jiang, Kai

    2016-11-15

    Glutathione (GSH) ultratrace change in mitochondria of cancer cells can mildly and effectively induce cancer cells apoptosis in early stage. Thus, if GSH ultratrace change in mitochondria of cancer cells could be recognized and imaged, it will be beneficial for fundamental research of cancer therapy. There have reported a lot of fluorescent probes for GSH, but the fluorescent probe with ultrasensitivity and high selectivity for the ratio imaging of GSH ultratrace changes in mitochondria of cancer cells is scarce. Herein, based on different reaction mechanism of sulfonamide under different pH, a sulfonamide-based reactive ratiometric fluorescent probe (IQDC-M) was reported for the recognizing and imaging of GSH ultratrace change in mitochondria of cancer cells. The detection limit of IQDC-M for GSH ultratrace change is low to 2.02nM, which is far less than 1.0‰ of endogenic GSH in living cells. And during the recognition process, IQDC-M can emit different fluorescent signals at 520nm and 592nm, which results in it recognizing GSH ultratrace change on ratio mode. More importantly, IQDC-M recognizing GSH ultratrace change specifically occurs in mitochondria of cancer cells because of appropriate water/oil amphipathy (log P) of IQDC-M. So, these make IQDC-M possible to image and monitor GSH ultratrace change in mitochondria during cancer cells apoptosis for the first time. PMID:27156018

  6. RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vasculature imaging.

    PubMed

    Yue, Xiling; Morales, Alma R; Githaiga, Grace W; Woodward, Adam W; Tang, Simon; Sawada, Junko; Komatsu, Masanobu; Liu, Xuan; Belfield, Kevin D

    2015-11-21

    Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue vasculature imaging, probes that can be excited via two-photon absorption (2PA) in the near-infrared (NIR) and subsequently emit in the NIR are essential. In this study, the enhancement of tissue image quality with RGD conjugates was investigated with new NIR-emitting pyranyl fluorophore derivatives in two-photon fluorescence microscopy. Linear and nonlinear photophysical properties of the new probes were comprehensively characterized; significantly the probes exhibited good 2PA over a broad spectral range from 700-1100 nm. Cell and tissue images were then acquired and examined, revealing deep penetration and high contrast with the new pyranyl RGD-conjugates up to 350 μm in tumor tissue. PMID:26351137

  7. ADAPT, a Novel Scaffold Protein-Based Probe for Radionuclide Imaging of Molecular Targets That Are Expressed in Disseminated Cancers.

    PubMed

    Garousi, Javad; Lindbo, Sarah; Nilvebrant, Johan; Åstrand, Mikael; Buijs, Jos; Sandström, Mattias; Honarvar, Hadis; Orlova, Anna; Tolmachev, Vladimir; Hober, Sophia

    2015-10-15

    Small engineered scaffold proteins have attracted attention as probes for radionuclide-based molecular imaging. One class of these imaging probes, termed ABD-Derived Affinity Proteins (ADAPT), has been created using the albumin-binding domain (ABD) of streptococcal protein G as a stable protein scaffold. In this study, we report the development of a clinical lead probe termed ADAPT6 that binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a theranostic biomarker for several approved targeting therapies. Surface-exposed amino acids of ABD were randomized to create a combinatorial library enabling selection of high-affinity binders to various proteins. Furthermore, ABD was engineered to enable rapid purification, to eradicate its binding to albumin, and to enable rapid blood clearance. Incorporation of a unique cysteine allowed site-specific conjugation to a maleimido derivative of a DOTA chelator, enabling radionuclide labeling, ¹¹¹In for SPECT imaging and ⁶⁸Ga for PET imaging. Pharmacologic studies in mice demonstrated that the fully engineered molecule (111)In/⁶⁸Ga-DOTA-(HE)3-ADAPT6 was specifically bound and taken up by HER2-expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models of human cancer. Unbound tracer underwent rapid renal clearance followed by high renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or PET at 1 hour after infusion. PET experiments demonstrated feasibility for discrimination of xenografts with high or low HER2 expression. Our results offer a preclinical proof of concept for the use of ADAPT probes for noninvasive in vivo imaging. PMID:26297736

  8. 350-μm side-view optical probe for imaging the murine brain in vivo from the cortex to the hypothalamus

    NASA Astrophysics Data System (ADS)

    Kim, Jun Ki; Choi, Jin Woo; Yun, Seok Hyun

    2013-05-01

    Miniature endoscopic probes offer a solution for deep brain imaging by overcoming the limited depth of intravital microscopy. We describe a small-diameter (350 μm) graded-index optical probe with a side-view design for in vivo cellular imaging of the mammalian brain. The side-view probe provides a unique view of the vertical network of neurons and penetrating blood vessels. At a given insertion site, the translational and rotational scanning of the probe provides access to a large tissue area (>) across the cortex, hippocampus, thalamus, and hypothalamus.

  9. Improved imaging of the carotid artery in the short-axis plane by a mechanical scanning ultrasonic probe.

    PubMed

    Kudo, Kazuki; Hasegawa, Hideyuki; Kanai, Hiroshi

    2007-03-01

    To image the intima-media complex of the carotid artery in a wider region, a method for measuring cross-sectional images in the arterial short-axis plane is presented. Using the proposed mechanical scanning system for an ultrasonic probe, cross-sectional images of a silicon rubber tube and a human carotid artery are measured in basic experiments and in in vivo experiments, respectively. These experiments show that this method successfully images the short-axis cross sections. Using the method proposed in this article, B-mode images in the short-axis plane can be accurately measured in a wider region than is possible with conventional methods. PMID:27278176

  10. Synthesis, relaxivity, and in vitro fluorescence imaging studies of a novel d-f heterometallic trinuclear complex as a potential bimodal imaging probe for MRI and optical imaging.

    PubMed

    Nithyakumar, A; Alexander, V

    2015-10-28

    A new trinuclear heterometallic Ru(II)-Gd complex of 4-aminopyridine appended DO3A (DO3A = 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) with 2,2'-bipyridine as ancillary ligands is synthesized and its relaxometry and in vitro fluorescence imaging studies are reported. The complex [Ru(bpy)2{Gd(DOTA-AMpy)(H2O)}2]Cl2 (7) exhibits a "per Gd" longitudinal relaxivity (r1p) of 5.80 and 14.30 mM(-1) s(-1) in aqueous solution and in the presence of HSA, respectively (20 MHz, pH = 7.4, PBS, 37 °C). The complex 7 exhibits an intense (1)MLCT absorption band at 480 nm and luminesces at 595 nm with a luminescence quantum yield of 3.2%. The fluorescence microscopy imaging study of HeLa cells incubated with 7 and stained with ethidium bromide and acridine orange confirms that the cells are viable throughout the imaging experiments and its cytotoxicity against HeLa cells, studied by the MTT assay, demonstrates its use for bioimaging studies. HeLa cell lines treated with the complex 7 and stained with Hoechst-33342 showed marked morphological signs of apoptosis in a dose-dependent manner by inducing changes in cell cycle arrest at the G2/M phase. Furthermore, apoptosis of HeLa cells, studied by the DNA ladder assay, indicates apoptotic cell death lending support for the antitumor activity of 7. A molecular docking study reveals that the complex 7 intercalates into the major groove of the DNA stabilized by hydrogen bonding and it binds with HSA by electrostatic- and hydrogen bonding interactions. The relaxometry, luminescence and fluorescence imaging studies indicate that the Ru(II)-Gd complex 7 has a good cell membrane permeability and could be considered as a potential bimodal imaging probe. PMID:26400754

  11. Theranostic Nanoshells: From Probe Design to Imaging and Treatment of Cancer

    PubMed Central

    Bardhan, Rizia; Lal, Surbhi; Joshi, Amit; Halas, Naomi J.

    2013-01-01

    CONSPECTUS Recent advances in theranostics have expanded our ability to design and construct multifunctional nanoparticles that will ultimately allow us to image and treat diseases in a single clinical procedure. Theranostic nanoparticles, combining targeting, therapeutic and diagnostic functions within a single nanoscale complex, have emerged as a result of this confluence of nanoscience and biomedicine. The theranostic capabilities of gold nanoshells -spherical, silica core, gold shell nanoparticles- have attracted tremendous attention over the past decade as nanoshells have emerged as a promising tool for cancer therapy and bioimaging enhancement. This account examines the design and synthesis of nanoshell-based theranostic agents, their plasmon-derived optical properties and their corresponding applications. Nanoshells illuminated with resonant light are either strong optical absorbers or scatterers, properties which give rise to their unique capabilities. In this account, we discuss the underlying physical principles contributing to the photothermal response of nanoshells. We elucidate the photophysics of nanoshell-induced fluorescence enhancement of weak near-infrared fluorophores. We then describe the application of nanoshells as a contrast agent for optical coherence tomography of breast carcinoma cells in vivo. We also examine the recent progress of nanoshells as a multimodal theranostic probe for near-infrared fluorescence and magnetic resonance imaging (MRI) combined with photothermal ablation of cancer cells. The design and preparation of nanoshell complexes is discussed, and their ability to enhance the photoluminescence of fluorophores while incorporating MR contrast is described. We show the theranostic potential of the multimodal nanoshells in vivo for imaging subcutaneous breast cancer tumors in animal models and their biodistribution in various tissues. We then discuss the potential of nanoshells as light-triggered gene therapy vectors. The

  12. Near-infrared fluorescence imaging of lymph nodes using a new enzyme sensing activatable macromolecular optical probe.

    PubMed

    Wunderbaldinger, Patrick; Turetschek, Karl; Bremer, Christoph

    2003-09-01

    The aim of this study was to validate the use of near infrared fluorescence imaging (NIRF) using enzyme-sensitive optical probes for lymph node detection. An optical contrast probe that is activated by cystein proteases, such as cathepsin B, was used to visualize lymph nodes by NIRF reflectance imaging. In order to quantitate the uptake of the optical probe in lymphatic tissue, the biodistribution was assessed using the Indium-111 labeled optical probe. Sixteen Balb-c mice were injected either intravenously (i.v.) or subcutaneously (s.c.) with the NIRF-probe (2 micromol cyanine (Cy)/animal; i.v., n=10; s.c., n=6) and imaged 24 h after injection. Signal intensities and target-to-background ratios of various lymph nodes were measured by manual regions of interest (ROIs). Additional signal intensity measurements were performed of excised lymph nodes (n=21) from i.v. injected mice (24 h after injection) and compared with excised lymph nodes (n=8) of non-injected mice. The probe employed in this study was lymphotropic with approximately 3-4% accumulation in lymph nodes (3.4+/-0.8% ID/g). Measurements of the excised lymph nodes (after i.v. injection) confirmed a significant increase in lymph node fluorescence signal from baseline 26+/-7.6 arbitary units (AU) to 146+/-10.9 AU (p<0.0001). A significant increase in lymph node fluorescence signal was also seen in vivo throughout the body after i.v. injection (96+/-7.8 AU) and/or regionally after s.c. injection (141+/-11.5 AU) in comparison with baseline autofluorescence (26+/-7.6 AU). Target-to-background ratio was significantly higher after s.c. injection (6.6%+/-0.81) compared with i.v. injection (4.8+/-0.67%). Detection and visualization of lymph nodes is feasible by NIRF imaging using a cystein-protease sensitive optical probe. PMID:12802615

  13. A flexible image fiber probe based speckle imaging for extraction of surface features with possible application in intra-cavity inspection

    NASA Astrophysics Data System (ADS)

    Guru, P. A. S.; Matham, Murukeshan V.; Chan, Kelvin H. K.

    2015-07-01

    Non-destructive inspection and non-invasive interrogation of surface features has always been a subject of discussion owing to the rapid advances in engineering and medical fields. Measurement of surface features which are miniature in size, inaccessible and of complex shape, has always posed challenges to conventional types of imaging and metrological systems. This paper, presents a methodology and a miniature image fiber probe configuration based on speckle technology for imaging such surface features, with possible application in intra cavity inspection. In the present work, a metal pipe is used as a test sample representing an engineering cavity. The acquired images of the intra cavity were subjected to image processing for contouring and size estimation. An analysis on the variation in the average speckle intensity, when the speckle image passes through an image fiber, is also carried out in this work. The obtained results indicate that the proposed probe configuration and related methodology can be used for inspection of cavity features and profiles of diffusive surfaces.

  14. In vivo imaging of prostate cancer using an anti-PSMA scFv fragment as a probe.

    PubMed

    Mazzocco, Claire; Fracasso, Giulio; Germain-Genevois, Coralie; Dugot-Senant, Nathalie; Figini, Mariangela; Colombatti, Marco; Grenier, Nicolas; Couillaud, Franck

    2016-01-01

    We aimed to evaluate a fluorescent-labeled single chain variable fragment (scFv) of the anti-PSMA antibody as a specific probe for the detection of prostate cancer by in vivo fluorescence imaging. An orthotopic model of prostate cancer was generated by injecting LNCaP cells into the prostate lobe. ScFvD2B, a high affinity anti-PSMA antibody fragment, was labeled using a near-infrared fluorophore to generate a specific imaging probe (X770-scFvD2B). PSMA-unrelated scFv-X770 was used as a control. Probes were injected intravenously into mice with prostate tumors and fluorescence was monitored in vivo by fluorescence molecular tomography (FMT). In vitro assays showed that X770-scFvD2B specifically bound to PSMA and was internalized in PSMA-expressing LNCaP cells. After intravenous injection, X770-scFvD2B was detected in vivo by FMT in the prostate region. On excised prostates the scFv probe co-localized with the cancer cells and was found in PSMA-expressing cells. The PSMA-unrelated scFv used as a control did not label the prostate cancer cells. Our data demonstrate that scFvD2B is a high affinity contrast agent for in vivo detection of PSMA-expressing cells in the prostate. NIR-labeled scFvD2B could thus be further developed as a clinical probe for imaging-guided targeted biopsies. PMID:26996325

  15. In vivo imaging of prostate cancer using an anti-PSMA scFv fragment as a probe

    PubMed Central

    Mazzocco, Claire; Fracasso, Giulio; Germain-Genevois, Coralie; Dugot-Senant, Nathalie; Figini, Mariangela; Colombatti, Marco; Grenier, Nicolas; Couillaud, Franck

    2016-01-01

    We aimed to evaluate a fluorescent-labeled single chain variable fragment (scFv) of the anti-PSMA antibody as a specific probe for the detection of prostate cancer by in vivo fluorescence imaging. An orthotopic model of prostate cancer was generated by injecting LNCaP cells into the prostate lobe. ScFvD2B, a high affinity anti-PSMA antibody fragment, was labeled using a near-infrared fluorophore to generate a specific imaging probe (X770-scFvD2B). PSMA-unrelated scFv-X770 was used as a control. Probes were injected intravenously into mice with prostate tumors and fluorescence was monitored in vivo by fluorescence molecular tomography (FMT). In vitro assays showed that X770-scFvD2B specifically bound to PSMA and was internalized in PSMA-expressing LNCaP cells. After intravenous injection, X770-scFvD2B was detected in vivo by FMT in the prostate region. On excised prostates the scFv probe co-localized with the cancer cells and was found in PSMA-expressing cells. The PSMA-unrelated scFv used as a control did not label the prostate cancer cells. Our data demonstrate that scFvD2B is a high affinity contrast agent for in vivo detection of PSMA-expressing cells in the prostate. NIR-labeled scFvD2B could thus be further developed as a clinical probe for imaging-guided targeted biopsies. PMID:26996325

  16. Intraoperative handheld probe for 3D imaging of pediatric benign vocal fold lesions using optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Benboujja, Fouzi; Garcia, Jordan; Beaudette, Kathy; Strupler, Mathias; Hartnick, Christopher J.; Boudoux, Caroline

    2016-02-01

    Excessive and repetitive force applied on vocal fold tissue can induce benign vocal fold lesions. Children affected suffer from chronic hoarseness. In this instance, the vibratory ability of the folds, a complex layered microanatomy, becomes impaired. Histological findings have shown that lesions produce a remodeling of sup-epithelial vocal fold layers. However, our understanding of lesion features and development is still limited. Indeed, conventional imaging techniques do not allow a non-invasive assessment of sub-epithelial integrity of the vocal fold. Furthermore, it remains challenging to differentiate these sub-epithelial lesions (such as bilateral nodules, polyps and cysts) from a clinical perspective, as their outer surfaces are relatively similar. As treatment strategy differs for each lesion type, it is critical to efficiently differentiate sub-epithelial alterations involved in benign lesions. In this study, we developed an optical coherence tomography (OCT) based handheld probe suitable for pediatric laryngological imaging. The probe allows for rapid three-dimensional imaging of vocal fold lesions. The system is adapted to allow for high-resolution intra-operative imaging. We imaged 20 patients undergoing direct laryngoscopy during which we looked at different benign pediatric pathologies such as bilateral nodules, cysts and laryngeal papillomatosis and compared them to healthy tissue. We qualitatively and quantitatively characterized laryngeal pathologies and demonstrated the added advantage of using 3D OCT imaging for lesion discrimination and margin assessment. OCT evaluation of the integrity of the vocal cord could yield to a better pediatric management of laryngeal diseases.

  17. Improved accuracy and speed in scanning probe microscopy by image reconstruction from non-gridded position sensor data.

    PubMed

    Ziegler, Dominik; Meyer, Travis R; Farnham, Rodrigo; Brune, Christoph; Bertozzi, Andrea L; Ashby, Paul D

    2013-08-23

    Scanning probe microscopy (SPM) has facilitated many scientific discoveries utilizing its strengths of spatial resolution, non-destructive characterization and realistic in situ environments. However, accurate spatial data are required for quantitative applications but this is challenging for SPM especially when imaging at higher frame rates. We present a new operation mode for scanning probe microscopy that uses advanced image processing techniques to render accurate images based on position sensor data. This technique, which we call sensor inpainting, frees the scanner to no longer be at a specific location at a given time. This drastically reduces the engineering effort of position control and enables the use of scan waveforms that are better suited for the high inertia nanopositioners of SPM. While in raster scanning, typically only trace or retrace images are used for display, in Archimedean spiral scans 100% of the data can be displayed and at least a two-fold increase in temporal or spatial resolution is achieved. In the new mode, the grid size of the final generated image is an independent variable. Inpainting to a few times more pixels than the samples creates images that more accurately represent the ground truth. PMID:23892397

  18. Improved accuracy and speed in scanning probe microscopy by image reconstruction from non-gridded position sensor data

    NASA Astrophysics Data System (ADS)

    Ziegler, Dominik; Meyer, Travis R.; Farnham, Rodrigo; Brune, Christoph; Bertozzi, Andrea L.; Ashby, Paul D.

    2013-08-01

    Scanning probe microscopy (SPM) has facilitated many scientific discoveries utilizing its strengths of spatial resolution, non-destructive characterization and realistic in situ environments. However, accurate spatial data are required for quantitative applications but this is challenging for SPM especially when imaging at higher frame rates. We present a new operation mode for scanning probe microscopy that uses advanced image processing techniques to render accurate images based on position sensor data. This technique, which we call sensor inpainting, frees the scanner to no longer be at a specific location at a given time. This drastically reduces the engineering effort of position control and enables the use of scan waveforms that are better suited for the high inertia nanopositioners of SPM. While in raster scanning, typically only trace or retrace images are used for display, in Archimedean spiral scans 100% of the data can be displayed and at least a two-fold increase in temporal or spatial resolution is achieved. In the new mode, the grid size of the final generated image is an independent variable. Inpainting to a few times more pixels than the samples creates images that more accurately represent the ground truth.

  19. Bimodal imaging probes for combined PET and OI: recent developments and future directions for hybrid agent development.

    PubMed

    Seibold, Uwe; Wängler, Björn; Schirrmacher, Ralf; Wängler, Carmen

    2014-01-01

    Molecular imaging--and especially positron emission tomography (PET)--has gained increasing importance for diagnosis of various diseases and thus experiences an increasing dissemination. Therefore, there is also a growing demand for highly affine PET tracers specifically accumulating and visualizing target structures in the human body. Beyond the development of agents suitable for PET alone, recent tendencies aim at the synthesis of bimodal imaging probes applicable in PET as well as optical imaging (OI), as this combination of modalities can provide clinical advantages. PET, due to the high tissue penetration of the γ-radiation emitted by PET nuclides, allows a quantitative imaging able to identify and visualize tumors and metastases in the whole body. OI on the contrary visualizes photons exhibiting only a limited tissue penetration but enables the identification of tumor margins and infected lymph nodes during surgery without bearing a radiation burden for the surgeon. Thus, there is an emerging interest in bimodal agents for PET and OI in order to exploit the potential of both imaging techniques for the imaging and treatment of tumor diseases. This short review summarizes the available hybrid probes developed for dual PET and OI and discusses future directions for hybrid agent development. PMID:24822177

  20. WE-G-BRF-09: Force- and Image-Adaptive Strategies for Robotised Placement of 4D Ultrasound Probes

    SciTech Connect

    Kuhlemann, I; Bruder, R; Ernst, F; Schweikard, A

    2014-06-15

    Purpose: To allow continuous acquisition of high quality 4D ultrasound images for non-invasive live tracking of tumours for IGRT, image- and force-adaptive strategies for robotised placement of 4D ultrasound probes are developed and evaluated. Methods: The developed robotised ultrasound system is based on a 6-axes industrial robot (adept Viper s850) carrying a 4D ultrasound transducer with a mounted force-torque sensor. The force-adaptive placement strategies include probe position control using artificial potential fields and contact pressure regulation by a PD controller strategy. The basis for live target tracking is a continuous minimum contact pressure to ensure good image quality and high patient comfort. This contact pressure can be significantly disturbed by respiratory movements and has to be compensated. All measurements were performed on human subjects under realistic conditions. When performing cardiac ultrasound, rib- and lung shadows are a common source of interference and can disrupt the tracking. To ensure continuous tracking, these artefacts had to be detected to automatically realign the probe. The detection is realised by multiple algorithms based on entropy calculations as well as a determination of the image quality. Results: Through active contact pressure regulation it was possible to reduce the variance of the contact pressure by 89.79% despite respiratory motion of the chest. The results regarding the image processing clearly demonstrate the feasibility to detect image artefacts like rib shadows in real-time. Conclusion: In all cases, it was possible to stabilise the image quality by active contact pressure control and automatically detected image artefacts. This fact enables the possibility to compensate for such interferences by realigning the probe and thus continuously optimising the ultrasound images. This is a huge step towards fully automated transducer positioning and opens the possibility for stable target tracking in

  1. Synthesis and Biological Evaluation of Water-soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers

    PubMed Central

    Sukerkar, Preeti A.; MacRenaris, Keith W.; Townsend, Taryn R.; Ahmed, Roshan A.; Burdette, Joanna E.; Meade, Thomas J.

    2011-01-01

    Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(−) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(−) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases. PMID:21972997

  2. Imaging of Fluoride Ion in Living Cells and Tissues with a Two-Photon Ratiometric Fluorescence Probe

    PubMed Central

    Zhu, Xinyue; Wang, Jianxi; Zhang, Jianjian; Chen, Zhenjie; Zhang, Haixia; Zhang, Xiaoyu

    2015-01-01

    A reaction-based two-photon (TP) ratiometric fluorescence probe Z2 has been developed and successfully applied to detect and image fluoride ion in living cells and tissues. The Z2 probe was designed designed to utilize an ICT mechanism between n-butylnaphthalimide as a fluorophore and tert-butyldiphenylsilane (TBDPS) as a response group. Upon addition of fluoride ion, the Si-O bond in the Z2 would be cleaved, and then a stronger electron-donating group was released. The fluorescent changes at 450 and 540 nm, respectively, made it possible to achieve ratiometric fluorescence detection. The results indicated that the Z2 could ratiometrically detect and image fluoride ion in living cells and tissues in a depth of 250 μm by two-photon microscopy (TPM). PMID:25594597

  3. Optical diagnostic suite (schlieren, interferometry, and grid image refractometry) on OMEGA EP using a 10-ps, 263-nm probe beam

    SciTech Connect

    Froula, D. H.; Boni, R.; Bedzyk, M.; Craxton, R. S.; Ehrne, F.; Ivancic, S.; Jungquist, R.; Shoup, M. J.; Theobald, W.; Weiner, D.; Kugland, N. L.; Rushford, M. C.

    2012-10-15

    A 10-ps, 263-nm (4{omega}) laser is being built to probe plasmas produced on the OMEGA EP [J. H. Kelly, L. J. Waxer, V. Bagnoud, I. A. Begishev, J. Bromage, B. E. Kruschwitz, T. E. Kessler, S. J. Loucks, D. N. Maywar, R. L. McCrory et al., J. Phys. IV France 133, 75-80 (2006)]. A suite of optical diagnostics (schlieren, interferometry, and grid image refractometry) has been designed to diagnose and characterize a wide variety of plasmas. Light scattered by the probe beam is collected by an f/4 catadioptric telescope and a transport system is designed to image with a near-diffraction-limited resolution ({approx}1 -{mu}m full width at half maximum) over a 5-mm field of view to a diagnostic table. The transport system provides a contrast greater than 1 : 10{sup 4} with respect to all wavelengths outside of the 263 {+-} 2 nm measurement range.

  4. Anti-epidermal growth factor receptor (anti-EGFR) antibody conjugated fluorescent nanoparticles probe for breast cancer imaging

    NASA Astrophysics Data System (ADS)

    Hun, Xu; Zhang, Zhujun

    2009-10-01

    Fluorescent nanoparticles (FNs) with unique optical properties may be useful as biosensors in living cancer cell imaging and cancer targeting. In this study, anti-EGFR antibody conjugated fluorescent nanoparticles (FNs) (anti-EGFR antibody conjugated FNs) probe was used to detect breast cancer cells. FNs with excellent character such as non-toxicity and photostability were first synthesized with a simple, cost-effective and environmentally friendly modified Stőber synthesis method, and then successfully modified with anti-EGFR antibody. This kind of fluorescence probe based on the anti-EGFR antibody conjugated FNs has been used to detect breast cancer cells with fluorescence microscopy imaging technology. The experimental results demonstrate that the anti-EGFR antibody conjugated FNs can effectively recognize breast cancer cells and exhibited good sensitivity and exceptional photostability, which would provide a novel way for the diagnosis and curative effect observation of breast cancer cells and offer a new method in detecting EGFR.

  5. Optical diagnostic suite (schlieren, interferometry, and grid image refractometry) on OMEGA EP using a 10-ps, 263-nm probe beam.

    PubMed

    Froula, D H; Boni, R; Bedzyk, M; Craxton, R S; Ehrne, F; Ivancic, S; Jungquist, R; Shoup, M J; Theobald, W; Weiner, D; Kugland, N L; Rushford, M C

    2012-10-01

    A 10-ps, 263-nm (4ω) laser is being built to probe plasmas produced on the OMEGA EP [J. H. Kelly, L. J. Waxer, V. Bagnoud, I. A. Begishev, J. Bromage, B. E. Kruschwitz, T. E. Kessler, S. J. Loucks, D. N. Maywar, R. L. McCrory et al., J. Phys. IV France 133, 75-80 (2006)]. A suite of optical diagnostics (schlieren, interferometry, and grid image refractometry) has been designed to diagnose and characterize a wide variety of plasmas. Light scattered by the probe beam is collected by an f/4 catadioptric telescope and a transport system is designed to image with a near-diffraction-limited resolution (~1 - μm full width at half maximum) over a 5-mm field of view to a diagnostic table. The transport system provides a contrast greater than 1 : 10(4) with respect to all wavelengths outside of the 263 ± 2 nm measurement range. PMID:23127030

  6. Submolecular Imaging by Noncontact Atomic Force Microscopy with an Oxygen Atom Rigidly Connected to a Metallic Probe.

    PubMed

    Mönig, Harry; Hermoso, Diego R; Díaz Arado, Oscar; Todorović, Milica; Timmer, Alexander; Schüer, Simon; Langewisch, Gernot; Pérez, Rubén; Fuchs, Harald

    2016-01-26

    In scanning probe microscopy, the imaging characteristics in the various interaction channels crucially depend on the chemical termination of the probe tip. Here we analyze the contrast signatures of an oxygen-terminated copper tip with a tetrahedral configuration of the covalently bound terminal O atom. Supported by first-principles calculations we show how this tip termination can be identified by contrast analysis in noncontact atomic force and scanning tunneling microscopy (NC-AFM, STM) on a partially oxidized Cu(110) surface. After controlled tip functionalization by soft indentations of only a few angstroms in an oxide nanodomain, we demonstrate that this tip allows imaging an organic molecule adsorbed on Cu(110) by constant-height NC-AFM in the repulsive force regime, revealing its internal bond structure. In established tip functionalization approaches where, for example, CO or Xe is deliberately picked up from a surface, these probe particles are only weakly bound to the metallic tip, leading to lateral deflections during scanning. Therefore, the contrast mechanism is subject to image distortions, artifacts, and related controversies. In contrast, our simulations for the O-terminated Cu tip show that lateral deflections of the terminating O atom are negligible. This allows a detailed discussion of the fundamental imaging mechanisms in high-resolution NC-AFM experiments. With its structural rigidity, its chemically passivated state, and a high electron density at the apex, we identify the main characteristics of the O-terminated Cu tip, making it a highly attractive complementary probe for the characterization of organic nanostructures on surfaces. PMID:26605698

  7. Functional luminal imaging probe topography: an improved method for characterizing esophageal distensibility in eosinophilic esophagitis

    PubMed Central

    Kahrilas, Peter J.; Xiao, Yinglian; Nicodème, Frédéric; Gonsalves, Nirmala; Hirano, Ikuo; Pandolfino, John E.

    2013-01-01

    Objectives: The aims of this study were to develop a new method for analysis and presentation of esophageal distensibility data using high-resolution impedance planimetry recordings during a volume-controlled distention. Methods: Two control subjects and six patients with eosinophilic esophagitis (EoE) with stricture, narrow caliber or normal endoscopy according to EndoFLIP studies were included for analysis. Median filtering and pulse detection techniques were applied to the pressure signal and a wavelet decomposition technique was applied to the 16 channels of raw esophageal diameter data to reduce vascular artifact, respiratory effect and remove esophageal contraction interference. These data were used to generate a functional luminal imaging probe (FLIP) topography plot that describes regional variation of cross-sectional area (CSA). A previously developed computer program was used to calculate and model the CSA-pressure data to derive the slope of line fitting and distension plateau for each individual subject. The results were compared among the four endoscopic phenotypes. Results: Patients with EoE and normal endoscopy had similar esophageal distensibility parameters to those of normal controls whereas patients with EoE and stricture or narrow caliber had much lower distensibility than patients with EoE and normal endoscopy. The FLIP topography plots provided a global assessment of the esophageal distensibility along the axial plane of measurement that differentiated patients with varying degrees of endoscopic abnormality. Conclusions: New techniques can be leveraged to improve data analysis and presentation using EndoFLIP assessment of the esophageal body in EoE. These techniques may be helpful in defining clinically relevant phenotypes and guiding treatment strategies and should be helpful in structuring future outcome trials. PMID:23503784

  8. Iridium(III) Anthraquinone Complexes as Two-Photon Phosphorescence Probes for Mitochondria Imaging and Tracking under Hypoxia.

    PubMed

    Sun, Lingli; Chen, Yu; Kuang, Shi; Li, Guanying; Guan, Ruilin; Liu, Jiangping; Ji, Liangnian; Chao, Hui

    2016-06-20

    In the present study, four mitochondria-specific and two-photon phosphorescence iridium(III) complexes, Ir1-Ir4, were developed for mitochondria imaging in hypoxic tumor cells. The iridium(III) complex has two anthraquinone groups that are hypoxia-sensitive moieties. The phosphorescence of the iridium(III) complex was quenched by the functions of the intramolecular quinone unit, and it was restored through two-electron bioreduction under hypoxia. When the probes were reduced by reductase to hydroquinone derivative products under hypoxia, a significant enhancement in phosphorescence intensity was observed under one- (λ=405 nm) and two-photon (λ=720 nm) excitation, with a two-photon absorption cross section of 76-153 GM at λ=720 nm. More importantly, these probes possessed excellent specificity for mitochondria, which allowed imaging and tracking of the mitochondrial morphological changes in a hypoxic environment over a long period of time. Moreover, the probes can visualize hypoxic mitochondria in 3D multicellular spheroids and living zebrafish through two-photon phosphorescence imaging. PMID:27145442

  9. Largely defocused probe scanning transmission electron microscopy for imaging local modulation of strain field in a hetero interface

    SciTech Connect

    Kim, Suhyun Jung, Younheum; Kim, Joong Jung; Lee, Sunyoung; Lee, Haebum; Oshima, Yoshifumi

    2014-10-13

    We present an innovative method for characterizing the strain field in three dimensions in a hetero interface. Largely defocused probe scanning transmission electron microscopy (LDP-STEM) was employed for imaging the inhomogeneous strain field in a germanium (Ge) layer deposited on a silicon (Si) substrate. In the LDP-STEM image, Ge-atomic columns that are relaxed or strained to the Si substrate in the Si/Ge hetero interface were observed to be distinguishable, allowing for the qualitative characterization of the coherency of the crystal growth. Our results revealed that the strain field is locally modulated along the in-plane direction in the Si/Ge hetero interface.

  10. Theranostic nanoshells: from probe design to imaging and treatment of cancer.

    PubMed

    Bardhan, Rizia; Lal, Surbhi; Joshi, Amit; Halas, Naomi J

    2011-10-18

    Recent advances in nanoscience and biomedicine have expanded our ability to design and construct multifunctional nanoparticles that combine targeting, therapeutic, and diagnostic functions within a single nanoscale complex. The theranostic capabilities of gold nanoshells, spherical nanoparticles with silica cores and gold shells, have attracted tremendous attention over the past decade as nanoshells have emerged as a promising tool for cancer therapy and bioimaging enhancement. This Account examines the design and synthesis of nanoshell-based theranostic agents, their plasmon-derived optical properties, and their corresponding applications. We discuss the design and preparation of nanoshell complexes and their ability to enhance the photoluminescence of fluorophores while maintaining their properties as MR contrast agents. In this Account, we discuss the underlying physical principles that contribute to the photothermal response of nanoshells. We then elucidate the photophysical processes that induce nanoshells to enhance the fluorescence of weak near-infrared fluorophores. Nanoshells illuminated with resonant light are either strong optical absorbers or scatterers, properties that give rise to their unique capabilities. These physical processes have been harnessed to visualize and eliminate cancer cells. We describe the application of nanoshells as a contrast agent for optical coherence tomography of breast carcinoma cells in vivo. Our recent studies examine nanoshells as a multimodal theranostic probe, using these nanoparticles for near-infrared fluorescence and magnetic resonance imaging (MRI) and for the photothermal ablation of cancer cells. Multimodal nanoshells show theranostic potential for imaging subcutaneous breast cancer tumors in animal models and the distribution of tumors in various tissues. Nanoshells also show promise as light-triggered gene therapy vectors, adding temporal control to the spatial control characteristic of nanoparticle-based gene

  11. Bimodal Imaging Probes for Combined PET and OI: Recent Developments and Future Directions for Hybrid Agent Development

    PubMed Central

    Seibold, Uwe; Wängler, Björn; Schirrmacher, Ralf; Wängler, Carmen

    2014-01-01

    Molecular imaging—and especially positron emission tomography (PET)—has gained increasing importance for diagnosis of various diseases and thus experiences an increasing dissemination. Therefore, there is also a growing demand for highly affine PET tracers specifically accumulating and visualizing target structures in the human body. Beyond the development of agents suitable for PET alone, recent tendencies aim at the synthesis of bimodal imaging probes applicable in PET as well as optical imaging (OI), as this combination of modalities can provide clinical advantages. PET, due to the high tissue penetration of the γ-radiation emitted by PET nuclides, allows a quantitative imaging able to identify and visualize tumors and metastases in the whole body. OI on the contrary visualizes photons exhibiting only a limited tissue penetration but enables the identification of tumor margins and infected lymph nodes during surgery without bearing a radiation burden for the surgeon. Thus, there is an emerging interest in bimodal agents for PET and OI in order to exploit the potential of both imaging techniques for the imaging and treatment of tumor diseases. This short review summarizes the available hybrid probes developed for dual PET and OI and discusses future directions for hybrid agent development. PMID:24822177

  12. Combining high-dispersion spectroscopy with high contrast imaging: Probing rocky planets around our nearest neighbors

    NASA Astrophysics Data System (ADS)

    Snellen, I.; de Kok, R.; Birkby, J. L.; Brandl, B.; Brogi, M.; Keller, C.; Kenworthy, M.; Schwarz, H.; Stuik, R.

    2015-04-01

    Context. Ground-based high-dispersion (R ~ 100 000) spectroscopy (HDS) is proving to be a powerful technique with which to characterize extrasolar planets. The planet signal is distilled from the bright starlight, combining ral and time-differential filtering techniques. In parallel, high-contrast imaging (HCI) is developing rapidly, aimed at spatially separating the planet from the star. While HDS is limited by the overwhelming noise from the host star, HCI is limited by residual quasi-static speckles. Both techniques currently reach planet-star contrast limits down to ~10-5, albeit for very different types of planetary systems. Aims: In this work, we discuss a way to combine HDS and HCI (HDS+HCI). For a planet located at a resolvable angular distance from its host star, the starlight can be reduced up to several orders of magnitude using adaptive optics and/or coronography. In addition, the remaining starlight can be filtered out using high-dispersion spectroscopy, utilizing the significantly different (or Doppler shifted) high-dispersion spectra of the planet and star. In this way, HDS+HCI can in principle reach contrast limits of ~10-5 × 10-5, although in practice this will be limited by photon noise and/or sky-background. In contrast to current direct imaging techniques, such as Angular Differential Imaging and Spectral Differential Imaging, it will work well at small working angles and is much less sensitive to speckle noise. For the discovery of previously unknown planets HDS+HCI requires a high-contrast adaptive optics system combined with a high-dispersion R ~ 100 000 integral field spectrograph (IFS). This combination currently does not exist, but is planned for the European Extremely Large Telescope. Methods: We present simulations of HDS+HCI observations with the E-ELT, both probing thermal emission from a planet at infrared wavelengths, and starlight reflected off a planet atmosphere at optical wavelengths. For the infrared simulations we use the

  13. Application of Tapping-Mode Scanning Probe Electrospray Ionization to Mass Spectrometry Imaging of Additives in Polymer Films

    PubMed Central

    Shimazu, Ryo; Yamoto, Yoshinari; Kosaka, Tomoya; Kawasaki, Hideya; Arakawa, Ryuichi

    2014-01-01

    We report the application of tapping-mode scanning probe electrospray ionization (t-SPESI) to mass spectrometry imaging of industrial materials. The t-SPESI parameters including tapping solvent composition, solvent flow rate, number of tapping at each spot, and step-size were optimized using a quadrupole mass spectrometer to improve mass spectrometry (MS) imaging of thin-layer chromatography (TLC) and additives in polymer films. Spatial resolution of approximately 100 μm was achieved by t-SPESI imaging mass spectrometry using a fused-silica capillary (50 μm i.d., 150 μm o.d.) with the flow rate set at 0.2 μL/min. This allowed us to obtain discriminable MS imaging profiles of three dyes separated by TLC and the additive stripe pattern of a PMMA model film depleted by UV irradiation. PMID:26819894

  14. Use of endoscopic distal attachment cap to enhance image stabilization in probe-based confocal laser endomicroscopy in colorectal lesions*

    PubMed Central

    Ussui, Vivian; Xu, Can; Crook, Julia E.; Diehl, Nancy N.; Hardee, Joy; Staggs, Estela G.; Shahid, Muhammad W.; Wallace, Michael B.

    2015-01-01

    Background and study aims: Colorectal cancer can be prevented through the use of colonoscopy with polypectomy. Most colon polyps are benign or low grade adenomas. However, currently all lesions need histopathologic analysis, which increases diagnostic costs and delays the final diagnosis. Confocal laser endomicroscopy (CLE) is a new technology that enables real-time endomicroscopy. However, there are challenges to maintaining a stable image with currently available systems. We conducted a small study to obtain a preliminary assessment of whether the use of an endoscopic distal attachment cap may enhance image quality of CLE in comparison with images obtained with free-hand acquisition. Patients and methods: Forty outpatients underwent colonoscopy for evaluation of colon polyps in a single academic medical center. Patients were assigned randomly to 1 of 2 study arms on the basis of whether an endoscopic distal attachment cap was used (n = 21, Cap Used) or not used (n = 19, No Cap) in the procedure. The quality of confocal images and probe stabilization was summarized. Results: A total of 81 polyps were identified. The proportion of polyps with images of high quality was 74 % (28/38) in the Cap Used group and 79 % (30/38) in the No Cap arm. Image stability was also similar with and without a cap. Diagnostic accuracy was estimated to be slightly higher in the Cap Used group for probe-based confocal laser endomicroscopy (pCLE; 78 % vs 70 %). This was also true for white-light and narrow-band imaging. Conclusions: This preliminary study did not yield any evidence to support that the use of an endoscopic distal attachment cap improves the quality of images obtained during CLE. PMID:26528511

  15. Photoacoustic imaging of a near-infrared fluorescent marker based on dual wavelength pump-probe excitation

    NASA Astrophysics Data System (ADS)

    Märk, Julia; Theiss, Christoph; Schmitt, Franz-Josef; Laufer, Jan

    2014-03-01

    Photoacoustic imaging has been used to determine the spatial distribution of fluorophores, such as exogenous dyes and genetically expressed proteins, from images acquired in phantoms and in vivo. Most methods involve the acquisition of multiwavelength images and rely on differences in the absorption spectra of the tissue chromophores to estimate the spatial distribution and abundance of the latter using spectral decomposition techniques, such as model based inversion schemes. However, the inversion of 3-D images can be computationally expensive. Experimental approaches to localising contrast agents may therefore be useful, especially if quantification is not essential. This work aims to develop a method for determining the spatial distribution of a near-infrared fluorescent cell marker from images acquired using dual wavelength excitation. The excitation wavelengths coincided with the absorption and emission spectrum of the fluorophore. The contrast mechanism relies on reducing the excited state lifetime of the fluorophore by inducing stimulated emission. This changes the amount of energy thermalized by the fluorophore, and hence the photoacoustic signal amplitude. Since this is not observed in endogenous chromophores, the background may be removed by subtracting two images acquired with and without pulse delay between the pump and probe pulses. To characterise the fluorophore, the signal amplitude is measured in a cuvette as a function of pulse delay, concentration, and fluence. The spatial distribution of the fluorophore is determined from images acquired in realistic tissue phantoms. This method may be suitable for in vivo applications, such as imaging of exogenous or genetically expressed fluorescent cell markers.

  16. Detection of enzyme activity in orthotopic murine breast cancer by fluorescence lifetime imaging using a fluorescence resonance energy transfer-based molecular probe

    NASA Astrophysics Data System (ADS)

    Solomon, Metasebya; Guo, Kevin; Sudlow, Gail P.; Berezin, Mikhail Y.; Edwards, W. Barry; Achilefu, Samuel; Akers, Walter J.

    2011-06-01

    Cancer-related enzyme activity can be detected noninvasively using activatable fluorescent molecular probes. In contrast to ``always-on'' fluorescent molecular probes, activatable probes are relatively nonfluorescent at the time of administration due to intramolecular fluorescence resonance energy transfer (FRET). Enzyme-mediated hydrolysis of peptide linkers results in reduced FRET and increase of fluorescence yield. Separation of signal from active and inactive probe can be difficult with conventional intensity-based fluorescence imaging. Fluorescence lifetime (FLT) measurement is an alternative method to detect changes in FRET. Thus, we investigate FLT imaging for in vivo detection of FRET-based molecular probe activation in an orthotopic breast cancer model. Indeed, the measured FLT of the enzyme-activatable molecular probe increases from 0.62 ns just after injection to 0.78 ns in tumor tissue after 4 h. A significant increase in FLT is not observed for an always-on targeted molecular probe with the same fluorescent reporter. These results show that FLT contrast is a powerful addition to preclinical imaging because it can report molecular activity in vivo due to changes in FRET. Fluorescence lifetime imaging exploits unique characteristics of fluorescent molecular probes that can be further translated into clinical applications, including noninvasive detection of cancer-related enzyme activity.

  17. Efficient two-photon fluorescent probe with red emission for imaging of thiophenols in living cells and tissues.

    PubMed

    Liu, Hong-Wen; Zhang, Xiao-Bing; Zhang, Jing; Wang, Qian-Qian; Hu, Xiao-Xiao; Wang, Peng; Tan, Weihong

    2015-09-01

    Thiophenols, a class of highly toxic and pollutant compounds, are widely used in industrial production. Some aliphatic thiols play important roles in living organisms. Therefore, the development of efficient methods to discriminate thiophenols from aliphatic thiols is of great importance. Although several one-photon fluorescent probes have been reported for thiophenols, two-photon fluorescent probes are more favorable for biological imaging due to its low background fluorescence, deep penetration depth, and so on. In this work, a two-photon fluorescent probe for thiophenols, termed NpRb1, has been developed for the first time by employing 2,4-dinitrobenzene-sulfonate (DNBS) as a recognition unit (also a fluorescence quencher) and a naphthalene-BODIPY-based through-bond energy transfer (TBET) cassette as a fluorescent reporter. The TBET system consists of a D-π-A structured two-photon naphthalene fluorophore and a red-emitting BODIPY. It displayed highly energy transfer efficiency (93.5%), large pseudo-Stokes shifts upon one-photon excitation, and red fluorescence emission (λem = 586 nm), which is highly desirable for bioimaging applications. The probe exhibited a 163-fold thiophenol-triggered two-photon excited fluorescence enhancement at 586 nm. It showed a high selectivity and excellent sensitivity to thiophenols, with a detection limit of 4.9 nM. Moreover, it was successfully applied for practical detection of thiophenol in water samples with a good recovery, two-photon imaging of thiophenol in living cells, and tissues with tissue-imaging depths of 90-220 μm, demonstrating its practical application in environmental samples and biological systems. PMID:26228351

  18. Hard X-ray imaging from the solar probe. [X ray telescope and mission planning

    NASA Technical Reports Server (NTRS)

    Hudson, H. S.

    1978-01-01

    The solar probe offers a platform with particular advantages for studying solar nonthermal plasma processes via the observations of hard X-radiation from energetic electrons in the chromosphere and corona, these include (1) high sensitivity, (2) a second line of sign (in addition to the earth's) that can aid in three dimensional reconstruction of the source distribution, and, (3) the possibility of correlation with direct measurements of the nonthermal particles from the probe itself.

  19. Self-Assembly of Peptide Amphiphiles Designed as Imaging Probes for 19F and Relaxation-Enhanced 1H imaging

    NASA Astrophysics Data System (ADS)

    Preslar, Adam Truett

    This work incorporates whole-body imaging functionality into peptide amphiphile (PA) nanostructures used for regenerative medicine to facilitate magnetic resonance imaging (MRI). Two strategies were employed: 1. Conjugation of gadolinium chelates to peptide nanostructures to monitor biomaterial degradation in vivo with MRI and inductively-coupled plasma-mass spectroscopy (ICP-MS) 2. Synthesis of perfluorinated moiety-bearing peptide amphiphiles for 19F-MRI. The Gd(III) chelate gadoteridol was conjugated by copper-catalyzed "click" chemistry to a series of PAs known to form cylindrical nanostructures. By fitting nuclear magnetic resonance dispersion (NMRD) profiles to the Solomon-Bloembergen-Morgan (SBM) equations, it was observed that the water exchange parameter (tauM) depended on thermal annealing or calcium ion cross-linking. The sequence C16V 3A3E3G(Gd) exhibited an acceleration of nearly 100 ns after thermal annealing and calcium addition. These gadolinium-labeled PAs were used to track in vivo degradation of gels within the tibialis anterior muscle in a murine model. The half-life of biomaterial degradation was determined to be 13.5 days by inductively coupled plasma mass spectrometry (ICP-MS) of Gd(III). Gel implants could be monitored by MRI for eight days before the signal dispersed due to implant degradation and dilution. Additionally, nanostructures incorporating highly fluorinated domains were investigated for use as MRI contrast agents. Short, perfluoroalkyane tails of seven or eight carbon atoms in length were grafted to PA sequences containing a V2A2 beta-sheet forming sequence. The V2A2 sequence is known to drive 1D nanostructure assembly. It was found that the sequences C7F13V2A 2E2 and C7F13V2A 2K3 formed 1D assemblies in water which transition from ribbon-like to cylindrical shape as pH increases from 4.5 to 8.0. Ribbon-like nanostructures had reduced magnetic resonance signal by T 2 relaxation quenching, whereas their cylindrical counterparts

  20. Correction: A versatile two-photon fluorescent probe for ratiometric imaging E. coliβ-galactosidase in live cells and in vivo.

    PubMed

    Zhang, Xue-Xiang; Wu, Hao; Li, Peng; Qu, Zong-Jin; Tan, Ming-Qian; Han, Ke-Li

    2016-08-01

    Correction for 'A versatile two-photon fluorescent probe for ratiometric imaging E. coliβ-galactosidase in live cells and in vivo' by Xue-Xiang Zhang et al., Chem. Commun., 2016, 52, 8283-8286. PMID:27388438

  1. Using carbon nanotube probes for high-resolution three-dimensional imaging of cells.

    PubMed

    Koehne, J E; Stevens, R M; Zink, T; Deng, Z; Chen, H; Weng, I C; Liu, F T; Liu, G Y

    2011-07-01

    While atomic force microscopy (AFM) has become a promising tool for visualizing membrane morphology of cells, many studies have reported the presence of artifacts such as cliffs on the edges of cells. These artifacts shield important structural features such as lamellopodia, filopodia, microvilli and membrane ridges, which represent characteristic status in signaling processes such as spreading and activation. These cliff-like edges arise from a premature contact of the probe side contact with the cell prior to the probe top apex-cell contact. Carbon nanotube (CNT) modified AFM probes were utilized to address this drawback. Using rat basophilic leukemia (RBL) cells, this work revealed that CNT probes diminish cliff-like artifacts and enabled visualization of entire membrane morphology and structural features in three dimensions. The high aspect ratio of CNT probes provides a very effective remedy to the cliff-like artifacts as well as tip convolution of conventional probes, which shall enhance the validity and application of AFM in cellular biology research. PMID:21741916

  2. Synthesis of a highly HOCl-selective fluorescent probe and its use for imaging HOCl in cells and organisms.

    PubMed

    Chen, Xiaoqiang; Lee, Kyung-Ah; Ren, Xintong; Ryu, Jae-Chan; Kim, Gyungmi; Ryu, Ji-Hwan; Lee, Won-Jae; Yoon, Juyoung

    2016-07-01

    During infection, nicotinamide adenine dinucleotide phosphate-oxidase of innate immune cells generates important microbicidal reactive oxygen species (ROS) such as hypochlorous acid (HOCl) to kill the invading pathogens. However, excess amounts of HOCl induce oxidative damage of functional biomolecules such as DNA and proteins, which may cause chronic inflammatory diseases. Herein, we outline protocols for the preparation of a rhodamine-based HOCl probe, as well as applications thereof, with which to detect HOCl in living cells and organisms. The probe (R19S) can be prepared from a commercially available rhodamine, rhodamine 6G, in two steps. When R19S is treated with HOCl, the sulfur atom is replaced by an oxygen atom, resulting in opening of the lactone ring; thus, nonfluorescent R19S is converted to highly fluorescent rhodamine 19 (R19). R19S exhibits high selectivity for HOCl over other ROS and high sensitivity in a weakly acidic environment. In addition, we describe fluorescence imaging assays of HOCl in mouse neutrophils and Drosophila targeted using this probe. The approximate amount of time required to synthesize the probe is 2-3 d, after which it can be used for up to 5 h in the bioimaging of living cells. PMID:27281649

  3. A bright approach to the immunoproteasome: development of LMP2/β1i-specific imaging probes.

    PubMed

    Carmony, Kimberly Cornish; Lee, Do-Min; Wu, Ying; Lee, Na-Ra; Wehenkel, Marie; Lee, Jason; Lei, Beilei; Zhan, Chang-Guo; Kim, Kyung-Bo

    2012-01-15

    While the constitutive, 26S proteasome plays an important role in regulating many important cellular processes, a variant form known as the immunoproteasome is thought to primarily function in adaptive immune responses. However, recent studies indicate an association of immunoproteasomes with many physiological disorders such as cancer, neurodegenerative, and inflammatory diseases. Despite this, the detailed functions of the immunoproteasome remain poorly understood. Immunoproteasome-specific probes are essential to gain insight into immunoproteasome function. Here, we describe for the first time the development of cell-permeable activity-based fluorescent probes, UK101-Fluor and UK101-B660, which selectively target the catalytically active LMP2/β1i subunit of the immunoproteasome. These probes facilitate rapid detection of the cellular localization of catalytically active immunoproteasomes in living cells, providing a valuable tool to analyze immunoproteasome functions. Additionally, as LMP2/β1i may serve as a potential tumor biomarker, an LMP2/β1i-targeting fluorescent imaging probe may be applicable to a rapid readout assay to determine tumor LMP2/β1i levels. PMID:21741845

  4. A bright approach to the immunoproteasome: Development of LMP2/β1i-specific imaging probes

    PubMed Central

    Carmony, Kimberly Cornish; Lee, Do-Min; Wu, Ying; Lee, Na-Ra; Wehenkel, Marie; Lee, Jason; Zhan, Chang-Guo; Kim, Kyung-Bo

    2011-01-01

    While the constitutive, 26S proteasome plays an important role in regulating many important cellular processes, a variant form known as the immunoproteasome is thought to primarily function in adaptive immune responses. However, recent studies indicate an association of immunoproteasomes with many physiological disorders such as cancer, neurodegenerative, and inflammatory diseases. Despite this, the detailed functions of the immunoproteasome remain poorly understood. Immunoproteasome-specific probes are essential to gain insight into immunoproteasome function. Here, we describe for the first time the development of the cell-permeable, activity-based fluorescent probes, UK101-Fluor and UK101-B660, which selectively target the catalytically active LMP2/β1i subunit of the immunoproteasome. These probes will facilitate rapid detection of the cellular localization of catalytically active immunoproteasomes in living cells, providing a valuable tool to analyze immunoproteasome functions. Additionally, as LMP2/β1i may serve as a potential tumor biomarker, an LMP2/β1i-targeting fluorescent imaging probe may be applicable to a rapid readout assay to determine tumor LMP2/β1i levels. PMID:21741845

  5. Effect of using different U/S probe Standoff materials in image geometry for interventional procedures: the example of prostate

    PubMed Central

    Diamantopoulos, Stefanos; Butt, Saeed; Katsilieri, Zaira; Kefala, Vasiliki; Zogal, Pawel; Sakas, George; Baltas, Dimos

    2011-01-01

    Purpose This study investigates the distortion of geometry of catheters and anatomy in acquired U/S images, caused by utilizing various stand-off materials for covering a transrectal bi-planar ultrasound probe in HDR and LDR prostate brachytherapy, biopsy and other interventional procedures. Furthermore, an evaluation of currently established water-bath based quality assurance (QA) procedures is presented. Material and methods Image acquisitions of an ultrasound QA setup were carried out at 5 MHz and 7 MHz. The U/S probe was covered by EA 4015 Silicone Standoff kit, or UA0059 Endocavity balloon filled either with water or one of the following: 40 ml of Endosgel®, Instillagel®, Ultraschall gel or Space OAR™ gel. The differences between images were recorded. Consequently, the dosimetric impact of the observed image distortion was investigated, using a tissue equivalent ultrasound prostate phantom – Model number 053 (CIRS Inc., Norfolk, VA, USA). Results By using the EA 4015 Silicone Standoff kit in normal water with sound speed of 1525 m/s, a 3 mm needle shift was observed. The expansion of objects appeared in radial direction. The shift deforms also the PTV (prostate in our case) and other organs at risk (OARs) in the same way leading to overestimation of volume and underestimation of the dose. On the other hand, Instillagel® and Space OAR™ “shrinks” objects in an ultrasound image for 0.65 mm and 0.40 mm, respectively. Conclusions The use of EA 4015 Silicone Standoff kit for image acquisition, leads to erroneous contouring of PTV and OARs and reconstruction and placement of catheters, which results to incorrect dose calculation during prostate brachytherapy. Moreover, the reliability of QA procedures lies mostly in the right temperature of the water used for accurate simulation of real conditions of transrectal ultrasound imaging. PMID:23346130

  6. Wide-field spectral imaging of human ovary autofluorescence and oncologic diagnosis via previously collected probe data

    NASA Astrophysics Data System (ADS)

    Renkoski, Timothy E.; Hatch, Kenneth D.; Utzinger, Urs

    2012-03-01

    With no sufficient screening test for ovarian cancer, a method to evaluate the ovarian disease state quickly and nondestructively is needed. The authors have applied a wide-field spectral imager to freshly resected ovaries of 30 human patients in a study believed to be the first of its magnitude. Endogenous fluorescence was excited with 365-nm light and imaged in eight emission bands collectively covering the 400- to 640-nm range. Linear discriminant analysis was used to classify all image pixels and generate diagnostic maps of the ovaries. Training the classifier with previously collected single-point autofluorescence measurements of a spectroscopic probe enabled this novel classification. The process by which probe-collected spectra were transformed for comparison with imager spectra is described. Sensitivity of 100% and specificity of 51% were obtained in classifying normal and cancerous ovaries using autofluorescence data alone. Specificity increased to 69% when autofluorescence data were divided by green reflectance data to correct for spatial variation in tissue absorption properties. Benign neoplasm ovaries were also found to classify as nonmalignant using the same algorithm. Although applied ex vivo, the method described here appears useful for quick assessment of cancer presence in the human ovary.

  7. The Descent Imager/Spectral Radiometer (DISR) Experiment on the Huygens Entry Probe of Titan

    NASA Astrophysics Data System (ADS)

    Tomasko, M. G.; Buchhauser, D.; Bushroe, M.; Dafoe, L. E.; Doose, L. R.; Eibl, A.; Fellows, C.; Farlane, E. M.; Prout, G. M.; Pringle, M. J.; Rizk, B.; See, C.; Smith, P. H.; Tsetsenekos, K.

    2002-07-01

    The payload of the Huygens Probe into the atmosphere of Titan includes the Descent Imager/Spectral Radiometer (DISR). This instrument includes an integrated package of several optical instruments built around a silicon charge coupled device (CCD) detector, a pair of linear InGaAs array detectors, and several individual silicon detectors. Fiber optics are used extensively to feed these detectors with light collected from three frame imagers, an upward and downward-looking visible spectrometer, an upward and downward looking near-infrared spectrometer, upward and downward looking violet phtotometers, a four-channel solar aerole camera, and a sun sensor that determines the azimuth and zenith angle of the sun and measures the flux in the direct solar beam at 940 nm. An onboard optical calibration system uses a small lamp and fiber optics to track the relative sensitivity of the different optical instruments relative to each other during the seven year cruise to Titan. A 20 watt lamp and collimator are used to provide spectrally continuous illumination of the surface during the last 100 m of the descent for measurements of the reflection spectrum of the surface. The instrument contains software and hardware data compressors to permit measurements of upward and downward direct and diffuse solar flux between 350 and 1700 nm in some 330 spectral bands at approximately 2 km vertical resolution from an alititude of 160 km to the surface. The solar aureole camera measures the brightness of a 6° wide strip of the sky from 25 to 75° zenith angle near and opposite the azimuth of the sun in two passbands near 500 and 935 nm using vertical and horizontal polarizers in each spectral channel at a similar vertical resolution. The downward-looking spectrometers provide the reflection spectrum of the surface at a total of some 600 locations between 850 and 1700 nm and at more than 3000 locations between 480 and 960 nm. Some 500 individual images of the surface are expected which can

  8. Complementary optical and nuclear imaging of caspase-3 activity using combined activatable and radio-labeled multimodality molecular probe

    NASA Astrophysics Data System (ADS)

    Lee, Hyeran; Akers, Walter J.; Cheney, Philip P.; Edwards, W. Barry; Liang, Kexian; Culver, Joseph P.; Achilefu, Samuel

    2009-07-01

    Based on the capability of modulating fluorescence intensity by specific molecular events, we report a new multimodal optical-nuclear molecular probe with complementary reporting strategies. The molecular probe (LS498) consists of tetraazacyclododecanetetraacetic acid (DOTA) for chelating a radionuclide, a near-infrared fluorescent dye, and an efficient quencher dye. The two dyes are separated by a cleavable peptide substrate for caspase-3, a diagnostic enzyme that is upregulated in dying cells. LS498 is radiolabeled with 64Cu, a radionuclide used in positron emission tomography. In the native form, LS498 fluorescence is quenched until caspase-3 cleavage of the peptide substrate. Enzyme kinetics assay shows that LS498 is readily cleaved by caspase-3, with excellent enzyme kinetic parameters kcat and KM of 0.55+/-0.01 s-1 and 1.12+/-0.06 μM, respectively. In mice, the initial fluorescence of LS498 is ten-fold less than control. Using radiolabeled 64Cu-LS498 in a controlled and localized in-vivo model of caspase-3 activation, a time-dependent five-fold NIR fluorescence enhancement is observed, but radioactivity remains identical in caspase-3 positive and negative controls. These results demonstrate the feasibility of using radionuclide imaging for localizing and quantifying the distribution of molecular probes and optical imaging for reporting the functional status of diagnostic enzymes.

  9. Azobenzene-caged sulforhodamine dyes: a novel class of ‘turn-on’ reactive probes for hypoxic tumor cell imaging

    NASA Astrophysics Data System (ADS)

    Chevalier, Arnaud; Piao, Wen; Hanaoka, Kenjiro; Nagano, Tetsuo; Renard, Pierre-Yves; Romieu, Anthony

    2015-12-01

    New sulforhodamine-based fluorescent ‘turn-on’ probes have been developed for the direct imaging of cellular hypoxia. Rapid access to this novel class of water-soluble ‘azobenzene-caged’ fluorophores was made possible through an easily-implementable azo-coupling reaction between a fluorescent primary arylamine derived from a sulforhodamine 101 scaffold (named SR101-NaphtNH 2 ) and a tertiary aniline whose N-substituents are neutral, cationic, or zwitterionic. The detection mechanism is based on the bioreductive cleavage of the azo bond that restores strong far-red fluorescence (emission maximum at 625 nm) by regenerating the original sulforhodamine SR101-NaphtNH 2 . This valuable fluorogenic response was obtained for the three ‘smart’ probes studied in this work, as shown by an in vitro assay using rat liver microsomes placed under aerobic and then under hypoxic conditions. Most importantly, the probe namely SR101-NaphtNH 2 -Hyp-diMe was successfully applied for imaging the hypoxic status of tumor cells (A549 cells).

  10. Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates

    PubMed Central

    Cole, Graham B.; Keum, Gyochang; Liu, Jie; Small, Gary W.; Satyamurthy, Nagichettiar; Kepe, Vladimir; Barrio, Jorge R.

    2010-01-01

    This work focuses on the development of specific substrates for estrogen sulfotransferase (SULT1E1) to produce molecular imaging probes for this enzyme. SULT1E1 is a key enzyme in estrogen homeostasis, playing a central role in the prevention and development of human disease. In vitro sulfation assays showed alkyl and aryl substitutions to a fused heterocyclic system modeled after β-naphthol (βN), based on compounds that interact with the estrogen receptor, rendered several molecules with enhanced specificity for SULT1E1 over SULT1A1*1, SULT1A1*2, SULT1A3, and SULT2A1. Several 6-hydroxy-2-arylbenzothiazoles tested demonstrated excellent affinity—Vmax/Km ratios—and specificity for SULT1E1. Km values ranged from 0.12–2.36 μM. A strong correlation was observed between polarity of the 4′-sustituent on the 2-aryl moiety (Hammett σp) and the log(Vmax/Km) (r = 0.964). Substrate sensitivity is influenced by the acidity of the 6-phenolic group demonstrated by correlating its 1H NMR chemical shift (δOH) with the log(Vmax/Km) (r = 0.963). Acidity is mediated by the electron withdrawing capacity of the 4′-substituent outlined by the correlation of the C-2 13C NMR chemical shift (δC2) with the log(Vmax/Km) (r = 0.987). 2-[4-(Methylamino)phenyl]-6-hydroxybenzothiazole (2b) was radiolabeled with carbon-11 (11C-(2b)) and used in vivo for microPET scanning and tissue metabolite identification. High PET signal was paralleled with the presence of radiolabeled 11C-(2b)-6-O-sulfate and the SULT1E1 protein detected by western blot. Because this and other members of this family presenting specificity for SULT1E1 can be labeled with carbon-11 or fluorine-18, in vivo assays of SULT1E1 functional activity are now feasible in humans. PMID:20304798

  11. Non-contact high resolution Bessel beam probe for diagnostic imaging of cornea and trabecular meshwork region in eye

    NASA Astrophysics Data System (ADS)

    Murukeshan, V. M.; Jesmond, Hong Xun J.; Shinoj, V. K.; Baskaran, M.; Tin, Aung

    2015-07-01

    Primary angle closure glaucoma is a major form of disease that causes blindness in Asia and worldwide. In glaucoma, irregularities in the ocular aqueous outflow system cause an elevation in intraocular pressure (IOP) with subsequent death of retinal ganglion cells, resulting in loss of vision. High resolution visualization of the iridocorneal angle region has great diagnostic value in understanding the disease condition which enables monitoring of surgical interventions that decrease IOP. None of the current diagnostic techniques such as goniophotography, ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (AS-OCT) and RetCam™ can image with molecular specificity and required spatial resolution that can delineate the trabecular meshwork structures. This paper in this context proposes new concepts and methodology using Bessel beams based illumination and imaging for such diagnostic ocular imaging applications. The salient features using Bessel beams instead of the conventional Gaussian beam, and the optimization challenges in configuring the probe system will be illustrated with porcine eye samples.

  12. DNA and RNA "traffic lights": synthetic wavelength-shifting fluorescent probes based on nucleic acid base substitutes for molecular imaging.

    PubMed

    Holzhauser, Carolin; Wagenknecht, Hans-Achim

    2013-08-01

    The DNA base substitute approach by the (S)-3-amino-1,2-propanediol linker allows placing two fluorophores in a precise way inside a given DNA framework. The double helical architecture around the fluorophores, especially the DNA-induced twist, is crucial for the desired photophysical interactions. Excitonic, excimer, and energy transfer interactions yield fluorescent DNA and RNA probes with dual emission color readout. Especially, our DNA and RNA "traffic light" that combines the green emission of TO with the red emission of TR represents an important tool for molecular imaging and can be applied as aptasensors and as probes to monitor the siRNA delivery into cells. The concept can be extended to the synthetically easier to access postsynthetic 2'-modifications and the NIR range. Thereby, the pool of tailor-made fluorescent nucleic acid conjugates can be extended. PMID:23796243

  13. Near-infrared fluorescence probe for the determination of acid phosphatase and imaging of prostate cancer cells.

    PubMed

    Lin, Zihan; Liu, Ziping; Zhang, Hao; Su, Xingguang

    2015-03-01

    In this paper, we developed a near-infrared mercaptopropionic acid (MPA)-capped CuInS2 quantum dot (QD) fluorescence probe for the detection of acid phosphatases (ACP), which is an important biomarker and indicator of prostate cancer. The fluorescence of CuInS2 QDs could be quenched by Cu(2+), and then the addition of adenosine-5'-triphosphate (ATP) could effectively turn on the quenched fluorescence due to the strong interaction between Cu(2+) and ATP. The ACP could catalyze the hydrolysis of ATP, which would disassemble the complex of Cu(2+)-ATP. Therefore, the recovered fluorescence could be quenched again by the addition of ACP. In our method, the limit of detection (LOD) is considerably low for ACP detection in solution. Using the CuInS2 QDs fluorescence probe, we successfully performed in vitro imaging of human prostate cancer cells. PMID:25632410

  14. Mitochondria-Targeted Fluorescent Probe for Imaging Hydrogen Peroxide in Living Cells.

    PubMed

    Xu, Jian; Zhang, Yan; Yu, Hui; Gao, Xudong; Shao, Shijun

    2016-01-19

    Hydrogen peroxide (H2O2), as a type of reactive oxygen species (ROS), can be endogenously produced from the mitochondrial electron transport chain in aerobic respiration and plays important roles in several physiological processes. However, the design and synthesis of fluorescent probes, which can detect mitochondrial H2O2 in living cells, still remain rare. Herein, we report the preparation of a novel cationic probe 1 (Mito-H2O2), which targets the mitochondria in living cells and is sensitive to the presence of H2O2. The probe Mito-H2O2 displays desired properties such as high specificity, "Turn-On" fluorescence response with suitable sensitivity, appreciable water solubility, and rapid response time (within 5 min). The sensing mechanism was confirmed by high-resolution mass spectroscopy analysis, and the mechanism of "Turn-On" fluorescent response was also determined using a density functional theory (DFT) calculation method. Moreover, as a biocompatible molecule, the probe Mito-H2O2 has been successfully applied for the detection of the intrinsically generated intracellular H2O2 in living cells, and the fluorescence colocalization studies indicate that the probe localizes solely in the mitochondria of HeLa cells. PMID:26695451

  15. Imaging of caspase-3 activation by a novel FRET probe composed of CFP and DsRed

    NASA Astrophysics Data System (ADS)

    Lin, Juquiang; Zhang, Zhihong; Liu, Bifeng; Luo, Qingming

    2006-01-01

    Caspases-3 is a kind of cysteine proteases and plays an important role in cell apoptosis. It has been reported that caspase-3 activation can be real-time detected in living cells by fluorescence resonance energy transfer (FRET) between an enhanced cyan fluorescent protein and enhanced yellow fluorescent protein. However, the large spectral overlap between cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) emission and the highly sensitivity to pH of YFP restricted their detecting sensitivity and reliability. CFP and red fluorescent protein (DsRed) possess superb wavelength separation of donor and acceptor emission spectra and DsRed was insensitive to pH, so the FRET probe composed of CFP and DsRed would be more suitable for imaging caspase-3 activation than the FRET probe composed of CFP and YFP. We constructed a vector that encoded CRS (caspase-3 recognition site) fused with CFP and DsRed (CFP-CRS-DsRed). In CFP-CRS-DsRed expressing tumor cells, FRET from CFP to DsRed could be detected. In the Clinical applications of cancer chemotherapy, cisplatin is one of the most broadly used drugs. It was already confirmed that caspase-3 was activated in HeLa cell treated by cisplatin. When the cells were stimulated with cisplatin, we found that the FRET efficient was remarkably decreased and then disappeared. It indicated that actived caspase-3 cleaved the CFP-CRS-DsRed fusion protein at CRS site. Thus, the FRET probe of CFP-CRS-DsRed could sensitively and reliably monitor caspase-3 activation in living cell. This probe will be highly useful for rapid-screening potential drugs that may target the apoptotic process and for imaging tumors in vivo.

  16. Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats.

    PubMed

    Kojima, Ryosuke; Takakura, Hideo; Kamiya, Mako; Kobayashi, Eiji; Komatsu, Toru; Ueno, Tasuku; Terai, Takuya; Hanaoka, Kenjiro; Nagano, Tetsuo; Urano, Yasuteru

    2015-12-01

    A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3 H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes. PMID:26474404

  17. Development of novel FP-based probes for live-cell imaging of nitric oxide dynamics

    PubMed Central

    Eroglu, Emrah; Gottschalk, Benjamin; Charoensin, Suphachai; Blass, Sandra; Bischof, Helmut; Rost, Rene; Madreiter-Sokolowski, Corina T.; Pelzmann, Brigitte; Bernhart, Eva; Sattler, Wolfgang; Hallström, Seth; Malinski, Tadeusz; Waldeck-Weiermair, Markus; Graier, Wolfgang F.; Malli, Roland

    2016-01-01

    Nitric oxide () is a free radical with a wide range of biological effects, but practically impossible to visualize in single cells. Here we report the development of novel multicoloured fluorescent quenching-based probes by fusing a bacteria-derived -binding domain close to distinct fluorescent protein variants. These genetically encoded probes, referred to as geNOps, provide a selective, specific and real-time read-out of cellular dynamics and, hence, open a new era of bioimaging. The combination of geNOps with a Ca2+ sensor allowed us to visualize and Ca2+ signals simultaneously in single endothelial cells. Moreover, targeting of the probes was used to detect signals within mitochondria. The geNOps are useful new tools to further investigate and understand the complex patterns of signalling on the single (sub)cellular level. PMID:26842907

  18. Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian-Cancer-Specific γ-Glutamyltranspeptidase.

    PubMed

    Wang, Feiyi; Zhu, Ying; Zhou, Li; Pan, Liang; Cui, Zhifen; Fei, Qiang; Luo, Sihang; Pan, Dun; Huang, Qing; Wang, Rui; Zhao, Chunchang; Tian, He; Fan, Chunhai

    2015-06-15

    γ-Glutamyltranspeptidase (GGT) is a tumor biomarker that selectively catalyzes the cleavage of glutamate overexpressed on the plasma membrane of tumor cells. Here, we developed two novel fluorescent in situ targeting (FIST) probes that specifically target GGT in tumor cells, which comprise 1) a GGT-specific substrate unit (GSH), and 2) a boron-dipyrromethene (BODIPY) moiety for fluorescent signalling. In the presence of GGT, sulfur-substituted BODIPY was converted to amino-substituted BODIPY, resulting in dramatic fluorescence variations. By exploiting this enzyme-triggered photophysical property, we employed these FIST probes to monitor the GGT activity in living cells, which showed remarkable differentiation between ovarian cancer cells and normal cells. These probes represent two first-generation chemodosimeters featuring enzyme-mediated rapid, irreversible aromatic hydrocarbon transfer between the sulfur and nitrogen atoms accompanied by switching of photophysical properties. PMID:25940513

  19. An Evanescent Microwave Probe for Super-Resolution Nondestructive Imaging of Metals, Semiconductors, Dielectrics, Composites and Biological Specimens

    NASA Technical Reports Server (NTRS)

    Pathak, P. S.; Tabib-Azar, M.; Ponchak, G.

    1998-01-01

    Using evanescent microwaves with decay lengths determined by a combination of microwave wavelength (lambda) and waveguide termination geometry, we have imaged and mapped material non-uniformities and defects with a resolving capability of lambda/3800=79 microns at 1 GHz. In our method a microstrip quarter wavelength resonator was used to generate evanescent microwaves. We imaged materials with a wide range of conductivities. Carbon composites, dielectrics (Duroid, polymers), semiconductors (3C-SiC, polysilicon, natural diamond), metals (tungsten alloys, copper, zinc, steel), high-temperature superconductors, and botanical samples were scanned for defects, residual stresses, integrity of brazed junctions, subsurface features, areas of different film thickness and moisture content. The evanescent microwave probe is a versatile tool and it can be used to perform very fast, large scale mapping of a wide range of materials. This method of characterization compares favorably with ultrasound testing, which has a resolution of about 0.1 mm and suffers from high absorption in composite materials and poor transmission across boundaries. Eddy current methods which can have a resolution on the order of 50 microns are restricted to evaluating conducting materials. Evanescent microwave imaging, with careful choice of operating frequency and probe geometry, can have a resolution of up to 1 micron. In this method we can scan hot and moving objects, sample preparation is not required, testing is non-destructive, non-invasive and non-contact, and can be done in air, in liquid or in vacuum.

  20. Coronal in vivo forward-imaging of rat brain morphology with an ultra-small optical coherence tomography fiber probe

    NASA Astrophysics Data System (ADS)

    Xie, Yijing; Bonin, Tim; Löffler, Susanne; Hüttmann, Gereon; Tronnier, Volker; Hofmann, Ulrich G.

    2013-02-01

    A well-established navigation method is one of the key conditions for successful brain surgery: it should be accurate, safe and online operable. Recent research shows that optical coherence tomography (OCT) is a potential solution for this application by providing a high resolution and small probe dimension. In this study a fiber-based spectral-domain OCT system utilizing a super-luminescent-diode with the center wavelength of 840 nm providing 14.5 μm axial resolution was used. A composite 125 μm diameter detecting probe with a gradient index (GRIN) fiber fused to a single mode fiber was employed. Signals were reconstructed into grayscale images by horizontally aligning A-scans from the same trajectory with different depths. The reconstructed images can display brain morphology along the entire trajectory. For scans of typical white matter, the signals showed a higher reflection of light intensity with lower penetration depth as well as a steeper attenuation rate compared to the scans typical for gray matter. Micro-structures such as axon bundles (70 μm) in the caudate nucleus are visible in the reconstructed images. This study explores the potential of OCT to be a navigation modality in brain surgery.

  1. (68)Ga/DOTA- and (64)Cu/NOTA-phthalocyanine conjugates as fluorescent/PET bimodal imaging probes.

    PubMed

    Ranyuk, Elena; Lebel, Réjean; Bérubé-Lauzière, Yves; Klarskov, Klaus; Lecomte, Roger; van Lier, Johan E; Guérin, Brigitte

    2013-09-18

    In this paper, we describe the synthesis and characterization of a series of new bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a fluorescence imaging unit and either (68)Ga/1,4,7,10-tetraazocyclododecane-N,N'N″,N'″-tetraacetic acid (DOTA) or (64)Cu/1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for PET imaging. The two moieties were linked through aliphatic chains of different lengths to modulate amphiphilicity. Labeling of DOTA- or NOTA-ZnPc conjugates with (68)Ga (t1/2 = 68 min) and (64)Cu (t1/2 = 12.7 h) was performed at 100 °C for 15 min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the (64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the (68)Ga/DOTA-ZnPc conjugate, which released up to 7% of free (68)Ga over a 3 h period. Based on in vitro plasma stability results, we performed biodistribution studies on two (64)Cu-labeled derivatives, which allowed us to select a single candidate for preliminary in vivo experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes. PMID:23978056

  2. Novel B,O-chelated fluorescent probe for nitric oxide imaging in Raw 264.7 macrophages and onion tissues.

    PubMed

    Chen, Jian-Bo; Zhang, Hui-Xian; Guo, Xiao-Feng; Wang, Hong; Zhang, Hua-Shan

    2013-10-24

    A novel fluorescent probe based on B,O-chelated dipyrromethene chromophore in far-visible and near-infrared spectral region (600-900 nm), boron chelated 8-(3,4-diaminophenyl)-3,5-bis(2-hydroxyphenyl)-4-bora-3a,4a-diaza-s-indancene (BOPB), has been first developed for nitric oxide (NO) imaging. BOPB, a turn-on fluorescent probe, can react with NO rapidly under physiological condition. The reaction product of BOPB with NO, BOPB-T, emits bright red fluorescence at 643 nm when excited at 622 nm. Meanwhile, BOPB-T displays high fluorescent quantum yield of 0.21 and good photostability. The selectivity for NO over other reactive oxygen/nitrogen species and ascorbic acid has been investigated and BOPB has good specificity for the detection of NO. MTT assay shows that the toxicity of BOPB (below 10 μM) to living cells can be neglected. Based on these investigations, BOPB has been used for NO imaging in Raw 264.7 cells and onion tissues. Meanwhile, mechanical injury to onion tissues results in a brighter fluorescence around the wound, which indicates that more NO has been produced in plant tissues in response to external stimuli. Our studies illustrate that BOPB has advantages of high sensitivity, low background interference and little photo damage on fluorescence imaging of NO. PMID:24120171

  3. Use of a Novel Rover-mounted Fluorescence Imager and Fluorescent Probes to Detect Biological Material in the Atacama Desert in Daylight

    NASA Technical Reports Server (NTRS)

    Weinstein, S.; Pane, D.; Warren-Rhodes, K.; Cockell, C.; Ernst, L. A.; Minkley, E.; Fisher, G.; Emani, S.; Wettergreen, D. S.; Wagner, M.

    2005-01-01

    We have developed an imaging system, the Fluorescence Imager (FI), for detecting fluorescence signals from sparse microorganisms and biofilms during autonomous rover exploration. The fluorescence signals arise both from naturally occurring chromophores, such as chlorophyll of cyanobacteria and lichens, and from fluorescent probes applied to soil and rocks. Daylight imaging has been accomplished by a novel use of a high-powered flashlamp synchronized to a CCD camera. The fluorescent probes are cell permanent stains that have extremely low intrinsic fluorescence (quantum yields less than 0.01) and a large fluorescence enhancement (quantum yields greater than 0.4) when bound to the target. Each probe specifically targets either carbohydrates, proteins, nucleic acids or membrane lipids, the four classes of macromolecules found in terrestrial life. The intent of the probes is to interrogate the environment for surface and endolithic life forms.

  4. Mapping Bronchial Carcinoma In Situ Lung Cancer Lesions By Combined Imaging Fluorescence Bronchoscopy And Ratioing Fluorometer Probe

    NASA Astrophysics Data System (ADS)

    Balchum, Oscar J.; Profio, A. Edward; Razum, Nickolas J.

    1988-06-01

    A two-component system of instrumentation and methods, IFB and RFP, when used in combination employing hematoporphyrin derivates, DHE, had highly satisfactory sensitivity (95%) and specificity (100%) for localizing carcinoma in situ lesions in the bronchi of individuals with early stage lung cancer, having a normal chest x-ray and detected by a positive sputum cytology test. The more detailed mapping of additional subjects may increase the specificity of RFP (Ratioing Fluorometer Probe) by itself to an adequate level. Digital computer subs traction of background antofluorescence may increase contrast to enhance the specificity of IFB (Imaging Fluorescence Bronchoscopy).

  5. Filling a GAP-An Optimized Probe for ER Ca(2+) Imaging In Vivo.

    PubMed

    Malli, Roland; Eroglu, Emrah; Waldeck-Weiermair, Markus; Graier, Wolfgang F

    2016-06-23

    In this issue of Cell Chemical Biology, Navas-Navarro et al. (2016) demonstrate that fusion of engineered derivatives of the long-known jellyfish proteins green fluorescent protein (GFP) and aequorin yield optimized genetically encoded fluorescent probes for detecting Ca(2+) signals within the endoplasmic reticulum (ER) of living animals. PMID:27341431

  6. Development of a high-speed VCSEL OCT system for real-time imaging of conscious patients larynx using a hand-held probe (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Rangarajan, Swathi; Chou, Li-Dek; Coughlan, Carolyn; Sharma, Giriraj; Wong, Brian J. F.; Ramalingam, Tirunelveli S.

    2016-02-01

    Fourier domain optical coherence tomography (FD-OCT) is a noninvasive imaging modality that has previously been used to image the human larynx. However, differences in anatomical geometry and short imaging range of conventional OCT limits its application in a clinical setting. In order to address this issue, we have developed a gradient-index (GRIN) lens rod-based hand-held probe in conjunction with a long imaging range 200 kHz Vertical-Cavity Surface Emitting Lasers (VCSEL) swept-source optical coherence tomography (SS-OCT) system for high speed real-time imaging of the human larynx in an office setting. This hand-held probe is designed to have a long and dynamically tunable working distance to accommodate the differences in anatomical geometry of human test subjects. A nominal working distance (~6 cm) of the probe is selected to have a lateral resolution <100 um within a depth of focus of 6.4 mm, which covers more than half of t