Counting constituents in molecular complexes by fluorescence photon antibunching

Energy Technology Data Exchange (ETDEWEB)

Fore, S; Laurence, T; Hollars, C; Huser, T

2007-04-17

Modern single molecule fluorescence microscopy offers new, highly quantitative ways of studying the systems biology of cells while keeping the cells healthy and alive in their natural environment. In this context, a quantum optical technique, photon antibunching, has found a small niche in the continuously growing applications of single molecule techniques to small molecular complexes. Here, we review some of the most recent applications of photon antibunching in biophotonics, and we provide a guide for how to conduct photon antibunching experiments at the single molecule level by applying techniques borrowed from time-correlated single photon counting. We provide a number of new examples for applications of photon antibunching to the study of multichromophoric molecules and small molecular complexes.

Fluorescence decay time imaging using an imaging photon detector with a radio frequency photon correlation system

Science.gov (United States)

Morgan, Christopher G.; Mitchell, A. C.; Murray, J. G.

1990-05-01

An imaging photon detector has been modified to incorporate fast timing electronics coupled to a custom built photon correlator interfaced to a RISC computer. Using excitation with intensity- muodulated light, fluorescence images can be readily obtained where contrast is determined by the decay time of emission, rather than by intensity. This technology is readily extended to multifrequency phase/demodulation fluorescence imaging or to differential polarised phase fluorometry. The potential use of the correlator for confocal imaging with a laser scanner is also briefly discussed.

Photon Upconversion and Molecular Solar Energy Storage by Maximizing the Potential of Molecular Self-Assembly.

Science.gov (United States)

Kimizuka, Nobuo; Yanai, Nobuhiro; Morikawa, Masa-Aki

2016-11-29

The self-assembly of functional molecules into ordered molecular assemblies and the fulfillment of potentials unique to their nanotomesoscopic structures have been one of the central challenges in chemistry. This Feature Article provides an overview of recent progress in the field of molecular self-assembly with the focus on the triplet-triplet annihilation-based photon upconversion (TTA-UC) and supramolecular storage of photon energy. On the basis of the integration of molecular self-assembly and photon energy harvesting, triplet energy migration-based TTA-UC has been achieved in varied molecular systems. Interestingly, some molecular self-assemblies dispersed in solution or organogels revealed oxygen barrier properties, which allowed TTA-UC even under aerated conditions. The elements of molecular self-assembly were also introduced to the field of molecular solar thermal fuel, where reversible photoliquefaction of ionic crystals to ionic liquids was found to double the molecular storage capacity with the simultaneous pursuit of switching ionic conductivity. A future prospect in terms of innovating molecular self-assembly toward molecular systems chemistry is also discussed.

Photon-momentum transfer in molecular photoionization

Science.gov (United States)

Chelkowski, Szczepan; Bandrauk, André D.

2018-05-01

In most models and theoretical calculations describing multiphoton ionization by infrared light, the dipole approximation is used. This is equivalent to setting the very small photon momentum to zero. Using numerical solutions of the (nondipole) three-dimensional time-dependent Schrödinger equation for one electron in a H2+ molecular ion we investigate the effect the photon-momentum transfer to the photoelectron in an H2+ ion in various regimes. We find that the photon-momentum transfer in a molecule is very different from the transfer in atoms due to two-center interference effects. The photon-momentum transfer is very sensitive to the symmetry of the initial electronic state and is strongly dependent on the internuclear distance and on the ellipticity of the laser.

Molecular Imaging Challenges With PET

CERN Document Server

Lecoq, P

2010-01-01

The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

X-ray photon-in/photon-out methods for chemical imaging

Energy Technology Data Exchange (ETDEWEB)

Marcus, Matthew A.

2010-03-24

Most interesting materials in nature are heterogeneous, so it is useful to have analytical techniques with spatial resolution sufficient to resolve these heterogeneities.This article presents the basics of X-ray photon-in/photon-out chemical imaging. This family of methods allows one to derive images reflectingthe chemical state of a given element in a complex sample, at micron or deep sub-micron scale. X-ray chemical imaging is relatively non-destructiveand element-selective, and requires minimal sample preparation. The article presents the basic concepts and some considerations of data takingand data analysis, along with some examples.

Molecular imaging: a new approach to nuclear cardiology

International Nuclear Information System (INIS)

Dobrucki, L.W.; Sinusas, A.J.

2005-01-01

Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk statification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentations will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutical angiogenesis

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

Science.gov (United States)

Davis, Margaret T.; Holmes, Sophie E.; Pietrzak, Robert H.; Esterlis, Irina

2018-01-01

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress. PMID:29862379

Multiple-Event, Single-Photon Counting Imaging Sensor

Science.gov (United States)

Zheng, Xinyu; Cunningham, Thomas J.; Sun, Chao; Wang, Kang L.

2011-01-01

The single-photon counting imaging sensor is typically an array of silicon Geiger-mode avalanche photodiodes that are monolithically integrated with CMOS (complementary metal oxide semiconductor) readout, signal processing, and addressing circuits located in each pixel and the peripheral area of the chip. The major problem is its single-event method for photon count number registration. A single-event single-photon counting imaging array only allows registration of up to one photon count in each of its pixels during a frame time, i.e., the interval between two successive pixel reset operations. Since the frame time can t be too short, this will lead to very low dynamic range and make the sensor merely useful for very low flux environments. The second problem of the prior technique is a limited fill factor resulting from consumption of chip area by the monolithically integrated CMOS readout in pixels. The resulting low photon collection efficiency will substantially ruin any benefit gained from the very sensitive single-photon counting detection. The single-photon counting imaging sensor developed in this work has a novel multiple-event architecture, which allows each of its pixels to register as more than one million (or more) photon-counting events during a frame time. Because of a consequently boosted dynamic range, the imaging array of the invention is capable of performing single-photon counting under ultra-low light through high-flux environments. On the other hand, since the multiple-event architecture is implemented in a hybrid structure, back-illumination and close-to-unity fill factor can be realized, and maximized quantum efficiency can also be achieved in the detector array.

Ghost imaging with paired x-ray photons

Science.gov (United States)

Schori, A.; Borodin, D.; Tamasaku, K.; Shwartz, S.

2018-06-01

We report the experimental observation of ghost imaging with paired x-ray photons, which are generated by parametric downconversion. We use the one-to-one relation between the photon energies and the emission angles and the anticorrelation between the k -vectors of the signal and the idler photons to reconstruct the images of slits with nominally zero background levels. Further extension of our procedure can be used for the observation of various quantum phenomena at x-ray wavelengths.

Imaging hydrogen flames by two-photon, laser-induced fluorescence

Science.gov (United States)

Miles, R.; Lempert, W.; Kumar, V.; Diskin, G.

1991-01-01

A nonintrusive multicomponent imaging system is developed which can image hydrogen, hot oxygen, and air simultaneously. An Ar-F excimer laser is injection-locked to cover the Q1 two-photon transition in molecular hydrogen which allows the observation of both hot oxygen and cold hydrogen. Rayleigh scattering from the water molecules occurs at the same frequency as the illuminating laser allowing analysis of the air density. Images of ignited and nonignited hydrogen jets are recorded with a high-sensitivity gated video camera. The images permit the analysis of turbulent hydrogen-core jet, the combustion zone, and the surrounding air, and two-dimensional spatial correlations can be made to study the turbulent structure and couplings between different regions of the flow field. The method is of interest to the study of practical combustion systems which employ hydrogen-air diffusion flames.

NIR-emitting molecular-based nanoparticles as new two-photon absorbing nanotools for single particle tracking

Science.gov (United States)

Daniel, J.; Godin, A. G.; Clermont, G.; Lounis, B.; Cognet, L.; Blanchard-Desce, M.

2015-07-01

In order to provide a green alternative to QDs for bioimaging purposes and aiming at designing bright nanoparticles combining both large one- and two-photon brightness, a bottom-up route based on the molecular engineering of dedicated red to NIR emitting dyes that spontaneously form fluorescent organic nanoparticles (FONs) has been implemented. These fully organic nanoparticles built from original quadrupolar dyes are prepared using a simple, expeditious and green protocol that yield very small molecular-based nanoparticles (radius ~ 7 nm) suspension in water showing a nice NIR emission (λem=710 nm). These FONs typically have absorption coefficient more than two orders larger than popular NIR-emitting dyes (such as Alexa Fluor 700, Cy5.5 ….) and much larger Stokes shift values (i.e. up to over 5500 cm-1). They also show very large two-photon absorption response in the 800-1050 nm region (up to about 106 GM) of major promise for two-photon excited fluorescence microscopy. Thanks to their brightness and enhanced photostability, these FONs could be imaged as isolated nanoparticles and tracked using wide-field imaging. As such, thanks to their size and composition (absence of heavy metals), they represent highly promising alternatives to NIR-emitting QDs for use in bioimaging and single particle tracking applications. Moreover, efficient FONs coating was achieved by using a polymeric additive built from a long hydrophobic (PPO) and a short hydrophilic (PEO) segment and having a cationic head group able to interact with the highly negative surface of FONs. This electrostatically-driven interaction promotes both photoluminescence and two-photon absorption enhancement leading to an increase of two-photon brightness of about one order of magnitude. This opens the way to wide-field single particle tracking under two-photon excitation

Molecular photosensitisers for two-photon photodynamic therapy.

Science.gov (United States)

Bolze, F; Jenni, S; Sour, A; Heitz, V

2017-11-30

Two-photon excitation has attracted the attention of biologists, especially after the development of two-photon excited microscopy in the nineties. Since then, new applications have rapidly emerged such as the release of biologically active molecules and photodynamic therapy (PDT) using two-photon excitation. PDT, which requires a light-activated drug (photosensitiser), is a clinically approved and minimally invasive treatment for cancer and for non-malignant diseases. This feature article focuses on the engineering of molecular two-photon photosensitisers for PDT, which should bring important benefits to the treatment, increase the treatment penetration depth with near-infrared light excitation, improve the spatial selectivity and reduce the photodamage to healthy tissues. After an overview of the two-photon absorption phenomenon and the methods to evaluate two-photon induced phototoxicity on cell cultures, the different classes of photosensitisers described in the literature are discussed. The two-photon PDT performed with historical one-photon sensitisers are briefly presented, followed by specifically engineered cyclic tetrapyrrole photosensitisers, purely organic photosensitisers and transition metal complexes. Finally, targeted two-photon photosensitisers and theranostic agents that should enhance the selectivity and efficiency of the treatment are discussed.

Single photon imaging and timing array sensor apparatus and method

Science.gov (United States)

Smith, R. Clayton

2003-06-24

An apparatus and method are disclosed for generating a three-dimension image of an object or target. The apparatus is comprised of a photon source for emitting a photon at a target. The emitted photons are received by a photon receiver for receiving the photon when reflected from the target. The photon receiver determines a reflection time of the photon and further determines an arrival position of the photon on the photon receiver. An analyzer is communicatively coupled to the photon receiver, wherein the analyzer generates a three-dimensional image of the object based upon the reflection time and the arrival position.

Rapid volumetric imaging with Bessel-Beam three-photon microscopy

Science.gov (United States)

Chen, Bingying; Huang, Xiaoshuai; Gou, Dongzhou; Zeng, Jianzhi; Chen, Guoqing; Pang, Meijun; Hu, Yanhui; Zhao, Zhe; Zhang, Yunfeng; Zhou, Zhuan; Wu, Haitao; Cheng, Heping; Zhang, Zhigang; Xu, Chris; Li, Yulong; Chen, Liangyi; Wang, Aimin

2018-01-01

Owing to its tissue-penetration ability, multi-photon fluorescence microscopy allows for the high-resolution, non-invasive imaging of deep tissue in vivo; the recently developed three-photon microscopy (3PM) has extended the depth of high-resolution, non-invasive functional imaging of mouse brains to beyond 1.0 mm. However, the low repetition rate of femtosecond lasers that are normally used in 3PM limits the temporal resolution of point-scanning three-photon microscopy. To increase the volumetric imaging speed of 3PM, we propose a combination of an axially elongated needle-like Bessel-beam with three-photon excitation (3PE) to image biological samples with an extended depth of focus. We demonstrate the higher signal-to-background ratio (SBR) of the Bessel-beam 3PM compared to the two-photon version both theoretically and experimentally. Finally, we perform simultaneous calcium imaging of brain regions at different axial locations in live fruit flies and rapid volumetric imaging of neuronal structures in live mouse brains. These results highlight the unique advantage of conducting rapid volumetric imaging with a high SBR in the deep brain in vivo using scanning Bessel-3PM.

Microsphere imaging with confocal microscopy and two photon microscopy

International Nuclear Information System (INIS)

Chun, Hyung Su; An, Kyung Won; Lee, Jai Hyung

2002-01-01

We have acquired images of polystyrene and fused-silica microsphere by using conventional optical microscopy, confocal microscopy and two-photon microscopy, and performed comparative analysis of these images. Different from conventional optical microscopy, confocal and two-photon microscopy had good optical sectioning capability. In addition, confocal microscopy and two-photon microscopy had better lateral resolution than conventional optical microscopy. These results are attributed to confocality and nonlinearity of confocal microscopy and two photon microscopy, respectively.

The performance of photon counting imaging with a Geiger mode silicon avalanche photodiode

International Nuclear Information System (INIS)

Qu, Hui-Ming; Zhang, Yi-Fan; Ji, Zhong-Jie; Chen, Qian

2013-01-01

In principle, photon counting imaging can detect a photon. With the development of low-level-light image intensifier techniques and low-level-light detection devices, photon counting imaging can now detect photon images under extremely low illumination. Based on a Geiger mode silicon avalanche photodiode single photon counter, an experimental system for photon counting imaging was built through two-dimensional scanning of a SPAD (single photon avalanche diode) detector. The feasibility of the imaging platform was validated experimentally. Two images with different characteristics, namely, the USAF 1951 resolution test panel and the image of Lena, were chosen to evaluate the imaging performance of the experimental system. The results were compared and analysed. The imaging properties under various illumination and scanning steps were studied. The lowest illumination limit of the SPAD photon counting imaging was determined. (letter)

Progress on molecular imaging

International Nuclear Information System (INIS)

Chen Quan; Zhang Yongxue

2011-01-01

Molecular imaging is a new era of medical imaging,which can non-invasively monitor biological processes at the cellular and molecular level in vivo, including molecular imaging of nuclear medicine, magnetic resonance molecular imaging, ultrasound molecular imaging,optical molecular imaging and molecular imaging with X-ray. Recently, with the development of multi-subjects amalgamation, multimodal molecular imaging technology has been applied in clinical imaging, such as PET-CT and PET-MRI. We believe that with development of molecular probe and multi-modal imaging, more and more molecular imaging techniques will be applied in clinical diagnosis and treatment. (authors)

Single photon image from PET with insertable collimator for boron neutron capture therapy

International Nuclear Information System (INIS)

Jung, Jooyoung; Suh, Tae Suk; Hong, Key Jo

2014-01-01

Boron neutron capture therapy (BNCT) is a radiation therapy technique for treating deep-seated brain tumors by irradiation with a thermal neutron in which boron-labelled low molecular weight compounds. Once completed, a single photon emission computed tomography (SPECT) scan is conducted to investigate for the region of therapy using an isotope exclusive to SPECT. In the case of an existing PET/SPECT combination system, at least two types of isotopes should be used for each scan with their purposes. Recently, researchers examined the effects of PET/SPECT dual modality on animal imaging systems. They reported that the PET/SPECT combination system was effective for simultaneous achievement of a single event and coincidence. The aim of our proposed system is to confirm the feasibility of extraction of two types of images from one PET module with an insertable collimator for brain tumor treatment during the BNCT. We attempted to acquire the PET and SPECT images simultaneously using only PET without an additional isotope. Single photon images were acquired using an insertable collimator on a PET detector

Two-Photon Ghost Image and Interference-Diffraction

Science.gov (United States)

Shih, Y. H.; Sergienko, A. V.; Pittman, T. B.; Strekalov, D. V.; Klyshko, D. N.

1996-01-01

One of the most surprising consequences of quantum mechanics is entanglement of two or more distance particles. The two-particle entangled state was mathematically formulated by Schrodinger. Based on this unusual quantum behavior, EPR defined their 'physical reality' and then asked the question: 'Can Quantum-Mechanical Description of Physical Reality Be Considered Complete?' One may not appreciate EPR's criterion of physical reality and insist that 'no elementary quantum phenomenon is a phenomenon until it is a recorded phenomenon'. Optical spontaneous parametric down conversion (SPDC) is the most effective mechanism to generate an EPR type entangled two-photon state. In SPDC, an optical beam, called the pump, is incident on a birefringent crystal. The pump is intense enough so that nonlinear effects lead to the conversion of pump photons into pairs of photons, historically called signal and idler. Technically, the SPDC is said to be type-1 or type-2, depending on whether the signal and idler beams have parallel or orthogonal polarization. The SPDC conversion efficiency is typically on the order of 10(exp -9) to 10(exp -11), depending on the SPDC nonlinear material. The signal and idler intensities are extremely low, only single photon detection devices can register them. The quantum entanglement nature of SPDC has been demonstrated in EPR-Bohm experiments and Bell's inequality measurements. The following two experiments were recently performed in our laboratory, which are more closely related to the original 1935 EPR gedankenezperiment. The first experiment is a two-photon optical imaging type experiment, which has been named 'ghost image' by the physics community. The signal and idler beams of SPDC are sent in different directions, so that the detection of the signal and idler photons can be performed by two distant photon counting detectors. An aperture object (mask) is placed in front of the signal photon detector and illuminated by the signal beam through a

Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging

International Nuclear Information System (INIS)

Ntziachristos, Vasilis; Bremer, Christoph; Weissleder, Ralph

2003-01-01

A recent development in biomedical imaging is the non-invasive mapping of molecular events in intact tissues using fluorescence. Underpinning to this development is the discovery of bio-compatible, specific fluorescent probes and proteins and the development of highly sensitive imaging technologies for in vivo fluorescent detection. Of particular interest are fluorochromes that emit in the near infrared (NIR), a spectral window, whereas hemoglobin and water absorb minimally so as to allow photons to penetrate for several centimetres in tissue. In this review article we concentrate on optical imaging technologies used for non-invasive imaging of the distribution of such probes. We illuminate the advantages and limitations of simple photographic methods and turn our attention to fluorescence-mediated molecular tomography (FMT), a technique that can three-dimensionally image gene expression by resolving fluorescence activation in deep tissues. We describe theoretical specifics, and we provide insight into its in vivo capacity and the sensitivity achieved. Finally, we discuss its clinical feasibility. (orig.)

Applications of two-photon fluorescence microscopy in deep-tissue imaging

Science.gov (United States)

Dong, Chen-Yuan; Yu, Betty; Hsu, Lily L.; Kaplan, Peter D.; Blankschstein, D.; Langer, Robert; So, Peter T. C.

2000-07-01

Based on the non-linear excitation of fluorescence molecules, two-photon fluorescence microscopy has become a significant new tool for biological imaging. The point-like excitation characteristic of this technique enhances image quality by the virtual elimination of off-focal fluorescence. Furthermore, sample photodamage is greatly reduced because fluorescence excitation is limited to the focal region. For deep tissue imaging, two-photon microscopy has the additional benefit in the greatly improved imaging depth penetration. Since the near- infrared laser sources used in two-photon microscopy scatter less than their UV/glue-green counterparts, in-depth imaging of highly scattering specimen can be greatly improved. In this work, we will present data characterizing both the imaging characteristics (point-spread-functions) and tissue samples (skin) images using this novel technology. In particular, we will demonstrate how blind deconvolution can be used further improve two-photon image quality and how this technique can be used to study mechanisms of chemically-enhanced, transdermal drug delivery.

Optical-based molecular imaging: contrast agents and potential medical applications

International Nuclear Information System (INIS)

Bremer, Christoph; Ntziachristos, Vasilis; Weissleder, Ralph

2003-01-01

Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in ''European Radiology'' [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. (orig.)

Three-photon imaging of ovarian cancer

Science.gov (United States)

Barton, Jennifer K.; Amirsolaimani, Babak; Rice, Photini; Hatch, Kenneth; Kieu, Khanh

2016-02-01

Optical imaging methods have the potential to detect ovarian cancer at an early, curable stage. Optical imaging has the disadvantage that high resolution techniques require access to the tissue of interest, but miniature endoscopes that traverse the natural orifice of the reproductive tract, or access the ovaries and fallopian tubes through a small incision in the vagina wall, can provide a minimally-invasive solution. We have imaged both rodent and human ovaries and fallopian tubes with a variety of endoscope-compatible modalities. The recent development of fiber-coupled femtosecond lasers will enable endoscopic multiphoton microscopy (MPM). We demonstrated two- and three-photon excited fluorescence (2PEF, 3PEF), and second- and third-harmonic generation microscopy (SHG, THG) in human ovarian and fallopian tube tissue. A study was undertaken to understand the mechanisms of contrast in these images. Six patients (normal, cystadenoma, and ovarian adenocarcinoma) provided ovarian and fallopian tube biopsies. The tissue was imaged with three-dimensional optical coherence tomography, multiphoton microscopy, and frozen for histological sectioning. Tissue sections were stained with hematoxylin and eosin, Masson's trichrome, and Sudan black. Approximately 1 μm resolution images were obtained with an excitation source at 1550 nm. 2PEF signal was absent. SHG signal was mainly from collagen. 3PEF and THG signal came from a variety of sources, including a strong signal from fatty connective tissue and red blood cells. Adenocarcinoma was characterized by loss of SHG signal, whereas cystic abnormalities showed strong SHG. There was limited overlap of two- and three- photon signals, suggesting that three-photon imaging can provide additional information for early diagnosis of ovarian cancer.

Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

International Nuclear Information System (INIS)

Bowsher, James; Giles, William; Yin, Fang-Fang; Yan, Susu; Roper, Justin

2014-01-01

Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

Energy Technology Data Exchange (ETDEWEB)

Bowsher, James, E-mail: james.bowsher@duke.edu; Giles, William; Yin, Fang-Fang [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Yan, Susu [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Roper, Justin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

2014-01-15

Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

Musculoskeletal imaging with a prototype photon-counting detector.

Science.gov (United States)

Gruber, M; Homolka, P; Chmeissani, M; Uffmann, M; Pretterklieber, M; Kainberger, F

2012-01-01

To test a digital imaging X-ray device based on the direct capture of X-ray photons with pixel detectors, which are coupled with photon-counting readout electronics. The chip consists of a matrix of 256 × 256 pixels with a pixel pitch of 55 μm. A monolithic image of 11.2 cm × 7 cm was obtained by the consecutive displacement approach. Images of embalmed anatomical specimens of eight human hands were obtained at four different dose levels (skin dose 2.4, 6, 12, 25 μGy) with the new detector, as well as with a flat-panel detector. The overall rating scores for the evaluated anatomical regions ranged from 5.23 at the lowest dose level, 6.32 at approximately 6 μGy, 6.70 at 12 μGy, to 6.99 at the highest dose level with the photon-counting system. The corresponding rating scores for the flat-panel detector were 3.84, 5.39, 6.64, and 7.34. When images obtained at the same dose were compared, the new system outperformed the conventional DR system at the two lowest dose levels. At the higher dose levels, there were no significant differences between the two systems. The photon-counting detector has great potential to obtain musculoskeletal images of excellent quality at very low dose levels.

Single Photon Counting Performance and Noise Analysis of CMOS SPAD-Based Image Sensors

Science.gov (United States)

Dutton, Neale A. W.; Gyongy, Istvan; Parmesan, Luca; Henderson, Robert K.

2016-01-01

SPAD-based solid state CMOS image sensors utilising analogue integrators have attained deep sub-electron read noise (DSERN) permitting single photon counting (SPC) imaging. A new method is proposed to determine the read noise in DSERN image sensors by evaluating the peak separation and width (PSW) of single photon peaks in a photon counting histogram (PCH). The technique is used to identify and analyse cumulative noise in analogue integrating SPC SPAD-based pixels. The DSERN of our SPAD image sensor is exploited to confirm recent multi-photon threshold quanta image sensor (QIS) theory. Finally, various single and multiple photon spatio-temporal oversampling techniques are reviewed. PMID:27447643

TU-G-207-01: CT Imaging Using Energy-Sensitive Photon-Counting Detectors

International Nuclear Information System (INIS)

Taguchi, K.

2015-01-01

Last few years has witnessed the development of novel of X-ray imaging modalities, such as spectral CT, phase contrast CT, and X-ray acoustic/fluorescence/luminescence imaging. This symposium will present the recent advances of these emerging X-ray imaging modalities and update the attendees with knowledge in various related topics, including X-ray photon-counting detectors, X-ray physics underlying the emerging applications beyond the traditional X-ray imaging, image reconstruction for the novel modalities, characterization and evaluation of the systems, and their practical implications. In addition, the concept and practical aspects of X-ray activatable targeted nanoparticles for molecular X-ray imaging will be discussed in the context of X-ray fluorescence and luminescence CT. Learning Objectives: Present background knowledge of various emerging X-ray imaging techniques, such as spectral CT, phase contrast CT and X-ray fluorescence/luminescence CT. Discuss the practical need, technical aspects and current status of the emerging X-ray imaging modalities. Describe utility and future impact of the new generation of X-ray imaging applications

In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH.

Science.gov (United States)

Yaseen, Mohammad A; Sakadžić, Sava; Wu, Weicheng; Becker, Wolfgang; Kasischke, Karl A; Boas, David A

2013-02-01

Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism.

Current applications of molecular imaging and luminescence-based techniques in traditional Chinese medicine.

Science.gov (United States)

Li, Jinhui; Wan, Haitong; Zhang, Hong; Tian, Mei

2011-09-01

Traditional Chinese medicine (TCM), which is fundamentally different from Western medicine, has been widely investigated using various approaches. Cellular- or molecular-based imaging has been used to investigate and illuminate the various challenges identified and progress made using therapeutic methods in TCM. Insight into the processes of TCM at the cellular and molecular changes and the ability to image these processes will enhance our understanding of various diseases of TCM and will provide new tools to diagnose and treat patients. Various TCM therapies including herbs and formulations, acupuncture and moxibustion, massage, Gua Sha, and diet therapy have been analyzed using positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and ultrasound and optical imaging. These imaging tools have kept pace with developments in molecular biology, nuclear medicine, and computer technology. We provide an overview of recent developments in demystifying ancient knowledge - like the power of energy flow and blood flow meridians, and serial naturopathies - which are essential to visually and vividly recognize the body using modern technology. In TCM, treatment can be individualized in a holistic or systematic view that is consistent with molecular imaging technologies. Future studies might include using molecular imaging in conjunction with TCM to easily diagnose or monitor patients naturally and noninvasively. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cardiovascular Molecular Imaging

International Nuclear Information System (INIS)

Lee, Kyung Han

2009-01-01

Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis. Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field

Photon-Counting Arrays for Time-Resolved Imaging

Directory of Open Access Journals (Sweden)

I. Michel Antolovic

2016-06-01

Full Text Available The paper presents a camera comprising 512 × 128 pixels capable of single-photon detection and gating with a maximum frame rate of 156 kfps. The photon capture is performed through a gated single-photon avalanche diode that generates a digital pulse upon photon detection and through a digital one-bit counter. Gray levels are obtained through multiple counting and accumulation, while time-resolved imaging is achieved through a 4-ns gating window controlled with subnanosecond accuracy by a field-programmable gate array. The sensor, which is equipped with microlenses to enhance its effective fill factor, was electro-optically characterized in terms of sensitivity and uniformity. Several examples of capture of fast events are shown to demonstrate the suitability of the approach.

Photon-number correlation for quantum enhanced imaging and sensing

Science.gov (United States)

Meda, A.; Losero, E.; Samantaray, N.; Scafirimuto, F.; Pradyumna, S.; Avella, A.; Ruo-Berchera, I.; Genovese, M.

2017-09-01

In this review we present the potentialities and the achievements of the use of non-classical photon-number correlations in twin-beam states for many applications, ranging from imaging to metrology. Photon-number correlations in the quantum regime are easily produced and are rather robust against unavoidable experimental losses, and noise in some cases, if compared to the entanglement, where losing one photon can completely compromise the state and its exploitable advantages. Here, we will focus on quantum enhanced protocols in which only phase-insensitive intensity measurements (photon-number counting) are performed, which allow probing the transmission/absorption properties of a system, leading, for example, to innovative target detection schemes in a strong background. In this framework, one of the advantages is that the sources experimentally available emit a wide number of pair-wise correlated modes, which can be intercepted and exploited separately, for example by many pixels of a camera, providing a parallelism, essential in several applications, such as wide-field sub-shot-noise imaging and quantum enhanced ghost imaging. Finally, non-classical correlation enables new possibilities in quantum radiometry, e.g. the possibility of absolute calibration of a spatial resolving detector from the on-off single-photon regime to the linear regime in the same setup.

Performance of three-photon PET imaging: Monte Carlo simulations

International Nuclear Information System (INIS)

Kacperski, Krzysztof; Spyrou, Nicholas M

2005-01-01

We have recently introduced the idea of making use of three-photon positron annihilations in positron emission tomography. In this paper, the basic characteristics of the three-gamma imaging in PET are studied by means of Monte Carlo simulations and analytical computations. Two typical configurations of human and small animal scanners are considered. Three-photon imaging requires high-energy resolution detectors. Parameters currently attainable by CdZnTe semiconductor detectors, the technology of choice for the future development of radiation imaging, are assumed. Spatial resolution is calculated as a function of detector energy resolution and size, position in the field of view, scanner size and the energies of the three-gamma annihilation photons. Possible ways to improve the spatial resolution obtained for nominal parameters, 1.5 cm and 3.2 mm FWHM for human and small animal scanners, respectively, are indicated. Counting rates of true and random three-photon events for typical human and small animal scanning configurations are assessed. A simple formula for minimum size of lesions detectable in the three-gamma based images is derived. Depending on the contrast and total number of registered counts, lesions of a few mm size for human and sub mm for small animal scanners can be detected

Molecular imaging in oncology

Energy Technology Data Exchange (ETDEWEB)

Schober, Otmar; Riemann, Burkhard (eds.) [Universitaetsklinikum Muenster (Germany). Klinik fuer Nuklearmedizin

2013-02-01

Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

Molecular imaging in oncology

International Nuclear Information System (INIS)

Schober, Otmar; Riemann, Burkhard

2013-01-01

Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

Volumetric Two-photon Imaging of Neurons Using Stereoscopy (vTwINS)

Science.gov (United States)

Song, Alexander; Charles, Adam S.; Koay, Sue Ann; Gauthier, Jeff L.; Thiberge, Stephan Y.; Pillow, Jonathan W.; Tank, David W.

2017-01-01

Two-photon laser scanning microscopy of calcium dynamics using fluorescent indicators is a widely used imaging method for large scale recording of neural activity in vivo. Here we introduce volumetric Two-photon Imaging of Neurons using Stereoscopy (vTwINS), a volumetric calcium imaging method that employs an elongated, V-shaped point spread function to image a 3D brain volume. Single neurons project to spatially displaced “image pairs” in the resulting 2D image, and the separation distance between images is proportional to depth in the volume. To demix the fluorescence time series of individual neurons, we introduce a novel orthogonal matching pursuit algorithm that also infers source locations within the 3D volume. We illustrate vTwINS by imaging neural population activity in mouse primary visual cortex and hippocampus. Our results demonstrate that vTwINS provides an effective method for volumetric two-photon calcium imaging that increases the number of neurons recorded while maintaining a high frame-rate. PMID:28319111

General perspectives for molecular nuclear imaging

International Nuclear Information System (INIS)

Chung, June Key

2004-01-01

Molecular imaging provides a visualization of normal as well as abnormal cellular processes at a molecular or genetic level rather than at an anatomical level. Conventional medical imaging methods utilize the imaging signals produced by nonspecific physico-chemical interaction. However, molecular imaging methods utilize the imaging signals derived from specific cellular or molecular events. Because molecular and genetic changes precede anatomical change in the course of disease development, molecular imaging can detect early events in disease progression. In the near future, through molecular imaging we can understand basic mechanisms of disease, and diagnose earlier and, subsequently, treat earlier intractable disease such as cancer, neuro-degenerative diseases, and immunologic disorders. In beginning period, nuclear medicine started as a molecular imaging, and has had a leading role in the field of molecular imaging. But recently molecular imaging has been rapidly developed. Besides nuclear imaging, molecular imaging methods such as optical imaging, magnetic resonance imaging are emerging. Each imaging modalities have their advantages and weaknesses. The opportunities from molecular imaging look bright. We should try nuclear medicine continues to have a leading role in molecular imaging

Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection.

Science.gov (United States)

Kojima, Akihiro; Gotoh, Kumiko; Shimamoto, Masako; Hasegawa, Koki; Okada, Seiji

2016-02-01

Iodine-131 is widely used for radionuclide therapy because of its β-particle and for diagnostic imaging employing its principal gamma ray. Since that principal gamma ray has the relatively high energy of 364 keV, small animal single-photon emission computed tomography (SPECT) imaging systems may be required to possess the ability to image such higher energy photons. The aim of this study was to investigate the possibility of imaging I-131 using its 284 keV photons instead of its 364 keV photons in a small animal SPECT imaging system dedicated to the detection of low-medium-energy photons (below 300 keV). The imaging system used was a commercially available preclinical SPECT instrument with CZT detectors that was equipped with multi-pinhole collimators and was accompanied by a CT imager. An energy window for I-131 imaging was set to a photopeak of 284 keV with a low abundance compared with 364 keV photons. Small line sources and two mice, one of each of two types, that were injected with NaI-131 were scanned. Although higher counts occurred at the peripheral region of the reconstructed images due to the collimator penetration by the 364 keV photons, the shape of the small line sources could be well visualized. The measured spatial resolution was relatively poor (~1.9 mm for full width at half maximum and ~3.9 mm for full width at tenth maximum). However, a good linear correlation between SPECT values and the level of I-131 radioactivity was observed. Furthermore, the uptake of NaI-131 to the thyroid gland for the two mice was clearly identified in the 3D-SPECT image fused with the X-ray CT image. We conclude that the use of an energy window set on the photopeak of 284 keV and the multi-pinhole collimator may permit I-131 imaging for a preclinical CZT-SPECT system that does not have the ability to acquire images using the 364 keV photons.

Computational methods for molecular imaging

CERN Document Server

Shi, Kuangyu; Li, Shuo

2015-01-01

This volume contains original submissions on the development and application of molecular imaging computing. The editors invited authors to submit high-quality contributions on a wide range of topics including, but not limited to: • Image Synthesis & Reconstruction of Emission Tomography (PET, SPECT) and other Molecular Imaging Modalities • Molecular Imaging Enhancement • Data Analysis of Clinical & Pre-clinical Molecular Imaging • Multi-Modal Image Processing (PET/CT, PET/MR, SPECT/CT, etc.) • Machine Learning and Data Mining in Molecular Imaging. Molecular imaging is an evolving clinical and research discipline enabling the visualization, characterization and quantification of biological processes taking place at the cellular and subcellular levels within intact living subjects. Computational methods play an important role in the development of molecular imaging, from image synthesis to data analysis and from clinical diagnosis to therapy individualization. This work will bring readers fro...

Molecular imaging in neurological diseases; Molekulare Bildgebung bei neurologischen Erkrankungen

Energy Technology Data Exchange (ETDEWEB)

Reimold, M.; Fougere, C. la [Universitaetsklinikum Tuebingen, Abteilung Nuklearmedizin und Klinische Molekulare Bildgebung, Department Radiologie, Tuebingen (Germany)

2016-07-15

In neurodegeneration and in neuro-oncology, the standard imaging procedure, magnetic resonance imaging (MRI), shows limited sensitivity and specificity. Molecular imaging with specific positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers allows various molecular targets and metabolic processes to be assessed and is thus a valuable adjunct to MRI. Two important examples are referred to here: amino acid transport for neuro-oncological issues, and the recently approved PET tracers for detecting amyloid depositions during the preclinical stage of Alzheimer's disease. This review discusses the clinical relevance and indications for the following nuclear medicine imaging procedures: amyloid PET, {sup 18}F-fluorodeoxyglucose (FDG)-PET, and dopamine transporter (DaT)-SPECT for the diagnosis of dementia and the differential diagnosis of Parkinson's disease, in addition to amino acid PET for the diagnosis of brain tumors and somatostatin receptor imaging in meningioma. (orig.) [German] Die Magnetresonanztomographie (MRT) weist als Standardverfahren bei neurodegenerativen und neuroonkologischen Fragestellungen eine eingeschraenkte Sensitivitaet und Spezifitaet auf. Die nuklearmedizinische molekulare Bildgebung mit spezifischen Positronenemissionstomographie(PET)- und single-photon-emission-computed-tomography(SPECT)-Tracern ermoeglicht die Darstellung verschiedener molekularer Targets bzw. Stoffwechselprozesse und stellt damit eine wichtige Ergaenzung zur MRT dar. Hier sei exemplarisch auf die Darstellung des Aminosaeuretransports im Rahmen neuroonkologischer Fragestellungen verwiesen, sowie auf die bereits im praeklinischen Stadium der Alzheimer-Demenz nachweisbaren Amyloidablagerungen mit hierfuer seit Kurzem zugelassenen PET-Tracern. Dieser Uebersichtsbeitrag bespricht die klinische Bedeutung bzw. die Indikationen der folgenden nuklearmedizinischen Untersuchungsverfahren: der Amyloid-PET, der {sup 18}F

Simulation of photon and charge transport in X-ray imaging semiconductor sensors

CERN Document Server

Nilsson, H E; Hjelm, M; Bertilsson, K

2002-01-01

A fully stochastic model for the imaging properties of X-ray silicon pixel detectors is presented. Both integrating and photon counting configurations have been considered, as well as scintillator-coated structures. The model is based on three levels of Monte Carlo simulations; photon transport and absorption using MCNP, full band Monte Carlo simulation of charge transport and system level Monte Carlo simulation of the imaging performance of the detector system. In the case of scintillator-coated detectors, the light scattering in the detector layers has been simulated using a Monte Carlo method. The image resolution was found to be much lower in scintillator-coated systems due to large light spread in thick scintillator layers. A comparison between integrating and photon counting readout methods shows that the image resolution can be slightly enhanced using a photon-counting readout. In addition, the proposed model has been used to study charge-sharing effects on the energy resolution in photon counting dete...

Image transfer by cascaded stack of photonic crystal and air layers

NARCIS (Netherlands)

Shen, C.; Michielsen, K.; Raedt, H. De

2006-01-01

We demonstrate image transfer by a cascaded stack consisting of two and three triangular-lattice photonic crystal slabs separated by air. The quality of the image transfered by the stack is sensitive to the air/photonic crystal interface termination and the frequency. Depending on the frequency and

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

Science.gov (United States)

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

MARS spectral molecular imaging of lamb tissue: data collection and image analysis

CERN Document Server

Aamir, R; Bateman, C.J.; Butler, A.P.H.; Butler, P.H.; Anderson, N.G.; Bell, S.T.; Panta, R.K.; Healy, J.L.; Mohr, J.L.; Rajendran, K.; Walsh, M.F.; Ruiter, N.de; Gieseg, S.P.; Woodfield, T.; Renaud, P.F.; Brooke, L.; Abdul-Majid, S.; Clyne, M.; Glendenning, R.; Bones, P.J.; Billinghurst, M.; Bartneck, C.; Mandalika, H.; Grasset, R.; Schleich, N.; Scott, N.; Nik, S.J.; Opie, A.; Janmale, T.; Tang, D.N.; Kim, D.; Doesburg, R.M.; Zainon, R.; Ronaldson, J.P.; Cook, N.J.; Smithies, D.J.; Hodge, K.

2014-01-01

Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 to 140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we ...

Statistical and physical content of low-energy photons in nuclear medicine imaging

International Nuclear Information System (INIS)

Gagnon, D.; Pouliot, N.; Laperriere, L.; Harel, F.; Gregoire, J.; Arsenault, A.

1990-01-01

Limit in the energy resolution of present gamma camera technology prevents a total rejection of Compton events: inclusion of bad photons in the image is inescapable. Various methods acquiring data over a large portion of the spectrum have already been described. This paper investigates the usefulness of low energy photons using statistical and physical models. Holospectral Imaging, for instance, exploits correlation between energy frames to build an information related transformation optimizing primary photon image. One can also use computer simulation to show that a portion of low energy photons is detected at the same location (pixel) as pure primary photons. These events are for instance: photons undergoing scatter interaction in the crystal; photons undergoing a small angle backscatter or forwardscatter interaction in the medium, photons backscattered by the Pyrex into the crystal. For a 140 keV source in 10 cm of water and a 1/4 inch thick crystal, more than 6% of all the photons detected do not have the primary energy and still are located in the right 4 mm pixel. Similarly, it is possible to show that more than 5% of all the photons detected at 140 keV deposit their energy in more than one pixel. These results give additional support to techniques considering low energy photons and more sophisticated ways to segregate between good and bad events

CMOS SPAD-based image sensor for single photon counting and time of flight imaging

OpenAIRE

Dutton, Neale Arthur William

2016-01-01

The facility to capture the arrival of a single photon, is the fundamental limit to the detection of quantised electromagnetic radiation. An image sensor capable of capturing a picture with this ultimate optical and temporal precision is the pinnacle of photo-sensing. The creation of high spatial resolution, single photon sensitive, and time-resolved image sensors in complementary metal oxide semiconductor (CMOS) technology offers numerous benefits in a wide field of applications....

THERANOSTICS: From Molecular Imaging Using Ga-68 Labeled Tracers and PET/CT to Personalized Radionuclide Therapy - The Bad Berka Experience

OpenAIRE

Richard P. Baum, Harshad R. Kulkarni

2012-01-01

The acronym THERANOSTICS epitomizes the inseparability of diagnosis and therapy, the pillars of medicine and takes into account personalized management of disease for a specific patient. Molecular phenotypes of neoplasms can be determined by molecular imaging with specific probes using positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), or optical methods, so that the treatment is specifically targeted against the tumor and...

SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

Science.gov (United States)

Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

2014-01-01

Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed. PMID:24897023

High-performance imaging of stem cells using single-photon emissions

Science.gov (United States)

Wagenaar, Douglas J.; Moats, Rex A.; Hartsough, Neal E.; Meier, Dirk; Hugg, James W.; Yang, Tang; Gazit, Dan; Pelled, Gadi; Patt, Bradley E.

2011-10-01

Radiolabeled cells have been imaged for decades in the field of autoradiography. Recent advances in detector and microelectronics technologies have enabled the new field of "digital autoradiography" which remains limited to ex vivo specimens of thin tissue slices. The 3D field-of-view (FOV) of single cell imaging can be extended to millimeters if the low energy (10-30 keV) photon emissions of radionuclides are used for single-photon nuclear imaging. This new microscope uses a coded aperture foil made of highly attenuating elements such as gold or platinum to form the image as a kind of "lens". The detectors used for single-photon emission microscopy are typically silicon detectors with a pixel pitch less than 60 μm. The goal of this work is to image radiolabeled mesenchymal stem cells in vivo in an animal model of tendon repair processes. Single-photon nuclear imaging is an attractive modality for translational medicine since the labeled cells can be imaged simultaneously with the reparative processes by using the dual-isotope imaging technique. The details our microscope's two-layer gold aperture and the operation of the energy-dispersive, pixellated silicon detector are presented along with the first demonstration of energy discrimination with a 57Co source. Cell labeling techniques have been augmented by genetic engineering with the sodium-iodide symporter, a type of reporter gene imaging method that enables in vivo uptake of free 99mTc or an iodine isotope at a time point days or weeks after the insertion of the genetically modified stem cells into the animal model. This microscopy work in animal research may expand to the imaging of reporter-enabled stem cells simultaneously with the expected biological repair process in human clinical trials of stem cell therapies.

A Multispectral Photon-Counting Double Random Phase Encoding Scheme for Image Authentication

Directory of Open Access Journals (Sweden)

Faliu Yi

2014-05-01

Full Text Available In this paper, we propose a new method for color image-based authentication that combines multispectral photon-counting imaging (MPCI and double random phase encoding (DRPE schemes. The sparsely distributed information from MPCI and the stationary white noise signal from DRPE make intruder attacks difficult. In this authentication method, the original multispectral RGB color image is down-sampled into a Bayer image. The three types of color samples (red, green and blue color in the Bayer image are encrypted with DRPE and the amplitude part of the resulting image is photon counted. The corresponding phase information that has nonzero amplitude after photon counting is then kept for decryption. Experimental results show that the retrieved images from the proposed method do not visually resemble their original counterparts. Nevertheless, the original color image can be efficiently verified with statistical nonlinear correlations. Our experimental results also show that different interpolation algorithms applied to Bayer images result in different verification effects for multispectral RGB color images.

A multispectral photon-counting double random phase encoding scheme for image authentication.

Science.gov (United States)

Yi, Faliu; Moon, Inkyu; Lee, Yeon H

2014-05-20

In this paper, we propose a new method for color image-based authentication that combines multispectral photon-counting imaging (MPCI) and double random phase encoding (DRPE) schemes. The sparsely distributed information from MPCI and the stationary white noise signal from DRPE make intruder attacks difficult. In this authentication method, the original multispectral RGB color image is down-sampled into a Bayer image. The three types of color samples (red, green and blue color) in the Bayer image are encrypted with DRPE and the amplitude part of the resulting image is photon counted. The corresponding phase information that has nonzero amplitude after photon counting is then kept for decryption. Experimental results show that the retrieved images from the proposed method do not visually resemble their original counterparts. Nevertheless, the original color image can be efficiently verified with statistical nonlinear correlations. Our experimental results also show that different interpolation algorithms applied to Bayer images result in different verification effects for multispectral RGB color images.

Single-photon compressive imaging with some performance benefits over raster scanning

International Nuclear Information System (INIS)

Yu, Wen-Kai; Liu, Xue-Feng; Yao, Xu-Ri; Wang, Chao; Zhai, Guang-Jie; Zhao, Qing

2014-01-01

A single-photon imaging system based on compressed sensing has been developed to image objects under ultra-low illumination. With this system, we have successfully realized imaging at the single-photon level with a single-pixel avalanche photodiode without point-by-point raster scanning. From analysis of the signal-to-noise ratio in the measurement we find that our system has much higher sensitivity than conventional ones based on point-by-point raster scanning, while the measurement time is also reduced. - Highlights: • We design a single photon imaging system with compressed sensing. • A single point avalanche photodiode is used without raster scanning. • The Poisson shot noise in the measurement is analyzed. • The sensitivity of our system is proved to be higher than that of raster scanning

Ballistic and snake photon imaging for locating optical endomicroscopy fibres

Science.gov (United States)

Tanner, M. G.; Choudhary, T. R.; Craven, T. H.; Mills, B.; Bradley, M.; Henderson, R. K.; Dhaliwal, K.; Thomson, R. R.

2017-01-01

We demonstrate determination of the location of the distal-end of a fibre-optic device deep in tissue through the imaging of ballistic and snake photons using a time resolved single-photon detector array. The fibre was imaged with centimetre resolution, within clinically relevant settings and models. This technique can overcome the limitations imposed by tissue scattering in optically determining the in vivo location of fibre-optic medical instruments. PMID:28966848

Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

Science.gov (United States)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

2015-08-01

Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.

Science.gov (United States)

Rempel, Brian P; Price, Eric W; Phenix, Christopher P

2017-01-01

Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.

Vertically Integrated Edgeless Photon Imaging Camera

Energy Technology Data Exchange (ETDEWEB)

Fahim, Farah [Fermilab; Deptuch, Grzegorz [Fermilab; Shenai, Alpana [Fermilab; Maj, Piotr [AGH-UST, Cracow; Kmon, Piotr [AGH-UST, Cracow; Grybos, Pawel [AGH-UST, Cracow; Szczygiel, Robert [AGH-UST, Cracow; Siddons, D. Peter [Brookhaven; Rumaiz, Abdul [Brookhaven; Kuczewski, Anthony [Brookhaven; Mead, Joseph [Brookhaven; Bradford, Rebecca [Argonne; Weizeorick, John [Argonne

2017-01-01

The Vertically Integrated Photon Imaging Chip - Large, (VIPIC-L), is a large area, small pixel (65μm), 3D integrated, photon counting ASIC with zero-suppressed or full frame dead-time-less data readout. It features data throughput of 14.4 Gbps per chip with a full frame readout speed of 56kframes/s in the imaging mode. VIPIC-L contain 192 x 192 pixel array and the total size of the chip is 1.248cm x 1.248cm with only a 5μm periphery. It contains about 120M transistors. A 1.3M pixel camera module will be developed by arranging a 6 x 6 array of 3D VIPIC-L’s bonded to a large area silicon sensor on the analog side and to a readout board on the digital side. The readout board hosts a bank of FPGA’s, one per VIPIC-L to allow processing of up to 0.7 Tbps of raw data produced by the camera.

Development of Optical Molecular Imaging System for the Acquisition of Bioluminescence Signals from Small Animals

International Nuclear Information System (INIS)

Lee, Byeong Il; Kim, Hyeon Sik; Jeong, Hye Jin; Lee, Hyung Jae; Moon, Seung Min; Kwon, Seung Young; Jeong, Shin Young; Bom, Hee Seung; Min, Jung Joon; Choi, Eun Seo

2009-01-01

Optical imaging is providing great advance and improvement in genetic and molecular imaging of animals and humans. Optical imaging system consists of optical imaging devices, which carry out major function for monitoring, tracing, and imaging in most of molecular in-vivo researches. In bio-luminescent imaging, small animals containing luciferase gene locally irradiate light, and emitted photons transmitted through skin of the small animals are imaged by using a high sensitive charged coupled device (CCD) camera. In this paper, we introduced optical imaging system for the image acquisition of bio-luminescent signals emitted from small animals. In the system, Nikon lens and four LED light sources were mounted at the inside of a dark box. A cooled CCD camera equipped with a control module was used. We tested the performance of the optical imaging system using effendorf tube and light emitting bacteria which injected intravenously into CT26 tumor bearing nude mouse. The performance of implemented optical imaging system for bio-luminescence imaging was demonstrated and the feasibility of the system in small animal imaging application was proved. We anticipate this system could be a useful tool for the molecular imaging of small animals adaptable for various experimental conditions in future

Nuclear medicine imaging instrumentations for molecular imaging

International Nuclear Information System (INIS)

Chung, Yong Hyun; Song, Tae Yong; Choi, Yong

2004-01-01

Small animal models are extensively utilized in the study of biomedical sciences. Current animal experiments and analysis are largely restricted to in vitro measurements and need to sacrifice animals to perform tissue or molecular analysis. This prevents researchers from observing in vivo the natural evolution of the process under study. Imaging techniques can provide repeatedly in vivo anatomic and molecular information noninvasively. Small animal imaging systems have been developed to assess biological process in experimental animals and increasingly employed in the field of molecular imaging studies. This review outlines the current developments in nuclear medicine imaging instrumentations including fused multi-modality imaging systems for small animal imaging

SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

Directory of Open Access Journals (Sweden)

Barbara Palumbo

2014-06-01

Full Text Available Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI is discussed.

Photons-based medical imaging - Radiology, X-ray tomography, gamma and positrons tomography, optical imaging; Imagerie medicale a base de photons - Radiologie, tomographie X, tomographie gamma et positons, imagerie optique

Energy Technology Data Exchange (ETDEWEB)

Fanet, H.; Dinten, J.M.; Moy, J.P.; Rinkel, J. [CEA Leti, Grenoble (France); Buvat, I. [IMNC - CNRS, Orsay (France); Da Silva, A. [Institut Fresnel, Marseille (France); Douek, P.; Peyrin, F. [INSA Lyon, Lyon Univ. (France); Frija, G. [Hopital Europeen George Pompidou, Paris (France); Trebossen, R. [CEA-Service hospitalier Frederic Joliot, Orsay (France)

2010-07-01

This book describes the different principles used in medical imaging. The detection aspects, the processing electronics and algorithms are detailed for the different techniques. This first tome analyses the photons-based techniques (X-rays, gamma rays and visible light). Content: 1 - physical background: radiation-matter interaction, consequences on detection and medical imaging; 2 - detectors for medical imaging; 3 - processing of numerical radiography images for quantization; 4 - X-ray tomography; 5 - positrons emission tomography: principles and applications; 6 - mono-photonic imaging; 7 - optical imaging; Index. (J.S.)

Neutron radiography imaging with 2-dimensional photon counting method and its problems

International Nuclear Information System (INIS)

Ikeda, Y.; Kobayashi, H.; Niwa, T.; Kataoka, T.

1988-01-01

A ultra sensitive neutron imaging system has been deviced with a 2-dimensional photon counting camara (ARGUS 100). The imaging system is composed by a 2-dimensional single photon counting tube and a low background vidicon followed with an image processing unit and frame memories. By using the imaging system, electronic neutron radiography (NTV) has been possible under the neutron flux less than 3 x 10 4 n/cm 2 ·s. (author)

Targeted molecular imaging

International Nuclear Information System (INIS)

Kim, E. Edmund

2003-01-01

Molecular imaging aims to visualize the cellular and molecular processes occurring in living tissues, and for the imaging of specific molecules in vivo, the development of reporter probes and dedicated imaging equipment is most important. Reporter genes can be used to monitor the delivery and magnitude of therapeutic gene transfer, and the time variation involved. Imaging technologies such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are able to non-invasively detect, measure, and report the simultaneous expression of multiple meaningful genes. It is believed that recent advances in reporter probes, imaging technologies and gene transfer strategies will enhance the effectiveness of gene therapy trials

Nanoplatform-based molecular imaging

National Research Council Canada - National Science Library

Chen, Xiaoyuan

2011-01-01

"Nanoplathform-Based Molecular Imaging provides rationale for using nanoparticle-based probes for molecular imaging, then discusses general strategies for this underutilized, yet promising, technology...

Molecular MR imaging

International Nuclear Information System (INIS)

Fleige, G.; Hamm, B.

2000-01-01

Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas. (orig.) [de

Bi-dimensional arrays of SPAD for time-resolved single photon imaging

International Nuclear Information System (INIS)

Tudisco, S.; Lanzano, L.; Musumeci, F.; Neri, L.; Privitera, S.; Scordino, A.; Condorelli, G.; Fallica, G.; Mazzillo, M.; Sanfilippo, D.; Valvo, G.

2009-01-01

Many scientific areas like astronomy, biophysics, biomedicine, nuclear and plasma science, etc. are interested in the development of a new time-resolved single photon imaging device. Such a device represents today one of the most challenging goals in the field of photonics. In collaboration with Catania R and D staff of ST-Microelectronics (STM) we created, during the last few years, a new avalanche photosensor-Single Photon Avalanche Diode (SPAD) able to detect and count, with excellent performance, single photons. Further we will discuss the possible realization of a single photon imaging device through the many elements integration (bi-dimensional arrays) of SPADs. In order to achieve the goal, it is also important to develop an appropriate readout strategy able to address the time information of each individual sensor and in order to read a great number of elements easily. First prototypes were designed and manufactured by STM and the results are reported here. In the paper we will discuss in particular: (i) sensor performance (gain, photodetection efficiency, timing, after-pulsing, etc.); (ii) array performance (layout, cross-talk, etc.); (iii) readout strategy (quenching, electronics), and (iv) first imaging results (general performance).

Infrared images of reflection nebulae and Orion's bar: Fluorescent molecular hydrogen and the 3.3 micron feature

International Nuclear Information System (INIS)

Burton, M.G.; Moorhouse, A.; Brand, P.W.J.L.; Roche, P.F.; Geballe, T.R.

1989-01-01

Images were obtained of the (fluorescent) molecular hydrogen 1-0 S(1) line, and of the 3.3 micron emission feature, in Orion's Bar and three reflection nebulae. The emission from these species appears to come from the same spatial locations in all sources observed. This suggests that the 3.3 micron feature is excited by the same energetic UV-photons which cause the molecular hydrogen to fluoresce

Introduction to basic molecular biologic techniques for molecular imaging researches

International Nuclear Information System (INIS)

Kang, Joo Hyun

2004-01-01

Molecular imaging is a rapidly growing field due to the advances in molecular biology and imaging technologies. With the introduction of imaging reporter genes into the cell, diverse cellular processes can be monitored, quantified and imaged non-invasively in vivo. These processes include the gene expression, protein-protein interactions, signal transduction pathways, and monitoring of cells such as cancer cells, immune cells, and stem cells. In the near future, molecular imaging analysis will allow us to observe the incipience and progression of the disease. These will make us easier to give a diagnosis in the early stage of intractable diseases such as cancer, neuro-degenerative disease, and immunological disorders. Additionally, molecular imaging method will be a valuable tool for the real-time evaluation of cells in molecular biology and the basic biological studies. As newer and more powerful molecular imaging tools become available, it will be necessary to corporate clinicians, molecular biologists and biochemists for the planning, interpretation, and application of these techniques to their fullest potential. In order for such a multidisciplinary team to be effective, it is essential that a common understanding of basic biochemical and molecular biologic techniques is achieved. Basic molecular techniques for molecular imaging methods are presented in this paper

Applications of photon-in, photon-out spectroscopy with third-generation, synchrotron-radiation sources

International Nuclear Information System (INIS)

Lindle, D.W.; Perera, R.C.C.

1991-01-01

This report discusses the following topics: Mother nature's finest test probe; soft x-ray emission spectroscopy with high-brightness synchrotron radiation sources; anisotropy and polarization of x-ray emission from atoms and molecules; valence-hole fluorescence from molecular photoions as a probe of shape-resonance ionization: progress and prospects; structural biophysics on third-generation synchrotron sources; ultra-soft x-ray fluorescence-yield XAFS: an in situ photon-in, photon-out spectroscopy; and x-ray microprobe: an analytical tool for imaging elemental composition and microstructure

Non-invasive imaging of skin cancer with fluorescence lifetime imaging using two photon tomography

Science.gov (United States)

Patalay, Rakesh; Talbot, Clifford; Alexandrov, Yuriy; Munro, Ian; Breunig, Hans Georg; König, Karsten; Warren, Sean; Neil, Mark A. A.; French, Paul M. W.; Chu, Anthony; Stamp, Gordon W.; Dunsby, Christopher

2011-07-01

Multispectral fluorescence lifetime imaging (FLIM) using two photon microscopy as a non-invasive technique for the diagnosis of skin lesions is described. Skin contains fluorophores including elastin, keratin, collagen, FAD and NADH. This endogenous contrast allows tissue to be imaged without the addition of exogenous agents and allows the in vivo state of cells and tissues to be studied. A modified DermaInspect® multiphoton tomography system was used to excite autofluorescence at 760 nm in vivo and on freshly excised ex vivo tissue. This instrument simultaneously acquires fluorescence lifetime images in four spectral channels between 360-655 nm using time-correlated single photon counting and can also provide hyperspectral images. The multispectral fluorescence lifetime images were spatially segmented and binned to determine lifetimes for each cell by fitting to a double exponential lifetime model. A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential.

Hemispherical Brillouin zone imaging of a diamond-type biological photonic crystal

Science.gov (United States)

Wilts, Bodo D.; Michielsen, Kristel; De Raedt, Hans; Stavenga, Doekele G.

2012-01-01

The brilliant structural body colours of many animals are created by three-dimensional biological photonic crystals that act as wavelength-specific reflectors. Here, we report a study on the vividly coloured scales of the diamond weevil, Entimus imperialis. Electron microscopy identified the chitin and air assemblies inside the scales as domains of a single-network diamond (Fd3m) photonic crystal. We visualized the topology of the first Brillouin zone (FBZ) by imaging scatterometry, and we reconstructed the complete photonic band structure diagram (PBSD) of the chitinous photonic crystal from reflectance spectra. Comparison with calculated PBSDs indeed showed a perfect overlap. The unique method of non-invasive hemispherical imaging of the FBZ provides key insights for the investigation of photonic crystals in the visible wavelength range. The characterized extremely large biophotonic nanostructures of E. imperialis are structurally optimized for high reflectance and may thus be well suited for use as a template for producing novel photonic devices, e.g. through biomimicry or direct infiltration from dielectric material. PMID:22188768

Cardiovascular molecular imaging of apoptosis

International Nuclear Information System (INIS)

Wolters, S.L.; Reutelingsperger, C.P.M.; Corsten, M.F.; Hofstra, L.; Narula, J.

2007-01-01

Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

Cardiovascular molecular imaging of apoptosis

Energy Technology Data Exchange (ETDEWEB)

Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

2007-06-15

Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy

Science.gov (United States)

Hunter, Jennifer J.; Masella, Benjamin; Dubra, Alfredo; Sharma, Robin; Yin, Lu; Merigan, William H.; Palczewska, Grazyna; Palczewski, Krzysztof; Williams, David R.

2011-01-01

In vivo two-photon imaging through the pupil of the primate eye has the potential to become a useful tool for functional imaging of the retina. Two-photon excited fluorescence images of the macaque cone mosaic were obtained using a fluorescence adaptive optics scanning laser ophthalmoscope, overcoming the challenges of a low numerical aperture, imperfect optics of the eye, high required light levels, and eye motion. Although the specific fluorophores are as yet unknown, strong in vivo intrinsic fluorescence allowed images of the cone mosaic. Imaging intact ex vivo retina revealed that the strongest two-photon excited fluorescence signal comes from the cone inner segments. The fluorescence response increased following light stimulation, which could provide a functional measure of the effects of light on photoreceptors. PMID:21326644

Multisite two-photon imaging of neurons on multielectrode arrays

Science.gov (United States)

Potter, Steve M.; Lukina, Natalia; Longmuir, Kenneth J.; Wu, Yan

2001-04-01

We wish to understand how neural systems store, recall, and process information. We are using cultured networks of cortical neurons grown on microelectrode arrays as a model system for studying the emergent properties of ensembles of living neurons. We have developed a 2-way communication interface between the cultured network and a computer- generated animal, the Neurally Controlled Animat. Neural activity is used to control the behavior of the Animat, and 2- photon time-lapse imaging is carried out in order to observe the morphological changes that might underlie changes in neural processing. The 2-photon microscope is ideal for repeated imaging over hours or days, with submicron resolution and little photodamage. We have designed a computer-controlled microscope stage that allows imaging several locations in sequence, in order to collect more image data. For the latest progress, see: http://www.caltech.edu/~pinelab/PotterGroup.htm.

In vivo two-photon imaging of retina in rabbits and rats.

Science.gov (United States)

Jayabalan, Gopal Swamy; Wu, Yi-Kai; Bille, Josef F; Kim, Samuel; Mao, Xiao Wen; Gimbel, Howard V; Rauser, Michael E; Fan, Joseph T

2018-01-01

The purpose of this study was to evaluate the retina using near-infrared (NIR) two-photon scanning laser ophthalmoscopy. New Zealand white rabbits, albino rats, and brown Norway rats were used in this study. An autofluorescence image of the retina, including the retinal cells and its associated vasculatures was obtained by a real-time scan using the ophthalmoscope. Furthermore, the retinal vessels, nerve fiber layers and the non-pigmented retina were recorded with two-photon fluorescein angiography (FA); and the choroidal vasculatures were recorded using two-photon indocyanine green angiography (ICGA). Two-photon ICGA was achieved by exciting a second singlet state at ∼398 nm. Simultaneous two-photon FA and two-photon ICGA were performed to characterize the retinal and choroidal vessels with a single injection. The minimum laser power threshold required to elicit two-photon fluorescence was determined. The two-photon ophthalmoscope could serve as a promising tool to detect and monitor the disease progression in animal models. Moreover, these high-resolution images of retinal and choroidal vessels can be acquired in a real-time scan with a single light source, requiring no additional filters for FA or ICGA. The combination of FA and ICGA using the two-photon ophthalmoscope will help researchers to characterize the retinal diseases in animal models, and also to classify the types (classic, occult or mixed) of choroidal neovascularization (CNV) in macular degeneration. Furthermore, the prototype can be adapted to image the retina of rodents and rabbits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Review: two-photon scanning systems for clinical high resolution in vivo tissue imaging

Science.gov (United States)

König, K.; Müller, J.; Höfer, M.; Müller, C.; Weinigel, M.; Bückle, R.; Elsner, P.; Kaatz, M.; Messerschmidt, B.

2008-02-01

The femtosecond laser multiphoton tomograph DermaInspect as well as high NA two-photon GRIN microendoscopes for in vivo tomography of human skin have been used to detect malignant melanoma as well as to study the diffusion and intradermal accumulation of topically applied cosmetical and pharmaceutical components. So far, more than 500 patients and volunteers in Europe, Australia, and Asia have been investigated with this unique tomograph. Near infrared 80 MHz picojoule femtosecond laser pulses were employed to excite endogenous fluorophores such as NAD(P)H, flavoproteins, melanin, and elastin as well as fluorescent components of a variety of ointments via a twophoton excitation process. In addition, collagen has been imaged by second harmonic generation. Using a two-PMT detection system, the ratio of elastin to collagen was determined during optical sectioning. A high submicron spatial resolution and 50 picosecond temporal resolution was achieved using galvoscan mirrors and piezodriven focusing optics as well as a time-correlated single photon counting module with a fast microchannel plate detector and fast photomultipliers. Individual intratissue cells, mitochondria, melanosomes, and the morphology of the nuclei as well as extracellular matrix elements could be clearly visualized due to molecular imaging and the calculation of fluorescence lifetime images. Nanoparticles and intratissue drugs have been detected non-invasively, in situ and over a period of up to 3 months. In addition, hydration effects and UV effects were studied by monitoring modifications of cellular morphology and autofluorescence. The system was used to observe the diffusion through the stratum corneum and the accumulation and release of functionalized nanoparticles along hair shafts and epidermal ridges. The DermaInspect been also employed to gain information on skin age and wound healing in patients with ulcers. Novel developments include a galvo/piezo-scan driven flexible articulated arm as

Photon detection with CMOS sensors for fast imaging

International Nuclear Information System (INIS)

Baudot, J.; Dulinski, W.; Winter, M.; Barbier, R.; Chabanat, E.; Depasse, P.; Estre, N.

2009-01-01

Pixel detectors employed in high energy physics aim to detect single minimum ionizing particle with micrometric positioning resolution. Monolithic CMOS sensors succeed in this task thanks to a low equivalent noise charge per pixel of around 10 to 15 e - , and a pixel pitch varying from 10 to a few 10 s of microns. Additionally, due to the possibility for integration of some data treatment in the sensor itself, readout times of 100μs have been reached for 100 kilo-pixels sensors. These aspects of CMOS sensors are attractive for applications in photon imaging. For X-rays of a few keV, the efficiency is limited to a few % due to the thin sensitive volume. For visible photons, the back-thinned version of CMOS sensor is sensitive to low intensity sources, of a few hundred photons. When a back-thinned CMOS sensor is combined with a photo-cathode, a new hybrid detector results (EBCMOS) and operates as a fast single photon imager. The first EBCMOS was produced in 2007 and demonstrated single photon counting with low dark current capability in laboratory conditions. It has been compared, in two different biological laboratories, with existing CCD-based 2D cameras for fluorescence microscopy. The current EBCMOS sensitivity and frame rate is comparable to existing EMCCDs. On-going developments aim at increasing this frame rate by, at least, an order of magnitude. We report in conclusion, the first test of a new CMOS sensor, LUCY, which reaches 1000 frames per second.

EDITORIAL: Molecular Imaging Technology

Science.gov (United States)

Asai, Keisuke; Okamoto, Koji

2006-06-01

'Molecular Imaging Technology' focuses on image-based techniques using nanoscale molecules as sensor probes to measure spatial variations of various species (molecular oxygen, singlet oxygen, carbon dioxide, nitric monoxide, etc) and physical properties (pressure, temperature, skin friction, velocity, mechanical stress, etc). This special feature, starting on page 1237, contains selected papers from The International Workshop on Molecular Imaging for Interdisciplinary Research, sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, which was held at the Sendai Mediatheque, Sendai, Japan, on 8 9 November 2004. The workshop was held as a sequel to the MOSAIC International Workshop that was held in Tokyo in 2003, to summarize the outcome of the 'MOSAIC Project', a five-year interdisciplinary project supported by Techno-Infrastructure Program, the Special Coordination Fund for Promotion of Science Technology to develop molecular sensor technology for aero-thermodynamic research. The workshop focused on molecular imaging technology and its applications to interdisciplinary research areas. More than 110 people attended this workshop from various research fields such as aerospace engineering, automotive engineering, radiotechnology, fluid dynamics, bio-science/engineering and medical engineering. The purpose of this workshop is to stimulate intermixing of these interdisciplinary fields for further development of molecular sensor and imaging technology. It is our pleasure to publish the seven papers selected from our workshop as a special feature in Measurement and Science Technology. We will be happy if this issue inspires people to explore the future direction of molecular imaging technology for interdisciplinary research.

Molecular single photon double K-shell ionization

International Nuclear Information System (INIS)

Penent, F.; Nakano, M.; Tashiro, M.; Grozdanov, T.P.; Žitnik, M.; Carniato, S.; Selles, P.; Andric, L.; Lablanquie, P.; Palaudoux, J.; Shigemasa, E.; Iwayama, H.; Hikosaka, Y.; Soejima, K.; Suzuki, I.H.; Kouchi, N.; Ito, K.

2014-01-01

We have studied single photon double K-shell ionization of small molecules (N 2 , CO, C 2 H 2n (n = 1–3), …) and the Auger decay of the resulting double core hole (DCH) molecular ions thanks to multi-electron coincidence spectroscopy using a magnetic bottle time-of-flight spectrometer. The relative cross-sections for single-site (K −2 ) and two-site (K −1 K −1 ) double K-shell ionization with respect to single K-shell (K −1 ) ionization have been measured that gives important information on the mechanisms of single photon double ionization. The spectroscopy of two-site (K −1 K −1 ) DCH states in the C 2 H 2n (n = 1–3) series shows important chemical shifts due to a strong dependence on the C-C bond length. In addition, the complete cascade Auger decay following single site (K −2 ) ionization has been obtained

Molecular imaging in neurology and neuroscience

International Nuclear Information System (INIS)

Schreckenberger, M.

2007-01-01

Molecular imaging in neurology and neuroscience is a suspenseful and fast developing tool in order to quantitatively image genomics and proteomics by means of direct and indirect markers. Because of its high-sensitive tracer principle, nuclear medicine imaging has the pioneering task for the methodical progression of molecular imaging. The current development of molecular imaging in neurology changes from the use of indirect markers of gene and protein expression to the direct imaging of the molecular mechanisms. It is the aim of this article to give a short review on the status quo of molecular imaging in neurology with emphasis on clinically relevant aspects. (orig.)

Molecular imaging in oncology

International Nuclear Information System (INIS)

Weber, W.A.

2007-01-01

Molecular imaging is generally defined as noninvasive and quantitative imaging of targeted macromolecules and biological processes in living organisms. A characteristic of molecular imaging is the ability to perform repeated studies and assess changes in biological processes over time. Thus molecular imaging lends itself well for monitoring the effectiveness of tumor therapy. In animal models a variety of techniques can be used for molecular imaging. These include optical imaging (bioluminescence and fluorescence imaging), magnetic resonance imaging (MRI) and nuclear medicine techniques. In the clinical setting, however, nuclear medicine techniques predominate, because so far only radioactive tracers provide the necessary sensitivity to study expression and function of macromolecules non-invasively in patients. Nuclear medicine techniques allows to study a variety of biological processes in patients. These include the expression of various receptors (estrogen, androgen, somatostatin receptors and integrins). In addition, tracers are available to study tumor cell proliferation and hypoxia. The by far most commonly used molecular imaging technique in oncology is, however, positron emission tomography (PET) with the glucose analog [ 18 F]fluorodeoxyglucose (FDG-PET). FDG-PET permits non-invasive quantitative assessment of the accelerated exogenous glucose use of malignant tumors. Numerous studies have now shown that reduction of tumor FDG-uptake during therapy allows early prediction of tumor response and patient survival. Clinical studies are currently underway to determine whether FDG-PET can be used to individualize tumor therapy by signaling early in the course of therapy the need for therapeutic adjustments in patients with likely non-responding tumors. (orig.)

Single photon imaging at ultra-high resolution

Energy Technology Data Exchange (ETDEWEB)

Bellazzini, R. [INFN sez. Pisa, Pisa (Italy); Spandre, G. [INFN sez. Pisa, Pisa (Italy)], E-mail: Gloria.Spandre@pi.infn.it; Minuti, M.; Brez, A.; Baldini, L.; Latronico, L.; Omodei, N.; Sgro, C.; Bregeon, J.; Razzano, M.; Pinchera, M. [INFN sez. Pisa, Pisa (Italy); Tremsin, A.; McPhate, J.; Vallerga, J.V.; Siegmund, O. [SSL, Berkeley (United States)

2008-06-11

We present a detection system capable of imaging both single photon/positive ion and multiple coincidence photons/positive ions with extremely high spatial resolution. In this detector the photoelectrons excited by the incoming photons are multiplied by microchannel plate(s) (MCP). The process of multiplication is spatially constrained within an MCP pore, which can be as small as 4 {mu}m for commercially available MCPs. An electron cloud originated by a single photoelectron is then encoded by a pixellated custom analog ASIC consisting of 105 K charge sensitive pixels of 50 {mu}m in size arranged on a hexagonal grid. Each pixel registers the charge with an accuracy of <100 electrons rms. Computation of the event centroid from the readout charges results in an accurate event position. A large number of simultaneous photons spatially separated by {approx}0.4 mm can be detected simultaneously allowing multiple coincidence operation for the experiments where a large number of incoming photons/positive ions have to be detected simultaneously. The experimental results prove that the spatial resolution of the readout system itself is {approx}3 {mu}m FWHM enabling detection resolution better than 6 {mu}m for the small pore MCPs. An attractive feature of the detection system is its capability to register the timing of each incoming photon/positive ion (in single photon detection mode) or of the first incoming particle (for the multiple coincidence detection) with an accuracy of {approx}130 ps FWHM. There is also virtually no dark count noise in the detection system making it suitable for low count rate applications.

Molecular cardiovascular imaging

International Nuclear Information System (INIS)

Schaefers, M.

2007-01-01

Although huge and long-lasting research efforts have been spent on the development of new diagnostic techniques investigating cardiovascular diseases, still fundamental challenges exist; the main challenge being the diagnosis of a suspected or known coronary artery disease or its consequences (myocardial infarction, heart failure etc.). Beside morphological techniques, functional imaging modalities are available in clinical diagnostic algorithms, whereas molecular cardiovascular imaging techniques are still under development. This review summarizes clinical-diagnostical challenges of modern cardiovascular medicine as well as the potential of new molecular imaging techniques to face these. (orig.)

First photon detection in transillumination imaging: A theoretical evaluation

International Nuclear Information System (INIS)

Behin-Ain, Setayesh

2003-01-01

This thesis is a theoretical evaluation of the (single) first photon detection (FPD) technique as a limiting case of time-resolved transillumination imaging (TI) for diagnostic purposes. It combines analytic and Monte Carlo (MC) simulation methods to derive the single photon statistics and to solve the radiative transfer equation (RTE) for a given source-medium-detector geometry. In order to efficiently simulate very early arriving photons, an Indeterministic Monte Carlo (IMC) technique based on path integrals is devised and validated. The IMC extends controlled MC techniques to accelerate and enhance the probability of detecting shorter trajectories thereby improving the statistics. The IMC technique provides a tool for the construction of a temporal point spread function (TPSF) of the emerging photons for the entire time scale. It is then used to predict the spatial resolution of these systems for shorter (sub-100 picosecond) time scales. The calculation of the TPSF at short time scales for a pulse made incident onto the medium enables the mathematical derivation of the temporal probability density functions (p.d.f.) for the first arriving photon, f 1 (t). This facilitates the investigation of a first photon detection (FPD) system as applied to a diagnostic TI configuration. A FPD system produces a signal representing f 1 (t) from which the mean transit time of the first arriving photon, t-bar 1 , may then be estimated for a sequence of incident pulses at each scan position. By rectilinear scanning across the medium, a two-dimensional (2-D) map of t-bar 1 can be created and displayed as a gray scale image. The application of FPD to TI is evaluated assuming an ideal detector capable of detecting the first arriving photon with 100% efficiency (infinite extinction coefficient). However, a model for a FPD system corresponding to a nonideal (single first photon) detector is also considered through the evaluation of the p.d.f. for the later (first, second,...) arriving

Small animal SPECT and its place in the matrix of molecular imaging technologies

International Nuclear Information System (INIS)

Meikle, Steven R; Kench, Peter; Kassiou, Michael; Banati, Richard B

2005-01-01

Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute ( -10 molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies. (topical review)

Visible-to-visible four-photon ultrahigh resolution microscopic imaging with 730-nm diode laser excited nanocrystals.

Science.gov (United States)

Wang, Baoju; Zhan, Qiuqiang; Zhao, Yuxiang; Wu, Ruitao; Liu, Jing; He, Sailing

2016-01-25

Further development of multiphoton microscopic imaging is confronted with a number of limitations, including high-cost, high complexity and relatively low spatial resolution due to the long excitation wavelength. To overcome these problems, for the first time, we propose visible-to-visible four-photon ultrahigh resolution microscopic imaging by using a common cost-effective 730-nm laser diode to excite the prepared Nd(3+)-sensitized upconversion nanoparticles (Nd(3+)-UCNPs). An ordinary multiphoton scanning microscope system was built using a visible CW diode laser and the lateral imaging resolution as high as 161-nm was achieved via the four-photon upconversion process. The demonstrated large saturation excitation power for Nd(3+)-UCNPs would be more practical and facilitate the four-photon imaging in the application. A sample with fine structure was imaged to demonstrate the advantages of visible-to-visible four-photon ultrahigh resolution microscopic imaging with 730-nm diode laser excited nanocrystals. Combining the uniqueness of UCNPs, the proposed visible-to-visible four-photon imaging would be highly promising and attractive in the field of multiphoton imaging.

Two-photon calcium imaging in mice navigating a virtual reality environment.

Science.gov (United States)

Leinweber, Marcus; Zmarz, Pawel; Buchmann, Peter; Argast, Paul; Hübener, Mark; Bonhoeffer, Tobias; Keller, Georg B

2014-02-20

In recent years, two-photon imaging has become an invaluable tool in neuroscience, as it allows for chronic measurement of the activity of genetically identified cells during behavior(1-6). Here we describe methods to perform two-photon imaging in mouse cortex while the animal navigates a virtual reality environment. We focus on the aspects of the experimental procedures that are key to imaging in a behaving animal in a brightly lit virtual environment. The key problems that arise in this experimental setup that we here address are: minimizing brain motion related artifacts, minimizing light leak from the virtual reality projection system, and minimizing laser induced tissue damage. We also provide sample software to control the virtual reality environment and to do pupil tracking. With these procedures and resources it should be possible to convert a conventional two-photon microscope for use in behaving mice.

Luminescence imaging of water during irradiation of X-ray photons lower energy than Cerenkov- light threshold

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Seiichi; Koyama, Shuji; Komori, Masataka [Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine (Japan); Toshito, Toshiyuki [Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya City West Medical Center (Japan)

2016-10-01

Luminescence imaging of water using X-ray photon irradiation at energy lower than maximum energy of ~200 keV is thought to be impossible because the secondary electrons produced in this energy range do not emit Cerenkov- light. Contrary to this consensus assumption, we show that the luminescence imaging of water can be achieved by X-ray irradiation at energy lower than 120 keV. We placed water phantoms on a table with a conventional X-ray imaging system, and luminescence images of these phantoms were measured with a high-sensitivity, cooled charge coupled device (CCD) camera during X-ray photon irradiation at energy below 120 keV. We also carried out such imaging of an acrylic block and plastic scintillator. The luminescence images of water phantoms taken during X-ray photon irradiation clearly showed X-ray photon distribution. The intensity of the X-ray photon images of the phantom increased almost proportionally to the number of X-ray irradiations. Lower-energy X-ray photon irradiation showed lower-intensity luminescence at the deeper parts of the phantom due to the higher X-ray absorption in the water phantom. Furthermore, lower-intensity luminescence also appeared at the deeper parts of the acrylic phantom due to its higher density than water. The intensity of the luminescence for water was 0.005% of that for plastic scintillator. Luminescence imaging of water during X-ray photon irradiation at energy lower than 120 keV was possible. This luminescence imaging method is promising for dose estimation in X-ray imaging systems.

Luminescence imaging of water during irradiation of X-ray photons lower energy than Cerenkov- light threshold

Science.gov (United States)

Yamamoto, Seiichi; Koyama, Shuji; Komori, Masataka; Toshito, Toshiyuki

2016-10-01

Luminescence imaging of water using X-ray photon irradiation at energy lower than maximum energy of 200 keV is thought to be impossible because the secondary electrons produced in this energy range do not emit Cerenkov- light. Contrary to this consensus assumption, we show that the luminescence imaging of water can be achieved by X-ray irradiation at energy lower than 120 keV. We placed water phantoms on a table with a conventional X-ray imaging system, and luminescence images of these phantoms were measured with a high-sensitivity, cooled charge coupled device (CCD) camera during X-ray photon irradiation at energy below 120 keV. We also carried out such imaging of an acrylic block and plastic scintillator. The luminescence images of water phantoms taken during X-ray photon irradiation clearly showed X-ray photon distribution. The intensity of the X-ray photon images of the phantom increased almost proportionally to the number of X-ray irradiations. Lower-energy X-ray photon irradiation showed lower-intensity luminescence at the deeper parts of the phantom due to the higher X-ray absorption in the water phantom. Furthermore, lower-intensity luminescence also appeared at the deeper parts of the acrylic phantom due to its higher density than water. The intensity of the luminescence for water was 0.005% of that for plastic scintillator. Luminescence imaging of water during X-ray photon irradiation at energy lower than 120 keV was possible. This luminescence imaging method is promising for dose estimation in X-ray imaging systems.

Multiband super-resolution imaging of graded-index photonic crystal flat lens

Science.gov (United States)

Xie, Jianlan; Wang, Junzhong; Ge, Rui; Yan, Bei; Liu, Exian; Tan, Wei; Liu, Jianjun

2018-05-01

Multiband super-resolution imaging of point source is achieved by a graded-index photonic crystal flat lens. With the calculations of six bands in common photonic crystal (CPC) constructed with scatterers of different refractive indices, it can be found that the super-resolution imaging of point source can be realized by different physical mechanisms in three different bands. In the first band, the imaging of point source is based on far-field condition of spherical wave while in the second band, it is based on the negative effective refractive index and exhibiting higher imaging quality than that of the CPC. However, in the fifth band, the imaging of point source is mainly based on negative refraction of anisotropic equi-frequency surfaces. The novel method of employing different physical mechanisms to achieve multiband super-resolution imaging of point source is highly meaningful for the field of imaging.

A parallel adaptive finite element simplified spherical harmonics approximation solver for frequency domain fluorescence molecular imaging

International Nuclear Information System (INIS)

Lu Yujie; Zhu Banghe; Rasmussen, John C; Sevick-Muraca, Eva M; Shen Haiou; Wang Ge

2010-01-01

Fluorescence molecular imaging/tomography may play an important future role in preclinical research and clinical diagnostics. Time- and frequency-domain fluorescence imaging can acquire more measurement information than the continuous wave (CW) counterpart, improving the image quality of fluorescence molecular tomography. Although diffusion approximation (DA) theory has been extensively applied in optical molecular imaging, high-order photon migration models need to be further investigated to match quantitation provided by nuclear imaging. In this paper, a frequency-domain parallel adaptive finite element solver is developed with simplified spherical harmonics (SP N ) approximations. To fully evaluate the performance of the SP N approximations, a fast time-resolved tetrahedron-based Monte Carlo fluorescence simulator suitable for complex heterogeneous geometries is developed using a convolution strategy to realize the simulation of the fluorescence excitation and emission. The validation results show that high-order SP N can effectively correct the modeling errors of the diffusion equation, especially when the tissues have high absorption characteristics or when high modulation frequency measurements are used. Furthermore, the parallel adaptive mesh evolution strategy improves the modeling precision and the simulation speed significantly on a realistic digital mouse phantom. This solver is a promising platform for fluorescence molecular tomography using high-order approximations to the radiative transfer equation.

Current state of molecular imaging research

International Nuclear Information System (INIS)

Grimm, J.; Wunder, A.

2005-01-01

The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly non-specific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments. (orig.)

Radiopharmaceuticals: nanoparticles like multi-functional systems for the obtaining in vivo of molecular images

International Nuclear Information System (INIS)

Ferro F, G.; Ramirez de la Cruz, F. M.; Ocampo G, B. E.; Morales A, E.; Santos C, C. L.; Mendoza S, A. N.

2010-01-01

The techniques of obtaining direct or indirect molecular images detect and register the space-temporary distribution of molecular or cellular processes for biochemical, biological, diagnostic and therapeutic applications. The advanced techniques of image like the nuclear magnetic resonance, the single photon emission computed tomography, the positron emission tomography and the images of optic fluorescence have been used successfully to detect these processes. On the other hand, the utility of the nanoparticles for any application is dependent of the physicochemical properties that present, being possible to modify their surface when making them react with different biomolecules what allows the formation of conjugates with specific molecular recognition. The joint of various protein molecules, peptides or oligonucleotides to the surface of a nanoparticle produce a multi-functional system able to increase the multivalent joints from the nanoparticles-biomolecules to their receivers for the obtaining of molecular images in vivo. The peptides stimulate, regulate or inhibit numerous functions of the life, acting mainly as information transmitters and activity coordinators of several tissues in the organism. The receivers of regulator peptides are over represented in numerous types of cancer cells and they are protein structures. These receivers have been used as white molecular of marked peptides, to locate primary malignant tumors and their metastasis, using the diagnostic techniques of molecular image mentioned above, which consist basically on the radio peptides use and conjugated peptides to fluoro chromes, to metallic nanoparticles and nano crystals. A summary of the work is presented carried out by the personnel of the Radio-active Materials and Chemistry Departments of the Instituto Nacional de Investigaciones Nucleares in this field. (Author)

Development of a calibration protocol for quantitative imaging for molecular radiotherapy dosimetry

International Nuclear Information System (INIS)

Wevrett, J.; Fenwick, A.; Scuffham, J.; Nisbet, A.

2017-01-01

Within the field of molecular radiotherapy, there is a significant need for standardisation in dosimetry, in both quantitative imaging and dosimetry calculations. Currently, there are a wide range of techniques used by different clinical centres and as a result there is no means to compare patient doses between centres. To help address this need, a 3 year project was funded by the European Metrology Research Programme, and a number of clinical centres were involved in the project. One of the required outcomes of the project was to develop a calibration protocol for three dimensional quantitative imaging of volumes of interest. Two radionuclides were selected as being of particular interest: iodine-131 ( 131 I, used to treat thyroid disorders) and lutetium-177 ( 177 Lu, used to treat neuroendocrine tumours). A small volume of activity within a scatter medium (water), representing a lesion within a patient body, was chosen as the calibration method. To ensure ease of use in clinical centres, an “off-the-shelf” solution was proposed – to avoid the need for in-house manufacturing. The BIODEX elliptical Jaszczak phantom and 16 ml fillable sphere were selected. The protocol was developed for use on SPECT/CT gamma cameras only, where the CT dataset would be used to correct the imaging data for attenuation of the emitted photons within the phantom. The protocol corrects for scatter of emitted photons using the triple energy window correction technique utilised by most clinical systems. A number of clinical systems were tested in the development of this protocol, covering the major manufacturers of gamma camera generally used in Europe. Initial imaging was performed with 131 I and 177 Lu at a number of clinical centres, but due to time constraints in the project, some acquisitions were performed with 177 Lu only. The protocol is relatively simplistic, and does not account for the effects of dead-time in high activity patients, the presence of background activity

Photon counting imaging and centroiding with an electron-bombarded CCD using single molecule localisation software

International Nuclear Information System (INIS)

Hirvonen, Liisa M.; Barber, Matthew J.; Suhling, Klaus

2016-01-01

Photon event centroiding in photon counting imaging and single-molecule localisation in super-resolution fluorescence microscopy share many traits. Although photon event centroiding has traditionally been performed with simple single-iteration algorithms, we recently reported that iterative fitting algorithms originally developed for single-molecule localisation fluorescence microscopy work very well when applied to centroiding photon events imaged with an MCP-intensified CMOS camera. Here, we have applied these algorithms for centroiding of photon events from an electron-bombarded CCD (EBCCD). We find that centroiding algorithms based on iterative fitting of the photon events yield excellent results and allow fitting of overlapping photon events, a feature not reported before and an important aspect to facilitate an increased count rate and shorter acquisition times.

Photon Counting Energy Dispersive Detector Arrays for X-ray Imaging.

Science.gov (United States)

Iwanczyk, Jan S; Nygård, Einar; Meirav, Oded; Arenson, Jerry; Barber, William C; Hartsough, Neal E; Malakhov, Nail; Wessel, Jan C

2009-01-01

The development of an innovative detector technology for photon-counting in X-ray imaging is reported. This new generation of detectors, based on pixellated cadmium telluride (CdTe) and cadmium zinc telluride (CZT) detector arrays electrically connected to application specific integrated circuits (ASICs) for readout, will produce fast and highly efficient photon-counting and energy-dispersive X-ray imaging. There are a number of applications that can greatly benefit from these novel imagers including mammography, planar radiography, and computed tomography (CT). Systems based on this new detector technology can provide compositional analysis of tissue through spectroscopic X-ray imaging, significantly improve overall image quality, and may significantly reduce X-ray dose to the patient. A very high X-ray flux is utilized in many of these applications. For example, CT scanners can produce ~100 Mphotons/mm(2)/s in the unattenuated beam. High flux is required in order to collect sufficient photon statistics in the measurement of the transmitted flux (attenuated beam) during the very short time frame of a CT scan. This high count rate combined with a need for high detection efficiency requires the development of detector structures that can provide a response signal much faster than the transit time of carriers over the whole detector thickness. We have developed CdTe and CZT detector array structures which are 3 mm thick with 16×16 pixels and a 1 mm pixel pitch. These structures, in the two different implementations presented here, utilize either a small pixel effect or a drift phenomenon. An energy resolution of 4.75% at 122 keV has been obtained with a 30 ns peaking time using discrete electronics and a (57)Co source. An output rate of 6×10(6) counts per second per individual pixel has been obtained with our ASIC readout electronics and a clinical CT X-ray tube. Additionally, the first clinical CT images, taken with several of our prototype photon-counting and

A small molecular pH-dependent fluorescent probe for cancer cell imaging in living cell.

Science.gov (United States)

Ma, Junbao; Li, Wenqi; Li, Juanjuan; Shi, Rongguang; Yin, Gui; Wang, Ruiyong

2018-05-15

A novel pH-dependent two-photon fluorescent molecular probe ABMP has been prepared based on the fluorophore of 2, 4, 6-trisubstituted pyridine. The probe has an absorption wavelength at 354 nm and corresponding emission wavelength at 475 nm with the working pH range from 2.20 to 7.00, especially owning a good liner response from pH = 2.40 to pH = 4.00. ABMP also has excellent reversibility, photostability and selectivity which promotes its ability in analytical application. The probe can be excited with a two-photon fluorescence microscopy and the fluorescence cell imaging indicated that the probe can distinguish Hela cancer cells out of normal cells with a two-photon fluorescence microscopy which suggested its potential application in tumor cell detection. Copyright © 2018 Elsevier B.V. All rights reserved.

DE-BLURRING SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY IMAGES USING WAVELET DECOMPOSITION

Directory of Open Access Journals (Sweden)

Neethu M. Sasi

2016-02-01

Full Text Available Single photon emission computed tomography imaging is a popular nuclear medicine imaging technique which generates images by detecting radiations emitted by radioactive isotopes injected in the human body. Scattering of these emitted radiations introduces blur in this type of images. This paper proposes an image processing technique to enhance cardiac single photon emission computed tomography images by reducing the blur in the image. The algorithm works in two main stages. In the first stage a maximum likelihood estimate of the point spread function and the true image is obtained. In the second stage Lucy Richardson algorithm is applied on the selected wavelet coefficients of the true image estimate. The significant contribution of this paper is that processing of images is done in the wavelet domain. Pre-filtering is also done as a sub stage to avoid unwanted ringing effects. Real cardiac images are used for the quantitative and qualitative evaluations of the algorithm. Blur metric, peak signal to noise ratio and Tenengrad criterion are used as quantitative measures. Comparison against other existing de-blurring algorithms is also done. The simulation results indicate that the proposed method effectively reduces blur present in the image.

Connotation and category of functional-molecular imaging

International Nuclear Information System (INIS)

Li Tianran; Tian Jiahe

2007-01-01

Function and molecular lmaging represent medical imaging' s direction. The review article introduce function and molecular's concept and category and its characteristic. Comparing with traditionary classics radiology, function and molecular imaging have many features, such as micro-mount and specificity and quantitative. There are many technology about function and molecular imaging. Function and molecular imaging is important ingredient of modern medical and play a considerable role. (authors)

Molecular engineering with artificial atoms: designing a material platform for scalable quantum spintronics and photonics

Science.gov (United States)

Doty, Matthew F.; Ma, Xiangyu; Zide, Joshua M. O.; Bryant, Garnett W.

2017-09-01

Self-assembled InAs Quantum Dots (QDs) are often called "artificial atoms" and have long been of interest as components of quantum photonic and spintronic devices. Although there has been substantial progress in demonstrating optical control of both single spins confined to a single QD and entanglement between two separated QDs, the path toward scalable quantum photonic devices based on spins remains challenging. Quantum Dot Molecules, which consist of two closely-spaced InAs QDs, have unique properties that can be engineered with the solid state analog of molecular engineering in which the composition, size, and location of both the QDs and the intervening barrier are controlled during growth. Moreover, applied electric, magnetic, and optical fields can be used to modulate, in situ, both the spin and optical properties of the molecular states. We describe how the unique photonic properties of engineered Quantum Dot Molecules can be leveraged to overcome long-standing challenges to the creation of scalable quantum devices that manipulate single spins via photonics.

Cherenkov detectors for spatial imaging applications using discrete-energy photons

Energy Technology Data Exchange (ETDEWEB)

Rose, Paul B.; Erickson, Anna S., E-mail: erickson@gatech.edu [Georgia Institute of Technology, Nuclear and Radiological Engineering, G.W. Woodruff School of Mechanical Engineering, 770 State St., Atlanta, Georgia 30332 (United States)

2016-08-14

Cherenkov detectors can offer a significant advantage in spatial imaging applications when excellent timing response, low noise and cross talk, large area coverage, and the ability to operate in magnetic fields are required. We show that an array of Cherenkov detectors with crude energy resolution coupled with monochromatic photons resulting from a low-energy nuclear reaction can be used to produce a sharp image of material while providing large and inexpensive detector coverage. The analysis of the detector response to relative transmission of photons with various energies allows for reconstruction of material's effective atomic number further aiding in high-Z material identification.

Photonics

CERN Document Server

Andrews, David L

2015-01-01

Discusses the basic physical principles underlying Biomedical Photonics, spectroscopy and microscopy This volume discusses biomedical photonics, spectroscopy and microscopy, the basic physical principles underlying the technology and its applications. The topics discussed in this volume are: Biophotonics; Fluorescence and Phosphorescence; Medical Photonics; Microscopy; Nonlinear Optics; Ophthalmic Technology; Optical Tomography; Optofluidics; Photodynamic Therapy; Image Processing; Imaging Systems; Sensors; Single Molecule Detection; Futurology in Photonics. Comprehensive and accessible cov

Molecular MR Imaging Probes

OpenAIRE

MAHMOOD, UMAR; JOSEPHSON, LEE

2005-01-01

Magnetic resonance imaging (MRI) has been successfully applied to many of the applications of molecular imaging. This review discusses by example some of the advances in areas such as multimodality MR-optical agents, receptor imaging, apoptosis imaging, angiogenesis imaging, noninvasive cell tracking, and imaging of MR marker genes.

Calibration of Cherenkov detectors for monoenergetic photon imaging in active interrogation applications

Energy Technology Data Exchange (ETDEWEB)

Rose, P.B., E-mail: prose6@gatech.edu; Erickson, A.S., E-mail: anna.erickson@me.gatech.edu

2015-11-01

Active interrogation of cargo containers using monoenergetic photons offers a rapid and low-dose approach to search for shielded special nuclear materials. Cherenkov detectors can be used for imaging of the cargo provided that gamma ray energies used in interrogation are well resolved, as the case in {sup 11}B(d,n-γ){sup 12}C reaction resulting in 4.4 MeV and 15.1 MeV photons. While an array of Cherenkov threshold detectors reduces low energy background from scatter while providing the ability of high contrast transmission imaging, thus confirming the presence of high-Z materials, these detectors require a special approach to energy calibration due to the lack of resolution. In this paper, we discuss the utility of Cherenkov detectors for active interrogation with monoenergetic photons as well as the results of computational and experimental studies of their energy calibration. The results of the studies with sources emitting monoenergetic photons as well as complex gamma ray spectrum sources, for example {sup 232}Th, show that calibration is possible as long as the energies of photons of interest are distinct.

SU-F-T-261: Reconstruction of Initial Photon Fluence Based On EPID Images

Energy Technology Data Exchange (ETDEWEB)

Seliger, T; Engenhart-Cabillic, R [Philipp University of Marburg, Marburg (Germany); Czarnecki, D; Maeder, U; Zink, K [Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen (Germany); Kussaether, R [MedCom GmbH, Darmstadt (Germany); Poppe, B [University Hospital for Medical Radiation Physics, Pius-Hospital, Medical Campus, Carl von Ossietzky University of Oldenburg (Germany)

2016-06-15

Purpose: Verifying an algorithm to reconstruct relative initial photon fluence for clinical use. Clinical EPID and CT images were acquired to reconstruct an external photon radiation treatment field. The reconstructed initial photon fluence could be used to verify the treatment or calculate the applied dose to the patient. Methods: The acquired EPID images were corrected for scatter caused by the patient and the EPID with an iterative reconstruction algorithm. The transmitted photon fluence behind the patient was calculated subsequently. Based on the transmitted fluence the initial photon fluence was calculated using a back-projection algorithm which takes the patient geometry and its energy dependent linear attenuation into account. This attenuation was gained from the acquired cone-beam CT or the planning CT by calculating a water-equivalent radiological thickness for each irradiation direction. To verify the algorithm an inhomogeneous phantom consisting of three inhomogeneities was irradiated by a static 6 MV photon field and compared to a reference flood field image. Results: The mean deviation between the reconstructed relative photon fluence for the inhomogeneous phantom and the flood field EPID image was 3% rising up to 7% for off-axis fluence. This was probably caused by the used clinical EPID calibration, which flattens the inhomogeneous fluence profile of the beam. Conclusion: In this clinical experiment the algorithm achieved good results in the center of the field while it showed high deviation of the lateral fluence. This could be reduced by optimizing the EPID calibration, considering the off-axis differential energy response. In further progress this and other aspects of the EPID, eg. field size dependency, CT and dose calibration have to be studied to realize a clinical acceptable accuracy of 2%.

Statistical x-ray computed tomography imaging from photon-starved measurements

Science.gov (United States)

Chang, Zhiqian; Zhang, Ruoqiao; Thibault, Jean-Baptiste; Sauer, Ken; Bouman, Charles

2013-03-01

Dose reduction in clinical X-ray computed tomography (CT) causes low signal-to-noise ratio (SNR) in photonsparse situations. Statistical iterative reconstruction algorithms have the advantage of retaining image quality while reducing input dosage, but they meet their limits of practicality when significant portions of the sinogram near photon starvation. The corruption of electronic noise leads to measured photon counts taking on negative values, posing a problem for the log() operation in preprocessing of data. In this paper, we propose two categories of projection correction methods: an adaptive denoising filter and Bayesian inference. The denoising filter is easy to implement and preserves local statistics, but it introduces correlation between channels and may affect image resolution. Bayesian inference is a point-wise estimation based on measurements and prior information. Both approaches help improve diagnostic image quality at dramatically reduced dosage.

In vivo three-photon imaging of deep cerebellum

Science.gov (United States)

Wang, Mengran; Wang, Tianyu; Wu, Chunyan; Li, Bo; Ouzounov, Dimitre G.; Sinefeld, David; Guru, Akash; Nam, Hyung-Song; Capecchi, Mario R.; Warden, Melissa R.; Xu, Chris

2018-02-01

We demonstrate three-photon microscopy (3PM) of mouse cerebellum at 1 mm depth by imaging both blood vessels and neurons. We compared 3PM and 2PM in the mouse cerebellum for imaging green (using excitation sources at 1300 nm and 920 nm, respectively) and red fluorescence (using excitation sources at 1680 nm and 1064 nm, respectively). 3PM enabled deeper imaging than 2PM because the use of longer excitation wavelength reduces the scattering in biological tissue and the higher order nonlinear excitation provides better 3D localization. To illustrate these two advantages quantitatively, we measured the signal decay as well as the signal-to-background ratio (SBR) as a function of depth. We performed 2-photon imaging from the brain surface all the way down to the area where the SBR reaches 1, while at the same depth, 3PM still has SBR above 30. The segmented decay curve shows that the mouse cerebellum has different effective attenuation lengths at different depths, indicating heterogeneous tissue property for this brain region. We compared the third harmonic generation (THG) signal, which is used to visualize myelinated fibers, with the decay curve. We found that the regions with shorter effective attenuation lengths correspond to the regions with more fibers. Our results indicate that the widespread, non-uniformly distributed myelinated fibers adds heterogeneity to mouse cerebellum, which poses additional challenges in deep imaging of this brain region.

Speckle imaging with the PAPA detector. [Precision Analog Photon Address

Science.gov (United States)

Papaliolios, C.; Nisenson, P.; Ebstein, S.

1985-01-01

A new 2-D photon-counting camera, the PAPA (precision analog photon address) detector has been built, tested, and used successfully for the acquisition of speckle imaging data. The camera has 512 x 512 pixels and operates at count rates of at least 200,000/sec. In this paper, technical details on the camera are presented and some of the laboratory and astronomical results are included which demonstrate the detector's capabilities.

Combined Raman and continuous-wave-excited two-photon fluorescence cell imaging

NARCIS (Netherlands)

Uzunbajakava, N.; Otto, Cornelis

2003-01-01

We demonstrate a confocal optical microscope that combines cw two-photon-excited fluorescence microscopy with confocal Raman microscopy. With this microscope fast image acquisition with fluorescence imaging can be used to select areas of interest for subsequent chemical analysis with spontaneous

THGEM based photon detector for Cherenkov imaging applications

CERN Document Server

Alexeev, M; Bradamante, F; Bressan, A; Chiosso, M; Ciliberti, P; Croci, G; Colantoni, M L; Dalla Torre, S; Duarte Pinto, S; Denisov, O; Diaz, V; Ferrero, A; Finger, M; Finger, M Jr; Fischer, H; Giacomini, G; Giorgi, M; Gobbo, B; Heinsius, F H; Herrmann, F; Jahodova, V; Königsmann, K; Lauser, L; Levorato, S; Maggiora, A; Martin, A; Menon, G; Nerling, F; Panzieri, D; Pesaro, G; Polak, J; Rocco, E; Ropelewski, L; Sauli, F; Sbrizzai, G; Schiavon, P; Schill, C; Schopferer, S; Slunecka, M; Sozzi, F; Steiger, L; Sulc, M; Takekawa, S; Tessarotto, F; Wollny, H

2010-01-01

We are developing a single photon detector for Cherenkov imaging counters. This detector is based on the use of THGEM electron multipliers in a multilayer design. The major goals of our project are ion feedback suppression down to a few per cent, large gain, fast response, insensitivity to magnetic fields, and a large detector size. We report about the project status and perspectives. In particular, we present a systematic study of the THGEM response as a function of geometrical parameters, production techniques and the gas mixture composition. The first figures obtained from measuring the response of a CsI coated THGEM to single photons are presented.

Development of gamma-photon/Cerenkov-light hybrid system for simultaneous imaging of I-131 radionuclide

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Seiichi; Suzuki, Mayumi; Kato, Katsuhiko [Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine (Japan); Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu [Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine (Japan); Ogata, Yoshimune [Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine (Japan); Hatazawa, Jun [Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine (Japan)

2016-09-11

Although iodine 131 (I-131) is used for radionuclide therapy, high resolution images are difficult to obtain with conventional gamma cameras because of the high energy of I-131 gamma photons (364 keV). Cerenkov-light imaging is a possible method for beta emitting radionuclides, and I-131 (606 MeV maximum beta energy) is a candidate to obtain high resolution images. We developed a high energy gamma camera system for I-131 radionuclide and combined it with a Cerenkov-light imaging system to form a gamma-photon/Cerenkov-light hybrid imaging system to compare the simultaneously measured images of these two modalities. The high energy gamma imaging detector used 0.85-mm×0.85-mm×10-mm thick GAGG scintillator pixels arranged in a 44×44 matrix with a 0.1-mm thick reflector and optical coupled to a Hamamatsu 2 in. square position sensitive photomultiplier tube (PSPMT: H12700 MOD). The gamma imaging detector was encased in a 2 cm thick tungsten shield, and a pinhole collimator was mounted on its top to form a gamma camera system. The Cerenkov-light imaging system was made of a high sensitivity cooled CCD camera. The Cerenkov-light imaging system was combined with the gamma camera using optical mirrors to image the same area of the subject. With this configuration, we simultaneously imaged the gamma photons and the Cerenkov-light from I-131 in the subjects. The spatial resolution and sensitivity of the gamma camera system for I-131 were respectively ~3 mm FWHM and ~10 cps/MBq for the high sensitivity collimator at 10 cm from the collimator surface. The spatial resolution of the Cerenkov-light imaging system was 0.64 mm FWHM at 10 cm from the system surface. Thyroid phantom and rat images were successfully obtained with the developed gamma-photon/Cerenkov-light hybrid imaging system, allowing direct comparison of these two modalities. Our developed gamma-photon/Cerenkov-light hybrid imaging system will be useful to evaluate the advantages and disadvantages of these two

Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators.

Science.gov (United States)

Chamberland, Simon; Yang, Helen H; Pan, Michael M; Evans, Stephen W; Guan, Sihui; Chavarha, Mariya; Yang, Ying; Salesse, Charleen; Wu, Haodi; Wu, Joseph C; Clandinin, Thomas R; Toth, Katalin; Lin, Michael Z; St-Pierre, François

2017-07-27

Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials. Here, we report ASAP2s, a novel voltage indicator with improved sensitivity. By imaging ASAP2s using random-access multi-photon microscopy, we demonstrate robust single-trial detection of action potentials in organotypic slice cultures. We also show that ASAP2s enables two-photon imaging of graded potentials in organotypic slice cultures and in Drosophila . These results demonstrate that the combination of ASAP2s and fast two-photon imaging methods enables detection of neural electrical activity with subcellular spatial resolution and millisecond-timescale precision.

Fluorescence based molecular in vivo imaging

International Nuclear Information System (INIS)

Ebert, Bernd

2008-01-01

Molecular imaging represents a modern research area that allows the in vivo study of molecular biological process kinetics using appropriate probes and visualization methods. This methodology may be defined- apart from the contrast media injection - as non-abrasive. In order to reach an in vivo molecular process imaging as accurate as possible the effects of the used probes on the biological should not be too large. The contrast media as important part of the molecular imaging can significantly contribute to the understanding of molecular processes and to the development of tailored diagnostics and therapy. Since more than 15 years PTB is developing optic imaging systems that may be used for fluorescence based visualization of tissue phantoms, small animal models and the localization of tumors and their predecessors, and for the early recognition of inflammatory processes in clinical trials. Cellular changes occur during many diseases, thus the molecular imaging might be of importance for the early diagnosis of chronic inflammatory diseases. Fluorescent dyes can be used as unspecific or also as specific contrast media, which allow enhanced detection sensitivity

Molecular ultrasound imaging: current status and future directions

International Nuclear Information System (INIS)

Deshpande, N.; Needles, A.; Willmann, J.K.

2010-01-01

Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre-clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic.

First observation of Cherenkov ring images using hybrid photon detectors

International Nuclear Information System (INIS)

Albrecht, E.; Wilkinson, G.; Bibby, J.H.; Giles, R.; Harnew, N.; Smale, N.; Brook, N.H.; Halley, A.W.; O'Shea, V.; French, M.; Gibson, V.; Wotton, S.A.; Schomaker, R.

1998-01-01

A ring-imaging Cherenkov detector, equipped with hybrid photon detectors, has been operated in a charged-particle beam. Focussed ring images from various particle types were detected using silica aerogel, air and C 4 F 10 gas radiators. The detector, a prototype for the CERN LHC-B experiment, is described and first observations are reported. (orig.)

First observation of Cherenkov ring images using hybrid photon detectors

Energy Technology Data Exchange (ETDEWEB)

Albrecht, E.; Wilkinson, G. [European Organization for Nuclear Research, Geneva (Switzerland). Div. Particle Physics Experiments; Barber, G.; Duane, A.; John, M.; Miller, D.G.; Websdale, D. [Imperial College of Science Technology and Medicine, Blackett Laboratory, Prince Consort Road, London SW7 2AZ (United Kingdom); Bibby, J.H.; Giles, R.; Harnew, N.; Smale, N. [University of Oxford, Department of Nuclear Physics, Keble Road, Oxford OX1 3RH (United Kingdom); Brook, N.H.; Halley, A.W.; O`Shea, V. [University of Glasgow, Department of Physics, Glasgow G12 8QQ (United Kingdom); French, M. [Rutherford Appleton Laboratory, Chilton, Didcot, Oxon OX11 0QX (United Kingdom); Gibson, V.; Wotton, S.A. [University of Cambridge, Cavendish Laboratory, Madingley Road, Cambridge CB3 0HE (United Kingdom); Schomaker, R. [Delft Electronic Products BV, 9300 AB Roden (Netherlands)

1998-07-11

A ring-imaging Cherenkov detector, equipped with hybrid photon detectors, has been operated in a charged-particle beam. Focussed ring images from various particle types were detected using silica aerogel, air and C{sub 4}F{sub 10} gas radiators. The detector, a prototype for the CERN LHC-B experiment, is described and first observations are reported. (orig.)

Possibility of single biomolecule imaging with coherent amplification of weak scattering x-ray photons.

Science.gov (United States)

Shintake, Tsumoru

2008-10-01

The number of photons produced by coherent x-ray scattering from a single biomolecule is very small because of its extremely small elastic-scattering cross section and low damage threshold. Even with a high x-ray flux of 3 x 10;{12} photons per 100-nm -diameter spot and an ultrashort pulse of 10 fs driven by a future x-ray free electron laser (x-ray FEL), it has been predicted that only a few 100 photons will be produced from the scattering of a single lysozyme molecule. In observations of scattered x rays on a detector, the transfer of energy from wave to matter is accompanied by the quantization of the photon energy. Unfortunately, x rays have a high photon energy of 12 keV at wavelengths of 1A , which is required for atomic resolution imaging. Therefore, the number of photoionization events is small, which limits the resolution of imaging of a single biomolecule. In this paper, I propose a method: instead of directly observing the photons scattered from the sample, we amplify the scattered waves by superimposing an intense coherent reference pump wave on it and record the resulting interference pattern on a planar x-ray detector. Using a nanosized gold particle as a reference pump wave source, we can collect 10;{4}-10;{5} photons in single shot imaging where the signal from a single biomolecule is amplified and recorded as two-dimensional diffraction intensity data. An iterative phase retrieval technique can be used to recover the phase information and reconstruct the image of the single biomolecule and the gold particle at the same time. In order to precisely reconstruct a faint image of the single biomolecule in Angstrom resolution, whose intensity is much lower than that of the bright gold particle, I propose a technique that combines iterative phase retrieval on the reference pump wave and the digital Fourier transform holography on the sample. By using a large number of holography data, the three-dimensional electron density map can be assembled.

A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: current state and future research opportunities.

Science.gov (United States)

Zürcher, Nicole R; Bhanot, Anisha; McDougle, Christopher J; Hooker, Jacob M

2015-05-01

Non-invasive positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are techniques used to quantify molecular interactions, biological processes and protein concentration and distribution. In the central nervous system, these molecular imaging techniques can provide critical insights into neurotransmitter receptors and their occupancy by neurotransmitters or drugs. In recent years, there has been an increase in the number of studies that have investigated neurotransmitters in autism spectrum disorder (ASD), while earlier studies mostly focused on cerebral blood flow and glucose metabolism. The underlying and contributing mechanisms of ASD are largely undetermined and ASD diagnosis relies on the behavioral phenotype. Discovery of biochemical endophenotypes would represent a milestone in autism research that could potentially lead to ASD subtype stratification and the development of novel therapeutic drugs. This review characterizes the prior use of molecular imaging by PET and SPECT in ASD, addresses methodological challenges and highlights areas of future opportunity for contributions from molecular imaging to understand ASD pathophysiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Angular correlations of photons from solution diffraction at a free-electron laser encode molecular structure

International Nuclear Information System (INIS)

Mendez, Derek; Watkins, Herschel; Qiao, Shenglan; Raines, Kevin S.; Lane, Thomas J.

2016-01-01

During X-ray exposure of a molecular solution, photons scattered from the same molecule are correlated. If molecular motion is insignificant during exposure, then differences in momentum transfer between correlated photons are direct measurements of the molecular structure. In conventional small- and wide-angle solution scattering, photon correlations are ignored. This report presents advances in a new biomolecular structural analysis technique, correlated X-ray scattering (CXS), which uses angular intensity correlations to recover hidden structural details from molecules in solution. Due to its intense rapid pulses, an X-ray free electron laser (XFEL) is an excellent tool for CXS experiments. A protocol is outlined for analysis of a CXS data set comprising a total of half a million X-ray exposures of solutions of small gold nanoparticles recorded at the Spring-8 Ångström Compact XFEL facility (SACLA). From the scattered intensities and their correlations, two populations of nanoparticle domains within the solution are distinguished: small twinned, and large probably non-twinned domains. Finally, it is shown analytically how, in a solution measurement, twinning information is only accessible via intensity correlations, demonstrating how CXS reveals atomic-level information from a disordered solution of like molecules.

Efficient multi-site two-photon functional imaging of neuronal circuits.

Science.gov (United States)

Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R

2016-12-01

Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms.

Imaging high energy photons with PILATUS II at the tagged photon beam at MAX-lab

Energy Technology Data Exchange (ETDEWEB)

Lee, V. [School of Physics, University of Melbourne, Parkville 3010 (Australia)], E-mail: leev@physics.unimelb.edu.au; Peake, D.J.; Sobott, B. [School of Physics, University of Melbourne, Parkville 3010 (Australia); Schroeder, B. [MAX-lab, Lund University, Lund (Sweden); Broennimann, Ch. [DECTRIS Ltd., Baden (Switzerland); Henrich, B. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Hansen, K. [MAX-lab, Lund University, Lund (Sweden); O' Keefe, G.J. [Centre for PET, Austin Hospital, Heidelberg, Victoria 3084 (Australia); School of Physics, University of Melbourne, Parkville 3010 (Australia); Taylor, G.N. [School of Physics, University of Melbourne, Parkville 3010 (Australia); Boland, M.J. [Australian Synchrotron, Clayton, Victoria 3168 (Australia); School of Physics, University of Melbourne, Parkville 3010 (Australia); Thompson, M.N.; Rassool, R.P. [School of Physics, University of Melbourne, Parkville 3010 (Australia)

2009-05-21

In photonuclear experiments precise location of the photon beam relative to the experimental sample is critical. Previously used techniques such as using photographic film to identify the position, intensity and centroid of the beam is time-consuming and a faster method is required. PILATUS is a single-photon-counting pixel detector developed at the Paul Scherrer Institute (PSI), Switzerland. It is a silicon-based, two-dimensional detector with a large dynamic range and zero readout noise. Designed as an X-ray detector, its optimal quantum efficiency is between 3 and 30 keV. This paper reports measurements carried out at the MAX-lab tagged photon facility in Lund, Sweden. The beam endpoint energy of approximately 200 MeV is far above the designed optimal energy detection range of PILATUS, and provides a critical test of the use of PILATUS under high energy conditions. The detector was placed in the photon beam and images were taken both downstream of other experiments, and in close range of a 19 mm collimator. The successful measurements demonstrate the versatility and robustness of the detector and provide an effective way of quickly and accurately monitoring beam position and profile in real time.

Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells

Science.gov (United States)

Han, Meng; Blindewald-Wittich, Almut; Holz, Frank G.; Giese, Günter; Niemz, Markolf H.; Snyder, Sarah; Sun, Hui; Yu, Jiayi; Agopov, Michael; La Schiazza, Olivier; Bille, Josef F.

2006-01-01

Degeneration of retinal pigment epithelial (RPE) cells severely impairs the visual function of retina photoreceptors. However, little is known about the events that trigger the death of RPE cells at the subcellular level. Two-photon excited autofluorescence (TPEF) imaging of RPE cells proves to be well suited to investigate both the morphological and the spectral characteristics of the human RPE cells. The dominant fluorophores of autofluorescence derive from lipofuscin (LF) granules that accumulate in the cytoplasm of the RPE cells with increasing age. Spectral TPEF imaging reveals the existence of abnormal LF granules with blue shifted autofluorescence in RPE cells of aging patients and brings new insights into the complicated composition of the LF granules. Based on a proposed two-photon laser scanning ophthalmoscope, TPEF imaging of the living retina may be valuable for diagnostic and pathological studies of age related eye diseases.

Simultaneous near field imaging of electric and magnetic field in photonic crystal nanocavities

NARCIS (Netherlands)

Vignolini, S.; Intonti, F.; Riboli, F.; Wiersma, D.S.; Balet, L.P.; Li, L.H.; Francardi, M.; Gerardino, A.; Fiore, A.; Gurioli, M.

2012-01-01

The insertion of a metal-coated tip on the surface of a photonic crystal microcavity is used for simultaneous near field imaging of electric and magnetic fields in photonic crystal nanocavities, via the radiative emission of embedded semiconductor quantum dots (QD). The photoluminescence intensity

X-ray imaging with photon counting hybrid semiconductor pixel detectors

CERN Document Server

Manolopoulos, S; Campbell, M; Snoeys, W; Heijne, Erik H M; Pernigotti, E; Raine, C; Smith, K; Watt, J; O'Shea, V; Ludwig, J; Schwarz, C

1999-01-01

Semiconductor pixel detectors, originally developed for particle physics experiments, have been studied as X-ray imaging devices. The performance of devices using the OMEGA 3 read-out chip bump-bonded to pixellated silicon semiconductor detectors is characterised in terms of their signal-to-noise ratio when exposed to 60 kVp X-rays. Although parts of the devices achieve values of this ratio compatible with the noise being photon statistics limited, this is not found to hold for the whole pixel matrix, resulting in the global signal-to-noise ratio being compromised. First results are presented of X-ray images taken with a gallium arsenide pixel detector bump-bonded to a new read-out chip, (MEDIPIX), which is a single photon counting read-out chip incorporating a 15-bit counter in every pixel. (author)

Polychromatic Iterative Statistical Material Image Reconstruction for Photon-Counting Computed Tomography

Directory of Open Access Journals (Sweden)

Thomas Weidinger

2016-01-01

Full Text Available This work proposes a dedicated statistical algorithm to perform a direct reconstruction of material-decomposed images from data acquired with photon-counting detectors (PCDs in computed tomography. It is based on local approximations (surrogates of the negative logarithmic Poisson probability function. Exploiting the convexity of this function allows for parallel updates of all image pixels. Parallel updates can compensate for the rather slow convergence that is intrinsic to statistical algorithms. We investigate the accuracy of the algorithm for ideal photon-counting detectors. Complementarily, we apply the algorithm to simulation data of a realistic PCD with its spectral resolution limited by K-escape, charge sharing, and pulse-pileup. For data from both an ideal and realistic PCD, the proposed algorithm is able to correct beam-hardening artifacts and quantitatively determine the material fractions of the chosen basis materials. Via regularization we were able to achieve a reduction of image noise for the realistic PCD that is up to 90% lower compared to material images form a linear, image-based material decomposition using FBP images. Additionally, we find a dependence of the algorithms convergence speed on the threshold selection within the PCD.

Molecular Biomedical Imaging Laboratory (MBIL)

Data.gov (United States)

Federal Laboratory Consortium — The Molecular Biomedical Imaging Laboratory (MBIL) is adjacent-a nd has access-to the Department of Radiology and Imaging Sciences clinical imaging facilities. MBIL...

Molecular imaging of transcriptional regulation during inflammation

Directory of Open Access Journals (Sweden)

Carlsen Harald

2010-04-01

Full Text Available Abstract Molecular imaging enables non-invasive visualization of the dynamics of molecular processes within living organisms in vivo. Different imaging modalities as MRI, SPECT, PET and optic imaging are used together with molecular probes specific for the biological process of interest. Molecular imaging of transcription factor activity is done in animal models and mostly in transgenic reporter mice, where the transgene essentially consists of a promoter that regulates a reporter gene. During inflammation, the transcription factor NF-κB is widely involved in orchestration and regulation of the immune system and almost all imaging studies in this field has revolved around the role and regulation of NF-κB. We here present a brief introduction to experimental use and design of transgenic reporter mice and a more extensive review of the various studies where molecular imaging of transcriptional regulation has been applied during inflammation.

RADIANCE AND PHOTON NOISE: Imaging in geometrical optics, physical optics, quantum optics and radiology.

Science.gov (United States)

Barrett, Harrison H; Myers, Kyle J; Caucci, Luca

2014-08-17

A fundamental way of describing a photon-limited imaging system is in terms of a Poisson random process in spatial, angular and wavelength variables. The mean of this random process is the spectral radiance. The principle of conservation of radiance then allows a full characterization of the noise in the image (conditional on viewing a specified object). To elucidate these connections, we first review the definitions and basic properties of radiance as defined in terms of geometrical optics, radiology, physical optics and quantum optics. The propagation and conservation laws for radiance in each of these domains are reviewed. Then we distinguish four categories of imaging detectors that all respond in some way to the incident radiance, including the new category of photon-processing detectors. The relation between the radiance and the statistical properties of the detector output is discussed and related to task-based measures of image quality and the information content of a single detected photon.

Diagnosis of basal cell carcinoma by two photon excited fluorescence combined with lifetime imaging

Science.gov (United States)

Fan, Shunping; Peng, Xiao; Liu, Lixin; Liu, Shaoxiong; Lu, Yuan; Qu, Junle

2014-02-01

Basal cell carcinoma (BCC) is the most common type of human skin cancer. The traditional diagnostic procedure of BCC is histological examination with haematoxylin and eosin staining of the tissue biopsy. In order to reduce complexity of the diagnosis procedure, a number of noninvasive optical methods have been applied in skin examination, for example, multiphoton tomography (MPT) and fluorescence lifetime imaging microscopy (FLIM). In this study, we explored two-photon optical tomography of human skin specimens using two-photon excited autofluorescence imaging and FLIM. There are a number of naturally endogenous fluorophores in skin sample, such as keratin, melanin, collagen, elastin, flavin and porphyrin. Confocal microscopy was used to obtain structures of the sample. Properties of epidermic and cancer cells were characterized by fluorescence emission spectra, as well as fluorescence lifetime imaging. Our results show that two-photon autofluorescence lifetime imaging can provide accurate optical biopsies with subcellular resolution and is potentially a quantitative optical diagnostic method in skin cancer diagnosis.

An area efficient readout architecture for photon counting color imaging

International Nuclear Information System (INIS)

Lundgren, Jan; O'Nils, Mattias; Oelmann, Bengt; Norlin, Boerje; Abdalla, Suliman

2007-01-01

The introduction of several energy levels, namely color imaging, in photon counting X-ray image sensors is a trade-off between circuit complexity and spatial resolution. In this paper, we propose a pixel architecture that has full resolution for the intensity and uses sub-sampling for the energy spectrum. The results show that this sub-sampling pixel architecture produces images with an image quality which is, on average, 2.4 dB (PSNR) higher than those for a single energy range architecture and with half the circuit complexity of that for a full sampling architecture

Molecular imaging promotes progress in orthopedic research.

Science.gov (United States)

Mayer-Kuckuk, Philipp; Boskey, Adele L

2006-11-01

Modern orthopedic research is directed towards the understanding of molecular mechanisms that determine development, maintenance and health of musculoskeletal tissues. In recent years, many genetic and proteomic discoveries have been made which necessitate investigation under physiological conditions in intact, living tissues. Molecular imaging can meet this demand and is, in fact, the only strategy currently available for noninvasive, quantitative, real-time biology studies in living subjects. In this review, techniques of molecular imaging are summarized, and applications to bone and joint biology are presented. The imaging modality most frequently used in the past was optical imaging, particularly bioluminescence and near-infrared fluorescence imaging. Alternate technologies including nuclear and magnetic resonance imaging were also employed. Orthopedic researchers have applied molecular imaging to murine models including transgenic mice to monitor gene expression, protein degradation, cell migration and cell death. Within the bone compartment, osteoblasts and their stem cells have been investigated, and the organic and mineral bone phases have been assessed. These studies addressed malignancy and injury as well as repair, including fracture healing and cell/gene therapy for skeletal defects. In the joints, molecular imaging has focused on the inflammatory and tissue destructive processes that cause arthritis. As described in this review, the feasibility of applying molecular imaging to numerous areas of orthopedic research has been demonstrated and will likely result in an increase in research dedicated to this powerful strategy. Molecular imaging holds great promise in the future for preclinical orthopedic research as well as next-generation clinical musculoskeletal diagnostics.

Molecular imaging in the era of personalized medicine.

Science.gov (United States)

Jung, Kyung-Ho; Lee, Kyung-Han

2015-01-01

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

Nanobody: the "magic bullet" for molecular imaging?

Science.gov (United States)

Chakravarty, Rubel; Goel, Shreya; Cai, Weibo

2014-01-01

Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases.

Single photon imaging. New instrumentation and techniques

International Nuclear Information System (INIS)

Muehllehner, G.; Colsher, J.

1981-01-01

The performance of Anger scintillation cameras continues to be enhanced through a series of small improvements which result in significantly better imaging characteristics. The most recent changes in camera design consist of: (1) the introduction of photomultipliers with better photocathode and electron collection efficiencies, (2) the use of thinner (3/8 or 1/4 in) crystals giving slightly better intrinsic resolution for low gamma-ray energies, (3) inclusion of a spatially varying energy window to compensate for variations of light collection efficiency, (4) event-by-event, real-time distortion removal for uniformity correction, and (5) introduction of new methods to improve the count-rate capability. Whereas some of these improvements are due to better understanding of the fundamentals of camera design, others are the result of technological advances in electronic components such as analogue-to-digital converters, microprocessors and high-density digital memories. The development of single photon tomography has developed along two parallel paths. Multipinhole and rotating slant-hole collimator attachments provide some degree of longitudinal tomography, and are currently being applied to cardiac imaging. At the same time rotating camera systems capable of transverse as well as longitudinal imaging are being refined technically and evaluated clinically. Longitudinal tomography is of limited use in quantitative studies and is likely to be an interim solution to three-dimensional imaging. Rotating camera systems, on the other hand, not only provide equal resolution in all three dimensions but are also capable of providing quantitative accuracy. This is the result of progress in attenuation correction and the design of special collimators. Single photon tomography provides a small but noticeable improvement in diagnostic accuracy which is likely to result in widespread use of rotating camera systems in the future

Optimization of a photon rejecter to separate electronic noise in a photon-counting detector

International Nuclear Information System (INIS)

Cho, Hyo-Min; Choi, Yu-Na; Lee, Seung-Wan; Lee, Young-Jin; Ryu, Hyun-Ju; Kim, Hee-Joung

2012-01-01

Photon-counting-based X-ray imaging technology provides the capability to count individual photons and to characterize photon energies. The cadmium telluride (CdTe)-based photon-counting detector is limited in capability, however, under a high X-ray flux. A photon rejecter composed of aluminum, for example, can reduce this limitation by modulating the incident number of photons. In addition to this function, the optimal photon rejecter can separate electronic noise, which degrades image quality. The aim of this work was to optimize a photon rejecter for high-quality image acquisition by removing electronic noise from the actual pulse signal. The images and spectra were acquired using a micro-focus X-ray source with a CdTe-based photon-counting detector. We acquired data with various types of photon-rejecter materials composed of aluminum (Al) and iodine at three different tube voltages (50, 70, and 90 kVp). A phantom composed of high-atomic-number materials was imaged to evaluate the efficiency of the photon rejecter. Photon rejecters composed of 1-mm Al, 10-mm Al, and a combination of 10-mm Al and iodine provided optimum capability at 50, 70, and 90 kVp, respectively. Each optimal combination of photon-rejecter material and voltage effectively separated electronic noise from the actual pulse signal and gave the highest contrast-to-noise ratio for materials on the image. These optimized types of photon rejecters can effectively discriminate electronic noise and improve image quality at different tube voltages.

Current perspectives in the use of molecular imaging to target surgical treatments for genitourinary cancers.

Science.gov (United States)

Greco, Francesco; Cadeddu, Jeffrey A; Gill, Inderbir S; Kaouk, Jihad H; Remzi, Mesut; Thompson, R Houston; van Leeuwen, Fijs W B; van der Poel, Henk G; Fornara, Paolo; Rassweiler, Jens

2014-05-01

Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery. Copyright © 2013

Molecular Imaging of Inflammation in Atherosclerosis

Science.gov (United States)

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

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

Directory of Open Access Journals (Sweden)

Nazanin Hakimzadeh

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

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

Science.gov (United States)

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

2017-01-01

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

Radiopharmaceuticals: nanoparticles like multi-functional systems for the obtaining in vivo of molecular images; Radiofarmacos: nanoparticulas como sistemas multifuncionales para la obtencion in vivo de imagenes moleculares

Energy Technology Data Exchange (ETDEWEB)

Ferro F, G.; Ramirez de la Cruz, F. M.; Ocampo G, B. E.; Morales A, E.; Santos C, C. L.; Mendoza S, A. N., E-mail: guillermina.ferro@inin.gob.m [ININ, Departamento de Materiales Radiactivos, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

2010-07-01

The techniques of obtaining direct or indirect molecular images detect and register the space-temporary distribution of molecular or cellular processes for biochemical, biological, diagnostic and therapeutic applications. The advanced techniques of image like the nuclear magnetic resonance, the single photon emission computed tomography, the positron emission tomography and the images of optic fluorescence have been used successfully to detect these processes. On the other hand, the utility of the nanoparticles for any application is dependent of the physicochemical properties that present, being possible to modify their surface when making them react with different biomolecules what allows the formation of conjugates with specific molecular recognition. The joint of various protein molecules, peptides or oligonucleotides to the surface of a nanoparticle produce a multi-functional system able to increase the multivalent joints from the nanoparticles-biomolecules to their receivers for the obtaining of molecular images in vivo. The peptides stimulate, regulate or inhibit numerous functions of the life, acting mainly as information transmitters and activity coordinators of several tissues in the organism. The receivers of regulator peptides are over represented in numerous types of cancer cells and they are protein structures. These receivers have been used as white molecular of marked peptides, to locate primary malignant tumors and their metastasis, using the diagnostic techniques of molecular image mentioned above, which consist basically on the radio peptides use and conjugated peptides to fluoro chromes, to metallic nanoparticles and nano crystals. A summary of the work is presented carried out by the personnel of the Radio-active Materials and Chemistry Departments of the Instituto Nacional de Investigaciones Nucleares in this field. (Author)

PET-based molecular imaging in neuroscience

International Nuclear Information System (INIS)

Jacobs, A.H.; Heiss, W.D.; Li, H.; Knoess, C.; Schaller, B.; Kracht, L.; Monfared, P.; Vollmar, S.; Bauer, B.; Wagner, R.; Graf, R.; Wienhard, K.; Winkeler, A.; Rueger, A.; Klein, M.; Hilker, R.; Galldiks, N.; Herholz, K.; Sobesky, J.

2003-01-01

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and ''phenotyping'' of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed. (orig.)

Reduction of CMOS Image Sensor Read Noise to Enable Photon Counting.

Science.gov (United States)

Guidash, Michael; Ma, Jiaju; Vogelsang, Thomas; Endsley, Jay

2016-04-09

Recent activity in photon counting CMOS image sensors (CIS) has been directed to reduction of read noise. Many approaches and methods have been reported. This work is focused on providing sub 1 e(-) read noise by design and operation of the binary and small signal readout of photon counting CIS. Compensation of transfer gate feed-through was used to provide substantially reduced CDS time and source follower (SF) bandwidth. SF read noise was reduced by a factor of 3 with this method. This method can be applied broadly to CIS devices to reduce the read noise for small signals to enable use as a photon counting sensor.

Photon migration in non-scattering tissue and the effects on image reconstruction

Science.gov (United States)

Dehghani, H.; Delpy, D. T.; Arridge, S. R.

1999-12-01

Photon propagation in tissue can be calculated using the relationship described by the transport equation. For scattering tissue this relationship is often simplified and expressed in terms of the diffusion approximation. This approximation, however, is not valid for non-scattering regions, for example cerebrospinal fluid (CSF) below the skull. This study looks at the effects of a thin clear layer in a simple model representing the head and examines its effect on image reconstruction. Specifically, boundary photon intensities (total number of photons exiting at a point on the boundary due to a source input at another point on the boundary) are calculated using the transport equation and compared with data calculated using the diffusion approximation for both non-scattering and scattering regions. The effect of non-scattering regions on the calculated boundary photon intensities is presented together with the advantages and restrictions of the transport code used. Reconstructed images are then presented where the forward problem is solved using the transport equation for a simple two-dimensional system containing a non-scattering ring and the inverse problem is solved using the diffusion approximation to the transport equation.

Photon migration in non-scattering tissue and the effects on image reconstruction

International Nuclear Information System (INIS)

Dehghani, H.; Delpy, D.T.; Arridge, S.R.

1999-01-01

Photon propagation in tissue can be calculated using the relationship described by the transport equation. For scattering tissue this relationship is often simplified and expressed in terms of the diffusion approximation. This approximation, however, is not valid for non-scattering regions, for example cerebrospinal fluid (CSF) below the skull. This study looks at the effects of a thin clear layer in a simple model representing the head and examines its effect on image reconstruction. Specifically, boundary photon intensities (total number of photons exiting at a point on the boundary due to a source input at another point on the boundary) are calculated using the transport equation and compared with data calculated using the diffusion approximation for both non-scattering and scattering regions. The effect of non-scattering regions on the calculated boundary photon intensities is presented together with the advantages and restrictions of the transport code used. Reconstructed images are then presented where the forward problem is solved using the transport equation for a simple two-dimensional system containing a non-scattering ring and the inverse problem is solved using the diffusion approximation to the transport equation. (author)

High contrast two-photon imaging of fingermarks

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Stoltzfus, Caleb R.; Rebane, Aleksander

2016-04-01

Optically-acquired fingermarks are widely used as evidence across law enforcement agencies as well as in the courts of law. A common technique for visualizing latent fingermarks on nonporous surfaces consists of cyanoacrylate fuming of the fingerprint material, followed by impregnation with a fluorescent dye, which under ultra violet (UV) illumination makes the fingermarks visible and thus accessible for digital recording. However, there exist critical circumstances, when the image quality is compromised due to high background scattering, high auto-fluorescence of the substrate material, or other detrimental photo-physical and photo-chemical effects such as light-induced damage to the sample. Here we present a novel near-infrared (NIR), two-photon induced fluorescence imaging modality, which significantly enhances the quality of the fingermark images, especially when obtained from highly reflective and/or scattering surfaces, while at the same time reducing photo-damage to sensitive forensic samples.

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

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

2017-07-01

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

FDTD Modeling of Nano- and Bio-Photonic Imaging

DEFF Research Database (Denmark)

Tanev, Stoyan; Tuchin, Valery; Pond, James

2010-01-01

to address newly emerging problems and not so much on its mathematical formulation. We will first discuss the application of a traditional formulation of the FDTD approach to the modeling of sub-wavelength photonics structures. Next, a modified total/scattered field FDTD approach will be applied...... to the modeling of biophotonics applications including Optical Phase Contrast Microscope (OPCM) imaging of cells containing gold nanoparticles (NPs) as well as its potential application as a modality for in vivo flow cytometry configurations.......In this paper we focus on the discussion of two recent unique applications of the Finite-Difference Time-Domain (FDTD) simulation method to the design and modeling of advanced nano- and bio-photonic problems. The approach that is adopted here focuses on the potential of the FDTD methodology...

A bioaccumulative cyclometalated platinum(II) complex with two-photon-induced emission for live cell imaging.

Science.gov (United States)

Koo, Chi-Kin; Wong, Ka-Leung; Man, Cornelia Wing-Yin; Lam, Yun-Wah; So, Leo King-Yan; Tam, Hoi-Lam; Tsao, Sai-Wah; Cheah, Kok-Wai; Lau, Kai-Chung; Yang, Yang-Yi; Chen, Jin-Can; Lam, Michael Hon-Wah

2009-02-02

The cyclometalated platinum(II) complex [Pt(L)Cl], where HL is a new cyclometalating ligand 2-phenyl-6-(1H-pyrazol-3-yl)pyridine containing C(phenyl), N(pyridyl), and N(pyrazolyl) donor moieties, was found to possess two-photon-induced luminescent properties. The two-photon-absorption cross section of the complex in N,N-dimethylformamide at room temperature was measured to be 20.8 GM. Upon two-photon excitation at 730 nm from a Ti:sapphire laser, bright-green emission was observed. Besides its two-photon-induced luminescent properties, [Pt(L)Cl] was able to be rapidly accumulated in live HeLa and NIH3T3 cells. The two-photon-induced luminescence of the complex was retained after live cell internalization and can be observed by two-photon confocal microscopy. Its bioaccumulation properties enabled time-lapse imaging of the internalization process of the dye into living cells. Cytotoxicity of [Pt(L)Cl] to both tested cell lines was low, according to MTT assays, even at loadings as high as 20 times the dose concentration for imaging for 6 h.

Thermally activated delayed fluorescence organic dots for two-photon fluorescence lifetime imaging

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He, Tingchao; Ren, Can; Li, Zhuohua; Xiao, Shuyu; Li, Junzi; Lin, Xiaodong; Ye, Chuanxiang; Zhang, Junmin; Guo, Lihong; Hu, Wenbo; Chen, Rui

2018-05-01

Autofluorescence is a major challenge in complex tissue imaging when molecules present in the biological tissue compete with the fluorophore. This issue may be resolved by designing organic molecules with long fluorescence lifetimes. The present work reports the two-photon absorption (TPA) properties of a thermally activated delayed fluorescence (TADF) molecule with carbazole as the electron donor and dicyanobenzene as the electron acceptor (i.e., 4CzIPN). The results indicate that 4CzIPN exhibits a moderate TPA cross-section (˜9 × 10-50 cm4 s photon-1), high fluorescence quantum yield, and a long fluorescence lifetime (˜1.47 μs). 4CzIPN was compactly encapsulated into an amphiphilic copolymer via nanoprecipitation to achieve water-soluble organic dots. Interestingly, 4CzIPN organic dots have been utilized in applications involving two-photon fluorescence lifetime imaging (FLIM). Our work aptly demonstrates that TADF molecules are promising candidates of nonlinear optical probes for developing next-generation multiphoton FLIM applications.

Molecular imaging. Fundamentals and applications

International Nuclear Information System (INIS)

Tian, Jie

2013-01-01

Covers a wide range of new theory, new techniques and new applications. Contributed by many experts in China. The editor has obtained the National Science and Technology Progress Award twice. ''Molecular Imaging: Fundamentals and Applications'' is a comprehensive monograph which describes not only the theory of the underlying algorithms and key technologies but also introduces a prototype system and its applications, bringing together theory, technology and applications. By explaining the basic concepts and principles of molecular imaging, imaging techniques, as well as research and applications in detail, the book provides both detailed theoretical background information and technical methods for researchers working in medical imaging and the life sciences. Clinical doctors and graduate students will also benefit from this book.

High sensitivity optical molecular imaging system

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An, Yu; Yuan, Gao; Huang, Chao; Jiang, Shixin; Zhang, Peng; Wang, Kun; Tian, Jie

2018-02-01

Optical Molecular Imaging (OMI) has the advantages of high sensitivity, low cost and ease of use. By labeling the regions of interest with fluorescent or bioluminescence probes, OMI can noninvasively obtain the distribution of the probes in vivo, which play the key role in cancer research, pharmacokinetics and other biological studies. In preclinical and clinical application, the image depth, resolution and sensitivity are the key factors for researchers to use OMI. In this paper, we report a high sensitivity optical molecular imaging system developed by our group, which can improve the imaging depth in phantom to nearly 5cm, high resolution at 2cm depth, and high image sensitivity. To validate the performance of the system, special designed phantom experiments and weak light detection experiment were implemented. The results shows that cooperated with high performance electron-multiplying charge coupled device (EMCCD) camera, precision design of light path system and high efficient image techniques, our OMI system can simultaneously collect the light-emitted signals generated by fluorescence molecular imaging, bioluminescence imaging, Cherenkov luminance and other optical imaging modality, and observe the internal distribution of light-emitting agents fast and accurately.

Two-Photon Autofluorescence Imaging Reveals Cellular Structures Throughout the Retina of the Living Primate Eye.

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Sharma, Robin; Williams, David R; Palczewska, Grazyna; Palczewski, Krzysztof; Hunter, Jennifer J

2016-02-01

Although extrinsic fluorophores can be introduced to label specific cell types in the retina, endogenous fluorophores, such as NAD(P)H, FAD, collagen, and others, are present in all retinal layers. These molecules are a potential source of optical contrast and can enable noninvasive visualization of all cellular layers. We used a two-photon fluorescence adaptive optics scanning light ophthalmoscope (TPF-AOSLO) to explore the native autofluorescence of various cell classes spanning several layers in the unlabeled retina of a living primate eye. Three macaques were imaged on separate occasions using a custom TPF-AOSLO. Two-photon fluorescence was evoked by pulsed light at 730 and 920 nm excitation wavelengths, while fluorescence emission was collected in the visible range from several retinal layers and different locations. Backscattered light was recorded simultaneously in confocal modality and images were postprocessed to remove eye motion. All retinal layers yielded two-photon signals and the heterogeneous distribution of fluorophores provided optical contrast. Several structural features were observed, such as autofluorescence from vessel walls, Müller cell processes in the nerve fibers, mosaics of cells in the ganglion cell and other nuclear layers of the inner retina, as well as photoreceptor and RPE layers in the outer retina. This in vivo survey of two-photon autofluorescence throughout the primate retina demonstrates a wider variety of structural detail in the living eye than is available through conventional imaging methods, and broadens the use of two-photon imaging of normal and diseased eyes.

Evaluation of conventional imaging performance in a research whole-body CT system with a photon-counting detector array.

Science.gov (United States)

Yu, Zhicong; Leng, Shuai; Jorgensen, Steven M; Li, Zhoubo; Gutjahr, Ralf; Chen, Baiyu; Halaweish, Ahmed F; Kappler, Steffen; Yu, Lifeng; Ritman, Erik L; McCollough, Cynthia H

2016-02-21

This study evaluated the conventional imaging performance of a research whole-body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x

Evaluation of conventional imaging performance in a research whole-body CT system with a photon-counting detector array

International Nuclear Information System (INIS)

Yu, Zhicong; Leng, Shuai; Li, Zhoubo; Chen, Baiyu; Yu, Lifeng; McCollough, Cynthia H; Jorgensen, Steven M; Ritman, Erik L; Gutjahr, Ralf; Kappler, Steffen; Halaweish, Ahmed F

2016-01-01

This study evaluated the conventional imaging performance of a research whole-body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x

Feasibility of photon-counting K-edge imaging in X-ray and computed tomographic systems: Monte Carlo simulation studies

International Nuclear Information System (INIS)

Lee, Seung-Wan; Choi, Yu-Na; Cho, Hyo-Min; Lee, Young-Jin; Ryu, Hyun-Ju; Kim, Hee-Joung

2011-01-01

Conventional X-ray systems and X-ray computed tomography (CT) systems, which use detectors operated in the integrating mode, are not able to reflect spectral information because the detector output is proportional to the energy fluence integrated over the whole spectrum. Photon-counting detectors have been considered as alternative devices. These detectors can measure the photon energy deposited by each event and improve the image quality. In this study, we investigated the feasibility of K-edge imaging using a photon-counting detector and evaluated the capability of material decomposition in X-ray images. The geometries of X-ray imaging systems equipped with cadmium telluride (CdTe) detectors and phantoms consisting of different materials were designed using Geant4 Application for Tomographic Emission (GATE) version 6.0. To observe the effect of a discontinuity in the attenuation due to the K-edge of a high atomic number material, we chose the energy windows to be one below and one above the K-edge absorption energy of the target material. The contrast-to-noise ratios (CNRs) of the target materials were increased at selective energy levels above the K-edge absorption energy because the attenuation is more dramatically increased at energies above the K-edge absorption energy of the material than at energies below that. The CNRs for the target materials in the K-edge image were proportional to the material concentration. The results of this study show that K-edge imaging can be carried out in conventional X-ray systems and X-ray CT systems using CdTe photon-counting detectors and that the target materials can be separated from background materials by using K-edge imaging. The photon-counting detector has potential to provide improved image quality, and this study will be used as a basis for future studies on photon-counting X-ray imaging.

Fluorenyl benzothiadiazole and benzoselenadiazole near-IR fluorescent probes for two-photon fluorescence imaging (Conference Presentation)

Science.gov (United States)

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 (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.

Whole brain imaging with Serial Two-Photon Tomography

Directory of Open Access Journals (Sweden)

Stephen P Amato

2016-03-01

Full Text Available Imaging entire mouse brains at submicron resolution has historically been a challenging undertaking and largely confined to the province of dedicated atlasing initiatives. The has limited systematic investigations into important areas of neuroscience, such as neural circuits, brain mapping and neurodegeneration. In this paper, we describe in detail Serial Two-Photon (STP tomography, a robust, reliable method for imaging entire brains with histological detail. We provide examples of how the basic methodology can be extended to other imaging modalities, such as optical coherence tomography, in order to provide unique contrast mechanisms. Furthermore we provide a survey of the research that STP tomography has enabled in the field of neuroscience, provide examples of how this technology enables quantitative whole brain studies, and discuss the current limitations of STP tomography-based approaches

Photon event distribution sampling: an image formation technique for scanning microscopes that permits tracking of sub-diffraction particles with high spatial and temporal resolutions.

Science.gov (United States)

Larkin, J D; Publicover, N G; Sutko, J L

2011-01-01

In photon event distribution sampling, an image formation technique for scanning microscopes, the maximum likelihood position of origin of each detected photon is acquired as a data set rather than binning photons in pixels. Subsequently, an intensity-related probability density function describing the uncertainty associated with the photon position measurement is applied to each position and individual photon intensity distributions are summed to form an image. Compared to pixel-based images, photon event distribution sampling images exhibit increased signal-to-noise and comparable spatial resolution. Photon event distribution sampling is superior to pixel-based image formation in recognizing the presence of structured (non-random) photon distributions at low photon counts and permits use of non-raster scanning patterns. A photon event distribution sampling based method for localizing single particles derived from a multi-variate normal distribution is more precise than statistical (Gaussian) fitting to pixel-based images. Using the multi-variate normal distribution method, non-raster scanning and a typical confocal microscope, localizations with 8 nm precision were achieved at 10 ms sampling rates with acquisition of ~200 photons per frame. Single nanometre precision was obtained with a greater number of photons per frame. In summary, photon event distribution sampling provides an efficient way to form images when low numbers of photons are involved and permits particle tracking with confocal point-scanning microscopes with nanometre precision deep within specimens. © 2010 The Authors Journal of Microscopy © 2010 The Royal Microscopical Society.

A novel high resolution, high sensitivity SPECT detector for molecular imaging of cardiovascular diseases

Science.gov (United States)

Cusanno, F.; Argentieri, A.; Baiocchi, M.; Colilli, S.; Cisbani, E.; De Vincentis, G.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M. L.; Majewski, S.; Marano, G.; Musico, P.; Musumeci, M.; Santavenere, F.; Torrioli, S.; Tsui, B. M. W.; Vitelli, L.; Wang, Y.

2010-05-01

Cardiovascular diseases are the most common cause of death in western countries. Understanding the rupture of vulnerable atherosclerotic plaques and monitoring the effect of innovative therapies of heart failure is of fundamental importance. A flexible, high resolution, high sensitivity detector system for molecular imaging with radionuclides on small animal models has been designed for this aim. A prototype has been built using tungsten pinhole and LaBr3(Ce) scintillator coupled to Hamamatsu Flat Panel PMTs. Compact individual-channel readout has been designed, built and tested. Measurements with phantoms as well as pilot studies on mice have been performed, the results show that the myocardial perfusion in mice can be determined with sufficient precision. The detector will be improved replacing the Hamamatsu Flat Panel with Silicon Photomultipliers (SiPMs) to allow integration of the system with MRI scanners. Application of LaBr3(Ce) scintillator coupled to photosensor with high photon detection efficiency and excellent energy resolution will allow dual-label imaging to monitor simultaneously the cardiac perfusion and the molecular targets under investigation during the heart therapy.

Molecular imaging II

International Nuclear Information System (INIS)

Semmler, Wolfhard; Schwaiger, Markus

2008-01-01

The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation. (orig.)

Molecular imaging in cardiovascular diseases

International Nuclear Information System (INIS)

Botnar, R.M.; Ebersberger, H.; Noerenberg, D.

2015-01-01

Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced.

Development of a compact scintillator-based high-resolution Compton camera for molecular imaging

Energy Technology Data Exchange (ETDEWEB)

Kishimoto, A., E-mail: daphne3h-aya@ruri.waseda.jp [Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo (Japan); Kataoka, J.; Koide, A.; Sueoka, K.; Iwamoto, Y.; Taya, T. [Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo (Japan); Ohsuka, S. [Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu, Shizuoka (Japan)

2017-02-11

The Compton camera, which shows gamma-ray distribution utilizing the kinematics of Compton scattering, is a promising detector capable of imaging across a wide range of energy. In this study, we aim to construct a small-animal molecular imaging system in a wide energy range by using the Compton camera. We developed a compact medical Compton camera based on a Ce-doped Gd{sub 3}Al{sub 2}Ga{sub 3}O{sub 12} (Ce:GAGG) scintillator and multi-pixel photon counter (MPPC). A basic performance confirmed that for 662 keV, the typical energy resolution was 7.4 % (FWHM) and the angular resolution was 4.5° (FWHM). We then used the medical Compton camera to conduct imaging experiments based on a 3-D imaging reconstruction algorithm using the multi-angle data acquisition method. The result confirmed that for a {sup 137}Cs point source at a distance of 4 cm, the image had a spatial resolution of 3.1 mm (FWHM). Furthermore, we succeeded in producing 3-D multi-color image of different simultaneous energy sources ({sup 22}Na [511 keV], {sup 137}Cs [662 keV], and {sup 54}Mn [834 keV]).

Has molecular imaging delivered to drug development?

Science.gov (United States)

Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.

2017-10-01

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

Evaluation of scintillators and semiconductor detectors to image three-photon positron annihilation for positron emission tomography

International Nuclear Information System (INIS)

Abuelhia, E.; Spyrou, N.M.; Kacperski, K.; College University, Middlesex Hospital, London

2008-01-01

Positron emission tomography (PET) is rapidly becoming the main nuclear imaging modality of the present century. The future of PET instrumentation relies on semiconductor detectors because of their excellent characteristics. Three-photon positron annihilation has been recently investigated as a novel imaging modality, which demands the crucial high energy resolution of semiconductor detector. In this work the evaluation of the NaI(Tl) scintillator and HPGe and CdZTe semiconductor detectors, to construct a simple three-photon positron annihilation scanner has been explored. The effect of detector and scanner size on spatial resolution (FWHM) is discussed. The characteristics: energy resolution versus count rate and point-spread function of the three-photon positron annihilation image profile from triple coincidence measurements were investigated. (author)

Two-photon excited autofluorescence imaging of freshly isolated frog retinas.

Science.gov (United States)

Lu, Rong-Wen; Li, Yi-Chao; Ye, Tong; Strang, Christianne; Keyser, Kent; Curcio, Christine A; Yao, Xin-Cheng

2011-06-01

The purpose of this study was to investigate cellular sources of autofluorescence signals in freshly isolated frog (Rana pipiens) retinas. Equipped with an ultrafast laser, a laser scanning two-photon excitation fluorescence microscope was employed for sub-cellular resolution examination of both sliced and flat-mounted retinas. Two-photon imaging of retinal slices revealed autofluorescence signals over multiple functional layers, including the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Using flat-mounted retinas, depth-resolved imaging of individual retinal layers further confirmed multiple sources of autofluorescence signals. Cellular structures were clearly observed at the PRL, ONL, INL, and GCL. At the PRL, the autofluorescence was dominantly recorded from the intracellular compartment of the photoreceptors; while mixed intracellular and extracellular autofluorescence signals were observed at the ONL, INL, and GCL. High resolution autofluorescence imaging clearly revealed mosaic organization of rod and cone photoreceptors; and sub-cellular bright autofluorescence spots, which might relate to connecting cilium, was observed in the cone photoreceptors only. Moreover, single-cone and double-cone outer segments could be directly differentiated.

Nanobody: The “Magic Bullet” for Molecular Imaging?

Science.gov (United States)

Chakravarty, Rubel; Goel, Shreya; Cai, Weibo

2014-01-01

Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases. PMID:24578722

Processing method of images obtained during the TESIS/CORONAS-PHOTON experiment

Science.gov (United States)

Kuzin, S. V.; Shestov, S. V.; Bogachev, S. A.; Pertsov, A. A.; Ulyanov, A. S.; Reva, A. A.

2011-04-01

In January 2009, the CORONAS-PHOTON spacecraft was successfully launched. It includes a set of telescopes and spectroheliometers—TESIS—designed to image the solar corona in soft X-ray and EUV spectral ranges. Due to features of the reading system, to obtain physical information from these images, it is necessary to preprocess them, i.e., to remove the background, correct the white field, level, and clean. The paper discusses the algorithms and software developed and used for the preprocessing of images.

High Dynamic Range Imaging at the Quantum Limit with Single Photon Avalanche Diode-Based Image Sensors †

Science.gov (United States)

Mattioli Della Rocca, Francescopaolo

2018-01-01

This paper examines methods to best exploit the High Dynamic Range (HDR) of the single photon avalanche diode (SPAD) in a high fill-factor HDR photon counting pixel that is scalable to megapixel arrays. The proposed method combines multi-exposure HDR with temporal oversampling in-pixel. We present a silicon demonstration IC with 96 × 40 array of 8.25 µm pitch 66% fill-factor SPAD-based pixels achieving >100 dB dynamic range with 3 back-to-back exposures (short, mid, long). Each pixel sums 15 bit-planes or binary field images internally to constitute one frame providing 3.75× data compression, hence the 1k frames per second (FPS) output off-chip represents 45,000 individual field images per second on chip. Two future projections of this work are described: scaling SPAD-based image sensors to HDR 1 MPixel formats and shrinking the pixel pitch to 1–3 µm. PMID:29641479

NEAR-IR TWO PHOTON MICROSCOPY IMAGING OF SILICA NANOPARTICLES FUNCTIONALIZED WITH ISOLATED SENSITIZED Yb(III) CENTERS

Energy Technology Data Exchange (ETDEWEB)

Lapadula, Giuseppe; Bourdolle, Adrien; Allouche, Florian; Conley, Matthew P.; Maron, Laurent; Lukens, Wayne W.; Guyot, Yannick; Andraud, Chantal; Brasselet, Sophie; Copé; ret, Christophe; Maury, Olivier; Andersen, Richard A.

2013-01-12

Bright nano objects emitting in the near infrared with a maximal cross section of 41.4 x 103 GM (Goppert Mayer), were prepared by implanting ca. 180 4,4 diethylaminostyryl 2,2 bipyridine (DEAS) Yb(III) complexes on the surface of 12 nm silica nanoparticles. The surface complexes ([DEAS Ln SiO2], Ln =Y,Yb) were characterized using IR, solid state NMR, UV Vis, EXAFS spectroscopies in combination with the preparation and characterization of similar molecular analogues by analytical techniques (IR, solution NMR, UV Vis, X ray crystallography) as well as DFT calculations. Starting from the partial dehydroxylation of the silica at 700 C on high vacuum having 0.8 OH.nm 2, the grafting of Ln(N(SiMe3)2)3 generate ≤SiO Ln(N(SiMe3)2)2, which upon thermal step and coordination of the DEAS chromophore yields (≤SiO)3Ln(DEAS). Surface and molecular analogues display similar properties, in terms of DEAS binding constants absorption maxima and luminescence properties (intense emission band assigned to a ligand centered CT fluorescence and life time) in the solid state, consistent with the molecular nature of the surface species. The densely functionalized nanoparticles can be dispersed via ultra-sonication in small ca. 15-20 nm aggregates (1 to 6 elementary particles) that were detected using two photon microscopy imaging at 720 nm excitation, making them promising nano objects for bio imaging.

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines

Directory of Open Access Journals (Sweden)

Ruijie Li

2018-04-01

Full Text Available In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs, we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Bi-photon imaging and diagnostics using ultra-small diagnostic probes engineered from semiconductor nanocrystals and single-domain antibodies

Science.gov (United States)

Hafian, Hilal; Sukhanova, Alyona; Chames, Patrick; Baty, Daniel; Pluot, Michel; Cohen, Jacques H. M.; Nabiev, Igor R.; Millot, Jean-Marc

2012-10-01

Semiconductor fluorescent quantum dots (QDs) have just demonstrated their numerous advantages over organic dyes in bioimaging and diagnostics. One of characteristics of QDs is a very large cross section of their twophoton absorption. A common approach to biodetection by means of QDs is to use monoclonal antibodies (mAbs) for targeting. Recently, we have engineered ultrasmall diagnostic nanoprobes (sdAb-QD) based on highly oriented conjugates of QDs with the single-domain antibodies (sdAbs) against cancer biomarkers. With a molecular weight of only 13 kDa (12-fold smaller than full-size mAbs) and extreme stability and capacity to refolding, sdAbs are the smallest functional Ab fragments capable of binding antigens with affinities comparable to those of conventional Abs. Ultrasmall diagnostic sdAb-QD nanoprobes were engineered through oriented conjugation of QDs with sdAbs. This study is the first to demonstrate the possibility of immunohistochemical imaging of colon carcinoma biomarkers with sdAb-QD conjugates by means of two-photon excitation. The optimal excitation conditions for imaging of the markers in clinical samples with sdAb-QD nanoprobes have been determined. The absence of sample autofluorescence significantly improves the sensitivity of biomarker detection with the use of the two-photon excitation diagnostic setup.

Inorganic Nanoparticles for Multimodal Molecular Imaging

Directory of Open Access Journals (Sweden)

Magdalena Swierczewska

2011-01-01

Full Text Available Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle-based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles.

[Future perspectives for diagnostic imaging in urology: from anatomic and functional to molecular imaging].

Science.gov (United States)

Macis, Giuseppe; Di Giovanni, Silvia; Di Franco, Davide; Bonomo, Lorenzo

2013-01-01

The future approach of diagnostic imaging in urology follows the technological progress, which made the visualization of in vivo molecular processes possible. From anatomo-morphological diagnostic imaging and through functional imaging molecular radiology is reached. Based on molecular probes, imaging is aimed at assessing the in vivo molecular processes, their physiology and function at cellular level. The future imaging will investigate the complex tumor functioning as metabolism, aerobic glycolysis in particular, angiogenesis, cell proliferation, metastatic potential, hypoxia, apoptosis and receptors expressed by neoplastic cells. Methods for performing molecular radiology are CT, MRI, PET-CT, PET-MRI, SPECT and optical imaging. Molecular ultrasound combines technological advancement with targeted contrast media based on microbubbles, this allowing the selective registration of microbubble signal while that of stationary tissues is suppressed. An experimental study was carried out where the ultrasound molecular probe BR55 strictly bound to prostate tumor results in strong enhancement in the early phase after contrast, this contrast being maintained in the late phase. This late enhancement is markedly significant for the detection of prostatic cancer foci and to guide the biopsy sampling. The 124I-cG250 molecular antibody which is strictly linked to cellular carbonic anhydrase IX of clear cell renal carcinoma, allows the acquisition of diagnostic PET images of clear cell renal carcinoma without biopsy. This WG-250 (RENCAREX) antibody was used as a therapy in metastatic clear cell renal carcinoma. Future advancements and applications will result in early cancer diagnosis, personalized therapy that will be specific according to the molecular features of cancer and leading to the development of catheter-based multichannel molecular imaging devices for cystoscopy-based molecular imaging diagnosis and intervention.

Radiation protection in image installations Preclinical Molecular; Protección radiológica en instalaciones de Imagen Molecular Preclínica

Energy Technology Data Exchange (ETDEWEB)

Martí-Climent, J. M.; Collantes, M.; Prieto, E.; Morán, V.; Ecay, M.; Peñuelas, I.

2014-07-01

The preclinical image includes several molecular imaging techniques using ionizing radiation, particularly the single photon emission computed tomography (SPECT), the positron emission tomography (PET) and the autoradiographic image. Each technique uses different probes which allow imaging of a variety of metabolic processes. Sometimes they are used together with X-ray equipment which can obtain anatomical images. Consequently, research performed in preclinical molecular imaging facilities should be done in a context in which radiation protection is applied. Within radiological risks to the staff operating such facilities, the irradiation produced to hands due to the administration of radiotracers and to animals manipulation should be of major concern; therefore training and shielding are important. The design of the radioactive facility will be determined by the various activities undertaken. In particular, it will depend on the various preclinical molecular imaging techniques that would be developed and on the functional relationship that the facility has with the institution in which it is placed; particularly the animal housing facility and radiopharmacy unit. [Spanish] La imagen preclínica engloba distintas técnicas de imagen molecular que utilizan radiaciones ionizantes, destacando la tomografía por emisión de fotón único (SPECT), la tomografía de emisión de positrones (PET) y la imagen autorradiográfica. Cada una de ellas utiliza distintas sondas que permiten obtener imágenes de una gran variedad de procesos metabólicos. En ocasiones se emplean junto a equipos de rayos X que permiten obtener imágenes anatómicas. En consecuencia, la investigación en las instalaciones de imagen molecular preclínica deberá realizarse en un contexto en el que se aplique la protección radiológica. De entre los riesgos radiológicos del personal que opera este tipo de instalaciones destaca la irradiación de las manos producida tanto por la administración de los

Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors.

Science.gov (United States)

Ale, Angelique; Schulz, Ralf B; Sarantopoulos, Athanasios; Ntziachristos, Vasilis

2010-05-01

The performance is studied of two newly introduced and previously suggested methods that incorporate priors into inversion schemes associated with data from a recently developed hybrid x-ray computed tomography and fluorescence molecular tomography system, the latter based on CCD camera photon detection. The unique data set studied attains accurately registered data of high spatially sampled photon fields propagating through tissue along 360 degrees projections. Approaches that incorporate structural prior information were included in the inverse problem by adding a penalty term to the minimization function utilized for image reconstructions. Results were compared as to their performance with simulated and experimental data from a lung inflammation animal model and against the inversions achieved when not using priors. The importance of using priors over stand-alone inversions is also showcased with high spatial sampling simulated and experimental data. The approach of optimal performance in resolving fluorescent biodistribution in small animals is also discussed. Inclusion of prior information from x-ray CT data in the reconstruction of the fluorescence biodistribution leads to improved agreement between the reconstruction and validation images for both simulated and experimental data.

Ralicon anodes for image photon counting fabricated by electron beam lithography

International Nuclear Information System (INIS)

Burton, W.M.

1982-01-01

The Anger wedge and strip anode event location system developed for microchannel plate image photon detectors at the Space Sciences Laboratory of the University of California, Berkeley, has been extended in the present work by the use of electron beam lithography (EBL). This method of fabrication can be used to produce optical patterns for the subsequent manufacture of anodes by conventional photo-etching methods and has also enabled anodes to be produced directly by EBL microfabrication techniques. Computer-aided design methods have been used to develop several types of RALICON (Readout Anodes of Lithographic Construction) for use in photon counting microchannel plate imaging detectors. These anodes are suitable for linear, two dimensional or radial position measurements and they incorporate novel design features made possible by the EBL fabrication technique which significantly extend their application relative to published wedge-strip anode designs. (author)

High-resolution wavefront shaping with a photonic crystal fiber for multimode fiber imaging

NARCIS (Netherlands)

Amitonova, L. V.; Descloux, A.; Petschulat, J.; Frosz, M. H.; Ahmed, G.; Babic, F.; Jiang, X.; Mosk, A. P.; Russell, P. S. J.; Pinkse, P.W.H.

2016-01-01

We demonstrate that a high-numerical-aperture photonic crystal fiber allows lensless focusing at an unparalleled res- olution by complex wavefront shaping. This paves the way toward high-resolution imaging exceeding the capabilities of imaging with multi-core single-mode optical fibers. We analyze

Singular value decomposition for photon-processing nuclear imaging systems and applications for reconstruction and computing null functions.

Science.gov (United States)

Jha, Abhinav K; Barrett, Harrison H; Frey, Eric C; Clarkson, Eric; Caucci, Luca; Kupinski, Matthew A

2015-09-21

Recent advances in technology are enabling a new class of nuclear imaging systems consisting of detectors that use real-time maximum-likelihood (ML) methods to estimate the interaction position, deposited energy, and other attributes of each photon-interaction event and store these attributes in a list format. This class of systems, which we refer to as photon-processing (PP) nuclear imaging systems, can be described by a fundamentally different mathematical imaging operator that allows processing of the continuous-valued photon attributes on a per-photon basis. Unlike conventional photon-counting (PC) systems that bin the data into images, PP systems do not have any binning-related information loss. Mathematically, while PC systems have an infinite-dimensional null space due to dimensionality considerations, PP systems do not necessarily suffer from this issue. Therefore, PP systems have the potential to provide improved performance in comparison to PC systems. To study these advantages, we propose a framework to perform the singular-value decomposition (SVD) of the PP imaging operator. We use this framework to perform the SVD of operators that describe a general two-dimensional (2D) planar linear shift-invariant (LSIV) PP system and a hypothetical continuously rotating 2D single-photon emission computed tomography (SPECT) PP system. We then discuss two applications of the SVD framework. The first application is to decompose the object being imaged by the PP imaging system into measurement and null components. We compare these components to the measurement and null components obtained with PC systems. In the process, we also present a procedure to compute the null functions for a PC system. The second application is designing analytical reconstruction algorithms for PP systems. The proposed analytical approach exploits the fact that PP systems acquire data in a continuous domain to estimate a continuous object function. The approach is parallelizable and

Singular value decomposition for photon-processing nuclear imaging systems and applications for reconstruction and computing null functions

Science.gov (United States)

Jha, Abhinav K.; Barrett, Harrison H.; Frey, Eric C.; Clarkson, Eric; Caucci, Luca; Kupinski, Matthew A.

2015-09-01

Recent advances in technology are enabling a new class of nuclear imaging systems consisting of detectors that use real-time maximum-likelihood (ML) methods to estimate the interaction position, deposited energy, and other attributes of each photon-interaction event and store these attributes in a list format. This class of systems, which we refer to as photon-processing (PP) nuclear imaging systems, can be described by a fundamentally different mathematical imaging operator that allows processing of the continuous-valued photon attributes on a per-photon basis. Unlike conventional photon-counting (PC) systems that bin the data into images, PP systems do not have any binning-related information loss. Mathematically, while PC systems have an infinite-dimensional null space due to dimensionality considerations, PP systems do not necessarily suffer from this issue. Therefore, PP systems have the potential to provide improved performance in comparison to PC systems. To study these advantages, we propose a framework to perform the singular-value decomposition (SVD) of the PP imaging operator. We use this framework to perform the SVD of operators that describe a general two-dimensional (2D) planar linear shift-invariant (LSIV) PP system and a hypothetical continuously rotating 2D single-photon emission computed tomography (SPECT) PP system. We then discuss two applications of the SVD framework. The first application is to decompose the object being imaged by the PP imaging system into measurement and null components. We compare these components to the measurement and null components obtained with PC systems. In the process, we also present a procedure to compute the null functions for a PC system. The second application is designing analytical reconstruction algorithms for PP systems. The proposed analytical approach exploits the fact that PP systems acquire data in a continuous domain to estimate a continuous object function. The approach is parallelizable and

Quantitative single-photon emission tomography for cerebral flow and receptor distribution imaging

International Nuclear Information System (INIS)

Budinger, T.F.

1985-01-01

Recently there has been renewed interest in single-photon emission tomography for two major reasons. First, correction methods have been devised for attenuation compensation, nonuniform resolution, and scattered radiation. Second, new radiopharmaceuticals with 1-5% uptake in the brain provide adequate statistics for quantitative imaging of flow using properly designed single-photon tomographic instruments. The lack of commercially available instruments designed specifically to optimize sensitivity for a resolution finer than 15 mm full width at half maximum (FWHM) seems now to be the major deterrent to the widespread use of single-photon emission tomography. But it appears now that some development in this respect also might lead to a widespread renewed interest in single-photon tomography of the brain. Major activities of the past few years can be placed in three distinct categories of instrumentation and methodology

A review of molecular imaging studies reaching the clinical stage

International Nuclear Information System (INIS)

Wong, Franklin C.; Kim, E. Edmund

2009-01-01

The practice of molecular imaging in the clinics is examined across various imaging modalities to assess the current status of clinical molecular imaging. The various physiologic and scientific bases of clinical molecular imaging are surveyed to assess the possibilities and opportunities for the deployment of the different imaging modalities in the near future. The requisites for successful candidate(s) of clinical molecular imaging are reviewed for future development.

Molecular Imaging Probe Development using Microfluidics

Science.gov (United States)

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

Translational research of optical molecular imaging for personalized medicine.

Science.gov (United States)

Qin, C; Ma, X; Tian, J

2013-12-01

In the medical imaging field, molecular imaging is a rapidly developing discipline and forms many imaging modalities, providing us effective tools to visualize, characterize, and measure molecular and cellular mechanisms in complex biological processes of living organisms, which can deepen our understanding of biology and accelerate preclinical research including cancer study and medicine discovery. Among many molecular imaging modalities, although the penetration depth of optical imaging and the approved optical probes used for clinics are limited, it has evolved considerably and has seen spectacular advances in basic biomedical research and new drug development. With the completion of human genome sequencing and the emergence of personalized medicine, the specific drug should be matched to not only the right disease but also to the right person, and optical molecular imaging should serve as a strong adjunct to develop personalized medicine by finding the optimal drug based on an individual's proteome and genome. In this process, the computational methodology and imaging system as well as the biomedical application regarding optical molecular imaging will play a crucial role. This review will focus on recent typical translational studies of optical molecular imaging for personalized medicine followed by a concise introduction. Finally, the current challenges and the future development of optical molecular imaging are given according to the understanding of the authors, and the review is then concluded.

PREFACE: I International Scientific School Methods of Digital Image Processing in Optics and Photonics

Science.gov (United States)

Gurov, I. P.; Kozlov, S. A.

2014-09-01

The first international scientific school "Methods of Digital Image Processing in Optics and Photonics" was held with a view to develop cooperation between world-class experts, young scientists, students and post-graduate students, and to exchange information on the current status and directions of research in the field of digital image processing in optics and photonics. The International Scientific School was managed by: Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO University) - Saint Petersburg (Russia) Chernyshevsky Saratov State University - Saratov (Russia) National research nuclear University "MEPHI" (NRNU MEPhI) - Moscow (Russia) The school was held with the participation of the local chapters of Optical Society of America (OSA), the Society of Photo-Optical Instrumentation Engineers (SPIE) and IEEE Photonics Society. Further details, including topics, committees and conference photos are available in the PDF

[Molecular imaging; current status and future prospects in USA].

Science.gov (United States)

Kobayashi, Hisataka

2007-02-01

The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

Experimental study of the evanescent-wave photonic sensors response in presence of molecular beacon conformational changes.

Science.gov (United States)

Ruiz-Tórtola, Ángela; Prats-Quílez, Francisco; Gónzalez-Lucas, Daniel; Bañuls, María-José; Maquieira, Ángel; Wheeler, Guy; Dalmay, Tamas; Griol, Amadeu; Hurtado, Juan; Bohlmann, Helge; Götzen, Reiner; García-Rupérez, Jaime

2018-04-17

An experimental study of the influence of the conformational change suffered by molecular beacon (MB) probes -upon the biorecognition of nucleic acid target oligonucleotides over evanescent wave photonic sensors- is reported. To this end, high sensitivity photonic sensors based on silicon photonic bandgap (PBG) structures were used, where the MB probes were immobilized via their 5' termination. Those MBs incorporate a biotin moiety close to their 3' termination in order to selectively bind a streptavidin molecule to them. The different photonic sensing responses obtained towards the target oligonucleotide detection, when the streptavidin molecule was bound to the MB probes or not, demonstrate the conformational change suffered by the MB upon hybridization, which promotes the displacement of the streptavidin molecule away from the surface of the photonic sensing structure. Schematic diagram of the PBG sensing structure on which the streptavidin-labeled MB probes were immobilized. This article is protected by copyright. All rights reserved.

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

International Nuclear Information System (INIS)

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

In vivo molecular and genomic imaging: new challenges for imaging physics.

Science.gov (United States)

Cherry, Simon R

2004-02-07

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

In vivo molecular and genomic imaging: new challenges for imaging physics

Energy Technology Data Exchange (ETDEWEB)

Cherry, Simon R [Department of Biomedical Engineering, University of California, Davis, CA (United States)

2004-02-07

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field. (topical review)

In vivo molecular and genomic imaging: new challenges for imaging physics

International Nuclear Information System (INIS)

Cherry, Simon R

2004-01-01

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field. (topical review)

Molecular imaging agents for SPECT (and SPECT/CT)

International Nuclear Information System (INIS)

Gnanasegaran, Gopinath; Ballinger, James R.

2014-01-01

The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

Molecular imaging agents for SPECT (and SPECT/CT)

Energy Technology Data Exchange (ETDEWEB)

Gnanasegaran, Gopinath [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); Ballinger, James R. [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

2014-05-15

The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

Cancer Stratification by Molecular Imaging

Directory of Open Access Journals (Sweden)

Justus Weber

2015-03-01

Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

Molecular imaging by cardiovascular MR.

Science.gov (United States)

Cyrus, Tillmann; Lanza, Gregory M; Wickline, Samuel A

2007-01-01

Do molecularly-targeted contrast agents have what it takes to usher in a paradigm shift as to how we will image cardiovascular disease in the near future? Moreover, are non-invasive vulnerable plaque detection and preemptive treatments with these novel nanoparticulate agents within reach for clinical applications? In this article, we attempt to make a compelling case for how the advent of molecularly-targeted nanoparticle technology may change the way we detect atherosclerotic lesions, determine their clinical significance and even provide non-invasive treatments. Focusing on imaging with cardiovascular MR, an overview of the latest developments in this rapidly evolving field of so-called "intelligent" contrast agents that are able to interrogate the vascular wall and various complementary advanced imaging technologies are presented.

Imaging Hybrid Photon Detectors with a Reflective Photocathode

CERN Document Server

Ferenc, D

2000-01-01

Modern epitaxially grown photocathodes, like GaAsP, bring a very high inherent quantum efficiency, but are rather expensive due to the complicated manufacturing and mounting process. We argue that such photocathodes could be used in reflective mode, in order to avoid the risky and expensive removal of the epitaxial growth substrate. Besides that the quantum efficiency should increase considerably. In this paper we present results of the development of large imaging Hybrid Photon Detectors (HPDs), particularly designed for such reflective photocathodes.

pH-Induced Modulation of One- and Two-Photon Absorption Properties in a Naphthalene-Based Molecular Probe.

Science.gov (United States)

Murugan, N Arul; Kongsted, Jacob; Ågren, Hans

2013-08-13

Presently, there is a great demand for small probe molecules that can be used for two-photon excitation microscopy (TPM)-based monitoring of intracellular and intraorganelle activity and pH. The candidate molecules should ideally possess a large two-photon absorption cross section with optical properties sensitive to pH changes. In the present work, we investigate the potential of a methoxy napthalene (MONAP) derivative for its suitability to serve as a pH sensor using TPM. Using an integrated approach rooted in hybrid quantum mechanics/molecular mechanics, the structures, dynamics, and the one- and two-photon properties of the probe in dimethylformamide solvent are studied. It is found that the protonated form is responsible for the optical property of MONAP at moderately low pH, for which the calculated pH-induced red shift is in good agreement with experiments. A 2-fold increase in the two-photon absorption cross section in the IR region of the spectrum is predicted for the moderately low pH form of the probe, suggesting that this can be a potential probe for pH monitoring of living cells. We also propose some design principles aimed at obtaining control of the absorption spectral range of the probe by structural tuning. Our work indicates that the integrated approach employed is capable of capturing the pH-induced changes in structure and optical properties of organic molecular probes and that such in silico tools can be used to draw structure-property relationships to design novel molecular probes suitable for a specific application.

Molecular Imaging and Precision Medicine in Prostate Cancer.

Science.gov (United States)

Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

2017-01-01

The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Visible light photon counters (VLPCs) for high rate tracking medical imaging and particle astrophysics

International Nuclear Information System (INIS)

Atac, M.

1998-02-01

This paper is on the operation principles of the Visible Light Photon Counters (VLPCs), application to high luminosity-high multiplicity tracking for High Energy Charged Particle Physics, and application to Medical Imaging and Particle Astrophysics. The VLPCs as Solid State Photomultipliers (SSPMS) with high quantum efficiency can detect down to single photons very efficiently with excellent time resolution and high avalanche gains

Improvement on image quality of single photon ECT with converging collimator system

International Nuclear Information System (INIS)

Murayama, Hideo; Nohara, Norimasa; Tanaka, Eiichi

1986-01-01

Single photon emission computed tomography (SPECT) with converging collimator system was proposed to improve quality of reconstructed images. The collimator system was designed to enhance sensitivity at the center region of field-of-view, where the probability photons escape the attenuating medium is smaller than at the off-center region. In order to evaluate efficiency of the improvement on image quality, the weighting function of projection, which is defined as relative sensitivity to the average on the lateral sampling of projection, was adopted to the image reconstruction algorithm of Radial Post Correction method. Statistical mean square noise in a reconstructed image was formulated in this method. Simulation studies using typical weighting function showed that center-enhanced weighting function brings effective improvement on image quality, especially, at the center region of cold area surrounded by annularly distributed activity. A new SPECT system was proposed as one example of the converging collimator systems. The system is composed of four gamma cameras with four fan-beam collimators, which have different focal distances one another. Simple simulation studies showed that the proposed system has reasonable center-enhanced weighting function, and the image quality based on the proposed system was fairly improved as compared with one based on uniform weighting function at the center region of the field-of-view. (author)

Multi-target molecular imaging and its progress in research and application

International Nuclear Information System (INIS)

Tang Ganghua

2011-01-01

Multi-target molecular imaging (MMI) is an important field of research in molecular imaging. It includes multi-tracer multi-target molecular imaging(MTMI), fusion-molecule multi-target imaging (FMMI), coupling-molecule multi-target imaging (CMMI), and multi-target multifunctional molecular imaging(MMMI). In this paper,imaging modes of MMI are reviewed, and potential applications of positron emission tomography MMI in near future are discussed. (author)

A study of molecular correlations observed in the small-angle photon scattering distributions of 60 KeV photons interacting with low-atomic-number media

International Nuclear Information System (INIS)

Bradley, D.A.

1988-01-01

A variant of the multisection filter and annular target geometry, with a designed angular acceptance of +-0.5 0 , has been utilised in measuring accurate, O(5%), absolute total differential scattering cross sections of 60 KeV photons for H 2 O, methyl methacrylate (C 5 H 8 O 2 ) n and nylon-6 (C 12 H 22 O 3 N 2 ) n in the angular scattering range of 2 0 -10 0 . The effects of molecular correlations manifest, to varying degree, in strong forward peaking of the scattered photon distribution. Comparison is made with available experiment and theory [pt

Deep brain two-photon NIR fluorescence imaging for study of Alzheimer's disease

Science.gov (United States)

Chen, Congping; Liang, Zhuoyi; Zhou, Biao; Ip, Nancy Y.; Qu, Jianan Y.

2018-02-01

Amyloid depositions in the brain represent the characteristic hallmarks of Alzheimer's disease (AD) pathology. The abnormal accumulation of extracellular amyloid-beta (Aβ) and resulting toxic amyloid plaques are considered to be responsible for the clinical deficits including cognitive decline and memory loss. In vivo two-photon fluorescence imaging of amyloid plaques in live AD mouse model through a chronic imaging window (thinned skull or craniotomy) provides a mean to greatly facilitate the study of the pathological mechanism of AD owing to its high spatial resolution and long-term continuous monitoring. However, the imaging depth for amyloid plaques is largely limited to upper cortical layers due to the short-wavelength fluorescence emission of commonly used amyloid probes. In this work, we reported that CRANAD-3, a near-infrared (NIR) probe for amyloid species with excitation wavelength at 900 nm and emission wavelength around 650 nm, has great advantages over conventionally used probes and is well suited for twophoton deep imaging of amyloid plaques in AD mouse brain. Compared with a commonly used MeO-X04 probe, the imaging depth of CRANAD-3 is largely extended for open skull cranial window. Furthermore, by using two-photon excited fluorescence spectroscopic imaging, we characterized the intrinsic fluorescence of the "aging pigment" lipofuscin in vivo, which has distinct spectra from CRANAD-3 labeled plaques. This study reveals the unique potential of NIR probes for in vivo, high-resolution and deep imaging of brain amyloid in Alzheimer's disease.

Label-free imaging immune cells and collagen in atherosclerosis with two-photon and second harmonic generation microscopy

Directory of Open Access Journals (Sweden)

Chunqiang Li

2016-01-01

Full Text Available Atherosclerosis has been recognized as a chronic inflammation disease, in which many types of cells participate in this process, including lymphocytes, macrophages, dendritic cells (DCs, mast cells, vascular smooth muscle cells (SMCs. Developments in imaging technology provide the capability to observe cellular and tissue components and their interactions. The knowledge of the functions of immune cells and their interactions with other cell and tissue components will facilitate our discovery of biomarkers in atherosclerosis and prediction of the risk factor of rupture-prone plaques. Nonlinear optical microscopy based on two-photon excited autofluorescence and second harmonic generation (SHG were developed to image mast cells, SMCs and collagen in plaque ex vivo using endogenous optical signals. Mast cells were imaged with two-photon tryptophan autofluorescence, SMCs were imaged with two-photon NADH autofluorescence, and collagen were imaged with SHG. This development paves the way for further study of mast cell degranulation, and the effects of mast cell derived mediators such as induced synthesis and activation of matrix metalloproteinases (MMPs which participate in the degradation of collagen.

Nanoshells for in vivo imaging using two-photon excitation microscopy

Energy Technology Data Exchange (ETDEWEB)

Gao Liang; Nammalvar, Vengadesan [Department of Bioengineering, Rice University, Houston, TX 77005 (United States); Vadakkan, Tegy J, E-mail: lg3@rice.edu, E-mail: venkyn@rice.edu [Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030 (United States)

2011-09-07

Gold nanoshells have been intensively investigated and applied to various biomedical fields because of their flexible optical tunability and biological compatibility. They hold great potential to serve as luminescent contrast agents excitable with near-infrared (NIR) lasers. In this paper, we describe the development of nanoshells with a peak of plasmon resonance at 800 nm and their subsequent use for in vivo blood vessel imaging using two-photon excitation microscopy at an excitation wavelength of 750 nm. We were able to image single nanoshell particles in blood vessels and generate optical contrast for blood vessel structure using luminescent signals. These results confirm the feasibility of engineering nanoshells with controlled optical properties for single-particle-based in vivo imaging.

Three-dimensional cell organization leads to almost immediate HRE activity as demonstrated by molecular imaging of MG-63 spheroids using two-photon excitation microscopy.

Science.gov (United States)

Indovina, Paola; Collini, Maddalena; Chirico, Giuseppe; Santini, Maria Teresa

2007-02-20

Hypoxia through HRE (hypoxia-responsive element) activity in MG-63 human osteosarcoma cells grown in monolayer and as very small, three-dimensional tumor spheroids was investigated using molecular imaging techniques. MG-63 cells were stably transfected with a vector constructed with multiple copies of the HRE sequence of the human vascular endothelial growth factor (VEGF) gene and with the enhanced green fluorescent protein (EGFP) coding sequence. During hypoxia when HIF-1alpha (hypoxia-inducible factor-1alpha) is stabilized, the binding of HIF-1 to the HRE sequences of the vector allows the transcription of EGFP and the appearance of fluorescence. Transfected monolayer cells were characterized by flow cytometric analysis in response to various hypoxic conditions and HIF-1alpha expression in these cells was assessed by Western blotting. Two-photon excitation (TPE) microscopy was then used to examine both MG-63-transfected monolayer cells and spheroids at 2 and 5 days of growth in normoxic conditions. Monolayer cells reveal almost no fluorescence, whereas even very small spheroids (HRE activation. This activation of the HRE sequences, which control a wide variety of genes, suggests that monolayer cells and spheroids of the MG-63 cell line have different genes activated and thus diverse functional activities.

Dual photon excitation microscopy and image threshold segmentation in live cell imaging during compression testing.

Science.gov (United States)

Moo, Eng Kuan; Abusara, Ziad; Abu Osman, Noor Azuan; Pingguan-Murphy, Belinda; Herzog, Walter

2013-08-09

Morphological studies of live connective tissue cells are imperative to helping understand cellular responses to mechanical stimuli. However, photobleaching is a constant problem to accurate and reliable live cell fluorescent imaging, and various image thresholding methods have been adopted to account for photobleaching effects. Previous studies showed that dual photon excitation (DPE) techniques are superior over conventional one photon excitation (OPE) confocal techniques in minimizing photobleaching. In this study, we investigated the effects of photobleaching resulting from OPE and DPE on morphology of in situ articular cartilage chondrocytes across repeat laser exposures. Additionally, we compared the effectiveness of three commonly-used image thresholding methods in accounting for photobleaching effects, with and without tissue loading through compression. In general, photobleaching leads to an apparent volume reduction for subsequent image scans. Performing seven consecutive scans of chondrocytes in unloaded cartilage, we found that the apparent cell volume loss caused by DPE microscopy is much smaller than that observed using OPE microscopy. Applying scan-specific image thresholds did not prevent the photobleaching-induced volume loss, and volume reductions were non-uniform over the seven repeat scans. During cartilage loading through compression, cell fluorescence increased and, depending on the thresholding method used, led to different volume changes. Therefore, different conclusions on cell volume changes may be drawn during tissue compression, depending on the image thresholding methods used. In conclusion, our findings confirm that photobleaching directly affects cell morphology measurements, and that DPE causes less photobleaching artifacts than OPE for uncompressed cells. When cells are compressed during tissue loading, a complicated interplay between photobleaching effects and compression-induced fluorescence increase may lead to interpretations in

Interaction of VUV-photons with molecules. Spectroscopy and dynamics of molecular superexcited states

International Nuclear Information System (INIS)

Hatano, Y.

2002-01-01

Complete text of publication follows. A survey is given of recent progress in experimental studies of the interaction of VUV-photons with molecules, i.e., those of photoabsorption, photoionization, and photodissociation of molecules in the excitation photon energy range of 10-50 eV, with a particular emphasis placed on current understanding of the spectroscopy and dynamics of formed molecular superexcited states. These studies are of great importance in understanding the interaction of ionizing radiation with matter. Molecules studied are ranged from simple diatomic and triatomic molecules to polyatomic molecules such as hydrocarbons. Most of the observed molecular superexcited states are assigned to high Rydber states which are vibrationally, doubly, or inner-core excited and converge to each of ion states. Non-Rydberg superexcited states are also observed. Dissociation into neutral fragments in comparison with ionization is of unexpectedly great importance in the observed decay of each of these state-assigned superexcited molecules. Dissociation dynamics as well as its products of superexcited states are remarkably different from those of lower excited states below about ionization thresholds. Some remarks are also presented of molecules in the condensed phase

In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy

Energy Technology Data Exchange (ETDEWEB)

Zhuo, Shuangmu, E-mail: shuangmuzhuo@gmail.com, E-mail: hanry-yu@nuhs.edu.sg [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Laser and Optoelectronics Technology, Fujian Normal University, Fuzhou 350007 (China); Yan, Jie [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, MD 11 #04-01A, 117599 Singapore (Singapore); Kang, Yuzhan [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Xu, Shuoyu [Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, 138602 Singapore (Singapore); Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, 117576 Singapore (Singapore); Peng, Qiwen [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, 138669 Singapore (Singapore); Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, 117576 Singapore (Singapore); Mechanobiology Institute, 5A Engineering Drive 1, T-Lab #05-01, 117411 Singapore (Singapore); and others

2014-07-14

Various structural features on the liver surface reflect functional changes in the liver. The visualization of these surface features with molecular specificity is of particular relevance to understanding the physiology and diseases of the liver. Using multi-photon microscopy (MPM), we have developed a label-free, three-dimensional quantitative and sensitive method to visualize various structural features of liver surface in living rat. MPM could quantitatively image the microstructural features of liver surface with respect to the sinuosity of collagen fiber, the elastic fiber structure, the ratio between elastin and collagen, collagen content, and the metabolic state of the hepatocytes that are correlative with the pathophysiologically induced changes in the regions of interest. This study highlights the potential of this technique as a useful tool for pathophysiological studies and possible diagnosis of the liver diseases with further development.

Dual CARS and SHG image acquisition scheme that combines single central fiber and multimode fiber bundle to collect and differentiate backward and forward generated photons

Science.gov (United States)

Weng, Sheng; Chen, Xu; Xu, Xiaoyun; Wong, Kelvin K.; Wong, Stephen T. C.

2016-01-01

In coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) imaging, backward and forward generated photons exhibit different image patterns and thus capture salient intrinsic information of tissues from different perspectives. However, they are often mixed in collection using traditional image acquisition methods and thus are hard to interpret. We developed a multimodal scheme using a single central fiber and multimode fiber bundle to simultaneously collect and differentiate images formed by these two types of photons and evaluated the scheme in an endomicroscopy prototype. The ratio of these photons collected was calculated for the characterization of tissue regions with strong or weak epi-photon generation while different image patterns of these photons at different tissue depths were revealed. This scheme provides a new approach to extract and integrate information captured by backward and forward generated photons in dual CARS/SHG imaging synergistically for biomedical applications. PMID:27375938

Molecular breast imaging: First results from Italian-National-Institute-of-Health clinical trials

Energy Technology Data Exchange (ETDEWEB)

Cusanno, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy)]. E-mail: francesco.cusanno@iss.infn.it; Cisbani, E. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Colilli, S. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Garibaldi, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Giuliani, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Gricia, M. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Lucentini, M. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Magliozzi, M.L. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Santanvenere, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Torrioli, S. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Cinti, M.N. [University La Sapienza, Rome (Italy); Pani, R. [University La Sapienza, Rome (Italy); Pellegrini, R. [University La Sapienza, Rome (Italy); Simonetti, G. [University Tor Vergata, Rome (Italy); Schillaci, O. [University Tor Vergata, Rome (Italy); Del Vecchio, S. [CNR Napoli, Naples (Italy); Salvatore, M. [CNR Napoli, Naples (Italy); Majewski, S. [Jefferson Lab, Newport News (United States); De Vincentis, G. [University La Sapienza, Rome (Italy); Scopinaro, F. [University La Sapienza, Rome (Italy)

2007-02-01

Dedicated high resolution detectors are needed for detection of small tumors by molecular imaging with radionuclides. Absorptive collimation are typically used for imaging single photon emitters, but it results in a strong reduction in efficiency. Systems based on electronic collimation offer higher efficiency but they are complex and expensive. In case of scintimammography, dual-head detectors increase sensitivity and cancel out the dependence of the lesion depth. In the system presented here, pixellated scintillator arrays (NaI:Tl) were coupled to arrays of PSPMT's, HPK H8500 Flat Panel. A dual-head detector having field of view of 100x100 mm{sup 2} and 150x200 mm{sup 2} were designed and built. The electronic system allows readout of all the anode pad signals. First clinical trials, performed in the framework of the Scintimammography project of Italian National Institute of Health and University of Tor Vergata in Rome, and University of Naples, are presented.

Molecular nuclear imaging for targeting and trafficking

International Nuclear Information System (INIS)

Bom, Hee Seung; Min, Jung Jun; Jeong, Hwan-Jeong

2006-01-01

Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99m Tc as a radionuclide. We developed 99m Tc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99m Tc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67 Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99m Tc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99m Tc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques

Molecular imaging in the framework of personalized cancer medicine.

Science.gov (United States)

Belkić, Dzevad; Belkić, Karen

2013-11-01

With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

Development of Quantification Method for Bioluminescence Imaging

International Nuclear Information System (INIS)

Kim, Hyeon Sik; Min, Jung Joon; Lee, Byeong Il; Choi, Eun Seo; Tak, Yoon O; Choi, Heung Kook; Lee, Ju Young

2009-01-01

Optical molecular luminescence imaging is widely used for detection and imaging of bio-photons emitted by luminescent luciferase activation. The measured photons in this method provide the degree of molecular alteration or cell numbers with the advantage of high signal-to-noise ratio. To extract useful information from the measured results, the analysis based on a proper quantification method is necessary. In this research, we propose a quantification method presenting linear response of measured light signal to measurement time. We detected the luminescence signal by using lab-made optical imaging equipment of animal light imaging system (ALIS) and different two kinds of light sources. One is three bacterial light-emitting sources containing different number of bacteria. The other is three different non-bacterial light sources emitting very weak light. By using the concept of the candela and the flux, we could derive simplified linear quantification formula. After experimentally measuring light intensity, the data was processed with the proposed quantification function. We could obtain linear response of photon counts to measurement time by applying the pre-determined quantification function. The ratio of the re-calculated photon counts and measurement time present a constant value although different light source was applied. The quantification function for linear response could be applicable to the standard quantification process. The proposed method could be used for the exact quantitative analysis in various light imaging equipment with presenting linear response behavior of constant light emitting sources to measurement time

Near-IR Two-Photon Fluorescent Sensor for K(+) Imaging in Live Cells.

Science.gov (United States)

Sui, Binglin; Yue, Xiling; Kim, Bosung; Belfield, Kevin D

2015-08-19

A new two-photon excited fluorescent K(+) sensor is reported. The sensor comprises three moieties, a highly selective K(+) chelator as the K(+) recognition unit, a boron-dipyrromethene (BODIPY) derivative modified with phenylethynyl groups as the fluorophore, and two polyethylene glycol chains to afford water solubility. The sensor displays very high selectivity (>52-fold) in detecting K(+) over other physiological metal cations. Upon binding K(+), the sensor switches from nonfluorescent to highly fluorescent, emitting red to near-IR (NIR) fluorescence. The sensor exhibited a good two-photon absorption cross section, 500 GM at 940 nm. Moreover, it is not sensitive to pH in the physiological pH range. Time-dependent cell imaging studies via both one- and two-photon fluorescence microscopy demonstrate that the sensor is suitable for dynamic K(+) sensing in living cells.

Monte Carlo simulation of photon scattering in x-ray absorption imaging of high-intensity discharge lamps

Energy Technology Data Exchange (ETDEWEB)

Curry, J J, E-mail: jjcurry@nist.go [National Institute of Standards and Technology, Gaithersburg, MD 20899-8422 (United States)

2010-06-16

Coherent and incoherent scattering of x-rays during x-ray absorption imaging of high-intensity discharge lamps have been studied with Monte Carlo simulations developed specifically for this purpose. The Monte Carlo code is described and some initial results are discussed. Coherent scattering, because of its angular concentration in the forward direction, is found to be the most significant scattering mechanism. Incoherent scattering, although comparably strong, is not as significant because it results primarily in photons being scattered in the rearward direction and therefore out of the detector. Coherent scattering interferes with the detected absorption signal because the path of a scattered photon through the object to be imaged is unknown. Although scattering is usually a small effect, it can be significant in regions of high contrast. At the discharge/wall interface, as many as 50% of the detected photons are scattered photons. The effect of scattering on analysis of Hg distributions has not yet been quantified.

Nanomedicine: Perspective and promises with ligand-directed molecular imaging

Energy Technology Data Exchange (ETDEWEB)

Pan Dipanjan [Department of Medicine, Washington University Medical School, St. Louis, MO (United States)], E-mail: dipanjan@wustl.edu; Lanza, Gregory M.; Wickline, Samuel A. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Caruthers, Shelton D. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Philips Healthcare, Andover, MA (United States)], E-mail: scaruthers@cmrl.wustl.edu

2009-05-15

Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

Nanomedicine: Perspective and promises with ligand-directed molecular imaging

International Nuclear Information System (INIS)

Pan Dipanjan; Lanza, Gregory M.; Wickline, Samuel A.; Caruthers, Shelton D.

2009-01-01

Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

Two-photon imaging and analysis of neural network dynamics

International Nuclear Information System (INIS)

Luetcke, Henry; Helmchen, Fritjof

2011-01-01

The glow of a starry night sky, the smell of a freshly brewed cup of coffee or the sound of ocean waves breaking on the beach are representations of the physical world that have been created by the dynamic interactions of thousands of neurons in our brains. How the brain mediates perceptions, creates thoughts, stores memories and initiates actions remains one of the most profound puzzles in biology, if not all of science. A key to a mechanistic understanding of how the nervous system works is the ability to measure and analyze the dynamics of neuronal networks in the living organism in the context of sensory stimulation and behavior. Dynamic brain properties have been fairly well characterized on the microscopic level of individual neurons and on the macroscopic level of whole brain areas largely with the help of various electrophysiological techniques. However, our understanding of the mesoscopic level comprising local populations of hundreds to thousands of neurons (so-called 'microcircuits') remains comparably poor. Predominantly, this has been due to the technical difficulties involved in recording from large networks of neurons with single-cell spatial resolution and near-millisecond temporal resolution in the brain of living animals. In recent years, two-photon microscopy has emerged as a technique which meets many of these requirements and thus has become the method of choice for the interrogation of local neural circuits. Here, we review the state-of-research in the field of two-photon imaging of neuronal populations, covering the topics of microscope technology, suitable fluorescent indicator dyes, staining techniques, and in particular analysis techniques for extracting relevant information from the fluorescence data. We expect that functional analysis of neural networks using two-photon imaging will help to decipher fundamental operational principles of neural microcircuits.

Two-photon imaging and analysis of neural network dynamics

Science.gov (United States)

Lütcke, Henry; Helmchen, Fritjof

2011-08-01

The glow of a starry night sky, the smell of a freshly brewed cup of coffee or the sound of ocean waves breaking on the beach are representations of the physical world that have been created by the dynamic interactions of thousands of neurons in our brains. How the brain mediates perceptions, creates thoughts, stores memories and initiates actions remains one of the most profound puzzles in biology, if not all of science. A key to a mechanistic understanding of how the nervous system works is the ability to measure and analyze the dynamics of neuronal networks in the living organism in the context of sensory stimulation and behavior. Dynamic brain properties have been fairly well characterized on the microscopic level of individual neurons and on the macroscopic level of whole brain areas largely with the help of various electrophysiological techniques. However, our understanding of the mesoscopic level comprising local populations of hundreds to thousands of neurons (so-called 'microcircuits') remains comparably poor. Predominantly, this has been due to the technical difficulties involved in recording from large networks of neurons with single-cell spatial resolution and near-millisecond temporal resolution in the brain of living animals. In recent years, two-photon microscopy has emerged as a technique which meets many of these requirements and thus has become the method of choice for the interrogation of local neural circuits. Here, we review the state-of-research in the field of two-photon imaging of neuronal populations, covering the topics of microscope technology, suitable fluorescent indicator dyes, staining techniques, and in particular analysis techniques for extracting relevant information from the fluorescence data. We expect that functional analysis of neural networks using two-photon imaging will help to decipher fundamental operational principles of neural microcircuits.

Two-photon imaging and analysis of neural network dynamics

Energy Technology Data Exchange (ETDEWEB)

Luetcke, Henry; Helmchen, Fritjof [Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich (Switzerland)

2011-08-15

The glow of a starry night sky, the smell of a freshly brewed cup of coffee or the sound of ocean waves breaking on the beach are representations of the physical world that have been created by the dynamic interactions of thousands of neurons in our brains. How the brain mediates perceptions, creates thoughts, stores memories and initiates actions remains one of the most profound puzzles in biology, if not all of science. A key to a mechanistic understanding of how the nervous system works is the ability to measure and analyze the dynamics of neuronal networks in the living organism in the context of sensory stimulation and behavior. Dynamic brain properties have been fairly well characterized on the microscopic level of individual neurons and on the macroscopic level of whole brain areas largely with the help of various electrophysiological techniques. However, our understanding of the mesoscopic level comprising local populations of hundreds to thousands of neurons (so-called 'microcircuits') remains comparably poor. Predominantly, this has been due to the technical difficulties involved in recording from large networks of neurons with single-cell spatial resolution and near-millisecond temporal resolution in the brain of living animals. In recent years, two-photon microscopy has emerged as a technique which meets many of these requirements and thus has become the method of choice for the interrogation of local neural circuits. Here, we review the state-of-research in the field of two-photon imaging of neuronal populations, covering the topics of microscope technology, suitable fluorescent indicator dyes, staining techniques, and in particular analysis techniques for extracting relevant information from the fluorescence data. We expect that functional analysis of neural networks using two-photon imaging will help to decipher fundamental operational principles of neural microcircuits.

Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application.

Science.gov (United States)

Rahman, Mahabubur; Watabe, Hiroshi

2018-05-01

Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid

Molecular Imaging in Nanotechnology and Theranostics.

Science.gov (United States)

Andreou, Chrysafis; Pal, Suchetan; Rotter, Lara; Yang, Jiang; Kircher, Moritz F

2017-06-01

The fields of biomedical nanotechnology and theranostics have enjoyed exponential growth in recent years. The "Molecular Imaging in Nanotechnology and Theranostics" (MINT) Interest Group of the World Molecular Imaging Society (WMIS) was created in order to provide a more organized and focused forum on these topics within the WMIS and at the World Molecular Imaging Conference (WMIC). The interest group was founded in 2015 and was officially inaugurated during the 2016 WMIC. The overarching goal of MINT is to bring together the many scientists who work on molecular imaging approaches using nanotechnology and those that work on theranostic agents. MINT therefore represents scientists, labs, and institutes that are very diverse in their scientific backgrounds and areas of expertise, reflecting the wide array of materials and approaches that drive these fields. In this short review, we attempt to provide a condensed overview over some of the key areas covered by MINT. Given the breadth of the fields and the given space constraints, we have limited the coverage to the realm of nanoconstructs, although theranostics is certainly not limited to this domain. We will also focus only on the most recent developments of the last 3-5 years, in order to provide the reader with an intuition of what is "in the pipeline" and has potential for clinical translation in the near future.

Photon Factory activity report, 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

The Photon Factory at the National Laboratory for High Energy Physics is a national facility for scientific research utilizing synchrotron radiation. Although the Photon Factory operator the linear injector, two light sources including the 2.5 GeV storage ring and the 6.5 GeV TRISTAN accumulation Ring as well as a major fraction of their beamlines and experimental station. This report is covered the period from October 1994 to September 1995. The total number of proposals by this PAC was 399 in 1995. Facility development projects currently in progress include the following, TRISTAN Super Light Facility (TSLF) project, VUV-FEL project, KEKB project and Slow-positron Source. This report contents outline of the Photon Factory, introduction, scientific disciplines, electronic properties of condensed matters, atomic and molecular science, X-ray imaging, radiobiology using synchrotron radiation, structural properties of condensed matters, structural properties of solid surfaces and adsorbates, structure and function of proteins, theoretical researches, experimental facilities, beamlines, new instrumentation, AR Upgrade, collaborations, projects, user`s short reports, list of published papers 1994/95. (S.Y.)

Photon Factory activity report, 1995

International Nuclear Information System (INIS)

1996-01-01

The Photon Factory at the National Laboratory for High Energy Physics is a national facility for scientific research utilizing synchrotron radiation. Although the Photon Factory operator the linear injector, two light sources including the 2.5 GeV storage ring and the 6.5 GeV TRISTAN accumulation Ring as well as a major fraction of their beamlines and experimental station. This report is covered the period from October 1994 to September 1995. The total number of proposals by this PAC was 399 in 1995. Facility development projects currently in progress include the following, TRISTAN Super Light Facility (TSLF) project, VUV-FEL project, KEKB project and Slow-positron Source. This report contents outline of the Photon Factory, introduction, scientific disciplines, electronic properties of condensed matters, atomic and molecular science, X-ray imaging, radiobiology using synchrotron radiation, structural properties of condensed matters, structural properties of solid surfaces and adsorbates, structure and function of proteins, theoretical researches, experimental facilities, beamlines, new instrumentation, AR Upgrade, collaborations, projects, user's short reports, list of published papers 1994/95. (S.Y.)

Photon Factory activity report, 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

The Photon Factory at the National Laboratory for High Energy Physics is a national facility for scientific research utilizing synchrotron radiation. Although the Photon Factory operator the linear injector, two light sources including the 2.5 GeV storage ring and the 6.5 GeV TRISTAN accumulation Ring as well as a major fraction of their beamlines and experimental station. This report is covered the period from October 1994 to September 1995. The total number of proposals by this PAC was 399 in 1995. Facility development projects currently in progress include the following, TRISTAN Super Light Facility (TSLF) project, VUV-FEL project, KEKB project and Slow-positron Source. This report contents outline of the Photon Factory, introduction, scientific disciplines, electronic properties of condensed matters, atomic and molecular science, X-ray imaging, radiobiology using synchrotron radiation, structural properties of condensed matters, structural properties of solid surfaces and adsorbates, structure and function of proteins, theoretical researches, experimental facilities, beamlines, new instrumentation, AR Upgrade, collaborations, projects, user`s short reports, list of published papers 1994/95. (S.Y.)

Molecular imaging in cervical cancer

International Nuclear Information System (INIS)

KHAN, Sairah R.; ROCKALL, Andrea G.; BARWICK, Tara D.

2016-01-01

Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed.

Photon-counting hexagonal pixel array CdTe detector: Spatial resolution characteristics for image-guided interventional applications.

Science.gov (United States)

Vedantham, Srinivasan; Shrestha, Suman; Karellas, Andrew; Shi, Linxi; Gounis, Matthew J; Bellazzini, Ronaldo; Spandre, Gloria; Brez, Alessandro; Minuti, Massimo

2016-05-01

High-resolution, photon-counting, energy-resolved detector with fast-framing capability can facilitate simultaneous acquisition of precontrast and postcontrast images for subtraction angiography without pixel registration artifacts and can facilitate high-resolution real-time imaging during image-guided interventions. Hence, this study was conducted to determine the spatial resolution characteristics of a hexagonal pixel array photon-counting cadmium telluride (CdTe) detector. A 650 μm thick CdTe Schottky photon-counting detector capable of concurrently acquiring up to two energy-windowed images was operated in a single energy-window mode to include photons of 10 keV or higher. The detector had hexagonal pixels with apothem of 30 μm resulting in pixel pitch of 60 and 51.96 μm along the two orthogonal directions. The detector was characterized at IEC-RQA5 spectral conditions. Linear response of the detector was determined over the air kerma rate relevant to image-guided interventional procedures ranging from 1.3 nGy/frame to 91.4 μGy/frame. Presampled modulation transfer was determined using a tungsten edge test device. The edge-spread function and the finely sampled line spread function accounted for hexagonal sampling, from which the presampled modulation transfer function (MTF) was determined. Since detectors with hexagonal pixels require resampling to square pixels for distortion-free display, the optimal square pixel size was determined by minimizing the root-mean-squared-error of the aperture functions for the square and hexagonal pixels up to the Nyquist limit. At Nyquist frequencies of 8.33 and 9.62 cycles/mm along the apothem and orthogonal to the apothem directions, the modulation factors were 0.397 and 0.228, respectively. For the corresponding axis, the limiting resolution defined as 10% MTF occurred at 13.3 and 12 cycles/mm, respectively. Evaluation of the aperture functions yielded an optimal square pixel size of 54 μm. After resampling to 54 �

Bioresponsive probes for molecular imaging:Concepts and in vivo applications

OpenAIRE

Duijnhoven, van, SMJ Sander; Robillard, MS Marc; Langereis, S Sander; Grüll, H Holger

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly ...

Optimisation of centroiding algorithms for photon event counting imaging

International Nuclear Information System (INIS)

Suhling, K.; Airey, R.W.; Morgan, B.L.

1999-01-01

Approaches to photon event counting imaging in which the output events of an image intensifier are located using a centroiding technique have long been plagued by fixed pattern noise in which a grid of dimensions similar to those of the CCD pixels is superimposed on the image. This is caused by a mismatch between the photon event shape and the centroiding algorithm. We have used hyperbolic cosine, Gaussian, Lorentzian, parabolic as well as 3-, 5-, and 7-point centre of gravity algorithms, and hybrids thereof, to assess means of minimising this fixed pattern noise. We show that fixed pattern noise generated by the widely used centre of gravity centroiding is due to intrinsic features of the algorithm. Our results confirm that the recently proposed use of Gaussian centroiding does indeed show a significant reduction of fixed pattern noise compared to centre of gravity centroiding (Michel et al., Mon. Not. R. Astron. Soc. 292 (1997) 611-620). However, the disadvantage of a Gaussian algorithm is a centroiding failure for small pulses, caused by a division by zero, which leads to a loss of detective quantum efficiency (DQE) and to small amounts of residual fixed pattern noise. Using both real data from an image intensifier system employing a progressive scan camera, framegrabber and PC, and also synthetic data from Monte-Carlo simulations, we find that hybrid centroiding algorithms can reduce the fixed pattern noise without loss of resolution or loss of DQE. Imaging a test pattern to assess the features of the different algorithms shows that a hybrid of Gaussian and 3-point centre of gravity centroiding algorithms results in an optimum combination of low fixed pattern noise (lower than a simple Gaussian), high DQE, and high resolution. The Lorentzian algorithm gives the worst results in terms of high fixed pattern noise and low resolution, and the Gaussian and hyperbolic cosine algorithms have the lowest DQEs

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation.

Science.gov (United States)

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi 3 + beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm 2 . The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation

Science.gov (United States)

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi3+ beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm2. The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

High-Sensitivity Semiconductor Photocathodes for Space-Born UV Photon-Counting and Imaging, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Many UV photon-counting and imaging applications, including space-borne astronomy, missile tracking and guidance, UV spectroscopy for chemical/biological...

Progress in Molecular Imaging in Endoscopy and Endomicroscopy for Cancer Imaging

Directory of Open Access Journals (Sweden)

Supang Khondee

2013-01-01

Full Text Available Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes.

Geiger-mode APD camera system for single-photon 3D LADAR imaging

Science.gov (United States)

Entwistle, Mark; Itzler, Mark A.; Chen, Jim; Owens, Mark; Patel, Ketan; Jiang, Xudong; Slomkowski, Krystyna; Rangwala, Sabbir

2012-06-01

The unparalleled sensitivity of 3D LADAR imaging sensors based on single photon detection provides substantial benefits for imaging at long stand-off distances and minimizing laser pulse energy requirements. To obtain 3D LADAR images with single photon sensitivity, we have demonstrated focal plane arrays (FPAs) based on InGaAsP Geiger-mode avalanche photodiodes (GmAPDs) optimized for use at either 1.06 μm or 1.55 μm. These state-of-the-art FPAs exhibit excellent pixel-level performance and the capability for 100% pixel yield on a 32 x 32 format. To realize the full potential of these FPAs, we have recently developed an integrated camera system providing turnkey operation based on FPGA control. This system implementation enables the extremely high frame-rate capability of the GmAPD FPA, and frame rates in excess of 250 kHz (for 0.4 μs range gates) can be accommodated using an industry-standard CameraLink interface in full configuration. Real-time data streaming for continuous acquisition of 2 μs range gate point cloud data with 13-bit time-stamp resolution at 186 kHz frame rates has been established using multiple solid-state storage drives. Range gate durations spanning 4 ns to 10 μs provide broad operational flexibility. The camera also provides real-time signal processing in the form of multi-frame gray-scale contrast images and single-frame time-stamp histograms, and automated bias control has been implemented to maintain a constant photon detection efficiency in the presence of ambient temperature changes. A comprehensive graphical user interface has been developed to provide complete camera control using a simple serial command set, and this command set supports highly flexible end-user customization.

Real-time imaging systems for superconducting nanowire single-photon detector arrays

Energy Technology Data Exchange (ETDEWEB)

Hofherr, Matthias

2014-07-01

Superconducting nanowire singe-photon detectors (SNSPD) are promising detectors in the field of applications, where single-photon resolution is required like in quantum optics, spectroscopy or astronomy. These cryogenic detectors gain from a broad spectrum in the optical and infrared range and deliver low dark counts and low jitter. This work provides a piece of deeper physical understanding of detector functionality in combination with highly engineered readout development. A detailed analysis focuses on the intrinsic detection mechanism of SNSPDs related to the detection in the infrared regime and the evolution of dark counts. With this fundamental knowledge, the next step is the development of a multi-pixel readout at cryogenic conditions. It is demonstrated, how two auspicious multi-pixel readout concepts can be realized, which enables statistical framing like in imaging applications using RSFQ electronics with fast framing rates and the readout of a detector array with continuous real-time single-photon resolution.

Bayesian inference on multiscale models for poisson intensity estimation: applications to photon-limited image denoising.

Science.gov (United States)

Lefkimmiatis, Stamatios; Maragos, Petros; Papandreou, George

2009-08-01

We present an improved statistical model for analyzing Poisson processes, with applications to photon-limited imaging. We build on previous work, adopting a multiscale representation of the Poisson process in which the ratios of the underlying Poisson intensities (rates) in adjacent scales are modeled as mixtures of conjugate parametric distributions. Our main contributions include: 1) a rigorous and robust regularized expectation-maximization (EM) algorithm for maximum-likelihood estimation of the rate-ratio density parameters directly from the noisy observed Poisson data (counts); 2) extension of the method to work under a multiscale hidden Markov tree model (HMT) which couples the mixture label assignments in consecutive scales, thus modeling interscale coefficient dependencies in the vicinity of image edges; 3) exploration of a 2-D recursive quad-tree image representation, involving Dirichlet-mixture rate-ratio densities, instead of the conventional separable binary-tree image representation involving beta-mixture rate-ratio densities; and 4) a novel multiscale image representation, which we term Poisson-Haar decomposition, that better models the image edge structure, thus yielding improved performance. Experimental results on standard images with artificially simulated Poisson noise and on real photon-limited images demonstrate the effectiveness of the proposed techniques.

Mannose-functionalized porous silica-coated magnetic nanoparticles for two-photon imaging or PDT of cancer cells

International Nuclear Information System (INIS)

Perrier, Marine; Gary-Bobo, Magali; Lartigue, Lenaïc; Brevet, David; Morère, Alain; Garcia, Marcel; Maillard, Philippe; Raehm, Laurence; Guari, Yannick; Larionova, Joulia; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille

2013-01-01

An original fluorophore engineered for two-photon excitation or a porphyrin derivative were entrapped in the silica shell of magnetic porous silica nanoparticles during the synthesis of the silica moiety without damaging the structure of the organic part. The mild conditions involved allowed obtaining microporous or mesoporous silica magnetic nanoparticles, respectively. Mannose was grafted on the surface of the nanoparticles to target MCF-7 breast cancer cells. The studies of magnetic properties of these hybrid nanoparticles show that they present a blocking temperature at 190 K. The nano-objects designed with the two-photon fluorophore were efficient for two-photon imaging of MCF-7 cancer cells, whereas the nano-objects with the photosensitizer efficiently killed cancer cells. The presence of the mannose moiety was demonstrated to improve both imaging and therapy properties.

Mannose-functionalized porous silica-coated magnetic nanoparticles for two-photon imaging or PDT of cancer cells

Energy Technology Data Exchange (ETDEWEB)

Perrier, Marine [UMR 5253 CNRS-UM2-ENSCM-UM1, Institut Charles Gerhardt Montpellier (France); Gary-Bobo, Magali [Faculte de Pharmacie, Universite Montpellier 1, Universite Montpellier 2, Institut des Biomolecules Max Mousseron UMR 5247 CNRS (France); Lartigue, Lenaiec; Brevet, David [UMR 5253 CNRS-UM2-ENSCM-UM1, Institut Charles Gerhardt Montpellier (France); Morere, Alain; Garcia, Marcel [Faculte de Pharmacie, Universite Montpellier 1, Universite Montpellier 2, Institut des Biomolecules Max Mousseron UMR 5247 CNRS (France); Maillard, Philippe [Universite Paris-Sud, UMR 176 CNRS, Institut Curie (France); Raehm, Laurence; Guari, Yannick, E-mail: yannick.guari@um2.fr; Larionova, Joulia; Durand, Jean-Olivier, E-mail: durand@univ-montp2.fr [UMR 5253 CNRS-UM2-ENSCM-UM1, Institut Charles Gerhardt Montpellier (France); Mongin, Olivier [Universite de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226 (France); Blanchard-Desce, Mireille [Universite Bordeaux, Institut des Sciences Moleculaires, UMR CNRS 5255 (France)

2013-05-15

An original fluorophore engineered for two-photon excitation or a porphyrin derivative were entrapped in the silica shell of magnetic porous silica nanoparticles during the synthesis of the silica moiety without damaging the structure of the organic part. The mild conditions involved allowed obtaining microporous or mesoporous silica magnetic nanoparticles, respectively. Mannose was grafted on the surface of the nanoparticles to target MCF-7 breast cancer cells. The studies of magnetic properties of these hybrid nanoparticles show that they present a blocking temperature at 190 K. The nano-objects designed with the two-photon fluorophore were efficient for two-photon imaging of MCF-7 cancer cells, whereas the nano-objects with the photosensitizer efficiently killed cancer cells. The presence of the mannose moiety was demonstrated to improve both imaging and therapy properties.

Selective two-photon excitation of a vibronic state by correlated photons.

Science.gov (United States)

Oka, Hisaki

2011-03-28

We theoretically investigate the two-photon excitation of a molecular vibronic state by correlated photons with energy anticorrelation. A Morse oscillator having three sets of vibronic states is used, as an example, to evaluate the selectivity and efficiency of two-photon excitation. We show that a vibrational mode can be selectively excited with high efficiency by the correlated photons, without phase manipulation or pulse-shaping techniques. This can be achieved by controlling the quantum correlation so that the photon pair concurrently has two pulse widths, namely, a temporally narrow width and a spectrally narrow width. Though this concurrence is seemingly contradictory, we can create such a photon pair by tailoring the quantum correlation between two photons.

THERANOSTICS: From Molecular Imaging Using Ga-68 Labeled Tracers and PET/CT to Personalized Radionuclide Therapy - The Bad Berka Experience.

Science.gov (United States)

Baum, Richard P; Kulkarni, Harshad R

2012-01-01

The acronym THERANOSTICS epitomizes the inseparability of diagnosis and therapy, the pillars of medicine and takes into account personalized management of disease for a specific patient. Molecular phenotypes of neoplasms can be determined by molecular imaging with specific probes using positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), or optical methods, so that the treatment is specifically targeted against the tumor and its environment. To meet these demands, we need to define the targets, ligands, coupling and labeling chemistry, the most appropriate radionuclides, biodistribution modifiers, and finally select the right patients for the personalized treatment. THERANOSTICS of neuroendocrine tumors (NETs) using Ga-68 labeled tracers for diagnostics with positron emission tomography/ computed tomography (PET/CT), and using Lu-177 or other metallic radionuclides for radionuclide therapy by applying the same peptide proves that personalized radionuclide therapy today is already a fact and not a fiction.

The Slope Imaging Multi-Polarization Photon-Counting Lidar: Development and Performance Results

Science.gov (United States)

Dabney, Phillip

2010-01-01

The Slope Imaging Multi-polarization Photon-counting Lidar is an airborne instrument developed to demonstrate laser altimetry measurement methods that will enable more efficient observations of topography and surface properties from space. The instrument was developed through the NASA Earth Science Technology Office Instrument Incubator Program with a focus on cryosphere remote sensing. The SIMPL transmitter is an 11 KHz, 1064 nm, plane-polarized micropulse laser transmitter that is frequency doubled to 532 nm and split into four push-broom beams. The receiver employs single-photon, polarimetric ranging at 532 and 1064 nm using Single Photon Counting Modules in order to achieve simultaneous sampling of surface elevation, slope, roughness and depolarizing scattering properties, the latter used to differentiate surface types. Data acquired over ice-covered Lake Erie in February, 2009 are documenting SIMPL s measurement performance and capabilities, demonstrating differentiation of open water and several ice cover types. ICESat-2 will employ several of the technologies advanced by SIMPL, including micropulse, single photon ranging in a multi-beam, push-broom configuration operating at 532 nm.

UPAR targeted molecular imaging of cancers with small molecule-based probes.

Science.gov (United States)

Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

2017-10-15

Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imaging of small children with a prototype for photon counting tomosynthesis

Science.gov (United States)

del Risco Norrlid, Lilián; Fredenberg, Erik; Hemmendorff, Magnus; Jackowski, Christian; Danielsson, Mats

2009-02-01

We present data on a first prototype for photon counting tomosynthesis imaging of small children, which we call photoncounting tomosynthesis (PCT). A photon counting detector can completely eliminate electronic noise, which makes it ideal for tomosynthesis because of the low dose in each projection. Another advantage is that the detector allows for energy sensitivity in later versions, which will further lower the radiation dose. In-plane resolution is high and has been measured to be 5 lp/mm, at least 4 times better than in CT, while the depth resolution was significantly lower than typical CT resolution. The image SNR decreased from 30 to 10 for a detail of 10 mm depth in increasing thickness of PMMA from 10 to 80 mm. The air kerma measured for PCT was 5.2 mGy, which leads to an organ dose to the brain of approximately 0.7 mGy. This dose is 96 % lower than a typical CT dose. PCT can be appealing for pediatric imaging since young children have an increased sensitivity to radiation induced cancers. We have acquired post mortem images of a newborn with the new device and with a state-of-the-art CT and compared the diagnostic information and dose levels of the two modalities. The results are promising but more work is needed to provide input to a next generation prototype that would be suitable for clinical trials.

Investigation of photon counting pixel detectors for X-ray spectroscopy and imaging

Energy Technology Data Exchange (ETDEWEB)

Talla, Patrick Takoukam

2011-04-07

The Medipix2 and Medipix3 detectors are hybrid pixelated photon counting detectors with a pixel pitch of 55 {mu}m. The sensor material used in this thesis was silicon. Because of their small pixel size they suffer from charge sharing i.e. an incoming photon can be registered by more than one pixel. In order to correct for charge sharing due to lateral diffusion of charge carriers, the Medipix3 detector was developed: with its Charge Summing Mode, the charge collected in a cluster of 2 x 2 pixel is added up and attributed to only one pixel whose counter is incremented. The adjustable threshold of the detectors allows to count the photons and to gain information on their energy. The main purposes of the thesis are to investigate spectral and imaging properties of pixelated photon counting detectors from the Medipix family such as Medipix2 and Medipix3. The investigations are based on simulations and measurements. In order to investigate the spectral properties of the detectors measurements were performed using fluorescence lines of materials such as molybdenum, silver but also some radioactive sources such as Am-241 or Cd-109. From the measured data, parameters like the threshold dispersion and the gain variation from pixel-to-pixel were extracted and used as input in the Monte Carlo code ROSI to model the responses of the detector to monoenergetic photons. The measured data are well described by the simulations for Medipix2 and for Medipix3 operating in Charge Summing Mode. Due to charge sharing and due to the energy dependence of attenuation processes in silicon and to Compton scattering the incoming and the measured spectrum differ substantially from each other. Since the responses to monoenergetic photons are known, a deconvolution was performed to determine the true incoming spectrum. Several direct and iterative methods were successfully applied on measured and simulated data of an X-ray tube and radioactive sources. The knowledge of the X-ray spectrum is

Investigation of photon counting pixel detectors for X-ray spectroscopy and imaging

International Nuclear Information System (INIS)

Talla, Patrick Takoukam

2011-01-01

The Medipix2 and Medipix3 detectors are hybrid pixelated photon counting detectors with a pixel pitch of 55 μm. The sensor material used in this thesis was silicon. Because of their small pixel size they suffer from charge sharing i.e. an incoming photon can be registered by more than one pixel. In order to correct for charge sharing due to lateral diffusion of charge carriers, the Medipix3 detector was developed: with its Charge Summing Mode, the charge collected in a cluster of 2 x 2 pixel is added up and attributed to only one pixel whose counter is incremented. The adjustable threshold of the detectors allows to count the photons and to gain information on their energy. The main purposes of the thesis are to investigate spectral and imaging properties of pixelated photon counting detectors from the Medipix family such as Medipix2 and Medipix3. The investigations are based on simulations and measurements. In order to investigate the spectral properties of the detectors measurements were performed using fluorescence lines of materials such as molybdenum, silver but also some radioactive sources such as Am-241 or Cd-109. From the measured data, parameters like the threshold dispersion and the gain variation from pixel-to-pixel were extracted and used as input in the Monte Carlo code ROSI to model the responses of the detector to monoenergetic photons. The measured data are well described by the simulations for Medipix2 and for Medipix3 operating in Charge Summing Mode. Due to charge sharing and due to the energy dependence of attenuation processes in silicon and to Compton scattering the incoming and the measured spectrum differ substantially from each other. Since the responses to monoenergetic photons are known, a deconvolution was performed to determine the true incoming spectrum. Several direct and iterative methods were successfully applied on measured and simulated data of an X-ray tube and radioactive sources. The knowledge of the X-ray spectrum is

Single Photon Detection with Semiconductor Pixel Arrays for Medical Imaging Applications

CERN Document Server

Mikulec, B

2000-01-01

This thesis explores the functioning of a single photon counting pixel detector for X-ray imaging. It considers different applications for such a device, but focuses mainly on the field of medical imaging. The new detector comprises a CMOS read-out chip called PCC containing 4096 identical channels each of which counts X-ray hits. The conversion of the X-rays to electric charge takes place in a semiconductor sensor which is segmented into 4096 matching square diodes of side length 170 um, the 'pixels'. The photon counting concept is based on setting a threshold in energy above which a hit is registered. The immediate advantages are the elimination of background and the in principle unlimited dynamic range. Moreover, this approach allows the use of an electronic shutter for arbitrary measurement periods. As the device was intended for operation in the energy range of ~10-70 keV, gallium arsenide was selected as the preferred sensor material. The development of this detector followed on from about 10 years of r...

Molecular and parametric imaging with iron oxides

International Nuclear Information System (INIS)

Matuszewski, L.; Bremer, C.; Tombach, B.; Heindel, W.

2007-01-01

Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression. This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging. (orig.) [de

Molecular imaging in biomedical research

International Nuclear Information System (INIS)

Jagannathan, N.R.

2007-01-01

Molecular imaging (MI) is a diverse technology that revolutionized preclinical, clinical and drug-discovery research. It integrates biology and medicine, and the technique presents a unique opportunity to examine living systems in vivo as a dynamic biological system. It is a hybrid technology that combines PET, SPECT, ultrasound, optical imaging and MR. Several MI methodologies are developed to examine the integrative functions of molecules, cells, organ systems and whole organisms. MI is superior to conventional diagnostic techniques in allowing better staging as well as to monitor the response of cancer/tumour to treatment. In addition, it helps visualization of specific molecular targets or pathways and cells in living systems and ultimately in the clinic. (author)

Evaluation of mixed-signal noise effects in photon-counting X-ray image sensor readout circuits

International Nuclear Information System (INIS)

Lundgren, Jan; Abdalla, Suliman; O'Nils, Mattias; Oelmann, Bengt

2006-01-01

In readout electronics for photon-counting pixel detectors, the tight integration between analog and digital blocks causes the readout electronics to be sensitive to on-chip noise coupling. This noise coupling can result in faulty luminance values in grayscale X-ray images, or as color distortions in a color X-ray imaging system. An exploration of simulating noise coupling in readout circuits is presented which enables the discovery of sensitive blocks at as early a stage as possible, in order to avoid costly design iterations. The photon-counting readout system has been simulated for noise coupling in order to highlight the existing problems of noise coupling in X-ray imaging systems. The simulation results suggest that on-chip noise coupling should be considered and simulated in future readout electronics systems for X-ray detectors

Nonlinear spatial mode imaging of hybrid photonic crystal fibers

DEFF Research Database (Denmark)

Petersen, Sidsel Rübner; Alkeskjold, Thomas Tanggaard; Laurila, Marko

2013-01-01

Degenerate spontaneous four wave mixing is studied for the rst time in a large mode area hybrid photonic crystal ber, where light con nement is achieved by combined index- and bandgap guiding. Four wave mixing products are generated on the edges of the bandgaps, which is veri ed by numerical and ...... and experimental results. Since the core mode is in resonance with cladding modes near the bandedges an unconventional measurement technique is used, in this work named nonlinear spatial mode imaging....

Translational Applications of Molecular Imaging and Radionuclide Therapy

International Nuclear Information System (INIS)

Welch, Michael J.; Eckelman, William C.; Vera, David

2005-01-01

Molecular imaging is becoming a larger part of imaging research and practice. The Office of Biological and Environmental Research of the Department of Energy funds a significant number of researchers in this area. The proposal is to partially fund a workshop to inform scientists working in nuclear medicine and nuclear medicine practitioners of the recent advances of molecular imaging in nuclear medicine as well as other imaging modalities. A limited number of topics related to radionuclide therapy will also be discussed. The proposal is to request partial funds for the workshop entitled ''Translational Applications of Molecular Imaging and Radionuclide Therapy'' to be held prior to the Society of Nuclear Medicine Annual Meeting in Toronto, Canada in June 2005. The meeting will be held on June 17-18. This will allow scientists interested in all aspects of nuclear medicine imaging to attend. The chair of the organizing group is Dr. Michael J. Welch. The organizing committee consists of Dr. Welch, Dr. William C. Eckelman and Dr. David Vera. The goal is to invite speakers to discuss the most recent advances of modern molecular imaging and therapy. Speakers will present advances made in in vivo tagging imaging assays, technical aspects of small animal imaging, in vivo imaging and bench to bedside translational study; and the role of a diagnostic scan on therapy selection. This latter topic will include discussions on therapy and new approaches to dosimetry. Several of these topics are those funded by the Department of Energy Office of Biological and Environmental Research

Development of a high-speed single-photon pixellated detector for visible wavelengths

CERN Document Server

Mac Raighne, Aaron; Mathot, Serge; McPhate, Jason; Vallerga, John; Jarron, Pierre; Brownlee, Colin; O’Shea, Val

2009-01-01

We present the development of a high-speed, single-photon counting, Hybrid Photo Detector (HPD). The HPD consists of a vacuum tube, containing the detector assembly, sealed with a transparent optical input window. Photons incident on the photocathode eject a photoelectron into a large electric field, which accelerates the incident electron onto a silicon detector. The silicon detector is bump bonded to a Medipix readout chip. This set-up allows for the detection and readout of low incident photon intensities at rates that are otherwise unattainable with current camera technology. Reported is the fabrication of the camera that brings together a range of sophisticated design and fabrication techniques and the expected theoretical imaging performance. Applications to cellular and molecular microscopy are also described in which single-photon-counting abilities at high frame rates are crucial

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

Science.gov (United States)

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

Photon-counting hexagonal pixel array CdTe detector: Spatial resolution characteristics for image-guided interventional applications

Energy Technology Data Exchange (ETDEWEB)

Vedantham, Srinivasan; Shrestha, Suman; Karellas, Andrew, E-mail: andrew.karellas@umassmed.edu; Shi, Linxi; Gounis, Matthew J. [Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 (United States); Bellazzini, Ronaldo; Spandre, Gloria; Brez, Alessandro; Minuti, Massimo [Istituto Nazionale di Fisica Nucleare (INFN), Pisa 56127, Italy and Pixirad Imaging Counters s.r.l., L. Pontecorvo 3, Pisa 56127 (Italy)

2016-05-15

Purpose: High-resolution, photon-counting, energy-resolved detector with fast-framing capability can facilitate simultaneous acquisition of precontrast and postcontrast images for subtraction angiography without pixel registration artifacts and can facilitate high-resolution real-time imaging during image-guided interventions. Hence, this study was conducted to determine the spatial resolution characteristics of a hexagonal pixel array photon-counting cadmium telluride (CdTe) detector. Methods: A 650 μm thick CdTe Schottky photon-counting detector capable of concurrently acquiring up to two energy-windowed images was operated in a single energy-window mode to include photons of 10 keV or higher. The detector had hexagonal pixels with apothem of 30 μm resulting in pixel pitch of 60 and 51.96 μm along the two orthogonal directions. The detector was characterized at IEC-RQA5 spectral conditions. Linear response of the detector was determined over the air kerma rate relevant to image-guided interventional procedures ranging from 1.3 nGy/frame to 91.4 μGy/frame. Presampled modulation transfer was determined using a tungsten edge test device. The edge-spread function and the finely sampled line spread function accounted for hexagonal sampling, from which the presampled modulation transfer function (MTF) was determined. Since detectors with hexagonal pixels require resampling to square pixels for distortion-free display, the optimal square pixel size was determined by minimizing the root-mean-squared-error of the aperture functions for the square and hexagonal pixels up to the Nyquist limit. Results: At Nyquist frequencies of 8.33 and 9.62 cycles/mm along the apothem and orthogonal to the apothem directions, the modulation factors were 0.397 and 0.228, respectively. For the corresponding axis, the limiting resolution defined as 10% MTF occurred at 13.3 and 12 cycles/mm, respectively. Evaluation of the aperture functions yielded an optimal square pixel size of 54 �

The development of nanobody probes for molecular imaging

International Nuclear Information System (INIS)

Ding Zhiling; Lan Xiaoli; Zhang Yongxue

2014-01-01

The nanobody is a novel antibody fragment, which has beneficial biophysical and pharmacokinetic properties, such as the small molecular weight, high affinity and specificity for antigen. Nanobody is ideally suitable for molecular imaging as a targeting probe that could label antigen at nmol level in vitro. In animal models of xenografted tumor, atherosclerotic plaques and brain disorders, the target tissues were specifically and clearly detected and the high tumor-to-blood (T/B) ratios were obtained. Structural or chemical modified nanobodies will have higher affinity and retention to target tissues, and be convenient for the application of molecular imaging. With the development of the related research, nanobody-based molecular imaging will be gradually transformed into the clinical applications, and play an important role in early diagnosis and therapeutic assessment. (authors)

3D molecular imaging SIMS

Energy Technology Data Exchange (ETDEWEB)

Gillen, Greg [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)]. E-mail: Greg.gillen@nist.gov; Fahey, Albert [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Wagner, Matt [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Mahoney, Christine [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)

2006-07-30

Thin monolayer and bilayer films of spin cast poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PHEMA), poly(lactic) acid (PLA) and PLA doped with several pharmaceuticals have been analyzed by dynamic SIMS using SF{sub 5} {sup +} polyatomic primary ion bombardment. Each of these systems exhibited minimal primary beam-induced degradation under cluster ion bombardment allowing molecular depth profiles to be obtained through the film. By combing secondary ion imaging with depth profiling, three-dimensional molecular image depth profiles have been obtained from these systems. In another approach, bevel cross-sections are cut in the samples with the SF{sub 5} {sup +} primary ion beam to produce a laterally magnified cross-section of the sample that does not contain the beam-induced damage that would be induced by conventional focussed ion beam (FIB) cross-sectioning. The bevel surface can then be examined using cluster SIMS imaging or other appropriate microanalysis technique.

Poster – 02: Positron Emission Tomography (PET) Imaging Reconstruction using higher order Scattered Photon Coincidences

Energy Technology Data Exchange (ETDEWEB)

Sun, Hongwei; Pistorius, Stephen [Department of Physics and Astronomy, University of Manitoba, CancerCare, Manitoba (Canada)

2016-08-15

PET images are affected by the presence of scattered photons. Incorrect scatter-correction may cause artifacts, particularly in 3D PET systems. Current scatter reconstruction methods do not distinguish between single and higher order scattered photons. A dual-scattered reconstruction method (GDS-MLEM) that is independent of the number of Compton scattering interactions and less sensitive to the need for high energy resolution detectors, is proposed. To avoid overcorrecting for scattered coincidences, the attenuation coefficient was calculated by integrating the differential Klein-Nishina cross-section over a restricted energy range, accounting only for scattered photons that were not detected. The optimum image can be selected by choosing an energy threshold which is the upper energy limit for the calculation of the cross-section and the lower limit for scattered photons in the reconstruction. Data was simulated using the GATE platform. 500,000 multiple scattered photon coincidences with perfect energy resolution were reconstructed using various methods. The GDS-MLEM algorithm had the highest confidence (98%) in locating the annihilation position and was capable of reconstructing the two largest hot regions. 100,000 photon coincidences, with a scatter fraction of 40%, were used to test the energy resolution dependence of different algorithms. With a 350–650 keV energy window and the restricted attenuation correction model, the GDS-MLEM algorithm was able to improve contrast recovery and reduce the noise by 7.56%–13.24% and 12.4%–24.03%, respectively. This approach is less sensitive to the energy resolution and shows promise if detector energy resolutions of 12% can be achieved.

Resonance Energy Transfer Molecular Imaging Application in Biomedicine

Directory of Open Access Journals (Sweden)

NIE Da-hong1,2;TANG Gang-hua1,3

2016-11-01

Full Text Available Resonance energy transfer molecular imaging (RETI can markedly improve signal intensity and tissue penetrating capacity of optical imaging, and have huge potential application in the deep-tissue optical imaging in vivo. Resonance energy transfer (RET is an energy transition from the donor to an acceptor that is in close proximity, including non-radiative resonance energy transfer and radiative resonance energy transfer. RETI is an optical imaging technology that is based on RET. RETI mainly contains fluorescence resonance energy transfer imaging (FRETI, bioluminescence resonance energy transfer imaging (BRETI, chemiluminescence resonance energy transfer imaging (CRETI, and radiative resonance energy transfer imaging (RRETI. RETI is the hot field of molecular imaging research and has been widely used in the fields of biology and medicine. This review mainly focuses on RETI principle and application in biomedicine.

Molecular Tuning of Phenylene-Vinylene Derivatives for Two-Photon Photosensitized Singlet Oxygen Production

DEFF Research Database (Denmark)

Nielsen, Christian B.; Arnbjerg, Jacob; Johnsen, Mette

2009-01-01

Substituent-dependent features and properties of the sensitizer play an important role in the photosensitized production of singlet oxygen, O2(a1Δg). In this work, we systematically examine the effect of molecular changes in the sensitizer on the efficiency of singlet oxygen production using......, as the sensitizer, oligophenylene-vinylene derivatives designed to optimally absorb light in a nonlinear two-photon process. We demonstrate that one cannot always rely on rule-of-thumb guidelines when attempting to construct efficient two-photon singlet oxygen sensitizers. Rather, as a consequence of behavior...... that can deviate from the norm, a full investigation of the photophysical properties of the system is generally required. For example, it is acknowledged that the introduction of a ketone moiety to the sensitizer chromophore often results in more efficient production of singlet oxygen. However, we show...

In vivo stepwise multi-photon activation fluorescence imaging of melanin in human skin

Science.gov (United States)

Lai, Zhenhua; Gu, Zetong; Abbas, Saleh; Lowe, Jared; Sierra, Heidy; Rajadhyaksha, Milind; DiMarzio, Charles

2014-03-01

The stepwise multi-photon activated fluorescence (SMPAF) of melanin is a low cost and reliable method of detecting melanin because the activation and excitation can be a continuous-wave (CW) mode near infrared (NIR) laser. Our previous work has demonstrated the melanin SMPAF images in sepia melanin, mouse hair, and mouse skin. In this study, we show the feasibility of using SMPAF to detect melanin in vivo. in vivo melanin SMPAF images of normal skin and benign nevus are demonstrated. SMPAF images add specificity for melanin detection than MPFM images and CRM images. Melanin SMPAF is a promising technology to enable early detection of melanoma for dermatologists.

Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

International Nuclear Information System (INIS)

Mahajan, A.; Goh, V.; Basu, S.; Vaish, R.; Weeks, A.J.; Thakur, M.H.; Cook, G.J.

2015-01-01

Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure–function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [ 18 F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed “theranostics”. Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. -- Highlights: •Molecular functional imaging (MFI) gives insight into the tumor biology and intratumoral heterogeneity. •It has potential role in identifying radiomic signatures associated with underlying gene-expression. •Radiomics can be used to create a road map

Monitoring molecular interactions using photon arrival-time interval distribution analysis

Science.gov (United States)

Laurence, Ted A [Livermore, CA; Weiss, Shimon [Los Angels, CA

2009-10-06

A method for analyzing/monitoring the properties of species that are labeled with fluorophores. A detector is used to detect photons emitted from species that are labeled with one or more fluorophores and located in a confocal detection volume. The arrival time of each of the photons is determined. The interval of time between various photon pairs is then determined to provide photon pair intervals. The number of photons that have arrival times within the photon pair intervals is also determined. The photon pair intervals are then used in combination with the corresponding counts of intervening photons to analyze properties and interactions of the molecules including brightness, concentration, coincidence and transit time. The method can be used for analyzing single photon streams and multiple photon streams.

A Silicon SPECT System for Molecular Imaging of the Mouse Brain.

Science.gov (United States)

Shokouhi, Sepideh; Fritz, Mark A; McDonald, Benjamin S; Durko, Heather L; Furenlid, Lars R; Wilson, Donald W; Peterson, Todd E

2007-01-01

We previously demonstrated the feasibility of using silicon double-sided strip detectors (DSSDs) for SPECT imaging of the activity distribution of iodine-125 using a 300-micrometer thick detector. Based on this experience, we now have developed fully customized silicon DSSDs and associated readout electronics with the intent of developing a multi-pinhole SPECT system. Each DSSD has a 60.4 mm × 60.4 mm active area and is 1 mm thick. The strip pitch is 59 micrometers, and the readout of the 1024 strips on each side gives rise to a detector with over one million pixels. Combining four high-resolution DSSDs into a SPECT system offers an unprecedented space-bandwidth product for the imaging of single-photon emitters. The system consists of two camera heads with two silicon detectors stacked one behind the other in each head. The collimator has a focused pinhole system with cylindrical-shaped pinholes that are laser-drilled in a 250 μm tungsten plate. The unique ability to collect projection data at two magnifications simultaneously allows for multiplexed data at high resolution to be combined with lower magnification data with little or no multiplexing. With the current multi-pinhole collimator design, our SPECT system will be capable of offering high spatial resolution, sensitivity and angular sampling for small field-of-view applications, such as molecular imaging of the mouse brain.

New bi-dimensional SPAD arrays for time resolved single photon imaging

Energy Technology Data Exchange (ETDEWEB)

Grasso, R. [INFN-Laboratori Nazionali del Sud and Sez., INFN di Catania, Via S. Sofia 62, 95125 Catania (Italy); Dipartimento di Fisica ed Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania (Italy); Centro Siciliano di Fisica Nucleare e Struttura della Materia, Viale A. Doria 6, 95125 Catania (Italy); Tudisco, S., E-mail: tudisco@lns.infn.it [INFN-Laboratori Nazionali del Sud and Sez., INFN di Catania, Via S. Sofia 62, 95125 Catania (Italy); Centro Siciliano di Fisica Nucleare e Struttura della Materia, Viale A. Doria 6, 95125 Catania (Italy); Piemonte, C. [FBK-Fondazione Bruno Kessler, Via S. Croce 77, 38122 Trento (Italy); Lo Presti, D. [INFN-Laboratori Nazionali del Sud and Sez., INFN di Catania, Via S. Sofia 62, 95125 Catania (Italy); Dipartimento di Fisica ed Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania (Italy); Anzalone, A. [INFN-Laboratori Nazionali del Sud and Sez., INFN di Catania, Via S. Sofia 62, 95125 Catania (Italy); Musumeci, F.; Scordino, A. [INFN-Laboratori Nazionali del Sud and Sez., INFN di Catania, Via S. Sofia 62, 95125 Catania (Italy); Dipartimento di Fisica ed Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania (Italy); Serra, N.; Zorzi, N. [FBK-Fondazione Bruno Kessler, Via S. Croce 77, 38122 Trento (Italy)

2013-08-01

Some of the first results concerning the electrical and optical performances of new bi-dimensional single photon avalanche diodes arrays for imaging applications are briefly presented. The planned arrays were realized at the Fondazione Bruno Kessler—Trento and tested at LNS–INFN. The proposed new solution, utilizing a new architecture with integrated quenching resistors, allows to simplify the electronic readout.

New bi-dimensional SPAD arrays for time resolved single photon imaging

International Nuclear Information System (INIS)

Grasso, R.; Tudisco, S.; Piemonte, C.; Lo Presti, D.; Anzalone, A.; Musumeci, F.; Scordino, A.; Serra, N.; Zorzi, N.

2013-01-01

Some of the first results concerning the electrical and optical performances of new bi-dimensional single photon avalanche diodes arrays for imaging applications are briefly presented. The planned arrays were realized at the Fondazione Bruno Kessler—Trento and tested at LNS–INFN. The proposed new solution, utilizing a new architecture with integrated quenching resistors, allows to simplify the electronic readout

Imaging immune response of skin mast cells in vivo with two-photon microscopy

Science.gov (United States)

Li, Chunqiang; Pastila, Riikka K.; Lin, Charles P.

2012-02-01

Intravital multiphoton microscopy has provided insightful information of the dynamic process of immune cells in vivo. However, the use of exogenous labeling agents limits its applications. There is no method to perform functional imaging of mast cells, a population of innate tissue-resident immune cells. Mast cells are widely recognized as the effector cells in allergy. Recently their roles as immunoregulatory cells in certain innate and adaptive immune responses are being actively investigated. Here we report in vivo mouse skin mast cells imaging with two-photon microscopy using endogenous tryptophan as the fluorophore. We studied the following processes. 1) Mast cells degranulation, the first step in the mast cell activation process in which the granules are released into peripheral tissue to trigger downstream reactions. 2) Mast cell reconstitution, a procedure commonly used to study mast cells functioning by comparing the data from wild type mice, mast cell-deficient mice, and mast-cell deficient mice reconstituted with bone marrow-derived mast cells (BMMCs). Imaging the BMMCs engraftment in tissue reveals the mast cells development and the efficiency of BMMCs reconstitution. We observed the reconstitution process for 6 weeks in the ear skin of mast cell-deficient Kit wsh/ w-sh mice by two-photon imaging. Our finding is the first instance of imaging mast cells in vivo with endogenous contrast.

THERANOSTICS: From Molecular Imaging Using Ga-68 Labeled Tracers and PET/CT to Personalized Radionuclide Therapy - The Bad Berka Experience

Directory of Open Access Journals (Sweden)

Richard P. Baum, Harshad R. Kulkarni

2012-01-01

Full Text Available The acronym THERANOSTICS epitomizes the inseparability of diagnosis and therapy, the pillars of medicine and takes into account personalized management of disease for a specific patient. Molecular phenotypes of neoplasms can be determined by molecular imaging with specific probes using positron emission tomography (PET, single photon emission computed tomography (SPECT, magnetic resonance imaging (MRI, or optical methods, so that the treatment is specifically targeted against the tumor and its environment. To meet these demands, we need to define the targets, ligands, coupling and labeling chemistry, the most appropriate radionuclides, biodistribution modifiers, and finally select the right patients for the personalized treatment. THERANOSTICS of neuroendocrine tumors (NETs using Ga-68 labeled tracers for diagnostics with positron emission tomography/ computed tomography (PET/CT, and using Lu-177 or other metallic radionuclides for radionuclide therapy by applying the same peptide proves that personalized radionuclide therapy today is already a fact and not a fiction.

Trends in the development of large area photon detectors for Cherenkov light imaging applications

CERN Document Server

Nappi, E

2003-01-01

Since the successful operations of hi-tech devices at OMEGA, DELPHI and SLD, the technique of Cherenkov light imaging has gone through an impressive and fruitful evolution driven by the conception of novel large area photon detectors. The well-assessed potentialities of thin CsI films, employed as reflective photoconverters in gas counters operated at atmospheric pressure, will be compared with the promising features of hybrid and multianode vacuum photomultipliers. Recently proposed single-photon gaseous detectors based on GEMs will also be reviewed.

Sensitivity of photon-counting based K-edge imaging in X-ray computed tomography.

Science.gov (United States)

Roessl, Ewald; Brendel, Bernhard; Engel, Klaus-Jürgen; Schlomka, Jens-Peter; Thran, Axel; Proksa, Roland

2011-09-01

The feasibility of K-edge imaging using energy-resolved, photon-counting transmission measurements in X-ray computed tomography (CT) has been demonstrated by simulations and experiments. The method is based on probing the discontinuities of the attenuation coefficient of heavy elements above and below the K-edge energy by using energy-sensitive, photon counting X-ray detectors. In this paper, we investigate the dependence of the sensitivity of K-edge imaging on the atomic number Z of the contrast material, on the object diameter D , on the spectral response of the X-ray detector and on the X-ray tube voltage. We assume a photon-counting detector equipped with six adjustable energy thresholds. Physical effects leading to a degradation of the energy resolution of the detector are taken into account using the concept of a spectral response function R(E,U) for which we assume four different models. As a validation of our analytical considerations and in order to investigate the influence of elliptically shaped phantoms, we provide CT simulations of an anthropomorphic Forbild-Abdomen phantom containing a gold-contrast agent. The dependence on the values of the energy thresholds is taken into account by optimizing the achievable signal-to-noise ratios (SNR) with respect to the threshold values. We find that for a given X-ray spectrum and object size the SNR in the heavy element's basis material image peaks for a certain atomic number Z. The dependence of the SNR in the high- Z basis-material image on the object diameter is the natural, exponential decrease with particularly deteriorating effects in the case where the attenuation from the object itself causes a total signal loss below the K-edge. The influence of the energy-response of the detector is very important. We observed that the optimal SNR values obtained with an ideal detector and with a CdTe pixel detector whose response, showing significant tailing, has been determined at a synchrotron differ by factors of

PET-based molecular nuclear neuro-imaging

International Nuclear Information System (INIS)

Kim, Jong Ho

2004-01-01

Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy

PET-based molecular nuclear neuro-imaging

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong Ho [Gil Medical Center, Gachon (Korea, Republic of)

2004-04-01

Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy.

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

Energy Technology Data Exchange (ETDEWEB)

Abdollahi, H

2014-06-01

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

International Nuclear Information System (INIS)

Abdollahi, H

2014-01-01

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

In Vivo Imaging of Molecularly Targeted Phage

Directory of Open Access Journals (Sweden)

Kimberly A. Kelly

2006-12-01

Full Text Available Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin and vascular cell adhesion molecule-1 as model targets, we show that: 1 fluorescently labeled phage retains target specificity on labeling; 2 in vivo distribution can be quantitated (detection thresholds of ~ 300 phage/mm3 tissue throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3 fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents.

Simultaneous morphological and functional imaging of the honeybee's brain by two-photon microscopy

International Nuclear Information System (INIS)

Haase, A.

2011-01-01

Thanks to its rather simply structured but highly performing brain, the honeybee (Apis mellifera) is an important model for neurobiological studies. Therefore there is a great need for new functional imaging modalities adapted to this species. Herein we give a detailed report on the development and performance of a platform for in vivo functional and morphological imaging of the honeybee's brain, focusing on its primary olfactory centres, the antennal lobes (ALs). The experimental setup consists of a two-photon microscope combined with a synchronized odour stimulus generator. Our imaging platform allows to simultaneously obtain both morphological measurements of the ALs functional units, the glomeruli, and in vivo calcium recording of their neural activity. We were able to record the characteristic glomerular response maps to odour stimuli applied to the bee's antennae. Our approach offers several advantages over the commonly used conventional fluorescence microscopy. Two-photon microscopy provides substantial enhancement in both spatial and temporal resolutions, while minimizing photo damage. Calcium recordings show a more than fourfold improvement in the functional signal with respect to the techniques available up to now. Finally, the extended penetration depth, thanks to the infrared excitation, allows the functional imaging of profound glomeruli which have not been optically accessible up to now.

Diversity of radioprobes targeted to tumor angiogenesis on molecular functional imaging

International Nuclear Information System (INIS)

Lu Xia; Zhang Huabei

2013-01-01

Molecular functional imaging could visualize, characterize, and measure the bio- logical processes including tumor angiogenesis at the molecular and cellular levels in humans and other living systems. The molecular probes labeled by a variety of radionuclide used in the field of the nuclear medicine play pivotal roles in molecular imaging of tumor angiogenesis. However, the regulatory role of different probes in tumor angiogenesis has not been systematically illustrated. The current status of tumor angiogenesis imaging with radiolabeled probes of peptide, monoclonal antibody as well as its fragment, especially nanoparticle-based probes to gain insights into the robust tumor angiogenesis development were summarized. It was recognized that only the probes such as nanoparticle-based probes, which truly target the tumor vasculature rather than tumor cells because of poor extravasation, are really tumor angiogenesis imaging agent. The research of molecular probe targeted to angiogenesis would meet its flourish just after the outstanding improvements in the in vivo stability and biocompatibility, tumor-targeting efficacy, and pharmacokinetics of tumor angiogenesis imaging probes are made. Translation to clinical applications will also be critical for the maximize benefits of these novel agents. The future of tumor angiogenesis imaging lies in liable imaging probes and multiple imaging modalities, imaging of protein-protein interactions, and quantitative molecular imaging. (authors)

Molecular Imaging and Therapy of Merkel Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Beylergil, Volkan, E-mail: beylergv@mskcc.org [Molecular and Imaging Therapy Service, Department of Radiology Box 77, Memorial Sloan-Kettering Cancer Center 1275 York Ave, New York, NY 10065 (United States); Carrasquillo, Jorge A. [Molecular and Imaging Therapy Service, Department of Radiology Box 77, Memorial Sloan-Kettering Cancer Center 1275 York Ave, New York, NY 10065 (United States); Department of Radiology, Weill Cornell Medical Center, New York, NY 10065 (United States)

2014-04-29

Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC), a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

Molecular Imaging and Therapy of Merkel Cell Carcinoma

Directory of Open Access Journals (Sweden)

Volkan Beylergil

2014-04-01

Full Text Available Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC, a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

Single pulse two photon fluorescence lifetime imaging (SP-FLIM) with MHz pixel rate.

Science.gov (United States)

Eibl, Matthias; Karpf, Sebastian; Weng, Daniel; Hakert, Hubertus; Pfeiffer, Tom; Kolb, Jan Philip; Huber, Robert

2017-07-01

Two-photon-excited fluorescence lifetime imaging microscopy (FLIM) is a chemically specific 3-D sensing modality providing valuable information about the microstructure, composition and function of a sample. However, a more widespread application of this technique is hindered by the need for a sophisticated ultra-short pulse laser source and by speed limitations of current FLIM detection systems. To overcome these limitations, we combined a robust sub-nanosecond fiber laser as the excitation source with high analog bandwidth detection. Due to the long pulse length in our configuration, more fluorescence photons are generated per pulse, which allows us to derive the lifetime with a single excitation pulse only. In this paper, we show high quality FLIM images acquired at a pixel rate of 1 MHz. This approach is a promising candidate for an easy-to-use and benchtop FLIM system to make this technique available to a wider research community.

Instruments for radiation measurement in life sciences (5). ''Development of imaging technology in life science''. 9. Advantages of RI and fluorescence in imaging

International Nuclear Information System (INIS)

Furukawa, Takako; Jin, Zhao-Hui

2009-01-01

Imaging has been used as an effective research tool in many fields. In recent years, ''molecular imaging'' has come to attract a major attention as it studies molecular events in living animals and humans. Variety of modalities is used in molecular imaging, sometimes in combination, and the machines and techniques are going through rapid progress. Two of popular modalities among them are fluorescence imaging and radioisotope (RI) imaging such as positron emission tomography (PET) and single photon emission tomography (SPECT). Fluorescence imaging provides rich selection in imaging probes and the resolution can reach into sub-cellular level. RI imaging, especially PET, is superior to the others in quantitative analysis and the direct applicability to humans. In this article the two imaging modalities are overviewed comparing their characteristics. (author)

Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

Directory of Open Access Journals (Sweden)

Qingqing Meng

2013-01-01

Full Text Available 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.

Bioresponsive probes for molecular imaging : Concepts and in vivo applications

NARCIS (Netherlands)

van Duijnhoven, S.M.J.; Robillard, M.S.; Langereis, S.; Grüll, H.

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

Bioresponsive probes for molecular imaging: concepts and in vivo applications

NARCIS (Netherlands)

Duijnhoven, S.M. van; Robillard, M.S.; Langereis, S.; Grull, H.

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

Near-field imaging of out-of-plane light scattering in photonic crystal slabs

DEFF Research Database (Denmark)

Volkov, Valentyn; Bozhevolnyi, Sergey; Taillaert, Dirk

2003-01-01

A collection scanning near-field optical microscope (SNOM) is used to image the propagating of light at telecommunication wavelengths (1520-1570 nm) along photonic crystal (PC) slabs, which combine slab waveguides with in-plane PCs consisting of one- and two-dimensional gratings. The efficient out...

The influence of photon depth of interaction and non-collinear spread of annihilation photons on PET image spatial resolution

International Nuclear Information System (INIS)

Sanchez-Crespo, Alejandro; Larsson, Stig A.

2006-01-01

The quality of PET imaging is impaired by parallax errors. These errors produce misalignment between the projected location of the true origin of the annihilation event and the line of response determined by the coincidence detection system. Parallax errors are due to the varying depths of photon interaction (DOI) within the scintillator and the non-collinear (NC) emission of the annihilation photons. The aim of this work was to address the problems associated with the DOI and the NC spread of annihilation photons and to develop a quantitative model to assess their impact on image spatial resolution losses for various commonly used scintillators and PET geometries. A theoretical model based on Monte Carlo simulations was developed to assess the relative influence of DOI and the NC spread of annihilation photons on PET spatial resolution for various scintillator materials (BGO, LSO, LuAP, GSO, NaI) and PET geometries. The results demonstrate good agreement between simulated, experimental and published overall spatial resolution for some commercial systems, with maximum differences around 1 mm in both 2D and 3D mode. The DOI introduces an impairment of non-stationary spatial resolution along the radial direction, which can be very severe at peripheral positions. As an example, the radial spatial resolution loss due to DOI increased from 1.3 mm at the centre to 6.7 mm at 20 cm from the centre of a BGO camera with a 412-mm radius in 2D mode. Including the NC, the corresponding losses were 3.0 mm at the centre and 7.3 mm 20 cm from the centre. Without a DOI detection technique, it seems difficult to improve PET spatial resolution and increase sensitivity by reducing the detector ring radius or by extending the detector in the axial direction. Much effort is expended on the design and configuration of smaller detector elements but more effort should be devoted to the DOI complexity. (orig.)

Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue

Science.gov (United States)

Scolaro, Loretta; Lorenser, Dirk; Madore, Wendy-Julie; Kirk, Rodney W.; Kramer, Anne S.; Yeoh, George C.; Godbout, Nicolas; Sampson, David D.; Boudoux, Caroline; McLaughlin, Robert A.

2015-01-01

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue. PMID:26137379

Development of low-dose photon-counting contrast-enhanced tomosynthesis with spectral imaging.

Science.gov (United States)

Schmitzberger, Florian F; Fallenberg, Eva Maria; Lawaczeck, Rüdiger; Hemmendorff, Magnus; Moa, Elin; Danielsson, Mats; Bick, Ulrich; Diekmann, Susanne; Pöllinger, Alexander; Engelken, Florian J; Diekmann, Felix

2011-05-01

To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60.7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. The use of contrast-enhanced tomographic mammography has been demonstrated successfully in

Perspectives in molecular imaging through translational research, human medicine, and veterinary medicine.

Science.gov (United States)

Berry, Clifford R; Garg, Predeep

2014-01-01

The concept of molecular imaging has taken off over the past 15 years to the point of the renaming of the Society of Nuclear Medicine (Society of Nuclear Medicine and Molecular Imaging) and Journals (European Journal of Nuclear Medicine and Molecular Imaging) and offering of medical fellowships specific to this area of study. Molecular imaging has always been at the core of functional imaging related to nuclear medicine. Even before the phrase molecular imaging came into vogue, radionuclides and radiopharmaceuticals were developed that targeted select physiological processes, proteins, receptor analogs, antibody-antigen interactions, metabolites and specific metabolic pathways. In addition, with the advent of genomic imaging, targeted genomic therapy, and theranostics, a number of novel radiopharmaceuticals for the detection and therapy of specific tumor types based on unique biological and cellular properties of the tumor itself have been realized. However, molecular imaging and therapeutics as well as the concept of theranostics are yet to be fully realized. The purpose of this review article is to present an overview of the translational approaches to targeted molecular imaging with application to some naturally occurring animal models of human disease. © 2013 Published by Elsevier Inc.

Live-cell imaging.

Science.gov (United States)

Cole, Richard

2014-01-01

It would be hard to argue that live-cell imaging has not changed our view of biology. The past 10 years have seen an explosion of interest in imaging cellular processes, down to the molecular level. There are now many advanced techniques being applied to live cell imaging. However, cellular health is often under appreciated. For many researchers, if the cell at the end of the experiment has not gone into apoptosis or is blebbed beyond recognition, than all is well. This is simply incorrect. There are many factors that need to be considered when performing live-cell imaging in order to maintain cellular health such as: imaging modality, media, temperature, humidity, PH, osmolality, and photon dose. The wavelength of illuminating light, and the total photon dose that the cells are exposed to, comprise two of the most important and controllable parameters of live-cell imaging. The lowest photon dose that achieves a measureable metric for the experimental question should be used, not the dose that produces cover photo quality images. This is paramount to ensure that the cellular processes being investigated are in their in vitro state and not shifted to an alternate pathway due to environmental stress. The timing of the mitosis is an ideal canary in the gold mine, in that any stress induced from the imaging will result in the increased length of mitosis, thus providing a control model for the current imagining conditions.

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

International Nuclear Information System (INIS)

Zhu, Aizhi; Shim, Hyunsuk

2011-01-01

Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with noninvasive procedures. In particular, PET imaging takes advantage of traditional diagnostic imaging techniques and introduces positron emitting probes to determine the expression of indicative molecular targets at different stages of cancer. 18F fluorodeoxyglucose ( 18F FDG), the only FDA approved oncological PET tracer, has been widely utilized in cancer diagnosis, staging, restaging, and even monitoring response to therapy; however, 18F FDG is not a tumor specific PET tracer. Over the last decade, many promising tumor specific PET tracer. Over the last decade, many promising tumor specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current non 18F FDG PET tracers in oncology that have been developed based on tumor characteristics such as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and tumor specific antigens and surface receptors

Molecular Imaging and nuclear medicine: expectations and requirements

International Nuclear Information System (INIS)

Rollo, F.D.

2003-01-01

Molecular Imaging with Nuclear Medicine offers earlier, more accurate and more specific diagnosis, as well as targeted molecular therapy, providing significant improvements in clinical outcomes. (orig.)

A molecular beam study of the one, two, and three photon photodissociation mechanism of the group VIB (Cr,Mo,W) hexacarbonyls at 248 nm

International Nuclear Information System (INIS)

Venkataraman, B.; Hou, H.; Zhang, Z.; Chen, S.; Bandukwalla, G.; Vernon, M.

1990-01-01

Photodissociation of the group VIB (Cr,Mo,W) hexacarbonyls has been studied at 248 nm using molecular beam photofragment spectroscopy. One, two and three photon processes have been observed. Analysis of the product velocity distributions shows that the photodissociation mechanism consists of sequential CO eliminations with the nth photon channel best described as the single photon photodissociation of the stable products of the n-1st photon channel. The product translational energy distribution for the first CO elimination step is quantitatively similar for all three hexacarbonyls and characteristic of a repulsive translational energy release. The product translational energy distributions of all subsequent CO elimination steps are accurately described by a simple, microcanonical model. Qualitative molecular orbital considerations suggest that the large product translational energy observed in the first CO elimination step results from a repulsive σ interaction between the closed shell CO ligand and an excited molecular orbital which has a significant admixture of metal (n+1)p z , (n+1)s and nd z 2 orbitals. This repulsive interaction is absent in the remaining CO elimination steps because there are vacancies in the coordination shell along the z axis

Rf-synchronized imaging for particle and photon beam characterizations

Energy Technology Data Exchange (ETDEWEB)

Lumpkin, A.H.

1993-07-01

The usefulness of imaging electro-optics for rf-driven accelerators can be enhanced by synchronizing the instruments to the system fundamental frequency or an appropriate subharmonic. This step allows one to obtain micropulse bunch length and phase during a series of linac bunches or storage ring passes. Several examples now exist of the use of synchroscan and dual-sweep streak cameras and/or image dissector tubes to access micropulse scale phenomena (10 to 30 ps) during linac and storage ring operations in the US, Japan, and Europe. As space permits, selections will be presented from the list of phase stability phenomena on photoelectric injectors, micropulse length during a macropulse, micropulse elongation effects, transverse Wakefield effects within a micropulse, and submicropulse phenomena on a stored beam. Potential applications to the subsystems of the Advanced Photon Source (APS) will be briefly addressed.

Fluorescent Pluronic nanodots for in vivo two-photon imaging

International Nuclear Information System (INIS)

Maurin, Mathieu; Vurth, Laeticia; Vial, Jean-Claude; Baldeck, Patrice; Stephan, Olivier; Marder, Seth R; Sanden, Boudewijn Van der

2009-01-01

We report the synthesis of new nanosized fluorescent probes based on bio-compatible polyethylene-polypropylene glycol (Pluronic) materials. In aqueous solution, mini-emulsification of Pluronic with a high fluorescent di-stryl benzene-modified derivative, exhibiting a two-photon absorption cross section as high as 2500 Goeppert-Mayer units at 800 nm, leads to nanoparticles exhibiting a hydrodynamic radius below 100 nm. We have demonstrated that these new probes with luminescence located in the spectral region of interest for bio-imaging (the yellow part of the visible spectrum) allow deep (500 μm) bio-imaging of the mice brain vasculature. The dose injected during our experiments is ten times lower when compared to the classical commercial rhodamine-B isothicyanate-Dextran system but gives similar results to homogeneous blood plasma staining. The mean fluorescent signal intensity stayed constant during more than 1 h.

Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes

NARCIS (Netherlands)

Briley-Saebo, Karen C.; Mulder, Willem J. M.; Mani, Venkatesh; Hyafil, Fabien; Amirbekian, Vardan; Aguinaldo, Juan Gilberto S.; Fisher, Edward A.; Fayad, Zahi A.

2007-01-01

The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of

Multiscale vision model for event detection and reconstruction in two-photon imaging data

DEFF Research Database (Denmark)

Brazhe, Alexey; Mathiesen, Claus; Lind, Barbara Lykke

2014-01-01

on a modified multiscale vision model, an object detection framework based on the thresholding of wavelet coefficients and hierarchical trees of significant coefficients followed by nonlinear iterative partial object reconstruction, for the analysis of two-photon calcium imaging data. The framework is discussed...... of the multiscale vision model is similar in the denoising, but provides a better segmenation of the image into meaningful objects, whereas other methods need to be combined with dedicated thresholding and segmentation utilities....

FocusStack and StimServer: a new open source MATLAB toolchain for visual stimulation and analysis of two-photon calcium neuronal imaging data.

Science.gov (United States)

Muir, Dylan R; Kampa, Björn M

2014-01-01

Two-photon calcium imaging of neuronal responses is an increasingly accessible technology for probing population responses in cortex at single cell resolution, and with reasonable and improving temporal resolution. However, analysis of two-photon data is usually performed using ad-hoc solutions. To date, no publicly available software exists for straightforward analysis of stimulus-triggered two-photon imaging experiments. In addition, the increasing data rates of two-photon acquisition systems imply increasing cost of computing hardware required for in-memory analysis. Here we present a Matlab toolbox, FocusStack, for simple and efficient analysis of two-photon calcium imaging stacks on consumer-level hardware, with minimal memory footprint. We also present a Matlab toolbox, StimServer, for generation and sequencing of visual stimuli, designed to be triggered over a network link from a two-photon acquisition system. FocusStack is compatible out of the box with several existing two-photon acquisition systems, and is simple to adapt to arbitrary binary file formats. Analysis tools such as stack alignment for movement correction, automated cell detection and peri-stimulus time histograms are already provided, and further tools can be easily incorporated. Both packages are available as publicly-accessible source-code repositories.

Molecular photonic imaging of cancer using light-emitting e. coli

International Nuclear Information System (INIS)

Park, Jae Hyo; Min, Jung Joon; Moon, Sung Min; Kim, Hyun Ju; Hong, Yeong Jin; Choy, Hyon E.; Bom, Hee Seung; Jeong, Jae Ho; Cho, Kyoung Oh

2005-01-01

Cancer research has long sought a magic bullet that would selectively target and destroy malignant cells. In this study, we exploited that E. coli injected into tumor-bearing mice selectively target and proliferate in solid tumors by employing optical imaging technique. Lux operon or GFP has been cloned into pUC19 plasmid to engineer pUC19Lux or pUC19gfp which was transformed into varying kinds of wild type (MG1655) or mutant E.coli strains. For stable expression, lux operon was cloned with asd (aspartate β-semialdehyde dehydrogenase) gene and transformed into asd defective E. coli (MG1655asd-/asd+lux). These bacteria were i.v. injected into tumor mice or directly into central necrosis of tumor. The imaging signal from wild type E.coli was detected initially at liver (20min), then migrated to and shine in the tumor mass until 2 weeks of injection which was consistently observed in immuno-defective (nude) and -competent (Balb/c) mice. Imaging signal of stbaly transformed strain (MG1655asd-/asd+lux) was stronger and longer-lasting than that of transiently transformed strain (MG1655lux). Flagella defective E. coli strain failed to reach tumor loci. Only a few amounts of stress regulatory defective E. coli strain arrived at but couldn't survive at the tumor loci. E. coli colonies expressing GFP was mostly observed at the border of central necrosis and peripheral proliferative areas in immunofluorescence studies. Directly injected MG1655ad-/asd+lux was transiently observed at central necrosis followed by spreading to the peripheral tumor mass which was consistent with the finding by tail vein injection. We successfully engineered E. coli strain stably expressing lux reporter gene. E. coli strongly targeted solid tumor regardless of host immune status. Our results support that the targeting of tumor by E.coli is an active process and would be applied as a delivery vehicle of varying imaging markers or therapeutic molecules

Molecular Imaging with Small Animal PET/CT

DEFF Research Database (Denmark)

Binderup, T.; El-Ali, H.H.; Skovgaard, D.

2011-01-01

is also described. In addition, the non-invasive nature of molecular imaging and the targets of these promising new tracers are attractive for other research areas as well, although these fields are much less explored. We present an example of an interesting research field with the application of small......Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in pre-clinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However...... in this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume measurements...

Information Optics and Photonics Algorithms, Systems, and Applications

CERN Document Server

Javidi, Bahram

2010-01-01

This book addresses applications, recent advances, and emerging areas in fields with applications in information optics and photonics systems. The objective of this book is to illustrate and discuss novel approaches, analytical techniques, models, and technologies that enhance sensing, measurement, processing, interpretation, and visualization of information using free space optics and photonics. The material in this book concentrates on integration of diverse fields for cross-disciplinary applications including bio-photonics, digitally enhanced sensing and imaging systems, multi-dimensional optical imaging and image processing, bio-inspired imaging, 3D visualization, 3D displays, imaging on the nano-scale, quantum optics, super resolution imaging, photonics for biological applications, and holographic information systems. As a result, this book is a useful resource for researchers, engineers, and graduate students who work in the diverse fields comprising information optics and photonics.

Molecular Imaging of Breast Cancer: Present and future directions

Directory of Open Access Journals (Sweden)

David eAlcantara

2014-12-01

Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

Estimation and correction of produced light from prompt gamma photons on luminescence imaging of water for proton therapy dosimetry

Science.gov (United States)

Yabe, Takuya; Komori, Masataka; Toshito, Toshiyuki; Yamaguchi, Mitsutaka; Kawachi, Naoki; Yamamoto, Seiichi

2018-02-01

Although the luminescence images of water during proton-beam irradiation using a cooled charge-coupled device camera showed almost the same ranges of proton beams as those measured by an ionization chamber, the depth profiles showed lower Bragg peak intensities than those measured by an ionization chamber. In addition, a broad optical baseline signal was observed in depths that exceed the depth of the Bragg peak. We hypothesize that this broad baseline signal originates from the interaction of proton-induced prompt gamma photons with water. These prompt gamma photons interact with water to form high-energy Compton electrons, which may cause luminescence or Cherenkov emission from depths exceeding the location of the Bragg peak. To clarify this idea, we measured the luminescence images of water during the irradiations of protons in water with minimized parallax errors, and also simulated the produced light by the interactions of prompt gamma photons with water. We corrected the measured depth profiles of the luminescence images by subtracting the simulated distributions of the produced light by the interactions of prompt gamma photons in water. Corrections were also conducted using the estimated depth profiles of the light of the prompt gamma photons, as obtained from the off-beam areas of the luminescence images of water. With these corrections, we successfully obtained depth profiles that have almost identical distributions as the simulated dose distributions for protons. The percentage relative height of the Bragg peak with corrections to that of the simulation data increased to 94% from 80% without correction. Also, the percentage relative offset heights of the deeper part of the Bragg peak with corrections decreased to 0.2%-0.4% from 4% without correction. These results indicate that the luminescence imaging of water has potential for the dose distribution measurements for proton therapy dosimetry.

Performance assessment of the single photon emission microscope: high spatial resolution SPECT imaging of small animal organs

International Nuclear Information System (INIS)

Mejia, J.; Reis, M.A.; Miranda, A.C.C.; Batista, I.R.; Barboza, M.R.F.; Shih, M.C.; Fu, G.; Chen, C.T.; Meng, L.J.; Bressan, R.A.; Amaro, E. Jr

2013-01-01

The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s -1 ·MBq -1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99m Tc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99m Tc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity

Performance assessment of the single photon emission microscope: high spatial resolution SPECT imaging of small animal organs

Energy Technology Data Exchange (ETDEWEB)

Mejia, J. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Reis, M.A. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Laboratório Interdisciplinar de Neurociências Clínicas, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Miranda, A.C.C. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Batista, I.R. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Laboratório Interdisciplinar de Neurociências Clínicas, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Barboza, M.R.F.; Shih, M.C. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Fu, G. [GE Global Research, Schenectady, NY (United States); Chen, C.T. [Department of Radiology, University of Chicago, Chicago, IL (United States); Meng, L.J. [Department of Nuclear, Plasma and Radiological Engineering, University of Illinois, Urbana-Champaign, IL (United States); Bressan, R.A. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Laboratório Interdisciplinar de Neurociências Clínicas, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Amaro, E. Jr [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil)

2013-11-06

The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s{sup -1}·MBq{sup -1} were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging {sup 99m}Tc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using {sup 99m}Tc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.

Performance assessment of the single photon emission microscope: high spatial resolution SPECT imaging of small animal organs

Directory of Open Access Journals (Sweden)

J. Mejia

2013-11-01

Full Text Available The single photon emission microscope (SPEM is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD. Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.

The research progress of nuclear medicine on cardiovascular molecular imaging

International Nuclear Information System (INIS)

Yin Xiaohua; Zhang Yongxue

2007-01-01

Cardiovascular molecular imaging is a rapidly evolving discipline and its clinical application is promising. Nuclear medicine is playing a leading role in this field with its special superiority of noninvasive, quantifiability, high sensitivity and specificity. It provides broad opportunities for exploring the pathophysiologic process of cardiovascular diseases and monitoring its gene therapy in the molecular level. In this review, we mainly discuss some basic knowledge on cardiovascular molecular imaging, and then focus on the applied research prospect of nuclear medicine radionuclide imaging. (authors)

Molecular-resolution imaging of pentacene on KCl(001

Directory of Open Access Journals (Sweden)

Julia L. Neff

2012-02-01

Full Text Available The growth of pentacene on KCl(001 at submonolayer coverage was studied by dynamic scanning force microscopy. At coverages below one monolayer pentacene was found to arrange in islands with an upright configuration. The molecular arrangement was resolved in high-resolution images. In these images two different types of patterns were observed, which switch repeatedly. In addition, defects were found, such as a molecular vacancy and domain boundaries.

Image acquisition and analysis for beam diagnostics, applications of the Taiwan photon source

International Nuclear Information System (INIS)

Liao, C.Y.; Chen, J.; Cheng, Y.S.; Hsu, K.T.; Hu, K.H.; Kuo, C.H.; Wu, C.Y.

2012-01-01

Design and implementation of image acquisition and analysis is in proceeding for the Taiwan Photon Source (TPS) diagnostic applications. The optical system contains screen, lens, and lighting system. A CCD camera with Gigabit Ethernet interface (GigE Vision) will be a standard image acquisition device. Image acquisition will be done on EPICS IOC via PV channel and analysis the properties by using Matlab tool to evaluate the beam profile (sigma), beam size position and tilt angle et al. The EPICS IOC integrated with Matlab as a data processing system is not only could be used in image analysis but also in many types of equipment data processing applications. Progress of the project will be summarized in this report. (authors)

Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

Energy Technology Data Exchange (ETDEWEB)

Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Diagnostic Radiology, ZARF Project, Center for Molecular Imaging Research MBMB, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

2011-09-15

Purpose: Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research. Materials and methods: The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells. Results: Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells. Conclusion: This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.

single photon emission tomography and positron emission tomography - Part 1 (October 2012), Part 2 (October 2010)

International Nuclear Information System (INIS)

Buvat, Irene

2010-10-01

The objective of this lecture is to present the single photon emission computed tomography (SPECT) and the positron emission tomography (PET) imaging techniques. Part 1 Content: 1 - Introduction: anatomic, functional and molecular imaging; 2 - Radiotracers: chemical and physical constraints, gamma photon emitters, positon emitters, radioisotopes production, emitters type and imaging techniques; 3 - Gamma cameras; 4 - Quantification in emission tomography: attenuation, scattering, un-stationary spatial resolution; 5 - Synthesis and conclusion. Part 2 content: 1 - Positon emitters; 2 - Positons detection: Coincidence detection (electronic collimation, PET detectors with gamma cameras, dedicated PET detectors, spectrometry); PET detectors type; time-of-flight PET; 2D PET; 3D PET; 3 - Quantification in emission tomography: detected events, attenuation, scattering, fortuitous coincidences, standardisation; 4 - Common SPECT and PET problems: partial volume effect, movement, tomographic reconstruction, calibration, dead time; 5 - Synthesis and conclusion

High-resolution, label-free two-photon imaging of diseased human corneas

Science.gov (United States)

Batista, Ana; Breunig, Hans Georg; König, Aisada; Schindele, Andreas; Hager, Tobias; Seitz, Berthold; König, Karsten

2018-03-01

The diagnosis of corneal diseases may be improved by monitoring the metabolism of cells and the structural organization of the stroma using two-photon imaging (TPI). We used TPI to assess the differences between nonpathological (NP) human corneas and corneas diagnosed with either keratoconus, Acanthamoeba keratitis, or stromal corneal scars. Images were acquired using a custom-built five-dimensional laser-scanning microscope with a broadband sub-15 femtosecond near-infrared pulsed excitation laser and a 16-channel photomultiplier tube detector in combination with a time-correlated single photon counting module. Morphological alterations of epithelial cells were observed for all pathologies. Moreover, diseased corneas showed alterations to the cells' metabolism that were revealed using the NAD(P)H free to protein-bound ratios. The mean autofluorescence lifetime of the stroma and the organization of the collagen fibers were also significantly altered due to the pathologies. We demonstrate that TPI can be used to distinguish between NP and diseased human corneas, based not only on alterations of the cells' morphology, which can also be evaluated using current clinical devices, but on additional morphological and functional features such as the organization of the stroma and the cells' metabolism. Therefore, TPI could become an efficient tool for diagnosing corneal diseases and better understanding the biological processes of the diseases.

Molecular imaging: High-resolution detectors for early diagnosis and therapy monitoring of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Garibaldi, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy)]. E-mail: Franco.garibaldi@iss.infn.it; Cisbani, E. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Colilli, S. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Cusanno, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Giuliani, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Gricia, M. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Lucentini, M. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Lo Meo, S. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Magliozzi, M.L. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Santanvenere, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Cinti, M.N. [University La Sapienza, Rome (Italy); Pani, R. [University La Sapienza, Rome (Italy); Pellegrini, R. [University La Sapienza, Rome (Italy); Simonetti, G. [University Tor Vergata, Rome (Italy); Schillaci, O. [University Tor Vergata, Rome (Italy); Del Vecchio, S. [CNR Napoli, Naples (Italy); Salvatore, M. [CNR Napoli, Naples (Italy); Majewski, S. [Jefferson Lab, Newport News, VA (United States); Lanza, R.C. [Massachusetts Institute of Technology, Cambridge, MA (United States); De Vincentis, G. [University La Sapienza, Rome (Italy); Scopinaro, F. [University La Sapienza, Rome (Italy)

2006-12-20

Dedicated high-resolution detectors are required for detection of small cancerous breast tumours by molecular imaging with radionuclides. Absorptive collimation is normally applied in imaging single photon emitters, but it results in a strong reduction in detection efficiency. Systems based on electronic collimation are complex and expensive. For these reasons simulations and measurements have been performed to design optimised dedicated high-resolution mini gamma camera. Critical parameters are contrast and signal-to-noise ratio (SNR). Intrinsic performance (spatial resolution, pixel identification, and response linearity and uniformity) were first optimised. Pixellated scintillator arrays (NaI(Tl)) of different pixel size were coupled to arrays of PSPMTs with different anode pad dimensions (6x6 mm{sup 2} and 3x3 mm{sup 2}). Detectors having a field of view (FOV) of 100x100 mm{sup 2} and 150x200 mm{sup 2} were designed and built. The electronic system allows read out of all the anode pad signals. The collimation technique was then considered and limits of coded aperture option were studied. Preliminary results are presented.

Fast imaging by photon counting application to long-baseline optical stellar interferometry

International Nuclear Information System (INIS)

Morel, Sebastien

1998-01-01

Image acquisition by photon counting in the visible spectrum with a high precision on photo-events dating is especially useful for ground-based observations. In the first part of this thesis, and after a review of several techniques for photon acquisition and processing, I introduce a new type of photon counting camera, noticeable for its high temporal resolution and its high maximum counting rate: the DELTA (Detector Enhancement by Linear-projections on Three Axes) camera. I describe the concept of this camera, and the engineering solutions (optics, electronics, computing) that could be used for its construction. The second part of my work regards fringe detection and tracking in ground-based and long- baseline optical stellar interferometry. After a statistical approach of the issue, I describe methods introducing a priori information in the data, in order to have a better detection efficiency. One of the proposed methods, using a priori information on the atmospheric piston, requires a precise photo-event dating, and therefore uses methods described in the first part. (author) [fr

Molecular Ultrasound Imaging for the Detection of Neural Inflammation

Science.gov (United States)

Volz, Kevin R.

Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was

A 3D imaging system integrating photoacoustic and fluorescence orthogonal projections for anatomical, functional and molecular assessment of rodent models

Science.gov (United States)

Brecht, Hans P.; Ivanov, Vassili; Dumani, Diego S.; Emelianov, Stanislav Y.; Anastasio, Mark A.; Ermilov, Sergey A.

2018-03-01

We have developed a preclinical 3D imaging instrument integrating photoacoustic tomography and fluorescence (PAFT) addressing known deficiencies in sensitivity and spatial resolution of the individual imaging components. PAFT is designed for simultaneous acquisition of photoacoustic and fluorescence orthogonal projections at each rotational position of a biological object, enabling direct registration of the two imaging modalities. Orthogonal photoacoustic projections are utilized to reconstruct large (21 cm3 ) volumes showing vascularized anatomical structures and regions of induced optical contrast with spatial resolution exceeding 100 µm. The major advantage of orthogonal fluorescence projections is significant reduction of background noise associated with transmitted or backscattered photons. The fluorescence imaging component of PAFT is used to boost detection sensitivity by providing low-resolution spatial constraint for the fluorescent biomarkers. PAFT performance characteristics were assessed by imaging optical and fluorescent contrast agents in tissue mimicking phantoms and in vivo. The proposed PAFT technology will enable functional and molecular volumetric imaging using fluorescent biomarkers, nanoparticles, and other photosensitive constructs mapped with high fidelity over robust anatomical structures, such as skin, central and peripheral vasculature, and internal organs.

On-chip steering of entangled photons in nonlinear photonic crystals.

Science.gov (United States)

Leng, H Y; Yu, X Q; Gong, Y X; Xu, P; Xie, Z D; Jin, H; Zhang, C; Zhu, S N

2011-08-16

One promising technique for working toward practical photonic quantum technologies is to implement multiple operations on a monolithic chip, thereby improving stability, scalability and miniaturization. The on-chip spatial control of entangled photons will certainly benefit numerous applications, including quantum imaging, quantum lithography, quantum metrology and quantum computation. However, external optical elements are usually required to spatially control the entangled photons. Here we present the first experimental demonstration of on-chip spatial control of entangled photons, based on a domain-engineered nonlinear photonic crystal. We manipulate the entangled photons using the inherent properties of the crystal during the parametric downconversion, demonstrating two-photon focusing and beam-splitting from a periodically poled lithium tantalate crystal with a parabolic phase profile. These experimental results indicate that versatile and precise spatial control of entangled photons is achievable. Because they may be operated independent of any bulk optical elements, domain-engineered nonlinear photonic crystals may prove to be a valuable ingredient in on-chip integrated quantum optics.

In vivo imaging of the morphology and changes in pH along the gastrointestinal tract of Japanese medaka by photonic band-gap hydrogel microspheres

International Nuclear Information System (INIS)

Du, Xuemin; Lei, Ngai-Yu; Hu, Peng; Lei, Zhang; Ong, Daniel Hock-Chun; Ge, Xuewu; Zhang, Zhicheng; Lam, Michael Hon-Wah

2013-01-01

Graphical abstract: -- Highlights: •Fabrication of pH-responsive photonic colloidal crystalline microspheres. •Specific photonic band-gap responses occurred in the pH range of 4–5. •Remarkably low in vivo toxicity to Japanese medaka (Oryzia latipes). •In vivo imaging of the morphology and pH along GI tract of Japanese medaka. •Demonstrates bio-imaging potentials of stimuli-responsive photonic materials. -- Abstract: Colloidal crystalline microspheres with photonic band-gap properties responsive to media pH have been developed for in vivo imaging purposes. These colloidal crystalline microspheres were constructed from monodispersed core–shell nano-size particles with poly(styrene-co-acrylic acid) (PS-co-PAA) cores and poly(acrylic acid-co-N-isopropylacrylamide) (PAA-co-PNIPAM) hydrogel shells cross-linked by N,N′-methylenebisacrylamide. A significant shift in the photonic band-gap properties of these colloidal crystalline microspheres was observed in the pH range of 4–5. This was caused by the discontinuous volume phase transition of the hydrogel coating, due to the protonation/deprotonation of its acrylic acid moieties, on the core–shell nano-sized particles within the microspheres. The in vivo imaging capability of these pH-responsive photonic microspheres was demonstrated on a test organism – Japanese medaka, Oryzia latipes – in which the morphology and change in pH along their gastrointestinal (GI) tracts were revealed under an ordinary optical microscope. This work illustrates the potential of stimuli-responsive photonic band-gap materials in tissue-/organ-level in vivo bio-imaging

Quality Assurance of Pixel Hybrid Photon Detectors for the LHCb Ring Imaging Cherenkov Counters

CERN Document Server

Carson, Laurence

Pion/kaon discrimination in the LHCb experiment will be provided by two Ring Imaging Cherenkov (RICH) counters. These use arrays of 484 Hybrid Photon Detectors (HPDs) to detect the Cherenkov photons emitted by charged particles traversing the RICH. The results from comprehensive quality assurance tests on the 550 HPDs manufactured for LHCb are described. Leakage currents, dead channel probabilities, dark count rates and ion feedback rates are reported. Furthermore, measurements carried out on a sample of tubes to determine the efficiency of the HPD pixel chip by measuring the summed analogue response from the backplane of the silicon sensor are described.

[Microdose clinical trial--impact of PET molecular imaging].

Science.gov (United States)

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

[Clinical application of high-pitch excretory phase images during dual-source CT urography with stellar photon detector].

Science.gov (United States)

Sun, Hao; Xue, Hua-dan; Jin, Zheng-yu; Wang, Xuan; Chen, Yu; He, Yong-lan; Zhang, Da-ming; Zhu, Liang; Wang, Yun; Qi, Bing; Xu, Kai; Wang, Ming

2014-10-01

To retrospectively evaluate the clinical feasibility of high-pitch excretory phase images during dual-source CT urography with Stellar photon detector. Totally 100 patients received dual-source CT high-pitch urinary excretory phase scanning with Stellar photon detector [80 kV, ref.92 mAs, CARE Dose 4D and CARE kV, pitch of 3.0, filter back projection reconstruction algorithm (FBP)] (group A). Another 100 patients received dual-source CT high-pitch urinary excretory phase scanning with common detector(100 kV, ref.140 mAs, CARE Dose 4D, pitch of 3.0, FBP) (group B). Quantitative measurement of CT value of urinary segments (Hounsfield units), image noise (Hounsfield units), and effective radiation dose (millisievert) were compared using independent-samples t test between two groups. Urinary system subjective opacification scores were compared using Mann-Whitney U test between two groups. There was no significant difference in subjective opacification score of intrarenal collecting system and ureters between two groups (all P>0.05). The group A images yielded significantly higher CT values of all urinary segments (all P0.05). The effective radiation dose of group A (1.1 mSv) was significantly lower than that of group B (3.79 mSv) (Ppitch low-tube-voltage during excretory phase dual-source CT urography with Stellar photon detector is feasible, with acceptable image noise and lower radiation dose.

Multi-photon vertical cross-sectional imaging with a dynamically-balanced thin-film PZT z-axis microactuator.

Science.gov (United States)

Choi, Jongsoo; Duan, Xiyu; Li, Haijun; Wang, Thomas D; Oldham, Kenn R

2017-10-01

Use of a thin-film piezoelectric microactuator for axial scanning during multi-photon vertical cross-sectional imaging is described. The actuator uses thin-film lead-zirconate-titanate (PZT) to generate upward displacement of a central mirror platform, micro-machined from a silicon-on-insulator (SOI) wafer to dimensions compatible with endoscopic imaging instruments. Device modeling in this paper focuses on existence of frequencies near device resonance producing vertical motion with minimal off-axis tilt even in the presence of multiple vibration modes and non-uniformity in fabrication outcomes. Operation near rear resonance permits large stroke lengths at low voltages relative to other vertical microactuators. Highly uniform vertical motion of the mirror platform is a key requirement for vertical cross-sectional imaging in the remote scan architecture being used for multi-photon instrument prototyping. The stage is installed in a benchtop testbed in combination with an electrostatic mirror that performs in-plane scanning. Vertical sectional images are acquired from 15 μm diameter beads and excised mouse colon tissue.

Construction of an efficient two-photon fluorescent probe for imaging nitroreductase in live cells and tissues

Science.gov (United States)

Zhou, Liyi; Gong, Liang; Hu, Shunqin

2018-06-01

Compared with traditional confocal microscopy, two-photon fluorescence microscopy (TPFM), which excites a two-photon (TP) fluorophore by near-infrared light, provides improved three-dimensional image resolution with increased tissue-image depth (>500 μm) and an extended observation time. Therefore, the development of novel functional TP fluorophores has attracted great attention in recent years. Herein, a novel TP fluorophore CM-NH2, which have the donor-π-acceptor (D-π-A)-structure, was designed and synthesized. We further used this dye developed a new type of TP fluorescent probe CM-NO2 for detecting nitroreductase (NTR). Upon incubated with NTR for 15 min, CM-NO2 displayed a 90-fold fluorescence enhancement at 505 nm and the maximal TP action cross-section value after reaction was detected and calculated to be 200 GM at 760 nm. The probe exhibited excellent properties such as high sensitivity, high selectivity, low cytotoxicity, and high photostability. Moreover, the probe was utilized to image the tumor hypoxia in live HeLa cells. Finally, using the CM-NO2 to image NTR in tissues was demonstrated.

Light at the end of the tunnel in radiation therapy: molecular imaging in radiation research

International Nuclear Information System (INIS)

Rao, V.L. Papineni

2013-01-01

Accurate dose delivery to malignant tissue in radiotherapy is quite important for enhancing the treatment efficacy while minimizing morbidity of surrounding normal tissues. Advances in therapeutic strategies and diagnosis technologies along with our understanding of the biology of tumor response to radiation therapy have paved way to allow nearly 60% of current cancer patients to be treated with Radiation Therapy. The confluence of molecular imaging and nanotechnology fields are bridging physics and medicine and are quickly making strides in opening new avenues and therapeutic strategies that complement radiation therapy - with a distinct footprint in immunotherapy, adoptive cell therapy, and targeted chemotherapy. Incorporating optical imaging in radiation therapy in my laboratory, we demonstrated that molecular probes can monitor radiation-induced physiological changes at the target and off-target sites using in vivo molecular imaging approaches. Further we show endogenous bioluminescence resulting from whole body irradiation, which is distinct from the Cherenkov radiation. Mice without anesthesia were held in ventilated mouse pie cage and subjected to 5 Gy X-ray irradiation using commercially available X-RAD320 irradiator (1 Gy/min; F2 beam hardening filter 1.5 mm Al, 0.25 mm Cu, 0.75 mm Sn,). The endogenous bioluminescence from the subjects was captured using cooled CCD camera. Significant increase (up to 100 fold) in the amounts of photons released as bioluminescence was detected during 5 min capture from the mice subjected to irradiation compared to that of the control. To determine the early inflammatory response, the reactive oxygen species (ROS) activity was monitored using L-012 (8-amino-5-chloro-7-phenylpyridol (3,4-d)pyridazine-1,4(2H,3H) dione), a chemiluminescence reporter. L-012 was administered (i.p) after 15 min of irradiation. Chemiluminescence resulting from the irradiation induced ROS activity, possible through the action of the

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

Energy Technology Data Exchange (ETDEWEB)

Tsui, B. [Johns Hopkins University (United States)

2016-06-15

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

International Nuclear Information System (INIS)

Tsui, B.

2016-01-01

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly

Photon correlation holography.

Science.gov (United States)

Naik, Dinesh N; Singh, Rakesh Kumar; Ezawa, Takahiro; Miyamoto, Yoko; Takeda, Mitsuo

2011-01-17

Unconventional holography called photon correlation holography is proposed and experimentally demonstrated. Using photon correlation, i.e. intensity correlation or fourth order correlation of optical field, a 3-D image of the object recorded in a hologram is reconstructed stochastically with illumination through a random phase screen. Two different schemes for realizing photon correlation holography are examined by numerical simulations, and the experiment was performed for one of the reconstruction schemes suitable for the experimental proof of the principle. The technique of photon correlation holography provides a new insight into how the information is embedded in the spatial as well as temporal correlation of photons in the stochastic pseudo thermal light.

Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions.

Science.gov (United States)

Choi, Hongyoon

2018-04-01

Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

Dipolar versus octupolar triphenylamine-based fluorescent organic nanoparticles as brilliant one- and two-photon emitters for (bio)imaging.

Science.gov (United States)

Parthasarathy, Venkatakrishnan; Fery-Forgues, Suzanne; Campioli, Elisa; Recher, Gaëlle; Terenziani, Francesca; Blanchard-Desce, Mireille

2011-11-18

Two related triphenylamine-based dipolar and octupolar fluorophores are used to prepare aqueous suspensions of fluorescent organic nanoparticles (FONs) via the reprecipitation method. The obtained spherical nanoparticles (30-40 nm in diameter) are fluorescent in aqueous solution (up to 15% fluorescence quantum yield) and exhibit extremely high one- and two-photon brightness, superior to those obtained for quantum dots. Despite the two chromophores showing similar fluorescence in solution, the fluorescence of FONs made from the octupolar derivative is significantly red-shifted compared to that generated by the dipolar FONs. In addition, the maximum two-photon absorption cross section of the FONs made from the octupolar derivative is 55% larger than that of the dipolar derivative FONs. The experimental observations provide evidence that the different molecular shape (rodlike versus three-branched) and charge distribution (dipolar versus octupolar) of the two chromophores strongly affect the packing inside the nanoparticles as well as their spectroscopic properties and colloidal stability in pure water. The use of these FONs as probes for biphotonic in-vivo imaging is investigated on Xenopus laevis tadpoles to test their utilization for angiography. When using FONs made from the octupolar dye, the formation of microagglomerates (2-5 μm scale) is observed in vivo, with subsequent lethal occlusion of the blood vessels. Conversely, the nanoparticles of the dipolar dye allow acute imaging of blood vessels thanks to their suitable size and brightness, while no toxic effect is observed. Such a goal cannot be achieved with the dissolved dye, which permeates the vessel walls. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Proceedings of II Molecular Imaging Symposium Cuba - Japan

International Nuclear Information System (INIS)

2016-01-01

In the Central Theater, University Hospital 'General Calixto Garcia' took place the II Symposium on Molecular Imaging Cuba Japan in the framework of the Scientific Convention for the 120th anniversary of the hospital. The event was organized by the hospital itself with the support of the Society of Medical Physics (medical physics section), CEADEN, the Embassy of Japan and the Theragnostic Compounds R&D Center Neuroscience Research Institute Gachon University, Incheon Korea. It was attended by 80 national scientific leaders and with the invaluable presence of Dr. Tatsuo IDO, Emeritus professor of Tohoku University (Sendai, Japan) who presented the results of the scientific papers presented this year in national and international events , referring to the new technologies of molecular imaging and the importance of medical physics in its development. During the meeting the importance of the new technologies of molecular imaging, its undisputed diagnosis intake and medical treatment and the value of human capital struggled to deal with the new technologies, the view that these are only used best when it is understood that they are multidisciplinary systems where each specialist and technical personnel plays an indispensable role. The challenge has medical physics to address these new technologies and the need for changes in the theoretical and practical training in the specialty. These analyzes will be given continuity in the next symposia molecular imaging. (author)

Development and characterisation of a visible light photon counting imaging detector system

CERN Document Server

Barnstedt, J

2002-01-01

We report on the development of a visible light photon counting imaging detector system. The detector concept is based on standard 25 mm diameter microchannel plate image intensifiers made by Proxitronic in Bensheim (Germany). Modifications applied to these image intensifiers are the use of three microchannel plates instead of two and a high resistance ceramics plate used instead of the standard phosphor output screen. A wedge and strip anode mounted directly behind the high resistance ceramics plate was used as a read out device. This wedge and strip anode picks up the image charge of electron clouds emerging from the microchannel plates. The charge pulses are fed into four charge amplifiers and subsequently into a digital position decoding electronics, achieving a position resolution of up to 1024x1024 pixels. Mounting the anode outside the detector tube is a new approach and has the great advantage of avoiding electrical feedthroughs from the anode so that the standard image intensifier fabrication process...

Molecular nuclear cardiac imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Dong Soo; Paeng, Jin Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2004-04-01

Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

Molecular nuclear cardiac imaging

International Nuclear Information System (INIS)

Lee, Dong Soo; Paeng, Jin Chul

2004-01-01

Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect

Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity

Directory of Open Access Journals (Sweden)

Kun Wang

2015-09-01

Full Text Available Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging (CLI, and optical image-guided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

Three-dimensional passive sensing photon counting for object classification

Science.gov (United States)

Yeom, Seokwon; Javidi, Bahram; Watson, Edward

2007-04-01

In this keynote address, we address three-dimensional (3D) distortion-tolerant object recognition using photon-counting integral imaging (II). A photon-counting linear discriminant analysis (LDA) is discussed for classification of photon-limited images. We develop a compact distortion-tolerant recognition system based on the multiple-perspective imaging of II. Experimental and simulation results have shown that a low level of photons is sufficient to classify out-of-plane rotated objects.

Molecular imaging of tumor blood vessels in prostate cancer.

Science.gov (United States)

Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

2009-05-01

In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

In vivo quantification of fluorescent molecular markers in real-time by ratio Imaging for diagnostic screening and image-guided surgery

NARCIS (Netherlands)

Bogaards, A.; Sterenborg, H. J. C. M.; Trachtenberg, J.; Wilson, B. C.; Lilge, L.

2007-01-01

Future applications of "molecular diagnostic screening" and "molecular image-guided surgery" will demand images of molecular markers with high resolution and high throughput (similar to >= 30 frames/second). MRI, SPECT, PET, optical fluorescence tomography, hyper-spectral fluorescence imaging, and

Gold Core Mesoporous Organosilica Shell Degradable Nanoparticles for Two-Photon Imaging and Gemcitabine Monophosphate Delivery

KAUST Repository

Rhamani, Saher

2017-09-12

The synthesis of gold core degradable mesoporous organosilica shell nanoparticles is described. The nanopaticles were very efficient for two-photon luminescence imaging of cancer cells and for in vitro gemcitabine monophosphate delivery, allowing promising theranostic applications in the nanomedicine field.

Gold Core Mesoporous Organosilica Shell Degradable Nanoparticles for Two-Photon Imaging and Gemcitabine Monophosphate Delivery

KAUST Repository

Rhamani, Saher; Chaix, Arnaud; Aggad, Dina; Hoang, Phuong Mai; Moosa, Basem; Garcia, Marcel; Gary-Bobo, Magali; Charnay, Clarence; Almalik, Abdulaziz; Durand, Jean-Olivier; Khashab, Niveen M.

2017-01-01

The synthesis of gold core degradable mesoporous organosilica shell nanoparticles is described. The nanopaticles were very efficient for two-photon luminescence imaging of cancer cells and for in vitro gemcitabine monophosphate delivery, allowing promising theranostic applications in the nanomedicine field.

Photon-counting-based diffraction phase microscopy combined with single-pixel imaging

Science.gov (United States)

Shibuya, Kyuki; Araki, Hiroyuki; Iwata, Tetsuo

2018-04-01

We propose a photon-counting (PC)-based quantitative-phase imaging (QPI) method for use in diffraction phase microscopy (DPM) that is combined with a single-pixel imaging (SPI) scheme (PC-SPI-DPM). This combination of DPM with the SPI scheme overcomes a low optical throughput problem that has occasionally prevented us from obtaining quantitative-phase images in DPM through use of a high-sensitivity single-channel photodetector such as a photomultiplier tube (PMT). The introduction of a PMT allowed us to perform PC with ease and thus solved a dynamic range problem that was inherent to SPI. As a proof-of-principle experiment, we performed a comparison study of analogue-based SPI-DPM and PC-SPI-DPM for a 125-nm-thick indium tin oxide (ITO) layer coated on a silica glass substrate. We discuss the basic performance of the method and potential future modifications of the proposed system.

Scanless functional imaging of hippocampal networks using patterned two-photon illumination through GRIN lenses

KAUST Repository

Moretti, Claudio

2016-09-12

Patterned illumination through the phase modulation of light is increasingly recognized as a powerful tool to investigate biological tissues in combination with two-photon excitation and light-sensitive molecules. However, to date two-photon patterned illumination has only been coupled to traditional microscope objectives, thus limiting the applicability of these methods to superficial biological structures. Here, we show that phase modulation can be used to efficiently project complex two-photon light patterns, including arrays of points and large shapes, in the focal plane of graded index (GRIN) lenses. Moreover, using this approach in combination with the genetically encoded calcium indicator GCaMP6, we validate our system performing scanless functional imaging in rodent hippocampal networks in vivo ~1.2 mm below the brain surface. Our results open the way to the application of patterned illumination approaches to deep regions of highly scattering biological tissues, such as the mammalian brain.

Photon statistics characterization of a single-photon source

International Nuclear Information System (INIS)

Alleaume, R; Treussart, F; Courty, J-M; Roch, J-F

2004-01-01

In a recent experiment, we reported the time-domain intensity noise measurement of a single-photon source relying on single-molecule fluorescence control. In this paper, we present data processing starting from photocount timestamps. The theoretical analytical expression of the time-dependent Mandel parameter Q(T) of an intermittent single-photon source is derived from ON↔OFF dynamics. Finally, source intensity noise analysis, using the Mandel parameter, is quantitatively compared with the usual approach relying on the time autocorrelation function, both methods yielding the same molecular dynamical parameters

Photon science 2008. Highlights and HASYLAB annual report

Energy Technology Data Exchange (ETDEWEB)

NONE

2009-07-01

The following topics are dealt with: A femtosecond X-ray/optical cross-correlator, ultrafast movies of nanoscale dynamics, massively parallel X-ray holography, clusters in super intense FLASH pulses, a chemical driven insulator-metal transition, tough silk, insight into the reactivity, the many faces of molecular assemblies in electronic devices, cooperative or self-centred electrons, visualizing a lost painting by Vincent van Gogh, metal contaminations in small water fleas, small-angle X-ray scattering as complement of crystallography, mapping the protein world, how metallic iron eats its own native oxide, hard X-ray diffraction imaging, the centre for free-electron laser science CFEL, the Hamburg EMBL unit, the Max-Planck unit for structural molecular biology, the GKSS Research Centre Geesthacht, the GFZ Helmholtz Centre Potsdam, the University of Hamburg on the DESY site, the light sources DORIS III, FLASH, PETRA III, and the European XFEL project, beamline enhancements and photon diagnostics at FLASH, undulator development for the European XFEL, special X-ray monochromators for PETRA III, high-power photon slits and shutters, the generation of brilliant beams, undulator demagnetization in LINAC based FELs, the control of experiments, advanced detection. (HSI)

Photon science 2008. Highlights and HASYLAB annual report

International Nuclear Information System (INIS)

2009-01-01

The following topics are dealt with: A femtosecond X-ray/optical cross-correlator, ultrafast movies of nanoscale dynamics, massively parallel X-ray holography, clusters in super intense FLASH pulses, a chemical driven insulator-metal transition, tough silk, insight into the reactivity, the many faces of molecular assemblies in electronic devices, cooperative or self-centred electrons, visualizing a lost painting by Vincent van Gogh, metal contaminations in small water fleas, small-angle X-ray scattering as complement of crystallography, mapping the protein world, how metallic iron eats its own native oxide, hard X-ray diffraction imaging, the centre for free-electron laser science CFEL, the Hamburg EMBL unit, the Max-Planck unit for structural molecular biology, the GKSS Research Centre Geesthacht, the GFZ Helmholtz Centre Potsdam, the University of Hamburg on the DESY site, the light sources DORIS III, FLASH, PETRA III, and the European XFEL project, beamline enhancements and photon diagnostics at FLASH, undulator development for the European XFEL, special X-ray monochromators for PETRA III, high-power photon slits and shutters, the generation of brilliant beams, undulator demagnetization in LINAC based FELs, the control of experiments, advanced detection. (HSI)

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

Energy Technology Data Exchange (ETDEWEB)

Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

2016-03-15

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

International Nuclear Information System (INIS)

Noerenberg, Dominik; Ebersberger, Hans U.; Diederichs, Gerd; Hamm, Bernd; Botnar, Rene M.; Makowski, Marcus R.

2016-01-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

Direct imaging of turbid media using long-time back-scattered photons, a numerical study

International Nuclear Information System (INIS)

Boulanger, Joan; Liu, Fengshan; El Akel, Azad; Charette, Andre

2006-01-01

Direct imaging is a convenient way to obtain information on the interior of a semi-transparent turbid material by non-invasive probing using laser beams. The major difficulty is linked to scattering which scrambles the directional information coming from the laser beam. It is found in this paper that the long-term multiple-scattered reflected photons may provide structural information on the inside of a material, which offers an interesting alternative to using information only from un-scattered or least-scattered photons as obtained from current direct imaging set-ups for thin media. Based on some observations on a non-homogeneous three layered 1-D slab irradiated by a laser pulse, a direct probing methodology making use of the long-term back-scattered photons is illustrated to recover inclusions positions in a turbid 2-D medium. First, the numerical model is presented. Second, an extended parametrical study is conducted on 1-D homogeneous and non-homogeneous slabs with different laser pulse durations. It is found that the reflected asymptotic logarithmic slope carries information about the presence of the inclusion and that short laser pulses are not necessary since only the decaying parts of the remanent optical signature is important. Longer laser pulses allow a higher level of energy injection and signal to noise ratio. Third, those observations are used for the probing of a 2-D non-homogeneous phantom. (author)

Contributions on biomedical imaging, with a side-look at molecular imaging; Beitraege zur biomedizinischen Bildgebung mit einem Seitenblick auf Molecular Imaging

Energy Technology Data Exchange (ETDEWEB)

Winkler, G. (ed.)

2004-05-01

This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.) [German] In diesem Bericht sind einige Beitraege zum Gebiet 'Bildgebende Verfahren in Biologie und Medizin' zusammengestellt. Sie stammen saemtlich aus dem Institut fuer Biomathematik und Biometrie, IBB, am Forschungszentrum fuer Umwelt und Gesundheit, GSF, in Muenchen/Neuherberg, und seinem engeren Umfeld. Ziel war es, zu sichten, was in und um diesen Themenkreis herum an Wissen und sonstiger Kompetenz hier vorhanden ist. Einige am IBB etablierte Gebiete wie Roentgen-Mammographie oder funktionelle Magnetresonanztherapie wurden ausgeblendet. Der Grund ist die Fokussierung auf ein nicht exakt definierbares, neues Gebiet der Bildgebung, das unter dem Namen 'Molecular Imaging' kursiert und derzeit Furore macht macht. (orig.)

Contributions on biomedical imaging, with a side-look at molecular imaging; Beitraege zur biomedizinischen Bildgebung mit einem Seitenblick auf Molecular Imaging

Energy Technology Data Exchange (ETDEWEB)

Winkler, G [ed.

2004-05-01

This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.) [German] In diesem Bericht sind einige Beitraege zum Gebiet 'Bildgebende Verfahren in Biologie und Medizin' zusammengestellt. Sie stammen saemtlich aus dem Institut fuer Biomathematik und Biometrie, IBB, am Forschungszentrum fuer Umwelt und Gesundheit, GSF, in Muenchen/Neuherberg, und seinem engeren Umfeld. Ziel war es, zu sichten, was in und um diesen Themenkreis herum an Wissen und sonstiger Kompetenz hier vorhanden ist. Einige am IBB etablierte Gebiete wie Roentgen-Mammographie oder funktionelle Magnetresonanztherapie wurden ausgeblendet. Der Grund ist die Fokussierung auf ein nicht exakt definierbares, neues Gebiet der Bildgebung, das unter dem Namen 'Molecular Imaging' kursiert und derzeit Furore macht macht. (orig.)

Dosimetry of FDG PET/CT and other molecular imaging applications in pediatric patients

International Nuclear Information System (INIS)

Gelfand, Michael J.

2009-01-01

Effective doses for PET and SPECT imaging of molecular imaging agents depend on the radiopharmaceutical, administered activity and the weight of the patient. Effective doses for the accompanying CT scan depend on the CT protocol being used. CT protocols can be designed to produce diagnostic quality images, localization images or attenuation correction data without imaging. In each case, the co-registered molecular imaging examination (PET or SPECT) and the CT study must be acquired without patient movement. For PET/CT, attention to the respiratory phase during the CT study is also of critical importance. In addition to the molecular imaging agents 18 F-FDG and 123 I-MIBG that are frequently used in children, additional PET and SPECT imaging agents may have promise for molecular imaging in children. (orig.)

Molecular imaging for theranostics in gastroenterology: one stone to kill two birds.

Science.gov (United States)

Ko, Kwang Hyun; Kown, Chang-Il; Park, Jong Min; Lee, Hoo Geun; Han, Na Young; Hahm, Ki Baik

2014-09-01

Molecular imaging in gastroenterology has become more feasible with recent advances in imaging technology, molecular genetics, and next-generation biochemistry, in addition to advances in endoscopic imaging techniques including magnified high-resolution endoscopy, narrow band imaging or autofluorescence imaging, flexible spectral imaging color enhancement, and confocal laser endomicroscopy. These developments have the potential to serve as "red flag" techniques enabling the earlier and accurate detection of mucosal abnormalities (such as precancerous lesions) beyond biomarkers, virtual histology of detected lesions, and molecular targeted therapy-the strategy of "one stone to kill two or three birds"; however, more effort should be done to be "blue ocean" benefit. This review deals with the introduction of Raman spectroscopy endoscopy, imaging mass spectroscopy, and nanomolecule development for theranostics. Imaging of molecular pathological changes in cells/tissues/organs might open the "royal road" to either convincing diagnosis of diseases that otherwise would only be detected in the advanced stages or novel therapeutic methods targeted to personalized medicine.

vECTlab-A fully integrated multi-modality Monte Carlo simulation framework for the radiological imaging sciences

International Nuclear Information System (INIS)