Gigacount/second photon detection with InGaAs avalanche photodiodes

We demonstrate high count rate single photon detection at telecom wavelengths using a thermoelectrically-cooled semiconductor diode. Our device consists of a single InGaAs avalanche photodiode driven by a 2 GHz gating frequency signal and coupled to a tuneable self-differencing circuit for enhanced detection sensitivity. We find the count rate is linear with the photon flux in the single photon detection regime over approximately four orders of magnitude, and saturates at 1 gigacount/s at high photon fluxes. This result highlights promising potential for APDs in high bit rate quantum information applications.

Surface acoustic waves in liquid helium for enhanced single-electron transport applications

High frequency Rayleigh and Sezawa modes propagating in the ZnO/GaAs system capable of operating immersed in liquid helium have been engineered. In the case of the Rayleigh mode, the strong attenuation produced by the liquid is counteracted by the strengthening of the mode induced by the ZnO. However, in the case of the Sezawa modes, the attenuation is strongly reduced taking advantage of the depth profile of their acoustic Poynting vectors, that extend deeper into the layered system, reducing the energy radiated into the fluid. Thus, both tailored modes will be suitable for acoustically-driven single-electron and single-photon devices in ZnO-coated GaAs-based systems with the best thermal stability provided by the liquid helium bath. © 2012 IEEE.

Emission characteristics of three final continuum electrons produced in low-energy double ionization of helium

The double ionization of helium by electron impact for 106 eV incident energy was studied in a kinematically complete experiment by using a reaction microscope. The pattern of the angular correlation of the three emitted electrons was analyzed by selecting different values of the recoil ion longitudinal momentum. The Wannier predicted geometry appears when the recoil ion carries the full initial projectile momentum. It was found that at this low impact energy, the outgoing electrons still remember the initial-state collision information.

Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

INTRODUCTION:Subclinical atherosclerosis (SCA) measures in multiple arterial beds are heritable phenotypes that are associated with increased incidence of cardiovascular disease. We conducted a genome-wide association study (GWAS) for SCA measurements in the community-based Framingham Heart Study.METHODS:Over 100,000 single nucleotide polymorphisms (SNPs) were genotyped (Human 100K GeneChip, Affymetrix) in 1345 subjects from 310 families. We calculated sex-specific age-adjusted and multivariable-adjusted residuals in subjects tested for quantitative SCA phenotypes, including ankle-brachial index, coronary artery calcification and abdominal aortic calcification using multi-detector computed tomography, and carotid intimal medial thickness (IMT) using carotid ultrasonography. We evaluated associations of these phenotypes with 70,987 autosomal SNPs with minor allele frequency [greater than or equal to] 0.10, call rate [greater than or equal to] 80%, and Hardy-Weinberg p-value [greater than or equal to] 0.001 in samples ranging from 673 to 984 subjects, using linear regression with generalized estimating equations (GEE) methodology and family-based association testing (FBAT). Variance components LOD scores were also calculated.RESULTS:There was no association result meeting criteria for genome-wide significance, but our methods identified 11 SNPs with p < 10-5 by GEE and five SNPs with p < 10-5 by FBAT for multivariable-adjusted phenotypes. Among the associated variants were SNPs in or near genes that may be considered candidates for further study, such as rs1376877 (GEE p < 0.000001, located in ABI2) for maximum internal carotid artery IMT and rs4814615 (FBAT p = 0.000003, located in PCSK2) for maximum common carotid artery IMT. Modest significant associations were noted with various SCA phenotypes for variants in previously reported atherosclerosis candidate genes, including NOS3 and ESR1. Associations were also noted of a region on chromosome 9p21 with CAC phenotypes that confirm associations with coronary heart disease and CAC in two recently reported genome-wide association studies. In linkage analyses, several regions of genome-wide linkage were noted, confirming previously reported linkage of internal carotid artery IMT on chromosome 12. All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:The results from this GWAS generate hypotheses regarding several SNPs that may be associated with SCA phenotypes in multiple arterial beds. Given the number of tests conducted, subsequent independent replication in a staged approach is essential to identify genetic variants that may be implicated in atherosclerosis.

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

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

Spectrotemporal CT data acquisition and reconstruction at low dose.

PURPOSE: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D+dual energy+time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. METHODS: The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction problem using the split Bregman method and GPU-based implementations of backprojection, reprojection, and kernel regression. Using a preclinical mouse model, the authors apply the proposed algorithm to study myocardial injury following radiation treatment of breast cancer. RESULTS: Quantitative 5D simulations are performed using the MOBY mouse phantom. Twenty data sets (ten cardiac phases, two energies) are reconstructed with 88 μm, isotropic voxels from 450 total projections acquired over a single 360° rotation. In vivo 5D myocardial injury data sets acquired in two mice injected with gold and iodine nanoparticles are also reconstructed with 20 data sets per mouse using the same acquisition parameters (dose: ∼60 mGy). For both the simulations and the in vivo data, the reconstruction quality is sufficient to perform material decomposition into gold and iodine maps to localize the extent of myocardial injury (gold accumulation) and to measure cardiac functional metrics (vascular iodine). Their 5D CT imaging protocol represents a 95% reduction in radiation dose per cardiac phase and energy and a 40-fold decrease in projection sampling time relative to their standard imaging protocol. CONCLUSIONS: Their 5D CT data acquisition and reconstruction protocol efficiently exploits the rank-sparse nature of spectral and temporal CT data to provide high-fidelity reconstruction results without increased radiation dose or sampling time.

Conditional production of superpositions of coherent states with inefficient photon detection

It is shown that a linear superposition of two macroscopically distinguishable optical coherent states can be generated using a single photon source and simple all-optical operations. Weak squeezing on a single photon, beam mixing with an auxiliary coherent state, and photon detecting with imperfect threshold detectors are enough to generate a coherent state superposition in a free propagating optical field with a large coherent amplitude (alpha>2) and high fidelity (F>0.99). In contrast to all previous schemes to generate such a state, our scheme does not need photon number resolving measurements nor Kerr-type nonlinear interactions. Furthermore, it is robust to detection inefficiency and exhibits some resilience to photon production inefficiency.

Single- and multiphoton detachment of K

Single- and multiphoton detachment rates have been calculated for K- using the R-matrix Floquet approach. Single-photon detachment rates, obtained at a laser field peak intensity of 10(9) W cm(-2), are discussed and compared with other theoretical work. Two-photon detachment rates at the same intensity have also been obtained, and similarities with results from earlier calculations for Li- and Na- are discussed. Three-photon rates are also presented at this laser intensity, and are compared and contrasted with those arising in the single-photon case, since both involve resonance structure with P-1(o) symmetry. The influence of resonances such as the 5s(2) S-1(e) doubly excited state and excitations of the residual atom are also considered.

Charge exchange emission from solar wind helium ions

Charge exchange X-ray and far-ultraviolet (FUV) aurorae can provide detailed insight into the interaction between solar system plasmas. Using the two complementary experimental techniques of photon emission spectroscopy and translation energy spectroscopy, we have studied state-selective charge exchange in collisions between fully ionized helium and target gasses characteristic of cometary and planetary atmospheres (H2O, CO2, CO, and CH4). The experiments were performed at velocities typical for the solar wind (200-1500 km s(-1)). Data sets are produced that can be used for modeling the interaction of solar wind alpha particles with cometary and planetary atmospheres. These data sets are used to demonstrate the diagnostic potential of helium line emission. Existing Extreme Ultraviolet Explorer (EUVE) observations of comets Hyakutake and Hale-Bopp are analyzed in terms of solar wind and coma characteristics. The case of Hale-Bopp illustrates well the dependence of the helium line emission to the collision velocity. For Hale-Bopp, our model requires low velocities in the interaction zone. We interpret this as the effect of severe post-bow shock cooling in this extraordinary large comet.

Charge exchange and dissociative processes in collisions of slow He2+ ions with H2O molecules

Experimental and theoretical studies of one-electron capture in collisions of He2+ ions with H2O molecules have been carried out in the range 0.025-12 keV amu(-1) corresponding to typical solar wind velocities of 70-1523 km s(-1). Translational energy spectroscopy (TES), photon emission spectroscopy (PES), and fragment ion spectroscopy were employed to identify and quantify the collision mechanisms involved. Cross sections for selective single electron capture into n=1, 2, and 3 states of the He+ ion were obtained using TES while PES provided cross sections for capture into the He+(2p) and He+(3p) states. Our model calculations show that He+(n=2) and He+(n=3) formation proceeds via a single-electron process governed by the nucleus-electron interaction. In contrast, the He+(1s) formation mechanism involves an exothermic two-electron process driven by the electron-electron interaction, where the potential energy released by the electron capture is used to remove a second electron thereby resulting in fragmentation of the H2O molecule. This process is found to become increasingly important as the collision energy decreases. The experimental cross sections are found to be in reasonable agreement with cross sections calculated using the Demkov and Landau-Zener models.

Collision mechanisms in one-electron capture by slow H and He- like ions of C, N and O in H and H-2

Translational energy spectroscopy (TES) has been used to study state-selective one-electron capture by H and He-like ions of C, N and O in both H and H-2 within the range 250-900 eV amu(- 1). The main collision mechanisms leading to state-selective electron capture have been identified, their relative importance assessed and compared, where possible, with theoretical predictions and with any previous measurements based on photon emission spectroscopy. For one-electron capture in H-2, the relative importance of contributions from non- dissociative and dissociative capture as well as from two- electron capture into autoionizing states is found to be strikingly different for the cases considered. Our TES measurements in atomic hydrogen provide an important extension of previous measurements to energies below 1000 eV amu(-1) and show that, as the impact energy decreases, electron capture becomes more selective until only a single n product channel is significant. These product main channels are well described by reaction windows calculated using a Landau-Zener approach. However, the same approach applied to the more complex energy- change spectra observed in H-2 is found to be less successful.

Non-invasive in vivo imaging in small animal research

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

(18)F-FDG PET-CT simulation for non-small-cell lung cancer: effect in patients already staged by PET-CT.

Purpose: Positron emission tomography (PET), in addition to computed tomography (CT), has an effect in target volume definition for radical radiotherapy (RT) for non–small-cell lung cancer (NSCLC). In previously PET-CT staged patients with NSCLC, we assessed the effect of using an additional planning PET-CT scan for gross tumor volume (GTV) definition. Methods and Materials: A total of 28 patients with Stage IA-IIIB NSCLC were enrolled. All patients had undergone staging PET-CT to ensure suitability for radical RT. Of the 28 patients, 14 received induction chemotherapy. In place of a RT planning CT scan, patients underwent scanning on a PET-CT scanner. In a virtual planning study, four oncologists independently delineated the GTVon the CT scan alone and then on the PET-CTscan. Intraobserver and interobserver variability were assessed using the concordance index (CI), and the results were compared using the Wilcoxon signed ranks test. Results: PET-CT improved the CI between observers when defining the GTVusing the PET-CT images compared with using CTalone for matched cases (median CI, 0.57 for CTand 0.64 for PET-CT, p = .032). The median of the mean percentage of volume change from GTVCT to GTVFUSED was 5.21% for the induction chemotherapy group and 18.88% for the RT-alone group. Using the Mann-Whitney U test, this was significantly different (p = .001). Conclusion: PET-CT RT planning scan, in addition to a staging PET-CT scan, reduces interobserver variability in GTV definition for NSCLC. The GTV size with PET-CT compared with CT in the RT-alone group increased and was reduced in the induction chemotherapy group.

Microcomputed tomography imaging in a rat model of delayed union/non-union fracture

We aimed to develop a clinically relevant delayed union/non-union fracture model to evaluate a cell therapy intervention repair strategy. Histology, three-dimensional (3D) micro-computed tomography (micro-CT) imaging and mechanical testing were utilized to develop an analytical protocol for qualitative and quantitative assessment of fracture repair. An open femoral diaphyseal osteotomy, combined with periosteal diathermy and endosteal excision, was held in compression by a four pin unilateral external fixator. Three delayed union/non-union fracture groups established at 6 weeks-(a) a control group, (b) a cell therapy group, and (c) a group receiving phosphate-buffered saline (PBS) injection alone-were examined subsequently at 8 and 14 weeks. The histological response was combined fibrous and cartilaginous non-unions in groups A and B with fibrous non-unions in group C. Mineralized callus volume/total volume percentage showed no statistically significant differences between groups. Endosteal calcified tissue volume/endosteal tissue volume, at the center of the fracture site, displayed statistically significant differences between 8 and 14 weeks for cell and PBS intervention groups but not for the control group. The percentage load to failure was significantly lower in the control and cell treatment groups than in the PBS alone group. High-resolution micro-CT imaging provides a powerful tool to augment characterization of repair in delayed union/non-union fractures together with outcomes such as histology and mechanical strength measurement. Accurate, nondestructive, 3D identification of mineralization progression in repairing fractures is enabled in the presence or absence of intervention strategies. (c) 2007 Orthopaedic Research Society.

Unintended cardiac irradiation during left-sided breast cancer radiotherapy

Objective: Cardiac irradiation during left-sided breast radiotherapy may lead to
deleterious cardiac side effects. Using image guided radiotherapy, it is possible
to exclude the heart from treatment fields and monitor reproducibility of virtual simulation (VS) fields at treatment delivery using electronic portal imaging (EPI). Retrospectively, we evaluate the incidence of cardiac irradiation at VS and subsequent unintended cardiac irradiation during treatment.

Methods: Patients receiving left-sided radiotherapy to the breast or chest wall,
treated with a glancing photon field technique during a four-month period, were
included. VS images and EPIs during radiotherapy delivery were visually assessed.
The presence of any portion of the heart within the treatment field at VS or during treatment was recorded. Central lung distance and maximum heart distance were recorded.

Results: Of 128 patients, 45 (35.1%) had any portion of the heart within the
planned treatment field. Of these, inclusion of the heart was clinically unavoidable in 25 (55.6%). Of those with no heart included in the treatment fields at VS, 41 (49.4%) had presence of the heart as assessed on EPI during treatment.

Conclusion: Unintended cardiac irradiation during left-sided breast radiotherapy treatment occurs in a sizeable proportion of patients.

Advances in knowledge: Despite the use of three-dimensional computed tomography simulation and cardiac shielding, sizeable proportions of patients receiving left-sided breast cancer radiotherapy have unintended cardiac irradiation.