Frequency domain fluorescent molecular tomography and molecular probes for small animal imaging

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 26, 2010).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Dissertation advisor: Dr. Ping Yu.Vita.Ph.D. University of Missouri--Columbia 2009.In this thesis, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique using a single source and detector pair for small animal imaging. In our system, the intensity of laser source is modulated to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from tissue by using a phasemeter. In parallel, we have developed and evaluated fluorescent Alexa Fluor 680 and Alexa Fluor 750-Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors on prostate and breast cancer for optical molecular imaging. Confocal fluorescence microscopic imaging of the molecular probes for in vitro PC-3 prostate and T-47D breast cancer cell lines indicated specific uptake, internalization and receptor blocking of these probes. In vivo investigations in severely compromised immunodeficient (SCID) mice bearing xenografted PC-3 prostate and T47-D breast cancer lesions demonstrated the ability of this new molecular probes to specifically target tumor tissue with a high selectively and affinity.Includes bibliographical reference

Characterizing transmissive diamond gratings as beam splitters for the hard X-ray single-shot spectrometer of the European XFEL

The European X-ray Free Electron Laser (EuXFEL) offers intense, coherent femtosecond pulses, resulting in characteristic peak brilliance values a billion times higher than that of conventional synchrotron facilities. Such pulses result in extreme peak radiation levels of the order of terawatts cm−2 for any optical component in the beam and can exceed the ablation threshold of many materials. Diamond is considered the optimal material for such applications due to its high thermal conductivity (2052 W mK−1 at 300 K) and low absorption for hard X-rays. Grating structures were fabricated on free-standing CVD diamond of 10 µm thickness with 500 µm silicon substrate support. The grating structures were produced by electron-beam lithography at the Laboratory for Micro- and Nanotechnology, Paul Scherrer Institut, Switzerland. The grating lines were etched to a depth of 1.2 µm, resulting in an aspect ratio of 16. The characterization measurements with X-rays were performed on transmissive diamond gratings of 150 nm pitch at the P10 beamline of PETRA III, DESY. In this paper, the gratings are briefly described, and a measured diffraction efficiency of 0.75% at 6 keV in the first-order diffraction is shown; the variation of the diffraction efficiency across the grating surface is presented

Wigner distribution of self-amplified spontaneous emission free-electron laser pulses and extracting its autocorrelation

The emerging concept of `beam by design' in free-electron laser (FEL) accelerator physics aims for accurate manipulation of the electron beam to tailor spectral and temporal properties of the radiation for specific experimental purposes, such as X-ray pump/X-ray probe and multiple wavelength experiments. `Beam by design' requires fast, efficient, and detailed feedback on the spectral and temporal properties of the generated X-ray radiation. Here a simple and cost-efficient method to extract information on the longitudinal Wigner distribution function of emitted FEL pulses is proposed. The method requires only an ensemble of measured FEL spectra and is rather robust with respect to accelerator fluctuations. The method is applied to both the simulated SASE spectra with known radiation properties as well as to the SASE spectra measured at the European XFEL revealing underlying non-linear chirp of the generated radiation. In the Appendices an intuitive understanding of time–frequency representations of chirped SASE radiation is provided

Development of a photoelectron spectrometer for hard x-ray photon diagnostics

The development and characterization of an angle-resolved photoelectron spectrometer, based on the electron time-of-flight concept, for hard x-ray photon diagnostics at the European Free-Electron Laser, are described. The instrument is meant to provide users and operators with pulse-resolved, non-invasive spectral distribution diagnostics, which in the hard x-ray regime is a challenge due to the poor cross-section and high kinetic energy of photoelectrons for the available target gases. We report on the performances of this instrument as obtained using hard x-rays at the PETRA III synchrotron at DESY in multibunch mode. Results are compared with electron trajectory simulations. We demonstrate a resolving power of 10 eV at incident photon energies up to at least 20 keV

Photon Diagnostics and Photon Beamlines Installations at the European XFEL

The European X-ray Free-Electron-Laser (XFEL.EU) is a new a 4th generation light facility which will deliver radiation with femtosecond and sub-Ångström resolutionat MHz repetition rates, and is currently under construction in the Hamburg metropolitan area in Germany. Special diagnostics for spontaneous radiation analysis is required to tune towards the lasing condition. Once lasing is achieved, diagnostic imagers, online monitors, and the photon beam transportsystem need to cope with extreme radiation intensities. In 2015 the installation of machine equipment in the photon area of the facility is in full swing. Thiscontribution presents the progress on final assemblies of photon diagnostics, the installation status of these devices as well as of the beam transport system, and recent design developments for diagnostic spectrometers and temporal diagnostics

Hard x-ray single-shot spectrometer at the European X-ray Free-Electron Laser

The European X-ray Free-Electron Laser Facility in Germany delivers x-ray pulses with femtosecond pulse duration at a repetition rate of up to 4.5 MHz. The free-electron laser radiation is created by the self-amplified spontaneous emission (SASE) process, whose stochastic nature gives rise to shot-to-shot fluctuations in most beam properties, including spectrum, pulse energy, spatial profile, wavefront, and temporal profile. Each spectrum consisting of many spikes varies in width and amplitude that appear differently within the envelope of the SASE spectrum. In order to measure and study the SASE spectrum, the HIgh REsolution hard X-ray single-shot (HIREX) spectrometer was installed in the photon tunnel of the SASE1 undulator beamline. It is based on diamond gratings, bent crystals as a dispersive element, and a MHz-repetition-rate strip detector. It covers a photon energy range of 3 keV–25 keV and a bandwidth of 0.5% of the SASE beam. The SASE spikes are resolved with 0.15 eV separation using the Si 440 reflection, providing a resolving power of 60 000 at a photon energy of 9.3 keV. The measured SASE bandwidth is 25 eV. In this paper, we discuss the design specifications, installation, and commissioning of the HIREX spectrometer. The spectral results using Si (110), Si (111), and C (110) crystals are presented

Diffraction properties of multilayer Laue lenses with an aperture of 102 µm and WSi2/Al bilayers

We report on the characterization of a multilayer Laue lens (MLL) with large acceptance, made of a novel WSi2/Al bilayer system. Fabrication of multilayers with large deposition thickness is required to obtain MLL structures with sufficient apertures capable of accepting the full lateral coherencelength of x-rays at typical nanofocusing beamlines. To date, the total deposition thickness has been limited by stress-buildup in the multilayer. We were able to grow WSi2/Al with low grown-in stress, and asses the degree of stress reduction. X-ray diffraction experiments were conducted at beamline 1-BM at the Advanced Photon Source. We used monochromatic x-rays with a photon energy of 12 keV and a bandwidth of ΔE/E=5.4·10−4. The MLL was grown with parallel layer interfaces, and was designed to have a large focal length of 9.6 mm. The mounted lens was 2.7 mm in width. We found and quantified kinks and bending of sections of the MLL. Sections with bending were found to partly have a systematic progression in the interface angles. We observed kinking in some, but not all, areas. The measurements are compared with dynamic diffraction calculations made with Coupled Wave Theory. Data are plotted showing the diffraction efficiency as a function of the externaltilting angle of the entire mounted lens. This way of plotting the data was found to provide an overview into the diffraction properties of the whole lens, and enabled the following layertilt analyses

Flexible Operation Modes for EuXFEL

A major challenge in single-linac - multiple undulator setups like EuXFEL is the generation of individual shaped photon pulses, in particular, when working in a mode where a single pulse train, or cw stream, feeds all undulator lines. This work presents the experimental verification of a flexible delivery scheme producing photon pulses for each of the three undulator lines with their electron bunches individually shaped in charge, compression and optics on a single RF pulse burst