Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment

This paper presents some initial experimental results obtained with a dual-head prototype single photon emission microscope system (SPEM) that is dedicated to mouse brain studies using I-125 labeled radiotracers. In particular, this system will be used for in vivo tacking of radiolabeled T cells in mouse brain. This system is based on the use of the intensified electron multiplying charge-coupled device (I-EMCCD) camera that offers the combination of an excellent intrinsic spatial resolution, a good signal-to-noise ratio, a large active area and a reasonable detection efficiency over an energy range between 27-140keV. In this study, the dual-head SPEM system was evaluated using both resolution phantoms and a mouse with locally injected T cells labelled with I-125. It was demonstrated that for a relatively concentrated source object, the current dual-head SPEM system is capable of visualizing the tiny amount of radioactivity (~12 nCi) carried by a very small number (<1000) of T cells. The current SPEM system design allows four or six camera heads to be installed in a stationary system configuration that offers a doubled or tripled sensitivity at a spatial resolution similar to that obtained with the dualhead system. This development would provide a powerful tool for in vivo and non-invasive tracking of radiolabeled T cells in mouse brain and potentially for other rodent brain imaging studies.

GM/CA CAT at Sector 23 of the Advanced Photon Source (APS) is an NIH funded facility for crystallographic structure determination of biological macromolecules by X-ray diffraction.A second generation Berkeley automounter is being integrated into the beamline control system at the 23-BM experimental station. This new device replaces the previous all-pneumatic gripper motions with a combination of pneumatics and XYZ motorized linear stages. The latter adds a higher degree of flexibility to the robot including auto-alignment capability, accommodation of a larger capacity sample Dewar of arbitrary shape, and support for advanced operations such as crystal washing, while preserving the overall simplicity and efficiency of the Berkeley automounter design.

Advances in 3D rapid-prototyping printers, 3D modeling software, and casting techniques allow for cost-effective fabrication of custom components in gamma-ray and X-ray imaging systems. Applications extend to new fabrication methods for custom collimators, pinholes, calibration and resolution phantoms, mounting and shielding components, and imaging apertures. Details of the fabrication process for these components, specifically the 3D printing process, cold casting with a tungsten epoxy, and lost-wax casting in platinum are presented.

Crews working on present-day jet aircraft are a large occupationally exposed group with a relatively high average effective dose from galactic cosmic radiation. Crews of future high-speed commercial aircraft flying at higher altitudes would be even more exposed. To help reduce the significant uncertainties in calculations of such exposures, the atmospheric ionizing radiation (AIR) project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on five flights of a NASA ER-2 high-altitude aircraft. The primary AIR instrument was a highly sensitive extended-energy multisphere neutron spectrometer with lead and steel shells placed within the moderators of two of its 14 detectors to enhance response at high energies. Detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using MCNPX. Neutron spectra were unfolded from the measured count rates using the new MAXED code. We have measured the cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and neutron effective dose and dose equivalent rates and their dependence on altitude and geomagnetic cutoff. The measured cosmic-ray neutron spectra have almost no thermal neutrons, a large "evaporation" peak near 1 MeV and a second broad peak near 100 MeV which contributes about 69% of the neutron effective dose. At high altitude, geomagnetic latitude has very little effect on the shape of the spectrum, but it is the dominant variable affecting neutron fluence rate, which was eight times higher at the northernmost measurement location than it was at the southernmost. The shape of the spectrum varied only slightly with altitude from 21 km down to 12 km (56-201 g cm-2 atmospheric depth), but was significantly different on the ground. In all cases, ambient dose equivalent was greater than effective dose for cosmic-ray neutrons.

We propose a new type of momentum spectrometer, which uses the R×B drift effect to disperse the charged particles in a uniformly curved magnetic field, and measures the particles with large phase space acceptance and high resolution. This kind of R×B spectrometer is designed for the momentum analyses of the decay electrons and protons in the PERC (Proton and Electron Radiation Channel) beam station, which provides a strong magnetic field to guide the charged particles in the instrument. Instead of eliminating the guiding field, the R×B spectrometer evolves the field gradually to the analysing field, and the charged particles can be adiabatically transported during the dispersion and detection. The drifts of the particles have similar properties as their dispersion in the normal magnetic spectrometer. Besides, the R×B spectrometer is especially ideal for the measurements of particles with low momenta and large incident angles. We present a design of the R×B spectrometer, which can be used in PERC. For the particles with solid angle smaller than 88 msr, the maximum aberration is below 10(-4). The resolution of the momentum spectra can reach 14.4 keV/c, if the particle position measurements have a resolution of 1 mm.

Recent advances have been made with the BazookaSPECT detector, a high-resolution CCD-based gamma camera which utilizes an MCP-based image intensifier for upfront optical gain. Operating the gamma camera at high frame rates leads to a massive amount of data throughput, thereby inducing the need for real-time processing. We have developed and implemented a list-mode algorithm which allows for real-time data acquisition and processing at high frame rates. This is accomplished with a graphics processing unit (GPU), which provides processing capabilities in addition to the CPU. We have also developed a gamma-ray microscope based on the BazookaSPECT detector and micro-coded apertures. Experimental phantom images show the gamma-ray microscope having an estimated reconstruction resolution of ~30 μm, an unprecedented resolution in gamma-ray imaging.

Simple theory predicts that the statistical noise variance in PET can be reduced by an order of magnitude by using time-of-flight (TOF) information. This reduction can be obtained by improving the coincidence timing resolution, and so would be achievable in clinical, whole body studies using with PET systems that differ little from existing cameras. The potential impact of this development is large, especially for oncology studies in large patients, where it is sorely needed. TOF PET was extensively studied in the 1980's but died away in the 1990's, as it was impossible to reliably achieve sufficient timing resolution without sacrificing other important PET performance aspects, such as spatial resolution and efficiency. Recent advances in technology (scintillators, photodetectors, and high speed electronics) have renewed interest in TOF PET, which is experiencing a rebirth. However, there is still much to be done, both in instrumentation development and evaluating the true benefits of TOF in modern clinical PET. This paper looks at what has been accomplished and what needs to be done before time-of-flight PET can reach its full potential.

Dedicated high-speed microCT systems are being developed for noninvasive screening of small animals. Such systems require scintillators with high spatial resolution, high light yield, and minimal persistence to ensure ghost free imaging. Unfortunately, the afterglow associated with conventional CsI:Tl microcolumnar films used in current high-speed systems introduces image lag, leading to substantial artifacts in reconstructed images, especially when the detector is operated at several hundreds of frames per second. At RMD, we have discovered that the addition of a second dopant, Eu(2+), to CsI:Tl crystals suppresses the afterglow by as much as a factor of 40 at 2 ms after a short excitation pulse of 20 ns, and by as much as a factor of 15 at 2 ms after a long excitation pulse of 100 ms. Our observations, supported by theoretical modeling, indicate that Eu(2+) ions introduce deep electron traps that alter the decay kinetics of the material, making it suitable for many high-speed imaging applications. Here we report on the fabrication and characterization of CsI:Tl,Eu microcolumnar films to determine if the remarkable afterglow properties of CsI:Tl,Eu crystals are preserved in the CsI:Tl,Eu microcolumnar films. Preliminary results indicate that the codoped microcolumnar films show a factor of 3.5 improvement in the afterglow compared to the standard CsI:Tl films.

We describe an instrument to record x-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an x-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several labs have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in x-ray diffraction that is not observed in healthy tissue. One observed periodicity (4.2 Å) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

A survey of the natural background dose equivalent received by Canadian Forces aircrew was conducted using neutron-sensitive bubble detectors (BDs) as the primary detection tool. Since this study was a new application for these detectors, the BD response to neutron dose equivalent (RD) was extended from thermal to 500 MeV in neutron energy. Based upon the extended RD, it was shown that the manufacturer's calibration can be scaled by 1.5 +/- 0.5 to give a BD sensitivity that takes into account recently recommended fluence-to-neutron dose equivalent conversion functions and the cosmogenic neutron spectrum encountered at jet altitudes. An investigation of the effects of systematic bias caused by the cabin environment (i.e., temperature, pressure and relative humidity) on the in-flight measurements was also conducted. Both simulated and actual aircraft climate tests indicated that the detectors are insensitive to the pressure and relative humidity variations encountered during routine jet aircraft operations. Long term conditioning tests also confirmed that the BD-PND model of detector is sensitive to variations in temperature to within +/- 20%. As part of the testing process, the in-flight measurements also demonstrated that the neutron dose equivalent is distributed uniformly throughout a Boeing 707 jet aircraft, indicating that both pilots and flight attendants are exposed to the same neutron field intensity to within experimental uncertainty.

Imaging microchannel plate (MCP) detectors with cross strip (XS) readout anodes require centroiding algorithms to determine the location of the amplified charge cloud from the incident radiation, be it photon or particle. We have developed a massively parallel XS readout electronic system that employs an amplifier and ADC for each strip and uses this digital data to calculate the centroid of each event in real time using a field programmable gate array (FPGA). Doing the calculations in real time in the front end electronics using an FPGA enables a much higher input event rate, nearly two orders of magnitude faster, by avoiding the bandwidth limitations of the raw data transfer to a computer. We report on our detailed efforts to optimize the algorithms used on both an 18 mm and 40 mm diameter XS MCP detector with strip pitch of 640 microns and read out with multiple 32 channel "Preshape32" ASIC amplifiers (developed at Rutherford Appleton Laboratory). Each strip electrode is continuously digitized to 12 bits at 50 MHz with all 64 digital channels (128 for the 40 mm detector) transferred to a Xilinx Virtex 5 FPGA. We describe how events are detected in the continuous data stream and then multiplexed into firmware modules that spatially and temporally filter and weight the input after applying offset and gain corrections. We will contrast a windowed "center of gravity" algorithm to a convolution with a special centroiding kernel in terms of resolution and distortion and show results with < 20 microns FWHM resolution at input rates > 1 MHz.

BACKGROUND: This study focuses on quantitative reconstruction of dynamic cardiac SPECT. MATERIAL AND METHODS: The Karhunen-Loeve (KL) transform is first applied to gated frames or sinogram data to de-correlate the dynamic information along the time direction. Then the Poisson noise is treated by a penalized weighted least-squares minimization, followed by an analytical inversion of the treated sinograms with attenuation compensation via the Novikov formula. The reconstruction is completed by inverse KL transform. RESULTS: Dynamic or gated cardiac sinograms were simulated from the NCAT phantom mimicking the human torso, and their reconstructions by the presented method showed significant improvement over the conventional methods of frame-by-frame reconstruction. CONCLUSION: This analytical reconstruction of dynamic SPECT is consistent and efficient with a good potential for practical use.

The currently largest perfect-crystal neutron interferometer with six beam splitters and two interference loops offers novel applications in neutron interferometry. The two additional lamellas can be used for quantitative measurements of a phase shift due to crystal diffraction in the vicinity of a Bragg condition. The arising phase, referred to as "Laue phase," reveals an extreme angular sensitivity, which allows the detection of beam deflections of the order of 10(-6) s of arc. Furthermore, a precise measurement of the Laue phase at different reflections might constitute an interesting opportunity for the extraction of fundamental quantities like the neutron-electron scattering length, gravitational short-range interactions in the sub-micron range and the Debye Waller factor. For that purpose several harmonics can be utilized at the interferometer instrument ILL-S18.

We have designed and built a small animal single photon emission computed tomography (SPECT) imaging system equipped with parallel-hole and multipinhole collimators and capable of circular or helical SPECT. Copper-beryllium parallel-hole collimators suitable for imaging the ~35 keV photons from the decay of (125)I have been built and installed to achieve useful spatial resolution over a range of object-detector distances and to reduce imaging time on our dual-detector array. To address the resolution limitations in the parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have incorporated multipinhole circular and helical SPECT in addition to expanding the parallel-hole SPECT capabilities. The pinhole SPECT system is based on a 110 mm diameter circular detector equipped with a pixellated NaI(Tl) scintillator array (1x1x5 mm(3)/pixel). The helical trajectory is accomplished by two stepping motors controlling the rotation of the detector-support gantry and displacement of the animal bed along the axis of rotation of the gantry. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using multipinhole circular or helical SPECT. Collimators with one, three and five 1 mm diameter pinholes have been implemented and compared in these tests. Our objective is to develop a system on which one may readily select a suitable mode of either parallel-hole SPECT or pinhole circular or helical SPECT for a variety of small animal imaging applications.

For whole-body computed tomography (CT) images of small rodents, a voxel resolution of at least 10⁻³ mm³ is needed for scale-equivalence to that currently achieved in clinical CT scanners (∼1 mm³) in adult humans. These “mini-CT” images generally require minutes rather than seconds to complete a scan. The radiation exposure resulting from these mini-CT scans, while higher than clinical CT scans, is below the level resulting in acute tissue damage. Hence, these scans are useful for performing clinical-type diagnostic and monitoring scans for animal models of disease and their response to treatment. “Micro-CT”, with voxel size <10⁻⁵ mm³, has been useful for imaging isolated, intact organs at an almost cellular level of resolution. Micro-CT has the great advantage over traditional microscopic methods in that it generates detailed three-dimensional images in relatively large, opaque volumes such as an intact rodent heart or kidney. The radiation exposure needed in these scans results in acute tissue damage if used in living animals.

We describe an MR-compatible SPECT camera for small animals. The SPECT camera system can be inserted into the bore of a state-of-the-art MRI system and allows researchers to acquire tomographic images from a mouse in-vivo with the MRI and the SPECT acquiring simultaneously. The SPECT system provides functional information, while MRI provides anatomical information. Until today it was impossible to operate conventional SPECT inside the MRI because of mutual interference. The new SPECT technology is based on semiconductor radiation sensors (CZT, ASICs), and it fits into conventional high field MRI systems with a minimum 12-cm bore size. The SPECT camera has an MR-compatible multi-pinhole collimator for mice with a ø25-mm field-of-view. For the work reported here we assembled a prototype SPECT camera system and acquired SPECT and MRI data from radioactive sources and resolution phantoms using the camera outside and inside the MRI.

Cryogenic microscopy allows one to view frozen hydrated biological and soft matter specimens with good structural preservation and a high degree of stability against radiation damage. We describe a liquid nitrogen-cooled anti-contamination device for cryogenic X-ray diffraction microscopy. The anti-contaminator greatly reduces the buildup of ice layers on the specimen due to condensation of residual water vapor in the experimental vacuum chamber. We show by coherent X-ray diffraction measurements that this leads to fivefold reduction of background scattering, which is important for far-field X-ray diffraction microscopy of biological specimens.

The performance of scintillation detectors for x rays and gamma rays is limited fundamentally by the statistics of the scintillation light and the resulting photoelectrons. This paper presents a new experimental approach to studying these statistics by observing correlations in the signals from two photodetectors. It is shown that the Fano factors (ratios of variance to mean), both for the number the photoelectrons produced on the photocathode of the photomultiplier and for the underlying number of scintillation photons, can be deduced from these correlations. For LaBr(3)(Ce) and 662 keV gamma rays, the photopeak signals obtained by photomultipliers on opposite faces of a thin sample are negatively correlated, and the Fano factor for the photoelectrons is significantly less than one. The inferred Fano factor for the optical photons is very small, indistinguishable from zero within experimental error.

The design and properties of a new cryogenic set-up for laser-microwave-laser hyperfine structure spectroscopy of antiprotonic helium - an experiment performed at the CERN-Antiproton Decelerator (AD), Geneva, Switzerland - are described. Similar experiments for (4)He have been performed at the AD for several years. Due to the usage of a liquid helium operated cryostat and therefore necessary refilling of coolants, a loss of up to 10% beamtime occurred. The decision was made to change the cooling system to a closed-circuit cryocooler. New hermetically sealed target cells with minimised (3)He gas volume and different dimensions of the microwave resonator for measuring the (3)He transitions were needed. A new set-up has been designed and tested at Stefan Meyer Institute in Vienna before being used for the 2009 and 2010 beamtimes at the AD.

There is considerable interest in developing silicon-based telescopes because of their compactness and low power requirements. Three such telescopes have been flown on board the Space Shuttle to measure the linear energy transfer spectra of trapped, galactic cosmic ray, and solar energetic particles. Dosimeters based on single silicon detectors have also been flown on the Mir orbital station. A comparison of the absorbed dose and radiation quality factors calculated from these telescopes with that estimated from measurements made with a tissue equivalent proportional counter show differences which need to be fully understood if these telescopes are to be used for astronaut radiation risk assessments. Instrument performance is complicated by a variety of factors. A Monte Carlo-based technique was developed to model the behavior of both single element detectors in a proton beam, and the performance of a two-element, wide-angle telescope, in the trapped belt proton field inside the Space Shuttle. The technique is based on: (1) radiation transport intranuclear-evaporation model that takes into account the charge and angular distribution of target fragments, (2) Landau-Vavilov distribution of energy deposition allowing for electron escape, (3) true detector geometry of the telescope, (4) coincidence and discriminator settings, (5) spacecraft shielding geometry, and (6) the external space radiation environment, including albedo protons. The value of such detailed modeling and its implications in astronaut risk assessment is addressed.

A frequent problem in imaging is assessing whether a new imaging system is an improvement over an existing standard. Observer performance methods, in particular the receiver operating characteristic (ROC) paradigm, are widely used in this context. In ROC analysis lesion location information is not used and consequently scoring ambiguities can arise in tasks, such as nodule detection, involving finding localized lesions. This paper reviews progress in the free-response ROC (FROC) paradigm in which the observer marks and rates suspicious regions and the location information is used to determine whether lesions were correctly localized. Reviewed are FROC data analysis, a search-model for simulating FROC data, predictions of the model and a method for estimating the parameters. The search model parameters are physically meaningful quantities that can guide system optimization.

Vacuum and extreme ultraviolet radiation from 8 - 24 eV generated at a synchrotron was used to postionize laser desorbed neutrals of antibiotic-treated biofilms and a modified fullerene using laser desorption postionization mass spectrometry (LDPI-MS). Results show detection of the parent ion, various fragments, and extracellular material from biofilms using LDPI-MS with both vacuum and extreme ultraviolet photons. Parent ions were observed for both cases, but extreme ultraviolet photons (16 - 24 eV) induced more fragmentation than vacuum ultraviolet (8 - 14 eV) photons.

A lens system consisting of two electrostatic quadrupole triplets has been designed and constructed at the Radiological Research Accelerator Facility (RARAF) of Columbia University. The lens system has been used to focus 6-MeV (4)He ions to a beam spot in air with a diameter of 0.8 µm. The quadrupole electrodes can withstand voltages high enough to focus (4)He ions up to 10 MeV and protons up to 5 MeV. The quadrupole triplet design is novel in that alignment is made through precise construction and the relative strengths of the quadrupoles are accomplished by the lengths of the elements, so that the magnitudes of the voltages required for focusing are nearly identical. The insulating sections between electrodes have had ion implantation to improve the voltage stability of the lens. The lens design employs Russian symmetry for the quadrupole elements.

The development of large-area flat-panel x-ray detectors (FPDs) has spurred investigation in a spectrum of advanced medical imaging applications, including tomosynthesis and cone-beam CT (CBCT). Recent research has extended image quality metrics and theoretical models to such applications, providing a quantitative foundation for the assessment of imaging performance as well as a general framework for the design, optimization, and translation of such technologies to new applications. For example, cascaded systems models of Fourier domain metrics, such as noise-equivalent quanta (NEQ), have been extended to these modalities to describe the propagation of signal and noise through the image acquisition and reconstruction chain and to quantify the factors that govern spatial resolution, image noise, and detectability. Moreover, such models have demonstrated basic agreement with human observer performance for a broad range of imaging conditions and imaging tasks. These developments in image science have formed a foundation for the knowledgeable development and translation of CBCT to new applications in image-guided interventions - for example, CBCT implemented on a mobile surgical C-arm for intraoperative 3D imaging. The ability to acquire high-quality 3D images on demand during surgical intervention overcomes conventional limitations of surgical guidance in the context of preoperative images alone. A prototype mobile C-arm developed in academic-industry partnership demonstrates CBCT with low radiation dose, sub-mm spatial resolution, and soft-tissue visibility potentially approaching that of diagnostic CT. Integration of the 3D imaging system with real-time tracking, deformable registration, endoscopic video, and 3D visualization offers a promising addition to the surgical arsenal in interventions ranging from head-and-neck / skull base surgery to spine, orthopaedic, thoracic, and abdominal surgeries. Cadaver studies show the potential for significant boosts in surgical performance under CBCT guidance, and early clinical trials demonstrate feasibility, workflow, and image quality within the surgical theatre.

Crystallographic end-stations require a significant investment in state-of-the-art equipment, as well as a significant effort in software development. The equipment often sits idle during annual maintenance shutdowns. In order to utilize the existing hardware and software during these shutdowns, we installed a sealed-tube microsource X-ray generator in the beamline 9-2 hutch at Stanford Synchrotron Radiation Laboratory. A multi-layer optic provides good flux and spectral purity. The small physical size of the source, the long optic to focus distance (635 mm) and the short source to optic distance (65 mm) allowed the use of existing beamline components, without any significant modification. The system replaces a short section of beam pipe upstream of the beam conditioning slits and shutter. The system can be installed and removed from the beamline in less than 1 day.The Joint Center for Structural Genomics (JCSG) and SSRL Structural Molecular Biology group developed the Stanford Automated Mounting (SAM) system and installed it on beamlines at SSRL. The JCSG relies on this system to test crystals for diffraction. The installation of the X-ray microsource in beamline 9-2 allowed crystal screening to continue during SSRL shutdowns. Using a standard screening protocol of two 10 minute exposures, separated by a 90° phi rotation, the system was capable of screening up to 400 crystals per week and was left to run unattended for up to 4 days. Over 8200 crystals were screened during the last four SSRL shutdown periods.An X-ray generator can also be useful for ongoing beamline development. Shutdown periods provide easier access to the experimental hardware, however, some tests require beam. The X-ray microsource offers the ability to conduct these tests during periods when users are not scheduled.