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.
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.
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.
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.
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.
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.
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.
We describe a concept for x-ray optics to feed a pair of macromolecular crystallography (MX) beamlines which view canted undulator radiation sources in the same storage ring straight section. It can be deployed at NSLS-II and at other low-emittance third-generation synchrotron radiation sources where canted undulators are permitted, and makes the most of these sources and beamline floor space, even when the horizontal angle between the two canted undulator emissions is as little as 1-2 mrad. The concept adopts the beam-separation principles employed at the 23-ID (GM/CA-CAT) beamlines at the Advanced Photon Source (APS), wherein tandem horizontally-deflecting mirrors separate one undulator beam from the other, following monochromatization by a double-crystal monochromator. The scheme described here would, in contrast, deliver the two tunable monochromatic undulator beams to separate endstations that address rather different and somewhat complementary purposes, with further beam conditioning imposed as required. A downstream microfocusing beamline would employ dual-stage focusing for work at the micron scale and, unique to this design, switch to single stage focusing for larger beams. On the other hand, the upstream, more highly automated beamline would only employ single stage focusing.
In order to accurately measure the photon flux and to assist in aligning the beam, we have designed a modified beam stop device based on a photo diode integrated with the beam stop. The beam stop contains a small CdWO(4) crystal that completely stops the X-rays and at the same time produces photoluminescence proportional to the X-ray flux. The light is then guided to a photosensitive diode, using a flexible light pipe, to monitor the flux. With this device we achieve the goal of stopping the primary X-ray beam and simultaneously monitoring the X-ray intensity, thus eliminating the need for integrating ion-chambers into the capillary or collimator mount.
Third generation synchrotron sources such as the Advanced Photon Source at Argonne National Laboratory, Argonne, IL, are outstanding tools for X-ray diffraction and scattering studies of non-crystalline biological materials. However, these studies are hindered by the lack of adequate detectors that can provide multiple frames of detailed structural information on the required millisecond time scale at the extremely high count rates available at the APS. RMD is developing a cost effective detector for time-resolved small angle X-ray scattering, using a cooled, 512x512 pixel electron multiplying CCD (EMCCD). This paper describes the detector design, its efficacy for time-resolved SAXS studies, and its imaging performance with frame rates of 30 to 500 fps.
We have developed a photon-counting High-temporal and High-spatial resolution, High-throughput 3-Dimensional detector (H33D) for biological imaging of fluorescent samples. The design is based on a 25 mm diameter S20 photocathode followed by a 3-microchannel plate stack, and a cross delay line anode. We describe the bench performance of the H33D detector, as well as preliminary imaging results obtained with fluorescent beads, quantum dots and live cells and discuss applications of future generation detectors for single-molecule imaging and high-throughput study of biomolecular interactions.
Hyperpolarized noble gas MRI is a new technique for imaging of gas spaces and tissues that have been hitherto difficult to image, making it a promising diagnostic tool. The unique properties of hyperpolarized species, particularly the non-renewability of the large non-equilibrium spin polarization, raises questions about the feasibility of hyperpolarized noble gas MRI methods. In this paper, the critical issue of T1 relaxation is discussed and it is shown that a substantial amount of polarization should reach the targets of interest for imaging. We analyse various pulse sequence designs, and point out that total scan times can be decreased so that they are comparable or shorter than tissue T1 values. Pulse sequences can be optimized to effectively utilize the non-renewable hyperpolarization, to enhance the SNR, and to eliminate image artifacts. Hyperpolarized noble gas MRI is concluded to be quite feasible.
Studies have shown that digital breast tomosynthesis (DBT) can improve breast cancer diagnosis by reconstructing 3D images. However, DBT scanners based on rotation gantry prolong the imaging time and reduce spatial resolution due to motion comparing with the regular two-view mammography. To obtain three dimension reconstruction images and maintain the high image quality of conventional mammography, we proposed a prototype stationary digital breast tomosynthesis system (s-DBT). The proposed s-DBT system acquires projection images without mechanical movement. The core component of the s-DBT system is a specially designed spatially distributed multi-beam x-ray tube based on the carbon nanotube field emission x-ray technology. The multi-beam x-ray source array enables collection of all projection images from different viewing angles without mechanical motion. Preliminary results show the s-DBT system can achieve a scan time comparable to the regular two-view mammography, and improve the spatial resolution comparing with rotating gantry DBT.
High resolution X-ray radiography and computed tomography are excellent techniques for non-destructive characterization of an object under investigation at a spatial resolution in the micrometer range. However, as the image contrast depends on both chemical composition and material density, no chemical information is obtained from this data. Furthermore, lab-based measurements are affected by the polychromatic X-ray beam, which results in beam hardening effects. New types of X-ray detectors which provide spectral information on the measured X-ray beam can help to overcome these limitations. In this paper, an energy dispersive CCD detector with high spectral resolution is characterized for use in high resolution radiography and tomography, where a focus is put on the experimental conditions and requirements of both measurement techniques.
Field emission offers an alternate method of electron production for Bremsstrahlung based X-ray tubes. Carbon nanotubes (CNTs) serve as very effective field emitters, allowing them to serve as electron sources for X-ray sources, with specific advantages over traditional thermionic tubes. CNT derived X-ray sources can create X-ray pulses of any duration and frequency, gate the X-ray pulse to any source and allow the placement of many sources in close proximity.We have constructed a number of micro-CT systems based on CNT X-ray sources for applications in small animal imaging, specifically focused on the imaging of the heart and lungs. This paper offers a review of the pre-clinical applications of the CNT based micro-CT that we have developed. We also discuss some of the current and potential clinical applications of the CNT X-ray sources.
It has been suggested that kVp of diagnostic X-ray devices (or maximal energy of x-ray photon spectra) should be monitored routinely; however a standardized noninvasive technique has yet to be developed and proposed. It is well known that the integral number of Compton scattered photons and the intensities of fluorescent x-ray lines registered after irradiation of some material by an x-ray beam are a function of the maximal beam energy. CdTe detectors have sufficient energy resolution to distinguish individual x-ray fluorescence lines and high efficiency for the photon energies in the diagnostic region. Our initial measurements have demonstrated that the different ratios of the integral number of Compton scattered photons and intensities of K and L fluorescent lines detected by CdTe detector are sensitive function of maximal photon energy and could be successfully applied for kVp monitoring.
We are developing room temperature compound semiconductor detectors for applications in energy-resolved high-flux single x-ray photon-counting spectral computed tomography (CT), including functional imaging with nanoparticle contrast agents for medical applications and non destructive testing (NDT) for security applications. Energy-resolved photon-counting can provide reduced patient dose through optimal energy weighting for a particular imaging task in CT, functional contrast enhancement through spectroscopic imaging of metal nanoparticles in CT, and compositional analysis through multiple basis function material decomposition in CT and NDT. These applications produce high input count rates from an x-ray generator delivered to the detector. Therefore, in order to achieve energy-resolved single photon counting in these applications, a high output count rate (OCR) for an energy-dispersive detector must be achieved at the required spatial resolution and across the required dynamic range for the application. The required performance in terms of the OCR, spatial resolution, and dynamic range must be obtained with sufficient field of view (FOV) for the application thus requiring the tiling of pixel arrays and scanning techniques. Room temperature cadmium telluride (CdTe) and cadmium zinc telluride (CdZnTe) compound semiconductors, operating as direct conversion x-ray sensors, can provide the required speed when connected to application specific integrated circuits (ASICs) operating at fast peaking times with multiple fixed thresholds per pixel provided the sensors are designed for rapid signal formation across the x-ray energy ranges of the application at the required energy and spatial resolutions, and at a sufficiently high detective quantum efficiency (DQE). We have developed high-flux energy-resolved photon-counting x-ray imaging array sensors using pixellated CdTe and CdZnTe semiconductors optimized for clinical CT and security NDT. We have also fabricated high-flux ASICs with a two dimensional (2D) array of inputs for readout from the sensors. The sensors are guard ring free and have a 2D array of pixels and can be tiled in 2D while preserving pixel pitch. The 2D ASICs have four energy bins with a linear energy response across sufficient dynamic range for clinical CT and some NDT applications. The ASICs can also be tiled in 2D and are designed to fit within the active area of the sensors. We have measured several important performance parameters including; the output count rate (OCR) in excess of 20 million counts per second per square mm with a minimum loss of counts due to pulse pile-up, an energy resolution of 7 keV full width at half maximum (FWHM) across the entire dynamic range, and a noise floor about 20keV. This is achieved by directly interconnecting the ASIC inputs to the pixels of the CdZnTe sensors incurring very little input capacitance to the ASICs. We present measurements of the performance of the CdTe and CdZnTe sensors including the OCR, FWHM energy resolution, noise floor, as well as the temporal stability and uniformity under the rapidly varying high flux expected in CT and NDT applications.
We are exploring a large area flat panel micro-channel plate photomultiplier tube (MCP PMT) under development for an application to time-of-flight positron emission tomography (TOF PET). High speed waveform sampling with transmission-lines is adopted for reading out the signal with precise time and space information with a small number of low-power channels. As a demonstration of the concept, detector modules have been built using 2″×2″ Photonis Planacon MCP PMTs (XP85022) and prototype transmission-line (TL) boards. The signals from the MCP PMT through the transmission-lines are sampled by DRS4 evaluation boards running at 5 giga-samples per second (GS/s). The event information is extracted by processing the digitized waveforms. For experimental tests, a single 3×3×10 mm(3) LYSO crystal is optically coupled to each MCP PMT; the detector responses to 511 keV annihilation photon from a (22)Na source are measured using the data taken in coincidence mode. As a preliminary result, we obtain a position resolution of ∼2.8 mm (0.3 mm) (FWHM) along (perpendicular to) the transmission-line, ∼309 ps (FWHM) for coincidence time resolution, and ∼14% (FWHM) of energy resolution at 511 keV. This initial result gives a promise that the large area MCP PMT is applicable to TOF PET.
A computer simulation study has been conducted to investigate the feasibility of a positron emission tomography (PET) detector design by using micro-channel plate (MCP) photomultiplier tubes (PMT) with transmission-line (TL) read-out and waveform sampling. The detector unit consisted of a 24×24 array of pixelated LSO crystals, each of which was 4×4×25 mm(3) in size, and two 102×102 mm(2) MCP-PMTs coupled to both sides of the scintillator array. The crystal (and TL) pitch was 4.25 mm and reflective medium was inserted between the crystals. The transport of the optical photons inside the scintillator were simulated by using the Geant4 package. The output pulses of the MCP-PMT/TL unit were formed by applying the measured single photo-electron response of the MCP-PMT/TL unit to each individual photon that interacts with the photo-cathode of the MCP-PMT. The waveforms of the pulses at both ends of the TL strips were measured and analyzed to produce energy and timing information for the detected event. An experimental setup was developed by employing a Photonis Planacon MCP-PMT (XP85022) and a prototype TL board for measuring the single photo-electron response of the MCP-PMT/TL. The simulation was validated by comparing the predicted output pulses to measurements obtained with a single MCP-PMT/TL coupled to an LSO crystal exposed to 511 keV gamma rays. The validated simulation was then used to investigate the performance of the proposed new detector design. Our simulation result indicates an energy resolution of ~11% at 511 keV. When using a 400-600 keV energy window, we obtain a coincidence timing resolution of ~323 ps FWHM and a coincidence detection efficiency of ~40% for normally-incident 511keV photons. For the positioning accuracy, it is determined by the pitch of the TLs (and crystals) in the direction normal to the TLs and measured to be ~2.5 mm in the direction parallel to the TLs. The energy and timing obtained at the front- and back-end of the scintillator array also show differences that are correlated with the depth of interaction of the event.
A new signal processing method for PET application has been developed, with discrete circuit components to measure energy and timing of a gamma interaction based solely on digital timing processing without using an amplitude-to-digital convertor (ADC) or a constant fraction discriminator (CFD). A single channel discrete component time-based readout (TBR) circuit was implemented in a PC board. Initial circuit functionality and performance evaluations have been conducted. Accuracy and linearity of signal amplitude measurement were excellent, as measured with test pulses. The measured timing accuracy from test pulses reached to less than 300 ps, a value limited mainly by the timing jitter of the prototype electronics circuit. Both suitable energy and coincidence timing resolutions (~18% and ~1.0 ns) have been achieved with 3 × 3 × 20 mm(3) LYSO scintillator and photomultiplier tube-based detectors. With its relatively simple circuit and low cost, TBR is expected to be a suitable front-end signal readout electronics for compact PET or other radiation detectors requiring the reading of a large number of detector channels and demanding high performance for energy and timing measurement.
Silicon based devices can extend PET-MR and SPECT-MR imaging to applications, where their advantages in performance outweigh benefits of high statistical counts.Silicon is in many ways an excellent detector material with numerous advantages, among others: excellent energy and spatial resolution, mature processing technology, large signal to noise ratio, relatively low price, availability, versatility and malleability. The signal in silicon is also immune to effects of magnetic field at the level normally used in MR devices. Tests in fields up to 7 T were performed in a study to determine effects of magnetic field on positron range in a silicon PET device. The curvature of positron tracks in direction perpendicular to the field's orientation shortens the distance between emission and annihilation point of the positron. The effect can be fully appreciated for a rotation of the sample for a fixed field direction, compressing range in all dimensions. A popular Ga-68 source was used showing a factor of 2 improvement in image noise compared to zero field operation. There was also a little increase in noise as the reconstructed resolution varied between 2.5 and 1.5 mm.A speculative applications can be recognized in both emission modalities, SPECT and PET.Compton camera is a subspecies of SPECT, where a silicon based scatter as a MR compatible part could inserted into the MR bore and the secondary detector could operate in less constrained environment away from the magnet. Introducing a Compton camera also relaxes requirements of the radiotracers used, extending the range of conceivable photon energies beyond 140.5 keV of the Tc-99m.In PET, one could exploit the compressed sub-millimeter range of positrons in the magnetic field. To exploit the advantage, detectors with spatial resolution commensurate to the effect must be used with silicon being an excellent candidate. Measurements performed outside of the MR achieving spatial resolution below 1 mm are reported.
We developed a technique for performing quantitative phase reconstructions from differential phase contrast images obtained using a configured detector in a scanning transmission X-ray microscope geometry. The technique uses geometric optics to describe the interaction of the X-ray beam with the specimen, which allows interpretation of the measured intensities in terms of the derivative of the phase thickness. Integration of the resulting directional derivatives is performed using a Fourier integration technique. We demonstrate the approach by reconstructing simulated measurements of a 0.5-µm-diameter gold sphere at 7-keV photon energy.
Statistical reconstruction has become popular in emission computed tomography but suffers slow convergence (to the MAP or ML solution). Methods proposed to address this problem include the fast but non-convergent OSEM and the convergent RAMLA  for the ML case, and the convergent BSREM , relaxed OS-SPS and modified BSREM  for the MAP case. The convergent algorithms required a user-determined relaxation schedule. We proposed fast convergent OS reconstruction algorithms for both ML and MAP cases, called COSEM (Complete-data OSEM), which avoid the use of a relaxation schedule while maintaining convergence. COSEM is a form of incremental EM algorithm. Here, we provide a derivation of our COSEM algorithms and demonstrate COSEM using simulations. At early iterations, COSEM-ML is typically slower than RAMLA, and COSEM-MAP is typically slower than optimized BSREM while remaining much faster than conventional MAP-EM. We discuss how COSEM may be modified to overcome these limitations.
Depth of Interaction (DOI) information can improve quality of reconstructed images acquired from Positron Emission Tomography (PET), especially in high resolution and compact scanners dedicated for breast, brain, or small animal imaging applications. Additionally, clinical scanners with time of flight capability can also benefit from DOI information. One of the most promising methods of determining DOI in a crystal involves reading the signal from two ends of a scintillation crystal, and calculating the signal ratio between the two detectors. This method is known to deliver a better DOI resolution with rough crystals compared to highly polished crystals. However, what is still not well studied is how much of a tradeoff is involved between spatial, energy, temporal, and DOI resolutions as a function of the crystal surface treatment and geometry with the use of Silicon Photomultipliers (SiPM) as the photo detectors. This study investigates the effects of different crystal surface finishes and geometries on energy, timing and DOI resolutions at different crystal depths. The results show that for LYSO scintillators of 1.5×1.5×20 mm(3) and 2×2×20 mm(3) with their surfaces finished from 0.5 to 30 micron roughness, almost the same energy and coincidence timing resolutions were maintained, around 15% and 2.4 ns respectively across different crystal depths, while the DOI resolutions were steadily improved from worse than 5 mm to better than 2 mm. They demonstrate that crystal roughness, with proper surface preparing, does not have a significant effect on the energy and coincidence timing resolutions in the crystals examined, and there does not appear to be a tradeoff between improving DOI resolution and degrading other detector performances. These results will be valuable to guide the selection of crystal surface conditions for developing a DOI measurable PET detector with a full array of LYSO scintillators coupled to SiPM arrays.
We describe a new head scanner developed for Proton Computed Tomography (pCT) in support of proton therapy treatment planning, aiming at reconstructing an accurate map of the stopping power (S.P.) in a phantom and, in the future, in patients. The system consists of two silicon telescopes which track the proton before and after the phantom/patient, and an energy detector which measures the residual energy or range of the proton to reconstruct the Water Equivalent Path Length (WEPL) in the phantom. Based on the experience of the existing prototype and extensive Geant4 simulations and CT reconstructions, the new pCT scanner will support clinically useful proton fluxes.
The development of detectors often lags the development in X-ray sources. However, advanced detectors are critical for fully utilizing and exploiting the capabilities of the new bright sources. We report on the development of a modular high frame rate detector for synchrotron applications such as small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS). The detector consists of four modules, each providing an imaging area of 5×5 cm(2) and capable of frame rates of 200 frames per second (fps) with full resolution, and 650 fps with smaller region of interest (ROI). Details of the detector design and experiments at synchrotron beamlines are discussed in the paper.
Positron emission tomography (PET) is a widely used technique in medical imaging and in studying small animal models of human disease. In the conventional approach, the 511 keV annihilation photons emitted from a patient or small animal are detected by a ring of scintillators such as LYSO read out by arrays of photodetectors. Although this has been a successful in achieving ~5mm FWHM spatial resolution in human studies and ~1mm resolution in dedicated small animal instruments, there is interest in significantly improving these figures. Silicon, although its stopping power is modest for 511 keV photons, offers a number of potential advantages over more conventional approaches. Foremost is its high spatial resolution in 3D: our past studies show that there is little diffculty in localizing 511 keV photon interactions to ~0.3mm. Since spatial resolution and reconstructed image noise trade off in a highly non-linear manner that depends on the PET instrument response, if high spatial resolution is the goal, silicon may outperform standard PET detectors even though it has lower sensitivity to 511 keV photons. To evaluate silicon in a variety of PET "magnifying glass" configurations, an instrument has been constructed that consists of an outer partial-ring of PET scintillation detectors into which various arrangements of silicon detectors can be inserted to emulate dual-ring or imaging probe geometries. Recent results have demonstrated 0.7 mm FWHM resolution using pad detectors having 16×32 arrays of 1.4mm square pads and setups have shown promising results in both small animal and PET imaging probe configurations. Although many challenges remain, silicon has potential to become the PET detector of choice when spatial resolution is the primary consideration.
Diogene, an electronic 4 pi detector, has been built and installed at the Saturne synchrotron in Saclay. The forward angular range (0 degree-6 degrees) is covered by 48 time-of-flight scintillator telescopes that provide charge identification. The trajectories of fragments emitted at larger angles are recorded in a cylindrical 0.4-m3 Pictorial Drift Chamber (PDC) surrounding the target. The PDC is inside a 1-T magnetic field; the axis of the PDC cylinder and the magnetic field are parallel to the beam. Good identification has been obtained for both positive and negative pi mesons and for hydrogen and helium isotopes. Multiplicities in relativistic nucleus-nucleus reactions up to 40 have been detected, limited mainly by the present electronics.
The introduction of silicon photomultipliers (SiPM) has facilitated construction of compact, efficient and magnetic field-hardened positron emission tomography (PET) scanners. To take full advantage of these devices, methods for using them to produce large field-of-view PET scanners are needed. In this investigation, we explored techniques to combine two SiPM arrays to form the building block for a small animal PET scanner. The module consists of a 26 × 58 array of 1.5 × 1.5mm(2) LYSO elements (spanning 41 × 91mm(2)) coupled to two SensL SiPM arrays. The SiPMs were read out with new multiplexing electronics developed for this project. To facilitate calculation of event position with multiple SiPM arrays it was necessary to spread scintillation light amongst a number of elements with a small light guide. This method was successful in permitting identification of all detector elements, even at the seam between two SiPM arrays. Since the performance of SiPMs is enhanced by cooling, the detector module was fitted with a cooling jacket, which allowed the temperature of the device and electronics to be controlled. Testing demonstrated that the peak-to-valley contrast ratio of the light detected from the scintillation array was increased by ∼45% when the temperature was reduced from 28 °C to 16 °C. Energy resolution for 511 keV photons improved slightly from 18.8% at 28 °C to 17.8% at 16 °C. Finally, the coincidence timing resolution of the module was found to be insufficient for time-of-flight applications (∼2100 ps at 14 °C). The first use of these new modules will be in the construction of a small animal PET scanner to be integrated with a 3T clinical magnetic resonance imaging scanner.
Physical positioning of scintillation crystal detector blocks in Positron Emission Tomography (PET) scanners is not always exact. We test a proof of concept methodology for the determination of the six degrees of freedom for detector block positioning errors by utilizing a rotating point source over stepped axial intervals. To test our method, we created computer simulations of seven Micro Crystal Element Scanner (MiCES) PET systems with randomized positioning errors. The computer simulations show that our positioning algorithm can estimate the positions of the block detectors to an average of one-seventh of the crystal pitch tangentially, and one-third of the crystal pitch axially. Virtual acquisitions of a point source grid and a distributed phantom show that our algorithm improves both the quantitative and qualitative accuracy of the reconstructed objects. We believe this estimation algorithm is a practical and accurate method for determining the spatial positions of scintillation detector blocks.
We investigated a scheme for concurrently detecting low- and high-energy emissions from (123)I with a stacked silicon double-sided strip detector (DSSD) and modular scintillation camera (Modcam) from the FastSPECT II design. We sequentially acquired both low- and high-energy emission images of an (123)I object with a prototype DSSD and a Modcam. A sandwich aperture increases spatial resolution in the low-magnification DSSD image via a smaller pinhole diameter and allows a higher magnification image on the Modcam. Molybdenum, the insert material, efficiently stops 20-30 keV photons due to its ∼20 keV K-edge. Theoretically, less than 10% of 159 keV photons interact in 0.035 cm thick sheet of molybdenum, while this thickness stops virtually all ∼30 keV photons. Thus, photons from both energy regions will be incident upon their respective detectors with little cross talk. With a multi-pinhole collimator, we can decode multiplexed images on the Modcam by making use of the lower-magnification DSSD image. This approach can provide an increase in system sensitivity compared to single-detector configurations. Using MCNP5 we examined the potential benefits and drawbacks of stacked detectors and the sandwich aperture for small-animal pinhole SPECT via the synthetic-collimator method. Simulation results encourage us to construct the novel aperture and use it with our new DSSDs designed for mounting in a transmission configuration.