This PDF file contains the front matter associated with SPIE Proceedings Volume 8143, including the Title Page, Copyright Information, Table of Contents, Introduction, and the Conference Committee listing.

Imaging arrays with sub-millimeter detector pixels that count and allocate energy to each detected photon are now being introduced into biomedical computed tomography scanners. Consequently, bremsstrahlung x-ray can provide the advantages of simultaneous recording of multiple quasi-monochromatic x-ray images which can be used for identification of various materials within the image field. This capability increases the inherent contrast within biomedical CT images and also introduces the ability to use high atomic weight "foreign" elements (e.g., strontium) which are surrogates for "native" biological elements (e.g., calcium) to monitor tissue function (e.g., bone deposition). Challenges for this methodology include limited maximum fluence due to photon pile-up, charge-sharing between contiguous pixels and heterogeneous pixel characteristics due to manufacturing difficulties.

The objective of this work is to develop an improved SPECT camera for dedicated prostate imaging. Complementing the recent advancements in agents for molecular prostate imaging, this device has the potential to assist in distinguishing benign from aggressive cancers, to improve site-specific localization of cancer, to improve accuracy of needle-guided prostate biopsy of cancer sites, and to aid in focal therapy procedures such as cryotherapy and radiation. Theoretical calculations show that the spatial resolution/detection sensitivity of the proposed SPECT camera can rival or exceed 3D PET and further signal-to-noise advantage is attained with the better energy resolution of the CZT modules. Based on photon transport simulation studies, the system has a reconstructed spatial resolution of 4.8 mm with a sensitivity of 0.0001. Reconstruction of a simulated prostate distribution demonstrates the focal imaging capability of the system.

Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of ^99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

New inversion methods for image reconstruction from Compton camera data are presented here. These methods depend upon which of two models is assumed for the data. Both of these models have been proposed previously by other researchers. Computer simulations of a mathematical phantom illustrate that a parallel projection of the distribution of the radioactivity can be produced from one positioning of the camera and a three-dimensional reconstruction of the distribution can be obtained by moving the camera 180 degrees around the distribution.

In recent years, operation of wide band-gap semiconductor detectors under high-flux irradiation in medical and security applications has called the attention of the scientific commnity. However, under high-flux irradiation, these detectors are limited by poor hole transport properties and other factors. In our studies, the build up of space charge as a function of time has been systematically investigated through direct comparison between experiments and charge transport simulations. In order to benchmark and calibrate our simulations, charge transport properties of CdZnTe detectors used in high-flux experiments were measured. Our results show that the polarization effect, caused by the build up of positive space charge as a function of time, initially distorts and eventually causes complete breakdown of the operating electric field.

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

We are developing a prototype gamma-ray imaging system that consists of two sets of movable, keel-edged copper-tungsten blades configured as crossed slits. These apertures can be positioned independently between the object and detector, producing an anamorphic image in which the axial and transaxial magnifications are not constrained to be equal. The detector is a 60 mm x 60 mm, millimeter thick, one-megapixel silicon double-sided strip detector. The flexible nature of this system allows the application of adaptive imaging techniques. We will discuss system details, calibration and acquisition methods, and our progress towards biological imaging applications.

Developments in room temperature cadmium telluride (CdTe) based solid state imaging arrays for energy-resolved photon-counting in medical x-ray imaging are discussed. A number of x-ray imaging applications can benefit from these developments including mammography, radiography, and computed tomography (CT). Energy-resolved photon-counting can provide reduced dose through optimal energy weighting, compositional analysis through multiple basis function material decomposition, and contrast enhancement through spectroscopic x-ray imaging of metal nanoparticles. Extremely high flux can occur in x-ray imaging and energy integrating detectors have been conventionally used. To achieve the benefits of energy resolved photon counting, imaging arrays with a large count rate range and good detection efficiency are required. Compound semiconductor radiation detectors with pixellated anode arrays electrically connected to application specific integrated circuits (ASICs) can provide fast, efficient, low-noise performance with adequate energy resolution however this can only be achieved with a careful optimization of the CdTe sensors and ASICs together. We have designed and constructed CdTe imaging arrays, 3 mm thick with a grid of electrical contacts inter-connected to a multi-channel channel ASICs. Arrays with a pixel pitch of 0.5 mm have achieved a counting range up to 20 million counts per second per square mm. Additionally, ASICs with a two dimensional array of pads has been fabricated and tested by connecting the inputs to 1 mm pitch CdTe sensors demonstrating 7 keV full width at half maximum energy resolution across a dynamic range of 30 keV to 140 keV for clinical CT.

10 Mcps photon counting was carried out using a detector consisting of a 2.0 mm-thick ZnO (zinc oxide) single-crystal scintillator and an MPPC (multipixel photon counter) module in an X-ray computed tomography (CT) system. The maximum count rate was 10 Mcps (mega counts per second) at a tube voltage of 70 kV and a tube current of 2.0 mA. Next, a photon-counting X-ray CT system consists of an X-ray generator, a turntable, a scan stage, a two-stage controller, the ZnO-MPPC detector, a counter card (CC), and a personal computer (PC). Tomography is accomplished by repeated linear scans and rotations of an object, and projection curves of the object are obtained by the linear scan with a scan velocity of 25 mm/s. The pulses of the event signal from the module are counted by the CC in conjunction with the PC. The exposure time for obtaining a tomogram was 600 s at a scan step of 0.5 mm and a rotation step of 1.0°, and photon-counting CT was accomplished using iodine-based contrast media.

X-ray fluorescence (XRF) analysis is useful for mapping various atoms in objects. Bremsstrahlung X-rays are selected using a 3.0 mm-thick aluminum filter, and these rays are absorbed by indium, cerium and gadolinium atoms in objects. Then XRF is produced from the objects, and photons are detected by a cadmium-telluride detector. The Kα photons are discriminated using a multichannel analyzer, and the number of photons is counted by a counter card. The objects are moved and scanned by an x-y stage in conjunction with a two-stage controller, and X-ray images obtained by atomic mapping are shown on a personal computer monitor. The scan steps of the x and y axes were both 2.5 mm, and the photon-counting time per mapping point was 0.5 s. We carried out atomic mapping using the X-ray camera, and Kα photons from cerium and gadolinium atoms were produced from cancerous regions in nude mice.

At the University of Arizona a research project is underway which addresses consistent color and gray-scale reproduction for digital color displays used in medical image interpretation. Now the University of Arizona can enter the field of ICC Profiling and Color Management. A color calibration facility was developed from ground up. Color calibration is presented for three color LCDs as is color accuracy. A PR670 Spectroradiometer was used to correct for errors of the pucks. A method was used to calculate the color accuracy and the ΔE values.

At the University of Arizona a research project is underway which addresses consistent color and consistent gray-scale reproduction for digital color displays used in medical image interpretation, specifically for Pathology. Now the University of Arizona can enter the field of ICC Profiling and Color Management. Of particular interest are Verification of PerfectLum Software, conformance and deviation and the maximum GSDF Error. Verification of PerfectLum Software seemed to be successful. FIT and LUM tests were performed to verify the conformance and the deviation was quantified. The maximum GSDF Error turned out to depend slightly on the bandwidth of the PR-670 Spectrophotometer. Measurements were made at two settings each of Normal and Fast. At the setting "Normal" the maximum GSDF Errors were 8.6% and 6.1 %. At the setting "Fast" the maximum GSDF Errors were 7.44 % and 5.76%. With respect to the results, all three objectives were met and the PerfectLum calibrated display was confirmed to the AAPM TG18 standards.

A description is given of the principle of operation, design and technical realization of a Compton spectrometer. In contrast to many other devices that have been discussed in the literature, the Compton spectrometer described here combines an electron-impact x-ray source with a room-temperature semiconductor detector. It is shown that the momentum resolution of the Compton spectrometer for the K characteristic lines emitted by the tube anode is adequate to resolve the Doppler broadening originating in electron momentum distributions of low atomic number elements, such as carbon, nitrogen and oxygen. Experimental Compton-broadened spectra from a range of common materials are presented. Methods to extract Compton profiles from the experimental spectra, by accounting for the continuous component of the x-ray tube emission and the multiplet nature of the characteristic lines, are illustrated. The application of this Compton spectrometer to material characterization is briefly discussed.

Pixellated semiconductor detectors, such as CdZnTe, CdTe, or TlBr, are used for gamma-ray imaging in medicine and astronomy. Data analysis for these detectors typically estimates the position (x, y, z) and energy (E) of each interacting gamma ray from a set of detector signals {S_i} corresponding to completed charge transport on the hit pixel and any of its neighbors that take part in charge sharing, plus the cathode. However, it is clear from an analysis of signal induction, that there are transient signal on all pixel electrodes during the charge transport and, when there is charge trapping, small negative residual signals on all electrodes. If we wish to optimally obtain the event parameters, we should take all these signals into account. We wish to estimate x,y,z and E from the set of all electrode signals, {S_i(t)}, including time dependence, using maximum-likelihood techniques[1]. To do this, we need to determine the probability of the electrode signals, given the event parameters {x, y, z, E}, i.e. Pr( {S_i(t)} | {x, y, z, E} ). Thus we need to map the detector response of all pixels, {S_i(t)}, for a large number of events with known x,y,z and E.In this paper we demonstrate the existence of the transient signals and residual signals and determine their magnitudes. They are typically 50-100 times smaller than the hit-pixel signals. We then describe development of an apparatus to measure the response of a 16-pixel semiconductor detector and show some preliminary results. We also discuss techniques for measuring the event parameters for individual gamma-ray interactions, a requirement for determining Pr( {S_i(t)} | {x, y, z, E}).

Multi-anode photomultiplier tubes (MAPMTs) offer high spatial resolution with their small size anodes that may range from 64 to 1024 in number per tube. In order to increase detector size, MAPMT modules can be arranged in arrays and combined in a single modular scintillation camera. However, then the large number of channels that require amplification and digitization become practically not feasible unless signals are combined or reduced in some manner. Conventional approaches use resistive charge division readouts with a centroid algorithm (or a variant of it) for simplicity in the electronic circuitry implementation and fast execution. However, coupling signals from many anodes may cause significant information loss and limit achievable resolution. In this study, a new approach for optimizing readout-electronics design for MAPMTs based on an analysis of information content in the signals is presented. An adaptive read-out scheme to be used with maximum-likelihood estimation methods is proposed. This scheme achieves precision in estimating event parameters that is close to what is achieved by retaining all signals.