Bradley E. Patt

Performance evaluation of A-SPECT: a high resolution desktop pinhole SPECT system for imaging small animals

Pinhole collimation of gamma rays to image distributions of radiolabeled tracers is considered promising for use in small animal imaging. The recent availability of transgenic mice, coupled with the development of /sup 125/I and /sup 99m/Tc labeled tracers, has allowed the study of a range of human disease models while creating demand for ultrahigh resolution imaging devices. We have developed a compact gamma camera that, in combination with pinhole collimation, allows for accessible, ultrahigh resolution in vivo single photon emission computed tomography (SPECT) imaging of small animals. The system is based on a pixilated array of NaI(Tl) crystals coupled to an array of position sensitive photomultiplier tubes. Interchangeable tungsten pinholes with diameters ranging from 0.5 to 3 mm are available, allowing the camera to be optimized for a variety of imaging situations. We use a three dimensional maximum likelihood expectation maximization algorithm to reconstruct the images. Our evaluation indicates that high quality, submillimeter spatial resolution images can be achieved in living mice. Reconstructed axial spatial resolution was measured to be 0.53, 0.74, and 0.96 mm full width at half maximum (FWHM) for rotation radii of 1, 2, and 3 cm, respectively, using the 0.5-mm pinhole. In this configuration, sensitivity is comparable to that of a high-resolution parallel hole collimator. SPECT images of hot- and cold-rod phantoms and a highly structured monkey brain phantom illustrate that high quality images can be obtained with the system. Images of living mice demonstrate the ability of the system to obtain high-resolution images in vivo. The effect of object size on the quantitative assessment of isotope distributions in an image was also studied.

Intraoperative probes and imaging probes

Abstract. Intraoperative probes have been employed to assist in the detection and removal of tumors for more than 50 years. For a period of about 40 years, essentially every detector type that could be miniaturized had been tested or at least suggested for use as an intraoperative probe. These detectors included basic Geiger-Müller (GM) tubes, scintillation detectors, and even state-of-the-art solid state detectors. The radiopharmaceuticals have progressed from 32PO4- injections for brain tumors to sophisticated monoclonal antibodies labeled with iodine-125 for colorectal cancers. The early work was mostly anecdotal, primarily interdisciplinary collaborations between surgeons and physical scientists. These collaborations produced a few publications, but never seemed to result in an ongoing clinical practice. In the mid 1980s, several companies offered basic gamma-detecting intraoperative probes as products. This led to the rapid development of radioimmunoguided surgery (RIGS) and sentinel node detection as regularly practiced procedures to assist in the diagnosis and treatment of cancer. In recent years intraoperative imaging probes have been developed. These devices add the ability to see the details of the detected activity, giving the potential of using the technique in a low-contrast environment. Intraoperative probes are now established as clinical devices, they have a commercial infrastructure to support their continued use, and there is ongoing research, both commercial and academic, that would seem to ensure continued progress and renewed interest in this slowly developing field.

Material separation in x-ray CT with energy resolved photon-counting detectors

PURPOSE The objective of the study was to demonstrate that, in x-ray computed tomography (CT), more than two types of materials can be effectively separated with the use of an energy resolved photon-counting detector and classification methodology. Specifically, this applies to the case when contrast agents that contain K-absorption edges in the energy range of interest are present in the object. This separation is enabled via the use of recently developed energy resolved photon-counting detectors with multiple thresholds, which allow simultaneous measurements of the x-ray attenuation at multiple energies. METHODS To demonstrate this capability, we performed simulations and physical experiments using a six-threshold energy resolved photon-counting detector. We imaged mouse-sized cylindrical phantoms filled with several soft-tissue-like and bone-like materials and with iodine-based and gadolinium-based contrast agents. The linear attenuation coefficients were reconstructed for each material in each energy window and were visualized as scatter plots between pairs of energy windows. For comparison, a dual-kVp CT was also simulated using the same phantom materials. In this case, the linear attenuation coefficients at the lower kVp were plotted against those at the higher kVp. RESULTS In both the simulations and the physical experiments, the contrast agents were easily separable from other soft-tissue-like and bone-like materials, thanks to the availability of the attenuation coefficient measurements at more than two energies provided by the energy resolved photon-counting detector. In the simulations, the amount of separation was observed to be proportional to the concentration of the contrast agents; however, this was not observed in the physical experiments due to limitations of the real detector system. We used the angle between pairs of attenuation coefficient vectors in either the 5-D space (for non-contrast-agent materials using energy resolved photon-counting acquisition) or a 2-D space (for contrast agents using energy resolved photon-counting acquisition and all materials using dual-kVp acquisition) as a measure of the degree of separation. Compared to dual-kVp techniques, an energy resolved detector provided a larger separation and the ability to separate different target materials using measurements acquired in different energy window pairs with a single x-ray exposure. CONCLUSIONS We concluded that x-ray CT with an energy resolved photon-counting detector with more than two energy windows allows the separation of more than two types of materials, e.g., soft-tissue-like, bone-like, and one or more materials with K-edges in the energy range of interest. Separating material types using energy resolved photon-counting detectors has a number of advantages over dual-kVp CT in terms of the degree of separation and the number of materials that can be separated simultaneously.

Pinhole SPECT of mice using the LumaGEM gamma camera

LumaGEM is a newly developed gamma camera for dedicated, small field of view, high spatial resolution imaging. The system consists of an array of 2/spl times/2/spl times/6 mm/sup 3/ NaI(Tl) pixels coupled to an array of position-sensitive photomultiplier tubes. It has a 125/spl times/125 mm/sup 2/ field of view. A pinhole collimator was used on LumaGEM to acquire SPECT images of mice that had transgenic modifications so as to model various diseases. Pinhole apertures of 1, 2 and 3 mm are interchangeable on the collimator and were used to acquire images. An iterative MLEM algorithm for pinhole SPECT was used to reconstruct the 128 projection images that covered 360/spl deg/ rotation. The reconstruction algorithm is based on a projector and backprojector pair implemented using a ray-tracing algorithm. The crucial reconstruction input parameters are the radius of rotation, center of rotation, and pinhole focal length. Ideal pinhole geometry is assumed, and no correction for attenuation has been made. The preliminary images presented here show detailed uptake in the mice subjects and are a convincing sign that animal SPECT can reach submillimeter spatial resolution and be a valuable tool in the study of diseases and the development of pharmaceuticals in animal models.

A 3D gantry single photon emission tomograph with hemispherical coverage for dedicated breast imaging

Abstract A novel tomographic gantry was designed, built and initially evaluated for single photon emission imaging of metabolically active lesions in the pendant breast and near chest wall. Initial emission imaging measurements with breast lesions of various uptake ratios are presented. Methods: A prototype tomograph was constructed utilizing a compact gamma camera having a field-of-view of Results: As iteration number increased for the tomographically measured data at all polar angles, contrasts increased while signal-to-noise ratios (SNRs) decreased in the expected way with OSEM reconstruction. The rollover between contrast improvement and SNR degradation of the lesion occurred at two to three iterations. The reconstructed tomographic data yielded SNRs with or without scatter correction that were >9 times better than the planar scans. There was up to a factor of ∼2.5 increase in total primary and scatter contamination in the photopeak window with increasing tilt angle from 15° to 45°, consistent with more direct line-of-sight of myocardial and liver activity with increased camera polar angle. Conclusion: This new, ultra-compact, dedicated tomographic imaging system has the potential of providing valuable, fully 3D functional information about small, otherwise indeterminate breast lesions as an adjunct to diagnostic mammography.

MicroCT with energy-resolved photon-counting detectors.

The goal of this paper was to investigate the benefits that could be realistically achieved on a microCT imaging system with an energy-resolved photon-counting x-ray detector. To this end, we built and evaluated a prototype microCT system based on such a detector. The detector is based on cadmium telluride (CdTe) radiation sensors and application-specific integrated circuit (ASIC) readouts. Each detector pixel can simultaneously count x-ray photons above six energy thresholds, providing the capability for energy-selective x-ray imaging. We tested the spectroscopic performance of the system using polychromatic x-ray radiation and various filtering materials with K-absorption edges. Tomographic images were then acquired of a cylindrical PMMA phantom containing holes filled with various materials. Results were also compared with those acquired using an intensity-integrating x-ray detector and single-energy (i.e. non-energy-selective) CT. This paper describes the functionality and performance of the system, and presents preliminary spectroscopic and tomographic results. The spectroscopic experiments showed that the energy-resolved photon-counting detector was capable of measuring energy spectra from polychromatic sources like a standard x-ray tube, and resolving absorption edges present in the energy range used for imaging. However, the spectral quality was degraded by spectral distortions resulting from degrading factors, including finite energy resolution and charge sharing. We developed a simple charge-sharing model to reproduce these distortions. The tomographic experiments showed that the availability of multiple energy thresholds in the photon-counting detector allowed us to simultaneously measure target-to-background contrasts in different energy ranges. Compared with single-energy CT with an integrating detector, this feature was especially useful to improve differentiation of materials with different attenuation coefficient energy dependences.

High resolution CsI(Tl)/Si-PIN detector development for breast imaging

High resolution multi-element (8/spl times/8) imaging arrays with collimators, size matched to discrete CsI(TI) scintillator arrays and Si-PIN photodetector arrays (PDAs) were developed as prototypes for larger arrays for breast imaging. Photodetector pixels were each 1.5/spl times/1.5 mm/sup 2/ with 0.25 mm gaps. A 16-element quadrant of the detector was evaluated with a segmented CsI(TI) scintillator array (1.5/spl times/1.5/spl times/6 mm/sup 3/ segments with 0.25 mm septa) coupled to the silicon array. The scintillator thickness of 6 mm corresponds to >85% total gamma efficiency at 140 keV. Pixel energy resolution of <8% FWHM was obtained for Tc-99m (140 keV). Electronic noise was 41 e/sup -/ RMS corresponding to a 3% FWHM contribution to the 140 keV photopeak. Detection efficiency uniformity (/spl plusmn//spl sigma/%) measured with a Tc-99m flood source was 4.3% for a /spl sim/10% energy photopeak window. Spatial resolution was 1.53 mm FWHM and pitch was 1.75 mm as measured from the Co-57 (122 keV) line spread function. Signal to background was 34 and contrast ([max-min]/[max+min]) was 0.94. The energy resolution and spatial characteristics of the new imaging detector exceed those of other scintillator based imaging detectors. A camera based on this technology will allow: (1) Improved Compton scatter rejection; (2) Detector positioning in close proximity to the breast to increase signal to noise; (3) Improved spatial resolution; and (4) Improved efficiency compared to high resolution collimated gamma cameras for the anticipated compressed breast geometries.

HgI/sub 2/ polycrystalline films for digital X-ray imagers

This paper describes recent results obtained with mercuric iodide (HgI/sub 2/) polycrystalline films that we have produced. The ultimate goal of this effort is to develop a new detector technology for digital X-ray imaging based on HgI/sub 2/ polycrystalline films coupled to large-area flat-panel amorphous silicon thin-film transistor-addressed readout arrays. We have employed two approaches for producing the polycrystalline films: 1) thermal evaporation (sublimation) and 2) deposition of films from various solutions. The 50- to 150-/spl mu/m-thick films were characterized with respect to their electrical properties and in response to ionizing radiation. The leakage current was about 40 pA/cm/sup 2/ at an operating bias voltage of /spl sim/50 V. Signals from the HgI/sub 2/ polycrystalline detectors, in response to ionizing radiation, compare favorably to the best published results for all high Z polycrystalline films grown elsewhere, including TlBr, PbI/sub 2/, and HgI/sub 2/.

New gamma-ray detector structures for electron only charge carrier collection utilizing high-Z compound semiconductors

High-Z compound semiconductors such as HgI2, CdTe, Cd1−xZnxTe and others offer the possibility of high efficiency gamma-detectors at room temperature. However, with traditional detector structures, energy resolution for high energies is practically always limited by poor hole collection characteristics. New detector structures have been developed which attempt to minimize the effects of the poor hole collection, so that essentially only the electrons contribute to the signal pulse formation. One new structure, introduced for the first time, is a lateral drift structure for high-Z compound semiconductor detectors. Energy resolutions of <3% FWHM at 122 keV and <1% FWHM at 662 keV were obtained for a 2 mm thick drift detector.

New Lutetium Silicate Scintillators

Cerium-doped lutecium orthosilicate (LSO) is the most promising scintillator discovered in almost five decades. It exhibits a unique combination of important properties for x and gamma-ray spectroscopy: high density, fast decay, and large light yield. However, the practical use of LSO is hindered by difficulties related to its fabrication as a single crystal by the Czochralski method. We report on the usefulness of the sol-gel process in obtaining lutecium silicate scintillators. Upon appropriate drying and firing, lutetium silicate crystals can be grown in a silica matrix. The bulk, polycrystalline transparent scintillators are characterized by XRD, optical absorption, light decay measurement and gamma-ray spectral response. Their properties are comparable to that of traditional LSO single crystals.