Design and performance of a compact and stationary microSPECT system

Purpose: Over the last ten years, there has been an extensive growth in the development of microSPECT imagers. Most of the systems are based on the combination of conventional, relatively large gamma cameras with poor intrinsic spatial resolution and multipinhole collimators working in large magnification mode. Spatial resolutions range from 0.58 to 0.76 mm while peak sensitivities vary from 0.06% to 0.4%. While pushing the limits of performance is of major importance, the authors believe that there is a need for smaller and less complex systems that bring along a reduced cost. While low footprint and low-cost systems can make microSPECT available to more researchers, the ease of operation and calibration and low maintenance cost are additional factors that can facilitate the use of microSPECT in molecular imaging. In this paper, the authors simulate the performance of a microSPECT imager that combines high space-bandwidth detectors and pinholes with truncated projection, resulting in a small and stationary system. Methods: A system optimization algorithm is used to determine the optimal SPECT systems, given our high resolutions detectors and a fixed field-of-view. These optimal system geometries are then used to simulate a Defrise disk phantom and a hot rod phantom. Finally, a MOBY mouse phantom, with realistic concentrations of Tc99m-tetrofosmin is simulated. Results: Results show that the authors can successfully reconstruct a Defrise disk phantom of 24 mm in diameter without any rotating system components or translation of the object. Reconstructed spatial resolution is approximately 800 mu m while the peak sensitivity is 0.23%. Finally, the simulation of the MOBY mouse phantom shows that the authors can accurately reconstruct mouse images. Conclusions: These results show that pinholes with truncated projections can be used in small magnification or minification mode to obtain a compact and stationary microSPECT system. The authors showed that they can reach state-of-the-art system performance and can successfully reconstruct images with realistic noise levels in a preclinical context. Such a system can be useful for dynamic SPECT imaging. 2013 American Association of Physicists in Medicine

Final Progress Report: SPECT Assay of Radiolabeled Monoclonal Antibodies

During the past project period, we proposed to collaborate closely with DOE’s Thomas Jefferson National Accelerator Facility (Jefferson Lab or JLab) to design a compact, ultra-high-resolution, high-sensitivity gamma camera for quantifying brain-tumor distributions of I-131. We also proposed to continue our on-going research in developing and evaluating pinhole collimation for quantitative ultra-high-resolution imaging of I-131-labeled MAbs. We have made excellent progress in accomplishing much of the research related to pinhole collimation. Many of the most significant results have been presented in peer-reviewed journal articles and conference proceedings. We have also made good progress in collaborating with JLab's Detector Group in developing a compact, ultra-high-resolution, gamma camera. A prototype I-131 imager was delivered to Duke on May 28, 2003. Our research results are summarized in the following sections. A. JLAB-DUKE DEDICATED BRAIN-TUMOR IMAGING SYSTEM A.1. Determination of Optimal Collimator Design During the current project period a prototype I-131 dedicated brain imager has been designed and built. Computer simulations and analysis of alternate designs were performed at Duke to determine an optimal collimator design. Collimator response was characterized by spatial resolution and sensitivity. Both geometric (non-penetrative) and penetrative sensitivities were considered in selecting an optimal collimator design. Based on these simulation results, two collimator designs were selected and built by external vendors. Initial imaging results were obtained using these collimators. B. INITIAL DEVELOPMENT OF SPECT RECONSTRUCTION SOFTWARE FOR JLAB-DUKE CAMERA B.1. Modeling Thick Septa and Collimator Holes: Geometrical-Phantom Study A geometrical phantom was designed to illuminate spatial resolution effects. The phantom includes a uniformly attenuating medium that consists of all voxels within an elliptical cylinder that is centered on the axis of rotation, infinitely long, and with minor and major diameters of 15.0 and 22.0cm. Computer-simulated projections of the phantom were created. We observed that thick septa create a periodic and strong variation in sensitivity across the surface of the gamma camera, as evident in these projections. C. PINHOLE POINT-RESPONSE FUNCTION (PRF) AND ROOT-MEAN-SQUARE (RMS) NOISE During the previous project period, we developed an accurate analytic expression to determine the sensitivity of pinhole collimation that included the effects of penetration. During the current project period, we have developed an accurate model of the point-response function (PRF) of pinhole collimators. D. COMPLETE SAMPLING: THEORETICAL AND COMPUTATIONAL DEVELOPMENTS During this project period, we have investigated the complete-sampling conditions for orbits of pinhole collimators and have published these data. We have made progress in both complete-sampling theory and also in computational methods. Pinhole collimation has similar complete sampling properties to cone-beam collimation. Complete sampling of an object cannot be obtained from the circular rotation of the aperture about the object. We have investigated helical-orbit pinhole SPECT scans as a method of obtaining completely sampled data. Helical orbits were evaluated because they offer the potential of a small ROR for high sensitivity and resolution combined with complete sampling. We compared reconstructions from simulated circular-orbit and simulated helical-orbit projection data and observed a marked improvement in image quality when helical-orbits are used for the data acquisition. E. PINHOLE CALIBRATION STUDIES We have begun a study of the effects of mechanical and electronic shifts on reconstruction that suggests that even very small shifts (a fraction of a millimeter) can introduce substantial artifacts in the reconstruction. We have acquired experimental calibration data using point sources. We fitted the centroids simultaneously to the expected mechanical and electronic components determined by an analytically derived equation. The mechanical and electronic shifts were determined using a maximum likelihood fit. The data show good agreement with expectation. The axial-shift results for the pinhole collimator demonstrated an approximately sinusoidal characteristic; that is, it is angularly dependent. To test the effect mechanical shift on reconstructed image quality, experimental data were acquired using a micro cold-rod phantom. The SPECT image that used the correct estimated mechanical shift was markedly improved compared with the other uncorrected SPECT images

The clinical utilities of multi-pinhole single photon emission computed tomography

Single photon emission computed tomography (SPECT) is an important imaging modality for various applications in nuclear medicine. The use of multi-pinhole (MPH) collimators can provide superior resolution-sensitivity trade-off when imaging small field-of-view compared to conventional parallel-hole and fan-beam collimators. Besides the very successful application in small animal imaging, there has been a resurgence of the use of MPH collimators for clinical cardiac and brain studies, as well as other small field-of-view applications. This article reviews the basic principles of MPH collimators and introduces currently available and proposed clinical MPH SPECT systems

Development and evaluation of quantitative imaging for improved estimation of radiopharmaceutical bio-distribution in small animal imaging

Quantitative imaging techniques like Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are an essential part of the treatment planning based on dosimetry in targeted radiation therapy. Apart from Fluorine-18 (18F), the potential of various other radionuclides with respect to the development of new radiopharmaceuticals which can be used for both diagnostic and therapeutic applications are increasingly under investigation. Three such radionuclides that are attractive for further research are Gallium-68 (68Ga), Copper-64 (64Cu) and Zirconium-89 (89Zr). To determine the performance of a PET or a SPECT, the National Electrical Manufacturing Association (NEMA) has published a standard set of protocols. However, there are limitations with the NEMA method with respect to the determination of the spatial resolution. Firstly, it does not take into account the overall behavior of the point spread function (PSF). Secondly, it has a very limited scope for a validation or a quality check criterion and thus the error of the calculated full width at half maximum (FWHM) cannot be determined. In the first part of this work, the aim was to quantitatively develop, evaluate and improve the performance characteristics of the PET and SPECT subsystem of the Albira II pre-clinical tri-modal system (Bruker BioSpin MRI GmbH, Ettlingen, Germany) for the radionuclides 18F, 68Ga, 64Cu and 89Zr (PET) and 99mT (SPECT). In this study, the sensitivity and spatial resolution characteristics of the systems based on a developed point source phantom were furthermore investigated for each of the radionuclides and compared with the NEMA protocol results based on measurements with a 22Na point source. In addition, a new set of protocols was developed for quantitative image reconstruction with the respective systems. In the second part of this work, an alternative method to accurately determine the PSF of an imaging system was developed to improve quantification accuracy in dosimetry. The developed method is based on 3-dimensional Gaussian fit functions taking into account the correction for the pixel size and the source dimension. Additionally, the effect of inaccurate determination of the PSF on the partial volume correction and hence the quantification of small structures in a diagnostic image was investigated. The ability of quantitative image reconstructions was determined based on the recovery coefficients that showed that upto 95% and 60% activity values could be recovered with the PET and SPECT systems, respectively. Overall the system performed satisfactory with respect to the linearity for the activity range (8-10) MBq generally used for pre-clinical imaging for all the investigated radionuclides. With respect to the determination of the system PSF, the method includes fitting of 3-dimensional functions, validation of fitting quality and choosing the best fit function based on the Akaike information criterion (AIC). The proposed method has advantages that it can better take into account the 3D distribution of the data and additionally yields an estimate for the error of the FWHM calculated from the estimated PSF. Furthermore, the investigation demonstrated that the PSF determined using the NEMA or another inadequate fit function can lead to a relative deviation of more than 40% for the recovery correction of small structures. Thus, the general method developed here can be used for obtaining robust and better reproducible PSFs for performing recovery corrections in PET/SPECT quantification studies and thus is a prerequisite for optimal evaluation of biokinetics in small animal studies

Reconstrucción y cuantificación de estudios SPECT en animal pequeño

[spa] Los sistemas SPECT de animal pequeño alcanzan una resolución espacial inferior al milímetro. Para conseguirlo, es necesario utilizar colimadores pinhole, ya que la imagen del objeto proyectada en la gammacámara a través del pequeño orificio del colimador puede estar ampliada respecto al objeto. Con el fin de optimizar el proceso de reconstrucción y obtener resoluciones submilimétricas utilizando equipos de pequeño formato equipados con un colimador pinhole, es necesario utilizar métodos de reconstrucción iterativos. Estos algoritmos ofrecen una calidad de imagen superior y una mejor exactitud en la cuantificación que los métodos de reconstrucción analíticos, al poder corregir las diferentes degradaciones sufridas en el proceso de formación de la imagen. A continuación se detalla el trabajo desarrollado y los principales resultados obtenidos para conseguir este objetivo: 1. Implementación de un programa de calibración para calcular los parámetros geométricos que describen la adquisición de un equipo SPECT equipado con colimador pinhole. 2. Desarrollo de un algoritmo de reconstrucción iterativa OSEM para la reconstrucción de estudios SPECT con colimador pinhole. 3. Adaptación el algoritmo de reconstrucción y el programa de calibración a un equipo SPECT con colimador pinhole de pequeño formato desarrollado en nuestro centro. La resolución tomográfica del equipo fue de 1 mm para radios de adquisición pequeños. Las imágenes reconstruidas de estudios en ratones muestran la viabilidad del equipo para su utilización con pequeños animales. 4. Incorporación en la matriz de transición del sistema la geometría del sistema, la penetración septal a través del colimador y la respuesta del detector. La resolución, el contraste y los coeficientes de recuperación mejoran al incorporar la penetración septal respecto a la modelización geométrica, aunque la mejora más importante se obtuvo al incluir la respuesta del detector. El número de iteraciones utilizadas en la reconstrucción debe limitarse para evitar la aparición de artefactos de anillo. Estos artefactos son de mayor importancia cuando la modelización del sistema incorpora la geometría, la penetración septal y la respuesta del detector. 5. Comparación del algoritmo de reconstrucción desarrollado con un algoritmo de reconstrucción que calcula la matriz de transición con técnicas de Monte Carlo. El tiempo de cálculo de la matriz de transición del sistema con la aproximación analítica fue tres órdenes de magnitud inferior al de la aproximación por Monte Carlo. La resolución y el contraste de las imágenes reconstruidas mediante ambas aproximaciones fueron similares. Las imágenes reconstruidas con el modelo Monte Carlo presentaban una relación señal/ruido sensiblemente más baja, posiblemente asociada a problemas de precisión en el cálculo de los elementos de matriz por la utilización de un número insuficiente de historias de fotones en el cálculo.[eng] Small animal SPECT systems can achieve a spatial resolution of less than 1 mm. Such resolution is possible thanks to pinhole collimators, which can amplify the gamma camera projection of the object, and by using iterative reconstruction methods. These methods improve image quality and offer better quantification accuracy than analytic reconstruction methods, by correcting the different degradations that occur during the image formation process. The work developed and the main results are detailed as follows: 1. A calibration program to calculate geometric parameters that describe the acquisition process of a SPECT system with a pinhole collimator was implemented. 2. An OSEM iterative reconstruction algorithm for SPECT studies acquired with a pinhole collimator was developed. 3. The reconstruction algorithm and the calibration program were adapted to an in-house developed small SPECT device with a pinhole collimator. Tomographic resolution was 1 mm for small acquisition radii. Image reconstruction of mice studies showed the viability of using the equipment with small animals. 4. System geometry, septal penetration through the collimator and detector were incorporated response to the transition matrix. In the first approach, the system geometry was incorporated. Resolution, contrast, and recovery coefficients improved when septal penetration was modeled, although the greatest improvement was obtained when detector response was included. Iterations had to be limited to avoid the appearance of ring-artifacts. 5. The reconstruction algorithm developed (analytical model) was compared with a reconstruction algorithm which calculates the transition matrix based on Monte Carlo techniques (Monte Carlo model). The computation time of the transition matrix system using the analytical approach was three orders of magnitude lower than the Monte Carlo approach. Resolution and contrast of the reconstructed images using the two approaches were similar. Images reconstructed with the Monte Carlo model presented a lower signal-to-noise ratio than images reconstructed with the analytical model, possibly due to accuracy problems associated with the matrix elements because of an insufficient number of photons in the calculation

An investigation into the limitations of myocardial perfusion imaging

Myocardial Perfusion Imaging (MPI) plays a very important role in the management of patients with suspected Coronary Artery Disease and its use has grown despite the shortcomings of the technique. Significant progress has been made in identifying the causes of these shortcomings and many solutions been suggested in the literature but the clinical sensitivity and specificity of the technique is still well below optimum. Monte Carlo Simulation is a very useful tool in identifying and guiding the understanding of the existing problems in MPI and this present study utilised this method to establish the basis of the simulations to be used and the way to analyse the results so that many of the causes of the attenuation defects, when using MPI, could be identified. This was achieved by investigating the effect that the different anatomical parts of the thorax have on the attenuation defects caused. A further aspect investigated was the impact that self-absorption in the heart has on these defects. The variability of these defects were further investigated by altering the position and orientation of the heart itself within the thorax and determining the effect it has on the attenuation defects caused. Results indicate that the attenuation caused is a very complicated process, that the self-absorption of the heart plays an extremely important role and the impact of the different positions and orientation of the heart inside the thorax are also significant. The distortion caused on the images by these factors was demonstrated by the intensity losses in the basal part and an over-estimation in the apical parts, which were clearly observable on the final clinical images, with the potential to affect clinical interpretation. Attenuation correction procedures using transmission sources, have been available for some time, but have not been adopted widely, amidst concern that they introduce additional artefacts. This study determined the effectiveness of these methods by establishing the level of correction obtained and whether additional artefacts were introduced. This included the effectiveness of the compensation achieved with the use of the latest commercially available comprehensive correction techniques. The technique investigated was “Flash3D" from Siemens providing transmission based attenuation correction, depth-dependent resolution recovery and scatter correction. The comparison between the defects and intensity losses predicted by the Monte Carlo Simulations and the corrections provided by this commercial correction technique revealed that solution is compensating almost entirely for these problems and therefore do provide substantial progress in overcoming the limitations of MPI. As a result of the improvements gained from applying these commercially available techniques and the accuracy established in this study for the mentioned technique it is strongly recommended that these new techniques be embraced by the wider Nuclear Medicine community so that the limitations in MPI can be reduced in clinical environment. Non-withstanding the above gains made there remains room for improvement by overcoming the of use transmission attenuation correction techniques by replacing them with emission based techniques. In this study two new related emission based attenuation correction techniques have been suggested and investigated and provide a promising prospect of overcoming these limitations

Development and Initial Evaluation of an MR Compatible Preclinical SPECT Insert for Simultaneous SPECT/MR Imaging

Multi-modality medical imaging systems have become increasingly important in research and clinical applications of biomedical imaging. Two complementary imaging modalities that have not yet been fully integrated into a multimodality system are Single Photon Emission Computed Tomography (SPECT) and Magnetic Resonance Imaging (MRI). To this end, our team has developed an MR compatible SPECT insert for simultaneous preclinical SPECT/MR imaging. The SPECT insert’s detector is composed of five rings Cadmium Zinc Telluride (CZT) detector modules and an interchangeable cylindrical multi-pinhole (MPH) collimator. This dissertation discusses several new and significant contributions made towards the development of our SPECT insert. We developed methods to determine optimized design parameters for MPH collimators for the SPECT insert. These methods were used to design two MPH collimators with different imaging resolutions. Simulation results demonstrated that both collimators can be used to obtain artifact-free SPECT images with the designed resolutions. We then developed novel techniques to fabricate the collimators using MR compatible materials. Without proper system calibration and data correction, SPECT images reconstructed from data acquired with our insert exhibit poor image quality. We developed a novel energy calibration method to identify the photopeak of the gamma photons from a Tc-99m source at all 24,320 detector pixels simultaneously and a two-stage detector uniformity correction method to identify and correct for non-uniformities and malfunctioning pixels in the detector modules. Additionally, a method was developed to correct for the drift of electron-hole pairs within the detector modules due to the Lorentz force when operating the SPECT insert inside a magnetic field. After applying the system calibration and correction methods to the acquired data, reconstructed SPECT images showed significant improvement in terms of resolution, uniformity, contrast, and artifact reduction. Finally the SPECT insert was evaluated experimentally as a standalone SPECT system and as an insert inside an MRI system for simultaneous SPECT/MR imaging through phantom and small animal studies. The experimental results demonstrated that the SPECT insert met design specifications. Most importantly, results demonstrate that the insert can be used to obtain high quality SPECT images during simultaneous SPECT/MR image acquisition

Advancements in image sensor technology for soft X-ray spectroscopy in space: CIS detectors for the Auroral X-ray Imaging Spectrometer

Soft X-rays with energies below 2 keV are of tremendous scientific utility for planetary science but are particularly challenging to detect and analyse due to their low energies and short attenuation lengths. Solid state image sensor based X-ray detectors, derived from charge coupled devices (CCDs) and CMOS image sensors (CISs), have the potential to capture information about a soft X-ray flux in the time, spatial, and energy domains, and so are a potent scientific tool. Developing X-ray detector technology is enabling the application of soft X-ray imaging spectrometers in ever more demanding environments, with the current state of the art CIS promising the potential for high temperature, Fano-limited, performance. This thesis investigates the use of solid state image sensors for soft- X-ray imaging spectroscopy in space-based applications. Specifically: an evaluation of the radiation damage experienced by the swept charge devices (SCDs) of the Chandrayaan-2 Large Area Soft X-ray Spectrometer (CLASS) which was shown to be within expectations and consistent with the requirements for continued science operation; and a study of X-ray detectors for the Auroral X-ray Imaging Spectrometer (AXIS) instrument aboard the Disturbed and quiet-time Ionosphere System at High Altitudes (DISHA) mission, resulting in the adoption of a novel CIS X-ray detector into the instrument design. The AXIS study has found that the newly developed CISs are now equal to their CCD counterparts in some soft X-ray imaging spectroscopy applications, potentially enabling new science targets to be pursued. The successful recommendation to change the AXIS instrument X-ray detector from the more mature EMCCD CCD201-20 of the baseline design, to the less mature but better performing CIS221-X and its derivatives represents a milestone in the development of CIS X-ray detector technology