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

Accurate molecular imaging of small animals taking into account animal models, handling, anaesthesia, quality control and imaging system performance

Small-animal imaging has become an important technique for the development of new radiotracers, drugs and therapies. Many laboratories have now a combination of different small-animal imaging systems, which are being used by biologists, pharmacists, medical doctors and physicists. The aim of this paper is to give an overview of the important factors in the design of a small animal, nuclear medicine and imaging experiment. Different experts summarize one specific aspect important for a good design of a small-animal experiment

Absolute quantitative total-body small-animal SPECT with focusing pinholes

Purpose: In pinhole SPECT, attenuation of the photon flux on trajectories between source and pinholes affects quantitative accuracy of reconstructed images. Previously we introduced iterative methods that compensate for image degrading effects of detector and pinhole blurring, pinhole sensitivity and scatter for multi-pinhole SPECT. The aim of this paper is (1) to investigate the accuracy of the Chang algorithm in rodents and (2) to present a practical Changbased method using body outline contours obtained with optical cameras. Methods: Here we develop and experimentally validate a practical method for attenuation correction based on a Chang first-order method. This approach has the advantage that it is employed after, and therefore independently from, iterative reconstruction. Therefore, no new system matrix has to be calculated for each specific animal. Experiments with phantoms and animals were performed with a highresolution focusing multi-pinhole SPECT system (USPECT-II, MILabs, The Netherlands). This SPECT system provides three additional optical camera images of the animal for each SPECT scan from which the animal contour can be estimated. Results: Phantom experiments demonstrated that an average quantification error of –18.7% was reduced to –1.7% when both window-based scatter correction and Chang correction based on the body outline from optical images were applied. Without scatter and attenuation correction, quantification errors in a sacrificed rat containing sources with known activity ranged from –23.6 to –9.3%. These errors were reduced to values between –6.3 and +4.3% (with an average magnitude of 2.1%) after applying scatter and Chang attenuation correction. Conclusion: We conclude that the modified Chang correction based on body contour combined with window-based scatter correction is a practical method for obtaining small-animal SPECT images with high quantitative accuracy.Radiation, Radionuclides and ReactorsApplied Science

Development of a Practical Calibration Procedure for a Clinical SPECT/MRI System Using a Single INSERT Prototype Detector and Multi-Mini Slit-Slat Collimator

In the context of the INSERT project, we have been developing a clinical SPECT insert for an MRI system, in order to perform simultaneous SPECT/MRI of the human brain. This system will consist of 20 CsI:Tl scintillation detectors, 5 cm wide and 10 cm long, with a 72-channel SiPM readout per detector, and a multi-mini slit-slat (MSS) collimator set up in a stationary partial ring. Additionally the system has a custom-built transmit/receive MR coil to ensure compatibility with the SPECT system. Due to the novel design of the system/collimator, existing geometric calibration methods are not suitable. Therefore we propose a novel and practical calibration procedure that consists of a set of specific independent measurements to determine the geometric parameters of the collimator. This procedure was developed utilising a prototype system that consists of a reduced-size single detector with a 36-channel SiPM-based readout and a single MSS collimator module. Validation was performed by reconstructing different imaging phantoms, using a rotating stage to simulate a tomographic acquisition. Regarding uniformity, the COV for the cylinder phantom reconstructed with correct calibration parameters is 6.7%, whereas the COV using incorrect parameters is 9.4%. The quality of the phantom reconstructions provide evidence of the applicability of the proposed method to the calibration of the prototype system. This procedure can be easily adapted for the final INSERT system

Multi-Isotope Multi-Pinhole SPECT Bildgebung in kleinen Labortieren: Experimentelle Messungen und Monte Carlo Simulationen

Single photon emission computed tomography (SPECT) in small laboratory animals has become an integral part of translational medicine. It enables non-invasive validation of drug targeting, safety and efficacy in living organisms, which is progressively gaining importance in pharmaceutical industry. The increasing demand for efficiency in pharmaceutical research could be addressed by novel multitracer study designs. Multi-isotope multi-pinhole sampling allows validation of multiple tracers in a single experiment and consolidation of consecutive research trials. Due to physical and technical limitations, however, image quality and quantification can be substantially reduced. Advanced corrective procedures are required to establish multi-isotope multi-pinhole SPECT as a reliable and quantitative imaging technique for widespread use. For this purpose, the present work aimed to investigate the technical capabilities and physical limitations of multi-isotope multi-pinhole SPECT imaging in small laboratory animals. Based on experimental measurements and Monte Carlo simulations, specific error sources have been identified and procedures for quantitative image correction have been developed. A Monte Carlo simulation model of a state-of-the art SPECT/CT system has been established to provide a generalized framework for in-silico optimization of imaging hardware, acquisition protocols and reconstruction algorithms. The findings of this work can be used to improve image quality and quantification of SPECT in-vivo data for multi-isotope applications. They guide through the laborious process of multi-isotope protocol optimization and support the 3R welfare initiative that aims to replace, reduce and refine animal experimentation.Die Einzelphotonen-Emissionscomputertomographie (SPECT) in kleinen Labortieren hat sich als wichtiger Bestandteil der translationalen Medizin etabliert. Sie ermöglicht die nicht-invasive Validierung der Zielgenauigkeit, Wirksamkeit und Sicherheit von Wirkstoffen in lebenden Organismen und gewinnt zunehmend an Bedeutung in der pharmazeutischen Industrie. Die Forderung nach mehr Effizienz in der pharmazeutischen Forschung könnte durch neuartige Multitracer-Studien adressiert werden. Die Multi-Isotopen Akquisition mit Multi-Pinhole Kollimatoren ermöglicht die Validierung mehrerer Tracer in einem einzelnen Experiment und die Konsolidierung konsekutiver Bildgebungsstudien. Aufgrund physikalischer und technischer Limitationen ist die Bildqualität und Quantifizierbarkeit bei diesem Verfahren jedoch häufig reduziert. Um die Multi-Isotopen SPECT als zuverlässige und quantitative Bildgebungsmethode für den breiten Einsatz zu etablieren sind komplexe Korrekturverfahren erforderlich. Ziel der vorliegenden Arbeit war daher, die technischen Möglichkeiten und physikalischen Limitationen der Multi-Isotopen SPECT-Bildgebung in kleinen Labortieren systematisch zu untersuchen. Mithilfe von experimentellen Messungen und Monte Carlo Simulationen wurden spezifische Fehlerquellen identifiziert und Verfahren zur quantitativen Bildkorrektur entwickelt. Zudem wurde das Monte-Carlo Modell eines neuartigen SPECT/CT-Systems etabliert, um eine Plattform für die in-silico Optimierung von Bildgebungshardware, Aufnahmeprotokollen und Rekonstruktionsalgorithmen zu schaffen. Die Ergebnisse dieser Arbeit können die Bildqualität und Quantifizierbarkeit von SPECT in-vivo Daten für Multi-Isotopen Anwendungen verbessern. Sie führen beispielhaft durch den Prozess der Multi-Isotopen Protokolloptimierung und unterstützen die 3R-Initiative mit dem Ziel, experimentelle Tierversuche zu vermeiden (Replace), zu vermindern (Reduce) und zu verbessern (Refine)

The role of preclinical SPECT in oncological and neurological research in combination with either CT or MRI

Preclinical imaging with SPECT combined with CT or MRI is used more and more frequently and has proven to be very useful in translational research. In this article, an overview of current preclinical research applications and trends of SPECT combined with CT or MRI, mainly in tumour imaging and neuroscience imaging, is given and the advan- tages and disadvantages of the different approaches are de- scribed. Today SPECT and CT systems are often integrated into a single device (commonly called a SPECT/CT system), whereas at present combined SPECT and MRI is almost always carried out with separate systems and fiducial markers to combine the separately acquired images. While preclinical SPECT/CT is most widely applied in oncology research, SPECT combined with MRI (SPECT/MRI when integrated in one system) offers the potential for both neuroscience applications and oncological applications. Today CT and MRI are still mainly used to localize radiotracer binding and to improve SPECT quantification, although both CT and MRI have additional potential. Future technology developments may include fast sequential or simultaneous acquisition of (dynamic) multimodality data, spectroscopy, fMRI along with high-resolution anatomic MRI, advanced CT procedures, and combinations of more than two modalities such as combina- tions of SPECT, PET, MRI and CT all together. This will all strongly depend on new technologies. With further advances in biology and chemistry for imaging molecular targets and (patho)physiological processes in vivo, the introduction of new imaging procedures and promising new radiopharmaceu- ticals in clinical practice may be accelerated

A versatile imaging system for in vivo small animal research

In vivo small animal imaging has become an essential technique for molecular biology studies. However, requirements of spatial resolution, sensitivity and image quality are quite challenging for the development of small-animal imaging systems. The capabilities of the system are also significant for carrying out small animal imaging in a wide range of biological studies. The goal of this dissertation is to develop a high-performance imaging system that can readily meet a wide range of requirements for a variety of small animal imaging applications. Several achievements have been made in order to fulfill this goal.;To supplement our system for parallel-hole single photon emission computed tomography (SPECT) based upon a 110 mm diameter circular detector, we have developed novel compact gamma cameras suitable for imaging an entire mouse. These gamma cameras facilitate multi-head (\u3e2) parallel-hole SPECT with the mouse in close proximity to the detector face in order to preserve spatial resolution. Each compact gamma cameras incorporates pixellated Nal(Tl) scintillators and a pair of Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMTs). Two types of copper-beryllium parallel-hole collimators have been designed. These provide high-sensitivity imaging of I-125 or excellent spatial resolution over a range of object-detector distances. Both phantom and animal studies have demonstrated that these gamma cameras perform well for planar scintigraphy and parallel-hole SPECT of mice.;To further address the resolution limitations in parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have developed novel multipinhole helical SPECT based upon a 110 mm diameter circular detector equipped with a pixellated Nal(Tl) scintillator array. A brass collimator has been designed and produced containing five 1 mm diameter pinholes. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using this new imaging technique.;These studies in small-animal imaging have been applied to in vivo biological studies related to human health issues including studies of the thyroid and breast cancer. A re-evaluation study of potassium iodide blocking efficiency in radioiodine uptake in mice suggests that the FDA-recommended human dose of stable potassium iodide may not be sufficient to effectively protect the thyroid from radioiodine contamination. Another recent study has demonstrated that multipinhole helical SPECT can resolve the fine structure of the mouse thyroid using a relatively low dose (200 muCi). Another preclinical study has focused on breast tumor imaging using a compact gamma camera and an endogenous reporter gene. In that ongoing study, mammary tumors are imaged at different stages. Preliminary results indicate different functional patterns in the uptake of radiotracers and their potential relationship with other tumor parameters such as tumor size.;In summary, we have developed a versatile imaging system suitable for in vivo small animal research as evidenced by a variety of applications. The modular construction of this system will allow expansion and further development as new needs and new opportunities arise

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