Distribution and dynamics of Tc-99m-pertechnetate uptake in the thyroid and other organs assessed by single-photon emission computed tomography in living mice

Background: Tc-99m pertechnetate is a well-known anion, used for clinical imaging of thyroid function. This gamma emitter is transported by the sodium iodide symporter but is not incorporated into thyroglobulin. Scintigraphy using Tc-99m pertechnetate or 123 iodide represents a powerful tool for the study of sodium iodide symporter activity in different organs of living animal models. However, in many studies that have been performed in mice, the thyroid could not be distinguished from the salivary glands. In this work, we have evaluated the use of a clinically dedicated single-photon emission computed tomography (SPECT) camera for thyroid imaging and assessed what improvements are necessary for the development of this technique. Methods: SPECT of the mouse neck region, with pinhole collimation and geometric calibration, was used for the individual measurement of Tc-99m pertechnetate uptake in the thyroid and the salivary glands. Uptake in the stomach was studied by planar whole-body imaging. Uptake kinetics and biodistribution studies were performed by sequential imaging. Results: This work has shown that thyroid imaging in living mice can be performed with a SPECT camera originally built for clinical use. Our experiments indicate that Tc-99m pertechnetate uptake is faster in the thyroid than in the salivary glands and the stomach. The decrease in Tc-99m pertechnetate uptake after injection of iodide or perchlorate as competitive inhibitors was also studied. The resulting rate decreases were faster in the thyroid than in the salivary glands or the stomach. Conclusions: We have shown that a clinically dedicated SPECT camera can be used for thyroid imaging. In our experiments, SPECT imaging allowed the analysis of Tc-99m pertechnetate accumulation in individual organs and revealed differences in uptake kinetics

Characterizing the parallax error in multi-pinhole micro-SPECT reconstruction

The usage of pinholes is very important in preclinical micro-SPECT. Pinholes can magnify the object onto the detector, resulting in better system resolutions than the detector resolution. The loss in sensitivity is usually countered by adding more pinholes, each projecting onto a specific part of the detector. As a result, gamma rays have an oblique incidence to the detector. This causes displacement and increased uncertainty in the position of the interaction of the gamma ray in the detector, also known as parallax errors or depth-of-interaction (DOI) errors. This in turn has a large influence on image reconstruction algorithms using ray tracers as a forward projector model, as the end-point of each ray on the detector has to be accurately known. In this work, we used GATE to simulate the FLEX Triumph-I system (Gamma Medica-Ideas, Northridge, CA), a CZT-based multi-pinhole micro-SPECT system. This system uses 5 mm thick CZT pixels, with 1.5 mm pixel pitch. The simulated information was then used to enhance the image resolution by accurately modeling the DOI. Two hundred point sources were simulated and rebinned to use the DOI information. This data was then used in a GPU-based iterative reconstruction algorithm taking the simulated DOI into account. The average displacement was then determined for all point sources, and the FWHM was calculated in three dimensions, by fitting the point sources with 3D Gaussians. We show that the displacement is reduced by 83% on average. We also show a 15% resolution gain when only 5 DOI levels are used

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

Analytical, experimental, and Monte Carlo system response matrix for pinhole SPECT reconstruction

PURPOSE: To assess the performance of two approaches to the system response matrix (SRM) calculation in pinhole single photon emission computed tomography (SPECT) reconstruction. METHODS: Evaluation was performed using experimental data from a low magnification pinhole SPECT system that consisted of a rotating flat detector with a monolithic scintillator crystal. The SRM was computed following two approaches, which were based on Monte Carlo simulations (MC-SRM) and analytical techniques in combination with an experimental characterization (AE-SRM). The spatial response of the system, obtained by using the two approaches, was compared with experimental data. The effect of the MC-SRM and AE-SRM approaches on the reconstructed image was assessed in terms of image contrast, signal-to-noise ratio, image quality, and spatial resolution. To this end, acquisitions were carried out using a hot cylinder phantom (consisting of five fillable rods with diameters of 5, 4, 3, 2, and 1 mm and a uniform cylindrical chamber) and a custom-made Derenzo phantom, with center-to-center distances between adjacent rods of 1.5, 2.0, and 3.0 mm. RESULTS: Good agreement was found for the spatial response of the system between measured data and results derived from MC-SRM and AE-SRM. Only minor differences for point sources at distances smaller than the radius of rotation and large incidence angles were found. Assessment of the effect on the reconstructed image showed a similar contrast for both approaches, with values higher than 0.9 for rod diameters greater than 1 mm and higher than 0.8 for rod diameter of 1 mm. The comparison in terms of image quality showed that all rods in the different sections of a custom-made Derenzo phantom could be distinguished. The spatial resolution (FWHM) was 0.7 mm at iteration 100 using both approaches. The SNR was lower for reconstructed images using MC-SRM than for those reconstructed using AE-SRM, indicating that AE-SRM deals better with the projection noise than MC-SRM. CONCLUSIONS: The authors' findings show that both approaches provide good solutions to the problem of calculating the SRM in pinhole SPECT reconstruction. The AE-SRM was faster to create and handle the projection noise better than MC-SRM. Nevertheless, the AE-SRM required a tedious experimental characterization of the intrinsic detector response. Creation of the MC-SRM required longer computation time and handled the projection noise worse than the AE-SRM.Nevertheless, the MC-SRM inherently incorporates extensive modeling of the system and therefore experimental characterization was not required

Analytical, experimental, and Monte Carlo system response matrix for pinhole SPECT reconstruction

Purpose: To assess the performance of two approaches to the system response matrix (SRM) calculation in pinhole single photon emission computed tomography (SPECT) reconstruction. Methods: Evaluation was performed using experimental data from a low magnification pinhole SPECT system that consisted of a rotating flat detector with a monolithic scintillator crystal. The SRM was computed following two approaches, which were based on Monte Carlo simulations (MC-SRM) and analytical techniques in combination with an experimental characterization (AE-SRM). The spatial response of the system, obtained by using the two approaches, was compared with experimental data. The effect of the MC-SRM and AE-SRM approaches on the reconstructed image was assessed in terms of image contrast, signal-to-noise ratio, image quality, and spatial resolution. To this end, acquisitions were carried out using a hot cylinder phantom (consisting of five fillable rods with diameters of 5, 4, 3, 2, and 1 mm and a uniform cylindrical chamber) and a custom-made Derenzo phantom, with center-to-center distances between adjacent rods of 1.5, 2.0, and 3.0 mm. Results: Good agreement was found for the spatial response of the system between measured data and results derived from MC-SRM and AE-SRM. Only minor differences for point sources at distances smaller than the radius of rotation and large incidence angles were found. Assessment of the effect on the reconstructed image showed a similar contrast for both approaches, with values higher than 0.9 for rod diameters greater than 1 mm and higher than 0.8 for rod diameter of 1 mm. The comparison in terms of image quality showed that all rods in the different sections of a custom-made Derenzo phantom could be distinguished. The spatial resolution (FWHM) was 0.7 mm at iteration 100 using both approaches. The SNR was lower for reconstructed images using MC-SRM than for those reconstructed using AE-SRM, indicating that AE-SRM deals better with the projection noise than MC-SRM. Conclusions: The authors' findings show that both approaches provide good solutions to the problem of calculating the SRM in pinhole SPECT reconstruction. The AE-SRM was faster to create and handle the projection noise better than MC-SRM. Nevertheless, the AE-SRM required a tedious experimental characterization of the intrinsic detector response. Creation of the MC-SRM required longer computation time and handled the projection noise worse than the AE-SRM.Nevertheless, the MC-SRM inherently incorporates extensive modeling of the system and therefore experimental characterization was not required

Third Generation Gamma Camera SPECT System

Single Photon Emission Computed Tomography (SPECT) is a non-invasive imaging modality, frequently used in myocardial perfusion imaging. The biggest challenges facing the majority of clinical SPECT systems are low sensitivity, poor resolution, and the relatively high radiation dose to the patient. New generation systems (GE Discovery, DSPECT) dedicated to cardiac imaging improve sensitivity by a factor of 5-8. The purpose of this work is to investigate a new gamma camera design with 21 hemi-ellipsoid detectors each with a pinhole collimator for Cardiac SPECT for further improvement in sensitivity, resolution, imaging time, and radiation dose. To evaluate the resolution of our hemi-ellipsoid system, GATE Monte-Carlo simulations were performed on point-sources, rod-sources, and NCAT phantoms. The purpose of point-source simulation is to obtain operating pinhole diameter by comparing the average FWHM (Full-width-half-maximum) of flat-detector system with curved hemi-ellipsoid detector system. The operating pinhole diameter for the curved hemi-ellipsoid detector was found to be 8.68mm. System resolution is evaluated using reconstructed rod-sources equally spaced within the region of interest. The results were compared with results of GE discovery system available in the literature. The system performance was also evaluated using the mathematical anthropomorphic NCAT (NURBS-based Cardiac Torso) phantom with a full (clinical) dose acquisition (25mCi) for 2 mins and an ultra-low-dose acquisition of 3mCi for 5.44mins. On rod-sources, the average resolution after reconstruction with resolution recovery in the entire region of interest (ROI) for cardiac imaging was 4.44mm, with standard deviation 2.84mm, compared to 6.9mm reported for GE Discovery (Kennedy et al, JNC, 2014). For NCAT studies improved sensitivity allowed a full-dose (25mCi) 2 min acquisition (ELL8.68mmFD) which yielded 3.79M LV counts. This is ~3.35 times higher compared to 1.13M LV counts acquired in 2 mins for clinical full-dose for state-of-the-art DSPECT. The increased sensitivity also allowed an ultra-low dose acquisition protocol (ELL8.68mmULD). This ultra-low-dose protocol yielded ~1.23M LV-counts which was comparable to the full-dose 2min acquisition for DSPECT. The estimated NCAT average FWHM at the LV wall after 12 iterations of the OSEM reconstruction was 4.95mm and 5.66mm around the mid-short-axis slices for ELL8.68mmFD and ELL8.68mmULD respectively

ALBIRA: A small animal PET/SPECT/CT imaging system

Purpose: The authors have developed a trimodal PET/SPECT/CT scanner for small animal imaging. The gamma ray subsystems are based on monolithic crystals coupled to multianode photomultiplier tubes (MA-PMTs), while computed tomography (CT) comprises a commercially available microfocus x-ray tube and a CsI scintillator 2D pixelated flat panel x-ray detector. In this study the authors will report on the design and performance evaluation of the multimodal system. Methods: X-ray transmission measurements are performed based on cone-beam geometry. Individual projections were acquired by rotating the x-ray tube and the 2D flat panel detector, thus making possible a transaxial field of view (FOV) of roughly 80 mm in diameter and an axial FOV of 65 mm for the CT system. The single photon emission computed tomography (SPECT) component has a dual head detector geometry mounted on a rotating gantry. The distance between the SPECT module detectors can be varied in order to optimize specific user requirements, including variable FOV. The positron emission tomography (PET) system is made up of eight compact modules forming an octagon with an axial FOV of 40 mm and a transaxial FOV of 80 mm in diameter. The main CT image quality parameters (spatial resolution and uniformity) have been determined. In the case of the SPECT, the tomographic spatial resolution and system sensitivity have been evaluated with a99mTc solution using single-pinhole and multi-pinhole collimators. PET and SPECT images were reconstructed using three-dimensional (3D) maximum likelihood and ordered subset expectation maximization (MLEM and OSEM) algorithms developed by the authors, whereas the CT images were obtained using a 3D based FBP algorithm. Results: CT spatial resolution was 85μm while a uniformity of 2.7% was obtained for a water filled phantom at 45 kV. The SPECT spatial resolution was better than 0.8 mm measured with a Derenzo-like phantom for a FOV of 20 mm using a 1-mm pinhole aperture collimator. The full width at half-maximum PET radial spatial resolution at the center of the field of view was 1.55 mm. The SPECT system sensitivity for a FOV of 20 mm and 15% energy window was 700 cps/MBq (7.8 × 10−2%) using a multi-pinhole equipped with five apertures 1 mm in diameter, whereas the PET absolute sensitivity was 2% for a 350–650 keV energy window and a 5 ns timing window. Several animal images are also presented. Conclusions: The new small animal PET/SPECT/CT proposed here exhibits high performance, producing high-quality images suitable for studies with small animals. Monolithic design for PET and SPECT scintillator crystals reduces cost and complexity without significant performance degradation.This study was supported by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) under Grant No. FIS2010-21216-CO2-01 and Valencian Local Government under Grant PROMETEO 2008/114. The authors also thank Brennan Holt for checking and correcting the text.Sánchez Martínez, F.; Orero Palomares, A.; Soriano Asensi, A.; Correcher Salvador, C.; Conde Castellanos, PE.; González Martínez, AJ.; Hernández Hernández, L.... (2013). ALBIRA: A small animal PET/SPECT/CT imaging system. Medical Physics. 40(5):5190601-5190611. https://doi.org/10.1118/1.4800798S5190601519061140

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