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Objectives: SPECT with sub-MBq amounts of tracer or sub- second time resolution would enable a wide range of new imaging protocols such as screening tracers with initially low yield or labeling efficiency, imaging low receptor densities or even performing SPECT outside regular radiation laboratories. To this end we developed dedicated ultra-high-sensitivity pinhole SPECT. Methods: A cylindrical collimator with 54 focused 2.0 mm diameter conical pinholes was manufactured and mounted in a U- SPECT+ stationary SPECT system (MILabs, The Netherlands). The system matrix for image reconstruction was calculated via a hybrid method based on both 99mTc point source measurements and ray-tracing analytical modeling. SPECT image reconstruction was performed using Pixel-based OSEM. Performance was evaluated with phantoms, and low-dose bone, dynamic kidney and cardiac mouse scans. Results: The peak sensitivity reaches 1,3% (13080 cps/MBq). Reconstructed spatial resolution (rod visibility in a micro-Jaszczak phantom) was 0.85 mm. Even with only a quarter MBq of activity, 30 minutes bone SPECT scans provided surprisingly high levels of details. Dynamic dual-isotope kidney and 99mTc-sestamibi cardiac scans were acquired with a time-frame resolution down to 1 s. Conclusions: The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a MBq of tracer activity or down to one second frame dynamics.

PET imaging of rodents is increasingly used in preclinical research, but its utility is limited by spatial resolution and signal-to-noise ratio of the images. A recently developed preclinical PET system uses a clustered-pinhole collimator, enabling high-resolution, simultaneous imaging of PET and SPECT tracers. Pinhole collimation strongly departs from traditional electronic collimation achieved via coincidence detection in PET. We investigated the potential of such a design by direct comparison to a traditional PET scanner.Two small-animal PET scanners, 1 with electronic collimation and 1 with physical collimation using clustered pinholes, were used to acquire data from Jaszczak (hot rod) and uniform phantoms. Mouse brain imaging using (18)F-FDG PET was performed on each system and compared with quantitative ex vivo autoradiography as a gold standard. Bone imaging using (18)F-NaF allowed comparison of imaging in the mouse body. Images were visually and quantitatively compared using measures of contrast and noise.Pinhole PET resolved the smallest rods (diameter, 0.85 mm) in the Jaszczak phantom, whereas the coincidence system resolved 1.1-mm-diameter rods. Contrast-to-noise ratios were better for pinhole PET when imaging small rods (1.1 mm) for a wide range of activity levels, but this reversed for larger rods. Image uniformity on the coincidence system (3%) was superior to that on the pinhole system (5%). The high (18)F-FDG uptake in the striatum of the mouse brain was fully resolved using the pinhole system, with contrast to nearby regions equaling that from autoradiography; a lower contrast was found using the coincidence PET system. For short-duration images (low-count), the coincidence system was superior.In the cases for which small regions need to be resolved in scans with reasonably high activity or reasonably long scan times, a first-generation clustered-pinhole system can provide image quality in terms of resolution, contrast, and the contrast-to-noise ratio superior to a traditional PET system.

Small-animal SPECT systems with stationary detectors and focusing multiple pinholes can achieve excellent resolution-sensitivity trade-offs. These systems are able to perform fast total-body scans by shifting the animal bed through the collimator using an automated xyz stage. However, so far, a large number of highly overlapping central fields of view have been used, at the cost of overhead time needed for animal repositioning and long image reconstruction times due to high numbers of projection views.To improve temporal resolution and reduce image reconstruction time for such scans, we have developed and tested spiral trajectories (STs) of the animal bed requiring fewer steps. In addition, we tested multiplane trajectories (MPTs) of the animal bed, which is the standard acquisition method of the U-SPECT-II system that is used in this study. Neither MPTs nor STs require rotation of the animal. Computer simulations and physical phantom experiments were performed for a wide range of numbers of bed positions. Furthermore, we tested STs in vivo for fast dynamic mouse scans.We found that STs require less than half the number of bed positions of MPTs to achieve sufficient sampling. The reduced number of bed positions made it possible to perform a dynamic total-body bone scan and a dynamic hepatobiliary scan with time resolutions of 60 s and 15 s, respectively.STs open up new possibilities for high throughput and fast dynamic radio-molecular imaging.

We present a new rodent SPECT system (U-SPECT-II) that enables molecular imaging of murine organs down to resolutions of less than half a millimeter and high-resolution total-body imaging. Methods: The U-SPECT-II is based on a triangular stationary detector set-up, an XYZ stage that moves the animal during scanning, and interchangeable cylindric collimators (each containing 75 pinhole apertures) for both mouse and rat imaging. A novel graphical user interface incorporating preselection of the field of view with the aid of optical images of the animal focuses the pinholes to the area of interest, thereby maximizing sensitivity for the task at hand. Images are obtained from list mode data using statistical reconstruction that takes system blurring into account to increase resolution. Results: For 99mTc, resolutions determined with capillary phantoms were smaller than 0.35 and 0.45 mm using the mouse collimator with 0.35- and 0.6-mm pinholes, respectively, and less than 0.8mm using the rat collimator with 1.0-mm pinholes. Peak geometric sensitivity is 0.07% and 0.18% for the mouse collimator with 0.35- and 0.6-mm pinholes, respectively, and 0.09% for the rat collimator. Resolution with 111In, compared with that with 99mTc, was barely degraded, and resolution with 125I was degraded by about 10%, with some additional distortion. In vivo, kidney, tumor, and bone images illustrated that U-SPECT-II could be used for novel applications in the study of dynamic biologic systems and radiopharmaceuticals at the suborgan level. Conclusion: Images and movies obtained with U-SPECT-II provide high-resolution radiomolecule visualization in rodents. Discrimination of molecule concentrations between adjacent volumes of about 0.04 µL in mice and 0.5 µL in rats with U-SPECT-II is readily possible.

(201)Tl-Chloride ((201)Tl) is a myocardial perfusion SPECT agent with excellent biochemical properties commonly used for assessing tissue viability. However, cardiac (201)Tl SPECT images are severely degraded by photons scattered in the thorax. Accurate correction for this scatter is complicated by the nonuniform density and varied sizes of thoraxes, by the additional attenuation and scatter caused by female patients' breasts, and by the energy spectrum of (201)Tl. Monte Carlo simulation is a general and accurate method well suited to modeling this scatter. METHODS: Statistical reconstruction that includes Monte Carlo modeling of scatter was compared with statistical reconstruction algorithms not corrected for scatter. In the ADS method, corrections for attenuation, detector response, and scatter (Monte Carlo-based) were implemented simultaneously via the dual-matrix ordered-subset expectation maximization algorithm with a Monte Carlo simulator as part of the forward projector. The ADS method was compared with the A method (ordered-subset expectation maximization with attenuation correction) and with the AD method (a method like the A method but with detector response modeling added). A dual-head SPECT system equipped with two (153)Gd scanning line sources was used for simultaneously acquiring transmission and emission data. Four clinically realistic phantom configurations (a large thorax and a small thorax, each with and without breasts) with a cardiac insert containing 2 cold defects were used to evaluate the proposed reconstruction algorithms. We compared the performance of the different algorithms in terms of noise properties, contrast-to-noise ratios, the contrast separability of perfusion defects, uniformity, and robustness to anatomic variations. RESULTS: The ADS method provided images with clearly better visual defect contrast than did the other methods. The contrasts achieved with the ADS method were 10%-24% higher than those achieved with the AD method and 11%-37% higher than those achieved with the A method. For a typical contrast level, the ADS method exhibited noise levels around 27% lower than the AD method and 34% lower than the A method. Compared with the other 2 algorithms, the ADS reconstructions were less sensitive to anatomic variations and had better image uniformity in the homogeneously perfused myocardium. Finally, we found that the improvements that can be achieved with Monte Carlo-based scatter correction are stronger for (201)Tl than for (99m)Tc imaging. CONCLUSION: Our results indicate that Monte Carlo-based scatter correction is suitable for (201)Tl cardiac imaging and that such correction simultaneously improves several image-quality metrics