The MOLECUBES β-CUBE scanner is the newest amongst commercially available preclinical PET scanners for dedicated small animal imaging. The scanner is compact, lightweight and utilizes a small footprint to facilitate bench-top imaging. It can be used individually, or in combination with the X-CUBE CT scanner, which provides the ability to perform all necessary PET data corrections and provide fully quantitative PET images. The PET detector comprises of an 8 mm thick monolithic LYSO scintillator read-out by an array of 3 mm  ×  3 mm Hamamatsu silicon photomultipliers. The monolithic scintillator provides the ability to measure depth-of-interaction which aids in the development of such a compact scanner. With a scanner diameter of 7.6 cm and axial length of 13 cm it is suitable for imaging both whole-body mice and rats. This paper presents the design and imaging performance of the β-CUBE scanner. NEMA NU4-2008 characterization and a variety of phantom and animal imaging studies to demonstrate the quantitative imaging performance of the PET scanner are presented. Spatial resolution of 1 mm is measured with a filtered-back projection reconstruction algorithm at the center of the scanner and DOI measurement helps maintain the excellent spatial resolution over the entire imaging FOV. An absolute peak sensitivity of 12.4% is measured with a 255-765 keV energy window. The scanner demonstrates good count-rate performance, with a peak NEC of 300 kcps and 160 kcps measured with ~900 µCi in the NEMA mouse and rat phantoms, respectively. Imaging data with the NEMA image quality phantom and Micro Derenzo phantoms demonstrate the ability to achieve good image quality and accurate quantitative data. Image uniformity of 7.4% and spill-over ratio of 8% were measured. The superior spatial resolution, excellent energy resolution and sensitivity also provide superior contrast recovery, with ~70% recovery for the 2 mm rods. While current commercial preclinical PET scanners have spatial resolution in the 1-2 mm range, the 1 mm volumetric resolution presents significant improvement over current commercially available preclinical PET scanners. In combination with the X-CUBE scanner it provides the ability to perform fully quantitative imaging with spatially co-registered high-resolution 3D PET-CT images.

When using a segmented attenuation map, at least five different tissue types should be considered: cortical bone, spongeous bone, soft tissue, lung, and air. Furthermore, the interpatient variability of lung attenuation coefficients should be taken into account. Limited misclassification from bone to soft tissue and from lung to air is acceptable, as these do not lead to relevant errors.

In single photon emission computed tomography, the choice of the collimator has a major impact on the sensitivity and resolution of the system. Traditional parallel-hole and fan-beam collimators used in clinical practice, for example, have a relatively poor sensitivity and subcentimeter spatial resolution, while in small-animal imaging, pinhole collimators are used to obtain submillimeter resolution and multiple pinholes are often combined to increase sensitivity. This paper reviews methods for production, sensitivity maximization, and task-based optimization of collimation for both clinical and preclinical imaging applications. New opportunities for improved collimation are now arising primarily because of (i) new collimator-production techniques and (ii) detectors with improved intrinsic spatial resolution that have recently become available. These new technologies are expected to impact the design of collimators in the future. The authors also discuss concepts like septal penetration, high-resolution applications, multiplexing, sampling completeness, and adaptive systems, and the authors conclude with an example of an optimization study for a parallel-hole, fan-beam, cone-beam, and multiple-pinhole collimator for different applications.

A new preclinical PET system based on dSiPMs, called DigiPET, is presented. The system is based on thin monolithic scintillation crystals and exhibits superior spatial resolution at low-cost compared to systems based on pixelated crystals. Current dedicated small-rodent PET scanners have a spatial resolution in the order of 1 mm. Most of them have a large footprint, requiring considerable laboratory space. For rodent brain imaging, a PET scanner with sub-millimeter resolution is desired. To achieve this, crystals with a pixel pitch down to 0.5 mm have been used. However, fine pixels are difficult to produce and will render systems expensive. In this work, we present the first results with a high-resolution preclinical PET scanner based on thin monolithic scintillators and a large solid angle. The design is dedicated to rat-brain imaging and therefore has a very compact geometry. Four detectors were placed in a square arrangement with a distance of 34.5 mm between two opposing detector modules, defining a field of view (FOV) of 32 × 32 × 32 mm(3). Each detector consists of a thin monolithic LYSO crystal of 32 × 32 × 2 mm(3) optically coupled to a digital silicon photomultiplier (dSiPM). Event positioning within each detector was obtained using the maximum likelihood estimation (MLE) method. To evaluate the system performance, we measured the energy resolution, coincidence resolving time (CRT), sensitivity and spatial resolution. The image quality was evaluated by acquiring a hot-rod phantom filled with (18)F-FDG and a rat head one hour after an (18)F-FDG injection. The MLE yielded an average intrinsic spatial resolution on the detector of 0.54 mm FWHM. We obtained a CRT of 680 ps and an energy resolution of 18% FWHM at 511 keV. The sensitivity and spatial resolution obtained at the center of the FOV were 6.0 cps kBq(-1) and 0.7 mm, respectively. In the reconstructed images of the hot-rod phantom, hot rods down to 0.7 mm can be discriminated. In conclusion, a compact PET scanner was built using dSiPM technology and thin monolithic LYSO crystals. Excellent spatial resolution and acceptable sensitivity were demonstrated. Promising results were also obtained in a hot-rod phantom and in rat-brain imaging.

We compared three μSPECT systems by acquiring and analysing mouse-sized phantoms including a contrast recovery phantom built in-house offering the ability to measure the hot contrast on a warm background in the submillimetre resolution range. We believe our evaluation addressed the differences in imaging potential for each system to realistically image tracer distributions in mouse-sized objects.

No abstract

The mouse model is widely used in a vast range of biomedical and preclinical studies. Thanks to the ability to detect and quantify biological processes at the molecular level in vivo, PET has become a well-established tool in these investigations. However, the need to visualize and quantify radiopharmaceuticals in anatomic structures of millimetre or less requires good spatial resolution and sensitivity from small-animal PET imaging systems.In previous work we have presented a proof-of-concept of a dedicated high-resolution small-animal PET scanner based on thin monolithic scintillator crystals and Digital Photon Counter photosensor. The combination of thin monolithic crystals and MLE positioning algorithm resulted in an excellent spatial resolution of 0.7 mm uniform in the entire field of view (FOV). However, the limitation of the scanner was its low sensitivity due to small thickness of the lutetium-yttrium oxyorthosilicate (LYSO) crystals (2 mm).Here we present an improved detector design for a small-animal PET system that simultaneously achieves higher sensitivity and sustains a sub-millimetre spatial resolution. The proposed detector consists of a 5 mm thick monolithic LYSO crystal optically coupled to a Digital Photon Counter. Mean nearest neighbour (MNN) positioning combined with depth of interaction (DOI) decoding was employed to achieve sub-millimetre spatial resolution. To evaluate detector performance the intrinsic spatial resolution, energy resolution and coincidence resolving time (CRT) were measured. The average intrinsic spatial resolution of the detector was 0.60 mm full-width-at-half-maximum (FWHM). A DOI resolution of 1.66 mm was achieved. The energy resolution was 23% FWHM at 511 keV and CRT of 529 ps were measured. The improved detector design overcomes the sensitivity limitation of the previous design by increasing the nominal sensitivity of the detector block and retains an excellent intrinsic spatial resolution.

Additive manufacturing is a very promising technique for the production of complex multipinhole collimators and may also be used for producing other complex collimators. The cost of this technique is only related to the amount of powder needed and the time it takes to have the collimator built. The timeframe from design to collimator production is significantly reduced.