PurposePETbox is a low cost bench top preclinical PET scanner dedicated to pharmacokinetic and pharmacodynamic mouse studies. A prototype system was developed at our institute, and this manuscript characterizes the performance of the prototype system.ProceduresThe PETbox detector consists of a 20 × 44 bismuth germanate crystal array with a thickness of 5 mm and cross-section size of 2.05 × 2.05 mm. Two such detectors are placed facing each other at a spacing of 5 cm, forming a dual-head geometry optimized for imaging mice. The detectors are kept stationary during the scan, making PETbox a limited angle tomography system. 3D images are reconstructed using a maximum likelihood and expectation maximization (ML–EM) method. The performance of the prototype system was characterized based on a modified set of the NEMA NU 4-2008 standards.ResultsIn-plane image spatial resolution was measured to be an average of 1.53 mm full width at half maximum for coronal images and 2.65 mm for the anterior–posterior direction. The volumetric reconstructed resolution was below 8 mm3 at most locations in the field of view (FOV). The sensitivity, scatter fraction, and noise equivalent count rate (NECR) were measured for different energy windows. With an energy window of 150 - 650 keV and a timing window of 20 ns optimized for mouse imaging, the peak absolute sensitivity was 3.99% at the center of FOV and a peak NECR of 20 kcps was achieved for a total activity of 3.2 MBq (86.8 μCi). Phantom and in vivo imaging studies were performed and demonstrated the utility of the system at low activity levels. The quantitation capabilities of the system were also characterized showing that despite the limited angle tomography, reasonably good quantification accuracy was achieved over a large dynamic range of activity levels.ConclusionsThe presented results demonstrate the potential of this new tomograph for small animal imaging.

PETbox is a low-cost benchtop PET scanner dedicated to high throughput preclinical imaging that is currently under development at our institute. This paper presents the design and characterization of the detectors that are used in the PETbox system. In this work, bismuth germanate scintillator was used for the detector, taking advantage of its high stopping power, high photoelectric event fraction, lack of intrinsic background radiation and low cost. The detector block was segmented into a pixelated array consisting of 20 × 44 elements, with a crystal pitch of 2.2 mm and a crystal cross section of 2 mm × 2 mm. The effective area of the array was 44 mm × 96.8 mm. The array was coupled to two Hamamatsu H8500 position sensitive photomultiplier tubes, forming a flat-panel type detector head with a sensitive area large enough to cover the whole body of a typical laboratory mouse. Two such detector heads were constructed and their performance was characterized. For one detector head, the energy resolution ranged from 16.1% to 38.5% full width at half maximum (FWHM), with a mean of 20.1%; for the other detector head, the energy resolution ranged from 15.5% to 42.7% FWHM, with a mean of 19.6%. The intrinsic spatial resolution was measured to range from 1.55 mm to 2.39 mm FWHM along the detector short axis and from 1.48 mm to 2.33 mm FWHM along the detector long axis, with an average of 1.78 mm. Coincidence timing resolution for the detector pair was measured to be 4.1 ns FWHM. These measurement results show that the detectors are suitable for our specific application.

We have measured longitudinal nuclear relaxation rates of 129 Xe in Xe-N 2 mixtures at densities below 0.5 amagats in a magnetic field of 8.0 T. We find that intrinsic spin relaxation in this regime is principally due to fluctuations in the intramolecular spin-rotation ͑SR͒ and chemical-shift-anisotropy ͑CSA͒ interactions, mediated by the formation of 129 Xe-Xe persistent dimers. Our results are consistent with previous work done in one case at much lower applied fields where the CSA interaction is negligible and in another case at much higher gas densities where transient xenon dimers mediate the interactions. We have verified that a large applied field suppresses the persistent-dimer mechanism, consistent with standard relaxation theory, allowing us to measure room-temperature gas-phase relaxation times T 1 for 129 Xe greater than 25 h at 8.0 T. These data also yield a maximum possible low-field T 1 for pure xenon gas at room temperature of 5.45± 0.2 h. The coupling strengths for the SR and CSA interactions that we extract are in fair agreement with estimates based both on previous experimental work and on ab initio calculations. Our results have potential implications for the production and storage of large quantities of hyperpolarized 129 Xe for use in various applications.

Murine models are used extensively in biological and translational research. For many of these studies it is necessary to access the vasculature for the injection of biologically active agents. Among the possible methods for accessing the mouse vasculature, tail vein injections are a routine but critical step for many experimental protocols. To perform successful tail vein injections, a high skill set and experience is required, leaving most scientists ill-suited to perform this task. This can lead to a high variability between injections, which can impact experimental results. To allow more scientists to perform their own tail vein injections and to decrease the variability between injections a vascular access system (VAS) that semi-automatically inserts a needle into the tail vein of a mouse was developed. The VAS uses near infrared (NIR) light, image processing techniques, computer controlled motors, and a pressure feedback system to insert the needle and to validate its proper placement within the vein. The VAS was tested by injecting a commonly used radiolabeled probe (FDG) into the tail veins of five mice. These mice were then imaged using micro-positron emission tomography (PET) to measure the percentage of the injected probe remaining in the tail. These studies showed that, on average, the VAS leaves 3.4% of the injected probe in the tail. With these preliminary results, the VAS system demonstrates the potential for improving the accuracy of tail vein injections in mice.

This paper develops an automated vascular access system (A-VAS) with novel vision-based vein and needle detection methods and real-time pressure feedback for murine drug delivery. Mouse tail vein injection is a routine but critical step for preclinical imaging applications. Due to the small vein diameter and external disturbances such as tail hair, pigmentation, and scales, identifying vein location is difficult and manual injections usually result in poor repeatability. To improve the injection accuracy, consistency, safety, and processing time, A-VAS was developed to overcome difficulties in vein detection noise rejection, robustness in needle tracking, and visual servoing integration with the mechatronics system.

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This paper develops an efficient vision-based real-time vein detection algorithm for preclinical vascular insertions. Mouse tail vein injections perform a routine but critical step in most preclinical applications. Compensating for poor manual injection stability and high skill requirements, Vascular Access System (VAS) has been developed so a trained technician can manually command the system to perform needle insertions and monitor the operation through a near-infrared camera. However, VAS’ vein detection algorithm requires much computation and is, therefore, difficult to reflect the real-time tail movement during an insertion. Furthermore, the detection performance is often disturbed by tail hair and skin pigmentation. In this work, an effective noise filtering algorithm is proposed based on convex optimization. Effectively eliminating false-positive detections and preserving cross-sectional continuity, this algorithm provides vein detection results approximately every 200 ms at the presence of tail hair and skin pigmentation. This developed real-time tail vein detection method is able to capture the tail movement during insertion, therefore allow for the development of an automated Vascular Access System (A-VAS) for preclinical injections.

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