PETbox4 is a new, fully tomographic bench top PET scanner dedicated to high sensitivity and high resolution imaging of mice. This manuscript characterizes the performance of the prototype system using the National Electrical Manufacturers Association (NEMA) NU 4–2008 standards, including studies of sensitivity, spatial resolution, energy resolution, scatter fraction, count-rate performance and image quality. The PETbox4 performance is also compared with the performance of PETbox, a previous generation limited angle tomography system. PETbox4 consists of four opposing flat-panel type detectors arranged in a box like geometry. Each panel is made by a 24 × 50 pixelated array of 1.82 × 1.82 × 7mm bismuth germanate (BGO) scintillation crystals with a crystal pitch of 1.90mm. Each of these scintillation arrays is coupled to two Hamamatsu H8500 photomultiplier tubes via a glass light guide. Volumetric images for a 45 × 45 × 95 mm field of view (FOV) are reconstructed with a maximum likelihood expectation maximization (ML-EM) algorithm incorporating a system model based on a parameterized detector response. With an energy window of 150–650 keV, the peak absolute sensitivity is approximately 18% at the center of FOV. The measured crystal energy resolution ranges from 13.5% to 48.3% full width at half maximum (FWHM), with a mean of 18.0%. The intrinsic detector spatial resolution is 1.5mm FWHM in both transverse and axial directions. The reconstructed image spatial resolution for different locations in the FOV ranges from 1.32mm to 1.93 mm, with an average of 1.46 mm. The peak noise equivalent count rate for the mouse-sized phantom is 35 kcps for a total activity of 1.5 MBq (40 µCi) and the scatter fraction is 28%. The standard deviation in the uniform region of the image quality phantom is 5.7%. The recovery coefficients range from 0.10 to 0.93. In comparison to the first generation two panel PETbox system, PETbox4 achieves substantial improvements on sensitivity and spatial resolution. The overall performance demonstrates that the PETbox4 scanner is suitable for producing high quality images for molecular imaging based biomedical research.

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.

The enantiopurification of racemic mixtures of chiral molecules is important for a range of applications. Recent work has shown that chiral group-directed photoisomerization is a promising approach to enantioenrich racemic mixtures of BINOL, but increased control of the diasteriomeric excess (de) is necessary for its broad utility. Here we develop a cavity quantum electrodynamics (QED) generalization of time-dependent density functional theory and demonstrate computationally that strong light–matter coupling can alter the de of the chiral group-directed photoisomerization of BINOL. The relative orientation of the cavity mode polarization and the molecules in the cavity dictates the nature of the cavity interactions, which either enhance the de of the (R)-BINOL diasteriomer (from 17% to ≈40%) or invert the favorability to the (S)-BINOL derivative (to ≈34% de). The latter outcome is particularly remarkable because it indicates that the preference in diasteriomer can be influenced via orientational control, without changing the chirality of the directing group. We demonstrate that the observed effect stems from cavity-induced changes to the Kohn–Sham orbitals of the ground state.

An integrated β-camera and microfluidic chip was developed that is capable of quantitative imaging of glycolysis radioassays using 18F-FDG in small cell populations down to a single cell. This paper demonstrates that the integrated system enables digital control and quantitative measurements of glycolysis in B-RafV600E–mutated melanoma cell lines in response to specific B-Raf inhibition. Methods The β-camera uses a position-sensitive avalanche photodiode to detect charged particle–emitting probes within a microfluidic chip. The integrated β-camera and microfluidic chip system was calibrated, and the linearity was measured using 4 different melanoma cell lines (M257, M202, M233, and M229). Microfluidic radioassays were performed with cell populations ranging from hundreds of cells down to a single cell. The M229 cell line has a homozygous B-RafV600E mutation and is highly sensitive to a B-Raf inhibitor, PLX4032. A microfluidic radioassay was performed over the course of 3 days to assess the cytotoxicity of PLX4032 on cellular 18F-FDG uptake. Results The β-camera is capable of imaging radioactive uptake of 18F-FDG in microfluidic chips. 18F-FDG uptake for a single cell was measured using a radioactivity concentration of 37 MBq/mL during the radiotracer incubation period. For in vitro cytotoxicity monitoring, the β-camera showed that exposure to 1 µM PLX4032 for 3 days decreased the 18F-FDG uptake per cell in highly sensitive M229 cells, compared with vehicle controls. Conclusion The integrated β-camera and microfluidic chip can provide digital control of live cell cultures and allow in vitro quantitative radioassays for multiple samples simultaneously.

Oncogenic kinase activity and the resulting aberrant growth and survival signaling is a common driving force of cancer. Accordingly, many successful molecularly targeted anti-cancer therapeutics are directed at inhibiting kinase activity. To assess kinase activity in minute patient samples, we have developed an immunocapture-based in vitro kinase assay on an integrated polydimethylsiloxane (PDMS) microfluidics platform that can reproducibly measure kinase activity from as few as 3,000 cells. For this platform, we adopted the standard radiometric 32P-ATP labeled phosphate transfer assay. Implementation on a microfluidic device required us to develop methods for repeated trapping and mixing of solid-phase affinity micro beads. We also developed a solid state beta-particle camera imbedded directly below the microfluidic device for real-time quantitative detection of the signal from this and other microfluidic radio bioassays. We demonstrate that the resulting integrated device can measure ABL kinase activity from BCR-ABL positive leukemia patient samples. The low sample input requirement of the device creates new potential for direct kinase activity experimentation and diagnostics on patient blood, bone marrow, and needle biopsy samples.