A prototype small-animal PET scanner was developed based on depth-encoding detectors using dual-ended readout of very small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. Methods The scanner consists of 16 tapered dual-ended readout detectors arranged in a ring of diameter 61 mm. The axial field of view is 7 mm and the transaxial field of view is 30 mm. The scintillator arrays consist of 14×14 lutetium oxyorthosilicate (LSO) elements, with a crystal size of 0.43×0.43 mm2 at the front end and 0.80×0.43 mm2 at the back end, and the crystal elements are 13 mm long. The arrays are read out by 8×8 mm2 and a 13×8 mm2 position-sensitive avalanche photodiodes (PSAPDs) placed at opposite ends of the array. Standard nuclear instrumentation module (NIM) electronics and a custom designed multiplexer are used for signal processing. Results The detector performance was measured and all except the very edge crystals could be clearly resolved. The average detector intrinsic spatial resolution in the axial direction was 0.61 mm. A depth of interaction resolution of 1.7 mm was achieved. The sensitivity of the scanner at center of the field of view was 1.02% for a lower energy threshold of 150 keV and 0.68% for a lower energy threshold of 250 keV. The spatial resolution within a field of view that can accommodate the entire mouse brain was ~0.6 mm using a 3D Maximum Likelihood-Expectation Maximization (ML-EM) reconstruction algorithm. Images of a micro hot-rod phantom showed that rods with diameter down to 0.5 mm could be resolved. First in vivo studies were obtained using 18F-fluoride and confirmed that 0.6 mm resolution can be achieved in the mouse head in vivo. Brain imaging studies with 18F-fluorodeoxyglucose were also acquired. Conclusion A prototype PET scanner achieving a spatial resolution approaching the physical limits for a small-bore PET scanner set by positron range and acolinearity was developed. Future plans are to add more detector rings to extend the axial field of view of the scanner and increase sensitivity.

We present a hybrid imaging modality, x-ray luminescence optical tomography (XLOT), in which collimated x-ray beams are used to excite phosphor-based contrast agents. Images are reconstructed from the optical signals, using the known x-ray beam location and spatial extent as priors. We demonstrate XLOT using phantom experiments with deep targets and show that the reconstructed signal varies by <12% when the depth changes from 4.2 to 7.7 mm. For simple source distributions, we find as few as two orthogonal projection measurements are sufficient for XLOT reconstruction.Hybrid imaging combines the strengths of two imaging modalities. Examples include photoacoustic tomography [1,2] and x-ray acoustic computed tomography [3], in which a pulsed laser or x-ray source, respectively, are used to generate ultrasound inside tissue. Another example is the emerging technique of x-ray luminescence computed tomography (XLCT) that combines the high sensitivity of optical detection with the high spatial resolution of x-ray imaging [4,5]. Here, we propose a related approach, x-ray luminescence optical tomography (XLOT), which utilizes a collimated x-ray beam to excite deep embedded targets together with optical propagation modeling, permitting reconstruction of the distribution of phosphor-particle-based contrast agents in turbid media overlaid on a structural CT image. This overcomes the ill-posedness of the inverse problem in fluorescence and bioluminescence optical tomography [6][7][8] and provides a pathway for high-resolution in vivo optical molecular imaging at significant depths inside tissue.In XLOT, collimated x-ray beams are used to excite contrast agents that have been injected into the subject and are based on phosphor particles such as Eu 3+ -doped gadolinium oxysulfide (GOS:Eu 3+ ). This phosphor has a high cross section for diagnostic energy x rays, excellent light yield, and the emitted light is primarily between 600 and 750 nm, which is good for tissue penetration (Fig. 1). Nanoscale x-ray excitable particles of GOS:Eu 3+ and other Eu 3+ -doped lanthanide compounds have been successfully synthesized [9][10]. These particles can be made biocompatible (e.g., using a gold shell) and ultimately functionalized for molecular imaging applications. *Corresponding author: cli32@ucmerced.edu. Figures 1 and 2(a) show the geometry for XLOT. A collimated x-ray beam is scanned across the sample. Optical photons emitted by GOS particles in the subject are detected with an electron-multiplying charge coupled device (EMCCD). Knowing the volume of the subject excited by the x-ray beam, and using this as prior information, EMCCD measurements are used to reconstruct images of luminescence intensity (proportional to particle concentration), using a model-based reconstruction method similar to fluorescence optical tomography [11]. XLOT retains the advantage of high sensitivity common to optical detection, but its spatial resolution is dependent primarily on the x-ray beam size and is independent of the target depth. The inver...

The performance of an 8 × 8 array of 6.0 × 6.0 mm2 (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4 mm, 1.5 mm, 1.35 mm and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 × 57.4 mm2, and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm. The performance of the SiPM array was characterized by measuring flood histogram decoding quality, energy resolution, timing resolution and saturation at several bias voltages (from 25.0 V to 30.0 V in 0.5 V intervals) and two different temperatures (5 °C and 20 °C). Results show that the best flood histogram was obtained at a bias voltage of 28.0 V and 5 °C and an array of polished LSO crystals with a pitch as small as 1.2 mm can be resolved. No saturation was observed up to a bias voltage of 29.5 V during the experiments, due to adequate light sharing between SiPMs. Energy resolution and timing resolution at 5 °C ranged from 12.7 ± 0.8% to 14.6 ± 1.4 % and 1.58 ± 0.13 ns to 2.50 ± 0.44 ns, for crystal array pitch sizes of 3.4 mm and 1.2 mm respectively. Superior flood histogram quality, energy resolution and timing resolution were obtained with larger crystal array pitch sizes and at lower temperature. Based on our findings, we conclude that this large-area SiPM array can serve as a suitable photodetector for high-resolution small-animal PET or dedicated human brain PET scanners.

A capacitive charge-division readout method for reading out a 2 × 2 array of 5 mm × 5 mm position-sensitive solid-state photomultipliers (PS-SSPM) was designed and evaluated. Using this analog multiplexing method, the 20 signals (16 position, 4 timing) from the PS-SSPM array are reduced to 5 signals (4 position, 1 timing), allowing the PS-SSPM array to be treated as an individual large-area PS-SSPM module. A global positioning approach can now be used, instead of individual positioning for each PS-SSPM in the array, ensuring that the entire light signal is utilized. The signal-to-noise ratio (SNR) and flood histogram quality at different bias voltages (27.5 V to 32.0 V at 0.5 V intervals) and a fixed temperature of 0 °C were evaluated by coupling a 6 × 6 array of 1.3 mm × 1.3 mm × 20 mm polished LSO crystals to the center of the PS-SSPM array. The timing resolution was measured at a fixed bias voltage of 31.0 V and a fixed temperature of 0 °C. All the measurements were evaluated and compared using capacitors with different values and tolerances. Capacitor values ranged from 0.051 nf to 10 nf, and the capacitance tolerance ranged from 1% to 20%. The results show that better performance was achieved using capacitors with smaller values and better capacitance tolerance. Using 0.2 nf capacitors, the SNR, energy resolution and timing resolution were 24.3, 18.2% and 8.8 ns at a bias voltage 31.0 V, respectively. The flood histogram quality was also evaluated by using a 10 × 10 array of 1 mm × 1 mm × 10 mm polished LSO crystals and a 10 × 10 array of 0.7 mm × 0.7 mm × 20 mm unpolished LSO crystals to determine the smallest crystal size resolvable. These studies showed that the high spatial resolution of the PS-SSPM was preserved allowing for 0.7 mm crystals to be identified. These results show that the capacitive charge-division analog signal processing method can significantly reduce the number of electronic channels, from 20 to 5, while retaining the excellent performance of the detector.

The leading edge timing pick-off technique is the simplest timing extraction method for PET detectors. Due to the inherent time-walk of the leading edge technique, corrections should be made to improve timing resolution, especially for time-of-flight PET. Time-walk correction can be done by utilizing the relationship between the threshold crossing time and the event energy on an event by event basis. In this paper, a time-walk correction method is proposed and evaluated using timing information from two identical detectors both using leading edge discriminators. This differs from other techniques that use an external dedicated reference detector, such as a fast PMT-based detector using constant fraction techniques to pick-off timing information. In our proposed method, one detector was used as reference detector to correct the time-walk of the other detector. Time-walk in the reference detector was minimized by using events within a small energy window (508.5 – 513.5 keV). To validate this method, a coincidence detector pair was assembled using two SensL MicroFB SiPMs and two 2.5 mm × 2.5 mm × 20 mm polished LYSO crystals. Coincidence timing resolutions using different time pick-off techniques were obtained at a bias voltage of 27.5 V and a fixed temperature of 20 °C. The coincidence timing resolution without time-walk correction were 389.0 ± 12.0 ps (425 –650 keV energy window) and 670.2 ± 16.2 ps (250–750 keV energy window). The timing resolution with time-walk correction improved to 367.3 ± 0.5 ps (425 – 650 keV) and 413.7 ± 0.9 ps (250 – 750 keV). For comparison, timing resolutions were 442.8 ± 12.8 ps (425 – 650 keV) and 476.0 ± 13.0 ps (250 – 750 keV) using constant fraction techniques, and 367.3 ± 0.4 ps (425 – 650 keV) and 413.4 ± 0.9 ps (250 – 750 keV) using a reference detector based on the constant fraction technique. These results show that the proposed leading edge based time-walk correction method works well. Timing resolution obtained using this method was equivalent to that obtained using a reference detector and was better than that obtained using constant fraction discriminators.