The most investigated semiconductor photosensor for MRIcompatible PET detectors is the avalanche photodiode (APD). However, the silicon photomultiplier (SiPM), also called the Geiger-mode APD, is gaining attention in the development of the next generation of PET/MRI systems because the SiPM has much better performance than the APD. We have developed an MRI-compatible PET system based on multichannel SiPM arrays to allow simultaneous PET/MRI. Methods: The SiPM PET scanner consists of 12 detector modules with a ring diameter of 13.6 cm and an axial extent of 3.2 cm. In each detector module, 4 multichannel SiPM arrays (with 4 · 4 channels arranged in a 2 · 2 array to yield 8 · 8 channels) were coupled with 20 · 18 Lu 1.9 Gd 0.1 SiO 5 :Ce crystals (each crystal is 1.5 · 1.5 · 7 mm) and mounted on a charge division network for multiplexing 64 signals into 4 position signals. Each detector module was enclosed in a shielding box to reduce interference between the PET and MRI scanners, and the temperature inside the box was monitored for correction of the temperature-dependent gain variation of the SiPM. The PET detector signal was routed to the outside of the MRI room and processed with a field programmable gate array-based data acquisition system. MRI compatibility tests and simultaneous PET/MRI acquisitions were performed inside a 3-T clinical MRI system with 4-cm loop receiver coils that were built into the SiPM PET scanner. Interference between the imaging systems was investigated, and phantom and mouse experiments were performed. Results: No radiofrequency interference on the PET signal or degradation in the energy spectrum and flood map was shown during simultaneous PET/MRI. The quality of the MRI scans acquired with and without the operating PET showed only slight degradation. The results of phantom and mouse experiments confirmed the feasibility of this system for simultaneous PET/MRI. Conclusion: Simultaneous PET/MRI was possible with a multichannel SiPM-based PET scanner, with no radiofrequency interference on PET signals or images and only slight degradation of the MRI scans. A hybrid PET/MRI scanner has many potential advantages, including a reduced radiation dose, better soft-tissue contrast on MRI than CT, an almost unlimited combination of functional and molecular information, and possible motion correction of the PET image using MRI data (1-4). However, simultaneous PET/MRI with a conventional photomultiplier tube (PMT)-based PET camera is technically challenging, because the PMT is highly sensitive to the magnetic field. Almost every property of the PMT PET signal is distorted within the magnetic field. For example, the energy spectrum of the PET detector is quite diminished because of the loss of PMT signal output, and the peak position of the scintillation crystal cannot be distinguished in the flood maps of block detectors (1). Therefore, if relatively long optical fiber bundles are not used, the PMT PET camera should be placed a distance from the MRI machine (5). Consequently, a longer scan time is...
Bismuth germanate (BGO) was a very attractive scintillator in early-generation positron emission tomography (PET) scanners. However, the major disadvantages of BGO are lower light yield and longer rise and decay time compared to currently popular scintillators such as LSO and LYSO. This results in poorer coincidence timing resolution and it has generally been assumed that BGO is not a suitable scintillator for time-of-flight (TOF) PET applications. However, when a 511-keV photon interacts in a scintillator, a number of Cerenkov photons are produced promptly by energetic electrons released by photoelectric or Compton interactions. If these prompt photons can be captured, they could provide a better timing trigger for PET. Since BGO has a high refractive index (increasing the Cerenkov light yield) and excellent optical transparency down to 320 nm (Cerenkov light yield is higher at shorter wavelengths), we hypothesized that the coincidence timing resolution of BGO can be significantly improved by efficient detection of the Cerenkov photons. However, since the number of Cerenkov photons is far less than the number of scintillation photons, and they are more abundant in the UV and blue part of the spectrum, photosensors need to have high UV/blue sensitivity, fast temporal response, and very low noise in order to trigger on the faint Cerenkov signal. In this respect, NUV-HD silicon photomultipliers (SiPMs) (FBK, Trento, Italy) are an excellent fit for our approach. In this study, coincidence events were measured using BGO crystals coupled with NUV-HD SiPMs. The existence and influence of Cerenkov photons on the timing measurements were studied using different configurations to exploit the directionality of the Cerenkov emissions. Coincidence resolving time values (FWHM) of ~270 ps from 2 × 3 × 2 mm3 BGO crystals and ~560 ps from 3 × 3 × 20 mm3 BGO crystals were obtained. To our knowledge, these are the best coincidence resolving time values reported for BGO to date. With these values, BGO can be considered as a relevant scintillator for TOF PET scanners, especially if photodetectors with even better near UV/blue response can be developed to further improve the efficiency of Cerenkov light detection.
This paper describes two novel time-to-digital converter (TDC) architectures. The first is a dual-phase tapped-delay-line (TDL) TDC architecture that allows us to minimize the clock skew problem that causes the highly nonlinear characteristics of the TDC. The second is a pipelined on-the-fly calibration architecture that continuously compensates the nonlinearity and calibrates the fine times using the most up-to-date bin widths without additional dead time. The two architectures were combined and implemented in a single Virtex-6 device (ML605, Xilinx) for time interval measurement. The standard uncertainty for the time intervals from 0 to 20 ns was less than 12.83 ps-RMS (root mean square). The resolution (i.e., the least significant bit, LSB) of the TDC was approximately 10 ps at room temperature. The differential nonlinearity (DNL) values were [-1.0, 1.91] and [-1.0, 1.88] LSB and the integral nonlinearity (INL) values were [-2.20, 2.60] and [-1.63, 3.93] LSB for the two different TDLs that constitute one TDC channel. During temperature drift from 10 to 50(°)C, the TDC with on-the-fly calibration maintained the standard uncertainty of 11.03 ps-RMS.
In this study, the effects of (-)-epigallocatechin-3-gallate (EGCG) and/or hinokitiol (beta-thujaplicin) on melanogenesis were investigated. Our results showed that both EGCG and hinokitiol significantly inhibited melanin synthesis in a concentration-dependent manner, and that their hypopigmenting effects were stronger than that of kojic acid, which is known to inhibit melanin formation in melanocytes and melanoma cells. Interestingly, EGCG did not show any additive hypopigmenting effect in combination with kojic acid, though EGCG did show a synergistic effect in combination with hinokitiol. Several reports indicate that the activation of extracellular signal-regulated kinase (ERK) induces microphthalmia-associated transcription factor (MITF) degradation. Accordingly, the effects of EGCG and hinokitiol on the ERK signaling pathway were examined. EGCG and hinokitiol induced neither ERK activation nor MITF degradation. On the other hand, both EGCG and hinokitiol reduced the protein levels of MITF and of tyrosinase, the rate limiting melanogenic enzyme, whereas kojic acid had no effect. In addition, hinokitiol strongly downregulated the activity of tyrosinase, whereas EGCG or kojic acid had only a little effect. These results show that both EGCG and hinokitiol reduce MITF production, and suggest that reduced tyrosinase activity by hinokitiol explains their synergistic effect on melanogenesis.
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