Improved scintillators for time-of-flight positron emission tomography

摘要/摘要我们提出通过寻找具有Lu2SiO5:Ce （LSO）的伽马射线阻止能力和LaBr3:Ce的光度、时序和能量分辨率的新闪烁体来显著提高正电子发射断层扫描的诊断成像能力。与LSO相比，将亮度从30,000光子/MeV提高到60,000光子/MeV，将衰减时间从40 ns减少到20 ns，将使定时分辨率提高2倍，有效飞行时间（TOF）灵敏度提高2倍。这是因为重建图像中统计噪声的方差与时间分辨率相同。此外，将能量分辨率从9%提高到4%将使组织散射光子的背景减少大约两倍。这些技术的进步将显著改善疾病的检测，特别是对肥胖患者和胸部门控成像，并将增加使用重复成像研究治疗对疾病的影响的能力。本研究将重点研究Ce3+和Pr3+活化的镥化合物，因为(1)在已知的高亮度闪烁体中，只有那些被Ce3+和Pr3+活化的闪烁体速度足够快，可以考虑用于TOF和3D PET(2)元素周期表中可以被Ce3+和Pr3+取代的三价元素产生高亮度闪烁体（Y, La， Gd和Lu）；镥的原子序数最高，而且(3)没有已知的高光度闪烁体含有比镥重的元素。因此，对于511kev湮灭光子，镥化合物具有较高的光度和良好的阻止能力。有数百种致密的镥化合物从未作为伽马射线闪烁探测器被探索过。我们建议使用LBNL开发的高通量设备来合成微晶形式的掺杂候选化合物，在x射线激发下表征它们的发射，生长最佳候选化合物的晶体，并测量它们的能量和时间分辨率。晶体的大小和形状，光电探测器和电子设备将类似于正电子发射层析成像仪。大约2000个微晶粉末样品（200种不同的掺杂化合物）将被合成和表征，大约50个最好的晶体将被生长和测量。第一原理和经验理论将被用来确定候选名单的优先级。LBNL在进行这项研究方面处于独特的地位，因为最近创建了(1)高通量闪烁体发现设施（由国土安全部资助）和(2)晶体生长设施（由能源部和国土安全部资助）。其中包括48个合成炉、一个x射线衍射仪、一个脉冲x射线系统、一个x射线发光光谱仪和14个三种不同类型的晶体生长炉。测量仪器有计算机控制的换样器，并自动将其数据上传到在线数据库。请注意，由于镥闪烁体固有的放射性，国土安全部不再资助其发展，能源部也不再资助国家实验室的核医学研究。

DESCRIPTION (provided by applicant): Improved Scintillators for Time-of-Flight Positron Emission Tomography Project Summary/Abstract We propose to significantly improve the diagnostic imaging capability of positron emission tomography by finding new scintillators with the gamma-ray stopping power of Lu2SiO5:Ce (LSO) and the luminosity, timing, and energy resolution of LaBr3:Ce. Compared with LSO, improving the luminosity from 30,000 photons/MeV to 60,000 photons/MeV and reducing the decay time from 40 ns to 20 ns will improve the timing resolution by a factor of two and the effective time-of-flight (TOF) sensitivity by a factor of two. This is because the variance of the statistical noise in the reconstructed image is reduced by the same factor as the timing resolution. Moreover, improving the energy resolution from 9% to 4% will reduce the background from tissue-scattered photons by about a factor of two. These advances in technology will significantly improve the detection of disease, especially in obese patients and for gated imaging of the thorax, and will increase the ability to use repeat imaging to study the effects of therapy on the disease. The proposed research will focus on Ce3+ and Pr3+ activated lutetium compounds because (1) of the known high-luminosity scintillators, only those activated with Ce3+ and Pr3+ are fast enough to be considered for TOF and 3D PET (2) of the trivalent elements in the periodic table that can be substituted with Ce3+ and Pr3+ to produce highly luminous scintillators (Y, La, Gd, and Lu), lutetium provides the highest atomic number and (3) no known high-luminosity scintillator contains an element heavier than lutetium. Thus, lutetium compounds have the highest promise of having both high luminosity and good stopping power for 511 keV annihilation photons. There are hundreds of dense lutetium compounds that have never been explored as gamma-ray scintillation detectors. We propose to use the high- throughput facilities developed at LBNL to synthesize doped candidate compounds in microcrystalline form, characterize their emissions under X-ray excitation, grow crystals of the best candidates, and measure the their energy and timing resolution. The crystal size and shape, and the photodetector and electronics will be similar to those used in a positron emission tomograph. Approximately 2,000 microcrystalline powder samples (of 200 different doped compounds) will be synthesized and characterized, and approximately 50 crystals of the best will be grown and measured. First-principles and empirical theory will be used to prioritize the candidate lists. LBNL is in a unique position to perform this research because of the recent creation of (1) the high-throughput scintillator discovery facility (funded by DHS) and (2) the crystal growth facility (funded by DOE and DHS). These contain 48 synthesis furnaces, an X-ray diffractometer, a pulsed X-ray system, an X-ray luminescence spectrometer, and 14 crystal growing furnaces of three different types. The measurement instruments have computer-controlled sample changers and automatically upload their data to an on-line database. Note that DHS does not fund the development of lutetium scintillators due to their inherent radioactivity and DOE no longer funds nuclear medicine research at the National Laboratories.