Development of a combined Gamma/Positron system for molecular imaging of the human brain at sub-500 micron spatial resolution

摘要 我们正在提出一种被称为“b+g”或“pamma-positron”的混合成像模式的新方法。 成像[Gri07]承诺同时克服1)单伽马射线光子的灵敏度极限 发射成像，2)区分两种不同的正电子发射同位素的挑战，以及3) 基于正电子探测的放射性同位素成像所固有的基于物理的空间分辨率限制 仅有湮灭光子[LAN14]。其目的是显著推进人脑的分子成像。 通过允许显示较小的亚结构，量化较少量的放射性示踪剂摄取，以及 在先进的多同位素研究中同时测量多种动态和空间摄取模式 大脑功能正常。使这一点可行所需的要素包括：i)探测器方法 湮灭和伽马射线光子，可以为精确的能量、位置和时间估计提供丰富的数据 对于光电和康普顿相互作用，ii)固件和软件中的处理算法，以分类和 最佳利用在有或无重合的情况下可能出现的各种信号组合，三) 基于包含发射、检测、正电子概率的可能性的重建算法 距离、非共线性和康普顿运动学，以及iv)衰减和被摄体的检测和补偿 如果不加以解决，运动效果将成为分辨率和图像质量的限制因素。 与早期使用液体氙气探测器完成b+g成像的努力不同[Gri07]，散射 作为PET扫描仪插件的探测器[Yos20]，或与闪烁配对的平面半导体探测器 摄像机[Lan14]，我们建议开发和演示单个探测器技术和关联 一种既可用于511keV湮没光子的数据处理方法，又可用于更高能量的单光子数据处理方法。 发射伽马射线。阿巴斯扎德(Abbaszadeh)和莱文(Levin)开创了一种边缘交叉条状镉锌 Telluride(CZT)探测器方法提供了一个理想的起始点[ABB16]。在他们的 属性是基于边缘几何的高阻挡能力，最大限度地减少视差的3D定位， 出色的能量分辨率，动态范围高达1.2 MeV，最大光子能量沉积 互动。此外，当光子经历初始散射和光电吸收时，这些 模块生成的数据向量允许对可以分析的两种交互的位置和能量进行估计 康普顿运动学[Abb17]。 我们将执行为期两年的模拟和原则证明阶段(UG3)，在该阶段中我们将演示b+g 使用边沿CZT模块进行检测并测量探测器特性，开发支持以下功能的模拟 重建，并展示了使用单一和多个同位素进行收购的情况。我们将开展为期三年的 UH3阶段，建立具有足够视野的断层成像系统，以研究复杂的 啮齿类动物大脑的动态模型和活体成像，作为人类大脑系统的设计性研究和先驱。

SUMMARY We are proposing a new approach to a hybrid imaging modality that has been called “b+g” or “pamma-positron” Imaging [Gri07] that promises to simultaneously overcome 1) the sensitivity limits of single-gamma-ray-photon emission imaging, 2) the challenge of distinguishing between two different positron-emitting isotopes, and 3) the physics-based spatial resolution limits inherent in radioisotope imaging based on detection of positron- annihilation photons alone [Lan14]. The intent is to significantly advance molecular imaging of the human brain by allowing visualization of smaller substructures, quantification of smaller amounts of radiotracer uptake, and simultaneous measurement of multiple dynamic and spatial uptake patterns in advanced multi-isotope studies of normal brain function. The required elements to make this feasible comprise i) a detector approach for annihilation and gamma-ray photons that can yield rich data for precise energy, position, and timing estimation for both photoelectric and Compton interactions, ii) processing algorithms in firmware and software to sort and make optimal use of the various combinations of signals that can occur with and without coincidence, iii) reconstruction algorithms based on likelihoods that incorporate probabilities of emission, detection, positron range, non-collinearity, and Compton kinematics, and iv) detection and compensation for attenuation and subject motion – effects that if not addressed will become limiting factors for resolution and image quality. In contrast to early efforts to accomplish b+g imaging with liquid xenon detectors [Gri07], scattering detectors as inserts into PET scanners [Yos20], or planar semiconductor detectors paired with scintillation cameras [Lan14], we propose instead to develop and demonstrate a single detector technology and associated data processing methods that can be used for both 511 keV annihilation photons and the higher-energy, singly- emitted gamma rays. Abbaszadeh (MPI) and Levin have pioneered an edge-on crossed-strip cadmium zinc telluride (CZT) detector approach to PET detectors that provides an ideal starting point [Abb16]. Among their attributes are high stopping power based on the edge-on geometry, 3D positioning that minimizes parallax, excellent energy resolution, and dynamic range up to 1.2 MeV in maximum photon energy deposited per interaction. Furthermore, when a photon undergoes an initial scatter followed by a photoelectric absorption, these modules yield data vectors that allow position and energy estimation for both interactions that can be analyzed with Compton kinematics [Abb17]. We will carry out a 2-year simulation and proof-of-principle phase (UG3) in which we demonstrate b+g detection with edge-on CZT modules and measure detector characteristics, develop simulations that support reconstructions, and demonstrate acquisitions with single and multiple isotopes. We will carry out a three-year UH3 phase to build a tomographic system with a field of view sufficient to investigate imaging of sophisticated dynamic phantoms and in vivo imaging of rodent brain, as a design study and precursor to a human brain system.