PET-EPRI

混合扫描仪的出现，结合互补的方式，已经彻底改变了成像;增强 临床实践和生物医学研究。标准范例是将联合收割机与解剖成像方法 （例如，X射线CT）与功能方法（例如，PET）。在这个项目中，我们提出了一个转变， 通过研究两种互补的功能成像方法的融合，我们特别 计划将PET扫描仪与电子顺磁共振成像（EPRI）扫描仪集成。EPRI是一个 相对较新的方法，能够映射组织的体内化学特性。一种组合式PET- EPRI扫描仪有望为微环境中的生理相互作用提供新的见解， 这是目前成像仪所能达到的。PET/EPRI系统的开发在技术上具有挑战性， 需要独特的方法来设计、构造和测试扫描仪。我们将使用一种新型的PET扫描仪 其用闪烁体的固体环代替离散探测器模块的环（空间分辨率= ~ 1 mm）。 这种设计消除了构造分立检测器模块所需的导电材料。使用环形 闪烁体由于消除了分立模块之间的间隙而导致高检测灵敏度（~10%）。它 还允许通过将光锥形状与深度相关联来估计检测器中的事件相互作用深度， 这是离散检测器不可能实现的能力。硅光电倍增管（SiPM）阵列， 受EPR系统中存在的磁场的影响，将用于检测闪烁体光。 EPRI系统将利用快速扫描方法生成从以下位置获得的光谱的空间图 分子探针（分辨率<1 mm）。我们计划使用嵌套设计，其中动物处理围栏， 其中系统的RF谐振器、屏蔽、EPR扫描线圈、PET扫描仪和梯度线圈组合在一起 一个紧凑的PET-EPRI插件。插入件将安装在计算机控制的台架上， 定位在EPR所需的电偶极磁体（400 G）内。便携式动物围栏将 包括基准标记网格，以便于与在我们小组的小动物上获得的图像配准， 核磁共振扫描仪。PET/EPRI扫描仪的初始测试将使用标准化测试方案进行 和模拟生理微环境的幻影。为了展示新的 系统，它将用于研究肿瘤细胞内外成分之间的相互作用 微环境本研究将利用自发发育的MMTV-PyMT转基因小鼠， 乳腺癌18F-氟脱氧葡萄糖（FDG）-PET成像将用于量化增强的区域。 糖酵解（细胞内组分），而EPR成像，使用多功能三苯甲基探针，将用于 随着增生的发展，在延长的时间点定量缺氧和酸性区域（细胞外组分）， 转移性乳腺癌由此产生的信息将有助于探索致癌的假设， 发展是一个进化的过程，并说明了组合PET-EPRI扫描仪的独特功能。

The advent of hybrid scanners, combining complementary modalities, has revolutionized imaging; enhancing clinical practice and biomedical research. The standard paradigm is to combine an anatomical imaging method (X-ray CT, for example) with a functional method (PET, for example). In this project we propose a shift of this paradigm by investigating the melding of two complementary, functional imaging methods. Specifically, we plan to integrate a PET scanner with an electron paramagnetic resonance imaging (EPRI) scanner. EPRI is a relatively new method, capable of mapping the in vivo chemical characteristics of tissue. A combined PET- EPRI scanner has the promise to provide new insights into physiologic interactions in microenvironments not currently attainable with current imagers. Development of the PET/EPRI system is technically challenging, requiring unique approaches to scanner design, construction and testing. We will utilize a novel PET scanner that replaces a ring of discrete detector modules with a solid annulus of scintillator (spatial resolution= ~1mm). This design eliminates conductive material needed to construct discrete detector modules. Use of annular scintillator results in high detection sensitivity (~10%) due to elimination of gaps between discrete modules. It also permits estimation of event depth-of-interactions in the detector by correlating light cone shape with depth, a capability not possible with discrete detectors. Arrays of silicon photomultipliers (SiPM), which are not affected by the presence of magnetic fields present in EPR systems, will be used to detect scintillator light. The EPRI system will utilize the rapid scanning method to produce spatial maps of spectra obtained from molecular probes (resolution <1mm). We plan to use a nested design in which the animal handling enclosure, where the system’s RF resonator, shielding, EPR scan coils, PET scanner and gradient coils are combined into a single, compact PET-EPRI insert. The insert will be mounted on a computer-controlled gantry, permitting positioning inside the electro-dipole magnet (400G) required for EPR. The portable animal enclosure will include a grid of fiducial markers to facilitate registration with images acquired on our group’s small animal, MRI scanner. Initial testing of the PET/EPRI scanner will be performed using standardized testing protocols and phantoms emulating physiologic microenvironments. To demonstrate the potential utility of the new system, it will be used in a study of the interaction between the intra-and extracellular components of tumor microenvironments. This investigation will utilize MMTV-PyMT-transgenic mice that spontaneously-develop breast cancer. 18F-fluorodeoxyglucose (FDG)-PET imaging will be used to quantify areas of enhanced glycolysis (intracellular component), while EPR imaging, using a multifunctional trityl probe, will be used to quantify hypoxic and acidic areas (extracellular component) at extended time points as hyperplasia evolves in to metastatic breast cancer. The resulting information will help explore the hypothesis that carcinogenic progression is an evolutionary process, and illustrate the unique capabilities of a combined PET-EPRI scanner.