PET-EPRI

PET-EPRI

• 批准号: 9759919
• 负责人: RAYMOND ROBERT RAYLMAN
• 金额: $ 59.33万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-08 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759919
• 关键词: Anatomy; Animals; Area; Biochemistry; Biological; Biomedical Research; Cell Proliferation; Characteristics; Chemicals; Complex; Computer software; Computers; Cone; Coupled; Detection; Development; Diagnosis; Electromagnetics; Electron Spin Resonance Spectroscopy; Elements; Event; Functional Imaging; Glycolysis; Goals; Heart Neoplasms; Human; Hybrids; Hyperplasia; Hypoxia; Image; Image Enhancement; Imaging technology; Incidence; Individual; Interruption; Investigation; Knowledge; Lead; Light; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Maps; Measurement; Metabolism; Metastatic breast cancer; Metastatic to; Methods; Modality; Molecular Probes; Mouse Mammary Tumor Virus; Mus; Neoplasms; Normal tissue morphology; Photons; Physiological; Physiology; Positioning Attribute; Positron-Emission Tomography; Process; Protocols documentation; Research; Research Personnel; Resolution; Scanning; Shapes; Silicon; Solid; Standardization; Structure; Surface; System; Systems Development; Systems Integration; Technology; Testing; Time; Tissues; Transgenic Mice; Translating; Tumor Markers; Tumor Tissue; X-Ray Computed Tomography; anatomic imaging; animal imaging; base; carcinogenesis; carcinogenicity; clinical practice; design; design and construction; detector; disorder prevention; experience; extracellular; fluorodeoxyglucose positron emission tomography; image registration; imager; imaging modality; imaging potential; imaging probe; imaging system; in vivo; insight; magnetic dipole; magnetic field; malignant breast neoplasm; novel; operation; photomultiplier; portability; pre-clinical; seal; software development; tool; tumor; tumor microenvironment

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.

混合扫描仪的出现结合了互补模式，使成像发生了革命性的变化；增强了 临床实践和生物医学研究。标准的范例是结合解剖成像方法 (例如，X射线CT)和功能方法(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来实现这一范式。具体来说，我们 计划将PET扫描仪与电子顺磁共振成像(EPRI)扫描仪集成在一起。EPRI是一家 相对较新的方法，能够绘制组织的体内化学特征图。一种组合的PET- EPRI扫描仪承诺为微环境中的生理相互作用提供新的见解，而不是 目前可以用现有的成像器来实现。PET/EPRI系统的开发在技术上具有挑战性， 需要独特的扫描仪设计、建造和测试方法。我们将使用一种新型的PET扫描仪 这将用实心闪烁体(空间分辨率=~1 mm)取代一环离散的探测器模块。 这种设计消除了构造分立探测器模块所需的导电材料。环状的使用 由于消除了离散模块之间的间隙，闪烁体具有很高的检测灵敏度(~10%)。它 还允许通过将光锥形状与深度相关来估计探测器中的事件相互作用深度， 这种能力是分立探测器所不能实现的。硅光电倍增管阵列(SiPM)，它们不是 受EPR系统中存在的磁场的影响，将被用于探测闪烁体光。 EPRI系统将利用快速扫描方法生成从以下地点获得的光谱空间地图 分子探针(分辨率<lt；1 mm)。我们计划使用嵌套式设计，在这种设计中，动物处理围栏， 系统的射频谐振器、屏蔽、EPR扫描线圈、PET扫描仪和梯度线圈组合在一起 制成一个紧凑的PET-EPRI插入物。如果允许，插入件将安装在计算机控制的龙门架上 在EPR所需的电偶极磁铁(400g)内定位。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取的图像配准， 核磁共振扫描仪。将使用标准化测试协议执行PET/EPRI扫描仪的初始测试 以及模拟生理微环境的幻影。以展示新的 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。这项研究将利用自发发育的MMTV-PYMT转基因小鼠 乳腺癌。18F-氟代脱氧葡萄糖(FDG)-PET成像将用于量化增强的区域 糖酵解(细胞内成分)，而EPR成像，使用多功能三苯基探针，将用于 随着增殖的进展，量化延长时间点的缺氧区和酸性区(细胞外成分) 转移性乳腺癌。由此产生的信息将有助于探索致癌的假设 进展是一个演变的过程，说明了PET-EPRI组合扫描仪的独特功能。