Multimodal Metabolic Imaging with Hybrid Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) Systems

使用混合正电子发射断层扫描和磁共振成像 (PET/MRI) 系统的多模态代谢成像

• 批准号: RGPIN-2015-05735
• 负责人: Thiessen, Jonathan
• 金额: $ 1.6万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=678802
• 关键词: Multimodal; Metabolic; Imaging; Hybrid; Positron

Modern imaging technologies such as magnetic resonance imaging (MRI) and positron emission tomography (PET) allow us to image, non-invasively, the inner workings of the body. PET creates three-dimensional images of radio-labelled, biologically active molecules that have been injected in a patient. The most commonly used PET tracer is a glucose analogue labelled with radioactive fluorine (FDG), which can be used to locate metabolically active regions, such as cancer cells or inflammation. FDG-PET is limited, however, to certain patients and studies due to limited resolution and additional radiation dose. An alternative method for imaging metabolism has been proposed using MRI. It relies on the chemical exchange between protons in metabolites such as glucose and the protons in water that comprise most of the MRI signal. Using MRI methods such as chemical exchange saturation transfer (CEST) and chemical exchange-sensitive spin lock (CESL) imaging, we can measure the change of signal due to chemical exchange and relate it to the concentration of different metabolites, such as glucose, creatine, and glutamate. If comparable to FDG-PET, this would allow the MRI to acquire metabolic images in patients that normally can't be exposed to radioactive tracers, such as pregnant women or young children. MRI can also acquire images with much higher resolution than PET, potentially probing the heterogeneity of metabolic signals.***Hybrid PET/MRI systems such as the Siemens Biograph mMR combine the sensitivity and specificity of PET with the anatomical, structural and functional capabilities of MRI, enabling new research into novel PET probes and multimodal imaging methods. In order to measure different metabolic and neurotransmitter processes simultaneously with PET/MRI, my lab is developing MRI methods sensitive to chemical exchange (CE) on hybrid PET/MRI systems. CE-MRI is capable of imaging metabolites such as glucose, creatine, or glutamate, at millimolar concentrations whereas PET is capable of detecting tracers with up to a billion-fold increase in sensitivity, but is limited to one PET probe of interest at a time. Measuring metabolic activity with CE-MRI would free the PET system to image low concentration, disease-specific PET probes, yielding simultaneous functional information that would be impossible to achieve with either imaging technology on its own. We believe that this could be one of the "killer applications" for PET/MRI.***In order to test new probes and develop new simultaneous PET/MRI methods, an MR-compatible PET insert is needed for simultaneous preclinical PET/MRI. Preclinical PET/MRI will play a key role in testing simultaneous CE-MRI and PET methods and translating them to human studies on the Biograph mMR. As a second research stream, I am developing methods and applications for a preclinical PET/MRI system that will complement the capabilities of our 3T PET/MRI.**

现代成像技术，如磁共振成像（MRI）和正电子发射断层扫描（PET）使我们能够无创地成像身体的内部运作。PET能生成经放射性标记的生物活性分子的三维图像，这些分子被注射到病人体内。最常用的PET示踪剂是用放射性氟（FDG）标记的葡萄糖类似物，可用于定位代谢活跃区域，如癌细胞或炎症。然而，由于有限的分辨率和额外的辐射剂量，FDG-PET仅限于某些患者和研究。一种替代方法的成像代谢已提出使用MRI。它依赖于代谢物（如葡萄糖）中的质子与水中的质子之间的化学交换，这些质子构成了大部分MRI信号。利用化学交换饱和转移（CEST）和化学交换敏感自旋锁（CESL）成像等MRI方法，我们可以测量化学交换引起的信号变化，并将其与葡萄糖、肌酸和谷氨酸等不同代谢物的浓度联系起来。如果与FDG-PET相媲美，这将使MRI能够获得通常无法暴露于放射性示踪剂的患者（如孕妇或幼儿）的代谢图像。MRI也可以获得比PET更高分辨率的图像，潜在地探测代谢信号的异质性。***混合PET/MRI系统，如西门子Biograph mMR，将PET的灵敏度和特异性与MRI的解剖、结构和功能能力相结合，使新的PET探针和多模态成像方法的研究成为可能。为了同时用PET/MRI测量不同的代谢和神经递质过程，我的实验室正在开发对混合PET/MRI系统的化学交换（CE）敏感的MRI方法。CE-MRI能够成像代谢物，如葡萄糖，肌酸，或谷氨酸，在毫摩尔浓度，而PET能够检测示踪剂高达十亿倍的灵敏度增加，但仅限于一个PET探针感兴趣的时间。使用CE-MRI测量代谢活动将使PET系统能够对低浓度、疾病特异性的PET探针进行成像，同时获得功能信息，这是单独使用任何一种成像技术都无法实现的。我们相信这可能是PET/MRI的“杀手级应用”之一。***为了测试新的探针和开发新的同时PET/MRI方法，需要一种mr兼容的PET插入物用于同时临床前PET/MRI。临床前PET/MRI将在同时测试CE-MRI和PET方法并将其转化为Biograph mMR上的人体研究中发挥关键作用。作为第二个研究流，我正在开发临床前PET/MRI系统的方法和应用，这将补充我们的3T PET/MRI的能力