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

磁共振成像(MRI)和正电子发射断层扫描(PET)等现代成像技术使我们能够非侵入性地对人体内部工作进行成像。PET创建了注射在患者体内的放射性标记的生物活性分子的三维图像。最常用的PET示踪剂是一种用放射性氟(FDG)标记的葡萄糖类似物，可用于定位代谢活跃的区域，如癌细胞或炎症。然而，由于分辨率和额外的辐射剂量有限，FDG-PET仅限于某些患者和研究。已经提出了一种使用核磁共振成像新陈代谢的替代方法。它依赖于代谢产物中的质子之间的化学交换，如葡萄糖和水中的质子之间的化学交换，这些质子构成了磁共振信号的大部分。利用化学交换饱和转移(CEST)和化学交换敏感自旋锁定(CESL)成像等磁共振方法，我们可以测量由于化学交换引起的信号变化，并将其与葡萄糖、肌酸、谷氨酸等不同代谢物的浓度联系起来。如果可以与FDG-PET相媲美，这将使MRI能够获得通常不能暴露于放射性示踪剂的患者的代谢图像，如孕妇或幼儿。核磁共振还可以获得比正电子发射计算机断层扫描更高分辨率的图像，有可能探测代谢信号的异质性。*西门子Biograph MMR等混合PET/核磁共振系统将正电子发射计算机断层扫描的灵敏度和特异性与核磁共振成像的解剖、结构和功能能力结合在一起，使人们能够对新型正电子发射断层扫描探头和多模式成像方法进行新的研究。为了用PET/MRI同时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系统中的化学交换(CE)敏感的MRI方法。CE-MRI能够以毫摩尔浓度成像葡萄糖、肌酸或谷氨酸等代谢物，而PET能够检测灵敏度高达10亿倍的示踪剂，但一次仅限于一个感兴趣的PET探针。用CE-MRI测量代谢活动将使PET系统自由成像低浓度、疾病特异性的PET探针，产生同时的功能信息，这是任何一种成像技术本身无法实现的。我们认为这可能是PET/MRI的“杀手级应用”之一。*为了测试新的探头和开发新的同步PET/MRI方法，需要一种与MR兼容的PET插入物来同时进行临床前PET/MRI。临床前PET/MRI将在同时测试CE-MRI和PET方法并将它们转化为Bioggraph MMR上的人体研究方面发挥关键作用。作为第二个研究方向，我正在开发临床前PET/MRI系统的方法和应用程序，该系统将补充我们3T PET/MRI的能力。**

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.**