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

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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.**