Non-invasive quantification of cerebral oxygen metabolism by hybrid positron emission tomography/magnetic resonance imaging

Lucas Diovani Lopes Narciso, The University of Western Ontario

Abstract

Although positron emission tomography (PET) remains the gold standard for quantifying cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂), the procedures are invasive and complex, requiring arterial sampling and accounting for blood-borne activity. Non-invasive methods generally require extracting an image-derived input function (IDIF) from the carotid arteries; however, these methods are sensitive to partial volume errors due to the poor spatial resolution of PET. Hybrid PET/magnetic resonance imaging (MRI) offers an alternative non-invasive approach by using MRI to calibrate PET data. PET/MR imaging of oxidative metabolism (PMROx) is a reference-based approach that uses whole-brain (WB) measurements of oxygen extraction fraction and CBF to calibrate [¹⁵O]O₂-PET data. Similarly, PET/MR imaging of CBF (PMRFlow) requires only WB CBF to calibrate dynamic [¹⁵O]H₂O-PET data. Both methods avoid the need for invasive arterial sampling while maintaining the ability to quantify CBF and CMRO₂.

This thesis contains the theoretical framework of PMROx, along with error analyses and an assessment on PET data acquired from healthy participants (n = 10), followed by its validation in an animal model by comparison to PET-alone measurements (n = 8). Additionally, the MRI-perfusion technique arterial spin labeling was used to further simplify PMROx by replacing [¹⁵O]H₂O-PET, and PMROx was demonstrated to be sensitive to anesthetics-induced changes in metabolism. The accuracy of a PMRFlow approach of obtaining the IDIF (PMRFlow_IDIF) from the WB [¹⁵O]H₂O time-activity curve (TAC) was assessed in a porcine model by comparison to PET-only CBF measurements (n = 12). The ability of the method to remove blood-borne signal was demonstrated by generating CBF images for healthy individuals (n = 13).

In summary, results demonstrated the feasibility of producing quantitative CBF and CMRO₂ images by PET/MRI without the need for invasive blood sampling. PMROx circumvents many of the complexities of traditional PET CMRO₂ imaging and has the potential to reduce PET imaging to [¹⁵O]O₂ only. PMRFlow_IDIF is an easy-to-implement method that benefits from the high signal-to-noise ratio of the WB TAC and does not require vessel segmentation. Future studies involving human participants are required to fully validate these approaches, both in the healthy brain and in disorders characterized by disruptions in cerebral hemodynamics and metabolism.