Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI

Abstract

Oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO 2 ) are key cerebral physiological parameters to identify at-risk cerebrovascular patients and understand brain health and function. PET imaging with [ 15 O]-oxygen tracers, either through continuous or bolus inhalation, provides non-invasive assessment of OEF and CMRO 2 . Numerous tracer delivery, PET acquisition, and kinetic modeling approaches have been adopted to map brain oxygenation. The purpose of this technical review is to critically evaluate different methods for [ 15 O]-gas PET and its impact on the accuracy and reproducibility of OEF and CMRO 2 measurements. We perform a meta-analysis of brain oxygenation PET studies in healthy volunteers and compare between continuous and bolus inhalation techniques. We also describe OEF metrics that have been used to detect hemodynamic impairment in cerebrovascular disease. For these patients, advanced techniques to accelerate the PET scans and potential synthesis with MRI to avoid arterial blood sampling would facilitate broader use of [ 15 O]-oxygen PET for brain physiological assessment.

“Aerobic glycolytic imaging” of human gliomas using combined pH-, oxygen-, and perfusion-weighted magnetic resonance imaging

“…There are other metabolic imaging approaches, such as 15 O PET and 17 O MRI ( Fan et al, 2020 , Zhu and Chen, 2017 ), which can potentially capture Warburg effect of gliomas. For example, 17 O MRI has detected decreased oxygen consumption in gliomas, presumably related to Warburg effect ( Paech et al, 2020 ).…”

Medullary vein architecture modulates the white matter BOLD cerebrovascular reactivity signal response to CO2: observations from high-resolution T2*weighted imaging at 7T

“…For healthy subjects, CBF 29 and CMRO 2 30, 31 are considerably lower in WM as compared to GM. Several studies have reported non-significant differences in the oxygen extraction fraction (OEF) between WM and GM in healthy subjects (see meta-analysis presented in Fan et al 2020 32 ) indicating a regional equilibrium between CBF and CMRO 2 . It follows that changes in venous hemoglobin saturation, along with venous CBV, will drive the WM BOLD signal contrast under hypercapnia.…”

PET Imaging for Oxidative Stress in Neurodegenerative Disorders Associated with Mitochondrial Dysfunction

“…Several MR contrast agents, such as paramagnetic nitroxide radicals (e.g., mito-TEMPO, 3-carbamoyl-PROXYL) and paramagnetic chemical exchange saturation transfer agents, have also been developed to evaluate the redox status in vivo [176][177][178]. As new MR techniques for imaging oxygen metabolism advance, the OEF and oxygen metabolism, as well as oxidative stress, will also be elucidated by MR imaging [179]. However, PET has the advantage of higher detection sensitivity at the nanomolar level [14], which suggests that the optimal approach will be multimodal imaging combining PET and MR [165,180].…”