Estimation of the regional cerebral metabolic rate of oxygen consumption with proton detected 17O MRI during precision 17O2 inhalation in swine

Abstract

Despite the importance of metabolic disturbances in many diseases, there are currently no clinically used methods for the detection of oxidative metabolism in vivo. To address this deficiency, 17O MRI techniques are scaled from small animals to swine as a large animal model of human inhalation and circulation. The hemispheric cerebral metabolic rate of oxygen consumption (CMRO2) is estimated in swine by detection of metabolically produced H217O by rapid T1ρ-weighted proton magnetic resonance imaging on a 1.5 Tesla clinical scanner. The 17O is delivered as oxygen gas by a custom, minimal-loss, precision-delivery breathing circuit and converted to H217O by oxidative metabolism. A model for gas arterial input is presented for the deeply breathing large animal. The arterial input function for recirculation of metabolic water is measured by arterial blood sampling and high field 17O spectroscopy. It is found that minimal metabolic water “wash-in” occurs before 60 seconds. A high temporal resolution pulse sequence is employed to measure CMRO2 during those 60 seconds after delivery begins. Only about one tidal volume of 17O enriched oxygen gas is used per measurement. Proton measurements of signal change due to metabolically produced water are correlated with 17O in vivo spectroscopy. Using these techniques, the hemispheric CMRO2 in swine is estimated to be 1.23 ± 0.26 μmol/g/min, consistent with existing literature values. All of the technology used to perform these CMRO2 estimates can easily be adapted to clinical MR scanners, and it is hoped that this work will lead to future studies of human disease.

In vivo oxygen-17 NMR for imaging brain oxygen metabolism at high field

“…Nevertheless, this method has been successfully applied to determining CBF where the absolute H 2 17 O concentration is not required [69], and to imaging the CBF changes in tumors [70]. Recently, it has also been attempted for estimating the CMRO 2 in the animal brain [71–73]. …”

In vivo 17 O MRS imaging – Quantitative assessment of regional oxygen consumption and perfusion rates in living brain

“…Several animal species commonly used in preclinical studies have been tested, which include mouse, rat, cat and swine at field strengths from 3T up to 16.4T; the results confirm the feasibility of dynamic in vivo 17 O MRS imaging for studying oxygen metabolism in these preclinical models [35, 38, 39, 48, 50–52]. This novel 17 O-MR based CMRO 2 imaging technique has been successfully applied to Huntington disease mouse brains and used as a metabolic imaging tool to assess the mitochondrial function in diseased brain in vivo by directly determining the cerebral oxygen consumption deficit under metabolic stress [51].…”

Depression of whole-brain oxygen extraction fraction is associated with poor outcome in pediatric traumatic brain injury

“…However, because of the global nature of our measurement it may be insensitive to small focal areas of ischemia. Future studies of OEF abnormalities in pediatric TBI patients will include concurrent regional measurements of CBF and OEF to further address the complexities of oxygen metabolism studies in diffuse brain injury (16,24,25). It is important to note that a subset of patients recovered clinically but had persistently low OEF values.…”