Regional differences in oxygen extraction fraction in human brain measured by integrated PET/MRI scanner with oxygen-15 labeled gases

Introduction: Measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) by PET with oxygen-15 labeled gases are useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. The OEF is used as an indicator of hemodynamic hypoperfusion. In the present study, the regional differences in OEF in normal brain were investigated in detail with consideration of systemic errors in PET measurements estimated by simulation studies.

Methods: The CBF, CBV, OEF, and CMRO2 were measured on nine healthy men by using integrated PET/MRI scanner with the steady-state method of oxygen-15 labeled gases, carbon monoxide (C15O), oxygen (15O2), and carbon dioxide (C15O2). During each PET scanning, arterial blood sampling was performed to measure the radioactivity concentration in the blood and plasma. The parametric images of CBF, CBV, OEF and CMRO2 were calculated with an attenuation correction using MRI with Dixon sequence. All parametric PET images were transformed into standard brain size and shape by linear and nonlinear parameters using SPM8. Regions of interest were drawn on all anatomically standardized parametric PET images. To estimate systemic errors in OEF caused by regional differences in distribution volume of oxygen-15 labeled water and caused by a mixture of gray and white matter, simulation studies were performed.

Results: OEF value in the cerebral neocortical regions ranged from 0.38 to 0.44 in average. OEF value in the cerebellum and centrum semiovale were 0.36±0.07 and 0.37±0.07, respectively (mean±SD). OEF value in the pons (0.28±0.08) was significantly smaller than the other brain regions. OEF value in the parahippocampal gyrus (0.33±0.08) was significantly smaller than the cerebral neocortical regions. OEF value in the lateral side of the occipital cortex (0.44±0.06) was largest among the cerebral cortical regions. Simulation studies revealed that errors in OEF caused by regional differences in distribution volume of oxygen-15 labeled water were within ± 1% and errors in OEF caused by a mixture of gray and white matter were around 0%.

Conclusions: Systemic errors in OEF measured by PET must be negligibly small. The similar regional distribution of OEF in brain were observed between the present results and previous reports. Smaller OEF in the pons indicates excessive blood flow is supplied as compared with oxygen demand in this region which plays a role of important functions for respiratory and circulation. Smaller OEF in the parahippocampal gyrus indicates also excessive blood flow is supplied as compared with oxygen demand in this region which is of central interest in the complex pathophysiology of Alzheimer’s disease. Largest OEF in the lateral side of the occipital cortex might be related to the longest vascular mean transit time in this region previously reported. The regional differences in OEF in brain must exist which might be related with physiological meanings.

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