A theoretical framework for quantification of cerebral metabolic rate of oxygen (CMRO2) using PET/MR

Objectives CMRO2 quantification using 15O-O2 PET requires separate cerebral blood flow (CBF) and volume (CBV) measurements and arterial catheterization to determine whole blood and plasma input functions. We develop a theoretical framework for CMRO2 estimation by combining kinetic models used for PET and MRI to examine the feasibility of a novel single step PET/MR.

Methods A multi-compartment kinetic model is used to examine the effects of various physiologic parameters and sources of variability on CMRO2 estimation. CBF, CBV, and dural venous sinus oxygen saturation (arterial spine labeling, dynamic susceptibility contrast, and T2-relaxation-under-spin-tagging) are combined with dynamic PET data and blood sampling to estimate regional CMRO2. Accuracy was determined by systematically or randomly varying the underlying physiological parameters and simulating PET and MR responses. A detailed model of blood oxygenation dependent (BOLD) signal was used to simulate task specific modulation of brain activity.

Results Our theoretical analysis suggests that systematic modality specific differences in CBF, CBV, and OEF measurements cancel out in CMRO2 estimation. The recirculating labeled water and arterial input function can be estimated from venous blood sampling combined with noninvasive measures (dural sinus venous saturation, total CBF, and arterial and venous blood pool tracer activity), eliminating the need for arterial catheterization. A calibrated BOLD methodology is described for measuring task specific modulations of CMRO2 and neurovascular coupling, as well as quantifying the venous blood volume fraction.

Conclusions CMRO2 is an important physiologic quantity. However, measuring CMRO2 using PET requires complicated steps not practical in most clinical settings. No reliable technique for measuring absolute CMRO2 using MRI exists. The advent of PET/MR makes it possible to measure CMRO2 more efficiently, less invasively, and with markedly less radiation than PET alone.

Research Support UCSD radiology & center for fMRI