Influence of residual oxygen-15-labeled carbon monoxide radioactivity on cerebral blood flow and oxygen extraction fraction in a dual-tracer autoradiographic method

Objective: Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with ¹⁵O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating ¹⁵O₂ and C¹⁵O₂ gases. In this protocol, before the sequential PET scan with ¹⁵O₂ and C¹⁵O₂ gases (¹⁵O₂-C ¹⁵O₂ PET scan), a PET scan with C¹⁵O should be preceded to obtain CBV image. C¹⁵O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C ¹⁵O might exist during a ¹⁵O₂-C ¹⁵O₂ PET scan. As the current DARG method assumes no residual C¹⁵O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C¹⁵O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C¹⁵O radioactivity. Methods: In the simulation, normal and ischemic conditions were considered. The ¹⁵O₂ and C ¹⁵O₂ PET count curves with the residual C¹⁵O PET counts were generated by the arterial input function with the residual C¹⁵O radioactivity. The amounts of residual C¹⁵O radioactivity were varied by changing the interval between the C¹⁵O PET scan and ¹⁵O₂-C¹⁵O₂ PET scan, and the absolute inhaled radioactivity of the C¹⁵O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C¹⁵O gas in the input function and PET counts. Results: Our simulations revealed that the CBF and OEF values were underestimated by the residual C¹⁵O radioactivity. The magnitude of this underestimation depended on the amount of C¹⁵O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. Conclusions: This study showed the influence of C ¹⁵O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C ¹⁵O, and the physiological condition.