Comparison of appearance time in brain between red blood cell and plasma using H₂¹⁵O and¹⁵O₂applying positron...

Background. The appearance time of blood components in the brain provides complementary information about cerebral microvascular dynamics. Plasma and red blood cells (RBCs) behave differently in the microcirculation: while plasma can pass through peripheral layers of capillaries, RBCs carry oxygen and are affected by phenomena such as the Fåhræus-Lindqvist effect and plasma skimming. Our study aims at visualizing these differencesin vivousing H₂¹⁵O PET to assess plasma appearance time (AT_Plasma) and¹⁵O₂PET to assess RBC appearance time (AT_RBC), and demonstrated that the relative delay of RBCs compared with plasma correlates with the oxygen extraction fraction (OEF).Methods. We retrospectively analyzed PET images obtained with¹⁵O₂and H₂¹⁵O administration in 40 patients, comprising a total of 63 scan data. Appearance time images were generated by fitting tissue curves both for the¹⁵O₂(AT_RBC) and H₂¹⁵O phases (AT_Plasma). AT_RBCand AT_Plasmavalues were extracted from regions of interest (ROIs) and compared. Additionally, differences between AT_RBCand AT_Plasma(ΔAT) were analyzed in relation to OEF.Results. AT_RBCand AT_Plasmaimages exhibited similar spatial distributions. A strong correlation was observed between them as AT_RBC= 0.80·AT_Plasma+ 1.8,r= 0.86), with a slope significantly less than unity, suggesting that RBCs flow faster than plasma. The difference between the two (ΔAT) showed a moderate correlation with OEF (r= 0.44), suggesting that higher OEF values are associated with slower RBC movement relative to plasma. This finding suggests that under certain ischemic conditions, RBC flow is more severely impaired than plasma flow.Conclusion. This study demonstrates that AT_RBCand AT_Plasmaare closely related measures of cerebral blood appearance time. The observed association between their difference and OEF suggests a potential link to ischemic pathology.