Reproducibility of cerebral blood flow, oxygen metabolism, and lactate and N-acetyl-aspartate concentrations measured using magnetic resonance imaging and spectroscopy

Abstract

In humans, resting cerebral perfusion, oxygen consumption and energy metabolism demonstrate large intersubject variation regardless of methodology. Whether a similar large variation is also present longitudinally in individual subjects is much less studied, but knowing the time variance in reproducibility is important when designing and interpreting longitudinal follow-up studies examining brain physiology. Therefore, we examined the reproducibility of cerebral blood flow (CBF), global cerebral metabolic rate of oxygen (CMRO₂), global arteriovenous oxygen saturation difference (A-V.O₂), and cerebral lactate and N-acetyl-aspartate (NAA) concentrations measured using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques through repeated measurements at 6 h, 24 h, 7 days and several weeks after initial baseline measurements in young healthy adults (N = 26, 13 females, age range 18-35 years). Using this setup, we calculated the correlation, limit of agreement (LoA) and within-subject coefficient of variation (CoV_WS) between baseline values and the subsequent repeated measurements to examine the longitudinal variation in individual cerebral physiology. CBF and CMRO₂ correlated significantly between baseline and all subsequent measurements. The strength of the correlations (R²) and reproducibility metrics (LoA and CoV_WS) demonstrated the best reproducibility for the within-day measurements and generally declined with longer time between measurements. Cerebral lactate and NAA concentrations also correlated significantly for all measurements, except between baseline and the 7-day measurement for lactate. Similar to CBF and CMRO₂, lactate and NAA demonstrated the best reproducibility for within-day repeated measurements. The gradual decline in reproducibility over time should be considered when designing and interpreting studies on brain physiology, for example, in the evaluation of treatment efficacy.

Keywords: N-acetyl-aspartate; arterial spin labelling; cerebral blood flow; cerebral lactate; cerebral metabolic rate of oxygen; phase contrast mapping; reproducibility.