Abstract
PurposeThe aim of the study was to investigate the components of day-to-day variability of repeated phase contrast mapping (PCM) magnetic resonance imaging measurements of global cerebral blood flow (gCBF).Materials and methodsTwo dataset were analyzed. In Dataset 1 duplicated PCM measurements of total brain flow were performed in 11 healthy young volunteers on two separate days applying a strictly standardized setup. For comparison PCM measurements obtained from a previously published study (Dataset 2) were analyzed in order to assess long-term variability in an aged population in a less strictly controlled setup. Global CBF was calculated by normalizing total brain flow to brain volume. On each day measurements of hemoglobin, caffeine and glucose were obtained. Linear mixed models were applied to estimate coefficients of variation (CV) of total (CVt), between-subject (CVb), within-subject day-to-day (CVw), and intra-session residual variability (CVr).ResultsIn Dataset 1 CVt, CVb, CVw and CVr were estimated to be 11%, 9.4%, 4% and 4.2%, respectively, and to 8.8%, 7.2%, 2.7% and 4.3%, respectively, when adjusting for hemoglobin and plasma caffeine. In Dataset 2 CVt, CVb and CVw were estimated to be 25.4%, 19.2%, and 15.0%, respectively, and decreased to 16.6%, 8.2% and 12.5%, respectively, when adjusting for the same covariates.DiscussionOur results suggest that short-term day-to-day variability of gCBF is relatively low compared to between-subject variability when studied in standardized conditions, whereas long-term variability in an aged population appears to be much larger when studied in less a standardized setup. The results further showed that from 20% to 35% of the total variability in gCBF can be attributed to the effects of hemoglobin and caffeine.
Highlights
Quantitative measurements of global cerebral blood flow are of general interest both for basic physiological investigations and for our understanding of brain aging and the pathophysiology of brain diseases [1] Many brain diseases are associated with altered gCBF, and several studies have reported that decreased total brain flow or gCBF may be associated with severity of vascular lesions and brain atrophy [2], impaired cognitive function [3] and may even predict overall future mortality in old age [4]
Our results suggest that short-term day-to-day variability of gCBF is relatively low compared to between-subject variability when studied in standardized conditions, whereas long-term variability in an aged population appears to be much larger when studied in less a standardized setup
The results further showed that from 20% to 35% of the total variability in gCBF can be attributed to the effects of hemoglobin and caffeine
Summary
Quantitative measurements of global cerebral blood flow (gCBF) are of general interest both for basic physiological investigations and for our understanding of brain aging and the pathophysiology of brain diseases [1] Many brain diseases are associated with altered gCBF, and several studies have reported that decreased total brain flow or gCBF may be associated with severity of vascular lesions and brain atrophy [2], impaired cognitive function [3] and may even predict overall future mortality in old age [4]. Previous studies investigating variability of gCBF measurements have mainly focused on separating between-subject variability from residual intra-session variability considered to reflect method imprecision [5,6,7]. These studies have confirmed large and similar betweensubject variability, whereas intra-session variability varies substantially depending on the method applied. Intra-subject variability is expected to increase over time and may depend on both the population studied and the experimental setup
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