Variability of physiological brain perfusion in healthy subjects - A systematic review of modifiers. Considerations for multi-center ASL studies

Abstract

Quantitative measurements of brain perfusion are influenced by perfusion-modifiers. Standardization of measurement conditions and correction for important modifiers is essential to improve accuracy and to facilitate the interpretation of perfusion-derived parameters. An extensive literature search was carried out for factors influencing quantitative measurements of perfusion in the human brain unrelated to medication use. A total of 58 perfusion modifiers were categorized into four groups. Several factors (e.g., caffeine, aging, and blood gases) were found to induce a considerable effect on brain perfusion that was consistent across different studies; for other factors, the modifying effect was found to be debatable, due to contradictory results or lack of evidence. Using the results of this review, we propose a standard operating procedure, based on practices already implemented in several research centers. Also, a theory of 'deep MRI physiotyping' is inferred from the combined knowledge of factors influencing brain perfusion as a strategy to reduce variance by taking both personal information and the presence or absence of perfusion modifiers into account. We hypothesize that this will allow to personalize the concept of normality, as well as to reach more rigorous and earlier diagnoses of brain disorders.

Keywords: Arterial spin labeling; cerebral perfusion; deep MRI physiotyping; physiology; variability.

Figure 1.

Schematic representation of the methodology applied to devise an ordinal classification of perfusion-modifiers based on the three modifier criteria.

Figure 2.

Effects of modifiers on global brain perfusion summarized as a color gradient: factors in the green area induce no effect, the blue and red areas represent global decrease and increase respectively. All factors are classified both according to their effect and the corresponding magnitude on global perfusion changes. Other factors, whose value is still unknown, are grouped around the grey rectangle.

Figure 3.

Absolute effects of A1- and A2-modifiers on cerebral perfusion: absolute quantitative information for global (G), grey matter (GM) and white matter (WM) reported in each study was plotted for each A1- and A2-modifier and the mean is visualized.

Figure 4.

Relative effects of A1- and A2-modifiers on cerebral perfusion: relative quantitative information for global (G), grey matter (GM) and white matter (WM) reported in each paper was plotted for each A1- and A2-modifier and the mean is visualized.