Opportunities and pitfalls in preclinical cerebral blood flow mapping using arterial spin labelling MRI: insights from multicentre data

Abstract

Cerebral blood flow (CBF) is a quantitative metric for mapping perfusion. While the prototypical MRI approach arterial spin labelling (ASL) is well-validated in humans, the reproducibility of rodent ASL mapping remains poor, limiting translational impact. To address this gap, we used both newly acquired and analysis of previously published data to illustrate biological and physical sources of variation in CBF measured with ASL. Via a meta-analysis, we quantified the variation in CBF reported from the cortex of healthy rodents. A total of 23 mouse studies (343 data points) and 5 rat studies (41 data points) met the inclusion criteria. We demonstrate that reported CBF values exhibit a broad variability (50-400 ml/100g/min) driven primarily by experimental confounds rather than physiological differences. Our meta-analysis explores which factors cause variance in perfusion rates measured. Our experimental data highlight biological factors, particularly the choice of anaesthesia (e.g., isoflurane vs. medetomidine) and strain variations, that alter baseline CBF. Our work, reflecting both state-of-the-art and conventional practice in preclinical imaging, highlights the need to account for multiple sources of variability. Establishing community guidelines for rigorous ASL calibration and physiological monitoring will support improved study design and accelerate translational alignment between rodent and human perfusion measurements. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/733736v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1e94d5org.highwire.dtl.DTLVardef@1bd5718org.highwire.dtl.DTLVardef@1a0fafcorg.highwire.dtl.DTLVardef@1bde97d_HPS_FORMAT_FIGEXP M_FIG C_FIG