Sensitivity of Multiphase Pseudocontinuous Arterial Spin Labelling (MP pCASL) Magnetic Resonance Imaging for Measuring Brain and Tumour Blood Flow in Mice.
Buck J., Larkin JR., Simard MA., Khrapitchev AA., Chappell MA., Sibson NR.
Brain and tumour blood flow can be measured noninvasively using arterial spin labelling (ASL) magnetic resonance imaging (MRI), but reliable quantification in mouse models remains difficult. Pseudocontinuous ASL (pCASL) is recommended as the clinical standard for ASL and can be improved using multiphase labelling (MP pCASL). The aim of this study was to optimise and validate MP pCASL MRI for cerebral blood flow (CBF) measurement in mice and to assess its sensitivity to tumour perfusion. Following optimization of the MP pCASL sequence, CBF data were compared with gold-standard autoradiography, showing close agreement. Subsequently, MP pCASL data were acquired at weekly intervals in models of primary and secondary brain tumours, and tumour microvessel density was determined histologically. MP pCASL measurements in a secondary brain tumour model revealed a significant reduction in blood flow at day 35 after induction, despite a higher density of blood vessels. Tumour core regions also showed reduced blood flow compared with the tumour rim. Similarly, significant reductions in CBF were found in a model of glioma 28 days after tumour induction, together with an increased density of blood vessels. These findings indicate that MP pCASL MRI provides accurate and robust measurements of cerebral blood flow in naïve mice and is sensitive to changes in tumour perfusion.