Author/Authors :
Buck, Jessica Department of Oncology - University of Oxford - Oxford, UK , Larkin, James R Department of Oncology - University of Oxford - Oxford, UK , Simard, Manon A Department of Oncology - University of Oxford - Oxford, UK , Khrapitchev, Alexandre A Department of Oncology - University of Oxford - Oxford, UK , Chappell, Michael A University of Oxford - Old Road Campus Research Building - Oxford - Oxford, UK , Sibson, Nicola R Department of Oncology - University of Oxford - Oxford, UK
Abstract :
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 dificult. Pseudocontinuous ASL (pCASL) is recommended as the clinical
standard for ASL and can be improved using multiphase labelling (MP pCASL). e 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. ese findings indicate that MP pCASL MRI provides
accurate and robust measurements of cerebral blood flow in na¨ıve mice and is sensitive to changes in tumour perfusion.