Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, OX3 7LE, Oxford, UK.
Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, Oxford, UK.
Contrast Media Mol Imaging. 2018 Nov 7;2018:4580919. doi: 10.1155/2018/4580919. eCollection 2018.
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.
脑和肿瘤的血流可以通过动脉自旋标记（ASL）磁共振成像（MRI）进行无创测量，但在小鼠模型中进行可靠的定量仍然很困难。伪连续 ASL（pCASL）被推荐为 ASL 的临床标准，并且可以通过多相标记（MP pCASL）进行改进。本研究旨在优化和验证 MP pCASL MRI 用于测量小鼠的脑血流（CBF），并评估其对肿瘤灌注的敏感性。在优化 MP pCASL 序列后，将 CBF 数据与金标准放射性自显影进行比较，结果显示非常吻合。随后，在原发性和继发性脑肿瘤模型中每周采集一次 MP pCASL 数据，并通过组织学确定微血管密度。在继发性脑肿瘤模型中，尽管血管密度较高，但在诱导后第 35 天，血流明显减少。肿瘤核心区域的血流也比肿瘤边缘减少。同样，在诱导肿瘤 28 天后的胶质瘤模型中也发现 CBF 明显降低，同时血管密度增加。这些发现表明，MP pCASL MRI 可提供未经处理的小鼠脑血流的准确和稳健测量值，并且对肿瘤灌注的变化敏感。
