title: Application of Arterial Spin Labelling as perfusion imaging in acute and chronic ischaemic stroke patients
Creators: name: Mohd, Zanariah Binti
Publisher: name: University of Glasgow
Year: 2023

description: The assessment of cerebral blood flow (CBF) perfusion is an important measure in clinical practice for evaluating the clinical and imaging outcomes in ischaemic stroke patients. Various imaging methods been applied to measure CBF, including applications of nuclear medicine, computed tomography perfusion (CTP) and contrast-enhanced Magnetic Resonance Imaging (MRI). However, each of these modalities has some disadvantages, such as excess radiation or contraindications to contrast agents, and limited repeatability. The thesis aimed to explore the clinical application of arterial spin labelling (ASL) as perfusion imaging among acute and chronic ischaemic stroke patients. Clinical and imaging data in this thesis were obtained from two prospective ischaemic stroke databases, namely WHISPER and XILOFIST. Both studies used ASL as one of the perfusion imaging methods. Methods and results. Before further studies, I conducted various detailed image post-processing steps to acquire the quantitative value of CBF from ASL raw data. The image post-processing steps include structural T1-image processing, creation of grey matter, white matter and lesion masks, distortion correction, and image coregistrations. These post-processing steps were performed using Statistical Parametric Mapping (SPM12) and Bayesian Inference for Arterial Spin Labelling (BASIL) software for studies in Chapter 3 until Chapter 6. In Chapter 3, two commonly used ASL sequences which were PCASL with multi-post labelling delays (multi-PLDs) and PASL (single-PLD), were compared to investigate their agreement. 35 subjects from WHISPER study underwent ASL scanning for both sequences. Grey matter and white matter CBF for these subjects were compared. Although there was a significant correlation between PCASL and PASL in measuring grey matter (r=0.997, p&lt;0.001) and white matter (r=0.991, p&lt;0.001) cerebral perfusion, the Bland-Altman analysis demonstrated large agreement between these ASL sequences suggesting the several systematic biases. These findings suggested that multi-PLDs PCASL sequence is recommended in patients with delayed blood flow, especially in ischaemic stroke patients. Further to this work, the assessment of reperfusion status among 63 WHISPER subjects was measured using PCASL sequence. Reperfusion index (RI) was established as a quantitative indicator by calculating the difference between the reperfusion among recanalised and non recanalised subjects. RI £ 0 – 0.4 indicated mild reperfusion, RI 0.41 to 0.70 indicated moderate reperfusion and RI 0.71 to 1.0 indicated high reperfusion. Correlation and predictions between ASL reperfusion index and clinical and imaging outcomes were statistically analysed. Reperfusion index was significantly correlated with infarct growth (r = 0.421, p&lt;0.001) and positively correlated with penumbra salvage (r = 0.297, p=0.021). Regression analyses showed reperfusion index was a significant independent predictor for early neurological improvement (OR 1.370, 95% CI 0.572 to 16.721; p&lt;0.036) and 90-day good functional outcome (OR 49.817; 95% CI 3.097 – 801.435; p=0.006). In Chapter 6, perfusion assessment of white matter hyperintensities (WMH) among 159 chronic ischaemic stroke patients was investigated in XILOFIST study. Baseline WMH volume and perfusion were calculated. Correlation and predictions between ASL volume and perfusion with associated WMH risk factors and WMH progression were analysed. The result of this study showed WMH perfusion was significantly associated with age and WMH volume. Furthermore, lower WMH perfusion was significantly associated with increased WMH burden as scored using Fazekas score. Conclusions. The studies presented in this thesis demonstrated the clinical application of ASL in quantifying cerebral blood flow among patients with acute and chronic ischaemic stroke. It is concluded that ASL is a suitable imaging technique for continuous cerebral perfusion assessments as it has no radiation risks and is noninvasive. In addition, the reperfusion index measured by ASL can serve as potential imaging biomarkers in predicting imaging and clinical outcomes.