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Title: Characterising peritumoural progression of glioblastoma using multimodal MRI
Author: Yan, Jiun-Lin
ISNI:       0000 0004 6424 1014
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2017
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Glioblastoma is a highly malignant tumor which mostly recurs locally around the resected contrast enhancement. However, it is difficult to identify tumor invasiveness pre-surgically, especially in non-enhancing areas. Thus, the aim of this thesis was to utilize multimodal MR technique to identify and characterize the peritumoral progression zone that eventually leads to tumor progression. Patients with newly diagnosed cerebral glioblastoma were included consecutively from our cohort between 2010 and2014. The presurgical MRI sequences included volumetric T1-weighted with contrast, FLAIR, T2-weighted, diffusion-weighted imaging, diffusion tensor and perfusion MR imaging. Postsurgical and follow-up MRI included structural and ADC images. Image deformation, caused by disease nature and surgical procedure, renders routine coregistration methods inadequate for MRIs comparison between different time points. Therefore, a two-staged non-linear semi-automatic coregistration method was developed from the modification of the linear FLIRT and non-linear FNIRT functions in FMRIB’s Software Library (FSL). Utilising the above mentioned coregistration method, a volumetric study was conducted to analyse the extent of resection based on different MR techniques, including T1 weighted with contrast, FLAIR and DTI measures of isotropy (DTI-p) and anisotropy (DTI-q). The results showed that patients can have a better clinical outcome with a larger resection of the abnormal DTI q areas. Further study of the imaging characteristics of abnormal peritumoural DTI-q areas, using MRS and DCS-MRI, showed a higher Choline/NAA ratio (p = 0.035), especially higher Choline (p = 0.022), in these areas when compared to normal DTI-q areas. This was indicative of tumour activity in the peritumoural abnormal DTI-q areas. The peritumoural progression areas were found to have distinct imaging characteristics. In these progression areas, compared to non-progression areas within a 10 mm border around the contrast enhancing lesion, there was higher signal intensity in FLAIR (p = 0.02), and T1C (p < 0.001), and there were lower intensity in ADC (p = 0.029) and DTI-p (p < 0.001). Further applying radiomics features showed that 35 first order features and 77 second order features were significantly different between progression and non-progression areas. By using supervised convolutional neural network, there was an overall accuracy of 92.4% in the training set (n = 37) and 78.5% in the validation set (n=14). In summary, multimodal MR imaging, particularly diffusion tensor imaging, can demonstrate distinct characteristics in areas of potential progression on preoperative MRI, which can be considered potential targets for treatment. Further application of radiomics and machine learning can be potentially useful when identifying the tumor invasive margin before the surgery.
Supervisor: Price, Stephen John Sponsor: Chung Gung Medical Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Glioblastoma ; MRI ; Tumour Progression ; Diffusion tensor imaging ; MRS ; Radiomics