Development of Novel MRI Biomarkers for the Early Detection of Tumour Recurrence from Treatment Induced Brain Injury

Abdulrahman Al Sayyari (2010). Development of Novel MRI Biomarkers for the Early Detection of Tumour Recurrence from Treatment Induced Brain Injury PhD Thesis, School of Medicine, The University of Queensland.

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Author Abdulrahman Al Sayyari
Thesis Title Development of Novel MRI Biomarkers for the Early Detection of Tumour Recurrence from Treatment Induced Brain Injury
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2010-06
Thesis type PhD Thesis
Supervisor Prof. Stephen Rose
Prof. Alan Coulthard
Prof. Graham Galloway
Total pages 121
Total colour pages 24
Total black and white pages 197
Subjects 11 Medical and Health Sciences
Abstract/Summary The rapid expansion of knowledge about the factors leading to cancerous proliferation of cells and the introduction of new drugs for the treatment of cancer, in conjunction with improved neurosurgical resectioning techniques and delivery of radiotherapy, now make it possible for brain tumours to be rationally treated. However, despite these major advances, the prognosis for patients with malignant brain tumours remains poor with a median survival rate of less than one year. Outcome measures that are commonly used to assess new therapies include mortality and radiographic treatment outcomes. Current neuroimaging strategies utilising computed tomography (CT), magnetic resonance imaging (MRI) and [F18] fluorodeoxyglucose (FDG) positron emission tomography (PET) do not reliably establish efficacy and long-term treatment outcome. A significant problem is the difficulty of differentiating residual or potential tumour regrowth from radiation-induced brain injury. Recurrent tumour (RT) and therapy-induced brain injury share many common radiological features, mainly due to damage of the blood-brain barrier (BBB). These include o T2 prolongation due to vasogenic oedema, gliosis or tumour on MRI o Enhancement after administration of contrast agent on T1-weighted MRI o Varying degrees of mass effect The aim of this research study was to investigate the role of two relatively new non-invasive MRI techniques, namely diffusion-weighted imaging (DWI) and susceptibility weighted imaging (SWI) to determine whether a tumour has been successfully treated or is regrowing despite treatment. Both of these techniques are ideally suited to monitor treatment progress; DWI can measure the microstructural integrity of brain tissue, whilst SWI has the potential to accurately delineate tumour necrosis and vascularity within the tumour and perilesional territory. In comparison to contrast enhanced T1-weighted MRI, post contrast SWI maps offer alternative contrast mechanisms for studying tumour recurrence and tissue injury associated with radiation injury. The innovative aspect of combining these two imaging modalities to measure early treatment response is that diffusion indices can be measured from actual brain / tumour tissue exhibiting perturbed BBB function rather than from necrotic or radiation injured tissue which have less specific BBB leakage profiles. Such an approach has the potential to increase the accuracy of monitoring treatment progress, especially delineating the early presence of possible tumour recurrence. Twenty three patients who were being treated for high-grade glial neoplasms took part in the study. All patients presented with new enhancing lesions on follow-up CE-T1. Recurrence or chemoradiation injury was confirmed from either histologic analysis or extensive clinical follow-up. Regions of enhancement on registered CE-SWI and CE-T1 images were extracted in a semiautomated fashion and transferred to coregistered ADC maps. This process required the development of an automated image processing pipeline for the robust determination and visualisation of ADC derived tissue signatures suitable for clinical practice. Significant differences in ADC measures defined within the enhancement volumes on serial MR images were analysed by using a nonparametric Kolmogorov-Smirnov approach and correlated with clinical follow-up diagnoses. Analysis of the serial data revealed that patients with a diagnosis of tumour recurrence had significantly reduced ADC measures within the enhancement volume delineated on CE-SWI. In contrast, patients with stable disease (SD) had significantly elevated ADC within the CE-SWI enhancement volume. The findings of an increase in enhancement volume delineated on serial CE-SWI maps, along with a concomitant reduction in ADC within this volume for patients with recurrent tumour, provide support for such an approach to be used to assist in follow-up patient management strategies.
Keyword ADC _ apparent diffusion coefficient; BBB _ blood-brain barrier; CE-SWI _ contrast-enhanced susceptibility-weighted imaging; CE-T1 _ contrast-enhanced T1-weighted imaging; FMRIB _ Functional Magnetic Resonance Imaging of the Brain; GBM _ glioblastoma multiform; MRI _ MR imaging; No E _ no constant enhancement; Pseudo _ evidence of a secondary pseudoprogressive lesion; RT _ recurrent tumour; SD _ stable disease; SWI _ susceptibility- weighted imaging; Vol _ volume; WHO _ World Health Organization
Additional Notes 34,38,42.44,65,69,77,78,79,80,83,84,87,88,90,91,93,94,95,96,104,105,120,121

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Created: Sat, 26 Feb 2011, 05:08:43 EST by Mr Abdulrahman Al Sayyari on behalf of Library - Information Access Service