published_or_final_version / Clinical Oncology / Master / Master of Philosophy

published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer ranked as the 5th most common in Hong Kong. We aimed to study the role of dynamic contrast-enhanced MRI (DCE-MRI) and dynamic 2-deoxy-2-[fluorine-18]fluoro -D-glucose positron emission tomography (FDG-PET) for characterizing NPC tumors in newly-diagnosed patients, and to quantitatively evaluate the intratumoral heterogeneity of NPC. In Chapter 2 we employed semi-quantitative analysis of DCE-MRI to study the dynamic enhancement pattern by analyzing the time-intensity curves in 25 NPC patients. Our findings suggested that high blood flow caused a high initial intensity enhancement rate (ER), and that neovasculature due to tumor angiogenesis in tumors of larger volume or higher T-stage caused more accumulation of contrast agent which can be detected by DCE-MRI. PET and semi-quantitative DCE-MRI parameters were not correlated and may reflect different physiological/molecular processes in the microenvironment of NPC tumor. However the major limitation of semi-quantitative analysis was that the physiological correlates of these parameters were unclear. In Chapter 3 we applied quantitative analysis of DCE-MRI to study the permeability and perfusion characteristics in the same cohort as in Chapter 2. Our findings implied that the permeability may be high compared to blood flow in NPC tumor. We also observed significant correlations between iAUC (the initial area under the time-intensity curve) by semi-quantitative analysis and ve (the volume fraction of extravascular extracellular space) by quantitative analysis, and between the two rate constants (kep’s) from these two methods, which showed that semi-quantitative analysis was a feasible alternative in reflecting the physiological characteristics of NPC. However, we did not observe any significant correlation between PET and DCE-MRI quantitative parameters, also suggesting that PET and DCE-MRI reflected different physiological information in NPC. In Chapter 4 we applied dynamic PET scan to study the glucose metabolism in 18 NPC tumors (16 included in DCE-MRI cohort). Our findings showed that the overall FDG uptake was mainly composed of the FDG in tissue compartment (Ki), which was governed by the phosphorylation (k3) but not the transport of FDG (K1). This finding may further indicate a potential role of the phosphorylation rate k3 in NPC. Dynamic PET parameters did not correlate with DCE-MRI, indicating that the two modalities reflect different molecular information in NPC. In Chapter 5, intratumoral heterogeneity in NPC tumors of 40 patients was studied using 18F-FDG PET scan. Our findings showed that as tumors grew to a larger volume and higher T-stage, they showed more heterogeneous glucose metabolism. It was found that more heterogeneous tumor was associated with worse disease-free survival, indicating that tumor metabolic heterogeneity may play an important role for NPC patient prognosis. To summarize, these results showed that DCE-MRI and dynamic PET improved our understanding about the physiological/molecular process of NPC, and, these two modalities reflected different physiological information in the microenvironment of NPC tumors. This indicated that the relationship between supply of nutrients such as glucose and blood flow/permeability is complex and not directly related. Moreover, intratumoral heterogeneity by PET scan was also of importance in prognostication. / published_or_final_version / Diagnostic Radiology / Doctoral / Doctor of Philosophy

Medical imaging informatics is one of the important research areas in radiology that studies how information available on medical images is retrieved, analyzed, and enhanced. Recent development in medical imaging informatics has resulted in improvement of diagnostic accuracy based on imaging examinations, as well as efficiency in clinical workflow. Computer aided diagnosis (CAD) and electronic patient record system (ePR) are both topics in medical imaging informatics that have matured from research concepts into commercially available computerized systems in clinical environment. The current challenges are to further broaden their scope of applications. In this thesis project, I developed a CAD system for interpreting PET/CT examinations and an ePR system for patient data integration in neurosurgery suites. Specifically, the CAD system in this project was designed to automatically diagnose nasopharyngeal carcinoma (NPC) on Positron emission tomography/computed tomography (PET/CT) examinations, which aimed to detect and classify both the primary NPC and its nodal metastasis. The regions of interests (ROIs) were segmented from the PET images and registered onto the CT in order to combine the imaging features from both modalities and the a priori anatomical knowledge of the suspicious lesion. These combined features were then classified by a support vector machine (SVM) to generate the final diagnosis result. The system was validated with 25 PET/CT examinations from 10 patients suffering from NPC, and the result produced by the system was compared to the gold standard of lesions manually contoured by experienced radiologists. The results confirmed that the system successfully distinguished all 53 genuine lesions from the mimickers due to normal physiological uptake and artifacts that also produced potentially confusing signals. The second part of the project involved development of an electronic patient record system (ePR) that integrated all the myriad of images and different types of clinical information before, during, and after neurosurgery operations, in order to enhance efficiency of work flow in this unique clinical environment. The system comprises of pre-, intra-, and post-operation modules which correspond to the different stages of the neurosurgery. The pre-op module was developed to store and categorize all images and data before the procedure to assist the surgeons in planning operation. The intra-op module integrates all the input signals, waveforms, images and videos that are produced by different imaging and physiological monitoring devices in the operation room during the surgery, and displays all the relevant information in a single large screen in real time to ease monitoring of the procedure. The post-op module helps surgeons to review all the data acquired from all the prior stages for follow-up of the treatment outcome. One-tumor case was utilized to test the pre-op module, and the signals and waveforms simulators were used to evaluate the performance of the intra-op module. In summary, two different medical informatics systems, a CAD and an ePR system were developed. Both showed promising results in laboratory tests. Future work would involve performance enhancement and feedback of the systems, and ultimately evaluation of these systems in the clinical environment. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy