published_or_final_version / abstract / toc / Diagnostic Radiology / Master / Master of Philosophy

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

Introduction Peritoneal metastasis is advanced disease and is usually widely disseminated at the time of discovery. It is crucial to detect peritoneal metastasis at an early stage and to allow precise patient selection for the right treatments. Both fluorodeoxyglucose positron emission tomography/computed tomography (FDGPET/CT) and magnetic resonance imaging (MRI) are used in peritoneal metastasis detection. Standardized uptake value (SUV), derived from FDGPET/ CT can evaluate glucose metabolism in cells, whilst apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI) is used for quantitative analysis of tumour cellularity. Amide proton transfer (APT) MRI is a novel imaging technique based on exchangeable amide protons as endogenous contrast agent and can measure the increased amide proton signal in malignant tissues indirectly through bulk water proton signals. This thesis aims to: 1) compare the diagnostic performance of FDG-PET/CT and MRI in peritoneal metastasis evaluation; 2) study the relationship between SUV and ADC in peritoneal metastasis; 3) investigate the feasibility of APT in peritoneal metastasis evaluation. Materials and Methods Patients with peritoneal metastasis detected on FDG-PET/CT were prospectively recruited for MRI. FDG-PET/CT and MRI images were reviewed independently by two radiologists in separate sessions. Diagnostic characteristics were calculated for both imaging techniques. SUVmax and SUVmean were obtained by placing ROIs on PET, while ADCmin and ADCmean were calculated by contouring lesions on DWI. APT MRI was performed using a single-slice turbo spin echo sequence, with a block of presaturation pulses at 33 frequency offsets. ROIs were placed on peritoneal metastasis and muscle on APT. Mean of integrated asymmetrical magnetic transfer ratio (MTRasym) over 3-4 ppm with respect to water resonance was calculated for peritoneal metastasis and muscle. Results Eight patients were recruited in this study with 128 anatomical sites evaluated. DWI/MRI had good diagnostic performance (sensitivity = 92%, specificity = 99%, accuracy = 98%) compared to that of FDG-PET/CT (sensitivity = 90%, specificity= 100%, accuracy = 98%). Thirty-four peritoneal metastases were selected for quantitative analysis. Significant inverse correlation was found between ADCmean and SUVmax (r = -0.528, p = 0.001) and between ADCmean and SUVmean (r = -0.548, p = 0.001). ADCmin was significantly and negatively correlated with SUVmax (r = -0.508, p = 0.002) and SUVmean (r = -0.513, p = 0.002). In the above study cohort, 6 patients underwent APT imaging with 8 peritoneal metastases evaluated. Seven lesions showed positive APT signal and one had negative APT signal. The mean APT signal for peritoneal metastasis was 2.28%±1.76%, significantly different from that of muscle (-2.79%±0.95%, p < 0.001). Conclusions In conclusion, both DWI/MRI and FDG-PET/CT had good diagnostic performance in peritoneal metastasis evaluation. The negative correlation between SUV and ADC suggested an inverse relationship between tissue metabolism and cellularity. APT MRI is feasible to generate sufficient contrast signal for peritoneal metastasis and has potential to discriminate peritoneal tumours from its surrounding soft tissue using integrated MTRasym as a quantitative marker. These functional indices allow understanding of the biological behaviours of peritoneal tumours and could act as adjuncts in peritoneal metastasis imaging. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

Submitted in fulfillment of Masters in Radiography, Durban University of Technology, Durban, 2007. / Aim/research questions The aim of the study was to evaluate CT-based treatment planning versus digitised image planning (standard planning technique) for carcinoma of the breast, using the four-field breast technique, in terms of the depth of supraclavicular and axillary nodes, the variability of the breast tissue and the dose inhomogeneity at the matchline. The variability of the depth of supraclavicular and axillary nodes has not been documented in any local or national studies. When simulating patients for treatment, it is evident that the anatomical variability of patient chest wall thickness, shape and size is a contributing factor towards the final treatment plan and dose distribution achieved. Therefore knowing the correct depth of the nodes and being able to clearly demarcate the breast tissue should result in a favourable dose administration. The following questions were addressed:  What is the dose to the supraclavicular nodes from both plans?  What is the dose to the axillary nodes from both plans?  How do the plans differ in terms of dose coverage to the supraclavicular and axillary nodes?  What is the relationship between the depth of the supraclavicular nodes and the patient separation? ii  What is the relationship between the depth of the axillary nodes and the patient separation?  Does the target volume receive adequate dose coverage from the plans?  How is dose to the heart volume affected by target coverage on both plans?  How is dose to the lung volume affected by target coverage on both plans?  What is the dose variability along the matchline?  Are the plans over dosing?  Are the plans under dosing? / M

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

Thesis (M.Tech.: Radiography)-Dept. of Radiography, Durban University of Technology, 2007 xxiv, 142 leaves, Annexures A-L / The aim of the study was to evaluate CT-based treatment planning versus digitised image planning (standard planning technique) for carcinoma of the breast, using the four-field breast technique, in terms of the depth of supraclavicular and axillary nodes, the variability of the breast tissue and the dose inhomogeneity at the matchline.

Introdução: A definição do volume-alvo macroscópico, principalmente referente a casos de câncer de pulmão, exige o maior número de informações possíveis no que diz respeito à localização, extensão e mobilidade tumoral. A literatura demonstra um importante avanço quando utilizada imagens metabólicas como é o caso da tomografia por emissão de pósitron/tomografia computadorizada (PET/CT), porém a sua aplicação nos planejamentos radioterápicos ainda é muito discutida devido ao seu grau de complexidade. Objetivos: Avaliar o impacto da PET/CT no delineamento tumoral em casos de câncer de pulmão não-pequenas células (CPNPC) e linfonodos regionais. Materiais e Métodos: Foram selecionados retrospectivamente estudos de PET/CT de 26 casos de câncer de pulmão. Todos foram confirmados por biópsia, sendo em sua totalidade CPNPC. Todos os estudos foram realizados em um equipamento de PET/CT dedicado com parâmetros de aquisição idênticos. A interpretação das imagens e posterior delineamento foram realizados por dois médicos experientes, um radioterapeuta e um nuclear/radiologista. Os parâmetros ótimos de visualização foram pré-definidos, sendo mandatórios para os delineamentos. Os delineamentos foram realizados em duas etapas principais. A primeira relacionada ao desenho tumoral somente pela CT e a segunda, após no mínimo duas semanas de descanso visual, referindo-se ao desenho tumoral pela PET/CT. Somente o volume tumoral macroscópico (GTV) e os linfonodos regionais aumentados ou PET positivos foram delineados. Índices de conformidades (IC) foram calculados, tanto interobservadores (11 casos), quanto intra-observador (26 casos). Para a comparação entre observadores e entre delineamentos em relação ao volume, foi considerado o teste não-paramétrico de Wilcoxon. As comparações em relação ao IC foram feitas usando-se o teste t de Student para amostras pareadas. Em todos os testes, valores de p <0,05 indicaram significância estatística. Os dados foram analisados com o programa computacional SPSS® Statistics 17.0 (EUA). Resultados: A análise dos dados demonstrou diferença significativa entre os volumes médios delineados na CT e na PET/CT (p = 0,02), com evidente redução volumétrica no delineamnto por PET/CT. Houve diferença significativa entre os volumes CT delineados pelos dois observadores (p = 0,03) e uma tendência a apresentar diferença significativa entre volumes PET/CT (p = 0,05). A avaliação volumétrica intraobservador foi significativa (p < 0,01) apenas para o médico nuclear/radiologista, com redução de até 51% do volume CT e uma relação entre modalidades de 2,11 ± 0,22. Na análise dos IC, não houveram diferenças significativas entre as duas modalidades de imagem (p = 0,598). A análise dos IC intra-observadores demonstrou que para o radioterapeuta a PET/CT apresenta um impacto de 46% (IC médio = 0,54 ± 0,06), já para o nuclear/radiologista, o impacto foi de 65% (IC médio = 0,35 ± 0,06), representando uma diferença significativa (p = 0,03) em relação ao IC entre o médicos observadores. Para a análise linfonodal a PET/CT apresentou importante diferença na visualização de linfonodos, alterando 10 dos 26 casos, sendo 9 para a positividade apenas na fusão. Conclusão: A PET/CT apresentou significativo impacto no desenho do GTV e linfonodos regionais para casos de CPNPC. / Introduction: The definition of gross target volume, especially concerning cases of lung cancer, requires the greatest amount of information possible with regard to location, tumor size and tumor mobility. The literature demonstrates an important advancement using metabolic images such as PET/CT, however, its application in radiotherapy planning is still controversial due to its complexity. Objectives: To assess the impact of PET/CT in tumor delineation in cases of non-small cell lung cancer and regional lymph nodes as additional findings. Materials and Methods: Retrospectively studies of PET/CT of 26 lung cancer cases were selected. All were confirmed by biopsy, in its entirety NSCLC. All studies were performed on a PET/CT with dedicated acquisition identical parameters. Image interpretation and subsequent delineation were performed by two experienced physicians, one radiotherapist and the another nuclear/radiologist. The optimal parameters display were pre-defined, being mandatory for the designs. Each case received an identification of three random letters to access the medical images to be analyzed. The delineation was made in two main steps. The first reference to the drawing only in tumor CT and the second, after two weeks of visual rest, referring to the drawing on tumor PET/CT. Only the gross tumor volume (GTV) and regional lymph nodes were enlarged or PET + outlined. Conformity index (CI) were calculated both interobserver (11 cases), and intra-observer (26 cases). For comparison between observers and between designs in relation to the volume, was considered the nonparametric Wilcoxon test. Comparisons regarding the conformity index were made using the Student t test for paired samples. To assess the degree of agreement regarding positive lymph nodes were estimated with kappa coefficients of agreement. In all tests, p values <0.05 were considered statistically significant. Data were analyzed with the software SPSS Statistics 17.0 (USA). Results: Data analysis showed significant difference between the average volumes delineated on CT and PET/CT (p = 0.02), with obvious volume reduction. Significant difference between the volumes delineated by CT observars medical distinct classes (p = 0.03) and a tendency to present significant difference between volumes PET / CT (p = 0.05). The intraobserver volumetric evaluation was significant (p <0.001) only for observer 2, being the nuclear medicine physician / radiologist, reducing up to 51% of the volume CT and a relationship between methods of 2.11 ± 0.22. In the analysis of CI, there were no significant differences between the two imaging modalities (p = 0.598).CI analysis showed that intra-observer to observer 1 PET / CT has an impact of 46% (average CI = 0.54 ± 0.06). The viewer 2, the impact was greater, 46% (average IC = 0.39 ± 0.03), representing a difference of opinion regarding the CI (p = 0.03) between the medical classes. To regional lymph nodes with PET/CT revealed an important difference in the visualization of lymph nodes, changing 10 of the 26 cases, 9 to positivity only in the image fusion.Conclusion: PET/CT has a significant impact on the design of the GTV and regional lymph nodes in cases of NSCLC.