Computerized cancer malignancy grading of fine needle aspirates

According to the World Health Organization, breast cancer is a leading cause of death among middle-aged women. Precise diagnosis and correct treatment significantly reduces the high number of deaths caused by breast cancer. Being successful in the treatment strictly relies on the diagnosis. Specifically, the accuracy of the diagnosis and the stage at which a cancer was diagnosed. Precise and early diagnosis has a major impact on the survival rate, which indicates how many patients will live after the treatment. For many years researchers in medical and computer science fields have been working together to find the approach for precise diagnosis. For this thesis, precise diagnosis means finding a cancer at as early a stage as possible by developing new computer aided diagnostic tools. These tools differ depending on the type of cancer and the type of the examination that is used for diagnosis. This work concentrates on cytological images of breast cancer that are produced during fine needle aspiration biopsy examination. This kind of examination allows pathologists to estimate the malignancy of the cancer with very high accuracy. Malignancy estimation is very important when assessing a patients survival rate and the type of treatment. To achieve precise malignancy estimation, a classification framework is presented. This framework is able to classify breast cancer malignancy into two malignancy classes and is based on features calculated according to the Bloom-Richardson grading scheme. This scheme is commonly used by pathologists when grading breast cancer tissue. In Bloom-Richardson scheme two types of features are assessed depending on the magnification. Low magnification images are used for examining the dispersion of the cells in the image while the high magnification images are used for precise analysis of the cells' nuclear features. In this thesis, different types of segmentation algorithms were compared to estimate the algorithm that allows for relatively fast and accurate nuclear segmentation. Based on that segmentation a set of 34 features was extracted for further malignancy classification. For classification purposes 6 different classifiers were compared. From all of the tests a set of the best preforming features were chosen. The presented system is able to classify images of fine needle aspiration biopsy slides with high accurac

Data-driven patient-specific breast modeling: a simple, automatized, and robust computational pipeline

Background: Breast-conserving surgery is the most acceptable option for breast cancer removal from an invasive and psychological point of view. During the surgical procedure, the imaging acquisition using Magnetic Image Resonance is performed in the prone configuration, while the surgery is achieved in the supine stance. Thus, a considerable movement of the breast between the two poses drives the tumor to move, complicating the surgeon's task. Therefore, to keep track of the lesion, the surgeon employs ultrasound imaging to mark the tumor with a metallic harpoon or radioactive tags. This procedure, in addition to an invasive characteristic, is a supplemental source of uncertainty. Consequently, developing a numerical method to predict the tumor movement between the imaging and intra-operative configuration is of significant interest. Methods: In this work, a simulation pipeline allowing the prediction of patient-specific breast tumor movement was put forward, including personalized preoperative surgical drawings. Through image segmentation, a subject-specific finite element biomechanical model is obtained. By first computing an undeformed state of the breast (equivalent to a nullified gravity), the estimated intra-operative configuration is then evaluated using our developed registration methods. Finally, the model is calibrated using a surface acquisition in the intra-operative stance to minimize the prediction error. Findings: The capabilities of our breast biomechanical model to reproduce real breast deformations were evaluated. To this extent, the estimated geometry of the supine breast configuration was computed using a corotational elastic material model formulation. The subject-specific mechanical properties of the breast and skin were assessed, to get the best estimates of the prone configuration. The final results are a Mean Absolute Error of 4.00 mm for the mechanical parameters E_breast = 0.32 kPa and E_skin = 22.72 kPa. The optimized mechanical parameters are congruent with the recent state-of-the-art. The simulation (including finding the undeformed and prone configuration) takes less than 20 s. The Covariance Matrix Adaptation Evolution Strategy optimizer converges on average between 15 to 100 iterations depending on the initial parameters for a total time comprised between 5 to 30 min. To our knowledge, our model offers one of the best compromises between accuracy and speed. The model could be effortlessly enriched through our recent work to facilitate the use of complex material models by only describing the strain density energy function of the material. In a second study, we developed a second breast model aiming at mapping a generic model embedding breast-conserving surgical drawing to any patient. We demonstrated the clinical applications of such a model in a real-case scenario, offering a relevant education tool for an inexperienced surgeon

Computer aided classification of histopathological damage in images of haematoxylin and eosin stained human skin

EngD ThesisExcised human skin can be used as a model to assess the potency, immunogenicity and contact sensitivity of potential therapeutics or cosmetics via the assessment of histological damage. The current method of assessing the damage uses traditional manual histological assessment, which is inherently subjective, time consuming and prone to intra-observer variability. Computer aided analysis has the potential to address issues surrounding traditional histological techniques through the application of quantitative analysis. This thesis describes the development of a computer aided process to assess the immune-mediated structural breakdown of human skin tissue. Research presented includes assessment and optimisation of image acquisition methodologies, development of an image processing and segmentation algorithm, identification and extraction of a novel set of descriptive image features and the evaluation of a selected subset of these features in a classification model. A new segmentation method is presented to identify epidermis tissue from skin with varying degrees of histopathological damage. Combining enhanced colour information with general image intensity information, the fully automated methodology segments the epidermis with a mean specificity of 97.7%, a mean sensitivity of 89.4% and a mean accuracy of 96.5% and segments effectively for different severities of tissue damage. A set of 140 feature measurements containing information about the tissue changes associated with different grades of histopathological skin damage were identified and a wrapper algorithm employed to select a subset of the extracted features, evaluating feature subsets based their prediction error for an independent test set in a Naïve Bayes Classifier. The final classification algorithm classified a 169 image set with an accuracy of 94.1%, of these images 20 were an unseen validation set for which the accuracy was 85.0%. The final classification method has a comparable accuracy to the existing manual method, improved repeatability and reproducibility and does not require an experienced histopathologist

Assessing the applied anatomy knowledge of medical students: the effect of visual resources on preparing them to become new doctors

Anatomical examinations are timed examinations that assess topographical and/or applied knowledge of anatomy with or without the inclusion of visual resources i.e. cadaveric resources, cadaveric images, radiology and/or clinical findings images. Although advances in the multimedia learning theories have led to greater understanding of how we process textual and visual material during learning, the evidence with regard to the use of illustrations within written assessments is scarce. This study investigates whether the presence or absence of images (cadaveric, clinical findings and radiological images) within clinically-oriented single-best-answer questions has a significant influence on medical students' performance. A questionnaire was also included to determine the effect of students’ characteristics and preferences in learning and assessments on their performance. Second year medical students (n=175) from six UK medical schools participated voluntarily. All questions were categorised as to whether their stimulus format was purely textual or included an associated image. The type of images and deep components of images (whether the question is referring to a bone or soft-tissue on the image) was also taken into consideration. Further investigation was carried out on the question-difficulty and the regional anatomy of the questions. These examination scores were then analysed along with students’ responses collected on the questionnaire. This was further illustrated with students’ feedback. The study demonstrates that inclusion of images, the deep component of an image, question difficulty and regional anatomy impact students’ performance. Moreover, students’ preferences play an important role in their performance. Anatomical and radiological images are critical in the medical profession in investigating and examining a patient’s anatomy, and this study set out a way to understand the effects of these images on commonly employed written assessments. This study has shown that image factors and student factors impact on the students’ performance. Further research is needed to refine these examinations

Numerical modeling of thermal bar and stratification pattern in Lake Ontario using the EFDC model

Thermal bar is an important phenomenon in large, temperate lakes like Lake Ontario. Spring thermal bar formation reduces horizontal mixing, which in turn, inhibits the exchange of nutrients. Evolution of the spring thermal bar through Lake Ontario is simulated using the 3D hydrodynamic model Environmental Fluid Dynamics Code (EFDC). The model is forced with the hourly meteorological data from weather stations around the lake, flow data for Niagara and St. Lawrence rivers, and lake bathymetry. The simulation is performed from April to July, 2011; on a 2-km grid. The numerical model has been calibrated by specifying: appropriate initial temperature and solar radiation attenuation coefficients. The existing evaporation algorithm in EFDC is updated to modified mass transfer approach to ensure correct simulation of evaporation rate and latent heatflux. Reasonable values for mixing coefficients are specified based on sensitivity analyses. The model simulates overall surface temperature profiles well (RMSEs between 1-2°C). The vertical temperature profiles during the lake mixed phase are captured well (RMSEs < 0.5°C), indicating that the model sufficiently replicates the thermal bar evolution process. An update of vertical mixing coefficients is under investigation to improve the summer thermal stratification pattern. Keywords: Hydrodynamics, Thermal BAR, Lake Ontario, GIS

The design of an undergraduate chiropractic curriculum

Evidence is provided to support Kierkegaard's phenomenology that only what is learned through experience is truly known. It is demonstrated that the chiropractic curriculum represents a unique area of investigation and that it is possible to define curriculum; to create a functional and integrative model which subsumes elements from the traditional, cyclical and process models; and to design an integrative, problem-based, evidence-based, experiential chiropractic curriculum. A taxonomy is proposed for curriculum design in four domains which deal respectively with a) curriculum processes which include the selection, motivation and interaction of curriculum developers, curriculum definitions and models, and an algorithm for curriculum design; b) curriculum organisation which addresses philosophical, sociological, cultural and psychological foundations, curriculum paradigms and a chiropractic conceptual framework; c) curriculum development which concerns design strategies, situational analysis, intent, content, design and organisation of learning experiences and assessment of student performance; and d) curriculum application, which includes the learning climate, quality management, management of change, self-evaluation and external accreditationCurriculum and Instructional StudiesM. Ed. (Didactics