An improved joint optimization of multiple level set functions for the segmentation of overlapping cervical cells

In this paper, we present an improved algorithm for the segmentation of cytoplasm and nuclei from clumps of overlapping cervical cells. This problem is notoriously difficult because of the degree of overlap among cells, the poor contrast of cell cytoplasm and the presence of mucus, blood, and inflammatory cells. Our methodology addresses these issues by utilizing a joint optimization of multiple level set functions, where each function represents a cell within a clump, that have both unary (intracell) and pairwise (intercell) constraints. The unary constraints are based on contour length, edge strength, and cell shape, while the pairwise constraint is computed based on the area of the overlapping regions. In this way, our methodology enables the analysis of nuclei and cytoplasm from both free-lying and overlapping cells. We provide a systematic evaluation of our methodology using a database of over 900 images generated by synthetically overlapping images of free-lying cervical cells, where the number of cells within a clump is varied from 2 to 10 and the overlap coefficient between pairs of cells from 0.1 to 0.5. This quantitative assessment demonstrates that our methodology can successfully segment clumps of up to 10 cells, provided the overlap between pairs of cells is <0.2. Moreover, if the clump consists of three or fewer cells, then our methodology can successfully segment individual cells even when the overlap is ∼0.5. We also evaluate our approach quantitatively and qualitatively on a set of 16 extended depth of field images, where we are able to segment a total of 645 cells, of which only ∼10% are free-lying. Finally, we demonstrate that our method of cell nuclei segmentation is competitive when compared with the current state of the art.Zhi Lu, Gustavo Carneiro, and Andrew P. Bradle

Medical image segmentation using edge-based active contours.

The main purpose of image segmentation using active contours is to extract the object of interest in images based on textural or boundary information. Active contour methods have been widely used in image segmentation applications due to their good boundary detection accuracy. In the context of medical image segmentation, weak edges and inhomogeneities remain important issues that may limit the accuracy of any segmentation method formulated using active contour models. This thesis develops new methods for segmentation of medical images based on the active contour models. Three different approaches are pursued: The first chapter proposes a novel external force that integrates gradient vector flow (GVF) field forces and balloon forces based on a weighting factor computed according to local image features. The proposed external force reduces noise sensitivity, improves performance over weak edges and allows initialization with a single manually selected point. The next chapter proposes a level set method that is based on the minimization of an objective energy functional whose energy terms are weighted according to their relative importance in detecting boundaries. This relative importance is computed based on local edge features collected from the adjacent region inside and outside of the evolving contour. The local edge features employed are the edge intensity and the degree of alignment between the images gradient vector flow field and the evolving contours normal. Finally, chapter 5 presents a framework that is capable of segmenting the cytoplasm of each individual cell and can address the problem of segmenting overlapping cervical cells using edge-based active contours. The main goal of our methodology is to provide significantly fully segmented cells with high accuracy segmentation results. All of the proposed methods are then evaluated for segmentation of various regions in real MRI and CT slices, X-ray images and cervical cell images. Evaluation results show that the proposed method leads to more accurate boundary detection results than other edge-based active contour methods (snake and level-set), particularly around weak edges

SISTEMA DE CLASIFICACIÓN DE CÉLULAS PATOLÓGICAS EN CITOLOGÍA CERVICAL

El cáncer de cuello uterino es el cuarto más frecuente en las mujeres de todo el mundo según la Organización Mundial de la Salud, aunque su incidencia ha disminuido mediante la aplicación de diversas políticas de prevención y tamizaje, siendo la principal el estudio de Papanicolaou. Dichas medidas han significado un aumento importante en la cantidad de trabajo de los médicos citopatólogos, llegando a producir sobrecarga y escasez de personal calificado. Siendo la observación de las imágenes microscópicas la etapa final del estudio, y la que más impacta en el trabajo de los médicos, proponemos la aplicación de métodos de Deep Learning y técnicas novedosas de visión computacional, a efectos brindar apoyo a los profesionales en esta tarea. Aunque el desarrollo del algoritmo que clasificará diferentes tipos de atipias aún se encuentra en etapa de desarrollo, aspiramos a colaborar en una reducción de carga de trabajo de los profesionales, con la posibilidad de beneficiar también a los pacientes mediante diagnósticos más rápidos y confiables. Además, se presenta un nuevo conjunto de datos de imágenes diversas de citología en base líquida, marcadas y etiquetadas según la clasificación del sistema Bethesda.

Development of a cell-based lab-on-a-chip sensor for detection of oral cancer biomarkers

textOral cancer is the sixth most common cancer worldwide and has been marked by high morbidity and poor survival rates that have changed little over the past few decades. Beyond prevention, early detection is the most crucial determinant for successful treatment and survival of cancer. Yet current methodologies for cancer diagnosis based upon pathological examination alone are insufficient for detecting early tumor progression and molecular transformation. Development of new diagnostic tools incorporating tumor biomarkers could enhance early detection by providing molecular-level insight into the biochemical and cellular changes associated with oral carcinogenesis. The work presented in this doctoral dissertation aims to address this clinical need through the development of new automated cellular analysis methods, incorporating lab-on-a-chip sensor techniques, for examination of molecular and morphological biomarkers associated with oral carcinogenesis. Using the epidermal growth factor receptor (EGFR) as a proof-of-principle biomarker, the sensor system demonstrated capacity to support rapid biomarker analysis in less than one-tenth the time of traditional methods and effectively characterized EGFR biomarker over-expression in oral tumor-derived cell lines. Successful extension from in vitro tumor cell lines to clinically relevant exfoliative brush cytology was demonstrated, providing a non-invasive method for sampling abnormal oral epithelium. Incorporation of exfoliative cytology further helped to define the important assay and imaging parameters necessary for dual molecular and morphological analysis in adherent epithelium. Next, this new sensor assay and method was applied in a small pilot study in order to secure an initial understanding of the diagnostic utility of such biosensor systems in clinical settings. Four cellular features were identified as useful indicators of cancerous or pre-cancerous conditions including, the nuclear area and diameter, nuclear-to-cytoplasm ratio, and EGFR biomarker expression. Further examination using linear regression and ROC curve analysis identified the morphological features as the best predictors of disease while a combination of all features may be ideal for classification of OSCC and pre-malignancy with high sensitivity and specificity. Further testing in a larger sample size is necessary to validate this regression model and the LOC sensor technique, but shows strong promise as a new diagnostic tool for early detection of oral cancer.Chemistry and Biochemistr