A Computer-Aided Method to Expedite the Evaluation of Prognosis for Childhood Acute Lymphoblastic Leukemia

This study presented a fully-automated computer-aided method (scheme) to detect metaphase chromosomes depicted on microscopic digital images, count the total number of chromosomes in each metaphase cell, compute the DNA index, and correlate the results to the prognosis of childhood acute lymphoblastic leukemia (ALL). The computer scheme first uses image filtering, threshold, and labeling algorithms to segment and count the number of the suspicious “chromosome,” and then computes a feature vector for each “detected chromosome.” Based on these features, a knowledge-based classifier is used to eliminate those “non-chromosome” objects (i.e., inter-phase cells, stain debris, and other kinds of background noises). Due to the possible overlap of the chromosomes, a classification criterion was used to identify the overlapped chromosomes and adjust the initially counted number of the total chromosomes in each image. In this preliminary study with 60 testing images (depicting metaphase chromosome cells) acquired from three pediatric patients, the computer scheme generated results matched with the diagnostic results provided by the clinical cytogeneticists. The results demonstrated the feasibility or potential of using a computerized method to replace the tedious and the reader-dependent diagnostic methods commonly used in genetic laboratories to date.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

COMPREHENSIVE PERFORMANCE EVALUATION AND OPTIMIZATION OF HIGH THROUGHPUT SCANNING MICROSCOPY FOR METAPHASE CHROMOSOME IMAGING

Specimen scanning is a critically important tool for diagnosing the genetic diseases in today’s hospital. In order to reduce the clinician’s work load, many investigations have been conducted on developing automatic sample screening techniques in the last twenty years. However, the currently commercialized scanners can only accomplish the low magnification sample screening (i.e. under 10× objective lens), and still require clinicians’ manual operation for the high magnification image acquisition and confirmation (i.e. under 100× objective lens). Therefore, a new high throughput scanning method is recently proposed to continuously scan the specimen and select the clinically analyzable cells. In the medical imaging lab, University of Oklahoma, a prototype of high throughput scanning microscopy is built based on the time delay integration (TDI) line scanning detector. This new scanning method, however, raises several technical challenges for evaluating and optimizing the performance. First, we need to use the clinical samples to compare this new prototype with the conventional two-step scanners. Second, the system DOF should be investigated to assess the impact on clinically analyzable metaphase chromosomes. Further, in order to achieve the optimal results, we should carefully assess and select the auto-focusing methods for the high throughput scanning system. Third, we need to optimize the scanning scheme by finding the optimal trade-off between the image quality and efficiency. Finally, analyzing the performance of the various image features is meaningful for improving the performance of the computer aided detection (CAD) scheme under the high throughput scanning condition. The purpose of this dissertation is to comprehensively evaluate the performance of the high throughput scanning prototype. The first technical challenge was solved by the first investigation, which utilized a number of 9 slides from five patients to compare the detecting performance of the high throughput scanning prototype. The second and third studies were performed for the second technical challenge. In the second study, we first theoretically computed the DOF of our prototype and then experimentally measured the system DOF. After that, the DOF impact was analyzed using cytogenetic images from different pathological specimens, under the condition of two objective lenses of 60× (dry, N.A. = 0.95) and 100× (oil, N.A. = 1.25). In the third study, five auto-focusing functions were investigated using metaphase chromosome images. The performance of these different functions was compared using four widely accepted criteria. The fourth and fifth investigations were designed for the third technical challenge. The fourth study objectively assessed chromosome band sharpness by a gradient sharpness function. The sharpness of the images captured from standard resolution target and several pathological chromosomes was objectively evaluated by the gradient sharpness function. The fifth study presented a new slide scanning scheme, which only applies the auto-focusing operations on limited locations. The focusing position was adjusted very quickly by linear interpolation for the other locations. The sixth study was aimed for the fourth technical challenge. The study investigated 9 different feature extraction methods for the CAD modules applied on our high throughput scanning prototype. A certain amount of images were first acquired from 200 bone marrow cells. Then the tested features were performed on these images and the images containing clinically meaningful chromosomes were selected using each feature individually. The identifying accuracy of each feature was evaluated using the receiver operating characteristic (ROC) method. In this dissertation, we have the following results. First, in most cases, we demonstrated that the high throughput scanning can select more diagnostic images depicting clinically analyzable metaphase chromosomes. These selected images were acquired with adequate spatial resolution for the following clinical interpretation. Second, our results showed that, for the commonly used pathological specimens, the metaphase chromosome band patterns are clinically recognizable when these chromosomes were obtained within 1.5 or 1.0 μm away from the focal plane, under the condition of applying the two 60× or 100× objective lenses, respectively. In addition, when scanning bone marrow and blood samples, the Brenner gradient and threshold pixel counting methods can achieve the optimal performance, respectively. Third, we illustrated that the optimal scanning speed of clinical samples is 0.8 mm/s, for which the captured image sharpness is optimized. When scanning the blood sample slide with an auto-focusing distance of 6.9 mm, the prototype obtained an adequate number of analyzable metaphase cells. More useful cells can be captured by increasing the auto-focusing operations, which may be needed for the high accuracy diagnosis. Finally, we found that the optimal feature for the online CAD scheme is the number of the labeled regions. When applying the offline CAD scheme, the satisfactory results can be achieved by combining four different features including the number of the labeled regions, average region area, average region pixel value, and the standard deviation of the either region circularity or distance. Although these investigations are encouraging, there exist several limitations. First, the number of the specimens is limited in most of the assessments. Second, some important impacts, such as the DOF of human eye and the sample thickness, are not considered. Third, more recently proposed algorithms and image features are not used for the evaluation. Therefore, several further studies are planned, which may provide more meaningful information for improving the scanning efficiency and image quality. In summary, we believe that the high throughput scanning may be extensively applied for diagnosing genetic diseases in the future

Semi-Automated Segmentation of Microbes in Color Images

ABSTRACT The goal of this work is to develop a system that can semi-automate the detection of multicolored foreground objects in digitized color images that contain complex and very noisy backgrounds. Although color image segmentation is considered a general problem, our application is microbiology where various colored stains are used to reveal information about the microbes without cultivation. Instead of providing a simple threshold, the proposed system offers an interactive environment whereby the user chooses multiple sample points to define the range of color pixels comprising the foreground microbes of interest. The system then uses the color and spatial distances of these target points to segment the microbes from the confusing background of pixels whose RGB values lie outside the newly defined range and finds the boundary of the foreground microbes using region-growing and mathematical morphology. Some other image processing methods are also applied to enhance the resultant image containing the colored microbes against a noise-free background. The prototype performs with 98% accuracy on a test set compared to manually edited ground truth data. The system described here will have many applications in image processing and analysis where one needs to segment typical pixel regions of similar but non-identical colors

Digital image analysis of mitotic chromosomes

Změny v počtu a ve struktuře chromozomů jsou příčinou řady vážných onemocnění. K odhalení chromozomálních změn slouží cytogenetická vyšetření, která nejčastěji vedou k sestavení karyotypu. Pro účely cytogenetických analýz se chromozomy vizualizují pomocí vhodných metod a nejčastěji se následně sestavují do karyotypu. Protože ruční stanovení karyotypu je časově i finančně náročné, vyvíjí se přístupy k automatickému karyotypování pomocí počítačového softwaru. Automatické karyotypovací systémy klasifikují chromozomy do tříd na základě identifikačních znaků, specifických pro každý chromozom. Automatickou klasifikaci však nejvíce limituje přítomnost překrývající se a silně ohnutých chromozomů, přítomných v téměř každé mitóze. Přesnost a spolehlivost karyotypovacích systémů stále závisí na zásahu uživatele. Cílem vývoje nových přístupů k automatickému karyotypování je tedy zejména překonání výše zmíněných problémů a dále vývoj takových klasifikačních metod, které umožňí klasifikaci chromozomů do párů bez lidské kontroly.Changes in chromosome number and structure may cause serious diseases. Cytogenetic tests leadin to set of karyotype are done for detecting these abnormalities. Chromosomes are visualised with proper methods and karyotype is made up most often. Manual karyotyping is time-consuming and expensive task. Because of this, researchers have been developing automated karyotyping systems. Karyotyping systems classify chromosomes into classes based on their characteristic features. Overlapping and bent chromosomes are limitations for automatic classification since they ocur at almost every mitosis. Accuracy and reliability of karyotyping systems still depend on the human intervention. Overcoming of these problems and development of fully automated system is the aim of modern approaches.

Graph matching using position coordinates and local features for image analysis

Encontrar las correspondencias entre dos imágenes es un problema crucial en el campo de la visión por ordenador i el reconocimiento de patrones. Es relevante para un amplio rango de propósitos des de aplicaciones de reconocimiento de objetos en las áreas de biometría, análisis de documentos i análisis de formas hasta aplicaciones relacionadas con la geometría desde múltiples puntos de vista tales cómo la recuperación de la pose, estructura desde el movimiento y localización y mapeo. La mayoría de las técnicas existentes enfocan este problema o bien usando características locales en la imagen o bien usando métodos de registro de conjuntos de puntos (o bien una mezcla de ambos). En las primeras, un conjunto disperso de características es primeramente extraído de las imágenes y luego caracterizado en la forma de vectores descriptores usando evidencias locales de la imagen. Las características son asociadas según la similitud entre sus descriptores. En las segundas, los conjuntos de características son considerados cómo conjuntos de puntos los cuales son asociados usando técnicas de optimización no lineal. Estos son procedimientos iterativos que estiman los parámetros de correspondencia y de alineamiento en pasos alternados. Los grafos son representaciones que contemplan relaciones binarias entre las características. Tener en cuenta relaciones binarias al problema de la correspondencia a menudo lleva al llamado problema del emparejamiento de grafos. Existe cierta cantidad de métodos en la literatura destinados a encontrar soluciones aproximadas a diferentes instancias del problema de emparejamiento de grafos, que en la mayoría de casos es del tipo "NP-hard". El cuerpo de trabajo principal de esta tesis está dedicado a formular ambos problemas de asociación de características de imagen y registro de conjunto de puntos como instancias del problema de emparejamiento de grafos. En todos los casos proponemos algoritmos aproximados para solucionar estos problemas y nos comparamos con un número de métodos existentes pertenecientes a diferentes áreas como eliminadores de "outliers", métodos de registro de conjuntos de puntos y otros métodos de emparejamiento de grafos. Los experimentos muestran que en la mayoría de casos los métodos propuestos superan al resto. En ocasiones los métodos propuestos o bien comparten el mejor rendimiento con algún método competidor o bien obtienen resultados ligeramente peores. En estos casos, los métodos propuestos normalmente presentan tiempos computacionales inferiores.Trobar les correspondències entre dues imatges és un problema crucial en el camp de la visió per ordinador i el reconeixement de patrons. És rellevant per un ampli ventall de propòsits des d’aplicacions de reconeixement d’objectes en les àrees de biometria, anàlisi de documents i anàlisi de formes fins aplicacions relacionades amb geometria des de múltiples punts de vista tals com recuperació de pose, estructura des del moviment i localització i mapeig. La majoria de les tècniques existents enfoquen aquest problema o bé usant característiques locals a la imatge o bé usant mètodes de registre de conjunts de punts (o bé una mescla d’ambdós). En les primeres, un conjunt dispers de característiques és primerament extret de les imatges i després caracteritzat en la forma de vectors descriptors usant evidències locals de la imatge. Les característiques son associades segons la similitud entre els seus descriptors. En les segones, els conjunts de característiques son considerats com conjunts de punts els quals son associats usant tècniques d’optimització no lineal. Aquests son procediments iteratius que estimen els paràmetres de correspondència i d’alineament en passos alternats. Els grafs son representacions que contemplen relacions binaries entre les característiques. Tenir en compte relacions binàries al problema de la correspondència sovint porta a l’anomenat problema de l’emparellament de grafs. Existeix certa quantitat de mètodes a la literatura destinats a trobar solucions aproximades a diferents instàncies del problema d’emparellament de grafs, el qual en la majoria de casos és del tipus “NP-hard”. Una part del nostre treball està dedicat a investigar els beneficis de les mesures de ``bins'' creuats per a la comparació de característiques locals de les imatges. La resta està dedicat a formular ambdós problemes d’associació de característiques d’imatge i registre de conjunt de punts com a instàncies del problema d’emparellament de grafs. En tots els casos proposem algoritmes aproximats per solucionar aquests problemes i ens comparem amb un nombre de mètodes existents pertanyents a diferents àrees com eliminadors d’“outliers”, mètodes de registre de conjunts de punts i altres mètodes d’emparellament de grafs. Els experiments mostren que en la majoria de casos els mètodes proposats superen a la resta. En ocasions els mètodes proposats o bé comparteixen el millor rendiment amb algun mètode competidor o bé obtenen resultats lleugerament pitjors. En aquests casos, els mètodes proposats normalment presenten temps computacionals inferiors

Echocardiography

The book "Echocardiography - New Techniques" brings worldwide contributions from highly acclaimed clinical and imaging science investigators, and representatives from academic medical centers. Each chapter is designed and written to be accessible to those with a basic knowledge of echocardiography. Additionally, the chapters are meant to be stimulating and educational to the experts and investigators in the field of echocardiography. This book is aimed primarily at cardiology fellows on their basic echocardiography rotation, fellows in general internal medicine, radiology and emergency medicine, and experts in the arena of echocardiography. Over the last few decades, the rate of technological advancements has developed dramatically, resulting in new techniques and improved echocardiographic imaging. The authors of this book focused on presenting the most advanced techniques useful in today's research and in daily clinical practice. These advanced techniques are utilized in the detection of different cardiac pathologies in patients, in contributing to their clinical decision, as well as follow-up and outcome predictions. In addition to the advanced techniques covered, this book expounds upon several special pathologies with respect to the functions of echocardiography