Urinary bladder segmentation in CT urography using deepâ learning convolutional neural network and level sets

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134923/1/mp4498.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134923/2/mp4498_am.pd

Endoscopic Fluorescence Imaging:Spectral Optimization and in vivo Characterization of Positive Sites by Magnifying Vascular Imaging

Since several decades, the physicians are able to access hollow organs with endoscopic methods, which serve both as diagnostic and surgical means in a wide range of disciplines of the modern medicine (e.g. urology, pneumology, gastroenterology). Unfortunately, white light (WL) endoscopy displays a limited sensitivity to early pre-cancerous lesions. Hence, several endoscopic methods based on fluorescence imaging have been developed to overcome this limitation. Both endogenous and exogenously-induced fluorescence have been investigated, leading to commercial products. Indeed, autofluorescence bronchoscopy, as well as porphyrin-based fluorescence cystoscopy, are now on the market. As a matter of fact, fluorescence-based endoscopic detection methods show very high sensitivity to pre-cancerous lesions, which are often overlooked in WL endoscopy, but they still lack specificity mainly due to the high false-positive rate. Although most of these false positives can easily be rejected under WL observation, tissue abnormalities such as inflammations, hyperplasia, and metaplasia are more difficult to identify, often resulting in supplementary biopsies. Therefore, the purpose of this thesis is to study novel, fast, and convenient method to characterize fluorescence positive spots in situ during fluorescence endoscopy and, more generally, to optimize the existing endoscopic setup. In this thesis, several clinical evaluations were conducted either in the tracheo-bronchial tree and the urinary bladder. In the urinary bladder, fluorescence imaging for detection of non-muscle invasive bladder cancer is based on the selective production and accumulation of fluorescing porphyrins, mainly protoporphyrin IX (PpIX), in cancerous tissues after the instillation of Hexvix® during one hour. In this thesis, we adapted a rigid cystoscope to perform high magnification (HM) cystoscopy in order to discriminate false from true fluorescence positive findings. Both white light and fluorescence modes are possible with the magnification cystoscope, allowing observation of the bladder wall with magnification ranging between 30× – for standard observation – and 650×. The optical zooming setup allows adjusting the magnification continuously in situ. In the high magnification regime, the smallest diameter of the field of view is 600 microns and the resolution is 2.5 microns, when in contact with the bladder wall. With this HM cystoscope, we characterized the superficial vascularization of the fluorescing sites in WL (370–700 nm) reflectance imaging in order to discriminate cancerous from non-cancerous tissues. This procedure allowed us to establish a classification based on observed vascular patterns. 72 patients subject to Hexvix® f luorescence cystoscopy were included in the study. Comparison of HM cystoscopy classification with histopathology results confirmed 32/33 (97%) cancerous biopsies, and rejected 17/20 (85%) non-cancerous lesions. No vascular alteration could be observed on the only positive lesion that was negative in HM mode, probably because this sarcomatoid carcinoma was not originating in the bladder mucosa. We established with this study that a magnification ranging between 80× and 100× is an optimal tradeoff to perform both macroscopic PDD and HM reflectance imaging. In order to make this approach more quantitative, different algorithms of image processing (vessel segmentation and skeletonisation, global information extraction) were also implemented in this thesis. In order to better visualize the vessels, we improved their contrast with respect to the background. Since hemoglobin is a very strong absorber, we targeted the two hemoglobin absorption peaks by placing appropriate bandpass filters (blue 405±50 nm, green 550±50 nm) in the light source. HM cystoscopy was then performed sequentially with WL, blue and green illumination. The two latter showed higher vessel-to-background contrast, identifying different layers of vascularization due to the light penetration depth. During fluorescence cystoscopy, we often observed that the images are somehow "blurred" by a greenish screen between endoscope tip and bladder mucosa. Since this effect is enhanced by the urine production, it is more visible with flexible scopes (lower flushing capabilities) and imaging systems that collect only autofluorescence as background. Indeed, when the bladder is not flushed regularly, greenish flows coming out of the ureters can easily be observed. For this reason, it is supposed that some fluorophores contained in the urine are excited by the photodetection excitation light, and appear greenish on the screen. This effect may impair the visualization of the bladder mucosa, and thus cancerous lesions, and lowers sensitivity of the fluorescence cystoscopy. In this thesis, we identified the main metabolites responsible for the liquid fluorescence, and optimized the spectral design accordingly. In the tracheo-bronchial tree, the fluorescence contrast is based on the sharp autofluorescence (AF) decrease on early cancerous lesions in the green spectral region (around 500 nm) and a relatively less important decrease in the red spectral region (> 600 nm) when excited with blue-violet light (around 410 nm). It has been shown over the last years, that this contrast may be attributed to a combined effect of epithelium thickening and higher concentration of hemoglobin in the tissues underneath the (pre-)cancerous lesions. In this thesis, we contributed to the definition of the input design of several new prototypes, that were subsequently tested in the clinical environment. We first showed that narrow-band excitation in the blue-violet could increase the tumor-to-normal spectral contrast in the green spectral region. Then, we quantified the intra- and inter-patient variations in the AF intensities in order to optimize the spectral response of the endoscopic fluorescence imaging system. For this purpose, we developed an endoscopic reference to be placed close to the bronchial mucosa during bronchoscopy. Finally, we evaluated a novel AF bronchoscope with blue-backscattered light on 144 patients. This new device showed increased sensitivity for pre-neoplastic lesions. Similar to what we observed in the bladder, it is likely that developing new imaging capabilities (including vascular imaging) will facilitate discriminating true from false positive in AF bronchoscopy. Here, we demonstrated that this magnification allowed us to resolve vessels with a diameter of about 30 µm. This resolution is likely to be sufficient to identify Shibuya's vascular criteria (loops, meshes, dotted vessels) on AF positive lesions. This criteria allow him to recognize pre-cancerous lesions, and thus can potentially decrease the false-positive rate with our AF imaging system. This magnification was also showed to be better for routine bronchoscopy, since it delivers sharper and more structured images to the operator

A systematic review of the applications of Expert Systems (ES) and machine learning (ML) in clinical urology.

BackgroundTesting a hypothesis for 'factors-outcome effect' is a common quest, but standard statistical regression analysis tools are rendered ineffective by data contaminated with too many noisy variables. Expert Systems (ES) can provide an alternative methodology in analysing data to identify variables with the highest correlation to the outcome. By applying their effective machine learning (ML) abilities, significant research time and costs can be saved. The study aims to systematically review the applications of ES in urological research and their methodological models for effective multi-variate analysis. Their domains, development and validity will be identified.MethodsThe PRISMA methodology was applied to formulate an effective method for data gathering and analysis. This study search included seven most relevant information sources: WEB OF SCIENCE, EMBASE, BIOSIS CITATION INDEX, SCOPUS, PUBMED, Google Scholar and MEDLINE. Eligible articles were included if they applied one of the known ML models for a clear urological research question involving multivariate analysis. Only articles with pertinent research methods in ES models were included. The analysed data included the system model, applications, input/output variables, target user, validation, and outcomes. Both ML models and the variable analysis were comparatively reported for each system.ResultsThe search identified n = 1087 articles from all databases and n = 712 were eligible for examination against inclusion criteria. A total of 168 systems were finally included and systematically analysed demonstrating a recent increase in uptake of ES in academic urology in particular artificial neural networks with 31 systems. Most of the systems were applied in urological oncology (prostate cancer = 15, bladder cancer = 13) where diagnostic, prognostic and survival predictor markers were investigated. Due to the heterogeneity of models and their statistical tests, a meta-analysis was not feasible.ConclusionES utility offers an effective ML potential and their applications in research have demonstrated a valid model for multi-variate analysis. The complexity of their development can challenge their uptake in urological clinics whilst the limitation of the statistical tools in this domain has created a gap for further research studies. Integration of computer scientists in academic units has promoted the use of ES in clinical urological research

Computational model of the human urinary bladder

La propuesta de una vejiga artificial es un obstáculo a trasponer. El cáncer de vejiga está entre los casos más frecuentes de enfermedades oncológicas en Estados Unidos y Europa. Ese cáncer es considerado un problema médico importante una vez que esa enfermedad presenta altas tasas de re-ocurrencia, muchas veces llevando a la remoción del órgano. La solución más sofisticada para remplazar ese órgano es la vejiga ileal, que consiste en una neovejiga hecha de tejido intestinal del enfermo. Desafortunadamente, esa solución presenta no solo problemas mecánicos funcionales, descritos en la literatura como problemas de vaciado y fuga, peo también problemas de orden biológica (como ejemplo pérdida ósea, debido a la absorción por el intestino de substancias que necesitan ser eliminadas del organismo). A través de la solicitación de la comunidad urológica del Hospital Clínico de Barcelona y con su experiencia en modelos numéricos para estructuras biomédicas, el Centro de Métodos Numéricos en Ingeniería (CIMNE) ha tenido la iniciativa de proporcionar actividad investigadora de la mecánica de la vejiga urinaria y de la simulación de interacción fluidoestructura para reproducir el llenado y vaciado de ese órgano con la orina. La simulación de la vejiga humana por el Método de los Elementos Finitos (FEM) y un completo entendimiento de la mecánica de ese órgano y de su interacción con la orina dará la posibilidad de proponer mejora en la geometría y de analizar materiales para la solución artificial en caso de remplazamiento de la vejiga. Para lograr ese objetivo, primeramente procedemos a una revisión bibliográfica de los modelos matemáticos del aparato urinario y un estudio comprehensivo de la fisiología y dinámica de la vejiga. Presentamos una revisión de las principales estructuras urológicas, riñón, uréter y uretra. Las estructuras anexas también son consideradas para entender las condiciones de contorno del problema estudiado. Posteriormente, proponemos el modelo constitutivo para estudiar la vejiga urinaria humana. El comportamiento del musculo detrusor durante llenado y vaciado de la vejiga con orina, su habilidad de retención de orina a baja presión debe ser correctamente representada por medio de la implementación de un modelo constitutivo no-lineal. El modelo matemático necesita representar las variables mecánicas que gobiernan ese órgano, y también las propiedades de la orina. El comportamiento no-lineal de tejidos vivos es implementado y validado con ejemplos de la literatura. La propiedad quasi-incompressible de la orina y las ecuaciones Navier-Stokes son consideradas para análisis del fluido. Para representar la geometría de la vejiga, implementamos un modelo computacional 3D a partir de imágenes de tomografía computadorizada de un cadáver adulto. Los datos son tratados para considerar las condiciones de contorno. Hemos construido dos modelos de malla: un mallado con tetrahedos de cuatro nodos y otro mallado con elementos de membrana de tres nodos. El esquema utilizado para calcular la interacción fluido-estructura debe ser adecuado para materiales de densidad muy parecidas. El análisis numérico de llenado y vaciado de la vejiga humana es validada con tests urodinámicos estandarizados. La parte final de la tesis, presentamos una simulación de una neo-vejiga, siendo el primer paso para representar numéricamente materiales artificiales para remplazamiento de la vejiga.The proposal of an artificial bladder is still a challenge to overcome. Bladder cancer is among the most frequent cases of oncologic diseases in United States and Europe. It is considered a major medical problem once this disease has high rates of reoccurrence, often leading to the extirpation of this organ. The most refined solution to replace this organ is the ileal bladder, which consists of a neobladder made of the patient’s intestinal tissue. Unfortunately this solution presents not only functional mechanical problems, described on the literature as voiding and leaking problems, but also biological ones (i.e. bone loss, given the absorption by the intestine of substances that should be eliminated from the organism). Urged by the urological community of the Hospital Clinic de Barcelona and backgrounded by its experience in the numerical simulation of biomedical structures, the Center of Numerical Methods in Engineering (CIMNE) had the initiative to provide the research of the mechanics of the urinary bladder and the simulation of fluid structure interaction (FSI) to account for the filling and voiding of this organ with urine. The Finite Element Method (FEM) simulation of the real bladder and the comprehensive understanding of the mechanics of this organ and its interaction with urine will give the possibility to propose geometrical improvements and study suitable materials for an artificial solution to address the cases on which the bladder needs to be removed. To reach this goal, first we proceeded to the bibliographic review of mathematical models of the urinary apparatus and to a comprehensive study of the physiology and dynamics of the bladder. A review of the major urological structures, kidney, ureter and urethra, takes place. To consider boundary conditions other surrounding structures to the urinary system are also studied. In the second part of the thesis, we propose the numerical model to study the human urinary bladder. The behavior of the detrusor muscle during filling and voiding of the bladder with urine and its ability to promote the storage of urine under low pressure need to be accurately represented, requiring the implementation of a non-linear constitutive model. The mathematical model needs to be capable to simulate the mechanical variables that govern this organ and the properties of the urine. The nonlinear behavior of living tissues is implemented and validated with examples from the literature. The quasi-incompressibility property of urine and the navierstokes equations for the fluid are taken into account. The geometry of the bladder needs to be taken into account, and the implementation of a 3D computational model obtained from the computerized tomography of a cadaver male adult is considered. The data has been treated to consider boundary conditions. Two models have been conceived: one meshed with four nodes tetrahedral and another meshed with shell elements. FSI must work for the simulation of filling and voiding of the bladder. Due to the close densities of the materials the scheme used to solve fluid-structure needs to be carefully selected. The proposed numerical model and the filling and voiding analysis are finally validated with standardized urodynamic tests. The final part of the thesis, the simulation of a neobladder is presented, being the first step to simulate numerically artificial materials for bladder replacement

Optical Diagnostics in Human Diseases

Optical technologies provide unique opportunities for the diagnosis of various pathological disorders. The range of biophotonics applications in clinical practice is considerably wide given that the optical properties of biological tissues are subject to significant changes during disease progression. Due to the small size of studied objects (from μm to mm) and despite some minimum restrictions (low-intensity light is used), these technologies have great diagnostic potential both as an additional tool and in cases of separate use, for example, to assess conditions affecting microcirculatory bed and tissue viability. This Special Issue presents topical articles by researchers engaged in the development of new methods and devices for optical non-invasive diagnostics in various fields of medicine. Several studies in this Special Issue demonstrate new information relevant to surgical procedures, especially in oncology and gynecology. Two articles are dedicated to the topical problem of breast cancer early detection, including during surgery. One of the articles is devoted to urology, namely to the problem of chronic or recurrent episodic urethral pain. Several works describe the studies in otolaryngology and dentistry. One of the studies is devoted to diagnosing liver diseases. A number of articles contribute to the studying of the alterations caused by diabetes mellitus and cardiovascular diseases. The results of all the presented articles reflect novel innovative research and emerging ideas in optical non-invasive diagnostics aimed at their wider translation into clinical practice