A non-invasive image based system for early diagnosis of prostate cancer.

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer

A review of artificial intelligence in prostate cancer detection on imaging

A multitude of studies have explored the role of artificial intelligence (AI) in providing diagnostic support to radiologists, pathologists, and urologists in prostate cancer detection, risk-stratification, and management. This review provides a comprehensive overview of relevant literature regarding the use of AI models in (1) detecting prostate cancer on radiology images (magnetic resonance and ultrasound imaging), (2) detecting prostate cancer on histopathology images of prostate biopsy tissue, and (3) assisting in supporting tasks for prostate cancer detection (prostate gland segmentation, MRI-histopathology registration, MRI-ultrasound registration). We discuss both the potential of these AI models to assist in the clinical workflow of prostate cancer diagnosis, as well as the current limitations including variability in training data sets, algorithms, and evaluation criteria. We also discuss ongoing challenges and what is needed to bridge the gap between academic research on AI for prostate cancer and commercial solutions that improve routine clinical care

Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images

Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces

Prostate biopsy tracking with deformation estimation

Transrectal biopsies under 2D ultrasound (US) control are the current clinical standard for prostate cancer diagnosis. The isoechogenic nature of prostate carcinoma makes it necessary to sample the gland systematically, resulting in a low sensitivity. Also, it is difficult for the clinician to follow the sampling protocol accurately under 2D US control and the exact anatomical location of the biopsy cores is unknown after the intervention. Tracking systems for prostate biopsies make it possible to generate biopsy distribution maps for intra- and post-interventional quality control and 3D visualisation of histological results for diagnosis and treatment planning. They can also guide the clinician toward non-ultrasound targets. In this paper, a volume-swept 3D US based tracking system for fast and accurate estimation of prostate tissue motion is proposed. The entirely image-based system solves the patient motion problem with an a priori model of rectal probe kinematics. Prostate deformations are estimated with elastic registration to maximize accuracy. The system is robust with only 17 registration failures out of 786 (2%) biopsy volumes acquired from 47 patients during biopsy sessions. Accuracy was evaluated to 0.76$\pm$0.52mm using manually segmented fiducials on 687 registered volumes stemming from 40 patients. A clinical protocol for assisted biopsy acquisition was designed and implemented as a biopsy assistance system, which allows to overcome the draw-backs of the standard biopsy procedure.Comment: Medical Image Analysis (2011) epub ahead of prin

Rapid Segmentation Techniques for Cardiac and Neuroimage Analysis

Recent technological advances in medical imaging have allowed for the quick acquisition of highly resolved data to aid in diagnosis and characterization of diseases or to guide interventions. In order to to be integrated into a clinical work flow, accurate and robust methods of analysis must be developed which manage this increase in data. Recent improvements in in- expensive commercially available graphics hardware and General-Purpose Programming on Graphics Processing Units (GPGPU) have allowed for many large scale data analysis problems to be addressed in meaningful time and will continue to as parallel computing technology improves. In this thesis we propose methods to tackle two clinically relevant image segmentation problems: a user-guided segmentation of myocardial scar from Late-Enhancement Magnetic Resonance Images (LE-MRI) and a multi-atlas segmentation pipeline to automatically segment and partition brain tissue from multi-channel MRI. Both methods are based on recent advances in computer vision, in particular max-flow optimization that aims at solving the segmentation problem in continuous space. This allows for (approximately) globally optimal solvers to be employed in multi-region segmentation problems, without the particular drawbacks of their discrete counterparts, graph cuts, which typically present with metrication artefacts. Max-flow solvers are generally able to produce robust results, but are known for being computationally expensive, especially with large datasets, such as volume images. Additionally, we propose two new deformable registration methods based on Gauss-Newton optimization and smooth the resulting deformation fields via total-variation regularization to guarantee the problem is mathematically well-posed. We compare the performance of these two methods against four highly ranked and well-known deformable registration methods on four publicly available databases and are able to demonstrate a highly accurate performance with low run times. The best performing variant is subsequently used in a multi-atlas segmentation pipeline for the segmentation of brain tissue and facilitates fast run times for this computationally expensive approach. All proposed methods are implemented using GPGPU for a substantial increase in computational performance and so facilitate deployment into clinical work flows. We evaluate all proposed algorithms in terms of run times, accuracy, repeatability and errors arising from user interactions and we demonstrate that these methods are able to outperform established methods. The presented approaches demonstrate high performance in comparison with established methods in terms of accuracy and repeatability while largely reducing run times due to the employment of GPU hardware

U-Net and its variants for medical image segmentation: theory and applications

U-net is an image segmentation technique developed primarily for medical image analysis that can precisely segment images using a scarce amount of training data. These traits provide U-net with a very high utility within the medical imaging community and have resulted in extensive adoption of U-net as the primary tool for segmentation tasks in medical imaging. The success of U-net is evident in its widespread use in all major image modalities from CT scans and MRI to X-rays and microscopy. Furthermore, while U-net is largely a segmentation tool, there have been instances of the use of U-net in other applications. As the potential of U-net is still increasing, in this review we look at the various developments that have been made in the U-net architecture and provide observations on recent trends. We examine the various innovations that have been made in deep learning and discuss how these tools facilitate U-net. Furthermore, we look at image modalities and application areas where U-net has been applied.Comment: 42 pages, in IEEE Acces

Validation Strategies Supporting Clinical Integration of Prostate Segmentation Algorithms for Magnetic Resonance Imaging

Segmentation of the prostate in medical images is useful for prostate cancer diagnosis and therapy guidance. However, manual segmentation of the prostate is laborious and time-consuming, with inter-observer variability. The focus of this thesis was on accuracy, reproducibility and procedure time measurement for prostate segmentation on T2-weighted endorectal magnetic resonance imaging, and assessment of the potential of a computer-assisted segmentation technique to be translated to clinical practice for prostate cancer management. We collected an image data set from prostate cancer patients with manually-delineated prostate borders by one observer on all the images and by two other observers on a subset of images. We used a complementary set of error metrics to measure the different types of observed segmentation errors. We compared expert manual segmentation as well as semi-automatic and automatic segmentation approaches before and after manual editing by expert physicians. We recorded the time needed for user interaction to initialize the semi-automatic algorithm, algorithm execution, and manual editing as necessary. Comparing to manual segmentation, the measured errors for the algorithms compared favourably with observed differences between manual segmentations. The measured average editing times for the computer-assisted segmentation were lower than fully manual segmentation time, and the algorithms reduced the inter-observer variability as compared to manual segmentation. The accuracy of the computer-assisted approaches was near to or within the range of observed variability in manual segmentation. The recorded procedure time for prostate segmentation was reduced using computer-assisted segmentation followed by manual editing, compared to the time required for fully manual segmentation

Contributions of biomechanical modeling and machine learning to the automatic registration of Multiparametric Magnetic Resonance and Transrectal Echography for prostate brachytherapy

El cáncer de próstata (CaP) es el primer cáncer por incidencia en hombres en países occidentales, y el tercero en mortalidad. Tras detectar en sangre una elevación del Antígeno Prostático Específico (PSA) o tras tacto rectal sospechoso se realiza una Resonancia Magnética (RM) de la próstata, que los radiólogos analizan para localizar las regiones sospechosas. A continuación, estas se biopsian, es decir, se toman muestras vivas que posteriormente serán analizadas histopatológicamente para confirmar la presencia de cáncer y establecer su grado de agresividad. Durante la biopsia se emplea típicamente Ultrasonidos (US) para el guiado y la localización de las lesiones. Sin embargo, estas no son directamente visibles en US, y el urólogo necesita usar software de fusión que realice un registro RM-US que transfiera la localizaciones marcadas en MR al US. Esto es fundamental para asegurar que las muestras tomadas provienen verdaderamente de la zona sospechosa. En este trabajo se compendian cinco publicaciones que emplean diversos algoritmos de Inteligencia Artificial (IA) para analizar las imágenes de próstata (RM y US) y con ello mejorar la eficiencia y precisión en el diagnóstico, biopsia y tratamiento del CaP: 1. Segmentación automática de próstata en RM y US: Segmentar la próstata consiste en delimitar o marcar la próstata en una imagen médica, separándola del resto de órganos o estructuras. Automatizar por completo esta tarea, que es previa a todo análisis posterior, permite ahorrar un tiempo significativo a radiólogos y urólogos, mejorando también la precisión y repetibilidad. 2. Mejora de la resolución de segmentación: Se presenta una metodología para mejorar la resolución de las segmentaciones anteriores. 3. Detección y clasificación automática de lesiones en RM: Se entrena un modelo basado en IA para detectar las lesiones como lo haría un radiólogo, asignándoles también una estimación del riesgo. Se logra mejorar la precisión diagnóstica, dando lugar a un sistema totalmente automático que podría implantarse para segunda opinión clínica o como criterio para priorización. 4. Simulación del comportamiento biomecánico en tiempo real: Se propone acelerar la simulación del comportamiento biomecánico de órganos blandos mediante el uso de IA. 5. Registro automático RM-US: El registro permite localizar en US las lesiones marcadas en RM. Una alta precisión en esta tarea es esencial para la corrección de la biopsia y/o del tratamiento focal del paciente (como braquiterapia de alta tasa). Se plantea el uso de la IA para resolver el problema de registro en tiempo casi real, utilizando modelos biomecánicos subyacentes.Prostate cancer (PCa) is the most common malignancy in western males, and third by mortality. After detecting elevated Prostate Specific Antigen (PSA) blood levels or after a suspicious rectal examination, a Magnetic Resonance (MR) image of the prostate is acquired and assessed by radiologists to locate suspicious regions. These are then biopsied, i.e. living tissue samples are collected and analyzed histopathologically to confirm the presence of cancer and establish its degree of aggressiveness. During the biopsy procedure, Ultrasound (US) is typically used for guidance and lesion localization. However, lesions are not directly visible in US, and the urologist needs to use fusion software to performs MR-US registration, so that the MR-marked locations can be transferred to the US image. This is essential to ensure that the collected samples truly come from the suspicious area. This work compiles five publications employing several Artificial Intelligence (AI) algorithms to analyze prostate images (MR and US) and thereby improve the efficiency and accuracy in diagnosis, biopsy and treatment of PCa: 1. Automatic prostate segmentation in MR and US: Prostate segmentation consists in delimiting or marking the prostate in a medical image, separating it from the rest of the organs or structures. Automating this task fully, which is required for any subsequent analysis, saves significant time for radiologists and urologists, while also improving accuracy and repeatability. 2. Segmentation resolution enhancement: A methodology for improving the resolution of the previously obtained segmentations is presented. 3. Automatic detection and classification of MR lesions: An AI model is trained to detect lesions as a radiologist would and to estimate their risk. The model achieves improved diagnostic accuracy, resulting in a fully automatic system that could be used as a second clinical opinion or as a criterion for patient prioritization. 4. Simulation of biomechanical behavior in real time: It is proposed to accelerate the simulation of biomechanical behavior of soft organs using AI. 5. Automatic MR-US registration: Registration allows localization of MR-marked lesions on US. High accuracy in this task is essential for the correctness of the biopsy and/or focal treatment procedures (such as high-rate brachytherapy). Here, AI is used to solve the registration problem in near-real time, while exploiting underlying biomechanically-compatible models