Intelligent contour extraction approach for accurate segmentation of medical ultrasound images

Introduction: Accurate contour extraction in ultrasound images is of great interest for image-guided organ interventions and disease diagnosis. Nevertheless, it remains a problematic issue owing to the missing or ambiguous outline between organs (i.e., prostate and kidney) and surrounding tissues, the appearance of shadow artifacts, and the large variability in the shape of organs.Methods: To address these issues, we devised a method that includes four stages. In the first stage, the data sequence is acquired using an improved adaptive selection principal curve method, in which a limited number of radiologist defined data points are adopted as the prior. The second stage then uses an enhanced quantum evolution network to help acquire the optimal neural network. The third stage involves increasing the precision of the experimental outcomes after training the neural network, while using the data sequence as the input. In the final stage, the contour is smoothed using an explicable mathematical formula explained by the model parameters of the neural network.Results: Our experiments showed that our approach outperformed other current methods, including hybrid and Transformer-based deep-learning methods, achieving an average Dice similarity coefficient, Jaccard similarity coefficient, and accuracy of 95.7 ± 2.4%, 94.6 ± 2.6%, and 95.3 ± 2.6%, respectively.Discussion: This work develops an intelligent contour extraction approach on ultrasound images. Our approach obtained more satisfactory outcome compared with recent state-of-the-art approaches . The knowledge of precise boundaries of the organ is significant for the conservation of risk structures. Our developed approach has the potential to enhance disease diagnosis and therapeutic outcomes

Co-registration of paired histological sections and MRI scans of the rabbit larynx

Co-registering images of different modalities, termed intermodal image registration, is an important tool in improving our understanding of how certain features detectable in one modality might manifest in the other. However, structural changes – usually the result of tissue processing or noise in image acquisition – can make matching difficult. In this thesis, I outline a pre-processing protocol for co-registration of paired histological sections and MRI scans as well as discuss different co-registration strategies using the rabbit larynx as a model system

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Caries detection in panoramic dental x-ray images

The detection of dentalcaries,in a preliminar stage are of most importance. There is a long history of dental caries. Over a million years ago, hominids such as Australopithecus suffered from cavities. Archaeological evidence shows that tooth decay is an ancient disease dating far into prehistory. Skulls dating from a million years ago through the Neolithic period show signs of caries. The increase of caries during the Neolithic period may be attributed to the increase of plant foods containing carbohydrates. The beginning of rice cultivation in South Asia is also believed to have caused an increase in caries. DentalCaries,alsoknownasdentaldecayortoothdecay,isdefinedasadisease of the hard tissues of the teeth caused by the action of microorganisms, found in plaque,onfermentablecarbohydrates(principallysugars). Attheindividuallevel, dental caries is a preventable disease. Given its dynamic nature the dental caries disease, once established, can be treated or reversed prior to significant cavitation taking place. There three types of dental caries [59], the first type is the Enamel Caries, that is preceded by the formation of a microbial dental plaque. Secondly the Dentinal Caries which begins with the natural spread of the process along the natural spread of great numbers of the dentinal tubules. Thirdly the Pulpal Caries that corresponds to the root caries or root surface caries. Primary diagnosis involves inspection of all visible tooth surfaces using a good light source, dental mirror and explorer. Dental radiographs (X-rays) may show dental caries before it is otherwise visible, particularly caries between the teeth. Large dental caries are often apparent to the naked eye, but smaller lesions can be difficult to identify. Visual and tactile inspection along with radiographs are employed frequently among dentists. At times, caries may be difficult to detect. Bacteriacanpenetratetheenameltoreachdentin,butthentheoutersurfacemaybe at first site intact. These caries, sometimes referred to as "hidden caries", in the preliminary stage X-ray are the only way to detect them, despite of the visual examinationofthetoothshowntheenamelintactorminimallyperforated. Without X-rays wouldn’t be possible to detect these problems until they had become severe and caused serious damage. [...

Medical image analysis methods for anatomical surface reconstruction using tracked 3D ultrasound

The thesis focuses on a study of techniques for acquisition and reconstruction of surface data from anatomical objects by means of tracked 3D ultrasound. In the context of the work two experimental scanning systems are developed and tested on both artificial objects and biological tissues. The first system is based on the freehand ultrasound principle and utilizes a conventional 2D ultrasound transducer coupled with an electromechanical 3D position tracker. The main properties and the basic features of this system are discussed. A number of experiments show that its accuracy in the close to ideal conditions reaches 1.2 mm RMS. The second proposed system implements the sequential triggered scanning approach. The system consists of an ultrasound machine, a workstation and a scanning body (a moving tank filled with liquid and a transducer fixation block) that performs transducer positioning and tracking functions. The system is tested on artificial and real bones. The performed experiments illustrate that it provides significantly better accuracy than the freehand ultrasound (about 0.2 mm RMS) and allows acquiring regular data with a good precision. This makes such a system a promising tool for orthopaedic and trauma surgeons during contactless X-ray-free examinations of injured extremities. The second major subject of the thesis concerns development of medical image analysis methods for 3D surface reconstruction and 2D object detection. We introduce a method based on mesh-growing surface reconstruction that is designed for noisy and sparse data received from 3D tracked ultrasound scanners. A series of experiments on synthetic and ultrasound data show an appropriate reconstruction accuracy. The reconstruction error is measured as the averaged distance between the faces of the mesh and the points from the cloud. Dependently on the initial settings of the method the error varies in range 0.04 - 0.2% for artificial data and 0.3 - 0.7 mm for ultrasound bone data. The reconstructed surfaces correctly interpolate the original point clouds and demonstrate proper smoothness. The next significant problem considered in the work is 2D object detection. Although medical object detection is not integrated into the developed scanning systems, it can be used as a possible further extension of the systems for automatic detection of specific anatomical structures. We analyse the existent object detection methods and introduce a modification of the one based on the popular Generalized Hough Transform (GHT). Unlike the original GHT, the developed method is invariant to rotation and uniform scaling, and uses an intuitive two-point parametrization. We propose several implementations of the feature-to-vote conversion function with the corresponding vote analysis principles. Special attention is devoted to a study of the hierarchical vote analysis and its probabilistic properties. We introduce a parameter space subdivision strategy that reduces the probability of vote peak omission, and show that it can be efficiently implemented in practice using the Gumbel probability distribution

Measurement, optimisation and control of particle properties in pharmaceutical manufacturing processes

Previously held under moratorium from 2 June 2020 until 6 June 2022.The understanding and optimisation of particle properties connected to their structure and morphology is a common objective for particle engineering applications either to improve materialhandling in the manufacturing process or to influence Critical Quality Attributes (CQAs) linked to product performance. This work aims to demonstrate experimental means to support a rational development approach for pharmaceutical particulate systems with a specific focus on droplet drying platforms such as spray drying. Micro-X-ray tomography (micro-XRT) is widely applied in areas such as geo- and biomedical sciences to enable a three dimensional investigation of the specimens. Chapter 4 elaborates on practical aspects of micro-XRT for a quantitative analysis of pharmaceutical solid products with an emphasis on implemented image processing and analysis methodologies. Potential applications of micro-XRT in the pharmaceutical manufacturing process can range from the characterisation of single crystals to fully formulated oral dosage forms. Extracted quantitative information can be utilised to directly inform product design and production for process development or optimisation. The non-destructive nature of the micro-XRT analysis can be further employed to investigate structure-performance relationships which might provide valuable insights for modelling approaches. Chapter 5 further demonstrates the applicability of micro-XRT for the analysis of ibuprofen capsules as a multi-particulate system each with a population of approximately 300 pellets. The in-depth analysis of collected micro-XRT image data allowed the extraction of more than 200 features quantifying aspects of the pellets’ size, shape, porosity, surface and orientation. Employed feature selection and machine learning methods enabled the detection of broken pellets within a classification model. The classification model has an accuracy of more than 99.55% and a minimum precision of 86.20% validated with a test dataset of 886 pellets from three capsules. The combination of single droplet drying (SDD) experiments with a subsequent micro-XRT analysis was used for a quantitative investigation of the particle design space and is described in Chapter 6. The implemented platform was applied to investigate the solidification of formulated metformin hydrochloride particles using D-mannitol and hydroxypropyl methylcellulose within a selected, pragmatic particle design space. The results indicate a significant impact of hydroxypropyl methylcellulose reducing liquid evaporation rates and particle drying kinetics. The morphology and internal structure of the formulated particles after drying are dominated by a crystalline core of D-mannitol partially suppressed with increasing hydroxypropyl methylcellulose additions. The characterisation of formulated metformin hydrochloride particles with increasing polymer content demonstrated the importance of an early-stage quantitative assessment of formulation-related particle properties. A reliable and rational spray drying development approach needs to assess parameters of the compound system as well as of the process itself in order to define a well-controlled and robust operational design space. Chapter 7 presents strategies for process implementation to produce peptide-based formulations via spray drying demonstrated using s-glucagon as a model peptide. The process implementation was supported by an initial characterisation of the lab-scale spray dryer assessing a range of relevant independent process variables including drying temperature and feed rate. The platform response was captured with available and in-house developed Process Analytical Technology. A B-290 Mini-Spray Dryer was used to verify the development approach and to implement the pre-designed spray drying process. Information on the particle formation mechanism observed in SDD experiments were utilised to interpret the characteristics of the spray dried material.The understanding and optimisation of particle properties connected to their structure and morphology is a common objective for particle engineering applications either to improve materialhandling in the manufacturing process or to influence Critical Quality Attributes (CQAs) linked to product performance. This work aims to demonstrate experimental means to support a rational development approach for pharmaceutical particulate systems with a specific focus on droplet drying platforms such as spray drying. Micro-X-ray tomography (micro-XRT) is widely applied in areas such as geo- and biomedical sciences to enable a three dimensional investigation of the specimens. Chapter 4 elaborates on practical aspects of micro-XRT for a quantitative analysis of pharmaceutical solid products with an emphasis on implemented image processing and analysis methodologies. Potential applications of micro-XRT in the pharmaceutical manufacturing process can range from the characterisation of single crystals to fully formulated oral dosage forms. Extracted quantitative information can be utilised to directly inform product design and production for process development or optimisation. The non-destructive nature of the micro-XRT analysis can be further employed to investigate structure-performance relationships which might provide valuable insights for modelling approaches. Chapter 5 further demonstrates the applicability of micro-XRT for the analysis of ibuprofen capsules as a multi-particulate system each with a population of approximately 300 pellets. The in-depth analysis of collected micro-XRT image data allowed the extraction of more than 200 features quantifying aspects of the pellets’ size, shape, porosity, surface and orientation. Employed feature selection and machine learning methods enabled the detection of broken pellets within a classification model. The classification model has an accuracy of more than 99.55% and a minimum precision of 86.20% validated with a test dataset of 886 pellets from three capsules. The combination of single droplet drying (SDD) experiments with a subsequent micro-XRT analysis was used for a quantitative investigation of the particle design space and is described in Chapter 6. The implemented platform was applied to investigate the solidification of formulated metformin hydrochloride particles using D-mannitol and hydroxypropyl methylcellulose within a selected, pragmatic particle design space. The results indicate a significant impact of hydroxypropyl methylcellulose reducing liquid evaporation rates and particle drying kinetics. The morphology and internal structure of the formulated particles after drying are dominated by a crystalline core of D-mannitol partially suppressed with increasing hydroxypropyl methylcellulose additions. The characterisation of formulated metformin hydrochloride particles with increasing polymer content demonstrated the importance of an early-stage quantitative assessment of formulation-related particle properties. A reliable and rational spray drying development approach needs to assess parameters of the compound system as well as of the process itself in order to define a well-controlled and robust operational design space. Chapter 7 presents strategies for process implementation to produce peptide-based formulations via spray drying demonstrated using s-glucagon as a model peptide. The process implementation was supported by an initial characterisation of the lab-scale spray dryer assessing a range of relevant independent process variables including drying temperature and feed rate. The platform response was captured with available and in-house developed Process Analytical Technology. A B-290 Mini-Spray Dryer was used to verify the development approach and to implement the pre-designed spray drying process. Information on the particle formation mechanism observed in SDD experiments were utilised to interpret the characteristics of the spray dried material

Characterising pattern asymmetry in pigmented skin lesions

Abstract. In clinical diagnosis of pigmented skin lesions asymmetric pigmentation is often indicative of melanoma. This paper describes a method and measures for characterizing lesion symmetry. The estimate of mirror symmetry is computed first for a number of axes at different degrees of rotation with respect to the lesion centre. The statistics of these estimates are the used to assess the overall symmetry. The method is applied to three different lesion representations showing the overall pigmentation, the pigmentation pattern, and the pattern of dermal melanin. The best measure is a 100% sensitive and 96% specific indicator of melanoma on a test set of 33 lesions, with a separate training set consisting of 66 lesions

Image Registration Workshop Proceedings

Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research

Segmentierung medizinischer Bilddaten und bildgestützte intraoperative Navigation

Die Entwicklung von Algorithmen zur automatischen oder semi-automatischen Verarbeitung von medizinischen Bilddaten hat in den letzten Jahren mehr und mehr an Bedeutung gewonnen. Das liegt zum einen an den immer besser werdenden medizinischen Aufnahmemodalitäten, die den menschlichen Körper immer feiner virtuell abbilden können. Zum anderen liegt dies an der verbesserten Computerhardware, die eine algorithmische Verarbeitung der teilweise im Gigabyte-Bereich liegenden Datenmengen in einer vernünftigen Zeit erlaubt. Das Ziel dieser Habilitationsschrift ist die Entwicklung und Evaluation von Algorithmen für die medizinische Bildverarbeitung. Insgesamt besteht die Habilitationsschrift aus einer Reihe von Publikationen, die in drei übergreifende Themenbereiche gegliedert sind: -Segmentierung medizinischer Bilddaten anhand von vorlagenbasierten Algorithmen -Experimentelle Evaluation quelloffener Segmentierungsmethoden unter medizinischen Einsatzbedingungen -Navigation zur Unterstützung intraoperativer Therapien Im Bereich Segmentierung medizinischer Bilddaten anhand von vorlagenbasierten Algorithmen wurden verschiedene graphbasierte Algorithmen in 2D und 3D entwickelt, die einen gerichteten Graphen mittels einer Vorlage aufbauen. Dazu gehört die Bildung eines Algorithmus zur Segmentierung von Wirbeln in 2D und 3D. In 2D wird eine rechteckige und in 3D eine würfelförmige Vorlage genutzt, um den Graphen aufzubauen und das Segmentierungsergebnis zu berechnen. Außerdem wird eine graphbasierte Segmentierung von Prostatadrüsen durch eine Kugelvorlage zur automatischen Bestimmung der Grenzen zwischen Prostatadrüsen und umliegenden Organen vorgestellt. Auf den vorlagenbasierten Algorithmen aufbauend, wurde ein interaktiver Segmentierungsalgorithmus, der einem Benutzer in Echtzeit das Segmentierungsergebnis anzeigt, konzipiert und implementiert. Der Algorithmus nutzt zur Segmentierung die verschiedenen Vorlagen, benötigt allerdings nur einen Saatpunkt des Benutzers. In einem weiteren Ansatz kann der Benutzer die Segmentierung interaktiv durch zusätzliche Saatpunkte verfeinern. Dadurch wird es möglich, eine semi-automatische Segmentierung auch in schwierigen Fällen zu einem zufriedenstellenden Ergebnis zu führen. Im Bereich Evaluation quelloffener Segmentierungsmethoden unter medizinischen Einsatzbedingungen wurden verschiedene frei verfügbare Segmentierungsalgorithmen anhand von Patientendaten aus der klinischen Routine getestet. Dazu gehörte die Evaluierung der semi-automatischen Segmentierung von Hirntumoren, zum Beispiel Hypophysenadenomen und Glioblastomen, mit der frei verfügbaren Open Source-Plattform 3D Slicer. Dadurch konnte gezeigt werden, wie eine rein manuelle Schicht-für-Schicht-Vermessung des Tumorvolumens in der Praxis unterstützt und beschleunigt werden kann. Weiterhin wurde die Segmentierung von Sprachbahnen in medizinischen Aufnahmen von Hirntumorpatienten auf verschiedenen Plattformen evaluiert. Im Bereich Navigation zur Unterstützung intraoperativer Therapien wurden Softwaremodule zum Begleiten von intra-operativen Eingriffen in verschiedenen Phasen einer Behandlung (Therapieplanung, Durchführung, Kontrolle) entwickelt. Dazu gehört die erstmalige Integration des OpenIGTLink-Netzwerkprotokolls in die medizinische Prototyping-Plattform MeVisLab, die anhand eines NDI-Navigationssystems evaluiert wurde. Außerdem wurde hier ebenfalls zum ersten Mal die Konzeption und Implementierung eines medizinischen Software-Prototypen zur Unterstützung der intraoperativen gynäkologischen Brachytherapie vorgestellt. Der Software-Prototyp enthielt auch ein Modul zur erweiterten Visualisierung bei der MR-gestützten interstitiellen gynäkologischen Brachytherapie, welches unter anderem die Registrierung eines gynäkologischen Brachytherapie-Instruments in einen intraoperativen Datensatz einer Patientin ermöglichte. Die einzelnen Module führten zur Vorstellung eines umfassenden bildgestützten Systems für die gynäkologische Brachytherapie in einem multimodalen Operationssaal. Dieses System deckt die prä-, intra- und postoperative Behandlungsphase bei einer interstitiellen gynäkologischen Brachytherapie ab