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Clinical diagnosis ideally relies on quantitative measures of disease. For a number of diseases, diagnostic guidelines require or at least recommend neuroimaging exams to support the clinical findings. As such, there is also an increasing interest to derive quantitative results from magnetic resonance imaging (MRI) examinations, i.e. images providing quantitative T1, T2, T2* tissue parameters. Quantitative MRI protocols, however, often require prohibitive long acquisition times (> 10 minutes), nor standards have been established to regulate and control MRI-based quantification. This work aims at exploring the technical feasibility to accelerate existing MRI acquisition schemes to enable a -3 minutes clinical imaging protocol of quantitative tissue parameters such as T2 and T2* and at identifying technical factors that are key elements to obtain accurate results. In the first part of this thesis, the signal model of an existing quantitative T2-mapping algorithm is expanded to explore the methodology for a broader use including the application to T2* and its use in the presence of imperfect imaging conditions and system related limitations of the acquisition process. The second part of this thesis is dedicated to optimize the iterative mapping algorithm for a robust clinical application including the integration on a clinical MR platform. This translation of technology is a major step to enable and validate such new methodology in a realistic clinical environment. The robustness and accuracy of the developed and implemented model is investigated by comparing with the "gold standard" information from fully sampled phantom and in-vivo MRI data.
Access, Handling and Visualization Tools for Multiple Data Types for Breast Cancer Decision Support
(2011)
Breast cancer is the most commonly diagnosed cancer among U.S women, besides skin cancer. More than 1 in 4 cancers among women are breast cancer. And though death rates have been decreasing since 1990, about 40,170 women in the U.S. were expected to die in 2009 from breast cancer. The progress of molecular profiling, in the last decade has revolutionized the understanding of cancer, but also introduced more complexity with new data such as gene expression, copy number variation, mutations and DNA methylation. These new data open up the possibility of differential diagnosis, much more precise prognosis as well as prediction of therapy response than any of the diagnostic tools that are available in the current practice. Additionally, epidemiological databases store clinically relevant information on hundreds of thousands of patients. However, with the abundance of all this information, clinicians will need new tools to access and visualize such data and use the information gained to treat new patients. The general problem will be to access, filter and analyze the data and then visualize them in a clinical context. This data ranges from clinico-pathological information, to molecular profiles from highthroughput genomic measurements and imaging data. Furthermore, data from patient populations is aggregated on epidemiological level and can be found under numerous clinical studies.
An architectural concept for implementing the socio-technical workflow of Digital Pathology in Chile
(2014)
Virtual Microscopy opens up the possibility to remotely access high quality images at large scales for scientific research, education, and clinical application. For clinical diagnostics, Digital Pathology (DP) presents a novel opportunity to reduce variability [Bauer et al., 2013] due to the reproducible access to Whole Slide Imaging, quantitative parameters (e.g. HER2 stained membrane) [Al-Janabi et al., 2012], second opinion and Quality Assurance [Ho et al., 2013]. Despite of the mentioned advantages, the challenge remains to incorporate DP into the pathologists workflow within a heterogeneous environment of systems and infrastructures [Stathonikos
et al., 2013]. Different issues must be solved in order to optimize the impact of DP in the daily clinical practice [Daniel et al., 2012] [Ho et al., 2006]. The integration needs precise planning and comprehensive evaluation for adopting this technology
[Stathonikos et al., 2013]. This thesis will focus on an organizational development approach based on a Socio-Technical System (STS). The socio-technical approach covers: (i) the technical issue: tissue-scanner, NDP.view, NDP.serve, analysis software, and (ii) the social issue: pathologists, technicians. In order to improve the integration, a joint optimization (of i and ii) is necessary. The developed STS approach will optimize the integration of DP towards improved workflows in clinical environments. The improved workflows will reduce the pathologists turnaround time, improve the certainty of the diagnostics, and provide a more effective patient care within the covered institutions. An overt multi-site Participatory Observation, Questionnaires, and Business Process Modelling Notation will be used to analyse the existing pathological workflows. Based on this, the system will be modelled with the 3lgm2 Toolkit [Winter et al., 2007] under consideration of various technical subsystems that are present in the clinical environment. Afterwards, the interfaces between subsystems and its possible interoperabilities will be evaluated, taking into account the different existing standards and guidelines for image processing and management, as well as business processes in DP. In order to analyse the existing preconditions a questionnaire will be evaluated to establish a robust and valid view. In addition, the overt participatory observation will support this elevation, giving a deeper insight on the social part. This observation also covers the technical side including the whole pathological process. The socio technical model will then reveal measurable potential for optimization with incorporated DP (e.g. higher throughput for slides). The organizational development approach consists of a Socio-Technical System based on overt multi-site participatory observations, questionnaires, business process modelling and 3LGM2, will optimize the use of Digital Pathology in the daily clinical practice and raise the acceptance to incorporate integrate the new technology within the dayly workflow through the user centred process of incorporation.
• Perform and evaluate a questionnaire and a participant observation of pathologists work days in private & public institutions
• Create and evaluate a 3lgm2 model
• Model the current pathological process (viewpoint of pathologist & technical assistant) & perform and evaluate a contextual inquiry to elevate the pathologists requirements & expectations towards the system
• Test the future WF according the model parameters.
This project will detect unsuspected interrelations and interdependencies within the socio- technical workflow with a pathology laboratory. The observation will reveal the action conformity as well as the environment in which the process has to be embedded. Furthermore it will establish an optimized workflow for a specific clinical environment to prepare the implementation of DP. Additionally it will be possible to
quantify digitized images in order to improve decision making and lastly to improve patient care. In the future it will be possible to extend automated image analysis in order to support clinical decision support. Depending on acceptance, this can lead towards an automated clinical decision support for cases with low complexity.
A considerable amount of research in the field of modern robotics deals with mobile agents and their autonomous operation in unstructured, dynamic, and unpredictable environments. Designing robust controllers that map sensory input to action in order to avoid obstacles remains a challenging task. Several biological concepts are amenable to autonomous navigation and reactive obstacle avoidance.
We present an overview of most noteworthy, elaborated, and interesting biologically-inspired approaches for solving the obstacle avoidance problem. We categorize these approaches into three groups: nature inspired optimization, reinforcement learning, and biorobotics. We emphasize the advantages and highlight potential drawbacks of each approach. We also identify the benefits of using biological principles in artificial intelligence in various research areas.
Aside from hardware, a major component of a Brain Computer Interface is the software that provides the tools for translating raw acquired brain signals into commands to control an application or a device. There’s a range of software, some proprietary, like MATLAB and some free and open source (FOSS), accessible under the GNU General Public License (GNU GPL). OpenViBE is one such freely accessible software. This thesis carries out a functionality and usability test of the platform, looking at its portability, architecture and communication protocols. To investigate the feasibility of reproducing the P300 xDAWN speller BCI presented by OpenViBE, users focused on a character on a 6x6 alphanumeric grid which contained a sequence of random flashes of the rows and columns. Visual stimulus is presented to a user every time the character they are focusing on is highlighted in a row or column. A TMSi analog-to-digital converter was used together with a 32-channel active electrode cap (actiCAP) to record user’s Electroencephalogram (EEG) which was then used in an offline session to train the spatial filter algorithm, and the classifier to identify the P300 evoked potentials, elicited as a user’s reaction to an external stimulus. In an online session, the users tried to spell with the application using the power of their brain signal. Aspects of evoked potentials (EP), both auditory (AEP) and visual (VEP) are further investigated as a validation of results of the P300 speller.
The aim of this master’s thesis is the design and implementation of a dedicated software system, for planning and implementation of occupational therapy intervention and research studies, in a driving simulator environment. In the first part, the concept based on user requirements is presented. It consists of architectural patterns and guidelines with the main focus on utility and application security. The result of this part is the design of a web application which supports integration in a clinical as well as a research environment. The second part presents the reference implementation of the previously introduced concept. It was developed under a case study in a research facility which hosts a driving simulator. A close cooperation and the influence the researcher’s experience led into a product which provides advanced usability for the target users. In conclusion, the thesis validated the concept indirectly under a testing phase of the reference implementation. It provides the base for a follow-up project to refine the software product and extend the concept to different fields of application.
Background: Stroke rehabilitation is a complex process that requires collaboration between stroke patients
and various health professionals. One important component of the rehabilitation is to set goals collaboratively with health professionals. The goal setting process can be time-consuming. In many cases, it is complicated for the patient and difficult to track for the health professionals. A simple user interface that supports patients, their family members and health professionals can help both sides to make the goal setting and attainment process easier.
Objectives: The aim is to design and develop a software for the goal attainment process of stroke patients with milder disabilities that facilitates goal setting process and the traceability of the goal progress for patients and health professionals.
Methods: Based on previous evaluated results, the web interface was developed and improved. Using this knowledge, a goal setting interface was added. To analyze the the goal setting process, goal attainment scaling (GAS) was included as well as parts of the International Classification of Functioning, Disability and Health (ICF) core set for stroke. The results were discussed afterwards in focus groups and evaluated based on two stroke patients, one family member and health professionals.
Results: We developed an interactive prototype, that can aid the rehabilitation at home by inserting
problems with ICF codes and different kinds of goals, creating new activities and tracing goal progress by reviewing the different goals. With the help of the GAS the outcome of the patient’s goals are visualized by a line chart presenting the positive or negative outcomes of the stroke rehabilitation.
Conclusion: The interactive prototype showed that it can support stroke patients during their rehabilitation
at home. A usability test indicated that the goal setting and attainment process was perceived as useful for patients and their family members. Small improvements have to be made to simplify use and error handling. For health professionals, the prototype could also simplify the documentation process by using ICF in the prototype, and also improving collaboration when using the tool for coordination.
Background: An important factor in approaching the challenges of chronic diseases, requiring long-term management and high costs, is the active participation of the patient in the care process. Objectives: Facing the problem of lacking patient-tailored, comprehensive health management software, the aim of this thesis is to generate ideas for a graphical user interface (GUI) to support stroke patients in the management of their individual care process. The objectives are to prototype a GUI for a patient e-service and to evaluate its usefulness and usability with stroke patients. Methods: A scenario-based, user-centered design method was used to envision ideas for the user interface. Static prototypes were realized with the tool Pencil and for the implementation of a dynamic prototype web programming techniques were used. For the evaluation of the prototypes the methods of focus group discussion and cooperative evaluation were applied. Results: The situation of a representative stroke patient and his interaction with the e-service were described in scenarios. Graphical user interfaces of the involved system views were derived from the scenarios and illustrated with static wireframe prototypes. A welcome screen, a care process timeline overview, and a diary with data sharing functionality were designed. The diary functionality was further examined by implementing a prototypical web application. During the evaluation, feedback for further improvements was gathered, and assumptions about the user information and functionality needs could be verified. Conclusion: The developed prototypes represent a suitable graphical user interface and visualizations to support stroke patients in the management of their care process. An overview of appointments on the welcome screen, a diary to document and monitor health, a timeline overview of all time-related health information and a selected sharing functionality were found to be important features of a personal health system for stroke patients.
Development and validation of a neural network for adaptive gait cycle detection from kinematic data
(2020)
(1) Background: Instrumented gait analysis is a tool for quantification of the different
aspects of the locomotor system. Gait analysis technology has substantially evolved over
the last decade and most modern systems provide real-time capability. The ability to
calculate joint angles with low delays paves the way for new applications such as real-time
movement feedback, like control of functional electrical stimulation in the rehabilitation
of individuals with gait disorders. For any kind of therapeutic application, the timely
determination of different gait phases such as stance or swing is crucial. Gait phases are
usually estimated based on heuristics of joint angles or time points of certain gait events.
Such heuristic approaches often do not work properly in people with gait disorders due to
the greater variability of their pathological gait pattern. To improve the current state-ofthe-
art, this thesis aims to introduce a data-driven approach for real-time determination
of gait phases from kinematic variables based on long short-term memory recurrent neural
networks (LSTM RNNs).
(2) Methods: In this thesis, 56 measurements with gait data of 11 healthy subjects,
13 individuals with incomplete spinal cord injury and 10 stroke survivors with walking
speeds ranging from 0.2 m
s up to 1 m
s were used to train the networks. Each measurement
contained kinematic data from the corresponding subject walking on a treadmill for 90
seconds. Kinematic data was obtained by measuring the positions of reflective markers on
body landmarks (Helen Hayes marker set) with a sample rate of 60Hz. For constructing a
ground truth, gait data was annotated manually by three raters. Two approaches, direct
regression of gait phases and estimation via detection of the gait events Initial Contact
and Final Contact were implemented for evaluation of the performance of LSTM RNNs.
For comparison of performance, the frequently cited coordinate- and velocity-based event
detection approaches of Zeni et al. were used. All aspects of this thesis have been
implemented within MATLAB Version 9.6 using the Deep Learning Toolbox.
(3) Results: The mean time difference between events annotated by the three raters
was −0.07 ± 20.17ms. Correlation coefficients of inter-rater and intra-rater reliability
yielded mainly excellent or perfect results. For detection of gait events, the LSTM RNN
algorithm covered 97.05% of all events within a scope of 50ms. The overall mean time
difference between detected events and ground truth was −11.62 ± 7.01ms. Temporal
differences and deviations were consistently small over different walking speeds and gait
pathologies. Mean time difference to the ground truth was 13.61 ± 17.88ms for the
coordinate-based approach of Zeni et al. and 17.18 ± 15.67ms for the velocity-based
approach. For estimation of gait phases, the gait phase was determined as a percentage.
Mean squared error to the ground truth was 0.95 ± 0.55% for the proposed algorithm
using event detection and 1.50 ± 0.55% for regression. For the approaches of Zeni et al.,
mean squared error was 2.04±1.23% for the coordinate-based approach and 2.24±1.34%
for the velocity-based approach. Regarding mean absolute error to the ground truth, the
proposed algorithm achieved a mean absolute error of 1.95±1.10% using event detection
and one of 7.25 ± 1.45% using regression. Mean absolute error for the coordinate-based
approach of Zeni et al. was 4.08±2.51% and 4.50±2.73% for the velocity-based approach.
(4) Conclusion: The newly introduced LSTM RNN algorithm offers a high recognition
rate of gait events with a small delay. Its performance outperforms several state-of-theart
gait event detection methods while offering the possibility for real-time processing
and high generalization of trained gait patterns. Additionally, the proposed algorithm
is easy to integrate into existing applications and contains parameters that self-adapt
to individuals’ gait behavior to further improve performance. In respect to gait phase
estimation, the performance of the proposed algorithm using event detection is in line
with current wearable state-of-the-art methods. Compared with conventional methods,
performance of direct regression of gait phases is only moderate. Given the results,
LSTM RNNs demonstrate feasibility regarding event detection and are applicable for
many clinical and research applications. They may be not suitable for the estimation
of gait phases via regression. For LSTM RNNs, it can be assumed, that with a more
optimal configuration of the networks, a much higher performance is achieved.
Medical imaging produces many images every day in clinical routine. Keeping up with the
daily image analysis task and this vast amount of data is quite a challenge for radiologists.
However, these analysis tasks can be automated with well-proven automatic segmentation
methods. Segmentation reviewing of an expert is necessary because learningbased
automatic segmentation methods may not perform well on exceptional image
data. Creating valid segmentations by reviewing them also improve the learning-based
methods.
Combining established standards with modern technologies creates a flexible environment
to efficiently evaluate multiple segmentation algorithm outputs based on different metrics
and visualizations and report these analysis results back to a clinical system environment.
The presented software system can inspect such quantitative results in a fast and intuitive
way, potentially improving the daily repetitive segmentation review and rework of a
research radiologist. The presented system is designed to be integrated into a virtual
distributed computing environment with other systems and analysis methods. Critical
factors for this particular environment are the handling of many patient data and routine
automated analysis with state of the art technology.
First experiments show that the time to review automatic segmentation results can be
roughly divided in half while the confidence of the radiologist is enhanced. The system
is also able to highlight individual slices which are essential for the expert’s review
decision. For this highlighting, different metric scores are compared and evaluated.