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This thesis presents a photmetric stereo method based on the work of Schulze [35], who in turn extended the research of Schroeder et al. [33,34] In this approach, three different lightings are obtained by illuminating the object by three colored light sources (red, green and blue). A video of the subject is captured from the front, the back and the side. The single frames are then extracted from the viedo, which are used for the 3D reconstruction of the subject. The aim of this work was to improve the presented method of Schulze with real patient subjects by getting a better sphere calibration and changing some parameters in the patient processing. As the graphical interface was implemented for persons with a technical background, it has been changed to become also more convenient to use for non-technically oriented staff
The Greifswald University Hospital in Germany conducts a research project called "Greifswald Approach to Individualized Medicine (GANI_MED)", which aims at improving patient care through personalized medicine. As a result of this project, there are multiple regional patient cohorts set up for different common diseases. The collected data of these cohorts will act as a resource for epidemiological research. Researchers are going to get the possibility to use this data for their study, by utilizing a variety of different descriptive metadata attributes. The actual medical datasets of the patients are integrated from multiple clinical information systems and medical devices. Yet, at this point in the process of defining a research query, researchers do not have proper tools to query for existing patient data. There are no tools available which offer a metadata catalogue that is linked to observational data, which would allow convenient research. Instead, researchers have to issue an application for selected variables that fit the conditions of their study, and wait for the results. That leaves the researchers not knowing in advance, whether there are enough (or any) patients fitting the specified inclusion and exclusion criteria. The "Informatics for Integrating Biology and the Bedside (i2b2)" framework has been assessed and implemented as a prototypical evaluation instance for solving this issue. i2b2 will be set up at the Institute for Community Medicine (ICM) at Greifswald, in order to act as a preliminary query tool for researchers. As a result, the development of a research data import routine and customizations of the i2b2 webclient were successfully performed. An important part of the solution is, that the metadata import can adapt to changes in the metadata. New metadata items can be added without changing the import program. The results of this work are discussed and a further outlook is described in this thesis.
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.
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.
Ambulant studies are dependent on the behavior and compliance of subjects in their home environment. Especially during interventions on the musculoskeletal system, monitoring physical activity is essential, even for research on nutritional, metabolic, or neuromuscular issues. To support an ambulant study at the German Aerospace Center (DLR), a pattern recognition system for human activity was developed. Everyday activi-ties of static (standing, sitting, lying) and dynamic nature (walking, ascending stairs, descending stairs, jogging) were under consideration. Two tri-axial accelerometers were attached to the hip and parallel to the tibia. Pattern characterizing features from the time domain (mean, standard deviation, absolute maximum) and the frequency domain (main frequencies, spectral entropy, autoregressive coefficients, signal magni-tude area) were extracted. Artificial neural networks (ANN) with a feedforward topology were trained with backpropagation as supervised learning algorithm. An evaluation of the resulting classifier was conducted with 14 subjects completing an activity protocol and a free chosen course of activities. An individual ANN was trained for each subject. Accuracies of 87,99 % and 71,23 % were approached in classifying the activity protocol and the free run, respectively. Reliabilities of 96,49 % and 76,77 % were measured. These performance parameters represent a working ambulant physical activity monitor-ing system.
Every year, hundreds of thousands of patients are affected by treatment failure or adverse drug reactions, many of which could be revented by pharmacogenomic testing. To address these deficiencies in care, clinics require
automated clinical decision support through computer based systems, which provide clinicians with patient-specific ecommendations. The primary knowledge needed for clinical pharmacogneomics is currently being
developed through textual and unstructured guidelines.
In this thesis, it is evaluated whether a web service can annotate clinically relevant genetic variants with guideline information using web services and identify areas of challenge. The proposed tool displays a formal representation of pharmacogenomic guideline information through a web service and existing resources. It enables the annotation of variant call format (VCF) files with clinical guideline information from the Pharmacogenomic Knowledge Base (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC).
The applicability of the web service to nnotate clinically relevant variants with pharmacogenomics guideline information is evaluated by translating five guidelines to a web service workflow and executing the process to annotate publically available genomes. The workflow finds genetic variants covered in CPIC guidelines and influenced drugs.
The results show that the web service could be used to annotate in real time clinically relevant variants with up-to-date pharmacogenomics guideline information, although several challenges such as translating variants into star allele nomenclature and the absence of a unique haplotype nomenclature
remain before the clinical implementation of this approach and the use on other drugs.
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.
eHMIS is a Ugandan Hospital Information System (HIS), which targets the Sub-Saharan market. In its first version all forms were programmed statically and adaptations were done by code modifications. In 2014 the development of a second version of eHMIS based on Java started.
This work aims at introducing dynamic forms to this new version. While forms that are significantly important to the workflow of the application will remain static, others are replaced by forms that are dynamically designed by the user. By that, the application will become more flexible and local and situational tailoring will be possible without inducing extra costs.
In this thesis the design, implementation and testing of dynamic forms in eHMIS is discussed. The architecture is based on the questionnaire resource of FHIR®. The module enables the user to create questions and group them into sections and questionnaires. For each question the type of answer expected and other constraints can be defined. A user interface covering all functions was designed, so that no programming skills are required. In a first step dynamic forms were integrated in the application's workflow for recording symptoms, though other fields of application are possible. For testing, a usability experiment was conducted in Tororo Hospital in Eastern Uganda, using the thinking aloud method. Results were analysed and evaluated to detect usability problems and gain a general impression of user satisfaction.
Segmentation of the Cerebrospinal Fluid from MRI Images for the Treatment of Disc Herniations
(2010)
About 80 percent of people are affected at some point in their lives by lower back pain, which is one of the most common neurological diseases and reasons for long-term disability in the United States. The symptoms are primarily caused by overly heavy lifting and/or overstretching of the back, leading to a rupture and an outward bulge of an intervertebral disc, which puts pressure on and pinches the nerve fibers of the spine. The most common form is a lumbar disc herniation between the fourth and fifth lumbar vertebra and between the fifth lumbar vertebra and the sacrum. In recent years the diagnosis of lower back pain has improved, mainly due to enhanced imaging techniques and imaging quality, but the surgical therapy remains hazardous. Reasons for this include low visibility when accessing the lumbar area and the high risk of causing permanent damage when touching the nerve fibers. A new approach for increasing patient safety is the segmentation and visualization of the cerebrospinal fluid in the lower lumbar region of the vertebral column. For this purpose a new fully-automatic and a semi-automatic approach were developed for separating the cerebrospinal fluid from its surroundings on T2-weighted MRI scans of the lumbar vertebra. While the fully-automatic algorithm is realized by a model-based searching method and a volume-based segmentation, the semi-automatic algorithm requires a seed point and performs the segmentation on individual axial planes through a combination of a region-based segmentation algorithm and a thresholding filter. Both algorithms have been applied to four T2-weighted MRI datasets and are compared with a gold-standard segmentation. The segmentation overlap with the gold-standard was 78.7 percent for the fully-automatic algorithm and 93.1 percent for the semi-automatic algorithm. In the pathological region the fully-automatic algorithm obtained a similarity of 56.6 percent, compared to 87.8 percent for the semi-automatic algorithm.
Quantitative assessment of Positron Emission Tomography (PET) imaging can be used for diagnosis and staging of tumors and monitoring of response in cancer treatment. In clinical practice, PET analysis is based on normalized indices such as those based on the Standardized Uptake Value (SUV). Although largely evaluated, these indices are considered quite unstable mainly because of the simplicity of their experimental protocol. Development and validation of more sophisticated methods for the purposes of clinical research require a common open platform that can be used both for prototyping and sharing of the analysis methods, and for their evaluation by clinical users. This work was motivated by the lack of such platform for longitudinal quantitative PET analysis. By following a prototype driven software development approach, an open source tool for quantitative analysis of tumor changes based on multi-study PET image data has been implemented. As a platform for this work, 3D Slicer 4, a free open source software application for medical image computing has been chosen. For the analysis and quantification of PET data, the implemented software tool guides the user through a series of workflow steps. In addition to the implementation of a guided workflow, the software was made extensible by integration of interfaces for the enhancement of segmentation and PET quantification algorithms. By offering extensibility, the PET analysis software tool was transformed into a platform suitable for prototyping and development of PET-specific segmentation and quantification methods. The accuracy, efficiency and usability of the platform were evaluated in reproducibility and usability studies. The results achieved in these studies demonstrate that the implemented longitudinal PET analysis software tool fulfills all requirements for the basic quantification of tumors in PET imaging and at the same time provides an efficient and easy to use workflow. Furthermore, it can function as a platform for prototyping of PET-specific segmentation and quantification methods, which in the future can be incorporated in the workflow.