22455 research outputs found
Sort by
Reproducibility in cancer research
Get PDFSince decades, human cell lines serve as indispensable tools in cancer research (1). While these research models are widely recognized and favorable due to their relatively easy usage and capability to provide invaluable insight into cancer biology, recent studies raised questions about their reliability (2–5). Over the past decade, researchers have identified significant challenges with the genomic stability of cancer cell lines in unnatural culture environments and the reproducibility of results obtained using these models (2,3,6,11). In the late 2010s, two pioneering studies have shed light on the genomic and phenotypic instability of highly mutated adult carcinoma cell lines: HeLa and MCF-7 (2,3). These studies revealed a remarkable diversity of the respective same cancer cell line across different laboratories, along with the instability of a cell line in prolonged cell culture leading to genomic and transcriptomic heterogeneity and consequential phenotypic variations (2,3).
These findings underscored the limitations in reproducibility associated with using human cell line models in cancer research. Nevertheless, while the implications of these observations on adult carcinoma cell lines are becoming increasingly apparent, the generalizability of such conclusions to other cancer cell lines remains largely unexplored.
This thesis aimed to investigate the level of variation in cancer cell lines with a lower mutational burden (oligomutated). To achieve this goal, Ewing sarcoma (EwS), a malignant pediatric bone cancer, was selected as a representative model due to its reputation for harboring minimal somatic mutation (7–9). EwS is caused by a chromosomal rearrangement that results in a chimeric oncogenic transcription factor (COTF), which plays a crucial role in regulating the transcription and biology of the tumor (8,10). The hypothesis was that EwS cell lines would exhibit greater genetic and phenotypic stability than adult carcinoma cell lines. Analyzing the molecular and phenotypic traits of 11 EwS cell line A-673 strains from various laboratories showed remarkable genomic and phenotypic uniformity, contrasting control groups of adult carcinoma HeLa and MCF-7 strains. Additionally, newly purchased A-673, HeLa and MCF-7 cell lines were subjected to a 12-months continuous cell culture for a longitudinal analysis. Notably, EwS cell line A-673 exhibited exceptional stability in terms of genomic and transcriptomic levels as well as drug sensitivity, when compared to adult carcinoma cell lines. Further, four additional EwS cell lines were included in the longitudinal analysis to investigate the observed stability in the A-673 cell line. The analysis revealed that although all five EwS cell lines showed higher stability than their adult carcinoma counterparts, varying degrees of (epi)genomic, transcriptomic, and phenotypic alterations were observed after 12 months of continuous passaging. This indicated that cell line stability is a spectrum even within the same cancer entity.
The observed remarkable stability of COTF-driven pediatric sarcoma cells underscores their potential as faithful models for cancer research and therapeutic drug testing. Since these cell line models could offer more consistent and reproducible outcomes, this discovery may have profound implications for preclinical studies, which may aid in the translation of research findings into clinical applications. Moreover, this thesis sheds light on the spectrum of reproducibility in in vitro scientific results, emphasizing the importance of carefully considering cell line characteristics in experimental design and result interpretation, even within the same tumor entity
Mesenchymal stem cell therapy using theranostic sodium iodide symporter effector gene in glioblastoma
Get PDFCharakterisierung des mitochondrial antiviral-signaling protein Interaktionspartners Optineurin
Get PDFEvaluation of non-invasive PET quantification instead of invasive gold-standard methods in preclinical and clinical applications
Get PDFBackground
Quantification of molecular processes by means of non-invasive positron emission tomography (PET) is a challenging task of nuclear medicine, involving oncological as well as neurological and cardiological questions. In this context, the pharmacokinetic and regional concentration of radiotracers are approximated using various models and methods and characterized in terms of specific parameters and parametric PET images. In order to develop such quantifying approaches, preclinical and clinical studies are necessary in which correlations and validations are performed with mostly invasive gold-standard methods.
Purpose
This thesis aimed at establishing and evaluating two approaches using non-invasive PET instead of invasive gold-standard methods to visualize cellular mechanisms in the context of radiation-induced cellular damage and cerebral processes in neurological issues.
Methods
First approach: Longitudinal PET imaging with the proliferation radiotracer 3'-[18F]fluoro-3'-deox- ythymidine ([18F]FLT) and apoptosis radiotracer 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]ML-10) was performed over a six-month period at defined time points in wild-type mice irradiated with different irradiation doses (0 Gy, 0.5 Gy, 1 Gy, 3 Gy). On the one hand, this was correlated and validated with histological and immunohistochemical examinations with Hematoxylin-Eosin (HE), Ki-67 and cleaved Caspase3 staining. On the other hand with analyses of white blood cells (WBC), red blood cells (RBC) and platelets (PLT). Furthermore, biodistribution studies with the radiotracers [18F]FLT and [18F]ML-10 were performed. Second approach: In healthy controls and patients with Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP), aggregated tau deposits were visualized by [18F]PI-2620 PET and, in this context, arterial input functions were obtained by continuous sampling of radial artery whole blood. These were validated with non-invasive image-derived input functions (IDIF) generated by manual and automated extraction of the carotid artery in the corresponding PET image. Volumes of distribution (VT) and volume of distribution ratios (VTr) were calculated with the input functions using Logan plots and compared with quantitative parameters such as standard uptake value ratios (SUVr) and distribution volume ratios (DVr) determined by simplified reference tissue modeling.
Results
First approach: The [18F]FLT signal of the hematopoietic bone marrow correlated strongly with blood parameters, especially WBC, and histological as well as immunohistochemical data. Regarding other organs, such as the gastrointestinal tract and thymus, there were some correlations between the data of [18F]FLT PET and invasive gold-standard methods, but also unexpected, non-correlating data that need further investigation, as it does the [18F]ML-10 signal of the hematopoietic bone marrow. The biodistribution data showed strong variations with high standard deviations, which were attributed to difficulties in the technical performance. Second approach: AIF highly correlated with IDIF regardless of the manual or automated extraction method. VT revealed considerable variance across groups, which was strongly reduced by calculating VTr. VTr and DVr outperformed VT and SUVr in detecting differences between healthy controls and PSP patients, whereas all quantification parameters performed similarly in comparison of healthy controls and AD patients.
Conclusion
With appropriate radiotracers, non-invasive PET can visualize and quantify biological processes such as proliferation and apoptosis or tau deposition in vivo. In the course of testing and evaluating these quantifications, there are often performed validations with invasive gold-standard methods: Histology is suitable for the validation of PET imaging cellular processes, the measurement of activity concentration in tissue or blood is suitable for the validation of image-based determinations of activity concentration. It is important to be aware of sources of error and limitations, even with gold-standard methods, as the example of biodistribution showed
Development of efficient methods for the computation of ground state energies, nuclear gradients, and nuclear magnetic resonance shieldings based on the adiabatic-connection fluctuation-dissipation theorem
Get PDFOne of the primary goals in quantum chemistry is to develop efficient and accurate methods for the computation of energetic parameters and molecular properties across a broad range of system sizes and complexities, enabling reliable predictions of experimental data. In this regard, the random phase approximation (RPA), a post-Kohn–Sham method derived from the adiabatic-connection fluctuation-dissipation theorem, has emerged as a highly promising method.
This thesis comprises a collection of novel methods for the computation of RPA energies as well as properties, derived from first- and second-order derivatives of the energy. The memory limitation problem, a common problem for electronic structure methods, is alleviated for the calculation of RPA energies by introducing a minimal overhead batching method based on a Lagrangian formalism, thereby extending RPA's applicability to very large systems that were out of reach before on a single compute node. This method facilitates efficient balancing between memory demands and resource utilization. Moreover, it is widely applicable and can be adapted for related electronic structure methods.
For RPA nuclear gradients—the first derivative of the RPA energy with respect to nuclear coordinates—an efficient method for incorporating the frozen-core approximation is introduced. This approach not only yields performance improvements but also ensures accurate results using atomic and auxiliary basis sets specifically designed to correlate valence electrons only, as is the case for most basis sets.
Furthermore, in previous work it has been shown, using numerical derivatives, that nuclear magnetic resonance (NMR) shieldings—the second mixed derivative of the energy with respect to the nuclear magnetic moment and the magnetic field—based on RPA yield accuracies comparable to coupled cluster singles and doubles. Motivated by this good performance, the thesis introduces, for the first time, the derivation and implementation of analytical NMR shieldings within RPA. Furthermore, to increase the efficiency of the method, a local resolution-of-the-identity (RI) metric is employed to introduce sparsity in the RI tensors, which is efficiently exploited using sparse matrix algebra techniques. Additionally, Cholesky decomposed density type matrices and an efficient batching scheme for memory intensive intermediates are utilized, thereby extending the applicability of the method to even larger systems.
Another promising method that improves upon many of the shortcomings of RPA, are σ-functionals. While they have been shown to achieve high accuracies for energetic data, nuclear gradients, and vibrational frequencies, NMR shieldings have not been comprehensively studied so far. This work closes that gap by carrying out an extensive benchmark study to investigate the accuracy of σ-functionals for NMR shieldings
Photon detection by converter layers using a micro-pattern gaseous detector
Get PDFMicro-Pattern Gaseous Detectors (MPGDs) have an excellent spatial and temporal resolution. They are high rate capable, cost-effective and scalable. Therefore, they are used in experiments like ATLAS for tracking of charged particles. Due to the low atomic number (Z<20) and density of the standard detector gas, MPGDs exhibit a poor detection efficiency for photons. For many applications in medical physics, like imaging or PET, an efficient photon detection with high spatial resolution is essential. To exploit the advantages of MPGDs for photon detection, this thesis aims to improve their photon detection efficiency while providing precise position information using a GEM (Gaseous Electron Multiplier) detector, a type of MPGDs.
The photon interaction cross-section increases for higher-Z materials in the keV energy range, where the photoelectric effect dominates. The novel approach is to arrange the converter layers in the drift region of the GEM detector in a stacked configuration perpendicular to its readout plane. This allows for multiple layers, each increasing the photon interaction probability. The converter layers are made of an insulating carrier material with copper strips (Z=29) on both sides. The photon conversion is investigated exemplarily using a 59.5 keV X-ray source. Photoelectrons exiting the converter material into the gas are guided downwards by an electric field into the active area of the GEM detector, providing 2D position. In case this 2D position allows for the interaction position on the converter layer to be unambiguously reproduced with high accuracy, the direction of a point source can be reconstructed.
Both, perpendicular and tilted configurations using 5 converter layers are investigated, whereby the tilted configuration is used for studying position reconstruction methods. A detailed simulation, including Geant4, ANSYS and Garfield++, is established to understand the physical processes in the converter layers and the detector. Simulation and measurement provide good agreement regarding the electron drift under various conditions of the electric guiding field, the deposited charge and detection efficiency when using converter layers of varying thickness and insulating materials. By optimizing the material properties, the detection efficiency is improved by a factor of 2 to (1.38±0.21) % compared to having no layers, with thin insulating material layers being favorable.
The analysis of the simulation results shows the interaction processes influencing the detection efficiency. Instead of directly detecting the photoelectrons produced in copper, 8 keV photons are emitted due to electron rearrangement following the photoelectric effect. This photon interacts with the gas creating an electron-ion pair. Unfortunately, the detected electrons carry no more information about the initial interaction position or the direction of the point source, since the 8 keV photon is emitted isotropically.
This work improves the detection efficiency for photons by material optimization of the converter layers and provides a detailed understanding of their working principle.
The detection efficiency for 511 keV photons, like in PET, in the GEM detector with converter layers is measured using a coincidence measurement setup including scintillation detectors. A 511 keV photon conversion efficiency of 0.31 % is determined with 9 converter layers, which is similar to the expected value from the simulation and about twice as high compared to a setup without converter layers.
Beyond that, new front-end electronics for the ATLAS detector was investigated. For the High Luminosity upgrade of the LHC, the readout electronics of the Monitored Drift Tube (MDT) chambers in the ATLAS detector will be replaced to ensure flawless performance at the increased collision rates. This includes a new Amplifier-Shaper-Discriminator (ASD2) chip. Its performance is investigated, and a testing procedure is developed to identify the best-performing ASD2 chips for the integration.Mikrostrukturierte Gasdetektoren (MPGDs) weisen eine hervorragende räumliche und zeitliche Auflösung und eine hohe Ratenfestigkeit auf, sind kostengünstig und skalierbar. Sie werden in Experimenten wie ATLAS zur Spurrekonstruktion geladener Teilchen eingesetzt. Aufgrund der niedrigen Ordnungszahl (Z<20) und Dichte des Standard-Detektorgases weisen MPGDs eine geringe Detektionseffizienz für Photonen auf. In der medizinischen Diagnostik, wie Bildgebung oder PET, ist eine effiziente Photonendetektion mit hoher räumlicher Auflösung entscheidend. Um die Vorteile von MPGDs für die Photonendetektion zu nutzen, soll diese Arbeit ihre Photonendetektionseffizienz verbessern und gleichzeitig präzise Positionsinformationen liefern. Dazu wird ein GEM-Detektor (Gaseous Electron Multiplier) genutzt, eine Art von MPGDs.
Der Wechselwirkungsquerschnitt von Photonen nimmt bei Materialien mit höherem Z im keV-Energiebereich zu, in dem der photoelektrische Effekt dominiert. Das neuartige Konzept besteht darin, Konverterschichten mit höherem Z im Driftbereich des GEM-Detektors in einer gestapelten Konfiguration senkrecht zu seiner Ausleseebene anzuordnen. Dies ermöglicht die Verwendung mehrerer Schichten, von denen jede die Wechselwirkungswahrscheinlichkeit erhöht. Die Konverterschichten bestehen aus einem isolierenden Trägermaterial mit Kupferstreifen (Z=29) und werden exemplarisch mit 59,5 keV Photonen untersucht. Die aus dem Konvertermaterial in das Gas austretenden Photoelektronen werden durch ein elektrisches Feld nach unten in den aktiven Bereich des GEM-Detektors geleitet, wo ihre 2D-Position bestimmt wird. Wenn aus dieser 2D-Position die Interaktionsposition auf der Konverterschicht mit hoher Genauigkeit eindeutig reproduziert werden kann, ermöglicht dies die Rekonstruktion der Richtung der Punktquelle.
Es werden senkrechte und geneigte Anordnungen mit je 5 Konverterschichten verwendet, wobei mit der geneigten Konfiguration Methoden zur Positionsrekonstruktion untersucht werden. Mit detaillierten Simulationen (Geant4, ANSYS und Garfield++) werden die physikalischen Prozesse in den Schichten und im Detektor analysiert. Simulation und Messung zeigen eine gute Übereinstimmung der Elektronenbewegung bei verschiedenen elektrischen Feldern, der deponierten Ladung und der Detektionseffizienz unter Verwendung von Konverterschichten mit unterschiedlicher Dicke und Isoliermaterialien. Durch Materialoptimierung wird die Detektionseffizienz im Vergleich zu einem Aufbau ohne Schichten um den Faktor 2 auf (1,38±0,21) % verbessert, wobei dünne Isolationsschichten bevorzugt werden.
Die ablaufenden Interaktionsprozesse der Simulation zeigt: anstatt der direkten Detektion des in Kupfer erzeugten Photoelektrons, ist der dominante detektierte Effekt die Emission eines 8 keV Photons, das durch die Elektronenumordnung nach dem photoelektrischen Effekt entsteht. Dieses Photon interagiert mit dem Gas und erzeugt ein Elektron-Ionen-Paar. Das detektierte Elektron enthält keine Informationen über die anfängliche Interaktionsposition oder die Richtung der Punktquelle, da das 8 keV Photon isotrop emittiert wird.
In dieser Arbeit wird die Detektionseffizienz für Photonen durch Materialoptimierung der Konverterschichten verbessert und ein detailliertes Verständnis ihrer Funktion geschaffen.
Die Detektionseffizienz des GEM-Detektors mit Konverterschichten für 511 keV-Photonen, wie sie bei der PET entstehen, wird mittels Koinzidenzmessung mit Szintillationsdetektoren bestimmt. Die Photonenkonversionseffizienz mit 9 Konverterschichten ist 0,31 %, welche dem erwarteten Wert entspricht und etwa doppelt so hoch ist verglichen ohne Schichten.
Im Rahmen dieser Arbeit wurde darüber hinaus noch eine Elektronikuntersuchung durchgeführt. Für das High-Luminosity-Upgrade des LHC Speicherrings am CERN werden die Ausleseelektronik der MDT-Kammern (Monitored Drift Tube) im ATLAS-Detektor ausgetauscht, um eine einwandfreie Funktionalität bei den erhöhten Kollisionsraten zu gewährleisten. Dies umfasst den neuen Amplifier-Shaper-Discriminator-Chip (ASD2). Seine Leistung wird untersucht und ein Testverfahren entwickelt, um die leistungsstärksten ASD2-Chips für die Integration zu ermitteln
Measurement invariance and change of affective and cognitive Theory of Mind in mental health patients
Get PDFTheory of Mind (ToM) is one of the most investigated aspects of social cognition and refers to a range of mental processes that allow humans to interpret, perceive, and respond to social cues, while accounting for a specific situation. ToM is the cognitive ability to ascribe mental states such as desires, beliefs, intentions and emotions to oneself and others (Apperly, 2012). It allows humans to predict and explain behavior. ToM can also be construed as a part of empathy, in this case ToM is equated to one aspect of empathy termed cognitive empathy. The second aspect of empathy is affective empathy, which refers to affective contagion (i.e., sharing the emotional experiences of others). The two systems of empathy rely on separate but interacting brain networks (Shamay-Tsoory, 2011).
ToM is not a monolithic ability; it includes two different facets, affective and cognitive ToM (Maleki et al., 2020; Shamay-Tsoory et al., 2007; Zabihzadeh et al., 2017). Cognitive ToM involves representing thoughts, intentions, or beliefs by making inferences about mental states through interpretation or prediction of others’ behaviors (i.e., understanding the intentions of others). Affective ToM involves representing emotions and feelings by decoding and discriminating the mental states of others based on available environmental information.
The importance of ToM is exemplified by the finding that ToM deficits have been reliably associated to mental disorders. For instance, individuals with alcohol use disorder (AUD) show medium to strong ToM impairments (Bora & Zorlu, 2017; Hanegraaf et al., 2021; Onuoha et al., 2016; Sanvicente-Vieira et al., 2017). ToM impairments are also common in patients with borderline personality disorder (BPD; Bora, 2021; Hanegraaf et al., 2021; Németh et al., 2018; Richman & Unoka, 2015). The ToM deficits shown by these groups are likely contributing to the interpersonal difficulties frequently seen among BPD and AUD patients (Hanegraaf et al., 2021). Further, both disorders are frequently comorbid. At the same time the two groups are marked by uniquely different socio-demographic characteristics. Even though both are marked by ToM deficits, the two disorders have been linked to different types of ToM deficits. People can show exceeding ToM, less ToM, or no ToM. Exceeding ToM implies over-interpretating others’ behaviors. Reduced ToM and no ToM imply a limited tendency to ascribe mental states to others, which is often marked by literal understanding (Vegni et al., 2021). By examining these two distinct clinical samples, which show characteristic symptoms, socio-demographic characteristics, and ToM deficits, a more comprehensive understanding of ToM abilities can be achieved.
Studies on socio-demographic characteristics such as sex or age have shown inconsistent results. There is some evidence that men outperform women (Russell et al., 2007), while in other studies sex differences are largely absent (Barrett et al., 1998; Derntl et al., 2010). Given the inconsistent results, further research is crucial to clarify sex influences on ToM. Studies about age indicate a decline in ToM in older adults (Bailey et al., 2008; Henry et al., 2013; Krych-Appelbaum et al., 2007). Hence, ToM development across the entire lifespan is relevant.
ToM research is plagued by the presence of a multitude of measures (Olderbak & Wilhelm, 2020; Quesque & Rossetti, 2020). According to Quesque and Rossetti (2020), ToM measures need to require test takers to represent others' mental states and to distinguish these from one’s own. These two criteria are fulfilled by the Movie for the Assessment of Social Cognition (MASC). The MACS is consistently employed across all three studies presented in this dissertation. While many ToM measures have been criticized for lacking validity (Pabst et al.,2022), the MASC (Dziobek et al., 2006) is considered both valid and reliable (Benito-Ruiz et al., 2022; Fossati et al., 2018). Nevertheless, it has created inconsistent findings. To enhance the understanding of the MASC’s psychometric properties, individual and situational factors that influence affective and cognitive ToM should be investigated to improve the understanding of ToM measurements in the clinical context. This dissertation presents findings from three articles. Article 1 tested invariance of the MASC over the duration of the test and depending on sex and age. Article 2 explored the impact of the interaction partner’s gender per item within the ToM measure. Article 3 presents findings on changes of ToM during inpatient treatment.
Article 1 explored ToM in a large clinical sample, including patients with AUD and Personality Disorders (PD). The study assessed the changes in cognitive and affective ToM within the MASC over the course of a test session. Results indicated a decrease in cognitive ToM and an improvement in affective ToM performance as the test progressed. This effect was moderated by age, older participants showed a more pronounced trend in affective ToM than younger. Sex differences were also observed, with women displaying higher affective ToM skills. Furthermore, individuals with PD generally showed better ToM abilities than those with AUD. These findings underscore the importance of considering individual (e.g., age, sex), and situational (test duration) variables when measuring ToM abilities, offering insight into potential reasons for inconsistent results in prior studies.
Article 2 examined ToM assessments by exploring how the gender of the interaction partners and the congruence of their perspective affect ToM measurement. Based on previous research, it was hypothesized that ToM scores vary with the social groups of the interaction partners. ToM performance is enhanced when the target and the perceiver share similar social groups and perspectives. Conversely, ToM performance is diminished when interaction partners have identical social groups but possess differing perspectives (Simpson & Todd, 2017). Article 2 assessed ToM in a large clinical sample, including individuals with AUD, and PD, and healthy controls (HC). A consistent pattern emerged, items with the same gender of interaction partners resulted in lower ToM abilities compared to items with different gender of interaction partners, within both clinical samples and HC. Within clinical samples, items with male targets resulted in better ToM performance compared to items with female targets, the smaller HC did not replicate this effect. The findings indicate that the gender of interaction partners serves as a significant moderator of ToM performance. However, the findings of this article need to be further investigated with studies in which the gender within items is systematically manipulated.
Article 3 focused on the effect inpatient psychotherapeutic treatment has on affective and cognitive ToM and related outcomes (like alcohol use and psychological symptoms) in individuals with AUD. This longitudinal study used the MASC to track changes in affective and cognitive ToM between admission and discharge. This longitudinal study was carried out within a naturalistic environment to increase the degree of clinical representativeness and the external validity of clinical care routine. All variables were assessed at admission and discharge of the inpatient stay. Article 3 investigated affective and cognitive ToM in a longitudinal study within individuals with AUD for the first time. It contributes to the expanding body of literature by demonstrating that only cognitive ToM improved following an eclectic abstinence-oriented inpatient treatment. It might be that more specific interventions are required to yield improvements in affective ToM. Moreover, the results of Article 3 reveal that initial ToM abilities positively correlated with a decrease in symptoms of depression and somatization, suggesting ToM's potential as a treatment target to improve psychological health not only in patients with BPD (Kvarstein et al., 2020), but also in those with AUD. These findings highlight the need for further research on ToM's relationship with psychological symptoms in AUD, emphasizing the value of incorporating ToM training into treatment programs. This fits with the current literature highlighting ToM’s vital role in the recovery process (Rupp et al., 2017) and the alleviation of comorbid symptoms in other mental disorders (Sondermann et al., 2020).
In conclusion, this dissertation explored the interactions of multiple individual and situational factors that influence ToM measurement. The studies showed that ToM measurements would be more consistent if age is accounted for. Future, ToM measures could balance the number of male and female items. The studies help to understand the heterogeneity in the previous findings. By differentiating between these two ToM facets within sizable clinical samples, while always relying on the MASC, this research enriches our understanding of the subject.
Previous findings highlight the significance of ToM across a spectrum of mental disorders, McLaren et al. (2022) provided a comprehensive examination of ToM exceeding in many mental disorders. Moreover, a systematic review by Cotter et al. (2018) emphasized the role of social cognitive processes as transdiagnostic clinical indicators across various clinical presentations, underscoring their importance in discerning disease progression, and treatment efficacy. Previous findings have led to the conclusion that ToM should be considered as a transdiagnostic factor essential for conceptualizing mental health. This was for instance recognized within the Research Domain Criteria (RDoC) framework (National Institute of Mental Health, 2020). This framework assesses dysfunctions across broad psychological and biological matrices and tries to overcome the limitations of categorical diagnostic models.
Especially the last article highlighted the potential relevance of ToM for therapeutic processes. To effectively integrate social cognition training within psychotherapeutic treatment programs, a more comprehensive understanding of ToM in clinical adult samples is necessary. Evidence supports that such integrative therapies can improve outcomes across various psychiatric disorders (Peyroux & Franck, 2014). This offers valuable insights for identifying and prioritizing therapeutic interventions in patients within clinical samples, specifically among patients with AUD and PD
Verarbeitung radiologischer Bilddaten zur Verbesserung der operativen Behandlung unfallchirurgisch-orthopädischer Patienten
Get PDFDie dem Habilitationsprojekt zugrunde liegende Idee ist die Nutzbarmachung von medizinischen (meist radiologischen) Bilddaten für die Verbesserung der Therapie im Fachgebiet Orthopädie und Unfallchirurgie. Das größte Potential für die Generierung eines Sekundärnutzens über den eigentlichen Primärnutzen dieser Daten (z.B. Röntgendiagnostik, Diagnosestellung) hinaus bietet die Weiterverarbeitung durch digitale Systeme bzw. Software. Durch den technischen Fortschritt stehen uns mittlerweile viele dazu notwendige Komponenten zur Verfügung, seien es leistungsfähige Hardware oder Softwarekomponenten, die man weiterentwickeln kann.
Die in dieser kumulativen Arbeit behandelten Forschungsprojekte basieren überwiegend auf folgenden Voraussetzungen für ihre Umsetzung:
1) Die medizinischen Rohdaten (z.B. Röntgenbilder oder CT (Computertomographie) / MRT (Magnetresonanztomographie)-Volumendaten) sind in großer Menge und hoher Qualität entweder bereits verfügbar, fallen bei der Behandlung der Patienten regelmäßig an oder können durch einfache technische Lösungen generiert werden.
2) Die technologische Lösung zur Verarbeitung der Daten, um diese für eine sekundäre Verwertung verfügbar zu machen, ist entweder bereits vorhanden, kann durch Hinzufügen eigener Softwarekomponenten erweitert oder mit vergleichsmäßig wenig Aufwand selbst entwickelt werden.
3) Die medizinische Expertise bezüglich des bisherigen Problems („problem owner“) sowie eine praxisnahe Lösungsvision kann durch enge Orientierung am klinischen Prozess generiert und in die Entwicklung des Projekts eingebracht werden.
Daraus resultiert die Notwendigkeit einer engen interdisziplinären Zusammenarbeit zumindest der Experten von Komponente 2 und 3 sowie der Zugriff auf qualitativ und quantitativ ausreichende Rohdaten (in vielen Fällen sog. DICOM Bilddaten, ein digitales medizinisches Bilddatenformat).
Die im Laufe der Jahre und durch die Weiterentwicklung unserer Arbeitsgruppe konkret identifizierten technischen Lösungsfelder im Rahmen der beschriebenen Grundidee sind:
Die Weiterverarbeitung von CT DICOM Daten zu einer 3D-Druck-Lösung für die Behandlung von Erkrankungen und Verletzungen des Skeletts
Die Entwicklung einer Methode zur Prüfung und Sicherstellung der Qualität von anatomischen 3D-Drucken zur Patientenbehandlung
Die Nutzung von radiologischen Bilddaten durch Augmented/Mixed/Virtual Reality zur Unterstützung von chirurgischen Eingriffen
Die Evaluierung von Systemen zur Röntgenbild-basierten Computer-Assisted-Surgery im realen Operationssaal
Verwendung von radiologischen Bilddaten und 3D-Druck zur Ausbildung in der Wirbelsäulenchirurgie
Die Nutzung von KI-Methoden und Signalanalyse zur Erweiterung der Kniegelenksdiagnostik
Diese verschiedenen Fragestellungen wurden im Rahmen der Veröffentlichungen wissenschaftlich behandelt und publiziert. Dieses Manuskript soll die hier aufgeführten Arbeiten zusammenfassen und in einen Zusammenhang bringen. Dafür werden die Inhalte dieser in verständlicher Sprache zusammengefasst und mit Illustrationen versehen. Erweitert wird dies mit einer Bewertung der Ergebnisse sowie einer Einschätzung, welche Bedeutung die Arbeit für das Fachgebiet der Unfallchirurgie und Orthopädie hat