Medical Technology for Health (MTH)

Improved Phenotyping of Cardiomypathy Patients by Means of Imaging-Driven Computational Modeling of Cardiac Biomechanics

Maria Garcia Hernandez — Thu, 30 Aug 2018 11:29:57 +0000

Improved Phenotyping of Cardiomypathy Patients by Means of Imaging-Driven Computational Modeling of Cardiac Biomechanics Maria Garcia H… Do, 30.08.2018 - 13:29

This project is a cooperation between the Institute of Biomedical Engineering (KIT, Karlsruhe) and the University Hospital in Heidelberg. The aim is to combine cardiovascular magnetic resonance imaging (CMR) with computational modeling of cardiac biomechanics in order to improve diagnosis of cardiomyopathy.

Before a cardiomyopathy case can be examined, a healthy case needs to be represented in-silico correctly. First, we agreed on a measurement protocol, which provides enough data for the computational model for both input and validation. (Note, that for the first examined case, which is a healthy volunteer, an invasive measurement cannot be conducted and therefore no blood pressure data over the whole heart cycle can be collected.) Second, the healthy volunteer underwent a cardiovascular magnetic resonance imaging procedure: 3D whole heart, 2 chamber view, 4 chamber view, 12 short axis slices Cine and strain encoded MRI (SENC).

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Medical Technology for Health (MTH)

Start date

01.01.2018

31.12.2018

Project management

Cardiovascular Imaging Research

Heidelberg University Hospital

Matthias Friedrich

Institute of Biomedical Engineering

Karlsruhe Institute of Technology

Invasions- und Genexpressionsanalysen im Urothelkarzinom der Harnblase: Entwicklung eines mikrofluidischen in vitro Lymphgefäßmodells

Maria Garcia Hernandez — Thu, 30 Aug 2018 11:42:51 +0000

Invasions- und Genexpressionsanalysen im Urothelkarzinom der Harnblase: Entwicklung eines mikrofluidischen in vitro Lymphgefäßmodells Maria Garcia H… Do, 30.08.2018 - 13:42

Das Urothelkarzinom der Blase zählt zu der häufigsten Krebserkrankung weltweit und weist eine hohe Morbidität bzw. Mortalität auf. Ein wichtiger Faktor bei der Progression im Urothelkarzinom der Blase ist die Lymphgefäßinvasion. Die molekularen Mechanismen, die bei der Progression und Invasion des Urothelkarzinoms der Blase eine Rolle spielen, sind nicht vollständig geklärt. Derartige molekulare und zelluläre Untersuchungen sind auf Grund der limitierten in vivo und in vitro Modelle eingeschränkt möglich.

Im Rahmen dieses Projekts wurde der Prototyp eines mikrofluidischen Gefäßsystems als artifizielles Modell des Lymphgefäßes bzw. Lymphknotens unter Berücksichtigung der rheologischen und physikalischen Eigenschaften entwickelt. Dazu wurden verschiedene Membranen als Gewebeschranke getestet und die Kultivierung von Lymphendothelzellen gelang auf PET-Membranen und PET-Gewebe. Die Zellen können über spezifische Ventilsysteme isoliert werden und stehen für weitere sensitive Genexpressionsanalysen wie der qRT-PCR zur Verfügung.

Für eine bessere physiologische Nachbildung der Lymph-Gewebe-Schranke wurde statt einer Membran ein Kollagen 1 Hydrogel verwendet, auf dem die Kultivierung von Lymphendothelzellen, primären Blasenfibroblasten und Blasenkarzinomzelllinien möglich ist.

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2018

31.12.2018

Project management

Medical Faculty Mannheim

University of Heidelberg

Philipp Erben

Institute of Microstructure Technology

Karlsruhe Institute of Technology

Andreas Guber

3D gedruckte Nano-Zellgerüstträger für die in situ Knorpelregeneration zur Behandlung von Gelenkknorpelschäden. Untersuchungen zum Zellrecruitment in einem Bioreaktor.

Regine Kleber — Mon, 12 Nov 2018 16:10:56 +0000

3D gedruckte Nano-Zellgerüstträger für die in situ Knorpelregeneration zur Behandlung von Gelenkknorpelschäden. Untersuchungen zum Zellrecruitment in einem Bioreaktor. Regine Kleber Mo, 12.11.2018 - 17:10

Im Rahmen des Projektes sollen künstliche Zellgerüstträger zur in situ Regeneration von hyalinem Knorpel zur Behandlung von Knorpelschäden mittels Nano 3D-Druck hergestellt werden. Durch den Einsatz der sog. „Zwei Photonen Lithographie“ (Nanoscribe) wird es möglich, im Nanometermaßstab genaue Zellgerüste additiv herzustellen. Durch solch einen additiven und hochpräzisen Aufbau der Zellgerüste sind komplexe Strukturen realisierbar, mit denen die anspruchsvollen mechanischen Eigenschaften von natürlichem hyalinem Knorpel realisiert werden können. Diese 3D Scaffolds sollen dabei als Gerüst für Stammzellen und anderen Zellen dienen und diesen ermöglichen, neue extrazelluläre Matrix zu produzieren und im Idealfall wieder gesundes hyalines Knorpelgewebe auszubilden.

Zuerst werden Vorversuche mit starren Scaffolds durchgeführt. Hierbei sollen zunächst optimale Parameter, wie z.B. Porengröße, Oberflächenqualität usw. sowie deren Einfluss auf die Besiedelung der Scaffolds durch verschiedene Zelltypen (z.B. Chondrosarcomzelllinie, Stammzellen) identifiziert werden.

Auf diesen Ergebnissen und auf KIT-Seite durchgeführten mechanischen Simulationen basierend werden elastisch verformbare Zellgerüstträger konstruiert und mittels 3D Druck hergestellt, die die mechanischen Eigenschaften des hyalinen Knorpels möglichst gut nachbilden sollen. Diese elastischen Scaffolds werden in einem Bioreaktor kontinuierlich mechanisch belastet und anschließend untersucht, ob unter den verwendeten Parametern ein erfolgreiches Zellrecruitment von Stammzellen aus einem unteren Reservoir des Bioreaktors in das daraufliegende Scaffold stattfindet. Dieser wichtige und entscheidende Vorgang wäre der Ausgangspunkt für eine in situ Regeneration von Knorpelgewebe, der den klinischen Gegebenheiten bei einer sog. Matrix assoziierten Chondrogenese (AMIC®) nahe kommt.

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2019

31.12.2019

Project management

Medical Faculty Mannheim / Experimental Orthopedics and Trauma Surgery

Heidelberg University

Research Group Schwarz

Institute of Microstructure Technology

Karlsruhe Institute of Technology

Andreas Guber

Magnetic resonance-guided opening of the blood-brain barrier using focused ultrasound for cell-mediated therapies of brain diseases

Maria Garcia Hernandez — Tue, 10 Dec 2019 14:40:42 +0000

Magnetic resonance-guided opening of the blood-brain barrier using focused ultrasound for cell-mediated therapies of brain diseases Maria Garcia H… Di, 10.12.2019 - 15:40

Cerebral amyloid angiopathy (CAA) is a neurodegenerative disorder and results in vascular dysfunction, microinfarcts and brain bleedings. Stem cells were found to be a potent regenerative therapy in the related Alzheimer’s disease, but their targeting is difficult since they are hindered by the blood-brain barrier (BBB). Focused ultrasound (FUS) provides a new strategy for stem cell application. It is able to open the BBB in a noninvasive, local and transient way. Its combination with magnetic resonance imaging (MRI) allows for guidance, targeting and monitoring in real time (MRgFUS). Challenges result from the acoustic pressure weakening deriving from the skull or targeting of the ultrasound focus. Additionally, settings and application protocols in pre-clinical studies with animal models differ significantly. Therefore, ultrasound parameters like frequency, burst duration, burst repetition frequency, total exposure time and acoustic pressure amplitude have to be fine-tuned for safe BBB opening. Furthermore, there is a tremendous lack of knowledge regarding to the formation of brain bleedings post FUS. The proposed HEiKA project aims at developing and evaluating a non-invasive and reliable BBB opening in mice to enable systemic administration of stem cells to brain parenchyma. In order to establish a reliable BBB opening protocol, we first focus on an adequate therapy planning using automated segmentation of mouse anatomy and estimation of the FUS parameters with acoustic or elastic simulations. Second, we will do animal experiments in a transgenic mouse model for CAA in order to estimate appropriate simulation parameters and to evaluate BBB opening protocols in aged animals. The long-term goal of our collaborative project is to examine the neuroprotective and regenerative effect of stem cells on amyloid metabolism and CAA. Findings of this proof of principle project will then be usable for further cell-based therapies in central nervous system (CNS) disorders.

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2020

31.12.2020

Project management

Neurologische Klinik

Medizinische Fakultät Mannheim

Marc Fatar

Institut für Prozessdatenverarbeitung und Elektronik

Karlsruher Institut für Technologie

Nicole Ruiter

A radiation free, deep learning based classification of craniofacial deformities on surface scans. Paving the methodical way towards a patient’s digital twin.

Maria Garcia Hernandez — Tue, 10 Dec 2019 14:42:03 +0000

A radiation free, deep learning based classification of craniofacial deformities on surface scans. Paving the methodical way towards a patient’s digital twin. Maria Garcia H… Di, 10.12.2019 - 15:42

We hereby apply for a HEiKA project funding for a cooperation between the Karlsruhe Institute of Technology (KIT), Institute for Biomedical Technology (IBT) and the University Hospital of Heidelberg (UNI-HD), Institute for Medical Biometry and Informatics, Research Group Medical Informatics (IMBI) and Department of Oral and Maxillofacial Surgery (CMF) and Department of Orthodontics. The goal of this project is to explore and develop an innovative application for convolutional neural networks (CNN) in clinical medicine. As both universities excel in their field of interest and research, we are looking forward using the existing knowledge to develop the basis to a self-adaptive digital model of a patient, which we refer to as a digital twin. The topic of the initial research project is to lay the groundwork to a deep learning based diagnostic tool, that shall be trained to determine severe growth anomalies such as premature cranial synostosis of the face and skull in infants from mild growth anomalies and classify those conditions. Additionally, to engage a clinically relevant question in a scientifically not predescribed way, we are looking into the training of neural networks (NNs) for other questions of clinical relevance such as diagnostic or predictive clinical models. The gained knowledge and established workflows will lay the basis to a larger scaled research project. As research on artificial intelligence (AI) in medicine is a growing topic, the practical but essential questions of data handling are the basis for further projects. The results are published from a clinical and computational point of view. The findings will then be used to submit a successful Deutsche Forschungsgemeinschaft (DFG) application. The working title of this following DFG project is “The patients digital twin – a deep learning based model for diagnostics and prediction of clinical data” and the application for a consequential third-party funding is a part of the research project.

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2020

31.12.2020

Project management

Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie

Universitätsklinikum Heidelberg

Christian Freudlsperger

Director Research Bridge MTH

Institut für Biomedizinische Technik

Karlsruher Institut für Technologie

Werner Nahm

Particle therapy beam monitoring with HV-CMOS sensors

Maria Garcia Hernandez — Tue, 10 Dec 2019 14:44:16 +0000

Particle therapy beam monitoring with HV-CMOS sensors Maria Garcia H… Di, 10.12.2019 - 15:44

Radiotherapy is an important pillar in the therapy of cancers and is prescribed to ~50% of cancer patients. Standard radiotherapy uses photon radiation whereas particle therapy uses high energy protons and carbon ions to destroy tumor cells in the body of patients. To achieve local tumor control a well-controlled particle beam in terms of position and dose is of utmost importance for the success of the therapy and the patient’s health. The beam control system requires precise and fast measurement of the dose and beam position which must be provided by the beam monitors. Currently, these are gas-filled detectors.

Looking at particle detectors in modern particle physics experiments we find solid-state devices, such as high-voltage complementary metal oxide semiconductor (HV-CMOS) sensors, are ubiquitous. They offer much better time and spatial resolution, which could be highly beneficial for use in a beam monitoring system for particle therapy. As ion beam therapy guided by magnetic resonance imaging (MR-guided) is being developed these days, HV-CMOS sensors shall be tested in the presence of magnetic fields. HV-CMOS sensors are thin (<150 μm) monolithic devices, which offer high spatial resolution and detection efficiency for ionizing particles as well as customizable on-chip data processing (like clustering, particle counting, signal charge integration, etc). Within this proposed project we want to explore the feasibility to apply this technology to the precise and fast monitoring of a therapeutic particle beam.

The two partners complement each other in an ideal way: the team from the Heidelberg Ion beam Therapy center (HIT) contributes the know-how on the beam delivery system and patient treatment, while the team from the Institute for Data Processing and Electronics (IPE) at KIT has proven expertise in delivering detector systems for extreme environments. HV-CMOS sensors have been pioneered by one of the PMs (I. Peric) and are being designed and developed at the KIT ASIC and Detector Lab (ADL) associated to the IPE.

Within this project an optimized test sensor will be designed and tested in beam at HIT. After successful evaluation of the pixel design a larger demonstrator sensor will be developed, which also includes the investigation of multi-sensor interconnection techniques to cover the required large area of 25 cm x 25 cm.

During this project we will also derive concepts for proper housing and mounting of the sensor as well as for a DAQ system capable to process and provide the required data for the therapy control system. These sensor developments and conceptual studies of the auxiliary systems will allow us to better quantify the budgetary needs and further development steps towards a prototype system for clinical use.

Forschungsbrücken

Medical Technology for Health (MTH)

Particle Physics, Astroparticle Physics and Cosmology (PAC)

Start date

01.01.2020

31.12.2020

Project management

Klinik für Radioonkologie und Strahlentherapie

Universitätsklinikum Heidelberg

Jürgen Debus

Institut für Prozessdatenverarbeitung und Elektronik

Karlsruher Institut für Technologie

Ivan Peric

3D bioprinting of heart tissue for transplantation - Effects of materials and endothelial factors on stem cell maturation to functional myocardial tissue

Maria Garcia Hernandez — Tue, 10 Dec 2019 14:46:14 +0000

3D bioprinting of heart tissue for transplantation - Effects of materials and endothelial factors on stem cell maturation to functional myocardial tissue Maria Garcia H… Di, 10.12.2019 - 15:46

Heart disease is the cause of most deaths worldwide. Although some patients can be treated by heart transplantation, thousands of patients suffer due to a lack of donor organs.

Therefore, it is important in the field of regenerative medicine to develop new therapies in order to meet the emergency. In this project, artificial heart tissue will be produced by 3D bioprinting. In a proof of principle study a prototype murine heart tissue will be produced in 3D in order to test its functionality, cell communication and tissue differentiation in vivo and ex vivo. In a second step, the structure will be prepared to be scaled to a size of a human heart.

Different cardiovascular cell types, differentiated from mouse embryonic stem cells (mESCs) will be printed in individually adapted hydrogels with different printing processes and spatial resolutions to produce an artificial heart that comes as close as possible to a murine heart in terms of shape, topography and functionality. Vascularization will be achieved by printing of sacrificial hydrogel structures to form a pre-formed vascular network, which will be subsequently colonized with endothelial cells. During and after the printing process, the artificial blood vessels will be perfused with a newly developed microperfusion system in order to supply the printed organ with oxygen and nutrients ex vivo. The printed organs will be further subjected to structural and functional testing in vitro and in vivo after transplantation in mice. Here, the role of endothelial-derived signals through direct cellular contacts or angiocrine signals on cardiomyocyte proliferation, survival and maturation will be investigated. Within this project, we will closely collaborate with the Tal Dvir’s group that has achieved a major breakthrough in the field of 3D bioprinting.

Forschungsbrücken

Medical Technology for Health (MTH)

Synthetic Biology (SB)

Start date

01.01.2020

31.12.2020

Project management

Vaskuläre Biologie und Medizin

Medizinische Fakultät Mannheim

Gergana Dobreva

Institute of Functional Interfaces (IFG)

Karlsruhe Institute of Technology

Research Group Schepers

Towards personalized therapy in retinal diseases - Development and evaluation of therapeutic performance parameters from OCT-Angiography images

Maria Garcia Hernandez — Thu, 10 Dec 2020 14:18:32 +0000

Towards personalized therapy in retinal diseases - Development and evaluation of therapeutic performance parameters from OCT-Angiography images Maria Garcia H… Do, 10.12.2020 - 15:18

We hereby apply for a HEiKA project funding for a cooperation between the Karlsruhe Institute of Technology (KIT), Institute for Biomedical Technology (IBT) and the Department of Ophthalmology at the University Hospital of Heidelberg (UNI-HD). The proposed project is driven by the recent development of the Optical Coherence Tomography Angiography (OCTA) in Ophthalmology. For decades, vasculature was visualized by invasive dye-based angiography. Limitations of this gold standard include dye induced adverse effects and time-consuming procedures. Moreover, dye-based angiography is only a two-dimensional study focusing on the superficial retinal circulation, without the ability to visualize the deeper capillary structures. OCTA combines the OCT technology with doppler photometrie. It visualizes the retinal vessels and capillaries in different axial depths which allows physicians a novel three-dimensional insight into the microvascularization of the retina and the morphological changes during therapy. No parametrization of the vascularization or morphology is established so far, therefore the assessment of the patient's condition is subjective. Using machine vision tools to parametrize the degree of vascularization and further on the vascularization across multiple layers provides the physicians valuable objective information and has the potential to detect early changes and thus increase patient’s visual outcome. OCTA technology is a powerful tool with still un-exploit applications. The results of this research will be published from a clinical and computational point of view and will lead to sequential research questions.

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2021

31.12.2021

Project management

Medical Faculty Heidelberg

University of Heidelberg

Ramin Khoramnia

Director Research Bridge MTH

Institut für Biomedizinische Technik

Karlsruher Institut für Technologie

Werner Nahm

Keep moving: unraveling the effects of rollator assistance on movement in older adults using a robotic rollator simulator

Maria Garcia Hernandez — Thu, 10 Dec 2020 14:21:03 +0000

Keep moving: unraveling the effects of rollator assistance on movement in older adults using a robotic rollator simulator Maria Garcia H… Do, 10.12.2020 - 15:21

2023

Herzog, M.; Krafft, F. C.; Stetter, B. J.; d’Avella, A.; Sloot, L. H.; Stein, T. (2023). Rollator usage lets young individuals switch movement strategies in sit-to-stand and stand-to-sit tasks. Scientific reports, 13, Article no: 16901. doi:10.1038/s41598-023-43401-6 https://www.nature.com/articles/s41598-023-43401-6

2021

The ability to move independently is fundamental to a person’s quality of life. Unfortunately, difficulty in walking or getting up from a chair is common among elderly. In these cases, rollators are often provided to lean on to, thereby aiming to improve balance or to compensate for weak legs. However, it is unclear if rollators affect movement and actually reduce weight on the legs or improve balance. These research gaps significantly delay further development of new and intelligent mobility systems. The steady increase in the aging population has given rise to the need for smart assistive devices to prolong independent living in older adults.

This proposal utilizes the unique availability of a state-of-the-art robot that can simulate rollator assistance, a fully equipped motion capture lab, as well as complementary expertise from HU and KIT to evaluate the effect of rollators on movement in young and elderly adults. We focus on sit-to-stand transitions and gait, as these movements are a prerequisite for many daily activities and often result in falls in older adults.

We aim to perform a collaborative experiment to analyze how rollator assistance affects movement as a function of levels of support (light touch vs complete support) and task difficulty (normal vs challenging situation). In accordance with their research focus, HU und KIT pursue individual but closely interwoven aims:

HU: Examine the effect of rollator support on posture, stability and joint loading.
KIT: Examine the effect of rollator support on motor coordination.

This is the first comprehensive biomechanical analysis of the human-rollator interaction during everyday tasks using a specialized robotic device. The study will provide a rich dataset that will be co-published in international journals and will support a joint DFG or EU proposal for a more comprehensive outlook on the role of smart assistive devices in fall detection and/or prevention.

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2021

31.12.2021

Project management

Institute of Computer Engineering

University of Heidelberg

Lizeth Sloot

Institute of Sports and Sports Science

KIT

Thorsten Stein

Untersuchungen an mittels FFF-3D-gedruckten Implantaten aus Zirkoniumdioxid

Maria Garcia Hernandez — Tue, 16 Jan 2024 16:27:31 +0000

Untersuchungen an mittels FFF-3D-gedruckten Implantaten aus Zirkoniumdioxid Maria Garcia H… Di, 16.01.2024 - 17:27

Während die Titanlegierung Ti6Al4V bisher den Werkstoffstandard für Zahnimplantate darstellt, gewinnt Zirkonoxid (ZrO2) in der Implantologie zunehmend an Bedeutung. Hintergrund sind vornehmlich ästhetische Vorteile, eine hohe Biokompatibilität sowie suffiziente mechanische Eigenschaften.

Als innovatives Forschungsfeld, etabliert sich ZrO2 zunehmend für die Herstellung von wurzelanalogen Implantaten (sog. ROI; „root-analogue implants“). Hierfür sind additive Fertigungsverfahren (3D-Druck) besonders geeignet, da sie die Gestaltung hochindividueller Designs zulassen und im Gegensatz zu substraktiven Fertigungsverfahren (Fräsen) nicht durch die Form der Schleifkörper limitiert sind. Weiter ist eine individuellere und präzisere Strukturierung der Oberfläche möglich, welche das Einwachsen des Implantates in den Kieferknochen begünstigt.

In diesem Projekt wird das Druckmaterial optimiert und verschiedene Strukturierungen der Oberfläche im Druckprozess entwickelt. Der Einfluss der Oberflächenstrukturierung auf die mechanischen Eigenschaften und die Zellansiedlung wird anschließend untersucht. Neben der biokompatiblen und biomechanischen Optimierung von ZrO2-Implantaten liegt der weitere Fokus auf der Interaktion zwischen Implantat und Knochen im Sinne der Osseointegration. Die Untersuchungen zur Osteoimmulogie befassen sich mit der Beeinflussung der Makrophagenpolarisierung durch Zirkoniumdioxidoberflächen und dessen Auswirkungen auf die langfristige Implantatstabilität. Die gezielte Modifikation der Implantatoberfläche zielt auf eine Förderung des Knochenanwachstums und eine stabile Verankerung im Kieferknochen ab.

Damit zielt die Weiterentwicklung von Zirkonoxid-Implantaten auf die Schaffung von langlebigen und funktionalen Lösungen ab, die gleichzeitig eine optimale Integration in den Kieferknochen gewährleisten. Darüber hinaus liegt ein Fokus auf der Bezahlbarkeit, um den Zugang zu dieser innovativen Technologie für eine breite Patientengruppe zu ermöglichen.

3D-Druckverfahren Fused Filament Fabrication (FFF) Beispiele gedruckter und gesinterter Gewinde

Forschungsbrücken

Medical Technology for Health (MTH)

Start date

01.01.2024

31.12.2024

Project management

Medizinische Fakultät der Universität Heidelberg (Poliklinik für Kieferorthopädie)

Heidelberg University

Institut für Angewandte Materialien - Werkstoffkunde (IAM-WK)

Karlsruhe Institute of Technology