Projects

The main objective of the project is the development of an organ-on-chip system for precision medicine, including the optimization of its use in companion diagnostics to individualize the treatment of tumor patients (with a focus on intestinal tumors) and prevent their metastasis in the micro- and macroenvironment. Organ-on-chip research requires close cooperation and integration with various research teams with interdisciplinary expertise:
(1) Molecular biology and cell culture technology (represented by Prof. Ulf Kahlert)
(2) Metrology and micro/nanotechnology (represented by Prof. Ulrike Steinmann)
(3) Medical imaging techniques and pharmacokinetic process modeling (represented by Prof. Christoph Hoeschen and Dr.-Ing. Melanie Fachet)
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Based on the developments in the Medirad project and the i-Violin project for determining image quality directly in patient data, an analysis tool is being developed which will be available as a software tool for clinics. It should now also be able to determine the image quality for cranial CT examinations directly in patient images. This objective image quality will be compared with subjective image quality.
The project is being carried out together with our University Hospital and the Municipal Hospital.
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Molecular medical imaging plays a crucial role in modern medical diagnosis, enabling early and personalized therapy for various diseases, especially cancer. However, existing in vivo medical imaging methods have limitations for molecular imaging in humans, such as low sensitivity to molecular processes, limited spatial and temporal resolution, or high exposure to ionizing radiation. To address these challenges, IMMPRINT aims to develop a proof-of-principle demonstrator for in vivo 3D imaging, utilizing X-ray dark-field imaging (DFI) and X-ray fluorescence computed tomography (XFCT) as a novel hybrid tool for personalised tumor profiling, with a specific focus on breast cancer (BC) disease.

DFI will aid the identification of suspicious tumor lesion sites at micrometer scales, followed by a detailed high spatial resolution molecular assessment at the local tumor level using XFCT. As a result of this approach, exposure to body-wide high ionizing radiation doses, as seen in nuclear medical imaging methods, can be confined to regions of interest, thus promoting patient safety. The DF-XFCT will rely on various pillars of innovative technology development, from novel detectors to integrated in vivo, in vitro bio-diagnostics. X-ray fluorescence is emitted when nanoparticles are excited by X-rays. Within IMMPRINT, distinct signatures of intra- and inter-tumor heterogeneity in BC will be identified, which are suitable for detection by specifically designed and targeted nanoparticles. The IMMPRINT system for hybrid DF-XFCT imaging will include standard clinical X-ray sources and will benefit from innovative detectors, enabling concurrent detection of DFI and XFCT, aimed at high spatial and energy resolution.

The unequally distributed data, which includes timing and energy information, requires the development of new methods to extract 3D imaging information from this data, providing insights into the functional, molecular, and anatomical properties of BC disease. The IMMPRINT imaging system will allow new approaches for better medical diagnosis and also new biomedical research. It will demonstrate the technical feasibility on the lab scale and potentially form the basis for the commercial development of a system. The consortium unites expertise from all fields mentioned above and is using nationally and internationally funded large-scale infrastructures.

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The main aims of IMAGEOMICS are to improve benefit/risk ratio of breast cancer (BC) patients by identifying patients with a predicted favourable response to combined radiotherapy (RT) and immunotherapy and to develop new imaging modality with increased diagnostic potential and reduced ionizing radiation exposure. These aims will be realized through the following specific objectives: a) investigate how RT influences immunogenic heterogeneity of BC cells of different molecular subtypes using in vitro and in vivo approaches; b) test the applicability of nanoparticles for X ray fluorescence computed tomography (XFCT) to be used for the detection of BC heterogeneity; c) to identify local and systemic signatures that predict patient benefit from combined RT and immunotherapy and test their clinical applicability; d) to integrate data retrieved from experimental models and human studies with epidemiological data to build up a protocol for optimal patient stratification.

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Lung tuberculosis is an infection of the lungs which had been assumed to be wiped out in modern developed countries. However, there is again a rising number of cases. In addition, due tot he large number of refugees there are additional needs for characterising possible infections early. This is especially true as tuberculosis is still one oft he most often infectual diseases worldwide. X-ray imaging is at least for young patients not an easy to justify procedure.  The gold standard for the diagnosis of tuberculosis is the cultural biology prove of Mycobacterium tuberculosis. This is quite a long and complicated procedure. It would be desirable to have a fast and easy diagnostic tool instead, because that could foster the in principle very effective therapy approaches, if applied in early stages. Since we know from earlier studies that breath gas analysis allows the detection of changes in the metabolism and especially those caused by infections we investigate the feasiblity to diagnose tuberculosis with breath gas analysis.

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Molecular imaging, such as Positron Emission Tomography has an important

impact in diagnostic, while it started only recently to be integrated into interventional procedures. Interventional molecular imaging
can provide guidance to localize a target; provide in-room, post-therapy assessment; monitoring of targeted therapeutics delivery.
Interventional molecular imaging is generally based on commercial whole-body PET/CT scanners, which limit the possibility of an entire surgical guidance
procedure, while on-site integration of dedicated devices would definitely benefit the entire guidance.
This project focuses on the study of a dedicated detector, and the potential impact of its integration in brain interventional procedures.

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An international research team will develop Europe-wide quality and safety standards for the use of ionizing radiation in the diagnosis and treatment of cancer. To this end, a European database with patient-specific diagnostic and therapy data as well as treatment recommendations will be set up. This database is intended to ensure comparable standards for the use of ionizing radiation across national borders and help doctors to reduce the radiation exposure of patients to a reasonable level, optimize it individually and thus improve the safety and quality of care for tumour patients throughout Europe.
The research project focuses on the question of the extent to which the quality of diagnostic imaging, for example computer tomography, is directly related to the dose administered and the success of radiotherapy and can be optimized in such a way that the patient's treatment can be carried out with as few side effects and as few long-term negative effects as possible for the individual patient.
To achieve this goal, the first step is to introduce software developed in preliminary projects to evaluate the image quality of CT scans in five participating European hospitals. Later, the procedures developed in Magdeburg and elsewhere are to be used in as many European hospitals as possible.
The i-Violin project is funded by the EU4Health health program and supports the goal of Europe's Beating Cancer Plan to ensure high standards in cancer treatment. The SAMIRA Action Plan and the strategic research agenda of ESR EuroSafe Imaging and EURAMED programs are also reflected in i-Violin. The partner institutions are the European Institute for Biomedical Imaging Research, the Otto von Guericke University Magdeburg, the University Medical Center of the Johannes Gutenberg University Mainz, the Polytechnic Institute of Coimbra in Portugal, the University of Crete, Greece, the Clinical Hospital Dubrava in Croatia, the University Medical Centre Ljubljana, Slovenia, KU Leuven in Belgium, the University College Dublin, and the National University of Ireland Dublin in Ireland as well as the Finnish Radiation and Nuclear Safety Authority in Finland.
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The overall objective of the 4-year SINFONIA project is to develop novel research methodologies and tools that will provide a comprehensive appraisal of the risk for detrimental effects to patients, workers, the public and the environment from radiation exposure during management of patients suspected or diagnosed with lymphoma and brain tumours.

SINFONIA will develop novel tools and methodologies that will be demonstrated on two suitable clinical examples i.e. lymphoma and brain tumours. However, SINFONIA research outcomes are not confined to the two specific types of diseases. Some of the procedures performed on lymphoma and brain tumour patients are also carried out on patients with other diseases and SINFONIA radiation dose and risk appraisal methods developed for these two groups of patients will be applicable to other diseases

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Around a third of patients with a depressive disorder (MDD) do not respond to at least two different antidepressant therapies. These patients need other treatment options as early as possible. Unfortunately, there are currently no non-invasive, easily and frequently applicable biomarkers that could facilitate the diagnosis of unipolar depressive disorder (MDD) or support decision-making on the choice of treatment. Since the lungs act as a gas exchanger between the internal and external environment, the effects of MDD could easily be assessed by analyzing exhaled breath. Such methods are already successfully used in alcohol testing and diabetes mellitus. In a pilot study of 25 patients with MDD and 25 healthy volunteers, we were able to find markers that differed significantly between the groups and that gave a good classification with an accuracy of over 80 % in test and validation samples. The aim of the study is to identify signatures from exhaled air that distinguish a depressive episode in MDD from a healthy state. Furthermore, it will be investigated by which factors (treatment, diet, environment) these signatures are influenced, whether the identified signatures can give indications of the course of the disease and whether they show parallels to the dysregulation of the cortisol response during awakening, which has been shown in depression. In a test sample, 80 patients with MDD according to DSM-V (40 currently free of antidepressant medication and 40 with ongoing antidepressant treatment) and 80 healthy subjects will be included. Furthermore, 40 patients with MDD (20 currently free of antidepressant medication and 20 with ongoing antidepressant treatment) and 40 healthy volunteers will be recruited in a confirmation sample. The clinical examinations and breath measurements will be repeated after 14 and 28 days. The breath will be analyzed using proton transfer reaction mass spectrometry (PTR-TOF-MS). In addition, the underlying substances are determined using GC-GC-TOF-MS. The environmental conditions and the collection method using "Tedlar" bags are controlled. In this way, we want to develop a marker that could support the diagnosis of depression, although this must then be demonstrated in a clinical biomarker study.
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In the field of medical physics and medical technology, the use of AI-based processes is particularly promising in the area of radiation protection, especially in medical imaging, which is responsible for almost 100% of civilization's radiation exposure of 1.9 mSv per year [Information from the Federal Government: Environmental radioactivity and radiation exposure in 2013]. Thanks to the new disruptive technologies of AI, an enormous dose-saving potential could be realized there.
The aim of the joint project is therefore to develop, implement and test AI processes to significantly reduce the radiation dose in medical imaging with ionizing radiation. This is to be achieved by improving image quality and radiation protection for medical imaging procedures based on ionizing radiation.
In order to enable a holistic/holistic and systematic approach, the project addresses interventional imaging in which both diagnostic and therapeutic goals are realized with the help of computed tomography, angiography and nuclear medicine.
A particular focus is on the development and establishment of intelligent algorithms for (I) dose reduction, (II) improvement of image quality and (III) reduction of motion artefacts as well as (IV) interventional characterization of tissue in medical radiation applications - applications that are all part of radiation protection. The focus here is on increasing safety for patients and medical staff, so that a valuable contribution can be made to the positive perception of AI among the general public.
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Radiation protection in medical applications is well established throughout Europe, however still facing challenges like large differences in procedures between countries, but even within a country or even within a hospital. In addition, new promising approaches like new technologies as e.g. artificial intelligence or personalized medicine approaches need to be investigated regarding their potential for medical radiation protection. The European Alliance for Medical Radiation Protection Research (EURAMED) platform has been found to promote such research in the EC research programme . Together with five other platforms research in the field of radiation protection is promoted basically in the EURATOM framework. Acknowledging the importance of medical applications as the largest man-made source of exposure and the great possibilities of applying ionizing radiation in medicine the EURATOM programme has launched a call for a coordination and support action to develop a strategic research agenda (SRA) on medical applications of ionizing radiation in general allowing to improve links to other programs like HEALTH or DIGITALIZATION.

A consortium called EURAMED rocc-n-roll has been put together to fulfil the task of developing such an SRA partially based on the existing EURAMED SRA on medical radiation protection. In addition it will also develop a roadmap describing how this research agenda can be implemented. An interlink document showing the potential distributions of the different European research programmes to such defined approaches will also be developed. All these documents need to be derived based on a broad consensus of all stakeholders especially also including the patients’ perspective. Therefore, EURAMED rocc-n-roll is based on a series of workshops and writing panels. The workshops will allow contributions by interested stakeholders in person or through members of the consortium.
OvGU is serving as the scientific coordinator of the project.

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According to Smith (Smith, 2011) brain disorders cost Europe almost €800 billion (US$1 trillion) a year - more than cancer, cardiovascular disease and diabetes together.

Major depressive disorders (MDD) can effectively be treated with psychotherapy and/or antidepressants. However, still one third of patients do not respond and would need different treatment options as early as possible (Kennedy and Giacobbe, 2007).
A possible new method for early detection could be breath gas analysis that already was implemented for alcohol tests and recently was found to be clinical applicability e.g. for diabetes detection. Because the lungs act as a gas exchanger between the internal system and external environment, the internal system in disorders like MDD may be assessed through the analysis of exhaled breath especially with respect to stress induced reactions.

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Molecular imaging today is either limited by systems that provide high resolution spatially and temporarilly but very poor sensitivity to contrast media or molecular markers (CT, MRI) or by such systems that provide high sensitivity but very poor spatial and especially temporal resolution (SPECT, PET). X-ray fluorescence would be an option to overcome such limitations, because in principle it could offer fast scanning, high spatial resolution and a good sensitivity. To gain such efficient approaches one needs scanning geometries with fast steerable X-ray sources which should be adjustable in their beam energy. Such imaging method would on the fly generate an anaomical image as well. We simulate such systems and try to set up demonstration experiments with our cooperation partners.

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We build systems for dark field and absorption based X-ray imaging systems using for example scanning beam technologies, develop and characterise corresponding detector systems and imaging geometries. The total systems for both different types of imaging systems will be simulated and transferred into prototypes.

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In order to optimize radiation protection for the patient and for optimal image acquisition, it is essential to know the distribution of radiopharmaceuticals in the body over time. As this is not trivial to measure for every patient, nuclear medicine data is recorded over time in cooperation with clinics. This is used to create dynamic compartment models and determine the parameters. The uncertainty in the determination of the parameters and the sensitivity of the model for the individual parameters are examined in order to determine which influencing parameters are particularly significant. Subsequently, real patient data can be compared with the model predictions in order to find optimized time schedules for imaging and optimized therapy parameters or to improve dosimetry for the patient.
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A newly designed especially developed breast CT system based on the newly developed CT d Or geometry and in this case based on an electron gun with a dedicated delineation system and a special target ring had been set-up. This would allow very fast scanning and a larger covering of the breast volume (closer tot he breast wall) than current breast CT systems, from which very few exist. However, the new geometry requires a very new approach for a detector system because it has tob e separated in columns and the electronics need tob e conserved and should not cover the source positions. We simulate the possible detector design, develop a prototype electronic system and a prototype detector

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Darkfield imaging relies on differences in the scatter component of the x-ray distribution due to differences instructural conditions oft he tissue. In many approaches this component is a side-product of phase contrast imaging. Since phase contrast imaging is strongly dependent on movements oft he patient and it will be dose intensive for applications in the human tissue characterisation for in vivo imaging, we are concentrating on darkfield X-ray imaging directly. A special system for dose-optimised imaging will be developed. We focus on breast imaging within the current project.

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New molecular imaging techniques based on monoenergetic X-ray sources and X-ray fluorescence imaging, for example, allow nanoparticles to be tracked in the body. If such nanoparticles are coupled to pharmaceuticals, it is possible to track their presence in the body at different points in time and thus ensure the optimal effectiveness of the pharmaceuticals. Imaging is not yet fully available, so the special reconstruction is to be developed in this project to enable 3D representations. In addition, the data must be fitted into kinetic models in order to be able to make predictions about the most likely courses of accumulation in the body.
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Medical imaging quality description is today either based on investigating with objective physical mathematical methods images of certain test objects or on subjective reader evaluations. The objective methods can be either based on methods applicable in the Fourier domain or those in the spatial domain. While analytics in the Fourier domain are often quite easy they are often difficult to interpret in terms of provided diagnostic performance. Image quality analysis in the spatial domain is on the other hand typically limited to very specific tasks and complicated to perform. Human reader studies very often result in very different results and are very time consuming. We want to develop a way to characterise patient images based on physical methods to describe image quality so that fast objective measurements correspond to human reader studies. That would allow qulaity assurance on real patient images in the future.

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The newly developed geometry for CT applications called WATCH allows a CT scan with variable resolution, in a lying as well as a sitting and standing patient position. It is an open system with easy access fort he radiologist and can be driven by a robot system. However, although the system and the used reconstruction should be very tolerant against movement errors, that would not be the case for geometrical misalignments. Therefore we focus on setting up the robot driven system with a 3D imaging detector and a calibration system. This calibration system can be used for standard CT as well.

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Time Of Flight (TOF) capability in PET imaging enhances Signal to Noise Ratio in inverse proportion to the temporal resolution. The Coincidence Resolving Time (CRT) in commercial PET scanners is about 500 ps (FWHM) but current technology limit approaches 10 ps CRT (FWHM) corresponding to 1.5 mm spatial resolution.

TOF increases lesion detection capability, the robustness of iterative reconstruction, and reduces bias in quantification through improved
attenuation, scatter, and random corrections. This investigation studies through simulations the possible enhancements in brain imaging of sub-100 ps CRT technology, in both static and dynamic brain studies.
We will develop prototyp PET detectors.

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CT imaging is the largest man-made source of ionising radiation to the public in developed countries as in Germany. Here more than 60% oft he effective dose delivered to patients is due to CT examinations. However, since only small parts oft he body are exposed to ionising radiation, there are quite large dosest o single organs. To evaluate the dose distributions and ist potential effects further it is necessary to determine dose distributions to various organs in detail. Since it is impossible to measure such doses inside the body simulations have tob e performed. There accuracy depends strongly on an exact characterisation oft he CT parameters including calibrating dose measurements and determination or characterisation o feg the bowtie filter of CT systems. There are various measurements developed and performed to characterise bowtie filters and dose values as a basis fort he following simulation of patient dose distributions.

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SAFIR (Small Animal Fast Insert for mRi) is an innovative, high rate PET detector insert for MRI to be used for quantitative dynamic small animal imaging inside the bore of a commercial 7T MRI preclinical scanner (Bruker 70/30, http://tinyurl.com/BrukerBiospec) at the University Zurich, Institute of Pharmacology and Toxicology. The project targets an unprecedented temporal resolution (about 5 seconds) and truly simultaneous PET/MR acquisition

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In cancer treatment both ion-beam therapy and alpha radionuclide therapy base their effectiveness on the high ionization density provided by hadrons. However the stochastic nature of the hadron interaction in tissue, and the complexity of the interaction patterns

require a better description of the radiobiological effect of hadrons in tissue that cannot be
adequately reflected, as in conventional radiation therapy, by a single dosimetric quantity,
e.g. mean absorbed dose to target volume. MedAustron, the Austrian centre for ion-beam therapy, in collaboration with the University of Rome, Tor Vergata is developing semi-conductor diamond detectors for dosimetry and microdosimetry in ion-beam therapy. The potential of such (micro)dosimeters with respect to alpha radionuclide target therapy, 90Y radio-embolization, and other treatment modalities is under investigation in the present project.

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