We understand the term interface research to mean a variety of approaches, all interacting with each other. On the one hand, we refer to the expansion and development of interdisciplinary competence interfaces between UKE and TUHH. On the other hand, we focus on bio-physical interfaces, e.g. between implants and bones, tissue and electrodes, or tumor cells and healthy tissue. Essential clinically and socio-economically significant disease patterns and related issues from regenerative medicine (cardiology, oncology, musculoskeletal diseases) can be traced back to interface phenomena.

Motion Analysis for monitoring musculoskeletal health in a Fish Model

Similar to humans, the physical mobility of zebrafish can be impaired due to aging or disease (e.g. osteoarthritis, scoliosis). While pathological locomotion patterns of individual fish may appear obvious to the observer, visual inspection remains difficult because of multiple moving objects, rendering the quantification of changes in mobility impossible. We design machine learning tracking algorithms to study the movement patterns of fish over long time periods and evaluate the physical performance, locomotion phenotypes, and treatment strategies in zebrafish models of skeletal disease.

Fiedler, Imke Astrid Kristina, et al. "Monitoring musculoskeletal health in zebrafish using machine learning-based locomotion tracking." Bone Reports 14 (2021): 100802.

Virtual reality-based Patient Training

Prevention of falls accompanied by severe injuries such as fracture is of high importance for our aging society. Beyond muscle function, bone quantity and quality-indices, in particular body-control and -coordination are considered to have major impact on preventing fractures by minimizing fall-events themselves. We investigate how virtual reality applications can enhance the training of elderly and reduce bone fractures.

Schmidt, Felix Nikolai, et al. "Development of a virtual reality-based training for the elderly with increased fracture risk to prevent falls and improve their balance." Bone reports 14 (2021): 100950.Neidhardt, M., et al. "VR-based body tracking to stimulate musculoskeletal training." arXiv preprint arXiv:2308.03375 (2023).

Influence of X-ray radiation on tissues

Doses of irradiation above 25 kGy are known to cause irreversible mechanical decay in bone tissue. However, the impact of irradiation doses absorbed in a clinical setting on the mechanical properties of bone remains unclear. In daily clinical practice and research, patients and specimens are exposed to irradiation due to diagnostic imaging tools, with doses ranging from milligray to Gray. The aim of this study was to investigate the influence of irradiation at these doses ranges on the mechanical performance of bone independent of inter-individual bone quality indices.

Schmidt FN, Hahn M, Stockhausen KE, Rolvien T, Schmidt C, Knopp T, Schulze C, Püschel K, Amling M, Busse B. Influence of X-rays and gamma-rays on the mechanical performance of human bone factoring out intraindividual bone structure and composition indices. Mater Today Bio. 2021 Nov 26;13:100169. doi: 10.1016/j.mtbio.2021.100169.
In our research projects we develop, extend and adapt methods from robotics and navigation, search and optimization, machine learning, and signal and image processing to realize systems and system components for clinical applications ranging from tissue characterization to radiosurgical treatments.

Robotics

We study methods to control and navigate robot motion, particularly for medical applications. Examples include robotic radiosurgery, robotic transcranial stimulation and robotic needle placement. We are interested in approaches to detect and compensate motion and deformation, e.g., due to respiration, pulsation, or soft tissue deformation. Moreoever, we are also interested in human-robot interaction and mobile robotics. At our lab, we have a number of navigation systems (e.g., optical and electro-magnetic) and various robots (starting from 0.01 mm repeatability) to realize experimental Setups.

Neidhardt, Maximilian, et al. "Robotic tissue sampling for safe post-mortem biopsy in infectious corpses." IEEE transactions on medical robotics and bionics 4.1 (2022): 94-105.
Gessert, Nils, Matthias Schlüter, and Alexander Schlaefer. "A deep learning approach for pose estimation from volumetric OCT data." Medical image analysis 46 (2018): 162-179.
Schlüter, Matthias, Christoph Fürweger, and Alexander Schlaefer. "Optimizing robot motion for robotic ultrasound-guided radiation therapy." Physics in Medicine & Biology 64.19 (2019): 195012.
Schlaefer, A., and A. Schweikard. "Stepwise multi‐criteria optimization for robotic radiosurgery." Medical physics 35.5 (2008): 2094-2103.

Planning and Optimization

We apply planning and optimization approaches in several research areas, including treatment planning for radiation therapy and brachytherapy, as well as optimization of robot configurations and movements.

Radiation therapy presents an effective and non-invasive option for cancer treatment. However, ionizing radiation can be harmful and the effects and side effects of irradiation need to be balanced. We also examine robotic biopsy, which similarly requires careful planning for safe and time efficient tissue sampling.

We develop algorithms and systems involving heuristic optimization, mathematical programming, and machine learning to identify the optimal trade-off among the various clinical objectives.

Gerlach, Stefan, et al. "AI-based optimization for US-guided radiation therapy of the prostate." International journal of computer assisted radiology and surgery (2022): 1-10.
Gerlach, Stefan, et al. "Feasibility and analysis of CNN‐based candidate beam generation for robotic radiosurgery." Medical physics 47.9 (2020): 3806-3815.
Schlüter, Matthias, et al. "Analysis and optimization of the robot setup for robotic-ultrasound-guided radiation therapy." International journal of computer assisted radiology and surgery 14.8 (2019): 1379-1387.
Schlaefer, A., and A. Schweikard. "Stepwise multi‐criteria optimization for robotic radiosurgery." Medical physics 35.5 (2008): 2094-2103.
The fracture risk of bone is not solely dependent on bone quantity; indeed, bone’s hierarchical structure has distinct features at multiple length scales, and thus the quality of the bone structure plays a large role in its resistance to fracture. Moreover, tissue interfaces between bone, muscle, and tendon are important for a healthy and functional musculoskeletal system. Using various tools for tissue analytics and simulation, we aim to better understand the factors contributing to a healthy musculoskeletal system.

Multi-scale Analysis of Tissue Hierarchy

Bone is a natural, hierarchical composite material consisting of proteins and minerals (mainly mineralized collagen fibrils), and water. Mineralized tissues including bones and teeth gain their high fracture resistance through a tissue-specific hierarchical makeup, and changes at any length scale can have an influence on the mechanical properties at the skeletal level. Analyzing the structure, composition, and mechanical properties of bone tissue helps to better understand bone in healthy and diseased conditions.

Zimmermann EA, Fiedler IAK, Busse B. Breaking new ground in mineralized tissue: Assessing tissue quality in clinical and laboratory studies. J Mech Behav Biomed Mater. 2021 Jan;113:104138. doi: 10.1016/j.jmbbm.2020.104138. Epub 2020 Oct 12Fiedler, I.A.K., Schmidt, F.N., Wölfel, E.M., Plumeyer, C., Milovanovic, P., Gioia, R., Tonelli, F., Bale, H.A., Jähn, K., Besio, R., Forlino, A. and Busse, B. (2018), Severely Impaired Bone Material Quality in Chihuahua Zebrafish Resembles Classical Dominant Human Osteogenesis Imperfecta. J Bone Miner Res, 33: 1489-1499.

Locomotion patterns and skeletal function

Over the course of evolution, different types of locomotion have emerged within vertebrate species, for example, swimming in bony fish, quadrupedal walking in mice, and bipedal walking in humans. Despite these differences, the fundamental composition of bone tissue as well as its genetic regulation has been largely conserved across species. We can detect specific structure-function relationships of mineralized tissues across species to better understand the musculoskeletal system.

Dietrich K, Fiedler IA, Kurzyukova A, López-Delgado AC, McGowan LM, Geurtzen K, Hammond CL, Busse B, Knopf F. Skeletal Biology and Disease Modeling in Zebrafish. J Bone Miner Res. 2021 Mar;36(3):436-458. doi: 10.1002/jbmr.4256Schmidt, F. N., Zimmermann, E. A., Walsh, F., Plumeyer, C., Schaible, E., Fiedler, I. A. K., Milovanovic, P., Rößle, M., Amling, M., Blanchet, C., Gludovatz, B., Ritchie, R. O., Busse, B., On the Origins of Fracture Toughness in Advanced Teleosts: How the Swordfish Sword's Bone Structure and Composition Allow for Slashing under Water to Kill or Stun Prey. Adv. Sci. 2019, 6, 1900287.Name des Quellennachweises
Research projects at the IBI cover imaging modalities such as magnetic particle imaging, magnetic resonance imaging and computed tomography. A special focus is placed on the development of image reconstruction techniques, which allow for an acceleration of measurements, mitigation of artifacts or the generation of new imaging contrasts.

Reconstruction-Based Artifact Reduction

In imaging, a variety of factors, such as technical imperfections, the complexity of the underlying physics or patient motion, can be a cause of artifacts. In many cases, the latter can be mitigated by a suitable extension of the established standard image reconstruction algorithms. Recently, we also started exploring modern data-driven approaches for the mitigation of artifacts.

Knopp, Tobias, et al. "Efficient Joint Estimation of Tracer Distribution and Background Signals in Magnetic Particle Imaging Using a Dictionary Approach." IEEE Transaction on Medical Imaging (2021).Gdaniec, Nadine et al. "Suppression of Motion Artifacts Caused by Temporally Recurring Tracer Distributions in Multi-Patch Magnetic Particle Imaging." IEEE Transactions on Medical Imaging (2020).

Multi-Contrast Imaging

While standard imaging often generates images with a single contrast, modern acquisition schemes also allow to obtain multiple image contrasts from a single acquisition. Importantly, this can lead to an increased diagonistic value by opening up new ways of characterizing the object being imaged. An important aspect of our research is the development and improvement of the image reconstruction methods required to enable multi-contrast imaging.

Molwitz, Isabel et al. "Fat Quantification in Dual-Layer Detector Spectral Computed Tomography." Investigative Radiology (2022).Möddel, Martin et al. "Estimating the Spatial Orientation of Immobilized Magnetic Nanoparticles with Parallel-Aligned Easy Axes." Physical Review Applied (2021).

Image Reconstruction Software

Modern imaging relies on more and more sophisticated image reconstruction algorithms, which often have a high computational complexity. To facilitate the development and the adoption of new image reconstruction methods, we develop suitable image reconstruction frameworks, which are both performant and highly accessible.

Knopp, Tobias and Grosser, Mirco. "MRIReco.jl: An MRI Reconstruction Framework written in Julia." Magnetic Resonance in Medicine (2021).Knopp, Tobias et al., "MPIReco.jl: Julia Package for Image Reconstruction in MPI", International Journal on Magnetic Particle Imaging (2019).)Knopp, Tobias et al. "MPIFiles.jl: A Julia Package for Magnetic Particle Imaging Files." Journal of Open Source Software (2019).