Research Phase and Master's Thesis in the M.Sc. Biomedical Engineering and Medical Physics

Are you interested in the prospects to manipulate biological structures with magnetic fields to intervene in central cellular processes relevant in biomedicine? Then you should be interested in this joint Master’s project between the Bucher Lab https://www.bucherlab.org/ and Westmeyer Lab https://www.westmeyerlab.org/ on using quantum technology based on nitrogen-vacancy (NV-)centers [1,2] to characterize and optimize biomagnetic nanostructures [3,4] in living mammalian cells.

Summary

NV-magnetometry to characterize and optimize biomagnetic nanostructures in mammalian cells

Your Profile

● an excellent and recent Bachelors's degree in (bio-)physics, biochemistry, biological engineering, biomedical engineering, or related academic programs,

● genuine interest in the powerful applications of NV-centers (https://en.wikipedia.org/wiki/Nitrogen-vacancy_center)

● previous experience with microscopy and mammalian cell culture,

● the ability to be self-motivated and work with an interdisciplinary team of bioengineers, biochemists, neuroscientists, and data scientists,

● excellent English language and organizational skills. ● an openness and mobility to collaborate with our partners at Max Planck Institutes, MIT, Caltech, and the University of Washington.

References:

[1] Bucher, D.B., Glenn, D.R., Park, H., Lukin, M.D., Walsworth, R.L., 2020. Hyperpolarization-Enhanced NMR Spectroscopy with Femtomole Sensitivity Using Quantum Defects in Diamond. Physical Review X 10, 021053. https://doi.org/10.1103/PhysRevX.10.021053

[2] Bucher, D.B., Craik, D.P.L.A., Backlund, M.P., Turner, M.J., Dor, O.B., Glenn, D.R., Walsworth, R.L., 2019. Quantum diamond spectrometer for nanoscale NMR and ESR spectroscopy. Nat Protoc 14, 2707–2747. https://doi.org/10.1038/s41596-019-0201-3

[3] Sigmund, F., Massner, C., Erdmann, P., Stelzl, A., Rolbieski, H., Desai, M., Bricault, S., Wörner, T.P., Snijder, J., Geerlof, A., Fuchs, H., Hrabe de Angelis, M., Heck, A.J.R., Jasanoff, A., Ntziachristos, V., Plitzko, J., Westmeyer, G.G., 2018. Bacterial encapsulins as orthogonal compartments for mammalian cell engineering. Nat Commun 9, 1990. https://doi.org/10.1038/s41467-018-04227-3

[4] Sigmund, F., Pettinger, S., Kube, M., Schneider, F., Schifferer, M., Schneider, S., Efremova, M.V., Pujol-Martí, J., Aichler, M., Walch, A., Misgeld, T., Dietz, H., Westmeyer, G.G., 2019. Iron-Sequestering Nanocompartments as Multiplexed Electron Microscopy Gene Reporters. ACS Nano 13, 8114–8123. https://doi.org/10.1021/acsnano.9b03140

Magnetic stimulation is an established method for diagnostic and therapeutical applications. Depending on whether stimulation is applied to the brain, the neck or any other part of the human body, requirements to the hardware can differ significantly. We want to design and construct a device which can be easily adapted for different stimulation methods. Besides a generic processing unit, modules should be exchangeable and extensible.

Character of thesis work:

This work includes the design and construction of different modules which are assembled to a complete and operational device. Hardware layout and tests are required as well as the programming of a microprocessor. Different operation modes should be tested and evaluated.

You should bring:

Basic knowledge in circuit design and programming (C, C++)

Comparisons of magnetic coils for inductive nerve stimulation are challenging and are mostly based on simulations. Those simulations rely on approximations and assumptions and often ignore issues like skin effect or proximity effect. Further, such calculations are time consuming and limited in accuracy and resolution. To determine the spatial field distribution along a nerve, we want to design a device that scans the electric field induced by a coil on a millimeter scale.

Character of thesis work:

Literature research on different field measurement methods and evaluate suitability; Design and construction of the device, including custom circuits and measurement environment; Evaluation of the device and exemplary measurement for different coil designs.

Question and tasks:

What methods are suitable to evaluate the electric field on a millimeter scale? Design and built the device; Determine the spatial field distribution for different coil designs; Investigate ohmic losses for solid coil wire and high frequency litz wire.

You should bring:

Interest in literature research, hardware design, experimental setup design.

Compton scattering is one of the two primary interactions of X-rays with matter in X-ray imaging (next to photoelectric absorption). In contrast to photoelectric absorption, Compton scattering is an inelastic scattering process during which X-ray photons are deflected and transfer some of their energy to the interaction partner, typically an electron. As a consequence, photons may still reach the detector after Compton interaction. In X-ray imaging, this leads to a smoothly varying background, which reduces contrast and is detrimental to quantitative imaging. Furthermore, the Compton scatter background is not uniform, but instead depends on the materials and their distribution within an imaged object. This makes a straight-forward analytical correction difficult, and existing tools to estimate the Compton background are limited in their accuracy and applicability.

The goal of this thesis is to develop methods to a) estimate the Compton scattering background from simple radiographs, and b) correct these images for it. This will be done using machine learning, in particular convolutional neural networks. The student will generate Monte-Carlo simulations based on the Geant4 platform, design and train neural networks, apply them for Compton scatter correction on clinical radiography images, and compare the results to existing approaches.

The project involves mostly data preparation, and computational work (85%, primarily Python, with potentially some C++ for Geant4), as well as experimental data collection (15%). The project will involve collaboration with the Radiology department at the TUM Hospital Klinikum rechts der Isar.

Basic experience in scientific programming, Monte-Carlo simulations, neural networks, and/or X-ray imaging are desirable.

For more information, please contact: Dr. Florian Schaff (florian.schaff@tum.de), or Prof. Franz Pfeiffer (franz.pfeiffer@tum.de).

This project will explore the use of latest hybrid-pixel photon-counting detectors for improving the image quality in 3D (cone-beam CT) dental imaging applications. More specifically, the project aims at the experimental evaluation of the potential benefits of applying spectral material decomposition for dental CT application. The work will include preclinical experiments using dedicated anthropomorphic head phantoms and subsequent image analysis and interpretation. The project will be carried out in close collaboration with the Department of Radiology at the TUM Klinikum Rechts der Isar and with an external industrial collaborator located in the Munich area.

Character of thesis work: experimental physics (30%) & image processing (70%)

For more information, please contact: Daniel Berthe (daniel.berthe@tum.de) or Franz Pfeiffer (franz.pfeiffer@tum.de)

Are you interested in discovering dynamic patterns of cellular processes across entire organs in living organisms ? Then you should be interested in this joint Master’s project between the Westmeyer Lab https://www.westmeyerlab.org/ and the Stiel Lab https://www.helmholtz-muenchen.de/ibmi/laboratories/cell-engineering/index.html on using new genetically controlled reporters for multispectral optoacoustic tomography (MSOT), an innovative technique to obtain “color information” with deeper tissue penetration than any other optical method.

Summary

Development and validation of new gene reporters for in vivo optoacoustic tomography.

Your Profile

● an excellent and recent Bachelors's degree in (bio-)physics, biochemistry, biological engineering, biomedical engineering, or related academic programs,

● genuine interest in the powerful applications of MSOT (https://en.wikipedia.org/wiki/Multispectral_optoacoustic_tomography)

● previous experience with microscopy and mammalian cell culture, and ideally work in animal models

● the ability to be self-motivated and work with an interdisciplinary team of bioengineers, biochemists, neuroscientists, and data scientists,

● excellent English language and organizational skills.

Please send your letter of motivation and your complete CV to Felix Sigmund (felix.sigmund@tum.de).

References:

[1] Stiel A.C., Deán-Ben X.L., Jiang Y., Ntziachristos V., Razansky D. and Westmeyer G.G. High-contrast imaging of reversibly switchable fluorescent proteins via temporally unmixed multispectral optoacoustic tomography. Optics Letters 40(3):367-370, 2015 https://www.osapublishing.org/ol/abstract.cfm?URI=ol-40-3-367

[2] Sigmund, F., Massner, C., Erdmann, P., Stelzl, A., Rolbieski, H., Desai, M., Bricault, S., Wörner, T.P., Snijder, J., Geerlof, A., Fuchs, H., Hrabe de Angelis, M., Heck, A.J.R., Jasanoff, A., Ntziachristos, V., Plitzko, J., Westmeyer, G.G., 2018. Bacterial encapsulins as orthogonal compartments for mammalian cell engineering. Nat Commun 9, 1990. https://doi.org/10.1038/s41467-018-04227-3

[3] Weidenfeld, I., Zakian, C., Duewell, P., Chmyrov, A., Klemm, U., Aguirre, J., Ntziachristos, V. and Stiel, AC. Homogentisic acid-derived pigment as a biocompatible label for optoacoustic imaging of macrophages. Nat Commun 10, 5056 (2019) https://doi:10.1038/s41467-019-13041-4

[4] Mishra K., Stankevych M., Fuenzalida-Werner JP., Grassmann S., Gujrati V., Huang Y., Klemm U., Buchholz VR., Ntziachristos V., Stiel AC. Multiplexed whole-animal imaging with reversibly switchable optoacoustic proteins. Science Advances 2020-06 (2020). DOI: 10.1126/sciadv.aaz6293

Regression of the diaphragm muscle during artificial respiration leads to severe problems with breathing for many patients. To avoid such regression, stimulation of the phrenic nerve is a promising solution. Magnetic stimulation of the phrenic nerve has been demonstrated. However, devices are too large and complex and hence, optimization is required. We want to adapt parameters like pulse shape and coil design to stimulate the phrenic nerve with minimum energy. Further, we want to evaluate the possibility of electric stimulation and compare it to the magnetic approach. Those problems can be addressed using simulations. To verify our results, we want to design an experimental setup involving the stimulation of the sciatic nerve in the forearm.

Character of thesis work:

Extensive literature research on different simulation approaches; Extend and adapt a software environment to implement simulations for magnetic and electric simulation; Calculate field data using FEM and similar methods; Data processing using python; Design an experimental setup to verify simulations;

Question and Tasks:

What is the optimal configuration to stimulate the phrenic nerve? How are magnetic and electric stimulation different on a cellular level and how can they be simulated? How precise are our simulations? How can we verify our results?

You should bring:

Basic data science skills, ideally familiar with python and git; Good understanding of field theory; Interest in literature research