Experimental Medical Physics

Background

X-ray microbeam radiation therapy (MBT) has been recognised as a unique therapeutic opportunity to alleviate the fundamental dose limitation. In MBT the treatment dose is modulated on the micrometre scale into planar, high dose “peaks” of a few micrometres width separated by a few 100 µm wide low dose regions called “valleys”. Preclinical studies have clearly demonstrated that MBT, with its spatial dose fractionation at the micrometre range, induces pronounced cytotoxic effects on tumour tissue while healthy tissues show a remarkably high functional tolerance, even after irradiation with MBT peak doses of up to 5000 Gy and associated dose rates of several kGy.s-1Differences in the microenvironment of tumour and normal tissue, such as the immune system, the vasculature and intercellular signalling cause this differential effect. 

FLASH radiation therapy is another innovative treatment strategy that uses dose rates above 100 Gy/s compared to conventional radiation therapy with dose rates in the order of a few Gy/min. FLASH irradiation showed in preclinical and recently first clinical applications strongly reduced adverse effects on normal tissue at equal doses, while the effect on the tumour remained unimpaired. The astonishing results of the first experiments with FLASH radiation therapy rapidly triggered a strong medical and commercial interest. 

FLASH and MBT are two exciting new developments in radiation oncology that have not yet reached clinical standard. A lack of mechanistic understanding for their effectiveness, challenges in dosimetry and quality assurance, and most importantly the unavailability of radiation sources facilitating the treatments are preventing the clinical translation.

PD Dr. Stefan Bartzsch
Arbeitsgruppenleiter
A novel x-ray source
3D-Modell einer komplexen wissenschaftlichen Quelleinheit zur Erzeugung oder Modulation von Strahlung, eingesetzt in der medizinischen Bildgebung oder Strahlenphysik.

Until recently, x-ray microbeam radiation therapy and x-ray FLASH therapy have only been possible at large synchrotrons, which are huge research facilities. We developed in our team compact alternatives and hence enable preclinical research independent of synchrotrons. We want to go further:

One of my primary objectives for the next five years is the set-up of the first clinically applicable microbeam radiation source based on line-focus X-ray tube technology. This technology enables x-ray beams from micrometre sized emitters (i.e. spatially coherent x-rays) with doses of several 10 probably up to 150 Gy/s. 

This ambitious deep-tech project brakes current x-ray tube records by orders of magnitude and involves innovative tools in electron acceleration and focusing in collaboration with the University of Mainz, enhancing the structure and material combinations in the X-ray target in partnership with the Research Centre Jülich, and establishing a modular pulsed high-voltage source in cooperation with the Hochschule München. 

Recent publications: 

  • Petrich, C., Winter, J., Dimroth, A., Wilkens, J. J., & Bartzsch, S. (2025). The compact line-focus X-ray tube for microbeam radiation therapy—Focal spot characterisation and collimator design. Physica Medica129, 104861.
  • Ahmed, M., Beyreuther, E., Gantz, S., Horst, F., Meyer, J., Pawelke, J., ... & Bartzsch, S. (2024). Design and dosimetric characterization of a transportable proton minibeam collimation system. Frontiers in Oncology14, 1473625.
  • Bartzsch, S. H., Corde, S., Crosbie, J. C., Day, L. R. J., Donzelli, M., Krisch, M., Lerch, M., Pellicioli, P., Smyth, L. M. L. & Tehei, M. (2020). Technical advances in X-ray microbeam radiation therapy. Physics in Medicine & Biology.
  • Bartzsch, S. and Oelfke, U., 2017. Line focus x-ray tubes—a new concept to produce high brilliance x-rays. Physics in Medicine & Biology, 62(22), p.8600.
Radiation chemistry
Darstellung eines EPR-Spektrums mit mehreren charakteristischen Peaks im Magnetfeldbereich von ca. 3470 bis 3540 mT, verwendet zur Analyse freier Radikale in biologischen Proben.

Understanding the underlying mechanisms of FLASH therapy and spatially fractionated radiation therapy is crucial to optimizing treatment efficacy. To this end, we are investigating the role of radiochemical interactions involving reactive oxygen species (ROS), examining the influence of radiochemical levels in cells and tissues on biological response, and analysing the impact of high-dose rates, radiation doses, and spatial fractionation on cell metabolism and intercellular signalling such as bystander effects. We employ various assays to detect ROS experimentally, for example by employing spin traps and electron spin resonance measurements.

Radiochemistry plays a major role between a few nanoseconds up to around 1 second after radiation absorption. There is growing evidence that this phase is crucial for an understanding of radiation therapy at high dose rates and spatial fractionation. Apart from experimental measurements of radiochemical species, we develop models of the evolution of reactive radiochemical species.

 

Recent publications:

  • Baikalov, A., Abolfath, R., Schüler, E., Mohan, R., Wilkens, J. J., & Bartzsch, S. (2023). Intertrack interaction at ultra-high dose rates and its role in the FLASH effect. Frontiers in Physics11, 1215422.
  • Abolfath, R., Baikalov, A., Fraile, A., Bartzsch, S., Schüler, E., & Mohan, R. (2023). A stochastic reaction–diffusion modeling investigation of FLASH ultra-high dose rate response in different tissues. Frontiers in Physics11, 1060910.
  • Abolfath, R., A. Baikalov, S. Bartzsch, N. Afshordi and R. Mohan (2022). "The effect of non-ionizing excitations on the diffusion of ion species and inter-track correlations in FLASH ultra-high dose rate radiotherapy." Physics in Medicine and Biology 67(10).
Biological mechanisms
Brain

The success of radiation treatment depends strongly on the tissue and tumour microenvironment – intracellular signalling, immune system, vasculature and oxidative stress. We aim to understand novel treatment strategies, such as FLASH and microbeams better by performing preclinical in vitro and in vivo studies. With various cutting-edge imaging techniques we decipher the secrets of radiation action in cells and tissue.

Focus of our investigations are radio-immune interactions in microbeam and minibeam radiation therapy, bystander signalling and oxidative stress and the role of vascular damage for the efficacy of microbeam radiation therapy.  

Publications:

  • Subramanian, N., Čolić, A., Santiago Franco, M., Stolz, J., Ahmed, M., Bicher, S., ... & Schmid, T. E. (2025). Superior Anti-Tumor Response After Microbeam and Minibeam Radiation Therapy in a Lung Cancer Mouse Model. Cancers17(1), 114.
  • Stolz, J., Rogal, K., Bicher, S., Winter, J., Ahmed, M., Raulefs, S., ... & Schmid, T. E. (2025). The Combination of Temporal and Spatial Dose Fractionation in Microbeam Radiation Therapy. Biomedicines13(3), 678.
  • Ahmed, M., Bicher, S., Combs, S. E., Lindner, R., Raulefs, S., Schmid, T. E., ... & Bartzsch, S. (2024). In vivo microbeam radiation therapy at a conventional small animal irradiator. Cancers16(3).
  • Steel, H., Brüningk, S. C., Box, C., Oelfke, U., & Bartzsch, S. H. (2021). Quantification of Differential Response of Tumour and Normal Cells to Microbeam Radiation in the Absence of FLASH Effects. Cancers, 13(13), 3238.
Treatment planning and dosimetry
Farbcodierte CT-Querschnittaufnahme des Brustkorbs mit geplanter Strahlendosisverteilung für einen Lungentumor; deutlich erkennbar sind Lungenstrukturen, Zielvolumen und angrenzende Risikoorgane.

Treatment planning is an essential step before any state-of-the-art radiotherapy treatment: It is required to estimate tumour control and potential side effects in organs at risk. In our team we develop innovative methods for dose calculation and biologically motivated treatment planning in spatially fractionated radiation therapy.

Part of the teams work is the implementation of fast and accurate dose calculation methods and a detailed characterization of source parameters. Together with partners at the Australian Synchrotron, we embedded these tools in a professional treatment planning system and we are now adapting it to our compact microbeam sources. The developed tools are used for retrospective treatment planning studies with the aim to establish the relevant field parameters and identify patient cohorts for first clinical applications in microbeam radiation therapy.

Dosimetry and quality assurance with micrometre sized beams is challenging. We established film dosimetry protocols with microscopic read-out and test various high-resolving dosimeters for future clinically relevant quality assurance protocols. 

 

Publications:

  • Bartzsch, S., Ahmed, M., Bicher, S., Stewart, R. D., Schmid, T. E., Combs, S. E., & Meyer, J. (2023). Equivalent Uniform Dose (EUD) and the Evaluation of Cell Survival in Spatially Fractionated Radiotherapy (SFRT). International Journal of Radiation Oncology, Biology, Physics117(2), e642.
  • Kraus, K. M., Winter, J., Zhang, Y., Ahmed, M., Combs, S. E., Wilkens, J. J., & Bartzsch, S. (2022). Treatment Planning Study for Microbeam Radiotherapy Using Clinical Patient Data. Cancers, 14(3), 685.
  • Hombrink G, Wilkens JJ, Combs SE, Bartzsch S, "Simulation and measurement of microbeam dose distribution in lung tissue." Physica Medica 75 (2020): 77-82.
  • Donzelli, M., Brauer-Krisch, E., Oelfke, U., Wilkens, J. J., & Bartzsch, S. (2018). Hybrid dose calculation: a dose calculation algorithm for microbeam radiation therapy. Physics in Medicine and Biology

Team

Postdocs:PhD students:Master students:
  • Mabroor Ahmed 
  • Liam Day
  • Kim Kraus
  • Johanna Winter
  • Monika Dehn 
  • Christian Petrich
  • Alexander Baikalov (PhD)
  • André Janes (PhD)
  • Mahadevan Ravichandran (PhD) 
  • Narayani Subramanian (PhD) 
  • Yating Zhang (PhD) 
  • Somayyeh Iranimobaraki
  • Ignacio Lazaro Bilbao
  • Antonia Athina Katsoli
  • Marie-Luise Schwaben
  • Ondrej Skrla
  • Patrizia Reinmuth
  • Haoming Chen

 


 

Prizes: 

  • Cancer Research UK Pioneer Award (2016)
  • DEGRO Innovation award (2023)
  • Medical Valley Award (2024)
  • Klee-Preis des VDE DGBMT (2024)

 

 

Research partners: 

  • The Institute of Cancer Research, London, UK
    • Prof Uwe Oelfke on in-vitro radiation biology of Microbeam Radiation Therapy
  • RMIT University, Melbourne, Australia
    • Prof Jeffrey Crosbie / Micah Barnes on Hybrid dose calculation in Varian Eclipse™
  • University of Wollongong, Australia
    • Prof Michael Lerch on online microbeam dosimetry with solid state detectors
  • MD Anderson, Houston, USA
    • Prof Emil Schueler on the role of reactive oxygen species in FLASH radiation therapy
  • University of Seattle, Seattle, USA
    • Prof Jürgen Meyer on the prediction of normal tissue damage and tumour control in proton minibeam radiation therapy
  • Helmholtz-Institute Mainz
    • Prof Kurt Aulenbacher on table-top cancer treatment with microbeams
  • Hochschule München, Munich
    • Prof Marek Galek on table-top cancer treatment with microbeams
  • Research Centre Jülich, Central Institute of Engineering, Electronics and Analytics 
    • Prof Ghaleb Natour & Prof Michael Butzek on table-top cancer treatment with microbeams
  • Helmholtz Centre Dresden Rossendorf, Dresden 
    • Dr. Elke Beyreuther & Dr. Jörg Pawelke on AI to apply precise Radiation Therapy
  • German Cancer Research Centre (DKFZ), Heidelberg
    • Prof Joao Seco on the radiochemistry in FLASH radiation therapy
  • Marburg ion-beam therapy centre
    • Dr. Kilian-Simon Baumann on measurement of reactive oxygen species in high dose rate radiation therapy

 

 

Where to find us

Our team is located at the Department of Radiation Oncology at the University Hospital rechts der Isar of the Technical University Munich (TUM) and the Institute of Radiation Medicine at the Helmholtz Centre Munich, lead by Prof. Dr. Stephanie Combs.

We are situated at three different sites in Munich:

Addresses:

Klinikum rechts der Isar

Ismaninger Straße 22
81675 Munich

Forschungs-Neutronenquelle Hein Maier-Leibnitz

Building UYM
Lichtenbergstraße 1
85748 Garching

Helmholtz Centre Munich

Institute for Radiation Medicine
Ingolstädter Landstraße 1
85764 Oberschleißheim


Telephone:

+49 89 3187 43042

E-Mail:

stefan.bartzsch@tum.de