Immunoimaging Team
Michael Breckwoldt, MD PhD
Imaging immune cell dynamics by magnetic resonance (MRI) is a major clinical challenge. This is especially relevant with the advent of novel cancer immunotherapies. The group aims to visualize immunological processes in the tumor microenvironment and in autoimmunity (glioma and multiple sclerosis models). We employ a variety of imaging methods using high field MRI at 9.4 Tesla (in cooperation with the Neuroradiology Department, University Hospital Heidelberg) and correlative optical methods to investigate the cellular and subcellular level (2 photon intravital microscopy in cooperation with the AG Winkler, ultramicroscopy of cleared specimen in cooperation with the AG Tews). We also use iron oxide nanoparticles and other innovative contrast agents for cell tracking of immune cell subsets in immunotherapeutic paradigms (active/ passive vaccination, checkpoint inhibition, adoptive transfer models). Our long-term goal is to define imaging “immune signatures” of response / resistance for treatment monitoring and translate such signatures into clinical practice.
Current projects
• MR-light microscopy based Imaging of innate immune responses using TLR7 agonist CDNP-R848
• Iron oxide nanoparticle imaging of innate and adaptive immune cells during immunotherapy
• Metabolic CEST imaging of the TME
• Visualization and characterization of immune responses in H3.3K27M mutated gliomas
• Assessing delivery and distribution of immunotherapies in the TME
For more information about the AG Immuno-Imaging click here.
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Team members
- • Michael Breckwoldt MD PhD Prof (apl.) - Team leader
• Ina Weidenfeld, PhD - PostDoc
• Kianush Karimian, MD - PostDoc and attending neuroradiology
• Berin Boztepe, M.Sc - PhD student
• Ralph Sinn, M.Sc - PhD student
• Marta Kowina, MD student
• Jonas Scheck, MD student
• Rosa Eurich Technician
• Manuel Fischer - MRI Technician
Publications
- Y Streibel*, MO Breckwoldt*, J Hunger, C Pan, M Fischer, V Turco, B Boztepe, H Fels-Palesandro, JG Scheck, V Sturm, K Karimian-Jazi, DA Agardy, G Annio, R Mustapha, I Weidenfeld, SS Soni11, Abdulrahman Alasa, CB Rodell, W Wick, S Heiland, F Winkler, M Platten, M Bendszus, R Sinkus and K Schregel, Reduced tumor stiffness is a novel imaging biomarker to assess treatment response to immunotherapy in a murine glioma model. Sci Rep, (IF 3.8), 2024 Jul 6;14(1):15613, *equal contribution
- V Turco, K Pfleiderer, J Hunger, NK Horvat, K Karimian-Jazi, K Schregel, M Fischer, G Brugnara, K Jaehne, V Sturm, Y Streibel, D Nguyen, S Altamura, DA Agardy, Shreya S. Soni, A Alsasa, T Bunse, M Schlesner, MU Muckenthaler, R Weissleder, W Wick, S Heiland, P Vollmuth, M Bendszus, CB Rodell, MO Breckwoldt# and M Platten#, T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles, Nature Commun, 2023, 14:771, #shared corresponding and senior authorship
- K Schregel#, L Heinz, J Hunger, C Pan, J Bode, M Fischer, V Sturm, V Venkataramani, K Karimian-Jazi, D Agardy, Y Streibel, R Zerelles, W Wick, S Heiland, T Bunse, B Tews, M Platten, F Winkler, M Bendszus and MO Breckwoldt#, A cellular ground truth to develop MRI signatures in glioma models by correlative light sheet microscopy and atlas-based co-registration,
J Neurosci, 2023 7:JN-RM-1470-22, #shared corresponding authorship - J Hunger, K Schregel, B Boztepe, DA Agardy, V Turco, K Karimian-Jazi, I Weidenfeld, Y Streibel, M Fischer, V Sturm, R Santarella-Mellwig, M Kilian, K Jähne, K Sahm, W Wick, L Bunse, S Heiland, T Bunse, M Bendszus, M Platten and MO Breckwoldt, In vivo nanoparticle-based T cell imaging can predict therapy 1 response towards adoptive T cell therapy in experimental glioma, Theranostics 2023, Sep 25;13(15):5170-5182
- Hahn A, Bode J, Alexander A, Karimian-Jazi K, Schregel K, Schwarz D, Sommerkamp AC, Krüwel T, Abdollahi A, Wick W, Platten M, Bendszus M, Tews B, Kurz FT, Breckwoldt MO. Large-scale characterization of the microvascular geometry in development and disease by tissue clearing and quantitative ultramicroscopy. J Cereb Blood Flow Metab. 2021
- Karimian-Jazi K, Munch P, Alexander A, Fischer M, Piechutta M, Karreman MA, Solecki GM , Berghoff AS, Pfleiderer K, Friedrich M, Deumelandt K, Kurz F T., Wick W, Heiland S, Bendszus M, Winkler F, Platten M, and Breckwoldt MO. Monitoring innate immune cell dynamics in the glioma microenvironment by magnetic resonance imaging and multiphoton microscopy (MR-MPM). Theranostics. 2020
- Breckwoldt MO, Bode J, Sahm F, Krüwel T, Solecki G, Hahn A, Wirthschaft P, Berghoff AS, Haas M, Venkataramani V, von Deimling A, Wick W, Herold-Mende C, Heiland S, Platten M, Bendszus M, Kurz FT, Winkler F, Tews B. Correlated MRI and Ultramicroscopy (MR-UM) of Brain Tumors Reveals Vast Heterogeneity of Tumor Infiltration and Neoangiogenesis in Preclinical Models and Human Disease. Front Neurosci. 2019
- M Costa da Silva, MO Breckwoldt, F Vinchi, MP Correia, A Stojanovic, CM Thielmann, M Meister, T Muley, A Warth, M Platten, MW Hentze, A Cerwenka, and MU Muckenthaler. Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages. Front Immunol. 2017
- K Kirschbaum, JK Sonner, M Zeller, K Deumelandt, J Bode, R Sharma, T Krüwel, M Fischer, A Hoffmann, M Costa da Silva, MU Muckenthaler, W Wick, B Tews, JW Chen, S Heiland, M Bendszus, M Platten and MO Breckwoldt. In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a mouse model of multiple sclerosis. PNAS. 2016
- MO Breckwoldt, J Bode, FT Kurz, A Hoffmann, K Ochs, M Ott, K Deumelandt, T Krüwel, D Schwarz, M Fischer, X Helluy, D Milford, K Kirschbaum, GM Solecki, S Chiblak, A Abdollahi, F Winkler, W Wick, M Platten, S Heiland, M Bendszus and B Tews. Correlated MR imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis. eLIFE. 2015
- MO Breckwoldt, FMJ Pfister, PM Bradley, P Marinković, PR Williams, MS Brill, et al., Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. Nature Medicine. 2014
Funding
Emmy Noether Programm: „Translational multimodality imaging of glioma hallmarks to assess the dynamics of the immune cell landscape and tumor cell invasion during targeted therapy".
