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journal article·2026-04Open access

Early Detection of Cell Death Using Transmembrane Water Exchange Magnetic Resonance Imaging

Athanasia Kaika, Luca Nagel, Ulrike Höckendorf, Bangwen Xie, Geoffrey J. Topping, Mathias Schillmaier, Irina Beer, Frits H. A. van Heijster, Julian Rauch, Tristan A. Kuder, Sandra Sühnel, Bernd Erber, Christian Lohrmann, Simone Ballke, Thomas Metzler, Katja Steiger, Philipp J. Jost, Natalia P. Ivleva, Philipp Paprottka, Jonathan Nadjiri, Kevin M. Brindle, Wolfgang A. Weber, Franz Schilling

Advanced Science· Volume 13· Issue 23
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Abstract

Abstract Cell death plays a key role in cancer progression and treatment. After its onset, cell membrane integrity is often compromised. Here, it is shown in cells, animals and humans that the transmembrane water exchange rate, measured using magnetic resonance filter‐exchange spectroscopy (FEXSY) or imaging (FEXI), and quantified by the apparent exchange rate (AXR), is an early biomarker of cell death. AXR measurements detect the onset of cell death in vivo earlier than diffusion‐weighted MRI (DWI) and in vitro with similar sensitivity as flow cytometry. 13 C magnetic resonance imaging (MRI) measurements of the malate/fumarate ratio (MFR), following injection of hyperpolarized [1,4‐ 13 C 2 ]fumarate, in tumors displaying diffuse necrosis, are correlated with AXR. AXR detects early treatment response in colorectal and lymphoma tumor models while the apparent diffusion coefficient (ADC) measured by DWI remains unchanged. AXR measurements in human uterine fibroids show sensitivity to post‐treatment changes soon after embolization, demonstrating clinical translatability of the method.
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Research context

OpenAlex topics: Advanced MRI Techniques and Applications · Lipid Membrane Structure and Behavior · MRI in cancer diagnosis

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Affiliations

Department of Nuclear Medicine TUM School of Medicine and Health TUM University Hospital Technical University of Munich Ismaninger Str. 22 81675 Munich Germany

Department of Internal Medicine III TUM School of Medicine and Health TUM University Hospital Technical University of Munich Ismaninger Str. 22 81675 Munich Germany

Cancer Research UK Cambridge Institute Li Ka Shing Centre University of Cambridge Robinson Way CB2 2RE Cambridge UK

Chair of Analytical Chemistry and Water Chemistry Institute of Water Chemistry TUM School of Natural Sciences (NAT, Dep. Chemistry) Technical University of Munich Lichtenbergstr. 4 85748 Garching Germany

Division of Medical Physics in Radiology German Cancer Research Center (DKFZ) Im Neuenheimer Feld 223 69120 Heidelberg Germany

Faculty of Physics and Astronomy Heidelberg University Im Neuenheimer Feld 226 69120 Heidelberg Germany

Comparative Experimental Pathology (CEP), Institute of Pathology TUM School of Medicine Technical University of Munich Trogerstr. 18 81675 Munich Germany

German Cancer Consortium (DKTK) partner site Munich, a partnership between DFKZ and TUM Im Neuenheimer Feld 280 69120 Heidelberg Germany

Department of Oncology University Clinic for Internal Medicine Medical University of Graz Auenbruggerplatz 15 8036 Graz Austria

Department of Interventional Radiology TUM School of Medicine and Health Technical University of Munich Ismaninger Str. 22 81675 Munich Germany

Department of Biochemistry University of Cambridge Tennis Court Road CB2 1QW Cambridge United Kingdom

Institute for Advanced Study Technical University of Munich Lichtenbergstr. 2 a 85748 Garching Germany

Bavarian Cancer Research Center (BZKF) 81675 Munich Germany

Munich Institute of Biomedical Engineering Technical University of Munich Boltzmannstr. 11 85748 Garching Germany

Funding

Deutsche Forschungsgemeinschaft · Cancer Research UK Therapeutic Discovery Laboratories

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