TY  - JOUR
A1  - Schreiber, Laura M.
A1  - Lohr, David
A1  - Baltes, Steffen
A1  - Vogel, Ulrich
A1  - Elabyad, Ibrahim A.
A1  - Bille, Maya
A1  - Reiter, Theresa
A1  - Kosmala, Aleksander
A1  - Gassenmaier, Tobias
A1  - Stefanescu, Maria R.
A1  - Kollmann, Alena
A1  - Aures, Julia
A1  - Schnitter, Florian
A1  - Pali, Mihaela
A1  - Ueda, Yuichiro
A1  - Williams, Tatiana
A1  - Christa, Martin
A1  - Hofmann, Ulrich
A1  - Bauer, Wolfgang
A1  - Gerull, Brenda
A1  - Zernecke, Alma
A1  - Ergün, Süleyman
A1  - Terekhov, Maxim
T1  - Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research
JF  - Frontiers in Cardiovascular Medicine
N2  - A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.
KW  - ultrahigh-field MRI
KW  - large animal models
KW  - translational research
KW  - research infrastructure
KW  - heart
KW  - organoid
KW  - pig
KW  - cardiovascular MRI
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-317398
SN  - 2297-055X
VL  - 10
ER  - 
TY  - JOUR
A1  - Rossow, Leonie
A1  - Veitl, Simona
A1  - Vorlová, Sandra
A1  - Wax, Jacqueline K.
A1  - Kuhn, Anja E.
A1  - Maltzahn, Verena
A1  - Upcin, Berin
A1  - Karl, Franziska
A1  - Hoffmann, Helene
A1  - Gätzner, Sabine
A1  - Kallius, Matthias
A1  - Nandigama, Rajender
A1  - Scheld, Daniela
A1  - Irmak, Ster
A1  - Herterich, Sabine
A1  - Zernecke, Alma
A1  - Ergün, Süleyman
A1  - Henke, Erik
T1  - LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
JF  - Oncogene
N2  - The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease. Inhibition of collagen stabilization by itself can reduce or enhance tumor growth depending on the tumor type. The mechanistical basis for this behavior is the dependence of the individual tumor on nutritional supply on one hand and on high tissue stiffness for FAK signaling on the other.
KW  - Cancer models
KW  - Cancer therapeutic resistance
KW  - Targeted therapies
KW  - Tumour angiogenesis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227008
VL  - 37
ER  -