Ulrich Flögel1,2,3, Anke Schlüter4, Christoph Jacoby1,2, Sebastian Temme1, J Paul Banga5, Anja Eckstein6, Jürgen Schrader1, Utta Berchner-Pfannschmidt5. 1. Experimental Cardiovascular Imaging, Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Germany. 2. Department of Cardiology, Pneumology and Angiology, University Hospital Düsseldorf, Germany. 3. Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-Universität Düsseldorf, Germany. 4. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, Germany. 5. Molecular Ophthalmology. 6. Ophthalmic Clinic, University Hospital Essen, Germany.
Abstract
PURPOSE: To evaluate key molecular and cellular features of Graves orbitopathy (GO) by simultaneous monitoring of alterations in morphology, inflammatory patterns, and tissue remodeling. METHODS: To this end, we utilized a murine model of GO induced by immunization with a human thyroid-stimulating hormone receptor A-subunit plasmid. Altogether, 52 mice were used: 27 GOs and 25 controls (Ctrl) immunized with β-galactasidose plasmid. From these, 17 GO and 12 Ctrl mice were subjected to multimodal MRI at 9.4T, whereas 23 mice only underwent histology. Beyond anatomical hydrogen-1 (1 H) MRI, we employed transverse relaxation time (T2 ) mapping for visualization of edema, chemical exchange saturation transfer (CEST) for detection of hyaluronan, and fluorine-19 (19 F) MRI for tracking of in situ-labeled immune cells after intravenous injection of perfluorcarbons (PFCs). RESULTS: 1 H/19 F MRI demonstrated substantial infiltration of PFC-loaded immune cells in peri and retro-orbital regions of GO mice, whereas healthy Ctrls showed only minor 19 F signals. In parallel, T2 mapping indicated onset of edema in periorbital tissue and adjacent ocular glands (P = 0.038/0.017), which were associated with enhanced orbital CEST signals in GO mice (P = 0.031). Concomitantly, a moderate expansion of retrobulbar fat (P = 0.029) was apparent; however, no signs for extraocular myopathy were detectable. 19 F MRI-based visualization of orbital inflammation exhibited the highest significance level to discriminate between GO and Ctrl mice (P = 0.006) and showed the best correlation with the clinical score (P = 0.0007). CONCLUSION: The present approach permits the comprehensive characterization of orbital tissue and holds the potential for accurate GO diagnosis in the clinical setting. Magn Reson Med 80:711-718, 2018.
PURPOSE: To evaluate key molecular and cellular features of Graves orbitopathy (GO) by simultaneous monitoring of alterations in morphology, inflammatory patterns, and tissue remodeling. METHODS: To this end, we utilized a murine model of GO induced by immunization with a human thyroid-stimulating hormone receptor A-subunit plasmid. Altogether, 52 mice were used: 27 GOs and 25 controls (Ctrl) immunized with β-galactasidose plasmid. From these, 17 GO and 12 Ctrl mice were subjected to multimodal MRI at 9.4T, whereas 23 mice only underwent histology. Beyond anatomical hydrogen-1 (1 H) MRI, we employed transverse relaxation time (T2 ) mapping for visualization of edema, chemical exchange saturation transfer (CEST) for detection of hyaluronan, and fluorine-19 (19 F) MRI for tracking of in situ-labeled immune cells after intravenous injection of perfluorcarbons (PFCs). RESULTS: 1 H/19 F MRI demonstrated substantial infiltration of PFC-loaded immune cells in peri and retro-orbital regions of GO mice, whereas healthy Ctrls showed only minor 19 F signals. In parallel, T2 mapping indicated onset of edema in periorbital tissue and adjacent ocular glands (P = 0.038/0.017), which were associated with enhanced orbital CEST signals in GO mice (P = 0.031). Concomitantly, a moderate expansion of retrobulbar fat (P = 0.029) was apparent; however, no signs for extraocular myopathy were detectable. 19 F MRI-based visualization of orbital inflammation exhibited the highest significance level to discriminate between GO and Ctrl mice (P = 0.006) and showed the best correlation with the clinical score (P = 0.0007). CONCLUSION: The present approach permits the comprehensive characterization of orbital tissue and holds the potential for accurate GO diagnosis in the clinical setting. Magn Reson Med 80:711-718, 2018.
Authors: Joice Maria Joseph; Maria Rosa Gigliobianco; Bita Mahdavi Firouzabadi; Roberta Censi; Piera Di Martino Journal: Pharmaceutics Date: 2022-02-09 Impact factor: 6.321
Authors: Stefan Hof; Carsten Marcus; Anne Kuebart; Jan Schulz; Richard Truse; Annika Raupach; Inge Bauer; Ulrich Flögel; Olaf Picker; Anna Herminghaus; Sebastian Temme Journal: Front Med (Lausanne) Date: 2022-05-16
Authors: Christine Quast; Frank Kober; Katrin Becker; Elric Zweck; Jasmina Hoffe; Christoph Jacoby; Vera Flocke; Isabella Gyamfi-Poku; Fabian Keyser; Kerstin Piayda; Ralf Erkens; Sven Niepmann; Matti Adam; Stephan Baldus; Sebastian Zimmer; Georg Nickenig; Maria Grandoch; Florian Bönner; Malte Kelm; Ulrich Flögel Journal: Basic Res Cardiol Date: 2022-05-29 Impact factor: 12.416
Authors: Anke Schlüter; Ulrich Flögel; Salvador Diaz-Cano; Gina-Eva Görtz; Kerstin Stähr; Michael Oeverhaus; Svenja Plöhn; Stefan Mattheis; Lars C Moeller; Stephan Lang; Nikolaos E Bechrakis; J Paul Banga; Anja Eckstein; Utta Berchner-Pfannschmidt Journal: Sci Rep Date: 2018-08-30 Impact factor: 4.379