@article{TraubGrondeyGassenmaieretal.2022, author = {Traub, Jan and Grondey, Katja and Gassenmaier, Tobias and Schmitt, Dominik and Fette, Georg and Frantz, Stefan and Boivin-Jahns, Val{\´e}rie and Jahns, Roland and St{\"o}rk, Stefan and Stoll, Guido and Reiter, Theresa and Hofmann, Ulrich and Weber, Martin S. and Frey, Anna}, title = {Sustained increase in serum glial fibrillary acidic protein after first ST-elevation myocardial infarction}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {18}, issn = {1422-0067}, doi = {10.3390/ijms231810304}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288261}, year = {2022}, abstract = {Acute ischemic cardiac injury predisposes one to cognitive impairment, dementia, and depression. Pathophysiologically, recent positron emission tomography data suggest astroglial activation after experimental myocardial infarction (MI). We analyzed peripheral surrogate markers of glial (and neuronal) damage serially within 12 months after the first ST-elevation MI (STEMI). Serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using ultra-sensitive molecular immunoassays. Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11\% female). The median (quartiles) of GFAP was 63.8 (47.0, 89.9) pg/mL and of NfL 10.6 (7.2, 14.8) pg/mL at study entry 0-4 days after STEMI. GFAP after STEMI increased in the first 3 months, with a median change of +7.8 (0.4, 19.4) pg/mL (p = 0.007). It remained elevated without further relevant increases after 6 months (+11.7 (0.6, 23.5) pg/mL; p = 0.015), and 12 months (+10.3 (1.5, 22.7) pg/mL; p = 0.010) compared to the baseline. Larger relative infarction size was associated with a higher increase in GFAP (ρ = 0.41; p = 0.009). In contrast, NfL remained unaltered in the course of one year. Our findings support the idea of central nervous system involvement after MI, with GFAP as a potential peripheral biomarker of chronic glial damage as one pathophysiologic pathway.}, language = {en} } @article{SchreiberLohrBaltesetal.2023, author = {Schreiber, Laura M. and Lohr, David and Baltes, Steffen and Vogel, Ulrich and Elabyad, Ibrahim A. and Bille, Maya and Reiter, Theresa and Kosmala, Aleksander and Gassenmaier, Tobias and Stefanescu, Maria R. and Kollmann, Alena and Aures, Julia and Schnitter, Florian and Pali, Mihaela and Ueda, Yuichiro and Williams, Tatiana and Christa, Martin and Hofmann, Ulrich and Bauer, Wolfgang and Gerull, Brenda and Zernecke, Alma and Erg{\"u}n, S{\"u}leyman and Terekhov, Maxim}, title = {Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research}, series = {Frontiers in Cardiovascular Medicine}, volume = {10}, journal = {Frontiers in Cardiovascular Medicine}, issn = {2297-055X}, doi = {10.3389/fcvm.2023.1068390}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317398}, year = {2023}, abstract = {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.}, language = {en} } @article{HockTerekhovStefanescuetal.2021, author = {Hock, Michael and Terekhov, Maxim and Stefanescu, Maria Roxana and Lohr, David and Herz, Stefan and Reiter, Theresa and Ankenbrand, Markus and Kosmala, Aleksander and Gassenmaier, Tobias and Juchem, Christoph and Schreiber, Laura Maria}, title = {B\(_{0}\) shimming of the human heart at 7T}, series = {Magnetic Resonance in Medicine}, volume = {85}, journal = {Magnetic Resonance in Medicine}, number = {1}, doi = {10.1002/mrm.28423}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218096}, pages = {182 -- 196}, year = {2021}, abstract = {Purpose Inhomogeneities of the static magnetic B\(_{0}\) field are a major limiting factor in cardiac MRI at ultrahigh field (≥ 7T), as they result in signal loss and image distortions. Different magnetic susceptibilities of the myocardium and surrounding tissue in combination with cardiac motion lead to strong spatio-temporal B\(_{0}\)-field inhomogeneities, and their homogenization (B0 shimming) is a prerequisite. Limitations of state-of-the-art shimming are described, regional B\(_{0}\) variations are measured, and a methodology for spherical harmonics shimming of the B\(_{0}\) field within the human myocardium is proposed. Methods The spatial B\(_{0}\)-field distribution in the heart was analyzed as well as temporal B\(_{0}\)-field variations in the myocardium over the cardiac cycle. Different shim region-of-interest selections were compared, and hardware limitations of spherical harmonics B\(_{0}\) shimming were evaluated by calibration-based B0-field modeling. The role of third-order spherical harmonics terms was analyzed as well as potential benefits from cardiac phase-specific shimming. Results The strongest B\(_{0}\)-field inhomogeneities were observed in localized spots within the left-ventricular and right-ventricular myocardium and varied between systolic and diastolic cardiac phases. An anatomy-driven shim region-of-interest selection allowed for improved B\(_{0}\)-field homogeneity compared with a standard shim region-of-interest cuboid. Third-order spherical harmonics terms were demonstrated to be beneficial for shimming of these myocardial B\(_{0}\)-field inhomogeneities. Initial results from the in vivo implementation of a potential shim strategy were obtained. Simulated cardiac phase-specific shimming was performed, and a shim term-by-term analysis revealed periodic variations of required currents. Conclusion Challenges in state-of-the-art B\(_{0}\) shimming of the human heart at 7 T were described. Cardiac phase-specific shimming strategies were found to be superior to vendor-supplied shimming.}, language = {en} } @unpublished{HeidenreichGassenmaierAnkenbrandetal.2021, author = {Heidenreich, Julius F. and Gassenmaier, Tobias and Ankenbrand, Markus J. and Bley, Thorsten A. and Wech, Tobias}, title = {Self-configuring nnU-net pipeline enables fully automatic infarct segmentation in late enhancement MRI after myocardial infarction}, edition = {accepted version}, doi = {10.1016/j.ejrad.2021.109817}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323418}, year = {2021}, abstract = {Purpose To fully automatically derive quantitative parameters from late gadolinium enhancement (LGE) cardiac MR (CMR) in patients with myocardial infarction and to investigate if phase sensitive or magnitude reconstructions or a combination of both results in best segmentation accuracy. Methods In this retrospective single center study, a convolutional neural network with a U-Net architecture with a self-configuring framework ("nnU-net") was trained for segmentation of left ventricular myocardium and infarct zone in LGE-CMR. A database of 170 examinations from 78 patients with history of myocardial infarction was assembled. Separate fitting of the model was performed, using phase sensitive inversion recovery, the magnitude reconstruction or both contrasts as input channels. Manual labelling served as ground truth. In a subset of 10 patients, the performance of the trained models was evaluated and quantitatively compared by determination of the S{\o}rensen-Dice similarity coefficient (DSC) and volumes of the infarct zone compared with the manual ground truth using Pearson's r correlation and Bland-Altman analysis. Results The model achieved high similarity coefficients for myocardium and scar tissue. No significant difference was observed between using PSIR, magnitude reconstruction or both contrasts as input (PSIR and MAG; mean DSC: 0.83 ± 0.03 for myocardium and 0.72 ± 0.08 for scars). A strong correlation for volumes of infarct zone was observed between manual and model-based approach (r = 0.96), with a significant underestimation of the volumes obtained from the neural network. Conclusion The self-configuring nnU-net achieves predictions with strong agreement compared to manual segmentation, proving the potential as a promising tool to provide fully automatic quantitative evaluation of LGE-CMR.}, language = {en} } @article{FreyGassenmaierHofmannetal.2020, author = {Frey, Anna and Gassenmaier, Tobias and Hofmann, Ulrich and Schmitt, Dominik and Fette, Georg and Marx, Almuth and Heterich, Sabine and Boivin-Jahns, Val{\´e}rie and Ertl, Georg and Bley, Thorsten and Frantz, Stefan and Jahns, Roland and St{\"o}rk, Stefan}, title = {Coagulation factor XIII activity predicts left ventricular remodelling after acute myocardial infarction}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {5}, doi = {10.1002/ehf2.12774}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236013}, pages = {2354-2364}, year = {2020}, abstract = {Aims Acute myocardial infarction (MI) is the major cause of chronic heart failure. The activity of blood coagulation factor XIII (FXIIIa) plays an important role in rodents as a healing factor after MI, whereas its role in healing and remodelling processes in humans remains unclear. We prospectively evaluated the relevance of FXIIIa after acute MI as a potential early prognostic marker for adequate healing. Methods and results This monocentric prospective cohort study investigated cardiac remodelling in patients with ST-elevation MI and followed them up for 1 year. Serum FXIIIa was serially assessed during the first 9 days after MI and after 2, 6, and 12 months. Cardiac magnetic resonance imaging was performed within 4 days after MI (Scan 1), after 7 to 9 days (Scan 2), and after 12 months (Scan 3). The FXIII valine-to-leucine (V34L) single-nucleotide polymorphism rs5985 was genotyped. One hundred forty-six patients were investigated (mean age 58 ± 11 years, 13\% women). Median FXIIIa was 118 \% (quartiles, 102-132\%) and dropped to a trough on the second day after MI: 109\%(98-109\%; P < 0.001). FXIIIa recovered slowly over time, reaching the baseline level after 2 to 6 months and surpassed baseline levels only after 12 months: 124 \% (110-142\%). The development of FXIIIa after MI was independent of the genotype. FXIIIa on Day 2 was strongly and inversely associated with the relative size of MI in Scan 1 (Spearman's ρ = -0.31; P = 0.01) and Scan 3 (ρ = -0.39; P < 0.01) and positively associated with left ventricular ejection fraction: ρ = 0.32 (P < 0.01) and ρ = 0.24 (P = 0.04), respectively. Conclusions FXIII activity after MI is highly dynamic, exhibiting a significant decline in the early healing period, with reconstitution 6 months later. Depressed FXIIIa early after MI predicted a greater size of MI and lower left ventricular ejection fraction after 1 year. The clinical relevance of these findings awaits to be tested in a randomized trial.}, language = {en} }