TY  - JOUR
A1  - Proetel, Ulrike
A1  - Pletsch, Nadine
A1  - Lauseker, Michael
A1  - Müller, Martin C.
A1  - Hanfstein, Benjamin
A1  - Krause, Stefan W.
A1  - Kalmanti, Lida
A1  - Schreiber, Annette
A1  - Heim, Dominik
A1  - Baerlocher, Gabriela M.
A1  - Hofmann, Wolf-Karsten
A1  - Lange, Elisabeth
A1  - Einsele, Hermann
A1  - Wernli, Martin
A1  - Kremers, Stephan
A1  - Schlag, Rudolf
A1  - Müller, Lothar
A1  - Hänel, Mathias
A1  - Link, Hartmut
A1  - Hertenstein, Bernd
A1  - Pfirrmann, Markus
A1  - Hochhaus, Andreas
A1  - Hasford, Joerg
A1  - Hehlmann, Rüdiger
A1  - Saußele, Susanne
T1  - Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV
JF  - Annals of Hematology
N2  - The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
KW  - chronic myeloid leukemia
KW  - older patients
KW  - different imatinib dose regimens
KW  - early applied higher imatinib dosages
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121574
SN  - 0939-5555
VL  - 93
IS  - 7
ER  - 
TY  - JOUR
A1  - Dech, Stefan
A1  - Holzwarth, Stefanie
A1  - Asam, Sarah
A1  - Andresen, Thorsten
A1  - Bachmann, Martin
A1  - Boettcher, Martin
A1  - Dietz, Andreas
A1  - Eisfelder, Christina
A1  - Frey, Corinne
A1  - Gesell, Gerhard
A1  - Gessner, Ursula
A1  - Hirner, Andreas
A1  - Hofmann, Matthias
A1  - Kirches, Grit
A1  - Klein, Doris
A1  - Klein, Igor
A1  - Kraus, Tanja
A1  - Krause, Detmar
A1  - Plank, Simon
A1  - Popp, Thomas
A1  - Reinermann, Sophie
A1  - Reiners, Philipp
A1  - Roessler, Sebastian
A1  - Ruppert, Thomas
A1  - Scherbachenko, Alexander
A1  - Vignesh, Ranjitha
A1  - Wolfmueller, Meinhard
A1  - Zwenzner, Hendrik
A1  - Kuenzer, Claudia
T1  - Potential and challenges of harmonizing 40 years of AVHRR data: the TIMELINE experience
JF  - Remote Sensing
N2  - Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper.
KW  - AVHRR
KW  - Earth Observation
KW  - harmonization
KW  - time series analysis
KW  - climate related trends
KW  - automatic processing
KW  - Europe
KW  - TIMELINE
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246134
SN  - 2072-4292
VL  - 13
IS  - 18
ER  - 
TY  - THES
A1  - Hofmann, Martin
T1  - Contributions to Extreme Value Theory in the Space C[0,1]
T1  - Beiträge zur Extremwerttheorie im Raum C[0,1]
N2  - We introduce some mathematical framework for extreme value theory in the space of continuous functions on compact intervals and provide basic definitions and tools. Continuous max-stable processes on [0,1] are characterized by their “distribution functions” G which can be represented via a norm on function space, called D-norm. The high conformity of this setup with the multivariate case leads to the introduction of a functional domain of attraction approach for stochastic processes, which is more general than the usual one based on weak convergence. We also introduce the concept of “sojourn time transformation” and compare several types of convergence on function space. Again in complete accordance with the uni- or multivariate case it is now possible to get functional generalized Pareto distributions (GPD) W via W = 1 + log(G) in the upper tail. In particular, this enables us to derive characterizations of the functional domain of attraction condition for copula processes. Moreover, we investigate the sojourn time above a high threshold of a continuous stochastic process. It turns out that the limit, as the threshold increases, of the expected sojourn time given that it is positive, exists if the copula process corresponding to Y is in the functional domain of attraction of a max-stable process. If the process is in a certain neighborhood of a generalized Pareto process, then we can replace the constant threshold by a general threshold function and we can compute the asymptotic sojourn time distribution.
N2  - Es wird ein Zugang zur Extremwerttheorie auf dem Raum C[0,1] gegeben. Nach Charakterisierung und Analyse standard max-stabiler Prozesse, wird ein "funktionaler Anziehungsbereich" für standard max-stabile Prozesse vorgeschlagen, der allgemeiner ist als der übliche, der mittels schwacher Konvergenz definiert wird. Schließlich werden Verweildauern stetiger Prozesse über hohen Schwellenwerten betrachtet.
KW  - Extremwertstatistik
KW  - stochastischer Prozess
KW  - Extremwerttheorie
KW  - extreme value theory
KW  - stochastic processes
KW  - functional D-norm
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74405
ER  - 
TY  - JOUR
A1  - Beck, Christine
A1  - Morbach, Henner
A1  - Beer, Meinrad
A1  - Stenzel, Martin
A1  - Tappe, Dennis
A1  - Gattenlöhner, Stefan
A1  - Hofmann, Ulrich
A1  - Raab, Peter
A1  - Girschick, Hermann J.
T1  - Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment
N2  - Introduction: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and treatment have rarely been reported. Methods: Thirty-seven children diagnosed with CNO were treated with naproxen continuously for the first 6 months. If assessment at that time revealed progressive disease or no further improvement, sulfasalazine and short-term corticosteroids were added. The aims of our short-term follow-up study were to describe treatment response in detail and to identify potential risk factors for an unfavorable outcome. Results: Naproxen treatment was highly effective in general, inducing a symptom-free status in 43% of our patients after 6 months. However, four nonsteroidal anti-inflammatory drug (NSAID) partial-responders were additionally treated with sulfasalazine and short-term corticosteroids. The total number of clinical detectable lesions was significantly reduced. Mean disease activity estimated by the patient/physician and the physical aspect of health-related quality of life including functional ability (global assessment/childhood health assessment questionnaire and childhood health assessment questionnaire) and pain improved significantly. Forty-one percent of our patients showed radiological relapses, but 67% of them were clinically silent. Conclusions: Most children show a favorable clinical course in the first year of anti-inflammatory treatment with NSAIDs. Relapses and new radiological lesions can occur at any time and at any site in the skeleton but may not be clinically symptomatic. Whole-body magnetic resonance imaging proved to be very sensitive for initial and follow-up diagnostics.
KW  - Mikrobiologie
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67792
ER  - 
TY  - JOUR
A1  - Hanfstein, Benjamin
A1  - Lauseker, Michael
A1  - Hehlmann, Rüdiger
A1  - Saussele, Susanne
A1  - Erben, Philipp
A1  - Dietz, Christian
A1  - Fabarius, Alice
A1  - Proetel, Ulrike
A1  - Schnittger, Susanne
A1  - Haferlach, Claudia
A1  - Krause, Stefan W.
A1  - Schubert, Jörg
A1  - Einsele, Hermann
A1  - Hänel, Mathias
A1  - Dengler, Jolanta
A1  - Falge, Christiane
A1  - Kanz, Lothar
A1  - Neubauer, Andreas
A1  - Kneba, Michael
A1  - Stengelmann, Frank
A1  - Pfreundschuh, Michael
A1  - Waller, Cornelius F.
A1  - Spiekerman, Karsten
A1  - Baerlocher, Gabriela M.
A1  - Pfirrmann, Markus
A1  - Hasford, Joerg
A1  - Hofmann, Wolf-Karsten
A1  - Hochhaus, Andreas
A1  - Müller, Martin C.
T1  - Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib
JF  - Haematologica
N2  - The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier: 00055874)
KW  - chronic myelogenous leukemia
KW  - polymerase-chain-reaktion
KW  - hybrid messenger RNA
KW  - chronic phase
KW  - cytogenetic response
KW  - no correlation
KW  - ABL gene
KW  - transcripts
KW  - breakpoint
KW  - survival
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115476
SN  - 1592-8721
VL  - 99
IS  - 9
ER  - 
TY  - JOUR
A1  - Saussele, Susanne
A1  - Hehlmann, Ruediger
A1  - Fabarius, Alice
A1  - Jeromin, Sabine
A1  - Proetel, Ulrike
A1  - Rinaldetti, Sebastien
A1  - Kohlbrenner, Katharina
A1  - Einsele, Hermann
A1  - Falge, Christine
A1  - Kanz, Lothar
A1  - Neubauer, Andreas
A1  - Kneba, Michael
A1  - Stegelmann, Frank
A1  - Pfreundschuh, Michael
A1  - Waller, Cornelius F.
A1  - Oppliger Leibundgut, Elisabeth
A1  - Heim, Dominik
A1  - Krause, Stefan W.
A1  - Hofmann, Wolf-Karsten
A1  - Hasford, Joerg
A1  - Pfirrmann, Markus
A1  - Müller, Martin C.
A1  - Hochhaus, Andreas
A1  - Lauseker, Michael
T1  - Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
JF  - Leukemia
N2  - Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.
KW  - Chronic myeloid leukaemia
KW  - Molecularly targeted therapy
KW  - Risk factors
KW  - Risk factors
KW  - Translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227528
VL  - 32
IS  - 5
ER  - 
TY  - JOUR
A1  - Rinaldetti, Sébastien
A1  - Pfirrmann, Markus
A1  - Manz, Kirsi
A1  - Guilhot, Joelle
A1  - Dietz, Christian
A1  - Panagiotidis, Panayiotidis
A1  - Spiess, Birgit
A1  - Seifarth, Wolfgang
A1  - Fabarius, Alice
A1  - Müller, Martin
A1  - Pagoni, Maria
A1  - Dimou, Maria
A1  - Dengler, Jolanta
A1  - Waller, Cornelius F.
A1  - Brümmendorf, Tim H.
A1  - Herbst, Regina
A1  - Burchert, Andreas
A1  - Janßen, Carsten
A1  - Goebeler, Maria Elisabeth
A1  - Jost, Philipp J.
A1  - Hanzel, Stefan
A1  - Schafhausen, Philippe
A1  - Prange-Krex, Gabriele
A1  - Illmer, Thomas
A1  - Janzen, Viktor
A1  - Klausmann, Martine
A1  - Eckert, Robert
A1  - Büschel, Gerd
A1  - Kiani, Alexander
A1  - Hofmann, Wolf-Karsten
A1  - Mahon, François-Xavier
A1  - Saussele, Susanne
T1  - Effect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial
JF  - Clinical Lymphoma, Myeloma & Leukemia
N2  - Within the EURO-SKI trial, 132 chronic phase CML patients discontinued imatinib treatment. RNA was isolated from peripheral blood in order to analyze the expression of MDR1, ABCG2 and OCT1. ABCG2 was predictive for treatment-free remission in Cox regression analysis. High transcript levels of the ABCG2 efflux transporter (>4.5 parts per thousand) were associated with a twofold higher risk of relapse. Introduction: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. Materials and Methods: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated. Results: The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (parts per thousand) was retained as the only significant variable (P=.02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P=.04). Patients with an ABCG2/GUSB transcript level >4.5 parts per thousand (n=93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (<= 4.5 parts per thousand; n=39) had a 12-month TFR rate of 72% (95% CI, 55%-82%). Conclusion: In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation. (C) 2018 The Authors. Published by Elsevier Inc.
KW  - ABCG2
KW  - Biomarker
KW  - CML
KW  - Imatinib
KW  - Prediction
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226281
VL  - 18
IS  - 4
ER  - 
TY  - JOUR
A1  - Lee, Ching Hua
A1  - Sutrisno, Amanda
A1  - Hofmann, Tobias
A1  - Helbig, Tobias
A1  - Liu, Yuhan
A1  - Ang, Yee Sin
A1  - Ang, Lay Kee
A1  - Zhang, Xiao
A1  - Greiter, Martin
A1  - Thomale, Ronny
T1  - Imaging nodal knots in momentum space through topolectrical circuits
JF  - Nature Communications
N2  - Knots are intricate structures that cannot be unambiguously distinguished with any single topological invariant. Momentum space knots, in particular, have been elusive due to their requisite finely tuned long-ranged hoppings. Even if constructed, probing their intricate linkages and topological "drumhead" surface states will be challenging due to the high precision needed. In this work, we overcome these practical and technical challenges with RLC circuits, transcending existing theoretical constructions which necessarily break reciprocity, by pairing nodal knots with their mirror image partners in a fully reciprocal setting. Our nodal knot circuits can be characterized with impedance measurements that resolve their drumhead states and image their 3D nodal structure. Doing so allows for reconstruction of the Seifert surface and hence knot topological invariants like the Alexander polynomial. We illustrate our approach with large-scale simulations of various nodal knots and an experiment which maps out the topological drumhead region of a Hopf-link. Topological phases with knotted configurations in momentum space have been challenging to realize. Here, Lee et al. provide a systematic design and measurement of a three-dimensional knotted nodal structure, and resolve its momentum space drumhead states via a topolectrical RLC-type circuit.
KW  - nodal knots
KW  - topolectrical circuits
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230407
VL  - 11
ER  - 
TY  - JOUR
A1  - Traub, Jan
A1  - Grondey, Katja
A1  - Gassenmaier, Tobias
A1  - Schmitt, Dominik
A1  - Fette, Georg
A1  - Frantz, Stefan
A1  - Boivin-Jahns, Valérie
A1  - Jahns, Roland
A1  - Störk, Stefan
A1  - Stoll, Guido
A1  - Reiter, Theresa
A1  - Hofmann, Ulrich
A1  - Weber, Martin S.
A1  - Frey, Anna
T1  - Sustained increase in serum glial fibrillary acidic protein after first ST-elevation myocardial infarction
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - myocardial infarction
KW  - STEMI
KW  - glial fibrillary acidic protein
KW  - GFAP
KW  - neurofilament light chain
KW  - NfL
KW  - glial damage
KW  - cardiac magnetic resonance imaging
KW  - MRI
KW  - infarction size
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288261
SN  - 1422-0067
VL  - 23
IS  - 18
ER  - 
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  -