@article{GottschalkRichterZiegleretal.2019, author = {Gottschalk, Michael G. and Richter, Jan and Ziegler, Christiane and Schiele, Miriam A. and Mann, Julia and Geiger, Maximilian J. and Schartner, Christoph and Homola, Gy{\"o}rgy A. and Alpers, Georg W. and B{\"u}chel, Christian and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Gloster, Andrew T. and Helbig-Lang, Sylvia and Kalisch, Raffael and Kircher, Tilo and Lang, Thomas and Lonsdorf, Tina B. and Pan{\´e}-Farr{\´e}, Christiane A. and Str{\"o}hle, Andreas and Weber, Heike and Zwanzger, Peter and Arolt, Volker and Romanos, Marcel and Wittchen, Hans-Ulrich and Hamm, Alfons and Pauli, Paul and Reif, Andreas and Deckert, J{\"u}rgen and Neufang, Susanne and H{\"o}fler, Michael and Domschke, Katharina}, title = {Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-019-0415-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227479}, year = {2019}, abstract = {Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.}, language = {en} } @article{PotreckMutkeWeylandetal.2021, author = {Potreck, Arne and Mutke, Matthias A. and Weyland, Charlotte S. and Pfaff, Johannes A. R. and Ringleb, Peter A. and Mundiyanapurath, Sibu and M{\"o}hlenbruch, Markus A. and Heiland, Sabine and Pham, Mirko and Bendszus, Martin and Hoffmann, Angelika}, title = {Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy}, series = {Translational Stroke Research}, volume = {12}, journal = {Translational Stroke Research}, number = {5}, issn = {1868-4483}, doi = {10.1007/s12975-020-00885-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308946}, pages = {799-807}, year = {2021}, abstract = {Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41-1.4) min-1 and was found in all 7 cases of hypoperfusion (100\%), in 10 of 16 cases of hyperperfusion (63\%), and in only three of 13 cases with unaffected perfusion (23\%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56-0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10-0.82]) compared to hyperperfusion (PPV = 0.93 [0.68-1.0]) or unaffected perfusion (PPV = 1.0 [0.75-1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.}, language = {en} } @article{AdolphFleischhackGaabetal.2021, author = {Adolph, Jonas E. and Fleischhack, Gudrun and Gaab, Christine and Mikasch, Ruth and Mynarek, Martin and Rutkowski, Stefan and Sch{\"u}ller, Ulrich and Pfister, Stefan M. and Pajtler, Kristian W. and Milde, Till and Witt, Olaf and Bison, Brigitte and Warmuth-Metz, Monika and Kortmann, Rolf-Dieter and Dietzsch, Stefan and Pietsch, Torsten and Timmermann, Beate and Tippelt, Stephan}, title = {Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies}, series = {Journal of Neuro-Oncology}, volume = {155}, journal = {Journal of Neuro-Oncology}, number = {2}, organization = {German GPOH HIT-Network}, issn = {0167-594X}, doi = {10.1007/s11060-021-03867-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308302}, pages = {193-202}, year = {2021}, abstract = {Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0-13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3-20.0) and 36.9 months (CI 29.7-53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74-1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50\%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.}, language = {en} } @article{GoepfertTraubSelletal.2023, author = {G{\"o}pfert, Dennis and Traub, Jan and Sell, Roxane and Homola, Gy{\"o}rgy A. and Vogt, Marius and Pham, Mirko and Frantz, Stefan and St{\"o}rk, Stefan and Stoll, Guido and Frey, Anna}, title = {Profiles of cognitive impairment in chronic heart failure—A cluster analytic approach}, series = {Frontiers in Human Neuroscience}, volume = {17}, journal = {Frontiers in Human Neuroscience}, doi = {10.3389/fnhum.2023.1126553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313429}, year = {2023}, abstract = {Background Cognitive impairment is a major comorbidity in patients with chronic heart failure (HF) with a wide range of phenotypes. In this study, we aimed to identify and compare different clusters of cognitive deficits. Methods The prospective cohort study "Cognition.Matters-HF" recruited 147 chronic HF patients (aged 64.5 ± 10.8 years; 16.2\% female) of any etiology. All patients underwent extensive neuropsychological testing. We performed a hierarchical cluster analysis of the cognitive domains, such as intensity of attention, visual/verbal memory, and executive function. Generated clusters were compared exploratively with respect to the results of cardiological, neurological, and neuroradiological examinations without correction for multiple testing. Results Dendrogram and the scree plot suggested three distinct cognitive profiles: In the first cluster, 42 patients (28.6\%) performed without any deficits in all domains. Exclusively, the intensity of attention deficits was seen in the second cluster, including 55 patients (37.4\%). A third cluster with 50 patients (34.0\%) was characterized by deficits in all cognitive domains. Age (p = 0.163) and typical clinical markers of chronic HF, such as ejection fraction (p = 0.222), 6-min walking test distance (p = 0.138), NT-proBNP (p = 0.364), and New York Heart Association class (p = 0.868) did not differ between clusters. However, we observed that women (p = 0.012) and patients with previous cardiac valve surgery (p = 0.005) prevailed in the "global deficits" cluster and the "no deficits" group had a lower prevalence of underlying arterial hypertension (p = 0.029). Total brain volume (p = 0.017) was smaller in the global deficit cluster, and serum levels of glial fibrillary acidic protein were increased (p = 0.048). Conclusion Apart from cognitively healthy and globally impaired HF patients, we identified a group with deficits only in the intensity of attention. Women and patients with previous cardiac valve surgery are at risk for global cognitive impairment when suffering HF and could benefit from special multimodal treatment addressing the psychosocial condition.}, language = {en} } @article{LehriederZapantisPhametal.2023, author = {Lehrieder, Dominik and Zapantis, Nikolaos and Pham, Mirko and Schuhmann, Michael Klaus and Haarmann, Axel}, title = {Treating seronegative neuromyelitis optica spectrum disorder with inebilizumab: a case report}, series = {Frontiers in Neurology}, volume = {14}, journal = {Frontiers in Neurology}, doi = {10.3389/fneur.2023.1297341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-354031}, year = {2023}, abstract = {Background Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively. Case presentation We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab. Conclusion Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive.}, language = {en} } @article{StebaniBlaimerZableretal.2023, author = {Stebani, Jannik and Blaimer, Martin and Zabler, Simon and Neun, Tilmann and Pelt, Dani{\"e}l M. and Rak, Kristen}, title = {Towards fully automated inner ear analysis with deep-learning-based joint segmentation and landmark detection framework}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-45466-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357411}, year = {2023}, abstract = {Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.}, language = {en} } @article{VogelRueckertGreineretal.2023, author = {Vogel, P. and R{\"u}ckert, M. A. and Greiner, C. and G{\"u}nther, J. and Reichl, T. and Kampf, T. and Bley, T. A. and Behr, V. C. and Herz, S.}, title = {iMPI: portable human-sized magnetic particle imaging scanner for real-time endovascular interventions}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-37351-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357794}, year = {2023}, abstract = {Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model.}, language = {en} } @phdthesis{Feick2024, author = {Feick, J{\"o}rn}, title = {Relevanz lokaler Blutgasparameter innerhalb des zerebralen Kollateralkreislaufs w{\"a}hrend akuter zerebraler Isch{\"a}mie}, doi = {10.25972/OPUS-35167}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351678}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {St{\"o}rungen der Ionen- und Blutgas Hom{\"o}ostase mit Verschiebungen von Na+ und K+ in der regionalen Hypoxie sind ein Kennzeichen der experimentellen zerebralen Isch{\"a}mie, wurden aber in ihrer Bedeutung f{\"u}r Schlaganfallpatienten noch nicht hinreichend untersucht. Wir berichten {\"u}ber eine prospektive, humane Querschnittsstudie an 366 Schlaganfallpatienten, die mit einer endovaskul{\"a}ren Rekanalisation bei einem akuten LVO der vorderen Zirkulation zwischen dem 18.Dezember 2018 und dem 31.August 2020 behandelt wurden. Im Rahmen der vorliegenden Dissertationsarbeit wurden intraprozedural arterielle Blutgasproben (1ml) aus dem lokal isch{\"a}mischen Kollateralkreislauf und der intraindividuellen systemischen Referenzlokalisation in 51 Patienten gewonnen. Die Probengewinnung mit Hilfe eines Mikrokatheters erfolgte nach einem bereits ver{\"o}ffentlichten Protokoll. Diese Arbeit weist in der Perakutphase eines Großgef{\"a}ßverschlusses signifikant nach, dass der lokal isch{\"a}mische paO2 (-4,29\%, paO2isch{\"a}misch=185,3 mmHg vs. paO2systemisch=193,6mmHg; p=0,035) und die Konzentration von K+ (-5,49\%, K+isch{\"a}misch=3,44mmol/L vs. K+systemisch=3,64mmol/L; p=0,0081) signifikant reduziert war. Wir beobachteten, dass der Na+:K+-Quotient in der Kollateralzirkulation (+3,29\%; Na+:K+-Quotientisch{\"a}misch=41,74 vs. Na+:K+-Quotientsystemisch=40,38; p=0,0048) im Vergleich zur systemischen Zirkulation signifikant erh{\"o}ht war, w{\"a}hrend die Na+-Konzentration signifikant positiv mit einer Zunahme des Infarktausmaßes assoziiert war (r=0,42, p=0,0033). Wir fanden eine alkaline Tendenz des zerebralen pH (+0,14\%, pHisch{\"a}misch=7,38 vs. pHsystemisch=7,37, p=0,0019), mit einer zeitabh{\"a}ngigen Verschiebung in den azidotischen Bereich (r=-0,36, p=0,0549). Schlussfolgernd deuten unsere Ergebnisse darauf hin, dass die durch den Schlaganfall verursachten Ver{\"a}nderungen der zerebralen Sauerstoffversorgung, der Ionenzusammensetzung und des S{\"a}ure-Basen-Gleichgewichts dynamisch auftreten, w{\"a}hrend der okklusiven Isch{\"a}mie fortschreiten und mit der akuten Gewebesch{\"a}digung im Zusammenhang stehen. W{\"u}nschenswert sind weitere prospektive Studien, um die Ergebnisse valide zu reproduzieren.}, subject = {Schlaganfall}, language = {de} } @phdthesis{Krumma2024, author = {Krumma, Judith Josefine Birgitta}, title = {Morphologie und bildgebende Ver{\"a}nderung in der Magnetresonanztomographie bei p{\"a}diatrischen Patienten/innen mit Rezidiven eines kranialen Ependymoms - Kohorte der Deutschen HIT- REZ Studie}, doi = {10.25972/OPUS-35149}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351498}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {In dieser Arbeit wurde einerseits retrospektiv untersucht, wie sich supratentorielle und infratentorielle Ependymome bildmorphologisch unterscheiden, ob Lokalrezidive eines Ependymoms dessen Bildeigenschaften teilen und welche Art von Rezidiven im Verlauf auftreten k{\"o}nnen. Die von uns beschriebenen Bildcharakteristika der Ependymome decken sich zum gr{\"o}ßten Teil mit bereits ver{\"o}ffentlichten Studien. Supratentorielle Ependymome unterscheiden sich signifikant in ihrer Bildmorphologie im Vergleich zu Ependymome der hintern Sch{\"a}delgrube. Alle p{\"a}diatrischen Ependymompatienten/innen in unserem Kollektiv erkrankten an mindestens einem Rezidiv. Am h{\"a}ufigsten traten Lokalrezidive gefolgt von Meningeosen im ersten Rezidiv auf. Seltener fanden sich transiente postradiogene L{\"a}sionen, Diffuse intrinsische Ponsgliome und extraneurale Metastasen. Der bildmorphologische Vergleich, Primarius versus Lokalrezidiv ergab {\"u}berwiegend {\"a}hnliche bildgebende Eigenschaften vor allem im Signalverhalten, Tumorbegrenzung und KM-Aufnahme sowie KM anreichernder Tumoranteil. Die kranielle Meningeose pr{\"a}sentierte sich zum ersten Rezidivzeitpunkt different zum Prim{\"a}rtumor. Die extraneuralen Metastasen hatten bildcharakteristisch {\"A}hnlichkeiten zum Prim{\"a}rtumor. Bei der Bewertung neuer intraparenchymaler L{\"a}sionen sollte immer der zeitliche Zusammenhang zur letzten Therapie und damit m{\"o}gliche vor{\"u}bergehende postradiologischen Ver{\"a}nderungen ber{\"u}cksichtigt werden. Letztlich ist das p{\"a}diatrische Ependymom und Ependymomrezidiv ein komplexes und immer noch unvollst{\"a}ndiges erfasstes Krankheitsbild. Durch umfangreichere Studien und die Zusammenf{\"u}hrung dieser Ergebnisse k{\"o}nnte schlussendlich die Komplexit{\"a}t des Krankheitsbildes und somit die Therapieoptionen verbessert werden. Durch unsere Studie gelang einerseits die Beschreibung und der Vergleich des prim{\"a}ren Ependymoms bez{\"u}glich supra- und infratentorieller Lokalisation und andererseits gelang eine neuroradiologische Beschreibung von Ependymomrezidiven im Vergleich zum prim{\"a}ren Ependymom, wodurch in Zukunft die Nachsorge der Ependymomrezidive und die Therapieoptionen optimiert werden k{\"o}nnten.}, subject = {Ependymom}, language = {de} } @article{Solymosi2022, author = {Solymosi, L{\´a}szl{\´o}}, title = {Clinical Neuroradiology: challenges and perspectives}, series = {Clinical Neuroradiology}, volume = {32}, journal = {Clinical Neuroradiology}, number = {3}, doi = {10.1007/s00062-022-01208-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324537}, pages = {601-602}, year = {2022}, abstract = {No abstract available.}, language = {en} }