TY - THES A1 - Herz, Stefan T1 - Dynamische Veränderungen der Homing-Rezeptor-Expression humaner T-Zellen im peripheren Blut T1 - The dynamics of surface marker expression on human peripheral blood T cells N2 - Dieses Projekt soll zur Entwicklung eines Bluttests beitragen, um bei allogen stammzelltransplantierten (allo-SZT) Patienten eine drohende akute Graft-versus-Host Disease (aGVHD) vorhersagen und von einer Infektionskomplikation unterscheiden zu können. Die aGVHD und opportunistische Infektionen, wie etwa eine Zytomegalievirus- Infektion, stellen die Hauptrisiken der allo-SZT dar. Eine durch einen prädiktiven Test verbesserte Vorhersage bzw. Differenzierung dieser beiden schweren omplikationen könnte zu einem breiteren Einsatz der allo-SZT führen. Eine Reihe von Erkenntnissen lassen die Vermutung zu, dass bestimmte Homing- Rezeptoren auf T-Zellen im peripheren Blut als Marker zur Vorhersage und Differenzierung zwischen einer aGVHD und Infektionskomplikationen dienen könnten. So wurde in Mausmodellen gezeigt, dass die Pathogenese der aGVHD ein streng zeitlich regulierter und organspezifischer Immunprozess ist. Alloreaktive T-Zellen müssen bestimmte Homing-Rezeptoren exprimieren, um in die Zielorgane der aGVHD (Gastrointestinaltrakt, Leber und Haut) einwandern zu können. Die Immunreaktion auf eine Infektion setzt ebenfalls voraus, dass in der adaptiven Immunantwort T-Zellen organ- und entzündungsspezifische Homing-Rezeptoren exprimieren. Eine zentrale Voraussetzung für einen prospektiven klinischen Test mit allo-SZT Patienten ist die Kenntnis der physiologischen Bandbreite der Oberflächenmarker auf T-Lymphozyten in Gesunden, um diese von pathophysiologischen Veränderungen unterscheiden zu können. Ziel dieser Arbeit war es daher, eine effiziente und zuverlässige Methode zu entwickeln, um das Homing-Rezeptor-Profil von humanen T-Zellen im peripheren Blut analysieren zu können. Dazu wurde ein urchflusszytometrie-Test mit 25 Oberflächenmarkern etabliert, die eine Rolle in der Pathogenese der aGVHD und bei Infektionen spielen könnten. Mit diesem Test wurde die Expression der Oberflächenmarker von 21 gesunden Probanden an 8 Zeitpunkten über einen Zeitraum von 3 Wochen analysiert. Die untersuchten Oberflächenmarker lassen sich dabei entsprechend ihrer Expressionsmuster in drei Kategorien einteilen, nämlich (I) zeitlich stabile niedrige, (II) zeitlich stabile hohe und (III) dynamisch schwankende Expression. Aufbauend auf diesen Ergebnissen für gesunde Probanden wurde am Universitätsklinikum Würzburg eine prospektive klinische Studie an aGVHD-Patienten begonnen. N2 - This project contributes to the development of a blood test to predict acute graft-versus- host disease (aGvHD) and to differentiate it from infectious complications in allogeneic hematopoietic cell transplantation (allo-HCT). aGvHD and opportunistic infections like Cytomegalovirus infections are major risks of allo-HCT. Such a predictive test could bring a major improvement in the prevention and treatment of aGvHD. The basic idea of this test is that certain homing receptors on peripheral blood T cells could serve as markers to predict and to differentiate between aGvHD and opportunistic infections. This is supported by several empirical findings. It has been recently demonstrated in murine in vivo imaging models that aGvHD pathogenesis is an organ specific process that is tightly regulated in time. Alloreactive T cells express certain homing receptors in order to reach the aGvHD target organs (intestinal tract, liver and skin). Also the immune response to an infection requires the expression of specific homing receptors on T cells. For a prospective clinical test with allo-HCT patients it is important to establish the physiological ranges of T cell surface markers of healthy individuals, to distinguish them from pathological changes. This project intends to establish an efficient and reliable method to analyze the homing receptor profile of human peripheral blood T cells. A multiplex flow cytometry test for cytotoxic and T helper cell subsets was developed to analyze the expression of 25 activation markers, organ specific homing receptors and inflammatory response receptors on human peripheral blood T cells that are likely to play a role in the pathogenesis of aGvHD and infections. With this test the surface marker profile of 21 healthy individuals was analyzed. The peripheral blood mononuclear cells were examined by flow cytometry at 8 points in time within 3 weeks. Preliminary mouse experiments in our group suggested these points in time as critical for subsequent prospective clinical studies. We found that the surface marker expression on peripheral blood cytotoxic and T helper cells in healthy probands can be subdivided into 3 categories: (I) constant low expression, (II) constant high expression and (III) T cell subsets that dynamically change the expression. These findings for healthy probands form the basis for a recently initiated clinical prospective study with allo-HCT patients at the University Hospital Würzburg. KW - T-Lymphozyt KW - graftversushostdisease KW - Homing-Rezeptor KW - Oberflächenmarker KW - Durchflusszytometrie KW - Graft-versus-Host-Disease Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-93907 ER - TY - JOUR A1 - Herz, Stefan A1 - Stefanescu, Maria R. A1 - Lohr, David A1 - Vogel, Patrick A1 - Kosmala, Aleksander A1 - Terekhov, Maxim A1 - Weng, Andreas M. A1 - Grunz, Jan-Peter A1 - Bley, Thorsten A. A1 - Schreiber, Laura M. T1 - Effects of image homogeneity on stenosis visualization at 7 T in a coronary artery phantom study: With and without B1-shimming and parallel transmission JF - PloS One N2 - Background To investigate the effects of B\(_1\)-shimming and radiofrequency (RF) parallel transmission (pTX) on the visualization and quantification of the degree of stenosis in a coronary artery phantom using 7 Tesla (7 T) magnetic resonance imaging (MRI). Methods Stenosis phantoms with different grades of stenosis (0%, 20%, 40%, 60%, 80%, and 100%; 5 mm inner vessel diameter) were produced using 3D printing (clear resin). Phantoms were imaged with four different concentrations of diluted Gd-DOTA representing established arterial concentrations after intravenous injection in humans. Samples were centrally positioned in a thorax phantom of 30 cm diameter filled with a custom-made liquid featuring dielectric properties of muscle tissue. MRI was performed on a 7 T whole-body system. 2D-gradient-echo sequences were acquired with an 8-channel transmit 16-channel receive (8 Tx / 16 Rx) cardiac array prototype coil with and without pTX mode. Measurements were compared to those obtained with identical scan parameters using a commercially available 1 Tx / 16 Rx single transmit coil (sTX). To assess reproducibility, measurements (n = 15) were repeated at different horizontal angles with respect to the B0-field. Results B\(_1\)-shimming and pTX markedly improved flip angle homogeneity across the thorax phantom yielding a distinctly increased signal-to-noise ratio (SNR) averaged over a whole slice relative to non-manipulated RF fields. Images without B\(_1\)-shimming showed shading artifacts due to local B\(_1\)\(^+\)-field inhomogeneities, which hampered stenosis quantification in severe cases. In contrast, B\(_1\)-shimming and pTX provided superior image homogeneity. Compared with a conventional sTX coil higher grade stenoses (60% and 80%) were graded significantly (p<0.01) more precise. Mild to moderate grade stenoses did not show significant differences. Overall, SNR was distinctly higher with B\(_1\)-shimming and pTX than with the conventional sTX coil (inside the stenosis phantoms 14%, outside the phantoms 32%). Both full and half concentration (10.2 mM and 5.1 mM) of a conventional Gd-DOTA dose for humans were equally suitable for stenosis evaluation in this phantom study. Conclusions B\(_1\)-shimming and pTX at 7 T can distinctly improve image homogeneity and therefore provide considerably more accurate MR image analysis, which is beneficial for imaging of small vessel structures. KW - stenosis KW - magnetic resonance imaging KW - thorax KW - in vivo imaging KW - coronary arteries KW - image processing KW - 3D printing KW - signal to noise ratio Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300129 VL - 17 IS - 6 ER - TY - JOUR A1 - Reichel, Thomas A1 - Herz, Stefan A1 - el Tabbakh, Mohammed A1 - Bley, Thorsten Alexander A1 - Plumhoff, Piet A1 - Rueckl, Kilian T1 - Less than 9.5-mm coracohumeral distance on axial magnetic resonance imaging scans predicts for subscapularis tear JF - JSES International N2 - Background Diagnosis of subscapularis (SSC) tendon lesions on magnetic resonance imaging (MRI) can be challenging. A small coracohumeral distance (CHD) has been associated with SSC tears. This study was designed to define a specific threshold value for CHD to predict SSC tears on axial MRI scans. Methods This retrospective study included 172 shoulders of 168 patients who underwent arthroscopic surgery for rotator cuff tear or glenohumeral instability. Diagnostic arthroscopy confirmed an SSC tear in 62 cases (36.0%, test group a), rotator cuff tear tears other than SSC in 71 cases (41.3%, control group b) and glenohumeral instability without any rotator cuff tear in 39 cases (22.7%, zero-sample group c). All patients had a preoperative MRI of the shoulder (1.5T or 3T). Minimum CHD was measured on axial fat-suppressed proton density-, T2-, or T1-weigthed sequences. Receiver operating characteristics analysis was used to determine the threshold value for CHD, and sensitivity and specificity were calculated. Results CHD measurement had a good interobserver reliability (Intraclass correlation coefficient 0.799). Mean CHD was highly significantly (P < .001) less for test group a (mean 7.3 mm, standard deviation ± 2.2) compared with control group b (mean 11.1 mm, standard deviation ± 2.3) or zero-sample group c (mean 13.6 mm, standard deviation ± 2.9). A threshold value of CHD <9.5 mm had a sensitivity of 83.6% and a specificity of 83.9% to predict SSC tears. Conclusion A CHD <9.5 mm on MRI is predictive of SSC lesions and a valuable tool to diagnose SSC tears. KW - subscapularis tear KW - coracohumeral distance KW - rotator cuff tear KW - coracohumeral impingement Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259118 VL - 5 IS - 3 ER - TY - JOUR A1 - Hock, Michael A1 - Terekhov, Maxim A1 - Stefanescu, Maria Roxana A1 - Lohr, David A1 - Herz, Stefan A1 - Reiter, Theresa A1 - Ankenbrand, Markus A1 - Kosmala, Aleksander A1 - Gassenmaier, Tobias A1 - Juchem, Christoph A1 - Schreiber, Laura Maria T1 - B\(_{0}\) shimming of the human heart at 7T JF - Magnetic Resonance in Medicine N2 - 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. KW - 7 T KW - B KW - cardiac MRI KW - shimming KW - ultrahigh field Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218096 VL - 85 IS - 1 SP - 182 EP - 196 ER - TY - JOUR A1 - Grunz, Jan-Peter A1 - Wenig, Andreas Max A1 - Kunz, Andreas Steven A1 - Veyhl-Wichmann, Maike A1 - Schmitt, Rainer A1 - Gietzen, Carsten Herbert A1 - Pennig, Lenhard A1 - Herz, Stefan A1 - Ergün, Süleyman A1 - Bley, Thorsten Alexander A1 - Gassenmaier, Tobias T1 - 3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT JF - European Radiology Experimental N2 - Background Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows. Methods A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDI\(_{vol(16 cm)}\)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDI\(_{vol(16 cm)}\) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used. Results The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100% of the cases by both readers for RD CBCT, 100% (R1) and 93.8% (R2) for LD CBCT, 62.6% and 43.8% for RD MDCT, and 0.0% and 0.0% for LD MDCT. Single-measure ICC was 0.95 (95% confidence interval 0.91–0.97; p < 0.001). Software-based assessment supported subjective findings with less “undecided” pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT. Conclusions In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction. KW - Cancellous bone KW - Cone-beam computed tomography KW - Elbow KW - Elbow joint KW - Multidetector computed tomography Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229877 VL - 4 ER - TY - JOUR A1 - Vogel, Patrick A1 - Markert, Jonathan A1 - Rückert, Martin A. A1 - Herz, Stefan A1 - Keßler, Benedikt A1 - Dremel, Kilian A1 - Althoff, Daniel A1 - Weber, Matthias A1 - Buzug, Thorsten M. A1 - Bley, Thorsten A. A1 - Kullmann, Walter H. A1 - Hanke, Randolf A1 - Zabler, Simon A1 - Behr, Volker C. T1 - Magnetic Particle Imaging meets computed tomography: first simultaneous imaging JF - Scientific Reports N2 - Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented. KW - Applied physics KW - Biomedical engineering KW - Imaging techniques Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202501 VL - 9 ER - TY - JOUR A1 - Herold, Volker A1 - Herz, Stefan A1 - Winter, Patrick A1 - Gutjahr, Fabian Tobias A1 - Andelovic, Kristina A1 - Bauer, Wolfgang Rudolf A1 - Jakob, Peter Michael T1 - Assessment of local pulse wave velocity distribution in mice using k-t BLAST PC-CMR with semi-automatic area segmentation. JF - Journal of Cardiovascular Magnetic Resonance N2 - Background: Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities. Methods: In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE\(^{(-/-)}\)-mice) at 12 adjacent locations along the abdominal aorta. Results: Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE\(^{(-/-)}\)-group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE \(^{(-/-)}\)-animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis. Conclusion: In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE\(^{(-/-)}\)-mice as a relevant model of atherosclerosis. KW - pulse wave velocity KW - ApoE\(^{(-/-)}\) KW - magnetic resonance imaging KW - phase contrast Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157696 VL - 19 IS - 77 ER -