@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{LohrTerekhovWengetal.2019, author = {Lohr, David and Terekhov, Maxim and Weng, Andreas Max and Schroeder, Anja and Walles, Heike and Schreiber, Laura Maria}, title = {Spin echo based cardiac diffusion imaging at 7T: An ex vivo study of the porcine heart at 7T and 3T}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0213994}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201376}, pages = {e0213994}, year = {2019}, abstract = {Purpose of this work was to assess feasibility of cardiac diffusion tensor imaging (cDTI) at 7 T in a set of healthy, unfixed, porcine hearts using various parallel imaging acceleration factors and to compare SNR and derived cDTI metrics to a reference measured at 3 T. Magnetic resonance imaging was performed on 7T and 3T whole body systems using a spin echo diffusion encoding sequence with echo planar imaging readout. Five reference (b = 0 s/mm\(^2\)) images and 30 diffusion directions (b = 700 s/mm\(^2\)) were acquired at both 7 T and 3 T using a GRAPPA acceleration factor R = 1. Scans at 7 T were repeated using R = 2, R = 3, and R = 4. SNR evaluation was based on 30 reference (b = 0 s/mm\(^2\)) images of 30 slices of the left ventricle and cardiac DTI metrics were compared within AHA segmentation. The number of hearts scanned at 7 T and 3 T was n = 11. No statistically significant differences were found for evaluated helix angle, secondary eigenvector angle, fractional anisotropy and apparent diffusion coefficient at the different field strengths, given sufficiently high SNR and geometrically undistorted images. R≥3 was needed to reduce susceptibility induced geometric distortions to an acceptable amount. On average SNR in myocardium of the left ventricle was increased from 29±3 to 44±6 in the reference image (b = 0 s/mm\(^2\)) when switching from 3 T to 7 T. Our study demonstrates that high resolution, ex vivo cDTI is feasible at 7 T using commercial hardware.}, language = {en} } @article{LohrTerekhovVeitetal.2020, author = {Lohr, David and Terekhov, Maxim and Veit, Franziska and Schreiber, Laura Maria}, title = {Longitudinal assessment of tissue properties and cardiac diffusion metrics of the ex vivo porcine heart at 7 T: Impact of continuous tissue fixation using formalin}, series = {NMR in Biomedicine}, volume = {33}, journal = {NMR in Biomedicine}, number = {7}, doi = {10.1002/nbm.4298}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215536}, year = {2020}, abstract = {In this study we aimed to assess the effects of continuous formalin fixation on diffusion and relaxation metrics of the ex vivo porcine heart at 7 T. Magnetic resonance imaging was performed on eight piglet hearts using a 7 T whole body system. Hearts were measured fresh within 3 hours of cardiac arrest followed by immersion in 10\% neutral buffered formalin. T\(_{2}\)* and T\(_{2}\) were assessed using a gradient multi-echo and multi-echo spin echo sequence, respectively. A spin echo and a custom stimulated echo sequence were employed to assess diffusion time-dependent changes in metrics of cardiac diffusion tensor imaging. SNR was determined for b = 0 images. Scans were performed for 5 mm thick apical, midcavity and basal slices (in-plane resolution: 1 mm) and repeated 7, 15, 50, 100 and 200 days postfixation. Eigenvalues of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) decreased significantly (P < 0.05) following fixation. Relative to fresh hearts, FA values 7 and 200 days postfixation were 90\% and 80\%, while respective relative ADC values at those fixation stages were 78\% and 92\%. Statistical helix and sheetlet angle distributions as well as respective mean and median values showed no systematic influence of continuous formalin fixation. Similar to changes in the ADC, values for T\(_{2}\), T\(_{2}\)* and SNR dropped initially postfixation. Respective relative values compared with fresh hearts at day 7 were 64\%, 79\% and 68\%, whereas continuous fixation restored T\(_{2}\), T\(_{2}\)* and SNR leading to relative values of 74\%, 100\%, and 81\% at day 200, respectively. Relaxation parameters and diffusion metrics are significantly altered by continuous formalin fixation. The preservation of microstructure metrics following prolonged fixation is a key finding that may enable future studies of ventricular remodeling in cardiac pathologies.}, language = {en} } @phdthesis{Lohr2021, author = {Lohr, David}, title = {Functional and Structural Characterization of the Myocardium}, doi = {10.25972/OPUS-23448}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234486}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Clinical practice in CMR with respect to cardiovascular disease is currently focused on tissue characterization, and cardiac function, in particular. In recent years MRI based diffusion tensor imaging (DTI) has been shown to enable the assessment of microstructure based on the analysis of Brownian motion of water molecules in anisotropic tissue, such as the myocardium. With respect to both functional and structural imaging, 7T MRI may increase SNR, providing access to information beyond the reach of clinically applied field strengths. To date, cardiac 7T MRI is still a research modality that is only starting to develop towards clinical application. In this thesis we primarily aimed to advance methods of ultrahigh field CMR using the latest 7T technology and its application towards the functional and structural characterization of the myocardium. Regarding the assessment of myocardial microstructure at 7T, feasibility of ex vivo DTI of large animal hearts was demonstrated. In such hearts a custom sequence implemented for in vivo DTI was evaluated and fixation induced alterations of derived diffusion metrics and tissue properties were assessed. Results enable comparison of prior and future ex vivo DTI studies and provide information on measurement parameters at 7T. Translating developed methodology to preclinical studies of mouse hearts, ex vivo DTI provided highly sensitive surrogates for microstructural remodeling in response to subendocardial damage. In such cases echocardiography measurements revealed mild diastolic dysfunction and impaired longitudinal deformation, linking disease induced structural and functional alterations. Complementary DTI and echocardiography data also improved our understanding of structure-function interactions in cases of loss of contractile myofiber tracts, replacement fibrosis, and LV systolic failure. Regarding the functional characterization of the myocardium at 7T, sequence protocols were expanded towards a dedicated 7T routine protocol, encompassing accurate cardiac planning and the assessment of cardiac function via cine imaging in humans. This assessment requires segmentation of myocardial contours. For that, artificial intelligence (AI) was developed and trained, enabling rapid automatic generation of cardiac segmentation in clinical data. Using transfer learning, AI models were adapted to cine data acquired using the latest generation 7T system. Methodology for AI based segmentation was translated to cardiac pathology, where automatic segmentation of scar tissue, edema and healthy myocardium was achieved. Developed radiofrequency hardware facilitates translational studies at 7T, providing controlled conditions for future method development towards cardiac 7T MRI in humans. In this thesis the latest 7T technology, cardiac DTI, and AI were used to advance methods of ultrahigh field CMR. In the long run, obtained results contribute to diagnostic methods that may facilitate early detection and risk stratification in cardiovascular disease.}, subject = {Diffusionsgewichtete Magnetresonanztomografie}, 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} } @article{HerzStefanescuLohretal.2022, author = {Herz, Stefan and Stefanescu, Maria R. and Lohr, David and Vogel, Patrick and Kosmala, Aleksander and Terekhov, Maxim and Weng, Andreas M. and Grunz, Jan-Peter and Bley, Thorsten A. and Schreiber, Laura M.}, title = {Effects of image homogeneity on stenosis visualization at 7 T in a coronary artery phantom study: With and without B1-shimming and parallel transmission}, series = {PloS One}, volume = {17}, journal = {PloS One}, number = {6}, doi = {10.1371/journal.pone.0270689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300129}, year = {2022}, abstract = {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.}, language = {en} } @article{ElabyadTerekhovLohretal.2020, author = {Elabyad, Ibrahim A. and Terekhov, Maxim and Lohr, David and Stefanescu, Maria R. and Baltes, Steffen and Schreiber, Laura M.}, title = {A Novel Mono-surface Antisymmetric 8Tx/16Rx Coil Array for Parallel Transmit Cardiac MRI in Pigs at 7T}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-020-59949-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229436}, year = {2020}, abstract = {A novel mono-surface antisymmetric 16-element transmit/receive (Tx/Rx) coil array was designed, simulated, constructed, and tested for cardiac magnetic resonance imaging (cMRI) in pigs at 7T. The cardiac array comprised of a mono-surface 16-loops with two central elements arranged antisymmetrically and flanked by seven elements on either side. The array was configured for parallel transmit (pTx) mode to have an eight channel transmit and 16-channel receive (8Tx/16Rx) coil array. Electromagnetic (EM) simulations, bench-top measurements, phantom, and MRI experiments with two pig cadavers (68 and 46 kg) were performed. Finally, the coil was used in pilot in-vivo measurements with a 60 kg pig. Flip angle (FA), geometry factor (g-factor), signal-to-noise ratio (SNR) maps, and high-resolution cardiac images were acquired with an in-plane resolution of 0.6 mm x 0.6 mm (in-vivo) and 0.3 mm x 0.3 mm (ex-vivo). The mean g-factor over the heart was 1.26 (R = 6). Static phase B-1(+) shimming in a pig body phantom with the optimal phase vectors makes possible to improve the B-1(+) homogeneity by factor > 2 and transmit efficiency by factor > 3 compared to zero phases (before RF shimming). Parallel imaging performed in the in-vivo measurements demonstrated well preserved diagnostic quality of the resulting images at acceleration factors up to R = 6. The described hardware design can be adapted for arrays optimized for animals and humans with a larger number of elements (32-64) while maintaining good decoupling for various MRI applications at UHF (e.g., cardiac, head, and spine).}, language = {en} } @article{BeyhoffLohrThieleetal.2020, author = {Beyhoff, Niklas and Lohr, David and Thiele, Arne and Foryst-Ludwig, Anna and Klopfleisch, Robert and Schreiber, Laura M. and Kintscher, Ulrich}, title = {Myocardial Infarction After High-Dose Catecholamine Application—A Case Report From an Experimental Imaging Study}, series = {Frontiers in Cardiovascular Medicine}, volume = {7}, journal = {Frontiers in Cardiovascular Medicine}, doi = {10.3389/fcvm.2020.580296}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217959}, year = {2020}, abstract = {Although heart failure following myocardial infarction (MI) represents a major health burden, underlying microstructural and functional changes remain incompletely understood. Here, we report on a case of unexpected MI after treatment with the catecholamine isoproterenol in an experimental imaging study in mice using different state-of-the-art imaging modalities. The decline in cardiac function was documented by ultrahigh-frequency echocardiography and speckle-tracking analyses. Myocardial microstructure was studied ex vivo at a spatial resolution of 100 × 100 × 100 μm\(^{3}\) using diffusion tensor magnetic resonance imaging (DT-MRI) and histopathologic analyses. Two weeks after ISO treatment, the animal showed an apical aneurysm accompanied by reduced radial strain in corresponding segments and impaired global systolic function. DT-MRI revealed a loss of contractile fiber tracts together with a disarray of remaining fibers as corresponding microstructural correlates. This preclinical case report provides valuable insights into pathophysiology and morphologic-functional relations of heart failure following MI using emerging imaging technologies.}, language = {en} } @article{AnkenbrandLohrSchloetelburgetal.2021, author = {Ankenbrand, Markus Johannes and Lohr, David and Schl{\"o}telburg, Wiebke and Reiter, Theresa and Wech, Tobias and Schreiber, Laura Maria}, title = {Deep learning-based cardiac cine segmentation: Transfer learning application to 7T ultrahigh-field MRI}, series = {Magnetic Resonance in Medicine}, volume = {86}, journal = {Magnetic Resonance in Medicine}, number = {4}, doi = {10.1002/mrm.28822}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257604}, pages = {2179-2191}, year = {2021}, abstract = {Purpose Artificial neural networks show promising performance in automatic segmentation of cardiac MRI. However, training requires large amounts of annotated data and generalization to different vendors, field strengths, sequence parameters, and pathologies is limited. Transfer learning addresses this challenge, but specific recommendations regarding type and amount of data required is lacking. In this study, we assess data requirements for transfer learning to experimental cardiac MRI at 7T where the segmentation task can be challenging. In addition, we provide guidelines, tools, and annotated data to enable transfer learning approaches by other researchers and clinicians. Methods A publicly available segmentation model was used to annotate a publicly available data set. This labeled data set was subsequently used to train a neural network for segmentation of left ventricle and myocardium in cardiac cine MRI. The network is used as starting point for transfer learning to 7T cine data of healthy volunteers (n = 22; 7873 images) by updating the pre-trained weights. Structured and random data subsets of different sizes were used to systematically assess data requirements for successful transfer learning. Results Inconsistencies in the publically available data set were corrected, labels created, and a neural network trained. On 7T cardiac cine images the model pre-trained on public imaging data, acquired at 1.5T and 3T, achieved DICE\(_{LV}\) = 0.835 and DICE\(_{MY}\) = 0.670. Transfer learning using 7T cine data and ImageNet weight initialization improved model performance to DICE\(_{LV}\) = 0.900 and DICE\(_{MY}\) = 0.791. Using only end-systolic and end-diastolic images reduced training data by 90\%, with no negative impact on segmentation performance (DICE\(_{LV}\) = 0.908, DICE\(_{MY}\) = 0.805). Conclusions This work demonstrates and quantifies the benefits of transfer learning for cardiac cine image segmentation. We provide practical guidelines for researchers planning transfer learning projects in cardiac MRI and make data, models, and code publicly available.}, language = {en} } @article{AnkenbrandShainbergHocketal.2021, author = {Ankenbrand, Markus J. and Shainberg, Liliia and Hock, Michael and Lohr, David and Schreiber, Laura M.}, title = {Sensitivity analysis for interpretation of machine learning based segmentation models in cardiac MRI}, series = {BMC Medical Imaging}, volume = {21}, journal = {BMC Medical Imaging}, number = {1}, doi = {10.1186/s12880-021-00551-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259169}, pages = {27}, year = {2021}, abstract = {Background Image segmentation is a common task in medical imaging e.g., for volumetry analysis in cardiac MRI. Artificial neural networks are used to automate this task with performance similar to manual operators. However, this performance is only achieved in the narrow tasks networks are trained on. Performance drops dramatically when data characteristics differ from the training set properties. Moreover, neural networks are commonly considered black boxes, because it is hard to understand how they make decisions and why they fail. Therefore, it is also hard to predict whether they will generalize and work well with new data. Here we present a generic method for segmentation model interpretation. Sensitivity analysis is an approach where model input is modified in a controlled manner and the effect of these modifications on the model output is evaluated. This method yields insights into the sensitivity of the model to these alterations and therefore to the importance of certain features on segmentation performance. Results We present an open-source Python library (misas), that facilitates the use of sensitivity analysis with arbitrary data and models. We show that this method is a suitable approach to answer practical questions regarding use and functionality of segmentation models. We demonstrate this in two case studies on cardiac magnetic resonance imaging. The first case study explores the suitability of a published network for use on a public dataset the network has not been trained on. The second case study demonstrates how sensitivity analysis can be used to evaluate the robustness of a newly trained model. Conclusions Sensitivity analysis is a useful tool for deep learning developers as well as users such as clinicians. It extends their toolbox, enabling and improving interpretability of segmentation models. Enhancing our understanding of neural networks through sensitivity analysis also assists in decision making. Although demonstrated only on cardiac magnetic resonance images this approach and software are much more broadly applicable.}, language = {en} }