Quantitative Gewebecharakterisierung mittels mechanischer Kenngrößen in präklinischen Kleintiermodellen

The biomechanical properties of the brain play an important role in vital functioning and disease development. Over the last decade, cerebral magnetic resonance elastography (MRE) has emerged as a valuable imaging technique, revealing important characteristics of tissue biomechanics in disease and health. However, state-of-the-art mouse brain MRE is limited by time-consuming multi-shot acquisition techniques and noise-sensitive single-frequency image reconstruction methods. Therefore, the purpose of this PhD project was the development of multifrequency mouse brain MRE based on a single-shot acquisition technique and noise-robust tomoelastography post-processing for high-resolution stiffness mapping. The feasibility of the method was demonstrated using three in vivo studies. In the first study, shear wave speed (SWS) as a surrogate of stiffness in different areas of the brain was measured. In the second study, the effect of body temperature on biophysical parameters of murine brain tissue was investigated in the normothermic to hypothermic range. Tomoelastography was combined with arterial spin labelling and diffusion-weighted imaging in order to determine the relationship between tissue stiffness, perfusion and diffusion. In the third study, mechanical brain alterations were continuously monitored during the critical phase of death in a mouse model of hypoxia. In ten animals, we quantified regional dependent SWS of 2.9 ± 0.2 m/s, 4.9 ± 0.5 m/s, 4.8 ± 0.8 m/s and 3.5 ± 0.3 m/s for the corpus callosum, hippocampus, diencephalon and cortex. In a group of six animals, we found that SWS decreased from hypothermia (28 ± 0.5 °C) to normothermia (38 ± 0.5 °C) by 6.2%, 10.1% and 7.4% in the whole brain, cortex and hippocampus, respectively. These SWS decreases were correlated with changes in water diffusion (30% increase) and blood perfusion (60% to 90% increase). Furthermore, in fourteen animals, brain death led to a 6% increase of SWS in the whole brain and 9% in the hippocampus when compared to in vivo values. Our novel multifrequency MRE method with tomoelastography processing provides mouse brain stiffness maps within shorter scan times and with greater detail resolution than a conventional MRE. Short scan times, in the order of only 40 seconds, open new horizons for continuous stiffness monitoring during different pathological processes in vivo. Clinical relevant biophysical processes in the brain, such as hypothermia and hypoxia, and the critical phase of brain death were monitored and investigated for the first time. The results show that stiffness varies across sub-regions in the murine brain, is inversely correlated with water diffusion and blood perfusion, and increases in hypoxia towards brain death. The new method contributes to the growing understanding of mechanical signatures of brain tissues and is potentially of great value for future studies of in vivo brain mechanical properties in health and disease.Die biomechanischen Eigenschaften von zerebralem Gewebe beeinflussen zahlreiche physiologische Prozesse im Gehirn. Die zerebrale Magnetresonanz-Elastographie (MRE) erwies sich dabei innerhalb des letzten Jahrzehnts als wertvolles nicht-invasives Bildgebungsverfahren und offenbarte wichtige biomechanische Merkmale im gesunden als auch kranken Gewebe. Die moderne MRE des Maushirns ist jedoch durch zeitaufwändige Multi-Shot-Bildaufnahemetechniken und rauschempfindliche monofrequente Bildrekonstruktionsmethoden begrenzt. Das Ziel dieser Promotion war die Entwicklung eines hochauflösenden Elastographie-Verfahrens mittels multifrequenter Maushirn-MRE auf der Grundlage von Einzelbildaufnahmetechniken und anschließender Tomoelastographie-Postprozessierung zur Minderung der Rauschempfindlichkeit. Die Durchführbarkeit der Methode wurde mit drei in-vivo-Studien nachgewiesen. In der ersten Studie wurden verschiedene Bereiche des Gehirns bezüglich der Scherwellengeschwindigkeit (SWS) als Surrogat der Steifigkeit vermessen. Die zweite Studie untersuchte den Einfluss der Körpertemperatur auf biophysikalische Parameter des murinen Hirngewebes im normothermen bis hypothermen Bereich. Die Tomoelastographie wurde mit arterieller Spin-Markierung und diffusionsgewichteter Bildgebung kombiniert, um mögliche Zusammenhänge zwischen Gewebesteifigkeit, Perfusion und Diffusion zu analysieren. Im Rahmen der dritten Studie wurden anhand eines hypoxischen Mausmodells die biomechanischen Veränderungen des Gehirns während der kritischen Phase des Todes kontinuierlich aufgenommen und überwacht. Für zehn Tiere wurden lokale SWS von 2,9 ± 0,2 m/s für das Corpus callosum, 4,9 ± 0,5 m/s für den Hippocampus, 4,8 ± 0,8 m/s für das Zwischenhirn und 3,5 ± 0,3 m/s für den Cortex cerebri quantifiziert. Anhand von sechs vermessenen Tieren konnte im gesamten Gehirn, Kortex und Hippocampus eine Abnahme der SWS von Hypo- (28 ± 0.5 °C) zu Normothermie (38 ± 0.5 °C) jeweils um 6,2%, 10,1% bzw. 7,4% festgestellt werden. Diese Abnahme der SWS korrelierte mit Veränderungen der Wasserdiffusion (30% Zunahme) und der Perfusion (60% bis 90% Zunahme). Darüber hinaus führte der Hirntod bei vierzehn Tieren zu einem Anstieg der SWS um 6% im gesamten Gehirn und 9% im Hippocampus gegenüber den in-vivo-Werten. Das implementierte neuartige Multifrequenz-MRE-Verfahren liefert innerhalb stark verkürzter Messzeiten Steifigkeitskarten vom Maushirn mit größerer Detailauflösung als bisherige MRE Methoden. Erstmals konnten somit klinisch relevante biophysikalische Prozesse im Gehirn wie die Hypothermie, die Hypoxie und die kritische Phase des Hirntodes beobachtet und untersucht werden. Die Ergebnisse zeigen, dass die Steifigkeit in den verschiedenen Subregionen des Gehirns der Maus variiert, mit der Wasserdiffusion und der Perfusion invers korreliert und durch Hypoxie im Rahmen des Hirntodes zunimmt. Die neuen Entwicklungen tragen zum wachsenden Verständnis der biomechanischen Eigenschaften des Hirngewebes bei

Assessing the rates of channel shifts, bend development and bank erosion hazard on the Sajó River (Hungary) by aerial and terrestrial photogrammetry

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UAS photogrammetry and object-based image analysis (GEOBIA): erosion monitoring at the Kazár badland, Hungary

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Assessing the rates of channel shifts, bend development and bank erosion hazard on the Sajó River (Hungary) by aerial and terrestrial photogrammetry

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UAS PHOTOGRAMMETRY AND OBJECT-BASED IMAGE ANALYSIS (GEOBIA): EROSION MONITORING AT THE KAZÁR BADLAND, HUNGARY

A remarkable badland valley is situated near Kazár, NE-Hungary, where rhyolite tuff outcrops as greyish white cliffs and white barren patches. The landform is shaped by gully and rill erosion processes. We performed a preliminary state UAS survey and created a digital surface model and ortophotograph. The flight was operated with manual control in order to perform a more optimal coverage of the aerial images. The overhanging forests induced overexposed photographs due to the higher contrast with the bare tuff surface. The multiresolution segmentation method allowed us to classify the ortophotograph and separate the tuff surface and the vegetation. The applied methods and final datasets in combination with the subsequent surveys will be used for detecting the recent erosional processes of the Kazár badland

Confirmation of a theory: reconstruction of an alluvial plain development in a flume experiment

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Inversion‐recovery MR elastography of the human brain for improved stiffness quantification near fluid–solid boundaries

Purpose: In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas. Methods: Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion. Results: Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P = .01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P = .18). The IR-MRE tissue-CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P < .001) and 39% smaller ventricle sizes than MRE (P < .001). Conclusions: Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media

Reduction of breathing artifacts in multifrequency magnetic resonance elastography of the abdomen

Purpose: With abdominal magnetic resonance elastography (MRE) often suffering from breathing artifacts, it is recommended to perform MRE during breath-hold. However, breath-hold acquisition prohibits extended multifrequency MRE examinations and yields inconsistent results when patients cannot hold their breath. The purpose of this work was to analyze free-breathing strategies in multifrequency MRE of abdominal organs. Methods: Abdominal MRE with 30, 40, 50, and 60 Hz vibration frequencies and single-shot, multislice, full wave-field acquisition was performed four times in 11 healthy volunteers: once with multiple breath-holds and three times during free breathing with ungated, gated, and navigated slice adjustment. Shear wave speed maps were generated by tomoelastography inversion. Image registration was applied for correction of intrascan misregistration of image slices. Sharpness of features was quantified by the variance of the Laplacian. Results: Total scan times ranged from 120 seconds for ungated free-breathing MRE to 376 seconds for breath-hold examinations. As expected, free-breathing MRE resulted in larger organ displacements (liver, 4.7 ± 1.5 mm; kidneys, 2.4 ± 2.2 mm; spleen, 3.1 ± 2.4 mm; pancreas, 3.4 ± 1.4 mm) than breath-hold MRE (liver, 0.7 ± 0.2 mm; kidneys, 0.4 ± 0.2 mm; spleen, 0.5 ± 0.2 mm; pancreas, 0.7 ± 0.5 mm). Nonetheless, breathing-related displacement did not affect mean shear wave speed, which was consistent across all protocols (liver, 1.43 ± 0.07 m/s; kidneys, 2.35 ± 0.21 m/s; spleen, 2.02 ± 0.15 m/s; pancreas, 1.39 ± 0.15 m/s). Image registration before inversion improved the quality of free-breathing examinations, yielding no differences in image sharpness to uncorrected breath-hold MRE in most organs (P > .05). Conclusion: Overall, multifrequency MRE is robust to breathing when considering whole-organ values. Respiration-related blurring can readily be corrected using image registration. Consequently, ungated free-breathing MRE combined with image registration is recommended for multifrequency MRE of abdominal organs

Microscopic multifrequency MR elastography for mapping viscoelasticity in zebrafish

Purpose: The zebrafish (Danio rerio) has become an important animal model in a wide range of biomedical research disciplines. Growing awareness of the role of biomechanical properties in tumor progression and neuronal development has led to an increasing interest in the noninvasive mapping of the viscoelastic properties of zebrafish by elastography methods applicable to bulky and nontranslucent tissues. Methods: Microscopic multifrequency MR elastography is introduced for mapping shear wave speed (SWS) and loss angle (φ) as markers of stiffness and viscosity of muscle, brain, and neuroblastoma tumors in postmortem zebrafish with 60 µm in-plane resolution. Experiments were performed in a 7 Tesla MR scanner at 1, 1.2, and 1.4 kHz driving frequencies. Results: Detailed zebrafish viscoelasticity maps revealed that the midbrain region (SWS = 3.1 ± 0.7 m/s, φ = 1.2 ± 0.3 radian [rad]) was stiffer and less viscous than telencephalon (SWS = 2.6 ± 0. 5 m/s, φ = 1.4 ± 0.2 rad) and optic tectum (SWS = 2.6 ± 0.5 m/s, φ = 1.3 ± 0.4 rad), whereas the cerebellum (SWS = 2.9 ± 0.6 m/s, φ = 0.9 ± 0.4 rad) was stiffer but less viscous than both (all p < .05). Overall, brain tissue (SWS = 2.9 ± 0.4 m/s, φ = 1.2 ± 0.2 rad) had similar stiffness but lower viscosity values than muscle tissue (SWS = 2.9 ± 0.5 m/s, φ = 1.4 ± 0.2 rad), whereas neuroblastoma (SWS = 2.4 ± 0.3 m/s, φ = 0.7 ± 0.1 rad, all p < .05) was the softest and least viscous tissue. Conclusion: Microscopic multifrequency MR elastography-generated maps of zebrafish show many details of viscoelasticity and resolve tissue regions, of great interest in neuromechanical and oncological research and for which our study provides first reference values