Even though there are no regulations on the interior noise level of passenger cars, it is a significant quality aspect both for customers and for car manufacturers. The reduction of many other car noise sources pushed tyre road noise to the forefront.What is more, well known phenomenon of the tyre acoustic cavity resonance (TCR), appearing around 225 Hz, makes the interior noise noticeably worse. Some techniques to mitigate this phenomenon right at the source are discussed in this thesis, however, these has not been adopted by the tyre nor car manufacturers yet.Therefore, there is a desire to minimise at least the transmission of the acoustic or vibration energy from the tyre to the compartment. This is where methods like TPA (Transfer Path Analysis) come into play.In this thesis, two different approaches to TPA are used to investigate transmission of the TCR energy.First, the coherence based road decomposition method is used to determine whether the TCR energy is transmitted by a structure-borne or an air-borne mechanism. The same method serves to identify if the TCR noise comes mainly from the front or the rear suspension.Second, the impedance matrix method was used to determine critical structure-borne transfer paths yielding clear results indicating two critical mounts at the rear suspension which dominate the transfer of vibro-acoustic energy. Subsequent physical modification of the critical mount was tested to verify the results of the transmission study.Moreover, deflection shape analysis of the tyre, rim, front and rear suspension was performed to identify possible amplification effects of the TCR phenomenon.

The bearing capacity of a road decreases greatly during spring thaw, when the previously frozen road begins to thaw. The extent of this decrease can be evaluated by making Falling Weight Deflectomter (FWD) measurements on the road, measuring the deflection of the road when an impact load is applied to it. The bearing capacity of the road can then be evaluated by backcalculating the layer modules with backcalculation programs, or through more simple calculations based on the deflection basin indices. Both analyses were carried out in this thesis with data from FWD measurements which were carried out on county road Lv 126 in Southern Sweden during the year 2010. The temperature and moisture content of the road were monitored during the same time. The aim with the thesis was to compare the two ways of analyses, and to find out if there is some relationship between them and the measured environmental data. The results showed that the base course layer and subbase decreased in stiffness during spring thaw about 50% while the decrease in the subgrade was 20%, compared to the backcalculated summer and autumn value. The results of the simple calculations from the deflection basin indices were well comparable to the backcalculation results. By comparing the backcalculated stiffness values to the moisture content measurements it was stated that the stiffness decreased as the moisture content increased.

Es wird erwartet, dass die Integration der Magnetresonanztomografie (MRT) in die Protonentherapie die Treffgenauigkeit bei der Strahlentherapie für Krebserkrankungen deutlich verbessern wird. Besonders für Tumoren in beweglichen Organen des Thorax oder des Abdomens könnte die MRT-integrierte Protonentherapie (MRiPT) eine Synchronisierung der Bestrahlung mit der Tumorposition ermöglichen, was zu einer verminderten Normalgewebsdosis und weniger Nebenwirkungen führen könnte. Bis heute ist solch eine Integration jedoch aufgrund fehlender Studien zu potenziellen gegenseitigen Störeinflüssen dieser beiden Systeme nicht vollzogen worden. Diese Arbeit widmete sich zwei solcher Störeinflüsse, und zwar der Ablenkung des Protonenstrahls im Magnetfeld des MRT- Scanners, und umgekehrt, dem Einfluss der elekromagnetischen Felder der Protonentherapieanlage und des Protonenstrahls selbst auf die MRT-Bilder. Obwohl vorangegangene Studien den derzeitigen Konsens aufgezeigt haben, dass die Trajektorie eines abgebremsten Protonenstrahls im homogenen Phantom in einem transversalen Magnetfeld vorhersagbar ist, zeigte sich im quantitativen Vergleich der publizierten Modelle, der im ersten Teil dieser Arbeit vorgestellt wurde, dass die Vorhersagen dieser Modelle nur für eine begrenzte Anzahl von Kombinationen aus Magnetfeldstärke und Protonenenergie übereinstimmen. Die Schwächen bestehender analytischer Modelle wurden deshalb analysiert und quantifiziert. Kritische Annahmen und die mangelnde Anwendbarkeit auf realistische, d.h. inhomogene Magnetfeldstärken und Patientengeometrien wurden als Hauptprobleme identifiziert. Um diese zu überwinden, wurde ein neues semianalytisches Modell namens RAMDIM entwickelt. Es wurde gezeigt, dass dieses auf realistischere Fälle anwendbar und genauer ist als existierende analytische Modelle und dabei schneller als Monte-Carlo-basierte Teilchenspursimulationen. Es wird erwartet, dass dieses Modell in der MRiPT Anwendung findet zur schnellen und genauen Ablenkungsberechnung, zur Betrahlungsplanoptimierung und bei der MRT-geführten Strahlnachführung. In einem zweiten Schritt wurde die magnetfeldinduzierte Protonenstrahlablenkung in einem gewebeähnlichen Material durch Filmdosimetrie erstmalig gemessen und mit Monte-Carlo-Simulationen verglichen. In einem transversalen Magnetfeld einer Flussdichte von 0,95 T wurde experimentell gezeigt, dass die laterale Versetzung des Bragg-Peaks für Protonenenergien zwischen 80 und 180 MeV in PMMA zwischen 1 und 10 mm liegt. Die Retraktion des Bragg-Peaks war ≤ 0,5 mm. Es wurde gezeigt, dass die gemessene Versetzung des Bragg-Peaks innerhalb von 0,8 mm mit Monte-Carlo-basierten Vorhersagen übereinstimmt. Diese Ergebnisse weisen darauf hin, dass die Protonenstrahlablenkung durch Monte-Carlo-Simulationen genau vorhersagbar ist und damit der Realisierbarkeit der MRiPT nicht im Wege steht. Im zweiten Teil dieser Arbeit wurde erstmalig ein MRT-Scanner in eine Protonenstrahlführung integriert. Hierfür wurde ein offener Niederfeld-MRT-Scanner am Ende einer statischen Forschungsstrahlführung einer Protonentherapieanlage platziert. Die durch das statische Magnetfeld des MRT-Scanners hervorgerufene Strahlablenkung wurde bei der Ausrichtung des MRT-Scanners berücksichtigt. Die sequenzabhängigen, veränderlichen Gradientenfelder hatten keinen messbaren Einfluss auf das transversale Strahlprofil hinter dem MRT-Scanner. Die Magnetfeldhomogenität des Scanners lag innerhalb der Herstellervorgaben und zeigte keinen relevanten Einfluss von Rotationen der Protonengantry im benachbarten Bestrahlungsraum. Eine magnetische Abschirmung war zum gleichzeitigen Betrieb des MRT-Scanners und der Protonentherapieanlage nicht notwendig. Dies beweist die Machbarkeit gleichzeitiger Bestrahlung und Bildgebung in einem ersten MRiPT Aufbau. Die MRT-Bildqualität des Aufbaus wurde darauffolgend anhand eines angepassten Standardprotokolls aus Spin-Echo- und Gradienten-Echo-Sequenzen quantifiziert und es wurde gezeigt, dass die Bildqualität sowohl ohne als auch mit gleichzeitiger Bestrahlung hinreichend ist. Alle bestimmten geometrischen Parameter stimmten mit den physikalischen Abmessungen des verwendeten Phantoms innerhalb eines Bildpixels überein. Wie es für Niederfeld-MRT-Scanner üblich ist, war das Signal-Rausch-Verhältnis (SNR) der MRT-Bilder gering, was im Vergleich zu den Standardkriterien zu einer geringen Bildhomogenität und zu einem hohen Geisterbildanteil im Bild führte. Außerdem wurde aufgrund von Unsicherheiten in der Hochfrequenzkalibrierung des MRT-Scanners eine starke Schwankung der vertikalen Phantomposition mit einem Interquartilabstand von bis zu 1,5 mm beobachtet. T2*-gewichtete Gradientenechosequenzen zeigten zudem aufgrund von Magnetfeldinho- mogenitäten relevante ortsabhängige Bildverzerrungen. Es wurde gezeigt, dass die meisten Bildqualitätsparameter mit und ohne gleichzeitige Betrahlung äquivalent sind. Es wurde jedoch ein signifikanter Betrahlungseinfluss in Form von einer vertikalen Bildverschiebung und einer Verminderung des SNR beobachtet, die durch eine Änderung im Magnetfeld des MRT-Scanners erklärt werden können, welche durch zu diesem Feld parallel ausgerichtete Komponenten im Fernfeld der Strahlführungsmagneten hervorgerufen wird. Während das verminderte SNR vermutlich irrelevant ist (Dif- ferenz im Median ≤ 1,5), ist die sequenzabhängige Bildverschiebung (Differenz im Median bis zu 0,7 mm) nicht immer vernachlässigbar. Diese Ergebisse zeigen, dass die MRT-Bilder durch gleichzeitige Bildgebung nicht schwerwiegend verfälscht werden, dass aber eine dedizierte Optimierung der Hochfrequenzkalibrierung und der MRT-Bildsequenzen notwendig ist. Im letzten Teil der Arbeit wurde gezeigt, dass ein stromabhängiger Einfluss des Protonenstrahls auf MRT-Bilder eines Wasserphantoms durch zwei verschiedene MRT-Sequenzen messbar gemacht und zur Reichweiteverifikation genutzt werden kann. Der Effekt war in verschiedenen Flüssigkeiten, jedoch nicht in viskosen und festen Materialen, nachweisbar und wurde auf Hitzekonvektion zurückgeführt. Es wird erwartet, dass diese Methode in der MRiPT für Konstanztests der Protonenreichweite bei der Maschinenqualitätssicherung nützlich sein wird. Zusammenfassend hat diese Arbeit die Genauigkeit der Vorhersage der Strahlablenkung quantifiziert und verbessert, sowie Potenzial und Realisierbarkeit einer gleichzeitigen MRT-Bildgebung und Protonenbestrahlung gezeigt. Die weitere Entwicklung eines ersten MRiPT-Prototyps ist demnach gerechtfertigt.:List of Figures v List of Tables vii 1 General Introduction 1 2 State of the Art: Proton Therapy and Magnetic Resonance Imaging 3 2.1 Proton Therapy 4 2.1.1 Physical Principle 4 2.1.2 Beam Delivery 7 2.1.3 Motion Management and the Role of Image Guidance 10 2.2 Magnetic Resonance Imaging 14 2.2.1 Physical Principle 14 2.2.2 Image Generation by Pulse Sequences 18 2.2.3 Image Quality 21 2.3 MR-Guided Radiotherapy 24 2.3.1 Offline MR Guidance 24 2.3.2 On-line MR Guidance 25 2.4 MR-Integrated Proton Therapy 28 2.4.1 Aims of this Thesis 32 3 Magnetic Field-Induced Beam Deflection and Bragg Peak Displacement 35 3.1 Analytical Description 36 3.1.1 Review of Analytical Models 36 3.1.2 New Model Formulation 41 3.1.3 Evaluation of Analytical and Numerical Models 44 3.1.4 Discussion 51 3.2 Monte Carlo Simulation and Experimental Verification 54 3.2.1 Verification Setup 54 3.2.2 Monte Carlo Simulation 56 3.2.3 Experimental Verification 60 3.2.4 Discussion 61 3.3 Summary 63 4 Integrated In-Beam MR System: Proof of Concept 65 4.1 Integration of a Low-Field MR Scanner and a Static Research Beamline 65 4.1.1 Proton Therapy System 66 4.1.2 MR Scanner 66 4.1.3 Potential Sources of Interference 67 4.1.4 Integration of Both Systems 68 4.2 Beam and Image Quality in the Integrated Setup 70 4.2.1 Beam Profile 70 4.2.2 MR Magnetic Field Homogeneity 72 4.2.3 MR Image Quality - Qualitative In Vivo and Ex Vivo Test 74 4.2.4 MR Image Quality - Quantitative Phantom Tests 77 4.3 Feasibility of MRI-based Range Verification 86 4.3.1 MR Sequences 86 4.3.2 Proton Beam Parameters 88 4.3.3 Target Material Dependence 91 4.3.4 Discussion 92 4.4 Summary 96 5 Discussion and Future Perspectives 99 6 Summary/Zusammenfassung 105 6.1 Summary 105 6.2 Zusammenfassung 108 Bibliography I Supplementary Information XXIX A Beam Deflection: Experimental Measurements XXIX A.1 Setup XXIX A.2 Film Handling and Evaluation XXX A.3 Uncertainty Estimation XXX B Beam Deflection: Monte Carlo Simulations XXXIII B.1 Magnetic Field Model XXXIII B.2 Uncertainty Estimation XXXIV C Integrated MRiPT Setup XXXVI C.1 Magnetic Field Map XXXVI C.2 Sequence Parameters XXXVI C.3 Image Quality Parameters XLII C.4 Range Verification Sequences XLII / The integration of magnetic resonance imaging (MRI) into proton therapy is expected to strongly increase the targeting accuracy in radiation therapy for cancerous diseases. Especially for tumours situated in mobile organs in the thorax and abdomen, MR-integrated proton therapy (MRiPT) could enable the synchronisation of irradiation to the tumour position, resulting in less dose to normal tissue and reduced side effects. However, such an integration has been hindered so far by a lack of scientific studies on the potential mutual interference between the two components. This thesis was dedicated to two of these sources of interference, namely the deflection of the proton beam by the magnetic field of the MR scanner and, vice versa, alterations of the MR image induced by the electromagnetic fields of the proton therapy facility and by the beam itself. Although previous work has indicated that there is general consensus that the trajectory of a slowing down proton beam in a homogeneous phantom inside a transverse magnetic field is predictable, a quantitative comparison of the published methods, as presented in the first part of this thesis, has shown that predictions of different models only agree for certain proton beam energies and magnetic flux densities. Therefore, shortcomings of previously published analytical methods have been analysed and quantified. The inclusion of critical assumptions and the lack of applicability to realistic, i.e. non-uniform, magnetic flux densities and patient anatomies have been identified as main problems. To overcome these deficiencies, a new semi-analytical model called RAMDIM has been developed. It was shown that this model is both applicable to more realistic setups and less assumptive than existing analytical approaches, and faster than Monte Carlo based particle tracking simulations. This model is expected to be useful in MRiPT for fast and accurate deflection estimations, treatment plan optimisation, and MR-guided beam tracking. In a second step, the magnetic field-induced proton beam deflection has been measured for the first time in a tissue-mimicking medium by film dosimetry and has been compared against Monte Carlo simulations. In a transverse magnetic field of 0.95 T, it was experimentally shown that the lateral Bragg peak displacement ranges between 1 mm and 10 mm for proton energies between 80 and 180 MeV in PMMA. Range retraction was found to be ≤ 0.5 mm. The measured Bragg peak displacement was shown to agree within 0.8 mm with Monte Carlo simulations. These results indicate that proton beam deflection in a homogeneous medium is accurately predictable for intermediate proton beam energies and magnetic flux densities by Monte Carlo simulations and therefore not impeding the feasibility of MRiPT. In the second part of this thesis, an MR scanner has been integrated into a proton beam line for the first time. For this purpose, an open low-field MR scanner has been placed at the end of a fixed horizontal proton research beam line in a proton therapy facility. The beam deflection induced by the static magnetic field of the scanner was taken into account for alignment of the beam and the FOV of the scanner. The pulse sequence-dependent dynamic gradient fields did not measurably affect the transverse beam profile behind the MR scanner. The MR magnetic field homogeneity was within the vendor’s specifications and not relevantly influenced by the rotation of the proton gantry in the neighbouring treatment room. No magnetic field compensation system was required for simultaneous operation of the MR scanner and the proton therapy system. These results proof that simultaneous irradiation and imaging is feasible in an in-beam MR setup. The MR image quality of the in-beam MR scanner was then quantified by an adapted standard protocol comprising spin and gradient echo imaging and shown to be acceptable both with and without simultaneous proton beam irradiation. All geometrical parameters agreed with the mechanical dimensions of the used phantom within one pixel width. As common for low-field MR scanners, the signal-to-noise ratio (SNR) of the MR images was low, which resulted in a low image uniformity and a high ghosting ratio in comparison to the standardised test criteria. Furthermore, a strong fluctuation of the vertical phantom position due to uncertainties in the pre-scan frequency calibration was observed, with an interquartile range of up to 1.5 mm. T2*-weighted gradient echo images showed relevant nonuniform deformations due to magnetic field inhomogeneities. Most image quality parameters were shown to be equivalent with and without simultaneous proton beam irradiation. However, a significant influence of simultaneous irradiation was observed as a shift of the vertical phantom position and a decrease in the SNR, both of which can be explained by a change in the B0 field of the MR scanner induced by components of the fringe field of the beam line magnets directed parallel to B0 . While the decrease in SNR is not expected to be relevant (median differences were within 1.5 ), the sequence-dependent phantom shift (median differences of up to 0.7 mm) can become non-negligible. These results show that the MR images are not severely distorted by simultaneous irradiation, but a dedicated optimisation of the pre-scan RF calibration and the MR sequences is required for MRiPT. Lastly, a current-dependent influence of the proton beam on the MR image was shown to be measurable in water in two different MR sequences, which allowed for range verification measurements. The effect was observed in different liquids but not in highly viscose and solid materials, and most probably induced by heat convection. This method is expected to be useful in MRiPT for consistency tests of the proton range during machine-specific quality assurance. In conclusion, this work has improved and quantified the accuracy of beam deflection predictions and shown the feasibility and potential of in-beam MR imaging, justifying further research towards a first MRiPT prototype.:List of Figures v List of Tables vii 1 General Introduction 1 2 State of the Art: Proton Therapy and Magnetic Resonance Imaging 3 2.1 Proton Therapy 4 2.1.1 Physical Principle 4 2.1.2 Beam Delivery 7 2.1.3 Motion Management and the Role of Image Guidance 10 2.2 Magnetic Resonance Imaging 14 2.2.1 Physical Principle 14 2.2.2 Image Generation by Pulse Sequences 18 2.2.3 Image Quality 21 2.3 MR-Guided Radiotherapy 24 2.3.1 Offline MR Guidance 24 2.3.2 On-line MR Guidance 25 2.4 MR-Integrated Proton Therapy 28 2.4.1 Aims of this Thesis 32 3 Magnetic Field-Induced Beam Deflection and Bragg Peak Displacement 35 3.1 Analytical Description 36 3.1.1 Review of Analytical Models 36 3.1.2 New Model Formulation 41 3.1.3 Evaluation of Analytical and Numerical Models 44 3.1.4 Discussion 51 3.2 Monte Carlo Simulation and Experimental Verification 54 3.2.1 Verification Setup 54 3.2.2 Monte Carlo Simulation 56 3.2.3 Experimental Verification 60 3.2.4 Discussion 61 3.3 Summary 63 4 Integrated In-Beam MR System: Proof of Concept 65 4.1 Integration of a Low-Field MR Scanner and a Static Research Beamline 65 4.1.1 Proton Therapy System 66 4.1.2 MR Scanner 66 4.1.3 Potential Sources of Interference 67 4.1.4 Integration of Both Systems 68 4.2 Beam and Image Quality in the Integrated Setup 70 4.2.1 Beam Profile 70 4.2.2 MR Magnetic Field Homogeneity 72 4.2.3 MR Image Quality - Qualitative In Vivo and Ex Vivo Test 74 4.2.4 MR Image Quality - Quantitative Phantom Tests 77 4.3 Feasibility of MRI-based Range Verification 86 4.3.1 MR Sequences 86 4.3.2 Proton Beam Parameters 88 4.3.3 Target Material Dependence 91 4.3.4 Discussion 92 4.4 Summary 96 5 Discussion and Future Perspectives 99 6 Summary/Zusammenfassung 105 6.1 Summary 105 6.2 Zusammenfassung 108 Bibliography I Supplementary Information XXIX A Beam Deflection: Experimental Measurements XXIX A.1 Setup XXIX A.2 Film Handling and Evaluation XXX A.3 Uncertainty Estimation XXX B Beam Deflection: Monte Carlo Simulations XXXIII B.1 Magnetic Field Model XXXIII B.2 Uncertainty Estimation XXXIV C Integrated MRiPT Setup XXXVI C.1 Magnetic Field Map XXXVI C.2 Sequence Parameters XXXVI C.3 Image Quality Parameters XLII C.4 Range Verification Sequences XLII

No description available.

The thesis deals with problems of control and diagnostics of electron beam technological devices which use electron beam for localised intensive heating of a material. A brief description of the electron beam welder MEBW-60/2 is included; the author has participated on its development and implementation. Main topics are the analysis of deflection system properties and the measurement of current distribution of the beam (so-called beam profiles). Geometrical aberrations, hysteresis, stability and dynamics of a single-stage magnetic x-y deflection system are described. Suitable measurement procedures and correction methods are introduced. Methods of transverse and longitudinal beam profile acquisition is presented using successive sampling of the local current density of the beam by a modified Faraday cup. The data processing and evaluation of characteristic beam parameters are shown. The presented methods were verified by fourteen experiments using the electron beam welder. The methods have proven to be useful in practical evaluation of the device properties.

Es wird erwartet, dass die Integration der Magnetresonanztomografie (MRT) in die Protonentherapie die Treffgenauigkeit bei der Strahlentherapie für Krebserkrankungen deutlich verbessern wird. Besonders für Tumoren in beweglichen Organen des Thorax oder des Abdomens könnte die MRT-integrierte Protonentherapie (MRiPT) eine Synchronisierung der Bestrahlung mit der Tumorposition ermöglichen, was zu einer verminderten Normalgewebsdosis und weniger Nebenwirkungen führen könnte. Bis heute ist solch eine Integration jedoch aufgrund fehlender Studien zu potenziellen gegenseitigen Störeinflüssen dieser beiden Systeme nicht vollzogen worden. Diese Arbeit widmete sich zwei solcher Störeinflüsse, und zwar der Ablenkung des Protonenstrahls im Magnetfeld des MRT- Scanners, und umgekehrt, dem Einfluss der elekromagnetischen Felder der Protonentherapieanlage und des Protonenstrahls selbst auf die MRT-Bilder. Obwohl vorangegangene Studien den derzeitigen Konsens aufgezeigt haben, dass die Trajektorie eines abgebremsten Protonenstrahls im homogenen Phantom in einem transversalen Magnetfeld vorhersagbar ist, zeigte sich im quantitativen Vergleich der publizierten Modelle, der im ersten Teil dieser Arbeit vorgestellt wurde, dass die Vorhersagen dieser Modelle nur für eine begrenzte Anzahl von Kombinationen aus Magnetfeldstärke und Protonenenergie übereinstimmen. Die Schwächen bestehender analytischer Modelle wurden deshalb analysiert und quantifiziert. Kritische Annahmen und die mangelnde Anwendbarkeit auf realistische, d.h. inhomogene Magnetfeldstärken und Patientengeometrien wurden als Hauptprobleme identifiziert. Um diese zu überwinden, wurde ein neues semianalytisches Modell namens RAMDIM entwickelt. Es wurde gezeigt, dass dieses auf realistischere Fälle anwendbar und genauer ist als existierende analytische Modelle und dabei schneller als Monte-Carlo-basierte Teilchenspursimulationen. Es wird erwartet, dass dieses Modell in der MRiPT Anwendung findet zur schnellen und genauen Ablenkungsberechnung, zur Betrahlungsplanoptimierung und bei der MRT-geführten Strahlnachführung. In einem zweiten Schritt wurde die magnetfeldinduzierte Protonenstrahlablenkung in einem gewebeähnlichen Material durch Filmdosimetrie erstmalig gemessen und mit Monte-Carlo-Simulationen verglichen. In einem transversalen Magnetfeld einer Flussdichte von 0,95 T wurde experimentell gezeigt, dass die laterale Versetzung des Bragg-Peaks für Protonenenergien zwischen 80 und 180 MeV in PMMA zwischen 1 und 10 mm liegt. Die Retraktion des Bragg-Peaks war ≤ 0,5 mm. Es wurde gezeigt, dass die gemessene Versetzung des Bragg-Peaks innerhalb von 0,8 mm mit Monte-Carlo-basierten Vorhersagen übereinstimmt. Diese Ergebnisse weisen darauf hin, dass die Protonenstrahlablenkung durch Monte-Carlo-Simulationen genau vorhersagbar ist und damit der Realisierbarkeit der MRiPT nicht im Wege steht. Im zweiten Teil dieser Arbeit wurde erstmalig ein MRT-Scanner in eine Protonenstrahlführung integriert. Hierfür wurde ein offener Niederfeld-MRT-Scanner am Ende einer statischen Forschungsstrahlführung einer Protonentherapieanlage platziert. Die durch das statische Magnetfeld des MRT-Scanners hervorgerufene Strahlablenkung wurde bei der Ausrichtung des MRT-Scanners berücksichtigt. Die sequenzabhängigen, veränderlichen Gradientenfelder hatten keinen messbaren Einfluss auf das transversale Strahlprofil hinter dem MRT-Scanner. Die Magnetfeldhomogenität des Scanners lag innerhalb der Herstellervorgaben und zeigte keinen relevanten Einfluss von Rotationen der Protonengantry im benachbarten Bestrahlungsraum. Eine magnetische Abschirmung war zum gleichzeitigen Betrieb des MRT-Scanners und der Protonentherapieanlage nicht notwendig. Dies beweist die Machbarkeit gleichzeitiger Bestrahlung und Bildgebung in einem ersten MRiPT Aufbau. Die MRT-Bildqualität des Aufbaus wurde darauffolgend anhand eines angepassten Standardprotokolls aus Spin-Echo- und Gradienten-Echo-Sequenzen quantifiziert und es wurde gezeigt, dass die Bildqualität sowohl ohne als auch mit gleichzeitiger Bestrahlung hinreichend ist. Alle bestimmten geometrischen Parameter stimmten mit den physikalischen Abmessungen des verwendeten Phantoms innerhalb eines Bildpixels überein. Wie es für Niederfeld-MRT-Scanner üblich ist, war das Signal-Rausch-Verhältnis (SNR) der MRT-Bilder gering, was im Vergleich zu den Standardkriterien zu einer geringen Bildhomogenität und zu einem hohen Geisterbildanteil im Bild führte. Außerdem wurde aufgrund von Unsicherheiten in der Hochfrequenzkalibrierung des MRT-Scanners eine starke Schwankung der vertikalen Phantomposition mit einem Interquartilabstand von bis zu 1,5 mm beobachtet. T2*-gewichtete Gradientenechosequenzen zeigten zudem aufgrund von Magnetfeldinho- mogenitäten relevante ortsabhängige Bildverzerrungen. Es wurde gezeigt, dass die meisten Bildqualitätsparameter mit und ohne gleichzeitige Betrahlung äquivalent sind. Es wurde jedoch ein signifikanter Betrahlungseinfluss in Form von einer vertikalen Bildverschiebung und einer Verminderung des SNR beobachtet, die durch eine Änderung im Magnetfeld des MRT-Scanners erklärt werden können, welche durch zu diesem Feld parallel ausgerichtete Komponenten im Fernfeld der Strahlführungsmagneten hervorgerufen wird. Während das verminderte SNR vermutlich irrelevant ist (Dif- ferenz im Median ≤ 1,5), ist die sequenzabhängige Bildverschiebung (Differenz im Median bis zu 0,7 mm) nicht immer vernachlässigbar. Diese Ergebisse zeigen, dass die MRT-Bilder durch gleichzeitige Bildgebung nicht schwerwiegend verfälscht werden, dass aber eine dedizierte Optimierung der Hochfrequenzkalibrierung und der MRT-Bildsequenzen notwendig ist. Im letzten Teil der Arbeit wurde gezeigt, dass ein stromabhängiger Einfluss des Protonenstrahls auf MRT-Bilder eines Wasserphantoms durch zwei verschiedene MRT-Sequenzen messbar gemacht und zur Reichweiteverifikation genutzt werden kann. Der Effekt war in verschiedenen Flüssigkeiten, jedoch nicht in viskosen und festen Materialen, nachweisbar und wurde auf Hitzekonvektion zurückgeführt. Es wird erwartet, dass diese Methode in der MRiPT für Konstanztests der Protonenreichweite bei der Maschinenqualitätssicherung nützlich sein wird. Zusammenfassend hat diese Arbeit die Genauigkeit der Vorhersage der Strahlablenkung quantifiziert und verbessert, sowie Potenzial und Realisierbarkeit einer gleichzeitigen MRT-Bildgebung und Protonenbestrahlung gezeigt. Die weitere Entwicklung eines ersten MRiPT-Prototyps ist demnach gerechtfertigt.:List of Figures v List of Tables vii 1 General Introduction 1 2 State of the Art: Proton Therapy and Magnetic Resonance Imaging 3 2.1 Proton Therapy 4 2.1.1 Physical Principle 4 2.1.2 Beam Delivery 7 2.1.3 Motion Management and the Role of Image Guidance 10 2.2 Magnetic Resonance Imaging 14 2.2.1 Physical Principle 14 2.2.2 Image Generation by Pulse Sequences 18 2.2.3 Image Quality 21 2.3 MR-Guided Radiotherapy 24 2.3.1 Offline MR Guidance 24 2.3.2 On-line MR Guidance 25 2.4 MR-Integrated Proton Therapy 28 2.4.1 Aims of this Thesis 32 3 Magnetic Field-Induced Beam Deflection and Bragg Peak Displacement 35 3.1 Analytical Description 36 3.1.1 Review of Analytical Models 36 3.1.2 New Model Formulation 41 3.1.3 Evaluation of Analytical and Numerical Models 44 3.1.4 Discussion 51 3.2 Monte Carlo Simulation and Experimental Verification 54 3.2.1 Verification Setup 54 3.2.2 Monte Carlo Simulation 56 3.2.3 Experimental Verification 60 3.2.4 Discussion 61 3.3 Summary 63 4 Integrated In-Beam MR System: Proof of Concept 65 4.1 Integration of a Low-Field MR Scanner and a Static Research Beamline 65 4.1.1 Proton Therapy System 66 4.1.2 MR Scanner 66 4.1.3 Potential Sources of Interference 67 4.1.4 Integration of Both Systems 68 4.2 Beam and Image Quality in the Integrated Setup 70 4.2.1 Beam Profile 70 4.2.2 MR Magnetic Field Homogeneity 72 4.2.3 MR Image Quality - Qualitative In Vivo and Ex Vivo Test 74 4.2.4 MR Image Quality - Quantitative Phantom Tests 77 4.3 Feasibility of MRI-based Range Verification 86 4.3.1 MR Sequences 86 4.3.2 Proton Beam Parameters 88 4.3.3 Target Material Dependence 91 4.3.4 Discussion 92 4.4 Summary 96 5 Discussion and Future Perspectives 99 6 Summary/Zusammenfassung 105 6.1 Summary 105 6.2 Zusammenfassung 108 Bibliography I Supplementary Information XXIX A Beam Deflection: Experimental Measurements XXIX A.1 Setup XXIX A.2 Film Handling and Evaluation XXX A.3 Uncertainty Estimation XXX B Beam Deflection: Monte Carlo Simulations XXXIII B.1 Magnetic Field Model XXXIII B.2 Uncertainty Estimation XXXIV C Integrated MRiPT Setup XXXVI C.1 Magnetic Field Map XXXVI C.2 Sequence Parameters XXXVI C.3 Image Quality Parameters XLII C.4 Range Verification Sequences XLII / The integration of magnetic resonance imaging (MRI) into proton therapy is expected to strongly increase the targeting accuracy in radiation therapy for cancerous diseases. Especially for tumours situated in mobile organs in the thorax and abdomen, MR-integrated proton therapy (MRiPT) could enable the synchronisation of irradiation to the tumour position, resulting in less dose to normal tissue and reduced side effects. However, such an integration has been hindered so far by a lack of scientific studies on the potential mutual interference between the two components. This thesis was dedicated to two of these sources of interference, namely the deflection of the proton beam by the magnetic field of the MR scanner and, vice versa, alterations of the MR image induced by the electromagnetic fields of the proton therapy facility and by the beam itself. Although previous work has indicated that there is general consensus that the trajectory of a slowing down proton beam in a homogeneous phantom inside a transverse magnetic field is predictable, a quantitative comparison of the published methods, as presented in the first part of this thesis, has shown that predictions of different models only agree for certain proton beam energies and magnetic flux densities. Therefore, shortcomings of previously published analytical methods have been analysed and quantified. The inclusion of critical assumptions and the lack of applicability to realistic, i.e. non-uniform, magnetic flux densities and patient anatomies have been identified as main problems. To overcome these deficiencies, a new semi-analytical model called RAMDIM has been developed. It was shown that this model is both applicable to more realistic setups and less assumptive than existing analytical approaches, and faster than Monte Carlo based particle tracking simulations. This model is expected to be useful in MRiPT for fast and accurate deflection estimations, treatment plan optimisation, and MR-guided beam tracking. In a second step, the magnetic field-induced proton beam deflection has been measured for the first time in a tissue-mimicking medium by film dosimetry and has been compared against Monte Carlo simulations. In a transverse magnetic field of 0.95 T, it was experimentally shown that the lateral Bragg peak displacement ranges between 1 mm and 10 mm for proton energies between 80 and 180 MeV in PMMA. Range retraction was found to be ≤ 0.5 mm. The measured Bragg peak displacement was shown to agree within 0.8 mm with Monte Carlo simulations. These results indicate that proton beam deflection in a homogeneous medium is accurately predictable for intermediate proton beam energies and magnetic flux densities by Monte Carlo simulations and therefore not impeding the feasibility of MRiPT. In the second part of this thesis, an MR scanner has been integrated into a proton beam line for the first time. For this purpose, an open low-field MR scanner has been placed at the end of a fixed horizontal proton research beam line in a proton therapy facility. The beam deflection induced by the static magnetic field of the scanner was taken into account for alignment of the beam and the FOV of the scanner. The pulse sequence-dependent dynamic gradient fields did not measurably affect the transverse beam profile behind the MR scanner. The MR magnetic field homogeneity was within the vendor’s specifications and not relevantly influenced by the rotation of the proton gantry in the neighbouring treatment room. No magnetic field compensation system was required for simultaneous operation of the MR scanner and the proton therapy system. These results proof that simultaneous irradiation and imaging is feasible in an in-beam MR setup. The MR image quality of the in-beam MR scanner was then quantified by an adapted standard protocol comprising spin and gradient echo imaging and shown to be acceptable both with and without simultaneous proton beam irradiation. All geometrical parameters agreed with the mechanical dimensions of the used phantom within one pixel width. As common for low-field MR scanners, the signal-to-noise ratio (SNR) of the MR images was low, which resulted in a low image uniformity and a high ghosting ratio in comparison to the standardised test criteria. Furthermore, a strong fluctuation of the vertical phantom position due to uncertainties in the pre-scan frequency calibration was observed, with an interquartile range of up to 1.5 mm. T2*-weighted gradient echo images showed relevant nonuniform deformations due to magnetic field inhomogeneities. Most image quality parameters were shown to be equivalent with and without simultaneous proton beam irradiation. However, a significant influence of simultaneous irradiation was observed as a shift of the vertical phantom position and a decrease in the SNR, both of which can be explained by a change in the B0 field of the MR scanner induced by components of the fringe field of the beam line magnets directed parallel to B0 . While the decrease in SNR is not expected to be relevant (median differences were within 1.5 ), the sequence-dependent phantom shift (median differences of up to 0.7 mm) can become non-negligible. These results show that the MR images are not severely distorted by simultaneous irradiation, but a dedicated optimisation of the pre-scan RF calibration and the MR sequences is required for MRiPT. Lastly, a current-dependent influence of the proton beam on the MR image was shown to be measurable in water in two different MR sequences, which allowed for range verification measurements. The effect was observed in different liquids but not in highly viscose and solid materials, and most probably induced by heat convection. This method is expected to be useful in MRiPT for consistency tests of the proton range during machine-specific quality assurance. In conclusion, this work has improved and quantified the accuracy of beam deflection predictions and shown the feasibility and potential of in-beam MR imaging, justifying further research towards a first MRiPT prototype.:List of Figures v List of Tables vii 1 General Introduction 1 2 State of the Art: Proton Therapy and Magnetic Resonance Imaging 3 2.1 Proton Therapy 4 2.1.1 Physical Principle 4 2.1.2 Beam Delivery 7 2.1.3 Motion Management and the Role of Image Guidance 10 2.2 Magnetic Resonance Imaging 14 2.2.1 Physical Principle 14 2.2.2 Image Generation by Pulse Sequences 18 2.2.3 Image Quality 21 2.3 MR-Guided Radiotherapy 24 2.3.1 Offline MR Guidance 24 2.3.2 On-line MR Guidance 25 2.4 MR-Integrated Proton Therapy 28 2.4.1 Aims of this Thesis 32 3 Magnetic Field-Induced Beam Deflection and Bragg Peak Displacement 35 3.1 Analytical Description 36 3.1.1 Review of Analytical Models 36 3.1.2 New Model Formulation 41 3.1.3 Evaluation of Analytical and Numerical Models 44 3.1.4 Discussion 51 3.2 Monte Carlo Simulation and Experimental Verification 54 3.2.1 Verification Setup 54 3.2.2 Monte Carlo Simulation 56 3.2.3 Experimental Verification 60 3.2.4 Discussion 61 3.3 Summary 63 4 Integrated In-Beam MR System: Proof of Concept 65 4.1 Integration of a Low-Field MR Scanner and a Static Research Beamline 65 4.1.1 Proton Therapy System 66 4.1.2 MR Scanner 66 4.1.3 Potential Sources of Interference 67 4.1.4 Integration of Both Systems 68 4.2 Beam and Image Quality in the Integrated Setup 70 4.2.1 Beam Profile 70 4.2.2 MR Magnetic Field Homogeneity 72 4.2.3 MR Image Quality - Qualitative In Vivo and Ex Vivo Test 74 4.2.4 MR Image Quality - Quantitative Phantom Tests 77 4.3 Feasibility of MRI-based Range Verification 86 4.3.1 MR Sequences 86 4.3.2 Proton Beam Parameters 88 4.3.3 Target Material Dependence 91 4.3.4 Discussion 92 4.4 Summary 96 5 Discussion and Future Perspectives 99 6 Summary/Zusammenfassung 105 6.1 Summary 105 6.2 Zusammenfassung 108 Bibliography I Supplementary Information XXIX A Beam Deflection: Experimental Measurements XXIX A.1 Setup XXIX A.2 Film Handling and Evaluation XXX A.3 Uncertainty Estimation XXX B Beam Deflection: Monte Carlo Simulations XXXIII B.1 Magnetic Field Model XXXIII B.2 Uncertainty Estimation XXXIV C Integrated MRiPT Setup XXXVI C.1 Magnetic Field Map XXXVI C.2 Sequence Parameters XXXVI C.3 Image Quality Parameters XLII C.4 Range Verification Sequences XLII

Introduction: Muscle fatigue can contribute to acute flare-ups of lower back pain with associated consequences such as pain, disability, lost work time, increased healthcare utilization, and increased opioid use and potential abuse. The SPINE Sense system is a wearable device with 16 high deflection nanocomposite strain gauge sensors on kinesiology tape which is adhered to the skin of the lower back. This device is used to correlate lumbar skin strains with the motion of the lumbar vertebrae and to phenotype lumbar spine motion. In this work it was hypothesized that the SPINE Sense device can be used to detect differences in biomechanical movements consequent to muscle fatigue. A human subject study was completed with 30 subjects who performed 14 functional movements before and after fatiguing their back muscles through the Biering-Sørensen endurance test with the SPINE Sense device on their lower back collecting skin strain data. Various features from the strain gauge sensors were extracted from these data and were used as inputs to a random forest classification machine learning model. The accuracy of the model was assessed under two training/validation conditions, namely a hold-out method and a leave-one-out method. The random forest classification models were able to achieve up to 84.22% and 78.37% accuracies for the hold-out and leave-one-out methods respectively. Additionally, a system usability study was performed by presenting the device to 32 potential users (clinicians and individuals with lower back pain) of their device. They received a scripted explanation of the use of the device and were then instructed to score it with the validated System Usability Score. In addition they were given the opportunity to voice concerns, questions, and offer any other additional feedback about the design and use of the device. The average System Usability Score from all participants from the system usability study was 72.03 with suggestions of improving the robustness of electrical connections and smaller profiles of accompanying electronics. Feedback from the potential users of the device was used to make more robust electrical connections and smaller wires and electronics modules. These improvements were achieved by making a two-piece design: one piece contains the sensors on kinesiology tape that is directly attached to the patient and the other one contains the wires sewn into stretch fabric to create stretchable electronic connections to the device. It is concluded that a machine-learning model of the data from the SPINE Sense device can classify lumbar motion with sufficient accuracy for clinical utility. It is also concluded that the device is usable and intuitive to use.

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This thesis deals with the use of the electronic measuring systems for monitoring structures. The first part of this work is focused on mapping the available measuring systems for monitoring deformations and strains, from the point of their measurement accuracy, the real advantages and disadvantages, including examples of monitoring of constructions. In the second part were selected measuring systems for monitoring strains and deflection interest structure. Subsequently, the measuring system with online recording into the tested roof structure was installed and the loading test was performed. Obtained data were compared with other two independent measurements. In the last part of the thesis, the measured values of each independent measurements were compared together, and with the values calculated from the mathematical model. The achieved results show that the installed monitoring system is capable to reliably measure deformation of the structure in real time and thus to warn the building administrator against the potential danger in advance.

This work investigates the feasibility of producing small scale, low aerodynamic loading wind tunnel models, using FDM 3D printing methods, that are both structurally and aerodynamically representative in the wind tunnel. To verify the applicability of this approach, a 2.07% scale model of the NASA CRM was produced, whose wings were manufacturing using a Finite Deposition Modeling 3D printer. Experimental data was compared to numerical simulations to determine percent difference in wake distribution and wingtip deflection for multiple configurations. Numerical simulation data taken in the form of CFD and FEA was used to validate data taken in the wind tunnel experiments. The experiment utilized a wake rake to measure 3 different spanwise locations of the wing for aerodynamic data, and a videogrammetry method was used to measure the deflection of the wingtips for structural data. Both numerical simulations and experiments were evaluated at Reynolds numbers of 258,000 and 362,000 at 0 degrees angle of attack, and 258,000 at 5 degrees angle of attack. Results indicate that the wing wake minimum in the wind tunnel test had shifted approximately 8.8mm at the wingtip for the Nylon 910 wing at 258,000 Reynolds number for 0 degrees angle of attack when compared to CFD. Videogrammetry results indicate that the wing deflected 5.9mm, and has an 18.6% difference from observed deflection in FEA. This reveals the potential for small scale wind tunnel models to be more representative of true flight behavior for low loading scenarios.