A method for simultaneously segmenting multiple anatomical brain structures from multi-modal MR images has been developed. An artificial neural network (ANN) was trained from a set of feature vectors created by a combination of high-resolution registration methods, atlas based spatial probability distributions, and a training set of 16 expert traced data sets. A set of feature vectors were adapted to increase performance of ANN segmentation; 1) a modified spatial location for structural symmetry of human brain, 2) neighbors along the priors' descent for directional consistency, and 3) candidate vectors based on the priors for the segmentation of multiple structures. The trained neural network was then applied to 8 data sets, and the results were compared with expertly traced structures for validation purposes. Comparing several reliability metrics, including a relative overlap, similarity index, and intraclass correlation of the ANN generated segmentations to a manual trace are similar or higher to those measures previously developed methods. The ANN provides a level of consistency between subjects and time efficiency comparing human labor that allows it to be used for very large studies.

Localized pH changes have been suggested to occur in the brain during normal function. However, a lack of methods for non-invasively measuring pH with high spatial and temporal resolution limits current knowledge of brain pH dynamics. Here I report that a magnetic resonance imaging (MRI) strategy named T1 relaxation in the rotating frame (T1ρ) is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide (CO2) or bicarbonate (HCO3). Moreover, T1ρ detected changes suggesting a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive 31P spectroscopy at the same site also suggest a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T1ρ correlated with blood oxygenation level dependent contrast (BOLD), although T1ρ was directly sensitive to blood oxygen content. These observations provide the strongest evidence thus far for localized pH fluctuations in the human brain during normal function. Furthermore, they suggest a novel functional imaging strategy based on pH that is independent of traditional fMRI contrast mechanisms. Possible sources of acidosis include local metabolism, which is likely to correlate with the degree of stimulation and the associated changes in local neural activity. Therefore, we hypothesized that T1ρ and pH changes would increase with increasing stimulation frequency. To test this hypothesis, we used a full-field visual flashing checkerboard and varied the frequency between 1, 4, and 7Hz. The response was imaged with T1ρ, BOLD, and 31P spectroscopy. Supporting our hypothesis, we found that increasing stimulation frequency increased responses measured by all three imaging modalities. The activation area detected by T1ρ overlapped to a large degree with that detected by BOLD, although the T1ρ response area was significantly smaller. 31P spectroscopy detected a greater acidosis with the higher stimulation frequencies. These observations suggest that, similar to the BOLD response, the magnitude of the T1ρ and pH response depends on stimulation frequency and is thus likely to be activity-dependent. Brain acidosis is the end product of energy metabolism. Metabolically active cells lower local pH, the detection of which could help pinpoint regions activated by sensory stimuli, emotion, or cognitive task. fMRI mostly relies on BOLD changes in the venous system while arterial spin labeling (ASL) enables changes in tissue perfusion resulting from local cerebral blood flow (CBF) changes. BOLD contrast can be significantly distant from the actual site of neuronal activity because it relies on changes of the local magnetic field within veins. The venous contribution results in a loss of spatial specificity and spatial resolution of the BOLD response. In addition, the hemodynamic response to brief periods of neural activity is delayed. However, ASL contrast originates predominantly from tissue and capillaries. Even though functional signal changes detected by ASL have superior spatial and temporal resolution as compared to BOLD contrast, ASL contrast still suffers from poor temporal resolution due to delays in the hemodynamic response resulting from neurovascular coupling. Therefore, the ability to measure pH dynamics may provide a more localized and direct measure of brain activity. We hypothesized that pH-sensitive T1ρ response in the visual cortex will temporally precede the hemodynamic response measured by functional imaging including BOLD and ASL contrast since local acidosis evoked by neural activity may drive the hemodynamic response. To test this hypothesis, dynamic imaging was performed using T1ρ, BOLD, and ASL while viewing a phase-encoded expanding ring stimulus which induces travelling waves of neural activity in the visual cortex. We calculated the phase maps for the eccentricity across their occipital cortices for each of functional signal and compared the T1ρ temporal resolution with the hemodynamic response. This study suggests that T1ρ signal has a higher temporal resolution as compared to the hemodynamic response. This is further evidence that the T1ρ signal is not sensitive to blood oxygenation or other blood factors that might alter T1ρ. In conclusion, T1ρ imaging has the potential to provide a new functional imaging marker that may be more specific to the area of brain activity. Therefore, it is possible that by non-invasively detecting pH dynamics in the human brain, T1ρ MRI could offer a novel, more direct approach to map brain function. A number of psychiatric and neurological disorders could potentially benefit from the ability to study dynamic pH changes.

Die vorliegende Arbeit untesucht die Darstellung tumoröser und entzündlicher muskuloskelettaler Läsionen mit der diffusionsgewichteten MRT-Bildgebung bei Kindern und Jugendlichen. Es sollten die Machbarkeit und die Zuverlässigkeit der Methode in der klinischen Routinebildgebung überprüft werden. Zusätzlich untersuchten wir den Einsatz von ADC-Werten zur Differenzierung von malignen und benignen Tumoren sowie bei inflammatorischen Knochen- und Weichteilbefunden. Wie die klassische MRT, ist die diffusionsgewichtete Bildgebung nicht-invasiv: da der Bildkontrast allein mittels magnetischer Feldgradienten erzielt wird, erfordert sie weder eine Injektion von Kontrastmitteln, noch den Einsatz von ionisierender Strahlung. Sie garantiert eine schnelle Aquisitionstechink um Artefakte zu begrenzen und die Untersuchungen kindergerechter zu gestalten. Die von uns erfassten Daten wurden in zwei unterschiedlichen Studien aufgeteilt. Die Erste Studie erfasst Ergebnisse bzgl. der Detektion und Dignitätsabschätzung kinderlicher muskuloskelettaler Tumoren mittels diffusionsgewichteten MRT Bilder. Das zweite Forschungsprojekt, befasst sich mit dem erstmaligen Einsatz der diffusionsgewichteten MRT zur Identifikation und Differenzierung von Knochenmarködem, Weichteilödem und Synovitis bei pädiatrischen Patienten. / This study investigates the presentation of tumorous and inflammatory musculoskeletal lesions by diffusion-weighted MRI imaging in children and adolescents. The feasibility and reliability of the method should be tested in clinical routine imaging. In addition, we investigated the use of ADC values ​​for the differentiation of malignant and benign tumors as well as for inflammatory bone and soft tissue findings. Like the classical MRI, diffusion-weighted imaging is non-invasive: since the image contrast is achieved solely by means of magnetic field gradients, it does not require either the injection of contrast agents or the use of ionizing radiations. This technique allows a quick aquisition to limit artefacts and to shape the investigations in a more child-friendly way. The data we collected were divided into two different studies. The first study records results concerning the detection and dignity-assessment of childhood musculoskeletal tumors using diffusion-weighted MRI images. The second research project deals with the initial use of diffusion-weighted MRI for the identification and differentiation of bone marrow edema, soft tissue edema and synovitis in Pediatric patients.

In dieser Studie wurden 280 Patienten, die im Zeitraum vom 01.01.2008 bis 30.06.2012 am Universitätsklinikum Würzburg aufgrund einer Raumforderung der Leber operiert wurden, analysiert. Davon konnten 150 Patienten mit insgesamt 385 Tumoren bewertet werden. Die zentrale Fragestellung der Arbeit beschäftigte sich damit, die Sensitivität der MR-DWI mit anderen präoperativen bildgebenden Untersuchungsmethoden zu bewerten. Bisherige Studien beschäftigten sich bereits mit dem Vergleich der MR-DWI mit anderen diagnostischen Verfahren. Jedoch wurden dabei nicht konkret die aus Sicht eines Chirurgen wichtigen Punkte detailliert beleuchtet. In dieser Arbeit wurden daher die Ergebnisse der Befunde der MR-DWI, CT und konventionellem MRT dem intraoperativen und histopathologisch gesichertem Endbefund gegenübergestellt und bezüglich der Parameter: Tumordignität, Tumoranzahl, Tumorgröße und Tumorlokalisation verglichen. Während die Sensitivität der MR-DWI zur Tumorlokalisation etwas unter der Sensitivität der CT und MRT lag, konnten für die Parameter Tumoranzahl und Tumordignität bessere Ergebnisse der MR-DWI als für die CT herausgestellt werden. Die Genauigkeit der DWI für diese beiden Punkte liegt nah bei der hohen Sensitivität der MRT. Jedoch müssen die sehr guten Ergebnisse der MRT in dieser Arbeit durch die geringe Anzahl der MRT Untersuchungen relativiert werden. Bezüglich der Tumoranzahl ergibt sich bei der MR-DWI die höchste Sensitivität, gefolgt von MRT und CT. Zusammenfassend kann gesagt werden, dass die MR-DWI wie auch die CT und MRT ein sehr sensitives Verfahren zur Detektion von Leberläsionen darstellt. Dabei müssen gewisse Vor- und Nachteile gegenüber den anderen Methoden abgewogen werden. Eine als ungünstig zu wertende Strahlenexposition besteht nicht, ebenso kein zusätzlicher zeitlicher Aufwand. In nahezu allen hier untersuchten Bereichen zeigte die MR-DWI vorrangig bessere Resultate als die CT. Im Vergleich mit der MRT konnten geringfügig niedrigere oder ähnlich gute Werte ermittelt werden. In Bezug auf die Tumoranzahl war die MR-DWI das sensitivste Verfahren. Um die hier erbrachten Ergebnisse zu sichern, sollten zukünftige Studien die Homogenität der Patienten sowie die Anzahl der CT, MRT und MR-DWI Untersuchungen erhöhen. Weiterhin könnten die Geräteeinstellungen bei der MRDWI an bestimmte Fragestellungen angepasst und so genauere Ergebnisse erzielt werden. Bruegel et al konnte für unterschiedliche Leberläsionen bereits die charakteristischen ADC-Werte ermitteln. In einer weiteren Studie von Kilickesmez wurden ebenfalls maligne und benigne Leberläsionen über die entsprechenden ADC-Werte voneinander abgegrenzt. Daraus ergab sich die Empfehlung, zur Diagnostik von Leberläsionen die konventionelle MRT mit der MRDWI zu ergänzen. Ein weiterer Ansatzpunkt ist die Reduktion von Störfaktoren für die MR-DWI und damit die Verbesserung der Bildbeurteilung. In einer Arbeit von Yu-Chun wurde beispielsweise die optimale Temperatur für die MR-DWI Schnittbildgebung am Tiermodell angewandt und so auf molekularer Ebene die Artefaktbildung reduziert. Eine Verbesserung konnte auch durch Ergänzung der MR-DWI mit anderen Verfahren nachgewiesen werden. MR-DWI in Verbindung mit Kontrastmittel ergab eine erhöhte Sensitivität für kleine HCC bis 2cm als Kontrastmittel-MRT ohne DWI. Es ist zu erwarten, dass die MR-DWI in Zukunft durch exaktere Einstellungen der b- Werte und ADC-Messungen in Abhängigkeit der zu untersuchenden Organregion, durch Reduktion störender Faktoren oder durch Kombination mit anderen bildgebenden Verfahren zur Optimierung der präoperativen Diagnostik bei Lebertumoren beiträgt. / Objective: This study was realized to compare the sensitivity of difusion weighted MRI (DWI) with sensitivity of MRI and CT to find liver tumors. There were 4 parameters determined which are most important for surgeons in pre-surgical preparation: number of tumors, dignity, size and localisation in liver. The comparison was based on these 4 parameters. Materials an methods: In a period of 4 years and 6 months (2008-2012) were analysed 150 patients with 385 tumors. All preoperative findings in DWI, MRI and CT have been compared with intraoperative ultrasound and histopathological results. Results: Referring to the number of tumors DWI was more sensitive (55,68%) than CT (47,41) or MRI (27,78%). Also, in finding hepatocellular carcinoma the DWI had better sensitivity (93,74%) than CT (80%) or MRI (47,67%). In the parameter of size the DWI had correlation in 67,65%, better than CT (61,05%) and worse than MRI (71,42%). A correct correlation of dignity was found in DWI in 71,59%, in MRI 77,78% and in CT 60,91%. The sensitivity in the parameter localisation of DWI was 76,92% in comparison with CT 81,73% and MRI 85,19%. We suspect that the DWI is more sensitive to movements of patients while examination is being proceed. Conclusion: DWI is a very sensitive method for finding liver tumors. In the parameter number of tumors and finding of HCC is more sensitive than CT or MRI. In dignity and size its sensitivity is compareable with CT or MRI and only in localisation the results are a little bit worse. To improve the method for the future it’s neccessary to investigate how to switch off the sensibility for movement and also optimize some frame factors.

Posttraumatic Stress Disorder (PTSD) is an anxiety disorder characterised by disturbed arousal, altered attention, and fear processing, and a reduction in the ability to perform cognitive tasks. Predominant neurophysiological models of PTSD have been focused on alterations in fear-related regulation, and few incorporate broader changes in generic executive control which may underlie many of the clinical symptoms and cognitive deficits in PTSD. This thesis aimed to investigate the neurophysiology of executive inhibitory control in PTSD using a Go/NoGo response inhibition task and converging functional imaging, structural imaging and electrophysiological measures. The first series of studies aimed to elucidate a normative neural network model of inhibitory control, and are consistent with normative control involving the activation of a mainly right-lateralised ventral lateral prefrontal cortex (VLPFC) network. Inhibitory control-related activation was found to be affected by levels of anxiety and changes in underlying neural structure; alterations in frontal cortical maturation and volume were related to additional activation of bilateral frontal cortical regions and the dorsal striatum, with anxiety increasing the demand on inhibitory control-related activation. In contrast to healthy participants, PTSD was associated with reduced inhibitory control as indexed by inhibitory behaviour, diminished activation of the right VLPFC, and slowed inhibition-related information processsing. PTSD participants relied on the greater activation of a left fronto-striatal inhibition network to support control, with the activation affected by levels of PTSD severity and comorbid anxiety. This left fronto-striatal activation in PTSD was related to underlying increases in fronto-striatal neural structure. Further, the ability to efficiently engage a left fronto-striatal network in PTSD during inhibitory control predicted better response to cognitive behavior for PTSD, consistent with the proposal that an improved ability to flexibly engage control systems may facilitate the resolution of PTSD symptoms. Taken together, this program of research extends current neurophysiological model of PTSD to show that PTSD involves a fundamental disturbance in the function and structure of key fronto-striatal response control networks associated with inhibitory control.

<p>The accuracy and precision of measurements of pulsating flow obtained with phase contrast magnetic resonance imaging (PC MRI) was studied. Measurements were carried out using known flow rates through a phantom connected to a pump that created pulsation in the flow. Repeated measurements were made in both the negative and positive encoding direction, using both breath-hold and non breath hold sequences. The obtained data was analyzed using code written in MATLAB and also using the FLOW software that is offered by the manufacturer of the MRI system.</p><p>A range of different flow velocities was scanned, and results show that the overall accuracy of the measurements is relatively good, with an average error of between 1.2% to 5.7% using the clinically employed flow calculation software. There is however indication of a systematic phase offset in the data that influences the measurements. The effect of the offset on the results depends on the direction of flow and the sequence used. The results also show the importance of properly selecting the area over which the flow rate is calculated.</p>

<p>The pumping performance of the heart is affected by the mechanical properties of the muscle fibre part of the cardiac wall, the myocardium. The myocardium has a complex structure, where muscle fibres have different orientations at different locations, and during the cardiac cycle, the myocardium undergoes large elastic deformations. Hence, myocardial strain pattern is complex. In this thesis work, a computation method for myocardial strain and a detailed map of myocardial transmural strain during the cardiac cycle are found by the use of surgically implanted metallic markers and beads. The strain is characterized in a local cardiac coordinate system. Thereafter, non-invasive phase contrast magnetic resonance imaging (PC-MRI) is used to compare strain at different myocardial regions. The difference in resolution between marker data and PC-MRI data is elucidated and some of the problems associated with the low resolution of PC-MRI are given.</p>

<p>Hospitals have limited budgets, making the cost of an examination important. A whole-body MRI scan is much less expensive than a PET-CT scan, making the MRI desirable in cases when the result from the MR machine will be sufficient. Also, unlike CT, MRI does not rely on ionizing radiation, which is known to increase the risk of developing cancer.</p><p>To make the most out of the MRI results, an efficient visualization of the data is important. The goal of this project was to develop an application that would facilitate radiologists’ evaluation of whole-body MRI data of lymphoma patients. This was achieved by introducing a fused image between two types of MRI images, offering simplified loading of all the study MRI data and creating a rotatable maximum intensity projection from which points can be selected and zoomed to in other types of images.</p><p>Unfortunately the loading of the data and some parts of the interaction is somewhat slow, which is something that needs to be addressed before this application could become a possibly useful tool for the radiologists.</p>

A prototype system which has integrated a linear accelerator (linac) with a magnetic resonance imager (MRI) has been constructed at the Cross Cancer Institute. The real time operation of a linac-MRI system will require proper radio frequency (RF) shielding such that the MRI images can be acquired without extraneous RF noise from the linac. This thesis reports on the steps taken to successfully RF-shield the linac from the MRI such that the two devices can operate independently of one another. The RF noise from functioning multileaf collimators (MLC) is measured using near field probes and MRI images are acquired with the MLC near the MRI. This included measuring the RF noise as a function of applied magnetic field strength. Several measurement and simulation scenarios are discussed to determine the major sources of RF noise generation from the modulator of a linac. Finally RF power density levels are reported internally and externally to the RF cage which houses the linac and the MRI. The shielding effectiveness of the RF cage has been measured in the frequency range 1 50 MHz and is presented. MRI images of two phantoms are presented during linac operation. The MLC studies illustrate that the small RF noise produced by functioning MLC motors can be effectively shielded to avoid signal-to-noise degradation in the MRI image. A functioning MLC can be incorporated into a linac-MRI unit. The RF noise source investigations of the modulator of a linac illustrate that the major source of RF noise involves the operation of a magnetron. These studies also eliminate the pulse forming network (PFN) coil and the grid voltage spikes on the thyratron as possible major sources of RF noise. The main result is that for linac-MRI systems the modulator of a linac should be housed in a separate RF cage from the MRI. Finally imaging work with the linac operating illustrates that the accelerating structure of a linac and an MRI can be housed within the same RF cage. The 6 MV linac can be operated to produce radiation with no experientially measurable degradation in image quality due to RF effects. / Medical Physics

Despite their unmatched soft-tissue contrast, Magnetic Resonance (MR) images suffer from wide-ranging image distortions; this has raised questions about their suitability as an imaging modality upon which to base conformal radiation therapy treatment plans. This thesis addresses image distortion as it relates to the implementation of MR-based radiation therapy treatment planning (MR-RTP). A grid phantom was imaged at 3T to determine the 3D distortion field using in-house software. Using multiple images, both machine- and object-related sources of distortion were separated such that individual evaluation of distortion sources is possible. Over the imaging volume, nonlinearities in the gradients led to peak-to-peak image distortions of up to 11 mm. For in-vivo distortion quantification, the method was augmented with a modified gradient echo sequence which measures the phase evolution due to underlying field inhomogeneities. The amount of distortion measured using this technique is dependent upon both patient anatomy and sequence parameters, but was found to contribute 5.7 mm at maximum. The methods presented can be combined to provide comprehensive distortion rectification such that mean residual image distortion is reduced to well below the pixel resolution. Finally, distortion quantification and correction methods were applied to a clinical MR-RTP study of prostate patients. The dosimetric consequences of distortion correction were investigated by comparing 3D conformal and intensity modulated radiation therapy plans developed based on both uncorrected and corrected MRI data sets. Total image distortions and those directly affecting the prostate and organs at risk (OARs) were assessed and target doses, OAR doses, and dose volume histograms were compared. Maximum distortion (from all sources) was 7.8 mm. With the exception of two patients, changes in plan dosimetry were insignificant (<2% / <1Gy). Two patients who were poorly position suffered larger distortions in the target region which led to dosimetric differences of up to 4.2%. / Medical Physics