Functional magnetic resonance imaging (fMRI) enables non-invasive investigation of the neural functions with excellent spatial resolution. Although fMRI has primarily been developed in young adult populations, its use is becoming widespread in paediatrics. However, there are many differences, both behavioural and physical, between adults and children requiring adjustments to imaging and analysis methodology to optimise the results in children. This thesis examines fMRI analysis methodology to improve the detection of developmental changes in the brain. The work uses an emotional and familiar face paradigm that elicits strong BOLD fMRI responses in the fusiform, a region that is still developing across childhood. This face paradigm also enables the comparison of the fusiform responses to the primary visual cortex to link to extensive results in the literature. Thirty five 4-8 year old children and fourteen adults (18-30 years old) were scanned. To address the concern of anatomical size differences between the brains of adults and children, the anatomical variability of the fusiform was measured and the validity of stereotaxic transformation into an adult template was confirmed for the children. To investigate the effect of threshold settings between the adults and children, individual subject analyses of the peak activation location, estimated signal percent change and noise values were calculated using the general linear model (GLM). Similar functional peak locations between individuals were quantitatively selected using a novel application of the activation likelihood estimation (ALE). Also, several different preprocessing steps were evaluated for their ability to correct for the increased motion frequently seen in children, in a quantitative framework (NPAIRS) using canonical variates analysis (CVA), a data driven multivariate model as well as the standard univariate GLM. Functional differences between the adults and the children were identified in the fusiform by applying these optimised procedures. The results of this thesis demonstrate that thresholding and preprocessing pipelines must be made in a group-specific fashion. These methods can also be extended to elderly populations, enabling the investigation of the complete ageing spectrum with fMRI.

Neuroscience research has followed two fairly distinct paths in investigating central neural mechanisms of pain and emotion. Rarely have studies been conducted which intentionally combined painful and emotional stimulation while observing brain function. Theories of emotion and pain processing predict an interaction between pain and emotion such that emotional states may serve to both increase or decrease pain. This increase or decrease may also correspond to different effects on different dimensions of the overall pain experience as defined in pain neuromatrix theory. Theories of emotion begin with emotions as interpretations of bodily states, to more contemporary theories focusing on the functions of emotions. These emotion theories predict neuroanotomic relations between emotion and pain in the brain. Similarly neuromatrix theory predicts an affective dimension of pain experience, which has been defined in terms of pain unpleasantness and secondary affect, emphasizing the role of emotion in pain experience. To further explore the relationship between pain and emotion, in the present study, painful heat stimulation is applied to the face while simultaneously conducting whole brain imaging using functional magnetic resonance imaging (fMRI). Also personal episodes involving anger, fear, and neutral emotion are recalled during fMRI both with, and without, painful heat stimulation. Similar brain regions are involved in processing pain, anger, and fear, and these responses compare favorably with those in the literature. The results also demonstrate that simultaneous emotional episode recall modulates the patterns of brain activity involved in pain. Anger recall especially seems to increase pain-related activity. The study allows greater understanding about the way that the brain's emotional processing networks for fear and anger affect pain experience and how pain affects the emotional processing network to produce affective experience, such as fear and anger, related to pain. Further application of these procedures to patients with chronic pain can aid understanding of central pathological mechanisms involved.

Resistance exercise using weights typically offers constant external load during coupled shortening (concentric) and lengthening (eccentric) muscle actions in sets of consecutive repetitions until failure. However, the constant external load and the inherent capability of skeletal muscle to produce greater force in the eccentric compared with the concentric action, would infer that most actions are executed with incomplete motor unit involvement. In contrast, use of the inertia of flywheels to generate resistance allows for maximal voluntary force to be produced throughout the concentric action, and for brief episodes of greater eccentric than concentric loading, i.e. “eccentric overload”. Thus, it was hypothesized that acute flywheel resistance exercise would induce greater motor unit and muscle use, and subsequent fatigue, compared with traditional weight stack/free weight resistance exercise. Furthermore, it was hypothesized that flywheel training would induce more robust neuromuscular adaptations compared with training using weights. A total of 43 trained and untrained men were investigated in these studies. Knee extensor muscle activation, fatigue response and muscle use were assessed during exercises by recording electromyographic signals and by means of functional magnetic resonance imaging, respectively. Flywheel resistance exercise provoked maximal or near maximal muscle activation from the first repetition, induced robust fatigue, and prompted more substantial motor unit and muscle use than weight stack/free weight resistance exercise in both novice and resistance trained men. Both prior to and following five weeks of unilateral knee extension training, the eccentric muscle activation was greater with flywheel than weight stack training. Furthermore, weight stack training generated greater increases of dynamic strength and neural adaptations, while flywheel training generated more prominent hypertrophy of individual quadriceps muscles and greater improvement of maximal isometric strength. Hence, due to the preferential metabolic cost of the concentric rather than eccentric actions, the maximal activation through the entire range of the concentric action within each repetition of a set during flywheel resistance exercise probably evoked the marked fatigue, and prompted more substantial muscle use than resistance exercise using weights. Furthermore, while any cause‐effect relationship remains to be determined, results of the pesent study suggest that brief episodes of “eccentric overload” amplify muscular adaptations following concentriceccentric resistance training.

MRI has been applied to directly detecting neuronal activity. The direct detection of multiple dendrite sites within the brain offers an important tool in the analysis of the brain for mapping cognition. In this, multiple dendrite contributions can be applied with the same model between the parallel and anti-parallel orientations depending on a spatial depolarization and re-polarization wave. Once the strength of the dendritic contribution was calculated, the spatially dependent phase shifts were theoretically modeled. In the construction of this column the dendrites were modeled as having cylindrical symmetry, uniform current density, and the intracellular current was taken as the primary current contribution to the volume dendrite model. The method examined the system using the known volume density of the dendrites treated with the current dipole model over a voxel. The maximum effect of the field strength, phase, and percent signal change was theoretically calculated. The maximum field was calculated as 1.07 nT, the maximum phase was calculated as 2.14 mrad, and the maximum percent signal increase was calculated as 0.217 %. / Overview of the basics of MRI imaging -- Overview of neural activation and imaging of the activation -- Theory and methods -- Results. / Department of Physics and Astronomy

It was hypothesized that superparamagnetic nanoparticles encapsulated in a silica shell with a fluorescent dye could be functionalized with axonal tracers and could be used for serial, non-invasive imaging with magnetic resonance imaging (MRI) for axon tract tracing. Nanoparticles functionalized with amine, octadecyl, silica, and biotinylated dextran amine were manufactured and characterized with MRI, scanning electron microscopy, and UV-visible, infrared, and fluorescence spectroscopy. Nanoparticle concentrations of 10 mM were not toxic to adult rat neural progenitor cells (NPCs) and labeled approximately 90% of cells. Nanoparticles were assessed for anterograde and retrograde tract tracing in adult rat models. With MRI and microscopy, the nanoparticles did not appear to trace axons but did provide an MRI signal for up to 3 weeks post implantation. While functionalized nanoparticles did not appear to trace axons, they are not toxic to NPCs and may be used as a MRI contrast agent in the neural axis.

The modern day radiotherapy treatments are almost exclusively based on computed tomography (CT) images. The CT images are acquired using x-rays, and therefore reflect the radiation interaction properties of the material. This information is used to perform accurate dose calculation by the treatment planning system, and the data is also well suited for creating digitally reconstructed radiographs for comparing patient set up at the treatment machine where x-ray images are routinely acquired for this purpose. The magnetic resonance (MR) scanner has many attractive features for radiotherapy purposes. The soft tissue contrast as compared to CT is far superior, and it is possible to vary the sequences in order to visualize different anatomical and physiological properties of an organ. Both of these properties may contribute to an increase in accuracy of radiotherapy treatment. Using the MR images by themselves for treatment planning is, however, problematic. MR data reflects the magnetic properties of protons, and thus have no connection to the radiointeraction properties of the material. MRI also has inherent difficulty in imaging bone, which will appear in images as areas of no signal similar to air. This makes both dose calculation and patient positioning at the treatment machine troublesome. There are several clinics that use MR images together with CT images to perform treatment planning. The images are registered to a common coordinate system, a process often described as image fusion. In these cases, the MR images are primarily used for target definition and the CT images are used for dose calculations. This method is now not ideal, however, since the image fusion may introduce systematic uncertainties into the treatment due to the fact that the tumor is often able to move relatively freely with respect to the patients’ bony anatomy and outer contour, especially when the image registration algorithms take the entire patient anatomy in the volume of interest into account. The work presented in the thesis “Integration of MRI into the radiotherapy workflow” aim towards investigating the possibilities of workflows based entirely on MRI without using image registration, as well as workflows using image registration methods that are better suited for targets that can move with respect to surrounding bony anatomy, such as the prostate. / Modern strålterapi av cancer baseras nästan helt på datortomografiska (CT) bilder. CT bilder tas med hjälp av röntgenfotoner, och återger därför hur det avbildade materialet växelverkar med strålning. Denna information används för att utföra noggranna dosberäkningar i ett dosplaneringssystem, och data från CT bilder lämpar sig också väl för att skapa digitalt rekonstruerade röntgenbilder vilka kan användas för att verifiera patientens position vid behandling. Bildgivande magnetresonanstomografi (MRI) har många egenskaper som är intressanta för radioterapi. Mjukdelskontrasten i MR bilder är överlägsen CT, och det är möjligt att i stor utstäckning variera sekvensparametrar för att synliggöra olika anatomiska och funktionella attribut hos ett organ. Dessa bägge egenskaper kan bidra till ökad noggrannhet i strålbehandling av cancer. Att använda enbart MR bilder som planeringsunderlag för radioterapi är dock problematiskt. MR data reflekterar magnetiska attribut hos protoner, och har därför ingen koppling till materialets egenskaper då det gäller strålningsväxelverkan. Dessutom är det komplicerat att avbilda ben med MR; ben uppträder som områden av signalförlust i bilderna, på samma sätt som luft gör. Detta gör det svårt att utföra noggranna dosberäkningar och positionera patienten vid behandling. Många moderna kliniker använder redan idag MR tillsammans med CT under dosplanering. Bilderna registreras till ett gemensamt koordinatsystem i en process som kallas bildfusion. I dessa fall används MR bilderna primärt som underlag för utlinjering av tumör, eller target, och CT bilderna används som grund för dosberäkningar. Denna metod är dock inte ideal, då bildregistreringen kan införa systematiska geometriska fel i behandlingen. Detta på grund av att tumörer ofta är fria att röra sig relativt patientens skelett och yttre kontur, och många bildregistreringsalgoritmer tar hänsyn till hela bildvolymen. Arbetet som presenteras i denna avhandling syftar till att undersöka möjligheterna med arbetsflöden som baseras helt på MR data utan bildregistrering, samt arbetsflöden som använder bildregistrerings-algoritmer som är bättre anpassade för tumörer som kan röra sig i förhållande till patientens övriga anatomi, som till exempel prostatacancer.

Ischaemic stroke is a complex disorder with many different aetiologies, but previous studies of stroke often did not differentiate aetiological subtypes of ischaemic stroke. However, different stroke subtypes may have different risk factors, and to target preventive treatments more effectively, we need to understand these associations. I studied the association of established vascular risk factors with different aetiological stroke subtypes in population-based cohorts of stroke patients. I studied Diffusion Weighted Magnetic Resonance Imaging (DWI) in patients with subacute minor stroke and TIA to determine whether DWI may be a useful addition to the management of such patients, and whether it may be a useful tool in future epidemiological studies of stroke. To determine whether carotid anatomy may be a risk factor for large vessel atheroma I studied angiographical data from the European Carotid Surgery Trial. My main findings are that the prevalence of risk factors differs between stroke subtypes. It also differs between hospitalised and non-hospitalised patients, highlighting that risk factor studies should be performed in population-based cohorts. Analysis of family history data suggests that future genetic studies may best be targeted at non-cardioembolic stroke and at younger patients, and that genetic studies of hypertension may help to unravel some of the genetic factors contributing to stroke risk. DWI is sensitive in subacute minor stroke, and inter- and intra-observer reproducibility are high. DWI frequently adds useful information and may influence patient management. More widespread use of DWI in patients with subacute stroke and TIA should be considered, and DWI may also be a useful tool in future epidemiological studies of stroke. Carotid anatomy varies considerably between individuals, is very asymmetrical within individuals, and it differs between men and women. These findings may partly explain differences in plaque development between individuals, asymmetrical plaque formation within individuals, and sex differences in the distribution of carotid plaque and in the prevalence of carotid atheroma in the general population. Carotid anatomy may be a risk factor for local plaque development. Although not amenable to treatment, knowing which anatomical configuration is associated with atheroma formation could help to identify high-risk individuals in whom other risk factors should be treated aggressively.

Reliving the past requires the integration of multi-modal sensory details into a coherent mental impression of the initial event. In most people, memory for life episodes, or Autobiographical Memory (AM), is rich in sensory-perceptual elements that provide the vivid impression of travelling back in time. Abundant evidence indicates that the hippocampus plays a central role in AM recollection, but much research is still needed to determine which AM attributes engage the hippocampus at retrieval. My work assessed the relationship between hippocampal function and the perceptual richness of memory episodes. I designed a paradigm that captured the complexity of AM, and that manipulated perceptual richness while controlling for other AM confounds, such as recency, rehearsal, personal relevance, and “story” content. Participants studied and recalled perceptually enriched and impoverished laboratory events (film clips and written narratives, respectively) matched for the complexity of their storyline. An AM condition was also included for comparison. I tested healthy individuals and participants with unilateral medial temporal lobe epilepsy (mTLE), a clinical population with well documented hippocampal damage, on this paradigm. Perceptual richness was greatly reduced in people with mTLE, an effect that was most salient in the perceptually enriched conditions (AM and film clips). In a functional MRI version of this paradigm conducted on healthy individuals, I identified neural regions sensitive to the perceptual richness of AM and laboratory events, which included the anterior portion of the right hippocampus and other regions known to play a role in imagery and visual processing. In patients with right-lateralized mTLE, activation in these brain regions was markedly reduced in all memory conditions, which was consistent with the reduced perceptual richness I observed behaviourally. I reveal a clear relationship between hippocampal function and the perceptual richness of episodic memory, suggesting that the hippocampus plays a central role among brain regions that support the integration of multi-modal details into enriched memory experiences. My findings also advance our knowledge of how pathology and the nature of memory representation affect the neural correlates of episodic memory.

Pulmonary arterial hypertension (PAH) alters pulmonary hemodynamics by changing the vascular wall mechanics. Currently, pulmonary vascular resistance is used clinically to assess the disease. However, the invasive nature of pressure measurements, needed for calculating the resistance, prevents longitudinal monitoring of patients during therapy. This work employs wave reflection as an alternative measure of the downstream stiffness and proposes a new method for wave reflection assessment using only non-invasive phase contrast magnetic resonance (PCMR) flow data. The feasibility of the proposed method was investigated in a numerical model of blood flow in the right pulmonary artery. Furthermore, it was validated experimentally using a flow phantom and compared with an existing invasive technique. Finally, the feasibility of the method was tested in a study of the right pulmonary artery of a volunteer. This approach may provide a non-invasive method to evaluate PAH and its response to therapy.

PURPOSE: The objective was to determine if particular magnetic resonance, clinical and demographic findings were associated with functional status prior to surgery and predictive of functional outcomes at follow-up. RESULTS: The study included 65 consecutive CSM patients. The modified Japanese Orthopaedic Association Scale (mJOA) was used as the primary outcome measure. Higher baseline mJOA scores were associated with younger age, shorter duration of symptoms, fewer compressed segments and less severe cord compression. Better post-operative mJOA scores were associated with younger age, shorter duration of symptoms and higher baseline scores. Using multivariate analysis, baseline and follow-up mJOA scores adjusted for baseline mjOA score were best predicted by age. CONCLUSION: Age and clinical severity scores at admission can both provide valuable information. However, MR imaging features of the spinal cord before surgery cannot accurately predict the functional prognosis for patients with CSM and hence alternative imaging approaches may be required.