Brain function has long been the realm of philosophy, psychology and psychiatry and since the mid 1800s, of histopathology. Through the advent of magnetic imaging in the end of the last century, an... Show moreBrain function has long been the realm of philosophy, psychology and psychiatry and since the mid 1800s, of histopathology. Through the advent of magnetic imaging in the end of the last century, an in vivo visualization of the human brain became available. This thesis describes the development of two unique techniques, imaging of diffusion of water protons and manganese enhanced imaging, that both allow for the depiction of white matter tracts. The reported studies show, that these techniques can be used for a three-dimensional depiction of fiber bundles and that quantitative measures reflecting fiber integrity and neuronal function can be extracted from such data. In clinical applications, the potential use of the developed methods is illustrated in human gliomas, as measure for fiber infiltration, and in spinal cord injury, to monitor potential neuroprotective and __regenerative medication. Show less
CADASIL is a hereditary cerebral small vessel disease, caused by a mutation in the NOTCH3 gene, leading to migraine with aura, cerebrovascular accidents and cognitive decline at young to middle... Show moreCADASIL is a hereditary cerebral small vessel disease, caused by a mutation in the NOTCH3 gene, leading to migraine with aura, cerebrovascular accidents and cognitive decline at young to middle adult age. MRI scans of the brain may show lacunar infarcts, white matter lesions and microbleeds. In this thesis MRI scans of the brains are used to investigate the disease course in CADASIL. It is shown that lacunar infarcts, white matter lesions and microbleeds are progressive in CADASIL patients. Vascular risk factors are not associated with rate of progression of these MRI abnormalities. However, the rate of disease progression can be predicted by measuring the amount of MRI abnormalities at baseline. Lacunar infarcts, microbleeds and increased white ventricular volume are strongly associated with cognitive decline in CADASIL. Progression of white matter hyperintensities can be predicted by measurements of cerebrovascular reactivity. Using high-field MRI we demonstrated that luminal diameters of lenticulostriate arteries are normal in CADASIL, and that lacunar infarcts in CADASIL are not the result of luminal narrowing of these vessels. High-field MRI also showed that CADASIL patients have an increased diffuse iron deposition in the putamen and caudate nucleus of the brain. Show less
This thesis evaluates the relationship between structural and functional aortic vessel wall alterations and end-organ damage in cross-sectional patient studies with use of MRI. These studies show... Show moreThis thesis evaluates the relationship between structural and functional aortic vessel wall alterations and end-organ damage in cross-sectional patient studies with use of MRI. These studies show that aortic pulse wave velocity (PWV) in DM1 patients is mainly determined by hypertension, whereas the effect of DM1 itself on aortic PWV is marginal. Increased aortic PWV in patients with hypertension is associated with aortic and carotid vessel wall alterations. Also, increased aortic PWV is associated with cardiac as well as cerebral damage both in hypertensive and DM1 patients. Furthermore, this thesis describes and evaluates the ability of more optimized cardiac MRI-techniques for assessment of cardiovascular disease. Right coronary artery flow can be accurately and reproducibly assessed using 3T VE MRI in healthy control subjects. Furthermore, the use of standardized 7T MRI protocols for assessment of LV volumes, function and flow provides similar quantitative results when compared to 1.5T MRI. Finally, 3D three-directional VE MRI better describes LV diastolic function as compared to 2D one-directional VE MRI in patients with ischemic heart failure. Show less
The general objective of this thesis was to investigate whether early clinical alterations and structural and functional brain markers could be detected in carriers of the Huntington__s disease... Show moreThe general objective of this thesis was to investigate whether early clinical alterations and structural and functional brain markers could be detected in carriers of the Huntington__s disease gene (referred to as carriers) who are still without manifest motor signs. We aimed to detect brain deficits using MRI and found smaller basal ganglia volumes in carriers compared to non carriers. Also, we demonstrated an increased amount of hypointensities in basal ganglia of carriers and suggested this may reflect excessive iron deposition. Furthermore, we showed strong associations between MRI characteristics and clinical variables suggesting that a combination of these measures may shed more light on the contribution of different kinds of pathological processes to the changing phenotype. When using memory activation during EEG registration early funcional brain changes, reflected in reduced alpha power, could be demonstrated in carriers. Furthermore, remarkably strong associations were found between the P3 Event-Related Potential and basal ganglia volumes. Subtle clinical abnormalities in motor function, executive function and memory could be demonstrated in carriers, especially over time. This study showed that several biomarkers provide new and important information on premanifest HD. The mulitfactorial approach offers new insights into the relation between clinical phenomena and abnormalities in the neural substrate Show less
Onderzocht werd of het mogelijk was om met MRI de maagfysiologie op non-invasieve wijze te onderzoeken. Allereerst werd de MRI gevalideerd met de barostatmethode, waarna de fysiologie van de maag... Show moreOnderzocht werd of het mogelijk was om met MRI de maagfysiologie op non-invasieve wijze te onderzoeken. Allereerst werd de MRI gevalideerd met de barostatmethode, waarna de fysiologie van de maag werd onderzocht bij gezonde proefpersonen. Dit bleek betrouwbare resultaten op te leveren. Hierna is een groep gezonden vergeleken met een groep pati_nten met functionele dyspepsie. Met MRI bleken verschillen tussen deze twee groepen duidelijk waarneembaar te zijn. In het laatste deel werd de werking van somatostatine op de maagfysiologie bij gezonden en bij patienten met functionele dyspepsie onderzocht. Met MRI bleek ook hier een effect van somatostatine aantoonbaar te zijn. Er werd geconcludeerd, dat het MRI goed mogelijk is om de maagfysiologie en het effect van medicamenten op de maagfysiologie op non-invasieve wijze te onderzoeken. Show less
This thesis describes the cost-effictiveness study and several substudies, using the same patient population. In chapter 2 we assessed the effectiveness of MR imaging in selecting patients with... Show moreThis thesis describes the cost-effictiveness study and several substudies, using the same patient population. In chapter 2 we assessed the effectiveness of MR imaging in selecting patients with nonacute knee symptoms for arthroscopy of the knee. In chapter 3 we discuss effectiveness and costs of MR imaging triaging these patients. In chapter 4 we determine in patients with nonacute knee symptoms and normal standardized physical examination the fraction of MR imaging studies showing arthroscopically treatable intraarticular pathology, thus evaluating whether one safely can refrain from MR imaging. In chapter 5 we discuss whether radiographs are needed when MR imaging is performed for nonacute knee symptoms anyway. The impact of bone bruise on presentation and short term course of knee complaints and the relation between bone bruise and (peri-)articular derangement is assessed in chapter 6. Show less
The objective of this thesis was to elucidate whether migraine is a true and independent risk factor for brain lesions. We summarized migraine symptoms, diagnostic criteria, epidemiologic data, and... Show moreThe objective of this thesis was to elucidate whether migraine is a true and independent risk factor for brain lesions. We summarized migraine symptoms, diagnostic criteria, epidemiologic data, and assumed pathophysiology. We described the existing literature on the relationship between migraine and ischemic stroke and cerebral white matter lesions (WML). The findings of the population-based CAMERA MRI-study are reported. Posterior circulation (cerebellar) infarcts occurred in 8% of migraineurs with aura (adjusted-OR 13.7). Female migraineurs were at increased risk of high-deep-WML-load (OR 2.0). Risks increased with attack frequency, suggestive of a causal relationship. We detailed on the infarcts and other infratentorial lesions. Findings of higher iron-concentration in deep brain nuclei in younger migraineurs suggest that repeated migraine attacks are associated with changes in regions known to be involved in central pain processing and migraine pathophysiology. In addition, we showed that migraineurs had more syncope-related autonomic-nervous-system symptoms, and we identified frequent syncope and orthostatic insufficiency as independent risk factors for high-DWML-load. With these data, there is now strong evidence that migraine is indeed an independent risk factor for silent brain lesions. The real extent of brain injury in migraine patients in the general population is likely underestimated. Show less
This thesis contains the results of imaging of adult zebrafish by using different MR approaches. We present the first high resolution mMR images of adult zebrafish. To achieve high spatial... Show moreThis thesis contains the results of imaging of adult zebrafish by using different MR approaches. We present the first high resolution mMR images of adult zebrafish. To achieve high spatial resolution we used a magnetic field of 9.4T, in combination with strong magnetic field gradients (1000 mT/m) and specialized radio frequency coils. To support imaging of living fish, we designed a special flow-through setup for continuous flow of aerated water to support living zebrafish inside the magnet. Clear morphological proton images were obtained by T2-weighted RARE sequences revealing many anatomical details in the entire intact zebrafish in vivo. We successfully implemented MRS at 9.4T and obtained for the first time detailed composition of zebrafish brain in vivo. Our results in this thesis suggest that zebrafish brain has similar metabolite profile as the human brain, which proves that zebrafish is a go od model organism to study human brain disorders. This thesis demonstrates also the application of high resolution mMRI methods to track spontaneous tumors in stable transgenic zebrafish models expressing a RAS oncoprotein and lacking P53 (mitf:Ras::mitf:GFP X p53-/-). Tumors were successfully visualized at different locations in live zebrafish. Show less
