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
The aim of this thesis was to explore the relation between visceral obesity and the accompanying metabolic disturbances, systemic inflammation and the atherosclerotic process. A newly developed... Show moreThe aim of this thesis was to explore the relation between visceral obesity and the accompanying metabolic disturbances, systemic inflammation and the atherosclerotic process. A newly developed magnetic resonance vessel wall imaging technique was implemented in phenotyping patients and as a therapeutic endpoint in a randomised controlled setting. A three step approach was chosen for this purpose. First, the magnetic resonance black blood vessel wall imaging technique at the magnetic field strength of 3 Tesla was developed and validated. Secondly, phenotyping of viscerally obese subjects was performed with special attention for the role of systemic inflammation and atherosclerosis. Finally, in the setting of a randomised controlled trial, the impact of reducing visceral obesity and systemic inflammation with lifestyle intervention and rosiglitazone treatment (PPARg agonist) on the progression of atherosclerosis was assessed. Show less
The main objective of the current thesis is to assess aortic wall elasticity and aortic dimensions and their impact on aortic valve competence and LV function in patients with a bicuspid aortic... Show moreThe main objective of the current thesis is to assess aortic wall elasticity and aortic dimensions and their impact on aortic valve competence and LV function in patients with a bicuspid aortic valve, transposition of the great arteries, tetralogy of Fallot and patients after the Ross procedure, with the use of MRI. In addition, MRI was also used to test whether a similar interaction is present between pulmonary artery dynamics and the right ventricle in the above mentioned entities. Chapter 2 reviews the 5 most common entities of inherited connective tissue disorders and classical congenital heart disease with intrinsic aortic wall abnormalities, with description of the potential role of MRI in their evaluation and management. Chapter 3 describes in vivo validation, as well as testing of reproducibility of aortic pulse wave velocity as assessed with MRI, as indicator of aortic elasticity. Chapter 4 studies aortic elasticity, aortic valve competence and LV function in non-stenotic bicuspid aortic valve patients. Chapters 5 and 6 describe aortic elasticity, aortic valve competence and LV function, and the results of pulmonary flow dynamics in relationship with right ventricular function in patients after the arterial switch operation, respectively. Chapter 7 addresses aortic dimensions and elasticity in conjunction with aortic valve and LV function in patients with repaired tetralogy of Fallot after pulmonary valve replacement. Chapter 8 describes the outcome of patients who have previously undergone the Ross procedure in our institution for a dysfunctioning aortic valve. Chapter 9 studies aortic elasticity, aortic valve competence and LV function in patients after the Ross procedure. Finally, Chapter 10 describes the results of pulmonary flow dynamics in relationship with right ventricular function in patients after the Ross procedure. In Chapter 11 all studies presented in this thesis are summarized and future directions are discussed. Show less
Early dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing... Show moreEarly dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing, but this is not directly visible from the outside. Many research is aimed at discovering early disease markers. However, research using EEG registration during conventional eyes closed conditions revealed little additional information. The yield of EEG research can be improved by probing the weakest spot, which, in case of dementia, is memory. Karin van der Hiele introduced memory tests during EEG registration and found that early abnormalities in brain functioning can then be observed in Alzheimer’s disease and Huntington’s disease. An interesting finding came to light: the EEG in dementia displays a lot of muscle activity which is normally filtered out. However, the researchers decided not to throw this activity away but to measure it. Interestingly, they found that the amount of muscle activity was related to cognition and to the number of depressive complaints. It may pay to keep an open mind regarding the nature of the parameter to be measured. Show less
Wall shear stress (WSS) exerted by flowing blood at the vessel wall, is defined as the velocity gradient at the vessel wall times the blood viscosity. Low WSS is related to atherosclerotic risk... Show moreWall shear stress (WSS) exerted by flowing blood at the vessel wall, is defined as the velocity gradient at the vessel wall times the blood viscosity. Low WSS is related to atherosclerotic risk profiles and WSS is low or oscillating at locations where plaque development is observed. In vivo cross-sectional images of blood flow suffer from limited resolution and lack of info on local viscosity. However, WSS can be assessed by modeling of velocity profiles and blood viscosity. Already with a first approximation of velocity profiles by an imprecise model, such as a paraboloid, and under the assumption of a constant (average) human blood viscosity, correlations between various cardiovascular risk factors and WSS were found. Also the effect of treatment with pravastatin on WSS has been demonstrated with this model. The more detailed the model, the more accurate WSS can be assessed. An accurate 4D WSS assessment can be obtained by application of a so-called Finite Element Method (FEM) calculation. Blood velocity was simulated for a certain vessel segment. A model of the vessel geometry composed of bricks (a so called mesh) was created in order to simulate the blood flow. Show less
Aging of the brain was studied by comparing follow-up MRI scans in 554 persons aged 70-82 years. Mean interval time between these scans was three years and scans were looked for changes in cerebral... Show moreAging of the brain was studied by comparing follow-up MRI scans in 554 persons aged 70-82 years. Mean interval time between these scans was three years and scans were looked for changes in cerebral infarcts, white matter lesions, cerebral blood flow, and brain volume. Besides this, the preventive effect of pravastatin on these changes was studied. During the study time there was progression of cerebral infarcts, white matter lesions and there was decline of cerebral blood flow and progression of brain atrophy. Treatment with pravastatin 40 mg/daily did not have a protective effect on these changes. Show less
Ischemic heart disease remains the leading cause of morbidity and mortality in the Western world. Ischemic cardiomyopathy is a frequent cause of chronic heart failure and has become a major problem... Show moreIschemic heart disease remains the leading cause of morbidity and mortality in the Western world. Ischemic cardiomyopathy is a frequent cause of chronic heart failure and has become a major problem in clinical cardiology. In recent years, magnetic resonance imaging (MRI) has been applied increasingly, in the evaluation of patients with CAD. A comprehensive cardiac MRI study including assessment of myocardial perfusion, myocardial function, both at rest and under stress, and delayed contrast-enhancement for myocardial viability imaging, and coronary magnetic resonance angiography for detecting stenosis can now be performed in a relatively short time. Therefore, MRI can be used to evaluate most aspects of the ischemic cascade. Moreover, MRI provides additional information for the surgeon needed to select the optimal surgical strategy, for instance including information on left and right ventricular function, the presence of aneurysms and ischemic mitral regurgitation. The aim of this thesis was to evaluate magnetic resonance imaging (MRI) techniques for the assessment of myocardial viability in patients with acute and chronic myocardial infarction. In addition, remodeling of the ventricles was investigated and evaluated. Show less
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19.... Show moreCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. Magnetic resonance (MR) imaging plays an important role in the diagnostic work-up of CADASIL patients. In this thesis we describe the presence of microbleeds and a new, highly characteristic radiological finding in CADASIL patients, the so called subcortical lacunar lesions (SLL). We describe the natural history of the various brain lesions that can be observed in CADASIL patients, the microbleeds, SLL, lacunar infarcts, and white matter hyperintensities (WMHs). Also included are the results of a study on the differences of the lesions seen in CADASIL as compared to the lesions that occur in multiple sclerosis, a disease with radiological and clinical similarities to CADASIL. We found that MR lesions develop in a predictable way during the course of the disease and that SLL and WMHs in the anterior temporal lobe are helpful radiological hallmarks for the of detection CADASIL. The WMHs in the anterior lobe especially in combination with one of the other CADASIL MR hallmarks should distinguish CADASIL patients from patients with multiple sclerosis. Show less
