Aims: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation... Show moreAims: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation of iron chelation therapy. Although magnetic resonance imaging (MRI) provides several quantitative measures of brain iron content, none of these have been validated for patients with a severely increased cerebral iron burden. We aimed to validate R 2 * as a quantitative measure of brain iron content in aceruloplasminemia, the most severely iron-loaded NBIA phenotype. Methods: Tissue samples from 50 gray-and white matter regions of a postmortem aceruloplasminemia brain and control subject were scanned at 1.5 T to obtain R 2 * , and biochemically analyzed with inductively coupled plasma mass spectrometry. For gray matter samples of the aceruloplasminemia brain, sample R 2 * values were compared with postmortem in situ MRI data that had been obtained from the same subject at 3 T - in situ R 2 * . Relationships between R 2 * and tissue iron concentration were determined by linear regression analyses. Results: Median iron concentrations throughout the whole aceruloplasminemia brain were 10 to 15 times higher than in the control subject, and R 2 * was linearly associated with iron concentration. For gray matter samples of the aceruloplasminemia subject with an iron concentration up to 1000 mg/kg, 91% of variation in R 2 * could be explained by iron, and in situ R 2 * at 3 T and sample R 2 * at 1.5 T were highly correlated. For white matter regions of the aceruloplasminemia brain, 85% of variation in R 2 * could be explained by iron. Conclusions: R 2 * is highly sensitive to variations in iron concentration in the severely iron-loaded brain, and might be used as a non-invasive measure of brain iron content in aceruloplasminemia and potentially other NBIA disorders. Show less
Bulk, M.; Abdelmoula, W.M.; Nabuurs, R.J.A.; Graaf, L.M. van der; Mulders, C.W.H.; Mulder, A.A.; ... ; Weerd, L. van der 2018
The prevalence of aortic dilation and related complications as rupture and dissection is higher in patients with a bicuspid aortic valve (BAV) as compared to patients with a tricuspid aortic valve ... Show moreThe prevalence of aortic dilation and related complications as rupture and dissection is higher in patients with a bicuspid aortic valve (BAV) as compared to patients with a tricuspid aortic valve (TAV), although not every individual carries this increased risk. It is therefore essential to identify those patients who are less susceptible for aortic wall pathology, as preventive ascending aortic surgery would not be necessary in this group. Since aortic diameter as a criterion for surgery is only decisive at population level, it would be very valuable to have tailored risk stratification at patient level. The purpose of this thesis was therefore to investigate the possibility to identify patients with BAV, without apparent dilation, with an increased susceptibility for future complications as aortic dilation and dissection. Furthermore the biological mechanism underlying aortic wall pathology in BAV was compared to a known genetically determined syndrome with an increased risk of aortopathy being Marfan syndrome. Show less
T2*-weighted imaging provides a non-invasive means to study susceptibility changes of substances such as myelin and iron in the brain. Particularly, phase images show an increased sensitivity to... Show moreT2*-weighted imaging provides a non-invasive means to study susceptibility changes of substances such as myelin and iron in the brain. Particularly, phase images show an increased sensitivity to magnetic susceptibility differences with increased field strengths. The primary goal of the thesis was to develop methods for quantitative analysis of human brain T2*-weighted images at ultrahigh field strength. Additionally, it was also aimed to investigate the use of textural features derived from whole-brain deformation field for classification of Alzheimer__s disease (AD). A framework for the detection of between-group textural differences in 7T T2*-weighted magnitude and phase images of subcortical structures was presented, and its application was demonstrated in Huntington__s disease. A novel algorithm for segmentation of the cerebral cortex from 7T T2*-weighted images was proposed and extensively validated. Subsequently, a highly automated method was proposed for quantification of regional changes in these images in terms of gray matter/white matter contrast and cortical profile. In addition to an analysis of aging effect using data of young and elderly healthy subjects, this method was also applied to compare early- and late- onset AD patients. The analysis techniques presented in this thesis can be useful tools for susceptibility studies using ultrahigh field MR images Show less
Paus, R.A. de; Crevel, R. van; Beek, R. van; Sahiratmadja, E.; Alisjahbana, B.; Marzuki, S.; ... ; Vosse, E. van de 2013
