Objective: To evaluate the clinically relevant abnormalities as visualized on CT and MR imaging in children with symmetric and asymmetric bilateral sensorineural hearing loss (SNHL), in relation to... Show moreObjective: To evaluate the clinically relevant abnormalities as visualized on CT and MR imaging in children with symmetric and asymmetric bilateral sensorineural hearing loss (SNHL), in relation to age and the severity of hearing loss.Study design: Retrospective cohort study.Setting: Tertiary referral otology and audiology center.Patients and diagnostic interventions: From January 2006 until January 2016, a total of 207 children diagnosed with symmetric and asymmetric bilateral SNHL were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss.Main outcome measures: Radiologic abnormalities associated with SNHL.Results: 302 scans were performed in 207 children (median age of 0.8 years old) with bilateral SNHL. The most frequently identified cause of bilateral SNHL was a malformation of the labyrinth. The combined diagnostic yield of CT and MR imaging was 32%. The diagnostic yield of MR (34%) was considerably higher than that of CT (20%). We found a higher rate of abnormalities in children with profound hearing loss (41%) compared to milder hearing loss (8-29%), and in asymmetric SNHL (52%) compared to symmetric SNHL (30%).Conclusion: Imaging is essential in the etiologic evaluation of children with bilateral SNHL. The highest diagnostic yield is found in children with bilateral asymmetric SNHL or profound SNHL. Based on our findings, MR is the primary imaging modality of choice in the etiological evaluation of children with bilateral SNHL because of its high diagnostic yield. Show less
Preclinical and clinical studies reveal that left-sided breast cancer radiotherapy is associated with an increased rate of major coronary events. Consequently, when irradiating women with left... Show morePreclinical and clinical studies reveal that left-sided breast cancer radiotherapy is associated with an increased rate of major coronary events. Consequently, when irradiating women with left-sided breast cancer, specific measures should be taken to decrease the heart dose as much as possible and to avoid radiation-induced coronary artery disease. This thesis focuses on several strategies to optimise the radiation treatment for patients with left-sided breast cancer. With respect to whole breast irradiation we concluded that: __ the routine use of MR images in addition to the CT scan, when delineating either the glandular breast tissue or the lumpectomy cavity, does not have added value. __ tangential IMRT technique combined with a breath-hold technique should be the treatment technique of choice for left-sided breast cancer. __ a breath-hold technique should and can be used in all left-sided breast cancer patients, regardless of age and breast size. __ breath-hold in left-sided whole breast radiotherapy results in a less pronounced increase of coronary calcium score and, hence, could result in less radiation-induced cardio vascular damage. Show less
Coronary artery disease(CAD) is one of the leading causes of mortality and morbidity worldwide. Clinically, it refers to atherosclerotic changes in the coronary arteries and is usually assessed... Show moreCoronary artery disease(CAD) is one of the leading causes of mortality and morbidity worldwide. Clinically, it refers to atherosclerotic changes in the coronary arteries and is usually assessed with a stress electrocardiogram and conventional coronary angiography(CCA). CCA, however, is an invasive technique and carries a small risk of complications. Non-invasive techniques such as coronary angiography with CT(CTCA), and myocardial perfusion imaging (MPI) with SPECT and MR are therefore used as gatekeeper tests before CCA. These techniques provide valuable information on both the coronary stenoses and their hemodynamic impact on the myocardial function. However, each of these techniques presents only one aspect of CAD. To achieve a higher level of accuracy and precision in CAD assessment, integration of information from different cardiac imaging modalities is essential. The goal of this thesis was therefore to develop techniques to realize this multimodal diagnostic image integration to enhance CAD diagnosis. To this end, we developed novel algorithms for near automated analysis of magnetic resonance based myocardial perfusion images. In addition, we developed and evaluated a new integration framework that allows comprehensive visualization of physiologic information from myocardial perfusion imaging -either with MR or SPECT and anatomical information from CTCA Show less
Currently, the raising awareness of the role of glucocorticoids in the onset of numerous (neuro)-pathologies constitutes the increasing necessity of understanding the mechanisms of action of... Show moreCurrently, the raising awareness of the role of glucocorticoids in the onset of numerous (neuro)-pathologies constitutes the increasing necessity of understanding the mechanisms of action of glucocorticoids in bodily processes and brain functioning. Glucocorticoids mediate their effects by binding to intracellular receptors which act as transcription factors. A remarkable and yet unexplained phenomenon described more than two decades ago, is the cell-specific effects glucocorticoids bring about on gene expression in brain. For example, while glucocorticoids suppress corticotrophin-releasing hormone (CRH) synthesis in the hypothalamus, production of CRH in the central nucleus of the amygdala (CeA) is stimulated by increased hormone levels. Inasmuch as the neuroanatomical distribution of the corticosteroid receptors does not satisfactorily explain these effects, it is of interest to decipher the role of recently discovered coregu lator proteins that modulate the direction and the magnitude of steroid receptor-driven transcription. Therefore, in the current thesis the expression and function of central coregulators was studied: the coactivators SRC1a and SRC1e along with the corepressors N-CoR and SMRT were found to be expressed in brain and involved in regulation of CRH gene expression. Finally, a method that allows detection of coregulator recruitment by steroid receptors in brain tissue was developed. Show less
Glucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the... Show moreGlucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), are ligand-inducible transcription factors. Therefore, changes in gene expression most likely underlie glucocorticoid-mediated genomic effects on neural function. In this thesis, the central aim was to gain more insight into the transcriptional changes that mediate the effects of acutely activated GRs on neural function. Two different biological substrates i.e. ex vivo hippocampal slices and neuronal catecholaminergic PC12 cells, were used to measure the transcriptional response after GR-activation. Using microarrays, an interesting time-dependent pattern of gene transcription was observed, shifting from exclusively downregulated genes 1 hour after GR-activation to both up and downregulated genes 3 hours afterwards. This pattern suggests that the fast genomic effects of glucocorticoids may be realized via transrepression, preceding a later wave of transactivation. Additionally, many new candidate genes were found that could potentially underlie (part of) the effects glucocorticoids mediate on hippocampal and catecholaminergic neuronal function. Hence, these candidate genes can be used to formulate new hypotheses on how glucocorticoids affect neural function and future research should therefore focus on testing these hypotheses. Show less
