14 Chapter 1 the brain could subsequently increase the OEF to maintain sufficient CMRO2. At the same time, previous studies have demonstrated extensive structural brain changes after radiotherapy, including cortical thinning59, grey and white matter volume loss60,61, and changes in white matter microstructure62–68. Following this research, it could be hypothesized that these structural changes lead to a decreased number of neurons and synapses and reduced neural communication, causing decreased brain metabolism and subsequently lower OEF. Interestingly, such a differential effect on OEF has already been illustrated in previous dementia research, whereby the effect on OEF varied depending on the type of dementia.69 In patients with vascular cognitive impairment, OEF was increased as a consequence of the vascular damage, while OEF was reduced in patient with Alzheimer’s Dementia most likely due to reduced brain metabolism. This underscores the importance of investigating these hemodynamic brain measures in parallel, as it provides insights into the underlying mechanism of the changes. However, these hemodynamic MRI measures have not yet been assessed in patients with BMs undergoing radiotherapy. As a result, it is still unclear whether and how these measures are influenced by either the presence of the BMs themselves or the subsequent cranial radiotherapy. THESIS OUTLINE In the pursuit of providing optimal care that considers both survival and quality of life, an integrative and multidisciplinary approach is not only essential in clinical practice, but also in research. To ensure patient-centered care, including treatmentshared decision making, thorough research is crucial to pinpoint the frequently occurring side-effects, accurately predict their occurrence in individual patients, and explore various avenues to proactively prevent them. This thesis aims to set the first steps by using a multidisciplinary approach to study radiation-induced brain injury. By simultaneously exploring neurocognitive functioning and the potential value of several potential MRI-biomarkers, this research can advance our understanding and pave the way for improved patient outcomes in the field of BMs radiotherapy. Part I: Neurocognitive functioning in patients with brain metastases The first part of this thesis will investigate neurocognitive functioning in patients with BMs both before and after radiotherapy. The aim is to provide comprehensive individual and group-level results that can deepen our understanding of this impact. By addressing these issues in detail, the hope is to offer insights that can subsequently be used in treatment-shared decision making in this population.
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