Maintaining cerebral blood flow From heart to brain

Brain function depends on a continuous provision of oxygen and nutrients. Interruption of blood supply to the brain for only a few seconds results already in loss of consciousness, emphasizing the need for tight regulation of CBF. Although CBF regulation by cerebrovascular control mechanisms (e.g. mechano- and chemoregulation) is often assumed to be sufficiently efficacious, also vascular patency and maintained cardiac function are considered important to secure blood supply to the brain. For instance, patients with carotid artery occlusive disease or chronic heart failure have a lower CBF and a higher prevalence of cognitive dysfunction. This thesis aims to delineate the human heart-brain connection from a physiological point of view according to three (overlapping) themes. The first part is concerned with the identification of physiological interventions that bring the circulatory system out of balance in a controlled and reproducible manner as well as with the implementation of these interventions in the MRI scanner. The second part addresses quantification of CBF by two different measurementmodalities and part three focuses on the heart-brain connection over the life-span.
Given the findings presented in this thesis we conclude that in healthy individuals CO is important for CBF control, especially when growing older. Since cardiac dysfunction is a feature of the aging population, this underscores the need to better understand, diagnose and treat cardiovascular diseases in relation to the perfusion of the brain and, in turn, cognitive performance. The finding that TCD determined changes in CBFv measured in a large brain-feeding artery do not match those in CBF at the tissue level as quantified with ASL-MRI, calls into question the nature of cerebral perfusion from which implications could be far reaching for either or both measurement modalities.