When studying for a doctoral degree (PhD), candidates submit a thesis that provides a critical review of the current state of knowledge of the thesis subject as well as the student’s own contributions to the subject. The distinguishing criterion of doctoral graduate research is a significant and original contribution to knowledge.
Once accepted, the candidate presents the thesis orally. This oral exam is open to the public.
There is increasing recognition that a deeper understanding of veins can provide important information about cerebral physiology and brain function in health and disease. The deoxyhemoglobin (dHb) in veins provides an important source of contrast for Magnetic Resonance Imaging (MRI). It can be used non-quantitatively via the Blood Oxygen-Level Dependent (BOLD) signal, or it can be used to extract quantitative biomarkers. This is because the paramagnetic properties of dHb causes local magnetic field distortions in and around blood veins, leading to phase shifts which are used in Quantitative Susceptibility Mapping (QSM) to reconstruct the susceptibility difference between veins and surrounding tissue. Furthermore, the susceptibility in each venous voxel is directly related to the Oxygen Extraction Fraction (OEF) and the Cerebral Metabolic Rate of Oxygen (CMRO2) through Fick’s principle. However, in the BOLD signal, we are mainly interested in dHb in capillaries, so dHb on draining veins generates uncertainty in the exact location of brain activity and biases the amplitude of the response measured. This may also influence BOLD derived connectivity measures.
This Ph.D. thesis consists of three original studies primarily investigating location and bias of veins as well as vascular and metabolic changes in individuals with higher risk of developing Alzheimer’s Disease (AD). In study one, the first normative 7 Tesla (T) Venous Neuroanatomy (VENAT) atlas was created from young healthy participants for future comparisons in aging and disease. In the second study, I investigated the influence of draining veins on different resting-state derived measures. Models were generated to predict the venous bias on six resting-state (rs) derived connectivity measures. In the final manuscript, I studied vascular and metabolic changes in individuals with genetic higher (Apolipoprotein E (ApoE) ɛ4) and lower risk (ApoE ɛ3) of developing AD. Individuals with ApoE ɛ4 showed, significant larger diameters and lower OEF in the Grey Matter (GM), as well as higher Cerebral Blood Flow (CBF) and CMRO2. Together, these studies unraveled new insights on the spatial organization of the neurovasculature, its influence on functional brain imaging and its relationship to AD risk factors.