High-resolution phase-contrast magnetic resonance imaging can now assess flow in proximal and distal cerebral arteries. The aim of this study was to describe how total cerebral blood flow (tCBF) is distributed into the vascular tree with regard to age, sex and anatomic variations. Forty-nine healthy young (mean 25 years) and 45 elderly (mean 71 years) individuals were included. Blood flow rate (BFR) in 21 intra-and extracerebral arteries was measured. Total cerebral blood flow was defined as BFR in the internal carotid plus vertebral arteries and mean cerebral perfusion as tCBF/brain volume. Carotid/vertebral distribution was 72%/28% and was not related to age, sex, or brain volume. Total cerebral blood flow (717 ± 123 mL/min) was distributed to each side as follows: middle cerebral artery (MCA), 21%; distal MCA, 6%; anterior cerebral artery (ACA), 12%, distal ACA, 4%; ophthalmic artery, 2%; posterior cerebral artery (PCA), 8%; and 20% to basilar artery. Deviating distributions were observed in subjects with 'fetal' PCA. Blood flow rate in cerebral arteries decreased with increasing age (P o 0.05) but not in extracerebral arteries. Mean cerebral perfusion was higher in women (women: 61 ± 8; men: 55 ± 6 mL/min/100 mL, P o 0.001). The study describes a new method to outline the flow profile of the cerebral vascular tree, including reference values, and should be used for grading the collateral flow system.

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [ 11 C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRIbased resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.dopamine | memory | hippocampus D opamine (DA) plays a key role in several cognitive processes (1-4). Reductions of D1 and D2 DA receptors (D1DRs and D2DRs) in aging (5-7) have been linked to agerelated cognitive deficits (8, 9). The D1DR system has been related to functions supported by the prefrontal cortex (PFC), such as working memory and executive functions (10-12), which may reflect the relatively high density of D1DRs in the PFC (13). However, the role of D2DRs is far less clear. D2DRs are present in the PFC at very low densities (13), and evidence supporting a role for the D2DR system in working memory and executive functions is elusive (10). Pharmacological (14, 15) and PET studies assessing striatal D2DR availability (or binding potential to nondisplacable tissue uptake; BP ND ) with [ 11 C]raclopride (16, 17) have yielded mixed findings in relation to cognition. It has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions (10,18,19). Supporting these claims, positive links between D2DR BP ND and episodic memory are commonly observed (20-23). PET imaging of hippocampal D2DR BP ND also provides support for this hypothesis, although some studies indicate that hippocampal D2DRs may be related to both episodic memory and PFC-based executive functions (22, 23), including verbal working memory (24). Medial temporal lobe regions have been implicated in working memory (25,26), and D2DR-mediated modulation may be exerted via hippocampal-cortical pathways (27). In addition, a [ 11 C]raclopride task-activation PET study demonstrated contributions of striatal D2DRs to a verbal working-memory task (11).Taken together, the specific role of the D2DR system in cognition remains unclear, likely due to the fact that past studies included small and age-hetero...

Purpose: To study measurement repeatability and physiological determinants on measurement stability for phase contrast MRI (PC-MRI) measurements of cyclic volume changes (DV) of brain arteries, veins, and cerebrospinal fluid (CSF) compartments. Materials and Methods:Total cerebral blood flow (tCBF), total internal jugular flow (tJBF) and spinal CSF flow at C2-C3 level and CSF in the aqueduct was measured using five repetitions in 20 healthy subjects. After subtracting net flow, waveforms were integrated to calculate DV of arterial, venous, and cerebrospinal fluid compartments. The intraclass correlation coefficient (ICC) was used to measure repeatability. Systematic errors were investigated by a series of phantom measurements.Results: For DV calculated from tCBF, tJBF and both CSF waveforms, the ICC was !0.85. DV from the tCBF waveform decreased linearly between repetitions (P ¼ 0.012). Summed CSF and venous volume being shifted out from the cranium was correlated with DV calculated from the tCBF waveform (r ¼ 0.75; P < 0.001). Systematic errors increased at resolutions <4 pixels per diameter.Conclusion: Repeatability of DV calculated from tCBF, tJBF, and CSF waveforms allows useful interpretations. The subject's time in the MR system and imaging resolution should be considered when interpreting volume changes. Summed CSF and venous volume changes was associated with arterial volume changes.

Excessive pulsatile flow caused by aortic stiffness is thought to be a contributing factor for several cerebrovascular diseases. The main purpose of this study was to describe the dampening of the pulsatile flow from the proximal to the distal cerebral arteries, the effect of aging and sex, and its correlation to aortic stiffness. Forty-five healthy elderly (mean age 71 years) and 49 healthy young (mean age 25 years) were included. Phase-contrast magnetic resonance imaging was used for measuring blood flow pulsatility index and dampening factor (proximal artery pulsatility index/distal artery pulsatility index) in 21 cerebral and extra-cerebral arteries. Aortic stiffness was measured as aortic pulse wave velocity. Cerebral arterial pulsatility index increased due to aging and this was more pronounced in distal segments of cerebral arteries. There was no difference in pulsatility index between women and men. Dampening of pulsatility index was observed in all cerebral arteries in both age groups but was significantly higher in young subjects than in elderly. Pulse wave velocity was not correlated with cerebral arterial pulsatility index. The increased pulsatile flow in elderly together with reduced dampening supports the pulse wave encephalopathy theory, since it implies that a higher pulsatile flow is reaching distal arterial segments in older subjects.

Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.Methods: Eleven healthy adult volunteers (age 46±10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head down tilt (HDT). The trans-lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from MRI and were used to adjust for hydrostatic effects. Results:The TLCPD (mm Hg) between IOP and ICP was 12.3±2.2 for supine, 19.8±4.6 for sitting and 6.6±2.5 for HDT. The expected 24-hour average TLCPD on earthassuming 8 h supine and 16 h upright-was estimated to be 17.3 mm Hg. By removing the hydrostatic effects on pressure, a corresponding 24 h-average TLCPD in microgravity environment was simulated to be 6.7 mmHg. Interpretation:We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma.