Cerebral blood flow and intracranial pulsatility studied with MRI : measurement, physiological and pathophysiological aspects

Sammanfattning: During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects. Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile stress were assessed in healthy elderly. The biomarkers were extracted from invasive CSF pressure measurements as well as 2D PCMRI acquisitions. The volumes of temporal cortex, frontal cortex and hippocampus were negatively related to the magnitude of cardiac-related intracranial pulsatility. Finally, a potentially improved workflow to assess the volume of arterial pulsatility using time resolved, four-dimensional phase contrast MRI measurements (4D PCMRI) was evaluated. The measurements showed good agreement with 2D PCMRI acquisitions. In conclusion, this work showed that 2D PCMRI is a feasible tool to study the pulsatile waveforms of cerebral blood and CSF flow. Conventional views regarding the magnitude and distribution of craniospinal compliance was challenged, with important implications regarding the understanding of how intracranial vascular pulsatility is absorbed. A first counterpoint to previous near-uniform observations of obstructions in the internal jugular veins in multiple sclerosis was provided. It was demonstrated that large cardiac- related intracranial pulsatility were related to smaller volumes of brain regions that are important in neurodegenerative diseases among elderly. This represents a strong rationale to further investigate the role of excessive intracranial pulsatility in cognitive impairment and dementia. For that work, 4D PCMRI will facilitate an effective analysis of cerebral blood flow and pulsatility.