Non-invasive mapping of the Cerebrovascular Reactivity with ASL, BOLD and VASO MRI using different stimuli in young and elderly healthy volunteers

A normally working cerebral hemodynamics is of vital importance for a proper
functioning of the human brain. An altered vascular reserve capacity and
failure of the vascular autoregulation of the brain is thought to be the cause
or a first manifestation of many cerebrovascular diseases. The Cerebrovascular
Reactivity (CVR) is a measure of the vascular reserve capacity of the brain.
For instance, it has been shown that Cerebrovascular Reactivity measurements
can be of prognostic value in the cerebrovascular pathologies like CADASIL.
In order to assess the value of CVR as a diagnostic/prognostic tool, first a
rigorous characterization of the measurement procedure should be performed.
Depending on its definition, CVR can be measured as the change in Cerebral
Blood Flow (CBF), Cerebral Blood Volume (CBV) or blood oxygen content following
the delivery of a stimulus. There are several MRI techniques frequently used in
clinic and research for the measurement of these hemodynamic parameters, namely
ASL, VASO and T2*-weighted imaging (BOLD) for the measurement of CBF, CBV and
blood oxygenation, respectively.
When measuring CVR using these techniques (ASL, BOLD and VASO MRI) a challenge
is needed to provoke a vascular response. There are several paradigms available
for this purpose, including hypercapnia, hypoxemia, breath holding,
administration of pharmacologically active substances (e.g. acetazolamide), and
neuronal activation. The latter can be achieved by carrying out a simple task,
e.g. finger tapping, or visual stimulation.
In summary, there are different possibilities to measure CVR using a
combination of one of the several MRI techniques and stimulus paradigms.
Currently it is unknown how the choice of a particular combination of technique
and vascular challenge affects the detectability of vascular changes. It is
therefore important to investigate the possible effects of this choice on the
measurement of CVR in young subjects versus elderly subjects and establish a
measurement protocol that can be applied in both clinical and research
settings.

The goal of this study is to perform an analysis of the ability of the
different combinations of MRI technique/stimulation delivery to measure the
cerebrovascular reactivity. In this study only the following stimulations will
be used for the activation of the intracerebral vasculature: neuronal
activation (visual stimulation), hypercapnia and hypoxia.
In the third part of this study, we will try to map the cerebrovascular
reactivity curve of CO2 in young healthy adults, while simultaneously
correcting for mean arterial blood pressure changes due to CO2.
In the last part we will study the middle cerebral artery (MCA) diameter
changes due to changes in arterial CO2 levels.

This study is divided into two parts. In the first stage 10 subjects will be
scanned to optimize the scan protocols for the different MRI scan techniques.
In the second part 15 young and 15 elderly subjects will be scanned with three
different MRI scan techniques (ASL, BOLD and VASO) while consecutively exposed
to three different stimuli (visual stimulation (neuronal activation),
hypercapnia and hypoxia). The CVR measurements acquired with different
techniques and under different conditions will be compared and also a
comparison of the results for the different age groups will be done.
Addendum: The third objective of this study is to map the CO2 cerebrovascular
reactivity with CBF measurements with arterial spin labeling MRI.
Addendum II: The fourth objective of this study is to assess weather the MCA
vessel diameter changes due to changes in blood CO2.

The risks for the participants are, as for standard MR scans, negligible. The
only matter of concern is the induction of blood gas changes which might pose a
risk for some subjects, especially the elderly. But because the subjects are
healthy and the induced gas changes are relatively small the risk is also
small. Furthermore in the past our research groups at LUMC have successfully
performed other studies in which similar gas changes were induced and thus have
the appropriate knowledge to perform these experiments.