Assessing brain hemodynamics using Arterial Spin Labeling.

The amount of oxygen that is extracted in the brain depends on the perfusion
pressure in the brain tissue. In cerebrovascular diseases this perfusion
pressure decreases. As a first reaction, the brain expands its vessels. When
this is not sufficient the brain tissue extracts more oxygen than normal. Two
parameters are used to describe this phenomenon; the Cerebrovascular Reactivity
(CVR) and the Oxygen Extraction Fraction (OEF).
The CVR tells us how much brain vessels can dilate. The OEF tells us how much
oxygen gets extracted from the blood. Both parameters are used to describe the
severity of a cerebrovascular disease.
Vessels dilate when there is a higher concentration of carbondioxide in the
blood. Arterial Spin Labeling (ASL) MRI enables us to measure perfusion in the
brain tissue. Combining ASL MRI with an increase in concentration of
carbondioxide enables us to measure the increase in perfusion, called the CVR.
The safest way to administer a higher carbondioxide concentration is with the
Respiract device. This is a device which delivers accurately a preset
carbondioxide-and oxygen concentration. This device can as well be used to
measure the OEF using a newly developed ASL technique.
Combining both parameters, the CVR and the OEF, enables us to get an insight in
the hemodynamics of brain tissue in individual patients.

This research consists of two parts.
In the first part we want to assess the the safety and feasibility of a
CO2-challenge in 20 healthy volunteers. At this time MRI sequences and the scan
protocol will be optimized as well.
After assessing the safety and feasibility of this CO2-challenge in healthy
volunteers we will report back to the METC before starting the second part of
this research.
In the second part of this research the CVR and the OEF will be measured in
patients with a cerebrovascular disease and in a healthy control group. The CVR
and OEF measured in the different patient populations will be compared with the
healthy control group.

This is a single center prospective study which consists of two parts and will
be performed in the UMC Utrecht.

In part 1 we will test the feasibility and safety of a CO2-challenge in 20
healthy volunteers. Furthermore, in these volunteers we will optimize the
sequences and the scan protocol in order to make sure the amount of
CO2-challenges is minimized were possible. After having finished this part of
the protocol we will report back to the METC before progressing to the
following part.

In part 2 the optimized scan protocol will be applied in 40 patients with
asymptomatic extracranial vascular disease (stenosis of 70-100%), 40 patients
with symptomatic extracranial vascular disease (stenosis of 70-100%) and 40
patients with symptomatic occlusion of the middle cerebral artery. In order to
compare our findings in these 3 patients groups with a healthy control group we
will apply the same scan protocol in a group of 40 healthy volunteers.

All subjects will be exposed to a CO2- challenge during an ASL MRI research in
which the CVR and OEF will be measured.
During this research 6 blocks of increased CO2-concentration will be
administered. The maximum duration of each block will be 3 minutes and this
will be interleaved by a block of normal air supply with a duration of minimum
3 minutes. The CO2-pressure will be increased to a maximum of 50 mmHg and this
in combination with a minimum O2-pressure of 100 mmHg.

The controlled gas breathing requires a closed breathing system. Therefore,
subjects have to breath through a mask. Further, CO2 end-tidal levels of 50
mmHg can induce an increased breathing frequency due to physiological stress.
However, end-tidal levels of 30-50 mmHg CO2 are within physiological ranges and
are experienced repeatedly by most people over the day. If patients experience
discomfort because of high arterial CO2 levels, they can open a valve in the
mask or we can switch immediately to 100% oxygen by pushing the red button on
the front of the gas blender. In the MRI they can squeeze as well the panic
button.
Risks associated with controlled gas breathing of high levels of CO2 are
minimized because the minimum O2 level in the gasses is 10% and the maximum
concentration of CO2 is 10%. The blood gas is controlled by a digitally
controlled gas blender steered by end-tidal blood gas PCO2 and PO2. So, CO2-,
O2- levels and breathing frequency are monitored online. An independent blood
oxygen saturation monitoring will be performed during the MRI measurements with
fingertip pulse oxymetry, respiratory tracking during the MRI exam will be
performed as well.
Before participating in this research all subjects will receive an extensive
explanation about the device and the procedure. When after this explanation a
subject decides to participate in this research, a second extensive explanation
will be given before applying the device. In order to get the subject
accustomed to the device and to the increase in CO2-values, a breathing test
outside the scanner area will be performed. At this time we will also show and
practice with the subject how to open the valve in the mask. When the subject
is positioned on the MRI-table he or she will receive the panic button and will
be able to practice squeezing in it.
The subject will be able to withdraw himself from this research at each moment
in time.
The risk of this research is estimated as minimum excess of negligible risk.