Feasibility test of a respiratory challenge in the MRI to image the vascularity of the brain and the head and neck area.

Respiratory challenges are used to assess the reactivity of the brain
vasculature to CO2 and O2 or to estimate the reactivity and oxygenation status
of a tumor. The reactivity of brain vasculature is a measure for the severity
of vascular brain diseases. In tumors, the reactivity is a measure of the
maturity of the vasculature and, thereby, of the level of malignancy. Moreover,
the reactivity of the vasculature shows the possibilities for improvement of
the oxygenation during therapy. Further, respiratory challenges can be used to
calibrate Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labelling (ASL)
MRI.
In dynamic CO2 and O2 enhanced MRI, a robust and repeatable challenge is
required to reliably correlate the challenge with the changes in blood flow and
blood oxygenation of the tumour. These respiratory challenges will be
controlled by a gas blender, the RespirAct, which modulates inspiration of O2
and CO2 to achieve a reliable and repeatable gas delivery and thereby arterial
blood gasses. The measurements will be performed at 3T and 7T. At 3T a lot of
experience is developed with brain reactivity measurements with MRI and
functional MRI of head and neck tumors. Since the availability of 3T scanners
is high, the tests might be easier repeated in other hospitals. At 7T, the
magnitude of expected changes will be larger. Therefore, more subtle changes
might appear on a 7T measurement.

The primary objective is to test the feasibility of MRI measurements at 3T and
7T under dynamic hypercapnic or hyperoxic conditions controlled by digitally
regulated respiratory challenges in volunteers.

This is a pilot study that will test the feasibility of the application of,
first, a respiratory challenge and, second, a respiratory challenge during an
MRI measurement at 3T or 7T. Several existing MRI techniques will be optimized
to measure the effect of the respiratory challenge. MRI techniques applied are
designed to measure the level of deoxygenated blood (BOLD), the amount of
dissolved molecular O2 (T1), the blood perfusion (ASL), the blood vessel index
(VSI) and the pH (Chemical Exchange Saturation Transfer (CEST)).

The controlled gas breathing requires a closed breathing system. Therefore,
subjects have to breathe through a mask. Further, CO2 end-tidal levels of 45-60
mmHg (baseline + 20 mmHg) can induce an increased breathing frequency due to
physiological stress. However, end-tidal levels of 30-60 mmHg CO2 are in
physiological ranges and are experienced repeatedly my most people over the
day. If patients experience discomfort because of high arterial CO2 levels,
they can open a valve in the mask or squeeze the panic button in the MRI and
the researcher can switch immediately to 100% oxygen by pushing the red button
on the front of the gas blender.

The safety of the RespirAct is guaranteed by the following features of the gas
blender and the actions that are taken:
- The minimum O2 level in all the gas mixtures is 10%.
- CO2 and O2 levels and breathing frequency is monitored constantly online.
- An independent blood oxygen saturation and respiratory rate monitoring will
be performed during the MRI measurements with fingertip pulse oximetry and a
pressure sensor for the respiratory rate.
- Everyone who will operate the RespirAct will be trained and certified by the
manufacturer.

Subjects will not benefit from the respiratory challenge with or without
combination with MRI.
Only one visit will be required for the brain measurements. For head and neck
measurements, the subject will be asked to participate for minimum 3 and
maximum 6 separate MRI sessions, besides the application of the custom-made
mask.

No risks are known for undergoing an MRI.