Arterial spin labelling for the assessment of cerebral autoregulation - a proof of principle

Cerebral hemodynamics are subject of research in many different research areas
and pathologies. Cerebral autoregulation (CA), the regulatory mechanisms of the
brain to maintain a constant blood flow, are an intriguing element in these
cerebral hemodynamics. Cerebral autoregulation has been investigated with
regard to many different pathologies, varying from traumatic brain injury to
Alzheimer*s disease. Still, there are limitations regarding the assessment of
cerebral autoregulation and as a result also a lack of understanding.
The tremendous increase in temporal resolution of measurements of blood flow
has had a strong impact on cerebral autoregulation research [1, 2]. On the
other hand, spatial resolution of these measurements has hardly increased over
time. With the development of new MR sequences it is now possible to achieve a
spatial resolution of several millimeters, with also a reasonable temporal
resolution [3, 4]. Also MR-sequences like arterial spin labeling (ASL) are
developing rapidly. Thus far, this has been at the expense of the temporal
resolution to such an extent that only static CA can be assessed [5]. However,
with further advancements it may already be possible to image cerebral blood
flow oscillations with a temporal resolution of 0.4 Hz. We recently received a
new sequence which, with further optimization is possibly able to measure
oscillations in blood pressure; dynamic CA.
Also, recently, a new MR-compatible NIBP device became available, the CareTaker
[6]. This suggests it may be possible to measure both oscillations in BP and in
cerebral perfusion in MRI simultaneously. Together, these reflect information
on the cerebral autoregulation. With the high spatial resolution of the MRI,
these measurements may give additional understanding to the not so well
understood mechanism of cerebral autoregulation.
However, it is not yet known what the reliability of those rapid ASL
measurements is and what magnitude of changes in perfusion they are able to
detect. Also, the feasibility of the MR-compatible NIBP device has yet to be
proven. Since spontaneous oscillations in BP and cerebral perfusion are quite
subtle, larger changes in BP and cerebral perfusion need to be induced using
paced breathing and the cold pressor test (CPT) [7, 8]. These will help in
assessing whether changes in cerebral blood flow will exceed the total noise of
the measurements (as ASL is known to have a low signal-to-noise ratio), both
for young as for elderly, who are known to have changes in their regulatory
mechanisms [9].
If the measurements work in the setting proposed in this study, we will in the
future be able to gain more insight in the effect of spatial differences in
regulatory mechanisms. This may help in explaining why in some subjects the
regulation is affected.

Primary Objective:
• To demonstrate that changes in blood pressure and cerebral perfusion (induced
with paced breathing and the Cold-pressor test) can be assessed in the MRI
using the combination of NIBP and rapid ASL measurements.

Secondary Objective(s):
• To assess whether rapid ASL measurements and NIBP measurements, using the
CareTaker, are feasible to perform in a research setting
• To assess the reliability of the rapid ASL measurements and NIBP
measurements, using the CareTaker
• To assess the magnitude of changes that can be detected with the rapid ASL
measurements and NIBP measurements

10 healthy volunteers, aged 18 - 40 yrs and 5 healthy elderly, aged 55-75 will
receive 2 measurements: one in the MRI and one within the hemodynamic lab of
the department of Geriatric medicine. In both, blood pressure (CareTaker or
CNAP500) and cerebral hemodynamics (either ASL or TCD/NIRS) are measured.
5-minute measurements are performed in supine position, in rest, with paced
breathing (0.1 Hz) and after 2 minutes rest during 3 minutes the CPT.
Paced breathing means breathing at a pace of 6 breaths per minute (10 s for
each breathing cycle), which is indicated via a screen (so subjects still
breath voluntarily). This induces oscillations in blood pressure and
consequently oscillations in cerebral blood flow.
The CPT is a test which activates the sympathetic nervous system by placing a
subject*s hand in a bucket of ice water (0 - 5 °C). There is peripheral
vasoconstriction, causing an increase in blood pressure. Also, the cerebral
perfusion tends to increase. This response is consistent within a subject.

The research does not have a direct advantage for the participating subjects.
However, load is minimal; total time in the MRI is approximately 30 min. There
is only one visit of in total approximately 1.5 - 2 hours. All measurements are
performed non-invasively and do not require big effort. The CPT is bothersome,
but not related to any damage or other health risk. Therefore we would say this
study is associated with *negligible risk*.