Functional Ultrasound (fUS)- and fMRI-imaging in Patients with a Skull Bone Defect (SBD)

Functional Ultrasound (fUS)-imaging is a new imaging modality combining unique
spatiotemporal resolution and penetrative depths with ease of use and
intra-operative applicability. In a currently ongoing study in the OR-setting,
we have applied functional Ultrasound (fUS)-imaging during neurosurgical
procedures as a new means of imaging tumor and functional brain tissue. So far,
fUS shows very promising functional and vascular results. However, for the
technique to reach clinical maturity, further validation and understanding of
especially the functional, hemodynamic signals is immensely valuable. The
current clinical gold standard for haemodynamics-based functional imaging is
functional Magnetic Resonance Imaging (fMRI). Being able to compare spatial and
temporal characteristics of our fUS-signal to fMRI-signal would be very
valuable cross-validation. However, the OR-setting very limiting in terms of
time and logistics. In this study we propose combining fUS and fMRI
measurements in an outpatient setting in subjects with a skull bone defect
(SBD), either with or without a plastic (e.g. PEEK) skull implant. Measuring
subjects with SBDs is particularly beneficial as 1) fUS, like all ultrasound
techniques, does not work well through an intact skull, requiring access to the
brain through a natural/surgical opening and 2) working with patients with an
already existing SBD in an outpatient setting allows for the necessary time to
optimize technical parameters during signal acquisition, and to repeat
measurements multiple times to gather larger amounts of data for powerful
analyses.

The main objective of this study is to further validate our fUS-technique by
comparing and contrasting the spatial and temporal patterns of fUS-defined
functional areas with results acquired using fMRI in the same human subject.

Observational Study

The subject will have no significant burden of the imaging process using fUS,
other than time investment. The majority of tasks we will ask the subject to
perform will be very similar to tasks that are usually performed in for example
the fMRI and form no burden. The tasks together will not take longer than 60
minutes for each imaging session, with a maximum of 6 sessions in total
(depending on the quality of the data). Sessions will be planned according to
the volunteer*s schedule, as much as possible. Additionally, the exposure
levels for the fUS imaging sequences (insonification with unfocussed beams) are
well below FDA limits and what is used in clinical scanners using focussed
transmissions.
Patients will also be asked to undergo one structural MRI session (optional)
and one fMRI session. The MRI session will be a maximum of 30 min. to acquire
recent, structural data on the patient*s face and head contour after PEEK. The
patient will only be subjected to this session if there are no recent,
post-PEEK MRIs available from the clinical setting. The fMRI session will be a
maximum of 60 min. and will consist of simple, functional paradigms similar to
those conventional in the clinical setting, such as small motor tasks (with or
without concomitant EMG-measurements), visual tasks or language-related tasks.
The fMRI session will be performed somewhere during the 6 fUS-sessions in
accordance with the patient*s schedule. Because the total scanning time in the
MRI-scanner will be contained to a maximum of 90 min., spread out over two
sessions, we think this burden can be considered to be reasonable. Subject
participation in the study will, however, lead to the benefit of further
determining and increasing the potential use of fUS as a new and highly
powerful imaging tool, which has the ability to present areas of functional
tissue deep inside the brain.