Realtime language mapping during awake brain surgery

De standard treatment of patients with gliomas in functional brain areas is
awake brain surgery with ESM (electrical stimulation mapping). The goal is to
resect as much tumor tissue as possible, while preserving as much function as
possible. Even though language is monitored during these surgeries, more than
50% of the patients have postoperative language deficits (aphasia). These
deficits result in a lower quality of life.

We would like to investigate if an extra intraoperative technique, functional
ultrasound (fUS), can be used as an addition to the existing intraoperative
language monitoring technique. This technique is based on (regular) ultrasound,
which is used regularly during awake surgeries. fUS offers images at thousands
of frames per second. Because of the high temporal resolution, this technique
is sensitive for very small Doppler shifts (also called µDoppler), such as
those caused by the moving blood inside brain vasculature. This technique can
measure local increases of CBV (cerebral blood volume) as a result of neural
activity. This is a continuation of a previous protocol in which the
intraoperative application of fUS showed to be informative: fUS seems to be
able to differentiate between functional and non-functional brain tissue. This
is the application of the technique which we would like to investigate further,
focussing on language specifically.

The primary goal is to compare functional (language) areas in the brain found
by preoperative fMRI, to those found during intraoperative ESM (electrical
stimulation mapping) and fUS (functional ultrasound) during awake craniotomies,
to see whether fUS can be used as an addition to the standard intraoperative
language mapping with ESM.

Secondary Objectives:
- Identify different aspects of language functioning in the brain using fUS and
a selection of language tasks.
- Relate intraoperative findings from language mapping to postoperative
language outcome.
- Relate language outcome to pre and postoperative fMRI findings, and relate
these timepoints to each other (preoperative language tests-
preoperative fMRI vs. postoperative language tests-postoperative fMRI)

The main goal is to be able to perform an even more specific intraoperative
language monitoring, in order to reduce postoperative language deficits and to
improve the quality of life in this patient group in the future.

Preoperatively we will extend the standard fMRI with max. 30 min. During the
fMRI specific language and motor tasks will be performed, which are similar to
the intraoperative tasks.

Intraoperatively, we will identify and image functional and adjacent
non-functional brain areas related to specific tasks using fUS, based on the
functional map created by using intraoperative electrocortical stimulation
mapping (ESM, the golden standard during
routine awake craniotomy surgery). The tasks used will range from muscle
movements to different language tasks. The imaging trial will last a total
maximum of 20 min.

Postoperatively an extra fMRI scan will be planned (max 60 min) within 8 weeks,
in which similar tasks will be performed as pre and intraoperatively. This scan
will be combined with another appointment for which the patient has to visit
the hospital, in order to avoid the need to visit the hospital only for the
study.

Preoperativly: Considering that it is standard procedure to plan a preoperative
fMRI, we don't expect that the extension of scan time will increase the burden
for the patient considerably.

Intraoperatively: as functional mapping using ESM and Ultrasound is already an
integral element of awake craniotomy surgery, the nature and extent of the
burden for the patient remains very limited. The patient will have no burden of
the imaging process using fUS and the specific tasks we will ask the patient to
perform will be very similar to the tasks already performed during ESM. The
tasks together will not take longer than 20 minutes, minimizing the extra time
necessary for surgery. In addition, as fUS-imaging is very similar to any type
of ultrasound imaging already used in a clinical setting and during awake
craniotomy surgery, there will be limited additional risks associated with
participation. Also, the exposure levels for the fUS imaging sequences
(insonification with unfocussed beams) are well below FDA limits.

Postoperatively: The addition of an extra fMRI scan can increase the burden of
the patient. However, since we will plan the scan on a day when the patient
will already visit the hospital for a (standard) appointment, the patient does
not need to visit the hospital specifically for the study. Because of this
overlap, we think that the additional burden of an extra scan will be limited.