Intra-operative functional Ultrasound (fUS)-imaging during spinal cord tumor removal surgery

A plethora of methods, tools and techniques have essentially contributed to our
understanding of the central nervous system. Today, on of the most promising
techniques is ultrasound imaging. Recent advances in computing power and the
ability to record raw ultrasound signals have enables a technique called
highframe-rate (HFR) ultrasound, which offers images at thousands of
frames-persecond. Because of the high temporal resolution, this technique is
sensitive for very small Doppler shifts (also called microDoppler), such as
those caused by the moving blood inside vasculature. The HFR ultrasound
technology too measure local increase of SCBV as a result of neural activity is
referred to as functional ultrasound (fUS). The clinical application of this
innovative technique of fUS could have a great benefit in fields such as that
of neurosurgery.

On a daily basis, neurosurgeons face the difficult task to identify and
distinguish spinal cord tumor tissue from functional healthy tissue, with the
ultimate aim of maximizing excision of pathological tissue and minimizing
postoperative neurological damage. However, visualization of healthy functional
neurological tissue, in relation to pathological tissue, both pre- and
intra-operatively, remains a significant challenge and bottleneck in the
treatment. With the introduction, adaptation and application of fUS to the
clinical field of neurosurgery, we will be equipped with a tool that enables us
to better delineate pathological from healthy tissue during surgery. Indeed, by
relying on the characteristic neurovascular changes that can be specifically
associated with functional or pathological neuronal tissue, fUS will allow us
to make image-guided decisions during neurosurgical dissection.

Firstly, to assess the ability of fUS to discriminate between functional and
non-functional spinal cord areas using electrical stimulation paradigms during
spinal cord tumor removal surgery. Secondly, to assess the ability of fUS to
discriminate between healthy vs. tumor tissue, based on differences in
microvasculature.

Based on the functional map created by using intra-operative neuro-monitoring
(IONM) (the golden standard during routine spinal surgery), we will identify
and image functional and adjacent non-functional spinal cord areas related to
specific electrical stimulation paradigms using fUS. The paradigms used will
range from motor evoked potentials to D-wave stimulation, and will be
alternated with reference tasks. In addition, we will perform healthy vs. tumor
tissue imaging. The imaging trial will last a total maximum of 30 min.

As functional mapping using IONM and ultrasound is already an integral element
of spinal cord tumor removal 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 electrical stimulation as the patient will be
under anesthesia. The stimulation paradigms used will be similar to the ones
conventional for IONM and will together take no langer than 30 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 spinal cord surgery, there will be limited additional risks
associated with participation. Also, the exposure levels for the fUS imaging
sequences (isonificiation with unfocussed beams) are well below FDA limits.
Patient 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 intra-operative imaging tool, which has the ability to present areas
of functional tissue deep inside the spinal cord and show differences in tissue
vascularity even when tumor tissue appears similar to healthy tissue in an
intra-operative setting.