Perioperative techniques for low grade glioma patients: validation of Diffusion Tensor Imaging tractography with subcortical stimulation and prediction of postoperative functional outcome with Resting State Functional Connectivity

Surgical resection of low grade gliomas prolongs survival and relieves
symptoms. However, because resection may also affect eloquent brain areas,
surgery comes with the risk of causing new neurological deficits. The gold
standard for determining the location of eloquent areas of the cerebrum is
intraoperative electrical stimulation mapping (ioESM), which does not yield
preoperative information, and significantly lengthens the surgical procedure.
Recently, functional Magnetic Resonance Imaging (fMRI) has been shown to be
reliable in locating eloquent regions of the cortex, while Diffusion Tensor
Imaging and Fiber Tractography (DTI-FT) can visualize the direction of fiber
tracts in the subcortical white matter. By having both fMRI and DTI-FT
information available in the operation room it becomes possible to map eloquent
regions of the cortex and subcortex. However, DTI-FT has not been adequately
validated.
If resection does affect eloquent areas, (worsening of) neurological deficits
can occur. In a significant percentage of patients this neurological worsening
turns out to be transient. A very probable explanation for the disappearance of
symptoms over time is postlesional functional reorganization of the brain, a
process that may be visualized using *resting state* fMRI. This technique can
visualize patterns of functional connectivity (resting state functional
connectivity: RSFC), which are shown to be different in healthy controls and
patient populations in which neurological functioning is disrupted. However,
whether these results can be conclusively correlated to the severity of
postoperative neurological deficit and eventual recovery in low grade glioma
patients remains to be established.

This study is designed (1) to validate white matter tracts derived from DTI-FT
with the results of ioESM, and (2) to develop RSFC analysis in order to
quantify changes in functional connectivity patterns in patients that recover
from neurosurgery-induced, transient, motor and language disabilities.

Our patients are scanned prior to surgery, 1 to 2 weeks after surgery, and 3
months after surgery. In this way we are able to assess anatomical (DTI-FT) and
functional (RSFC) brain connectivity changes due to tumour (prior to surgery),
due to resection (1 to 2 weeks after surgery), and the final outcome (3 months
after surgery). Testing of motor, language and cognition of patients takes also
place in the UMC in Utrecht with the same timeline as the scanning sessions
(prior to surgery, 1 to 2 weeks after surgery, and 3 months after surgery).
These test findings are correlated to DTI-FT and RSFC findings to investigate
whether there is a relationship between resection of critical anatomical tracts
and functional areas and postoperative loss of motor and language functions
(functional outcome of the patients). A group of healthy volunteers will be
included to assess the test-retest reliablility of DTI-FT and RSFC. Because the
motor, language and cognition tests are standardized, healthy volunteers are
only scanned following the same timeline as for the patients.

There are no known risks associated with MRI acquisition. MRI has been used as
a diagnostic, clinical tool for over twenty years now. FMRI, DTI and RSFC
involve the same technique as clinical MRI, and thus pose no known risks for
subjects. Furthermore, there are no known risks associated with the digital
monitoring of (sub) cortical stimulation during surgery. Patients will have to
come three times at the UMC therefore travel costs are refunded. Healthy
volunteers will receive a financial compensation for their participation.
Overall, patients are not expected to immediately benefit from the DTI and RSFC
analysis results. However, it is well possible that in the (near) future these
non-invasive procedures will become, just as fMRI, a useful tool in presurgical
planning and planning during operation.