Accurate delineation of glioma infiltration by advanced PET/MR neuro-imaging

Extensive resection of diffuse infiltrative glioma (WHO grade 2-4) improves
patient survival (Smith, J Clin Oncol 2008; Stummer, Neurosurg 2008). Standard
MRI is used preoperatively to determine the target volume for resection as well
as postoperatively to determine residual tumor before starting
chemo-radiotherapy. Standard MRI, however, quite poorly detects glioma
infiltration into surrounding normal brain tissue, leading to suboptimal
resections and inadequate radiation therapy fields. Innovative imaging
techniques such as advanced PET and MRI hold potential to provide more accurate
delineation of glioma infiltration. A PET/MRI facility, which will be available
in the Neuroimaging Center Amsterdam in 2012 as first in The Netherlands, can
combine these techniques in one diagnostic session. The accuracy of these
techniques for delineation of glioma infiltration has not been addressed.

(1) to assess the diagnostic accuracy of advanced neuroimaging compared with
standard MRI for the detection of diffuse glioma infiltration within the brain
in newly diagnosed patients, (2) to histopathologically and molecularly
characterize the central and infiltrative glioma areas and correlate the
results with imaging findings.

A monocenter prospective diagnostic observational study in 40 patients
undergoing resective glioma surgery. Patients will have preoperative advanced
neuroimaging in addition to standard MRI. Serial neuronavigated biopsies in and
around the glioma boundaries obtained immediately preceding resective surgery
will provide quantitative histopathological characteristics of the regions of
interest, enabling comparison with quantitative measurements in the imaging
modalities at the same biopsy sites. The study consist of two phases: eight
patients in phase I as a pilot project to optimize imaging methodology and
thirty-two patients in phase II to complete data acquisition for comparison of
diagnostic accuracies.

We hypothesize that a combination of F18-fluoro-choline PET, MR spectroscopy
using the choline to N-acetyl-aspartate index and standard MRI has superior
accuracy compared to standard MRI alone. In addition, the biopsies of glioma
infiltration will be compared to those from the core of the tumor to identify
differentially expressed molecular targets as candidates for future PET tracer
development.
Translation of this information into the clinic should improve delineation of
glioma target volume, facilitating optimization of resective surgery and
radiation therapy, resulting in better and prolonged survival. We will aim at a
follow-up project with randomized comparison of advanced and standard
neuroimaging-guided therapy with patient survival as primary outcome measure,
with the potential to define a new standard of care.