Spatial analysis and validation of glioblastoma on 7 T MRI

Currently, patients with a glioblastoma multiforme (GBM) are treated with a
combination of different therapeutic modalities including resection, concurrent
chemo- and radiotherapy and adjuvant temozolomide. However, survival is still
poor and most of these tumours recur within one to two years within the
previously irradiated target volume.

The radiation target volume encompasses both the contrast-enhanced lesion on
T1-weighted magnetic resonance imaging (MRI), plus a 1.5 - 2 cm isotropic
margin in order to include microscopic speculated growth. These margins result
in a high dose to surrounding healthy appearing brain tissue. Moreover, the
short progression-free survival indicates a possible geographical miss. There
is a clear need for novel imaging techniques in order to better determine the
degree of tumour extent at the time of treatment and to minimize the dose to
healthy brain tissue.

The development of Ultra-High Field (UHF) MRI at a magnetic field strength of
7T provides an increased ability to detect, quantify and monitor tumour
activity and determine post-treatment effects on the normal brain tissue as a
result of a higher resolution, greater coverage and shorter scan times compared
to 1.5T and 3T images. Up to now, only few investigators have examined the use
of UHF MRI in patients with malignant brain tumours. These studies show its
potential to assess tumour microvasculature and post-radiation effects such as
microhaemorrhages.
This study analyzes the accuracy of the 7T MRI in identifying the gross tumour
volume (GTV) in patients with an untreated GBM by comparing 3T MRI images to 7T
images. Based on these images an extra biopsy per patient will be taken if
considered safe. These biopsies will be taken from suspected regions of GBM
based on 7T MRI that do not appear as such on 3T MRI. We hypothesize that with
the 7T MRI the GTV can be more accurately and extensively identified when
compared to the 3T MRI.

Primary objective
* to determine GTV in patients with an untreated GBM with 7T MRI without
contrast-enhancement.

Secondary objective
* to compare the GTV as created based on 7T MRI to the GTV based on 3T MRI.
* to determine the clinical target volume (CTV) in patients with a GBM with 7T
MRI and compare it with the CTV based on 3T MRI.
* to assess the visibility of the organs at risk (OAR) on 7T MRI compared with
3T MRI.
* to assess tumour heterogeneity in (micro)vasculature within the GTV in
patients with a GBM with 7T MRI compared with 3T MRI
* to assess the visibility of white matter tracts within the central nervous
system on 7T MRI compared with 3T MRI
* to assess the tolerability and side effects of the 7T MRI compared with 3T
MRI.

Prior to inclusion of patients, two healthy volunteers will be used to optimize
the 7T MRI sequences.

This pilot study is a diagnostic accuracy study.
Subjects will receive a 7T MRI scan without gadolinium contrast agent prior to
the biopsy. This MRI scan will be compared to the standard 3T neuro-navigation
MRI scan in order to determine the exact location of ROI on the 7T MRI. If
considered safe, a study biopsy will be taken from this ROI (see below).
Further treatment and follow-up will be according to standard protocol for
patients with GBM.
Four to six weeks after the start of radiotherapy 2 radiation-oncologists, a
resident radiation-oncology, a neuro-radiologist and a radiation technician
will individually delineate the GTV, CTV and organs at risk on the 7T MR
images. In order to assess intra-observer variability this delineation will be
repeated after two months for both the 3T MRI and 7T MRI.

One biopsy per patient will be taken from the ROI in addition to the standard
diagnostic biopsies. Both an experienced neuro-radiologist and neuro-surgeon
will assess the optimal location for the extra biopsy. The neuro-surgeon will
also assess the optimal biopsy tract. The extra biopsy will only be taken if
considered safe by the neuro-surgeon.

There are no immediate potential benefit for the subjects except the
satisfaction to participate in this study in order to improve general knowledge.
The U.S. Food and Drug Administration considers clinical MR systems using
static magnetic fields up to 8.0 Tesla as a *non-significant risk* for adult
patients. Acute side effects may include vertigo, nausea, a metallic taste and
phosphenes. Furthermore during the exam subjects may experience claustrophobia
and palpitations.
The biopsies hold a small risk of additional permanent morbidity (3.6 * 4.7%),
including haemorrhagic complications, and mortality (0 * 1.5%).