Metabolic MRI in brain cancer and epilepsy

Glioblastoma is the most common brain tumor in adults. Glioblastoma patients
face a dismal prognosis, with a median overall survival of only 12-18 months
after diagnosis. Despite extensive research on new therapies, this survival
rate has not changed significantly over decades. Better understanding of
glioblastoma pathophysiology is of utmost importance.

Metabolic reprogramming is the central hallmark of cancer, and itis thought
that metabolic alterations precede morphological tissue changes in cancerous
tissue. Imaging tumor metabolism will give insights in brain tumor
pathophysiology. Here we aim to develop a fast, repeatable and non-invasive
metabolic MRI protocol to detect two important aspects of metabolic
reprogramming in glioblastoma: (1) the Warburg effect and (2) altered
phospholipid metabolism. The metabolic MRI protocol will be dedicated to image
these altered metabolic pathways, using two complementary techniques: deuterium
metabolic imaging (DMI) and 31P-MR spectroscopic imaging (31P-MRSI),
respectively.

In order to assess the extent of measurable metabolic disruption, we will also
include patients with epilepsy in this study. Epilepsy results in disrupted
brain metabolism (glutamate, glutamine, GABA), but likely in a more subtle way
than in glioblastomas. Furthermore, epilepsy patients with PET hypometabolism
exhibit a disturbance in glucose metabolism and epilepsy often occurs as a
symptom of glioblastomas. Therefore, it is useful to have an idea of the degree
of (measurable) metabolic disruption resulting from epilepsy alone.

Develop a fast metabolic MRI protocol, based on DMI and 31P-MRSI at ultra-high
field MRI, to investigate the Warburg effect and phospholipid metabolism in
glioblastoma and to asses metabolic disruption in epilepsy.

Observational study. The study consist of two parts. First scan parameters will
be evaluated, optimized an validated in a optimization study (part 1). Then we
will characterize brain tumor metabolism and evaluate treatment effects (part
2a) and characterize metabolic disruptions in epilepsy (part 2b).

Subjects participating in part 1 will visit the UMC Utrecht once or twice.
Subjects will be subjected to 4-hour fast and upon arrival an intravenous
access site will be installed in a vein in the arm for frequent blood sampling
(i.e. every 10 min, 5-10 ml). Only in part 1 The metabolic MRI scan will take
120-150 min.

Glioblastoma patients participating in part 2 will visit the UMC Utrecht three
times. Epilepsy patients in part 2 will vist the UMC Utrecht once. Subjects
will be subjected to 4-hour fast. During each visit they will undergo a 7T
metabolic MRI scan of ~60 minutes. Before each scan, they will receive an oral
dose of deuterated glucose (max 0.75 g/kg, with a maximum of 60 g) dissolved in
water (0.2 g/ml).

The intake of above mentioned amounts of deuterated glucose, and drawing of the
above mentioned amount of blood (only in part 1) does not affect the health of
participants. Deuterium (2H) is a stable, non-radioactive, isotope of hydrogen,
and biologically, deuterated glucose behave similarly to normal glucose. No
adverse effects have been observed with oral administration of deuterated
glucose at the dosage which will be used in this study.

MRI is a safe and reliable technique for subjects without contra-indications
for undergoing MRI and is widely used in clinical examinations and scientific
research. Subjects included in the study will have no contra-indications for
MRI and they will be screened again for standard contra-indications before
undergoing the MRI examination(s).

Patients will not have a direct benefit from participating. However, the
outcome of this study will aid in better understanding of tumor physiology,
which may improve diagnosis and treatment evaluation and the consequent
individual treatment decisions