Non-invasive assessment of local glucose levels and the uptake and metabolism of glucose in tumour in the human brain using Magnetic Resonance at 3T.

In general tumours are recognised by an increased glucose consumption. In
experimental tumours is found out that the glucose metabolism is dominated by
anaerobe processes with lactate as endproduct (Warburg effect). The level of
anaerobe metabolism is characteristic for the malignancy of the tumour. The
abnormal metabolism is important for the determination of the type of treatment
of the tumour, however, it can also be used to characterise the tumour with
non-invasive imaging techniques. Although signs for anearobe glucose metabolism
in human tumour exist, it has never been possible to measure this in a direct
way. 13C-MR spectroscopy is the only method to investigate human metabolic
processes in a dynamic and non-invasive way. This method is used in a few
animal studies to investigate tumour and it showed that it is possible to
determine the level of anearobe metabolism [1-3].

1. Bhujwalla, Z.M., et al., Glucose metabolism in RIF-1 tumors after reduction
in blood flow: an in vivo 13C and 31P NMR study. Magn Reson Med, 1994. 32(3):
p. 303-9.
2. Poptani, H., et al., Cyclophosphamide treatment modifies tumor oxygenation
and glycolytic rates of RIF-1 tumors: 13C-Magnetic resonance spectroscopy,
Eppendorf electrode, and redox scanning. Cancer Res, 2003. 63(24): p. 8813-20.
3. Nielsen, F.U., et al., Effect of changing tumor oxygenation on glycolytic
metabolism in a murine C3H mammary carcinoma assessed by in vivo nuclear
magnetic resonance spectroscopy. Cancer Res, 2001. 61(13): p. 5318-25.

To develop a non-invasive MR method to measure the local changes in glucose
metabolism of human brain tumour, in order to answer to the question:
Is the tumour glucose metabolism anaerobic?

The following MR measurement will be performed at a magnetic field strenght of
3T during an euglycemic clamp. During the 13C MRS measurement 13C-labeled
glucose will be used to apply the euglycemic clamp.
A:MR imaging to locate the tumour in the brain
B:1H MRS to determine brain metabolites in tumour and normal brain
C:13C MRS to determine the glucose signals and metabole products of glucose in
the tumour and normal brain
These measurements are performed successively in 8 patients and take about 2 to
3 hours per patient.

The intervention is the application of an euglycemic clamp.

-During the measurements the patient lays down on the bed in the MR scanner.
The head is positioned inside a head-coil. We try to comfort the patient as
much as possible while he is inside the scanner. The patient is allowed to
listen to music or to watch a movie via a mirror on the head-coil. The MR
scanner is a magnet with a narrow tunnel in which the patient is laid down on
the bed, this is why claustrofobia is an exclusion criterium. The researcher
and a doctor will be present during the entire measurement.
-The introduction of a catheter can be painfull and can cause bruises. When the
catheter is removed local redness, swelling or bruises can occur. This will be
healed in a few days. Because of the introduction of an arterial cathether the
patient gets a pressure bandage after the measurements. After the session a
bread meal is provided for the patient. The amount of blood that will be taken
during the measurements will not exceed 140ml.
-MR spectroscopy uses non-ionising radiofrequent (RF) radiation combined with a
static magnetic field for which the American FDA security guidelines are
formulated. These guidelines will be followed.
-13C-labeled glucose, which is used for 13C MRS contains the non-radioactief
isotope 13C and can be used safely.