Evaluation of the healthy liver using new magnetic resonance imaging and spectroscopy methods at 3.0T and 7.0T

Hepatic steatosis prevalence is steadily rising, largely due to the obesity
epidemic. Non-alcoholic fatty liver disease (NAFLD) can progress from simple
steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and
ultimately hepatocellular carcinoma. Importantly, the subgroup of patients with
NASH is at the highest risk of disease progression. It is therefore imperative
to distinguish the NASH patients from those with simple steatosis. The
reference standard for diagnosis is a liver biopsy, which is prone to increased
morbidity and mortality, sampling error and large inter- and intraobserver
variability. Several imaging techniques are available for the diagnosis and
follow-up of NAFLD. Recent publications have renewed interest in phosphorus
MR-spectroscopy (31P-MRS). This technique can be used to identify
phosphor-containing metabolites, such as ATP and NADPH. The latter plays in
important role in fibrosis development and is seen as a marker of inflammatory
and especially fibrinogenic activity in the liver. Recent evidence points in
the direction of an increase in NAPDH level in NASH, but not in simple
steatosis. It could therefore be of use in distinguishing between these two
groups. We aim to determine normal values of liver phosphorus metabolite ratios
using 31P-MRS measurements at the 3.0T. An increase in a MRI-scanner*s field
strength increases the spectral quality of the spectra it generates, meaning
metabolites are identified more easily. This is mainly due to a higher
signal-to-noise ratio (SNR). One of the two Dutch 7T MRI scanners is located at
the University Medical Center Utrecht. We aim to use this high field strength
MRI scanner to perform 31P-MRS with a half-volume coil and compare these
results to 31P-MRS using the current standard at a field strength of 3.0T with
a surface coil. Lastly, diffusion tensor imaging MRI (DTI-MRI) - a method that
images the molecular movement of water - can be used to identify liver
fibrosis. The latter is seen in NASH patients, but not in those with simple
steatosis. It potentially is another method to distinguish NASH from simple
steatosis. We aim to use DTI-MRI to generate ADC- and FA-maps of the liver and
determine normal values of these parameters. To assess liver fat percentage we
will use proton MR-Spectroscopy (1H-MRS), a validated methodology for this
purpose.

Primary:
- To determine default values of liver phosphorus metabolite ratios using
31P-MRS at 3.0T in healthy volunteers
- To determine default values of fractional anisotropy (FA) and apparent
diffusion coefficient (ADC) in the liver using DTI-MRI at 3.0T in healthy
volunteers

Secundary:
- To evaluate the added value of 31P-MRS at 7.0T using a quadrature volume coil
compared to the current 31P-MRS standard at 3.0T using a surface coil in
healthy volunteers.

This is a two centre observational study.

No substantial risks or benefits are associated with the aforementioned
diagnostic procedures. Travel expenses are reimbursed and subjects will receive
¤85.- (2 sessions) or ¤140,- (3 sessions) for time spent. The procedure
requires all 30 subjects to visit the AMC Amsterdam twice for two separate
MRI-sessions at 3.0T. Furthermore, 10 subjects out of 30 will be asked to visit
the UMC Utrecht once for one MRI-scan at 7.0T. The examinations at 3.0T will
each take circa 50-60 minutes in the MRI-scanner, while the examination at 7.0T
will take circa 40-50 minutes. During the MRI-scans subjects will have to lie
still. Alll subjects will be asked to fast 4 hours prior to each MRI-scan, i.e.
no eating or drinking except water or tea (without sugar). No contrast agent
will be administered. MRI-scans are save non-invasive, non-ionizing
examinations.