This study will use magnetic resonance spectroscopy (MRS) to measure in the brain the
transfer of C as it is naturally metabolized from glucose to specific chemical
transmitters. From this method, we can measure the rate of production of an important
excitatory neurotransmitter (glutamate) as well as an inhibitory neurotransmitter (GABA).
13C is a stable (i.e., non-radioactive) isotope of carbon with a natural abundance of ~1%.
Following infusion of [13C]glucose and/or [13C]acetate, in vivo MRS (magnetic resonance
spectroscopy) can monitor the rate of flux of the 13C atom from glucose and/or acetate to
glutamate to glutamine. Thus, this procedure can provide measure of glutamate (GLU) and
glutamine (GLN) turnover in brain. We have established parameters to obtain these
measurements in nonhuman primate brain. The current protocol seeks approval to optimize MRS
parameters and to develop new MRS techniques for human brain using the GE 3T, the Siemens 3T,
and the Siemens 7T device.
Study population: All subjects will be aged 18 65 years, without serious medical illnesses
and meet criteria listed in Section VI A.
Design: Subjects will receive either oral administration of [13C]glucose or an intravenous
infusion of [13C]glucose and/or [13C]acetate to approximately double their plasma glucose
levels. The plasma acetate level will remain within the physiological range observed in
humans (Lebon et al, 2002). While lying in the 3T or 7T device, serial data acquisitions will
be obtained over ~2 h to optimize the experimental conditions so as to measure the 13C
signals from GLU, GLN and other metabolisms in brain.
Outcome measures: The primary goal of this study is to measure GLU/GLN turnover in brain.
With no additional data acquisition, we can also obtain information on the synthesis of GABA,
the major inhibitory neurotransmitter in brain. GLU is converted to GABA via the enzyme
glutamic acid decarboxylase (GAD). While monitoring the transfer of 13C signal from GLU to
GLN, we can simultaneously measure the transfer of 13C signal from GLU to GABA and thereby
measure the activity of GAD (Li et al 2005). In addition to directly measure 13C signals, 13C
labeling to brain metabolites can also be measured indirectly by detecting proton MRS during
[13C]glucose and/or [13C]acetate.
- INCLUSION CRITERIA:
Age: 18-65 years
Abnormal fasting blood glucose level (normal values are 70-115 mg/dL); All subjects must
have a fasting blood glucose level of within the normal values of 70-115 mg/dL
Serious medical illness (including diabetes) as determined from H&P or laboratory testing;
All subjects must meet none of the Axis I diagnoses
Prescription psychotropic medication; drug free period must be greater than 3 weeks for
anticholinergics and benzodiazepine and greater than 8 weeks for fluoxetine,
Pregnancy; All women with child-bearing potential will have a blood and/or urine pregnancy
test within 24 hours prior to the MRS study to exclude pregnancy
Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the
Unable to lay on one's back for MRI/MRS scans
Positive HIV test