Positron Emission Tomography (PET) to Study Brain Signaling
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 10/8/2017 |
| Start Date: | January 10, 2000 |
| End Date: | June 12, 2015 |
Positron Emission Tomography Imaging of Activation-Induced Signal Transduction in Human Brain
This study uses positron emission tomography (PET) to examine brain function and signaling
involving phospholipids, and to see how signaling is related to blood flow. Much of the brain
is composed of fatty molecules called phospholipids. These molecules are involved in the way
brain cells signal each other to direct brain function. Brain disease may change
phospholipids and disturb brain structure and signaling. Studies of brain phospholipid
composition and metabolism may help clarify how the brain works in healthy people or stops
working effectively in disease states.
Healthy volunteers between 18 and 45 years of age may be eligible for this study. Candidates
are screened with a medical history, physical examination, and blood and urine tests.
Participants undergo magnetic resonance imaging (MRI) and PET scanning as follows:
MRI
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For
this procedure, the subject lies on a table that is moved into a metal cylinder (the scanner)
and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning
process. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45
and 90 minutes. Subjects may be asked to lie still for up to 30 minutes at a time.
PET
For the PET scan, a catheter (thin plastic tube) is inserted into an artery in the subject's
wrist or elbow crease to collect blood samples during the procedure, and a second catheter is
placed in a vein in the opposite arm to inject radioactive tracers. The subject lies on the
scanner bed, wearing a special facemask and goggles. The mask helps hold the head still
during the scans, and the goggles either block all light or administer bright flashing
lights. Radioactive water is injected into the vein, followed by a 1-minute PET scan to
measure brain blood flow. This is repeated three more times. Then, a radioactive fatty acid
is injected into the vein, followed by a 1-hour PET scan to measure brain phospholipid
metabolism. This is repeated once. The images of blood flow and phospholipid metabolism in
the different regions of the brain under the conditions of darkness and during visual
stimulation provide information on how and where the brain responds to visual stimulation.
The entire procedure takes about 3 hours.
involving phospholipids, and to see how signaling is related to blood flow. Much of the brain
is composed of fatty molecules called phospholipids. These molecules are involved in the way
brain cells signal each other to direct brain function. Brain disease may change
phospholipids and disturb brain structure and signaling. Studies of brain phospholipid
composition and metabolism may help clarify how the brain works in healthy people or stops
working effectively in disease states.
Healthy volunteers between 18 and 45 years of age may be eligible for this study. Candidates
are screened with a medical history, physical examination, and blood and urine tests.
Participants undergo magnetic resonance imaging (MRI) and PET scanning as follows:
MRI
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For
this procedure, the subject lies on a table that is moved into a metal cylinder (the scanner)
and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning
process. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45
and 90 minutes. Subjects may be asked to lie still for up to 30 minutes at a time.
PET
For the PET scan, a catheter (thin plastic tube) is inserted into an artery in the subject's
wrist or elbow crease to collect blood samples during the procedure, and a second catheter is
placed in a vein in the opposite arm to inject radioactive tracers. The subject lies on the
scanner bed, wearing a special facemask and goggles. The mask helps hold the head still
during the scans, and the goggles either block all light or administer bright flashing
lights. Radioactive water is injected into the vein, followed by a 1-minute PET scan to
measure brain blood flow. This is repeated three more times. Then, a radioactive fatty acid
is injected into the vein, followed by a 1-hour PET scan to measure brain phospholipid
metabolism. This is repeated once. The images of blood flow and phospholipid metabolism in
the different regions of the brain under the conditions of darkness and during visual
stimulation provide information on how and where the brain responds to visual stimulation.
The entire procedure takes about 3 hours.
Objective
The binding of neurotransmitters and certain drugs to neuroreceptors in the brain is
considered to modify cognition and behavior by activating certain receptor-coupled effector
enzymes and initiating signal transduction cascades. One of these effector enzymes is
phospholipase A2 (PLA2), which when activated will release arachidonic acid (AA) from
phospholipids and initiate the AA cascade (Fitzpatrick and Soberman, 2001). AA and its
eicosanoid metabolites have multiple biological actions. We have developed an imaging method
to quantify and localize brain signal transduction involving PLA2 and AA in unanesthetized
rats and monkeys, using quantitative autoradiography or positron emission tomography (PET),
and radiolabeled AA. The aim of this protocol is to extend this method to humans with PET,
when brain imaging AA signaling in two experimental conditions (dark and visual flash
stimulation at a frequency of 3 Hz or 8Hz) in the same subject in the same PET session.
Radioactive [1-11C]AA will be injected intravenously in each condition, and PET will be used
to measure its incorporation coefficient k* in individual brain regions. Animal studies and
modeling have shown that the incorporation coefficient is proportion to PLA2 activation and
the release of AA from brain phospholipids (Rapoport, 2003). In addition, [15O]H20 will be
injected in each condition to measure regional cerebral blood flow (rCBF). Based on our prior
studies in human subjects of rCBF during visual activation by flashing lights at different
frequencies (Mentis et al., 1997; Mentis et al., 1998; Mentis et al., 1996), we hypothesize
that statistically significant increments in rCBF and [11C]AA incorporation into brain will
be increased during visual activation compared with the dark (unactivated) condition. These
increments should be evident in primary visual cortex, association visual cortex, thalamus,
and frontal cortex. If our hypothesis proves correct and our method to measure [11C]AA
incorporation both during stimulation and in the dark proves feasible in the same subject in
the PET session, we believe that the method could be applied generally in humans to examine
brain PLA2-related signal transduction during physiological or pharmacological activation and
in healthy aging (Giovacchini et al., In press) and disease, particularly Parkinson and
Alzheimer disease (Hayakawa et al., 2001; Nariai et al., 1991).
Study population
We plan to study 30 normal volunteers, each of whom will be subjected two stimulation
conditions in the same PET session, visual stimulation at a frequency of 3 or 8 Hz, or a dark
condition (0 Hz).
Design
Each PET scan session will last approximately 3 hours. Each subject will receive a total of
four [15O]H20 injections to measure regional cerebral blood flow (rCBF), and two [11C]AA
infusions to measure incorporation k* for AA during a single PET scan session. He/she will
have an arterial catheter and venous line inserted during the entire session, and one
transmission scan at the beginning of the session. The order of the scans will be randomized.
The order of 4 blood flow scans will be: Rest-Photic Activation-Photic Activation-Rest OR
Photic Activation-Rest-Rest-Photic Activation. The order of two [C11]AA scans will be
Rest-Photic Stimulation Or Photic Stimulation-Rest.
Stimulation will be conducted via LED goggles at a flash frequency of 3 Hz and 8 Hz, evenly
divided among the 30 subjects, and at 0 Hz (dark condition). Statistical parametric mapping
and other statistical procedures will be used to identify brain regions in which k* for AA
and/or rCBF is elevated at 3 Hz compared with the dark condition; at 8 Hz compared with the
dark condition; and at 8 Hz compared with 3 Hz condition.
The binding of neurotransmitters and certain drugs to neuroreceptors in the brain is
considered to modify cognition and behavior by activating certain receptor-coupled effector
enzymes and initiating signal transduction cascades. One of these effector enzymes is
phospholipase A2 (PLA2), which when activated will release arachidonic acid (AA) from
phospholipids and initiate the AA cascade (Fitzpatrick and Soberman, 2001). AA and its
eicosanoid metabolites have multiple biological actions. We have developed an imaging method
to quantify and localize brain signal transduction involving PLA2 and AA in unanesthetized
rats and monkeys, using quantitative autoradiography or positron emission tomography (PET),
and radiolabeled AA. The aim of this protocol is to extend this method to humans with PET,
when brain imaging AA signaling in two experimental conditions (dark and visual flash
stimulation at a frequency of 3 Hz or 8Hz) in the same subject in the same PET session.
Radioactive [1-11C]AA will be injected intravenously in each condition, and PET will be used
to measure its incorporation coefficient k* in individual brain regions. Animal studies and
modeling have shown that the incorporation coefficient is proportion to PLA2 activation and
the release of AA from brain phospholipids (Rapoport, 2003). In addition, [15O]H20 will be
injected in each condition to measure regional cerebral blood flow (rCBF). Based on our prior
studies in human subjects of rCBF during visual activation by flashing lights at different
frequencies (Mentis et al., 1997; Mentis et al., 1998; Mentis et al., 1996), we hypothesize
that statistically significant increments in rCBF and [11C]AA incorporation into brain will
be increased during visual activation compared with the dark (unactivated) condition. These
increments should be evident in primary visual cortex, association visual cortex, thalamus,
and frontal cortex. If our hypothesis proves correct and our method to measure [11C]AA
incorporation both during stimulation and in the dark proves feasible in the same subject in
the PET session, we believe that the method could be applied generally in humans to examine
brain PLA2-related signal transduction during physiological or pharmacological activation and
in healthy aging (Giovacchini et al., In press) and disease, particularly Parkinson and
Alzheimer disease (Hayakawa et al., 2001; Nariai et al., 1991).
Study population
We plan to study 30 normal volunteers, each of whom will be subjected two stimulation
conditions in the same PET session, visual stimulation at a frequency of 3 or 8 Hz, or a dark
condition (0 Hz).
Design
Each PET scan session will last approximately 3 hours. Each subject will receive a total of
four [15O]H20 injections to measure regional cerebral blood flow (rCBF), and two [11C]AA
infusions to measure incorporation k* for AA during a single PET scan session. He/she will
have an arterial catheter and venous line inserted during the entire session, and one
transmission scan at the beginning of the session. The order of the scans will be randomized.
The order of 4 blood flow scans will be: Rest-Photic Activation-Photic Activation-Rest OR
Photic Activation-Rest-Rest-Photic Activation. The order of two [C11]AA scans will be
Rest-Photic Stimulation Or Photic Stimulation-Rest.
Stimulation will be conducted via LED goggles at a flash frequency of 3 Hz and 8 Hz, evenly
divided among the 30 subjects, and at 0 Hz (dark condition). Statistical parametric mapping
and other statistical procedures will be used to identify brain regions in which k* for AA
and/or rCBF is elevated at 3 Hz compared with the dark condition; at 8 Hz compared with the
dark condition; and at 8 Hz compared with 3 Hz condition.
- INCLUSION CRITERIA:
All subjects must have normal values on screening measures to be in the study.
Age between 18 and 45 years.
EXCLUSION CRITERIA:
Past or current medical condition that would interfere with brain function- history of
alcoholism; psychiatric or neurological illness; head trauma with loss of consciousness;
history of exposure to central nervous system toxin; history of central nervous system
infection; metabolic, endocrine, connective tissue disease; hypertension or other
cardiovascular disorder; abnormal renal, liver or pulmonary function; blood or coagulation
disease; malignancy; psychopharmacological treatment; neurodegenerative or
neurodevelopmental disorder; stroke; epilepsy; sensitivity to flashing lights. Subjects
requiring regular medication.
Subjects demonstrated by drug screening to have taken controlled substance.
For female subjects, pregnancy or current breast-feeding (nursing).
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
