Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00044200
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2002-08-21
Brief Title:
Positron Emission Tomography PET to Study Brain Signaling
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Positron Emission Tomography Imaging of Activation-Induced Signal Transduction in Human Brain
Status:
COMPLETED
Status Verified Date:
2015-06-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 subjects 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
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 subjects 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
Detailed Description:
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 1-11CAA 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 15OH20 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 11CAA 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 11CAA 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 15OH20 injections to measure regional cerebral blood flow rCBF and two 11CAA infusions to measure incorporation k for AA during a single PET scan session Heshe 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 C11AA 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 andor 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 1-11CAA 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 15OH20 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 11CAA 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 11CAA 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 15OH20 injections to measure regional cerebral blood flow rCBF and two 11CAA infusions to measure incorporation k for AA during a single PET scan session Heshe 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 C11AA 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-N-0057 | None | None | None |