Protocol Number: 00-N-0057

Title:

Positron Emission Tomography Imaging of Activation-Induced Signal Transduction in Human Brain

Number:

00-N-0057

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 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.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

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).

Special Instructions: Currently Not Provided

Keywords:

Phospholipase A2

Arachidonic Acid

Blood Flow

Coupling

Neurotransmission

PET

Signal Transduction

Activation

Brain

[15O]H20

Recruitment Keywords:

None

Conditions:

Healthy

Investigational Drug(s):

15-O-Water

Investigational Device(s):

None

Contacts:

Giuseppe Esposito, M.D.
National Institutes of Health
Building 10
Room 1C401
10 Center Drive
Bethesda, Maryland 20892
Phone: (301) 402-1962
Fax: (410) 558-8318

Electronic Address: espositogi@grc.nia.nih.gov

Citations:

Arai T, Wakabayashi S, Channing MA, Dunn BB, Der MG, Bell JM, Herscovitch P, Eckelman WC, Rapoport SI, Chang MC. Incorporation of [1-carbon-11]palmitate in monkey brain using PET. J Nucl Med. 1995 Dec;36(12):2261-7.

Axelrod J. Phospholipase A2 and G proteins. Trends Neurosci. 1995 Feb;18(2):64-5. Review. No abstract available.

Axelrod J. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans. 1990 Aug;18(4):503-7. Review.

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