This study will use magnetic resonance imaging (MRI) to examine the role of prostaglandins-a
type of fatty acid with hormone-like actions-in the regulation of brain blood flow. The
results will provide information on how to better use this technique to study brain
function, which, in turn, may lead to a better understanding of certain illnesses and more
Healthy normal volunteers 18 years of age and older may be eligible for this study.
Participants will fill out a health questionnaire and undergo a history, physical
examination and MRI studies. MRI is a diagnostic tool that uses a strong magnetic field and
radio waves instead of X-rays to show structural and chemical changes in tissues. During
the scanning, the subject lies on a table in a narrow cylinder containing a magnetic field.
An intercom system allows the subject to speak with the staff member performing the study at
all times during the procedure. Four separate studies will be done-two carbon dioxide
inhalation studies and two functional activation studies-as follows:
Carbon dioxide inhalation (indomethacin): This study is done in two parts. In both parts,
an MRI brain scan is done. During the scan, the subject inhales an air mixture containing
6% carbon dioxide through a facemask or mouthpiece. Blood pressure and heart rate are
monitored during inhalation of the mixture. For the second part of the study,
indomethacin-a non-steroidal anti-inflammatory drug-is injected through a catheter (thin
flexible tube) in an arm vein. Indomethacin inhibits prostaglandin production. Total scan
time averages between 45 and 90 minutes, with a maximum of 2 hours.
Carbon dioxide inhalation (rofecoxib and celecoxib): This study is identical to the one
above, except either rofecoxib or celecoxib is given instead of indomethacin. Both of these
drugs are also non-steroidal anti-inflammatory drugs that inhibit prostaglandin production.
Unlike indomethacin, rofecoxib and celecoxib are given orally instead of through a vein, so,
to allow time for the drug to be absorbed, the second scan is delayed for 2 hours.
Functional activation (indomethacin): This study is done in two parts. In both parts, a MRI
brain scan is done. During the study, the subject performs a simple motor task, such as
finger tapping. For the second part of the study, indomethacin is injected through a
catheter in an arm vein.
Functional activation (rofecoxib and celecoxib): This study is identical to the indomethacin
functional activation study, except either rofecoxib or celecoxib is given instead of
indomethacin. Because they are given orally instead of through a vein, the second scan is
delayed 2 hours to allow time for the drug to be absorbed.
Advances in MR perfusion imaging have provided clinical researchers with the opportunity to
quantify regional increases in cerebral blood flow. The purpose of this study is to
investigate in humans the role of prostaglandins in the regulation of cerebral blood flow
during hypercapnia and functional activation. For this investigation the increase in
cerebral blood flow associated with either hypercapnia or functional activation will be
measured before and after the administration of pharmacological agents that inhibit the
production of prostaglandins. In the hypercapnia study cerebral blood flow will be
increased by inhalation of an air mixture containing 6% CO2. For the functional activation
study cerebral blood flow will be increased by a sensory motor task.
Any healthy normal volunteer above the age of 18 who is capable of giving informed
Subjects will be excluded for the following reasons.
They have contraindications to MR scanning, such as the following: aneurysm clip,
implanted neural stimulator, implanted cardiac pacemaker or autodefibrillator, cochlear
implant, ocular foreign body (e.g., metal shavings), or insulin pump.
They have panic disorder or migraine (because of possible complications with CO2
They have cirrhosis, any renal dysfunction, or a chronic respiratory illness (such as
They have allergies to sulfonamide drugs or cyclo-oxygenase inhibitors (NSAIDS).