Multiple Sclerosis Clinical Trial
Official title:
Using MR Perfusion Imaging and Hypercapnia to Study Angiogenesis in Multiple Sclerosis Patients
This study will use magnetic resonance imaging (MRI) to examine and compare changes in blood
flow and blood volume in the brains of normal volunteers and patients with multiple
sclerosis (MS). Patients with MS-an inflammatory disease that attacks the brain and
spine-may have new blood vessel formation (called angiogenesis) within the brain that may or
may not contribute to the disease or help in repairing the brain. It is not known if these
new vessels behave in the same way as the naturally occurring vessels. MRI uses a strong
magnetic field and radio waves to generate brain images that provide information on brain
chemistry, function, and blood flow. The results of this study may lead to a better
understanding of MS.
Healthy normal volunteers and patients with multiple sclerosis 18 years of age and older may
be eligible for this study. Normal volunteers must have no history of signs or symptoms of
central nervous system disease. Patients with MS will be recruited from the NIH
Neuroimmunology MS clinic.
All participants will undergo MRI. For this procedure, the subject lies still on a table
that slides into a narrow metal cylinder (the MRI scanner). Scanning varies from 20 minutes
to 3 hours, with most scans lasting between 45 and 90 minutes. During the scan, the subject
wears earplugs to muffle loud knocking noises caused by electrical switching of the radio
frequency circuits. The subject can communicate with the MRI staff at all times during the
procedure.
During the scan, the subject wears a mask and breathes in room air or air containing 6%
carbon dioxide (CO2). (Room air contains approximately 0.04% CO2, which is about 150 times
less than the 6% CO2. Air that is normally breathed out contains about 5% CO2.) Breathing 6%
CO2 increases the amount of blood flow in the brain that can be measured using MRI. The
total duration of a single 6 percent CO2 inhalation will not exceed 10 minutes.
A catheter (thin plastic tube) is placed in a vein in the subject's arm before he or she
enters the scanner. At some point during the scan, a contrast agent called gadolinium DTPA
is injected into the vein through the catheter. This agent enables clearer images of the
brain.
Advances in MR perfusion imaging have provided clinical researchers with the opportunity to quantify regional cerebral blood flow (CBF). Recently, new vessel proliferation and formation (angiogenesis) has been observed in autopsy and biopsy specimens from patients with multiple sclerosis (MS). Newly formed MS lesions, showed strikingly increased numbers of new vessels and similar patterns were observed in and around older lesions, areas of remyelination (new myelin formation on axons, shadow plaques) and normal-appearing brain tissue. The purpose of this study is to compare CBF of MS patients, to age- and gender-matched healthy controls. CBF will be measured while subjects are inhaling room air and the increase in CBF while inhaling a mixture of room air and a known concentration of carbon dioxide (hypercapnia) will be compared. If significant new vessels growth has occurred in the brains of MS patients then this new vessel formation (neovascularization) may be reflected by a change in CBF. Comparing the CBF response to hypercapnia will determine if the newly formed vasculature includes properly functioning blood vessels. Normal cerebral blood vessels are exquisitely sensitive to the carbon dioxide in arterial blood and an increase in carbon dioxide causes CBF to increase through dilatation or relaxation of the muscles surrounding the blood vessels. In the future, changes in the hypercapnia-induced CBF response between MS patients and controls may help to monitor the treatment of the disease. ;
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