Duchenne Muscular Dystrophy (DMD) is a genetic muscle condition seen in boys. DMD causes weakness in muscles first affecting the large hip and shoulder muscles and later the smaller muscles of the body. This weakness results in a decreased ability to walk and to perform other daily tasks. The purpose of this research study is to learn more about possible changes that occur in muscles of the arms and legs in boys with DMD. We hope to develop an improved imaging procedure to follow the progression of this disease in people with DMD and to help evaluate upcoming treatments for this disease.
We will compare the muscles of people with DMD with muscles of healthy people of the same age and monitor disease progression in boys with DMD over a 5 year period. The amount of muscle damage and fat that we measure will also be related to performance in daily activities such as walking and the loss of muscle strength. In a small group of subjects we will also assess the effect of corticosteroid drugs on the muscles.
First, Magnetic Resonance Imaging (MRI), and Magnetic Resonance Spectroscopy (MRS) measurements will be performed on the subjects' muscles. The MRI technique allows us to get pictures of the muscles and MRS gives us biochemical information of the muscles. This technique is non-invasive and allows us to get these pictures without going inside the body. We will use the picture and biochemical information to tell the difference between damaged muscle, healthy muscle and fat inside of the muscles. After this is completed, muscle strength and functional tests such as walking and using the arms to do daily tasks will be performed.
In order to participate in this study you must have the gene abnormality (mutation) associated with DMD. All boys with DMD who are between 5 and 18 years of age are eligible for this project; with the exception of those with implants (materials or devices that are not MR compatible). Also we will not be able to include boys who have had an injury to their legs or arms that makes their muscles weaker. The boys who choose to participate in this study will be required to attend one or two session each of MRI/MRS, strength, and functional testing at regular intervals (6 or 12 months) over a period of 5 years. We anticipate that measurements will be performed at up to eight different time points depending on functional status.
MRI and MRS
Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS)
MRI is a procedure that allows doctors to look inside the body by using a scanner that sends out a strong magnetic field and radio waves. This procedure is completely painless, non invasive and uses NO radiation. During the scan participants will lie on a padded table inside the magnet. A series of images (pictures) will be taken from one of the subject's thighs and lower legs. The scanning period takes up to 90 minutes for the arms and 60 minutes for the legs, during which time it is extremely important to lie still to insure the clarity of the images produced. Similar to taking a regular photograph, if you move the picture will be blurry and out of focus.
During the entire period of time in the scanner, one of the investigators will be present with each participating boy, making sure he is comfortable and at ease. One parent will also be allowed in the scan room during the imaging. Although the measurement is painless, it is somewhat noisy inside the magnet due to a hammering sound made by the magnet. Disposable earplugs and headphones will be provided to the boys to reduce the noise while the scanner is operating. In addition the child will be able to watch a movie while in the scanner. This helps the time go by quickly.
While you are in the magnet we will also perform MRS measurements. This procedure will give us information regarding the makeup of a subject's muscles and uses the same scanner as the MRI. Like the MRI, this procedure is completely painless, non invasive and uses NO radiation. This technique will give us biochemical information about the subject's muscles and will help us tell the difference between damaged muscle, healthy muscle, water, and fat inside of the muscles. These measurements will be performed at the same time as the MRI procedure.
Muscle and Functional Performance tests
Arm muscles will be tested using one of the strength testing devices. Subjects will be asked to squeeze a handle or push or pull with their arm as hard as they can in order to determine the muscle strength. The arm will not move during the testing itself. Subjects may be asked to repeat this procedure as many as three to eight times. We might also test the muscle strength manually by demonstrating a movement and then asking the boy to perform the movement with his arms. Subjects may be asked to perform motor tasks such as getting up from the floor, climbing 4 stairs, and walking at different speeds and distances for up to 6 minutes. The boys will be allowed to rest at anytime if they become tired.
We will ask for information regarding the medication each subject takes as well as each boy's stage of puberty.
The entire testing session should last between 4-6 hours.
How does the magnet work?
By using magnetic resonance imaging (MRI), scientists at the University of Florida, Oregon Health Science Center, and the Children's Hospital of Philadelphia are able to take pictures of the inside of a person’s body. Similar to a CAT scan or an X-Ray, MRI machines are able to look through the skin at muscles, bones, or organs. MRI does not use radiation and there are no known side effects from its use.
The magnets we use are different than the magnets that are attached to a refrigerator door that may hold your shopping list or favorite picture. The magnet we use is made by repeatedly coiling wires around the bore (the shell around the tube). If you've seen a spool of thread, this is a similar idea. These coils of wire are then put into a bath of liquid helium. This is the same material that is in helium balloons, only it is cooled down until it is a liquid instead of a gas. Once the wires are cooled, electricity is run through them until they produce a magnetic field--a magnetic field that is much greater than the earth's own magnetic field. All of this activity is inside the magnet and invisible to the person being scanned. When the images are taken the boys will hear a lot of banging and clanking. This is perfectly normal and although the sound is loud there is no cause for alarm. The noise is made by the wires shaking in their casings which is caused by the electricity running through them. We will give the boys earplugs and headphones to cover their ears while they are inside the magnet and this will help to decrease the sound while they are being scanned. [See the picture below]
When the images are taken, we are actually taking pictures of the water molecules inside the body. Since our body is made up mostly of water (about 70%), this is handy! We'll take a number of different pictures from a number of different angles and use them to get an overall idea of what is going on in each boy's body. Similar to a camera, any movement will cause the pictures to be blurry, so it is very important while in the MRI for each person to stay very still!