Double Push Acoustic Radiation Force (DP ARF) Ultrasound for Monitoring Muscle Degeneration in Duchenne Muscular Dystrophy

Double Push Acoustic Radiation Force (DP ARF) imaging will be performed in 3 cohorts of up to 10 boys with DMD and in age-matched boys with no known neuromuscular disorders.

The first DMD cohort will enroll at age 5-6, the second at age 7-8, and the third at age 9-10. The rectus femoris (RF), cranial sartorius (CS), gastrocnemius (GAST), and lateral deltoid (DT) muscles will be targeted for their known phenotypic variation in response to dystrophin deficiency. The RF undergoes early necrosis and fatty deposition, the CS is thought to be relatively spared, and the GAST seems to undergo true hypertrophy. The DT, which undergoes hypertrophy like the GAST, will also be examined to determine if the impact of dystrophin deficiency varies between upper and lower limbs. All boys will be imaged 3 times annually for 4 years. In addition to DP ARF imaging every 4 mos, the boys will undergo standard quantitative muscle testing (QMT) and timed function tests (TFT) of time to standing, 6-minute walk, and 30-feet walk. Age at loss of ambulation will also be recorded for each boy. Boys with DMD generally loose ambulation by age 10, so we expect that the 20 boys in the 7-11 and 9-13 aged cohorts will lose ambulation over the course of this study. The 10 boys in the 5-9 aged cohort will likely not lose ambulation during the study. Because the primary objective of this clinical investigation is to evaluate the potential of DP ARF imaging as a relevant surrogate for monitoring disease progression and response to therapies, the focus of the study will be on correlating DP ARF results to change in functional degeneration and time to loss of ambulation.

There are two experimental components to this study beyond what is standard practice for DMD patients: 1) DP ARF ultrasound imaging of the rectus femoris (RF), cranial sartorius (CS), gastrocnemius (GAST), and lateral deltoid (DT) muscles and 2) standard quantitative muscle testing (QMT) and timed function tests (TFTs) of time to standing, 6-minute walk, and 30-feet walk repeated every four months (three times annually) throughout the four-year duration of the study.

This study will commence with DP ARF ultrasound imaging in the Clinical Neurophysiology Laboratory during the patient volunteer's first regularly scheduled research visit. Patient volunteers are expected to be outpatients. However, if a patient volunteer is an inpatient, DP ARF ultrasound imaging may be performed at the patient volunteer's hospital bedside. Immediately following DP ARF examination, the patient volunteer will undergo QMT and TFTs in the Physical Therapy Department. QMT and TFT will be conducted by trained physical therapists. DP ARF ultrasound imaging, QMT and TFT will be repeated as described above at each of the patient volunteers' twelve regularly scheduled research visits over the four-year study duration. Whenever possible, we will schedule research visits to coincide with other clinical visits to UNC. The patients' parents or caregivers will be compensated $50 per visit to defray the costs of travel to UNC, parking and lunch.

DP ARF will also be performed in 30 boys ages 5-14 with no known neuromuscular disorders. Imaging will be performed as described for the boys with DMD. The DP ARF results obtained in boys with no known neuromuscular disorders will be compared to those obtained in boys with neuromuscular disorders to serve as a control for changes in muscle mechanical property to occur with normal muscle growth and development.