Magnetic Resonance and Optical Imaging of Dystrophic and Damaged Muscle

The overall objective of this proposal is to validate the potential of Optical Imaging
techniques to be able to detect and quantify muscle damage in a population affected by
Duchenne Muscular Dystrophy, a muscle wasting disease, and in a healthy population that has
undergone temporal muscle damage resulting from an exercising intervention.

Duchenne Muscular Dystrophy is a relentlessly progressive degenerative muscle wasting
disease, clinically characterized by progressive muscle weakness, a loss of ambulation, and
premature mortality. Currently, no known cure exists and treatments that benefit patients
diagnosed with Duchenne Muscular Dystrophy are limited. New approaches, such as cell therapy,
gene transfer, and pharmacological interventions have shown promising results in animal
models and human studies with great potential to develop as effective therapeutic treatments.
One of the major limitations of testing these interventions; however. is the lack of
effective methods to monitor cellular and tissue changes taking place in the response to
therapy. The ability to determine cellular and tissue specific changes in damaged muscles in
real time, non-invasively, repeatedly, without exposure to any harmful radiations, with
minimal patient discomfort, and at low operating cost would enable high throughput and faster
investigation of potential therapies.

The proposed study focuses on the development of Optical Imaging technologies in the near
infrared range of wavelengths to differentiate damaged from normal muscle tissue. Near
infrared light (700 - 900 nm) has demonstrated the ability to deeply penetrate through
biological tissue, skin, and muscle without appreciable attenuation or auto-fluorescence.

The investigators anticipate that Indocyanine Green enhanced Optical Imaging can be used to
image exercise induced acute muscle damage in healthy individuals and damaged muscle and in
boys with Duchenne Muscular Dystrophy. It is anticipated that this work may fulfill the need
for imaging biomarkers that monitor and quantify cellular damage, muscle perfusion, and drug
delivery - non-invasively, using benign light, repeatedly, and in real time, with the
intention of accelerating the testing of efficacy in clinical trials for neuromuscular
disorders. The study is designed to determine the ability of Optical Imaging as a reliable,
safe, relatively inexpensive, and facile tool to detect and quantify muscle damage.
Investigators anticipate that this type of imaging modality will provide clinically useful
information for diagnostic and prognostic purposes in patients with neuromuscular diseases,
especially boys with Duchenne Muscular Dystrophy.

Inclusion Criteria for Duchenne Muscular Dystrophy subjects:

- Diagnosis of Duchenne muscular dystrophy confirmed by 1) clinical history with
features before the age of 5 years, 2) physical examination, 3) elevated serum
creatine kinase level, and 4) absence of dystrophin expression as determined by immune
stain or Wester blot (<2%) and/or DNA confirmation of dystrophin mutation

- Must be between 10-15 years of age.

- Must be male.

Inclusion Criteria for unaffected subjects:

- Must be older than 18 years of age.

- Must be male.

Exclusion Criteria for unaffected and Duchenne Muscular Dystrophy subjects:

- Contraindication to an Magnetic Resonance examination (e.g. aneurysm clip, severe
claustrophobia, magnetic implants)

- Presence of a condition in patients that impacts muscle function or muscle metabolism
(e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)

- Medical condition leading to developmental delay or impaired motor control (e.g.
cerebral palsy)

- Unstable medical condition (e.g. uncontrolled seizure disorder)

- Behavioral problems causing an inability to cooperate during testing

- Control subjects who are participating in sport specific training 2 times or more per
week

- History of allergy to iodides