Contrast-Enhanced Near-Infrared Optical Imaging Detects Exacerbation and Amelioration of Murine Muscular Dystrophy

Abstract

Assessment of muscle pathology is a key outcome measure to measure the success of clinical trials studying muscular dystrophies; however, few robust minimally invasive measures exist. Indocyanine green (ICG)-enhanced near-infrared (NIR) optical imaging offers an objective, minimally invasive, and longitudinal modality that can quantify pathology within muscle by imaging uptake of ICG into the damaged muscles. Dystrophic mice lacking dystrophin (mdx) or gamma-sarcoglycan (Sgcg−/−) were compared to control mice by NIR optical imaging and magnetic resonance imaging (MRI). We determined that optical imaging could be used to differentiate control and dystrophic mice, visualize eccentric muscle induced by downhill treadmill running, and restore the membrane integrity in Sgcg−/− mice following adeno-associated virus (AAV) delivery of recombinant human SGCG (desAAV8hSGCG). We conclude that NIR optical imaging is comparable to MRI and can be used to detect muscle damage in dystrophic muscle as compared to unaffected controls, monitor worsening of muscle pathology in muscular dystrophy, and assess regression of pathology following therapeutic intervention in muscular dystrophies.

Skeletal muscle in health and disease

“…But it is becoming increasingly clear that other features of the injury environment play important roles in modulating the sequence of regeneration events. Investigation of the fate of satellite cells (Cousins et al, 2004;Robertson et al, 1990;Tierney et al, 2018a;Webster et al, 2016), myofibre necrosis (Chrzanowski et al, 2017;Filareto et al, 2018) and myofibre regeneration (Baudy et al, 2011) in the context of inflammation (Martinez et al, 2015) in in vivo models are more informative as to the extent of participation of other cells and of the intercellular environment. Recently available markers have shown a complex diversity of myogenetic clones that remain stable during growth and ageing of normal muscle (Tierney et al, 2018b), implying that asymmetric division (Box 1) of a stem cell compartment is a major component of muscle formation and maintenance.…”

Real‐time visualization of skeletal muscle necrosis in mice and swine through NIR‐II/I fluorescence imaging

“…Taking advantage of these characteristics, ICG is generally helpful in dealing with angiographs [20]. Diagnosis of diseases like vessel injury [11], thrombus formation, or evaluating intraoperative blood flow [21], as limb trauma [22], flap design and reconstruction [23], and estimating muscle flap [24]. Extreme trauma is usually followed by severe skeletal muscle injury.…”