Neuromuscular diseases result in
muscle weakness, disability, and,
in many instances, death. Preclinical models form the bedrock of research
into these disorders, and the development of
in vivo
and potentially translational biomarkers for the accurate identification
of disease is crucial. Spontaneous Raman spectroscopy can provide
a rapid, label-free, and highly specific molecular fingerprint of
tissue, making it an attractive potential biomarker. In this study,
we have developed and tested an
in vivo
intramuscular
fiber optic Raman technique in two mouse models of devastating human
neuromuscular diseases, amyotrophic lateral sclerosis, and Duchenne
muscular dystrophy (SOD1
G93A
and
mdx
,
respectively). The method identified diseased and healthy muscle with
high classification accuracies (area under the receiver operating
characteristic curves (AUROC): 0.76–0.92). In addition, changes
in diseased muscle over time were also identified (AUROCs 0.89–0.97).
Key spectral changes related to proteins and the loss of α-helix
protein structure. Importantly,
in vivo
recording
did not cause functional motor impairment and only a limited, resolving
tissue injury was seen on high-resolution magnetic resonance imaging.
Lastly, we demonstrate that
ex vivo
muscle from human
patients with these conditions produced similar spectra to those observed
in mice. We conclude that spontaneous Raman spectroscopy of muscle
shows promise as a translational research tool.