Abstract
.Significance: Current methods for analyzing pathological muscle tissue are time consuming and rarely quantitative, and they involve invasive biopsies. Faster and less invasive diagnosis of muscle disease may be achievable using marker-free in vivo optical sensing methods.Aim: It was speculated that changes in the biochemical composition and structure of muscle associated with pathology could be measured quantitatively using visible wavelength optical spectroscopy techniques enabling automated classification.Approach: A fiber-optic autofluorescence (AF) and diffuse reflectance (DR) spectroscopy device was manufactured. The device and data processing techniques based on principal component analysis were validated using in situ measurements on healthy skeletal and cardiac muscle. These methods were then applied to two mouse models of genetic muscle disease: a type 1 neurofibromatosis (NF1) limb-mesenchyme knockout () and a muscular dystrophy mouse (mdx).Results: Healthy skeletal and cardiac muscle specimens were separable using AF and DR with receiver operator curve areas (ROC-AUC) of . AF and DR analyses showed optically separable changes in quadriceps muscle (ROC-AUC >0.97) with no differences detected in the heart (ROC-AUC <0.67), which does not undergo gene deletion in this model. Changes in AF spectra in mdx muscle were seen between the 3 week and 10 week time points (ROC-AUC = 0.96) and were not seen in the wild-type controls (ROC-AUC = 0.58).Conclusion: These findings support the utility of in vivo fiber-optic AF and DR spectroscopy for the assessment of muscle tissue. This report highlights that there is considerable scope to develop this marker-free optical technology for preclinical muscle research and for diagnostic assessment of clinical myopathies and dystrophies.
Highlights
Optical technologies capable of real-time quantitative analysis of tissue structure and biochemical composition have the potential to revolutionize medical diagnostics
For diffuse reflectance (DR) measurements, overlapping confidence intervals (CIs) were observed across all wavelengths for all skeletal muscle groups, whereas cardiac muscle was separable from only quadriceps and gastrocnemius groups at ∼560 nm, and from tibialis anterior only between 630 and 895 nm [Fig. 2(e)]
We describe the design of a minimally invasive marker-free method of optical spectroscopy suitable to the real-time in vivo analysis of muscle tissue
Summary
Optical technologies capable of real-time quantitative analysis of tissue structure and biochemical composition have the potential to revolutionize medical diagnostics. Established noninvasive imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, offer faster, reliable, and interpreted anatomical data with some compositional information These modalities suffer from a variety of limitations including long acquisition times, ionizing radiation exposure, poor contrast between soft tissue types, the need for use of exogenous contrast agents, and large and expensive hardware.[1,2,3] Alongside these methods, a range of optical techniques that utilize custom-engineered exogenous fluorescent markers of disease have emerged; these include small molecule organic fluorophores,[4] quantum dots,[5] carbon nanotubes,[6] and various other nanomaterials.[7,8] considerable scope remains for developing minimally invasive spectroscopic devices [e.g., based on autofluorescence (AF) or diffuse reflectance (DR)] that can be used in the absence of specific probes or dyes. Fluorescent biological molecules include a variety of amino acids, structural proteins, enzymes, coenzymes, vitamins, lipids, and porphyrins, each of which possesses distinctive excitation/emission spectra.[9,10] Their distributions vary between tissue types, and their individual fluorescence properties can be affected by their molecular environment,[11] pH, and temperature,[13] making AF spectroscopy a powerful diagnostic tool
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