Rapid identification of human muscle disease with fibre optic Raman spectroscopy

Alix, James J P; Plesia, Maria; Lloyd, Gavin R.; Dudgeon, Alexander P.; Kendall, Catherine; Hewamadduma, Channa; Hadjivassiliou, Marios; McDermott, Christopher J.; Gorman, Gráinne; Taylor, Robert W.; Shaw, Pamela J.; Day, John C C

doi:10.1039/d1an01932e

Cited by 14 publications

(17 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous in vivo preclinical work with a Raman‐only probe, we were able to discriminate between neurogenic and myopathic pathology, and different stages of disease 5,9 . Ex vivo human muscle biopsy analyses with the same Raman‐only probe were also promising in identifying muscle pathology, including different types of muscle disease 10,11 . Thus, while we did not study different types of muscle pathology on this occasion, we anticipate that optical EMG should be capable of providing similar information, enabling discrimination between different neuromuscular disorders and different stages of disease.…”

Section: Discussionmentioning

confidence: 92%

“…Using a fiber optic Raman spectroscopy probe in which optical fibers were passed down a standard hypodermic needle, we developed an in vivo preclinical methodology capable of identifying neurogenic and myogenic disease 5 and monitoring disease state 9 . Using the same probe, we have also demonstrated the diagnostic potential of the technique to identify muscle disease in human biopsy specimens 10,11 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combining electromyography and Raman spectroscopy: optical EMG

et al. 2023

Self Cite

View full text Add to dashboard Cite

Introduction/AimsElectromyography (EMG) remains a key component of the diagnostic work‐up for suspected neuromuscular disease, but it does not provide insight into the molecular composition of muscle which can provide diagnostic information. Raman spectroscopy is an emerging neuromuscular biomarker capable of generating highly specific, molecular fingerprints of tissue. Here, we present “optical EMG,” a combination of EMG and Raman spectroscopy, achieved using a single needle.MethodsAn optical EMG needle was created to collect electrophysiological and Raman spectroscopic data during a single insertion. We tested functionality with in vivo recordings in the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), using both transgenic (n = 10) and non‐transgenic (NTg, n = 7) mice. Under anesthesia, compound muscle action potentials (CMAPs), spontaneous EMG activity and Raman spectra were recorded from both gastrocnemius muscles with the optical EMG needle. Standard concentric EMG needle recordings were also undertaken. Electrophysiological data were analyzed with standard univariate statistics, Raman data with both univariate and multivariate analyses.ResultsA significant difference in CMAP amplitude was observed between SOD1G93A and NTg mice with optical EMG and standard concentric needles (p = .015 and p = .011, respectively). Spontaneous EMG activity (positive sharp waves) was detected in transgenic SOD1G93A mice only. Raman spectra demonstrated peaks associated with key muscle components. Significant differences in molecular composition between SOD1G93A and NTg muscle were identified through the Raman spectra.DiscussionOptical EMG can provide standard electrophysiological data and molecular Raman data during a single needle insertion and represents a potential biomarker for neuromuscular disease.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Combining electromyography and Raman spectroscopy: optical EMG

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The balance between α‐helix and β‐sheet structures appears to be a robust biomarker of muscle health, noted not only in the preceding microscope/probe analysis on human tissue but also in our previous work in mice [5], human samples using more standard PCA feature extraction [6, 7] and the work of Gautam et al in fly models of myopathy [26]. Biomarkers of disease that cross the preclinical/clinical divide and can provide an equivalent readout of disease state in both settings are a priority area in fatal neuromuscular conditions [27–29].…”

Section: Resultsmentioning

confidence: 99%

Non‐negative matrix factorisation of Raman spectra finds common patterns relating to neuromuscular disease across differing equipment configurations, preclinical models and human tissue

Alix

Plesia

Schooling

et al. 2022

J Raman Spectroscopy

Self Cite

View full text Add to dashboard Cite

Raman spectroscopy shows promise as a biomarker for complex nerve and muscle (neuromuscular) diseases. To maximise its potential, several challenges remain. These include the sensitivity to different instrument configurations, translation across preclinical/human tissues and the development of multivariate analytics that can derive interpretable spectral outputs for disease identification. Nonnegative matrix factorisation (NMF) can extract features from high-dimensional data sets and the nonnegative constraint results in physically realistic outputs. In this study, we have undertaken NMF on Raman spectra of muscle obtained from different clinical and preclinical settings. First, we obtained and combined Raman spectra from human patients with mitochondrial disease and healthy volunteers, using both a commercial microscope and in-house fibre optic probe. NMF was applied across all data, and spectral patterns common to both equipment configurations were identified. Linear

show abstract

“…It is rapid and label‐free, requiring no sample preparation. Biomedical applications of the technology are gaining momentum across many different areas, 4 including neuromuscular diseases 2,5,6 …”

Section: Introductionmentioning

confidence: 99%

“…Biomedical applications of the technology are gaining momentum across many different areas, 4 including neuromuscular diseases. 2,5,6 Microscope formats are traditionally used to evaluate tissue or biofluid samples, but recent developments in fiber optic technology are of increasing interest. 7 Such methods hold the promise of targeting light to an area of interest in vivo to provide a rapid assessment of tissue health.…”

mentioning

confidence: 99%

Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy: An assessment using the mdx model and human muscle

et al. 2022

Self Cite

View full text Add to dashboard Cite

Introduction/Aims: Raman spectroscopy is an emerging technique for the evaluation of muscle disease. In this study we evaluate the ability of in vivo intramuscular Raman spectroscopy to detect the effects of voluntary running in the mdx model of Duchenne muscular dystrophy (DMD). We also compare mdx data with muscle spectra from human DMD patients.Methods: Thirty 90-day-old mdx mice were randomly allocated to an exercised group (48-hour access to a running wheel) and an unexercised group (n = 15 per group). In vivo Raman spectra were collected from both gastrocnemius muscles and histopathological assessment subsequently performed. Raman data were analyzed using principal component analysis-fed linear discriminant analysis (PCA-LDA). Exercised and unexercised mdx muscle spectra were compared with human DMD samples using cosine similarity.Results: Exercised mice ran an average of 6.5 km over 48 hours, which induced a significant increase in muscle necrosis (P = .03). PCA-LDA scores were significantly different between the exercised and unexercised groups (P < .0001) and correlated significantly with distance run (P = .01). Raman spectra from exercised mice more closely resembled human spectra than those from unexercised mice.Discussion: Raman spectroscopy provides a readout of the biochemical alterations in muscle in both the mdx mouse and human DMD muscle.

show abstract

Rapid identification of human muscle disease with fibre optic Raman spectroscopy

Abstract: The diagnosis of muscle disorders (“myopathies”) can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and...

Cited by 14 publications

References 40 publications

Combining electromyography and Raman spectroscopy: optical EMG

Combining electromyography and Raman spectroscopy: optical EMG

Non‐negative matrix factorisation of Raman spectra finds common patterns relating to neuromuscular disease across differing equipment configurations, preclinical models and human tissue

Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy: An assessment using the mdx model and human muscle

Contact Info

Product

Resources

About