Optical polarization tractography revealed significant fiber disarray in skeletal muscles of a mouse model for Duchenne muscular dystrophy

Wang, Y.; Zhang, K.; Wasala, Nalinda B.; Duan, Dongsheng; Yao, Gang

doi:10.1364/boe.6.000347

Cited by 19 publications

(22 citation statements)

References 18 publications

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“…Calcium deposits serve as a histological hallmark of DMD but not obviously of other myopathies, e.g., myotonic dystrophy type 1 [ 17 ]. Until now, analyses were performed either histologically or with gross anatomy imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), or recently optical coherence tomography [ 18 – 21 ]. While histological sectioning offers highly detailed examination of single slices, it seems vastly time- and labor-consuming, not suitable for performing comprehensive analyses on the entire organs/organism.…”

Section: Introductionmentioning

confidence: 99%

Whole-body clearing, staining and screening of calcium deposits in the mdx mouse model of Duchenne muscular dystrophy

et al. 2018

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BackgroundDuchenne muscular dystrophy (DMD) is a fatal, X-linked genetic disorder. Although DMD is the most common form of muscular dystrophy, only two FDA-approved drugs were developed to delay its progression. In order to assess therapies for treating DMD, several murine models have recently been introduced. As the wide variety of murine models enlighten mechanisms underlying DMD pathology, the question on how to monitor the progression of the disease within the entire musculoskeletal system still remains to be answered. One considerable approach to monitor such progression is histological evaluation of calcium deposits within muscle biopsies. Although accurate, histology is limited to small tissue area and cannot be utilized to evaluate systemic progression of DMD. Therefore, we aimed to develop a methodology suitable for rapid and high-resolution screening of calcium deposits within the entire murine organism.MethodsProcedures were performed on adult male C57BL/10-mdx and adult male C57BL mice. Animals were sacrificed, perfused, paraformaldehyde-fixed, and subjected to whole-body clearing using optimized perfusion-based CUBIC protocol. Next, cleared organisms were stained with alizarin red S to visualize calcium deposits and subjected to imaging.ResultsStudy revealed presence of calcium deposits within degenerated muscles of the entire C57BL/10-mdx mouse organism. Calcified deposits were observed within skeletal muscles of the forelimb, diaphragm, lumbar region, pelvic region, and hindlimb. Calcified deposits found in quadriceps femoris, triceps brachii, and spinalis pars lumborum were characterized. Analysis of cumulative frequency distribution showed different distribution characteristics of calcified deposits in quadriceps femoris muscle in comparison to triceps brachii and spinalis pars lumborum muscles (p < 0.001) and quadriceps femoris vs spinalis pars lumborum (p < 0.001). Differences between the number of calcified deposits in selected muscles, their volume, and average volume were statistically significant.ConclusionsIn aggregate, we present new methodology to monitor calcium deposits in situ in the mouse model of Duchenne muscular dystrophy. Sample imaging with the presented setup is feasible and applicable for whole-organ/body imaging. Accompanied by the development of custom-made LSFM apparatus, it allows targeted and precise characterization of calcium deposits in cleared muscles. Hence, presented approach might be broadly utilized to monitor degree to which muscles of the entire organism are affected by the necrosis and how is it altered by the treatment or physical activity of the animal. We believe that this would be a valuable tool for studying organs alternations in a wide group of animal models of muscle dystrophy and bone-oriented diseases.Electronic supplementary materialThe online version of this article (10.1186/s13395-018-0168-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Whole-body clearing, staining and screening of calcium deposits in the mdx mouse model of Duchenne muscular dystrophy

et al. 2018

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“…However, OPT can nondestructively image fiber orientation and birefringence at different depths from the tissue surface, which is not feasible in PLM. Recent studies have demonstrated that OPT can be potentially applied to image fiber structures in skeletal muscle, 31 heart muscle, 32 and blood vessels. 33 In this study, we showed that OPT can image collagen fiber orientation in the superficial layer of the articular cartilage.…”

Section: Introductionmentioning

confidence: 99%

Nondestructive imaging of fiber structure in articular cartilage using optical polarization tractography

et al. 2016

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Collagen fiber orientation plays an important role in determining the structure and function of the articular cartilage. However, there is currently a lack of nondestructive means to image the fiber orientation from the cartilage surface. The purpose of this study is to investigate whether the newly developed optical polarization tractography (OPT) can image fiber structure in articular cartilage. OPT was applied to obtain the depth-dependent fiber orientation in fresh articular cartilage samples obtained from porcine phalanges. For comparison, we also obtained collagen fiber orientation in the superficial zone of the cartilage using the established split-line method. The direction of each split-line was quantified using image processing. The orientation measured in OPT agreed well with those obtained from the split-line method. The correlation analysis of a total of 112 split-lines showed a greater than 0.9 coefficient of determination (R2) between the split-line results and OPT measurements obtained between 40 and 108???m in depth. In addition, the thickness of the superficial layer can also be assessed from the birefringence images obtained in OPT. These results support that OPT provides a nondestructive way to image the collagen fiber structure in articular cartilage. This technology may be valuable for both basic cartilage research and clinical orthopedic applications.

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“…The simplest explanation is that the amount of ongoing necrosis of dystrophic muscles was much higher in the Bl10/ mdx , compared with D2/ mdx , mice. The new technology OPT (optical polarization tractography) allows to reconstruct organization of a whole fiber and may be useful to look deeper at all histological aspects, especially in mixed fast/slow muscles like the tibialis anterior [ 13, 14 ].…”

Section: Histological Measuresmentioning

confidence: 99%

“Of Mice and Measures”: A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic

Gordish‐Dressman

Willmann

Pazze

et al. 2018

JND

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A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a candidate to study the efficacy of therapeutic approaches for Duchenne muscular dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase the severity of the dystropathology, with disease modifiers that also occur in DMD patients, making them attractive for efficacy studies and drug development. This workshop aimed at collecting and consolidating available data on the pathological features and the natural history of these new D2/mdx mice, for comparison with classic mdx mice and controls, and to identify gaps in information and their potential value. The overall aim is to establish guidance on how to best use the D2/mdx mouse model in preclinical studies.

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Optical polarization tractography revealed significant fiber disarray in skeletal muscles of a mouse model for Duchenne muscular dystrophy

Cited by 19 publications

References 18 publications

Whole-body clearing, staining and screening of calcium deposits in the mdx mouse model of Duchenne muscular dystrophy

Whole-body clearing, staining and screening of calcium deposits in the mdx mouse model of Duchenne muscular dystrophy

Nondestructive imaging of fiber structure in articular cartilage using optical polarization tractography

“Of Mice and Measures”: A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic

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