Image-based modelling of skeletal muscle oxygenation

Zeller‐Plumhoff, Berit; Roose, Tiina; Clough, Geraldine F.; Schneider, Philipp

doi:10.1098/rsif.2016.0992

Cited by 14 publications

(7 citation statements)

References 153 publications

(238 reference statements)

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“…Capillary networks are the fundamental site of oxygen (O 2 ) exchange in the microcirculation. Given their complexity and scale, understanding how capillary networks participate in microvascular oxygen exchange has proven challenging, but not insurmountable (Pittman, 2013;Zeller-Plumhoff et al 2017b;Poole, 2019). Skeletal muscle comprises the largest organ by mass and largest capillary bed in the body (Poole et al 2013), and impaired microvascular oxygen exchange in skeletal muscle contributes to exercise limitation in ageing, and for patients with diabetes, congestive heart failure and COPD (Poole et al 2020).…”

Section: Introductionmentioning

confidence: 99%

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The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks

Mendelson

Milkovich

Hunter

et al. 2021

The Journal of Physiology

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Key points The capillary module, consisting of parallel capillaries from arteriole to venule, is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres. Using intravital video microscopy of resting extensor digitorum longus muscle in rats, we demonstrated the capillary fascicle as a series of interconnected modules forming continuous columns that align naturally with the dimensions of the muscle fascicle. We observed structural heterogeneity for module topology, and functional heterogeneity in space and time for capillary‐red blood cell (RBC) haemodynamics within a module and between modules. We found that module RBC haemodynamics were independent of module resistance, providing direct evidence for microvascular flow regulation at the level of the capillary module. The capillary fascicle is an updated paradigm for characterizing blood flow and RBC distribution in skeletal muscle capillary networks. Abstract Capillary networks are the fundamental site of oxygen exchange in the microcirculation. The capillary module (CM), consisting of parallel capillaries from terminal arteriole (TA) to post‐capillary venule (PCV), is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres, requiring co‐ordination from numerous modules. It has previously been recognized that TAs and PCVs interact with multiple CMs, creating interconnected networks. Using label‐free intravital video microscopy of resting extensor digitorum longus muscle in rats, we found that these networks form continuous columns of linked CMs spanning thousands of microns, herein denoted as the capillary fascicle (CF); this structure aligns naturally with the dimensions of the muscle fascicle. We measured capillary‐red blood cell (RBC) haemodynamics and module topology (n = 9 networks, 327 modules, 1491 capillary segments). The average module had length 481 μm, width 157 μm and 9.51 parallel capillaries. We observed structural heterogeneity for CM topology, and functional heterogeneity in space and time for capillary‐RBC haemodynamics within a module and between modules. There was no correlation between capillary RBC velocity and lineal density. A passive inverse relationship between module length and haemodynamics was remarkably absent, providing direct evidence for microvascular flow regulation at the level of the CM. In summary, the CF is an updated paradigm for characterizing RBC distribution in skeletal muscle, and strengthens the theory of capillary networks as major contributors to the signal that regulates capillary perfusion.

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Section: Introductionmentioning

confidence: 99%

“…Given their complexity and scale, understanding how capillary networks participate in microvascular oxygen exchange has proven challenging, but not insurmountable (Pittman, 2013; Zeller‐Plumhoff et al . 2017 b ; Poole, 2019). Skeletal muscle comprises the largest organ by mass and largest capillary bed in the body (Poole et al .…”

Section: Introductionmentioning

confidence: 99%

The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks

Mendelson

Milkovich

Hunter

et al. 2021

The Journal of Physiology

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“…The capability of synchrotron radiation CT has previously been used to generate 3D data sets of soft tissue for subsequent finite element modelling. This is demonstrated by Zeller-Plumhoff et al [15,16] in the context of oxygen diffusion in murine muscle. High resolution CT can also enable the analysis of morphological measures in biological systems and their functional importance [16].…”

Section: Introductionmentioning

confidence: 70%

Using high resolution X-ray computed tomography to create an image based model of a lymph node

Cooper

Zeller‐Plumhoff

Clough

et al. 2018

Journal of Theoretical Biology

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Lymph nodes are an important part of the immune system. They filter the lymphatic fluid as it is transported from the tissues before being returned to the blood stream. The fluid flow through the nodes influences the behaviour of the immune cells that gather within the nodes and the structure of the node itself. Measuring the fluid flow in lymph nodes experimentally is challenging due to their small size and fragility. In this paper, we present high resolution X-ray computed tomography images of a murine lymph node. The impact of the resulting visualized structures on fluid transport are investigated using an image based model. The high contrast between different structures within the lymph node provided by phase contrast X-ray computed tomography reconstruction results in images that, when related to the permeability of the lymph node tissue, suggest an increased fluid velocity through the interstitial channels in the lymph node tissue. Fluid taking a direct path from the afferent to the efferent lymphatic vessel, through the centre of the node, moved faster than the fluid that flowed around the periphery of the lymph node. This is a possible mechanism for particles being moved into the cortex.

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“…The last phase of IBM is the parameter estimation and validation part to check whether the output of the formulated model correlates with the desired output or not. A lot of studies have been done on various diseases with IBM [ 150–152 ].…”

Section: Future Directionmentioning

confidence: 99%

Tracing the footsteps of autophagy in computational biology

Sarmah

Bairagi

Chatterjee

2020

Briefings in Bioinformatics

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Autophagy plays a crucial role in maintaining cellular homeostasis through the degradation of unwanted materials like damaged mitochondria and misfolded proteins. However, the contribution of autophagy toward a healthy cell environment is not only limited to the cleaning process. It also assists in protein synthesis when the system lacks the amino acids’ inflow from the extracellular environment due to diet consumptions. Reduction in the autophagy process is associated with diseases like cancer, diabetes, non-alcoholic steatohepatitis, etc., while uncontrolled autophagy may facilitate cell death. We need a better understanding of the autophagy processes and their regulatory mechanisms at various levels (molecules, cells, tissues). This demands a thorough understanding of the system with the help of mathematical and computational tools. The present review illuminates how systems biology approaches are being used for the study of the autophagy process. A comprehensive insight is provided on the application of computational methods involving mathematical modeling and network analysis in the autophagy process. Various mathematical models based on the system of differential equations for studying autophagy are covered here. We have also highlighted the significance of network analysis and machine learning in capturing the core regulatory machinery governing the autophagy process. We explored the available autophagic databases and related resources along with their attributes that are useful in investigating autophagy through computational methods. We conclude the article addressing the potential future perspective in this area, which might provide a more in-depth insight into the dynamics of autophagy.

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Image-based modelling of skeletal muscle oxygenation

Cited by 14 publications

References 153 publications

The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks

The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks

Using high resolution X-ray computed tomography to create an image based model of a lymph node

Tracing the footsteps of autophagy in computational biology

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