scholarly journals Correlating Local Volumetric Tissue Strains with Global Lung Mechanics Measurements

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 439
Author(s):  
Hari Arora ◽  
Ria Mitchell ◽  
Richard Johnston ◽  
Marinos Manolesos ◽  
David Howells ◽  
...  

The mechanics of breathing is a fascinating and vital process. The lung has complexities and subtle heterogeneities in structure across length scales that influence mechanics and function. This study establishes an experimental pipeline for capturing alveolar deformations during a respiratory cycle using synchrotron radiation micro-computed tomography (SR-micro-CT). Rodent lungs were mechanically ventilated and imaged at various time points during the respiratory cycle. Pressure-Volume (P-V) characteristics were recorded to capture any changes in overall lung mechanical behaviour during the experiment. A sequence of tomograms was collected from the lungs within the intact thoracic cavity. Digital volume correlation (DVC) was used to compute the three-dimensional strain field at the alveolar level from the time sequence of reconstructed tomograms. Regional differences in ventilation were highlighted during the respiratory cycle, relating the local strains within the lung tissue to the global ventilation measurements. Strains locally reached approximately 150% compared to the averaged regional deformations of approximately 80–100%. Redistribution of air within the lungs was observed during cycling. Regions which were relatively poorly ventilated (low deformations compared to its neighbouring region) were deforming more uniformly at later stages of the experiment (consistent with its neighbouring region). Such heterogenous phenomena are common in everyday breathing. In pathological lungs, some of these non-uniformities in deformation behaviour can become exaggerated, leading to poor function or further damage. The technique presented can help characterize the multiscale biomechanical nature of a given pathology to improve patient management strategies, considering both the local and global lung mechanics.

2019 ◽  
Vol 16 (154) ◽  
pp. 20180965 ◽  
Author(s):  
K. Robson Brown ◽  
D. Bacheva ◽  
R. S. Trask

In Nature, despite the diversity of materials, patterns and structural designs, the majority of biomineralized systems share a common feature: the incorporation of multiple sets of discrete elements across different length scales. This paper is the first to assess whether the design features observed in the hexactinellid sea sponge Euplectella aspergillum can be transferred and implemented for the development of new structurally efficient engineering architectures manufactured by three-dimensional (3D) additive manufacturing (AM). We present an investigation into the design and survival strategies found in the biological system and evaluate their translation into a scaled engineering analogue assessed experimentally and through finite-element (FE) simulations. Discrete sections of the skeletal lattice were evaluated and tested in an in situ compression fixture using micro-computed tomography (μCT). This methodology permitted the characterization of the hierarchical organization of the siliceous skeleton; a multi-layered arrangement with a fusion between struts to improve the local energy-absorbing capabilities. It was observed that the irregular overlapping architecture of spicule–nodal point sub-structure offers unique improvements in the global strength and stiffness of the structure. The 3D data arising from the μCT of the skeleton were used to create accurate FE models and replication through 3D AM. The printed struts in the engineering analogue were homogeneous, comprising bonded ceramic granular particles (10–100 µm) with an outer epoxy infused shell. In these specimens, the compressive response of the sample was expected to be dynamic and catastrophic, but while the specimens showed a similar initiation and propagation failure pattern to E. aspergillum , the macroscopic deformation behaviour was altered from the expected predominantly brittle behaviour to a more damage tolerant quasi-brittle failure mode. In addition, the FE simulation of the printed construct predicted the same global failure response (initiation location and propagation directionality) as observed in E. aspergillum . The ability to mimic directly the complex material construction and design features in E. aspergillum is currently beyond the latest advances in AM. However, while acknowledging the material-dominated limitations, the results presented here highlight the considerable potential of direct mimicry of biomineralized lattice architectures as future light-weight damage tolerant composite structures.


Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.


Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


Author(s):  
M. Boublik ◽  
N. Robakis ◽  
J.S. Wall

The three-dimensional structure and function of biological supramolecular complexes are, in general, determined and stabilized by conformation and interactions of their macromolecular components. In the case of ribosomes, it has been suggested that one of the functions of ribosomal RNAs is to act as a scaffold maintaining the shape of the ribosomal subunits. In order to investigate this question, we have conducted a comparative TEM and STEM study of the structure of the small 30S subunit of E. coli and its 16S RNA.The conventional electron microscopic imaging of nucleic acids is performed by spreading them in the presence of protein or detergent; the particles are contrasted by electron dense solution (uranyl acetate) or by shadowing with metal (tungsten). By using the STEM on freeze-dried specimens we have avoided the shearing forces of the spreading, and minimized both the collapse of rRNA due to air drying and the loss of resolution due to staining or shadowing. Figure 1, is a conventional (TEM) electron micrograph of 30S E. coli subunits contrasted with uranyl acetate.


Author(s):  
G. Jacobs ◽  
F. Theunissen

In order to understand how the algorithms underlying neural computation are implemented within any neural system, it is necessary to understand details of the anatomy, physiology and global organization of the neurons from which the system is constructed. Information is represented in neural systems by patterns of activity that vary in both their spatial extent and in the time domain. One of the great challenges to microscopists is to devise methods for imaging these patterns of activity and to correlate them with the underlying neuroanatomy and physiology. We have addressed this problem by using a combination of three dimensional reconstruction techniques, quantitative analysis and computer visualization techniques to build a probabilistic atlas of a neural map in an insect sensory system. The principal goal of this study was to derive a quantitative representation of the map, based on a uniform sample of afferents that was of sufficient size to allow statistically meaningful analyses of the relationships between structure and function.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dalal Al Hasan ◽  
Ameen Yaseen ◽  
Mohammad Al Roudan ◽  
Lee Wallis

Abstract Background The objective of this study was to describe the epidemiology of severe hypoglycaemia in Kuwait, aiming to provide a preliminary background to update the current guidelines and improve patient management. Method This was a prospective analysis of severe hypoglycaemia cases retrieved from emergency medical services (EMS) archived data between 1 January and 30 June 2020. The severe hypoglycaemia cases were then sub-grouped based on EMS personal initial management and compared in terms of scene time, transportation rate, complications and outcomes. The primary outcomes were GCS within 10–30 min and normal random blood glucose (RBS) within 10–30 min. Results A total of 167 cases met the inclusion criteria. The incidence of severe hypoglycaemia in the national EMS was 11 per 100,000. Intramuscular glucagon was used on scene in 89% of the hypoglycaemic events. Most of the severe hypoglycaemia patients regained normal GCS on scene (76.5%). When we compared the two scene management strategies for severe hypoglycaemia cases, parenteral glucose administration prolonged the on-scene time (P = .002) but was associated with more favourable scene outcomes than intramuscular glucagon, with normal GCS within 10–30 min (P = .05) and normal RBS within 10–30 min (P = .006). Conclusion: Severe hypoglycaemia is not uncommon during EMS calls. Appropriate management by EMS personals is fruitful, resulting in favourable scene outcomes and reducing the hospital transportation rate. More research should be invested in improving and structuring the prehospital management of severe hypoglycaemia. One goal is to clarify the superiority of parenteral glucose over intramuscular glucagon in the prehospital setting.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
M. Asada-Utsugi ◽  
K. Uemura ◽  
M. Kubota ◽  
Y. Noda ◽  
Y. Tashiro ◽  
...  

AbstractN-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angad Malhotra ◽  
Matthias Walle ◽  
Graeme R. Paul ◽  
Gisela A. Kuhn ◽  
Ralph Müller

AbstractMethods to repair bone defects arising from trauma, resection, or disease, continue to be sought after. Cyclic mechanical loading is well established to influence bone (re)modelling activity, in which bone formation and resorption are correlated to micro-scale strain. Based on this, the application of mechanical stimulation across a bone defect could improve healing. However, if ignoring the mechanical integrity of defected bone, loading regimes have a high potential to either cause damage or be ineffective. This study explores real-time finite element (rtFE) methods that use three-dimensional structural analyses from micro-computed tomography images to estimate effective peak cyclic loads in a subject-specific and time-dependent manner. It demonstrates the concept in a cyclically loaded mouse caudal vertebral bone defect model. Using rtFE analysis combined with adaptive mechanical loading, mouse bone healing was significantly improved over non-loaded controls, with no incidence of vertebral fractures. Such rtFE-driven adaptive loading regimes demonstrated here could be relevant to clinical bone defect healing scenarios, where mechanical loading can become patient-specific and more efficacious. This is achieved by accounting for initial bone defect conditions and spatio-temporal healing, both being factors that are always unique to the patient.


Vascular ◽  
2021 ◽  
pp. 170853812199650
Author(s):  
Joseph Edwards ◽  
Hossam Abdou ◽  
Neerav Patel ◽  
Marta J Madurska ◽  
Kelly Poe ◽  
...  

Objectives Swine ( Sus Scrofa) are utilized broadly in research settings, given similarities to human vessel size and function; however, there are some important differences for clinicians to understand in order to interpret and perform translational research. This review article uses angiograms acquired in the course of a translational research program to present a description of the functional anatomy of the swine. Methods Digital subtraction angiography and computed tomography angiography were obtained throughout the course of multiple studies utilizing power injection with iodinated contrast. Subtracted two-dimensional images and three-dimensional multiplanar reformations were utilized post image acquisition to create maximal intensity projections and three-dimensional renderings of using open-source software (OsiriX). These imaging data are presented along with vessel measurements for reference. Results An atlas highlighting swine vascular anatomy, with an emphasis on inter-species differences that may influence how studies are conducted and interpreted, was compiled. Conclusions Swine are utilized in broad-reaching fields for preclinical research. While many similarities between human and swine vasculature exist, there are important differences to consider when conducting and interpreting research. This review article highlights these differences and presents accompanying images to inform clinicians gaining experience in swine research.


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