scholarly journals Micro Computed Tomography as an Accessible Imaging Platform for Exploring Organism Development and Human Disease Modeling

2018 ◽  
Author(s):  
Todd A. Schoborg ◽  
Samantha L. Smith ◽  
Lauren N. Smith ◽  
H. Douglas Morris ◽  
Nasser M. Rusan

ABSTRACTUnderstanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here we present an optimized method for non-invasive imaging of Drosophila melanogaster at high resolution using micro computed tomography (μ-CT). Our method allows for rapid processing of intact animals at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use the power of μ-CT imaging to model human diseases through the characterization of microcephaly in the fly. Our work demonstrates that μ-CT is a versatile and accessible tool that complements standard imaging techniques, capable of uncovering novel biological mechanisms that have remained undocumented due to limitations of current methods.

2014 ◽  
Vol 88 (4) ◽  
pp. 633-635 ◽  
Author(s):  
Imran A. Rahman ◽  
Selena Y. Smith

‘Virtual paleontology’ entails the use of computational methods to assist in the three-dimensional (3-D) visualization and analysis of fossils, and has emerged as a powerful approach for research on the history of life. Three-dimensional imaging techniques allow poorly understood or previously unknown anatomies of fossil plants, invertebrates, and vertebrates, as well as microfossils and trace fossils, to be described in much greater detail than formerly possible, and are applicable to a wide range of preservation types and specimen sizes (Table 1). These methods include non-destructive high-resolution scanning technologies such as conventional X-ray micro-tomography and synchrotron-based X-ray tomography. In addition, form and function can be rigorously investigated through quantitative analysis of computer models, for example finite-element analysis.


2019 ◽  
Vol 2 ◽  
Author(s):  
Francesco Simone Mensa ◽  
Federica Spani ◽  
Andrea Di Giulio

The genus Paussus is a highly specialized, charismatic group of ground beetles (Carabidae) classified in the subfamily Paussinae. All species of Paussus are obligate myrmecophiles (associates of ants). As with many other myrmecophilous or termitophilous beetles, Paussus have undergone extreme phenotypic adaptations for life with ants, at the level of head, antennae, and prothorax. Host data suggest that Paussus species are likely to be species-specific ant parasites, and the structural modifications of antennae and other body parts are likely under selection by their host ants. Investigating anatomical structures have been fundamental to better understand living organisms, and their interplay with the surrounding environment, which could induce significant morphological variation. In the last few years, bio-imaging techniques paired with geometric morphometrics (GM) overcame the limits of traditional anatomical studies, becoming widely non-invasive and highly informative for both internal and external characters. The use of Computed Tomography (CT) scanners definitively allowed to advance in the knowledge of either known or neglected biological structures. For this project, we used X-ray micro-computed tomography, in order to acquire 2D serial, cross-sections of various paussines samples, with a resolution between 0.954 and 2.44 micrometers. The 2D images in high resolution are then processed using a high-performance computer system and Thermo Scientific™ Amira™ Software and Thermo Scientific™ Avizo™ Software for the reconstruction of 3D models. With these models, we will be able to conduct a morphological study of the most variable parts in the body of the genus Paussus using 3D geometric morphometrics (3D GM), as these integrative techniques allows to describe in a quantitative way even subtle differences between structures, so as to determine whether the striking diversity of phenotypes is caused by the host or by other factors, overlapping the results obtained with the molecular part of phylogeny. These innovative practices help to deepen the meaning of shape in insect biology, from both structural and evolutionary views. They will allow, in particular, to describe the relationship between phylogeny and functional morphology in the extremely variable species of the subfamily Paussinae.


2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Frank Stahnisch

AbstractIn theoretical accounts of the neurosciences, investigative research programs have often been separated into the morphological and physiological tradition. The morphological tradition is seen as describing the structure and form of the external and interior parts of the brain and spinal cord. The physiological tradition is interpreted as a compilation of those approaches which investigate cerebral functions particularly in their dynamic interactions. It must be regarded as an open question, though, whether the distinction between the morphological and physiological tradition in modern clinical and basic neuroscience has now become obsolete with the most recent neuroimaging techniques, such as fMRI, PET scans, SPECT, etc. Taken at face value, these new imaging techniques seem to relate, overlap, and even identify the anatomical with the functional substrate, when mapping individual patterns of neural activity across the visually delineated morphological structures. The particular focus of this review article is primarily on the morphological tradition, beginning with German neuroanatomist Samuel Thomas Soemmerring and leading to recent approaches in the neurohistological work of neuroscience centres in the United States and morphophysiological neuroimaging techniques in Canada. Following some landmark research steps in neuroanatomy detailed in the first section, this article analyzes the changing trajectories to an integrative theory of the brain in its second section. An examination of the relationship between form and function within the material culture of neuroscience in the third and final part, will further reveal an astonishingly heterogeneous investigative and conceptual terrain.


2018 ◽  
Vol 46 (5) ◽  
pp. 511-529 ◽  
Author(s):  
Aurore Varela ◽  
Jacquelin Jolette

Bone is a unique tissue with turnover, metabolic, and cellular activities that vary through development to aging and with a mineralized matrix in which the current state and the history of a bone coexist. Qualitative histopathology often lacks sensitivity to detect changes in bone formation, mineralization and resorption, which often requires chronic dosing to result in structural changes such as variation in bone mass and geometry. A large panel of modalities can be used to fully analyze the health of the skeleton, including biomarker evaluation in serum or urine, imaging techniques ranging from radiology to computed tomography, biomechanical testing, and undecalcified tissue processing with bone histomorphometry. The use of clinically relevant biomarkers provides an important noninvasive, sensitive, rapid, and real-time tool to monitor bone activity at the whole skeleton level when conducting safety assessments in a preclinical setting. Imaging modalities also allow in vivo longitudinal assessments with a powerful, noninvasive and clinically translatable tools to monitor drug effects. Different imaging modalities are used in the preclinical studies to evaluate the bone tissues: standard radiography, dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), micro-computed tomography, and high-resolution pQCT. Bone histomorphometry is an important tool that provides sensitive evaluation to detect effects of test articles on bone resorption, formation, mineralization, remodeling rates and growth to address a potential target- or class-related theoretical bone liability. Ultimately, the measurement of bone mechanical properties in pharmaceutical testing is critical to understand the potential effects of that pharmaceutical on bone health and fracture risk. Important considerations are required for including these different techniques in toxicology rodents and nonrodent studies, to actually integrate these into safety assessment.


2020 ◽  
Author(s):  
Neil Marr ◽  
Mark Hopkinson ◽  
Andrew P. Hibbert ◽  
Andrew A. Pitsillides ◽  
Chavaunne T. Thorpe

ABSTRACTBACKGROUND3-dimensional imaging modalities for optically dense connective tissues such as tendons are limited and typically have a single imaging methodological endpoint. Here, we have developed a bimodal procedure that utilises fluorescence-based confocal microscopy and x-ray micro-computed tomography for the imaging of adult tendons to visualise and analyse extracellular sub-structure and cellular composition in small and large animal species.RESULTSUsing fluorescent immunolabelling and optical clearing, we visualised the expression of the basement membrane protein laminin-α4 in 3D throughout whole rat Achilles tendons and equine superficial digital flexor tendon 5 mm segments. This revealed a complex network of laminin-α4 within the tendon core that predominantly localises to the interfascicular matrix compartment. Furthermore, we implemented a chemical drying process capable of creating contrast densities enabling visualisation and quantification of both fascicular and interfascicular matrix volume and thickness by x-ray micro-computed tomography. We also demonstrated that both modalities can be combined using reverse clarification of fluorescently labelled tissues prior to chemical drying to enable bimodal imaging of a single sample.CONCLUSIONSWhole-mount imaging of tendon allowed us to identify the presence of an extensive network of laminin-α4 within tendon, the complexity of which cannot be appreciated using traditional 2D imaging techniques. Creating contrast for x-ray micro-computed tomography imaging of tendon using chemical drying is not only simple and rapid, but also markedly improves on previously published methods. Combining these methods provides the ability to gain spatio-temporal information and quantify tendon substructures to elucidate the relationship between morphology and function.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sergi Llambrich ◽  
Jens Wouters ◽  
Uwe Himmelreich ◽  
Mara Dierssen ◽  
James Sharpe ◽  
...  

Abstract Up to 40% of congenital diseases present disturbances of brain and craniofacial development resulting in simultaneous alterations of both systems. Currently, the best available method to preclinically visualize the brain and the bones simultaneously is to co-register micro-magnetic resonance (µMR) and micro-computed tomography (µCT) scans of the same specimen. However, this requires expertise and access to both imaging techniques, dedicated software and post-processing knowhow. To provide a more affordable, reliable and accessible alternative, recent research has focused on optimizing a contrast-enhanced µCT protocol using iodine as contrast agent that delivers brain and bone images from a single scan. However, the available methods still cannot provide the complete visualization of both the brain and whole craniofacial complex. In this study, we have established an optimized protocol to diffuse the contrast into the brain that allows visualizing the brain parenchyma and the complete craniofacial structure in a single ex vivo µCT scan (whiceCT). In addition, we have developed a new technique that allows visualizing the brain ventricles using a bilateral stereotactic injection of iodine-based contrast (viceCT). Finally, we have tested both techniques in a mouse model of Down syndrome, as it is a neurodevelopmental disorder with craniofacial, brain and ventricle defects. The combined use of viceCT and whiceCT provides a complete visualization of the brain and bones with intact craniofacial structure of an adult mouse ex vivo using a single imaging modality.


2020 ◽  
Author(s):  
Anabela Bensimon-Brito ◽  
Giulia L. M. Boezio ◽  
João Cardeira-da-Silva ◽  
Astrid Wietelmann ◽  
Christian S. M. Helker ◽  
...  

AbstractMammalian models have been instrumental to investigate adult heart function and human disease. However, electrophysiological differences with human hearts and high costs emphasize the need for additional models. The zebrafish is a well-established genetic model to study cardiac development and function; however, analysis of cardiac phenotypes in adult specimens is particularly challenging as they are opaque. Here, we optimized and combined multiple imaging techniques including echocardiography, magnetic resonance imaging and micro-computed tomography to identify and analyze cardiac phenotypes in adult zebrafish. Using alk5a/tgfbr1a mutants as a case study, we observed morphological and functional cardiac defects, which were undetected with conventional approaches. Correlation analysis of multiple parameters revealed an association between hemodynamic defects and structural alterations of the heart, as observed clinically. Thus, we report a comprehensive and sensitive platform to identify otherwise indiscernible cardiac phenotypes in adult zebrafish, a model with clear advantages to study cardiac function and disease.


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