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      Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT)

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          Abstract

          Microfocus CT (micro-CT) has traditionally been used in industry and preclinical studies, although it may find new applicability in the routine clinical setting. It can provide high-resolution three-dimensional digital imaging data sets to the same level of detail as microscopic examination without the need for tissue dissection. Micro-CT is already enabling non-invasive detailed internal assessment of various tissue specimens, particularly in breast imaging and early gestational fetal autopsy, not previously possible from more conventional modalities such as MRI or CT. In this review, we discuss the technical aspects behind micro-CT image acquisition, how early work with small animal studies have informed our knowledge of human disease and the imaging performed so far on human tissue specimens. We conclude with potential future clinical applications of this novel and emerging technique.

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          Most cited references56

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          MicroCT for comparative morphology: simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues

          Background Comparative, functional, and developmental studies of animal morphology require accurate visualization of three-dimensional structures, but few widely applicable methods exist for non-destructive whole-volume imaging of animal tissues. Quantitative studies in particular require accurately aligned and calibrated volume images of animal structures. X-ray microtomography (microCT) has the potential to produce quantitative 3D images of small biological samples, but its widespread use for non-mineralized tissues has been limited by the low x-ray contrast of soft tissues. Although osmium staining and a few other techniques have been used for contrast enhancement, generally useful methods for microCT imaging for comparative morphology are still lacking. Results Several very simple and versatile staining methods are presented for microCT imaging of animal soft tissues, along with advice on tissue fixation and sample preparation. The stains, based on inorganic iodine and phosphotungstic acid, are easier to handle and much less toxic than osmium, and they produce high-contrast x-ray images of a wide variety of soft tissues. The breadth of possible applications is illustrated with a few microCT images of model and non-model animals, including volume and section images of vertebrates, embryos, insects, and other invertebrates. Each image dataset contains x-ray absorbance values for every point in the imaged volume, and objects as small as individual muscle fibers and single blood cells can be resolved in their original locations and orientations within the sample. Conclusion With very simple contrast staining, microCT imaging can produce quantitative, high-resolution, high-contrast volume images of animal soft tissues, without destroying the specimens and with possibilities of combining with other preparation and imaging methods. Such images are expected to be useful in comparative, developmental, functional, and quantitative studies of morphology.
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            Diffusible iodine‐based contrast‐enhanced computed tomography (diceCT): an emerging tool for rapid, high‐resolution, 3‐D imaging of metazoan soft tissues

            Abstract Morphologists have historically had to rely on destructive procedures to visualize the three‐dimensional (3‐D) anatomy of animals. More recently, however, non‐destructive techniques have come to the forefront. These include X‐ray computed tomography (CT), which has been used most commonly to examine the mineralized, hard‐tissue anatomy of living and fossil metazoans. One relatively new and potentially transformative aspect of current CT‐based research is the use of chemical agents to render visible, and differentiate between, soft‐tissue structures in X‐ray images. Specifically, iodine has emerged as one of the most widely used of these contrast agents among animal morphologists due to its ease of handling, cost effectiveness, and differential affinities for major types of soft tissues. The rapid adoption of iodine‐based contrast agents has resulted in a proliferation of distinct specimen preparations and scanning parameter choices, as well as an increasing variety of imaging hardware and software preferences. Here we provide a critical review of the recent contributions to iodine‐based, contrast‐enhanced CT research to enable researchers just beginning to employ contrast enhancement to make sense of this complex new landscape of methodologies. We provide a detailed summary of recent case studies, assess factors that govern success at each step of the specimen storage, preparation, and imaging processes, and make recommendations for standardizing both techniques and reporting practices. Finally, we discuss potential cutting‐edge applications of diffusible iodine‐based contrast‐enhanced computed tomography (diceCT) and the issues that must still be overcome to facilitate the broader adoption of diceCT going forward.
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              High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice.

              Detailed anatomical atlases can provide considerable interpretive power in studies of both human and rodent neuroanatomy. Here we describe a three-dimensional atlas of the mouse brain, manually segmented into 62 structures, based on an average of 32 mum isotropic resolution T(2)-weighted, within skull images of forty 12 week old C57Bl/6J mice, scanned on a 7 T scanner. Individual scans were normalized, registered, and averaged into one volume. Structures within the cerebrum, cerebellum, and brainstem were painted on each slice of the average MR image while using simultaneous viewing of the coronal, sagittal and horizontal orientations. The final product, which will be freely available to the research community, provides the most detailed MR-based, three-dimensional neuroanatomical atlas of the whole brain yet created. The atlas is furthermore accompanied by ancillary detailed descriptions of boundaries for each structure and provides high quality neuroanatomical details pertinent to MR studies using mouse models in research.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                The British Journal of Radiology
                BJR
                British Institute of Radiology
                0007-1285
                1748-880X
                July 2017
                July 2017
                : 90
                : 1075
                : 20170113
                Affiliations
                [1 ]Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
                [2 ]UCL Great Ormond Street Institute of Child Health, London, UK
                [3 ]Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
                Article
                10.1259/bjr.20170113
                5594989
                28368658
                b865de58-eff6-410f-93c3-e601df21319b
                © 2017
                History

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