<i>In vivo</i> assessment of emphysema in mice by high resolution <scp>X</scp>‐ray microtomography

Постнов, А. А.; Meurrens, Kris; Weiler, H.; Dyck, D. Van; Xu, H.; Terpstra, Piter; Clerck, Nora M. De

doi:10.1111/j.1365-2818.2005.01510.x

Cited by 44 publications

(42 citation statements)

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“…9,18) However, studies reveal lowest value is Ϫ800 HU and never reached Ϫ950 HU in murine emphysematous lung. 29,30) In addition, mean density of murine normal lung is around Ϫ500 to Ϫ600 HU by ours and Plathow et al 20) and around Ϫ400 HU, 20,29,30) which is quite different from that of human (Ϫ700 HU).…”

Section: Discussionmentioning

confidence: 95%

Sequential and Quantitative Analysis of a Murine Model of Elastase-Induced Emphysema

Kawakami

Matsuo

Yoshiura

et al. 2008

Biological & Pharmaceutical Bulletin

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Chronic obstructive pulmonary disease (COPD) is one of the serious causative diseases in death of aging people.1) Emphysema, one of COPD, is characterized as destruction of airway wall and small airway inflammation.1) An imbalance between elastinolytic proteases and their natural inhibitors is thought to play a role in the pathogenesis of emphysema. One animal model of emphysema is made by administrating of elastase into the lungs.2-4) Cigarette smoke-induced emphysema is another common model of emphysema. A study of elastase-deficient mice has revealed that elastase is also critical in smoke-induced emphysema.5) As several months are required to establish cigarette smoke-induced emphysema, the elastase-induced model is more convenient for assessing drug effects.To quantitatively assess the murine model of emphysema, historical assessment using mean linear intercept (Lm) has been used. 6) Because the elastase-induced destruction of airway wall is not homogenous, random several views are taken to estimate the destruction.The non-homogenous region of the disease is also applicable for human. In human, noninvasive computed tomography (CT) is commonly used for diagnosis and disease staging by assessing areas of low attenuation.1,7) The primary benefits of CT monitoring are the ability to assess the lungs in their entirety and the ability to follow the same mice over time.Micro-computed tomography has been developed, resulting in low-noise CT images in a small animal. CT images are used to follow-up tumor growth in the lung.8) High respiration rates of mice cause difficulty for high quality of images of the lung. Although invasive methods using tracheostomy enable high quality images, 9,10) we employed free-breathing method to take the images serially in a deeply-anesthetized condition, in which respiration rates were reduced. The purpose of present study is to clarify whether the kinetics of a murine elastase-induced emphysema model can be assessed using CT and to compare the results with morphological analysis. MATERIALS AND METHODSAdministration of Elastase C57BL/6N mice were obtained from Charles River Japan (Kanagawa, Japan) and bred in the animal facilities of Musashino University School of Medicine under specific pathogen-free (SPF) conditions. Care and use of animals followed the guidelines of the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research.Four cycles of sequential CT analysis were performed using 26 mice, six of which were also under histological examination at the end points. For histological analysis only, 12 mice were used for each time points, and in 8 different time points were examined. Another six mice were employed under CT and histological analysis once at the same day.Mice were anesthetized with ether or intraperitoneal injection of ketamine (90 mg/kg) and xylazine (1 mg/kg) and given intranasal administration of 0.3 or 1.2 units of porcine pancreatic elastase (Sigma-Aldrich, St. Louis, MO, U.S.A.) in 30 ml saline solution. Control mice were intra...

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Section: Discussionmentioning

confidence: 95%

Sequential and Quantitative Analysis of a Murine Model of Elastase-Induced Emphysema

Kawakami

Matsuo

Yoshiura

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Micro-CT has recently been applied for emphysema assessment in mice, including exact disease location and estimation of the degree of damage in the lung parenchymal tissue (3)(4)(5). Because of tissue destruction in emphysema, the damaged regions of the lung show lower attenuation, related to tissue density dependent absorption in CT.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Żurek

Boyer

Caramelle

et al. 2011

Magnetic Resonance in Med

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Ultrashort echo time (550 ms) MR imaging was implemented to track the emphysema development in mice lung challenged with elastase. Two parameters, namely, signal intensity and T 2 *, were used to monitor the disease evolution. Nine mice were imaged before and at 24 h as well as at 3 and 8 weeks after elastase instillation. Five mice instilled with saline served as controls. At week 8, the mean normalized signal intensity 6 SD was 0.89 6 0.20 for healthy controls and 0.64 6 0.10 for animals with emphysema. Similarly, a reduced value of T 2 * (1.27 6 0.35 ms vs 0.96 6 0.18 ms) was found in the emphysema group. The mean signal intensity drop and the reduction of T 2 * were prominent at 3 weeks following elastase instillation and stabilized between 3 and 8 weeks. The results indicated an excellent agreement between MR findings and histological morphometry (signal intensity, r 5 20.78, P 5 0.004; T 2 *, r 5 20.78, P 5 0.001). This result shows that proton MRI allows structural changes at alveolar level to be monitored longitudinally. This technique, applied routinely in preclinical trials will represent a valuable tool for assessment of drug therapy efficacy. Magn Reson Med 68:898-904,

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“…For instance, as a traditional utilization of X-ray imaging, micro CT is a key approach for evaluation of lung pathology changes such as emphysema in mice (Postnov et al, 2005). Similar to animal MRI, micro CT allows intact organ, even the whole intact animal, to be studied in vivo.…”

Section: Quantitative Analysis and Computer-assisted Image Datamentioning

confidence: 99%

Modern Imaging Technologies in Toxicologic Pathology: An Overview

Ying

Monticello

2006

Toxicol Pathol

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Modern imaging technology, now utilized in most biomedical research areas (bioimaging), enables the detection and visualization of biological processes at various levels of the molecule, organelle, cell, tissue, organ and/or whole body. In toxicologic pathology, the impact of modern imaging technology is becoming apparent from digital histopathology to novel molecular imaging for in vivo studies. This overview summarizes recent progresses in digital microscopy imaging and newly developed digital slide techniques. Applications of virtual microscopy imaging are discussed and compared to traditional optical microscopy reading. New generation digital pathology approaches, including automatic slide inspection, digital slide databases and image management are briefly introduced. Commonly used in vivo preclinical imaging technologies are also summarized. While most of these new imaging techniques are still undergoing rapid development, it is important that toxicologic pathologists embrace and utilize these technologies as advances occur.

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In vivo assessment of emphysema in mice by high resolution X‐ray microtomography

Cited by 44 publications

References 12 publications

Sequential and Quantitative Analysis of a Murine Model of Elastase-Induced Emphysema

Sequential and Quantitative Analysis of a Murine Model of Elastase-Induced Emphysema

Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Modern Imaging Technologies in Toxicologic Pathology: An Overview

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