Evaluation of micro-CT for emphysema assessment in mice: comparison with non-radiological techniques

Artaechevarria, Xabier; Blanco, David; Biurrun, Gabriel de; Ceresa, Mario; Pérez-Martín, Daniel; Bastarrika, Gorka; de-Torres, Juan P.; Zulueta, Javier J.; Montuenga, Luis M.; Ortiz‐de‐Solórzano, Carlos; Muñoz-Barrutia, Arrate

doi:10.1007/s00330-010-1982-5

Cited by 39 publications

(58 citation statements)

References 25 publications

(35 reference statements)

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“…Noninvasive, serial imaging of animal models should ideally result in quantitative datasets that allow for longitudinal assessment, comparisons between different groups, including the effect of therapeutic interventions, and detailed topographic information documenting the extent of disease in individual animals. Micro-CTbased protocols for the quantification of a variety of pulmonary emphysema models in mice have been proposed, and agreement with current gold standard evaluation of histopathology has been reported (2,8,21). We also have recently reported the use of micro-CT to monitor the progression of emphysematous changes in an exacerbation mouse model of COPD by a single administration of elastase followed by lipopolysaccharide (14).…”

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confidence: 71%

“…Lung parenchyma was arbitrarily defined as a region with X-ray attenuation values between Ϫ1,200 and Ϫ300 HU, and intrapulmonary and surrounding extrapulmonary tissues (e.g., airways, large pulmonary vessels, heart, mediastinal structures, and diaphragm) were excluded. LAA thresholds were arbitrarily established to less than Ϫ700 HU because %LAA of a normal mouse was Ͻ5% referring to a previous publication (2), and it was also set high to make the difference between the groups clearer. The %LAA was calculated using the ratio of the total LAA volume to the end-expiratory lung volume.…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of cigarette smoke-induced emphysema in mice using quantitative micro-computed tomography

Sasaki

Chubachi

Kameyama

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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T. Evaluation of cigarette smokeinduced emphysema in mice using quantitative micro-computed tomography. Am J Physiol Lung Cell Mol Physiol 308: L1039-L1045, 2015. First published March 27, 2015 doi:10.1152/ajplung.00366.2014.-Chronic cigarette smoke (CS) exposure provokes variable changes in the lungs, and emphysema is an important feature of chronic obstructive pulmonary disease. The usefulness of micro-computed tomography (CT) to assess emphysema in different mouse models has been investigated, but few studies evaluated the dynamic structural changes in a CS-induced emphysema mouse model. A novel micro-CT technique with respiratory and cardiac gating has resulted in high-quality images that enable processing for further quantitative and qualitative analyses. Adult female C57BL/6J mice were repeatedly exposed to mainstream CS, and micro-CT scans were performed at 0, 4, 12, and 20 wk. Emphysema was also histologically quantified at each time point. Air-exposed mice and mice treated with intratracheal elastase served as controls and comparisons, respectively. End-expiratory lung volume, corresponding to functional residual volume, was defined as the calculated volume at the phase of end-expiration, and it evaluated air trapping. The end-expiratory lung volumes of CS-exposed mice were significantly larger than those of air controls at 12 and 20 wk, which was in line with alveolar enlargement and destruction by histological quantification. However, CS exposure neither increased low attenuation volume nor decreased the average lung CT value at any time point, unlike the elastase-instilled emphysema model. CSexposed mice had rather higher average lung CT values at 4 and 12 wk. This is the first study characterizing a CS-induced emphysema model on micro-CT over time in mice. Moreover, these findings extend our understanding of the distinct pathophysiology of CSinduced emphysema in mice. chronic obstructive pulmonary disease; mouse THE DEFINING FEATURE OF CHRONIC obstructive pulmonary disease (COPD) is irreversible airflow obstruction caused by elevated resistance in the small airways and increased lung compliance due to emphysema and lung destruction (12). Emphysema is defined pathologically as the permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls, without obvious fibrosis (5). The severity of emphysema is clinically evaluated as low attenuation area (LAA) volume divided by total lung volume (%LAA) on high-resolution computed tomography (CT) (17). It has been reported that high %LAA of lung is related to high mortality, frequent exacerbations, and poor quality of life among COPD patients (11).Although no current animal model recapitulates all features of human COPD (26), different mouse models of emphysema are available, including intratracheal instillation of elastase, cigarette smoke (CS) exposure, and genetic alteration (24). The elastase-induced pulmonary emphysema model is known to induce severe dose-dependent alveolar destruction with rapid onse...

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confidence: 71%

Section: Methodsmentioning

confidence: 99%

Evaluation of cigarette smoke-induced emphysema in mice using quantitative micro-computed tomography

Sasaki

Chubachi

Kameyama

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…24,25 The value of this imaging technique has been studied in disease models of lung fibrosis, lung emphysema and lung neoplasms. [26][27][28][29][30] Nevertheless, this technique has not been used for the assessment of invasive aspergillosis in small animals. Magnetic resonance imaging (MRI) provides images with good spatial resolution and excellent soft tissue contrast, thereby creating the potential to distinguish between different pathological processes occurring within the lung, such as inflammation or necrosis.…”

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confidence: 99%

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

Poelmans

Hillen

Vanherp

et al. 2016

Laboratory Investigation

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Invasive aspergillosis is an emerging threat to public health due to the increasing use of immune suppressive drugs and the emergence of resistance against antifungal drugs. To deal with this threat, research on experimental disease models provides insight into the pathogenesis of infections caused by susceptible and resistant Aspergillus strains and by assessing their response to antifungal drugs. However, standard techniques used to evaluate infection in a preclinical setting are severely limited by their invasive character, thereby precluding evaluation of disease extent and therapy effects in the same animal. To enable non-invasive, longitudinal monitoring of invasive pulmonary aspergillosis in mice, we optimized computed tomography (CT) and magnetic resonance imaging (MRI) techniques for daily follow-up of neutropenic BALB/c mice intranasally infected with A. fumigatus spores. Based on the images, lung parameters (signal intensity, lung tissue volume and total lung volume) were quantified to obtain objective information on disease onset, progression and extent for each animal individually. Fungal lung lesions present in infected animals were successfully visualized and quantified by both CT and MRI. By using an advanced MR pulse sequence with ultrashort echo times, pathological changes within the infected lung became visually and quantitatively detectable at earlier disease stages, thereby providing valuable information on disease onset and progression with high sensitivity. In conclusion, these noninvasive imaging techniques prove to be valuable tools for the longitudinal evaluation of dynamic disease-related changes and differences in disease severity in individual animals that might be readily applied for rapid and cost-efficient drug screening in preclinical models in vivo.

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“…The mean density of the lungs reported here are similar to those reported by Plathow et al (32) for C57BL/6J female mice of the same age (Ϫ561 HUs) without respiratory gating. Other studies have reported both higher and lower mean densities (2,3,12,24,33,52). The varying values can be explained by the use of the isopressure breath-hold respiratorygating technique for image acquisition, variations in the ages or strains of the animals, or differences in the scaling of images into CT values (10).…”

Section: Discussionmentioning

confidence: 97%

Characterization of spontaneous air space enlargement in mice lacking microfibrillar-associated protein 4

Holm

Wulf-Johansson

Hvidsten

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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protein 4 (MFAP4) is localized to elastic fibers in blood vessels and the interalveolar septa of the lungs and is further present in bronchoalveolar lavage. Mfap4 has been previously suggested to be involved in elastogenesis in the lung. We tested this prediction and aimed to characterize the pulmonary function changes and emphysematous changes that occur in Mfap4-deficient (Mfap4 Ϫ/Ϫ ) mice. Significant changes included increases in total lung capacity and compliance, which were evident in Mfap4 Ϫ/Ϫ mice at 6 and 8 mo but not at 3 mo of age. Using in vivo breath-hold gated microcomputed tomography (micro-CT) in 8-mo-old Mfap4 Ϫ/Ϫ mice, we found that the mean density of the lung parenchyma was decreased, and the low-attenuation area (LAA) was significantly increased by 14% compared with Mfap4 ϩ/ϩ mice. Transmission electron microscopy (TEM) did not reveal differences in the organization of elastic fibers, and there was no difference in elastin content, but a borderline significant increase in elastin mRNA expression in 3-mo-old mice. Stereological analysis showed that alveolar surface density in relation to the lung parenchyma and total alveolar surface area inside of the lung were both significantly decreased in Mfap4 Ϫ/Ϫ mice by 25 and 15%, respectively. The data did not support an essential role of MFAP4 in pulmonary elastic fiber organization or content but indicated increased turnover in young Mfap4 Ϫ/Ϫ mice. However, Mfap4 Ϫ/Ϫ mice developed a spontaneous loss of lung function, which was evident at 6 mo of age, and moderate air space enlargement, with emphysema-like changes.air space enlargement; gene deficiency; MFAP4 MFAP4 IS A 36-KDA GLYCOPROTEIN composed of a short NH 2 -terminal region comprising one cysteine residue and an ArgGly-Asp (RGD) integrin-binding motif, followed by a COOHterminal fibrinogen-related domain (FReD) (51). The MFAP4 protein is a disulfide-linked dimer that forms higher homooligomeric structures via noncovalent interactions (26,38). FReDs are found in various human proteins involved in distinct functions, including innate immunity, tissue growth, and remodeling (43).MFAP4 is considered to be the human homolog to a 36-kDa microfibril-associated glycoprotein (MAGP-36) originally found to be localized to the elastin-microfibril interface in the porcine aorta (23). MFAP4 was later detected in a variety of both elastic and nonelastic tissues in various species

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Evaluation of micro-CT for emphysema assessment in mice: comparison with non-radiological techniques

Cited by 39 publications

References 25 publications

Evaluation of cigarette smoke-induced emphysema in mice using quantitative micro-computed tomography

Evaluation of cigarette smoke-induced emphysema in mice using quantitative micro-computed tomography

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

Characterization of spontaneous air space enlargement in mice lacking microfibrillar-associated protein 4

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