High-Resolution X-ray Microtomography for the Detection of Lung Tumors in Living Mice

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

doi:10.1593/neo.03481

Cited by 73 publications

(78 citation statements)

References 14 publications

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“…If microscopic structures are to be imaged with micro-CT, image resolution needs to be higher than that required for "mini" CT. For instance, because murine alveolar diameter is ‫ف‬ 40 m and alveolar membranes are Ͻ 10 m thick, adequate imaging of these structures requires voxels of the order of 5 m. Despite this high resolution, the entire volume of the lung must be imaged because some diseases start in small localized regions; the entire lung is searched so the initiation site is not missed (4).…”

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confidence: 99%

Micro-Computed Tomography of the Lungs and Pulmonary-Vascular System

Ritman¹

2005

Proceedings of the American Thoracic Society

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Three-dimensional imaging of the intact lung and its vasculature is essential if the hierarchical and volumetric aspects of its structures and functions are to be quantitated. Although this is possible with clinical multislice helical CT scanners, the spatial resolution does not scale down adequately for small rodents for which cubic voxel dimensions of 50-100 m are required. Micro-computed tomography (micro-CT) provides the necessary spatial resolution of 3D images of the intact thoracic contents. Micro-CT can provide higher resolution so that basic micro-architectural structures, such as alveoli, can be individually visualized and quantitated. Dynamic events, such as the respiratory and cardiac cycles, can be imaged at multiple time points throughout a representative cycle by coordinating the scan sequence (i.e., gating) to the cycle phase of a sequence of cycles. Fusion of the micro-CT image data with other image data, such as micro-SPECT or histology, can enhance the information content beyond the mainly structural information provided by micro-CT. Conventional attenuation-based X-ray imaging can involve significant X-ray exposures at high spatial resolutions, and this could affect the phenotype (e.g., via interstitial fibrosis) and genotype (e.g., via mutation), so its use in longitudinal studies using micro-CT may be limited in some cases. However, because of recent developments in which the phase shift or refraction of X-rays rather than attenuation is used, the X-ray exposure may be significantly reduced.Keywords: microarchitecture; pulmonary hypertension; alveoli; airways Micro-computed tomography (micro-CT) is a rapidly developing imaging capability that has been described in detail elsewhere (1). This development is driven in large measure by the fact that because mice are rapidly becoming the experimental animals of choice for many research endeavors, there is motivation to scale clinical imaging capabilities down to the mouse level. There are several aspects to the scaling of the spatial and temporal resolution and volume scanned (2). One is to scale so as to generate a transaxial tomographic image equivalent to a clinical scan. Thus, with clinical multislice helical scanning, CT of the thorax generates 3D images that are approximately 300 to 400 mm in transverse diameter and are made up of voxels (a 3D picture-element or pixel) ‫ف‬ 1 mm 3 in volume. A "mini" CT scanner that is scaled to a proportional voxel resolution in a mouse (with a 20 mm thoracic diameter) would involve voxels ‫ف‬ 75 m in diameter. The mouse's lungs have a combined volume of about 1.3 cm 3 ; therefore, in the mouse a 3D volume of at least 2 cm 3 must be imaged to capture the entire lung. How- ever, the mouse heart and respiratory rate are much higher than in humans, so cardio-respiratory dynamic processes are much more difficult to image in mice than in humans (3) because the micro-CT scan durations are generally limited by the rate of X-ray production. If microscopic structures are to be imaged with micro-CT, image resolution...

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confidence: 99%

Micro-Computed Tomography of the Lungs and Pulmonary-Vascular System

Ritman¹

2005

Proceedings of the American Thoracic Society

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“…HRCT findings regarding tumor size were validated by histopathological examination and correlated closely with necropsy findings (r=0.953; p<0.0001), suggesting that HRCT scanning may be used in the future to evaluate tumor growth and volume without euthanasia, thus avoiding time and resource-consuming procedures. Other recently published studies using experimental models 10,12,13 found the HRCT scanning technique to be an efficient tool for diagnosing lung nodules and to be less costly than magnetic resonance imaging 20 . The efficacy of HRCT scanning in the detection and measurement of tumors, as demonstrated by our study, makes it a suitable and non-invasive technique for diagnosing lung tumors, monitoring tumor growth and evaluating response to anticancer drugs in vivo in animals submitted to implantation with tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…Later Howard et al 8 and Johnston et al 7 improved the technique by using cervical tracheotomy for the insertion of an ultrafine intrabronchial catheter, thus making it possible to implant cells on the periphery of the pulmonary parenchyma. None of the studies above used computed tomography (CT) to detect the presence of lung tumors in the animals, although a few other and more recent experimental studies have reported using CT scans with small animals 10,12,13 . The objectives of this study were a) to develop a technically simple rat lung tumor model with intrabronchial implantation of cells of Walker's carcinosarcoma by cervical tracheotomy, and b) to diagnose tumors in vivo using high-resolution computed tomography (HRCT) with subsequent correlation of findings from necropsy and histopathological examination.…”

Section: Introductionmentioning

confidence: 99%

Experimental rat lung tumor model with intrabronchial tumor cell implantation

et al. 2008

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Purpose: The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Methods: Sixtytwo female Wistar rats weighing 208 ± 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10 5 to 5×10 5 tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from highresolution computed tomography (HRCT) with findings from necropsia and determining time of survival. Results: The tumor take rate was 94.7% for implants with 4×10 5 tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. Conclusion: The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.Key words: Lung neoplasms; Walker-256 carcinoma; rats. RESUMO Objetivo: O objetivo foi desenvolver um modelo de tumor de pulmão em rato que permita o teste de fármacos no tratamento deste câncer. Métodos: Sessenta e dois ratos Wistar fêmeas, peso médio de 208±20 g, foram anestesiados com tribromoetanol 2,5% IP (1ml/100g de rato), traqueostomizados e intubados com cateter ultrafino para injetar células do tumor de Walker. Na 1 a etapa, estabeleceu-se a técnica do implante de células tumorais por via intrabrônquica e o índice de pega tumoral, usando-se de 10 5 a 5×10 5 células. Na 2 a , avaliou-se o volume tumoral e a correlação dos achados obtidos na tomografia computadorizada de alta resolução (TCAR) de tórax com os da necropsia e verificou-se a sobrevida. Resultados: O índice de pega foi de 94,7, com o implante de 4×10 5 células do tumor; as medidas do tumor feitas na TCAR e comparadas com as da necropsia foram semelhantes (r=0, 953, p<0,0001); a sobrevida mediana foi de 11 dias; e a mortalidade cirúrgica de 4,8 %. Conclusão: O modelo mostrou-se viável, com alto índice de pega, mortalidade cirúrgica desprezível, de execução simples e fácil reprodutibilidade. A TCAR revelou alta acurácia no diagnóstico, localização e mensuração das lesões tumorais, credenciando-se para a monitorização de crescimento tumoral nesse modelo.Descritores: Neoplasias Pulmonares; Carcinoma 256 de Walker; Ratos.

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“…X-ray Imaging and Micro CT: X-ray imaging and micro CT can be useful for visualizing and measuring pathologic alterations of lung and bone micro-architectures (Ritman, 2002;Lee et al, 2003;Barck et al, 2004;Langheinrich et al, 2004a), organ vasculature (Langheinrich et al, 2004b;Ritman, 2005), and morphologic quantification of tumors (De Clerck et al, 2004;Gasser et al, 2005). 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).…”

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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High-Resolution X-ray Microtomography for the Detection of Lung Tumors in Living Mice

Cited by 73 publications

References 14 publications

Micro-Computed Tomography of the Lungs and Pulmonary-Vascular System

Micro-Computed Tomography of the Lungs and Pulmonary-Vascular System

Experimental rat lung tumor model with intrabronchial tumor cell implantation

Modern Imaging Technologies in Toxicologic Pathology: An Overview

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