Potential Applications of Flat-Panel Volumetric CT in Morphologic, Functional Small Animal Imaging

Greschus, Susanne; Kießling, Fabian; Lichy, Matthias P.; Moll, Jens; Mueller, Margareta M.; Savai, Rajkumar; Rose, Frank; Ruppert, Clemens; Günther, Andreas; Luecke, Marcus; Fusenig, Norbert E.; Semmler, Willi; Traupe, Horst

doi:10.1593/neo.05160

Cited by 67 publications

(60 citation statements)

References 30 publications

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“…16 FpVCT has already been described as a system for noninvasive imaging of different organ systems in preclinical research. 17 In combination with the administration of contrast agents, fpVCT allows accurate measurements of tumor volumes, vessel formation 18 and morphological changes within the tumor over time in subcutaneous and orthotopic tumor models in longitudinal studies. 19 FpVCT has also been used in monitoring skeletal structures, 20,21 including progression of osteolytic lesions, 22 as well as for the evaluation of therapy responses in vivo over time.…”

Section: Uiccmentioning

confidence: 99%

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Jannasch

Dullin

Heinlein

et al. 2009

Intl Journal of Cancer

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Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm 3 ) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns. ' UICCKey words: flat-panel volume computed tomography; in vivo imaging; murine transgenic tumor models; tumor angiogenesis Accompanying the rapid progress in deciphering the human and mouse genome, many transgenic mouse models have been generated. Weissleder and Mahmood already assumed in 2001 that more than 25 million transgenic and knockout mice would be raised that year for experimental studies, accounting for over 90% of all mammals in research.1 These mouse models offer the opportunity to study gene functions in their biological context in a much more physiological way than any other approach. Especially cancer research benefits from the advantages of these transgenic mice in elucidating the role of a specific gene in tumor growth and spread as well as angiogenesis. One promising model in addressing such questions is the WAP-T transgenic mouse. [2][3][4] In these mice, the SV40 early gene region is induced specifically in differentiating mammary epithelial cells upon activation of the WAPpromoter during late pregnancy and lactation, and drives mammary carcinogenesis in mammary epithelial cells re-expressing the transgene after involution of the mammary glands. The SV40 early region mainly serves to functionally eliminate the p53 and pRb tumor suppressors by binding to the SV40 large T-antigen 5 and to change the specificity of the phosphatase PP2A 6 by its interaction with SV40 small T-antigen, thereby...

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Section: Uiccmentioning

confidence: 99%

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Jannasch

Dullin

Heinlein

et al. 2009

Intl Journal of Cancer

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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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“…Quantification of micro structure function relationship of tissues and the designing tissue structures, including characterizing micro-architecture of tissue scaffolds by micro-CT has helped to design and fabricate of tailor-made tissue microstructures. Recent advances in micro-CT imaging [15], such as faster detectors, slip-ring technology, and dedicated rodent scanners, have made it possible to obtain high-resolution CT images with an isotropic spatial resolution of 0.075-0.15 mm [16][17]. Noninvasive imaging of ventilation has been shown to be sensitive to a variety of lung diseases [18].…”

Section: Non-invasive Imaging Data Acquisitionmentioning

confidence: 99%

Computational Approaches in Tissue Engineering

Sah¹,

Sadanand²,

Pramanik³

2011

IJCA

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Scaffolds designed with intricate and controlled interior architecture represent a challenging problem for tissue engineering. Various scaffold-fabricating techniques allow the creation of complex micro-structure but with irregular pore characteristics, resulting in inappropriate & asymmetrical structures not suitable for tissue engineering applications. Computer-Aided Tissue Engineering (CATE) integrates advanced technologies from Biology, Information Science and Engineering for Tissue Engineering applications. In particulars, computer-aided design (CAD), medical image processing, computer-aided manufacturing (CAM), and solid freeform fabrication (SFF) are employed for simulation, design and manufacturing of tissue scaffolds with controlled and regular pore architecture. CATE application to the design and fabrication of scaffolds can guide to improve the biomimetic and biological features of the scaffolds. This paper aims to understand the principles behind various computer aided approaches being utilized for tissue engineering applications particularly cell-scaffold implant modeling, designing and manufacturing.

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Potential Applications of Flat-Panel Volumetric CT in Morphologic, Functional Small Animal Imaging

Cited by 67 publications

References 30 publications

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Experimental rat lung tumor model with intrabronchial tumor cell implantation

Computational Approaches in Tissue Engineering

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