Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.
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PURPOSE: To provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT. METHODS: Primary lung tumors were generated in LSL-Kras(G12D); p53(FL/FL) mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed-two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues. RESULTS: Dual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R(2) = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements. CONCLUSIONS: Dual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT.
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Published Version (Please cite this version)10.1371/journal.pone.0088129
Publication InfoAshton, Jeffrey R; Clark, Darin P; Moding, Everett J; Ghaghada, Ketan; Kirsch, David G; West, Jennifer L; & Badea, Cristian T (2014). Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study. PLoS One, 9(2). pp. e88129. 10.1371/journal.pone.0088129. Retrieved from https://hdl.handle.net/10161/11255.
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Professor in Radiology
Dr. Cristian T. Badea is a Professor in the Department of Radiology and faculty in the Departments of Biomedical Engineering and Medical Physics. His research interests are in the physics and biomedical applications of computed tomography (CT), micro-CT, tomosynthesis, and image reconstruction algorithms.
Barbara Levine University Distinguished Professor
My clinical interests are the multi-modality care of patients with bone and soft tissue sarcomas and developing new sarcoma therapies. My laboratory interests include utilizing mouse models of cancer to study cancer and radiation biology in order to develop new cancer therapies in the pre-clinical setting.
Fitzpatrick Family University Distinguished Professor of Engineering
Jennifer West’s research in biomaterials and tissue engineering involves the synthesis, development, and application of novel, biofunctional materials, and the use of biomaterials and engineering approaches to study biological problems. Current projects include the design of ECM-mimetic hydrogel materials, novel microfabrication strategies for biomimetic patterning, and nanoparticle theranostics.
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