Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.
Abstract
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.
Type
Journal articleSubject
AnimalsBiomarkers, Tumor
Blood Volume
Contrast Media
Gold
Iodine
Liposomes
Lung
Lung Neoplasms
Mice
Microvessels
Nanoparticles
Radionuclide Imaging
Reproducibility of Results
Tumor Burden
X-Ray Microtomography
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https://hdl.handle.net/10161/11255Published Version (Please cite this version)
10.1371/journal.pone.0088129Publication Info
Ashton, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Cristian Tudorel Badea
Professor in Radiology
Our lab's research focus lies primarily in developing novel quantitative imaging systems,
reconstruction algorithms and analysis methods. My major expertise is in preclinical
CT.
Currently, we are particularly interested in developing novel strategies for spectral
CT imaging using nanoparticle-based contrast agents for theranostics (i.e. therapy
and diagnostics).
We are also engaged in developin
Darin Clark
Assistant Professor in Radiology
David Guy Kirsch
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.
Jennifer L West
Adjunct Professor of Biomedical 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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