Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.

Ashton, Jeffrey R

Clark, Darin P

Moding, Everett J

Ghaghada, Ketan

Kirsch, David G

West, Jennifer L

Badea, Cristian T

Kalin, Tanya V

United States

2015-12-21T10:38:44Z

2014

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.

http://www.ncbi.nlm.nih.gov/pubmed/24520351

PONE-D-13-36649

1932-6203

https://hdl.handle.net/10161/11255

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0088129

Animals

Biomarkers, Tumor

Blood Volume

Contrast Media

Gold

Iodine

Liposomes

Lung

Lung Neoplasms

Mice

Microvessels

Nanoparticles

Radionuclide Imaging

Reproducibility of Results

Tumor Burden

X-Ray Microtomography

Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.

Journal article

Badea, Cristian T|0000-0002-1850-2522

http://www.ncbi.nlm.nih.gov/pubmed/24520351

e88129

2

Basic Science Departments

Biomedical Engineering

Cell Biology

Chemistry

Clinical Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Mechanical Engineering and Materials Science

Pharmacology & Cancer Biology

Pratt School of Engineering

Radiation Oncology

Radiology

School of Medicine

Trinity College of Arts & Sciences

Published online

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