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Dual-energy micro-CT for quantifying the time-course and staining characteristics of ex-vivo animal organs treated with iodine- and gadolinium-based contrast agents.

ABSTRACT: Chemical staining of soft-tissues can be used as a strategy to increase their low inherent contrast in X-ray absorption micro-computed tomography (micro-CT), allowing to obtain fast three-dimensional structural information of animal organs. Though some staining agents are commonly used in this context, little is known about the staining agents' ability to stain specific types of tissues; the times necessary to provide a sufficient contrast; and the effect of staining solution in distorting the tissue. Here we contribute to studies of animal organs (mouse heart and lungs) using staining combined with dual-energy micro-CT (DECT). DECT was used in order to obtain an additional quantitative measure for the amount of staining agents within the sample in 3D maps. Our results show that the two staining solutions used in this work diffuse differently in the tissues studied, the staining times of some tens of?minutes already produce high-quality micro-CT images and, at the concentrations applied in this work, the staining solutions tested do not cause relevant tissue distortions. While one staining solution provides images of the general morphology of the organs, the other reveals organs' features in the order of a hundred micrometers.

SUBMITTER: Martins de Souza E Silva J

PROVIDER: S-EPMC5727238 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Dual-energy micro-CT for quantifying the time-course and staining characteristics of ex-vivo animal organs treated with iodine- and gadolinium-based contrast agents.

Martins de Souza E Silva Juliana J Utsch Julian J Kimm Melanie A MA Allner Sebastian S Epple Michael F MF Achterhold Klaus K Pfeiffer Franz F

Scientific reports 20171212 1

Chemical staining of soft-tissues can be used as a strategy to increase their low inherent contrast in X-ray absorption micro-computed tomography (micro-CT), allowing to obtain fast three-dimensional structural information of animal organs. Though some staining agents are commonly used in this context, little is known about the staining agents' ability to stain specific types of tissues; the times necessary to provide a sufficient contrast; and the effect of staining solution in distorting the t ...[more]

PMID: 29234002

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Project description:Advances in computed tomography (CT) hardware have propelled the development of novel CT contrast agents. In particular, the spectral capabilities of x-ray CT can facilitate simultaneous imaging of multiple contrast agents. This approach is particularly useful for functional imaging of solid tumors by simultaneous visualization of multiple targets or architectural features that govern cancer development and progression. Nanoparticles are a promising platform for contrast agent development. While several novel imaging moieties based on high atomic number elements are being explored, iodine (I) and gadolinium (Gd) are particularly attractive because of their existing approval for clinical use. In this work, we investigate the in vivo discrimination of I and Gd nanoparticle contrast agents using both dual energy micro-CT with energy integrating detectors (DE-EID) and photon counting detector (PCD)-based spectral micro-CT. Simulations and phantom experiments were performed using varying concentrations of I and Gd to determine the imaging performance with optimized acquisition parameters. Quantitative spectral micro-CT imaging using liposomal-iodine (Lip-I) and liposomal-Gd (Lip-Gd) nanoparticle contrast agents was performed in sarcoma bearing mice for anatomical and functional imaging of tumor vasculature. Iterative reconstruction provided high sensitivity to detect and discriminate relatively low I and Gd concentrations. According to the Rose criterion applied to the experimental results, the detectability limits for I and Gd were approximately 2.5 mg ml-1 for both DE-EID CT and PCD micro-CT, even if the radiation dose was approximately 3.8 times lower with PCD micro-CT. The material concentration maps confirmed expected biodistributions of contrast agents in the blood, liver, spleen and kidneys. The PCD provided lower background signal and better simultaneous visualization of tumor vasculature and intratumoral distribution patterns of nanoparticle contrast agent compared to DE-EID decompositions. Preclinical spectral CT systems such as this could be useful for functional characterization of solid tumors, simultaneous quantitative imaging of multiple targets and for identifying clinically-relevant applications that benefit from the use of spectral imaging. Additionally, it could aid in the development nanoparticles that show promise in the developing field of cancer theranostics (therapy and diagnostics) by measuring vascular tumor biomarkers such as fractional blood volume and the delivery of liposomal chemotherapeutics.

Project description:PurposeTo 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.MethodsPrimary 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.ResultsDual-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.ConclusionsDual-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.

Dataset Information

Dual-energy micro-CT for quantifying the time-course and staining characteristics of ex-vivo animal organs treated with iodine- and gadolinium-based contrast agents.

Publications

Dual-energy micro-CT for quantifying the time-course and staining characteristics of ex-vivo animal organs treated with iodine- and gadolinium-based contrast agents.

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