In vivocharacterization of tumor vasculature using iodine and gold nanoparticles and dual energy micro-CT

Abstract

Tumor blood volume and vascular permeability are well established indicators of tumor angiogenesis and important predictors in cancer diagnosis, planning, and treatment. In this work, we establish a novel preclinical imaging protocol which allows quantitative measurement of both metrics simultaneously. First, gold nanoparticles are injected and allowed to extravasate into the tumor, and then liposomal iodine nanoparticles are injected. Combining a previously optimized dual energy micro-CT scan using high-flux polychromatic x-ray sources (energies: 40 kVp, 80 kVp) with a novel post-reconstruction spectral filtration scheme, we are able to decompose the results into 3D iodine and gold maps, allowing simultaneous measurement of extravasated gold and intravascular iodine concentrations. Using a digital resolution phantom, the mean limits of detectability (mean CNR = 5) for each element are determined to be 2.3 mg/mL (18 mM) for iodine and 1.0 mg/mL (5.1 mM) for gold, well within the observed in vivo concentrations of each element (I: 0-24 mg/mL, Au: 0-9 mg/mL) and a factor of 10 improvement over the limits without post-reconstruction spectral filtration. Using a calibration phantom, these limits are validated and an optimal sensitivity matrix for performing decomposition using our micro-CT system is derived. Finally, using a primary mouse model of soft-tissue sarcoma, we demonstrate the in vivo application of the protocol to measure fractional blood volume and vascular permeability over the course of five days of active tumor growth.

Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging

“…Preclinical GNPs as contrast agents are available for tumor or kidney imaging [40][41][42][43] but have never been considered to image early-stage inflammation via the detection of inflammation-associated cells like macrophages. Furthermore, until now, their impact on metabolic activities of these cells has not been evaluated.…”

Application of micro-computed tomography to microstructure studies of the medicinal fungus Hericium coralloides

“…The underlying monomitic tissue could not be identified with this form of preparation. Because several studies have demonstrated that iodine staining generates high resolution micro-CT images of soft tissue (Hanson and Bagi 2004, Jeffery et al 2011, Aslanidi et al 2013, Clark et al 2013), the same sample was treated with an iodine-based contrast medium (ULTRAVIST 370, Bayer, Germany) to improve the contrast of the specimen; however, this caused over-contrasting. Subsequently the same specimen was critical-point dried after dehydration in graded ethanol to remove the excess of contrast agent.…”

Image-based modelling of skeletal muscle oxygenation

“…It is also possible to perfuse the vasculature with nanoparticles, which are small particles of a high atomic number material with dimensions of about 100 nm. This can be, for example, a suspension of gold nanoparticles [102,103], liposomal iodine nanoparticles [104] or bismuth sulfide (Bi 2 S 3 ) nanoparticles. Nanoparticles can also be used for in vivo mCT imaging [101].…”

“…The size of the nanoparticles used can be varied depending on the vasculature investigated. For example, as tumour vasculature is leaky, larger particles may be beneficial or by contrast, smaller particles can be used in order to determine tumour permeability [102]. Owing to the segmentation difficulties arising from staining methods, perfusion methods should be the method of choice for absorption-based mCT of the microvasculature in skeletal muscle.…”