Characteristics of Gadolinium Oxide Nanoparticles as Contrast Agents for Terahertz Imaging
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- Lee, D., Kim, H., Kim, T. et al. J Infrared Milli Terahz Waves (2011) 32: 506. doi:10.1007/s10762-011-9776-7
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For the application of gadolinium oxide (Gd2O3) nanoparticles as terahertz contrast agents, their optical properties in a solvent were studied using terahertz time-domain spectroscopy. The power absorption and refractive index of the samples were measured with various concentrations of nanoparticles. The power absorption was extremely large, as much as three orders of magnitude higher than that of water, so that a few ppms of Gd2O3 nanoparticles were distinguished in terms of their power absorption capacity. The results show that the interaction between the terahertz electromagnetic waves and the Gd2O3 nanoparticles is strong enough to allow their exploitation as contrast agents for terahertz medical imaging.
KeywordsTerahertz time-domain spectroscopyTerahertz imagingGadolinium oxideNanoparticle
Terahertz (THz) technology has many potential applications in medicine and biology, because THz electromagnetic waves are sensitive to water molecules and because the characteristic energies of biological molecules lie in the THz region . One of the promising applications of THz technology in medicine is the diagnosis of cancer due to the change in the THz characteristics of tumors that mainly result from the alteration of the cell structure and the water content. With this principle, skin and breast cancer were diagnosed [2–4], although the difference between the malignant and benign tissues was too slight to allow the technology to be utilized in clinics.
The most conventional way of diagnosing different kind of cancer is with the use of the magnetic resonance imaging (MRI) technique. The MRI technique has recently adopted nanoparticle probes to enhance the sensitivity of its measurements . Nanoparticles have also been used to improve the THz image quality and have significantly increased the sensitivity of cancer detection .
Many kinds of nanoparticles have been developed for MRI, which include magnetic gold nanocomposites , biodegradable nanoparticles , and smart drug-loaded polymer gold nanoshells . Nano-sized colloidal metal oxides have recently been synthesized. Among them, gadolinium oxide (Gd2O3) nanoparticles (GONPs) are receiving attention as candidate multi-functional contrast agents that can be targeted towards a specific cell by attaching an antigen or an antibody to them . Gadolinium is a paramagnetic material that has been used as the core of contrast agents such as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) for T1 imaging in MRI. The Gd-DTPA has low toxicity but it is easily removed by renal excretion due to its low molecular weight. Therefore, a new gadolinium composite that has the form of a nano-sized colloidal nanoparticle has been required. The gadolinium composite can also be a good THz contrast agent because gadolinium significantly absorbs electromagnetic waves.
In this paper, the characteristics of nanoplate-shaped GONPs as a potential contrast agents for THz molecular imaging are studied. Fundamental issues on molecular imaging, such as sensitivity and quantification, are also discussed.
The THz optical properties of the GONP samples with various concentrations were measured via conventional terahertz time-domain spectroscopy (THz-TDS) . The femtosecond pulses produced by a Ti:sapphire laser were separated into two paths. One of the beams, the pump beam, generated THz waves on a p-InAs wafer, and the other, the probe beam, was guided to the detector that consisted of a photoconductive dipole antenna fabricated on a low-temperature-grown GaAs wafer. The generated THz pulses proceeded to the detector through the quartz cell, and the transmitted signal was measured using a photoconductive sampling technique by which the DC signals were read on a lock-in amplifier with respect to the change in the optical path length between the pump and the probe beams. The quartz cell that contained the GONP samples dispersed in toluene was rectangular parallelepiped-shaped, with a path length of 10 mm and a window thickness of 1.25 mm. The entire setup, including the sample cell, was kept in a tight box purged with dry air to avoid the absorption by water vapors.
In summary, the concentration-dependent optical constants of GONPs with THz-TDS were measured. It was found that even a few μMs of GONPs could be detected due to their power absorption capacity, which is almost three orders of magnitude larger than that of water. Therefore, GONPs can significantly improve the contrast in THz images. To quantify THz images, the aggregation problem of GONPs must be solved via encapsulation. The encapsulation can be done with biocompatible materials. By coating, GONPs will become a safer material for human body compared with Gd-DTPA which is based on Gd3+ ion. It can also be modified and engineered to be a target specific contrast agent by antibody phase conjugating. Although GONPs were initially proposed as multi-functional contrast agents for MRI, they can also be utilized as contrast agents for molecular imaging with THz waves. The MRI technology has difficulty to acquire the images from a surface that is not surrounded by water such as human skin or digestive organs. THz medical imaging technology, however, has uniqueness on the surface measurement of biological samples such as epithelial cancers. Therefore, THz imaging along with nanoparticle contrast agents can be one of the strongest imaging technique for certain diagnosis .
This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (Nos. 2009–0083512, 2009–0054519, 2009–0076933, 2009–0093432, and 2009–0084187), by the grant of the Korean Health Technology R&D Project (No. A101954) funded by the Ministry for Health, Welfare & Family Affairs, Republic of Korea, and by Korea Small and Medium Business Administration in 2010 (00042838–1). DKL acknowledges the support of the Seoul Science Fellowship program.