Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

BACKGROUND: X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. PURPOSE: In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. METHODS: By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50 kV X-rays, respectively. An amount of 40 mg GNPs (1.9 nm in diameter) suspended in 0.20 ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60 min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. RESULTS: Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2 min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08 wt%. CONCLUSIONS: A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Radiosensitization by Au-nanofilm at micrometer level using confocal Raman spectroscopy.

PURPOSE: To measure the radiosensitization by an Au-nanofilm (GNF) at a micrometer level on a radiochromic film (RCF) using confocal Raman spectroscopy (CRS). METHODS: Unlaminated radiochromic films were irradiated by 200 kVp x-ray from 0.3 to 50 Gy to obtain a calibration curve. Raman spectra of these films were measured by positioning the postirradiated RCF perpendicular to the CRS monochromatic beam and reading a depth profile of the film along the lateral axis. The Raman peak corresponding to the C ≡ C peak was obtained from a region of interest of 100 × 5 µm2 . To investigate the radiosensitization by GNF, two sets of RCF, one attached to a 100-nm thick GNF and the other without GNF were irradiated at 0.5 Gy by 50 and 120 kVp X-rays. The spatial resolution of the CRS on the RCF was quantified by the modulation transfer function method (MTF). Thus, in the spatial resolution determined by MTF, the doses deposited on the films were evaluated. The dose enhancement factor (DEF) was obtained in the measurable micro-size by comparing doses deposited on the RCFs with and without GNF. To verify the experimental results, Monte Carlo simulations following the experimental set up were performed using Geant4. In addition, analytical calculations for the radiosensitization by GNF were carried out. RESULTS: The confocal Raman spectroscopy on the RCF achieved a spatial resolution of ~6 µm. An experimental DEF within the first 6 µm depth from the surface of RCF was found to be 17.9 for 50 kVp and 14.7 for 120 kVp. The DEF for the same depth obtained by MC and analytical calculations was 13.53 and 9.75 for 50 kVp, and 10.63 and 6.67 for 120 kVp, respectively. CONCLUSIONS: The experimental DEF as a function of the distance from GNF was consistent with data from previous studies and the MC simulations, supporting that CRS in conjunction with the RCF is a feasible micrometer-resolution dosimeter.