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

Abstract

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

A High-Sensitivity Benchtop X-Ray Fluorescence Emission Tomography (XFET) System With a Full-Ring of X-Ray Imaging-Spectrometers and a Compound-Eye Collimation Aperture

“…The radiation dose delivered to the acrylic phantom with an acquisition time of 10 minutes per scan position and filtered incident X-ray spectrum would be ~3.26 Gy. This dose, although, is lower by a factor of two compared to the studies showing similar imaging detection limits [ 43 ], [ 44 ], is still relatively high for preclinical in-vivo applications [ 33 ], [ 48 ], [ 49 ]. Moreover, the long imaging time of the current system configuration further impedes its in-vivo applicability.…”

“…Optimization studies on the positioning of multiple detectors have been reported to further improve the SNR based on the anisotropic angular-energy distribution of the Compton scattering photons [ 40 ], [ 41 ], [ 42 ]. Jung et al [ 48 ] and Kim et al [ 49 ] have developed a dynamic dual modality in-vivo XRF imaging system to obtain both the functional and anatomical information on the same imaging bed and to study the accumulation and washout biodistribution of metal nanoparticles in mice. Recently, Moktan et al [ 43 ] and Manohar et al [ 44 ] demonstrated a detection limit of less than 0.3 mg/mL for AuNP using a CdTe (Amptek Inc.) detector coupled with a lead collimator and cone-beam X-rays illuminating the entire 3-cm diameter phantom.…”

Atomic spectrometry update: review of advances in the analysis of clinical and biological materials, foods and beverages

“…The use of XRF spectrometry for biochemical research has received some interest in this review period. Kim and co-workers 191 combined XRF spectrometry and computed tomography (CT) to investigate the in vivo biodistribution of Au NPs. A transmission CT detector was installed in an existing pinhole XRF instrument, enabling dual detection.…”

Review of Development and Recent Advances in Biomedical X-ray Fluorescence Imaging

“…Besides the use of pencil-beam setups with near-monochromatic incident radiation, in vivo biodistribution measurements of gold nanoparticles (GNPs) have also been demonstrated with polychromatic fan-beam X-rays [ 37 ]. The combination of a transmission CT detector installed in an existing pinhole XRF imaging system using a two-dimensional cadmium zinc telluride (CZT) camera allows to acquire functional and anatomic information on the same platform [ 38 ]. The pinhole XRF system used in [ 38 ] comprised a tungsten fan-beam collimator, a lead pinhole collimator and a CZT camera, reaching a spatial resolution of 4.4 mm.…”

“…The combination of a transmission CT detector installed in an existing pinhole XRF imaging system using a two-dimensional cadmium zinc telluride (CZT) camera allows to acquire functional and anatomic information on the same platform [ 38 ]. The pinhole XRF system used in [ 38 ] comprised a tungsten fan-beam collimator, a lead pinhole collimator and a CZT camera, reaching a spatial resolution of 4.4 mm. Due to the different optimal energy spectra for XRF and CT imaging (high energies above the K-edge of GNPs for XRF and low energies to produce sufficient contrast on CT), images had to be sequentially acquired on the same platform [ 38 ].…”