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Title: SU-G-IeP3-07: High-Resolution, High-Sensitivity Imaging and Quantification of Intratumoral Distributions of Gold Nanoparticles Using a Benchtop L-Shell XRF Imaging System

Abstract

Purpose: To demonstrate the ability to perform high-resolution imaging and quantification of sparse distributions of gold nanoparticles (GNPs) within ex vivo tumor samples using a highly-sensitive benchtop L-shell x-ray fluorescence (XRF) imaging system. Methods: An optimized L-shell XRF imaging system was assembled using a tungsten-target x-ray source (operated at 62 kVp and 45 mA). The x-rays were filtered (copper: 0.08 mm & aluminum: 0.04 mm) and collimated (lead: 5 cm thickness, 3 cm aperture diameter) into a cone-beam in order to irradiate small samples or objects. A collimated (stainless steel: 4 cm thickness, 2 mm aperture diameter) silicon drift detector, capable of 2D translation, was placed at 90° with respect to the beam to acquire XRF/scatter spectra from regions of interest. Spectral processing involved extracting XRF signal from background, followed by attenuation correction using a Compton scatter-based normalization algorithm. Calibration phantoms with water/GNPs (0 and 0.00001–10 mg/cm{sup 3}) were used to determine the detection limit of the system at a 10-second acquisition time. The system was then used to map the distribution of GNPs within a 12×11×2 mm{sup 3} slice excised from the center of a GNP-loaded ex vivo murine tumor sample; a total of 110 voxels (2.65×10{sup −3} cm{supmore » 3}) were imaged with 1.3-mm spatial resolution. Results: The detection limit of the current cone-beam benchtop L-shell XRF system was 0.003 mg/cm{sup 3} (3 ppm). Intratumoral GNP concentrations ranging from 0.003 mg/cm{sup 3} (3 ppm) to a maximum of 0.055 mg/cm{sup 3} (55 ppm) and average of 0.0093 mg/cm{sup 3} (9.3 ppm) were imaged successfully within the ex vivo tumor slice. Conclusion: The developed cone-beam benchtop L-shell XRF imaging system can immediately be used for imaging of ex vivo tumor samples containing low concentrations of GNPs. With minor finetuning/optimization, the system can be directly adapted for performing routine preclinical in vivo imaging tasks. Supported by NIH/NCI grant R01CA155446 This investigation was supported by NIH/NCI grant R01CA155446.« less

Authors:
; ; ;  [1];  [1];  [2]
  1. UT MD Anderson Cancer Center, Houston, TX (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22649400
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; BIOMEDICAL RADIOGRAPHY; DISTRIBUTION; GOLD; IMAGES; NANOPARTICLES; NEOPLASMS; SPATIAL RESOLUTION; STAINLESS STEELS; X RADIATION; X-RAY FLUORESCENCE ANALYSIS; X-RAY SOURCES

Citation Formats

Manohar, N, Diagaradjane, P, Krishnan, S, Cho, S, Reynoso, F, and Washington University School of Medicine, St. Louis, MO. SU-G-IeP3-07: High-Resolution, High-Sensitivity Imaging and Quantification of Intratumoral Distributions of Gold Nanoparticles Using a Benchtop L-Shell XRF Imaging System. United States: N. p., 2016. Web. doi:10.1118/1.4957056.
Manohar, N, Diagaradjane, P, Krishnan, S, Cho, S, Reynoso, F, & Washington University School of Medicine, St. Louis, MO. SU-G-IeP3-07: High-Resolution, High-Sensitivity Imaging and Quantification of Intratumoral Distributions of Gold Nanoparticles Using a Benchtop L-Shell XRF Imaging System. United States. doi:10.1118/1.4957056.
Manohar, N, Diagaradjane, P, Krishnan, S, Cho, S, Reynoso, F, and Washington University School of Medicine, St. Louis, MO. Wed . "SU-G-IeP3-07: High-Resolution, High-Sensitivity Imaging and Quantification of Intratumoral Distributions of Gold Nanoparticles Using a Benchtop L-Shell XRF Imaging System". United States. doi:10.1118/1.4957056.
@article{osti_22649400,
title = {SU-G-IeP3-07: High-Resolution, High-Sensitivity Imaging and Quantification of Intratumoral Distributions of Gold Nanoparticles Using a Benchtop L-Shell XRF Imaging System},
author = {Manohar, N and Diagaradjane, P and Krishnan, S and Cho, S and Reynoso, F and Washington University School of Medicine, St. Louis, MO},
abstractNote = {Purpose: To demonstrate the ability to perform high-resolution imaging and quantification of sparse distributions of gold nanoparticles (GNPs) within ex vivo tumor samples using a highly-sensitive benchtop L-shell x-ray fluorescence (XRF) imaging system. Methods: An optimized L-shell XRF imaging system was assembled using a tungsten-target x-ray source (operated at 62 kVp and 45 mA). The x-rays were filtered (copper: 0.08 mm & aluminum: 0.04 mm) and collimated (lead: 5 cm thickness, 3 cm aperture diameter) into a cone-beam in order to irradiate small samples or objects. A collimated (stainless steel: 4 cm thickness, 2 mm aperture diameter) silicon drift detector, capable of 2D translation, was placed at 90° with respect to the beam to acquire XRF/scatter spectra from regions of interest. Spectral processing involved extracting XRF signal from background, followed by attenuation correction using a Compton scatter-based normalization algorithm. Calibration phantoms with water/GNPs (0 and 0.00001–10 mg/cm{sup 3}) were used to determine the detection limit of the system at a 10-second acquisition time. The system was then used to map the distribution of GNPs within a 12×11×2 mm{sup 3} slice excised from the center of a GNP-loaded ex vivo murine tumor sample; a total of 110 voxels (2.65×10{sup −3} cm{sup 3}) were imaged with 1.3-mm spatial resolution. Results: The detection limit of the current cone-beam benchtop L-shell XRF system was 0.003 mg/cm{sup 3} (3 ppm). Intratumoral GNP concentrations ranging from 0.003 mg/cm{sup 3} (3 ppm) to a maximum of 0.055 mg/cm{sup 3} (55 ppm) and average of 0.0093 mg/cm{sup 3} (9.3 ppm) were imaged successfully within the ex vivo tumor slice. Conclusion: The developed cone-beam benchtop L-shell XRF imaging system can immediately be used for imaging of ex vivo tumor samples containing low concentrations of GNPs. With minor finetuning/optimization, the system can be directly adapted for performing routine preclinical in vivo imaging tasks. Supported by NIH/NCI grant R01CA155446 This investigation was supported by NIH/NCI grant R01CA155446.},
doi = {10.1118/1.4957056},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}
  • Purpose: To develop a proof-of-principle L-shell x-ray fluorescence (XRF) imaging system that locates and quantifies sparse concentrations of gold nanoparticles (GNPs) using a benchtop polychromatic x-ray source and a silicon (Si)-PIN diode x-ray detector system.Methods: 12-mm-diameter water-filled cylindrical tubes with GNP concentrations of 20, 10, 5, 0.5, 0.05, 0.005, and 0 mg/cm{sup 3} served as calibration phantoms. An imaging phantom was created using the same cylindrical tube but filled with tissue-equivalent gel containing structures mimicking a GNP-loaded blood vessel and approximately 1 cm{sup 3} tumor. Phantoms were irradiated by a 3-mm-diameter pencil-beam of 62 kVp x-rays filtered by 1 mmmore » aluminum. Fluorescence/scatter photons from phantoms were detected at 90° with respect to the beam direction using a Si-PIN detector placed behind a 2.5-mm-diameter lead collimator. The imaging phantom was translated horizontally and vertically in 0.3-mm steps to image a 6 mm × 15 mm region of interest (ROI). For each phantom, the net L-shell XRF signal from GNPs was extracted from background, and then corrected for detection efficiency and in-phantom attenuation using a fluorescence-to-scatter normalization algorithm.Results: XRF measurements with calibration phantoms provided a calibration curve showing a linear relationship between corrected XRF signal and GNP mass per imaged voxel. Using the calibration curve, the detection limit (at the 95% confidence level) of the current experimental setup was estimated to be a GNP mass of 0.35 μg per imaged voxel (1.73 × 10{sup −2} cm{sup 3}). A 2D XRF map of the ROI was also successfully generated, reasonably matching the known spatial distribution as well as showing the local variation of GNP concentrations.Conclusions: L-shell XRF imaging can be a highly sensitive tool that has the capability of simultaneously imaging the spatial distribution and determining the local concentration of GNPs presented on the order of parts-per-million level within subcentimeter-sized ex vivo samples and superficial tumors during preclinical animal studies.« less
  • Purpose: Gold nanoparticles (AuNP) are multifunctional platforms ideal for drug delivery, targeted imaging and radiosensitization. We have investigated quantitative imaging of AuNPs using on board imager (OBI) cone beam computed tomography (CBCT). To this end, we also present, for the first time, a novel method for k-edge imaging of AuNP by filter-based spectral shaping. Methods: We used a digital 25 cm diameter water phantom, embedded with 3 cm spheres filled with AuNPs of different concentrations (0 mg/ml – 16 mg/ml). A poly-energetic X-ray spectrum of 140 kVp from a conventional X-ray tube is shaped by balanced K-edge filters to createmore » an excess of photons right above the K-edge of gold at 80.7 keV. The filters consist of gold, tin, copper and aluminum foils. The phantom with appropriately assigned attenuation coefficients is forward projected onto a detector for each energy bin and then integrated. FKD reconstruction is performed on the integrated projections. Scatter, detector efficiency and noise are included. Results: We found that subtracting the results of two filter sets (Filter A:127 µm gold foil with 254 µm tin, 330 µm copper and 1 mm aluminum, and Filter B: 635 µm tin with 264 µm copper and 1 mm aluminum), provides substantial image contrast. The resulting filtered spectra match well below 80.7 keV, while maintaining sufficient X-ray quanta just above that. Voxel intensities of AuNP containing spheres increase linearly with AuNP concentration. K-edge imaging provides 18% more sensitivity than the tin filter alone, and 38% more sensitivity than the gold filter alone. Conclusion: We have shown that it is feasible to quantitatively detect AuNP distributions in a patient-sized phantom using clinical CBCT and K-edge spectral shaping.« less
  • Purpose: Deconvolution is a widely used tool in the field of image reconstruction algorithm when the linear imaging system has been blurred by the imperfect system transfer function. However, due to the nature of Gaussian-liked distribution for point spread function (PSF), the components with coherent high frequency in the image are hard to restored in most of the previous scanning imaging system, even the relatively accurate PSF is acquired. We propose a novel method for deconvolution of images which are obtained by using shape-modulated PSF. Methods: We use two different types of PSF - Gaussian shape and donut shape -more » to convolute the original image in order to simulate the process of scanning imaging. By employing deconvolution of the two images with corresponding given priors, the image quality of the deblurred images are compared. Then we find the critical size of the donut shape compared with the Gaussian shape which has similar deconvolution results. Through calculation of tightened focusing process using radially polarized beam, such size of donut is achievable under same conditions. Results: The effects of different relative size of donut and Gaussian shapes are investigated. When the full width at half maximum (FWHM) ratio of donut and Gaussian shape is set about 1.83, similar resolution results are obtained through our deconvolution method. Decreasing the size of donut will favor the deconvolution method. A mask with both amplitude and phase modulation is used to create a donut-shaped PSF compared with the non-modulated Gaussian PSF. Donut with size smaller than our critical value is obtained. Conclusion: The utility of donutshaped PSF are proved useful and achievable in the imaging and deconvolution processing, which is expected to have potential practical applications in high resolution imaging for biological samples.« less
  • Purpose: Accurate values for Kerma-Area-Product (KAP) are needed for patient dosimetry and quality control for exams utilizing radiographic and/or fluoroscopic imaging. The KAP measured using a typical direct KAP meter built with parallel-plate transmission ionization chamber is not precise and depends on the energy spectrum of diagnostic x-rays. This study compared the accuracy and reproducibility of KAP derived from system parameters with values measured with a direct KAP meter. Methods: IEC tolerance for displayed KAP is specified up to ± 35% above 2.5 Gy-cm{sup 2} and manufacturer’s specifications are typically ± 25%. KAP values from the direct KAP meter driftsmore » with time leading to replacement or re-calibration. More precise and consistent KAP is achievable utilizing a database of known radiation output for various system parameters. The integrated KAP meter was removed from a radiography system. A total of 48 measurements of air kerma were acquired at x-ray tube potential from 40 to 150 kVp with 10 kVp increment using ion chamber type external dosimeter at free-in-air geometry for four different types of filter combinations following the manufacturer’s service procedure. These data were used to create updated correction factors that determine air kerma computationally for given system parameters. Results of calculated KAP were evaluated against results using a calibrated ion chamber based dosimeter and a computed radiography imaging plate to measure x-ray field size. Results: The accuracy of calculated KAP from the system parameters was better within 4% deviation in all diagnostic x-ray tube potentials tested from 50 to 140 kVp. In contrast, deviations of up to 25% were measured from KAP displayed from the direct KAP meter. Conclusion: The “calculated KAP” approach provides the nominal advantage of improved accuracy and precision of displayed KAP as well as reduced cost of calibrating or replacing integrated KAP meters.« less
  • We combine resonant scattering with (ptychographic) scanning coherent diffraction microscopy to determine the chemical state of gold nanoparticles with high spatial resolution. Ptychographic images of the sample are recorded for a series of energies around the gold L{sub 3} absorption edge. From these data, chemical information in the form of absorption and resonant scattering spectra is reconstructed at each location in the sample. For gold nanoparticles of about 100 nm diameter, a spatial resolution of about 20-30 nm is obtained. In the future, this microscopy approach will open the way to operando studies of heterogeneous catalysts on the nanometer scale.