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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. 2016. "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 = 2016,
month = 6
}
  • 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
  • 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.
  • 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
  • Angiogenesis is widely investigated in conjunction with cancer development, in particular because of the possibility of early stage detection and of new therapeutic strategies. However, such studies are negatively affected by the limitations of imaging techniques in the detection of microscopic blood vessels (diameter 3-5 {micro}m) grown under angiogenic stress. We report that synchrotron-based X-ray imaging techniques with very high spatial resolution can overcome this obstacle, provided that suitable contrast agents are used. We tested different contrast agents based on gold nanoparticles (AuNPs) for the detection of cancer-related angiogenesis by synchrotron microradiology, microtomography and high resolution X-ray microscopy. Among themmore » only bare-AuNPs in conjunction with heparin injection provided sufficient contrast to allow in vivo detection of small capillary species (the smallest measured lumen diameters were 3-5 {micro}m). The detected vessel density was 3-7 times higher than with other nanoparticles. We also found that bare-AuNPs with heparin allows detecting symptoms of local extravascular nanoparticle diffusion in tumor areas where capillary leakage appeared. Although high-Z AuNPs are natural candidates as radiology contrast agents, their success is not guaranteed, in particular when targeting very small blood vessels in tumor-related angiography. We found that AuNPs injected with heparin produced the contrast level needed to reveal--for the first time by X-ray imaging--tumor microvessels with 3-5 {micro}m diameter as well as extravascular diffusion due to basal membrane defenestration. These results open the interesting possibility of functional imaging of the tumor microvasculature, of its development and organization, as well as of the effects of anti-angiogenic drugs.« less
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