Research ArticleAPPLIED SCIENCES AND ENGINEERING

Determination of topographical radiation dose profiles using gel nanosensors

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Science Advances  15 Nov 2019:
Vol. 5, no. 11, eaaw8704
DOI: 10.1126/sciadv.aaw8704
  • Fig. 1 Digital images and UV-visible spectra of different gel nanosensor formulations exposed to therapeutic doses of x-rays

    (A) Images of gel nanosensors fabricated in 24-well cell culture plates and containing different concentrations of C14TAB (24.5 to 73.5 mM) upon exposure to various doses of ionizing radiation (0- to 10-Gy x-rays); Na2S wait time was 5 min after irradiation, and incubation time was 10 min. Images were acquired 1 hour after irradiation. A visible increase in intensity in the maroon color is observed with increasing doses of ionizing radiation for most C14TAB concentrations used. (B to F) Absorbance spectra (300 to 990 nm) of the same gel nanosensors containing (B) 24.5 mM, (C) 31 mM, (D) 37 mM, (E) 49 mM, and (F) 73.5 mM irradiated using different radiation doses. Characteristic absorbance peaks between 500- and 600-nm wavelengths are indicative of gold nanoparticles formed in the gels. The corresponding radiation doses are mentioned in the legend with increasing radiation dose (top to bottom). A.U., arbitrary units. Photo credit: Sahil Inamdar, Arizona State University.

  • Fig. 2 Topographical visualization and quantification of radiation doses using gel nanosensors.

    (A) Gel nanosensor (left) before irradiation, (middle) top half irradiated with 4 Gy and image acquired 2 min after irradiation, and (right) image acquired 1 hour after irradiation. A visible increase in color intensity in the nonirradiated lower half indicates bleed over of color and loss of topographical information. (B) I: 1.5% (w/v) agarose gel (left) 2 min after irradiation and (right) 1 hour after irradiation; II: 2% (w/v) agarose gel (left) 2 min after irradiation and (right) 1 hour after irradiation indicates that the increase in agarose weight percentage does not preserve topographical dose information. (C) Gel nanosensor incubated with 5 mM sodium sulfide (Na2S) and various sodium halides with a wait time of 10 min and incubation time of 10 min; images were acquired after 1 hour. No loss of topographical information is observed upon incubation with sodium sulfide. All gels were fabricated in 24-well plates. (D) Colorimetric response of the gel nanosenor irradiated on one-half with a 2-Gy x-ray dose. A visible appearance of maroon color in the irradiated region illustrates the ability of the gel nanosensor to visualize topographical dose profiles. Each black square box (labeled 1 to 11) on the gel nanosensor corresponds to a grid of size ≈2 × 2 mm, whose absorbance at 540 nm is determined. Grids starting from 1 to 5 are regions exposed to ionizing radiation, 6 is the grid at the edge of the irradiation field, and grids from 7 to 11 are regions outside the field of irradiation. (E) Dose fall-off profile for the gel nanosensor irradiated by 2 Gy on one-half. The delivered and predicted radiation doses are comparable, which indicates the efficacy of the gel nanosensor in visualizing and retaining topographical information. In all cases, Na2S was added for 10-min incubation time after a wait time of 30 min. Radiation doses predicted by the gel nanosensor as compared with the delivered radiation dose as obtained from the treatment planning system. Asterisks indicate statistically significant differences (P < 0.05) between the delivered dose and the dose predicted by the gel nanosensor (n = 3 independent experiments). (F) Representative image of a petri dish containing the gel nanosensor formulation (≈3 mm thick and ≈10 cm diameter) irradiated with a 1 cm × 1 cm square field of x-ray radiation. From the left, each square indicates increasing radiation dose from (I) 0.5 Gy (red box), 1 Gy, and 1.5 Gy; (II) 2, 2.5, 3, and 3.5 Gy; and (III) 4, 4.5, and 5 Gy; the black box in image (II) shows 0 Gy. (G) Visualization of a complex topographical dose pattern (ASU letters) generated using a 2-Gy x-ray dose. The petri dish has a diameter of ≈10 cm. In (F) and (G), the gel nanosensors contain 24.5 mM C14TAB, and Na2S was added after a wait time of 30 min and incubation time of 10 min; a representative image from three independent experiments is shown. Photo credit: Sahil Inamdar, Arizona State University.

  • Fig. 3 Radiation-induced gold nanoparticle formation visualized and quantified using TEM images.

    TEM images showing the formation of nanoparticles for two different surfactant concentrations of (A) 37 mM and (B) 24.5 mM with a gold salt concentration of 0.25 mM after exposure to various levels of ionizing radiation. Na2S was added after a wait time of 30 min in all cases and incubated for 10 min. Histograms of particle size distribution (diameter), determined using analysis of TEM images, are shown below each corresponding micrograph; quasi-spherical geometry was assumed for the nanoparticles. The histograms show distribution for a range of nanoparticle size (e.g., distribution between 39 and 49 nm is indicated as 39, 49, and so on). (C) Table showing average nanoparticle size (nm) ± 1 SD about the mean as a function of radiation dose for the two surfactant concentrations 24.5 and 37 mM.

  • Fig. 4 Gel nanosensor enabled topographical detection and quantification of clinical radiation doses in anthropomorphic head and neck phantoms.

    (A) Anthropomorphic head and neck phantom treated with an irregularly shaped x-ray radiation field below the left eye. (B) Image of the gel nanosensor positioned on the anthropomorphic phantom in the radiation field mimicking a conventional radiotherapy session. (C) Axial view of the treatment planning image along the central axis of the radiation beam representing an irregularly shaped radiation field used to deliver a complex radiation pattern under the eye of the phantom. The core of the crescent-shaped treatment region receives a radiation dose of 2.3 Gy (highlighted in red), and regions receiving lower doses are highlighted with different colors going outward (from green to light pink). (D) Visual image of the dose pattern on the gel nanosensor formed after delivery of 2.3 Gy. Only the irradiated region develops a maroon color, while the nonirradiated region remains colorless. (E) Expected topographical dose “heat map” profile of the radiation dose delivered to the gel placed in the phantom. The expected profile is generated from the treatment plan in the dose delivery system. In these figures, red and blue colors indicate higher and lower radiation doses, respectively. (F) Topographical doses predicted by the irradiated gel nanosensor. Absorbance values of ≈2 mm × 2 mm grids were quantified using a calibration curve to generate the topographical dose profile. The anticipated dose received by the core of the crescent-shaped profile (2.3 Gy) is comparable to the dose profile predicted by the gel nanosensor (2.3 Gy), which demonstrates the capability of the gel nanosensor to qualitatively and quantitatively detect complex topographical dose profiles. The four independent experiments leading to these average values are shown in fig. S12. Photo credit: Sahil Inamdar, Arizona State University.

  • Fig. 5 Gel nanosensor enabled topographical detection and quantification of radiation delivered to canine patient A undergoing clinical radiotherapy.

    Representative image of (A) half of the gel nanosensor and (B) half of the radiographic film positioned in the radiation field delivered to canine patient A. (C) Treatment planning software depicting the delivery of a 2-Gy dose delivered to the surface of patient A (neon green edge along the rectangular gray box indicates the region receiving the 2-Gy dose). (D) The irradiated region received a dose of 2 Gy (highlighted in red squares), with irradiation dose dropping to a minimal radiation 0.1 Gy (highlighted in blue squares) outside the field of irradiation. A color change is visible in both the (E) gel nanosensor whose color changes to maroon and (F) radiographic film whose color changes to dark green after irradiation. The predicted dose map in the gel nanosensor (Na2S addition wait time of 30 min and incubation time of 10 min) and radiographic film are shown below each corresponding sensor (see Materials and Methods for details). Similarity in the dose profiles indicates the efficacy of the gel nanosensor for clinical dosimetry. The time for readout of the gel nanosensor was 1 hour after irradiation, while the radiochromic film required >24 hours of developing time before readout. All experiments were carried out three independent times. Photo credit: Sahil Inamdar, Arizona State University.

  • Fig. 6 Gel nanosensor enabled simultaneous detection and quantification of topographical and full-area doses delivered to canine patient B undergoing clinical radiotherapy.

    (A) Representative image of the gel nanosensor placed on the treated region, which was delivered a radiation dose of 3 Gy. (B) Representative image of the final setup of canine patient B. Half of the gel nanosensor and the Gafchromic EBT3 film is placed on the radiation field on top of the bolus, which was delivered a radiation dose of 1.5 Gy (image does not contain the gel nanosensor and the Gafchromic EBT3). (C) Treatment planning software depicting the delivery of a 3-Gy dose delivered to the skin of patient B (neon green edge indicates the region receiving the 3-Gy dose) (D) Expected dose delivered to the skin of the patient and (E) surface dose (1.5 cm above the bolus). A color change is easily visible in both the (F) gel nanosensor (maroon) and (G) radiographic film (dark green) after irradiation. The heat map of the predicted dose for both the gel nanosensor and radiographic film is depicted below each corresponding sensor (see Materials and Methods for details). The dose profiles are similar in all cases, indicating the efficacy of the gel nanosensor to clinical dosimetry. The time for readout of the gel nanosensor was 1 hour, while the radiochromic film required >24 hours before readout. All experiments were performed three times independently. Photo credit: Sahil Inamdar, Arizona State University.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/11/eaaw8704/DC1

    Fig. S1. Schematic illustration of the proposed mechanism for the formation of gold nanoparticles upon irradiation with ionizing radiation.

    Fig. S2. Plot of peak absorbance at 540 nm versus radiation dose shows the gel nanosensor response as a function of C14TAB concentration and a fixed wait time of 5 min for Na2S addition in all cases.

    Fig. S3. Images of gel nanosensors, fabricated in 24-well plates and containing 37 mM C14TAB, irradiated with different radiation doses (0 to 10 Gy).

    Fig. S4. Effect of wait time before Na2S addition on gel nanosensor response.

    Fig. S5. Effect of wait time before Na2S addition following irradiation on gel nanosensor response.

    Fig. S6. Schematic illustration of the proposed mechanism used for detecting spatial dose distribution.

    Fig. S7. Effect of gold salt concentration on the gel nanosensor response and estimation of precursor gold ion conversion to gold nanoparticles.

    Fig. S8. Gel nanosensor fabricated in six-well plates (≈3.5 cm diameter and same thickness as before, i.e., ≈3 mm) with 37 mM C14TAB and 0.25 mM gold salt was carried out before evaluation as a sensor for the detection of therapeutically relevant radiation doses.

    Fig. S9. Elemental analyses of nanoparticles.

    Fig. S10. Response of the gel nanosensor to varying agarose pore size distribution was evaluated by modulating the weight percentage of agarose used during fabrication.

    Fig. S11. Confocal reflectance microscopy imaging of the gel nanosensor and images depicting ascorbic acid diffusion along the depth of the gel nanosensor.

    Fig. S12. Four independent experiments showing topographical radiation dose profiles for the gel nanosensor in a head and neck phantom; the average values of these four independent data are presented in Fig. 4.

    Fig. S13. Schematic illustration of the canine patient set up for topographical dosimetry and visualization using gel nanosensors.

    Fig. S14. Evaluation of photostability, photobleaching, and long-term storage response of the gel nanosensors.

    Reference (45)

  • Supplementary Materials

    This PDF file includes:

    • Fig. S1. Schematic illustration of the proposed mechanism for the formation of gold nanoparticles upon irradiation with ionizing radiation.
    • Fig. S2. Plot of peak absorbance at 540 nm versus radiation dose shows the gel nanosensor response as a function of C14TAB concentration and a fixed wait time of 5 min for Na2S addition in all cases.
    • Fig. S3. Images of gel nanosensors, fabricated in 24-well plates and containing 37 mM C14TAB, irradiated with different radiation doses (0 to 10 Gy).
    • Fig. S4. Effect of wait time before Na2S addition on gel nanosensor response.
    • Fig. S5. Effect of wait time before Na2S addition following irradiation on gel nanosensor response.
    • Fig. S6. Schematic illustration of the proposed mechanism used for detecting spatial dose distribution.
    • Fig. S7. Effect of gold salt concentration on the gel nanosensor response and estimation of precursor gold ion conversion to gold nanoparticles.
    • Fig. S8. Gel nanosensor fabricated in six-well plates (≈3.5 cm diameter and same thickness as before, i.e., ≈3 mm) with 37 mM C14TAB and 0.25 mM gold salt was carried out before evaluation as a sensor for the detection of therapeutically relevant radiation doses.
    • Fig. S9. Elemental analyses of nanoparticles.
    • Fig. S10. Response of the gel nanosensor to varying agarose pore size distribution was evaluated by modulating the weight percentage of agarose used during fabrication.
    • Fig. S11. Confocal reflectance microscopy imaging of the gel nanosensor and images depicting ascorbic acid diffusion along the depth of the gel nanosensor.
    • Fig. S12. Four independent experiments showing topographical radiation dose profiles for the gel nanosensor in a head and neck phantom; the average values of these four independent data are presented in Fig. 4.
    • Fig. S13. Schematic illustration of the canine patient set up for topographical dosimetry and visualization using gel nanosensors.
    • Fig. S14. Evaluation of photostability, photobleaching, and long-term storage response of the gel nanosensors.
    • Reference (45)

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