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Research ArticleSpecial Contribution

MIRD Pamphlet No. 25: MIRDcell V2.0 Software Tool for Dosimetric Analysis of Biologic Response of Multicellular Populations

Behrooz Vaziri, Han Wu, Atam P. Dhawan, Peicheng Du, Roger W. Howell and In collaboration with the SNMMI MIRD Committee:
Journal of Nuclear Medicine September 2014, 55 (9) 1557-1564; DOI: https://doi.org/10.2967/jnumed.113.131037
Behrooz Vaziri
1Division of Radiation Research, Department of Radiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey
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Han Wu
1Division of Radiation Research, Department of Radiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey
2Office of Research and Department of Microbiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey
3Department of Electrical and Computer Engineering, New Jersey Institute of Technology, Newark, New Jersey; and
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Atam P. Dhawan
3Department of Electrical and Computer Engineering, New Jersey Institute of Technology, Newark, New Jersey; and
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Peicheng Du
4High Performance and Research Computing, IST, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, Newark, New Jersey
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Roger W. Howell
1Division of Radiation Research, Department of Radiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey
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  • FIGURE 1.
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    FIGURE 1.

    Screenshot of “Source Radiation” tab. This tab provides 3 options for selecting radioactivity to be placed in labeled cells: (1) Predefined MIRD radionuclide (top left). Radiation spectra are available for predefined radionuclides that include average β-particle energies (“β Average Energy Spectrum”) or complete β-particle spectrum (“β Full Energy Spectrum”). (2) Monoenergetic particle emitter (top right). Here, user can select either α particle or electron and can specify particle yield per disintegration and energy. (3) User-created radionuclide (lower left). User can create a radionuclide that includes a variety of selectable radiations (α, Auger electron, β−, and β+). Data are streamed into bottom right box, input data for calculation.

  • FIGURE 2.
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    FIGURE 2.

    Screenshot of “Cell Source/Target” tab. Source region (red) in cell that contains radiopharmaceutical can be selected as cell, cell surface, nucleus, or cytoplasm (top left). Selectable target regions (blue) include cell, nucleus, or cytoplasm (top left). Cell and cell nucleus are represented by concentric shells of unit density water with cell radius (RC) and cell nucleus radius (RN), which can be set as desired (bottom left).

  • FIGURE 3.
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    FIGURE 3.

    Screenshot of “Multicellular Geometry < 1-D Cell Pair.” This subtab enables rapid calculation of self-dose to labeled cell and cross-dose to neighboring cell that lies at some distance (i.e., 16 μm between centers in this example). Self- and cross-doses per unit cumulated activity in source cell (Gy Bq−1 s−1), also known as S value (2,35), are reported for selected source radiation (i.e., 90Y in this example) in box labeled “Result.” Calculation can be repeated for different cell separation distances (top left).

  • FIGURE 4.
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    FIGURE 4.

    Screenshots of “Multicellular Geometry < 2-D Colony < 2-D Colony.” (A) Here, user can select multicellular geometry wherein cell population lies on plane. In “Cell Geometry” box, cell population can be constrained to different selectable shapes including circle (shown), ellipse, and rectangle (top left). Dimensions of each shape are provided by user (i.e., circle with 66-μm radius in this example). In “Cell Labeling” box, activity can be distributed among cell population according to selectable labeling methods: uniform (shown), normal, and lognormal. Mean activity per cell, residence time, and percentage of cells that are labeled can be specified. On selecting parameters and clicking “Compute,” resulting multicellular geometry is plotted on right in a manner that indicates whether cell is labeled (red) or unlabeled (green), and transparency represents whether cell is dead (transparent) or alive (opaque). (B) Histogram of activity per cell. This example shows uniform distribution of activity among labeled cells (each labeled cell has same activity). (C) Plot of surviving fraction of cells.

  • FIGURE 5.
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    FIGURE 5.

    Screenshot of “Multicellular Geometry < 3-D Cluster < 3-D Cluster.” (A) User can select multicellular geometry wherein cell population is contained within 3-D geometry. In “Cell Geometry” box, cell population can be constrained to different selectable shapes including sphere (shown), ellipsoid, and cone. Dimensions of each shape are provided by user (i.e., sphere with 65-μm radius in this example). In “Cell Labeling” box, activity can be distributed among cell population according to selectable labeling distributions: uniform, normal, and lognormal (shown). Mean activity per cell, residence time, and percentage of cells that are labeled can be specified. When parameters are selected and “Compute” is clicked, the resulting multicellular geometry is plotted on right in a manner that indicates whether cell is labeled (red) or unlabeled (green), and transparency represents whether cell is dead (transparent) or alive (opaque). (B) Histogram of activity per cell. Small number of labeled cells (in this case it is 172) magnifies stochastic aspects of distribution in such a small population. Repeated clicking of “Compute” tab shows variations in distribution when Monte Carlo calculations are repeated. (C) Plot of surviving fraction of cells.

  • FIGURE 6.
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    FIGURE 6.

    Examples of additional geometries available in “Multicellular Geometry < 3-D Cluster < 3-D Cluster.” These are 3-D cluster shapes with 50% of cells labeled. Cluster shapes are sphere, rod, cone, and ellipsoid. Cells are labeled (red) or unlabeled (green), and transparency represents whether cell is dead (transparent) or alive (opaque).

  • FIGURE 7.
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    FIGURE 7.

    Comparison of experimental cell survival data (symbols) and theoretic cell survival data (solid lines; calculated with MIRDcell, version 2.0.9) for α-particle emitter 210Po in multicellular clusters. Experimental data are from Neti et al. (30), where 100%, 10%, or 1% of cells in cluster are labeled with 210Po. Inset shows full datasets for 1% labeling case. Modeling parameters are described fully in worked example 2 in online supplement.

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Journal of Nuclear Medicine: 55 (9)
Journal of Nuclear Medicine
Vol. 55, Issue 9
September 1, 2014
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MIRD Pamphlet No. 25: MIRDcell V2.0 Software Tool for Dosimetric Analysis of Biologic Response of Multicellular Populations
Behrooz Vaziri, Han Wu, Atam P. Dhawan, Peicheng Du, Roger W. Howell, In collaboration with the SNMMI MIRD Committee:
Journal of Nuclear Medicine Sep 2014, 55 (9) 1557-1564; DOI: 10.2967/jnumed.113.131037

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MIRD Pamphlet No. 25: MIRDcell V2.0 Software Tool for Dosimetric Analysis of Biologic Response of Multicellular Populations
Behrooz Vaziri, Han Wu, Atam P. Dhawan, Peicheng Du, Roger W. Howell, In collaboration with the SNMMI MIRD Committee:
Journal of Nuclear Medicine Sep 2014, 55 (9) 1557-1564; DOI: 10.2967/jnumed.113.131037
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Keywords

  • dosimetry
  • radionuclide
  • multicellular cluster
  • cell survival
  • nonuniform activity distribution
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