**Investigating energy deposition within cell populations using Monte
Carlo simulations**

PAK Oliver and RM Thomson, PHYSICS IN MEDICINE AND BIOLOGY, 63, 155018 (2018).

DOI: 10.1088/1361-6560/aacf7b

In this work, we develop multicellular models of healthy and cancerous human soft tissues, which are used to investigate energy deposition in subcellular targets, quantify the microdosimetric spread in a population of cells, and determine how these results depend on model details. Monte Carlo (MC) tissue models combining varying levels of detail on different length scales are developed: microscopically-detailed regions of interest (>1500 explicitly-modelled cells) are embedded in bulk tissue phantoms irradiated by photons (20 keV-1.25 MeV). Specific energy (z; energy imparted per unit mass) is scored in nuclei and cytoplasm compartments using the EGSnrc user-code egs_chamber; specific energy mean, (z) over bar, standard deviation, sigma(z), and distribution, f (z, D), are calculated for a variety of macroscopic doses, D. MC- calculated f (z, D) are compared with normal distributions having the same mean and standard deviation. For similar to mGy doses, there is considerable variation in energy deposition (microdosimetric spread) throughout a cell population: e.g. for 30 keV photons irradiating melanoma with 7.5 mu m cell radius and 3 mu m nuclear radius, sigma(z)/(z) over bar for nuclear targets is 170%, and the fraction of nuclei receiving no energy deposition, f(z)(=)(0), is 0.31 for a dose of 10 mGy. If cobalt-60 photons are considered instead, then sigma(z)/(z) over bar decreases to 84%, and f(z=0) decreases to 0.036. These results correspond to randomly arranged cells with cell/nucleus sizes randomly sampled from a normal distribution with a standard deviation of 1 mu m. If cells are arranged in a hexagonal lattice and cell/nucleus sizes are uniform throughout the population, then sigma(z)/(z) over bar decreases to 106% and 68% for 30 keV and cobalt-60, respectively; f(z=0) decreases to 0.25 and 0.000 94 for 30 keV and cobalt-60, respectively. Thus, specific energy distributions are sensitive to cell/nucleus sizes and their distributions: variations in specific energy deposited over a cell population are underestimated if targets are assumed to be uniform in size compared with more realistic variation in target size. Bulk tissue dose differs from (z) over bar for nuclei (cytoplasms) by up to 21% (12%) across all cell/nucleus sizes, bulk tissues, and incident photon energies, considering a 50 mGy dose level. Overall, results demonstrate the importance of microdosimetric considerations at low doses, and indicate the sensitivity of energy deposition within subcellular targets to incident photon energy, dose level, elemental compositions, and microscopic tissue model.

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