Numerical dosimetric analysis of low-energy positrons in living biological samples

Positron Annihilation Spectroscopy (PAS) probes the nanoscale free volume and electronic environment of cells and tissues through the formation and decay of positronium, and is potentially non destructive when operated at sufficiently low dose rates. Extending PAS from a bulk, drop-casted and contact-based technique to a depth-resolved intravital setting for living tissues requires moderated, monoenergetic positron beams in the 5−20keV range. In this case, the absorbed dose that such beams deliver to living matter has never been quantified. We present a numerical framework that couples positron transport to a time-resolved radiobiological model to provide the first estimate of cellular viability during PAS. The mass stopping power of a Liver Endothelial Cell monolayer is herein computed and cell survival is then evaluated with a Linear-Quadratic model extended in time to include sub-lethal damage repair and ultra-high dose rate (FLASH) sparing. Three delivery regimes, continuous, pulsed and trap-based bunched, are compared over implantation energies of 5−100keV. As a case study, we explore the action of a continuous positron beam utilizing a 22Na source, operating near the highest performance currently achieved with this technology and modeled at its maximum potential. Naturally, to perform true non-destructive spectroscopy, the beam intensity must be deliberately scaled down to avoid damaging the cells. We confirmed that biological sample viability is governed not by the temporal structure of the beam but by the time-averaged flux delivered to the sample. In order to collect 106 annihilation events for a positron lifetime spectrum before the radiation reduces the surviving fraction below 90% in the 5−20keV window required for depth-resolved analysis, a 30−50mCi22Na is required, along with a digital system for the detection of at least 105counts/sec. These results define the dose-driven viability limits of future intravital PAS and frame depth-resolved spectroscopy of living cells as an instrumental challenge for next-generation positron beam systems.