Validation of combined Monte Carlo and photokinetic simulations for the outcome correlation analysis of benzoporphyrin derivative-mediated photodynamic therapy on mice

Abstract

We compare previously reported benzoporphyrin derivative (BPD)-mediated photodynamic therapy (PDT) results for reactive singlet oxygen concentration (also called singlet oxygen dose) on mice with simulations using a computational device, Dosie™, that calculates light transport and photokinetics for PDT in near real-time. The two sets of results are consistent and validate the use of the device in PDT treatment planning to predict BPD-mediated PDT outcomes in mice animal studies based on singlet oxygen dose, which showed a much better correlation with the cure index than the conventional light dose.

Keywords: medical device; photodynamic therapy; solid cancer therapy.

Fig. 1

Schematic diagram for Dosie™ integrated computer and software computational device. The computer includes both a GPU and a multicore CPU. The software first performs a MC simulation of light transport that is followed by a PK simulation.

Fig. 2

Dosie™ GUI screenshots: MC fluence rate results using 0.50-mm voxels for an incident fluence rate of $50{\mathrm{mW}/\mathrm{cm}}^2$. Volume rendering is done to visualize 3-D fluence rate map in the upper left view, whereas other views show three 2-D cross-sections (slices) of the map—sagittal, coronal, and transverse views.

Fig. 3

YZ slice of Dosie™’s MC fluence rate results using 0.50-mm voxels through the center of the target volume for an incident fluence rate of $50{\mathrm{mW}/\mathrm{cm}}^2$.

Fig. 4

The ratio (fluence rate in tissue)/(fluence rate in air) versus depth in tissue that compares an analytical fit to Dosie™’s MC results.

Fig. 5

YZ slice of Dosie™’s PK ${[{{}^1\mathrm{O}}_2]}_{rx}$ results through the center of the target volume shown for an incident fluence rate of $50\mathrm{mW}/{\mathrm{cm}}^2$ for 600 s and for 0.50-mm voxels.

Fig. 6

Comparison of Dosie™’s PK results to Penn results for 1-mm, 0.50-mm, and 0.25-mm voxels.

Fig. 7

Penn experimental cure index (CI) data from Ref.  versus Dosie™ calculated singlet oxygen dose, ${[{{}^1\mathrm{O}}_2]}_{rx}$, at 3 mm below the target surface for 0.50-mm grid. The CI error bars and the expression for the solid line, $\mathrm{CI}=1.08/(1+3490\times \exp (-8.301\times {[{{}^1\mathrm{O}}_2]}_{rx}))$ are from Ref. .

Fig. 8

Cure index versus conventional light dose (in-air incident fluence on the target surface). Data taken from Ref. .