Radiation source personalization for nanoparticle-enhanced radiotherapy using dynamic contrast-enhanced MRI in the treatment planning process

Abstract

Nanoparticle-enhanced radiotherapy offers the potential to selectively increase the radiation dose imparted to the tumor while at the same time sparing the healthy structures around it. Among the recommendations of an interdisciplinary group for the clinical translation of this treatment modality, is the developing of methods to quantify the effects that the nanoparticle concentration has on the radiation dosimetry and incorporate these effects into the treatment planning process. In this work, using Monte Carlo simulations and dynamic contrast-enhanced MRI images, treatment plans for nanoparticle-enhanced radiotherapy are calculated in order to evaluate the effects that realistic distributions of the nanoparticles have on the resultant plans and to devise treatment strategies to account for these effects, including the selection of the proper x-ray source configuration in terms of energy and collimation. Dynamic contrast-enhanced MRI studies were obtained for two treatment sites, namely brain and breast. A model to convert the MRI signal to contrast agent concentration was applied to each set of images. Two treatment modalities, 3D conformal radiotherapy and Stereotactic Body Radiation Therapy, were evaluated at three different x-ray spectra, namely 6 MV from a linear accelerator, 110 kVp and 220 kVp from a tungsten target. For the breast patient, as the nanoparticle distribution varies markedly with time, the treatment plans were obtained at two different times after administration. It was determined that maximum doses to the healthy structures around the tumor are mostly determined by the minimum nanoparticle concentration in the tumor. The presence of highly hypoxic or necrotic tissue, which fails to accumulate the nanoparticles, or leakage of the contrast agent into the surrounding healthy tissue, make irradiation with conventional conformal radiotherapy unfeasible for kilovoltage beam energies, as the uniform beam apertures lack the ability to compensate for the non-uniform distribution of the nanoparticles. Therefore, proper quantification of the nanoparticle distribution not only in the target volume but also in the surrounding tissues and structures is crucial for the proper planning of nanoparticle-enhanced radiotherapy and a treatment delivery with a high-degree of freedom, such as small-field stereotactic body radiotherapy, should be the method of choice for this treatment modality.