Patient specific, imaging-informed modeling of rhenium-186 nanoliposome delivery via convection-enhanced delivery in glioblastoma multiforme

Convection-enhanced delivery of rhenium-186 (Re-186)-nanoliposomes is a promising approach to provide precise delivery of large localized doses of radiation for patients with recurrent glioblastoma multiforme. Current approaches for treatment planning utilizing convection-enhanced delivery are designed for small molecule drugs and not for larger particles such as Re-186-nanoliposomes. To enable the treatment planning for Re-186-nanoliposomes delivery, we have developed a computational fluid dynamics approach to predict the distribution of nanoliposomes for individual patients. In this work, we construct, calibrate, and validate a family of computational fluid dynamics models to predict the spatio-temporal distribution of Re-186-nanoliposomes within the brain, utilizing patient-specific pre-operative magnetic resonance imaging (MRI) to assign material properties for an advection-diffusion transport model. The model family is calibrated to single photon emission computed tomography (SPECT) images acquired during and after the infusion of Re-186-nanoliposomes for five patients enrolled in a Phase I/II trial (NCT Number NCT01906385), and is validated using a leave-one-out bootstrapping methodology for predicting the final distribution of the particles. After calibration, our models are capable of predicting the mid-delivery and final spatial distribution of Re-186-nanoliposomes with a Dice value of 0.69 +/- 0.18 and a concordance correlation coefficient of 0.88 +/- 0.12 (mean +/- 95% confidence interval), using only the patient-specific, pre-operative MRI data, and calibrated model parameters from prior patients. These results demonstrate a proof-of-concept for a patient-specific modeling framework, which predicts the spatial distribution of nanoparticles. Further development of this approach could enable optimizing catheter placement for future studies employing convection-enhanced delivery.

Automated summary

The study presents a computational fluid dynamics approach to predict the spatial distribution of Re-186-nanoliposomes for individual patients with recurrent glioblastoma multiforme. The models were calibrated and validated using patient-specific pre-operative MRI data and showed potential for optimizing catheter placement in future studies using convection-enhanced delivery.