Abstract

Convection-enhanced delivery (CED) of Rhenium-186 nanoliposomes (RNL) is a promising approach to provide precise delivery of large, localized doses of radiation with the goal of extending overall survival for patients with recurrent GBM. A central component of successful CED, is achieving optimal catheter placement for delivery of the therapy. While surgical planning software exists for this purpose, current approaches are designed for small molecules and therefore are not appropriate for larger particles like RNL. To address this concern, we have developed a mathematical model to predict the distribution of RNL via CED on a patient-specific basis. The model is defined on the 3D brain domain which consists of 1) pressure and flow fields generated by accounting for catheter infusion, flow through brain, and fluid loss into capillaries, and 2) the transport of RNL governed by an advection-diffusion equation. We utilize pre-operative MRI to assign patient-specific tissue geometry and properties (e.g., diffusivity, conductivity), and calibrate the model with SPECT measurements within 24 h post the RNL delivery. This model is implemented on one patient enrolled in NCT01906385. The accuracy of model calibration and prediction is evaluated by the Dice score and concordance correlation coefficient (CCC) between modeled and measured distributions of RNL. Our model calibration achieves Dice scores of 0.80, 0.81, 0.69 and CCC of 0.92, 0.93, 0.73 for RNL distributions at the mid-delivery, end of delivery, and 24 h after the delivery, respectively. Long-term model prediction achieves Dice scores of 0.69 and 0.52 at 144 h and 196 h after the delivery, respectively, and CCC of 0.57 and 0.31. Preliminary results demonstrate a proof-of-concept for a patient-specific model to predict the spatiotemporally-resolved distribution of nanoparticles. Ongoing efforts focus on improving our model by accounting backflow and angle of catheter placement, and applying to more patients. Funding: NIH R01CA235800, CPRIT RR160005.