Modeling the Relationship between Fluorodeoxyglucose Uptake and Tumor Radioresistance as a Function of the Tumor Microenvironment

High fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tumors has often been correlated with increasing local failure and shorter overall survival, but the radiobiological mechanisms of this uptake are unclear. We explore the relationship between FDG-PET uptake and tumor radioresistance using a mechanistic model that considers cellular status as a function of microenvironmental conditions, including proliferating cells with access to oxygen and glucose, metabolically active cells with access to glucose but not oxygen, and severely hypoxic cells that are starving. However, it is unclear what the precise uptake levels of glucose should be for cells that receive oxygen and glucose versus cells that only receive glucose. Different potential FDG uptake profiles, as a function of the microenvironment, were simulated. Predicted tumor doses for 50% control (TD50) in 2 Gy fractions were estimated for each assumed uptake profile and for various possible cell mixtures. The results support the hypothesis of an increased avidity of FDG for cells in the intermediate stress state (those receiving glucose but not oxygen) compared to well-oxygenated (and proliferating) cells

IMRT QA using machine learning: A multi-institutional validation.

PurposeTo validate a machine learning approach to Virtual intensity-modulated radiation therapy (IMRT) quality assurance (QA) for accurately predicting gamma passing rates using different measurement approaches at different institutions.MethodsA Virtual IMRT QA framework was previously developed using a machine learning algorithm based on 498 IMRT plans, in which QA measurements were performed using diode-array detectors and a 3%local/3 mm with 10% threshold at Institution 1. An independent set of 139 IMRT measurements from a different institution, Institution 2, with QA data based on portal dosimetry using the same gamma index, was used to test the mathematical framework. Only pixels with ≥10% of the maximum calibrated units (CU) or dose were included in the comparison. Plans were characterized by 90 different complexity metrics. A weighted poison regression with Lasso regularization was trained to predict passing rates using the complexity metrics as input.ResultsThe methodology predicted passing rates within 3% accuracy for all composite plans measured using diode-array detectors at Institution 1, and within 3.5% for 120 of 139 plans using portal dosimetry measurements performed on a per-beam basis at Institution 2. The remaining measurements (19) had large areas of low CU, where portal dosimetry has a larger disagreement with the calculated dose and as such, the failure was expected. These beams need further modeling in the treatment planning system to correct the under-response in low-dose regions. Important features selected by Lasso to predict gamma passing rates were as follows: complete irradiated area outline (CIAO), jaw position, fraction of MLC leafs with gaps smaller than 20 or 5 mm, fraction of area receiving less than 50% of the total CU, fraction of the area receiving dose from penumbra, weighted average irregularity factor, and duty cycle.ConclusionsWe have demonstrated that Virtual IMRT QA can predict passing rates using different measurement techniques and across multiple institutions. Prediction of QA passing rates can have profound implications on the current IMRT process

Optimal Transport for Kernel Gaussian Mixture Models

The Wasserstein distance from optimal mass transport (OMT) is a powerful mathematical tool with numerous applications that provides a natural measure of the distance between two probability distributions. Several methods to incorporate OMT into widely used probabilistic models, such as Gaussian or Gaussian mixture, have been developed to enhance the capability of modeling complex multimodal densities of real datasets. However, very few studies have explored the OMT problems in a reproducing kernel Hilbert space (RKHS), wherein the kernel trick is utilized to avoid the need to explicitly map input data into a high-dimensional feature space. In the current study, we propose a Wasserstein-type metric to compute the distance between two Gaussian mixtures in a RKHS via the kernel trick, i.e., kernel Gaussian mixture models.Comment: 17 pages, 5 figures, 2 table