Abstract

Quantitative analysis of dynamic positron emission tomography (PET) data usually involves minimizing a cost function with nonlinear regression, wherein the choice of starting parameter values and the presence of local minima affect the bias and variability of the estimated kinetic parameters. These nonlinear methods can also require lengthy computation time, making them unsuitable for use in clinical settings. Kinetic modeling of PET aims to estimate the rate parameter k3, which is the binding affinity of the tracer to a biological process of interest and is highly susceptible to noise inherent in PET image acquisition. We have developed linearized kinetic models for kinetic analysis of dynamic contrast enhanced computed tomography (DCE‐CT)/PET imaging, including a 2‐compartment model for DCE‐CT and a 3‐compartment model for PET. Use of kinetic parameters estimated from DCE‐CT can stabilize the kinetic analysis of dynamic PET data, allowing for more robust estimation of k3. Furthermore, these linearized models are solved with a non‐negative least squares algorithm and together they provide other advantages including: 1) only one possible solution and they do not require a choice of starting parameter values, 2) parameter estimates are comparable in accuracy to those from nonlinear models, 3) significantly reduced computational time. Our simulated data show that when blood volume and permeability are estimated with DCE‐CT, the bias of k3 estimation with our linearized model is 1.97 ± 38.5% for 1,000 runs with a signal‐to‐noise ratio of 10. In summary, we have developed a computationally efficient technique for accurate estimation of k3 from noisy dynamic PET data.

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