Dynamic contrast-enhanced MRI (DCE-MRI) parameters have been shown to be biomarkers for treatment response in glioblastoma (GBM). However, variations in analysis and measurement methodology complicate determination of biological changes measured via DCE. The aim of this study is to quantify DCE-MRI variations attributable to analysis methodology and image quality in GBM patients. The Extended Tofts model (eTM) and Leaky Tracer Kinetic Model (LTKM), with manually and automatically segmented vascular input functions (VIFs), were used to calculate perfusion kinetic parameters from 29 GBM patients with double-baseline DCE-MRI data. DCE-MRI images were acquired 2–5 days apart with no change in treatment. Repeatability of kinetic parameters was quantified with Bland–Altman and percent repeatability coefficient (%RC) analysis. The perfusion parameter with the least RC was the plasma volume fraction (vp), with a %RC of 53%. The extra-cellular extra-vascular volume fraction (ve) %RC was 82% and 81%, for extended Tofts-Kety Model (eTM) and LTKM respectively. The %RC of the volume transfer rate constant (Ktrans) was 72% for the eTM, and 82% for the LTKM, respectively. Using an automatic VIF resulted in smaller %RCs for all model parameters, as compared to manual VIF. As much as 72% change in Ktrans (eTM, autoVIF) can be attributable to non-biological changes in the 2–5 days between double-baseline imaging. Poor Ktrans repeatability may result from inferior temporal resolution and short image acquisition time. This variation suggests DCE-MRI repeatability studies should be performed institutionally, using an automatic VIF method and following quantitative imaging biomarkers alliance guidelines.
Contrast transport models are widely used to quantify blood flow and transport in dynamic contrast-enhanced magnetic resonance imaging. These models analyze the time course of the contrast agent concentration, providing diagnostic and prognostic value for many biological systems. Thus, ensuring accuracy and repeatability of the model parameter estimation is a fundamental concern. In this work, we analyze the structural and practical identifiability of a class of nested compartment models pervasively used in analysis of MRI data. We combine artificial and real data to study the role of noise in model parameter estimation. We observe that although all the models are structurally identifiable, practical identifiability strongly depends on the data characteristics. We analyze the impact of increasing data noise on parameter identifiability and show how the latter can be recovered with increased data quality. To complete the analysis, we show that the results do not depend on specific tissue characteristics or the type of enhancement patterns of contrast agent signal.
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a routine method to noninvasively quantify perfusion dynamics in tissues. The standard practice for analyzing DCE-MRI data is to fit an ordinary differential equation to each voxel. Recent advances in data science provide an opportunity to move beyond existing methods to obtain more accurate measurements of fluid properties. Here, we developed a localized convolutional function regression that enables simultaneous measurement of interstitial fluid velocity, diffusion, and perfusion in 3D. We validated the method computationally and experimentally, demonstrating accurate measurement of fluid dynamics in situ and in vivo. Applying the method to human MRIs, we observed tissue-specific differences in fluid dynamics, with an increased fluid velocity in breast cancer as compared to brain cancer. Overall, our method represents an improved strategy for studying interstitial flows and interstitial transport in tumors and patients. We expect that our method will contribute to the better understanding of cancer progression and therapeutic response.
Enhancing the process of generating entirely automated visualization schemes of complex fluid flow patterns within brain tumors is critical for gaining insights into their movements and behaviors. This study focused on optimizing and automating the processing of 3D volumetric and vector field data sets obtained from DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) scans. It is crucial to maintain performance, preserve data quality and resolution, and provide an accessible platform for biomedical scientists. In this paper, we represent an innovative approach to enhance fluid flow visualization of brain tumors through scalable visualization techniques. New techniques have been designed, benchmarked, and authenticated to produce X3D visualizations in Web3D environments using Python, and ParaView. The proposed approach does not only enhance fluid flow visualization in the context of brain tumor research but also provides a reproducible and transparent framework for future studies with both human and mouse scans.
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a routine method to non-invasively quantify perfusion dynamics in tissues. The standard practice for analyzing DCE-MRI data is to fit an ordinary differential equation to each voxel. Recent advances in data science provide an opportunity to move beyond existing methods to obtain more accurate measurements of fluid properties. Here, we developed a localized convolutional function regression that enables simultaneous measurement of interstitial fluid velocity, diffusion, and perfusion in 3D. We validated the method computationally and experimentally, demonstrating accurate measurement of fluid dynamics in situ and in vivo . Applying the method to human MRIs, we observed tissue-specific differences in fluid dynamics, with an increased fluid velocity in breast cancer as compared to brain cancer. Overall, our method represents an improved strategy for studying interstitial flows and interstitial transport in tumors and patients. We expect that it will contribute to the better understanding of cancer progression and therapeutic response. One-Sentence Summary: A physics-informed computational method enables accurate and efficient measurement of fluid dynamics in individual patient tumors and demonstrates differences between tissues.