TY - JOUR
T1 - A novel approach to tracer-kinetic modeling for (macromolecular) dynamic contrast-enhanced MRI
AU - Jacobs, Igor
AU - Strijkers, Gustav J.
AU - Keizer, Henk M.
AU - Janssen, Henk M.
AU - Nicolay, Klaas
AU - Schabel, Matthias C.
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Purpose To develop a novel tracer-kinetic modeling approach for multi-agent dynamic contrast-enhanced MRI (DCE-MRI) that facilitates separate estimation of parameters characterizing blood flow and microvascular permeability within one individual. Methods Monte Carlo simulations were performed to investigate the performance of the constrained multi-agent model. Subsequently, multi-agent DCE-MRI was performed on tumor-bearing mice (n = 5) on a 7T Bruker scanner on three measurement days, in which two dendrimer-based contrast agents having high and intermediate molecular weight, respectively, along with gadoterate meglumine, were sequentially injected within one imaging session. Multi-agent data were simultaneously fit with the gamma capillary transit time model. Blood flow, mean capillary transit time, and bolus arrival time were constrained to be identical between the boluses, while extraction fractions and washout rate constants were separately determined for each agent. Results Simulations showed that constrained multi-agent model regressions led to less uncertainty and bias in estimated tracer-kinetic parameters compared with single-bolus modeling. The approach was successfully applied in vivo, and significant differences in the extraction fraction and washout rate constant between the agents, dependent on their molecular weight, were consistently observed. Conclusion A novel multi-agent tracer-kinetic modeling approach that enforces self-consistency of model parameters and can robustly characterize tumor vascular status was demonstrated.
AB - Purpose To develop a novel tracer-kinetic modeling approach for multi-agent dynamic contrast-enhanced MRI (DCE-MRI) that facilitates separate estimation of parameters characterizing blood flow and microvascular permeability within one individual. Methods Monte Carlo simulations were performed to investigate the performance of the constrained multi-agent model. Subsequently, multi-agent DCE-MRI was performed on tumor-bearing mice (n = 5) on a 7T Bruker scanner on three measurement days, in which two dendrimer-based contrast agents having high and intermediate molecular weight, respectively, along with gadoterate meglumine, were sequentially injected within one imaging session. Multi-agent data were simultaneously fit with the gamma capillary transit time model. Blood flow, mean capillary transit time, and bolus arrival time were constrained to be identical between the boluses, while extraction fractions and washout rate constants were separately determined for each agent. Results Simulations showed that constrained multi-agent model regressions led to less uncertainty and bias in estimated tracer-kinetic parameters compared with single-bolus modeling. The approach was successfully applied in vivo, and significant differences in the extraction fraction and washout rate constant between the agents, dependent on their molecular weight, were consistently observed. Conclusion A novel multi-agent tracer-kinetic modeling approach that enforces self-consistency of model parameters and can robustly characterize tumor vascular status was demonstrated.
KW - cancer imaging
KW - dynamic contrast-enhanced MRI
KW - macromolecular contrast agents
KW - perfusion and permeability
KW - tracer-kinetic modeling
KW - tumor vasculature
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U2 - 10.1002/mrm.25704
DO - 10.1002/mrm.25704
M3 - Article
C2 - 25846802
AN - SCOPUS:84926432004
SN - 0740-3194
VL - 75
SP - 1142
EP - 1153
JO - Magnetic Resonance in Medicine
JF - Magnetic Resonance in Medicine
IS - 3
ER -