A Laplace-Domain Transport Dominance Spectrum for Characterizing Acute Radiation-Induced Vascular Response In DCE-MRI
Abstract
Purpose
Dynamic contrast-enhanced (DCE)-MRI is widely used to assess vascular perfusion and permeability; however, conventional time-domain pharmacokinetic models often conflate flow- and leakage-driven transport. This study introduces a Laplace-domain framework to quantify frequency-resolved transport dominance and characterize acute vascular responses to whole-brain irradiation in a preclinical brain tumor model.
Methods
Twenty rats with intracranial U251N tumors underwent 7T DCE-MRI before radiotherapy (RT) and again within 1-5 hours after a single 20Gy whole-brain RT dose. Longitudinal-relaxation-rate changes (ΔR₁) were transformed into the Laplace-domain to derive a blood-to-tissue transfer function based on the Extended-Tofts model. Three physiologically nested models, Model-1 (no-leakage), Model-2 (vascular-outflow), and Model-3 (bidirectional-exchange), were probabilistically combined on a voxel-wise basis in both time- and frequency-domains. From the real and imaginary components of the probabilistic transfer function, a bounded Transport-Dominance-Spectrum, TDS(ω), was computed to quantify the relative dominance of leakage versus flow across temporal scales and assess RT-induced changes.
Results
Radiotherapy induced distinct, model-specific, frequency-dependent changes in TDS(ω). Model-1 regions (normal brain tissue) showed a monotonic post-RT increase from +3.2% at low-frequencies to +19% at high-frequencies, consistent with emerging fast leakage while remaining flow-dominated at longer time scales. Model-2 regions at the tumor rim showed redistribution, with reduced low-frequency dominance (≈−0.6 to−0.8%) and increased high-frequency dominance (up-to +6.2%), indicating enhanced long-time-scale flow with faster leakage post-RT. In contrast, Model-3 regions in highly permeable tumor tissue showed strong suppression of sustained leakage dominance, with low-to-mid frequency decreases up to −14–16% and partial recovery at higher frequencies.
Conclusion
Laplace-domain analysis using the TDS demonstrates that acute radiation does not uniformly increase or decrease permeability, but instead reweights flow- and leakage-driven transport in a tissue- and time-scale–dependent manner. This framework provides a mechanistically interpretable, quantitatively sensitive tool for early assessment of radiation-induced vascular response and a robust alternative to conventional time-domain DCE-MRI modeling.