Simultaneous Measurement of Quantitative Pharmacokinetic Parameters In Brain Tumors Pre- and Post-Laser Ablation
Abstract
Purpose
To evaluate the effects of Laser Interstitial Thermal Therapy (LITT) on drug delivery to malignant brain tumors (MB) by quantitatively measuring perfusion (blood flow and blood volume) and permeability using low-dose contrast-enhanced MRI.
Methods
Twelve MB patients treated with LITT underwent pre- and post-operative MRI scans, including axial 3D MPRAGE, T1 mapping, DSC, DCE, and contrast-enhanced T1 weighted imaging. DSC and DCE were performed using a body weight adjusted half dose of gadolinium, resulting in a single total dose (0.1mmol/kg). Permeability (min-1) and capillary-level blood flow ml/100g/min) were derived from DCE and DSC scans, respectively. T1-REQUIRE was used to generate T1 maps for signal-to-concentration conversion, and Patlak modeling was applied to determine permeability (K1). Quantitative cerebral blood flow (qCBF) and volume (qCBV) were obtained by applying leakage correction and the Bookend technique. Pre- and post-LITT tumor values were compared using a Wilcoxon signed-rank test.
Results
qCBF values in healthy white and gray matter were consistent with literature values, and pre-LITT K1 values were within expected ranges. Tumor permeability significantly decreased following LITT (p<0.05), with an average reduction of -45%±38% the original K1. qCBF showed no significant change, however, qCBV decreased by -70%±17%. No significant perfusion changes were detected in healthy brain tissue. Increased permeability was observed in regions surrounding the tumor.
Conclusion
We have developed a protocol that quantitatively measures both permeability and perfusion with a single gadolinium dose. Simultaneous measurement of blood flow and permeability will be instrumental in quantifying drug flow into tumors. Decreases in K1 and qCBV following LITT are consistent with biological expectations, while stability of healthy tissue parameters supports robustness across scans. Increased permeability in tumor peripheries post-LITT may enhance drug delivery across the blood–brain barrier.