Prediction of Subtle Thermal Histopathological Change Using a Novel Analysis of Gd-DTPA Kinetics

Abstract

Purpose: To investigate Gd-DTPA kinetics as predictors of histopathological changes following focused ultrasound (FUS) thermal ablation for improved planning and assessment. Materials and Methods: Twenty-nine FUS lesions were created in the thigh muscle of eight rabbits under MR-guidance at 1.5 Tesla. Three rabbits were killed at four hours; and 11 lesions were analyzed with histopathology. Temperature-sensitive MRI using proton-resonant frequency-shift was used for time-dependent temperature measurements. Analysis of the uptake kinetics of Gd-DTPA was performed after Gd-DTPA injection, within 20 minutes after heating and again at two hours after heating. The resulting kinetic maps, permeability (Ktrans) and leakage space (υ e), were correlated to peak temperatures, T2-weighted MR, and histopathology. Results: Images of Ktrans and υe reveal regions of histopathological change not visible on conventional post-therapy MR. At early times after heating, υe predicts the area of injury more accurately than T2 (7 ± 2% vs. 25 ± 6% underestimation). A circular region of extensive structural/ vascular disruption is indicated only on Ktras maps. The sharp decrease in Ktrans at the boundary of this region occurs at 47.5 ± 0.5°C, and may be a better estimate of cell death than the conventional method of temperature threshold (55°C for coagulation) used in therapy planning. Conclusion: Our results suggest Gd-DTPA kinetics can predict different histopathological changes following FUS ablation and may be valuable for early prediction. © 2003 Wiley-Liss, Inc.