Prediction of subtle thermal histopathological change using a novel analysis of Gd-DTPA kinetics

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 (ve), were correlated to peak temperatures, T2-weighted MR, and histopathology. Results Images of Ktrans and ve reveal regions of histopathological change not visible on conventional post-therapy MR. At early times after heating, ve 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 Ktrans 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. J. Magn. Reson. Imaging 2003;18:585–598. © 2003 Wiley-Liss, Inc.