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 MRguidance 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 (K trans ) and leakage space (v e ), were correlated to peak temperatures, T 2 -weighted MR, and histopathology.Results: Images of K trans and v e reveal regions of histopathological change not visible on conventional posttherapy MR. At early times after heating, v e predicts the area of injury more accurately than T 2 (7 Ϯ 2% vs. 25 Ϯ 6% underestimation). A circular region of extensive structural/ vascular disruption is indicated only on K trans maps. The sharp decrease in K trans at the boundary of this region occurs at 47.5 Ϯ 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.

Quantitative MRI-based temperature mapping based on the proton resonant frequency shift: Review of validation studies

“…To find the threshold, these studies either evaluated the temperature information just inside and outside the edges of the thermal lesions [36][37][38][39] or they compared this information in the centre of the heated zones for cases that did or did not produce thermal damage [40][41][42]. Typically, they evaluated the peak temperature rise achieved for a given heating time and sometimes the accumulated thermal dose and compared these values to MRI-detected tissue damage and histology.…”

Real-Time Iterative Monitoring of Radiofrequency Ablation Tumor Therapy with 15O-Water PET Imaging

“…An advantage of the 15 O-water imaging technique is that it directly monitors the tumor physiologic change in relationship to the coagulation of the tumor caused by the thermal ablation. Contrast-enhanced MRI has also been investigated for the real-time monitoring of thermal ablation (10,11,13). Although MRI contrast agents, such as Gd-diethylenetriaminepentaacetic acid, may be useful for monitoring thermal ablation, their kinetics of tumor accumulation after RF ablation could be different from 15 O-water because of their decreased ability to penetrate through blood vessels into the tumor interstitial space.…”

“…An immediate effect of thermal ablation is the coagulation of tumor vasculature and the formation of a coagulation zone that covers either the whole tumor or a portion of the tumor (4). Because of the coagulation zone formation, blood-perfusion contrast agents may prove to be useful tools for the real-time monitoring of the coverage by thermal ablation (10).…”

“…To assess the therapy coverage by thermal ablation, the use of contrast-enhanced CT, MRI, and ultrasound imaging has been investigated (9)(10)(11)(12)(13)(14)(15). In addition, MRI thermometry has been used in the real-time monitoring of the temperature distribution in the ablation site (16).…”

Treatment monitoring and thermometry for therapeutic focused ultrasound

“…Functional or dynamic contrast enhanced (DCE) MR imaging involves the intravenous injection of contrast agent and the acquisition of MR images as a function of time in order to look at the relative uptake and natural washout of contrast agent. One group has performed dynamic studies 20 min and 2 h after FUS exposure using T 1 -w (FSPGR) and T 2 -w (FSE) sequences [81]. They calculated vessel permeability, K trans , and the extravascular, extracellular volume fraction (or leakage space) v e .…”