Improving Thermal Dose Accuracy in Magnetic Resonance-Guided Focused Ultrasound Surgery: Long-Term Thermometry Using a Prior Baseline as a Reference

Magnetic resonance-guided focused ultrasound (MRgFUS) has been used in clinical trials to ablate soft tissue tumors such as breast tumors, uterine fibroids, and prostate tumors. Some of these trials aimed to show safety and feasibility through partial tumor ablation.1–5 More recently, patient studies have targeted total tumor volume ablation, including large uterine fibroid volumes (>~75 cc).6,7 For malignant tumors, ablation of the entire tumor is a necessity if MRgFUS is to be considered as an alternative to surgery; while even for benign tumors, such as uterine fibroids, achieving total ablation results in more durable symptomatic relief.8 Total tumor ablation demands a highly accurate method to assess treatment efficacy. MR thermometry-derived thermal dose mapping is the primary method used to assess tumor ablation during an MRgFUS procedure.9 MR-derived proton resonance frequency shift (PRF) thermometry provides a change in temperature, which is then used to calculate thermal dose; neither absolute temperature nor absolute dose are calculated using these methods.10 Because these are not absolute measurements, the standard method does not account for local accumulation of heat over the course of a treatment, which can cause errors in thermometry, and thus, errors in the estimated thermal dose delivered to tissue (Fig. 1).11,12 Underestimation of thermometry and thermal dose may result in unnecessary additional sonications of tissue that has already been ablated through sonication of adjacent areas; these extra sonications provide no benefit, while increasing risks to the patient, such as skin burns. Targeting already treated tissue also prolongs the procedure time, which is a major criticism of volumetric MRgFUS compared to alternative therapies.13–15 FIGURE 1 Sonication thermometry protocol. a: At timepoint ta0 a baseline reference image prior to turning on ultrasound is acquired. Images are acquired every 3.2 seconds throughout the sonication period. The final image tafinal is acquired after the ultrasound ... Another consequence of inaccurate thermometry is the commonly reported mismatch between thermal dose treatment volume (TDV) and nonperfused volume (NPV), which is the clinically accepted standard of in vivo ablation efficacy.7,16–19 There is potential for disagreement between the two in vivo measures (TDV, NPV) of treatment volume, as they are derived from different physical phenomena; TDV is based on temperature-dependent image-based phase accrual during treatment surpassing the threshold of 240 equivalent minutes, while NPV is based on the ability of contrast agent to reach the tissue after treatment. Because the interactions of MRI contrast and focused ultrasound ablation are not well established, contrast injections are administered only after the MRgFUS treatment is completed.20,21 In the majority of the cases reporting mismatch, immediate posttreatment NPV exceeded thermal dose. This mismatch becomes more profound with increasing target volumes, with the error between TDV and NPV reported to be between 38%–53% for volumes >125 cc.7 A recent preclinical treat and resect study found that the thermal dose volume underestimated ablated areas compared with both NPV and histology immediately post treatment.22 While thermal ablation of tumor vessels, which could result in disproportionately larger NPVs, has been posited as one explanation for this discrepancy17,23,24; clearly, the clinical success of MRgFUS in volumetric tumor ablation depends on improving the reliability and accuracy of intraoperative treatment monitoring and assessment. The purpose of this study was three-fold: 1) to investigate if MRgFUS desmoid treatments suffered from a mismatch between thermal dose volume and NPV; 2) to improve thermal dose mapping by accounting for accumulated heat using a prior baseline thermometry method; and 3) to assess how much of the discrepancy between TDV and NPV remained after this improvement.