MRI-guided High-Intensity Focused Ultrasound of Breast Cancer

Abstract

Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) is a promising technique for completely noninvasive tumor ablation. This thesis focuses on its application for the treatment of patients with breast cancer. The first part of the thesis describes the role of breast MRI for the diagnosis and selection of patients with early-stage breast cancer. The added diagnostic value of dynamic contrast-enhanced 3T breast MRI was investigated in patients with nonpalpable, suspicious breast lesions at conventional imaging. Breast MRI showed to provide additional diagnostic information over clinical information and conventional imaging. Furthermore, breast MRI was used to assess the eligibility of patients for minimally invasive breast cancer therapy based on tumor proximity to critical organs. Results showed that, if a safety margin of 10 mm to skin and pectoral muscle is required without treatment margin, 72.3% of patients would be eligible for minimally invasive treatment. Older patients with prognostically favorable tumors were more likely to be eligible for minimally invasive therapy than other patients if tumor location was considered. The second part of the thesis focuses on the technical aspects of MR-HIFU for breast tumor ablation. First, a dedicated MR-HIFU breast platform was presented, which was specifically developed for the treatment of tumors in the breast. The system is equipped with a wide aperture transducer that targets the breast laterally. The lateral sonication approach reduces the risk of heating critical organs in the thoracic cage. In addition, the wide aperture of the transducer decreases the risk of skin burns by lowering the energy density on the skin. Second, the effects of HIFU ablation and thermal exposure on ex vivo human breast tissue were reported. During these experiments, irreversible tissue deformations were observed upon HIFU ablation, which indicate that it may be necessary to monitor tissue deformations during MR-HIFU treatment in patients. In addition, a slow decline in breast tissue temperature was observed after HIFU ablation, which may result in an increased risk of heat accumulation during successive sonications. Third, the precision of rapid, multi-slice proton resonance frequency shift (PRFS)-based MR thermometry was evaluated. Two correction methods for respiration-induced artifacts were tested. In volunteers and patients, both correction methods improved the precision of the temperature measurements to below 3 ̊C. Moreover, the spatial targeting accuracy and precision of sonications with the dedicated MR-HIFU breast platform were investigated and proved to be 2.5 and 1.7 mm, respectively. The third and final part of the thesis reports the results of a phase I study assessing the safety and feasibility of tumor ablation in breast cancer patients with the dedicated MR-HIFU breast platform. Ten patients with breast cancer underwent partial tumor ablation before they underwent surgical resection. No major adverse events were observed. In all patients with adequate heating (> 55 ̊C) in the tumor, one or more areas with tumor necrosis were observed during histopathological analysis. In conclusion, MR-HIFU ablation in breast cancer patients with the dedicated MR-HIFU breast platform was proven to be safe and feasible.