1438 affected area was treated again with FUS ablation. Gianfelice et al. used MRI follow-up at 10 days, 1, 3 and 6 months post-treatment to detect residual disease after FUS ablation in high-risk surgical patients [46]. Additional to imaging, after 6 months, multiple LCNBs were performed through different areas of the ablation zone. In case of residual tumour, a second FUS procedure was performed and followed by another targeted LCNB 1 month later. The technique of LCNB for residual tumour detection along the ablation zone margins was also used by Wu et al. They performed LCNB at 2 weeks, 3 months, 6 months and 12 months post-treatment [33]. In case of residual tumour patients were subsequently treated with modified radical mastectomy. Although no definitive guidelines are available today, the combination of con- trast-enhanced breast MRI and multiple LCNBs for residual tumour detection appears to be the most promising strategy for candidates after FUS treatment where the treated tumour is left in situ. Selection of appropriate patients for FUS ablation Another important issue for successful FUS ablation is appropriate patient selection. Some breast cancer patients cannot be scheduled for FUS ablation for technical reasons. For FUS treatment a distance of at least 1 cm between the tumour and the skin (to avoid skin burn) and tumour and chest wall (to prevent heat accumulation in the underlying ribs and lung) is required [35]. For MRI-guided FUS ablation, it is also required that, apart from the standard MRI contra-indication, patients must lie still in the closed bore MRI magnet for a long period of time, which can be physically and psychologically difficult, especially in anxious or claustrophobic patients [27]. When FUS ablation is performed for curative treatment of breast cancer, preferentially, patients with large tumours (>5 cm) should not be selected for FUS ablation as increased tumour size significantly increases the treatment time and the probability of complete tumour necrosis decreases substantially [42]. Although there are no guidelines concerning the inclusion of patients based on the tumour size, results from the breast cancer radiofrequency ablation studies showed consistent 100% ablation in patients treated with breast cancers ≤2 cm in size [29, 53]. Another issue that needs to be investigated is the effect of different biological tumour characteristics, i.e., ER/PR and her2neu status of the breast cancer cells, on the outcome of the FUS ablation. So far, no data are available addressing this issue. Additionally, patients diagnosed with extensive DCIS should be excluded from FUS ablation. The diagnostic value of MRI for detecting and predicting tumour size of DCIS is still controversial. Although a recent study showed a high sensitivity of MRI (up to 98%) for the detection of DCIS [54], other study results revealed that MRI tends to under- or overestimate the extent of DCIS tumours in 17– 77% and 11–19% of the patients [55–57], hence the use of image-guided FUS ablation may result in overtreatment or more importantly undertreatment of the DCIS component. When FUS ablation is applied for local tumour control in non-surgical candidates with locally advanced breast cancer or metastatic breast disease, the two issues of tumour size and extensive intradutcal tumour component are less important [46]. In these patients it is important that FUS ablation is a well-tolerated, low-morbidity, and repeatable method for tumour ablation that allows local disease control. Impact of FUS ablation on sentinel node procedure For breast cancer patients, information about the presence of metastases in regional axillary lymph nodes is an important prognostic factor. Sentinel lymph node biopsy (SLNB) is a validated minimally invasive diagnostic procedure used to determine the status of regional lymph nodes for staging purposes [58–61]. Theoretically, FUS might affect the accuracy of the sentinel lymph node procedure by obstructing or alternating the anatomy of breast lymphatics or lymph drainage. Zippel et al. performed sentinel node biopsy in two of their patients treated with FUS [43]. Although a small group, there were no technical problems in finding the sentinel node by the use of contrast agent and radio-isotope-guided surgery. Vargas, et al. conducted a study to determine the success rate of SLNB in patients enrolled in a clinical trial of pre- operative focussed microwave phased-array tumour abla- tion [60]. Sentinel nodes were found with an overall success rate of 91%, which is comparable with other reports on success rate of SLNB in the literature [58, 59, 61]. Although these results imply that there might be no impairment in the ability to perform sentinel node biopsy after ablation with focussed ultrasound, further investiga- tion is necessary. Potential future applications of FUS ablation Although most of the FUS research focusses on thermal ablation for localized thermal treatment of breast cancer, it has been reported that thermal and mechanical damage of a primary tumour by FUS may trigger systemic biological responses in vivo as well. FUS tumour ablation creates a large amount of tumour antigens in the form of necrotic cells and damaged tumour cells, which may trigger dendritic cell activation. This mechanism may play a critical role in FUS-induced anti-tumour immune response. This hypothesis was recently tested in mice implanted with adenocarcinomas and treated with thermal and mechanical FUS ablation in order to assess FUS-induced effects on the mice’s immunological response, as expressed by in vivo dendritic cell activity [62]. The results confirmed that