Technical and clinical developments in the MR-HIFU treatment of uterine fibroids and bone metastases

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) offers an incision-free treatment with a low risk of side effects for several conditions including uterine fibroids and painful bone metastases. These two conditions are indications where MR-HIFU provides several advantages over standard treatment and has the potential to improve the clinical management of these conditions. Currently, MR-HIFU is not widely available to patients in the Netherlands due to the lack of reimbursement by health insurers.

This thesis covers several clinical and technical developments in the MR-HIFU treatment of uterine fibroids and painful bone metastases, and contributes to beter utilization of the potential of MR-HIFU and clarification of its role in the care pathway.

The first part of this thesis describes the possibilities of medical imaging to visualize the blood supply of uterine fibroids.

The second part of the thesis focuses on a limitation in the MR-HIFU treatment of uterine fibroids: the inability to adequately monitor treatment progression during the procedure. Between MR-HIFU heatings (sonications) at different locations in a fibroid, it is not possible to determine whether the fibroid has already been sufficiently treated. In this part of the thesis, methods were investigated to monitor the MR-HIFU treatment progression of uterine fibroids without using a contrast agent. These methods are based on processing of diffusion-weighted MRI images (DWI).

The third part of this thesis focuses on the outcomes of the MR-HIFU treatment of uterine fibroids. It contains a commentary on a multi-center prospective cohort study on the MR-HIFU treatment of uterine fibroids. Furthermore, a deep learning-based method was designed and validated to automatically quantify treatment outcomes of the MR-HIFU treatment of uterine fibroids using MRI scans.

In addition to the benefits regarding the non-invasive treatment of uterine fibroids, MR-HIFU offers (potential) advantages for a range of other indications at various stages of clinical adoption. Local palliation for pain caused by bone metastases is an indication where MR-HIFU potentially offers substantial advantages over standard treatment. The standard treatment for local palliation in painful bone metastases is external beam radiotherapy (EBRT). A major advantage of MR-HIFU is the considerably shorter time to pain reduction.

Because the role of MR-HIFU in the management of painful bone metastases was not exactly clear and data regarding cost-effectiveness was lacking, a study protocol was written in part four of this thesis for a randomized controlled trial (RCT) on the cost-effectiveness of MR-HIFU versus EBRT versus MR-HIFU + EBRT (1:1:1 ratio) in painful bone metastases: the FURTHER-study. The primary outcome of the study is pain response fourteen days after inclusion in the study. Pain response will be measured with a pain diary, questionnaires, and phone calls. Patients will be followed for six months.

The results of the FURTHER-study will provide more clarity on the role of MR-HIFU in the management of painful bone metastases and may contribute to the clinical adoption of MR-HIFU for this indication.