Translating MR Interventions into Clinical Workflow: MR-Guided HIFU
Holger Grull1
1University of Cologne, Germany

Synopsis

MR-HIFU is a non-invasive method to heat tissue to ablative or hyperthermic temperatures. For therapy planning and temperature monitoring, this treatment is performed under MR guidance offering high resolution anatomical images as well as near-real time temperature mapping. Currently clinical use is restricted to CE-applications such as ablation of uterine fibroids, osteoid osteomas or desmoid tumors. In this presentation, we showcase the research and clinical translation of treatment of facet joint arthritis and pancreatic cancer from small to large animal models to clinical trials. Regulatory hurdles that need to be addressed will be discussed including the clinical trials.

Introduction

High Intensity Focused Ultrasound (HIFU) allows non-invasive heating of tissue inside the body. In principle, any temperature increase can be achieved modulating acoustic power and sonication duration to achieve hyperthermic (41<T/ºC< 43 ) or ablative temperatures (T/ºC>55). For spatial targeting and therapy planning as well as temperature control during sonication, the HIFU intervention is performed under MR guidance using a system where the HIFU transducer is integrated in the MR patient table (MR-HIFU) [1]. Currently, several MR-HIFU applications are CE-labeled for clinical use such as treatment of uterine fibroids, adenomyosis, osteoid osteomas, bone metastasis or desmoid tumors [1,2]. Above applications comprise the main use of MR-HIFU at the department of radiology at University Hospital of Cologne.

New Application and Clinical Translation

In our department, we perform research to broaden the application space beyond the current CE label. Two new possible applications are currently addressed which is pain reduction induced by facet joint arthritis and treatment of pancreatic cancer. The latter comprise ablation of the primary tumor [3] and a hyperthermia-induced drug delivery step using a drug encapsulated in temperature sensitive liposomes [4]. In this talk, we will showcase the development steps over the past years moving from small animals [5-7] into large animals [3,4,8] models into clinical trials that will start in due time this year. The talk will also highlight regulatory hurdles important to consider for clinical translation of new medical devices.

Acknowledgements

We would like thank the BMBF, Germany, for financial support of these projects (Förderkennzeichen 13GW0337D and 13GW0364D).

References

1.Siedek, F. et al. Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU): Overview of Emerging Applications (Part 2). Röfo - Fortschritte Auf Dem Gebiet Der Röntgenstrahlen Und Der Bildgebenden Verfahren 191, 531–539 (2019).

2.Siedek, F. et al. Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU): Technical Background and Overview of Current Clinical Applications (Part 1). Röfo - Fortschritte Auf Dem Gebiet Der Röntgenstrahlen Und Der Bildgebenden Verfahren 191, 522–530 (2019).

3.Sebeke, L. C. et al. Feasibility study of MR-guided pancreas ablation using high-intensity focused ultrasound in a healthy swine model. Int J Hyperther 37, 786–798 (2020).

4.Sebeke, L. C. et al. Hyperthermia-induced doxorubicin delivery from thermosensitive liposomes via MR-HIFU in a pig model. J Control Release 343, 798–812 (2022).

5.Hijnen, N. et al. Thermal combination therapies for local drug delivery by magnetic resonance-guided high-intensity focused ultrasound. Proc National Acad Sci 114, E4802–E4811 (2017).

6.Smet, M. de, Heijman, E., Langereis, S., Hijnen, N. M. & Grüll, H. Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: An in vivo proof-of-concept study. J Control Release 150, 102–110 (2011).

7.Smet, M. de et al. Magnetic Resonance Guided High-Intensity Focused Ultrasound Mediated Hyperthermia Improves the Intratumoral Distribution of Temperature-Sensitive Liposomal Doxorubicin. Invest Radiol 48, 395–405 (2013).

8.Sebeke, L. C. et al. Visualization of thermal washout due to spatiotemporally heterogenous perfusion in the application of a model-based control algorithm for MR-HIFU mediated hyperthermia. Int J Hyperther 38, 1174–1187 (2021).9.Sebeke, L. et al. Model predictive control for MR-HIFU-mediated, uniform hyperthermia. Int J Hyperther 36, 1040–1050 (2019).

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)