Real-Time Magnetic Resonance Guided Focused Ultrasound for Painful Bone Metastases

Summary

Magnetic resonance could offer real-time monitoring of the position and temperature of focused ultrasound in thermal ablation for painful bone metastases, regardless of cancer type or previous local treatments. Our innovative method of quality assurance could facilitate the application of this effective and safe treatment.

Abstract

Bones are one of the most common sites of cancer metastasis, which usually causes pain and impairs quality of life. Radiation therapy combined with opioids is the standard treatment for painful bone metastases. This treatment achieves effective pain control in 60−74% of patients, but limited treatment choices with limited benefits are available for recurrent or residual painful bone metastases after radiotherapy. More than 40% of patients still experience moderate to severe bone pain after reirradiation. Magnetic resonance-guided focused ultrasound (MRgFUS) combines high-intensity focused ultrasound, which achieves thermal ablation of bone metastases and subsequent pain reduction, with real-time magnetic resonance (MR) thermometry to monitor the temperature of anatomic MR images, with an accuracy of 1 °C, spatial resolution of 1 mm, and temporal resolution within 3 s. As well as being increasingly used clinically for controlling metastatic bone pain, the use of MRgFUS for other diseases has also been tested. However, the use of MR software as a thermometer is the only technique available to verify the accuracy of the software and assure energy delivery. Here, we describe an efficient method of quality assurance we developed for thermal detection and energy delivery before each MRgFUS treatment and also propose a modified workflow to expedite the treatment course as well as to reduce patients' pain during the procedure.

Introduction

Bones are one of the most common sites of cancer metastasis, which usually causes pain and impairs quality of life. Radiation therapy (RT) combined with opioids is the standard treatment for painful bone metastases. This treatment achieves effective pain control in 60−74% of patients¹. However, limited treatment choices are available for recurrent or residual metastatic bone pain after RT. Reirradiation, surgical intervention, percutaneous cryoablation, or radiofrequency ablation and increased doses of systemic opioids and analgesics are options with limited indications and usually with side effects. Moreover, these secondary treatments have yielded unsatisfactory results: more than 40% of patients continue to experience moderate to severe bone pain after reirradiation².

High-intensity focused ultrasound systems integrate ultrasounds from multiple angles into one spot, transferring acoustic energy at ablative temperatures of more than 65 °C³. This noninvasive technique has been used for thermal ablation at various sites and for various types of lesions^4,5. Generally, focused ultrasound systems generate acoustic energy at frequencies of 200 kHz-4 MHz^6,7, producing an intensity in the focal point on the order of 100-10,000 W/cm². At these energy levels, the focused ultrasound beams trigger a rise in cell temperature over the treated volume of tissue. The temperature rise varies according to the tissue absorption coefficient, predicted using Arrhenius analysis or the Sapareto-Dewey isoeffect thermal dose relationship. To achieve better control and a more rapid temperature increase, focal volumes of 0.2−5 mm³ are suggested for each sonication. Therefore, the ablation of larger areas requires tiling of multiple sonications to cover a large volume and to create homogeneous thermal damage. In addition to causing damage as a result of thermal effects, focused ultrasound also creates microbubbles because of physical factors such as rectified diffusion in the treated area. When the size of microbubbles reaches a cutoff, they eventually implode, causing microshock waves and affecting surrounding tissues. This parallel nonthermal effect also contributes to tissue injury and tumor necrosis.

Unlike other image guidance techniques, such as ultrasound imaging, magnetic resonance (MR) imaging provides a three-dimensional image of anatomy with clear resolution images of soft tissue and quantitative temperature monitoring. The mapping software of quantitative MR thermometry can calculate the thermal change in degrees Celsius and then superimpose the respective locations onto the anatomic MR images⁸. By detecting the proton resonance frequency shift in water hydrogen, which corresponds to approximately 0.01 ppm per degree Celsius, the temperature-sensitive MR sequence can control energy deposition, with an accuracy of 1 °C for measurement of thermal changes, a spatial resolution of 1 mm, and a temporal resolution within 3 s^9,10. With this extended software, the MR device could provide diagnostic images and also detect thermal changes within seconds, mapping these onto the anatomical images during the whole treatment course. Despite the development of such an innovative technique, few articles describe qualitative security during each treatment course. Here we aim to share our protocol and experiences with MRgFUS.

Protocol

Taipei Medical University Joint Institutional Review Board approval was obtained for this study. NOTE: The same protocol, validated in Kao et al.11, has been used to treat 138 cases between 2015 and 2019. The inclusion criteria for treatment enrollment were 1) the presence of a solitary distinguishable painful bone metastasis; 2) no administration of previous local therapy to the targeted bone lesion; and 3) the ability to access the targeted bone lesion with MRgFUS (<s…

Representative Results

A 68-year-old male patient was diagnosed with hepatocellular carcinoma (HCC) in October 2012. He received a left lobectomy on October 18, 2012, and pathology reported an 8.8 cm HCC. After operation, he experienced lower back pain and soreness, and an MRI on November 2, 2012 revealed a large metastatic mass involving the left sacrum, ilium, and gluteal soft tissue. Because of tumor compression and pain reaching 6 points on the visual analogue scale (VAS), he received RT with 45 Gy in 15 fr…

Discussion

Several studies have demonstrated that MRgFUS is safe and efficient for controlling pain from recurrent or residual bone metastases after RT^12,13. For 64.3-72.0% of patients, metastatic bone pain persists after RT and opioids. Studies have also determined MRgFUS has limited toxicity and a tolerable treatment course.

MRgFUS received approval for use in metastatic bone pain in 2011 by the Conformité Européenne and in 2012 by th…

Materials

1L degasseed water pouch	InSightec	ASM001480	for good ultrasound beam transmission
CT scan	Philips	Brilliance Big Bore 16 Slice CT, 7387	Acquire CT images for positioning
EXABLATE	InSightec	EXABLATE 2000	System for non-invasive tumor ablation through Focal Ultrasound (FUS) treatment under Magnetic Resonance (MR) guidance
Gel Pad ASSY	InSightec	SET999014	Transmission gel pad for single Body treatment.
MR scan	GE	HDxT	Acquire MR images for contouring and planning
MRI contrast	Guerbet	Dotarem	Enhance MR for acquiring images
Patient accessory kit	InSightec	SET000016	clinical applications single use treatment kit
Patient plastic drape	InSightec	DTP000067	Cover the panel of ultrasound transducer. Deposible, hygiene use
Pelvic RF coil	GE	ASM000956	Enhance MR for acquiring images
phantom	ATS Labs ATS Labs Inc	Model TxS-100	for calibration
ultrasound transmission gel	InSightec	SET000885	gel for calibration prior MR-guided FUS treatment