Magnetic resonance-guided focused ultrasound treatment of facet joint pain: summary of preclinical phase

STUDY DESIGN: A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted to test the feasibility, safety, and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for treating facet joint pain. OBJECTIVE: The goal of the current study was to develop a novel method for accurate and safe noninvasive facet joint ablation using MRgFUS. SUMMARY OF BACKGROUND DATA: Facet joints are a common source of chronic back pain. Direct facet joint interventions include medial branch nerve ablation and intra-articular injections, which are widely used, but limited in the short and long term. MRgFUS is a breakthrough technology that enables accurate delivery of high-intensity focused ultrasound energy to create a localized temperature rise for tissue ablation, using MR guidance for treatment planning and real-time feedback. METHODS: We validated the feasibility, safety, and efficacy of MRgFUS for facet joint ablation using the ExAblate 2000® System (InSightec Ltd., Tirat Carmel, Israel) and confirmed the system's ability to ablate the edge of the facet joint and all terminal nerves innervating the joint. A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted. RESULTS: The experiments showed that targeting the facet joint with energies of 150–450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Treating with reduced diameter of the acoustic beam is recommended since a narrower beam improves access to the targeted areas. CONCLUSIONS: MRgFUS can safely and effectively target and ablate the facet joint. These results are highly significant, given that this is the first study to demonstrate the potential of MRgFUS to treat facet joint pain

Ultrasound-mediated targeted drug delivery with a novel cyclodextrin-based drug carrier by mechanical and thermal mechanisms

Various mechanisms for ultrasound-mediated targeted drug delivery have been investigated in the past several decades. Cyclodextrins are already known for their ability to encapsulate various drugs in their lipophilic cavity; this paper reports evaluation of the potential of a cyclodextrin-based nanocarrier as a drug delivery vehicle, using cell monolayers in vitro in conjunction with ultrasound as the release mechanism. The application of ultrasound to the cell monolayers results in both thermal and mechanical effects; a current challenge is to differentiate between these effects. In this study, the cell uptake routes of doxorubicin encapsulated in the cyclodextrin-based carrier were investigated, examining individually the thermal and the mechanical effects of focused ultrasound for drug release. Exploiting mechanical effects, the uptake of encapsulated doxorubicin into cancer cells was increased by a factor of up to 5.5 when ultrasound was applied. Thermal application of FUS increased the cellular uptake of encapsulated doxorubicin by a factor of up to 9.6. Hyperthermia without focused ultrasound resulted in an increase by a factor of up to 5.7

Invitro investigation of the individual contributions of ultrasound-induced stable and inertial cavitation in targeted drug delivery

Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization