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

Utility of the Polestar N30 low-field MRI system for resecting non-enhancing intra-axial brain lesions

Background. To determine the utility of an intraoperative magnetic resonance imaging (iMRI) system, the Polestar N30, for enhancing the resection control of non-enhancing intra-axial brain lesions. Materials and methods. Seventy-three patients (60 males [83.3%], mean age 37 years) with intra-axial brain lesions underwent resection at Sheba Medical Centre using the Polestar between February 2012 and the end of August 2018. Demographic and imaging data were retrospectively analysed. Thirty-five patients had a non-enhancing lesion (48%). Results. Complete resection was planned for 60/73 cases after preoperative imaging. Complete resection was achieved in 59/60 (98.3%) cases. After iMRI, additional resection was performed in 24/73 (32.8%) cases, and complete resection was performed in 17/60 (28.8%) cases in which a complete resection was intended. In 6/13 (46%) patients for whom incomplete resection was intended, further resection was performed. The extent of resection was extended mainly for non-enhancing lesions: 16/35 (46%) as opposed to only 8/38 (21%) for enhancing lesions. Further resection was not significantly associated with sex, age, intended resection, recurrence, or affected side. Univariate analysis revealed non-eloquent area, intended complete resection, and enhancing lesions to be predictive factors for complete resection, and non-enhancing lesions and scan time to be predictive factors for an extended resection. Non-enhancement was the only independent factor for extended resection. Conclusions. The Polestar N30 is useful for evaluating residual non-enhancing intra-axial brain lesions and achieving maximal resection

Localized RNAi Therapeutics of Chemoresistant Grade IV Glioma Using Hyaluronan-Grafted Lipid-Based Nanoparticles

Glioblastoma multiforme (GBM) is one of the most infiltrating, aggressive, and poorly treated brain tumors. Progress in genomics and proteomics has paved the way for identifying potential therapeutic targets for treating GBM, yet the vast majority of these leading drug candidates for the treatment of GBM are ineffective, mainly due to restricted passages across the blood–brain barrier. Nanoparticles have been emerged as a promising platform to treat different types of tumors due to their ability to transport drugs to target sites while minimizing adverse effects. Herein, we devised a localized strategy to deliver RNA interference (RNAi) directly to the GBM site using hyaluronan (HA)-grafted lipid-based nanoparticles (LNPs). These LNPs having an ionized lipid were previously shown to be highly effective in delivering small interfering RNAs (siRNAs) into various cell types. LNP’s surface was functionalized with hyaluronan (HA), a naturally occurring glycosaminoglycan that specifically binds the CD44 receptor expressed on GBM cells. We found that HA-LNPs can successfully bind to GBM cell lines and primary neurosphers of GBM patients. HA-LNPs loaded with Polo-Like Kinase 1 (PLK1) siRNAs (siPLK1) dramatically reduced the expression of PLK1 mRNA and cumulated in cell death even under shear flow that simulate the flow of the cerebrospinal fluid compared with control groups. Next, a human GBM U87MG orthotopic xenograft model was established by intracranial injection of U87MG cells into nude mice. Convection of Cy3-siRNA entrapped in HA-LNPs was performed, and specific Cy3 uptake was observed in U87MG cells. Moreover, convection of siPLK1 entrapped in HA-LNPs reduced mRNA levels by more than 80% and significantly prolonged survival of treated mice in the orthotopic model. Taken together, our results suggest that RNAi therapeutics could effectively be delivered in a localized manner with HA-coated LNPs and ultimately may become a therapeutic modality for GBM