Local hyperthermia with MR‐guided focused ultrasound: Spiral trajectory of the focal point optimized for temperature uniformity in the target region

Purpose: To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions.Materials and Methods: Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping.Results: Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage $3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days. Conclusion:This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.

Section: Discussionmentioning

confidence: 99%

In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low‐frequency‐ultrasound‐induced blood–brain barrier opening in swine

Liu

Chen

Yang

et al. 2011

“…This can be achieved by measuring the thermal changes in the tissue during the treatment with magnetic resonance (MR) temperaturesensitive imaging (MRTI). MRTI can be used to estimate the thermal dose delivered to the tissue in real time, but the measurement has typically been limited to one imaging plane (1)(2)(3)(4)(5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

MRI‐guided thermal therapy of transplanted tumors in the canine prostate using a directional transurethral ultrasound applicator

Hazle

Diederich

Kangasniemi

et al. 2002

110

Purpose: To evaluate MRI-based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model. Materials and Methods:Transmissible venereal tumors (TVT) were grown in the right lobe of the prostate in four dogs. High-temperature thermal therapy was selectively applied to the tumor-bearing lobe using a transurethral ultrasound applicator with a 180°directional heating pattern. Temperature-sensitive MRI (MRTI) using a fast interleaved gradient-echo echo-planar (iGE-EPI) imaging sequence was used for cumulative thermal dose calculations in multiple image planes during the treatment. The results from MRTI-based dose maps and post-treatment MRI were compared to those from histologic analysis.Results: MRTI monitoring in multiple planes across the prostate guided the use and control of a directive ultrasound applicator for the selective ablation of the sections of the prostate that contained implanted tumors. Findings in gadolinium enhanced MRI obtained immediately after thermal therapy slightly underestimated the size of tissue necrosis after treatment, as verified by histopathologic analysis. Conclusion:The use of multiplanar MRTI with a transurethral ultrasound applicator shows significant potential for selective thermal ablation of prostate tumor and tissue.

“…To avoid this unwanted damage, it is necessary to wait between each sonication to allow the tissue to cool. While strategies have been developed to avoid this thermal build-up (56) or use it to one's advantage (57,58), they are only feasible for certain tumor sizes and geometries.…”

Section: Cavitation-enhanced Sonicationmentioning

confidence: 99%

“…Such phased array devices will develop further to their full potential through the implementation of treatment plans that include beam aberration correction (80) and the optimization of thermal dose delivery (81). Fully automatic closed-loop feedback to control heating (40,57,81,82) combined with robust motion detection and correction schemes for the MR thermometry (31)(32)(33)83) will also likely reach the clinic for MRgFUS.…”

Section: Future Development Of Technologymentioning

confidence: 99%

Current status and future potential of MRI‐guided focused ultrasound surgery

Jólesz

McDannold

2008

112

The combination of the imaging abilities of magnetic resonance imaging (MRI) with the ability to delivery energy to targets deep in the body noninvasively with focused ultrasound presents a disruptive technology with the potential to significantly affect healthcare. MRI offers precise targeting, visualization, and quantification of temperature changes and the ability to immediately evaluate the treatment. By exploiting different mechanisms, focused ultrasound offers a range of therapies, ranging from thermal ablation to targeted drug delivery. This article reviews recent preclinical and tests clinical of this technology. WHILE ITS POTENTIAL has been recognized for decades (1-4), focused ultrasound (FUS) therapy has been in the incubation phase for a long time. Although it has been tested in numerous animal experiments, its widespread clinical realization has lagged, primarily due to the lack of intraprocedural accurate temperature monitoring. When the idea of MRI-guidance was introduced in connection with FUS and MRI thermometry during sonication was demonstrated (5,6), it was anticipated that MR-guided FUS surgery (MRgFUS) would be widely accepted clinically within a few years. Despite these early expectations, there has been relatively slow progress in the clinical implementation of MRgFUS.Early development concentrated primarily on breast tumors (benign fibroadenoma (7,8) and malignant breast cancer (9,10)). These early implementations of the MRgFUS technology motivated the improvement of transducer technology from single-element transducers to MRI-compatible multielement phase arrays (11). There was also significant progress in MRI thermometry and its use to monitor and control sonications. Importantly, too, methods were developed to robustly quantify temperature changes (12). At first, only 2D temperature maps were obtained by MRI to allow for accurate targeting of the beam (13). Later these thermal images were used to generate maps of the thermal dose (14) that could then be used to tailor the energy deposition using closed-loop feedback control (15). This preclinical work led to the development of the first commercial system by InSightec (Haifa, Israel), the Exablate 2000, the first implementation of a fully integrated MRgFUS system that combined a phased array transducer, a computer-controlled robotic positioner, and a workstation that integrated control based on MR thermometry.The early limited clinical trials of breast tumor treatment (8 -10,16,17) were followed by the first major clinical application: the noninvasive therapy of benign uterine fibroids (18,19). The successful Phase I trial was followed by a multicenter . These clinical trials led to the approval of this technology for the treatment of uterine fibroids in several countries, including the United States. Examples of MR thermometry and postablation imaging of a uterine fibroid ablation are shown in Figure 1.The success of uterine fibroid ablation has invigorated the entire field. Technology has rapidly improved and clinical applications ke...