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Jacquelyn MacDonell, Niravkumar Patel, Sebastian Rubino, Goutam Ghoshal, Gregory Fischer, E. Clif Burdette, Roy Hwang, and Julie G. Pilitsis

Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors’ interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery.

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Goutam Ghoshal, Lucy Gee, Tamas Heffter, Emery Williams, Corinne Bromfield, Laurie Rund, John M. Ehrhardt, Chris J. Diederich, Gregory S. Fischer, Julie G. Pilitsis, and E. Clif Burdette

OBJECTIVE

Minimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator.

METHODS

Using an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson’s disease to investigate the feasibility of its application in brain.

RESULTS

Thermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson’s disease.

CONCLUSIONS

The authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

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Daniel M. Sciubba, E. Clif Burdette, Jennifer J. Cheng, William A. Pennant, Joseph C. Noggle, Rory J. Petteys, Christopher Alix, Chris J. Diederich, Gabor Fichtinger, Ziya L. Gokaslan, and Kieran P. Murphy

Object

Radiofrequency ablation (RFA) has proven to be effective for treatment of malignant and benign tumors in numerous anatomical sites outside the spine. The major challenge of using RFA for spinal tumors is difficulty protecting the spinal cord and nerves from damage. However, conforming ultrasound energy to match the exact anatomy of the tumor may provide successful ablation in such sensitive locations. In a rabbit model of vertebral body tumor, the authors have successfully ablated tumors using an acoustic ablator placed percutaneously via computed tomography fluoroscopic (CTF) guidance.

Methods

Using CTF guidance, 12 adult male New Zealand White rabbits were injected with VX2 carcinoma cells in the lowest lumbar vertebral body. At 21 days, a bone biopsy needle was placed into the geographical center of the lesion, down which an acoustic ablator was inserted. Three multisensor thermocouple arrays were placed around the lesion to provide measurement of tissue temperature during ablation, at thermal doses ranging from 100 to 1,000,000 TEM (thermal equivalent minutes at 43°C), and tumor volumes were given a tumoricidal dose of acoustic energy. Animals were monitored for 24 hours and then sacrificed. Pathological specimens were obtained to determine the extent of tumor death and surrounding tissue damage. Measured temperature distributions were used to reconstruct volumetric doses of energy delivered to tumor tissue, and such data were correlated with pathological findings.

Results

All rabbits were successfully implanted with VX2 cells, leading to a grossly apparent spinal and paraspinal tissue mass. The CTF guidance provided accurate placement of the acoustic ablator in all tumors, as corroborated through gross and microscopic histology. Significant tumor death was noted in all specimens without collateral damage to nearby nerve tissue. Tissue destruction just beyond the margin of the tumor was noted in some but not all specimens. No neurological deficits occurred in response to ablation. Reconstruction of measured temperature data allowed accurate assessment of volumetric dose delivered to tissues.

Conclusions

Using a rabbit intravertebral tumor model, the authors have successfully delivered tumoricidal doses of acoustic energy via a therapeutic ultrasound ablation probe placed percutaneously with CTF guidance. The authors have thus established the first technical and preclinical feasibility study of controlled ultrasound ablation of spinal tumors in vivo.

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Abigail Hellman, Teresa Maietta, Alicia Clum, Kanakaharini Byraju, Nataly Raviv, Michael D. Staudt, Erin Jeannotte, Goutam Ghoshal, Damian Shin, Paul Neubauer, Emery Williams, Tamas Heffter, Clif Burdette, Jiang Qian, Julia Nalwalk, and Julie G. Pilitsis

OBJECTIVE

The authors’ laboratory has previously demonstrated beneficial effects of noninvasive low intensity focused ultrasound (liFUS), targeted at the dorsal root ganglion (DRG), for reducing allodynia in rodent neuropathic pain models. However, in rats the DRG is 5 mm below the skin when approached laterally, while in humans the DRG is typically 5–8 cm deep. Here, using a modified liFUS probe, the authors demonstrated the feasibility of using external liFUS for modulation of antinociceptive responses in neuropathic swine.

METHODS

Two cohorts of swine underwent a common peroneal nerve injury (CPNI) to induce neuropathic pain. In the first cohort, pigs (14 kg) were iteratively tested to determine treatment parameters. liFUS penetration to the L5 DRG was verified by using a thermocouple to monitor tissue temperature changes and by measuring nerve conduction velocity (NCV) at the corresponding common peroneal nerve (CPN). Pain behaviors were monitored before and after treatment. DRG was evaluated for tissue damage postmortem. Based on data from the first cohort, a treatment algorithm was developed, parameter predictions were verified, and neuropathic pain was significantly modified in a second cohort of larger swine (20 kg).

RESULTS

The authors performed a dose-response curve analysis in 14-kg CPNI swine. Specifically, after confirming that the liFUS probe could reach 5 cm in ex vivo tissue experiments, the authors tested liFUS in 14-kg CPNI swine. The mean ± SEM DRG depth was 3.79 ± 0.09 cm in this initial cohort. The parameters were determined and then extrapolated to larger animals (20 kg), and predictions were verified. Tissue temperature elevations at the treatment site did not exceed 2°C, and the expected increases in the CPN NCV were observed. liFUS treatment eliminated pain guarding in all animals for the duration of follow-up (up to 1 month) and improved allodynia for 5 days postprocedure. No evidence of histological damage was seen using Fluoro-Jade and H&E staining.

CONCLUSIONS

The results demonstrate that a 5-cm depth can be reached with external liFUS and alters pain behavior and allodynia in a large-animal model of neuropathic pain.