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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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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.