Non-invasive central nervous system assessment of a porcine model of neuropathic pain demonstrates increased latency of somatosensory-evoked potentials.

BACKGROUND: The study of chronic pain and its treatments requires a robust animal model with objective and quantifiable metrics. Porcine neuropathic pain models have been assessed with peripheral pain recordings and behavioral responses, but thus far central nervous system electrophysiology has not been investigated. This work aimed to record non-invasive, somatosensory-evoked potentials (SEPs) via electroencephalography in order to quantitatively assess chronic neuropathic pain induced in a porcine model. NEW METHOD: Peripheral neuritis trauma (PNT) was induced unilaterally in the common peroneal nerve of domestic farm pigs, with the contralateral leg serving as the control for each animal. SEPs were generated by stimulation of the peripheral nerves distal to the PNT and were recorded non-invasively using transcranial electroencephalography (EEG). The P30 wave of the SEP was analyzed for latency changes. RESULTS: P30 SEPs were successfully recorded with non-invasive EEG. PNT resulted in significantly longer P30 SEP latencies (p < 0.01 [n = 8]) with a median latency increase of 14.3 [IQR 5.0 - 17.5] ms. Histological results confirmed perineural inflammatory response and nerve damage around the PNT nerves. COMPARISON WITH EXISTING METHOD(S): Control P30 SEPs were similar in latency and amplitude to those previously recorded invasively in healthy pigs. Non-invasive recordings have numerous advantages over invasive measures. CONCLUSIONS: P30 SEP latency can serve as a quantifiable neurological measure that reflects central nervous system processing in a porcine model of chronic pain. Advancing the development of a porcine chronic pain model will facilitate the translation of experimental therapies into human clinical trials.

Evaluation of MRI protocols for the assessment of lumbar facet joints after MR-guided focused ultrasound treatment.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) might be a very safe and effective minimally invasive technique to treat facet joint pain caused by arthritis and other degenerative changes. However, there are still safety concerns for this treatment and challenges regarding MR imaging and temperature mapping due to susceptibility effects between the bone and soft tissue near the joint, which has resulted in poor MR image quality. The goal of this research was to evaluate multiple magnetic resonance imaging (MRI) pulse sequences for characterizing ablated lumbar facet joint lesions created by high-intensity focused ultrasound (FUS) and compare the findings to histological tissue assessment. In particular, we investigated the use of T2-weighted MRI to assess treatment effects without contrast administration. METHODS: An IACUC approved study (n = 6 pigs) was performed using a 3T widebore MRI system equipped with an MRgFUS system. Facet joints of the lumbar vertebra were ablated using 1-MHz frequency and multiple sonication energies (300-800 J). In addition to T2-weighted MRI for treatment planning, T1-, T2-, and T2*-weighted and perfusion MRI sequences were applied. Signal intensity ratios of the lesions were determined. Histopathology was used to characterize cellular changes. RESULTS: Ablation of the facet joint, using MRgFUS, was successful in all animals. T2-weighted images showed high signal intensity in the edematous facet joint and adjacent muscle, while delayed contrast-enhanced T1-weighted images showed an enhanced ring surrounding the target volume. T2*-weighted GRE images revealed inconsistent lesion visualization. Histopathology confirmed the presence of cellular coagulation (shrinkage), extracellular expansion (edema), and hemorrhage in the bone marrow. CONCLUSIONS: MRgFUS provided sufficient precision and image quality for visualization and characterization of ablated facet joints directly after ablation. MRI may help in monitoring the efficacy of FUS ablation without contrast after treating patients with back pain.

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array.

PURPOSE: Feasibility of targeted and volumetric hyperthermia (40-45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy. METHODS: The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm(2), ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). RESULTS: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm(2)). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13-23 cm(3) volumes for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm(2), in 4.5-5.8 cm(3) volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm(2), and in ∼6.0 cm(3) for curvilinear (cylindrical) beam patterns at 0.75 W/cm(2). Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm(2), 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations. CONCLUSIONS: The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.