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Non-thermal Electroporation Ablation of Epileptogenic Zones Stops Seizures in Mice While Providing Reduced Vascular Damage and Accelerated Tissue Recovery.

ABSTRACT: In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.

SUBMITTER: Acerbo E

PROVIDER: S-EPMC8740210 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To evaluate the use of contrast material-enhanced magnetic resonance (MR) imaging with conventional T1-weighted gradient-recalled echo (GRE) and inversion-recovery (IR)-prepared GRE methods to quantitatively measure the size of irreversible electroporation (IRE) ablation zones in the liver in a rat model.All studies were approved by the institutional animal care and use committee and were performed in accordance with institutional guidelines. Seventeen adult male Sprague-Dawley rats were divided into four groups. Rats in groups 1-3 (n = 15 total) underwent IRE performed by using different IRE parameters after gadopentetate dimeglumine administration. Rats in group 4 (n = 2) underwent IRE ablation without prior gadopentetate dimeglumine injection to serve as control animals. MR imaging measurements (with conventional T1-weighted GRE and IR-prepared GRE methods) were performed 2 hours after IRE to predict the IRE ablation zones, which were correlated with pathology-confirmed necrosis areas 24 hours after IRE by using the Spearman correlation coefficient. Bland-Altman plots were also generated to investigate the agreement between MR imaging-measured ablation zones and reference standard histologic measurements of corresponding ablation zones.The necrotic areas measured on the pathology images were well correlated with the hyperintense regions measured on T1-weighted GRE images (r = 0.891, P < .001) and normal tissue-nulled IR images (r = 0.874, P < .001); pathology measurements were also well correlated with the smaller hyperintense regions measured on those IR images with inversion times specifically selected to null signal from the peripheral penumbra surrounding the ablation zone (r = 0.939, P < .001). Bland-Altman plots indicated that these penumbra-nulled IR images provided more accurate predictions of IRE ablation zones, with T1-weighted GRE measurements tending to overestimate ablation zone sizes.Contrast-enhanced MR imaging permits accurate depiction of ablated tissue zones after IRE procedures. IR-prepared contrast-enhanced MR imaging can be used to quantitatively measure IRE ablation zones in the liver.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100645/-/DC1.

Project description:Objective: Electrical stimulation (ES) potentially delineates epileptogenic cortex through induction of typical seizures. Although frequently employed, its value for epilepsy surgery remains controversial. Similarly, ES is used to identify symptomatogenic zones, but with greater success and a long-standing evidence base. Recent work points to new seizure symptoms such as ictal central apnea (ICA) that may enhance presurgical hypotheses. The aims of this review are 2-fold: to determine the value of ES-induced seizures (ESIS) in epilepsy surgery and to analyze current evidence on ICA as a new surrogate of symptomatogenic cortex. Methods: Three databases were searched for ESIS. Investigators independently selected studies according to pre-specified criteria. Studies reporting postoperative outcome in patients with ESIS were included in a meta-analysis. For ES-induced apnea, a thorough search was performed and reference list searching was employed. Results: Of 6,314 articles identified for ESIS, 25 were considered eligible to be reviewed in full text. Fourteen studies were included in the qualitative synthesis (1,069 patients); six studies were included in the meta-analysis (530 patients). The meta-analysis showed that favorable outcome is associated with ESIS prior to surgery (OR: 2.02; 95% CI: 1.332-3.08). In addition, the overall estimation of the occurrence of favorable outcome among cases with ESIS is 68.13% (95% CI: 56.62-78.7). On the other hand, recent studies have shown that stimulation of exclusively mesial temporal lobe structures elicits central apnea and represents symptomatogenic anatomic substrates of ICA. This is in variance with traditional teaching that mesial temporal ES is non-symptomatogenic. Conclusions: ES is a tool highly likely to aid in the delineation of the epileptogenic zone, since ESIS is associated with favorable postoperative outcomes (Engel I). There is an urgent need for prospective evaluation of this technique, including effective stimulation parameters and surgical outcomes, that will provide knowledge base for practice. In addition, ES-induced apnea studies suggest that ICA, especially when it is the first or only clinical sign, is an important semiological feature in localizing the symptomatogenic zone to mesial temporal lobe structures, which must be considered in SEEG explorations where this is planned, and in surgical resection strategies.

Project description:BackgroundTherapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.MethodsA combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.ResultsNo visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.ConclusionsH-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.

Project description:PURPOSE:The goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors. METHODS:The 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002-2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis. RESULTS:A 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p?=?0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p?=?0.004). CONCLUSIONS:Volumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors. KEY POINTS:• More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

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Non-thermal Electroporation Ablation of Epileptogenic Zones Stops Seizures in Mice While Providing Reduced Vascular Damage and Accelerated Tissue Recovery.

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