The effect of blood flow on magnetic resonance imaging of non thermal irreversible electroporation.
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ABSTRACT:
SUBMITTER: Hjouj M
PROVIDER: S-EPMC3812656 | biostudies-other | 2013
REPOSITORIES: biostudies-other
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Project description:The blood-brain-barrier (BBB) presents a significant obstacle to the delivery of systemically administered chemotherapeutics for the treatment of brain cancer. Irreversible electroporation (IRE) is an emerging technology that uses pulsed electric fields for the non-thermal ablation of tumors. We hypothesized that there is a minimal electric field at which BBB disruption occurs surrounding an IRE-induced zone of ablation and that this transient response can be measured using gadolinium (Gd) uptake as a surrogate marker for BBB disruption. The study was performed in a Good Laboratory Practices (GLP) compliant facility and had Institutional Animal Care and Use Committee (IACUC) approval. IRE ablations were performed in vivo in normal rat brain (n = 21) with 1-mm electrodes (0.45 mm diameter) separated by an edge-to-edge distance of 4 mm. We used an ECM830 pulse generator to deliver ninety 50-μs pulse treatments (0, 200, 400, 600, 800, and 1000 V/cm) at 1 Hz. The effects of applied electric fields and timing of Gd administration (-5, +5, +15, and +30 min) was assessed by systematically characterizing IRE-induced regions of cell death and BBB disruption with 7.0-T magnetic resonance imaging (MRI) and histopathologic evaluations. Statistical analysis on the effect of applied electric field and Gd timing was conducted via Fit of Least Squares with α = 0.05 and linear regression analysis. The focal nature of IRE treatment was confirmed with 3D MRI reconstructions with linear correlations between volume of ablation and electric field. Our results also demonstrated that IRE is an ablation technique that kills brain tissue in a focal manner depicted by MRI (n = 16) and transiently disrupts the BBB adjacent to the ablated area in a voltage-dependent manner as seen with Evan's Blue (n = 5) and Gd administration.
| S-EPMC3511570 | biostudies-literature
Project description:Irreversible electroporation (IRE) is gaining importance in routine clinical practice for nonthermal ablation of solid tumors. For its success, it is extremely important that the coverage and exposure time of the treated tumor to the electric field is within the specified range. Measurement of electric field distribution during the electroporation treatment can be achieved using magnetic resonance electrical impedance tomography (MREIT). Here, we show improved MREIT-enabled electroporation monitoring of IRE-treated tumors by predicting IRE-ablated tumor areas during IRE of mouse tumors in vivo. The in situ prediction is enabled by coupling MREIT with a corresponding Peleg-Fermi mathematical model to obtain more informative monitoring of IRE tissue ablation by providing cell death probability in the IRE-treated tumors. This technique can potentially be used in electroporation-based clinical applications, such as IRE tissue ablation and electrochemotherapy, to improve and assure the desired treatment outcome.
| S-EPMC5583379 | biostudies-literature
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.
| S-EPMC3258292 | biostudies-literature
Project description:Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon in which certain electric fields delivered across the cell membrane in tissue, cause cell death, without affecting the extracellular matrix. "Minimally invasive regenerative surgery" is a new medical modality for treatment of end-stage organ or tissue failure in which exogenous cells are implanted in a decellularized niche in tissue, formed by the delivery of NTIRE electric fields across a targeted volume of tissue. We anticipate that the success of the procedure will depend on the time of implantation relative to the application of NTIRE. This study was performed to elucidate the histological and molecular events that occur within 24 h after NTIRE, in the context of optimal criteria for the time of implantation. To this end, we examined the histology of NTIRE treated rat liver with H&E, Masson trichrome and TUNEL staining. Western blot was used to examine pro and cleaved caspase-3 (marker for apoptosis), pro and cleaved caspase-1 and gasdermin D (markers for pyroptosis), and RIP3 and MLKL (markers for necroptosis). The key findings are that, complete hepatocytes disintegration within an intact extracellular matrix is seen at 6 h and, new hepatocytes are seen in the treated region at 24 h, after NTIRE. There is no evidence of apoptotic cell death from NTIRE, contrary to commonly made claims in the NTIRE literature. However, molecular pathways of pyroptosis and necroptosis, programed necrosis associated with inflammation, are activated at 6 h after NTIRE and are not evident at 24 h after NTIRE. These are fundamental new findings of basic value to the field of NTIRE in all its applications. Taken together the results suggest the hypothesis that an optimal time for implantation is about 24 h after NTIRE. Future studies in which exogenous cells are implanted at different times after NTIRE are required to examine this hypothesis.
| S-EPMC5990035 | biostudies-literature
Project description:Irreversible electroporation is a new, minimal-invasive image-guided treatment to treat tumors near or around vulnerable structures, such as central liver tumors.
To investigate the safety and efficacy of IRE in the treatment of colorectal liver metastases, patients with resectable colorectal liver metastases undergo IRE and resection of the metastases in the same session. After resection, the specimen is examined macroscopically to determine vitality using a specific vitality staining (triphenyl-tetrazoliumchloride) and to visualize the exact ablation zone. Subsequently, histopathologic examination is used to determine type of cell death and the microscopic ablation zone.
The investigators hypothesize that IRE is a safe effective method to treat colorectal liver metastasis and that cell damage and cell death is demonstrated as soon as 1 hour after the procedure.
| 2140639 | ecrin-mdr-crc
Project description:Cerebral blood flow is an important parameter in many diseases and functional studies that can be accurately measured in humans using arterial spin labelling (ASL) MRI. However, although rat models are frequently used for preclinical studies of both human disease and brain function, rat CBF measurements show poor consistency between studies. This lack of reproducibility is due, partly, to the smaller size and differing head geometry of rats compared to humans, as well as the differing analysis methodologies employed and higher field strengths used for preclinical MRI. To address these issues, we have implemented, optimised and validated a multiphase pseudo-continuous ASL technique, which overcomes many of the limitations of rat CBF measurement. Three rat strains (Wistar, Sprague Dawley and Berlin Druckrey IX) were used, and CBF values validated against gold-standard autoradiography measurements. Label positioning was found to be optimal at 45°, while post-label delay was optimised to 0.55 s. Whole brain CBF measures were 109 ± 22, 111 ± 18 and 100 ± 15 mL/100 g/min by multiphase pCASL, and 108 ± 12, 116 ± 14 and 122 ± 16 mL/100 g/min by autoradiography in Wistar, SD and BDIX cohorts, respectively. Tumour model analysis shows that the developed methods also apply in disease states. Thus, optimised multiphase pCASL provides robust, reproducible and non-invasive measurement of CBF in rats.
| S-EPMC6681434 | biostudies-literature
Project description:PurposeWe aimed to design and evaluate a deep learning-based method to automatically predict the time-varying in-plane blood flow velocity within the cardiac cavities in long-axis cine MRI, validated against 4D flow.MethodsA convolutional neural network (CNN) was implemented, taking cine MRI as the input and the in-plane velocity derived from the 4D flow acquisition as the ground truth. The method was evaluated using velocity vector end-point error (EPE) and angle error. Additionally, the E/A ratio and diastolic function classification derived from the predicted velocities were compared to those derived from 4D flow.ResultsFor intra-cardiac pixels with a velocity > 5 cm/s, our method achieved an EPE of 8.65 cm/s and angle error of 41.27°. For pixels with a velocity > 25 cm/s, the angle error significantly degraded to 19.26°. Although the averaged blood flow velocity prediction was under-estimated by 26.69%, the high correlation (PCC = 0.95) of global time-varying velocity and the visual evaluation demonstrate a good agreement between our prediction and 4D flow data. The E/A ratio was derived with minimal bias, but with considerable mean absolute error of 0.39 and wide limits of agreement. The diastolic function classification showed a high accuracy of 86.9%.ConclusionUsing a deep learning-based algorithm, intra-cardiac blood flow velocities can be predicted from long-axis cine MRI with high correlation with 4D flow derived velocities. Visualization of the derived velocities provides adjunct functional information and may potentially be used to derive the E/A ratio from conventional CMR exams.
| S-EPMC10160163 | biostudies-literature
Project description:Irreversible electroporation (IRE), also referred to as nonthermal pulsed field ablation (PFA), is an attractive focal ablation modality for solid tumors and cardiac tissue due to its ability to destroy aberrant cells with limited disruption of the underlying tissue architecture. Despite its nonthermal cell death mechanism, application of electrical energy results in Joule heating that, if ignored, can cause undesired thermal injury. Engineered thermal mitigation (TM) technologies including phase change materials (PCMs) and active cooling (AC) have been reported and tested as a potential means to limit thermal damage. However, several variables affect TM performance including the pulsing paradigm, electrode geometry, PCM composition, and chosen active cooling parameters, meaning direct comparisons between approaches are lacking. In this study, we developed a computational model of conventional bipolar and monopolar probes with solid, PCM-filled, or actively cooled cores to simulate clinical IRE treatments in pancreatic tissue. This approach reveals that probes with integrated PCM cores can be tuned to drastically limit thermal damage compared to existing solid probes. Furthermore, actively cooled probes provide additional control over thermal effects within the probe vicinity and can altogether abrogate thermal damage. In practice, such differences in performance must be weighed against the increased time, expense, and effort required for modified probes compared to existing solid probes.
| S-EPMC8823459 | biostudies-literature
Project description:BackgroundBright-blood and black-blood cardiovascular magnetic resonance (CMR) techniques are frequently employed together during a clinical exam because of their complementary features. While valuable, existing black-blood CMR approaches are flow dependent and prone to failure. We aim to assess the effectiveness and reliability of ferumoxytol enhanced (FE) Half-Fourier Single-shot Turbo Spin-echo (HASTE) imaging without magnetization preparation pulses to yield uniform intra-luminal blood signal suppression by comparing FE-HASTE with pre-ferumoxytol HASTE imaging.MethodsThis study was IRB-approved and HIPAA compliant. Consecutive patients who were referred for FE-CMR between June 2013 and February 2017 were enrolled. Qualitative image scores reflecting the degree and reliability of blood signal suppression were based on a 3-point Likert scale, with 3 reflecting perfect suppression. For quantitative evaluation, homogeneity indices (defined as standard deviation of the left atrial signal intensity) and signal-to-noise ratios (SNR) for vascular lumens and cardiac chambers were measured.ResultsOf the 340 unique patients who underwent FE-CMR, HASTE was performed in 257. Ninety-three patients had both pre-ferumoxytol HASTE and FE-HASTE, and were included in this analysis. Qualitative image scores reflecting the degree and reliability of blood signal suppression were significantly higher for FE-HASTE images (2.9 [IQR 2.8-3.0] vs 1.8 [IQR 1.6-2.1], p < 0.001). Inter-reader agreement was moderate (k = 0.50, 95% CI 0.45-0.55). Blood signal suppression was more complete on FE-HASTE images than on pre-ferumoxytol HASTE, as indicated by lower mean homogeneity indices (24.5 [IQR 18.0-32.8] vs 108.0 [IQR 65.0-170.4], p < 0.001) and lower blood pool SNR for all regions (5.6 [IQR 3.2-10.0] vs 21.5 [IQR 12.5-39.4], p < 0.001).ConclusionFE-HASTE black-blood imaging offers an effective, reliable, and simple approach for flow independent blood signal suppression. The technique holds promise as a fast and routine complement to bright-blood cardiovascular imaging with ferumoxytol.
| S-EPMC5745904 | biostudies-literature
Project description:Genome wide DNA methylation profiling of normal and tumour prostate samples. The Illumina Infinium MethylationEPIC Human DNA methylation oligonucleotide beads was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Comparative assessment was carried out.
2018-12-01 | GSE101908 | GEO