Experimental study on ablative stabilization of Rayleigh-Taylor instability of laser-irradiated targets

NASA Astrophysics Data System (ADS)

Shigemori, Keisuke; Sakaiya, Tatsuhiko; Otani, Kazuto; Fujioka, Shinsuke; Nakai, Mitsuo; Azechi, Hiroshi; Shiraga, Hiroyuki; Tamari, Yohei; Okuno, Kazuki; Sunahara, Atsushi; Nagatomo, Hideo; Murakami, Masakatsu; Nishihara, Katsunobu; Izawa, Yasukazu

2004-09-01

Hydrodynamic instabilities are key issues of the physics of inertial confinement fusion (ICF) targets. Among the instabilities, Rayleigh-Taylor (RT) instability is the most important because it gives the largest growth factor in the ICF targets. Perturbations on the laser irradiated surface grow exponentially, but the growth rate is reduced by ablation flow. The growth rate γ is written as Takabe-Betti formula: γ = [kg/(1+kL)]1/2-βkm/pa, where k is wave number of the perturbation, g is acceleration, L is density scale-length, β is a coefficient, m is mass ablation rate per unit surface, and ρa is density at the ablation front. We experimentally measured all the parameters in the formula for polystyrene (CH) targets. Experiments were done on the HIPER laser facility at Institute of Laser Engineering, Osaka University. We found that the β value in the formula is ~ 1.7, which is in good agreements with the theoretical prediction, whereas the β for certain perturbation wavelengths are larger than the prediction. This disagreement between the experiment and the theory is mainly due to the deformation of the cutoff surface, which is created by non-uniform ablation flow from the ablation surface. We also found that high-Z doped plastic targets have multiablation structure, which can reduce the RT growth rate. When a low-Z target with high-Z dopant is irradiated by laser, radiation due to the high-Z dopant creates secondary ablation front deep inside the target. Since, the secondary ablation front is ablated by x-rays, the mass ablation rate is larger than the laser-irradiated ablation surface, that is, further reduction of the RT growth is expected. We measured the RT growth rate of Br-doped polystyrene targets. The experimental results indicate that of the CHBr targets show significantly small growth rate, which is very good news for the design of the ICF targets.

Computational Modeling of Ablation on an Irradiated Target

NASA Astrophysics Data System (ADS)

Mehmedagic, Igbal; Thangam, Siva

2017-11-01

Computational modeling of pulsed nanosecond laser interaction with an irradiated metallic target is presented. The model formulation involves ablation of the metallic target irradiated by pulsed high intensity laser at normal atmospheric conditions. Computational findings based on effective representation and prediction of the heat transfer, melting and vaporization of the targeting material as well as plume formation and expansion are presented along with its relevance for the development of protective shields. In this context, the available results for a representative irradiation from 1064 nm laser pulse is used to analyze various ablation mechanisms, variable thermo-physical and optical properties, plume expansion and surface geometry. Funded in part by U. S. Army ARDEC, Picatinny Arsenal, NJ.

Targeted multifunctional gold-based nanoshells for magnetic resonance-guided laser ablation of head and neck cancer.

PubMed

Melancon, Marites P; Lu, Wei; Zhong, Meng; Zhou, Min; Liang, Gan; Elliott, Andrew M; Hazle, John D; Myers, Jeffrey N; Li, Chun; Stafford, R Jason

2011-10-01

Image-guided thermal ablation of tumors is becoming a more widely accepted minimally invasive alternative to surgery for patients who are not good surgical candidates, such as patients with advanced head and neck cancer. In this study, multifunctional superparamagnetic iron oxide coated with gold nanoshell (SPIO@Au NS) that have both optical and magnetic properties was conjugated with the targeting agent, C225 monoclonal antibody, against epidermal growth factor receptor (EGFR). C225-SPIO@Au NS have an average a diameter of 82 ± 4.4 nm, contain 142 ± 15 antibodies per nanoshell, have an absorption peak in the near infrared (~800 nm), and have transverse relaxivity (r(2)) of 193 and 353 mM(-1) s(-1) versus Feridex™ of 171 and 300 mM(-1) s(-1), using 1.5 T and 7 T MR scanners, respectively. Specific targeting of the synthesized C225-SPIO@Au NS was tested in vitro using A431 cells and oral cancer cells, FaDu, OSC19, and HN5, all of which overexpress EGFR. Selective binding was achieved using C225-SPIO@Au NS but not with the non-targeting PEG-SPIO@Au NS and blocking group (excess of C225 + C225-SPIO@Au NS). In vivo biodistribution on mice bearing A431 tumors also showed selective targeting of C225-SPIO@Au NS compared with the non-targeting and blocking groups. The selective photothermal ablation of the nanoshells shows that without laser treatment there were no cell death and among the groups that were treated with laser at a power of 36 W/cm(2) for 3 min, only the cells treated with C225-SPIO@Au NS had cell killing (p < 0.001). In summary, successful synthesis and characterization of targeted C225-SPIO@Au NS demonstrating both superparamagnetic and optical properties has been achieved. We have shown both in vitro and in vivo that these nanoshells are MR-active and can be selectively heated up for simultaneous imaging and photothermal ablation therapy. Published by Elsevier Ltd.

Enhanced laser proton acceleration by target ablation on a femtosecond laser system

NASA Astrophysics Data System (ADS)

Liao, Q.; Wu, M. J.; Gong, Z.; Geng, Y. X.; Xu, X. H.; Li, D. Y.; Shou, Y. R.; Zhu, J. G.; Li, C. C.; Yang, M.; Li, T. S.; Lu, H. Y.; Ma, W. J.; Zhao, Y. Y.; Lin, C.; Yan, X. Q.

2018-06-01

Proton acceleration during the interaction of an ultraintense (6 × 1019 W/cm2) femtosecond (fs) laser pulse with a thin (2.5 μm) foil target pre-ablated by a picosecond (ps) pulse is experimentally and numerically investigated. Enhancements in both proton cut-off energy and charge are observed with the target ablation due to a large number of energetic electrons generated from the preformed preplasma in front of the target. The enhanced proton beams are successfully collected at 4-9 MeV with ±4% energy spread and then transported to the irradiating platform. The results show that for the interaction between fs laser pulse and μm-thickness target, proton energy and charge can be enhanced by target ablation using a ps laser pulse, which is valuable for application like cancer radiotherapy.

Genetic Ablation of Parietal Cells in Transgenic Mice: A New Model for Analyzing Cell Lineage Relationships in the Gastric Mucosa

NASA Astrophysics Data System (ADS)

Canfield, Victor; West, A. Brian; Goldenring, James R.; Levenson, Robert

1996-03-01

The gastric mucosa of mammalian stomach contains several differentiated cell types specialized for the secretion of acid, digestive enzymes, mucus, and hormones. Understanding whether each of these cell lineages is derived from a common stem cell has been a challenging problem. We have used a genetic approach to analyze the ontogeny of progenitor cells within mouse stomach. Herpes simplex virus 1 thymidine kinase was targeted to parietal cells within the gastric mucosa of transgenic mice, and parietal cells were ablated by treatment of animals with the antiherpetic drug ganciclovir. Ganciclovir treatment produced complete ablation of parietal cells, dissolution of gastric glands, and loss of chief and mucus-producing cells. Termination of drug treatment led to the reemergence of all major gastric epithelial cell types and restoration of glandular architecture. Our results imply the existence of a pluripotent stem cell for the gastric mucosa. Parietal cell ablation should provide a model for analyzing cell lineage relationships within the stomach as well as mechanisms underlying gastric injury and repair.

Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

PubMed

Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

2018-05-09

Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

High-intensity interstitial ultrasound for thermal ablation of focal cancer targets in prostate

NASA Astrophysics Data System (ADS)

Salgaonkar, Vasant A.; Scott, Serena; Kurhanewicz, John; Diederich, Chris J.

2017-03-01

Recent advances in image based techniques such as multi-parametric MRI (MP-MRI) can provide precise targeting of focal disease in the prostate. Thermal ablation of such cancer targets while avoiding rectum, urethra, neurovascular bundles (NVB) and sphincter is clinically challenging. The approach described here employs multi-element ultrasound linear arrays designed for transperineal placement within prostate. They consist of independently powered sectored tubular transducers (6.5 - 8.0 MHz) that provide spatial control of energy deposition in angle and length. Volumetric ablation strategies were investigated through patient-specific biothermal models based on Pennes bioheat transfer equation. The acoustic and heat transfer models used here have been validated in several previous simulation and experimental studies. Focal disease sites in prostate were identified through multi-parametric MR images of representative patient cases (n=3). Focal cancer lesions and critical anatomy (prostate, urethra, rectum, bladder, seminal vesicles) were manually segmented (Mimics, Materialise) and converted to 3D finite element meshes (3-Matic, Materialise). The chosen test cases consisted of patients with medium and large sized glands and models of bulk tissue ablation covered volumes in a single quadrant in posterior prostate, hemi-gland targets and "hockey-stick" targets (lesions in three quadrants). Ultrasound applicator placement was determined such that devices were positioned along the prostate periphery while avoiding surrounding anatomy. Transducer sector angles were chosen based on applicator location within limits of fabrication practicability. Thermal models were numerically solved using finite element methods (FEM) in COMSOL Multiphysics. Temperature and thermal dose distributions were calculated to determine treated volumes (> 240 CEM43C, >52 °C) and safety profiles (<10 CEM43C, <45 °C) for nerve, rectal and urethral sparing. Modeling studies indicated that focal

Investigations of the Cavitation and Damage Thresholds of Histotripsy and Applications in Targeted Tissue Ablation

NASA Astrophysics Data System (ADS)

Vlaisavljevich, Eli

ablation were investigated in an intact in vivo rodent model, showing that the liver homogenate resulting from histotripsy-induced tissue fractionation was completely resorbed over the course of 28 days. In the final part of this dissertation, a novel ablation method combining histotripsy with acoustically sensitive nanodroplets was developed for targeted cancer cell ablation, demonstrating the potential of using nanodroplet-mediated histotripsy (NMH) for targeted, multi-focal ablation. Studies demonstrated that lower frequency and higher boiling point perfluorocarbon droplets can improve NMH therapy. The role of positive and negative pressure on cavitation nucleation in NMH was also investigated, showing that NMH cavitation nucleation is caused directly from the peak negative pressure of the incident wave, similar to histotripsy bubbles generated above the intrinsic threshold. Overall, the results of this dissertation provide significant insight into the physical mechanisms underlying histotripsy tissue ablation and will help to guide the future development of histotripsy for clinical applications such as the treatment of liver cancer.

Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model.

PubMed

Arvanitis, Costas D; Vykhodtseva, Natalia; Jolesz, Ferenc; Livingstone, Margaret; McDannold, Nathan

2016-05-01

OBJECT Transcranial MRI-guided focused ultrasound (TcMRgFUS) is an emerging noninvasive alternative to surgery and radiosurgery that is undergoing testing for tumor ablation and functional neurosurgery. The method is currently limited to central brain targets due to skull heating and other factors. An alternative ablative approach combines very low intensity ultrasound bursts and an intravenously administered microbubble agent to locally destroy the vasculature. The objective of this work was to investigate whether it is feasible to use this approach at deep brain targets near the skull base in nonhuman primates. METHODS In 4 rhesus macaques, targets near the skull base were ablated using a clinical TcMRgFUS system operating at 220 kHz. Low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes in conjunction with the ultrasound contrast agent Definity, which was administered as a bolus injection or continuous infusion. The acoustic power level was set to be near the inertial cavitation threshold, which was measured using passive monitoring of the acoustic emissions. The resulting tissue effects were investigated with MRI and with histological analysis performed 3 hours to 1 week after sonication. RESULTS Thirteen targets were sonicated in regions next to the optic tract in the 4 animals. Inertial cavitation, indicated by broadband acoustic emissions, occurred at acoustic pressure amplitudes ranging from 340 to 540 kPa. MRI analysis suggested that the lesions had a central region containing red blood cell extravasations that was surrounded by edema. Blood-brain barrier disruption was observed on contrast-enhanced MRI in the lesions and in a surrounding region corresponding to the prefocal area of the FUS system. In histology, lesions consisting of tissue undergoing ischemic necrosis were found in all regions that were sonicated above the inertial cavitation threshold. Tissue damage in prefocal areas was found in several cases, suggesting that in

Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features

PubMed Central

Koivunen, Peppi; Koivunen, Jussi P.

2014-01-01

Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can mediate adaptive resistance to oncogene ablative therapy. When pharmacological ablation of ALK oncogene was accompanied with PI3K inhibitor or salinomycin therapy, cancer stem-like cell features were reversed which was accompanied with decreased colony formation. Furthermore, co-targeting was able to block the formation of acquired resistance in H3122 line. The results suggest that cells with cancer stem-like cell features can mediate adaptive resistance to targeted therapies. Since these cells follow the stochastic model, concurrent therapy with an oncogene ablating agent and a stem-like cell-targeting drug is needed for maximal therapeutic efficiency. PMID:25238228

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

PubMed

Petrusca, Lorena; Viallon, Magalie; Breguet, Romain; Terraz, Sylvain; Manasseh, Gibran; Auboiroux, Vincent; Goget, Thomas; Baboi, Loredana; Gross, Patrick; Sekins, K Michael; Becker, Christoph D; Salomir, Rares

2014-01-16

Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Experimental validation of this new ballistic marker method was performed for

Highly versatile SPION encapsulated PLGA nanoparticles as photothermal ablators of cancer cells and as multimodal imaging agents.

PubMed

Sivakumar, Balasubramanian; Aswathy, Ravindran Girija; Romero-Aburto, Rebeca; Mitcham, Trevor; Mitchel, Keith A; Nagaoka, Yutaka; Bouchard, Richard R; Ajayan, Pulickel M; Maekawa, Toru; Sakthikumar, Dasappan Nair

2017-02-28

We have designed versatile polymeric nanoparticles with cancer cell specific targeting capabilities via aptamer conjugation after the successful encapsulation of curcumin and superparamagnetic iron oxide nanoparticles (SPIONs) inside a PLGA nanocapsule. These targeted nanocomposites were selectively taken up by tumor cells, under in vitro conditions, demonstrating the effectiveness of the aptamer targeting mechanism. Moreover, the nanocomposite potentially functioned as efficient multiprobes for optical, magnetic resonance imaging (MRI) and photoacoustic imaging contrast agents in the field of cancer diagnostics. The hyperthermic ability of these nanocomposites was mediated by SPIONs upon NIR-laser irradiation. In vitro cytotoxicity was shown by curcumin-loaded nanoparticles as well as the photothermal ablation of cancer cells mediated by the drug-encapsulated nanocomposite demonstrated the potential therapeutic effect of the nanocomposite. In short, we portray the aptamer-conjugated nanocomposite as a multimodal material capable of serving as a contrast agent for MR, photoacoustic and optical imaging. Furthermore, the nanocomposite functions as a targetable drug nanocarrier and a NIR-laser inducible hyperthermic material that is capable of ablating PANC-1 and MIA PaCa-2 cancer cell lines.

[Research on cells ablation characters by laser plasma].

PubMed

Han, Jing-hua; Zhang, Xin-gang; Cai, Xiao-tang; Duan, Tao; Feng, Guo-ying; Yang, Li-ming; Zhang, Ya-jun; Wang, Shao-peng; Li, Shi-wen

2012-08-01

The study on the mechanism of laser ablated cells is of importance to laser surgery and killing harmful cells. Three radiation modes were researched on the ablation characteristics of onion epidermal cells under: laser direct irradiation, focused irradiation and the laser plasma radiation. Based on the thermodynamic properties of the laser irradiation, the cell temperature rise and phase change have been analyzed. The experiments show that the cells damage under direct irradiation is not obvious at all, but the focused irradiation can cause cells to split and moisture removal. The removal shape is circular with larger area and rough fracture edges. The theoretical analysis found out that the laser plasma effects play a key role in the laser ablation. The thermal effects, radiation ionization and shock waves can increase the deposition of laser pulses energy and impact peeling of the cells, which will greatly increase the scope and efficiency of cell killing and is suitable for the cell destruction.

Modeling of beam-target interaction during pulsed electron beam ablation of graphite: Case of melting

NASA Astrophysics Data System (ADS)

Ali, Muddassir; Henda, Redhouane

2017-02-01

A one-dimensional thermal model based on a two-stage heat conduction equation is employed to investigate the ablation of graphite target during nanosecond pulsed electron beam ablation. This comprehensive model accounts for the complex physical phenomena comprised of target heating, melting and vaporization upon irradiation with a polyenergetic electron beam. Melting and vaporization effects induced during ablation are taken into account by introducing moving phase boundaries. Phase transition induced during ablation is considered through the temperature dependent thermodynamic properties of graphite. The effect of electron beam efficiency, power density, and accelerating voltage on ablation is analyzed. For an electron beam operating at an accelerating voltage of 15 kV and efficiency of 0.6, the model findings show that the target surface temperature can reach up to 7500 K at the end of the pulse. The surface begins to melt within 25 ns from the pulse start. For the same process conditions, the estimated ablation depth and ablated mass per unit area are about 0.60 μm and 1.05 μg/mm2, respectively. Model results indicate that ablation takes place primarily in the regime of normal vaporization from the surface. The results obtained at an accelerating voltage of 15 kV and efficiency factor of 0.6 are satisfactorily in good accordance with available experimental data in the literature.

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver

PubMed Central

2014-01-01

Background Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. Methods The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. Results At the end of the procedure, no ultrasound indication of the marker’s presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Conclusions Experimental validation of this

High throughput solar cell ablation system

DOEpatents

Harley, Gabriel; Pass, Thomas; Cousins, Peter John; Viatella, John

2014-10-14

A solar cell is formed using a solar cell ablation system. The ablation system includes a single laser source and several laser scanners. The laser scanners include a master laser scanner, with the rest of the laser scanners being slaved to the master laser scanner. A laser beam from the laser source is split into several laser beams, with the laser beams being scanned onto corresponding wafers using the laser scanners in accordance with one or more patterns. The laser beams may be scanned on the wafers using the same or different power levels of the laser source.

High throughput solar cell ablation system

DOEpatents

Harley, Gabriel; Pass, Thomas; Cousins, Peter John; Viatella, John

2012-09-11

A solar cell is formed using a solar cell ablation system. The ablation system includes a single laser source and several laser scanners. The laser scanners include a master laser scanner, with the rest of the laser scanners being slaved to the master laser scanner. A laser beam from the laser source is split into several laser beams, with the laser beams being scanned onto corresponding wafers using the laser scanners in accordance with one or more patterns. The laser beams may be scanned on the wafers using the same or different power levels of the laser source.

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

PubMed Central

Xu, Meiyu; Kobets, Andrew; Du, Jung-Chieh; Lennington, Jessica; Li, Lina; Banasr, Mounira; Duman, Ronald S.; Vaccarino, Flora M.; DiLeone, Ralph J.; Pittenger, Christopher

2015-01-01

Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbumin-expressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or d-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS. PMID:25561540

Mechanistic Comparison of "Nearly Missed" Versus "On-Target" Rotor Ablation.

PubMed

Yamazaki, Masatoshi; Avula, Uma Mahesh R; Berenfeld, Omer; Kalifa, Jérôme

2015-08-01

This study used advanced optical mapping techniques to examine atrial fibrillation (AF) dynamics before and after 2 distinct electrogram-based ablation strategies: complex fractionated atrial electrograms (CFAEs) and DFmax/rotor ablation. Among the electrogram analytical features proposed to unravel the atrial regions that perpetuate AF, CFAEs, highest dominant frequency sites (DFmax), and, more recently, phase analysis-enabled rotor mapping have received the largest attention. Still, the mechanisms by which these approaches modulate AF dynamics and lead to AF termination are unknown. In Langendorff-perfused sheep hearts, AF was maintained by the continuous perfusion of acetylcholine and high-resolution endocardial-epicardial optical videos were recorded from the left atrial free wall and the posterior left atrium. Then, DFmax/rotor regions (n = 7), or CFAE regions harboring the highest wavebreak density (HWD) (n = 5), were targeted with a 4F ablation catheter (5 to 15 W, 30 to 60 s/point). Thereafter, we examined the changes in AF dynamics and whether AF terminated. DFmax/rotor point ablation resulted in a significant decrease in DFmax values. In 2 animals AF terminated, whereas in the remaining 5 animals the post-ablation DFmax domain remained in the vicinity of its pre-ablation location. However, after HWD/CFAEs density ablation, DFmax values did not change, AF did not terminate, and post-ablation DFmax domains relocated from the left atrial free wall to the pulmonary vein-posterior left atrium region. In another group of hearts (n = 12), we observed that upon a progressive increase in acetylcholine concentration-mimicking the acute electrophysiological changes occurring after ablation-3-dimensional rotors drifted from one atrial region to another along large gradients of myocardial thickness. "On-target" DFmax/rotor ablation leads to the annihilation of the fibrillation-driving rotor. This translates into large decreases in AF frequency or AF termination. In

Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation.

PubMed

Shammas, Ronnie L; Fales, Andrew M; Crawford, Bridget M; Wisdom, Amy J; Devi, Gayathri R; Brown, David A; Vo-Dinh, Tuan; Hollenbeck, Scott T

2017-04-01

Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics. To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar-labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells. Efficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar-labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models. Gold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar-labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.

Plasmonic nanodiamonds: targeted core-shell type nanoparticles for cancer cell thermoablation.

PubMed

Rehor, Ivan; Lee, Karin L; Chen, Kevin; Hajek, Miroslav; Havlik, Jan; Lokajova, Jana; Masat, Milan; Slegerova, Jitka; Shukla, Sourabh; Heidari, Hamed; Bals, Sara; Steinmetz, Nicole F; Cigler, Petr

2015-02-18

Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell are designed and synthesized. The architecture of particles is analyzed and confirmed in detail using electron tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor are demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeted delivery of carbon nanotubes to cancer cells

NASA Astrophysics Data System (ADS)

Chakravarty, Pavitra

CD22 is broadly expressed on human B cell lymphomas. Monoclonal anti-CD22 antibodies (MAbs) alone, or coupled to toxins, have been used to selectively target these tumors both in severe combined immunodeficient (SCID) mice with xenografted human lymphomas and in patients. Single-walled carbon nanotubes (CNTs) attached to antibodies or peptides represent another approach to targeting cancer cells. CNTs convert absorbed near-infrared (NIR) light into heat, which can thermally ablate cells in the vicinity of the CNTs. We have made MAb-CNT constructs where the MAb was either noncovalently or covalently coupled to CNTs, and investigated their ability to bind specifically to cells and to thermally ablate them after exposure to NIR light. The specific binding of these MAb-CNT constructs to antigen-positive and antigen-negative cells was demonstrated in vitro by using CD22+CD25 - Daudi cells, CD22-CD25+ phytohemagglutinin (PHA)-activated normal human peripheral blood mononuclear cells (PBMCs) and CNTs coupled non-covalently or covalently to either anti-CD22 or anti-CD25. We then demonstrated that the MAb-CNTs could bind to tumor cells expressing the relevant antigen but not to cells lacking the antigen. Furthermore we showed that, following exposure to NIR light, the cells could be thermally ablated. We also determined the stability of the MAb-CNTs in conditions designed to mimic the in vivo environment, i.e. mouse serum at 37°C. We then use the intrinsic Raman signature of CNTs to study the circulation and tissue distribution of intravenously injected MAb-CNTs in a murine xenograft model of lymphoma in vivo over a period of 24 hrs. We demonstrated that the MAb-CNTs have a short half-life in blood and that most of them are cleared by the reticuloendothelial system (RES). In the current embodiment, these constructs would therefore be of limited effectiveness in vivo.

Combining Electrolysis and Electroporation for Tissue Ablation.

PubMed

Phillips, Mary; Rubinsky, Liel; Meir, Arie; Raju, Narayan; Rubinsky, Boris

2015-08-01

Electrolytic ablation is a method that operates by delivering low magnitude direct current to the target region over long periods of time, generating electrolytic products that destroy cells. This study was designed to explore the hypothesis stating that electrolytic ablation can be made more effective when the electrolysis-producing electric charges are delivered using electric pulses with field strength typical in reversible electroporation protocols. (For brevity we will refer to tissue ablation protocols that combine electroporation and electrolysis as E(2).) The mechanistic explanation of this hypothesis is related to the idea that products of electrolysis generated by E(2) protocols can gain access to the interior of the cell through the electroporation permeabilized cell membrane and therefore cause more effective cell death than from the exterior of an intact cell. The goal of this study is to provide a first-order examination of this hypothesis by comparing the charge dosage required to cause a comparable level of damage to a rat liver, in vivo, when using either conventional electrolysis or E(2) approaches. Our results show that E(2) protocols produce tissue damage that is consistent with electrolytic ablation. Furthermore, E(2) protocols cause damage comparable to that produced by conventional electrolytic protocols while delivering orders of magnitude less charge to the target tissue over much shorter periods of time. © The Author(s) 2014.

Setup for functional cell ablation with lasers: coupling of a laser to a microscope.

PubMed

Sweeney, Sean T; Hidalgo, Alicia; de Belle, J Steven; Keshishian, Haig

2012-06-01

The selective removal of cells by ablation is a powerful tool in the study of eukaryotic developmental biology, providing much information about their origin, fate, or function in the developing organism. In Drosophila, three main methods have been used to ablate cells: chemical, genetic, and laser ablation. Each method has its own applicability with regard to developmental stage and the cells to be ablated, and its own limitations. The primary advantage of laser-based ablation is the flexibility provided by the method: The operations can be performed in any cell pattern and at any time in development. Laser-based techniques permit manipulation of structures within cells, even to the molecular level. They can also be used for gene activation. However, laser ablation can be expensive, labor-intensive, and time-consuming. Although live cells can be difficult to image in Drosophila embryos, the use of vital fluorescent imaging methods has made laser-mediated cell manipulation methods more appealing; the methods are relatively straightforward. This article provides the information necessary for setting up and using a laser microscope for lasesr ablation studies.

Characteristic properties of laser ablation of translucent targets

NASA Astrophysics Data System (ADS)

Platonov, V. V.; Kochurin, E. A.; Osipov, V. V.; Lisenkov, V. V.; Zubarev, N. M.

2018-07-01

This study reveals the characteristic features of the laser ablation of the solid Nd:Y2O3 targets, such as the dynamics of the laser plume, the crater depth, and the weight and size distribution of liquid melt droplets. The ablation was initiated by the ytterbium fiber laser radiation pulses with constant energy (0.67 J) and with different power densities. The dependence on the power density of such parameters as the injection time of drops, mass distribution of drops, crater depth, and productivity of synthesis of nonopowder was revealed. To explain the formation of deep craters a model was proposed, stating that the formation of liquid droplets is a consequence of the Kelvin–Helmholtz instability’s appearing and developing on the border between the liquid melt on the crater’s wall and the vapor flow from the crater. The increment of this instability and its characteristic size was determined.

Plasmonic Nanodiamonds – Targeted Core-shell Type Nanoparticles for Cancer Cell Thermoablation

PubMed Central

Rehor, Ivan; Lee, Karin L.; Chen, Kevin; Hajek, Miroslav; Havlik, Jan; Lokajova, Jana; Masat, Milan; Slegerova, Jitka; Shukla, Sourabh; Heidari, Hamed; Bals, Sara

2015-01-01

Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell is designed and synthesized. The architecture of particles is analyzed and confirmed in detail using 3-dimensional transmission electron microscope tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor is demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser. PMID:25336437

Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9

PubMed Central

Mandal, Pankaj K.; Ferreira, Leonardo M. R.; Collins, Ryan; Meissner, Torsten B.; Boutwell, Christian L.; Friesen, Max; Vrbanac, Vladimir; Garrison, Brian S.; Stortchevoi, Alexei; Bryder, David; Musunuru, Kiran; Brand, Harrison; Tager, Andrew M.; Allen, Todd M.; Talkowski, Michael E.; Rossi, Derrick J.; Cowan, Chad A.

2014-01-01

SUMMARY Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9 mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4+ T cells and CD34+ hematopoietic stem and progenitor cells (HSPCs). Use of single RNA guides led to highly efficient mutagenesis in HSPCs but not in T cells. A dual guide approach improved gene deletion efficacy in both cell types. HSPCs that had undergone genome editing with CRISPR/Cas9 retained multi-lineage potential. We examined predicted on- and off-target mutations via target capture sequencing in HSPCs and observed low levels of off-target mutagenesis at only one site. These results demonstrate that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy. PMID:25517468

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation

PubMed Central

Burke, Caitlin W.; Price, Richard J.

2010-01-01

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas. PMID:21206463

Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

PubMed

Burke, Caitlin W; Price, Richard J

2010-12-15

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Generation Of Functional Insulin-Producing Cells In The Gut By Foxo1 Ablation

PubMed Central

Talchai, Chutima; Xuan, Shouhong; Kitamura, Tadahiro; DePinho, Ronald A.; Accili, Domenico

2012-01-01

Restoration of regulated insulin secretion is the ultimate goal of type 1 diabetes therapy. Here we show that, surprisingly, somatic ablation of Foxo1 in Neurog3+ enteroendocrine progenitor cells gives rise to gut insulin-positive cells (Ins+) that express markers of mature β-cells, and secrete bioactive insulin as well as C-peptide in response to glucose and sulfonylureas. Lineage tracing experiments show that gut Ins+ cells arise cell-autonomously from Foxo1-deficient cells. Inducible Foxo1 ablation in adult mice also results in the generation of gut Ins+ cells. Following ablation by the β-cell toxin, streptozotocin, gut Ins+ cells regenerate and produce insulin, reversing hyperglycemia in mice. The data indicate that Neurog3+ enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins+ cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes. PMID:22406641

Bone Marrow Cells Expressing Clara Cell Secretory Protein Increase Epithelial Repair After Ablation of Pulmonary Clara Cells

PubMed Central

Bustos, Martha L; Mura, Marco; Marcus, Paula; Hwang, David; Ludkovski, Olga; Wong, Amy P; Waddell, Thomas K

2013-01-01

We have previously reported a subpopulation of bone marrow cells (BMC) that express Clara cell secretory protein (CCSP), generally felt to be specific to lung Clara cells. Ablation of lung Clara cells has been reported using a transgenic mouse that expresses thymidine kinase under control of the CCSP promoter. Treatment with ganciclovir results in permanent elimination of CCSP+ cells, failure of airway regeneration, and death. To determine if transtracheal delivery of wild-type bone marrow CCSP+ cells is beneficial after ablation of lung CCSP+ cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP+ or CCSP− BMC. Compared with mice administered CCSP− cells, mice treated with CCSP+ cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. Although donor CCSP+ cells did not substantially repopulate the airway, their administration resulted in increased host ciliated cells, better preservation of airway epithelium, reduction of inflammatory cells, and an increase in animal survival time. Administration of CCSP+ BMC is beneficial after permanent ablation of lung Clara cells by increasing bronchial epithelial repair. Therefore, CCSP+ BMC could be important for treatment of lung diseases where airways re-epithelialization is compromised. PMID:23609017

Ablation of film stacks in solar cell fabrication processes

DOEpatents

Harley, Gabriel; Kim, Taeseok; Cousins, Peter John

2013-04-02

A dielectric film stack of a solar cell is ablated using a laser. The dielectric film stack includes a layer that is absorptive in a wavelength of operation of the laser source. The laser source, which fires laser pulses at a pulse repetition rate, is configured to ablate the film stack to expose an underlying layer of material. The laser source may be configured to fire a burst of two laser pulses or a single temporally asymmetric laser pulse within a single pulse repetition to achieve complete ablation in a single step.

Impact of High-Z Coatings on the Ablation Pressure of Laser Driven Targets.

NASA Astrophysics Data System (ADS)

Mostovych, Andrew; Oh, Jaechul; Schmitt, Andrew; Weaver, James

2007-11-01

Recent hydrodynamic experiments [1] with planar high-Z coated targets at the Naval Research Laboratory and spherical implosion experiments with high-Z coated shell targets [2] at the Omega facility all show significant improvement in target stability as a result of the high-Z coatings. For better understanding of the hydrodynamic processes it is important to know the changes in ablation pressure as a result of the high-Z layers. Using the Nike Laser, we have conducted new experiments to measure the change in shock speed of planar CH targets that are irradiated with and without the presence of a 200 Ang. gold high-Z coating. The evolution of shock propagation inside the targets is diagnosed with VISAR probing while average shock velocities are also measured by shock breakout detection from the stepped rear surface of the targets. We find that the high-Z layers produce a time dependent ablation pressure which is detected via the observation of non-steady shocks in the targets. Experimental results and comparisons to hydrodynamic simulations will be presented. Work supported by U. S. Department of Energy. [1] S.P. Obenschain et al., Phys. Plasmas 9, 2234 (2002). [2] A.N. Mostovych et al., APS Abstracts DPPFO3002M, (2005).

Surface Modification of ICF Target Capsules by Pulsed Laser Ablation

DOE PAGES

Carlson, Lane C.; Johnson, Michael A.; Bunn, Thomas L.

2016-06-30

Topographical modifications of spherical surfaces are imprinted on National Ignition Facility (NIF) target capsules by extending the capabilities of a recently developed full surface (4π) laser ablation and mapping apparatus. The laser ablation method combines the precision, energy density and long reach of a focused laser beam to pre-impose sinusoidal modulations on the outside surface of High Density Carbon (HDC) capsules and the inside surface of Glow Discharge Polymer (GDP) capsules. Sinusoidal modulations described in this paper have sub-micron to 10’s of microns vertical scale and wavelengths as small as 30 μm and as large as 200 μm. The modulatedmore » patterns are created by rastering a focused laser fired at discrete capsule surface locations for a specified number of pulses. The computer program developed to create these raster patterns uses inputs such as laser beam intensity profile, the material removal function, the starting surface figure and the desired surface figure. The patterns are optimized to minimize surface roughness. Lastly, in this paper, simulated surfaces are compared with actual ablated surfaces measured using confocal microscopy.« less

Gold nanorods coupled with upconverting nanophosphors for targeted thermal ablation and imaging of bladder cancer cells (Conference Presentation)

NASA Astrophysics Data System (ADS)

Cho, Suehyun K.; Su, Lih-Jen; Flaig, Thomas W.; Park, Wounjhang

2016-09-01

NaYF4:Yb3+,Er3+ upconverting nanophosphors (UCNPs) are robust and stable nanoparticles that absorb near-infrared (NIR) photons and emit green and red visible photons through energy transfer upconversion. This mechanism provides UCNPs several advantages as a bioimaging agent over traditional fluorescence imaging agent in that NIR excitation allows high-contrast imaging without autofluorescence and that they can be used for deep-tissue imaging. However, additional surface modification of UCNPs is necessary for them to be biocompatible. We use an amphiphilic polymer (poly(maleic anhydride-alt-octadecene) (PMAO) and a hetero-functional polyethylene glycol with amine and thiol ends (NH2-PEG-SH)) to make the UCNPs water-soluble. This reaction yields a carboxylic group that allows functionalization with anti-epidermal growth factor receptor (aEGFR), which provides specific binding of UCNPs to EGFR-expressing bladder cancer cells. Additionally, the thiol ends of the PEGylated UCNPs are able to bind with gold nanorods (AuNRs) to create UCNP-AuNR complexes. The localized surface plasmon of the AuNR then allow localized heating of HTB9 bladder cancer cells, enabling in situ cell killing upon detection by UCNP fluorescence. Here, we report a successful synthesis, surface modification and conjugation of aEGFR functionalized UCNP-AuNR complexes and in vitro imaging and thermal ablation studies using them. Synthesis and surface modification of UCNP-AuNR complexes are confirmed by electron microscopy. Then, a combination of brightfield, NIR confocal fluorescence, and darkfield microscopy on the UCNP-AuNR treated bladder cancer cells revealed successful cancer targeting and imaging capabilities of the complex. Finally, cell viability assay showed that NIR irradiation of UCNP-AuNR conjugated cells resulted highly selective cell killing.

Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by "electric field sinks".

PubMed

Golberg, Alexander; Bruinsma, Bote G; Uygun, Basak E; Yarmush, Martin L

2015-02-16

Irreversible electroporation (IRE) is an emerging, minimally invasive technique for solid tumors ablation, under clinical investigation for cancer therapy. IRE affects only the cell membrane, killing cells while preserving the extracellular matrix structure. Current reports indicate tumors recurrence rate after IRE averaging 31% of the cases, of which 10% are local recurrences. The mechanisms for these recurrences are not known and new explanations for incomplete cell death are needed. Using finite elements method for electric field distribution, we show that presence of vascular structures with blood leads to the redistribution of electric fields leading to the areas with more than 60% reduced electric field strength in proximity to large blood vessels and clustered vessel structures. In an in vivo rat model of liver IRE ablation, we show that cells located in the proximity of larger vessel structures and in proximity of clustered vessel structures appear less affected by IRE ablation than cells in the tissue parenchyma or in the proximity of small, more isolated vessels. These findings suggest a role for "electric field sinks" in local tumors recurrences after IRE and emphasize the importance of the precise mapping of the targeted organ structure and conductivity for planning of electroporation procedures.

Subtotal Ablation of Parietal Epithelial Cells Induces Crescent Formation

PubMed Central

Sicking, Eva-Maria; Fuss, Astrid; Uhlig, Sandra; Jirak, Peggy; Dijkman, Henry; Wetzels, Jack; Engel, Daniel R.; Urzynicok, Torsten; Heidenreich, Stefan; Kriz, Wilhelm; Kurts, Christian; Ostendorf, Tammo; Floege, Jürgen; Smeets, Bart

2012-01-01

Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established an inducible transgenic mouse to allow subtotal ablation of PECs. Proteinuria developed during doxycycline-induced cellular ablation but fully reversed 26 days after termination of doxycycline administration. The ablation of PECs was focal, with only 30% of glomeruli exhibiting histologic changes; however, the number of PECs was reduced up to 90% within affected glomeruli. Ultrastructural analysis revealed disruption of PEC plasma membranes with cytoplasm shedding into Bowman’s space. Podocytes showed focal foot process effacement, which was the most likely cause for transient proteinuria. After >9 days of cellular ablation, the remaining PECs formed cellular extensions to cover the denuded Bowman’s capsule and expressed the activation marker CD44 de novo. The induced proliferation of PECs persisted throughout the observation period, resulting in the formation of typical cellular crescents with periglomerular infiltrate, albeit without accompanying proteinuria. In summary, subtotal ablation of PECs leads the remaining PECs to react with cellular activation and proliferation, which ultimately forms cellular crescents. PMID:22282596

Epicardial Radiofrequency Ablation Failure During Ablation Procedures for Ventricular Arrhythmias: Reasons and Implications for Outcomes.

PubMed

Baldinger, Samuel H; Kumar, Saurabh; Barbhaiya, Chirag R; Mahida, Saagar; Epstein, Laurence M; Michaud, Gregory F; John, Roy; Tedrow, Usha B; Stevenson, William G

2015-12-01

Radiofrequency ablation (RFA) from the epicardial space for ventricular arrhythmias is limited or impossible in some cases. Reasons for epicardial ablation failure and the effect on outcome have not been systematically analyzed. We assessed reasons for epicardial RFA failure relative to the anatomic target area and the type of heart disease and assessed the effect of failed epicardial RFA on outcome after ablation procedures for ventricular arrhythmias in a large single-center cohort. Epicardial access was attempted during 309 ablation procedures in 277 patients and was achieved in 291 procedures (94%). Unlimited ablation in an identified target region could be performed in 181 cases (59%), limited ablation was possible in 22 cases (7%), and epicardial ablation was deemed not feasible in 88 cases (28%). Reasons for failed or limited ablation were unsuccessful epicardial access (6%), failure to identify an epicardial target (15%), proximity to a coronary artery (13%), proximity to the phrenic nerve (6%), and complications (<1%). Epicardial RFA was impeded in the majority of cases targeting the left ventricular summit region. Acute complications occurred in 9%. The risk for acute ablation failure was 8.3× higher (4.5-15.0; P<0.001) after no or limited epicardial RFA compared with unlimited RFA, and patients with unlimited epicardial RFA had better recurrence-free survival rates (P<0.001). Epicardial RFA for ventricular arrhythmias is often limited even when pericardial access is successful. Variability of success is dependent on the target area, and the presence of factors limiting ablation is associated with worse outcomes. © 2015 American Heart Association, Inc.

Nanosecond laser ablation of target Al in a gaseous medium: explosive boiling

NASA Astrophysics Data System (ADS)

Mazhukin, V. I.; Mazhukin, A. V.; Demin, M. M.; Shapranov, A. V.

2018-03-01

An approximate mathematical description of the processes of homogeneous nucleation and homogeneous evaporation (explosive boiling) of a metal target (Al) under the influence of ns laser radiation is proposed in the framework of the hydrodynamic model. Within the continuum approach, a multi-phase, multi-front hydrodynamic model and a computational algorithm are designed to simulate nanosecond laser ablation of the metal targets immersed in gaseous media. The proposed approach is intended for modeling and detailed analysis of the mechanisms of heterogeneous and homogeneous evaporation and their interaction with each other. It is shown that the proposed model and computational algorithm allow modeling of interrelated mechanisms of heterogeneous and homogeneous evaporation of metals, manifested in the form of pulsating explosive boiling. Modeling has shown that explosive evaporation in metals is due to the presence of a near-surface temperature maximum. It has been established that in nanosecond pulsed laser ablation, such exposure regimes can be implemented in which phase explosion is the main mechanism of material removal.

CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma: specific technical aspects and clinical results.

PubMed

Sommer, C M; Lemm, G; Hohenstein, E; Bellemann, N; Stampfl, U; Goezen, A S; Rassweiler, J; Kauczor, H U; Radeleff, B A; Pereira, P L

2013-06-01

This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. We included 22 consecutive patients (3 women; age 74.2 ± 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 ± 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 ± 13.6 min and 43.7 ± 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 ± 8.8 months, local recurrence-free survival was 14.4 ± 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 ± 16.6 ml/min/1.73 m(2) before RF ablation vs. 47.2 ± 11.9 ml/min/1.73 m(2) after RF ablation; not significant). CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model.

PubMed

Yang, Xiaoping; Su, Lih-Jen; La Rosa, Francisco G; Smith, Elizabeth Erin; Schlaepfer, Isabel R; Cho, Suehyun K; Kavanagh, Brian; Park, Wounjhang; Flaig, Thomas W

2017-07-27

Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. The optimal approach for an individual treatment was 2.1 W/cm 2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity ( n  = 16) compared to mice treated with laser alone ( n  = 14) at the end of the study ( p  = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels ( p  = 0.045). Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.

Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by “electric field sinks”

PubMed Central

Golberg, Alexander; Bruinsma, Bote G.; Uygun, Basak E.; Yarmush, Martin L.

2015-01-01

Irreversible electroporation (IRE) is an emerging, minimally invasive technique for solid tumors ablation, under clinical investigation for cancer therapy. IRE affects only the cell membrane, killing cells while preserving the extracellular matrix structure. Current reports indicate tumors recurrence rate after IRE averaging 31% of the cases, of which 10% are local recurrences. The mechanisms for these recurrences are not known and new explanations for incomplete cell death are needed. Using finite elements method for electric field distribution, we show that presence of vascular structures with blood leads to the redistribution of electric fields leading to the areas with more than 60% reduced electric field strength in proximity to large blood vessels and clustered vessel structures. In an in vivo rat model of liver IRE ablation, we show that cells located in the proximity of larger vessel structures and in proximity of clustered vessel structures appear less affected by IRE ablation than cells in the tissue parenchyma or in the proximity of small, more isolated vessels. These findings suggest a role for “electric field sinks” in local tumors recurrences after IRE and emphasize the importance of the precise mapping of the targeted organ structure and conductivity for planning of electroporation procedures. PMID:25684630

Generation of Demyelination Models by Targeted Ablation of Oligodendrocytes in the Zebrafish CNS

PubMed Central

Chung, Ah-Young; Kim, Pan-Soo; Kim, Suhyun; Kim, Eunmi; Kim, Dohyun; Jeong, Inyoung; Kim, Hwan-Ki; Ryu, Jae-Ho; Kim, Cheol-Hee; Choi, June; Seo, Jin-Ho; Park, Hae-Chul

2013-01-01

Demyelination is the pathological process by which myelin sheaths are lost from around axons, and is usually caused by a direct insult targeted at the oligodendrocytes in the vertebrate central nervous system (CNS). A demyelinated CNS is usually remyelinated by a population of oligodendrocyte progenitor cells, which are widely distributed throughout the adult CNS. However, myelin disruption and remyelination failure affect the normal function of the nervous system, causing human diseases such as multiple sclerosis. In spite of numerous studies aimed at understanding the remyelination process, many questions still remain unanswered. Therefore, to study remyelination mechanisms in vivo, a demyelination animal model was generated using a transgenic zebrafish system in which oligodendrocytes are conditionally ablated in the larval and adult CNS. In this transgenic system, bacterial nitroreductase enzyme (NTR), which converts the prodrug metronidazole (Mtz) into a cytotoxic DNA cross-linking agent, is expressed in oligodendrocyte lineage cells under the control of the mbp and sox10 promoter. Exposure of transgenic zebrafish to Mtz-containing media resulted in rapid ablation of oligodendrocytes and CNS demyelination within 48 h, but removal of Mtz medium led to efficient remyelination of the demyelinated CNS within 7 days. In addition, the demyelination and remyelination processes could be easily observed in living transgenic zebrafish by detecting the fluorescent protein, mCherry, indicating that this transgenic system can be used as a valuable animal model to study the remyelination process in vivo, and to conduct high-throughput primary screens for new drugs that facilitate remyelination. PMID:23807048

Pulse laser ablation of Au, Ag, and Cu metal targets in liquid for nanoparticle production

NASA Astrophysics Data System (ADS)

Herbani, Y.; Irmaniar; Nasution, R. S.; Mujtahid, F.; Masse, S.

2018-03-01

We have fabricated metal and oxide nanoparticles using pulse laser ablation of Au, Ag, and Cu metal targets immersed in water. While laser ablation of Au and Ag targets in water produced metal nanoparticles which were stable for a month even without any dispersant, we found CuO nanoparticles for Cu target due to rapid oxidation of Cu in water resulted in its poor stability. Au, Ag, and CuO nanoparticles production were barely identified by naked eyes for their distinctive colour of red, yellow, and dark green colloidal suspensions, respectively. It was also verified using UV-Vis spectrometer that Au, Ag, and CuO colloidal nanoparticles have their respective surface plasmon resonance at 520, 400, and 620 nm. TEM observation showed that particle sizes for all the fabricated nanoparticles were in the range of 20 – 40 nm with crystalline structures.

Live imaging of targeted cell ablation in Xenopus: a new model to study demyelination and repair

PubMed Central

Kaya, F.; Mannioui, A.; Chesneau, A.; Sekizar, S.; Maillard, E.; Ballagny, C.; Houel-Renault, L.; Du Pasquier, D.; Bronchain, O.; Holtzmann, I.; Desmazieres, A.; Thomas, J.-L.; Demeneix, B. A.; Brophy, P. J.; Zalc, B.; Mazabraud, A.

2012-01-01

Live imaging studies of the processes of demyelination and remyelination have so far been technically limited in mammals. We have thus generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the central nervous system (CNS). In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein (MBP) regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the E. coli nitroreductase (NTR) selection enzyme. This enzyme converts the innocuous pro-drug metronidazole (MTZ) to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR tadpoles display a graded oligodendrocyte ablation in response to MTZ, which depends on the exposure time to MTZ. MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage. After cessation of MTZ treatment, remyelination proceeded spontaneously, but was strongly accelerated by retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR line as a novel in vivo model for the study of demyelination/remyelination processes and for large-scale screens of therapeutic agents promoting myelin repair. PMID:22973012

Ablation of post-surgical intra-atrial reentrant tachycardia. Predilection target sites and mapping approach.

PubMed

Anné, W; van Rensburg, H; Adams, J; Ector, H; Van de Werf, F; Heidbüchel, H

2002-10-01

Atrial arrhythmias are a frequent complication of atrial surgery. The location of these tachycardias is very diverse due to the individual difference in the original anatomy, surgical corrections, and effects of atrial fibrosis. Nevertheless some recurrent patterns are emerging. Forty-five patients underwent 51 ablation procedures between September 1995 and March 2001 using conventional mapping and temperature-controlled ablation. A duadecapolar catheter was swept from anterior to posterior in the right (and/or left) atrium, allowing for rapid mapping followed by entrainment confirmation. Twenty-eight patients had corrected congenital heart disease, 17 surgery for acquired heart disease. One hundred and sixteen arrhythmias were found, 86 circuits were targeted, 81 with success (94%). Despite the heterogeneous anatomy, the same targets were often encountered: the posterior isthmus between the inferior vena cava and the tricuspid ring (62%), the gap between the inferior vena cava and the atriotomy scar (49%), and the region around the atriopulmonary connection in Fontans (two out of four patients). After a mean follow-up of 24 months, 13 patients had a recurrent arrhythmia (29%) after their last procedure. There was a significant association between the number of circuits found during the initial procedure and the likelihood of recurrent arrhythmias. Knowledge of anatomical predilection sites and mapping the right (and/or left) atrium with a 'sweeping Halo technique' allow for effective ablation of most post-surgical atrial tachycardias. Severely damaged atria with multiple arrhythmias may require 'preventive' ablation of all recognizable channels.

Nanoparticle mediated ablation of breast cancer cells using a nanosecond pulsed electric field

NASA Astrophysics Data System (ADS)

Burford, Christopher

In the past, both nanomaterials and various heating modalities have been researched as means for treating cancers. However, many of the current methodologies have the flaws of inconsistent tumor ablation and significant destruction of healthy cells. Based on research performed using constant radiofrequency electric fields and metallic nanoparticles (where cell necrosis is induced by the heating of these nanoparticles) we have developed a modality that simlarly uses functionalized metallic nanoparticles, specific for the T47D breast cancer cell line, and nanosecond pulsed electric fields as the hyperthermic inducer. Using both iron oxide and gold nanoparticles the results of our pilot studies indicated that up to 90% of the cancer cells were ablated given the optimal treatment parameters. These quantities of ablated cells were achieved using a cumulative exposure time 6 orders of magnitude less than most in vitro radiofrequency electric field studies.

Tumor abolition and antitumor immunostimulation by physico-chemical tumor ablation.

PubMed

Keisari, Yona

2017-01-01

Tumor ablation by thermal, chemical and radiological sources has received substantial attention for the treatment of many localized malignancies. The primary goal of most ablation procedures is to eradicate all viable malignant cells within a designated target volume through the application of energy or chemicals. Methods such as radiotherapy, chemical and biological ablation, photodynamic therapy, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and electric-based ablation have been developed for focal malignancies. In recent years a large volume of data emerged on the effect of in situ tumor destruction (ablation) on inflammatory and immune components resulting in systemic anti-tumor reactions. It is evident that in situ tumor ablation can involve tumor antigen release, cross presentation and the release of DAMPS and make the tumor its own cellular vaccine. Tumor tissue destruction by in situ ablation may stimulate antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) attracted to this microenvironment, will undergo maturation after internalizing cellular debris containing tumor antigens and will be exposed to damage associated molecular pattern (DAMP). Mature DCs can mediate antigen-specific cellular immunity via presentation of processed antigens to T cells. The immunomodulatory properties, exhibited by in situ ablation could portend a future collaboration with immunotherapeutic measures. In this review are summarized and discuss the preclinical and clinical studies pertinent to the phenomena of stimulation of specific anti-tumor immunity by various ablation modalities and the immunology related measures used to boost this response.

Laser ablation of Drosophila embryonic motoneurons causes ectopic innervation of target muscle fibers

NASA Technical Reports Server (NTRS)

Chang, T. N.; Keshishian, H.

1996-01-01

We have tested the effects of neuromuscular denervation in Drosophila by laser-ablating the RP motoneurons in intact embryos before synaptogenesis. We examined the consequences of this ablation on local synaptic connectivity in both 1st and 3rd instar larvae. We find that the partial or complete loss of native innervation correlates with the appearance of alternate inputs from neighboring motor endings and axons. These collateral inputs are found at ectopic sites on the denervated target muscle fibers. The foreign motor endings are electrophysiologically functional and are observed on the denervated muscle fibers by the 1st instar larval stage. Our data are consistent with the existence of a local signal from the target environment, which is regulated by innervation and influences synaptic connectivity. Our results show that, despite the stereotypy of Drosophila neuromuscular connections, denervation can induce local changes in connectivity in wild-type Drosophila, suggesting that mechanisms of synaptic plasticity may also be involved in normal Drosophila neuromuscular development.

Trapped ventricle after laser ablation of a subependymal giant cell astrocytoma complicated by intraventricular gadolinium extravasation: case report.

PubMed

Karsy, Michael; Patel, Daxa M; Bollo, Robert J

2018-05-01

Magnetic resonance imaging-guided stereotactic laser ablation of intracranial targets, including brain tumors, has expanded dramatically over the past decade, but there have been few reports of complications, especially those occurring in a delayed fashion. Laser ablation of subependymal giant cell astrocytomas (SEGAs) is an attractive alternative to maintenance immunotherapy in some children with tuberous sclerosis complex (TSC); however, the effect of treatment on disease progression and the nature and frequency of potential complications remains largely unknown. The authors report the case of a 5-year-old boy with TSC who underwent stereotactic laser ablation of a SEGA at the right foramen of Monro on 2 separate occasions. After the second ablation, immediate posttreatment MRI revealed gadolinium extravasation from the tumor into the lateral ventricle. Nine months later, the patient presented with papilledema and delayed obstructive hydrocephalus secondary to intraventricular adhesions causing a trapped right lateral ventricle. This was successfully treated with endoscopic septostomy. The authors discuss the potential cause and clinical management of a delayed complication not previously reported after a relatively novel surgical therapy.

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model.

PubMed

Huisman, Merel; Staruch, Robert M; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A; Burns, Dennis K; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

PubMed Central

Huisman, Merel; Staruch, Robert M.; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A.; Burns, Dennis K.; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Purpose Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Methods Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining. Results All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Conclusion Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may

Thermal Ablation of T1c Renal Cell Carcinoma: A Comparative Assessment of Technical Performance, Procedural Outcome, and Safety of Microwave Ablation, Radiofrequency Ablation, and Cryoablation.

PubMed

Zhou, Wenhui; Arellano, Ronald S

2018-04-06

To evaluate perioperative outcomes of thermal ablation with microwave (MW), radiofrequency (RF), and cryoablation for stage T1c renal cell carcinoma (RCC). A retrospective analysis of 384 patients (mean age, 71 y; range, 22-88 y) was performed between October 2006 and October 2016. Mean radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines; preoperative aspects and dimensions used for anatomic classification; and centrality index scores were 6.3, 7.9, and 2.7, respectively. Assessment of pre- and postablation serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate was performed to assess functional outcomes. Linear regression analyses were performed to compare sedation medication dosages among the three treatment cohorts. Univariable and multivariable logistic regression analyses were performed to compare rates of residual disease and complications among treatment modalities. A total of 437 clinical stage T1N0M0 biopsy-proven RCCs measuring 1.2-6.9 cm were treated with computed tomography (CT)-guided MW ablation (n = 44; 10%), RF ablation (n = 347; 79%), or cryoablation (n = 46; 11%). There were no significant differences in patient demographic or tumor characteristics among cohorts. Complication rates and immediate renal function changes were similar among the three ablation modalities (P = .46 and P = .08, respectively). MW ablation was associated with significantly decreased ablation time (P < .05), procedural time (P < .05), and dosage of sedative medication (P < .05) compared with RF ablation and cryoablation. CT-guided percutaneous MW ablation is comparable to RF ablation or cryoablation for the treatment of stage T1N0M0 RCC with regard to treatment response and is associated with shorter treatment times and less sedation than RF ablation or cryoablation. In addition, the safety profile of CT-guided MW ablation is noninferior to those of RF ablation or

Ablation of breast cancer cells using trastuzumab-functionalized multi-walled carbon nanotubes and trastuzumab-diphtheria toxin conjugate.

PubMed

Oraki Kohshour, Mojtaba; Mirzaie, Sako; Zeinali, Majid; Amin, Mansour; Said Hakhamaneshi, Mohammad; Jalili, Ali; Mosaveri, Nader; Jamalan, Mostafa

2014-03-01

Trastuzumab (Herceptin(®) ) is a monoclonal antibody (mAb) for specific ablation of HER2-overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano-immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2-overexpressing SK-BR-3 and also HER2-negative MCF-7 cancer cell lines were examined. Cells treated with trastuzumab-MWCNT conjugates were irradiated with near-infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab-MWCNT and trastuzumab-DT conjugates were significantly efficient in the specific killing of SK-BR-3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab-DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT-immunoconjugates. In conclusion, our data demonstrated that trastuzumab-MWCNT is a promising nano-immunoconjugate for killing of HER2-overexpressing cancerous cells. © 2013 John Wiley & Sons A/S.

Txnip ablation reduces vascular smooth muscle cell inflammation and ameliorates atherosclerosis in apolipoprotein E knockout mice.

PubMed

Byon, Chang Hyun; Han, Tieyan; Wu, Judy; Hui, Simon T

2015-08-01

Inflammation of vascular smooth muscle cells (VSMC) is intimately linked to atherosclerosis and other vascular inflammatory disease. Thioredoxin interacting protein (Txnip) is a key regulator of cellular sulfhydryl redox and a mediator of inflammasome activation. The goals of the present study were to examine the impact of Txnip ablation on inflammatory response to oxidative stress in VSMC and to determine the effect of Txnip ablation on atherosclerosis in vivo. Using cultured VSMC, we showed that ablation of Txnip reduced cellular oxidative stress and increased protection from oxidative stress when challenged with oxidized phospholipids and hydrogen peroxide. Correspondingly, expression of inflammatory markers and adhesion molecules were diminished in both VSMC and macrophages from Txnip knockout mice. The blunted inflammatory response was associated with a decrease in NF-ĸB nuclear translocation. Loss of Txnip in VSMC also led to a dramatic reduction in macrophage adhesion to VSMC. In vivo data from Txnip-ApoE double knockout mice showed that Txnip ablation led to 49% reduction in atherosclerotic lesion in the aortic root and 71% reduction in the abdominal aorta, compared to control ApoE knockout mice. Our data show that Txnip plays an important role in oxidative inflammatory response and atherosclerotic lesion development in mice. The atheroprotective effect of Txnip ablation implicates that modulation of Txnip expression may serve as a potential target for intervention of atherosclerosis and inflammatory vascular disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Radiofrequency Ablation for Tumor-Related Massive Hematuria

PubMed Central

Neeman, Ziv; Sarin, Shawn; Coleman, Jonathan; Fojo, Tito; Wood, Bradford J.

2008-01-01

To determine whether radiofrequency (RF) ablation targeting the tumor-collecting system interface has a durable effect in patients with transfusion-dependent kidney tumor-related hematuria, four patients aged 61-71 years were successfully treated with RF ablation, with a mean follow up of 12 months. Baseline creatinine levels varied from 2.0 mg/dL to 3.7 mg/dL. All patients had received red blood cell transfusions in the days and hours before RF ablation. No subsequent surgical or interventional procedures were required for management of hematuria. Gross hematuria resolved in 24-48 hours in all four patients. Two of the patients are alive with stable renal function and two died of causes unrelated to treatment. RF ablation may be an effective therapeutic option for transfusion-dependent cancer-related hematuria in patients with renal insufficiency, solitary kidney, or comorbidities, or after failed conventional therapies in patients who are not candidates for surgery. PMID:15758142

Radiofrequency ablation for tumor-related massive hematuria.

PubMed

Neeman, Ziv; Sarin, Shawn; Coleman, Jonathan; Fojo, Tito; Wood, Bradford J

2005-03-01

To determine whether radiofrequency (RF) ablation targeting the tumor-collecting system interface has a durable effect in patients with transfusion-dependent kidney tumor-related hematuria, four patients aged 61-71 years were successfully treated with RF ablation, with a mean follow up of 12 months. Baseline creatinine levels varied from 2.0 mg/dL to 3.7 mg/dL. All patients had received red blood cell transfusions in the days and hours before RF ablation. No subsequent surgical or interventional procedures were required for management of hematuria. Gross hematuria resolved in 24-48 hours in all four patients. Two of the patients are alive with stable renal function and two died of causes unrelated to treatment. RF ablation may be an effective therapeutic option for transfusion-dependent cancer-related hematuria in patients with renal insufficiency, solitary kidney, or comorbidities, or after failed conventional therapies in patients who are not candidates for surgery.

Solar cell contact formation using laser ablation

DOEpatents

Harley, Gabriel; Smith, David D.; Cousins, Peter John

2015-07-21

The formation of solar cell contacts using a laser is described. A method of fabricating a back-contact solar cell includes forming a poly-crystalline material layer above a single-crystalline substrate. The method also includes forming a dielectric material stack above the poly-crystalline material layer. The method also includes forming, by laser ablation, a plurality of contacts holes in the dielectric material stack, each of the contact holes exposing a portion of the poly-crystalline material layer; and forming conductive contacts in the plurality of contact holes.

Solar cell contact formation using laser ablation

DOEpatents

Harley, Gabriel; Smith, David; Cousins, Peter

2012-12-04

The formation of solar cell contacts using a laser is described. A method of fabricating a back-contact solar cell includes forming a poly-crystalline material layer above a single-crystalline substrate. The method also includes forming a dielectric material stack above the poly-crystalline material layer. The method also includes forming, by laser ablation, a plurality of contacts holes in the dielectric material stack, each of the contact holes exposing a portion of the poly-crystalline material layer; and forming conductive contacts in the plurality of contact holes.

Solar cell contact formation using laser ablation

DOEpatents

Harley, Gabriel; Smith, David D.; Cousins, Peter John

2014-07-22

The formation of solar cell contacts using a laser is described. A method of fabricating a back-contact solar cell includes forming a poly-crystalline material layer above a single-crystalline substrate. The method also includes forming a dielectric material stack above the poly-crystalline material layer. The method also includes forming, by laser ablation, a plurality of contacts holes in the dielectric material stack, each of the contact holes exposing a portion of the poly-crystalline materiat layer; and forming conductive contacts in the plurality of contact holes.

Dual beam optical system for pulsed laser ablation film deposition

DOEpatents

Mashburn, Douglas N.

1996-01-01

A laser ablation apparatus having a laser source outputting a laser ablation beam includes an ablation chamber having a sidewall, a beam divider for dividing the laser ablation beam into two substantially equal halves, and a pair of mirrors for converging the two halves on a surface of the target from complementary angles relative to the target surface normal, thereby generating a plume of ablated material emanating from the target.

Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted

NASA Technical Reports Server (NTRS)

Farrell, E. R.; Keshishian, H.

1999-01-01

In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.

Dual beam optical system for pulsed laser ablation film deposition

DOEpatents

Mashburn, D.N.

1996-09-24

A laser ablation apparatus having a laser source outputting a laser ablation beam includes an ablation chamber having a sidewall, a beam divider for dividing the laser ablation beam into two substantially equal halves, and a pair of mirrors for converging the two halves on a surface of the target from complementary angles relative to the target surface normal, thereby generating a plume of ablated material emanating from the target. 3 figs.

Targeted Interneuron Ablation in the Mouse Hippocampus Can Cause Spontaneous Recurrent Seizures

PubMed Central

2017-01-01

Abstract The death of GABAergic interneurons has long been hypothesized to contribute to acquired epilepsy. These experiments tested the hypothesis that focal interneuron lesions cause acute seizures [i.e., status epilepticus (SE)] and/or chronic epilepsy [i.e., persistent spontaneous recurrent seizures (SRSs)]. To selectively ablate interneurons, Gad2-ires-Cre mice were injected unilaterally in the CA1 area of the dorsal hippocampus with an adeno-associated virus containing the diphtheria toxin receptor (DTR). Simultaneously, an electrode, connected to a miniature telemetry device, was positioned at the injection site for chronic recordings of local field potentials (LFPs). Two weeks after virus transfection, intraperitoneal injection of DT consistently caused focal, specific, and extensive ablation of interneurons. Long-term, continuous monitoring revealed that all mice with DT-induced interneuron lesions had SRSs. Seizures lasted tens of seconds and interseizure intervals were several hours (or days); therefore, these interneuron lesions did not induce SE. The SRSs occurred 3-5 d after DT treatment, which is the estimated time required for DT-induced cell death; therefore, induction of SRSs occurred without the latent period typical of acquired epilepsy. In five of six DT-treated mice, SRSs stopped within days, suggesting that the DT-induced interneuron lesions did not usually cause epilepsy. In one mouse, however, SRSs occurred for ≥34 d after interneuron ablation, similar to epilepsy after experimental SE. Sham control mice had no detectable seizures, confirming that the SRSs were due to ablation of interneurons. These data show that selective interneuron ablation consistently caused SRSs but not SE; and, at least under the conditions used here, interneuron lesions rarely led to persistent SRSs (i.e., epilepsy). PMID:28785726

Laser ablation of a silicon target in chloroform: formation of multilayer graphite nanostructures

NASA Astrophysics Data System (ADS)

Abderrafi, Kamal; García-Calzada, Raúl; Sanchez-Royo, Juan F.; Chirvony, Vladimir S.; Agouram, Saïd; Abargues, Rafael; Ibáñez, Rafael; Martínez-Pastor, Juan P.

2013-04-01

With the use of high-resolution transmission electron microscopy, selected area electron diffraction and x-ray photoelectron spectroscopy methods of analysis we show that the laser ablation of a Si target in chloroform (CHCl3) by nanosecond UV pulses (40 ns, 355 nm) results in the formation of about 50-80 nm core-shell nanoparticles with a polycrystalline core composed of small (5-10 nm) Si and SiC mono-crystallites, the core being coated by several layers of carbon with the structure of graphite (the shell). In addition, free carbon multilayer nanostructures (carbon nano-onions) are also found in the suspension. On the basis of a comparison with similar laser ablation experiments implemented in carbon tetrachloride (CCl4), where only bare (uncoated) Si nanoparticles are produced, we suggest that a chemical (solvent decomposition giving rise to highly reactive CH-containing radicals) rather than a physical (solvent atomization followed by carbon nanostructure formation) mechanism is responsible for the formation of graphitic shells. The silicon carbonization process found for the case of laser ablation in chloroform may be promising for silicon surface protection and functionalization.

Genetic ablation of root cap cells in Arabidopsis

NASA Technical Reports Server (NTRS)

Tsugeki, R.; Fedoroff, N. V.

1999-01-01

The root cap is increasingly appreciated as a complex and dynamic plant organ. Root caps sense and transmit environmental signals, synthesize and secrete small molecules and macromolecules, and in some species shed metabolically active cells. However, it is not known whether root caps are essential for normal shoot and root development. We report the identification of a root cap-specific promoter and describe its use to genetically ablate root caps by directing root cap-specific expression of a diphtheria toxin A-chain gene. Transgenic toxin-expressing plants are viable and have normal aerial parts but agravitropic roots, implying loss of root cap function. Several cell layers are missing from the transgenic root caps, and the remaining cells are abnormal. Although the radial organization of the roots is normal in toxin-expressing plants, the root tips have fewer cytoplasmically dense cells than do wild-type root tips, suggesting that root meristematic activity is lower in transgenic than in wild-type plants. The roots of transgenic plants have more lateral roots and these are, in turn, more highly branched than those of wild-type plants. Thus, root cap ablation alters root architecture both by inhibiting root meristematic activity and by stimulating lateral root initiation. These observations imply that the root caps contain essential components of the signaling system that determines root architecture.

Nonthermal ablation of deep brain targets: A simulation study on a large animal model

PubMed Central

Top, Can Barış; White, P. Jason; McDannold, Nathan J.

2016-01-01

Purpose: Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low-duty-cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood–brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects. Methods: The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI-guided FUS system. Low-duty-cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models. Results: The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive

Ablation of human skin mast cells in situ by lysosomotropic agents.

PubMed

Hagforsen, Eva; Paivandy, Aida; Lampinen, Maria; Weström, Simone; Calounova, Gabriela; Melo, Fabio R; Rollman, Ola; Pejler, Gunnar

2015-07-01

Mast cells are known to have a detrimental impact on numerous types of inflammatory skin diseases such as contact dermatitis, atopic eczema and cutaneous mastocytosis. Regimens that dampen skin mast cell-mediated activities can thus offer an attractive therapeutic option under such circumstances. As mast cells are known to secrete a large array of potentially pathogenic compounds, both from preformed stores in secretory lysosomes (granules) and after de novo synthesis, mere inhibition of degranulation or interference with individual mast cell mediators may not be sufficient to provide an effective blockade of harmful mast cell activities. An alternative strategy may therefore be to locally reduce skin mast cell numbers. Here, we explored the possibility of using lysosomotropic agents for this purpose, appreciating the fact that mast cell granules contain bioactive compounds prone to trigger apoptosis if released into the cytosolic compartment. Based on this principle, we show that incubation of human skin punch biopsies with the lysosomotropic agents siramesine or Leu-Leu methyl ester preferably ablated the mast cell population, without causing any gross adverse effects on the skin morphology. Subsequent analysis revealed that mast cells treated with lysosomotropic agents predominantly underwent apoptotic rather than necrotic cell death. In summary, this study raises the possibility of using lysosomotropic agents as a novel approach to targeting deleterious mast cell populations in cutaneous mastocytosis and other skin disorders negatively influenced by mast cells. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Toward single-cell analysis by plume collimation in laser ablation electrospray ionization mass spectrometry.

PubMed

Stolee, Jessica A; Vertes, Akos

2013-04-02

Ambient ionization methods for mass spectrometry have enabled the in situ and in vivo analysis of biological tissues and cells. When an etched optical fiber is used to deliver laser energy to a sample in laser ablation electrospray ionization (LAESI) mass spectrometry, the analysis of large single cells becomes possible. However, because in this arrangement the ablation plume expands in three dimensions, only a small portion of it is ionized by the electrospray. Here we show that sample ablation within a capillary helps to confine the radial expansion of the plume. Plume collimation, due to the altered expansion dynamics, leads to greater interaction with the electrospray plume resulting in increased ionization efficiency, reduced limit of detection (by a factor of ~13, reaching 600 amol for verapamil), and extended dynamic range (6 orders of magnitude) compared to conventional LAESI. This enhanced sensitivity enables the analysis of a range of metabolites from small cell populations and single cells in the ambient environment. This technique has the potential to be integrated with flow cytometry for high-throughput metabolite analysis of sorted cells.

Life-threatening hematuria requiring transcatheter embolization following radiofrequency ablation of renal cell carcinoma.

PubMed

Roach, H; Whittlestone, T; Callaway, M P

2006-01-01

Radiofrequency ablation is increasingly being acknowledged as a valid treatment for renal cell carcinoma in patients in whom definitive curative resection is deemed either undesirable or unsafe. A number of published series have shown the technique to have encouraging results and relatively low complication rates. In this article, we report a case of delayed life-threatening hematuria requiring transcatheter embolization of a bleeding intrarenal artery in a patient who had undergone imaging-guided radiofrequency ablation of a 3 cm renal cell carcinoma. To our knowledge, such a complication has not been reported previously.

FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation

PubMed Central

Szlachcic, Anna; Pala, Katarzyna; Zakrzewska, Malgorzata; Jakimowicz, Piotr; Wiedlocha, Antoni; Otlewski, Jacek

2012-01-01

Fibroblast growth factor receptors (FGFRs) are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we designed, constructed, and characterized FGFR-targeted gold nanoconjugates suitable for infrared-induced thermal ablation (localized heating leading to cancer cell death) based on gold nanoparticles (AuNPs). We showed that a recombinant ligand of all FGFRs, human fibroblast growth factor 1 (FGF1), can be used as an agent targeting covalently bound AuNPs to cancer cells overexpressing FGFRs. To assure thermal stability, protease resistance, and prolonged half-life of the targeting protein, we employed highly stable FGF1 variant that retains the biological activities of the wild type FGF1. Novel FGF1 variant, AuNP conjugates are specifically internalized only by the cells expressing FGFRs, and they significantly reduce their viability after irradiation with near-infrared light (down to 40% of control cell viability), whereas the proliferation potential of cells lacking FGFRs is not affected. These results demonstrate the feasibility of FGF1-coated AuNPs for targeted cancer therapy. PMID:23226697

Millisecond laser ablation of molybdenum target in reactive gas toward MoS2 fullerene-like nanoparticles with thermally stable photoresponse.

PubMed

Song, Shu-Tao; Cui, Lan; Yang, Jing; Du, Xi-Wen

2015-01-28

As a promising material for photoelectrical application, MoS2 has attracted extensive attention on its facile synthesis and unique properties. Herein, we explored a novel strategy of laser ablation to synthesize MoS2 fullerene-like nanoparticles (FL-NPs) with stable photoresponse under high temperature. Specifically, we employed a millisecond pulsed laser to ablate the molybdenum target in dimethyl trisulfide gas, and as a result, the molybdenum nanodroplets were ejected from the target and interacted with the highly reactive ambient gas to produce MoS2 FL-NPs. In contrast, the laser ablation in liquid could only produce core-shell nanoparticles. The crucial factors for controlling final nanostructures were found to be laser intensity, cooling rate, and gas reactivity. Finally, the MoS2 FL-NPs were assembled into a simple photoresponse device which exhibited excellent thermal stability, indicating their great potentialities for high-temperature photoelectrical applications.

Similarities and differences in ablative and non-ablative iron oxide nanoparticle hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Mazur, Courtney M.; Petryk, James D.; Hoopes, P. Jack

2015-03-01

The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. It has been demonstrated by many research groups that ablative temperatures and cytotoxicity can be produced with locally NP-based hyperthermia. Such ablative NP techniques have demonstrated the potential for success. Much attention has also been given to the fact that NP may be administered systemically, resulting in a broader cancer therapy approach, a lower level of tumor NP content and a different type of NP cancer therapy (most likely in the adjuvant setting). To use NP based hyperthermia successfully as a cancer treatment, the technique and its goal must be understood and utilized in the appropriate clinical context. The parameters include, but are not limited to, NP access to the tumor (large vs. small quantity), cancer cell-specific targeting, drug carrying capacity, potential as an ionizing radiation sensitizer, and the material properties (magnetic characteristics, size and charge). In addition to their potential for cytotoxicity, the material properties of the NP must also be optimized for imaging, detection and direction. In this paper we will discuss the differences between, and potential applications for, ablative and non-ablative magnetic nanoparticle hyperthermia.

B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells

PubMed Central

Shen, Ping; Brown, Sheila; Lampropoulou, Vicky; Roch, Toralf; Lawrie, Sarah; Fan, Boli; O’Connor, Richard A.; Anderton, Stephen M.; Bar-Or, Amit; Fillatreau, Simon; Gray, David

2012-01-01

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS. PMID:22547654

Percutaneous CT-guided radiofrequency ablation of renal cell carcinoma: efficacy of organ displacement by injection of 5% dextrose in water into the retroperitoneum.

PubMed

Arellano, Ronald S; Garcia, Rodrigo G; Gervais, Debra A; Mueller, Peter R

2009-12-01

The objective of this study was to evaluate the effectiveness of CT-guided injection of 5% dextrose in water solution (D5W) into the retroperitoneum to displace organs adjacent to renal cell carcinoma. An interventional radiology database was searched to identify the cases of patients who underwent CT-guided percutaneous radiofrequency ablation of biopsy-proven renal cell carcinoma in which D5W was injected into the retroperitoneal space to displace structures away from the targeted renal tumor. The number of organs displaced and the distance between the renal tumor and adjacent organs before and after displacement with D5W were assessed. The cases of 135 patients with 139 biopsy-proven renal cell carcinomas who underwent 154 percutaneous CT-guided radiofrequency ablation procedures were found in the search. Thirty-one patients with 33 renal cell carcinomas underwent 36 ablation procedures after injection of D5W into the retroperitoneal space. Fifty-five organs were displaced away from renal cell carcinoma with this technique. The average distance between adjacent structures and renal cell carcinomas before displacement was 0.36 cm (range, 0.1-1.0 cm). The average distance between structures and adjacent renal cell carcinomas after displacement was 1.94 cm (range, 1.1-4.3 cm) (p < 0.0001). The average volume of D5W used to achieve organ displacement was 273.5 mL. No complications were associated with this technique. CT-guided injection of D5W into the retroperitoneum is an effective method for displacing vital structures away from renal cell carcinoma.

Cold Atmospheric Plasma for Selectively Ablating Metastatic Breast Cancer Cells

PubMed Central

Wang, Mian; Holmes, Benjamin; Cheng, Xiaoqian; Zhu, Wei; Keidar, Michael; Zhang, Lijie Grace

2013-01-01

Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atomospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone marrow derived human mesenchymal stem cells (MSCs) were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy. PMID:24040051

Bipolar radiofrequency ablation of the kidney: comparison with monopolar radiofrequency ablation.

PubMed

Nakada, Stephen Y; Jerde, Travis J; Warner, Thomas F; Wright, Andrew S; Haemmerich, Dieter; Mahvi, David M; Lee, Fred T

2003-12-01

We report initial ex vivo and in vivo studies using bipolar radiofrequency (RF) ablation of porcine kidneys. An internal ground electrode is positioned in the kidney opposite the RF electrode, resulting in ablation of all the intervening renal tissue. Ex vivo preparations of 10 porcine kidneys were perfused continuously with Ringer's solution and treated with either standard external grounded RF (N = 3) or bipolar RF ablation with 1 (N = 2), 2 (N = 3), or 3 (N = 2) cm of separation between the ground probe and the RF probe using a Model 30 RITA generator (RITA, Mountain View, CA). Target temperatures were 90 degrees C for 8 minutes. Gross and histologic assessments were made acutely. Four domestic pigs were treated with monopolar RF ablation of the lower pole of one kidney and bipolar RF with a 12-mm separation between the probes of the contralateral lower pole. Animals were harvested 48 hours later to maximize tissue damage for gross measurements and histologic evaluation. Ex vivo studies revealed grossly monopolar lesions 1.5 cm in maximum diameter and 1.75 cm(3) in volume. In comparison, bipolar lesions were 2.8 cm in maximum diameter and 10.3 cm(3) in volume using 3 cm of electrode separation. There was histologic evidence of cell death in all specimens. In vivo studies showed two distinct gross lesions with RF: one blanched and one hemorrhagic. Using bipolar RF, larger blanched lesions were achievable than with monopolar RF (2.80 cm(3) v 1.63 cm(3)). Overall, the combinations of blanched and hemorrhagic lesions were similar with monopolar and bipolar RF (5.01 v 5.31 cm(3)). Histologic evaluation verified cell death in the blanched lesions and rare areas of normal tissue in the hemorrhagic lesions. As shown by ex vivo data, bipolar RF can create larger lesions than does monopolar RF. In vivo, at 48 hours, both blanched and hemorrhagic gross lesions were seen using RF. In this model, blanched lesions predominated when performing bipolar RF.

Laser-induced thermal ablation of cancerous cell organelles.

PubMed

Letfullin, Renat R; Szatkowski, Scott A

2017-07-01

By exploiting the physical changes experienced by cancerous organelles, we investigate the feasibility of destroying cancerous cells by single and multipulse modes of laser heating. Our procedure consists of two primary steps: determining the normal and cancerous organelles optical properties and simulating the heating of all of the major organelles in the cell to find the treatment modes for the laser ablation of cancerous organelles without harming healthy cells. Our simulations show that the cancerous nucleus can be selectively heated to damaging temperatures, making this nucleus a feasible therapeutic particle and removing the need for nanoparticle injection. Because of the removal of this extra step, the procedure we propose is simpler and safer for the patient.

Generating mouse models of degenerative diseases using Cre/lox-mediated in vivo mosaic cell ablation

PubMed Central

Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Okano, Hideyuki; Edge, Albert S.B.

2011-01-01

Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic β cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies. PMID:21576819

Conformal needle-based ultrasound ablation using EM-tracked conebeam CT image guidance

NASA Astrophysics Data System (ADS)

Burdette, E. Clif; Banovac, Filip; Diederich, Chris J.; Cheng, Patrick; Wilson, Emmanuel; Cleary, Kevin R.

2011-03-01

Numerous studies have demonstrated the efficacy of interstitial ablative approaches for the treatment of renal and hepatic tumors. Despite these promising results, current systems remain highly dependent on operator skill, and cannot treat many tumors because there is little control of the size and shape of the zone of necrosis, and no control over ablator trajectory within tissue once insertion has taken place. Additionally, tissue deformation and target motion make it extremely difficult to accurately place the ablator device into the target. Irregularly shaped target volumes typically require multiple insertions and several sequential thermal ablation procedures. This study demonstrated feasibility of spatially tracked image-guided conformal ultrasound (US) ablation for percutaneous directional ablation of diseased tissue. Tissue was prepared by suturing the liver within a pig belly and 1mm BBs placed to serve as needle targets. The image guided system used integrated electromagnetic tracking and cone-beam CT (CBCT) with conformable needlebased high-intensity US ablation in the interventional suite. Tomographic images from cone beam CT were transferred electronically to the image-guided tracking system (IGSTK). Paired-point registration was used to register the target specimen to CT images and enable navigation. Path planning is done by selecting the target BB on the GUI of the realtime tracking system and determining skin entry location until an optimal path is selected. Power was applied to create the desired ablation extent within 7-10 minutes at a thermal dose (>300eqm43). The system was successfully used to place the US ablator in planned target locations within ex-vivo kidney and liver through percutaneous access. Targeting accuracy was 3-4 mm. Sectioned specimens demonstrated uniform ablation within the planned target zone. Subsequent experiments were conducted for multiple ablator positions based upon treatment planning simulations. Ablation zones in

Smart Plasmonic Glucose Nanosensors as Generic Theranostic Agents for Targeting-Free Cancer Cell Screening and Killing.

PubMed

Chen, Limei; Li, Haijuan; He, Haili; Wu, Haoxi; Jin, Yongdong

2015-07-07

Fast and accurate identification of cancer cells from healthy normal cells in a simple, generic way is very crucial for early cancer detection and treatment. Although functional nanoparticles, like fluorescent quantum dots and plasmonic Au nanoparticles (NPs), have been successfully applied for cancer cell imaging and photothermal therapy, they suffer from the main drawback of needing time-consuming targeting preparation for specific cancer cell detection and selective ablation. The lack of a generic and effective method therefore limits their potential high-throughput cancer cell preliminary screening and theranostic applications. We report herein a generic in vitro method for fast, targeting-free (avoiding time-consuming preparations of targeting moiety for specific cancer cells) visual screening and selective killing of cancer cells from normal cells, by using glucose-responsive/-sensitive glucose oxidase-modified Ag/Au nanoshells (Ag/Au-GOx NSs) as a smart plasmonic theranostic agent. The method is generic to some extent since it is based on the distinct localized surface plasmon resonance (LSPR) responses (and colors) of the smart nanoprobe with cancer cells (typically have a higher glucose uptake level) and normal cells.

NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells.

PubMed

She, Zhi-Gang; Chang, Yunchao; Pang, Hong-Bo; Han, Wenlong; Chen, Hou-Zao; Smith, Jeffrey W; Stallcup, William B

2016-01-01

Obesity and hyperlipidemia are critical risk factors for atherosclerosis. Because ablation of NG2 proteoglycan in mice leads to hyperlipidemia and obesity, we investigated the impact of NG2 ablation on atherosclerosis in apoE null mice. Immunostaining indicates that NG2 expression in plaque, primarily by synthetic smooth muscle cells, increases during atherogenesis. NG2 ablation unexpectedly results in decreased (30%) plaque development, despite aggravated obesity and hyperlipidemia. Mechanistic studies reveal that NG2-positive plaque synthetic smooth muscle cells in culture can sequester low-density lipoprotein to enhance foam-cell formation, processes in which NG2 itself plays direct roles. In agreement with these observations, low-density lipoprotein retention and lipid accumulation in the NG2/ApoE knockout aorta is 30% less than that seen in the control aorta. These results indicate that synthetic smooth muscle cell-dependent low-density lipoprotein retention and foam cell formation outweigh obesity and hyperlipidemia in promoting mouse atherogenesis. Our study sheds new light on the role of synthetic smooth muscle cells during atherogenesis. Blocking plaque NG2 or altering synthetic smooth muscle cells function may be promising therapeutic strategies for atherosclerosis. © 2015 American Heart Association, Inc.

Conditional Lineage Ablation to Model Human Diseases

NASA Astrophysics Data System (ADS)

Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

1998-09-01

Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

Laboratory Simulations of Micrometeoroid Ablation

NASA Astrophysics Data System (ADS)

Thomas, Evan Williamson

Each day, several tons of meteoric material enters Earth's atmosphere, the majority of which consist of small dust particles (micrometeoroids) that completely ablate at high altitudes. The dust input has been suggested to play a role in a variety of phenomena including: layers of metal atoms and ions, nucleation of noctilucent clouds, effects on stratospheric aerosols and ozone chemistry, and the fertilization of the ocean with bio-available iron. Furthermore, a correct understanding of the dust input to the Earth provides constraints on inner solar system dust models. Various methods are used to measure the dust input to the Earth including satellite detectors, radar, lidar, rocket-borne detectors, ice core and deep-sea sediment analysis. However, the best way to interpret each of these measurements is uncertain, which leads to large uncertainties in the total dust input. To better understand the ablation process, and thereby reduce uncertainties in micrometeoroid ablation measurements, a facility has been developed to simulate the ablation of micrometeoroids in laboratory conditions. An electrostatic dust accelerator is used to accelerate iron particles to relevant meteoric velocities (10-70 km/s). The particles are then introduced into a chamber pressurized with a target gas, and they partially or completely ablate over a short distance. An array of diagnostics then measure, with timing and spatial resolution, the charge and light that is generated in the ablation process. In this thesis, we present results from the newly developed ablation facility. The ionization coefficient, an important parameter for interpreting meteor radar measurements, is measured for various target gases. Furthermore, experimental ablation measurements are compared to predictions from commonly used ablation models. In light of these measurements, implications to the broader context of meteor ablation are discussed.

Pulsed laser ablation of borax target in vacuum and hydrogen DC glow discharges

NASA Astrophysics Data System (ADS)

Kale, A. N.; Miotello, A.; Mosaner, P.

2006-09-01

The aim of our experiment was to produce a material with B sbnd H bonds for applications in hydrogen storage and generation. By using KrF excimer laser ( λ = 248 nm) ablation of borax (Na 2B 4O 7) target, thin films were deposited on KBr and silicon substrates. Ablation was performed both in vacuum and in hydrogen atmosphere. DC glow discharge technique was utilized to enhance hydrogen gas ionization. Experiments were performed using laser fluence from 5 to 20 J/cm 2. Films were deposited under gas pressure of 1 × 10 -5 to 5 × 10 -2 mbar and substrate temperatures of 130-450 °C. Scanning electron microscopy analysis of films showed presence of circular particulates. Film thickness, roughness and particulates number increased with increase in laser fluence. Energy dispersive X-ray spectroscopy analysis shows that sodium content in the particulates is higher than in the target. This effect is discussed in terms of atomic arrangements (both at surface and bulk) in systems where ionic and covalent bonds are present and by looking at the increased surface/bulk ratio of the particulates with respect to the deposited films. The Fourier transform infrared spectroscopy measurements showed presence of B sbnd O stretching and B sbnd O sbnd B bending bonds. Possible reasons for absence of B sbnd H bonds are attributed to binding enthalpy of the competing molecules.

Optimal approach for complete liver tumor ablation using radiofrequency ablation: a simulation study.

PubMed

Givehchi, Sogol; Wong, Yin How; Yeong, Chai Hong; Abdullah, Basri Johan Jeet

2018-04-01

To investigate the effect of radiofrequency ablation (RFA) electrode trajectory on complete tumor ablation using computational simulation. The RFA of a spherical tumor of 2.0 cm diameter along with 0.5 cm clinical safety margin was simulated using Finite Element Analysis software. A total of 86 points inside one-eighth of the tumor volume along the axial, sagittal and coronal planes were selected as the target sites for electrode-tip placement. The angle of the electrode insertion in both craniocaudal and orbital planes ranged from -90° to +90° with 30° increment. The RFA electrode was simulated to pass through the target site at different angles in combination of both craniocaudal and orbital planes before being advanced to the edge of the tumor. Complete tumor ablation was observed whenever the electrode-tip penetrated through the epicenter of the tumor regardless of the angles of electrode insertion in both craniocaudal and orbital planes. Complete tumor ablation can also be achieved by placing the electrode-tip at several optimal sites and angles. Identification of the tumor epicenter on the central slice of the axial images is essential to enhance the success rate of complete tumor ablation during RFA procedures.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

PubMed

Xiong, Liang; Liu, Yu; Zhou, Mingmin; Wang, Guangji; Quan, Dajun; Shen, Caijie; Shuai, Wei; Kong, Bin; Huang, Congxin; Huang, He

2018-05-31

The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis.

PubMed

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B

2009-05-19

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5-E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1-independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis.

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis

PubMed Central

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B.

2009-01-01

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5–E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1–independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis. PMID:19416849

Targeted Ablation of CML Stem Cells

DTIC Science & Technology

2007-01-01

centuries .12 More recently, PTL has been found to have several other properties, including antitumor activity, inhibition of DNA synthesis, and...as a chemopreventive agent in a UVB-induced skin cancer animal model. 21 PTL is a potent inhibitor of NF-B activation and has been shown to directly...diluted in phosphate buffer saline (PBS). Ara-C was obtained from Sigma ( St Louis, MO). Total cell numbers were determined before and after culture for

In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy.

PubMed

Tang, Hailin; Guo, Yuan; Peng, Li; Fang, Hui; Wang, Zhigang; Zheng, Yuanyi; Ran, Haitao; Chen, Yu

2018-05-09

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe 3 O 4 -FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T 2 -weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.

Process and structures for fabrication of solar cells with laser ablation steps to form contact holes

DOEpatents

Harley, Gabriel; Smith, David D; Dennis, Tim; Waldhauer, Ann; Kim, Taeseok; Cousins, Peter John

2013-11-19

Contact holes of solar cells are formed by laser ablation to accomodate various solar cell designs. Use of a laser to form the contact holes is facilitated by replacing films formed on the diffusion regions with a film that has substantially uniform thickness. Contact holes may be formed to deep diffusion regions to increase the laser ablation process margins. The laser configuration may be tailored to form contact holes through dielectric films of varying thickness.

Molybdenum oxide nanocolloids prepared by an external field-assisted laser ablation in water

NASA Astrophysics Data System (ADS)

Spadaro, Salvatore; Bonsignore, Martina; Fazio, Enza; Cimino, Francesco; Speciale, Antonio; Trombetta, Domenico; Barreca, Francesco; Saija, Antonina; Neri, Fortunato

2018-01-01

he synthesis of extremely stable molybdenum oxide nanocolloids by pulsed laser ablation was studied. This green technique ensures the formation of contaminant-free nanostructures and the absence of by-products. A focused picosecond pulsed laser beam was used to ablate a solid molybdenum target immersed in deionized water. Molybdenum oxide nearly spherical nanoparticles with dimensions within few nanometers (20-100 nm) are synthesized when the ablation processes were carried out, in water, at room temperature and 80°C. The application of an external electric field during the ablation process induces a nanostructures reorganization, as indicated by Scanning-Transmission Electron Microscopy images analysis. The ablation products were also characterized by some spectroscopic techniques: conventional UV-vis optical absorption, atomic absorption, dynamic light scattering, micro-Raman and X-ray photoelectron spectroscopies. Finally, NIH/3T3 mouse fibroblasts were used to evaluate cell viability by the sulforhodamine B assay

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

PubMed Central

Paszkiewicz, Paulina J.; Fräßle, Simon P.; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C.; Riddell, Stanley R.; Busch, Dirk H.

2016-01-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies. PMID:27760047

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.

PubMed

Paszkiewicz, Paulina J; Fräßle, Simon P; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Drexler, Ingo; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C; Riddell, Stanley R; Busch, Dirk H

2016-11-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies.

Treatment planning for prostate focal laser ablation in the face of needle placement uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cepek, Jeremy, E-mail: jcepek@robarts.ca; Fenster, Aaron; Lindner, Uri

2014-01-15

Purpose: To study the effect of needle placement uncertainty on the expected probability of achieving complete focal target destruction in focal laser ablation (FLA) of prostate cancer. Methods: Using a simplified model of prostate cancer focal target, and focal laser ablation region shapes, Monte Carlo simulations of needle placement error were performed to estimate the probability of completely ablating a region of target tissue. Results: Graphs of the probability of complete focal target ablation are presented over clinically relevant ranges of focal target sizes and shapes, ablation region sizes, and levels of needle placement uncertainty. In addition, a table ismore » provided for estimating the maximum target size that is treatable. The results predict that targets whose length is at least 5 mm smaller than the diameter of each ablation region can be confidently ablated using, at most, four laser fibers if the standard deviation in each component of needle placement error is less than 3 mm. However, targets larger than this (i.e., near to or exceeding the diameter of each ablation region) require more careful planning. This process is facilitated by using the table provided. Conclusions: The probability of completely ablating a focal target using FLA is sensitive to the level of needle placement uncertainty, especially as the target length approaches and becomes greater than the diameter of ablated tissue that each individual laser fiber can achieve. The results of this work can be used to help determine individual patient eligibility for prostate FLA, to guide the planning of prostate FLA, and to quantify the clinical benefit of using advanced systems for accurate needle delivery for this treatment modality.« less

[Premature outflow tract ventricular contraction combined with complete bundle branch block: the characteristic electrocardiographic and ablation target potential features].

PubMed

Di, C Y; Wan, Z; Li, K; Ding, Y S; Lin, W H

2017-12-01

Objective: To explore the characteristics of electrocardiogram(ECG) and target potential features of premature ventricular contraction (PVC) in patients with complete left/right bundle branch block (CL/RBBB) and compare with those without CL/RBBB. Methods: A retrospective analysis was done in 8 outflow tract PVC patients with CL/RBBB, who successfully underwent radiofrequency ablation from August 2009 to June 2017. According to the bundle branch block chamber, patients were divided into the complete right bundle branch block (CRBBB) group ( n= 4) and the complete left bundle branch block (CLBBB) group ( n= 4). The control group were those who successfully underwent ablation at the same position as the above two groups but without CL/RBBB. The characteristics of ECG and target potential features were compared among groups. Results: One case in the CRBBB group was successfully ablated in the great cardiac vein with precordial R/S>1 transition at V(1) and one case in the CLBBB group was successfully ablated in the right coronary cusp with precordial R/S>1 transition at V(2), while other 6 cases were all with precordial R/S>1 transition at lead V(4). Precordial R/S>1 transition was not later than sinus rhythm (SR) in the CLBBB group. No statistical difference was found in the QRS complex duration between SR and PVC in the CL/RBBB patients [(134.38±23.80)ms vs (156.75±25.93)ms, P> 0.05], while statistical difference was shown in the control group [(92.63±5.76)ms vs (140.25±15.97)ms, P< 0.05]. Conclusion: Bundle branch block can lead to misjudgment of PVC origin with CL/RBBB during sinus rhythm, thus the origin chamber of the PVC should be determined according to the mapping and ablation result.

Subcellular analysis by laser ablation electrospray ionization mass spectrometry

DOEpatents

Vertes, Akos; Stolee, Jessica A; Shrestha, Bindesh

2014-12-02

In various embodiments, a method of laser ablation electrospray ionization mass spectrometry (LAESI-MS) may generally comprise micro-dissecting a cell comprising at least one of a cell wall and a cell membrane to expose at least one subcellular component therein, ablating the at least one subcellular component by an infrared laser pulse to form an ablation plume, intercepting the ablation plume by an electrospray plume to form ions, and detecting the ions by mass spectrometry.

Ablative Hypofractionated Radiation Therapy Enhances Non-Small Cell Lung Cancer Cell Killing via Preferential Stimulation of Necroptosis In Vitro and In Vivo.

PubMed

Wang, Huan-Huan; Wu, Zhi-Qiang; Qian, Dong; Zaorsky, Nicholas G; Qiu, Ming-Han; Cheng, Jing-Jing; Jiang, Chao; Wang, Juan; Zeng, Xian-Liang; Liu, Chun-Lei; Tian, Li-Jun; Ying, Guo-Guang; Meng, Mao-Bin; Hao, Xi-Shan; Yuan, Zhi-Yong

2018-05-01

To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT). Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo. Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05). Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof-of-Concept from Experimental Studies to Clinical VF

PubMed Central

KRUMMEN, DAVID E.; HAYASE, JUSTIN; VAMPOLA, STEPHEN P.; HO, GORDON; SCHRICKER, AMIR A.; LALANI, GAUTAM G.; BAYKANER, TINA; COE, TAYLOR M.; CLOPTON, PAUL; RAPPEL, WOUTER-JAN; OMENS, JEFFREY H.; NARAYAN, SANJIV M.

2016-01-01

Introduction Recent work has suggested a role for organized sources in sustaining ventricular fibrillation (VF). We assessed whether ablation of rotor substrate could modulate VF inducibility in canines, and used this proof-of-concept as a foundation to suppress antiarrhythmic drug-refractory clinical VF in a patient with structural heart disease. Methods and Results In 9 dogs, we introduced 64-electrode basket catheters into one or both ventricles, used rapid pacing at a recorded induction threshold to initiate VF, and then defibrillated after 18±8 seconds. Endocardial rotor sites were identified from basket recordings using phase mapping, and ablation was performed at nonrotor (sham) locations (7 ± 2 minutes) and then at rotor sites (8 ± 2 minutes, P = 0.10 vs. sham); the induction threshold was remeasured after each. Sham ablation did not alter canine VF induction threshold (preablation 150 ± 16 milliseconds, postablation 144 ± 16 milliseconds, P = 0.54). However, rotor site ablation rendered VF noninducible in 6/9 animals (P = 0.041), and increased VF induction threshold in the remaining 3. Clinical proof-of-concept was performed in a patient with repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Following biventricular basket insertion, VF was induced and then defibrillated. Mapping identified 4 rotors localized at borderzone tissue, and rotor site ablation (6.3 ± 1.5 minutes/site) rendered VF noninducible. The VF burden fell from 7 ICD shocks in 8 months preablation to zero ICD therapies at 1 year, without antiarrhythmic medications. Conclusions Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation. PMID:26179310

Laser ablation for the synthesis of carbon nanotubes

DOEpatents

Holloway, Brian C; Eklund, Peter C; Smith, Michael W; Jordan, Kevin C; Shinn, Michelle

2012-11-27

Single walled carbon nanotubes are produced in a novel apparatus by the laser-induced ablation of moving carbon target. The laser used is of high average power and ultra-fast pulsing. According to various preferred embodiments, the laser produces and output above about 50 watts/cm.sup.2 at a repetition rate above about 15 MHz and exhibits a pulse duration below about 10 picoseconds. The carbon, carbon/catalyst target and the laser beam are moved relative to one another and a focused flow of "side pumped", preheated inert gas is introduced near the point of ablation to minimize or eliminate interference by the ablated plume by removal of the plume and introduction of new target area for incidence with the laser beam. When the target is moved relative to the laser beam, rotational or translational movement may be imparted thereto, but rotation of the target is preferred.

Laser ablation for the synthesis of carbon nanotubes

DOEpatents

Holloway, Brian C.; Eklund, Peter C.; Smith, Michael W.; Jordan, Kevin C.; Shinn, Michelle

2010-04-06

Single walled carbon nanotubes are produced in a novel apparatus by the laser-induced ablation of moving carbon target. The laser used is of high average power and ultra-fast pulsing. According to various preferred embodiments, the laser produces an output above about 50 watts/cm.sup.2 at a repetition rate above about 15 MHz and exhibits a pulse duration below about 10 picoseconds. The carbon, carbon/catalyst target and the laser beam are moved relative to one another and a focused flow of "side pumped", preheated inert gas is introduced near the point of ablation to minimize or eliminate interference by the ablated plume by removal of the plume and introduction of new target area for incidence with the laser beam. When the target is moved relative to the laser beam, rotational or translational movement may be imparted thereto, but rotation of the target is preferred.

Laser ablation for the synthesis of carbon nanotubes

NASA Technical Reports Server (NTRS)

Holloway, Brian C. (Inventor); Eklund, Peter C. (Inventor); Smith, Michael W. (Inventor); Jordan, Kevin C. (Inventor); Shinn, Michelle (Inventor)

2010-01-01

Single walled carbon nanotubes are produced in a novel apparatus by the laser-induced ablation of moving carbon target. The laser used is of high average power and ultra-fast pulsing. According to various preferred embodiments, the laser produces an output above about 50 watts/cm.sup.2 at a repetition rate above about 15 MHz and exhibits a pulse duration below about 10 picoseconds. The carbon, carbon/catalyst target and the laser beam are moved relative to one another and a focused flow of side pumped, preheated inert gas is introduced near the point of ablation to minimize or eliminate interference by the ablated plume by removal of the plume and introduction of new target area for incidence with the laser beam. When the target is moved relative to the laser beam, rotational or translational movement may be imparted thereto, but rotation of the target is preferred.

Laser ablation for the synthesis of carbon nanotubes

NASA Technical Reports Server (NTRS)

Holloway, Brian C. (Inventor); Eklund, Peter C. (Inventor); Smith, Michael W. (Inventor); Jordan, Kevin C. (Inventor); Shinn, Michelle (Inventor)

2012-01-01

Single walled carbon nanotubes are produced in a novel apparatus by the laser-induced ablation of moving carbon target. The laser used is of high average power and ultra-fast pulsing. According to various preferred embodiments, the laser produces and output above about 50 watts/cm.sup.2 at a repetition rate above about 15 MHz and exhibits a pulse duration below about 10 picoseconds. The carbon, carbon/catalyst target and the laser beam are moved relative to one another and a focused flow of "side pumped", preheated inert gas is introduced near the point of ablation to minimize or eliminate interference by the ablated plume by removal of the plume and introduction of new target area for incidence with the laser beam. When the target is moved relative to the laser beam, rotational or translational movement may be imparted thereto, but rotation of the target is preferred.

Characterization of Pancreatic Cancer Cell Thermal Response to Heat Ablation or Cryoablation.

PubMed

Baumann, Kenneth W; Baust, John M; Snyder, Kristi K; Baust, John G; Van Buskirk, Robert G

2017-08-01

One of the most lethal carcinomas is pancreatic cancer. As standard treatment using chemotherapy and radiation has shown limited success, thermal regimens (cryotherapy or heat ablation) are emerging as viable alternatives. Although promising, our understanding of pancreatic cancer response to thermal ablation remains limited. In this study, we investigated the thermal responses of 2 pancreatic cancer cell lines in an effort to identify the minimum lethal temperature needed for complete cell death to provide guidance for in vivo applications. PANC-1 and BxPC-3 were frozen (-10°C to -25°C) or heated (45°C-50°C) in single and repeated exposure regimes. Posttreatment survival and recovery were analyzed using alamarBlue assay over a 7-day interval. Modes of cell death were assessed using fluorescence microscopy (calcein acetoxymethyl ester/propidium iodide) and flow cytometry (YO-PRO-1/propidium iodide). Freezing to -10°C resulted in minimal cell death. Exposure to -15°C had a mild impact on PANC-1 survival (93%), whereas BxPC-3 was more severely damaged (33%). Exposure to -20°C caused a significant reduction in viability (PANC-1 = 23%; BxPC-3 = 2%) whereas -25°C yielded complete death. Double freezing exposure was more effective than single exposure. Repeat exposure to -15°C resulted in complete death of BxPC-3, whereas -20°C severely impacted PANC-1 (7%). Heating to 45°C resulted in minimum cell death. Exposure to 48°C yielded a slight increase in cell loss (PANC-1 = 85%; BxPC-3 = 98%). Exposure to 50°C caused a significant decline (PANC-1 = 70%; BxPC-3 = 9%) with continued deterioration to 0%. Double heating to 45°C resulted in similar effects observed in single exposures, whereas repeated 48°C resulted in significant increases in cell death (PANC-1 = 68%; BxPC-3 = 29%). In conclusion, we observed that pancreatic cancer cells were completely destroyed at temperatures <-25°C or >50°C using single thermal exposures. Repeated exposures resulted in

Ablation as targeted perturbation to rewire communication network of persistent atrial fibrillation

PubMed Central

Tao, Susumu; Way, Samuel F.; Garland, Joshua; Chrispin, Jonathan; Ciuffo, Luisa A.; Balouch, Muhammad A.; Nazarian, Saman; Spragg, David D.; Marine, Joseph E.; Berger, Ronald D.; Calkins, Hugh

2017-01-01

Persistent atrial fibrillation (AF) can be viewed as disintegrated patterns of information transmission by action potential across the communication network consisting of nodes linked by functional connectivity. To test the hypothesis that ablation of persistent AF is associated with improvement in both local and global connectivity within the communication networks, we analyzed multi-electrode basket catheter electrograms of 22 consecutive patients (63.5 ± 9.7 years, 78% male) during persistent AF before and after the focal impulse and rotor modulation-guided ablation. Eight patients (36%) developed recurrence within 6 months after ablation. We defined communication networks of AF by nodes (cardiac tissue adjacent to each electrode) and edges (mutual information between pairs of nodes). To evaluate patient-specific parameters of communication, thresholds of mutual information were applied to preserve 10% to 30% of the strongest edges. There was no significant difference in network parameters between both atria at baseline. Ablation effectively rewired the communication network of persistent AF to improve the overall connectivity. In addition, successful ablation improved local connectivity by increasing the average clustering coefficient, and also improved global connectivity by decreasing the characteristic path length. As a result, successful ablation improved the efficiency and robustness of the communication network by increasing the small-world index. These changes were not observed in patients with AF recurrence. Furthermore, a significant increase in the small-world index after ablation was associated with synchronization of the rhythm by acute AF termination. In conclusion, successful ablation rewires communication networks during persistent AF, making it more robust, efficient, and easier to synchronize. Quantitative analysis of communication networks provides not only a mechanistic insight that AF may be sustained by spatially localized sources and

Different degrees of somatotroph ablation compromise pituitary growth hormone cell network structure and other pituitary endocrine cell types.

PubMed

Waite, Eleanor; Lafont, Chrystel; Carmignac, Danielle; Chauvet, Norbert; Coutry, Nathalie; Christian, Helen; Robinson, Iain; Mollard, Patrice; Le Tissier, Paul

2010-01-01

We have generated transgenic mice with somatotroph-specific expression of a modified influenza virus ion channel, (H37A)M2, leading to ablation of GH cells with three levels of severity, dependent on transgene copy number. GH-M2(low) mice grow normally and have normal-size pituitaries but 40-50% reduction in pituitary GH content in adult animals. GH-M2(med) mice have male-specific transient growth retardation and a reduction in pituitary GH content by 75% at 42 d and 97% by 100 d. GH-M2(high) mice are severely dwarfed with undetectable pituitary GH. The GH secretory response of GH-M2(low) and GH-M2(med) mice to GH-releasing peptide-6 and GHRH was markedly attenuated. The content of other pituitary hormones was affected depending on transgene copy number: no effect in GH-M2(low) mice, prolactin and TSH reduced in GH-M2(med) mice, and all hormones reduced in GH-M2(high) mice. The effect on non-GH hormone content was associated with increased macrophage invasion of the pituitary. Somatotroph ablation affected GH cell network organization with limited disruption in GH-M2(low) mice but more severe disruption in GH-M2(med) mice. The remaining somatotrophs formed tight clusters after puberty, which contrasts with GHRH-M2 mice with a secondary reduction in somatotrophs that do not form clusters. A reduction in pituitary beta-catenin staining was correlated with GH-M2 transgene copy number, suggesting M2 expression has an effect on cell-cell communication in somatotrophs and other pituitary cell types. GH-M2 transgenic mice demonstrate that differing degrees of somatotroph ablation lead to correlated secondary effects on cell populations and cellular network organization.

Evaluation of a Thermoprotective Gel for Hydrodissection During Percutaneous Microwave Ablation: In Vivo Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreland, Anna J., E-mail: ajmoreland@gmail.com; Lubner, Meghan G., E-mail: mlubner@uwhealth.org; Ziemlewicz, Timothy J., E-mail: tziemlewicz@uwhealth.org

2015-06-15

PurposeTo evaluate whether thermoreversible poloxamer 407 15.4 % in water (P407) can protect non-target tissues adjacent to microwave (MW) ablation zones in a porcine model.Materials and MethodsMW ablation antennas were placed percutaneously into peripheral liver, spleen, or kidney (target tissues) under US and CT guidance in five swine such that the expected ablation zones would extend into adjacent diaphragm, body wall, or bowel (non-target tissues). For experimental ablations, P407 (a hydrogel that transitions from liquid at room temperature to semi-solid at body temperature) was injected into the potential space between target and non-target tissues, and the presence of a gel barriermore » was verified on CT. No barrier was used for controls. MW ablation was performed at 65 W for 5 min. Thermal damage to target and non-target tissues was evaluated at dissection.ResultsAntennas were placed 7 ± 3 mm from the organ surface for both control and gel-protected ablations (p = 0.95). The volume of gel deployed was 49 ± 27 mL, resulting in a barrier thickness of 0.8 ± 0.5 cm. Ablations extended into non-target tissues in 12/14 control ablations (mean surface area = 3.8 cm{sup 2}) but only 4/14 gel-protected ablations (mean surface area = 0.2 cm{sup 2}; p = 0.0005). The gel barrier remained stable at the injection site throughout power delivery.ConclusionWhen used as a hydrodissection material, P407 protected non-targeted tissues and was successfully maintained at the injection site for the duration of power application. Continued investigations to aid clinical translation appear warranted.« less

Nanosecond laser-metal ablation at different ambient conditions

NASA Astrophysics Data System (ADS)

Elsied, Ahmed M.; Dieffenbach, Payson C.; Diwakar, Prasoon K.; Hassanein, Ahmed

2018-05-01

Ablation of metals under different ambient conditions and laser fluences, was investigated through series of experiments. A 1064 nm, 6 ns Nd:YAG laser was used to ablate 1 mm thick metal targets with laser energy ranging from 2 mJ to 300 mJ. The experiments were designed to study the effect of material properties, laser fluence, ambient gas, and ambient pressure on laser-metal ablation. The first experiment was conducted under vacuum to study the effect of laser fluence and material properties on metal ablation, using a wide range of laser fluences (2 J/cm2 up to 300 J/cm2) and two different targets, Al and W. The second experiment was conducted at atmospheric pressure using two different ambient gases air and argon, to understand the effect of ambient gas on laser-metal ablation process. The third experiment was conducted at two different pressures (10 Torr and 760 Torr) using the same ambient gas to investigate the effect of ambient pressure on laser-metal ablation. To compare the different ablation processes, the amount of mass ablated, ablation depth, crater profile and melt formation were measured using White Light Profilometer (WLP). The experimental results show that at low laser fluence: the ablated mass, ablation depth, and height of molten layer follow a logarithmic function of the incident laser fluence. While, at high laser fluence they follow a linear function. This dependence on laser fluence was found to be independent on ambient conditions and irradiated material. The effect of ambient pressure was more pronounced than the effect of ambient gas type. Plasma shielding effect was found to be very pronounced in the presence of ambient gas and led to significant reduction in the total mass ablation.

Targeted delivery of peptide-conjugated biocompatible gold nanoparticles into cancer cell nucleus

NASA Astrophysics Data System (ADS)

Qian, Wei; Curry, Taeyjuana; Che, Yong; Kopelman, Raoul

2013-02-01

Nucleus remains a significant target for nanoparticles with diagnostic and therapeutic applications because both genetic information of the cell and transcription machinery reside there. Novel therapeutic strategies (for example, gene therapy), enabled by safe and efficient delivery of nanoparticles and drug molecules into the nucleus, are heralded by many as the ultimate treatment for severe and intractable diseases. However, most nanomaterials and macromolecules are incapable of reaching the cell nucleus on their own, because of biological barriers carefully honed by evolution including cellular membrane and nuclear envelope. In this paper, we have demonstrated an approach of fabrication of biocompatible gold nanoparticle (Au NP)-based vehicles which can entering into cancer cell nucleus by modifying Au NPs with both PEG 5000 and two different peptides (RGD and nuclear localization signal (NLS) peptide). The Au NPs used were fabricated via femtosecond laser ablation of Au bulk target in deionized water. The Au NPs produced by this method provide chemical free, virgin surface, which allows us to carry out "Sequential Conjugation" to modify their surface with PEG 5000, RGD, and NLS. "Sequential Conjugation" described in this presentation is very critical for the fabrication of Au NP-based vehicles capable of entering into cancer cell nucleus as it enables the engineering and tuning surface chemistries of Au NPs by independently adjusting amounts of PEG and peptides bound onto surface of Au NPs so as to maximize their nuclear targeting performance and biocompatibility regarding the cell line of interest. Both optical microscopy and transmission electron microscopy (TEM) are used to confirm the in vitro targeted nuclear delivery of peptide-conjugated biocompatible Au NPs by showing their presence in the cancer cell nucleus.

Radiofrequency ablation versus nephron-sparing surgery for small unilateral renal cell carcinoma: cost-effectiveness analysis.

PubMed

Pandharipande, Pari V; Gervais, Debra A; Mueller, Peter R; Hur, Chin; Gazelle, G Scott

2008-07-01

To evaluate the relative cost-effectiveness of percutaneous radiofrequency (RF) ablation versus nephron-sparing surgery (NSS) in patients with small (cell carcinoma (RCC), given a commonly accepted level of societal willingness to pay. A decision-analytic Markov model was developed to estimate life expectancy and lifetime costs for 65-year-old patients with a small RCC treated with RF ablation or NSS. The model incorporated RCC presence, treatment effectiveness and costs, and short- and long-term outcomes. An incremental cost-effectiveness analysis was performed to identify treatment preference under an assumed $75,000 per quality-adjusted life-year (QALY) societal willingness-to-pay threshold level, within proposed ranges for guiding implementation of new health care interventions. The effect of changes in key parameters on strategy preference was addressed in sensitivity analysis. By using base-case assumptions, NSS yielded a minimally greater average quality-adjusted life expectancy than did RF ablation (2.5 days) but was more expensive. NSS had an incremental cost-effectiveness ratio of $1,152,529 per QALY relative to RF ablation, greatly exceeding $75,000 per QALY. Therefore, RF ablation was considered preferred and remained so if the annual probability of post-RF ablation local recurrence was up to 48% higher relative to that post-NSS. NSS preference required an estimated NSS cost reduction of $7500 or RF ablation cost increase of $6229. Results were robust to changes in most model parameters, but treatment preference was dependent on the relative probabilities of local recurrence after RF ablation and NSS, the short-term costs of both, and quality of life after NSS. RF ablation was preferred over NSS for small RCC treatment at a societal willingness-to-pay threshold level of $75,000 per QALY. This result was robust to changes in most model parameters, but somewhat dependent on the relative probabilities of post-RF ablation and post-NSS local

Benefits of Moderate-Z Ablators for Direct-Drive Inertial Confinement Fusion

NASA Astrophysics Data System (ADS)

Lafon, M.; Betti, R.; Anderson, K. S.; Collins, T. J. B.; Skupsky, S.; McKenty, P. W.

2014-10-01

Control of hydrodynamic instabilities and DT-fuel preheating by hot electrons produced by laser-plasma interaction is crucial in inertial confinement fusion. Moderate- Z ablators have been shown to reduce the laser imprinting on target and suppress the generation of hot electrons from the two-plasmon-decay instability. These results have motivated the use of ablators of higher- Z than pure plastic in direct-drive-ignition target designs for the National Ignition Facility (NIF). Two-dimensional radiation-hydrodynamic simulations assess the robustness of these ignition designs to laser imprint and capsule nonuniformities. The complex behavior of the hydrodynamic stability of mid- Z ablators is investigated through single and multimode simulations. A polar-drive configuration is developed within the NIF Laser System specifications for each ablator material. The use of multilayer ablators is also investigated to enhance the hydrodynamic stability. Results indicate that ignition target designs using mid- Z ablators exhibit good hydrodynamic properties, leading to high target gain for direct-drive implosions on the NIF. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944 and the Office of Fusion Energy Sciences Number DE-FG02-04ER54786.

Comprehensive studies of ultrashort laser pulse ablation of tin target at terawatt power

NASA Astrophysics Data System (ADS)

Elsied, Ahmed M.; Diwakar, Prasoon K.; Hassanein, Ahmed

2018-01-01

The fundamental properties of ultrashort laser interactions with metals using up to terawatt power were comprehensively studied, i.e., specifically mass ablation, nanoparticle formation, and ion dynamics using multitude of diagnostic techniques. Results of this study can be useful in many fields of research including spectroscopy, micromachining, thin film fabrication, particle acceleration, physics of warm dense matter, and equation-of-state determination. A Ti:Sapphire femtosecond laser system (110 mJ maximum energy, 40 fs, 800 nm, P-polarized, single pulse mode) was used, which delivered up to 3 terawatt laser power to ablate 1 mm tin film in vacuum. The experimental analysis includes the effect of the incident laser fluence on the ablated mass, size of the ablated area, and depth of ablation using white light profilometer. Atomic force microscope was used to measure the emitted particles size distribution at different laser fluence. Faraday cup (FC) detector was used to analyze the emitted ions flux by measuring the velocity, and the total charge of the emitted ions. The study shows that the size of emitted particles follows log-normal distribution with peak shifts depending on incident laser fluence. The size of the ablated particles ranges from 20 to 80 nm. The nanoparticles deposited on the wafer tend to aggregate and to be denser as the incident laser fluence increases as shown by AFM images. Laser ablation depth was found to increase logarithmically with laser fluence then leveling off at laser fluence > 400 J/cm2. The total ablated mass tends to increase logarithmically with laser fluence up to 60 J/cm2 while, increases gradually at higher fluence due to the increase in the ablated area. The measured ion emitted flux shows a linear dependence on laser fluence with two distinct regimes. Strong dependence on laser fluence was observed at fluences < 350 J/cm2. Also, a slight enhancement in ion velocity was observed with increasing laser fluence up to 350 J

Low pressure laser ablation coupled to inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Fliegel, Daniel; Günther, Detlef

2006-07-01

The particle size distribution in laser ablation inductively coupled plasma mass spectrometry is known to be a critical parameter for complete vaporization of particles. Any strategy to reduce the particle size distribution of laser generated aerosols has the potential to increase the ion signal intensity and to reduce fractionation effects. Due to the fact that vapor generation, nucleation, condensation, and agglomeration take place within an extremely short period of time, ablation under atmospheric pressure might not allow influencing these processes while under reduced pressure condition the cooling of the aerosol and therefore the condensation is expected to be slower. In this study, a low pressure laser ablation cell for the generation of laser aerosols was coupled to an ICP-MS. In contrast to the previously developed trapped ablation mode, the newly designed cell allows the adjustment of the pressure in the ablation cell between 20 and 1400 mbar prior to the ablation. Ablation experiments carried out using this configuration showed a dependence of the aerosol properties (size distribution and particle structure) on the ablation cell pressure. The intensity ratio U/Th measured as a figure of merit for complete vaporization within the ICP indicated a change in the aerosol structure at approximately 500 mbar toward smaller particle size. A significant difference between low pressure and at ambient pressure ablated aerosol was observed. The intensity ratios (U/Th) of the ablated sample moves closer to the bulk composition at lower pressures at the expense of sensitivity. Therefore the decrease in the ICP-MS signal intensity in the low pressure cell can be attributed to vapor deposition within the ablation cell walls. Moreover, scanning electron microscope images of aerosols collected on filters after the low pressure ablation cell suggest the possibility of a slower cooling velocity of the aerosol, which was observed in the condensed material on the surface of

Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in a murine model.

PubMed

Liu, James; Abshire, Caleb; Carry, Connor; Sholl, Andrew B; Mandava, Sree Harsha; Datta, Amrita; Ranjan, Manish; Callaghan, Cameron; Peralta, Donna V; Williams, Kristen S; Lai, Weil R; Abdel-Mageed, Asim B; Tarr, Matthew; Lee, Benjamin R

2017-02-01

To investigate tyrosine kinase inhibitors (TKI) and gold nanorods (AuNRs) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma (RCC) mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urological cancers. Likewise, the use of nanoparticles in photothermal tumour ablation, although early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNRs and activated with photothermal ablation have shown significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model. Immunologically naïve nude mice (athymic nude-Foxn1 nu ) were injected subcutaneously bilaterally in both flanks (n = 36) with 2.5 × 10 6 cells of a human metastatic renal cell carcinoma cell line (RCC 786-O). Subcutaneous xenograft tumours developed into 1-cm palpable nodules. AuNRs encapsulated in human serum albumin protein (HSA) nanoparticles were synthesised with or without a TKI and injected directly into the tumour nodule. Irradiation was administered with an 808-nm light-emitting diode laser for 6 min. Mice were humanely killed 14 days after irradiation; tumours were excised, formalin fixed, paraffin embedded, and evaluated for size and the percentage of necrosis by a genitourinary pathologist. The untreated contralateral flank tumours were used as controls. In mice that did not receive irradiation, TKI alone yielded 4.2% tumour necrosis on the injected side and administration of HSA-AuNR-TKI alone yielded 11.1% necrosis. In the laser-ablation models, laser ablation alone yielded 62% necrosis and when paired with HSA-AuNR there was 63.4% necrosis. The combination of laser irradiation and HSA-AuNR-TKI had cell kill rate of 100%. In the absence of laser irradiation, TKI treatment alone or when delivered via nanoparticles produced moderate necrosis. Irradiation

Percutaneous thermal ablation for stage IA non-small cell lung cancer: long-term follow-up.

PubMed

Narsule, Chaitan K; Sridhar, Praveen; Nair, Divya; Gupta, Avneesh; Oommen, Roy G; Ebright, Michael I; Litle, Virginia R; Fernando, Hiran C

2017-10-01

Surgical resection is the most effective curative therapy for non-small cell lung cancer (NSCLC). However, many patients are unable to tolerate resection secondary to poor reserve or comorbid disease. Radiofrequency ablation (RFA) and microwave ablation (MWA) are methods of percutaneous thermal ablation that can be used to treat medically inoperable patients with NSCLC. We present long-term outcomes following thermal ablation of stage IA NSCLC from a single center. Patients with stage IA NSCLC and factors precluding resection who underwent RFA or MWA from July 2005 to September 2009 were studied. CT and PET-CT scans were performed at 3 and 6 month intervals, respectively, for first 24 months of follow-up. Factors associated with local progression (LP) and overall survival (OS) were analyzed. Twenty-one patients underwent 21 RFA and 4 MWA for a total of 25 ablations. Fifteen patients had T1a and six patients had T1b tumors. Mean follow-up was 42 months, median survival was 39 months, and OS at three years was 52%. There was no significant difference in median survival between T1a nodules and T1b nodules (36 vs . 39 months, P=0.29) or for RFA and MWA (36 vs . 50 months, P=0.80). Ten patients had LP (47.6%), at a median time of 35 months. There was no significant difference in LP between T1a and T1b tumors (22 vs . 35 months, P=0.94) or RFA and MWA (35 vs . 17 months, P=0.18). Median OS with LP was 32 months compared to 39 months without LP (P=0.68). Three patients underwent repeat ablations. Mean time to LP following repeat ablation was 14.75 months. One patient had two repeat ablations and was disease free at 40-month follow-up. Thermal ablation effectively treated or controlled stage IA NSCLC in medically inoperable patients. Three-year OS exceeded 50%, and LP did not affect OS. Therefore, thermal ablation is a viable option for medically inoperable patients with early stage NSCLC.

Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ran, E-mail: jliubme@tsinghua.edu.cn, E-mail: liuran@tsinghua.edu.cn; Liu, Jing, E-mail: jliubme@tsinghua.edu.cn, E-mail: liuran@tsinghua.edu.cn; Wang, Jia

Hyperthermia (42-46°C), treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated tomore » quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR) based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl) than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures.« less

Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

NASA Astrophysics Data System (ADS)

Liu, Ran; Wang, Jia; Liu, Jing

2015-07-01

Hyperthermia (42-46°C), treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated to quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR) based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl) than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures.

Modelling of pulsed electron beam induced graphite ablation: Sublimation versus melting

NASA Astrophysics Data System (ADS)

Ali, Muddassir; Henda, Redhouane

2017-12-01

Pulsed electron beam ablation (PEBA) has recently emerged as a very promising technique for the deposition of thin films with superior properties. Interaction of the pulsed electron beam with the target material is a complex process, which consists of heating, phase transition, and erosion of a small portion from the target surface. Ablation can be significantly affected by the nature of thermal phenomena taking place at the target surface, with subsequent bearing on the properties, stoichiometry and structure of deposited thin films. A two stage, one-dimensional heat conduction model is presented to describe two different thermal phenomena accounting for interaction of a graphite target with a polyenergetic electron beam. In the first instance, the thermal phenomena are comprised of heating, melting and vaporization of the target surface, while in the second instance the thermal phenomena are described in terms of heating and sublimation of the graphite surface. In this work, the electron beam delivers intense electron pulses of ∼100 ns with energies up to 16 keV and an electric current of ∼400 A to a graphite target. The temperature distribution, surface recession velocity, ablated mass per unit area, and ablation depth for the graphite target are numerically simulated by the finite element method for each case. Based on calculation findings and available experimental data, ablation appears to occur mainly in the regime of melting and vaporization from the surface.

Viral Vector-Based Targeting of miR-21 in Cardiac Nonmyocyte Cells Reduces Pathologic Remodeling of the Heart

PubMed Central

Ramanujam, Deepak; Sassi, Yassine; Laggerbauer, Bernhard; Engelhardt, Stefan

2016-01-01

Systemic inhibition of miR-21 has proven effective against myocardial fibrosis and dysfunction, while studies in cardiac myocytes suggested a protective role in this cell type. Considering potential implications for therapy, we aimed to determine the cell fraction where miR-21 exerts its pathological activity. We developed a viral vector-based strategy for gene targeting of nonmyocyte cardiac cells in vivo and compared global to cardiac myocyte-specific and nonmyocyte-specific deletion of miR-21 in chronic left ventricular pressure overload. Murine moloney virus and serotype 9 of adeno-associated virus were engineered to encode improved Cre recombinase for genetic deletion in miR-21fl/fl mice. Pericardial injection of murine moloney virus-improved Cre recombinase to neonates achieved highly selective genetic ablation of miR-21 in nonmyocyte cardiac cells, identified as cardiac fibroblasts and endothelial cells. Upon left ventricular pressure overload, cardiac function was only preserved in mice with miR-21 deficiency in nonmyocyte cardiac cells, but not in mice with global or cardiac myocyte-specific ablation. Our data demonstrate that miR-21 exerts its pathologic activity directly in cardiac nonmyocytes and encourage further development of antimiR-21 therapy toward cellular tropism. PMID:27545313

Non-immune cells equipped with T cell receptor-like signaling for cancer cell ablation

PubMed Central

Kojima, Ryosuke; Scheller, Leo; Fussenegger, Martin

2017-01-01

The ability to engineer custom cell-contact-sensing output devices into human non-immune cells would be useful for extending the applicability of cell-based cancer therapies and avoiding risks associated with engineered immune cells. Here, we have developed a new class of synthetic T-cell receptor-like signal-transduction device that functions efficiently in human non-immune cells and triggers release of output molecules specifically upon sensing contact with a target cell. This device employs an interleukin signaling cascade, whose OFF/ON switching is controlled by biophysical segregation of a transmembrane signal-inhibitory protein from the sensor cell/target cell interface. We further showed that designer non-immune cells equipped with this device driving expression of a membrane-penetrator/prodrug-activating enzyme construct could specifically kill target cells in the presence of the prodrug, indicating its potential usefulness for target-cell-specific, cell-based enzyme-prodrug cancer therapy. Our study also contributes to advancement of synthetic biology by extending available design principles to transmit extracellular information to cells. PMID:29131143

Percutaneous microwave ablation of renal cell carcinoma using a high power microwave system: focus upon safety and efficacy.

PubMed

Filippiadis, D K; Gkizas, C; Chrysofos, M; Siatelis, A; Velonakis, G; Alexopoulou, E; Kelekis, A; Brountzos, E; Kelekis, N

2017-12-04

Percutaneous ablation is an expanding, minimally invasive approach for small- to medium-sized renal masses. The purpose of this study is to review safety, and mid-term efficacy of percutaneous microwave ablation (MWA) for Renal Cell Carcinoma (RCC) treatment using a high power microwave system. Institutional database research identified 50 consecutive patients with a single lesion resembling renal cell carcinoma in CT and MRI who underwent percutaneous microwave ablation using a high power microwave system. All patients underwent biopsy on the same session with ablation using an 18G semi-automatic soft tissue biopsy needle. Contrast-enhanced computed tomography or magnetic resonance imaging was used for post-ablation follow-up. Patient and tumour characteristics, microwave technique, complications and pattern of recurrence were evaluated. Mean patient age was 74 years (male-female: 31-19). Average lesion size was 3.1 cm (range 2.0-4.3 cm). Biopsy results report RCC (n = 48), inflammatory myofibroblastic tumour (n = 1), and non-diagnostic sample (n = 1). The 3-year overall survival was 95.8% (46/48). Two patients died during the 3-year follow-up period due to causes unrelated to the MW ablation and to the RCC. Minor complications including haematomas requiring nothing but observation occurred at 4% (2/50) of the cases. Local recurrence of 6.25% (3/48) was observed with 2/3 cases being re-treated achieving a total clinical success of 97.9% (47/48 lesions). Percutaneous microwave ablation of RCC using a high power microwave system is a safe and efficacious technique for the treatment of small- to medium-sized renal masses.

A clinically feasible treatment protocol for magnetic resonance-guided high-intensity focused ultrasound ablation in the liver.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Bartels, Lambertus W; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2015-01-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) allows for noninvasive thermal ablation under real-time temperature imaging guidance. The purpose of this study was to assess the feasibility and safety of MR-HIFU ablation of liver tissue in a clinically acceptable setting. The experimental protocol was designed with a clinical ablation procedure of a small malignant tumor in mind; the procedures were performed within a clinically feasible time frame and care was taken to avoid adverse events. The main outcome was the size and quality of the ablated liver tissue volume on imaging and histology. Secondary outcomes were safety and treatment time. Healthy pigs (n = 10) under general anesthesia were positioned on a clinical MR-HIFU system, which consisted of an HIFU tabletop with a skin cooling system integrated into a 1.5-T MR scanner. A liver tissue volume was ablated with multiple sonication cells (4 × 4 × 10 mm, 450 W). Both MR thermometry and sonication were respiratory-gated using a pencil beam navigator on the diaphragm. Contrast-enhanced T1-weighted (CE-T1w) imaging was performed for treatment evaluation. Targeted total treatment time was 3 hours. The abdominal wall, liver, and adjacent organs were inspected postmortem for thermal damage. Ablated tissue volumes were processed for cell viability staining. The ablated volumes were analyzed using MR imaging, MR thermometry, and cell viability histology. Eleven volume ablations were performed in 10 animals, resulting in a median nonperfused volume (NPV) on CE-T1w imaging of 1.6 mL (interquartile range [IQR], 0.8-2.3; range, 0.7-3.0). Cell viability histology showed a damaged volume of 1.5 mL (IQR, 1.1-1.8; range, 0.7-2.3). The NPV was confluent in 10 of the 11 cases. The ablated tissue volume on cell viability histology was confluent in all 9 available cases. In all cases, there was a good correspondence between the aspects of the NPV on CE-T1w and the ablated volume on cell viability

Gold Nanoparticles as a Photothermal Agent in Cancer Therapy: The Thermal Ablation Characteristic Length.

PubMed

Grosges, Thomas; Barchiesi, Dominique

2018-05-31

In cancer therapy, the thermal ablation of diseased cells by embedded nanoparticles is one of the known therapies. It is based on the absorption of the energy of the illuminating laser by nanoparticles. The resulting heating of nanoparticles kills the cell where these photothermal agents are embedded. One of the main constraints of this therapy is preserving the surrounding healthy cells. Therefore, two parameters are of interest. The first one is the thermal ablation characteristic length, which corresponds to an action distance around the nanoparticles for which the temperature exceeds the ablation threshold. This critical geometric parameter is related to the expected conservation of the body temperature in the surroundings of the diseased cell. The second parameter is the temperature that should be reached to achieve active thermal agents. The temperature depends on the power of the illuminating laser, on the size of nanoparticles and on their physical properties. The purpose of this paper is to propose behavior laws under the constraints of both the body temperature at the boundary of the cell to preserve surrounding cells and an acceptable range of temperature in the target cell. The behavior laws are deduced from the finite element method, which is able to model aggregates of nanoparticles. We deduce sensitivities to the laser power and to the particle size. We show that the tuning of the temperature elevation and of the distance of action of a single nanoparticle is not significantly affected by variations of the particle size and of the laser power. Aggregates of nanoparticles are much more efficient, but represent a potential risk to the surrounding cells. Fortunately, by tuning the laser power, the thermal ablation characteristic length can be controlled.

Sphere-enhanced microwave ablation (sMWA) versus bland microwave ablation (bMWA): technical parameters, specific CT 3D rendering and histopathology.

PubMed

Gockner, T L; Zelzer, S; Mokry, T; Gnutzmann, D; Bellemann, N; Mogler, C; Beierfuß, A; Köllensperger, E; Germann, G; Radeleff, B A; Stampfl, U; Kauczor, H U; Pereira, P L; Sommer, C M

2015-04-01

This study was designed to compare technical parameters during ablation as well as CT 3D rendering and histopathology of the ablation zone between sphere-enhanced microwave ablation (sMWA) and bland microwave ablation (bMWA). In six sheep-livers, 18 microwave ablations were performed with identical system presets (power output: 80 W, ablation time: 120 s). In three sheep, transarterial embolisation (TAE) was performed immediately before microwave ablation using spheres (diameter: 40 ± 10 μm) (sMWA). In the other three sheep, microwave ablation was performed without spheres embolisation (bMWA). Contrast-enhanced CT, sacrifice, and liver harvest followed immediately after microwave ablation. Study goals included technical parameters during ablation (resulting power output, ablation time), geometry of the ablation zone applying specific CT 3D rendering with a software prototype (short axis of the ablation zone, volume of the largest aligned ablation sphere within the ablation zone), and histopathology (hematoxylin-eosin, Masson Goldner and TUNEL). Resulting power output/ablation times were 78.7 ± 1.0 W/120 ± 0.0 s for bMWA and 78.4 ± 1.0 W/120 ± 0.0 s for sMWA (n.s., respectively). Short axis/volume were 23.7 ± 3.7 mm/7.0 ± 2.4 cm(3) for bMWA and 29.1 ± 3.4 mm/11.5 ± 3.9 cm(3) for sMWA (P < 0.01, respectively). Histopathology confirmed the signs of coagulation necrosis as well as early and irreversible cell death for bMWA and sMWA. For sMWA, spheres were detected within, at the rim, and outside of the ablation zone without conspicuous features. Specific CT 3D rendering identifies a larger ablation zone for sMWA compared with bMWA. The histopathological signs and the detectable amount of cell death are comparable for both groups. When comparing sMWA with bMWA, TAE has no effect on the technical parameters during ablation.

The contemporary role of ablative treatment approaches in the management of renal cell carcinoma (RCC): focus on radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), and cryoablation.

PubMed

Klatte, Tobias; Kroeger, Nils; Zimmermann, Uwe; Burchardt, Martin; Belldegrun, Arie S; Pantuck, Allan J

2014-06-01

Currently, most of renal tumors are small, low grade, with a slow growth rate, a low metastatic potential, and with up to 30 % of these tumors being benign on the final pathology. Moreover, they are often diagnosed in elderly patients with preexisting medical comorbidities in whom the underlying medical conditions may pose a greater risk of death than the small renal mass. Concerns regarding overdiagnosis and overtreatment of patients with indolent small renal tumors have led to an increasing interest in minimally invasive, ablative as an alternative to extirpative interventions for selected patients. To provide an overview about the state of the art in radiofrequency ablation (RFA), high-intensity focused ultrasound, and cryoablation in the clinical management of renal cell carcinoma. A PubMed wide the literature search of was conducted. International consensus panels recommend ablative techniques in patients who are unfit for surgery, who are not considered candidates for or elect against elective surveillance, and who have small renal masses. The most often used techniques are cryoablation and RFA. These ablative techniques offer potentially curative outcomes while conferring several advantages over extirpative surgery, including improved patient procedural tolerance, faster recovery, preservation of renal function, and reduction in the risk of intraoperative and postsurgical complications. While it is likely that outcomes associated with ablative modalities will improve with further advances in technology, their application will expand to more elective indications as longer-term efficacy data become available. Ablative techniques pose a valid treatment option in selected patients.

Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy

PubMed Central

Kimm, Simon Y.; Tarin, Tatum V.; Monette, Sébastien; Srimathveeravalli, Govindarajan; Gerber, Daniel; Durack, Jeremy C.; Solomon, Stephen B.; Scardino, Peter T.; Scherz, Avigdor

2016-01-01

Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non–tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee–approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material–enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P < .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 μm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were

Experimental ablation of the pancreas with high intensity focused ultrasound (HIFU) in a porcine model.

PubMed

Xie, Biao; Li, Yu-Yuan; Jia, Lin; Nie, Yu-Qiang; Du, Hong; Jiang, Shu-Man

2010-12-17

The aim of this study was to determine the feasibility and safety of high intensity focused ultrasound's (HIFU) in pancreatic diseases. Twelve pigs were divided into three groups. The pancreases of pigs in Group A were ablated directly with HIFU, but those in Group B and C ablated by extracorporeal HIFU. The pigs in Group C were sacrificed at day 7 after HIFU. Serological parameters were determined pre-operation and post-operation. The entire pancreas was removed for histological examination. Each animal tolerate the HIFU ablation well. The complete necrosis was observed in targeted regions. The margins of the necrotic regions were clearly delineated from the surrounding normal tissues. Infiltration of inflammatory cells and phorocytosis on the boundary were found in group C. Blood and urine amylase levels were relatively steady after HIFU. No acute pancreatitis or severe complications occurred. In conclusion, HIFU ablation on the pancreas was safe and effective in experimental pigs.

Experimental ablation of the pancreas with high intensity focused ultrasound (HIFU) in a porcine model

PubMed Central

Xie, Biao; Li, Yu-Yuan; Jia, Lin; Nie, Yu-Qiang; Du, Hong; Jiang, Shu-Man

2011-01-01

The aim of this study was to determine the feasibility and safety of high intensity focused ultrasound's (HIFU) in pancreatic diseases. Twelve pigs were divided into three groups. The pancreases of pigs in Group A were ablated directly with HIFU, but those in Group B and C ablated by extracorporeal HIFU. The pigs in Group C were sacrificed at day 7 after HIFU. Serological parameters were determined pre-operation and post-operation. The entire pancreas was removed for histological examination. Each animal tolerate the HIFU ablation well. The complete necrosis was observed in targeted regions. The margins of the necrotic regions were clearly delineated from the surrounding normal tissues. Infiltration of inflammatory cells and phorocytosis on the boundary were found in group C. Blood and urine amylase levels were relatively steady after HIFU. No acute pancreatitis or severe complications occurred. In conclusion, HIFU ablation on the pancreas was safe and effective in experimental pigs. PMID:21197259

Planarization of Isolated Defects on ICF Target Capsule Surfaces by Pulsed Laser Ablation

DOE PAGES

Alfonso, Noel; Carlson, Lane C.; Bunn, Thomas L.

2016-08-09

Demanding surface quality requirements for inertial confinement fusion (ICF) capsules motivated the development of a pulsed laser ablation method to reduce or eliminate undesirable surface defects. The pulsed laser ablation technique takes advantage of a full surface (4π) capsule manipulation system working in combination with an optical profiling (confocal) microscope. Based on the defect topography, the material removal rate, the laser pulse energy and its beam profile, a customized laser raster pattern is derived to remove the defect. The pattern is a table of coordinates and number of pulses that dictate how the defect will be vaporized until its heightmore » is level with the capsule surface. This paper explains how the raster patterns are optimized to minimize surface roughness and how surface roughness after laser ablation is simulated. The simulated surfaces are compared with actual ablated surfaces. Large defects are reduced to a size regime where a tumble finishing process produces very high quality surfaces devoid of high mode defects. The combined polishing processes of laser ablation and tumble finishing have become routine fabrication steps for National Ignition Facility capsule production.« less

Patterned femtosecond-laser ablation of Xenopus laevis melanocytes for studies of cell migration, wound repair, and developmental processes

PubMed Central

Mondia, Jessica P.; Adams, Dany S.; Orendorff, Ryan D.; Levin, Michael; Omenetto, Fiorenzo G.

2011-01-01

Ultrafast (femtosecond) lasers have become an important tool to investigate biological phenomena because of their ability to effect highly localized tissue removal in surgical applications. Here we describe programmable, microscale, femtosecond-laser ablation of melanocytes found on Xenopus laevis tadpoles, a technique that is applicable to biological studies in development, regeneration, and cancer research. We illustrate laser marking of individual melanocytes, and the drawing of patterns on melanocyte clusters to help track their migration and/or regeneration. We also demonstrate that this system can upgrade scratch tests, a technique used widely with cultured cells to study cell migration and wound healing, to the more realistic in vivo realm, by clearing a region of melanocytes and monitoring their return over time. In addition, we show how melanocyte ablation can be used for loss-of-function experiments by damaging neighboring tissue, using the example of abnormal tail regeneration following localized spinal cord damage. Since the size, shape, and depth of melanocytes vary as a function of tadpole age and melanocyte location (head or tail), an ablation threshold chart is given. Mechanisms of laser ablation are also discussed. PMID:21833375

Patterned femtosecond-laser ablation of Xenopus laevis melanocytes for studies of cell migration, wound repair, and developmental processes.

PubMed

Mondia, Jessica P; Adams, Dany S; Orendorff, Ryan D; Levin, Michael; Omenetto, Fiorenzo G

2011-08-01

Ultrafast (femtosecond) lasers have become an important tool to investigate biological phenomena because of their ability to effect highly localized tissue removal in surgical applications. Here we describe programmable, microscale, femtosecond-laser ablation of melanocytes found on Xenopus laevis tadpoles, a technique that is applicable to biological studies in development, regeneration, and cancer research. We illustrate laser marking of individual melanocytes, and the drawing of patterns on melanocyte clusters to help track their migration and/or regeneration. We also demonstrate that this system can upgrade scratch tests, a technique used widely with cultured cells to study cell migration and wound healing, to the more realistic in vivo realm, by clearing a region of melanocytes and monitoring their return over time. In addition, we show how melanocyte ablation can be used for loss-of-function experiments by damaging neighboring tissue, using the example of abnormal tail regeneration following localized spinal cord damage. Since the size, shape, and depth of melanocytes vary as a function of tadpole age and melanocyte location (head or tail), an ablation threshold chart is given. Mechanisms of laser ablation are also discussed.

Tracked 3D ultrasound in radio-frequency liver ablation

NASA Astrophysics Data System (ADS)

Boctor, Emad M.; Fichtinger, Gabor; Taylor, Russell H.; Choti, Michael A.

2003-05-01

Recent studies have shown that radio frequency (RF) ablation is a simple, safe and potentially effective treatment for selected patients with liver metastases. Despite all recent therapeutic advancements, however, intra-procedural target localization and precise and consistent placement of the tissue ablator device are still unsolved problems. Various imaging modalities, including ultrasound (US) and computed tomography (CT) have been tried as guidance modalities. Transcutaneous US imaging, due to its real-time nature, may be beneficial in many cases, but unfortunately, fails to adequately visualize the tumor in many cases. Intraoperative or laparoscopic US, on the other hand, provides improved visualization and target imaging. This paper describes a system for computer-assisted RF ablation of liver tumors, combining navigational tracking of a conventional imaging ultrasound probe to produce 3D ultrasound imaging with a tracked RF ablation device supported by a passive mechanical arm and spatially registered to the ultrasound volume.

Sphere-Enhanced Microwave Ablation (sMWA) Versus Bland Microwave Ablation (bMWA): Technical Parameters, Specific CT 3D Rendering and Histopathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gockner, T. L., E-mail: theresa.gockner@med.uni-heidelberg.de; Zelzer, S., E-mail: s.zelzer@dkfz-heidelberg.de; Mokry, T., E-mail: theresa.mokry@med.uni-heidelberg.de

PurposeThis study was designed to compare technical parameters during ablation as well as CT 3D rendering and histopathology of the ablation zone between sphere-enhanced microwave ablation (sMWA) and bland microwave ablation (bMWA).MethodsIn six sheep-livers, 18 microwave ablations were performed with identical system presets (power output: 80 W, ablation time: 120 s). In three sheep, transarterial embolisation (TAE) was performed immediately before microwave ablation using spheres (diameter: 40 ± 10 μm) (sMWA). In the other three sheep, microwave ablation was performed without spheres embolisation (bMWA). Contrast-enhanced CT, sacrifice, and liver harvest followed immediately after microwave ablation. Study goals included technical parameters during ablation (resulting power output,more » ablation time), geometry of the ablation zone applying specific CT 3D rendering with a software prototype (short axis of the ablation zone, volume of the largest aligned ablation sphere within the ablation zone), and histopathology (hematoxylin-eosin, Masson Goldner and TUNEL).ResultsResulting power output/ablation times were 78.7 ± 1.0 W/120 ± 0.0 s for bMWA and 78.4 ± 1.0 W/120 ± 0.0 s for sMWA (n.s., respectively). Short axis/volume were 23.7 ± 3.7 mm/7.0 ± 2.4 cm{sup 3} for bMWA and 29.1 ± 3.4 mm/11.5 ± 3.9 cm{sup 3} for sMWA (P < 0.01, respectively). Histopathology confirmed the signs of coagulation necrosis as well as early and irreversible cell death for bMWA and sMWA. For sMWA, spheres were detected within, at the rim, and outside of the ablation zone without conspicuous features.ConclusionsSpecific CT 3D rendering identifies a larger ablation zone for sMWA compared with bMWA. The histopathological signs and the detectable amount of cell death are comparable for both groups. When comparing sMWA with bMWA, TAE has no effect on the technical parameters during ablation.« less

Femtosecond laser ablation and nanoparticle formation in intermetallic NiAl

NASA Astrophysics Data System (ADS)

Jorgensen, David J.; Titus, Michael S.; Pollock, Tresa M.

2015-10-01

The ablation behavior of a stoichiometric intermetallic compound β-NiAl subjected to femtosecond laser pulsing in air has been investigated. The single-pulse ablation threshold for NiAl was determined to be 83 ± 4 mJ/cm2 and the transition to the high-fluence ablation regime occurred at 2.8 ± 0.3 J/cm2. Two sizes of nanoparticles consisting of Al, NiAl, Ni3Al and NiO were formed and ejected from the target during high-fluence ablation. Chemical analysis revealed that smaller nanoparticles (1-30 nm) tended to be rich in Al while larger nanoparticles (>100 nm) were lean in Al. Ablation in the low-fluence regime maintained this trend. Redeposited material and nanoparticles remaining on the surface after a single 3.7 J/cm2 pulse, one hundred 1.7 J/cm2 pulses, or one thousand 250 mJ/cm2 pulses were enriched in Al relative to the bulk target composition. Further, the surface of the irradiated high-fluence region was depleted in Al indicating that the fs laser ablation removal rate of the intermetallic constituents in this regime does not scale with the individual pure element ablation thresholds.

Regeneration in the Pituitary After Cell-Ablation Injury: Time-Related Aspects and Molecular Analysis.

PubMed

Willems, Christophe; Fu, Qiuli; Roose, Heleen; Mertens, Freya; Cox, Benoit; Chen, Jianghai; Vankelecom, Hugo

2016-02-01

We recently showed that the mouse pituitary holds regenerative competence. Young-adult GHCre/iDTR mice, expressing diphtheria toxin (DT) receptor in GH-producing cells, regenerate the GH(+) cells, as ablated by 3-day DT treatment (3DT), up to 60% after 5 months. The pituitary's stem cells participate in this restoration process. Here, we characterized this regenerative capacity in relation to age and recovery period and started to search for underlying molecular mechanisms. Extending the recovery period (up to 19 mo) does not result in higher regeneration levels. In addition, the regenerative competence disappears at older age, coinciding with a reduction in pituitary stem cell number and fitness. Surprisingly, prolonging DT treatment of young-adult mice to 10 days (10DT) completely blocks the regeneration, although the stem cell compartment still reacts by promptly expanding, and retains in vitro stem cell functionality. To obtain a first broad view on molecular grounds underlying reparative capacity and/or failure, the stem cell-clustering side population was analyzed by whole-genome expression analysis. A number of stemness factors and components of embryonic, epithelial-mesenchymal transition, growth factor and Hippo pathways are higher expressed in the stem cell-clustering side population of the regenerating pituitary (after 3DT) when compared with the basal gland and to the nonregenerating pituitary (after 10DT). Together, the regenerative capacity of the pituitary is limited both in age-related terms and final efficacy, and appears to rely on stem cell-associated pathway activation. Dissection of the molecular profiles may eventually identify targets to induce or boost regeneration in situations of (injury-related) pituitary deficiency.

The effect of asteroid topography on surface ablation deflection

NASA Astrophysics Data System (ADS)

McMahon, Jay W.; Scheeres, Daniel J.

2017-02-01

Ablation techniques for deflecting hazardous asteroids deposit energy into the asteroid's surface, causing an effective thrust on the asteroid as the ablating material leaves normal to the surface. Although it has long been recognized that surface topography plays an important role in determining the deflection capabilities, most studies to date have ignored this aspect of the model. This paper focuses on understanding the topography for real asteroid shapes, and how this topography can change the deflection performance of an ablation technique. The near Earth asteroids Golevka, Bennu, and Itokawa are used as the basis for this study, as all three have high-resolution shape models available. This paper shows that naive targeting of an ablation method without accounting for the surface topography can lower the deflection performance by up to 20% in the cases studied in terms of the amount of acceleration applied in the desired direction. If the ablation thrust level is assumed to be 100 N, as used elsewhere in the literature, this misapplication of thrust translates to tens of kilometers per year in decreased semimajor axis change. However, if the ablation method can freely target any visible point on the surface of the asteroid, almost all of this performance can be recovered.

Anti-TROP2 conjugated hollow gold nanospheres as a novel nanostructure for targeted photothermal destruction of cervical cancer cells

NASA Astrophysics Data System (ADS)

Liu, Ting; Tian, Jiguang; Chen, Zhaolong; Liang, Ying; Liu, Jiao; Liu, Si; Li, Huihui; Zhan, Jinhua; Yang, Xingsheng

2014-08-01

Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L-1) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). γH2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment.

Diagnosis and ablation of multiform fascicular tachycardia.

PubMed

Sung, Raphael K; Kim, Albert M; Tseng, Zian H; Han, Frederick; Inada, Keiichi; Tedrow, Usha B; Viswanathan, Mohan N; Badhwar, Nitish; Varosy, Paul D; Tanel, Ronn; Olgin, Jeffrey E; Stephenson, William G; Scheinman, Melvin

2013-03-01

Fascicular tachycardia (FT) is an uncommon cause of monomorphic sustained ventricular tachycardia (VT). We describe 6 cases of FT with multiform QRS morphologies. Six of 823 consecutive VT cases were retrospectively analyzed and found attributable to FT with multiform QRS patterns, with 3 cases exhibiting narrow QRS VT as well. All underwent electrophysiology study including fascicular potential mapping, entrainment pacing, and electroanatomic mapping. The first 3 cases describe similar multiform VT patterns with successful ablation in the upper mid septum. Initially, a right bundle branch block (RBBB) VT with superior axis was induced. Radiofrequency catheter ablation (RFCA) targeting the left posterior fascicle (LPF) resulted in a second VT with RBBB inferior axis. RFCA in the upper septum just apical to the LBB potential abolished VT in all cases. Cases 4 and 5 showed RBBB VT with alternating fascicular block compatible with upper septal dependent VT, resulting in bundle branch reentrant VT (BBRT) after ablation of LPF and left anterior fascicle (LAF). Finally, Cases 5 and 6 demonstrated spontaneous shift in QRS morphology during VT, implicating participation of a third fascicle. In Case 6, successful ablation was achieved over the proximal LAF, likely representing insertion of the auxiliary fascicle near the proximal LAF. Multiform FTs show a reentrant mechanism using multiple fascicular branches. We hypothesize that retrograde conduction over the septal fascicle produces alternate fascicular patterns as well as narrow VT forms. Ablation of the respective fascicle was successful in abolishing FT but does not preclude development of BBRT unless septal fascicle is targeted and ablated. © 2012 Wiley Periodicals, Inc.

MR thermometry analysis of sonication accuracy and safety margin of volumetric MR imaging-guided high-intensity focused ultrasound ablation of symptomatic uterine fibroids.

PubMed

Kim, Young-sun; Trillaud, Hervé; Rhim, Hyunchul; Lim, Hyo K; Mali, Willem; Voogt, Marianne; Barkhausen, Jörg; Eckey, Thomas; Köhler, Max O; Keserci, Bilgin; Mougenot, Charles; Sokka, Shunmugavelu D; Soini, Jouko; Nieminen, Heikki J

2012-11-01

To evaluate the accuracy of the size and location of the ablation zone produced by volumetric magnetic resonance (MR) imaging-guided high-intensity focused ultrasound ablation of uterine fibroids on the basis of MR thermometric analysis and to assess the effects of a feedback control technique. This prospective study was approved by the institutional review board, and written informed consent was obtained. Thirty-three women with 38 uterine fibroids were treated with an MR imaging-guided high-intensity focused ultrasound system capable of volumetric feedback ablation. Size (diameter times length) and location (three-dimensional displacements) of each ablation zone induced by 527 sonications (with [n=471] and without [n=56] feedback) were analyzed according to the thermal dose obtained with MR thermometry. Prospectively defined acceptance ranges of targeting accuracy were ±5 mm in left-right (LR) and craniocaudal (CC) directions and ±12 mm in anteroposterior (AP) direction. Effects of feedback control in 8- and 12-mm treatment cells were evaluated by using a mixed model with repeated observations within patients. Overall mean sizes of ablation zones produced by 4-, 8-, 12-, and 16-mm treatment cells (with and without feedback) were 4.6 mm±1.4 (standard deviation)×4.4 mm±4.8 (n=13), 8.9 mm±1.9×20.2 mm±6.5 (n=248), 13.0 mm±1.2×29.1 mm±5.6 (n=234), and 18.1 mm±1.4×38.2 mm±7.6 (n=32), respectively. Targeting accuracy values (displacements in absolute values) were 0.9 mm±0.7, 1.2 mm±0.9, and 2.8 mm±2.2 in LR, CC, and AP directions, respectively. Of 527 sonications, 99.8% (526 of 527) were within acceptance ranges. Feedback control had no statistically significant effect on targeting accuracy or ablation zone size. However, variations in ablation zone size were smaller in the feedback control group. Sonication accuracy of volumetric MR imaging-guided high-intensity focused ultrasound ablation of uterine fibroids appears clinically acceptable and may be

Induced Ablation of Ghrelin Cells in Adult Mice Does Not Decrease Food Intake, Body Weight, or Response to High Fat Diet

PubMed Central

McFarlane, Matthew R.; Brown, Michael S.; Goldstein, Joseph L.; Zhao, Tong-Jin

2014-01-01

SUMMARY Injection of the peptide hormone ghrelin stimulates food intake in mice and humans. However, mice born without ghrelin demonstrate no significant loss of appetite. This paradox suggests either that compensation develops in mice born without ghrelin or that ghrelin is not essential for appetite control. To distinguish these possibilities, we generated transgenic mice (Ghrl-DTR) that express the diphtheria toxin receptor in ghrelin-secreting cells. Injection of diphtheria toxin in adulthood ablated ghrelin cells and reduced plasma ghrelin by 80-95%. Ghrelin cell-ablated mice exhibited no loss of appetite or body weight and no resistance to a high fat diet. To stimulate food intake in mice by ghrelin injection, we had to raise plasma levels many-fold above normal. Like germline ghrelin-deficient mice, the ghrelin cell-ablated mice developed profound hypoglycemia when subjected to prolonged calorie restriction, confirming that ghrelin acts to maintain blood glucose under famine conditions. PMID:24836560

Experimental setup for the laboratory investigation of micrometeoroid ablation using a dust accelerator.

PubMed

Thomas, Evan; Simolka, Jonas; DeLuca, Michael; Horányi, Mihály; Janches, Diego; Marshall, Robert A; Munsat, Tobin; Plane, John M C; Sternovsky, Zoltan

2017-03-01

A facility has been developed to simulate the ablation of micrometeoroids in laboratory conditions. An electrostatic dust accelerator is used to generate iron particles with velocities of 10-70 km/s. The particles are then introduced into a chamber pressurized with a target gas, where the pressure is adjustable between 0.01 and 0.5 Torr, and the particle partially or completely ablates over a short distance. An array of biased electrodes above and below the ablation path is used to collect the generated ions/electrons with a spatial resolution of 2.6 cm along the ablating particles' path, thus allowing the study of the spatiotemporal evolution of the process. For completely ablated particles, the total collected charge directly yields the ionization coefficient of a given dust material-target gas combination. The first results of this facility measured the ionization coefficient of iron atoms with N 2 , air, CO 2 , and He target gases for impact velocities >20 km/s, and are reported by Thomas et al. [Geophys. Res. Lett. 43, 3645 (2016)]. The ablation chamber is also equipped with four optical ports that allow for the detection of the light emitted by the ablating particle. A multichannel photomultiplier tube system is used to observe the ablation process with a spatial and temporal resolution of 0.64 cm and 90 ns. The preliminary results indicate that it is possible to calculate the velocity of the ablating particle from the optical observations, and in conjunction with the spatially resolved charge measurements allow for experimental validation of ablation models in future studies.

Experimental setup for the laboratory investigation of micrometeoroid ablation using a dust accelerator

NASA Astrophysics Data System (ADS)

Thomas, Evan; Simolka, Jonas; DeLuca, Michael; Horányi, Mihály; Janches, Diego; Marshall, Robert A.; Munsat, Tobin; Plane, John M. C.; Sternovsky, Zoltan

2017-03-01

A facility has been developed to simulate the ablation of micrometeoroids in laboratory conditions. An electrostatic dust accelerator is used to generate iron particles with velocities of 10-70 km/s. The particles are then introduced into a chamber pressurized with a target gas, where the pressure is adjustable between 0.01 and 0.5 Torr, and the particle partially or completely ablates over a short distance. An array of biased electrodes above and below the ablation path is used to collect the generated ions/electrons with a spatial resolution of 2.6 cm along the ablating particles' path, thus allowing the study of the spatiotemporal evolution of the process. For completely ablated particles, the total collected charge directly yields the ionization coefficient of a given dust material-target gas combination. The first results of this facility measured the ionization coefficient of iron atoms with N2, air, CO2, and He target gases for impact velocities >20 km/s, and are reported by Thomas et al. [Geophys. Res. Lett. 43, 3645 (2016)]. The ablation chamber is also equipped with four optical ports that allow for the detection of the light emitted by the ablating particle. A multichannel photomultiplier tube system is used to observe the ablation process with a spatial and temporal resolution of 0.64 cm and 90 ns. The preliminary results indicate that it is possible to calculate the velocity of the ablating particle from the optical observations, and in conjunction with the spatially resolved charge measurements allow for experimental validation of ablation models in future studies.

Experimental Setup for the Laboratory Investigation of Micrometeoroid Ablation Using a Dust Accelerator

NASA Technical Reports Server (NTRS)

Thomas, Evan; Simolka, Jonas; DeLuca, Michael; Horanyi, Mihaly; Janches, Diego; Marshall, Robert A.; Munsat, Tobin; Plane, John M. C.; Sternovsky, Zoltan

2017-01-01

A facility has been developed to simulate the ablation of micrometeoroids in laboratory conditions. An electrostatic dust accelerator is used to generate iron particles with velocities of 10-70 kilometers. The particles are then introduced into a chamber pressurized with a target gas, where the pressure is adjustable between 0.01 and 0.5 Torr, and the particle partially or completely ablates over a short distance. An array of biased electrodes above and below the ablation path is used to collect the generated ions/electrons with a spatial resolution of 2.6 centimeters along the ablating particles path, thus allowing the study of the spatiotemporal evolution of the process. For completely ablated particles, the total collected charge directly yields the ionization coefficient of a given dust material-target gas combination. The first results of this facility measured the ionization coefficient of iron atoms with N2, air, CO2, and He target gases for impact velocities greater than 20 kilometers per second, and are reported by Thomas et al. The ablation chamber is also equipped with four optical ports that allow for the detection of the light emitted by the ablating particle. A multichannel photomultiplier tube system is used to observe the ablation process with a spatial and temporal resolution of 0.64 centimeters and 90 nanoseconds. The preliminary results indicate that it is possible to calculate the velocity of the ablating particle from the optical observations, and in conjunction with the spatially resolved charge measurements allow for experimental validation of ablation models in future studies.

Laser ablation of basal cell carcinomas guided by confocal microscopy

NASA Astrophysics Data System (ADS)

Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

2016-02-01

Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

Radiofrequency ablation in primary non-small cell lung cancer: What a radiologist needs to know

PubMed Central

Bhatia, Shivank; Pereira, Keith; Mohan, Prasoon; Narayanan, Govindarajan; Wangpaichitr, Medhi; Savaraj, Niramol

2016-01-01

Lung cancer continues to be one of the leading causes of death worldwide. In advanced cases of lung cancer, a multimodality approach is often applied, however with poor local control rates. In early non-small cell lung cancer (NSCLC), surgery is the standard of care. Only 15-30% of patients are eligible for surgical resection. Improvements in imaging and treatment delivery systems have provided new tools to better target these tumors. Stereotactic body radiation therapy (SBRT) has evolved as the next best option. The role of radiofrequency ablation (RFA) is also growing. Currently, it is a third-line option in stage 1 NSCLC, when SBRT cannot be performed. More recent studies have demonstrated usefulness in recurrent tumors and some authors have also suggested combination of RFA with other modalities in larger tumors. Following the National Lung Screening Trial (NLST), screening by low-dose computed tomography (CT) has demonstrated high rates of early-stage lung cancer detection in high-risk populations. Hence, even considering the current role of RFA as a third-line option, in view of increasing numbers of occurrences detected, the number of potential RFA candidates may see a steep uptrend. In view of all this, it is imperative that interventional radiologists be familiar with the techniques of lung ablation. The aim of this article is to discuss the procedural technique of RFA in the lung and review the current evidence regarding RFA for NSCLC. PMID:27081229

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction.

PubMed

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-08-09

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP.

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction

PubMed Central

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-01-01

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP. PMID:27437775

Numerical design of RF ablation applicator for hepatic cancer treatment

NASA Astrophysics Data System (ADS)

Rakhmadi, Aditya; Basari

2017-02-01

Currently, cancer has become one of health problems that is difficult to be overcomed. This disease is not only difficult to be cured, but also to be detected and may cause death. For this reason, RF ablation treatment method is proposed to cure cancer. RF ablation therapy is a method in which an applicator is inserted into the body to kill cancer cells by heating the cells. The cancer cells are exposed to the temperature more than 60°C in short duration (few second to few minutes) so thus cell destruction occurs locally. For the sake of the successful treatment, a minimally invasive method is selected in order for perfect local temperature distribution in cancer cells can be achieved. In this paper, a coax-fed dipole-type applicator with interstitial irradiation technique is proposed aimed at RF ablation into hepatic cells. Numerical simulation is performed to obtain a suitable geometric dimension at operating frequency around 2.45 GHz, in order to localize the ablation area. The proposed applicator is inserted into a simple phantom representing an adult human body model in which normal and cancerous liver cells. The simulated results show that the proposed applicator is able to operate at center frequency of 2.355 GHz with blood droplet-type ablation zone and the temperature around the cancer cell by 60°C can be achieved.

Off to the Organelles - Killing Cancer Cells with Targeted Gold Nanoparticles

PubMed Central

Kodiha, Mohamed; Wang, Yi Meng; Hutter, Eliza; Maysinger, Dusica; Stochaj, Ursula

2015-01-01

Gold nanoparticles (AuNPs) are excellent tools for cancer cell imaging and basic research. However, they have yet to reach their full potential in the clinic. At present, we are only beginning to understand the molecular mechanisms that underlie the biological effects of AuNPs, including the structural and functional changes of cancer cells. This knowledge is critical for two aspects of nanomedicine. First, it will define the AuNP-induced events at the subcellular and molecular level, thereby possibly identifying new targets for cancer treatment. Second, it could provide new strategies to improve AuNP-dependent cancer diagnosis and treatment. Our review summarizes the impact of AuNPs on selected subcellular organelles that are relevant to cancer therapy. We focus on the nucleus, its subcompartments, and mitochondria, because they are intimately linked to cancer cell survival, growth, proliferation and death. While non-targeted AuNPs can damage tumor cells, concentrating AuNPs in particular subcellular locations will likely improve tumor cell killing. Thus, it will increase cancer cell damage by photothermal ablation, mechanical injury or localized drug delivery. This concept is promising, but AuNPs have to overcome multiple hurdles to perform these tasks. AuNP size, morphology and surface modification are critical parameters for their delivery to organelles. Recent strategies explored all of these variables, and surface functionalization has become crucial to concentrate AuNPs in subcellular compartments. Here, we highlight the use of AuNPs to damage cancer cells and their organelles. We discuss current limitations of AuNP-based cancer research and conclude with future directions for AuNP-dependent cancer treatment. PMID:25699096

Laser Ablated Carbon Nanodots for Light Emission.

PubMed

Reyes, Delfino; Camacho, Marco; Camacho, Miguel; Mayorga, Miguel; Weathers, Duncan; Salamo, Greg; Wang, Zhiming; Neogi, Arup

2016-12-01

The synthesis of fluorescent carbon dots-like nanostructures (CNDs) obtained through the laser ablation of a carbon solid target in liquid environment is reported. The ablation process was induced in acetone with laser pulses of 1064, 532, and 355 nm under different irradiation times. Close-spherical amorphous CNDs with sizes between 5 and 20 nm, whose abundance strongly depends on the ablation parameters were investigated using electron microscopy and was confirmed using absorption and emission spectroscopies. The π- π* electronic transition at 3.76 eV dominates the absorption for all the CNDs species synthesized under different irradiation conditions. The light emission is most efficient due to excitation at 3.54 eV with the photoluminescence intensity centered at 3.23 eV. The light emission from the CNDs is most efficient due to ablation at 355 nm. The emission wavelength of the CNDs can be tuned from the near-UV to the green wavelength region by controlling the ablation time and modifying the ablation and excitation laser wavelength.

Design options for improved performance with high-density carbon ablators and low-gas fill hohlraum targets

NASA Astrophysics Data System (ADS)

Berzak Hopkins, L.; Divol, L.; Lepape, S.; Meezan, N. B.; Dewald, E.; Ho, D.; Khan, S.; Pak, A.; Ralph, J.; Ross, J. S.

2016-10-01

Recent simulation-based and experimental work using high-density carbon ablators in unlined uranium hohlraums with 0.3 mg/cc helium fill have demonstrated round implosions with minimal evolution of Legendre moment P2 during burn. To extend this promising work, design studies have been performed to explore potential performance improvements with larger capsules, while maintaining similar case-to-capsule target ratios. We present here the results of these design studies, which will motivate a series of upcoming experiments at the National Ignition Facility. Prepared by LLNL under Contract DE-AC52-07NA27344.

Ablation of Rotor and Focal Sources Reduces Late Recurrence of Atrial Fibrillation Compared to Trigger Ablation Alone

PubMed Central

Narayan, Sanjiv M.; Baykaner, Tina; Clopton, Paul; Schricker, Amir; Lalani, Gautam; Krummen, David E.; Shivkumar, Kalyanam; Miller, John M.

2014-01-01

Objectives To determine if ablation that targets patient-specific AF-sustaining substrates (rotors or focal sources) is more durable than trigger ablation alone at preventing late AF recurrences. Background Late recurrence substantially limits the efficacy of pulmonary vein (PV) isolation for AF, and is associated with PV reconnection and the emergence of new triggers. Methods We performed 3 year follow-up of the CONFIRM trial, in which 92 consecutive AF patients (70.7% persistent) underwent novel computational mapping to reveal a median of 2 (IQR 1–2) rotors or focal sources in 97.7% of patients during AF. Ablation comprised source (Focal Impulse and Rotor Modulation, FIRM) then conventional ablation in n=27 (FIRM-guided), and conventional ablation alone in n=65 (FIRM-blinded). Patients were followed with implanted ECG monitors when possible (85.2% FIRM guided, 23.1% FIRM-blinded). Results On 890 days follow-up (median; IQR 224–1563) compared FIRM-blinded therapy, patients receiving FIRM-guided ablation maintained higher freedom from AF after 1.2±0.4 procedures (median 1, IQR 1–1) (77.8% vs 38.5%; p=0.001) and a single procedure (p>0.001), and higher freedom from all atrial arrhythmias (p=0.003). Freedom from AF was higher when ablation directly or coincidentally passed through sources than when it missed sources (p>0.001). CONCLUSIONS FIRM-guided ablation is more durable than conventional trigger-based ablation at preventing 3 year AF recurrence. Future studies should investigate how ablation of patient-specific AF-sustaining rotors and focal sources alters the natural history of arrhythmia recurrence. PMID:24632280

Real time determination of the laser ablated mass by means of electric field-perturbation measurement

NASA Astrophysics Data System (ADS)

Pacheco, P.; Álvarez, J.; Sarmiento, R.; Bredice, F.; Sánchez-Aké, C.; Villagrán-Muniz, M.; Palleschi, V.

2018-04-01

A Nd:YAG ns-pulsed laser was used to ablate Al, Cd and Zn targets, which were placed between the plates of a planar charged capacitor. The plasma generates a transient redistribution of the electrical charges on the plates that can be measured as a voltage drop across a resistor connected to the ground plate. This signal is proportional to the capacitor applied voltage, the distance between the plates and the total number of ions produced in the ablation process which in turn is related to the laser energy and the ablated mass. After a series of pulses, the targets were weighed on a thermogravimetric balance to measure the ablated mass. Our results show that the electrical signal measured on the resistor is univocally related to the ablated mass from the target. Therefore, after a proper calibration depending on the material and the experimental geometry, the electrical signal can be used for real time quantitative measurement of the ablated mass in pulsed laser generated plasma experiments. The experiments were repeated on an aluminum target, with and without the presence of the external electric field in order to determine the possible influence of the applied electric field on the ablated mass.

Aerospace Laser Ignition/Ablation Variable High Precision Thruster

NASA Technical Reports Server (NTRS)

Campbell, Jonathan W. (Inventor); Edwards, David L. (Inventor); Campbell, Jason J. (Inventor)

2015-01-01

A laser ignition/ablation propulsion system that captures the advantages of both liquid and solid propulsion. A reel system is used to move a propellant tape containing a plurality of propellant material targets through an ignition chamber. When a propellant target is in the ignition chamber, a laser beam from a laser positioned above the ignition chamber strikes the propellant target, igniting the propellant material and resulting in a thrust impulse. The propellant tape is advanced, carrying another propellant target into the ignition chamber. The propellant tape and ignition chamber are designed to ensure that each ignition event is isolated from the remaining propellant targets. Thrust and specific impulse may by precisely controlled by varying the synchronized propellant tape/laser speed. The laser ignition/ablation propulsion system may be scaled for use in small and large applications.

Experimental scaling law for mass ablation rate from a Sn plasma generated by a 1064 nm laser

NASA Astrophysics Data System (ADS)

Burdt, Russell A.; Yuspeh, Sam; Sequoia, Kevin L.; Tao, Yezheng; Tillack, Mark S.; Najmabadi, Farrokh

2009-08-01

The ablation depth in planar Sn targets irradiated with a pulsed 1064 nm laser was investigated over laser intensities from 3×1011 to 2×1012 W/cm2. The ablation depth was measured by irradiating a thin layer of Sn evaporated onto a Si wafer, and looking for signatures of Si ions in the expanding plasma with spectroscopic and particle diagnostics. It was found that ablation depth scales with laser intensity to the (5/9)th power, which is consistent with analytical models of steady-state laser ablation, as well as empirical formulae from previous studies of mass ablation rate in overlapping parameter space. In addition, the scaling of mass ablation rate with atomic number of the target as given by empirical formulae in previous studies using targets such as C and Al, are shown to remain valid for the higher atomic number of the target (Z =50) used in these experiments.

Dehydroxymethylepoxyquinomicin selectively ablates T-CAEBV cells.

PubMed

Zhang, Hui; Yang, Wen-Tao; Wang, Zhao; Yao, Chun-Mei; Wang, Xiao-Fang; Tian, Zhi-Qing; Jin, Ying-Ying; Wang, Lin-Lin; Chen, Tong-Xin

2015-01-01

Chronic active Epstein-Barr virus infection (CAEBV) represents a new subtype of lymphoproliferative disorders characterized by high morbidity and mortality rates and often leads to malignant transformation of infected cells. Efficient therapeutic strategies are presently unavailable; therefore, the development of therapies to prevent CAEBV-mediated transformation and disease progression is crucial. Here, we used microarray analysis and luciferase reporter assays to reveal the potential role of activated nuclear factor kappa B (NF-kB) in T cell type of-CAEBV infection. Using a series of cellular and molecular experiments, we demonstrated that dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kB inhibitor, can selectively induce apoptosis in SNT-16 cells infected with CAEBV. Mechanistic studies suggested that DHMEQ induces SNT-16 cell apoptosis through NF-kB inhibition coupled with oxidative stress generation. Thus, activated NF-kB could be a new target for CAEBV therapeutics. Owing to its selective targeting ability, DHMEQ may be a candidate for a novel therapeutic regimen to control the progression of CAEBV infections.

Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

PubMed

Machado, Yoan; Duinkerken, Sanne; Hoepflinger, Veronika; Mayr, Melissa; Korotchenko, Evgeniia; Kurtaj, Almedina; Pablos, Isabel; Steiner, Markus; Stoecklinger, Angelika; Lübbers, Joyce; Schmid, Maximillian; Ritter, Uwe; Scheiblhofer, Sandra; Ablinger, Michael; Wally, Verena; Hochmann, Sarah; Raninger, Anna M; Strunk, Dirk; van Kooyk, Yvette; Thalhamer, Josef; Weiss, Richard

2017-11-28

Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14 + dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Reflectance confocal microscopy-guided laser ablation of basal cell carcinomas: initial in vivo results

NASA Astrophysics Data System (ADS)

Sierra, Heidy; Cordova, Miguel; Yelamos, Oriol; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

2017-02-01

Laser ablation offers a procedure for precise, fast and minimally invasive removal of superficial and early nodular basal cell carcinomas (BCCs). However, the lack of histopathological confirmation has been a limitation toward widespread use in the clinic. A reflectance confocal microscopy (RCM) imaging-guided laser ablation approach offers cellular-level histopathology-like feedback directly on the patient, which may guide and help improve the efficacy of this procedure. We performed an initial study on 44 BCCs on 21 patients in vivo (based in an ex vivo bench-top study reported in our earlier papers), using a pulsed erbium: ytterbium aluminum garnet laser and a contrast agent (aluminum chloride). Initial 10 lesions, the RCM imaging-guided detection of either presence of residual tumor or complete clearance was immediately confirmed with histopathology. Additionally, 34 BCCs on 15 patients were treated with RCM imaging-guided laser ablation, and the clearance of tumor is currently being monitored with follow-up imaging (i. e., no histopathology) at 3, 6 and 18 months. Thus far, the imaging resolution appears to be sufficient and consistent for monitoring efficacy in the wound, both immediately post-ablation and subsequently during recovery. The efficacy appears to be promising. However, further investigation and optimization to image over the entire wound (without missing any areas) need to be investigated.

Carbon Dioxide Laser Ablation of Basal Cell Carcinoma with Visual Guidance by Reflectance Confocal Microscopy: A Proof of Principle Pilot Study

PubMed Central

Hibler, B.P.; Sierra, H.; Cordova, M.; Phillips, W.; Rajadhyaksha, M.; Nehal, K.S.; Rossi, A.M.

2016-01-01

Background Laser ablation is an alternative, non-surgical treatment modality for low-risk basal cell carcinoma (BCC); however, lack of confirmative tumour destruction or residual tumour presence has been a limiting factor to adoption. Reflectance confocal microscopy (RCM) provides non-invasive, cellular-level resolution imaging of the skin and is capable of identifying tumour. Objective To evaluate the use of RCM to guide carbon dioxide (CO2) laser ablation of BCC, confirm destruction, and correlate findings with histology. Methods RCM was used pre-ablation to evaluate for features of BCC. Ablation was performed with a CO2 laser, and the response rapidly assessed using handheld RCM to evaluate for residual tumour. Confirmative pathology was used to verify confocal imaging. Results RCM imaging identified tumour pre-ablation with features not identified on normal, surrounding skin. Post-ablation, RCM documented complete removal of tumour in six cases and residual tumour in two. Histologic examination identified the ablated area and confirmed clearance of tumour in the six aforementioned cases and corroborated confocal findings for residual tumour in the other two cases. Conclusions We report successful treatment of superficial and nodular BCC using CO2 laser ablation augmented by RCM imaging for pre-ablation guidance and verification of tumour removal post-ablation. Akin to complete circumferential and deep margin control techniques, using RCM helps to map peripheral and deep BCC margins to hone in on areas exhibiting persistent tumour after ablation. CO2 laser ablation visually guided by RCM can help circumvent previously cited limiting factors of laser ablation for tumour destruction by providing cellular-level resolution imaging of tumour and margin assessment in between each laser pass and post-ablation. PMID:26800657

Micrometeoroid ablation simulated in the laboratory

NASA Astrophysics Data System (ADS)

Sternovsky, Zoltan; Thomas, Evan W.; DeLuca, Michael; Horanyi, Mihaly; Janches, Diego; Munsat, Tobin L.; Plane, John M. C.

2016-04-01

A facility is developed to simulate the ablation of micrometeoroids in laboratory conditions, which also allows measuring the ionization probability of the ablated material. An electrostatic dust accelerator is used to generate iron and meteoric analog particles with velocities 10-50 km/s. The particles are then introduced into a cell filled with nitrogen, air or carbon dioxide gas with pressures adjustable in the 0.02 - 0.5 Torr range, where the partial or complete ablation of the particle occurs over a short distance. An array of biased electrodes is used to collect the ionized products with spatial resolution along the ablating particles' path, allowing thus the study of the temporal resolution of the process. A simple ablation model is used to match the observations. For completely ablated particles the total collected charge directly yields the ionization efficiency for. The measurements using iron particles in N2 and air are in relatively good agreement with earlier data. The measurements with CO2 and He gases, however, are significantly different from the expectations.

Real-time estimation of lesion depth and control of radiofrequency ablation within ex vivo animal tissues using a neural network.

PubMed

Wang, Yearnchee Curtis; Chan, Terence Chee-Hung; Sahakian, Alan Varteres

2018-01-04

Radiofrequency ablation (RFA), a method of inducing thermal ablation (cell death), is often used to destroy tumours or potentially cancerous tissue. Current techniques for RFA estimation (electrical impedance tomography, Nakagami ultrasound, etc.) require long compute times (≥ 2 s) and measurement devices other than the RFA device. This study aims to determine if a neural network (NN) can estimate ablation lesion depth for control of bipolar RFA using complex electrical impedance - since tissue electrical conductivity varies as a function of tissue temperature - in real time using only the RFA therapy device's electrodes. Three-dimensional, cubic models comprised of beef liver, pork loin or pork belly represented target tissue. Temperature and complex electrical impedance from 72 data generation ablations in pork loin and belly were used for training the NN (403 s on Xeon processor). NN inputs were inquiry depth, starting complex impedance and current complex impedance. Training-validation-test splits were 70%-0%-30% and 80%-10%-10% (overfit test). Once the NN-estimated lesion depth for a margin reached the target lesion depth, RFA was stopped for that margin of tissue. The NN trained to 93% accuracy and an NN-integrated control ablated tissue to within 1.0 mm of the target lesion depth on average. Full 15-mm depth maps were calculated in 0.2 s on a single-core ARMv7 processor. The results show that a NN could make lesion depth estimations in real-time using less in situ devices than current techniques. With the NN-based technique, physicians could deliver quicker and more precise ablation therapy.

Enhanced Radiofrequency Ablation With Magnetically Directed Metallic Nanoparticles.

PubMed

Nguyen, Duy T; Tzou, Wendy S; Zheng, Lijun; Barham, Waseem; Schuller, Joseph L; Shillinglaw, Benjamin; Quaife, Robert A; Sauer, William H

2016-05-01

Remote heating of metal located near a radiofrequency ablation source has been previously demonstrated. Therefore, ablation of cardiac tissue treated with metallic nanoparticles may improve local radiofrequency heating and lead to larger ablation lesions. We sought to evaluate the effect of magnetic nanoparticles on tissue sensitivity to radiofrequency energy. Ablation was performed using an ablation catheter positioned with 10 g of force over prepared ex vivo specimens. Tissue temperatures were measured and lesion volumes were acquired. An in vivo porcine thigh model was used to study systemically delivered magnetically guided iron oxide (FeO) nanoparticles during radiofrequency application. Magnetic resonance imaging and histological staining of ablated tissue were subsequently performed as a part of ablation lesion analysis. Ablation of ex vivo myocardial tissue treated with metallic nanoparticles resulted in significantly larger lesions with greater impedance changes and evidence of increased thermal conductivity within the tissue. Magnet-guided localization of FeO nanoparticles within porcine thigh preps was demonstrated by magnetic resonance imaging and iron staining. Irrigated ablation in the regions with greater FeO, after FeO infusion and magnetic guidance, created larger lesions without a greater incidence of steam pops. Metal nanoparticle infiltration resulted in significantly larger ablation lesions with altered electric and thermal conductivity. In vivo magnetic guidance of FeO nanoparticles allowed for facilitated radiofrequency ablation without direct infiltration into the targeted tissue. Further research is needed to assess the clinical applicability of this ablation strategy using metallic nanoparticles for the treatment of cardiac arrhythmias. © 2016 American Heart Association, Inc.

Structure and properties of nanoparticles fabricated by laser ablation of Zn metal targets in water and ethanol

NASA Astrophysics Data System (ADS)

Svetlichnyi, V. A.; Lapin, I. N.

2013-10-01

Size characteristics, structure, and spectral and luminescent properties of nanoparticles fabricated by laser ablation of zinc metal targets in water and ethanol are experimentally investigated upon excitation by Nd:YAG-laser radiation (1064 nm, 7 ns, and 15 Hz). It is demonstrated that zinc oxide nanoparticles with average sizes of 10 nm (in water) and 16 nm (in ethanol) are formed in the initial stage as a result of ablation. The kinetics of the absorption and luminescence spectra, transmission electron microscopy, and x-ray structural analysis demonstrate that during long storage of water dispersions and their drying, nanoparticles efficiently interact with carbon dioxide gas of air that leads to the formation of water-soluble Zn(CO3)2(OH)6. In ethanol, Zn oxidation leads to the formation of stable dispersions of ZnO nanoparticles with 99% of the wurtzite phase; in this case, the fluorescence spectra of ZnO nanoparticles change with time, shifting toward longer wavelength region from 550 to 620 nm, which is caused by the changed nature of defects.

Improving Thermal Ablation Delineation With Electrode Vibration Elastography Using a Bidirectional Wave Propagation Assumption

PubMed Central

DeWall, Ryan J.; Varghese, Tomy

2013-01-01

Thermal ablation procedures are commonly used to treat hepatic cancers and accurate ablation representation on shear wave velocity images is crucial to ensure complete treatment of the malignant target. Electrode vibration elastography is a shear wave imaging technique recently developed to monitor thermal ablation extent during treatment procedures. Previous work has shown good lateral boundary delineation of ablated volumes, but axial delineation was more ambiguous, which may have resulted from the assumption of lateral shear wave propagation. In this work, we assume both lateral and axial wave propagation and compare wave velocity images to those assuming only lateral shear wave propagation in finite element simulations, tissue-mimicking phantoms, and bovine liver tissue. Our results show that assuming bidirectional wave propagation minimizes artifacts above and below ablated volumes, yielding a more accurate representation of the ablated region on shear wave velocity images. Area overestimation was reduced from 13.4% to 3.6% in a stiff-inclusion tissue-mimicking phantom and from 9.1% to 0.8% in a radio-frequency ablation in bovine liver tissue. More accurate ablation representation during ablation procedures increases the likelihood of complete treatment of the malignant target, decreasing tumor recurrence. PMID:22293748

Improving thermal ablation delineation with electrode vibration elastography using a bidirectional wave propagation assumption.

PubMed

DeWall, Ryan J; Varghese, Tomy

2012-01-01

Thermal ablation procedures are commonly used to treat hepatic cancers and accurate ablation representation on shear wave velocity images is crucial to ensure complete treatment of the malignant target. Electrode vibration elastography is a shear wave imaging technique recently developed to monitor thermal ablation extent during treatment procedures. Previous work has shown good lateral boundary delineation of ablated volumes, but axial delineation was more ambiguous, which may have resulted from the assumption of lateral shear wave propagation. In this work, we assume both lateral and axial wave propagation and compare wave velocity images to those assuming only lateral shear wave propagation in finite element simulations, tissue-mimicking phantoms, and bovine liver tissue. Our results show that assuming bidirectional wave propagation minimizes artifacts above and below ablated volumes, yielding a more accurate representation of the ablated region on shear wave velocity images. Area overestimation was reduced from 13.4% to 3.6% in a stiff-inclusion tissue-mimicking phantom and from 9.1% to 0.8% in a radio-frequency ablation in bovine liver tissue. More accurate ablation representation during ablation procedures increases the likelihood of complete treatment of the malignant target, decreasing tumor recurrence. © 2012 IEEE

Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.

PubMed

Chen, Kaiyun; Zhu, Shuguang; Xiang, Guoan; Duan, Xiaopeng; He, Jiwen; Chen, Guihua

2016-05-01

To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.

Activation of the mouse Oct4 promoter in medaka embryonic stem cells and its use for ablation of spontaneous differentiation.

PubMed

Hong, Yunhan; Winkler, Christoph; Liu, Tongming; Chai, Guixuan; Schartl, Manfred

2004-07-01

The determination and maintenance of the cell fate is ultimately due to differential gene activity. In the mouse, expression of the transcription factor Oct4 is high in totipotent inner cell mass, germ cells and undifferentiated embryonic stem (ES) cells, but dramatically reduced or extinct upon differentiation. Here, we show that medaka blastula embryos and cells of the ES cell line MES1 are able to activate the Oct4 promoter. Ectopic expression of a fusion gene for beta-galactosidase and neomycin resistance from the Oct4 promoter conferred resistance to G418. G418 selection led to a homogeneous population of undifferentiated ES cells which were able to undergo induced or directed differentiation into various cell types including neuron-like cells and melanocytes. Furthermore, GFP-labeled GOF18geo-MES1 cells after differentiation ablation were able to contribute to a wide variety of organ systems derived from all the three germ layers. Most importantly, we show that drug ablation of differentiation on the basis of Oct4 promoter is a useful tool to improve ES cell cultivation and chimera formation: MES1 cells after differentiation ablation appeared to be better donors than the parental MES1 line, as the permissive number of input donor cells increases from 100 to 200, resulting in an enhanced degree of chimerism. Taken together, some transcription factors and cis-acting regulatory sequences controlling totipotency-specific gene expression appear to be conserved between mammals and fish, and medaka ES cells offer an in vitro system for characterizing the expression of totipotency-specific genes such as putative Oct4 homologs from fish.

Ablation of the MiR-17-92 MicroRNA Cluster in Germ Cells Causes Subfertility in Female Mice.

PubMed

Wang, Jian; Xu, Bo; Tian, Geng G; Sun, Tao; Wu, Ji

2018-01-01

Oogenesis is a highly complex process that is intricately regulated by interactions of multiple genes and signaling molecules. However, the underlying molecular mechanisms are poorly understood. There is emerging evidence that microRNAs contribute to oogenesis. Here, we aimed to investigate the role of miR-17-92 cluster in regulating oogenesis. The miR-17-92 cluster was genetically ablated in germ cells of female mice by applying the Cre-loxp system for conditional gene knockout. Mating experiment, superovulation and histological analysis were used to assess the fertility of the model female mice. TUNEL assay was used to identify apoptotic cells in ovaries. The expression level of apoptosis- and follicular atresia- related genes was evaluated by qRT-PCR. Western blotting was performed to detect protein expression. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-17-92 cluster. Deletion of miR-17-92 cluster in germ cells of female mice caused increased oocyte degradation and follicular atresia, perturbed oogenesis, and ultimately led to subfertility. Genes involved in follicular atresia and the mitochondrial apoptotic pathway were obviously up-regulated. Furthermore, we verified that miR-19a regulated oogenesis at the post-transcriptional level by targeting Bmf in the ovaries of miR-17-92 cluster conditional knockout female mice. The miR-17-92 cluster is an important regulator of oogenesis. These findings will assist in better understanding the etiology of disorders in oogenesis and in developing new therapeutic targets for female infertility. © 2018 The Author(s). Published by S. Karger AG, Basel.

Targeting dendritic cells--why bother?

PubMed

Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

2013-04-11

Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

Left Atrial Anatomy Relevant to Catheter Ablation

PubMed Central

Sánchez-Quintana, Damián; Cabrera, José Angel; Saremi, Farhood

2014-01-01

The rapid development of interventional procedures for the treatment of arrhythmias in humans, especially the use of catheter ablation techniques, has renewed interest in cardiac anatomy. Although the substrates of atrial fibrillation (AF), its initiation and maintenance, remain to be fully elucidated, catheter ablation in the left atrium (LA) has become a common therapeutic option for patients with this arrhythmia. Using ablation catheters, various isolation lines and focal targets are created, the majority of which are based on gross anatomical, electroanatomical, and myoarchitectual patterns of the left atrial wall. Our aim was therefore to review the gross morphological and architectural features of the LA and their relations to extracardiac structures. The latter have also become relevant because extracardiac complications of AF ablation can occur, due to injuries to the phrenic and vagal plexus nerves, adjacent coronary arteries, or the esophageal wall causing devastating consequences. PMID:25057427

Tracing the plasma interactions for pulsed reactive crossed-beam laser ablation

NASA Astrophysics Data System (ADS)

Chen, Jikun; Stender, Dieter; Pichler, Markus; Döbeli, Max; Pergolesi, Daniele; Schneider, Christof W.; Wokaun, Alexander; Lippert, Thomas

2015-10-01

Pulsed reactive crossed-beam laser ablation is an effective technique to govern the chemical activity of plasma species and background molecules during pulsed laser deposition. Instead of using a constant background pressure, a gas pulse with a reactive gas, synchronized with the laser beam, is injected into vacuum or a low background pressure near the ablated area of the target. It intercepts the initially generated plasma plume, thereby enhancing the physicochemical interactions between the gaseous environment and the plasma species. For this study, kinetic energy resolved mass-spectrometry and time-resolved plasma imaging were used to study the physicochemical processes occurring during the reactive crossed beam laser ablation of a partially 18O substituted La0.6Sr0.4MnO3 target using oxygen as gas pulse. The characteristics of the ablated plasma are compared with those observed during pulsed laser deposition in different oxygen background pressures.

Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.

PubMed

Ma, Xiaojun; Lin, Yuezhen; Lin, Ligen; Qin, Guijun; Pereira, Fred A; Haymond, Morey W; Butte, Nancy F; Sun, Yuxiang

2012-08-01

The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes. However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion. We investigated the effects of GHS-R on glucose homeostasis in Ghsr-ablated ob/ob mice (Ghsr(-/-):ob/ob). Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice. Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance. Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency. Of note, Ghsr ablation in ob/ob mice did not affect the islet size; the average islet size of Ghsr(-/-):ob/ob mice is similar to that of ob/ob mice. In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions. The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.

Conditional Müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model

PubMed Central

Shen, Weiyong; Fruttiger, Marcus; Zhu, Ling; Chung, Sook H.; Barnett, Nigel L.; Kirk, Joshua K.; Lee, SoRa; Coorey, Nathan J.; Killingsworth, Murray; Sherman, Larry S.; Gillies, Mark C.

2014-01-01

Müller cells are the major glia of the retina that serve numerous functions essential to retinal homeostasis, yet the contribution of Müller glial dysfunction to retinal diseases remains largely unknown. We have developed a transgenic model using a portion of the regulatory region of the retinaldehyde binding protein 1 gene for conditional Müller cell ablation and the consequences of primary Müller cell dysfunction have been studied in adult mice. We found that selective ablation of Müller cells led to photoreceptor apoptosis, vascular telangiectasis, blood-retinal barrier breakdown and, later, intraretinal neovascularization. These changes were accompanied by impaired retinal function and an imbalance between vascular endothelial growth factor-A (VEGF-A) and pigment epithelium derived factor. Intravitreal injection of cilliary neurotrophic factor inhibited photoreceptor injury but had no effect on the vasculopathy. Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not protect photoreceptors. Our findings show that Müller glial deficiency may be an important upstream cause of retinal neuronal and vascular pathologies in retinal diseases. Combined neuroprotective and anti-angiogenic therapies may be required to treat Müller cell deficiency in retinal diseases and in other parts of the central nervous system associated with glial dysfunction. PMID:23136411

Comparison of remote magnetic navigation ablation and manual ablation of idiopathic ventricular arrhythmia after failed manual ablation.

PubMed

Kawamura, Mitsuharu; Scheinman, Melvin M; Tseng, Zian H; Lee, Byron K; Marcus, Gregory M; Badhwar, Nitish

2017-01-01

Catheter ablation for idiopathic ventricular arrhythmia (VA) is effective and safe, but efficacy is frequently limited due to an epicardial origin and difficult anatomy. The remote magnetic navigation (RMN) catheter has a flexible catheter design allowing access to difficult anatomy. We describe the efficacy of the RMN for ablation of idiopathic VA after failed manual ablation. Among 235 patients with idiopathic VA referred for catheter ablation, we identified 51 patients who were referred for repeat ablation after a failed manual ablation. We analyzed the clinical characteristics, including the successful ablation site and findings at electrophysiology study, in repeat procedures conducted using RMN as compared with manual ablation. Among these patients, 22 (43 %) underwent repeat ablation with the RMN and 29 (57 %) underwent repeat ablation with a manual ablation. Overall, successful ablation rate was significantly higher using RMN as compared with manual ablation (91 vs. 69 %, P = 0.02). Fluoroscopy time in the RMN was 17 ± 12 min as compared with 43 ± 18 min in the manual ablation (P = 0.009). Successful ablation rate in the posterior right ventricular outflow tract (RVOT) plus posterior-tricuspid annulus was higher with RMN as compared with manual ablation (92 vs. 50 %, P = 0.03). Neither groups exhibited any major complications. The RMN is more effective in selected patients with recurrent idiopathic VA after failed manual ablation and is associated with less fluoroscopy time. The RMN catheters have a flexible design enabling them to access otherwise difficult anatomy including the posterior tricuspid annulus and posterior RVOT.

Factors affecting tumor ablation during high intensity focused ultrasound treatment.

PubMed

Hassanuddin, Aizan; Choi, Jun-Ho; Seo, Dong-Wan; Ryu, Choong Heon; Kim, Su-Hui; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2014-07-01

High intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment. HIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated. Bone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone. During HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.

Natural Killer Cell Immunotherapy Targeting Cancer Stem Cells

PubMed Central

Luna, Jesus I; Grossenbacher, Steven K.; Murphy, William J; Canter, Robert J

2017-01-01

Introduction Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with “stem-cell” like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. In this report, we review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert Opinion Unlike cytotoxic cancer treatments, NK cells are able to target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells. PMID:27960589

Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

PubMed

Kwon, Ronald Y; Meays, Diana R; Meilan, Alexander S; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A

2012-01-01

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading

Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

PubMed Central

Kwon, Ronald Y.; Meays, Diana R.; Meilan, Alexander S.; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A.

2012-01-01

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading

Heat Stress-Induced PI3K/mTORC2-Dependent AKT Signaling Is a Central Mediator of Hepatocellular Carcinoma Survival to Thermal Ablation Induced Heat Stress

PubMed Central

Thompson, Scott M.; Callstrom, Matthew R.; Jondal, Danielle E.; Butters, Kim A.; Knudsen, Bruce E.; Anderson, Jill L.; Lien, Karen R.; Sutor, Shari L.; Lee, Ju-Seog; Thorgeirsson, Snorri S.; Grande, Joseph P.; Roberts, Lewis R.; Woodrum, David A.

2016-01-01

Thermal ablative therapies are important treatment options in the multidisciplinary care of patients with hepatocellular carcinoma (HCC), but lesions larger than 2–3 cm are plagued with high local recurrence rates and overall survival of these patients remains poor. Currently no adjuvant therapies exist to prevent local HCC recurrence in patients undergoing thermal ablation. The molecular mechanisms mediating HCC resistance to thermal ablation induced heat stress and local recurrence remain unclear. Here we demonstrate that the HCC cells with a poor prognostic hepatic stem cell subtype (Subtype HS) are more resistant to heat stress than HCC cells with a better prognostic hepatocyte subtype (Subtype HC). Moreover, sublethal heat stress rapidly induces phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dependent-protein kinase B (AKT) survival signaling in HCC cells in vitro and at the tumor ablation margin in vivo. Conversely, inhibition of PI3K/mTOR complex 2 (mTORC2)-dependent AKT phosphorylation or direct inhibition of AKT function both enhance HCC cell killing and decrease HCC cell survival to sublethal heat stress in both poor and better prognostic HCC subtypes while mTOR complex 1 (mTORC1)-inhibition has no impact. Finally, we showed that AKT isoforms 1, 2 and 3 are differentially upregulated in primary human HCCs and that overexpression of AKT correlates with worse tumor biology and pathologic features (AKT3) and prognosis (AKT1). Together these findings define a novel molecular mechanism whereby heat stress induces PI3K/mTORC2-dependent AKT survival signaling in HCC cells and provide a mechanistic rationale for adjuvant AKT inhibition in combination with thermal ablation as a strategy to enhance HCC cell killing and prevent local recurrence, particularly at the ablation margin. PMID:27611696

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, J.W.K.

1987-10-14

Hybrid-drive implosion systems for ICF targets are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator surroundingly disposed around fusion fuel. The ablator is first compressed to higher density by a laser system, or by an ion beam system, that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system that is optimized for this second phase of operation of the target. The fusion fuel is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion. 3 figs.

Avoiding Complications in Bone and Soft Tissue Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurup, A. Nicholas, E-mail: kurup.anil@mayo.edu; Schmit, Grant D., E-mail: schmit.grant@mayo.edu; Morris, Jonathan M., E-mail: morris.jonathan@mayo.edu

As with percutaneous ablation of tumors in the liver, lungs, and kidneys, ablation of bone and non-visceral soft tissue tumors carries risk, primarily from collateral damage to vital structures in proximity to the target tumor. Certain risks are of particular interest when ablating bone and non-visceral soft tissue tumors, namely neural or skin injury, bowel injury, fracture, and gas embolism from damaged applicators. Ablation of large volume tumors also carries special risk. Many techniques may be employed by the interventional radiologist to minimize complications when treating tumors in the musculoskeletal system. These methods include those to depict, displace, or monitormore » critical structures. Thus, measures to provide thermoprotection may be active, such as careful ablation applicator placement and use of various displacement techniques, as well as passive, including employment of direct temperature, radiographic, or neurophysiologic monitoring techniques. Cementoplasty should be considered in certain skeletal locations at risk of fracture. Patients treated with large volume tumors should be monitored for renal dysfunction and properly hydrated. Finally, ablation applicators should be cautiously placed in the constrained environment of intact bone.« less

ACUTE TERMINATION OF HUMAN ATRIAL FIBRILLATION BY IDENTIFICATION AND CATHETER ABLATION OF LOCALIZED ROTORS AND SOURCES

PubMed Central

Shivkumar, Kalyanam; Ellenbogen, Kenneth A.; Hummel, John D.; Miller, John M.; Steinberg, Jonathan S.

2012-01-01

Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. METHODS We prospectively enrolled the first (n=14, 11 males) consecutive patients undergoing FIRM guided ablation for persistent (n=11) and paroxysmal AF at 5 centers. A 64 pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10 % cycle length prolongation). Conventional ablation was performed only after FIRM guided ablation. RESULTS 12/14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9±0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n=8 (4.9±3.9 min at the primary source), and organization in n=4. Total FIRM time for all patients was 12.3±8.6 min. CONCLUSIONS FIRM guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. PMID:23130890

Percutaneous laser ablation of benign and malignant thyroid nodules.

PubMed

Papini, Enrico; Bizzarri, Giancarlo; Pacella, Claudio M

2008-10-01

Percutaneous image-guided procedures, largely based on thermal ablation, are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. In several uncontrolled clinical trials and in two randomized clinical trials, laser ablation has demonstrated a good efficacy and safety for the shrinkage of benign cold thyroid nodules. In hyperfunctioning nodules, laser ablation induced a nearly 50% volume reduction with a variable frequency of normalization of thyroid-stimulating hormone levels. Laser ablation has been tested for the palliative treatment of poorly differentiated thyroid carcinomas, local recurrences or distant metastases. Laser ablation therapy is indicated for the shrinkage of benign cold nodules in patients with local pressure symptoms who are at high surgical risk. The treatment should be performed only by well trained operators and after a careful cytological evaluation. Laser ablation does not seem to be consistently effective in the long-term control of hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy. Laser ablation may be considered for the cytoreduction of tumor tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid malignancy that are not amenable to surgical or radioiodine treatment.

Androgen Ablation Augments Prostate Cancer Vaccine Immunogenicity Only When Applied After Immunization

PubMed Central

Koh, Yi T.; Gray, Andrew; Higgins, Sean A.; Hubby, Bolyn; Kast, W. Martin

2009-01-01

Background Androgen ablation (AA) causes apoptosis of normal and neoplastic prostate cells. It is a standard treatment for advanced prostate cancer. Androgen ablation-mediated immunological effects include bone marrow hyperplasia, thymic regeneration, T and B cell lymphopoeisis and restoration of age-related peripheral T cell dysfunction. Androgens also regulate the transcription of several cytokines. Dendritic cells (DC) are the most potent antigen presenting cells that can activate antigen-specific naïve T cells. Despite myriad clinical trials involving DC-based prostate cancer immunotherapies, the effects of AA on DC function remain largely uncharacterized. Therefore, we investigated the effects of AA on DC and whether it could improve the efficacy of prostate cancer immunotherapy. Methods Cytokine expression changes due to AA were quantified by multiplex ELISA. Flow cytometry was used to assess AA-mediated effects on DC maturation and expression of costimulatory markers. Mixed leukocyte reactions and cell-mediated lysis assays elucidated the role of androgens in DC function. The effect of AA on the efficacy of vaccination against a prostate tumor-associated antigen was tested using Elispot assays. Results Androgen ablation increased dendritic cell maturation and costimulatory marker expression, but had no effect on DC costimulatory function. However, DC isolated from castrated mice increased the expression of key cytokines by antigen-experienced T cells while decreasing their expression in naïve cells. Finally, androgen ablation improved immune responses to vaccination only when applied after immunization. Conclusion Androgen ablation causes differential effects of DC on primary and secondary T cell responses, thus augmenting vaccine immunogenicity only when applied after immunization. PMID:19143030

Ablation of Persistent Atrial Fibrillation Targeting Low-Voltage Areas With Selective Activation Characteristics.

PubMed

Jadidi, Amir S; Lehrmann, Heiko; Keyl, Cornelius; Sorrel, Jérémie; Markstein, Viktor; Minners, Jan; Park, Chan-Il; Denis, Arnaud; Jaïs, Pierre; Hocini, Mélèze; Potocnik, Clemens; Allgeier, Juergen; Hochholzer, Willibald; Herrera-Sidloky, Claudia; Kim, Steve; Omri, Youssef El; Neumann, Franz-Josef; Weber, Reinhold; Haïssaguerre, Michel; Arentz, Thomas

2016-03-01

Complex-fractionated atrial electrograms and atrial fibrosis are associated with maintenance of persistent atrial fibrillation (AF). We hypothesized that pulmonary vein isolation (PVI) plus ablation of selective atrial low-voltage sites may be more successful than PVI only. A total of 85 consecutive patients with persistent AF underwent high-density atrial voltage mapping, PVI, and ablation at low-voltage areas (LVA < 0.5 mV in AF) associated with electric activity lasting > 70% of AF cycle length on a single electrode (fractionated activity) or multiple electrodes around the circumferential mapping catheter (rotational activity) or discrete rapid local activity (group I). The procedural end point was AF termination. Arrhythmia freedom was compared with a control group (66 patients) undergoing PVI only (group II). PVI alone was performed in 23 of 85 (27%) patients of group I with low amount (< 10% of left atrial surface area) of atrial low voltage. Selective atrial ablation in addition to PVI was performed in 62 patients with termination of AF in 45 (73%) after 11 ± 9 minutes radiofrequency delivery. AF-termination sites colocalized within LVA in 80% and at border zones in 20%. Single-procedural arrhythmia freedom at 13 months median follow-up was achieved in 59 of 85 (69%) patients in group I, which was significantly higher than the matched control group (31/66 [47%], P < 0.001). There was no significant difference in the success rate of patients in group I with a low amount of low voltage undergoing PVI only and patients requiring PVI+selective low-voltage ablation (P = 0.42). Ablation of sites with distinct activation characteristics within/at borderzones of LVA in addition to PVI is more effective than conventional PVI-only strategy for persistent AF. PVI only seems to be sufficient to treat patients with left atrial low voltage < 10%. © 2016 American Heart Association, Inc.

Fabrication and characterization of a cell electrostimulator device combining physical vapor deposition and laser ablation

NASA Astrophysics Data System (ADS)

Aragón, Angel L.; Pérez, Eliseo; Pazos, Antonio; Bao-Varela, Carmen; Nieto, Daniel

2017-08-01

In this work we present the process of fabrication and optimization of a prototype of a cell electrostimulator device for medical application combining physical vapor deposition and laser ablation. The fabrication of the first prototype begins with a deposition of a thin layer of 200 nm of aluminium on a borosilicate glass substrate using physical vapor deposition (PVD). In the second stage the geometry design of the electrostimulator is made in a CAD-like software available in a Nd:YVO4 Rofin Power line 20E, operating at the fundamental wavelength of 1064 nm and 20 ns pulse width. Choosing the proper laser parameters the negative of the electrostimulator desing is ablated. After that the glass is assembled between two polycarbonate sheets and a thick sheet of polydimethylsiloxane (PDMS). The PDMS sheet has a round hole in where cells are placed. There is also included a thin soda-lime silicate glass (100 μm) between the electrostimulator and the PMDS to prevent the cells for being in contact with the electric circuit. In order to control the electrical signal applied to the electrostimulator is used a digital I/O device from National Instruments (USB-6501) which provides 5 V at the output monitored by a software programmed in LabVIEW. Finally, the optical and electrical characterization of the cell electrostimulator device is presented.

[Evaluation and results of ablative therapies in prostate cancer].

PubMed

Renard-Penna, R; Sanchez-Salas, R; Barret, E; Cosset, J M; de Vergie, S; Sapetti, J; Ingels, A; Gangi, A; Lang, H; Cathelineau, X

2017-11-01

To perform a state of the art about methods of evaluation and present results in ablative therapies for localized prostate cancer. A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 102 articles were analysed. Analyse the results of ablative therapies is presently difficult considering the heterogeneity of indications, techniques and follow-up. However, results from the most recent and homogeneous studies are encouraging. Oncologically, postoperative biopsies (the most important criteria) are negative (without any tumor cells in the treated area) in 75 to 95%. Functionally, urinary and sexual pre-operative status is spared (or recovered early) in more than 90% of the patients treated. More and more studies underline also the correlation between the results and the technique used considering the volume of the gland and, moreover, the "index lesion" localization. The post-treatment pathological evaluation by biopsies (targeted with MRI or, perhaps in a near future, with innovative ultrasonography) is the corner stone of oncological evaluation of ablative therapies. Ongoing trials will allow to standardize the follow-up and determine the best indication and the best techniques in order to optimize oncological and functional results for each patient treated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging

PubMed Central

Stein, Liana R; Imai, Shin-ichiro

2014-01-01

Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPCs during aging, giving rise to the possibility that Nampt-mediated NAD+ biosynthesis is a mediator of age-associated functional declines in NSPCs. PMID:24811750

Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

PubMed Central

Kang, Tae Wook; Rhim, Hyunchul

2015-01-01

Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

Navigational Guidance and Ablation Planning Tools for Interventional Radiology.

PubMed

Sánchez, Yadiel; Anvari, Arash; Samir, Anthony E; Arellano, Ronald S; Prabhakar, Anand M; Uppot, Raul N

Image-guided biopsy and ablation relies on successful identification and targeting of lesions. Currently, image-guided procedures are routinely performed under ultrasound, fluoroscopy, magnetic resonance imaging, or computed tomography (CT) guidance. However, these modalities have their limitations including inadequate visibility of the lesion, lesion or organ or patient motion, compatibility of instruments in an magnetic resonance imaging field, and, for CT and fluoroscopy cases, radiation exposure. Recent advances in technology have resulted in the development of a new generation of navigational guidance tools that can aid in targeting lesions for biopsy or ablations. These navigational guidance tools have evolved from simple hand-held trajectory guidance tools, to electronic needle visualization, to image fusion, to the development of a body global positioning system, to growth in cone-beam CT, and to ablation volume planning. These navigational systems are promising technologies that not only have the potential to improve lesion targeting (thereby increasing diagnostic yield of a biopsy or increasing success of tumor ablation) but also have the potential to decrease radiation exposure to the patient and staff, decrease procedure time, decrease the sedation requirements, and improve patient safety. The purpose of this article is to describe the challenges in current standard image-guided techniques, provide a definition and overview for these next-generation navigational devices, and describe the current limitations of these, still evolving, next-generation navigational guidance tools. Copyright © 2017 Elsevier Inc. All rights reserved.

Radio-frequency ablation: new technology for palliative treatment of hematuria in disseminated renal cell carcinoma.

PubMed

Matuszewski, Margin; Krajka, Kazimierz

2007-01-01

Hematuria is often a significant symptom in patients with disseminated renal cell carcinoma. We present a case in which the minimally invasive procedure of radio-frequency ablation was used in a patient with serious hematuria. The procedure was completely successful and there were no complications. In our opinion it may be recommended in such a situation.

High-intensity focused ultrasound ablation induced apoptosis in human hepatocellular carcinoma.

PubMed

Yi, Jiang; Wu, Liguo; Liu, Zhou; Zou, Haibo; Li, Ning; Chen, Heping; Liu, Jinheng; Li, Tao; Zhang, Gang

2014-01-01

To evaluate the effect of high-intensity ultrasound (HIFU) ablation on human hepatocellular carcinoma tissues and apoptotic proteins (bcl-2 and p-53). Patients with hepatocellular carcinoma at stage B were treated with HIFU ablation. Levels of bcl-2 and p53 protein and the apoptosis rate were evaluated both in the pre-treatment and post-treatment tissue specimens using immunochemistry and TUNEL methods, respectively. After HIFU ablation, p53 protein levels were significantly increased around the coagulation necrosis area, whereas, the level of bcl-2 was significantly decreased. More apoptosis cells were found post ablation compared with those in the pretreatment tissues. Additionally, no significant correlation was found between p53/bcl-2 levels and apoptotic index. HIFU ablation may exert promote the apoptosis of hepatocellular carcinoma cells and the effect has a closely association with the change of p53 and bcl-2 expression.

Infrared thermography and thermocouple mapping of radiofrequency renal ablation to assess treatment adequacy and ablation margins.

PubMed

Ogan, Kenneth; Roberts, William W; Wilhelm, David M; Bonnell, Leonard; Leiner, Dennis; Lindberg, Guy; Kavoussi, Louis R; Cadeddu, Jeffrey A

2003-07-01

The primary disadvantage of renal tumor RF ablation is the inability to monitor the intraoperative propagation of the RF lesion with real-time imaging. We sought to assess whether adequately lethal temperatures are obtained at the margins of the intended ablation zone using laparoscopic thermography to monitor radiofrequency (RF) lesions in real time, thermocouple measurements, and histopathologic evaluation. Renal RF lesions were created under direct laparoscopic vision in the upper (1 cm diameter) and lower (2 cm) poles of the right kidney in 5 female pigs. The RF lesions were produced with the RITA generator and probe, set at 105 degrees C for 5-minute ablations. During RF treatment, a laparoscopic infrared (IR) camera measured the surface parenchymal temperatures, as did multiple thermocouples. The pigs were then either immediately killed (n = 3) or allowed to live for 2 weeks (n = 2). The kidneys were removed to correlate the temperature measurements with histologic analysis of the ablated lesion. Using a threshold temperature of greater than 70 degrees C for visual "temperature" color change, the IR camera identified the region of pathologic necrosis of the renal parenchyma during RF ablation. Thermocouple measurements demonstrated that the temperatures at the intended ablation radius reached 77.5 degrees C at the renal surface and 83.7 degrees C centrally, and temperatures 5 mm beyond the set radius reached 52.6 degrees C at the surface and 47.7 degrees C centrally. The average diameter of the gross lesion on the surface of the kidney measured 17.1 mm and 22.4 mm for 1-cm and 2-cm ablations, respectively. These surface measurements correlated with an average diameter of 16.1 mm and 15.9 mm (1-cm and 2-cm ablations, respectively) as measured with the IR camera. All cells within these ablation zones were nonviable by nicotinamide adenine dinucleotide diaphorase analysis. The average depth of the lesions measured 19 mm (1-cm ablation) and 25 mm (2-cm ablation

Induction of rapid and selective cell necrosis in Drosophila using Bacillus thuringiensis Cry toxin and its silkworm receptor.

PubMed

Obata, Fumiaki; Tanaka, Shiho; Kashio, Soshiro; Tsujimura, Hidenobu; Sato, Ryoichi; Miura, Masayuki

2015-07-08

Genetic ablation of target cells is a powerful tool to study the origins and functions of cells, tissue regeneration, or pathophysiology in a human disease model in vivo. Several methods for selective cell ablation by inducing apoptosis have been established, using exogenous toxins or endogenous proapoptotic genes. However, their application is limited to cells with intact apoptotic machinery. Herein, we established a method for inducing rapid and selective cell necrosis by the pore-forming bacterial toxin Cry1Aa, which is specifically active in cells expressing the Cry1Aa receptor (CryR) derived from the silkworm Bombyx mori. We demonstrated that overexpressing CryR in Drosophila melanogaster tissues induced rapid cell death of CryR-expressing cells only, in the presence of Cry1Aa toxin. Cry/CryR system was effective against both proliferating cells in imaginal discs and polyploid postmitotic cells in the fat body. Live imaging analysis of cell ablation revealed swelling and subsequent osmotic lysis of CryR-positive cells after 30 min of incubation with Cry1Aa toxin. Osmotic cell lysis was still triggered when apoptosis, JNK activation, or autophagy was inhibited, suggesting that Cry1Aa-induced necrotic cell death occurred independently of these cellular signaling pathways. Injection of Cry1Aa into the body cavity resulted in specific ablation of CryR-expressing cells, indicating the usefulness of this method for in vivo cell ablation. With Cry toxins from Bacillus thuringiensis, we developed a novel method for genetic induction of cell necrosis. Our system provides a "proteinous drill" for killing target cells through physical injury of the cell membrane, which can potentially be used to ablate any cell type in any organisms, even those that are resistant to apoptosis or JNK-dependent programmed cell death.

Cooperative tumour cell membrane targeted phototherapy

NASA Astrophysics Data System (ADS)

Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

2017-06-01

The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

Modelling ultrafast laser ablation

NASA Astrophysics Data System (ADS)

Rethfeld, Baerbel; Ivanov, Dmitriy S.; E Garcia, Martin; Anisimov, Sergei I.

2017-05-01

This review is devoted to the study of ultrafast laser ablation of solids and liquids. The ablation of condensed matter under exposure to subpicosecond laser pulses has a number of peculiar properties which distinguish this process from ablation induced by nanosecond and longer laser pulses. The process of ultrafast ablation includes light absorption by electrons in the skin layer, energy transfer from the skin layer to target interior by nonlinear electronic heat conduction, relaxation of the electron and ion temperatures, ultrafast melting, hydrodynamic expansion of heated matter accompanied by the formation of metastable states and subsequent formation of breaks in condensed matter. In case of ultrashort laser excitation, these processes are temporally separated and can thus be studied separately. As for energy absorption, we consider peculiarities of the case of metal irradiation in contrast to dielectrics and semiconductors. We discuss the energy dissipation processes of electronic thermal wave and lattice heating. Different types of phase transitions after ultrashort laser pulse irradiation as melting, vaporization or transitions to warm dense matter are discussed. Also nonthermal phase transitions, directly caused by the electronic excitation before considerable lattice heating, are considered. The final material removal occurs from the physical point of view as expansion of heated matter; here we discuss approaches of hydrodynamics, as well as molecular dynamic simulations directly following the atomic movements. Hybrid approaches tracing the dynamics of excited electrons, energy dissipation and structural dynamics in a combined simulation are reviewed as well.

Microwave ablation devices for interventional oncology.

PubMed

Ward, Robert C; Healey, Terrance T; Dupuy, Damian E

2013-03-01

Microwave ablation is one of the several options in the ablation armamentarium for the treatment of malignancy, offering several potential benefits when compared with other ablation, radiation, surgical and medical treatment modalities. The basic microwave system consists of the generator, power distribution system and antennas. Often under image (computed tomography or ultrasound) guidance, a needle-like antenna is inserted percutaneously into the tumor, where local microwave electromagnetic radiation is emitted from the probe's active tip, producing frictional tissue heating, capable of causing cell death by coagulation necrosis. Half of the microwave ablation systems use a 915 MHz generator and the other half use a 2450 MHz generator. To date, there are no completed clinical trials comparing microwave devices head-to-head. Prospective comparisons of microwave technology with other treatment alternatives, as well as head-to-head comparison with each microwave device, is needed if this promising field will garner more widespread support and use in the oncology community.

Low work function surface layers produced by laser ablation using short-wavelength photons

DOEpatents

Balooch, Mehdi; Dinh, Long N.; Siekhaus, Wigbert J.

2000-01-01

Short-wavelength photons are used to ablate material from a low work function target onto a suitable substrate. The short-wavelength photons are at or below visible wavelength. The elemental composition of the deposit is controlled by the composition of the target and the gaseous environment in which the ablation process is performed. The process is carried out in a deposition chamber to which a short-wavelength laser is mounted and which includes a substrate holder which can be rotated, tilted, heated, or cooled. The target material is mounted onto a holder that spins the target during laser ablation. In addition, the deposition chamber is provided with a vacuum pump, an external gas supply with atomizer and radical generator, a gas generator for producing a flow of molecules on the substrate, and a substrate cleaning device, such as an ion gun. The substrate can be rotated and tilted, for example, whereby only the tip of an emitter can be coated with a low work function material.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-08-02

Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-01-01

Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

Pulsed laser ablation of complex oxides: The role of congruent ablation and preferential scattering for the film stoichiometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wicklein, S.; Koehl, A.; Dittmann, R.

2012-09-24

By combining structural and chemical thin film analysis with detailed plume diagnostics and modeling of the laser plume dynamics, we are able to elucidate the different physical mechanisms determining the stoichiometry of the complex oxides model material SrTiO{sub 3} during pulsed laser deposition. Deviations between thin film and target stoichiometry are basically a result of two effects, namely, incongruent ablation and preferential scattering of lighter ablated species during their motion towards the substrate in the O{sub 2} background gas. On the one hand, a progressive preferential ablation of the Ti species with increasing laser fluence leads to a regime ofmore » Ti-rich thin film growth at larger fluences. On the other hand, in the low laser fluence regime, a more effective scattering of the lighter Ti plume species results in Sr rich films.« less

Hydrodynamic cavitation kills prostate cells and ablates benign prostatic hyperplasia tissue.

PubMed

Itah, Zeynep; Oral, Ozlem; Perk, Osman Yavuz; Sesen, Muhsincan; Demir, Ebru; Erbil, Secil; Dogan-Ekici, A Isin; Ekici, Sinan; Kosar, Ali; Gozuacik, Devrim

2013-11-01

Hydrodynamic cavitation is a physical phenomenon characterized by vaporization and bubble formation in liquids under low local pressures, and their implosion following their release to a higher pressure environment. Collapse of the bubbles releases high energy and may cause damage to exposed surfaces. We recently designed a set-up to exploit the destructive nature of hydrodynamic cavitation for biomedical purposes. We have previously shown that hydrodynamic cavitation could kill leukemia cells and erode kidney stones. In this study, we analyzed the effects of cavitation on prostate cells and benign prostatic hyperplasia (BPH) tissue. We showed that hydrodynamic cavitation could kill prostate cells in a pressure- and time-dependent manner. Cavitation did not lead to programmed cell death, i.e. classical apoptosis or autophagy activation. Following the application of cavitation, we observed no prominent DNA damage and cells did not arrest in the cell cycle. Hence, we concluded that cavitation forces directly damaged the cells, leading to their pulverization. Upon application to BPH tissues from patients, cavitation could lead to a significant level of tissue destruction. Therefore similar to ultrasonic cavitation, we propose that hydrodynamic cavitation has the potential to be exploited and developed as an approach for the ablation of aberrant pathological tissues, including BPH.

The effect of graphitic target density on carbon nanotube synthesis by pulsed laser ablation method

NASA Astrophysics Data System (ADS)

Kazeimzadeh, Fatemeh; Malekfar, Rasoul; Houshiar, Mahboubeh

2018-01-01

Carbon nanotube (CNT) was synthesized by pulsed laser ablation (PLA) of a graphitic target in vacuum chamber filled by argon gas. The effect of different condition of target preparation on the amount and quality of carbon nanotube generation was investigated. The graphite powder with 2 at% micrometer nickel (Ni) powder was mixed and packed in to a mold using a hydraulic press device at a pressure of 1000 kg/cm3. The obtained pellet which contained the mixture powder provided the carbon source for CNTs formation in PLA method. Two pellets with the pressure time of 15 and 200 min was prepared. It has been shown that the time which graphitic target is under pressure is an effective parameter that can increase the amount of produced CNTs. Field emission scanning electron microscopy (FESEM) images show that if the density of graphitic target is increased by raising up the pressure time, CNTs can grow even under the condition in which usually no nanotube can be formed. It can be due to the elimination of the distances between the graphite and catalyst grains that causes the catalysis performance improvement. The experiment was performed for nanometer cobalt ferrite (CoFe2O4) together with Ni catalyst particles too. The diameter of synthesized CNPs was larger in the case of pure nickel that is related to the size of catalysts. Moreover, it was also observed that the production rate of the nanotubes increased for high density targets. This shows that the results are independent of the type of catalyst.

Global microwave endometrial ablation for menorrhagia treatment

NASA Astrophysics Data System (ADS)

Fallahi, Hojjatollah; Å ebek, Jan; Frattura, Eric; Schenck, Jessica; Prakash, Punit

2017-02-01

Thermal ablation is a dominant therapeutic option for minimally invasive treatment of menorrhagia. Compared to other energy modalities for ablation, microwaves offer the advantages of conformal energy delivery to tissue within short times. The objective of endometrial ablation is to destroy the endometrial lining of the uterine cavity, with the clinical goal of achieving reduction in bleeding. Previous efforts have demonstrated clinical use of microwaves for endometrial ablation. A considerable shortcoming of most systems is that they achieve ablation of the target by translating the applicator in a point-to-point fashion. Consequently, treatment outcome may be highly dependent on physician skill. Global endometrial ablation (GEA) not only eliminates this operator dependence and simplifies the procedure but also facilitates shorter and more reliable treatments. The objective of our study was to investigate antenna structures and microwave energy delivery parameters to achieve GEA. Another objective was to investigate a method for automatic and reliable determination of treatment end-point. A 3D-coupled FEM electromagnetic and heat transfer model with temperature and frequency dependent material properties was implemented to characterize microwave GEA. The unique triangular geometry of the uterus where lateral narrow walls extend from the cervix to the fundus forming a wide base and access afforded through an endocervical approach limit the overall diameter of the final device. We investigated microwave antenna designs in a deployed state inside the uterus. The impact of ablation duration on treatment outcome was investigated. Prototype applicators were fabricated and experimentally evaluated in ex vivo tissue to verify the simulation results and demonstrate proof-of-concept.

CRISPR/Cas9 mediated generation of stable chondrocyte cell lines with targeted gene knockouts; analysis of an aggrecan knockout cell line.

PubMed

Yang, Maozhou; Zhang, Liang; Stevens, Jeff; Gibson, Gary

2014-12-01

The Swarm rat chondrosarcoma (RCS) cell lines derived from a spontaneous neoplasm in a rat spine several decades ago have provided excellent models of chondrosarcoma tumor development. In addition the robust chondrocyte phenotype (expression of a large panel of genes identical to that seen in normal rat cartilage) and the ability to generate cell clones have facilitated their extensive use in the identification of chondrocyte proteins and genes. The clustered regularly interspersed short palindromic repeat (CRISPR) technology employing the RNA-guided nuclease Cas9 has rapidly dominated the genome engineering field as a unique and powerful gene editing tool. We have generated a stable RCS cell line (RCS Cas9) expressing the nuclease Cas9 that enables the editing of any target gene or non-coding RNA by simple transfection with a guide RNA. As proof of principle, stable cell lines with targeted ablation of aggrecan expression (Acan KO) were generated and characterized. The studies show that stable chondrocyte cell lines with targeted genome editing can be quickly generated from RCS Cas9 cells using this system. The Acan KO cell lines also provided a tool for characterizing the response of chondrocytes to aggrecan loss and the role of aggrecan in chondrosarcoma development. Loss of aggrecan expression while not affecting the chondrocyte phenotype resulted in a much firmer attachment of cells to their substrate in culture. Large changes in the expression of several genes were observed in response to the absence of the proteoglycan matrix, including those for several small leucine rich proteoglycans (SLRPs), transcription factors and membrane transporters. Acan KO cells failed to form a substantial chondrosarcoma when injected subcutaneously in nude mice consistent with previous suggestions that the glycosaminoglycan-rich matrix surrounding the chondrosarcoma protects it from destruction by the host immune system. The studies provide new understanding of aggrecan

Ablation article and method

NASA Technical Reports Server (NTRS)

Erickson, W. D.; Sullivan, E. M. (Inventor)

1973-01-01

An ablation article, such as a conical heat shield, having an ablating surface is provided with at least one discrete area of at least one seed material, such as aluminum. When subjected to ablation conditions, the seed material is ablated. Radiation emanating from the ablated seed material is detected to analyze ablation effects without disturbing the ablation surface. By providing different seed materials having different radiation characteristics, the ablating effects on various areas of the ablating surface can be analyzed under any prevailing ablation conditions. The ablating article can be provided with means for detecting the radiation characteristics of the ablated seed material to provide a self-contained analysis unit.

Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models.

PubMed

Wong, Andrew W; Fite, Brett Z; Liu, Yu; Kheirolomoom, Azadeh; Seo, Jai W; Watson, Katherine D; Mahakian, Lisa M; Tam, Sarah M; Zhang, Hua; Foiret, Josquin; Borowsky, Alexander D; Ferrara, Katherine W

2016-01-01

Magnetic resonance-guided focused ultrasound (MRgFUS) facilitates noninvasive image-guided conformal thermal therapy of cancer. Yet in many scenarios, the sensitive tissues surrounding the tumor constrain the margins of ablation; therefore, augmentation of MRgFUS with chemotherapy may be required to destroy remaining tumor. Here, we used 64Cu-PET-CT, MRI, autoradiography, and fluorescence imaging to track the kinetics of long-circulating liposomes in immunocompetent mammary carcinoma-bearing FVB/n and BALB/c mice. We observed a 5-fold and 50-fold enhancement of liposome and drug concentration, respectively, within MRgFUS thermal ablation-treated tumors along with dense accumulation within the surrounding tissue rim. Ultrasound-enhanced drug accumulation was rapid and durable and greatly increased total tumor drug exposure over time. In addition, we found that the small molecule gadoteridol accumulates around and within ablated tissue. We further demonstrated that dilated vasculature, loss of vascular integrity resulting in extravasation of blood cells, stromal inflammation, and loss of cell-cell adhesion and tissue architecture all contribute to the enhanced accumulation of the liposomes and small molecule probe. The locally enhanced liposome accumulation was preserved even after a multiweek protocol of doxorubicin-loaded liposomes and partial ablation. Finally, by supplementing ablation with concurrent liposomal drug therapy, a complete and durable response was obtained using protocols for which a sub-mm rim of tumor remained after ablation.

Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

PubMed

van den Bijgaart, Renske J E; Eikelenboom, Dylan C; Hoogenboom, Martijn; Fütterer, Jurgen J; den Brok, Martijn H; Adema, Gosse J

2017-02-01

Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

The cis decoy against the estrogen response element suppresses breast cancer cells via target disrupting c-fos not mitogen-activated protein kinase activity.

PubMed

Wang, Li Hua; Yang, Xiao Yi; Zhang, Xiaohu; Mihalic, Kelly; Xiao, Weihua; Farrar, William L

2003-05-01

Breast cancer, the most common malignancy in women, has been demonstrated to be associated with the steroid hormone estrogen and its receptor (ER), a ligand-activated transcription factor. Therefore, we developed a phosphorothiolate cis-element decoy against the estrogen response element (ERE decoy) to target disruption of ER DNA binding and transcriptional activity. Here, we showed that the ERE decoy potently ablated the 17beta-estrogen-inducible cell proliferation and induced apoptosis of human breast carcinoma cells by functionally affecting expression of c-fos gene and AP-1 luciferase gene reporter activity. Specificity of the decoy was demonstrated by its ability to directly block ER binding to a cis-element probe and transactivation. Moreover, the decoy failed to inhibit ER-mediated mitogen-activated protein kinase signaling pathways and cell growth of ER-negative breast cancer cells. Taken together, these data suggest that estrogen-mediated cell growth of breast cancer cells can be preferentially restricted via targeted disruption of ER at the level of DNA binding by a novel and specific decoy strategy applied to steroid nuclear receptors.

Thermal fixation of swine liver tissue after magnetic resonance-guided high-intensity focused ultrasound ablation.

PubMed

Courivaud, Frédéric; Kazaryan, Airazat M; Lund, Alice; Orszagh, Vivian C; Svindland, Aud; Marangos, Irina Pavlik; Halvorsen, Per Steinar; Jebsen, Peter; Fosse, Erik; Hol, Per Kristian; Edwin, Bjørn

2014-07-01

The aim of this study was to investigate experimental conditions for efficient and controlled in vivo liver tissue ablation by magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) in a swine model, with the ultimate goal of improving clinical treatment outcome. Histological changes were examined both acutely (four animals) and 1 wk after treatment (five animals). Effects of acoustic power and multiple sonication cycles were investigated. There was good correlation between target size and observed ablation size by thermal dose calculation, post-procedural MR imaging and histopathology, when temperature at the focal point was kept below 90°C. Structural histopathology investigations revealed tissue thermal fixation in ablated regions. In the presence of cavitation, mechanical tissue destruction occurred, resulting in an ablation larger than the target. Complete extra-corporeal MR-guided HIFU ablation in the liver is feasible using high acoustic power. Nearby large vessels were preserved, which makes MR-guided HIFU promising for the ablation of liver tumors adjacent to large veins. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Inorganic fullerene-like molybdenum selenide with good biocompatibility synthesized by laser ablation in liquids

NASA Astrophysics Data System (ADS)

Wu, Xiaoju; Tian, Xiumei; Chen, Tongming; Zeng, Ao; Yang, Guowei

2018-07-01

The fabrication of inorganic fullerene-like nanoparticles (IFNPs) is an attractive idea due to their unique structures and various potential applications. To date, IFNPs have been made from numerous compounds with layered two-dimensional structures, based on various synthetic methods. Here we have demonstrated for the first time that inorganic fullerene-like molybdenum selenide nanoparticles (MoSe2 IFNPs) can be synthesized by laser ablating a molybdenum selenide target in 30 vol % ethanol/water mixture at ambient temperature and pressure. The formation mechanism was proposed to elucidate the production of MoSe2 IFNPs in the process of laser ablation in liquids (LAL). The appropriate solvent facilitates the condensation of the plasma plume created by LAL to planar MoSe2. Then, laser-induced high temperature and high pressure lead to the formation of a vacancy in the planar MoSe2, causing the generation of nucleation and growth of the MoSe2 IFNPs. In addition, a CCK-8 (cell counting kit-8) assay and a cell viability assay were performed to examine the cytotoxic behavior and the effect on cell viability of MoSe2 IFNPs. The results show that MoSe2 IFNPs are reasonably nontoxic and biocompatible with the given cells, showing they have significant potential in biomedical applications.

Inorganic fullerene-like molybdenum selenide with good biocompatibility synthesized by laser ablation in liquids.

PubMed

Wu, Xiaoju; Tian, Xiumei; Chen, Tongming; Zeng, Ao; Yang, Guowei

2018-07-20

The fabrication of inorganic fullerene-like nanoparticles (IFNPs) is an attractive idea due to their unique structures and various potential applications. To date, IFNPs have been made from numerous compounds with layered two-dimensional structures, based on various synthetic methods. Here we have demonstrated for the first time that inorganic fullerene-like molybdenum selenide nanoparticles (MoSe 2 IFNPs) can be synthesized by laser ablating a molybdenum selenide target in 30 vol % ethanol/water mixture at ambient temperature and pressure. The formation mechanism was proposed to elucidate the production of MoSe 2 IFNPs in the process of laser ablation in liquids (LAL). The appropriate solvent facilitates the condensation of the plasma plume created by LAL to planar MoSe 2 . Then, laser-induced high temperature and high pressure lead to the formation of a vacancy in the planar MoSe 2 , causing the generation of nucleation and growth of the MoSe 2 IFNPs. In addition, a CCK-8 (cell counting kit-8) assay and a cell viability assay were performed to examine the cytotoxic behavior and the effect on cell viability of MoSe 2 IFNPs. The results show that MoSe 2 IFNPs are reasonably nontoxic and biocompatible with the given cells, showing they have significant potential in biomedical applications.

Strict sequential catheter ablation strategy targeting the pulmonary veins and superior vena cava for persistent atrial fibrillation.

PubMed

Yoshiga, Yasuhiro; Shimizu, Akihiko; Ueyama, Takeshi; Ono, Makoto; Fukuda, Masakazu; Fumimoto, Tomoko; Ishiguchi, Hironori; Omuro, Takuya; Kobayashi, Shigeki; Yano, Masafumi

2018-08-01

An effective catheter ablation strategy, beyond pulmonary vein isolation (PVI), for persistent atrial fibrillation (AF) is necessary. Pulmonary vein (PV)-reconduction also causes recurrent atrial tachyarrhythmias. The effect of the PVI and additional effect of a superior vena cava (SVC) isolation (SVCI) was strictly evaluated. Seventy consecutive patients with persistent AF who underwent a strict sequential ablation strategy targeting the PVs and SVC were included in this study. The initial ablation strategy was a circumferential PVI. A segmental SVCI was only applied as a repeat procedure when patients demonstrated no PV-reconduction. After the initial procedure, persistent AF was suppressed in 39 of 70 (55.7%) patients during a median follow-up of 32 months. After multiple procedures, persistent AF was suppressed in 46 (65.7%) and 52 (74.3%) patients after receiving the PVI alone and PVI plus SVCI strategies, respectively. In 6 of 15 (40.0%) patients with persistent AF resistant to PVI, persistent AF was suppressed. The persistent AF duration independently predicted persistent AF recurrences after multiple PVI alone procedures [HR: 1.012 (95% confidence interval: 1.006-1.018); p<0.001] and PVI plus SVCI strategies [HR: 1.018 (95% confidence interval: 1.011-1.025); p<0.001]. A receiver-operating-characteristic analysis for recurrent persistent AF indicated an optimal cut-off value of 20 and 32 months for the persistent AF duration using the PVI alone and PVI plus SVCI strategies, respectively. The outcomes of the PVI plus SVCI strategy were favorable for patients with shorter persistent AF durations. The initial SVCI had the additional effect of maintaining sinus rhythm in some patients with persistent AF resistant to PVI. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Confocal microscopy to guide laser ablation of basal cell carinoma: a preliminary feasibility study

NASA Astrophysics Data System (ADS)

Larson, Bjorg A.; Sierra, Heidy; Chen, Jason; Rajadhyaksha, Milind

2013-03-01

Laser ablation may be a promising method for removal of skin lesions, with the potential for better cosmetic outcomes and reduced scarring and infection. An obstacle to implementing laser ablation is that the treatment leaves no tissue for histopathological analysis. Pre-operative and intra-operative mapping of BCCs using confocal microscopy may guide the ablation of the tumor until all tumor is removed. We demonstrate preliminary feasibility of confocal microscopy to guide laser ablation of BCCs in freshly excised tissue from Mohs surgery. A 2940 nm Er:YAG laser provides efficient ablation of tumor with reduced thermal damage to the surrounding tissue.

Real time ablation rate measurement during high aspect-ratio hole drilling with a 120-ps fiber laser.

PubMed

Mezzapesa, Francesco P; Sibillano, Teresa; Di Niso, Francesca; Ancona, Antonio; Lugarà, Pietro M; Dabbicco, Maurizio; Scamarcio, Gaetano

2012-01-02

We report on the instantaneous detection of the ablation rate as a function of depth during ultrafast microdrilling of metal targets. The displacement of the ablation front has been measured with a sub-wavelength resolution using an all-optical sensor based on the laser diode self-mixing interferometry. The time dependence of the laser ablation process within the depth of aluminum and stainless steel targets has been investigated to study the evolution of the material removal rate in high aspect-ratio micromachined holes.

Method for materials deposition by ablation transfer processing

DOEpatents

Weiner, Kurt H.

1996-01-01

A method in which a thin layer of semiconducting, insulating, or metallic material is transferred by ablation from a source substrate, coated uniformly with a thin layer of said material, to a target substrate, where said material is desired, with a pulsed, high intensity, patternable beam of energy. The use of a patternable beam allows area-selective ablation from the source substrate resulting in additive deposition of the material onto the target substrate which may require a very low percentage of the area to be covered. Since material is placed only where it is required, material waste can be minimized by reusing the source substrate for depositions on multiple target substrates. Due to the use of a pulsed, high intensity energy source the target substrate remains at low temperature during the process, and thus low-temperature, low cost transparent glass or plastic can be used as the target substrate. The method can be carried out atmospheric pressures and at room temperatures, thus eliminating vacuum systems normally required in materials deposition processes. This invention has particular application in the flat panel display industry, as well as minimizing materials waste and associated costs.

Method for materials deposition by ablation transfer processing

DOEpatents

Weiner, K.H.

1996-04-16

A method in which a thin layer of semiconducting, insulating, or metallic material is transferred by ablation from a source substrate, coated uniformly with a thin layer of said material, to a target substrate, where said material is desired, with a pulsed, high intensity, patternable beam of energy. The use of a patternable beam allows area-selective ablation from the source substrate resulting in additive deposition of the material onto the target substrate which may require a very low percentage of the area to be covered. Since material is placed only where it is required, material waste can be minimized by reusing the source substrate for depositions on multiple target substrates. Due to the use of a pulsed, high intensity energy source the target substrate remains at low temperature during the process, and thus low-temperature, low cost transparent glass or plastic can be used as the target substrate. The method can be carried out atmospheric pressures and at room temperatures, thus eliminating vacuum systems normally required in materials deposition processes. This invention has particular application in the flat panel display industry, as well as minimizing materials waste and associated costs. 1 fig.

Experimental study on ablation of leiomyoma by combination high-intensity focused ultrasound and iodized oil in vitro.

PubMed

Liang, Zhi-Gang; Gao, Yi; Ren, Xiao-Yan; Sun, Cui; Gu, Heng-Fang; Mou, Meng; Xiao, Yan-Bing

2017-10-01

The aim of the current study was to investigate whether iodized oil (IO) enhances high-intensity focused ultrasound (HIFU) ablation of uterine leiomyoma and to determine the features of hyperechoic changes in the target region. Forty samples of uterine leiomyoma were randomly divided into an experimental group and a control group. In the experimental group, the leiomyoma was ablated by HIFU 30 min after 1 mL of iodized oil had been injected into the center of the myoma. The hyperechoic values and areas in the target region were observed by B-modal ultrasound after HIFU ablation. The samples were cut successively into slices and stained by triphenyltetrazolium chloride (TTC) solution within 1 h after HIFU ablation. The diameters of TTC-non-stained areas were measured and tissues in the borderline of the TTC-stained and -non-stained areas were observed pathologically. All procedures in the control group were the same as those in the experimental group except IO was replaced by physiological saline. The hyperechoic value in the target region in the experimental group was higher than that in the control group 4 min after HIFU ablation (P < 0.05). Hyperechoic areas in the target region as well as TTC-non-stained volumes in the experimental group were greater than those in the control group (P < 0.05). Routine pathologic observation showed that coagulation necrosis of leiomyoma occurred in the target region in both groups. IO causes coagulation necrosis, enlarges tissue damage, and postpones the attenuation of hyperechoic changes in the target region when HIFU ablation is carried out for leiomyoma in vitro. © 2017 Japan Society of Obstetrics and Gynecology.

Emerging molecular therapies targeting myocardial infarction-related arrhythmias.

PubMed

Driessen, Helen E; van Veen, Toon A B; Boink, Gerard J J

2017-04-01

Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate. Devices can terminate rapid rhythms but at best indirectly affect the underlying disease, while ablation, even when appropriately targeted, induces additional tissue damage. In contrast, exploration of gene and cell therapies are expected to provide a targeted, non-destructive, and potentially regenerative approach to ischaemia- and infarction-related arrhythmias. Although these approaches are in the early stages of development, they carry substantial potential to advance arrhythmia prevention and treatment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish

PubMed Central

Hagerman, Gordon F.; Noel, Nicole C. L.; Cao, Sylvia Y.; DuVal, Michèle G.; Oel, A. Phillip; Allison, W. Ted

2016-01-01

Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration. PMID:27893779

Single-element ultrasound transducer for combined vessel localization and ablation.

PubMed

Chen, Wen-Shiang; Shen, Che-Chou; Wang, Jen-Chieh; Ko, Chung-Ting; Liu, Hao-Li; Ho, Ming-Chih; Chen, Chiung-Nien; Yeh, Chih-Kuang

2011-04-01

This report describes a system that utilizes a single high-intensity focused ultrasound (HIFU) transducer for both the localization and ablation of arteries with internal diameters of 0.5 and 1.3 mm. In vitro and in vivo tests were performed to demonstrate both the imaging and ablation functionalities of this system. For imaging mode, pulsed acoustic waves (3 cycles for in vitro and 10 cycles for in vivo tests, 2 MPa peak pressure) were emitted from the 2-MHz HIFU transducer, and the backscattered ultrasonic signal was collected by the same transducer to calculate Doppler shifts in the target region. The maximum signal amplitude of the Doppler shift was used to determine the location of the target vessel. The operation mode was then switched to the therapeutic mode and vessel occlusion was successfully produced by high-intensity continuous HIFU waves (12 MPa) for 60 s. The system was then switched back to imaging mode for residual flow to determine the need for a second ablation treatment. The new system might be used to target and occlude unwanted vessels such as vasculature around tumors, and to help with tumor destruction. © 2011 IEEE

Numerical study of double-pulse laser ablation of Al

NASA Astrophysics Data System (ADS)

Förster, G. D.; Lewis, Laurent J.

2018-06-01

The effect of double laser pulses (DPs) on the ablation process in solids is studied using a hybrid two-temperature model combining a continuum description of the conduction band electrons with a classical molecular dynamics (MD) approach for the ions. The study is concerned with double pulses with delays in the range of 0-50 ps and absorbed laser fluences of 0.5, 1.0, and 1.5 J/m 2 [i.e., 1-3 times the ablation threshold for single-pulse ablation (SP)], taking Al as a generic example of simple metals. A detailed analysis, including the assessment of thermodynamic pathways and cavitation rates, leads to a comprehensive picture of the mechanisms active during the different stages of the ablation process initiated by DPs. This study provides an explanation for several phenomena observed in DP ablation experiments. In particular, with respect to SP ablation, crater depths are reduced, which can be explained by the compensation of the rarefaction wave from the first laser pulse with the compression wave from the second pulse, or, at higher fluences and larger delays, by the fact that the target surface is shielded with matter ablated by the first laser pulse. Also, we discuss how smoother surface structures obtained using DPs may be related to features found in the simulations—viz., reduced mechanical strain and peak lattice temperatures. Finally, vaporization appears to be enhanced in DP ablation, which may improve the resolution of emission spectra.

Plume dynamics from UV pulsed ablation of Al and Ti

NASA Astrophysics Data System (ADS)

Bauer, William; Perram, Glen; Haugan, Timothy

2016-12-01

Pulsed laser ablation of Al and Ti with a < 3.3 J/cm2 KrF laser and Ar background pressure of up to 1 Torr was performed to study the ablated plume. Mass loss experiments revealed the number of ablated atoms per pulse increases by 30% for Ti and 20% for Al as pressure decreases from 1 Torr to vacuum. Optical emission imaging performed using a gated ICCD revealed a strong dependence of shock front parameters, defined by the Sedov-Taylor blast and classical drag models, on background pressure. Spatially resolved optical emission spectroscopy from Al I, Al II, Ti I, and Ti II revealed ion temperatures of 104 K that decreased away from the target surface along the surface normal and neutral temperatures of 103 K independent of target distance. Comparison between kinetic energy in the shock and internal excitation energy reveals that nearly 100% of the energy is partitioned into shock front kinetic energy and 1% into internal excitation.

Monitoring of thermal dose during ablation therapy using quantum dot-mediated fluorescence thermometry.

PubMed

Bensalah, Karim; Tuncel, Altug; Hanson, Willard; Stern, Joshua; Han, Bumsoo; Cadeddu, Jeffrey

2010-12-01

The objective of this study was to demonstrate the feasibility of quantum dot (QD)-mediated fluorescence thermometry to monitor thermal dose in an in-vitro thermal ablation zone generated by laser-heated gold nanoshells (LGNS). Hyperthermic cell death of human prostate cancer cell line (PC-3) was determined after various heating settings and correlated to the thermal conditions using an Arrhenius model prior to LGNS ablation. PC-3 cells with gold nanoshells (GNS) and QDs were exposed to a near-infrared laser and QD excitation light. When the cells were heated by GNS, local temperature was measured using the temperature-dependent fluorescence intensity of QDs. Using the predetermined Arrhenius model, the thermal dose (i.e., cell death of PC-3 cells) by LGNS was estimated with local temperatures measured with QD-mediated thermometry. The estimated thermal dose was confirmed with calcein-acetoxy-methylester viability assay. For PC-3 cell line, the activation energy and frequency factor of the Arrhenius model were 86.78 kcal/mol and 6.35 × 10(55) Hz, respectively. During LGNS ablation of PC-3 cells, QD-mediated temperature measurement showed that the temperature of the laser spot increased rapidly to ∼58 °C ± 4 °C. The estimated thermal dose showed that cell death reached to ∼90% in 120 seconds. The death cell zone observed after staining corresponded to a peak area of the temperature profile generated after analysis of the QD fluorescence intensity. This study shows that the QD fluorescence thermometry can accurately monitor the PC-3 cell death by LGNS ablation. This approach holds promises for a better monitoring of thermal ablation procedures in clinical practice.

Influence of the laser pulse repetition rate and scanning speed on the morphology of Ag nanostructures fabricated by pulsed laser ablation of solid target in water

NASA Astrophysics Data System (ADS)

Nikolov, A. S.; Balchev, I. I.; Nedyalkov, N. N.; Kostadinov, I. K.; Karashanova, D. B.; Atanasova, G. B.

2017-11-01

Nanostructures of noble metal were produced by pulsed laser ablation in liquid. A solid Ag target was immersed in double distilled water and a CuBr laser in a master oscillator—power amplifier configuration oscillating at 511 nm and emitting pulses with duration of 30 ns at a repetition rate of up to 20 kHz was employed to produce different colloids. The impact was studied of the laser pulse repetition rate and the beam scanning speed on the morphology of the nanostructures formed. Further, the optical extinction spectra of the colloids in the UV/VIS range were measured and used to make an indirect assessment of the changes in the shape and size distribution of the nanostructures. The transmission values in the near UV range were used to estimate the efficiency of the ablation process under the different experimental conditions implemented. A visualization of the nanostructures was made possible by transmission electron microscopy (TEM). The structure and phase composition of the nanoparticles were studied by high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED), while the alteration of the target surface caused by the impact of the high-repetition-rate laser illumination was investigated by X-ray photoelectron spectroscopy (XPS). The optimal conditions were determined yielding the highest efficiency in terms of amount of ablated material.

Oligodendrocyte ablation affects the coordinated interaction between granule and Purkinje neurons during cerebellum development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collin, Ludovic; Doretto, Sandrine; Department of Psychiatry and Human Behavior, University of California Irvine, 3226 Gillespie Neuroscience Research Facility, Irvine CA 92697

2007-08-01

Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS) classically known to be devoted to the formation of myelin sheaths around most axons of the vertebrate brain. We have addressed the role of these cells during cerebellar development, by ablating OLs in vivo. Previous analyses had indicated that OL ablation during the first six postnatal days results into a striking cerebellar phenotype, whose major features are a strong reduction of granule neurons and aberrant Purkinje cells development. These two cell types are highly interconnected during cerebellar development through the production of molecules that help their proliferation, differentiationmore » and maintenance. In this article, we present data showing that OL ablation has major effects on the physiology of Purkinje (PC) and granule cells (GC). In particular, OL ablation results into a reduction of sonic hedgehog (Shh), Brain Derived Neurotrophic Factor (BDNF), and Reelin (Rln) expression. These results indicate that absence of OLs profoundly alters the normal cerebellar developmental program.« less

Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

NASA Astrophysics Data System (ADS)

Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

2016-04-01

Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

Ablation-cooled material removal with ultrafast bursts of pulses

NASA Astrophysics Data System (ADS)

Kerse, Can; Kalaycıoğlu, Hamit; Elahi, Parviz; Çetin, Barbaros; Kesim, Denizhan K.; Akçaalan, Önder; Yavaş, Seydi; Aşık, Mehmet D.; Öktem, Bülent; Hoogland, Heinar; Holzwarth, Ronald; Ilday, Fatih Ömer

2016-09-01

The use of femtosecond laser pulses allows precise and thermal-damage-free removal of material (ablation) with wide-ranging scientific, medical and industrial applications. However, its potential is limited by the low speeds at which material can be removed and the complexity of the associated laser technology. The complexity of the laser design arises from the need to overcome the high pulse energy threshold for efficient ablation. However, the use of more powerful lasers to increase the ablation rate results in unwanted effects such as shielding, saturation and collateral damage from heat accumulation at higher laser powers. Here we circumvent this limitation by exploiting ablation cooling, in analogy to a technique routinely used in aerospace engineering. We apply ultrafast successions (bursts) of laser pulses to ablate the target material before the residual heat deposited by previous pulses diffuses away from the processing region. Proof-of-principle experiments on various substrates demonstrate that extremely high repetition rates, which make ablation cooling possible, reduce the laser pulse energies needed for ablation and increase the efficiency of the removal process by an order of magnitude over previously used laser parameters. We also demonstrate the removal of brain tissue at two cubic millimetres per minute and dentine at three cubic millimetres per minute without any thermal damage to the bulk.

Ablation-cooled material removal with ultrafast bursts of pulses.

PubMed

Kerse, Can; Kalaycıoğlu, Hamit; Elahi, Parviz; Çetin, Barbaros; Kesim, Denizhan K; Akçaalan, Önder; Yavaş, Seydi; Aşık, Mehmet D; Öktem, Bülent; Hoogland, Heinar; Holzwarth, Ronald; Ilday, Fatih Ömer

2016-09-01

The use of femtosecond laser pulses allows precise and thermal-damage-free removal of material (ablation) with wide-ranging scientific, medical and industrial applications. However, its potential is limited by the low speeds at which material can be removed and the complexity of the associated laser technology. The complexity of the laser design arises from the need to overcome the high pulse energy threshold for efficient ablation. However, the use of more powerful lasers to increase the ablation rate results in unwanted effects such as shielding, saturation and collateral damage from heat accumulation at higher laser powers. Here we circumvent this limitation by exploiting ablation cooling, in analogy to a technique routinely used in aerospace engineering. We apply ultrafast successions (bursts) of laser pulses to ablate the target material before the residual heat deposited by previous pulses diffuses away from the processing region. Proof-of-principle experiments on various substrates demonstrate that extremely high repetition rates, which make ablation cooling possible, reduce the laser pulse energies needed for ablation and increase the efficiency of the removal process by an order of magnitude over previously used laser parameters. We also demonstrate the removal of brain tissue at two cubic millimetres per minute and dentine at three cubic millimetres per minute without any thermal damage to the bulk.

Focusing geometry-induced size tailoring of silver nanoparticles obtained by laser ablation in water

NASA Astrophysics Data System (ADS)

Stasic, Jelena; Joksic, Gordana; Zivkovic, Ljiljana; Mihailescu, Ion N.; Ghica, Corneliu; Kuncser, Andrei; Trtica, Milan

2014-10-01

Silver nanoparticles were obtained by picosecond laser ablation in water at 1064 nm, using focusing geometry to design the particles’ size. The position of the target surface with respect to the focal point strongly influences the NPs’ size: above and in the focus it is up to 20 nm and below focus ≤ 150 nm. Generated particles have a spherical shape. The solutions were further employed on human cells and the tests showed a deteriorating effect on DNA.

Structural characterization of ultrathin Cr-doped ITO layers deposited by double-target pulsed laser ablation

NASA Astrophysics Data System (ADS)

Cesaria, Maura; Caricato, Anna Paola; Leggieri, Gilberto; Luches, Armando; Martino, Maurizio; Maruccio, Giuseppe; Catalano, Massimo; Grazia Manera, Maria; Rella, Roberto; Taurino, Antonietta

2011-09-01

In this paper we report on the growth and structural characterization of very thin (20 nm) Cr-doped ITO films, deposited at room temperature by double-target pulsed laser ablation on amorphous silica substrates. The role of Cr atoms in the ITO matrix is carefully investigated with increasing doping content by transmission electron microscopy (TEM). Selected-area electron diffraction, conventional bright field and dark field as well as high-resolution TEM analyses, and energy dispersive x-ray spectroscopy demonstrate that (i) crystallization features occur despite the low growth temperature and small thickness, (ii) no chromium or chromium oxide secondary phases are detectable, regardless of the film doping levels, (iii) the films crystallize as crystalline flakes forming large-angle grain boundaries; (iv) the observed flakes consist of crystalline planes with local bending of the crystal lattice. Thickness and compositional information about the films are obtained by Rutherford back-scattering spectrometry. Results are discussed by considering the combined effects of growth temperature, smaller ionic radius of the Cr cation compared with the trivalent In ion, doping level, film thickness, the double-target doping technique and peculiarities of the pulsed laser deposition method.

Intrahepatic radiofrequency ablation versus electrochemical treatment in vivo.

PubMed

Czymek, Ralf; Nassrallah, Jan; Gebhard, Maximilian; Schmidt, Andreas; Limmer, Stefan; Kleemann, Markus; Bruch, Hans-Peter; Hildebrand, Philipp

2012-06-01

Radiofrequency ablation (RFA) and electrochemical treatment (ECT) are two methods of local liver tumour ablation. The objective of this study was to compare these methods when applied in proximity to vessels in vivo. In a total of ten laparotomised pigs, we used ECT (Group A, four animals) and RFA (Group B, four animals) to create four areas of ablation per animal under ultrasound guidance within 10 mm of a vessel. Group C consisted of two control animals. Chemical laboratory tests were performed immediately before and after each procedure and on days 1, 3 and 7 after surgery. Following the last tests, the livers were harvested for morphological evaluation. The mean duration of surgery was 5 h 40 min in Group A (ECT), 2 h 47 min in Group B (RFA), and 2 h 30 min in Group C (control animals). After ECT, the harvested livers showed a mean volume of necrosis of 1.84 cm(3) ± 0.88 at the anode and 2.59 cm(3) ± 1.06 at the cathode. The presence of vessels did not influence the formation of necrotic zones. Ablation time was 67 min when a charge of 200 coulombs was delivered. We measured pH values of 1.2 (range: 0.9-1.7) at the anode and 11.7 (range: 11.0-12.1) at the cathode. In one of the 16 RFA ablations (6%), the target temperature was not reached and the procedure was discontinued. After 14 of 16 RFA procedures (88%), morphological analysis showed incomplete ablation in perivascular sites. Both ECT and RFA were associated with a reversible increase in monocyte, C-reactive protein (CRP) and aspartate aminotransferase (AST) levels. There was no significant increase in interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and IL-6. In the majority of cases, intrahepatic RFA in vivo leads to incomplete necrosis in proximity to vessels and the presence of histologically intact perivascular cells. Without a reduction in liver perfusion, the central application of RFA should be considered problematic. ECT is a safe alternative. It is not associated

Laser selective microablation of sensitized intracellular components within auditory receptor cells

NASA Astrophysics Data System (ADS)

Harris, David M.; Evans, Burt N.; Santos-Sacchi, Joseph

1995-05-01

A laser system can be coupled to a light microscope for laser microbeam ablation and trapping of single cells in vitro. We have extended this technology by sensitization of target structures with vital dyes to provide selective ablation of specific subcellular components. Isolated auditory receptor cells (outer hair cells, OHCs) are known to elongate and contract in response to electrical, chemical and mechanical stimulation. Various intracellular structures are candidate components mediating motility of OHCs, but the exact mechanism(s) is currently unknown. In ongoing studies of OHC motility, we have used the microbeam for selective ablation of lateral wall components and of an axial cytoskeletal core that extends from the nucleus to the cell apex. Both the area beneath the subsurface cistemae of the lateral wall and the core are rich in mitochondria. OHCs isolated from guinea pig cochlea are suspended in L- 15 medium containing 2.0 (mu) M Rhodamine 123, a porphyrin with an affinity for mitochondria. A spark-pumped nitrogen laser pumping a dye cell (Coumarin 500) was aligned on the optical axis of a Nikon Optiphot-2 to produce a 3 ns, 0.5 - 10 micrometers spot (diameter above ablation threshold w/50X water immersion, N.A. 0.8), and energy at the target approximately equals 10 (mu) J/pulse. At short incubation times in Rh123 irradiation caused local blebbing or bulging of cytoplastic membrane and thus loss of the OHC's cylindrical shape. At longer Rh123 incubation times when the central axis of the cell was targeted we observed cytoplasmic clearing, immediate cell elongation (approximately equals 5%) and clumping of core material at nuclear and apical attachments. Experiments are underway to examine the significance of these preliminary observations.

Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof-of-principle pilot study.

PubMed

Hibler, B P; Sierra, H; Cordova, M; Phillips, W; Rajadhyaksha, M; Nehal, K S; Rossi, A M

2016-06-01

Laser ablation is an alternative, nonsurgical treatment modality for low-risk basal cell carcinoma (BCC). However, lack of confirmative tumour destruction or residual tumour presence has been a limiting factor to its adoption. Reflectance confocal microscopy (RCM) provides noninvasive, cellular-level resolution imaging of the skin and is capable of identifying tumour. To evaluate the use of RCM to guide carbon dioxide (CO2 ) laser ablation of BCC, confirm destruction and correlate findings with histology. RCM was used preablation to evaluate for features of BCC. Ablation was performed with a CO2 laser, and the response rapidly assessed using handheld RCM to evaluate for residual tumour. Confirmative pathology was used to verify confocal imaging. Preablation RCM imaging identified tumour with features not identified on normal, surrounding skin. Postablation, RCM documented complete removal of tumour in six cases and residual tumour in two. Histological examination identified the ablated area and confirmed clearance of tumour in the six aforementioned cases and corroborated confocal findings for residual tumour in the other two cases. We report successful treatment of superficial and nodular BCC using CO2 laser ablation augmented by RCM imaging for preablation guidance and verification of tumour removal postablation. Akin to complete circumferential and deep margin control techniques, using RCM helps to map peripheral and deep BCC margins to hone in on areas exhibiting persistent tumour after ablation. CO2 laser ablation visually guided by RCM can help circumvent previously cited limiting factors of laser ablation for tumour destruction by providing cellular-level resolution imaging of tumour and margin assessment in between each laser pass and postablation. © 2016 British Association of Dermatologists.

Nonequilibrium Ablation of Phenolic Impregnated Carbon Ablator

NASA Technical Reports Server (NTRS)

Milos, Frank S.; Chen, Yih K.; Gokcen, Tahir

2012-01-01

In previous work, an equilibrium ablation and thermal response model for Phenolic Impregnated Carbon Ablator was developed. In general, over a wide range of test conditions, model predictions compared well with arcjet data for surface recession, surface temperature, in-depth temperature at multiple thermocouples, and char depth. In this work, additional arcjet tests were conducted at stagnation conditions down to 40 W/sq cm and 1.6 kPa. The new data suggest that nonequilibrium effects become important for ablation predictions at heat flux or pressure below about 80 W/sq cm or 10 kPa, respectively. Modifications to the ablation model to account for nonequilibrium effects are investigated. Predictions of the equilibrium and nonequilibrium models are compared with the arcjet data.

Innovative approach for in-vivo ablation validation on multimodal images

NASA Astrophysics Data System (ADS)

Shahin, O.; Karagkounis, G.; Carnegie, D.; Schlaefer, A.; Boctor, E.

2014-03-01

Radiofrequency ablation (RFA) is an important therapeutic procedure for small hepatic tumors. To make sure that the target tumor is effectively treated, RFA monitoring is essential. While several imaging modalities can observe the ablation procedure, it is not clear how ablated lesions on the images correspond to actual necroses. This uncertainty contributes to the high local recurrence rates (up to 55%) after radiofrequency ablative therapy. This study investigates a novel approach to correlate images of ablated lesions with actual necroses. We mapped both intraoperative images of the lesion and a slice through the actual necrosis in a common reference frame. An electromagnetic tracking system was used to accurately match lesion slices from different imaging modalities. To minimize the liver deformation effect, the tracking reference frame was defined inside the tissue by anchoring an electromagnetic sensor adjacent to the lesion. A validation test was performed using a phantom and proved that the end-to-end accuracy of the approach was within 2mm. In an in-vivo experiment, intraoperative magnetic resonance imaging (MRI) and ultrasound (US) ablation images were correlated to gross and histopathology. The results indicate that the proposed method can accurately correlate invivo ablations on different modalities. Ultimately, this will improve the interpretation of the ablation monitoring and reduce the recurrence rates associated with RFA.

Biofunctionalized Hybrid Magnetic Gold Nanoparticles as Catalysts for Photothermal Ablation of Colorectal Liver Metastases.

PubMed

White, Sarah B; Kim, Dong-Hyun; Guo, Yang; Li, Weiguo; Yang, Yihe; Chen, Jeane; Gogineni, Venkateswara R; Larson, Andrew C

2017-12-01

Purpose To demonstrate that anti-MG1 conjugated hybrid magnetic gold nanoparticles (HNPs) act as a catalyst during photothermal ablation (PTA) of colorectal liver metastases, and thus increase ablation zones. Materials and Methods All experiments were performed with approval of the institutional animal care and use committee. Therapeutic and diagnostic multifunctional HNPs conjugated with anti-MG1 monoclonal antibodies were synthesized, and the coupling efficiency was determined. Livers of 19 Wistar rats were implanted with 5 × 10 6 rat colorectal liver metastasis cell line cells. The rats were divided into three groups according to injection: anti-MG1-coupled HNPs (n = 6), HNPs only (n = 6), and cells only (control group, n = 7). Voxel-wise R2 and R2* magnetic resonance (MR) imaging measurements were obtained before, immediately after, and 24 hours after injection. PTA was then performed with a fiber-coupled near-infrared (808 nm) diode laser with laser power of 0.56 W/cm 2 for 3 minutes, while temperature changes were measured. Tumors were assessed for necrosis with hematoxylin-eosin staining. Organs were analyzed with inductively coupled plasma mass spectrometry to assess biodistribution. Therapeutic efficacy and tumor necrosis area were compared by using a one-way analysis of variance with post hoc analysis for statistically significant differences. Results The coupling efficiency was 22 μg/mg (55%). Significant differences were found between preinfusion and 24-hour postinfusion measurements of both T2 (repeated measures analysis of variance, P = .025) and T2* (P < .001). Significant differences also existed for T2* measurements between the anti-MG1 HNP and HNP-only groups (P = .034). Mean temperature ± standard deviation with PTA in the anti-MG1-coated HNP, HNP, and control groups was 50.2°C ± 7.8, 51°C ± 4.4, and 39.5°C ± 2.0, respectively. Inductively coupled plasma mass spectrometry revealed significant tumor targeting and splenic sequestration

Theoretical analyses of the refractive implications of transepithelial PRK ablations.

PubMed

Arba Mosquera, Samuel; Awwad, Shady T

2013-07-01

To analyse the refractive implications of single-step, transepithelial photorefractive keratectomy (TransPRK) ablations. A simulation for quantifying the refractive implications of TransPRK ablations has been developed. The simulation includes a simple modelling of corneal epithelial profiles, epithelial ablation profiles as well as refractive ablation profiles, and allows the analytical quantification of the refractive implications of TransPRK in terms of wasted tissue, achieved optical zone (OZ) and induced refractive error. Wasted tissue occurs whenever the actual corneal epithelial profile is thinner than the applied epithelial ablation profile, achieved OZ is reduced whenever the actual corneal epithelial profile is thicker than the applied epithelial ablation profile and additional refractive errors are induced whenever the actual difference centre-to-periphery in the corneal epithelial profile deviates from the difference in the applied epithelial ablation profile. The refractive implications of TransPRK ablations can be quantified using simple theoretical simulations. These implications can be wasted tissue (∼14 µm, if the corneal epithelial profile is thinner than the ablated one), reduced OZ (if the corneal epithelial profile is thicker than ablated one, very severe for low corrections) and additional refractive errors (∼0.66 D, if the centre-to-periphery progression of the corneal epithelial profile deviates from the progression of the ablated one). When TransPRK profiles are applied to normal, not previously treated, non-pathologic corneas, no specific refractive implications associated to the transepithelial profile can be anticipated; TransPRK would provide refractive outcomes equal to those of standard PRK. Adjustments for the planned OZ and, in the event of retreatments, for the target sphere can be easily derived.

Experimental Investigation of the Properties of an Acoustic Wave Induced by Laser Ablation of a Solid Target in Water-Confined Plasma Propulsion

NASA Astrophysics Data System (ADS)

Zheng, Zhiyuan; Gao, Hua; Gao, Lu; Xing, Jie

2014-11-01

Acoustic waves generated in nanosecond pulsed-laser ablation of a solid target in both air and water-confined environments were measured experimentally. It was found that the amplitude of the acoustic wave tended to decrease with an increase in water thickness. The waves were analyzed by means of fast Fourier transform. It was shown that there are several frequency components in the acoustic waves with the dominant frequency shifting from high frequency to low frequency as the thickness of the water layer increases. Furthermore, strong acoustic pressure led to enhancement of the coupling of the laser energy to the target in laser plasma propulsion.

Targeting B Cells and Plasma Cells in Autoimmune Diseases

PubMed Central

Hofmann, Katharina; Clauder, Ann-Katrin; Manz, Rudolf Armin

2018-01-01

Success with B cell depletion using rituximab has proven the concept that B lineage cells represent a valid target for the treatment of autoimmune diseases, and has promoted the development of other B cell targeting agents. Present data confirm that B cell depletion is beneficial in various autoimmune disorders and also show that it can worsen the disease course in some patients. These findings suggest that B lineage cells not only produce pathogenic autoantibodies, but also significantly contribute to the regulation of inflammation. In this review, we will discuss the multiple pro- and anti-inflammatory roles of B lineage cells play in autoimmune diseases, in the context of recent findings using B lineage targeting therapies. PMID:29740441

[Magnetic navigation for ablation of cardiac arrhythmias].

PubMed

Chen, Jian; Hoff, Per Ivar; Solheim, Eivind; Schuster, Peter; Off, Morten Kristian; Ohm, Ole-Jørgen

2010-08-12

The first use of magnetic navigation for radiofrequency ablation of supraventricular tachycardias, was published in 2004. Subsequently, the method has been used for treatment of most types of tachyarrhythmias. This paper provides an overview of the method, with special emphasis on usefulness of a new remote-controlled magnetic navigation system. The paper is based on our own scientific experience and literature identified through a non-systematic search in PubMed. The magnetic navigation system consists of two external electromagnets (to be placed on opposite sides of the patient), which guide an ablation catheter (with a small magnet at the tip of the catheter) to the target area in the heart. The accuracy of this procedure is higher than that with manual navigation. Personnel can be quickly trained to use remote magnetic navigation, but the procedure itself is time-consuming, particularly for patients with atrial fibrillation. The major advantage is a considerably lower radiation burden to both patient and operator, in some studies more than 50 %, and a corresponding reduction in physical strain on the operator. The incidence of procedure-related complications seems to be lower than that observed with use of manually operated ablation catheters. Work is ongoing to improve magnetic ablation catheters and methods that can simplify mapping procedures and improve efficacy of arrhythmia ablation. The basic cost for installing a complete magnetic navigation laboratory may be three times that of a conventional electrophysiological laboratory. The new magnetic navigation system has proved to be applicable during ablation for a variety of tachyarrhythmias, but is still under development.

Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

PubMed

Kumar, S; Peng, X; Daley, J; Yang, L; Shen, J; Nguyen, N; Bae, G; Niu, H; Peng, Y; Hsieh, H-J; Wang, L; Rao, C; Stephan, C C; Sung, P; Ira, G; Peng, G

2017-04-17

Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in replication and HR repair. Here we demonstrate that DNA2 is overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90-95% of cases. In addition, depletion of DNA2 significantly reduces pancreatic cancer cell survival and xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition. Finally, we develop a robust high-throughput biochemistry assay to screen for inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion, including decreased DNA double strand break end resection and attenuation of HR repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2 selectively attenuates the growth of various cancer cells with oncogene-induced replication stress. Taken together, our findings open a new avenue to develop a new class of anticancer drugs by targeting druggable nuclease DNA2. We propose DNA2 inhibition as new strategy in cancer therapy by targeting

Ablation of atrial-ventricular junction tissues via the coronary sinus using cryo balloon technology.

PubMed

Avitall, Boaz; Lafontaine, Daniel; Rozmus, Grzegorz; Adoni, Naveed; Dehnee, Abed; Urbonas, Arvydas; Le, Khoi M; Aleksonis, Dinas

2005-04-01

The coronary sinus (CS) can provide access to targets across and within the atrioventricular (AV) junction. In 12 dogs (32 +/- 3 Kg), cryo balloons (10-19 mm) were applied to regions of the AV junction for 3 minutes at a temperature of -75.9( composite function) +/- 9(composite function)C (ranging -57 to -83). Electrical activity and pacing within the CS were assessed pre and post ablation and at least 3 months later in 9 dogs. In the 3 other dogs, hearts were examined immediately after cryo ablation. CS and circumflex angiography was performed pre and post ablation. The hearts, CS, and Cx were then examined for structural injury. The AV junction was sectioned and the hearts were immersed in Tetrazolium, and the lesions were inspected for transmurality across the AV groove. In 3/12 dogs the distal CS cryo lesions resulted in inferior ST segment depression that resolved within 5 minutes. There was no arrhythmia or hemodynamic changes. No CS electrical activity was noted post ablation. The pacing threshold increased from 2 +/- 2.3 mA to 7.4 +/- 3.6 mA (p < 0.001). Pathological examination of 3 acute hearts revealed hematomas. There was no pericardial effusion. No evidence of stenosis or thrombosis was seen within the CS and the circumflex artery. After 3 months of recovery, transmural lesions across the AV groove were present in all of the targeted AV regions. Intra-CS cryo balloon ablation is safe and can potentially replace endocardial RF ablation targeting the AV junction and the CS muscular sleeve.

Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

PubMed Central

Kumar, Sandeep; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Viswanathan, Suresh; Bloomfield, Stewart A.

2017-01-01

The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma. PMID:28604388

Three-dimension finite-element analyses of multiple electrodes bipolar RF global endometrial ablation

NASA Astrophysics Data System (ADS)

Hu, Tao; Panhao, Tang; Xiao, Jiahua

2015-03-01

Radio-frequency ablation (RFA) is a minimally invasive surgical procedure to thermally ablate the targeted diseased tissue. There have been many finite-element method (FEM) studies of cardiac and hepatic RFA, but hardly find any FEM study on endometrial ablation for abnormal uterine bleeding. In this paper, a FEM model was generated to analyze the temperature distribution of bipolar RF global endometrial ablation with three pairs of bipolar electrodes placed at the perimeter of the uterine cavity. COMSOL was utilized to calculate the RF electric fields and temperature fields by numerically solving the bioheat equation in the triangle uterine cavity range. The 55°C isothermal surfaces show the shape of the ablation dimensions (depth and width), which reasonably matched the experimental results.

Bioavailable nanoparticles obtained in laser ablation of a selenium target in water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuzmin, P G; Shafeev, Georgii A; Voronov, Valerii V

The process of producing colloidal solutions of selenium nanoparticles in water using the laser ablation method is described. The prospects of using nanoparticles of elementary selenium as a nutrition source of this microelement are discussed. (nanoparticles)

Intrapleural fluid infusion for MR-guided high-intensity focused ultrasound ablation in the liver dome.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2014-12-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because of the presence of air in the costophrenic angle. In this study, we used a porcine liver model and a clinical MR-HIFU system to assess the feasibility and safety of using intrapleural fluid infusion (IPI) to create an acoustic window for MR-HIFU ablation in the liver dome. Healthy adult Dalland land pigs (n = 6) under general anesthesia were used with animal committee approval. Degassed saline (200-800 mL) was infused into the intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was used to perform sonications (4-mm treatment cells, 300-450 W, 20-30 seconds) in the liver dome under real-time MR thermometry. An intercostal firing technique was used to prevent rib heating in one experiment. Technical success was defined as a temperature increase (>10°C) in the target area. After termination, the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or intercostal muscle. An acoustic window was established in all animals. A temperature increase in the target area was achieved in all animals (max. 47°C-67°C). MR thermometry showed no heating outside the target area. Intercostal firing effectively reduced rib heating (55°C vs. 42°C). Postmortem examination revealed no unwanted thermal damage. One complication occurred, in the first experiment, because of an ill-suited needle (displacement of the needle). The results indicate that IPI may be used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable tissue coagulation, IPI must be combined with an intercostal sonication technique. Considering the proportion of patients with tumors in the liver dome, IPI widens the applicability of MR-HIFU ablation for liver tumors considerably. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Laser ablation-inductively coupled plasma mass spectrometry: an emerging technology for detecting rare cells in tissue sections.

PubMed

Managh, Amy J; Hutchinson, Robert W; Riquelme, Paloma; Broichhausen, Christiane; Wege, Anja K; Ritter, Uwe; Ahrens, Norbert; Koehl, Gudrun E; Walter, Lisa; Florian, Christian; Schlitt, Hans J; Reid, Helen J; Geissler, Edward K; Sharp, Barry L; Hutchinson, James A

2014-09-01

Administering immunoregulatory cells to patients as medicinal agents is a potentially revolutionary approach to the treatment of immunologically mediated diseases. Presently, there are no satisfactory, clinically applicable methods of tracking human cells in patients with adequate spatial resolution and target cell specificity over a sufficient period of time. Laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) represents a potential solution to the problem of detecting very rare cells in tissues. In this article, this exquisitely sensitive technique is applied to the tracking of gold-labeled human regulatory macrophages (Mregs) in immunodeficient mice. Optimal conditions for labeling Mregs with 50-nm gold particles were investigated by exposing Mregs in culture to variable concentrations of label: Mregs incubated with 3.5 × 10(9) particles/ml for 1 h incorporated an average of 3.39 × 10(8) Au atoms/cell without loss of cell viability. Analysis of single, gold-labeled Mregs by LA-ICP-MS registered an average of 1.9 × 10(5) counts/cell. Under these conditions, 100% labeling efficiency was achieved, and label was retained by Mregs for ≥36 h. Gold-labeled Mregs adhered to glass surfaces; after 24 h of culture, it was possible to colabel these cells with human-specific (154)Sm-tagged anti-HLA-DR or (174)Yb-tagged anti-CD45 mAbs. Following injection into immunodeficient mice, signals from gold-labeled human Mregs could be detected in mouse lung, liver, and spleen for at least 7 d by solution-based inductively coupled plasma mass spectrometry and LA-ICP-MS. These promising results indicate that LA-ICP-MS tissue imaging has great potential as an analytical technique in immunology. Copyright © 2014 by The American Association of Immunologists, Inc.

Comparison of the Three NIF Ablators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kritcher, A. L.; Clark, D. S.; Haan, S. W.

Indirect drive implosion experiments on NIF have now been performed using three different ablator materials: glow discharge polymer (GDP) or CH, high density carbon (HDC, which we also refer to as diamond), and sputtered beryllium (Be). It has been appreciated for some time that each of these materials has specific advantages and disadvantages as an ICF ablator.[1-4] In light of experiments conducted on NIF in the last few years, how do these ablators compare? Given current understanding, is any ablator more or less likely to reach ignition on NIF? Has the understanding of their respective strengths and weaknesses changed sincemore » NIF experiments began? How are those strengths and weaknesses highlighted by implosion designs currently being tested or planned for testing soon? This document aims to address these questions by combining modern simulation results with a survey of the current experimental data base. More particularly, this document is meant to fulfill an L2 Milestone for FY17 to “Document our understanding of the relative advantages and disadvantages of CH, HDC, and Be designs.” Note that this document does not aim to recommend a down-selection of the current three ablator choices. It is intended only to gather and document the current understanding of the differences between these ablators and thereby inform the choices made in planning future implosion experiments. This document has two themes: (i) We report on a reanalysis project in which post-shot simulations were done on a common basis for layered shots using each ablator. This included data from keyholes, 2D ConA, and so forth, from each campaign, leading up to the layered shots. (“Keyholes” are shots dedicated to measuring the shock timing in a NIF target, as described in Ref. 5. “2DConAs” are backlit implosions in which the symmetry of the implosion is measured between about half and full convergence, as described in Ref. 6.) This set of common-basis postshot simulations is

Pathological proof of cellular death in radiofrequency ablation therapy and correlation with flash echo imaging--an experiment study.

PubMed

Fujiki, Kei

2004-01-01

The aims of this study were to clarify the geographic distribution of complete cell death in the radiofrequency ablated area in a porcine liver experiment, and to evaluate the efficacy of ultrasonography using contrast media in detecting the area of Radiofrequency-induced cell death. Radiofrequency ablation was performed at 3 sites in each liver in seven swine with a RF2000TM radiofrequency generator using an expandable type needle electrode. The ablation area was investigated histologically by Hematoxylin-Eosin staining and NADH staining. The area of radiofrequency-induced cell death was correlated to the ultrasonographic findings using contrast media, by means of contrast harmonic imaging, flash echo imaging-subtraction and flash echo imaging-power Doppler. The ablation area showed three distinct regions. Although the HE staining did not indicate necrosis, the NADH staining showed a complete loss of cellular activity in the inner and middle layers of the ablation area. However, in the outer layer cells displaying cellular integrity were intermingled with the necrotic cells, indicating that some of the cells in this layer had a chance to survive. Further, in some cases the outer layer of the ablated area had irregular margins. The flash-echo power-doppler images were accurately correlated in size and shape to the pathologically proved region of complete cell death in the radiofrequency-induced lesions. In the marginal part of the radiofrequency ablation area, cell death was incomplete. Flash echo imaging-power doppler was a useful and sensitive real time imaging technique for accurate evaluation of the region of complete cell death.

Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models

PubMed Central

Wong, Andrew W.; Fite, Brett Z.; Liu, Yu; Kheirolomoom, Azadeh; Seo, Jai W.; Watson, Katherine D.; Mahakian, Lisa M.; Tam, Sarah M.; Zhang, Hua; Foiret, Josquin; Borowsky, Alexander D.; Ferrara, Katherine W.

2015-01-01

Magnetic resonance–guided focused ultrasound (MRgFUS) facilitates noninvasive image-guided conformal thermal therapy of cancer. Yet in many scenarios, the sensitive tissues surrounding the tumor constrain the margins of ablation; therefore, augmentation of MRgFUS with chemotherapy may be required to destroy remaining tumor. Here, we used 64Cu-PET-CT, MRI, autoradiography, and fluorescence imaging to track the kinetics of long-circulating liposomes in immunocompetent mammary carcinoma–bearing FVB/n and BALB/c mice. We observed a 5-fold and 50-fold enhancement of liposome and drug concentration, respectively, within MRgFUS thermal ablation–treated tumors along with dense accumulation within the surrounding tissue rim. Ultrasound-enhanced drug accumulation was rapid and durable and greatly increased total tumor drug exposure over time. In addition, we found that the small molecule gadoteridol accumulates around and within ablated tissue. We further demonstrated that dilated vasculature, loss of vascular integrity resulting in extravasation of blood cells, stromal inflammation, and loss of cell-cell adhesion and tissue architecture all contribute to the enhanced accumulation of the liposomes and small molecule probe. The locally enhanced liposome accumulation was preserved even after a multiweek protocol of doxorubicin-loaded liposomes and partial ablation. Finally, by supplementing ablation with concurrent liposomal drug therapy, a complete and durable response was obtained using protocols for which a sub-mm rim of tumor remained after ablation. PMID:26595815

Pharmacologic suppression of target cell recognition by engineered T cells expressing chimeric T-cell receptors.

PubMed

Alvarez-Vallina, L; Yañez, R; Blanco, B; Gil, M; Russell, S J

2000-04-01

Adoptive therapy with autologous T cells expressing chimeric T-cell receptors (chTCRs) is of potential interest for the treatment of malignancy. To limit possible T-cell-mediated damage to normal tissues that weakly express the targeted tumor antigen (Ag), we have tested a strategy for the suppression of target cell recognition by engineered T cells. Jurkat T cells were transduced with an anti-hapten chTCR tinder the control of a tetracycline-suppressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then reacted with hapten-coated target cells at different effector to target cell ratios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreased and recognition of the hapten-coated target cells was completely suppressed. Tetracycline-mediated suppression of target cell recognition by engineered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.

Embryonic ablation of neuronal VGF increases energy expenditure and reduces body weight

PubMed Central

Jiang, Cheng; Lin, Wei-Jye; Sadahiro, Masato; Shin, Andrew C.; Buettner, Christoph; Salton, Stephen R.

2016-01-01

Germline ablation of VGF, a secreted neuronal, neuroendocrine, and endocrine peptide precursor, results in lean, hypermetabolic, and infertile adult mice that are resistant to diet-, lesion-, and genetically-induced obesity and diabetes (Hahm et al., 1999, 2002). To assess whether this phenotype is predominantly driven by reduced VGF expression in developing and/or adult neurons, or in peripheral endocrine and neuroendocrine tissues, we generated and analyzed conditional VGF knockout mice, obtained by mating loxP-flanked (floxed) Vgf mice with either pan-neuronal Synapsin-Cre- or forebrain alpha-CaMKII-Cre-recombinase-expressing transgenic mice. Adult male and female mice, with conditional ablation of the Vgf gene in embryonic neurons had significantly reduced body weight, increased energy expenditure, and were resistant to diet-induced obesity. Conditional forebrain postnatal ablation of VGF in male mice, primarily in adult excitatory neurons, had no measurable effect on body weight nor on energy expenditure, but led to a modest increase in adiposity, partially overlapping the effect of AAV-Cre-mediated targeted ablation of VGF in the adult ventromedial hypothalamus and arcuate nucleus of floxed Vgf mice (Foglesong et al., 2016), and also consistent with results of icv delivery of the VGF-derived peptide TLQP-21 to adult mice, which resulted in increased energy expenditure and reduced adiposity (Bartolomucci et al., 2006). Because the lean, hypermetabolic phenotype of germline VGF knockout mice is to a great extent recapitulated in Syn-Cre+/−,Vgfflpflox/flpflox mice, we conclude that the metabolic profile of germline VGF knockout mice is largely the result of VGF ablation in embryonic CNS neurons, rather than peripheral endocrine and/or neuroendocrine cells, and that in forebrain structures such as hypothalamus, VGF and/or VGF-derived peptides play uniquely different roles in the developing and adult nervous system. PMID:28024880

Embryonic ablation of neuronal VGF increases energy expenditure and reduces body weight.

PubMed

Jiang, Cheng; Lin, Wei-Jye; Sadahiro, Masato; Shin, Andrew C; Buettner, Christoph; Salton, Stephen R

2017-08-01

Germline ablation of VGF, a secreted neuronal, neuroendocrine, and endocrine peptide precursor, results in lean, hypermetabolic, and infertile adult mice that are resistant to diet-, lesion-, and genetically-induced obesity and diabetes (Hahm et al., 1999, 2002). To assess whether this phenotype is predominantly driven by reduced VGF expression in developing and/or adult neurons, or in peripheral endocrine and neuroendocrine tissues, we generated and analyzed conditional VGF knockout mice, obtained by mating loxP-flanked (floxed) Vgf mice with either pan-neuronal Synapsin-Cre- or forebrain alpha-CaMKII-Cre-recombinase-expressing transgenic mice. Adult male and female mice, with conditional ablation of the Vgf gene in embryonic neurons had significantly reduced body weight, increased energy expenditure, and were resistant to diet-induced obesity. Conditional forebrain postnatal ablation of VGF in male mice, primarily in adult excitatory neurons, had no measurable effect on body weight nor on energy expenditure, but led to a modest increase in adiposity, partially overlapping the effect of AAV-Cre-mediated targeted ablation of VGF in the adult ventromedial hypothalamus and arcuate nucleus of floxed Vgf mice (Foglesong et al., 2016), and also consistent with results of icv delivery of the VGF-derived peptide TLQP-21 to adult mice, which resulted in increased energy expenditure and reduced adiposity (Bartolomucci et al., 2006). Because the lean, hypermetabolic phenotype of germline VGF knockout mice is to a great extent recapitulated in Syn-Cre +/- ,Vgf flpflox/flpflox mice, we conclude that the metabolic profile of germline VGF knockout mice is largely the result of VGF ablation in embryonic CNS neurons, rather than peripheral endocrine and/or neuroendocrine cells, and that in forebrain structures such as hypothalamus, VGF and/or VGF-derived peptides play uniquely different roles in the developing and adult nervous system. Copyright © 2016 Elsevier Ltd. All rights

Photoacoustic characterization of the left atrium wall: healthy and ablated tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Iskander-Rizk, Sophinese; Kruizinga, Pieter; van der Steen, Antonius F. W.; van Soest, Gijs

2017-03-01

Radio-frequency ablation (RFA) creates a thermal lesion in the atrial wall, with clearly recognizable optical and structural changes to the tissue. This can be detected by photoacoustic (PA) imaging, and used for monitoring of lesion depth, lesion functionality, and limiting excessive ablation. Porcine left atrium tissue can be split into three visually distinguishable regions, a thick white endocardium, pinkish myocardium and a thin gelatinous epicardium. In this study, we characterize the layered left atrium tissue in terms of the relevant photoacoustic parameters (wavelength, frequency content, imaging depth, lesion contrast). Previous studies in the literature targeted the photoacoustic characterization of fresh and ablated ventricular myocardium in the range of 650nm to 900nm. In this study we target the characterization of fresh and ablated left atrial tissue from 410nm to 1000nm, including the endocardium and epicardium. We generate the photoacoustic signals using a tunable pulsed laser source, and record those signals using either a broadband 1 mm hydrophone or a L12-3v transducer connected to the Verasonics machine for more realistic conditions. Initial experiments on fresh porcine tissue show that the presence of the endocardium and epicardium layers do affect the photoacoustic signal received. The signal recorded is representative of the difference in optical and mechanical properties between the layers. Ablated and non-ablated tissue also present differences in spectra. The determined optical contrast could be used in the PA monitoring of RFA lesion to monitor the extension of the lesion to the edge of the myocardium-epicardium border avoiding complications related to over ablation.

Predictive analysis of optical ablation in several dermatological tumoral tissues

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

Laser-Ablation (U-Th)/He Geochronology

NASA Astrophysics Data System (ADS)

Hodges, K.; Boyce, J.

2003-12-01

Over the past decade, ultraviolet laser microprobes have revolutionized the field of 40Ar/39Ar geochronology. They provide unprecedented information about Ar isotopic zoning in natural crystals, permit high-resolution characterization of Ar diffusion profiles produced during laboratory experiments, and enable targeted dating of multiple generations of minerals in thin section. We have modified the analytical protocols used for 40Ar/39Ar laser microanalysis for use in (U-Th)/He geochronologic studies. Part of the success of the 40Ar/39Ar laser microprobe stems from fact that measurements of Ar isotopic ratios alone are sufficient for the calculation of a date. In contrast, the (U-Th)/He method requires separate analysis of U+Th and 4He. Our method employs two separate laser microprobes for this process. A target mineral grain is placed in an ultrahigh vacuum chamber fitted with a window of appropriate composition to transmit ultraviolet radiation. A focused ArF (193 nm) excimer laser is used to ablate tapered cylindrical pits on the surface of the target. The liberated material is scrubbed with a series of getters in a fashion similar to that used for 40Ar/39Ar geochronology, and the 4He abundance is determined using a quadrupole mass spectrometer with well-calibrated sensitivity. A key requirement for calculation of the 4He abundance in the target is a precise knowledge of the volume of the ablation pit. This is the principal reason why we employ the ArF excimer for 4He analysis rather than a less-expensive frequency-multiplied Nd-YAG laser; the excimer creates tapered cylindrical pits with extremely reproducible and easily characterized geometry. After 4He analysis, U and Th are measured on the same sample surface using the more familiar technique of laser-ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Our early experiments have been done using a frequency-quintupled Nd-YAG microprobe (213nm), While the need to analyze U+Th and He in separate

c-Raf in KRas Mutant Cancers: A Moving Target.

PubMed

McCormick, Frank

2018-02-12

Therapies for KRas cancers remain a major clinical need. In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these cancers. c-Raf ablation caused regression of advanced KRas G12V /Trp53 tumors, without obvious systemic toxicity and without affecting MAPK signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

In-vivo optical imaging of hsp70 expression to assess collateral tissue damage associated with infrared laser ablation of skin

PubMed Central

Wilmink, Gerald J.; Opalenik, Susan R.; Beckham, Joshua T.; Mackanos, Mark A.; Nanney, Lillian B.; Contag, Christopher H.; Davidson, Jeffrey M.; Jansen, E. Duco

2013-01-01

Laser surgical ablation is achieved by selecting laser parameters that remove confined volumes of target tissue and cause minimal collateral damage. Previous studies have measured the effects of wavelength on ablation, but neglected to measure the cellular impact of ablation on cells outside the lethal zone. In this study, we use optical imaging in addition to conventional assessment techniques to evaluate lethal and sublethal collateral damage after ablative surgery with a free-electron laser (FEL). Heat shock protein (HSP) expression is used as a sensitive quantitative marker of sublethal damage in a transgenic mouse strain, with the hsp70 promoter driving luciferase and green fluorescent protein (GFP) expression (hsp70A1-L2G). To examine the wavelength dependence in the mid-IR, laser surgery is conducted on the hsp70A1-L2G mouse using wavelengths targeting water (OH stretch mode, 2.94 μm), protein (amide-II band, 6.45 μm), and both water and protein (amide-I band, 6.10 μm). For all wavelengths tested, the magnitude of hsp70 expression is dose-dependent and maximal 5 to 12 h after surgery. Tissues treated at 6.45 μm have approximately 4× higher hsp70 expression than 6.10 μm. Histology shows that under comparable fluences, tissue injury at the 2.94-μm wavelength was 2× and 3× deeper than 6.45 and 6.10 μm, respectively. The 6.10-μm wavelength generates the least amount of epidermal hyperplasia. Taken together, this data suggests that the 6.10-μm wavelength is a superior wavelength for laser ablation of skin. PMID:19021444

Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of Ranbp2 in Cone Photoreceptors

PubMed Central

Cho, Kyoung-in; Yu, Minzhong; Hao, Ying; Qiu, Sunny; Pillai, Indulekha C. L.; Peachey, Neal S.; Ferreira, Paulo A.

2013-01-01

Non-autonomous cell-death is a cardinal feature of the disintegration of neural networks in neurodegenerative diseases, but the molecular bases of this process are poorly understood. The neural retina comprises a mosaic of rod and cone photoreceptors. Cone and rod photoreceptors degenerate upon rod-specific expression of heterogeneous mutations in functionally distinct genes, whereas cone-specific mutations are thought to cause only cone demise. Here we show that conditional ablation in cone photoreceptors of Ran-binding protein-2 (Ranbp2), a cell context-dependent pleiotropic protein linked to neuroprotection, familial necrotic encephalopathies, acute transverse myelitis and tumor-suppression, promotes early electrophysiological deficits, subcellular erosive destruction and non-apoptotic death of cones, whereas rod photoreceptors undergo cone-dependent non-autonomous apoptosis. Cone-specific Ranbp2 ablation causes the temporal activation of a cone-intrinsic molecular cascade highlighted by the early activation of metalloproteinase 11/stromelysin-3 and up-regulation of Crx and CoREST, followed by the down-modulation of cone-specific phototransduction genes, transient up-regulation of regulatory/survival genes and activation of caspase-7 without apoptosis. Conversely, PARP1+-apoptotic rods develop upon sequential activation of caspase-9 and caspase-3 and loss of membrane permeability. Rod photoreceptor demise ceases upon cone degeneration. These findings reveal novel roles of Ranbp2 in the modulation of intrinsic and extrinsic cell death mechanisms and pathways. They also unveil a novel spatiotemporal paradigm of progression of neurodegeneration upon cell-specific genetic damage whereby a cone to rod non-autonomous death pathway with intrinsically distinct cell-type death manifestations is triggered by cell-specific loss of Ranbp2. Finally, this study casts new light onto cell-death mechanisms that may be shared by human dystrophies with distinct retinal spatial

Anti-EGFR Antibody Conjugation of Fucoidan-Coated Gold Nanorods as Novel Photothermal Ablation Agents for Cancer Therapy.

PubMed

Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Oh, Yun-Ok; Song, Kyeongeun; Seo, Hansu; Oh, Junghwan

2017-05-03

The development of novel photothermal ablation agents as cancer nanotheranostics has received a great deal of attention in recent decades. Biocompatible fucoidan (Fu) is used as the coating material for gold nanorods (AuNRs) and subsequently conjugated with monoclonal antibodies against epidermal growth factor receptor (anti-EGFR) as novel photothermal ablation agents for cancer nanotheranostics because of their excellent biocompatibility, biodegradability, nontoxicity, water solubility, photostability, ease of surface modification, strongly enhanced absorption in near-infrared (NIR) regions, target specificity, minimal invasiveness, fast recovery, and prevention of damage to normal tissues. Anti-EGFR Fu-AuNRs have an average particle size of 96.37 ± 3.73 nm. Under 808 nm NIR laser at 2 W/cm 2 for 5 min, the temperature of the solution containing anti-EGFR Fu-AuNRs (30 μg/mL) increased by 52.1 °C. The anti-EGFR Fu-AuNRs exhibited high efficiency for the ablation of MDA-MB-231 cells in vitro. In vivo photothermal ablation exhibited that tumor tissues fully recovered without recurrence and finally were reconstructed with normal tissues by the 808 nm NIR laser irradiation after injection of anti-EGFR Fu-AuNRs. These results suggest that the anti-EGFR Fu-AuNRs would be novel photoablation agents for future cancer nanotheranostics.

Microwave ablation versus radiofrequency ablation in the kidney: high-power triaxial antennas create larger ablation zones than similarly sized internally cooled electrodes.

PubMed

Laeseke, Paul F; Lee, Fred T; Sampson, Lisa A; van der Weide, Daniel W; Brace, Christopher L

2009-09-01

To determine whether microwave ablation with high-power triaxial antennas creates significantly larger ablation zones than radiofrequency (RF) ablation with similarly sized internally cooled electrodes. Twenty-eight 12-minute ablations were performed in an in vivo porcine kidney model. RF ablations were performed with a 200-W pulsed generator and either a single 17-gauge cooled electrode (n = 9) or three switched electrodes spaced 1.5 cm apart (n = 7). Microwave ablations were performed with one (n = 7), two (n = 3), or three (n = 2) 17-gauge triaxial antennas to deliver 90 W continuous power per antenna. Multiple antennas were powered simultaneously. Temperatures 1 cm from the applicator were measured during two RF and microwave ablations each. Animals were euthanized after ablation and ablation zone diameter, cross-sectional area, and circularity were measured. Comparisons between groups were performed with use of a mixed-effects model with P values less than .05 indicating statistical significance. No adverse events occurred during the procedures. Three-electrode RF (mean area, 14.7 cm(2)) and single-antenna microwave (mean area, 10.9 cm(2)) ablation zones were significantly larger than single-electrode RF zones (mean area, 5.6 cm(2); P = .001 and P = .0355, respectively). No significant differences were detected between single-antenna microwave and multiple-electrode RF. Ablation zone circularity was similar across groups (P > .05). Tissue temperatures were higher during microwave ablation (maximum temperature of 123 degrees C vs 100 degrees C for RF). Microwave ablation with high-power triaxial antennas created larger ablation zones in normal porcine kidneys than RF ablation with similarly sized applicators.

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

PubMed Central

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

2013-01-01

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

MicroRNA‐199b Modulates Vascular Cell Fate During iPS Cell Differentiation by Targeting the Notch Ligand Jagged1 and Enhancing VEGF Signaling

PubMed Central

Chen, Ting; Kelaini, Sophia; Cochrane, Amy; Guha, Shaunta T.; Hu, Yanhua; Stitt, Alan W.; Xu, Qingbo

2015-01-01

Abstract Aims: Recent ability to derive endothelial cells (ECs) from induced pluripotent stem (iPS) cells holds a great therapeutic potential for personalized medicine and stem cell therapy. We aimed that better understanding of the complex molecular signals that are evoked during iPS cell differentiation toward ECs may allow specific targeting of their activities to enhance cell differentiation and promote tissue regeneration. Methods and Results: In this study, we have generated mouse iPS cells from fibroblasts using established protocol. When iPS cells were cultivated on type IV mouse collagen‐coated dishes in differentiation medium, cell differentiation toward vascular lineages were observed. To study the molecular mechanisms of iPS cell differentiation, we found that miR‐199b is involved in EC differentiation. A step‐wise increase in expression of miR‐199 was detected during EC differentiation. Notably, miR‐199b targeted the Notch ligand JAG1, resulting in vascular endothelial growth factor (VEGF) transcriptional activation and secretion through the transcription factor STAT3. Upon shRNA‐mediated knockdown of the Notch ligand JAG1, the regulatory effect of miR‐199b was ablated and there was robust induction of STAT3 and VEGF during EC differentiation. Knockdown of JAG1 also inhibited miR‐199b‐mediated inhibition of iPS cell differentiation toward smooth muscle markers. Using the in vitro tube formation assay and implanted Matrigel plugs, in vivo, miR‐199b also regulated VEGF expression and angiogenesis. Conclusions: This study indicates a novel role for miR‐199b as a regulator of the phenotypic switch during vascular cell differentiation derived from iPS cells by regulating critical signaling angiogenic responses. Stem Cells 2015;33:1405–1418 PMID:25535084

Human immune cell targeting of protein nanoparticles - caveospheres

NASA Astrophysics Data System (ADS)

Glass, Joshua J.; Yuen, Daniel; Rae, James; Johnston, Angus P. R.; Parton, Robert G.; Kent, Stephen J.; de Rose, Robert

2016-04-01

Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.

Spatiotemporal Variability of Great Lakes Basin Snow Cover Ablation Events

NASA Astrophysics Data System (ADS)

Suriano, Z. J.; Leathers, D. J.

2017-12-01

In the Great Lakes basin of North America, annual runoff is dominated by snowmelt. This snowmelt-induced runoff plays an important role within the hydrologic cycle of the basin, influencing soil moisture availability and driving the seasonal cycle of spring and summer Lake levels. Despite this, relatively little is understood about the patterns and trends of snow ablation event frequency and magnitude within the Great Lakes basin. This study uses a gridded dataset of Canadian and United States surface snow depth observations to develop a regional climatology of snow ablation events from 1960-2009. An ablation event is defined as an inter-diurnal snow depth decrease within an individual grid cell. A clear seasonal cycle in ablation event frequency exists within the basin and peak ablation event frequency is latitudinally dependent. Most of the basin experiences peak ablation frequency in March, while the northern and southern regions of the basin experience respective peaks in April and February. An investigation into the inter-annual frequency of ablation events reveals ablation events significantly decrease within the northeastern and northwestern Lake Superior drainage basins and significantly increase within the eastern Lake Huron and Georgian Bay drainage basins. In the eastern Lake Huron and Georgian Bay drainage basins, larger ablation events are occurring more frequently, and a larger impact to the hydrology can be expected. Trends in ablation events are attributed primarily to changes in snowfall and snow depth across the region.

Histopathology of breast cancer after magnetic resonance-guided high-intensity focused ultrasound and radiofrequency ablation.

PubMed

Knuttel, Floortje M; Waaijer, Laurien; Merckel, Laura G; van den Bosch, Maurice A A J; Witkamp, Arjen J; Deckers, Roel; van Diest, Paul J

2016-08-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation and radiofrequency ablation (RFA) are being researched as possible substitutes for surgery in breast cancer patients. The histopathological appearance of ablated tissue has not been studied in great detail. This study aimed to compare histopathological features of breast cancer after MR-HIFU ablation and RFA. MR-HIFU ablation and RFA were performed in- and ex-vivo. Tumours in six mastectomy specimens were partially ablated with RFA or MR-HIFU. In-vivo MR-HIFU ablation was performed 3-6 days before excision; RFA was performed in the operation room. Tissue was fixed in formalin and processed to haematoxylin and eosin (H&E) and cytokeratin-8 (CK-8)-stained slides. Morphology and cell viability were assessed. Ex-vivo ablation resulted in clear morphological changes after RFA versus subtle differences after MR-HIFU. CK-8 staining was decreased or absent. H&E tended to underestimate the size of thermal damage. In-vivo MR-HIFU resulted in necrotic-like changes. Surprisingly, some ablated lesions were CK-8-positive. Histopathology after in-vivo RFA resembled ex-vivo RFA, with hyper-eosinophilic stroma and elongated nuclei. Lesion borders were sharp after MR-HIFU and indistinct after RFA. Histopathological differences between MR-HIFU-ablated tissue and RF-ablated tissue were demonstrated. CK-8 was more reliable for cell viability assessment than H&E when used directly after ablation, while H&E was more reliable in ablated tissue left in situ for a few days. Our results contribute to improved understanding of histopathological features in breast cancer lesions treated with minimally invasive ablative techniques. © 2016 John Wiley & Sons Ltd.

Fluorescent carbon and graphene oxide nanoparticles synthesized by the laser ablation in liquid

NASA Astrophysics Data System (ADS)

Małolepszy, A.; Błonski, S.; Chrzanowska-Giżyńska, J.; Wojasiński, M.; Płocinski, T.; Stobinski, L.; Szymanski, Z.

2018-04-01

The results of synthesis of the fluorescent carbon dots (CDots) from graphite target and reduced graphene oxide (rGO) nanoparticles performed by the nanosecond laser ablation in polyethylene glycol 200 (PEG200) are shown. Two-step laser irradiation (first graphite target, next achieved suspension) revealed a very effective production of CDots. However, the ablation in PEG appeared to be effective with 1064 nm laser pulse in contrast to the ablation with 355 nm laser pulse. In the case of rGO nanoparticles similar laser irradiation procedure was less efficient. In both cases, received nanoparticles exhibited strong, broadband photoluminescence with a maximum dependent on the excitation wavelength. The size distribution for obtained CDots was evaluated using the DLS technique and HRTEM images. The results from both methods show quite good agreement in nanoparticle size estimation although the DLS method slightly overestimates nanoparticle's diameter.

Thermal Ablation in the Management of Adrenal Metastasis Originating from Non-small Cell Lung Cancer: A 5-year Single-center Experience

PubMed Central

Botsa, Evanthia I; Thanou, Ioanna L; Papatheodoropoulou, Aspasia T; Thanos, Loukas I

2017-01-01

Background: Treatment of adrenal metastasis from lung carcinoma may prolong survival in the selected patients. However, not all patients can undergo surgery; thus, minimally invasive ablation procedures such as radiofrequency ablation (RFA) and microwave ablation (MWA) have gained acceptance as alternative treatment methods. This study summarized a 5-year single-center experience regarding the evaluation of safety and efficacy of computed tomography (CT)-guided thermal ablation in the management of adrenal metastasis originating from non-small cell lung cancer (NSCLC). Methods: The data of NSCLC patients ablated for adrenal metastasis at the Department of Diagnostic Imaging and Interventional Radiology, General Hospital Sotiria, were retrospectively analyzed. Patients were divided into two groups: RFA group and MWA group according to the therapeutic approaches. Preprocedural blood tests included measurement of international normalized ratio, partial thromboplastin time, and platelet enumeration. A dual-phase contrast-enhanced spiral CT was performed immediately after the procedure to assess the immediate response after ablation and to screen for related complications. Follow-up was performed with CT or magnetic resonance imaging at 1, 3, 6 months and 1 year after ablation and every 6 months thereafter. Results: A total of 99 ablation sessions in 71 patients with adrenal metastasis originating from NSCLC were included in the final analysis. Self-limited, postablation syndrome occurred in 16/99 (16.1%) of ablation sessions. All procedures were technically successful. Immediate postablation imaging showed no contrast enhancement of the ablated tumor in all patients. Follow-up imaging at 3 months revealed local tumor progression in 8 (22.8%) patients of the RFA group and 7 (19.4%) patients of MWA group, all of them underwent a second session successfully. The 1-year assessment revealed local recurrence of the ablated tumor in six patients (17.1%) of RFA group and seven

Global ablation techniques.

PubMed

Woods, Sarah; Taylor, Betsy

2013-12-01

Global endometrial ablation techniques are a relatively new surgical technology for the treatment of heavy menstrual bleeding that can now be used even in an outpatient clinic setting. A comparison of global ablation versus earlier ablation technologies notes no significant differences in success rates and some improvement in patient satisfaction. The advantages of the newer global endometrial ablation systems include less operative time, improved recovery time, and decreased anesthetic risk. Ablation procedures performed in an outpatient surgical or clinic setting provide advantages both of potential cost savings for patients and the health care system and improved patient convenience. Copyright © 2013. Published by Elsevier Inc.

Percutaneous Irreversible Electroporation Lung Ablation: Preliminary Results in a Porcine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deodhar, Ajita; Monette, Sebastien; Single, Gordon W.

2011-12-15

Objective: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent 'pores' in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. Materials and Methods: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized withmore » the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. Results: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. Conclusion: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.« less

Unsteady motion of laser ablation plume by vortex induced by the expansion of curved shock wave

NASA Astrophysics Data System (ADS)

Tran, D. T.; Mori, K.

2017-02-01

There are a number of industrial applications of laser ablation in a gas atmosphere. When an intense pulsed laser beam is irradiated on a solid surface in the gas atmosphere, the surface material is ablated and expands into the atmosphere. At the same time, a spherical shock wave is launched by the ablation jet to induce the unsteady flow around the target surface. The ablated materials, luminously working as tracer, exhibit strange unsteady motions depending on the experimental conditions. By using a high-speed video camera (HPV-X2), unsteady motion ablated materials are visualized at the frame rate more than 106 fps, and qualitatively characterized.

Targeted BikDD expression kills androgen-dependent and castration-resistant prostate cancer cells

PubMed Central

Xie, Xiaoming; Kong, Yanan; Tang, Hailin; Yang, Lu; Hsu, Jennifer L; Hung, Mien-Chie

2014-01-01

Targeted gene therapy is a promising approach for treating prostate cancer after the discovery of prostate cancer-specific promoters such as prostate-specific antigen, rat probasin, and human glandular kallikrein. However, these promoters are androgen-dependent, and after castration or androgen ablation therapy, they become much less active or sometimes inactive. Importantly, the disease will inevitably progress from androgen-dependent (ADPC) to castration-resistant prostate cancer (CRPC) at which treatments fail and high mortality ensues. Therefore, it is critical to develop a targeted gene therapy strategy that is effective in both ADPC and CRPC to eradicate recurrent prostate tumors. The human telomerase reverse transcriptase-VP16-Gal4-WPRE integrated systemic amplifier composite (T-VISA) vector we previously developed which targets transgene expression in ovarian and breast cancer is also active in prostate cancer. To further improve its effectiveness based on androgen response in ADPC progression, the ARR2 element (two copies of androgen response region from rat probasin promoter) was incorporated into T-VISA to produce AT-VISA. Under androgen analog (R1881) stimulation, the activity of AT-VISA was increased to a level greater than or comparable to the cytomegalovirus (CMV) promoter in ADPC and CRPC cells, respectively. Importantly, AT-VISA demonstrated little or no expression in normal cells. Systemic administration of AT-VISA-BikDD encapsulated in liposomes repressed prostate tumor growth and prolonged mouse survival in orthotopic animal models as well as in the transgenic adenocarcinoma mouse prostate model, indicating that AT-VISA-BikDD has therapeutic potential to treat ADPC and CRPC safely and effectively in preclinical setting. PMID:24785255

Radiofrequency ablation of hepatocellular carcinoma: pros and cons.

PubMed

Rhim, Hyunchul; Lim, Hyo K

2010-09-01

Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents.

Radiofrequency Ablation of Hepatocellular Carcinoma: Pros and Cons

PubMed Central

Lim, Hyo K.

2010-01-01

Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents. PMID:21103289

High-Precision Photothermal Ablation Using Biocompatible Palladium Nanoparticles and Laser Scanning Microscopy

PubMed Central

2018-01-01

Herein, we report a straightforward method for the scalable preparation of Pd nanoparticles (Pd-NPs) with reduced inherent cytotoxicity and high photothermal conversion capacity. These Pd-NPs are rapidly taken up by cells and able to kill labeled cancer cells upon short exposure to near-infrared (NIR) light. Following cell treatment with Pd-NPs, ablated areas were patterned with high precision by laser scanning microscopy, allowing one to perform cell migration assays with unprecedented accuracy. Using coherent Raman microscopy, cells containing Pd-NPs were simultaneously ablated and imaged. This novel methodology was combined with intravital imaging to mediate microablation of cancerous tissue in tumor xenografts in mice. PMID:29320154

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.

PubMed

Lujan, Heidi L; Palani, Gurunanthan; Chen, Ying; Peduzzi, Jean D; Dicarlo, Stephen E

2009-05-01

Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).

Rear-side picosecond laser ablation of indium tin oxide micro-grooves

NASA Astrophysics Data System (ADS)

Liu, Peng; Wang, Wenjun; Mei, Xuesong; Liu, Bin; Zhao, Wanqin

2015-06-01

A comparative study of the fabrication of micro-grooves in indium tin oxide films by picosecond laser ablation for application in thin film solar cells is presented, evaluating the variation of different process parameters. Compared with traditional front-side ablation, rear-side ablation results in thinner grooves with varying laser power at a certain scan speed. In particular, and in contrast to front-side ablation, the width of the micro-grooves remains unchanged when the scan speed was changed. Thus, the micro-groove quality can be optimized by adjusting the scan speed while the groove width would not be affected. Furthermore, high-quality micro-grooves with ripple free surfaces and steep sidewalls could only be achieved when applying rear-side ablation. Finally, the formation mechanism of micro-cracks on the groove rims during rear-side ablation is analyzed and the cracks can be almost entirely eliminated by an optimization of the scan speed.

[Percutaneous lung thermo-ablation].

PubMed

Palussière, Jean; Catena, Vittorio; Gaubert, Jean-Yves; Buy, Xavier; de Baere, Thierry

2017-05-01

Percutaneous lung thermo-ablation has steadily been developed over the past 15years. Main indications are early stage non-small cell lung carcinoma (NSCLC) for non-surgical patients and slow evolving localized metastatic disease, either spontaneous or following a general treatment. Radiofrequency, being the most evaluated technique, offers a local control rate of about 80-90% for tumors <3 cm in diameter. With excellent tolerance and very few complications, radiofrequency may be proposed for patients with a chronic disease. Other ablation techniques under investigation such as microwaves and cryotherapy could allow overcoming radiofrequency limits. Furthermore, stereotactic radiotherapy proposed for the same indications is efficient. Comparative studies are warranted to differentiate these techniques in terms of efficacy, tolerance and cost-effectiveness. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Percutaneous Microwave Ablation in the Spleen for Treatment of Hypersplenism in Cirrhosis Patients.

PubMed

Jiang, XiangWu; Gao, Fei; Ma, Yan; Feng, ShuFen; Liu, XueLian; Zhou, HongKe

2016-01-01

The aim of this study was to estimate the feasibility and therapeutic effectiveness of percutaneous microwave ablation in the treatment of hypersplenism in cirrhosis. Forty-one cirrhosis patients with hypersplenism were treated with ultrasonography-guided percutaneous microwave ablation between February 2007 and August 2011. Peripheral blood cell counts, portal vein diameter, splenic vein diameter, and blood flow of splenic vein were evaluated before and after the operation, and complications of the treatment were also investigated. All patients were followed up for 24 months. The levels of platelets and white blood cells were increased, while the splenic vein diameter narrowed gradually after the therapy and 24 months later. Moreover, patients received percutaneous microwave ablation had much lower splenic venous flow velocity. The portal vein diameter did not change significantly 6 months after the treatment, although it narrowed gradually within 3 months after the treatment. Furthermore, no complications such as uncontrollable bleeding, splenic abscess, spleen rupture, and damage in surrounding organ happened after the therapy. Graded percutaneous microwave ablation, as a minimally invasive therapy, could damage the spleen, increase the levels of platelets and white blood cells, and reduce portal hypertension effectively without serious complications. Percutaneous microwave ablation is an effective, safe, and feasible method for cirrhosis patients with hypersplenism.

Ion separation effects in mixed-species ablators for inertial-confinement-fusion implosions

NASA Astrophysics Data System (ADS)

Amendt, Peter; Bellei, Claudio; Ross, J. Steven; Salmonson, Jay

2015-02-01

Recent efforts to demonstrate significant self-heating of the fuel and eventual ignition at the National Ignition Facility make use of plastic (CH) ablators [O. A. Hurricane et al., Phys. Plasmas 21, 056314 (2014), 10.1063/1.4874330]. Mainline simulation techniques for modeling CH capsule implosions treat the ablator as an average-atom fluid and neglect potential species separation phenomena. The mass-ablation process for a mixture is shown to lead to the potential for species separation, parasitic energy loss according to thermodynamic arguments, and reduced rocket efficiency. A generalized plasma barometric formula for a multispecies concentration gradient that includes collisionality and steady flows in spherical geometry is presented. A model based on plasma expansion into a vacuum is used to interpret reported experimental evidence for ablator species separation in an inertial-confinement-fusion target [J. S. Ross et al., Rev. Sci. Instrum. 83, 10E323 (2012)]. The possibility of "runaway" hydrogen ions in the thermoelectric field of the ablation front is conjectured.

Ion separation effects in mixed-species ablators for inertial-confinement-fusion implosions.

PubMed

Amendt, Peter; Bellei, Claudio; Ross, J Steven; Salmonson, Jay

2015-02-01

Recent efforts to demonstrate significant self-heating of the fuel and eventual ignition at the National Ignition Facility make use of plastic (CH) ablators [O. A. Hurricane et al., Phys. Plasmas 21, 056314 (2014)]. Mainline simulation techniques for modeling CH capsule implosions treat the ablator as an average-atom fluid and neglect potential species separation phenomena. The mass-ablation process for a mixture is shown to lead to the potential for species separation, parasitic energy loss according to thermodynamic arguments, and reduced rocket efficiency. A generalized plasma barometric formula for a multispecies concentration gradient that includes collisionality and steady flows in spherical geometry is presented. A model based on plasma expansion into a vacuum is used to interpret reported experimental evidence for ablator species separation in an inertial-confinement-fusion target [J. S. Ross et al., Rev. Sci. Instrum. 83, 10E323 (2012)]. The possibility of "runaway" hydrogen ions in the thermoelectric field of the ablation front is conjectured.

Clinical impact of rotor ablation in atrial fibrillation: a systematic review.

PubMed

Parameswaran, Ramanathan; Voskoboinik, Aleksandr; Gorelik, Alexandra; Lee, Geoffrey; Kistler, Peter M; Sanders, Prashanthan; Kalman, Jonathan M

2018-01-11

Rotor mapping and ablation have gained favour over the recent years as an emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their efficacy, however, has been a topic of great debate with variable outcomes across centres. The aim of this study was to systematically review the recent medical literature to determine the medium-term outcomes of rotor ablation in patients with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (PeAF). A systematic search of the contemporary scientific literature (PubMed and EMBASE) was performed in August 2017. Only studies assessing arrhythmia-free survival from rotor ablation of AF were included. We used the random-effects model to assess the primary outcome of pooled medium-term single-procedure AF-free survival for both PAF and PeAF. Success rates from multiple procedures and complication rates were also examined. We included 11 observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence interval 5.6-86.3%] at a mean follow-up period of 13.8 ± 1.8 months for PAF and 59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 ± 6 months for PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and 88.3% for PeAF). The mean complication rate of rotor ablation among the reported studies was 3.4%. The wide variability in success rate between different centres performing rotor ablations suggests that the optimal ablation strategy, particularly targeting rotors, is unclear. Results from randomized studies are necessary before this technique can be considered as an established clinical tool. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Robotically assisted ablation produces more rapid and greater signal attenuation than manual ablation.

PubMed

Koa-Wing, Michael; Kojodjojo, Pipin; Malcolme-Lawes, Louisa C; Salukhe, Tushar V; Linton, Nick W F; Grogan, Aaron P; Bergman, Dale; Lim, Phang Boon; Whinnett, Zachary I; McCarthy, Karen; Ho, Siew Yen; O'Neill, Mark D; Peters, Nicholas S; Davies, D Wyn; Kanagaratnam, Prapa

2009-12-01

Robotic remote catheter ablation potentially provides improved catheter-tip stability, which should improve the efficiency of radiofrequency energy delivery. Percentage reduction in electrogram peak-to-peak voltage has been used as a measure of effectiveness of ablation. We tested the hypothesis that improved catheter-tip stability of robotic ablation can diminish signals to a greater degree than manual ablation. In vivo NavX maps of 7 pig atria were constructed. Separate lines of ablation were performed robotically and manually, recording pre- and postablation peak-to-peak voltages at 10, 20, 30, and 60 seconds and calculating signal amplitude reduction. Catheter ablation settings were constant (25W, 50 degrees , 17 mL/min, 20-30 g catheter tip pressure). The pigs were sacrificed and ablation lesions correlated with NavX maps. Robotic ablation reduced signal amplitude to a greater degree than manual ablation (49 +/- 2.6% vs 29 +/- 4.5% signal reduction after 1 minute [P = 0.0002]). The mean energy delivered (223 +/- 184 J vs 231 +/- 190 J, P = 0.42), power (19 +/- 3.5 W vs 19 +/- 4 W, P = 0.84), and duration of ablation (15 +/- 9 seconds vs 15 +/- 9 seconds, P = 0.89) was the same for manual and robotic. The mean peak catheter-tip temperature was higher for robotic (45 +/- 5 degrees C vs 42 +/- 3 degrees C [P < 0.0001]). The incidence of >50% signal reduction was greater for robotic (37%) than manual (21%) ablation (P = 0.0001). Robotically assisted ablation appears to be more effective than manual ablation at signal amplitude reduction, therefore may be expected to produce improved clinical outcomes.

Analysis of iodinated contrast delivered during thermal ablation: is material trapped in the ablation zone?

PubMed

Wu, Po-Hung; Brace, Chris L

2016-08-21

Intra-procedural contrast-enhanced CT (CECT) has been proposed to evaluate treatment efficacy of thermal ablation. We hypothesized that contrast material delivered concurrently with thermal ablation may become trapped in the ablation zone, and set out to determine whether such an effect would impact ablation visualization. CECT images were acquired during microwave ablation in normal porcine liver with: (A) normal blood perfusion and no iodinated contrast, (B) normal perfusion and iodinated contrast infusion or (C) no blood perfusion and residual iodinated contrast. Changes in CT attenuation were analyzed from before, during and after ablation to evaluate whether contrast was trapped inside of the ablation zone. Visualization was compared between groups using post-ablation contrast-to-noise ratio (CNR). Attenuation gradients were calculated at the ablation boundary and background to quantitate ablation conspicuity. In Group A, attenuation decreased during ablation due to thermal expansion of tissue water and water vaporization. The ablation zone was difficult to visualize (CNR  =  1.57  ±  0.73, boundary gradient  =  0.7  ±  0.4 HU mm(-1)), leading to ablation diameter underestimation compared to gross pathology. Group B ablations saw attenuation increase, suggesting that iodine was trapped inside the ablation zone. However, because the normally perfused liver increased even more, Group B ablations were more visible than Group A (CNR  =  2.04  ±  0.84, boundary gradient  =  6.3  ±  1.1 HU mm(-1)) and allowed accurate estimation of the ablation zone dimensions compared to gross pathology. Substantial water vaporization led to substantial attenuation changes in Group C, though the ablation zone boundary was not highly visible (boundary gradient  =  3.9  ±  1.1 HU mm(-1)). Our results demonstrate that despite iodinated contrast being trapped in the ablation zone, ablation visibility

Particle-in-cell simulations for virtual cathode oscillator including foil ablation effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Gursharn; Chaturvedi, S.

2011-06-15

We have performed two- and three-dimensional, relativistic, electromagnetic, particle-in-cell simulations of an axially extracted virtual cathode oscillator (vircator). The simulations include, for the first time, self-consistent dynamics of the anode foil under the influence of the intense electron beam. This yields the variation of microwave output power as a function of time, including the role of anode ablation and anode-cathode gap closure. These simulations have been done using locally developed particle-in-cell (PIC) codes. The codes have been validated using two vircator designs available from the literature. The simulations reported in the present paper take account of foil ablation due tomore » the intense electron flux, the resulting plasma expansion and shorting of the anode-cathode gap. The variation in anode transparency due to plasma formation is automatically taken into account. We find that damage is generally higher near the axis. Also, at all radial positions, there is little damage in the early stages, followed by a period of rapid erosion, followed in turn by low damage rates. A physical explanation has been given for these trends. As a result of gap closure due to plasma formation from the foil, the output microwave power initially increases, reaches a near-flat-top and then decreases steadily, reaching a minimum around 230 ns. This is consistent with a typical plasma expansion velocity of {approx}2 cm/{mu}s reported in the literature. We also find a significant variation in the dominant output frequency, from 6.3 to 7.6 GHz. This variation is small as long as the plasma density is small, up to {approx}40 ns. As the AK gap starts filling with plasma, there is a steady increase in this frequency.« less

Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells

PubMed Central

Chauveau, Anne; Aucher, Anne; Eissmann, Philipp; Vivier, Eric; Davis, Daniel M.

2010-01-01

Membrane nanotubes are membranous tethers that physically link cell bodies over long distances. Here, we present evidence that nanotubes allow human natural killer (NK) cells to interact functionally with target cells over long distances. Nanotubes were formed when NK cells contacted target cells and moved apart. The frequency of nanotube formation was dependent on the number of receptor/ligand interactions and increased on NK cell activation. Most importantly, NK cell nanotubes contained a submicron scale junction where proteins accumulated, including DAP10, the signaling adaptor that associates with the activating receptor NKG2D, and MHC class I chain-related protein A (MICA), a cognate ligand for NKG2D, as occurs at close intercellular synapses between NK cells and target cells. Quantitative live-cell fluorescence imaging suggested that MICA accumulated at small nanotube synapses in sufficient numbers to trigger cell activation. In addition, tyrosine-phosphorylated proteins and Vav-1 accumulated at such junctions. Functionally, nanotubes could aid the lysis of distant target cells either directly or by moving target cells along the nanotube path into close contact for lysis via a conventional immune synapse. Target cells moving along the nanotube path were commonly polarized such that their uropods faced the direction of movement. This is the opposite polarization than for normal cell migration, implying that nanotubes can specifically drive target cell movement. Finally, target cells that remained connected to an NK cell by a nanotube were frequently lysed, whereas removing the nanotube using a micromanipulator reduced lysis of these target cells. PMID:20212116

Focused US system for MR imaging-guided tumor ablation.

PubMed

Cline, H E; Hynynen, K; Watkins, R D; Adams, W J; Schenck, J F; Ettinger, R H; Freund, W R; Vetro, J P; Jolesz, F A

1995-03-01

To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized.

Design and evaluation of a new Peltier-cooled laser ablation cell with on-sample temperature control.

PubMed

Konz, Ioana; Fernández, Beatriz; Fernández, M Luisa; Pereiro, Rosario; Sanz-Medel, Alfredo

2014-01-27

A new custom-built Peltier-cooled laser ablation cell is described. The proposed cryogenic cell combines a small internal volume (20 cm(3)) with a unique and reliable on-sample temperature control. The use of a flexible temperature sensor, directly located on the sample surface, ensures a rigorous sample temperature control throughout the entire analysis time and allows instant response to any possible fluctuation. In this way sample integrity and, therefore, reproducibility can be guaranteed during the ablation. The refrigeration of the proposed cryogenic cell combines an internal refrigeration system, controlled by a sensitive thermocouple, with an external refrigeration system. Cooling of the sample is directly carried out by 8 small (1 cm×1 cm) Peltier elements placed in a circular arrangement in the base of the cell. These Peltier elements are located below a copper plate where the sample is placed. Due to the small size of the cooling electronics and their circular allocation it was possible to maintain a peephole under the sample for illumination allowing a much better visualization of the sample, a factor especially important when working with structurally complex tissue sections. The analytical performance of the cryogenic cell was studied using a glass reference material (SRM NIST 612) at room temperature and at -20°C. The proposed cell design shows a reasonable signal washout (signal decay within less than 10 s to background level), high sensitivity and good signal stability (in the range 6.6-11.7%). Furthermore, high precision (0.4-2.6%) and accuracy (0.3-3.9%) in the isotope ratio measurements were also observed operating the cell both at room temperature and at -20°C. Finally, experimental results obtained for the cell application to qualitative elemental imaging of structurally complex tissue samples (e.g. eye sections from a native frozen porcine eye and fresh flower leaves) demonstrate that working in cryogenic conditions is critical in such

Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype

PubMed Central

Capote, Joana; Martinez, Leonel; Vetrone, Sylvia; Barton, Elisabeth R.; Sweeney, H. Lee; Miceli, M. Carrie

2016-01-01

In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors. PMID:27091452

Ablation enhancement of silicon by ultrashort double-pulse laser ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xin; Shin, Yung C.

In this study, the ultrashort double-pulse ablation of silicon is investigated. An atomistic simulation model is developed to analyze the underlying physics. It is revealed that the double-pulse ablation could significantly increase the ablation rate of silicon, compared with the single pulse ablation with the same total pulse energy, which is totally different from the case of metals. In the long pulse delay range (over 1 ps), the enhancement is caused by the metallic transition of melted silicon with the corresponding absorption efficiency. At ultrashort pulse delay (below 1 ps), the enhancement is due to the electron excitation by the first pulse.more » The enhancement only occurs at low and moderate laser fluence. The ablation is suppressed at high fluence due to the strong plasma shielding effect.« less

Ablation of atrial fibrillation with concomitant cardiac surgery.

PubMed

Gillinov, A Marc; Saltman, Adam E

2007-01-01

Atrial fibrillation is present in approximately 35% of patients presenting for mitral valve surgery and in 1 to 6% of adult patients undergoing other forms of cardiac surgery. If left untreated, atrial fibrillation is associated with increased morbidity, and, in some subgroups, increased mortality. Therefore, concomitant management of the arrhythmia is indicated in most cardiac surgery patients with preexisting atrial fibrillation. Although the cut-and-sew Cox-maze III procedure is extremely effective, it has been supplanted by newer operations that rely on alternate energy sources to create lines of conduction block. Early and mid-term results are good with a variety of technologies. Choice of lesion set remains a matter of debate, but results of ablation appear to be enhanced by a biatrial lesion set. Targeted areas for improvement in concomitant ablation include acceptance of uniform standards for reporting results, development of improved technology for ablation and intraoperative assessment, and creation of instrumentation that facilitates minimally invasive approaches.

Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis.

PubMed

Keller, Steve A; Paxian, Marcus; Lee, Sun M; Clemens, Mark G; Huynh, Toan

2005-03-01

Prostaglandins, synthesized by cyclooxygenase (COX), play an important role in the pathophysiology of inflammation. Severe injuries result in immunosuppression, mediated, in part, by maladaptive changes in macrophages. Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on liver function and damage after trauma and sepsis. To ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received sham operations. After 24 h, liver samples were obtained, and mRNA and protein expression were determined by PCR, Western blot, and immunohistochemistry. Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT) levels were determined to assess liver function and damage, respectively. One-way analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess statistical significance. After CLP alone, FFx+CLP, and GdCl3+FFx+CLP, clearance of ICG decreased. Plasma ALT levels increased in parallel with severity of injury. Kupffer cell depletion attenuated the increased ALT levels after FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By contrast, COX-2 protein increased after CLP and was potentiated by sequential stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be Kupffer cells. In this study, sequential stress increased hepatic COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways may contribute to the inflammatory response leading to increased mortality after sequential stress.

The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.

PubMed

Varano, Gabriele; Raffel, Simon; Sormani, Martina; Zanardi, Federica; Lonardi, Silvia; Zasada, Christin; Perucho, Laura; Petrocelli, Valentina; Haake, Andrea; Lee, Albert K; Bugatti, Mattia; Paul, Ulrike; Van Anken, Eelco; Pasqualucci, Laura; Rabadan, Raul; Siebert, Reiner; Kempa, Stefan; Ponzoni, Maurilio; Facchetti, Fabio; Rajewsky, Klaus; Casola, Stefano

2017-06-08

Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR - ) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR + ) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR + tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR - tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR - lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR - tumour cells.

Cell-specific targeting by heterobivalent ligands.

PubMed

Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

2011-07-20

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

Cell-Specific Targeting by Heterobivalent Ligands

PubMed Central

Josan, Jatinder S.; Handl, Heather L.; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M.; Vagner, Josef; Mash, Eugene A.; Hruby, Victor J.; Gillies, Robert J.

2012-01-01

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach—to specifically target combinations of cell-surface receptors using heteromultivalent ligands (“receptor combination approach”). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle4, DPhe7]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20–50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH2. Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging. PMID:21639139

Ablation effects in oxygen-lead fragmentation at 2.1 GeV/nucleon

NASA Technical Reports Server (NTRS)

Townsend, L. W.

1984-01-01

The mechanism of particle evaporation was used to examine ablation effects in the fragmentation of 2.1 GeV/nucleon oxygen nuclei by lead targets. Following the initial abrasion process, the excited projectile prefragment is assumed to statistically decay in a manner analogous to that of a compound nucleus. The decay probabilities for the various particle emission channels are calculated by using the EVAP-4 Monte Carlo computer program. The input excitation energy spectrum for the prefragment is estimated from the geometric ""clean cut'' abrasion-ablation model. Isotope production cross sections are calculated and compared with experimental data and with the predictions from the standard geometric abrasion-ablation fragmentation model.

New Experimental Results of Simulating Micrometeoroid Ablation in the Laboratory

NASA Astrophysics Data System (ADS)

Sternovsky, Zoltan; Thomas, Evan; DeLuca, Michael; Janches, Diego; Munsat, Tobin; Plane, John

2017-04-01

A facility is developed to simulate the ablation of micrometeoroids in laboratory conditions, which also allows measuring the ionization probability of the ablated material. An electrostatic dust accelerator is used to generate iron, aluminum and meteoric analog particles with velocities 10-50 km/s. The particles are then introduced into a cell filled with nitrogen, air or carbon dioxide gas with pressures adjustable in the 0.02 - 0.5 Torr range, where the partial or complete ablation of the particle occurs over a short distance. An array of biased electrodes is used to collect the ionized products with spatial resolution along the ablating particles' path, allowing thus the study of the temporal resolution of the process. A new optical observation setup using a 64 channel PMT system was added to the setup to allow the observation of the ablating particle and deceleration of the particle from the neutral drag. A simple ablation model is used to match the observations. For completely ablated particles the total collected charge directly yields the ionization efficiency. The measurements using iron particles in N2 and air are in relatively good agreement with earlier data. The new experimental data using aluminum particles suggest that the neutral drag acting of the particle is smaller than expected.

Endometrial Ablation

MedlinePlus

... or lighter levels. If ablation does not control heavy bleeding, further treatment or surgery may be needed. ... ablation is used to treat many causes of heavy bleeding. In most cases, women with heavy bleeding ...

Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer.

PubMed

Kim, Hye-Young; Cho, Yunhee; Kang, HyeokGu; Yim, Ye-Seal; Kim, Seok-Jun; Song, Jaewhan; Chun, Kyung-Hee

2016-08-02

Wee1 is a member of the Serine/Threonine protein kinase family and is a key regulator of cell cycle progression. It has been known that WEE1 is highly expressed and has oncogenic functions in various cancers, but it is not yet studied in gastric cancers. In this study, we investigated the oncogenic role and therapeutic potency of targeting WEE1 in gastric cancer. At first, higher expression levels of WEE1 with lower survival probability were determined in stage 4 gastric cancer patients or male patients with accompanied lymph node metastasis. To determine the function of WEE1 in gastric cancer cells, we determined that WEE1 ablation decreased the proliferation, migration, and invasion, while overexpression of WEE1 increased these effects in gastric cancer cells. We also validated the clinical application of WEE1 targeting by a small molecule, AZD1775 (MK-1775), which is a WEE1 specific inhibitor undergoing clinical trials. AZD1775 significantly inhibited cell proliferation and induced apoptosis and cell cycle arrest in gastric cancer cells, which was more effective in WEE1 high-expressing gastric cancer cells. Moreover, we performed combination treatments with AZD1775 and anti-cancer agents, 5- fluorouracil or Paclitaxel in gastric cancer cells and in gastric cancer orthotopic-transplanted mice to maximize the therapeutic effect and safety of AZD1775. The combination treatments dramatically inhibited the proliferation of gastric cancer cells and tumor burdens in stomach orthotopic-transplanted mice. Taken together, we propose that WEE1 is over-expressed and could enhance gastric cancer cell proliferation and metastasis. Therefore, we suggest that WEE1 is a potent target for gastric cancer therapy.

Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer

PubMed Central

Kim, Hye-Young; Cho, Yunhee; Kang, HyeokGu; Yim, Ye-Seal; Kim, Seok-Jun; Song, Jaewhan; Chun, Kyung-Hee

2016-01-01

Wee1 is a member of the Serine/Threonine protein kinase family and is a key regulator of cell cycle progression. It has been known that WEE1 is highly expressed and has oncogenic functions in various cancers, but it is not yet studied in gastric cancers. In this study, we investigated the oncogenic role and therapeutic potency of targeting WEE1 in gastric cancer. At first, higher expression levels of WEE1 with lower survival probability were determined in stage 4 gastric cancer patients or male patients with accompanied lymph node metastasis. To determine the function of WEE1 in gastric cancer cells, we determined that WEE1 ablation decreased the proliferation, migration, and invasion, while overexpression of WEE1 increased these effects in gastric cancer cells. We also validated the clinical application of WEE1 targeting by a small molecule, AZD1775 (MK-1775), which is a WEE1 specific inhibitor undergoing clinical trials. AZD1775 significantly inhibited cell proliferation and induced apoptosis and cell cycle arrest in gastric cancer cells, which was more effective in WEE1 high-expressing gastric cancer cells. Moreover, we performed combination treatments with AZD1775 and anti-cancer agents, 5- fluorouracil or Paclitaxel in gastric cancer cells and in gastric cancer orthotopic-transplanted mice to maximize the therapeutic effect and safety of AZD1775. The combination treatments dramatically inhibited the proliferation of gastric cancer cells and tumor burdens in stomach orthotopic-transplanted mice. Taken together, we propose that WEE1 is over-expressed and could enhance gastric cancer cell proliferation and metastasis. Therefore, we suggest that WEE1 is a potent target for gastric cancer therapy. PMID:27363019

Systemic Ablation of MMP-9 Triggers Invasive Growth and Metastasis of Pancreatic Cancer via Deregulation of IL6 Expression in the Bone Marrow.

PubMed

Grünwald, Barbara; Vandooren, Jennifer; Gerg, Michael; Ahomaa, Kaarin; Hunger, Annique; Berchtold, Sonja; Akbareian, Sophia; Schaten, Susanne; Knolle, Percy; Edwards, Dylan R; Opdenakker, Ghislain; Krüger, Achim

2016-11-01

Matrix metalloproteinase 9 (MMP-9/Gelatinase B) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and plays a central role in tumor cell invasion and metastasis. Here we complemented mechanistic insights in the cancer biology of MMP-9 and investigated the effects of specific long-term loss-of-function, by genetic ablation, of MMP-9 on PDAC initiation and progression in the well-established KPC mouse model of spontaneous PDAC. Tumor growth and progression were analyzed by histopathology and IHC. Invasive growth of PDAC cells was analyzed by both in vitro (proliferation, survival, migration, invasion assays) and in vivo (experimental metastasis assays) methods. Retroviral shRNAi was used to knockdown target genes (MMP-9, IL6R). Gene expression was analyzed by qRT-PCR, immunoblot, ELISA, in situ hybridization, and zymography. PDAC tumors from MMP-9-deficient mice were dramatically larger, more invasive, and contained more stroma. Yet, ablation of MMP-9 in PDAC cells did not directly promote invasive growth. Interestingly, systemic ablation of MMP-9 led to increased IL6 levels resulting from abrogation of MMP-9-dependent SCF signaling in the bone marrow. IL6 levels in MMP-9 -/- mice were sufficient to induce invasive growth and STAT3 activation in PDAC cells via IL6 receptor (IL6R). Interference with IL6R blocked the increased invasion and metastasis of PDAC cells in MMP-9-deficient hosts. In conclusion, ablation of systemic MMP-9 initiated fatal communication between maintenance of physiological functions of MMP-9 in the bone marrow and invasive growth of PDAC via the IL6/IL6R/STAT3 axis. Thus, the beneficial effects of host MMP-9 on PDAC are an important caveat for the use of systemic MMP-9 inhibitors in cancer. Mol Cancer Res; 14(11); 1147-58. ©2016 AACR. ©2016 American Association for Cancer Research.

Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT

Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

PubMed

Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

2013-08-01

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p < 0.01). This study revealed that the complete peripheral necrosis barrier within the target tissues can defined using linear-scanned HIFU in an isolated porcine liver perfusion model. Additionally, the flow rate in the major hepatic vessels may play an important role in the use of the peripheral ablation mode, and this novel mode of ablation may enhance the therapeutic efficacy and tolerability of the

Intraoperative microwave ablation of pulmonary malignancies with tumor permittivity feedback control: ablation and resection study in 10 consecutive patients.

PubMed

Wolf, Farrah J; Aswad, Bassam; Ng, Thomas; Dupuy, Damian E

2012-01-01

To determine histologic changes induced by microwave ablation (MWA) in patients with pulmonary malignancy by using an ablation system with tumor permittivity feedback control, enabling real-time modulation of energy power and frequency. Institutional review board approval and patient informed consent were obtained for this prospective HIPAA-complaint ablation and resection study. Between March 2009 and January 2010, 10 patients (four women, six men; mean age, 71 years; age range, 52-82 years) underwent intraoperative MWA of pulmonary malignancies. Power (10-32 W) and frequency (908-928 MHz) were continuously adjusted by the generator to maintain a temperature of 110°-120°C at the 14-gauge antenna tip for one 10-minute application. After testing for an air leak, tumors were resected surgically. Gross inspection, slicing, and hematoxylin-eosin (10 specimens) and nicotinamide adenine dinucleotide (six specimens) staining were performed. Tumors included adenocarcinomas (n = 5), squamous cell carcinomas (n = 3), and metastases from endometrial (n = 1) and colorectal (n = 1) primary carcinomas. Mean maximum tumor diameter was 2.4 cm (range, 0.9-5.0 cm), and mean maximum volume was 8.6 cm(3) (range, 0.5-52.7 cm(3)). One air leak was detected. Five of 10 specimens were grossly measurable, revealing a mean maximum ablation zone diameter of 4.8 cm (range, 3.0-6.5 cm) and a mean maximum ablation zone volume of 15.1 cm(3) (range, 7.3-25.1 cm(3)). At hematoxylin-eosin staining, coagulation necrosis was observed in all ablation zones, extended into the normal lung in nine of 10 specimens, and up to blood vessel walls without evidence of vessel (>4 mm) thrombosis. Nicotinamide adenine dinucleotide staining enabled confirmation of no viability within ablation zones extending into normal lung in five of six specimens. MWA with tumor permittivity feedback control results in cytotoxic intratumoral temperatures and extension of ablation zones into aerated peritumoral pulmonary

Prospective study of atrial fibrillation termination during ablation guided by automated detection of fractionated electrograms.

PubMed

Porter, Michael; Spear, William; Akar, Joseph G; Helms, Ray; Brysiewicz, Neil; Santucci, Peter; Wilber, David J

2008-06-01

Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested. In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 +/- 18 sites/patient were identified (20 +/- 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow-up was 1 year. One-year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF. Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long-term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.

Treatment of Atrial Fibrillation By The Ablation Of Localized Sources

PubMed Central

Narayan, Sanjiv M.; Krummen, David E.; Shivkumar, Kalyanam; Clopton, Paul; Rappel, Wouter-Jan; Miller, John M.

2012-01-01

Objectives We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (Focal Impulse and Rotor Modulation, FIRM) may improve outcome from AF ablation. Background Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome. Methods We recruited 92 individuals during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-Guided) followed by conventional ablation (n=36), or conventional ablation alone (n=71; FIRM-Blinded). Results Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1±1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided versus 20% of FIRM-Blinded cases (p<0.001). FIRM ablation alone at the primary source terminated AF in 2.5 minutes (median; IQR 1.0–3.1). Total ablation time did not differ between groups (57.8±22.8 versus 52.1±17.8 minutes, p=0.16). During 273 days (median; IQR 132–681 days) after a single procedure, FIRM-Guided cases had higher freedom from AF (82.4% versus 44.9%; p<0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, ECG monitoring. Adverse events did not differ between groups. CONCLUSIONS Localized electrical rotors and focal impulse sources are prevalent sustaining-mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment

A hypothesis of target cell formation in sickle cell disease.

PubMed

Wong, P

2016-08-01

A fraction of erythrocytes appear as target cells in stained blood smears in sickle cell disease, due to a inheritance of the hemoglobin variant Hb S, polymerizing upon deoxygenation. These cells appear in a three dimension as thin cups. A process of their formation in this disease is proposed based on a band 3-based mechanism of the erythrocyte shape control, able to explain the erythrocyte echinocytosis by glucose depletion. It indicates that their formation is due to a stomatocytogenic slow outward transport of the dibasic form of endogenous Pi with an H(+) by band 3, promoted by the decrease of the Donnan ratio, which decreases cell pH and volume, attributed by a decrease of cell KCl concentration by the higher efflux of K(+)Cl(-) cotransport and Ca(2+) activation of the Gardos channel. Its implications are briefly discussed with respect to target cells per se, target cell formation in other hemoglobinopathies, acquired and inherited disorders of the lipid metabolism and dehydrated hereditary stomatocytosis as well as a stomatocyte presence in a double heterozygote of Hb S and Hb C and of an involvement of the process of target cell formation in acanthocytosis in acquired and inherited disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

12P-conjugated PEG-modified gold nanorods combined with near-infrared laser for tumor targeting and photothermal therapy.

PubMed

Zhan, Tao; Li, Pengfei; Bi, Shan; Dong, Biao; Song, Hongwei; Ren, Hui; Wang, Liping

2012-09-01

Gold nanorods have been reported as potential tumor photothermal therapy in vivo and in vitro. However, development of the safe and efficient tumor-targeting gold nanorods for in vivo localized tumor therapy is still a challenge. In our present study, we synthesized the PEG modified gold nanorods and demonstrated its negligible cytotoxicity in vitro. These nanorods also have been demonstrated to efficiently ablate the different kinds of tumor cells in vitro after exposure to the near-infrared laser. When the PEG modified gold nanorods conjugated with the 12P (sequence: TACHQHVRMVRP), this conjugate showed great tumor-targeting and hyperthermia effects on the human liver cancer cell line HepG2 in vitro when coupled with the near-infrared laser treatment. To determine the potential hyperthermia effect of PEG modified gold nanorods or 12P conjugate on tumor cells in vivo, the mice hepatic cancer cells were used to induce the subcutaneous tumor-bearing model in ICR mice. The significant inhibition effects of near-infrared laser mediated PEG modified gold nanorods or 12P conjugate on the tumor growth were observed. These composite results suggest that the 12P-conjugated PEG modified gold nanorods exhibit great biocompatible, particular tumor-targeting and effective photothermal ablation of tumor cells, which warrant the potential therapeutic value of this conjugate for further application in in vivo localized tumor therapy.

Saphenous Venous Ablation with Hot Contrast in a Canine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prasad, Amit; Qian Zhong; Kirsch, David

2008-01-15

Purpose. To determine the feasibility, efficacy, and safety of thermal ablation of the saphenous vein with hot contrast medium. Methods. Twelve saphenous veins of 6 dogs were percutaneously ablated with hot contrast medium. In all animals, ablation was performed in the vein of one leg, followed by ablation in the contralateral side 1 month later. An occlusion balloon catheter was placed in the infragenicular segment of the saphenous vein via a jugular access to prevent unwanted thermal effects on the non-target segment of the saphenous vein. After inflation of the balloon, 10 ml of hot contrast medium was injected undermore » fluoroscopic control through a sheath placed in the saphenous vein above the ankle. A second 10 ml injection of hot contrast medium was made after 5 min in each vessel. Venographic follow-up of the ablated veins was performed at 1 month (n = 12) and 2 months (n = 6). Results. Follow-up venograms showed that all ablated venous segments were occluded at 1 month. In 6 veins which were followed up to 2 months, 4 (66%) remained occluded, 1 (16%) was partially patent, and the remaining vein (16%) was completely patent. In these latter 2 cases, an inadequate amount of hot contrast was delivered to the lumen due to a closed balloon catheter downstream which did not allow contrast to displace blood within the vessel. Discussion. Hot contrast medium thermal ablation of the saphenous vein appears feasible, safe, and effective in the canine model, provided an adequate amount of embolization agent is used.« less

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chiachien Jake; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Christie, Alana

Purpose: Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases. Methods and Materials: We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure weremore » analyzed with χ{sup 2}, Kaplan-Meier, and log-rank tests. Results: In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%-95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P<.0001), palliative-intent radiation therapy (HR, 4.63; P=.0189), spinal location (HR, 5.36; P=.0041), previous systemic therapy status (0-1 vs >1; HR, 3.52; P=.0217), and BED <115 Gy (HR, 3.45; P=.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P=.0014 and P=.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively. Conclusions: SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate

Radiofrequency ablation of liver tumors (I): biological background.

PubMed

Vanagas, Tomas; Gulbinas, Antanas; Pundzius, Juozas; Barauskas, Giedrius

2010-01-01

Majority of patients suffering from liver tumors are not candidates for surgery. Currently, minimal invasive techniques have become available for local destruction of hepatic tumors. Radiofrequency ablation is based on biological response to tissue hyperthermia. The aim of this article is to review available biological data on tissue destruction mechanisms. Experimental evidence shows that tissue injury following thermal ablation occurs in two distinct phases. The initial phase is direct injury, which is determined by energy applied, tumor biology, and tumor microenvironment. The temperature varies along the ablation zone and this is reflected by different morphological changes in affected tissues. The local hyperthermia alters metabolism, exacerbates tissue hypoxia, and increases thermosensitivity. The second phase - indirect injury - is observed after the cessation of heat stimulus. This phase represents a balance of several promoting and inhibiting mechanisms, such as induction of apoptosis, heat shock proteins, Kupffer cell activation, stimulation of the immune response, release of cytokines, and ischemia-reperfusion injury. A deeper understanding of the underlying mechanisms may possibly lead to refinements in radiofrequency ablation technology, resulting in advanced local tumor control and prolonged overall survival.

Evolving phage vectors for cell targeted gene delivery.

PubMed

Larocca, David; Burg, Michael A; Jensen-Pergakes, Kristen; Ravey, Edward Prenn; Gonzalez, Ana Maria; Baird, Andrew

2002-03-01

We adapted filamentous phage vectors for targeted gene delivery to mammalian cells by inserting a mammalian reporter gene expression cassette (GFP) into the vector backbone and fusing the pIII coat protein to a cell targeting ligand (i.e. FGF2, EGF). Like transfection with animal viral vectors, targeted phage gene delivery is concentration, time, and ligand dependent. Importantly, targeted phage particles are specific for the appropriate target cell surface receptor. Phage have distinct advantages over existing gene therapy vectors because they are simple, economical to produce at high titer, have no intrinsic tropism for mammalian cells, and are relatively simple to genetically modify and evolve. Initially transduction by targeted phage particles was low resulting in foreign gene expression in 1-2% of transfected cells. We increased transduction efficiency by modifying both the transfection protocol and vector design. For example, we stabilized the display of the targeting ligand to create multivalent phagemid-based vectors with transduction efficiencies of up to 45% in certain cell lines when combined with genotoxic treatment. Taken together, these studies establish that the efficiency of phage-mediated gene transfer can be significantly improved through genetic modification. We are currently evolving phage vectors with enhanced cell targeting, increased stability, reduced immunogenicity and other properties suitable for gene therapy.

Echo decorrelation imaging of ex vivo HIFU and bulk ultrasound ablation using image-treat arrays

NASA Astrophysics Data System (ADS)

Fosnight, Tyler R.; Hooi, Fong Ming; Colbert, Sadie B.; Keil, Ryan D.; Barthe, Peter G.; Mast, T. Douglas

2017-03-01

In this study, the ability of ultrasound echo decorrelation imaging to map and predict heat-induced cell death was tested using bulk ultrasound thermal ablation, high intensity focused ultrasound (HIFU) thermal ablation, and pulse-echo imaging of ex vivo liver tissue by a custom image-treat array. Tissue was sonicated at 5.0 MHz using either pulses of unfocused ultrasound (N=12) (7.5 s, 50.9-101.8 W/cm2 in situ spatial-peak, temporal-peak intensity) for bulk ablation or focused ultrasound (N=21) (1 s, 284-769 W/cm2 in situ spatial-peak, temporal-peak intensity and focus depth of 10 mm) for HIFU ablation. Echo decorrelation and integrated backscatter (IBS) maps were formed from radiofrequency pulse-echo images captured at 118 frames per second during 5.0 s rest periods, beginning 1.1 s after each sonication pulse. Tissue samples were frozen at -80˚C, sectioned, vitally stained, imaged, and semi-automatically segmented for receiver operating characteristic (ROC) analysis. ROC curves were constructed to assess prediction performance for echo decorrelation and IBS. Logarithmically scaled mean echo decorrelation in non-ablated and ablated tissue regions before and after electronic noise and motion correction were compared. Ablation prediction by echo decorrelation and IBS was significant for both focused and bulk ultrasound ablation. The log10-scaled mean echo decorrelation was significantly greater in regions of ablation for both HIFU and bulk ultrasound ablation. Echo decorrelation due to electronic noise and motion was significantly reduced by correction. These results suggest that ultrasound echo decorrelation imaging is a promising approach for real-time prediction of heat-induced cell death for guidance and monitoring of clinical thermal ablation, including radiofrequency ablation and HIFU.

Survey Of CO{sub 2} Laser Ablation Propulsion With Polyoxymethylene Propellant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinko, John E.; Sasoh, Akihiro

Polyoxymethylene (POM) has been widely studied as a laser propulsion propellant paired to CO{sub 2} laser radiation. POM is a good test case for studying ablation properties of polymer materials, and within limits, for study of general trends in laser ablation-induced impulse. Despite many studies, there is no general understanding of POM ablation that takes into account the ambient pressure, spot area, fluence, and effects from confinement and combustion. This paper reviews and synthesizes CO{sub 2} laser ablation propulsion research using POM targets. Necessary directions for future study are indicated to address incomplete regions of the various parameter spaces. Literaturemore » data is compared in terms of propulsion parameters such as momentum coupling coefficient and specific impulse, within a range of fluences from about 1-500 J/cm{sup 2}, ambient pressures from about 10{sup -2}-10{sup 5} Pa, and laser spot areas from about 0.01-10 cm{sup 2}.« less

Role of Rotors in the Ablative Therapy of Persistent Atrial Fibrillation

PubMed Central

Schricker, Amir A; Zaman, Junaid; Narayan, Sanjiv M

2015-01-01

Atrial fibrillation (AF) ablation is increasingly used to maintain sinus rhythm yet its results are sub-optimal, especially in patients with persistent AF or prior unsuccessful procedures. Attempts at improvement have often targeted substrates that sustain AF after it is triggered, yet those mechanisms are debated. Many studies now challenge the concept that AF is driven by self-sustaining disordered wavelets, showing instead that localised drivers (rotors) may drive disorder via a process known as fibrillatory conduction. Novel mapping using wide-area recordings, physiological filtering and phase analysis demonstrates rotors in human AF. Contact mapping with focal impulse and rotor modulation (FIRM) shows that localised ablation at sources can improve procedural success in many populations on long-term follow up and some newer approaches to rotor mapping are qualitatively similar. This review critically evaluates the data on rotor mapping and ablation, which advances our conceptual understanding of AF and holds the promise of substantially improving ablative outcomes in patients with persistent AF. PMID:26835100

Dental ablation with 1064 nm, 500 ps, Diode pumped solid state laser: A preliminary study.

PubMed

Sozzi, Michele; Fornaini, Carlo; Cucinotta, Annamaria; Merigo, Elisabetta; Vescovi, Paolo; Selleri, Stefano

2013-01-01

The Er:YAG laser in conservative dentistry is. good alternative to conventional instruments. Though several studies show the advantages of these devices, some drawbacks and unsolved problems are still present, such as the cost of the device and the large dimensions of the equipment. In the present study, the effectiveness of dental surface ablation with a picosecond infrared diode-pumped solid-state (DPSS) laser was investigated. In vitro tests on extracted human teeth were carried out, with assessment of the ablation quality in the tooth and thermal increase inside the pulp chamber. A solid-state picosecond laser was used for the experiments. The samples were exposed to laser energy at 1064 nm at a frequency of 30 kHz and a 500 ps pulse width. The target teeth were cooled during exposures. The internal temperature of the pulp chamber was monitored with. thermocouple. Optical microscope images showed effective ablation with the absence of carbonisation and micro-cracks. The cooling maintained the temperature rise in the pulp chamber below the permitted 5.5°C. The main problem with the use of lasers in dentistry when teeth are the target is the heat generated in the pulp chamber of the target teeth. With lasers operating in the femtosecond mode, a better management of the internal temperature is possible, but is offset by the high cost of such devices. With the ps domain system used in the present study together with cooling using chilled water, effective and clean ablation could be achieved with a controlled thermal effect in the pulp chamber. In this preliminary study with a picosecond domain DPSS laser using water cooling for the target, effective hard tissue ablation was achieved keeping the thermal increase in the pulp within the permitted range. The results suggest that this system could be used in clinical practice with appropriate modifications.

Cell death, perfusion and electrical parameters are critical in models of hepatic radiofrequency ablation

PubMed Central

Hall, Sheldon K.; Ooi, Ean H.; Payne, Stephen J.

2015-01-01

Abstract Purpose: A sensitivity analysis has been performed on a mathematical model of radiofrequency ablation (RFA) in the liver. The purpose of this is to identify the most important parameters in the model, defined as those that produce the largest changes in the prediction. This is important in understanding the role of uncertainty and when comparing the model predictions to experimental data. Materials and methods: The Morris method was chosen to perform the sensitivity analysis because it is ideal for models with many parameters or that take a significant length of time to obtain solutions. A comprehensive literature review was performed to obtain ranges over which the model parameters are expected to vary, crucial input information. Results: The most important parameters in predicting the ablation zone size in our model of RFA are those representing the blood perfusion, electrical conductivity and the cell death model. The size of the 50 °C isotherm is sensitive to the electrical properties of tissue while the heat source is active, and to the thermal parameters during cooling. Conclusions: The parameter ranges chosen for the sensitivity analysis are believed to represent all that is currently known about their values in combination. The Morris method is able to compute global parameter sensitivities taking into account the interaction of all parameters, something that has not been done before. Research is needed to better understand the uncertainties in the cell death, electrical conductivity and perfusion models, but the other parameters are only of second order, providing a significant simplification. PMID:26000972

Increased sensitivity to ionizing radiation by targeting the homologous recombination pathway in glioma initiating cells.

PubMed

Lim, Yi Chieh; Roberts, Tara L; Day, Bryan W; Stringer, Brett W; Kozlov, Sergei; Fazry, Shazrul; Bruce, Zara C; Ensbey, Kathleen S; Walker, David G; Boyd, Andrew W; Lavin, Martin F

2014-12-01

Glioblastoma is deemed the most malignant form of brain tumour, particularly due to its resistance to conventional treatments. A small surviving group of aberrant stem cells termed glioma initiation cells (GICs) that escape surgical debulking are suggested to be the cause of this resistance. Relatively quiescent in nature, GICs are capable of driving tumour recurrence and undergo lineage differentiation. Most importantly, these GICs are resistant to radiotherapy, suggesting that radioresistance contribute to their survival. In a previous study, we demonstrated that GICs had a restricted double strand break (DSB) repair pathway involving predominantly homologous recombination (HR) associated with a lack of functional G1/S checkpoint arrest. This unusual behaviour led to less efficient non-homologous end joining (NHEJ) repair and overall slower DNA DSB repair kinetics. To determine whether specific targeting of the HR pathway with small molecule inhibitors could increase GIC radiosensitivity, we used the Ataxia-telangiectasia mutated inhibitor (ATMi) to ablate HR and the DNA-dependent protein kinase inhibitor (DNA-PKi) to inhibit NHEJ. Pre-treatment with ATMi prior to ionizing radiation (IR) exposure prevented HR-mediated DNA DSB repair as measured by Rad51 foci accumulation. Increased cell death in vitro and improved in vivo animal survival could be observed with combined ATMi and IR treatment. Conversely, DNA-PKi treatment had minimal impact on GICs ability to resolve DNA DSB after IR with only partial reduction in cell survival, confirming the major role of HR. These results provide a mechanistic insight into the predominant form of DNA DSB repair in GICs, which when targeted may be a potential translational approach to increase patient survival. Copyright © 2014. Published by Elsevier B.V.

Successful catheter ablation of a left anterior accessory pathway from the non-coronary cusp of the aortic valve.

PubMed

Laranjo, Sérgio; Oliveira, Mário; Trigo, Conceição

2015-08-01

Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp.

MR-guided high-intensity focused ultrasound ablation of breast cancer with a dedicated breast platform.

PubMed

Merckel, Laura G; Bartels, Lambertus W; Köhler, Max O; van den Bongard, H J G Desirée; Deckers, Roel; Mali, Willem P Th M; Binkert, Christoph A; Moonen, Chrit T; Gilhuijs, Kenneth G A; van den Bosch, Maurice A A J

2013-04-01

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

Repeated Radiofrequency Ablation Combined With Ablated Lesion Elimination and Transarterial Chemoembolization Improves the Outcome of Solitary Huge Hepatocellular Carcinomas 10 cm or Larger

PubMed Central

Ke, Shan; Gao, Jun; Kong, Jian; Ding, Xue-Mei; Niu, Hai-Gang; Xin, Zong-Hai; Ning, Chun-Min; Guo, Shi-Gang; Li, Xiao-Long; Zhang, Long; Dong, Yong-Hong; Sun, Wen-Bing

2016-01-01

Abstract This study investigated the effectiveness of a new strategy, repeated radiofrequency (RF) ablation combined with ablated lesion elimination following transarterial chemoembolization (TACE)/transarterial embolization (TAE), for solitary huge hepatocellular carcinoma (SHHCC) 10 cm or larger. From July 2008 to October 2015, 39 consecutive patients with SHHCC were screened. Of these, 12 were treated with TACE/TAE and repeated RF ablation (TACE/TAE + RF ablation group) and the remaining 27 patients were treated with the aforementioned new strategy (new strategy group). Local tumor progression (LTP)-free survival, intrahepatic distant recurrence (IDR)-free survival, and overall survival (OS) rates were obtained using the Kaplan–Meier method. Univariate and multivariate analyses were performed on several clinicopathological variables to identify factors affecting long-term outcome and intrahepatic recurrence. Correlation analysis was also performed. The 1-, 2-, and 3-year LTP-free survival rates and OS rates were significantly higher in the new strategy group than in the TACE/TAE + RF ablation group (82.9% vs 58.3%, 73.9% vs 29.2%, 18.5% vs 9.7%, P = 0.002; 92.0% vs 75.0%, 84.0% vs 33.3%, 32.7% vs 16.7%, P = 0.025). However, there was no significant difference between the 2 groups in the 1-, 2-, and 3-year IDR-free survival rates (P = 0.108). Using univariate analysis, alpha-fetoprotein (AFP > 200 ng/mL), ablative margin (AM > 1.0 cm), and well-differentiated cells were found to be significant factors for predicting LTP, IDR, and OS. Surgical elimination was found to be a significant factor only for predicting OS. In multivariate analyses, AFP (>200 ng/mL), AM (>1.0 cm), and well-differentiated cells were found to be significant independent factors linked to LTP, IDR, and OS. Correlation analysis indicated that AM > 1.0 cm was strongly associated with surgical elimination (P < 0.001, correlation coefficient = 0.877). For patients

Microwave Ablation Compared with Radiofrequency Ablation for Breast Tissue in an Ex Vivo Bovine Udder Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Westphal, Saskia, E-mail: swestphal@ukaachen.de; Isfort, Peter, E-mail: isfort@hia.rwth-aachen.de

2012-08-15

Purpose: To compare the effectiveness of microwave (MW) ablation with radiofrequency (RF) ablation for treating breast tissue in a nonperfused ex vivo model of healthy bovine udder tissue. Materials and Methods: MW ablations were performed at power outputs of 25W, 35W, and 45W using a 915-MHz frequency generator and a 2-cm active tip antenna. RF ablations were performed with a bipolar RF system with 2- and 3-cm active tip electrodes. Tissue temperatures were continuously monitored during ablation. Results: The mean short-axis diameters of the coagulation zones were 1.34 {+-} 0.14, 1.45 {+-} 0.13, and 1.74 {+-} 0.11 cm for MWmore » ablation at outputs of 25W, 35W, and 45W. For RF ablation, the corresponding values were 1.16 {+-} 0.09 and 1.26 {+-} 0.14 cm with electrodes having 2- and 3-cm active tips, respectively. The mean coagulation volumes were 2.27 {+-} 0.65, 2.85 {+-} 0.72, and 4.45 {+-} 0.47 cm{sup 3} for MW ablation at outputs of 25W, 35W, and 45W and 1.18 {+-} 0.30 and 2.29 {+-} 0.55 cm{sup 3} got RF ablation with 2- and 3-cm electrodes, respectively. MW ablations at 35W and 45W achieved significantly longer short-axis diameters than RF ablations (P < 0.05). The highest tissue temperature was achieved with MW ablation at 45W (P < 0.05). On histological examination, the extent of the ablation zone in MW ablations was less affected by tissue heterogeneity than that in RF ablations. Conclusion: MW ablation appears to be advantageous with respect to the volume of ablation and the shape of the margin of necrosis compared with RF ablation in an ex vivo bovine udder.« less

Benign thyroid nodule unresponsive to radiofrequency ablation treated with laser ablation: a case report.

PubMed

Oddo, Silvia; Balestra, Margherita; Vera, Lara; Giusti, Massimo

2018-05-11

Radiofrequency ablation and laser ablation are safe and effective techniques for reducing thyroid nodule volume, neck symptoms, and cosmetic complaints. Therapeutic success is defined as a nodule reduction > 50% between 6 and 12 months after the procedure, but a percentage of nodules inexplicably do not respond to thermal ablation. We describe the case of a young Caucasian woman with a solid benign thyroid nodule who refused surgery and who had undergone radiofrequency ablation in 2013. The nodule did not respond in terms of either volume reduction or improvement in neck symptoms. After 2 years, given the patient's continued refusal of thyroidectomy, we proposed laser ablation. The nodule displayed a significant volume reduction (- 50% from radiofrequency ablation baseline volume, - 57% from laser ablation baseline), and the patient reported a significant improvement in neck symptoms (from 6/10 to 1/10 on a visual analogue scale). We conjecture that some benign thyroid nodules may be intrinsically resistant to necrosis when one specific ablation technique is used, but may respond to another technique. To the best of our knowledge, this is the first description of the effect of performing a different percutaneous ablation technique in a nodule that does not respond to radiofrequency ablation.

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping.

PubMed

Zaman, Junaid A B; Narayan, Sanjiv M

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.

Stability analysis of unsteady ablation fronts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Betti, R.; McCrory, R.L.; Verdon, C.P.

1993-08-01

The linear stability analysis of unsteady ablation fronts, is carried out for a semi-infinite uniform medium. For a laser accelerated target, it is shown that a properly selected modulation of the laser intensity can lead to the dynamic stabilization or growth-rate reduction of a large portion of the unstable spectrum. The theory is in qualitative agreement with the numerical results obtained by using the two-dimensional hydrodynamic code ORCHID.

Stability analysis of unsteady ablation fronts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Betti, R.; McCrory, R.L.; Verdon, C.P.

1993-11-08

The linear stability analysis of unsteady ablation fronts is carried out for a semi-infinite uniform medium. For a laser accelerated target, it is shown that a properly selected modulation of the laser intensity can lead to the dynamic stabilization or growth-rate reduction of a large portion of the unstable spectrum. The theory is in qualitative agreement with the numerical results obtained by using the two-dimensional hydrodynamic code ORCHID.

Statistical Modeling of Single Target Cell Encapsulation

PubMed Central

Moon, SangJun; Ceyhan, Elvan; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems. PMID:21814548

Ablation of multi-wavelet re-entry: general principles and in silico analyses.

PubMed

Spector, Peter S; Correa de Sa, Daniel D; Tischler, Ethan S; Thompson, Nathaniel C; Habel, Nicole; Stinnett-Donnelly, Justin; Benson, Bryce E; Bielau, Philipp; Bates, Jason H T

2012-11-01

Catheter ablation strategies for treatment of cardiac arrhythmias are quite successful when targeting spatially constrained substrates. Complex, dynamic, and spatially varying substrates, however, pose a significant challenge for ablation, which delivers spatially fixed lesions. We describe tissue excitation using concepts of surface topology which provides a framework for addressing this challenge. The aim of this study was to test the efficacy of mechanism-based ablation strategies in the setting of complex dynamic substrates. We used a computational model of propagation through electrically excitable tissue to test the effects of ablation on excitation patterns of progressively greater complexity, from fixed rotors to multi-wavelet re-entry. Our results indicate that (i) focal ablation at a spiral-wave core does not result in termination; (ii) termination requires linear lesions from the tissue edge to the spiral-wave core; (iii) meandering spiral-waves terminate upon collision with a boundary (linear lesion or tissue edge); (iv) the probability of terminating multi-wavelet re-entry is proportional to the ratio of total boundary length to tissue area; (v) the efficacy of linear lesions varies directly with the regional density of spiral-waves. We establish a theoretical framework for re-entrant arrhythmias that explains the requirements for their successful treatment. We demonstrate the inadequacy of focal ablation for spatially fixed spiral-waves. Mechanistically guided principles for ablating multi-wavelet re-entry are provided. The potential to capitalize upon regional heterogeneity of spiral-wave density for improved ablation efficacy is described.

The modified stepwise ablation guided by low-dose ibutilide in chronic atrial fibrillation trial (The MAGIC-AF Study).

PubMed

Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

2016-05-21

Complex fractionated atrial electrograms (CFAE) are targeted during persistent atrial fibrillation (AF) ablation. However, many CFAE sites are non-specific resulting in extensive ablation. Ibutilide has been shown to reduce left atrial surface area exhibiting CFAE. We hypothesized that ibutilide administration prior to CFAE ablation would identify sites critical for persistent AF maintenance allowing for improved procedural efficacy and long-term freedom from atrial arrhythmias. Two hundred patients undergoing a first-ever persistent AF catheter ablation procedure were randomly assigned to receive either 0.25 mg of intravenous ibutilide or saline placebo upon completion of pulmonary vein isolation. Complex fractionated atrial electrogram sites were then targeted with ablation. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Similar procedural characteristics (procedure, fluoroscopy, and ablation times) were observed with both strategies despite a greater reduction in left atrial surface area with CFAE sites (8 vs. 1%, P < 0.0001) and AF termination during CFAE ablation with ibutilide compared with placebo (75 vs. 57%, P = 0.007). The primary efficacy endpoint was achieved in 56% of patients receiving ibutilide and 49% receiving placebo (P = 0.35). No significant differences in peri-procedural complications were observed in both groups. Despite a reduction in CFAE area and greater AF termination during CFAE ablation, procedural characteristics and clinical outcomes were unchanged when CFAE ablation was guided by ibutilide administration. ClinicalTrials.gov number: NCT01014741. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Effects of material composition on the ablation performance of low density elastomeric ablators

NASA Technical Reports Server (NTRS)

Tompkins, S. S.; Kabana, W. P.

1973-01-01

The ablation performance of materials composed of various concentrations of nylon, hollow silica spheres, hollow phenolic spheres, and four elastomeric resins was determined. Both blunt-body and flat-panel specimens were used, the cold-wall heating-rate ranges being 0.11 to 0.8 MW/sq m, respectively. The corresponding surface pressure ranges for these tests were 0.017 to 0.037 atmosphere and 0.004 to 0.005 atmosphere. Some of the results show that (1) the addition of nylon significantly improved the ablation performance, but the nylon was not compatible with one resin system; (2) panel and blunt-body specimen data do not show the same effect of phenolic sphere content on ablation effectiveness; and (3) there appears to be an optimum concentration of hollow silica spheres for good ablation performance. The composition of an efficient, nonproprietary ablator for lifting body application is identified and the ablation performance of this ablator is compared with the performance of three commercially available materials.

[Radiofrequency ablation in the multimodal treatment of liver metastases--preliminary report].

PubMed

Burcoveanu, C; Dogaru, C; Diaconu, C; Grecu, F; Dragomir, Cr; Pricop, Adriana; Balan, G; Drug, V L

2007-01-01

Although the "gold standard" in the multimodal treatment of liver primary and secondary tumors is the surgical ablation, the rate of resection, despite the last decades advances, remains still low (10 - 20%). In addition, the interest for non-surgical ablation therapies is increasing. Among them, regional or systemic chemotherapy, intra-arterial radiotherapy as well as locally targeted therapies--cryotherapy, alcohol instillation and radiofrequency (RF) are the most valuable options as alternative to the surgical approach. Between February 2005 - January 2007, 9 patients with liver metastases underwent open RF ablation of their secondaries in the III-rd Surgical Unit, "St. Spiridon" Hospital. An Elektrotom 106 HiTT Berchtold device with a 60W power generator and a 15 mm monopolar active electrode was used. Destruction of the tumors was certified with intraoperative ultrasound examination. Pre- and postoperative CarcinoEmbryonic Antigen (CEA) together with imaging follow-up was carried out, in order to determine local or systemic recurrencies. Six patients died between 6 month - 4 years after the RF ablation. Median survival is 29.2 months. RF ablation is a challenge alternative in non-resectable liver tumors.

Oxidant-induced DNA damage of target cells.

PubMed Central

Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

1988-01-01

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

Local ablative treatments for hepatocellular carcinoma: An updated review

PubMed Central

Facciorusso, Antonio; Serviddio, Gaetano; Muscatiello, Nicola

2016-01-01

Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in

Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells

PubMed Central

Herrmann, Andreas; Kortylewski, Marcin; Kujawski, Maciej; Zhang, Chunyan; Reckamp, Karen; Armstrong, Brian; Wang, Lin; Kowolik, Claudia; Deng, Jiehui; Robert, Figlin; Yu, Hua

2010-01-01

Improving effector T cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Stat3 in the myeloid compartment constrains Th-1 type immunity, dampening natural and induced antitumor immune responses. We have recently developed an in vivo siRNA delivery platform by conjugating a TLR9 agonist with siRNA that efficiently targets myeloid and B cells. Here we show that either ablating the Stat3 alleles in the myeloid compartment and B cells combined with CpG triggering or administrating the CpG-Stat3siRNA conjugates drastically augments effector functions of adoptively transferred CD8+ T cells. Specifically, we demonstrate that both approaches are capable of increasing dendritic cell and CD8+ T cell engagement in tumor draining lymph nodes. Furthermore, both approaches can significantly activate the transferred CD8+ T cells in vivo, upregulating effector molecules such as perforin, granzyme B and IFN-γ. Intravital multiphoton microscopy reveals that Stat3 silencing combined with CpG triggering greatly increases killing activity and tumor infiltration of transferred T cells. These results suggest the use of CpG-Stat3siRNA, and possibly other Stat3 inhibitors, as a potent adjuvant to improve T cell therapies. PMID:20841481

Combined treatment of tyrosine kinase inhibitor labeled gold nanorod encapsulated albumin with laser thermal ablation in a renal cell carcinoma model

USDA-ARS?s Scientific Manuscript database

This manuscript served to characterize and evaluate Human Serum Albumin-encapsulated Nanoparticles (NPs) for drug delivery of a tyrosine kinase inhibitor combined with induction of photothermal ablation (PTA) combination therapy of Renal Cell Carcinoma (RCC). RCC is the most common type of kidney c...

A Chelator-Free Multifunctional [64Cu]-CuS Nanoparticle Platform for Simultaneous Micro-PET/CT Imaging and Photothermal Ablation Therapy

PubMed Central

Zhou, Min; Zhang, Rui; Huang, Miao; Lu, Wei; Song, Shaoli; Melancon, Marites P.; Tian, Mei; Liang, Dong; Li, Chun

2010-01-01

We synthesized and evaluated a novel class of chelator-free [64Cu]-CuS nanoparticles (NPs) suitable for both PET imaging and as photothermal coupling agents for photothermal ablation. [64Cu]-CuS NPs were simple to make, possessed excellent stability, and allowed robust noninvasive micro-PET imaging. Furthermore, CuS NPs displayed strong absorption in the near-infrared (NIR) region (peak 930 nm), passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (~11 nm diameter), strong NIR absorption, and integration of 64Cu as a structural component makes [64Cu]-CuS NPs ideally suited for multifunctional molecular imaging and therapy. PMID:20942456

Laser ablation under different electron heat conduction models in inertial confinement fusion

NASA Astrophysics Data System (ADS)

Li, Shuanggui; Ren, Guoli; Huo, Wen Yi

2018-06-01

In this paper, we study the influence of three different electron heat conduction models on the laser ablation of gold plane target. Different from previous studies, we concentrate on the plasma conditions, the conversion efficiency from laser into soft x rays and the scaling relation of mass ablation, which are relevant to hohlraum physics study in indirect drive inertial confinement fusion. We find that the simulated electron temperature in corona region is sensitive to the electron heat conduction models. For different electron heat conduction models, there are obvious differences in magnitude and spatial profile of electron temperature. For the flux limit model, the calculated conversion efficiency is sensitive to flux limiters. In the laser ablation of gold, most of the laser energies are converted into x rays. So the scaling relation of mass ablation rate is quite different from that of low Z materials.

PHOTONICS AND NANOTECHNOLOGY Pulsed laser ablation of binary semiconductors: mechanisms of vaporisation and cluster formation

NASA Astrophysics Data System (ADS)

Bulgakov, A. V.; Evtushenko, A. B.; Shukhov, Yu G.; Ozerov, I.; Marin, W.

2010-12-01

Formation of small clusters during pulsed ablation of two binary semiconductors, zinc oxide and indium phosphide, in vacuum by UV, visible, and IR laser radiation is comparatively studied. The irradiation conditions favourable for generation of neutral and charged ZnnOm and InnPm clusters of different stoichiometry in the ablation products are found. The size and composition of the clusters, their expansion dynamics and reactivity are analysed by time-of-flight mass spectrometry. A particular attention is paid to the mechanisms of ZnO and InP ablation as a function of laser fluence, with the use of different ablation models. It is established that ZnO evapourates congruently in a wide range of irradiation conditions, while InP ablation leads to enrichment of the target surface with indium. It is shown that this radically different character of semiconductor ablation determines the composition of the nanostructures formed: zinc oxide clusters are mainly stoichiometric, whereas InnPm particles are significantly enriched with indium.

Femtosecond laser ablation of dentin and enamel: relationship between laser fluence and ablation efficiency.

PubMed

Chen, Hu; Liu, Jing; Li, Hong; Ge, Wenqi; Sun, Yuchun; Wang, Yong; Lü, Peijun

2015-02-01

The objective was to study the relationship between laser fluence and ablation efficiency of a femtosecond laser with a Gaussian-shaped pulse used to ablate dentin and enamel for prosthodontic tooth preparation. A diode-pumped thin-disk femtosecond laser with wavelength of 1025 nm and pulse width of 400 fs was used for the ablation of dentin and enamel. The laser spot was guided in a line on the dentin and enamel surfaces to form a groove-shaped ablation zone under a series of laser pulse energies. The width and volume of the ablated line were measured under a three-dimensional confocal microscope to calculate the ablation efficiency. Ablation efficiency for dentin reached a maximum value of 0.020 mm3∕J when the laser fluence was set at 6.51 J∕cm2. For enamel, the maximum ablation efficiency was 0.009 mm3∕J at a fluence of 7.59 J∕cm2.Ablation efficiency of the femtosecond laser on dentin and enamel is closely related to the laser fluence and may reach a maximum when the laser fluence is set to an appropriate value. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

Contemporary Tools and Techniques for Substrate Ablation of Ventricular Tachycardia in Structural Heart Disease.

PubMed

Hutchinson, Mathew D; Garza, Hyon-He K

2018-02-24

As we have witnessed in other arenas of catheter-based therapeutics, ventricular tachycardia (VT) ablation has become increasingly anatomical in its execution. Multi-modality imaging provides anatomical detail in substrate characterization, which is often complex in nonischemic cardiomyopathy patients. Patients with intramural, intraseptal, and epicardial substrates provide challenges in delivering effective ablation to the critical arrhythmia substrate due to the depth of origin or the presence of adjacent critical structures. Novel ablation techniques such as simultaneous unipolar or bipolar ablation can be useful to achieve greater lesion depth, though at the expense of increasing collateral damage. Disruptive technologies like stereotactic radioablation may provide a tailored approach to these complex patients while minimizing procedural risk. Substrate ablation is a cornerstone of the contemporary VT ablation procedure, and recent data suggest that it is as effective and more efficient that conventional activation guided ablation. A number of specific targets and techniques for substrate ablation have been described, and all have shown a fairly high success in achieving their acute procedural endpoint. Substrate ablation also provides a novel and reproducible procedural endpoint, which may add predictive value for VT recurrence beyond conventional programmed stimulation. Extrapolation of outcome data to nonischemic phenotypes requires caution given both the variability in substrate nonischemic distribution and the underrepresentation of these patients in previous trials.

Sphenopalatine ganglion: block, radiofrequency ablation and neurostimulation - a systematic review.

PubMed

Ho, Kwo Wei David; Przkora, Rene; Kumar, Sanjeev

2017-12-28

Sphenopalatine ganglion is the largest collection of neurons in the calvarium outside of the brain. Over the past century, it has been a target for interventional treatment of head and facial pain due to its ease of access. Block, radiofrequency ablation, and neurostimulation have all been applied to treat a myriad of painful syndromes. Despite the routine use of these interventions, the literature supporting their use has not been systematically summarized. This systematic review aims to collect and summarize the level of evidence supporting the use of sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were reviewed for studies on sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Studies included in this review were compiled and analyzed for their treated medical conditions, study design, outcomes and procedural details. Studies were graded using Oxford Center for Evidence-Based Medicine for level of evidence. Based on the level of evidence, grades of recommendations are provided for each intervention and its associated medical conditions. Eighty-three publications were included in this review, of which 60 were studies on sphenopalatine ganglion block, 15 were on radiofrequency ablation, and 8 were on neurostimulation. Of all the studies, 23 have evidence level above case series. Of the 23 studies, 19 were on sphenopalatine ganglion block, 1 study on radiofrequency ablation, and 3 studies on neurostimulation. The rest of the available literature was case reports and case series. The strongest evidence lies in using sphenopalatine ganglion block, radiofrequency ablation and neurostimulation for cluster headache. Sphenopalatine ganglion block also has evidence in treating trigeminal neuralgia, migraines, reducing the needs of analgesics after endoscopic sinus surgery and reducing pain associated with nasal packing

Localization of gaps during redo ablations of paroxysmal atrial fibrillation: Preferential patterns depending on the choice of cryoballoon ablation or radiofrequency ablation for the initial procedure.

PubMed

Galand, Vincent; Pavin, Dominique; Behar, Nathalie; Auffret, Vincent; Fénéon, Damien; Behaghel, Albin; Daubert, Jean-Claude; Mabo, Philippe; Martins, Raphaël P

2016-11-01

Pulmonary vein (PV) isolation, using cryoballoon or radiofrequency ablation, is the cornerstone therapy for symptomatic paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drugs. One-third of the patients have recurrences, mainly due to PV reconnections. To describe the different locations of reconnection sites in patients who had previously undergone radiofrequency or cryoballoon ablation, and to compare the characteristics of the redo procedures in both instances. Demographic data and characteristics of the initial ablation (cryoballoon or radiofrequency) were collected. Number and localization of reconduction gaps, and redo characteristics were reviewed. Seventy-four patients scheduled for a redo ablation of paroxysmal AF were included; 38 had been treated by radiofrequency ablation and 36 by cryoballoon ablation during the first procedure. For the initial ablation, procedural and fluoroscopy times were significantly shorter for cryoballoon ablation (147.8±52.6min vs. 226.6±64.3min [P<0.001] and 37.0±17.7min vs. 50.8±22.7min [P=0.005], respectively). Overall, an identical number of gaps was found during redo procedures of cryoballoon and radiofrequency ablations. However, a significantly higher number of gaps were located in the right superior PV for patients first ablated with radiofrequency (0.9±1.0 vs. 0.5±0.9; P=0.009). Gap localization displayed different patterns. Although not significant, redo procedures of cryoballoon ablation were slightly shorter and needed shorter durations of radiofrequency to achieve PV isolation. During redo procedures, gap localization pattern is different for patients first ablated with cryoballoon or radiofrequency ablation, and right superior PV reconnections occur more frequently after radiofrequency ablation. Redo ablation of a previous cryoballoon ablation appears to be easier. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Miniaturization of Microwave Ablation Antennas

NASA Astrophysics Data System (ADS)

Luyen, Hung

Microwave ablation (MWA) is a promising minimally invasive technique for the treatment of various types of cancers as well as non-oncological diseases. In MWA, an interstitial antenna is typically used to deliver microwave energy to the diseased tissue and heat it up to lethal temperature levels that induce cell death. The desired characteristics of the interstitial antenna include a narrow diameter to minimize invasiveness of the treatment, a low input reflection coefficient at the operating frequency, and a localized heating zone. Most interstitial MWA antennas are fed by coaxial cables and designed for operation at either 915 MHz or 2.45 GHz. Coax-fed MWA antennas are commonly equipped with coaxial baluns to achieve localized heating. However, the conventional implementation of coaxial baluns increases the overall diameters of the antennas and therefore make them more invasive. It is highly desirable to develop less invasive antennas with shorter active lengths and smaller diameters for MWA applications. In this work, we demonstrate the feasibility of using higher frequency microwaves for tissue ablation and present several techniques for decreasing diameters of MWA antennas. First, we investigated MWA at higher frequencies by conducting numerical and experimental studies to compare ablation performance at 10 GHz and 1.9 GHz. Simulation and ex vivo ablation experiment results demonstrate comparable ablation zone dimensions achieved at these two frequencies. Operating at higher frequencies enables interstitial antennas with shorter active lengths. This can be combined with smaller-diameter antenna designs to create less invasive applicators or allow integration of multiple radiating elements on a single applicator to have better control and customization of the heating patterns. Additionally, we present three different coax-fed antenna designs and a non-coaxial-based balanced antenna that have smaller-diameter configurations than conventional coax-fed balun

Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Koneva, Irina I.; Oginsky, Alexander O.; La Francesca, Saverio; Lapotko, Dmitri O.

2010-01-01

Background The accuracy, selectivity and safety of surgical and laser methods for tissue elimination are often limited at microscale. Materials and methods We developed a novel agent, the plasmonic nanobubble (PNB), for optically guided selective elimination of the target tissue with micrometer precision. PNBs were tested in vitro in the two different models of superficial tumors and vascular plaques. Results PNBs were selectively generated around gold nanoparticles (delivered to the target tissues) with short laser pulses. Monolayers of cancerous cells and atherosclerotic plaque tissue were eliminated with PNBs with micrometer accuracy and without thermal and mechanical damage to collateral normal tissues. The effect of the PNB was dynamically controlled through the fluence of laser pulses (532 nm, duration 0.5 and 10 ns) and was guided through the optical scattering by PNB. Conclusions plasmonic nanobubbles were shown to provide precise, tunable, selective and guided ablation of tissue at a microcscopic level and could be employed as a new generation of surgical tools. PMID:21176913

Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Koneva, Irina I; Oginsky, Alexander O; La Francesca, Saverio; Lapotko, Dmitri O

2011-03-01

The accuracy, selectivity, and safety of surgical and laser methods for tissue elimination are often limited at microscale. We developed a novel agent, the plasmonic nanobubble (PNB), for optically guided selective elimination of the target tissue with micrometer precision. PNBs were tested in vitro in the two different models of superficial tumors and vascular plaques. PNBs were selectively generated around gold nanoparticles (delivered to the target tissues) with short laser pulses. Monolayers of cancerous cells and atherosclerotic plaque tissue were eliminated with PNBs with micrometer accuracy and without thermal and mechanical damage to collateral normal tissues. The effect of the PNB was dynamically controlled through the fluence of laser pulses (532 nm, duration 0.5 and 10 ns) and was guided through the optical scattering by PNB. Plasmonic nanobubbles were shown to provide precise, tunable, selective, and guided ablation of tissue at a microscopic level and could be employed as a new generation of surgical tools. Copyright © 2011 Elsevier Inc. All rights reserved.

Thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism.

PubMed

Duan, Ya-Qi; Liang, Ping

2013-05-01

Many studies have been conducted on splenic thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In this article, we review the evolution and current status of radiofrequency and microwave ablation in the treatment of spleen diseases. All publications from 1990 to 2011 on radiofrequency and microwave ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism were retrieved by searching PubMed. Thermal ablation in the spleen for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism can preserve part of the spleen and maintain splenic immunologic function. Thermal ablation for assisting hemostasis in partial splenectomy minimizes blood loss during operation. Thermal ablation for spleen trauma reduces the number of splenectomy and the amount of blood transfusion. Thermal ablation for splenic metastasis is minimally invasive and can be done under the guidance of an ultrasound, which helps shorten the recovery time. Thermal ablation for hypersplenism increases platelet (PLT) and white blood cell (WBC) counts and improves liver function. It also helps to maintain splenic immunologic function and even improves splenic immunologic function in the short-term. In conclusion, thermal ablative approaches are promising for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In order to improve therapeutic effects, directions for future studies may include standardized therapeutic indications, prolonged observation periods and enlarged sample sizes.

Engineering a light-activated caspase-3 for precise ablation of neurons in vivo

PubMed Central

Smart, Ashley D.; Pache, Roland A.; Thomsen, Nathan D.; Kortemme, Tanja; Davis, Graeme W.; Wells, James A.

2017-01-01

The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila. Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV–induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms. PMID:28893998