An Analysis of Microwave Ablation Parameters for Treatment of Liver Tumors from the 3D-IRCADb-01 Database.

Simulation techniques are powerful tools for determining the optimal conditions necessary for microwave ablation to be efficient and safe for treating liver tumors. Owing to the complexity and computational resource consumption, most of the existing numerical models are two-dimensional axisymmetric models that emulate actual three-dimensional cancers and the surrounding tissue, which is often far from reality. Different tumor shapes and sizes require different input powers and ablation times to ensure the preservation of healthy tissues that can be determined only by the full three-dimensional simulations. This study aimed to tailor microwave ablation therapeutic conditions for complete tumor ablation with an adequate safety margin, while avoiding injury to the surrounding healthy tissue. Three-dimensional simulations were performed for a multi-slot microwave antenna immersed in two tumors obtained from the 3D-IRCADb-01 liver tumors database. The temperature dependence of the dielectric and thermal properties of healthy and tumoral liver tissues, blood perfusion, and water content are crucial for calculating the correct ablation time and, thereby, the correct ablation process. The developed three-dimensional simulation model may help practitioners in planning patient-individual procedures by determining the optimal input power and duration of the ablation process for the actual shape of the tumor. With proper input power, necrotic tissue is placed mainly in the tumor, and only a small amount of surrounding tissue is damaged.

On Efficacy of Microwave Ablation in the Thermal Treatment of an Early-Stage Hepatocellular Carcinoma.

Microwave ablation at 2.45 GHz is gaining popularity as an alternative therapy to hepatic resection with a higher overall survival rate than external beam radiation therapy and proton beam therapy. It also offers better long-term recurrence-free overall survival when compared with radiofrequency ablation. To improve the design and optimization of microwave ablation procedures, numerical models can provide crucial information. A three-dimensional model of the antenna and targeted tissue without homogeneity assumptions are the most realistic representation of the physical problem. Due to complexity and computational resources consumption, most of the existing numerical studies are based on using two-dimensional axisymmetric models to emulate actual three-dimensional cancers and surrounding tissue, which is often far from reality. The main goal of this study is to develop a fully three-dimensional model of a multislot microwave antenna immersed into liver tissue affected by early-stage hepatocellular carcinoma. The geometry of the tumor is taken from the 3D-IRCADb-01 liver tumors database. Simulations were performed involving the temperature dependence of the blood perfusion, dielectric and thermal properties of both healthy and tumoral liver tissues. The water content changes during the ablation process are also included. The optimal values of the input power and the ablation time are determined to ensure complete treatment of the tumor with minimal damage to the healthy tissue. It was found that a multislot antenna is designed to create predictable, large, spherical zones of the ablation that are not influenced by varying tissue environments. The obtained results may be useful for determining optimal conditions necessary for microwave ablation to be as effective as possible for treating early-stage hepatocellular carcinoma, with minimized invasiveness and collateral damages.

Finite Element Analysis of the Microwave Ablation Method for Enhanced Lung Cancer Treatment.

Knowledge of the frequency dependence of the dielectric properties of the lung tissues and temperature profiles are essential characteristics associated with the effective performance of microwave ablation. In microwave ablation, the electromagnetic wave propagates into the biological tissue, resulting in energy absorption and providing the destruction of cancer cells without damaging the healthy tissue. As a consequence of the respiratory movement of the lungs, however, the accurate prediction of the microwave ablation zone has become an exceptionally demanding task. For that purpose, numerical modeling remains a primordial tool for carrying out a parametric study, evaluating the importance of the inherent phenomena, and leading to better optimization of the medical procedure. This paper reports on simulation studies on the effect of the breathing process on power dissipation, temperature distribution, the fraction of damage, and the specific absorption rate during microwave ablation. The simulation results obtained from the relative permittivity and conductivity for inflated and deflated lungs are compared with those obtained regardless of respiration. It is shown that differences in the dielectric properties of inflated and deflated lungs significantly affect the time evolution of the temperature and its maximum value, the time, the fraction of damage, and the specific absorption rate. The fraction of damage determined from the degree of tissue injury reveals that the microwave ablation zone is significantly larger under dynamic physical parameters. At the end of expiration, the ablation lesion area is more concentrated around the tip and slot of the antenna, and the backward heating effect is smaller. The diffuse increase in temperature should reach a certain level to destroy cancer cells without damaging the surrounding tissue. The obtained results can be used as a guideline for determining the optimal conditions to improve the overall success of microwave ablation.

Application of multi-component fluid model in studies of the origin of skin burns during electrosurgical procedures.

This paper reports on safety challenges regarding spark created when the applied electric field exceeds the dielectric breakdown strength as a source of complication during electrosurgery. Despite the unquestionable benefits of electrosurgery, such as minimal chances of infection and fast recovery time, the interaction of the electrosurgical tool with the tissue may result in tissue damage and force feedback to the tool. Some risks of complications often depend on a surgeon's knowledge of instruments and safety aspects of technical equipment that can be eliminated by clarifying the causation and conditions of their development. Current trends in electrosurgery include computational algorithms and methods to control the effect of delivered energy to the patient. For this study, calculations were performed by using the COMSOL simulation package based on a multi-component plasma fluid model. The emphasis is put on conditions that lead to the breakdown of the dielectric medium. It was found that breakdown occurs most easily when both electrodes are cylindrical. For configurations with one or two spherical electrodes, breakdown voltages are higher up to 25% and 48%, respectively. With decreasing the cathode radius, the breakdown voltage may decrease even to 41%. On the other hand, the temperature increase lowers the breakdown voltage. Also, electrical asymmetries appear to be a response to the non-symmetry of the electric field between the electrodes causing differences in the breakdown voltage between 36% and 70%. The results presented here could be very useful for the design of surgical devices to prevent potential complications of electrosurgical procedures.

Fast quantification of whisky lactone in oak wood by ion mobility spectrometer.

An Ion Mobility Spectrometry (IMS) apparatus has been used to detect the ß-methyl-γ-octalactone (Whisky Lactone - WL) standard in the air and as well WL vapours originating from the oak wood samples. The IMS was equipped with Atmospheric Pressure Chemical Ionisation (APCI) ion source based on a Corona Discharge (CD) and was operated in the positive polarity. The IMS spectrum of WL exhibits two peaks, a monomer with reduced ion mobility value K0 = 1.39 cm2V-1s-1 and dimer K0 = 1.09 cm2V-1s-1. Using Ion Mobility orthogonal acceleration Time of Flight mass spectrometer (IMS-oaTOF MS) these peaks were identified as protonated monomer M.H+.(H2O)0,1 and dimer M2.H+ ions respectively. The limit of detection study resulted in LOD for WL of 50 ppbv. Detection of WL from oak wood samples of different "Quality Level" (QL) categories (categories 1 to 10), indicated strong correlation between the QL category number and the response of the IMS.

Isomer and conformer selective atmospheric pressure chemical ionisation of dimethyl phthalate.

In this work we have studied the ionisation mechanism of Atmospheric Pressure Chemical Ionisation (ACPI) for three isomers of dimethyl phthalate (dimethyl phthalate - DMP (ortho- isomer), dimethyl isophthalate - DMIP (meta) and dimethyl terephthalate - DMTP (para)) using Ion Mobility Spectrometry (IMS) and IMS combined with an orthogonal acceleration Time of Flight Mass Spectrometer (oa-TOF MS). The molecules were chemically ionised using reactant ions H+·(H2O)n (n = 3 and 4). The positive IMS and IMS-oaTOF mass spectra of the isomers showed significant differences in the ion mobilities and in the ion composition. The IMS - oaTOF spectra consisted of clusters of ions M·H+·(H2O)n with different degrees of hydration (n = 0, 1, 2, 3) for different isomers. In the case of the DMP isomer, we have observed almost exclusive formation of M·H+ by proton transfer ionisation, while in the case of DMIP and DMTP, hydrated ions M·H+·(H2O)n (n = 1, 2, 3) and M·H+·(H2O)n (n = 0, 1, 2) respectively were detected, formed via adduct formation reactions. This behaviour was elucidated by differences in ionisation processes. In order to elucidate the ionisation processes we have carried out DFT calculations of the structures and energies of the neutral and protonated and hydrated isomers (for different conformers) and their corresponding proton affinities (PA) and hydration energies.

Effect of Basicity and Structure on the Hydration of Protonated Molecules, Proton-Bound Dimer and Cluster Formation: An Ion Mobility-Time of Flight Mass Spectrometry and Theoretical Study.

Protonation, hydration, and cluster formation of ammonia, formaldehyde, formic acid, acetone, butanone, 2-ocatanone, 2-nonanone, acetophenone, ethanol, pyridine, and its derivatives were studied by IMS-TOFMS technique equipped with a corona discharge ion source. It was found that tendency of the protonated molecules, MH+, to participate in hydration or cluster formation depends on the basicity of M. The molecules with higher basicity were hydrated less than those with lower basicity. The mass spectra of the low basic molecules such as formaldehyde exhibited larger clusters of MnH+(H2O)n, while for compounds with high basicity such as pyridine, only MH+ and MH+M peaks were observed. The results of DFT calculations show that enthalpies of hydrations and cluster formation decrease as basicities of the molecules increases. Using comparison of mass spectra of formic acid, formaldehyde, and ethanol, effect of structure on the cluster formation was also investigated. Formation of symmetric (MH+M) and asymmetric proton-bound dimers (MH+N) was studied by ion mobility and mass spectrometry techniques. Both theoretical and experimental results show that asymmetric dimers are formed more easily between molecules (M and N) with comparable basicity. As the basicity difference between M and N increases, the enthalpy of MH+N formation decreases.

Study of Atmospheric Pressure Chemical Ionization Mechanism in Corona Discharge Ion Source with and without NH3 Dopant by Ion Mobility Spectrometry combined with Mass Spectrometry: A Theoretical and Experimental Study.

Ionization of 2-nonanone, cyclopentanone, acetophenone, pyridine, and di- tert-butylpyridine (DTBP) in a corona discharge (CD) atmospheric pressure chemical ionization (APCI) ion source was studied using ion mobility (IMS) and time-of-flight mass spectrometry (TOF-MS). The IMS and MS spectra were recorded in the absence and presence of ammonia dopant. Without NH3 dopant, the reactant ion (RI) was H+(H2O) n, n = 3,4, and the MH+(H2O) x clusters were produced as product ions. Modeling of hydration shows that the amount of hydration ( x) depends on basicity of M, temperature and water concentration of drift tube. In the presence of ammonia (NH4+(H2O) n as RI) two kinds of product ions, MH+(H2O) x and MNH4+(H2O) x, were produced, depending on the basicity of M. With NH4+(H2O) n as RI, the product ions of pyridine and DTBP with higher basicity were MH+(H2O) x while cyclopentanone, 2-nonanone, and acetophenone with lower basicity produce MNH4+(H2O) x. To interpret the formation of product ions, the interaction energies of M-H+, H+-NH3, and H+-OH2 in the M-H+-NH3 and M-H+-OH2 and M-H+-M complexes were computed by B3LYP/6-311++G(d,p) method. It was found that for a molecule M with high basicity, the M-H+ interaction is strong leading in weakening of the H+-NH3, and H+-OH2 interactions in the M-H+-NH3 and M-H+-OH2 complexes.

Quantitative aspects of microchip isotachophoresis for high precision determination of main components in pharmaceuticals.

Although microchip electrophoresis (MCE) is intended to provide reliable quantitative data, so far there is only limited attention paid to these important aspects. This study gives a general overview of key aspects to be followed to reach high-precise determination using isotachophoresis (ITP) on the microchip with conductivity detection. From the application point of view, the procedure for the determination of acetate, a main component in the pharmaceutical preparation buserelin acetate, was developed. Our results document that run-to-run fluctuations in the sample injection volume limit the reproducibility of quantitation based on the external calibration. The use of a suitable internal standard (succinate in this study) improved the repeatability of the precision of acetate determination from six to eight times. The robustness of the procedure was studied in terms of impact of fluctuations in various experimental parameters (driving current, concentration of the leading ions, pH of the leading electrolyte and buffer impurities) on the precision of the ITP determination. The use of computer simulation programs provided means to assess the ITP experiments using well-defined theoretical models. A long-term validity of the calibration curves on two microchips and two MCE equipments was verified. This favors ITP over other microchip electrophoresis techniques, when chip-to-chip or equipment-to-equipment transfer of the analytical method is required. The recovery values in the range of 98-101 % indicate very accurate determination of acetate in buserelin acetate, which is used in the treatment of hormone-dependent tumors. This study showed that microchip ITP is suitable for reliable determination of main components in pharmaceutical preparations.

Laser desorption-ion mobility spectrometry as a useful tool for imaging of thin layer chromatography surface.

We present a novel method for coupling thin layer chromatography (TLC) with ion mobility spectrometry (IMS) using laser desorption technique (LD). After separation of the compounds by TLC, the TLC surface was sampled by the LD-IMS without any further manipulation or preparation. The position of the laser was fixed and the TLC plate was moved in desired directions by the motorized micro-positioning stage. The method was successfully applied to analyze the TLC plates containing explosives (tri nitro toluene, 1,3,5-trinitro- 1,3,5-triazacyclohexane, pentaerythritol tetranitrate, 2,4-dinitro toluene and 3,4-dinitro toluene), amino acids (alanine, proline and isoleucine), nicotine and diphenylamine mixtures and detection limits for these compounds were determined. Combination of TLC with LD-IMS technique offers additional separation dimension, allowing separation of overlapping TLC analytes. The time for TLC sampling by LD-IMS was less than 80s. The scan rate for LD is adjustable so that fast and effective analysis of the mixtures is possible with the proposed method.

Direct Liquid Sampling for Corona Discharge Ion Mobility Spectrometry.

We present a new technique suitable for direct liquid sampling and analysis by ion mobility spectrometry (IMS). The technique is based on introduction of a droplet stream to the IMS reaction region. The technique was successfully used to detect explosives dissolved in methanol and oil as well as to analyze amino acids and dipeptides. One of the main advantages of this technique is its ability to analyze liquid samples without the requirement of any special solution.

Using corona discharge-ion mobility spectrometry for detection of 2,4,6-Trichloroanisole.

In this work possible application of the corona discharge-ion mobility spectrometer (CD-IMS) for detection of 2,4,6-Trichloroanisole (TCA) has been investigated. We applied CD-IMS interfaced with orthogonal acceleration time of flight mass spectrometer (CD-IMS-oaTOF) to study the ion processes within the CD-IMS technique. The CD-IMS instrument was operated in two modes, (i) standard and (ii) reverse flow modes resulting in different chemical ionisation schemes by NO3(-)(HNO3)n (n=0,1,2) and O2(-)(H2O)n (n=0,1,2), respectively. The O2(-)(H2O)n ionisation was associated with formation of Cl(-) and (TCA-CH3)(-) ions from TCA. The NO3(-)(HNO3)n ionisation, resulted in formation of NO3(-)(HNO3)(TCA-Cl) adduct ions. Limit of detection (LOD) for TCA was determined in gas (100 ppb) and solid phases (150 ng).

A corona discharge atmospheric pressure chemical ionization source with selective NO(+) formation and its application for monoaromatic VOC detection.

We have developed a new type of corona discharge (CD) for atmospheric pressure chemical ionization (APCI) for application in ion mobility spectrometry (IMS) as well as in mass spectrometry (MS). While the other CD-APCI sources are able to generate H3O(+)·(H2O)n as the major reactant ions in N2 or in zero air, the present CD-APCI source has the ability to generate up to 84% NO(+)·(H2O)n reactant ions in zero air. The change of the working gas from zero air to N2 allows us to change the major reactant ions from NO(+)·(H2O)n to H3O(+)·(H2O)n. In this paper we present the description of the new CD-APCI and discuss the processes associated with the NO(+) formation. The selective formation of NO(+)·(H2O)n reactant ions offers chemical ionization based on these ions which can be of great advantage for some classes of chemicals. We demonstrate here a significant increase in the sensitivity of the IMS-MS instrument for monoaromatic volatile organic compound (VOC) detection upon NO(+)·(H2O)n chemical ionization.

Corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry for monitoring of volatile organic compounds.

We demonstrate the application of corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry (CD IMS-oaTOF) for volatile organic compounds (VOCs) monitoring. Two-dimensional (2D) IMS-oaTOF spectra of VOCs were recorded in nearly real time. The corona discharge atmospheric pressure chemical ionization (APCI) source was operated in positive mode in nitrogen and air. The CD ion source generates in air H(3)O(+)(H(2)O)(n) and NO(+). The NO(+) offers additional possibility for selective ionization and for an increase of the sensitivity of monoaromatic compounds. In addition to H(3)O(+)(H(2)O)(n) and NO(+), we have carried out ionization of VOCs using acetone as dopant gas ((CH(3))(2)COH(+)). Sixteen model VOCs (tetrahydrofuran, butanol, n-propanol, iso-propano, acetone, methanol, ethanol, toluene, benzene, amomnia, dioxan, triethylamine, acetonitrile, formaldehyde, m-xylene, 2,2,2-trifluoroethylamine) were tested using these ionization techniques.

Specific O2⁻ generation in corona discharge for ion mobility spectrometry.

This study deals with O(2)(-) generation in corona discharge (CD) in point to plane geometry for single flow ion mobility spectrometry (IMS) with gas outlet located behind the ionization source. We have designed CD of special geometry in order to achieve the high O(2)(-) yield. Using this ion source we have achieved in zero air conditions that up to 74% all negative ions were O(2)(-) or O(2)(-)(H(2)O). It has been demonstrated that the non-electronegative nitrogen positively influences the efficiency of O(2)(-) generation in O(2)/N(2) mixtures. The reduced ion mobility of 2.27 cm(2)V(-1)s(-1) has been measured for O(2)(-)/O(2)(-)(H(2)O) ions in zero air. Additional ions detected in zero air (less than 200 ppb CO(2)) using the mass spectrometric and IMS technique were, NO(2)(-), N(2)O(2)(-) (2.37 cm(2)V(-1)s(-1)), NO(3)(-), N(2)O(3)(-) and N(2)O(3)(-)(H(2)O). The CO(3)(-) and CO(4)(-) ions have been detected after the introduction of 5 ppm CO(2) into zero air.

Ion mobility spectrometry for monitoring high-purity oxygen.

The ability of the ion mobility spectrometry (IMS) technique with a negative corona discharge (CD) ion source to detect trace amounts of impurities in high-purity O(2) has been explored. The processes of the formation of negative ions in negative CD IMS have been studied using the ion mobility spectrometry/mass spectrometry (IMS/MS) technique. The CD IMS and CD IMS/MS spectra of 5.0 and 6.0 oxygen with and without additional purification (CO(2) and H(2)O removal) have been measured. It has been proven that the trace amounts of N(2) in high-purity O(2) can be monitored using the CD IMS and/or CD IMS/MS technique.