Design and construction of a Maxwell-type induction coil for magnetic nanoparticle hyperthermia.

Purpose: We describe a modified Helmholtz induction coil, or Maxwell coil, that generates alternating magnetic fields (AMF) having field uniformity (≤10%) within a = 3000 cm3 volume of interest for magnetic hyperthermia research.Materials and methods: Two-dimensional finite element analysis (2D-FEA) was used for electromagnetic design of the induction coil set and to develop specifications for the required matching network. The matching network and induction coil set were fabricated using best available practices and connected to a 120 kW industrial induction heating power supply. System performance was evaluated by magnetic field mapping with a magnetic field probe, and tests were performed using gel phantoms.Results: Tests verified that the system generated a target peak AMF amplitude along the coil axis of ∼35 kA/m (peak) at a frequency of 150 ± 10 kHz while maintaining field uniformity to >90% of peak for a volume of ∼3000 cm3.Conclusions: The induction coil apparatus comprising three independent loops, i.e., Maxwell-type improves upon the performance of simple solenoid and Helmholtz coils by providing homogeneous flux density fields within a large volume while minimizing demands on power and stray fields. Experiments with gel phantoms and analytical calculations show that future translational research efforts should be devoted to developing strategies to reduce the impact of nonspecific tissue heating from eddy currents; and, that an inductor producing a homogeneous field has significant clinical potential for deep-tissue magnetic fluid hyperthermia.

Luteolin induces growth arrest in colon cancer cells through involvement of Wnt/ß-catenin/GSK-3ß signaling.

Cancer is a multistep process that typically occurrs over an extended period of time, beginning with initiation followed by promotion and progression. Colon cancer is the leading cause of morbidity and mortality worldwide. For a variety of reasons, patients prefer naturally occurring dietary substances over synthetic agents to prevent cancer. Luteolin, a bioflavonoid, possesses antioxidant, anti-inflammatory, and antiproliferative effects. We analyzed the in vitro anticancer and apoptosis-inducing property of luteolin using HCT-15 colon adenocarcinoma cells. Cell viability was assessed using trypan blue assay at different concentrations. Luteolin at a concentration of 100 µM (IC50) decreased the expressions of non-P-ß-catenin, phosphorylated (inactive) glycogen synthase kinase-3ß, and cyclin D1 expressions in HCT-15 cells, which were confirmed by Western blot analysis. Luteolin also promoted substantial cell cycle arrest at the G2/M phase in HCT-15 cells, and it induces apoptosis in HCT-15 cells, as revealed by flow cytometric analysis. Furthermore, Western blot analysis showed that luteolin treatment enhanced the expression of Bax and caspase-3, whereas the expression of Bcl-2 was suppressed. Together, the results of this study revealed that luteolin can act as a potent inhibitor of HCT-15 proliferation and can be used as an agent against colon cancer.

Method to reduce non-specific tissue heating of small animals in solenoid coils.

PURPOSE: Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus limiting effectiveness and safety. We aim to develop methods that minimise excess heating of mice exposed to AMFs for cancer therapy experiments. MATERIALS AND METHODS: Numerical and experimental data were obtained to characterise thermal management properties of water using a continuous, custom water jacket in a four-turn simple solenoid. Theoretical data were obtained with method-of-moments (MoM) numerical field calculations and finite element method (FEM) thermal simulations. Experimental data were obtained from gel phantoms and mice exposed to AMFs having amplitude >50 kA/m and frequency of 160 kHz. RESULTS: Water has a high specific heat and thermal conductivity, is diamagnetic, polar, and nearly transparent to magnetic fields. We report at least a two-fold reduction of temperature increase from gel phantom and animal models when a continuous layer of circulating water was placed between the sample and solenoid, compared with no water. Thermal simulations indicate the superior efficiency in thermal management by the developed continuous single chamber cooling system over a double chamber non-continuous system. Further reductions of heating were obtained by regulating water temperature and flow for active cooling. CONCLUSIONS: These results demonstrate the potential value of a contiguous layer of circulating water to permit sustained exposure to high intensity alternating magnetic fields at this frequency for research using small animal models exposed to AMFs.

Modified Solenoid Coil That Efficiently Produces High Amplitude AC Magnetic Fields With Enhanced Uniformity for Biomedical Applications.

In this paper, we describe a modified solenoid coil that efficiently generates high amplitude alternating magnetic fields (AMF) having field uniformity (≤10%) within a 125-cm3 volume of interest. Two-dimensional finite element analysis (2D-FEA) was used to design a coil generating a targeted peak AMF amplitude along the coil axis of ~100 kA/m (peak-to-peak) at a frequency of 150 kHz while maintaining field uniformity to >90% of peak for a specified volume. This field uniformity was realized by forming the turns from cylindrical sections of copper plate and by adding flux concentrating rings to both ends of the coil. Following construction, the field profile along the axes of the coil was measured. An axial peak field value of 95.8 ± 0.4 kA/m was measured with 650 V applied to the coil and was consistent with the calculated results. The region of axial field uniformity, defined as the distance over which field ≥90% of peak, was also consistent with the simulated results. We describe the utility of such a device for calorimetric measurement of nanoparticle heating for cancer therapy and for magnetic fluid hyperthermia in small animal models of human cancer.

Designing passive MRI-safe implantable conducting leads with electrodes.

PURPOSE: The presence of implanted electronic devices with conducting leads and electrodes are contraindicated for magnetic resonance imaging (MRI), denying many patients its potential benefits. The prime concern is MRI's radio frequency (RF) fields, which can cause elevated local specific absorption rates (SARs) and potential heat injury. The purpose of this article is to develop and compare a range of passive implantable "MRI-safe" lead designs. METHODS: Conducting leads incorporating different lengths (3-75 cm), insulation thicknesses (0-105 microm), resistances (100-3000 omega), coiled conductors (inner diameter < or = 1.2 mm), high-impedance (135-2700 omega) RF traps, and single-coiled and triple-coiled coaxial-wound "billabong" leads with reversed coil sections that oppose and reduce the induced current, are investigated both experimentally using local temperature measurements, and by numerical full-wave electromagnetic field analysis of the local SAR, in three different-sized bioanalogous model saline-gel phantoms at 1.5 T MRI and 4 W/kg exposure. RESULTS: In all designs, the maximum computed 1 g average SAR and experimental temperature rise occur at the bare electrodes. Electrode heating increases with lead insulation thickness and peaks for uncoiled leads 25-50 cm long. A reasonable match between computed SAR and the point SAR estimated from thermal sensors obtained by approximating the computation volume to that of the thermal probes. Factors that maximize the impedance of leads with resistive, coiled, RF trap and billabong elements can effectively limit heating below 1-2 degrees, but folded lead configurations can be a concern. The RF trap and billabong designs can both support multiple conductors and electrodes, with billabong prototype leads also heating <1 degrees C when tested for 3 T MRI. CONCLUSIONS: Lead insulation and length strongly affect implanted lead safety to RF exposure during MRI. Lead designs employing impedance and reversed winding sections offer hope for the development of passive, MRI-safe, implantable conducting leads for future human use.

Noise figure limits for circular loop MR coils.

Circular loops are the most common MR detectors. Loop arrays offer improved signal-to-noise ratios (SNRs) and spatial resolution, and enable parallel imaging. As loop size decreases, loop noise increases relative to sample noise, ultimately dominating the SNR. Here, relative noise contributions from the sample and the coil are quantified by a coil noise figure (NF), NF(coil), which adds to the conventional system NF. NF(coil) is determined from the ratio of unloaded-to-loaded coil quality factors Q. Losses from conductors, capacitors, solder joints, eddy currents in overlapped array coils, and the sample are measured and/or computed from 40 to 400 MHz using analytical and full-wave numerical electromagnetic analysis. The Qs are measured for round wire and tape loops tuned from 50 to 400 MHz. NF(coil) is determined as a function of the radius, frequency, and number of tuning capacitors. The computed and experimental Qs and NF(coil)s agree within approximately 10%. The NF(coil) values for 3 cm-diameter wire coils are 3 dB, 1.9 dB, 0.8 dB, 0.2 dB, and 0.1 dB, at 1T, 1.5T, 3T, 7T, and 9.4T, respectively. Wire and tape perform similarly, but tape coils in arrays have substantial eddy current losses. The ability to characterize and reliably predict component- and geometry-associated coil losses is key to designing SNR-optimized loop and phased-array detectors.

Optimized quadrature surface coil designs.

BACKGROUND: Quadrature surface MRI/MRS detectors comprised of circular loop and figure-8 or butterfly-shaped coils offer improved signal-to-noise-ratios (SNR) compared to single surface coils, and reduced power and specific absorption rates (SAR) when used for MRI excitation. While the radius of the optimum loop coil for performing MRI at depth d in a sample is known, the optimum geometry for figure-8 and butterfly coils is not. MATERIALS AND METHODS: The geometries of figure-8 and square butterfly detector coils that deliver the optimum SNR are determined numerically by the electromagnetic method of moments. Figure-8 and loop detectors are then combined to create SNR-optimized quadrature detectors whose theoretical and experimental SNR performance are compared with a novel quadrature detector comprised of a strip and a loop, and with two overlapped loops optimized for the same depth at 3 T. The quadrature detection efficiency and local SAR during transmission for the three quadrature configurations are analyzed and compared. RESULTS: The SNR-optimized figure-8 detector has loop radius r8 approximately 0.6d, so r8/r0 approximately 1.3 in an optimized quadrature detector at 3 T. The optimized butterfly coil has side length approximately d and crossover angle of > or = 150 degrees at the center. CONCLUSIONS: These new design rules for figure-8 and butterfly coils optimize their performance as linear and quadrature detectors.

Optimizing the intrinsic signal-to-noise ratio of MRI strip detectors.

An MRI detector is formed from a conducting strip separated by a dielectric substrate from a ground plane, and tuned to a quarter-wavelength. By distributing discrete tuning elements along the strip, the geometric design may be adjusted to optimize the signal-to-noise ratio (SNR) for a given application. Here a numerical electromagnetic (EM) method of moments (MoM) is applied to determine the length, width, substrate thickness, dielectric constant, and number of tuning elements that yield the best intrinsic SNR (ISNR) of the strip detector at 1.5 Tesla. The central question of how strip performance compares with that of a conventional optimized loop coil is also addressed. The numerical method is validated against the known ISNR performance of loop coils, and its ability to predict the tuning capacitances and performance of seven experimental strip detectors of varying length, width, substrate thickness, and dielectric constant. We find that strip detectors with low-dielectric constant, moderately thin-substrate, and length about 1.3 (+/-0.2) times the depth of interest perform best. The ISNR of strips is comparable to that of loops (i.e., higher close to the detector but lower at depth). The SNR improves with two inherently-decoupled strips, whose sensitivity profile is well-suited to parallel MRI. The findings are summarized as design "rules of thumb."

Branchio-oculo-facial syndrome.

Branchio-oculo-facial syndrome (BOFS) is a very rare autosomal dominant disorder with incomplete penetrance and variable expression; with phenotypic variation ranging from mild to severe forms, involving eye, ear, oral and craniofacial structure. We report three members of one family, showing great variability in its phenotypic expression and review the recent literature.

Purification, potency and immunogenicity analysis of Vero cell culture-derived rabies vaccine: a comparative study of single-step column chromatography and zonal centrifuge purification.

Continuous Vero cell lines are more suitable for large-scale production of rabies vaccine. The purification of Vero cell-derived rabies vaccine is critical because of the residual cellular DNA and serum proteins. The perfection of techniques using column chromatography with different matrix material, gel filtration and zonal centrifugation is of paramount importance for the optimal purification of rabies vaccine, leaving minimal residual cellular DNA, below the permissible level of 100 pg per dose and serum protein content of 1 ppm. In this study the potency, immunogenicity and safety of Vero cell-derived rabies vaccines were compared following purification by densely or loosely packed DEAE-sepharose CL-6B columns with different bed heights or by zonal centrifugation. The optimal virus recovery and maximum removal of substrate DNA and serum proteins were achieved only when the sepharose CL-6B column bed height was maintained at a thickness of 2-2.5 cm. The rabies virus material was purified by layering over the matrix without applying pressure. DEAE-sepharose CL-6B column purification using a simplified, cost effective technique as described in this study enhances the antigen yield by 50% in comparison with zonal purification.

Postcholecystectomy surgical site infection by Salmonella enterica var. Weltevreden.

BACKGROUND: Surgical site infections (SSI) are the most common complication of gastrointestinal surgery. The most common endogenous organisms encountered are the enteric pathogens. METHODS: We report a rare case of S. enterica var. Weltevreden as a cause of SSI after cholecystectomy and common bile duct exploration. Pertinent literature is reviewed. RESULTS: The infection was due to bile spillage and contamination during surgery. The organism was found to be sensitive only to imipenem, and the patient recovered following intravenous treatment with that carbapenem. CONCLUSIONS: This case illustrates the fact that cholecystectomy with bile spillage is a definite risk factor for SSI. Although controversial, isolation of the pathogen from the bile and the surgical site must be made to allow this rare pathogen to be identified. Appropriate antibiotic could then be directed against the pathogen.

Detection of dual-gene expression in arteries using an optical imaging method.

We evaluate the in vivo use of an optical imaging method to detect the vascular expression of green fluorescent protein (GFP) or red fluorescent protein (RFP), and to detect the simultaneous expression of GFP and RFP after transduction into arteries by a dual-promoter lentiviral vector driving their concurrent expression. This method involves using a charge-coupled device camera to detect fluorescence, a fiber optic probe to transmit light, and optical filters to distinguish each marker. In animal models, these vectors are locally delivered to target arteries, whereas the gene for a nonfluorescent cell-surface protein is transduced into contralateral arteries as the sham control. The images show distinct areas of bright fluorescence from GFP and RFP along the target arteries on excitation; no exogenous fluorescence is observed in the controls. Measured signal intensities from arteries transduced with the single- and dual-promoter vectors exceed the autofluorescence signal from the controls. Transgene expression of GFP and RFP in vivo is confirmed with confocal microscopy. We demonstrate the use of an optical imaging method to concurrently detect two distinct fluorescent proteins, potentially permitting the expression of multiple transgenes and their localization in the vasculature to be monitored.

MRI-guided coronary catheterization and PTCA: A feasibility study on a dog model.

The aim of this work was to demonstrate the feasibility of MRI-guided coronary artery catheterization and intervention in a dog model. Experiments were performed on 10 healthy dogs. A 9F introducer sheath was placed through a right carotid artery cutdown. A prototype 0.014-inch coronary MRI guidewire, a prototype 7 French MRI-guiding catheter, and two flexible surface coils were connected to a GE 1.5 T CV/i scanner for simultaneous visualization of the guidewire, guiding catheter, and chest anatomy. Images were displayed in real time on an in-room monitor. A nongated, single-slice fast gradient-echo sequence was used to obtain real-time images of the catheters and background anatomy during the intervention. Fifteen selective catheterizations were attempted in the coronary arteries, and all were successful. Selective injection of diluted gadolinium into the MRI-guiding catheter provided dynamic 2D projection coronary angiography in all cases, confirming successful catheterization. Percutaneous transluminal coronary angioplasty (PTCA) was attempted after two catheterizations, and all attempts were successful. Inflation of the balloon angioplasty catheter was performed successfully in the left anterior and circumflex arteries. Our results indicate that coronary artery catheterization and intracoronary balloon angioplasty are feasible with MRI guidance only. MRI guidance may be used as an alternative to X-ray guidance in coronary artery interventions in the future.

Process standardization for optimal virus recovery and removal of substrate DNA and bovine serum proteins in Vero cell-derived rabies vaccine.

Purification of a rabies vaccine by a single zonal centrifugation run was replaced by two runs with optimal standardization of the sucrose density gradient. As a result, significant reductions in the levels of substrate DNA and bovine serum protein in the Vero cell-derived human rabies vaccine were achieved. Following many trials, for the first run, loading of the 3.2-l capacity K-3 rotor with 1800 ml of 60% sucrose solution and 1400 ml of vaccine PBS buffer solution gave a satisfactory linear gradient. However, after the first run, the substrate DNA and bovine serum contents exceeded the required levels. After protamine sulphate and Tween-80 treatment of the concentrated inactivated material, a second run using the same procedure as in the first run was tried. However, these purification procedures resulted in low virus recovery. To achieve optimal virus recovery, and removal of substrate DNA and bovine serum protein, the peak fractions from the first run as indicated by the haemagglutination, sucrose concentration, and optical density values were pooled and the sucrose concentration of the pooled fractions was increased to 60%. A second (flotation) run was then carried out. Using this method, the virus recovery rate was more than 95% that of the first run, and the levels of cellular DNA and bovine serum protein were well within the acceptable limits of less than 100 pg/dose and one part per million, respectively. The substrate DNA was quantified by both radioactive labeling and non-radioactive biotin labeling methods. For the quantification of calf serum protein, a counter-immunoelectrophoresis method was developed and effectively applied. A potency assay was performed using the National Institutes of Health (NIH) and well-standardized in vitro single radial immuno diffusion (SRD) methods. Finally, an immunogenicity study was conducted with human volunteers and the results were confirmed by a rapid fluorescent focus inhibition test (RFFIT).