Feasibility of Real-Time Magnetic Resonance Imaging for Catheter Guidance in Electrophysiology Studies
Background— Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance.
Methods and Results— An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images ( 5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients.
Conclusions— To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.
Complete article: http://circ.ahajournals.org/cgi/content/full/circulationaha;118/3/223
Measurement of Pleural Temperature During Radiofrequency Ablation of Lung Tumors to Investigate Its Relationship to Occurrence of Pneumothorax or Pleural Effusion
The purpose of this study was to investigate the relationship between pleural temperature and pneumothorax or pleural effusion after radiofrequency (RF) ablation of lung tumors. The pleural temperature was measured immediately outside the lung surface nearest to the tumor with a fiber-type thermocouple during 25 ablation procedures for 34 tumors in 22 patients. The procedures were divided into two groups depending on the highest pleural temperature: P-group I and P-group II, with highest pleural temperatures of <40°C and ≥40°C, respectively. The incidence of pneumothorax or pleural effusion was compared between the groups. Multiple variables were compared between the groups to determine the factors that affect the pleural temperature. The overall incidence of pneumothorax and pleural effusion was 56% (14/25) and 20% (5/25), respectively. Temperature data in five ablation procedures were excluded from the analyses because these were affected by the pneumothorax. P-group I and P-group II comprised 10 procedures and 10 procedures, respectively. The incidence of pleural effusion was significantly higher in P-group II (4/10) than in P-group I (0/10) (p = 0.043). However, the incidence of pneumothorax did not differ significantly (p = 0.50) between P-group I (4/10) and P-group II (5/10). Factors significantly affecting the pleural temperature were distance between the electrode and the pleura (p < 0.001) and length of the lung parenchyma between the electrode and the pleura (p < 0.001). We conclude that higher pleural temperature appeared to be associated with the occurrence of pleural effusion and not with that of pneumothorax.
Complete article: http://www.springerlink.com/content/l6q811x131288141/
Real-Time MRI Guided Atrial Septal Puncture and Balloon Septostomy in Swine
Background— Cardiac perforation during atrial septal puncture (ASP) might be avoided by improved image guidance. X-ray fluoroscopy (XRF), which guides ASP, visualizes tissue poorly and does not convey depth information. Ultrasound is limited by device shadows and constrained imaging windows. Alternatively, real-time MRI (rtMRI) provides excellent tissue contrast in any orientation and may enable ASP and balloon atrial septostomy (BAS) in swine.
Materials and Methods— Custom MRI catheters incorporated “active” (receiver antenna) and “passive” (iron or gadolinium) elements. Wholly rtMRI-guided transfemoral ASP and BAS were performed in 10 swine in a 1.5T interventional suite. Hemodynamic results were measured with catheters and velocity encoded MRI.
Results— Successful ASP was performed in all 10 animals. Necropsy confirmed septostomy confined within the fossa ovalis in all. BAS was successful in 9/10 animals. Antenna failure in a re-used needle led to inadvertent vena cava tear prior to BAS in one animal. ASP in the same animal was easily performed using a new needle. rtMRI illustrated clear device-tissue-lumen relationships in multiple orientations, and facilitated simple ASP and BAS. The mean procedure time was 19 ± 10 minutes. Septostomy achieved a mean left to right shunt ratio of 1.3:1 in these healthy animals.
Conclusion— Interactive rtMRI permits rapid transcatheter ASP and BAS in swine. Further technical development may enable novel applications.
Complete article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463249/
New MR-Compatible Thermometer for MR-Guided Surgery
Introduction— Interventional magnetic resonance (MR)-guided surgery has remarkable potential. Both targeting and ablation of tumor or nerve can be handled in situ at the MR housing, and the methodology has drawn recent attention as a minimally invasive therapy. In the MR environment, basic physiological parameters needed for anesthesia, including body temperature, must be measured. Among MR-compatible monitors on the market, temperature monitoring has posed technical difficulty in the MR environment. A thermistor, a commonly used sensor, contains a ferromagnetic substance. A liquid crystal thermometer was used to avoid this problem, but its temperature resolution was inadequate for clinical use. A thermocouple with a looping conductor had been noted to present the possibility for burn injury. In addition, the MR image is affected by RF field distortion from the radiofrequency (RF)-induced current on the cable. In principle, these conventional means of temperature monitoring, detection of trace voltage and signal transport, pose technical difficulties under strong RF oscillation. An application of alternative robust technology of signal detection and transport, that can endure a strong RF field, were explored. We therefore applied an optical temperature sensor and fiber transport system to temperature monitoring, and examined the clinical validity in MR-guided surgery.
Method— We adapted an optical sensor FOT-L and signal conditioner FTI-10 (FISO Technology, Canada). In the laboratory, accuracy was checked by simultaneous measurement with the sensor and a standard platinum resistor (Pt100) at the range of 35.8 and 37.8° celsius. In the MRI suite, room temperatures at the center of the magnet with 2 Tesla (T) (Signa SP, GE, Waukesha, WI) and outside of 10 mT line were measured and their temperature monitoring was confirmed to be functional within the magnet. The rectal temperature of ten patients was monitored during MR-guided surgery under patient consent.
Results— The optical temperature was plotted against Pt100 temperature from the simultaneous measurement. Equation (1): t(FOT-L) = 0.9657*t(Pt100) + 0.2730 was derived with the linear least square method, where t(FOL-T) and t(Pt100) denote the temperatures from the optical and Pt100 thermometers, respectively. With ±0.01° (±SD), optical thermometer is sufficiently accurate for clinical applications. With RF pulses during MR image capturing, optical temperature monitoring was confirmed to be functional within the magnet. Rectal temperature of ten MR-guided surgery patients was measured. The measurement was stable and MR image were not distorted. No burn injury or other reactions were observed nearby the sensor.
Conclusion— We concluded that in MR-guided surgery optical thermometer is clinically safe and reliable without causing monitoring failure, burn injury, and significant MR image degradation.
MR Imaging and Cardiac Pacemakers: In Vitro Evaluation and in Vivo Studies in 51 Patients at 0.5 T
PURPOSE— To evaluate the safety and feasibility of magnetic resonance (MR) imaging at 0.5 T in patients with implanted cardiac pacemakers.
MATERIALS AND METHODS— Twenty-one models of pacemakers and 44 pacemaker electrodes were exposed to in vitro MR imaging with continuous registration of pacemaker output and temperature at the lead tip. Prior to MR imaging examination, pacemakers were programmed to an asynchronous mode (A00, V00, or D00). Pacemakers were examined before and after MR imaging. Forty-four patients with implanted pacemakers underwent 51 MR imaging examinations under cardiologic surveillance, continuous electrocardiography, pulse oximetry, and capnographic monitoring.
RESULTS— MR imaging was safely performed in all patients. None of the pacemakers displayed a pacing dysfunction at MR imaging. No changes occurred in the programmed parameters in any device tested in vivo or in vitro. Maximum increases in the temperature at the lead tips were8.90°Cat a specific absorption rate (SAR) of 0.6 W/kg and 23.50°C under a worst-case radio-frequency (RF) heating condition with an SAR of 1.3 W/kg.
CONCLUSION— MR imaging at 0.5 T can be safely performed in patients with implanted pacemakers in carefully selected clinical circumstances when appropriate strategies (programming to an asynchronous mode, adequate monitoring techniques, limited RF exposure) are used.
Complete article: http://radiology.rsna.org/content/215/3/869.full
Measuring Local RF Heating in MRI: Simulating Perfusion in a Perfusionless Phantom
Purpose— To overcome conflicting methods of local RF heating measurements by proposing a simple technique for predicting in vivo temperature rise by using a gel phantom experiment.
Materials and Methods— In vivo temperature measurements are difficult to conduct reproducibly; fluid phantoms introduce convection, and gel phantom lacks perfusion. In the proposed method the local temperature rise is measured in a gel phantom at a timepoint that the phantom temperature would be equal to the perfused body steady-state temperature value. The idea comes from the fact that the steady-state temperature rise in a perfused body is smaller than the steady-state temperature increase in a perfusionless phantom. Therefore, when measuring the temperature on a phantom there will be the timepoint that corresponds to the perfusion time constant of the body part.
Results— The proposed method was tested with several phantom and in vivo experiments. Instead, an overall average of 30.8% error can be given as the amount of underestimation with the proposed method. This error is within the variability of in vivo experiments (45%).
Conclusion— With the aid of this reliable temperature rise prediction the amount of power delivered by the scanner can be controlled, enabling safe MRI examinations of patients with implants.
Complete article: http://bme.bilkent.edu.tr/Papers/2007Akcafulltext.pdf
Safety of Brain 3-T MR Imaging with Transmit-Receive Head Coil in Patients with Cardiac Pacemakers: Pilot Prospective Study with 51 Examinations
Purpose: To evaluate the safety and feasibility of 3-T magnetic resonance (MR) imaging of the brain in patients with implanted cardiac pacemakers (PMs) by using a transmit-receive head coil.
Materials and Methods: The study protocol was approved by the institutional review board. Signed informed consent was obtained from all subjects. In vitro testing at 3 T was performed with 32 PMs and 45 PM leads that were evaluated for force and torque (by using a floating platform) and radiofrequency (RF)-related heating by using a transmit-receive head coil (maximum specific absorption rate, 3.2 W/kg). Patient examinations at 3 T were performed in 44 patients with a cardiac PM and a strong clinical need; patients underwent a total of 51 MR examinations of the brain by using a transmit-receive head coil to minimize RF exposure of the PM system. An electrocardiograph and pulse oximetry were used for continuous monitoring during MR imaging. The technical and functional PM status was assessed prior to and immediately after MR imaging and at 3 months thereafter. Serum troponin I level was measured before and 12 hours after imaging to detect myocardial thermal injury. PM reprogramming was performed prior to MR imaging depending on the patient's intrinsic heart rate (<60 beats per minute, asynchronous pacing; ≥60 beats per minute, sense-only mode).
Results: For in vitro testing, the maximum translational force was 2150 mN (mean, 374.38 mN ± 392.75 [standard deviation]), and maximum torque was 17.8 × 10−3 N · m (mean, [2.29 ± 4.08] × 10−3 N · m). The maximum temperature increase was 2.98°C (mean, 0.16°C ± 0.45). For patient examinations, all MR examinations (51 of 51) were completed safely. There were no significant (P < .05) changes in lead impedance, pacing capture threshold level, or serum troponin I level.
Conclusion: MR imaging of the brain at 3 T in patients with a cardiac PM can be performed safely when dedicated safety precautions (including the use of a transmit-receive head coil) are taken.
Complete article: http://radiology.rsna.org/content/249/3/991.full
SSFP-Based MR Thermometry
Of the various techniques employed to quantify temperature changes by MR, proton resonance frequency (PRF) shift-basedphase-difference imaging (PDI) is the most accurate and widely used. However, PDI is associated with various artifacts. Motivated by these limitations, we developed a new method to monitor temperature changes by MRI using the balanced steady-state free precession (balanced-SSFP) pulse sequence. Magnitude images obtained with the SSFP pulse sequence were used to find the PRF shift, which is proportional to temperature change. Spatiotemporal temperature maps were successfully reconstructed with this technique in gel phantom experiments and a rabbit model. The results show that the balanced-SSFP-based method is a promising new technique for monitoring temperature.
Complete article: HERE
Non-invasive temperature imaging with thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetic acid (TmDOTMA-)
Non-invasive thermometry using hyperfine-shifted MR signals from paramagnetic lanthanide complexes has attracted attention recently because the chemical shifts of these complexes are many times more sensitive to temperature than the water 1H signal. Among all the lanthanide complexes examined thus far, thulium tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTMA-) appears to be the most suitable for MR thermometry. In this paper, the feasibility of imaging the methyl 1H signal from TmDOTMA- using a frequency-selective radiofrequency excitation pulse and chemical shift-selective (CHESS) water suppression is demonstrated. A temperature imaging method using a phase-sensitive spin-echo imaging sequence was validated in phantom experiments. A comparison of regional temperature changes measured with fiber-optic probes and the temperatures calculated from the phase shift near each probe showed that the accuracy of imaging the temperature with TmDOTMA- is at least 0.1-0.2°C. The feasibility of imaging temperature changes in an intact rat at 0.5-0.6 mmol/kg dose in only a few minutes is demonstrated. Similar to commonly used MRI contrast agents, the lanthanide complex does not cross the blood-brain barrier. TmDOTMA- may prove useful for temperature imaging in many biomedical applications but further studies relating to acceptable dose and signal-to-noise ratio are necessary before clinical applications.
Complete article: http://www3.interscience.wiley.com/journal/112226481/abstract
Heat-induced changes in intracellular Na+, pH and bioenergetic status in superfused RIF-1 tumour cells determined by 23Na and 31P magnetic resonance spectroscopy
The acute effects of hyperthermia on intracellular Na+ (Na ), bioenergetic status and intracellular pH (pHi) were investigated in superfused Radiation Induced Fibrosarcoma–1 (RIF-1) tumour cells using shift-reagent-aided 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy. Hyperthermia at 45°C for 30 min produced a 50% increase in Na , a 0.42 unit decrease in pHi and a 40–45% decrease in NTP/Pi. During post-hyperthermia superfusion at 37°C, pHi and NTP/Pi recovered to the baseline value, but Na initially decreased and then increased to the hyperthermic level 60 min after heating. Hyperthermia at 42°C caused only a 15–20% increase in Na . In the presence of 3 µM 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na+/H+ exchanger, the increase in Na during 45°C hyperthermia was attenuated, suggesting that the heat-induced increase in Na was mainly due to an increase in Na+/H+ anti-porter activity. EIPA did not prevent hyperthermia-induced acidification. This suggests that pHi is controlled by other ion exchange mechanisms in addition to the Na+/H+ exchanger. EIPA increased the thermo-sensitivity of the RIF-1 tumour cells only slightly as measured by cell viability and clonogenic assays. The hyperthermia-induced irreversible increase in Na suggests that changes in transmembrane ion gradients play an important role in cell damage induced by hyperthermia.
DESIGN, CONSTRUCTION, AND TESTING OF THE IN VITRO EXPOSURE SYSTEM FOR THE EUROPEAN “CEMFEC” PROJECT
The european CEMFEC project (Combined effects of ElectroMagnetic Fields and Environmental Carcinogens) is based on both in vitro and in vivo laboratory 900 MHz exposures. For the in vitro exposure device the design procedure had as a starting point the choice of the rectangular waveguide as the basic structure. Commercially available components were preferred, by reducing to a minimum custom made parts; thus the construction reduced to the assembly of few simple devices. The preliminary design was based on the results of a series of measurements, while numerical tests (simulations) played the key role in defining the final configuration of the exposure system. A thermostating system for the waveguide chamber was provided by external circulation of water (30 m of plastic tube -8 mm inner diameter- winding about the waveguide). A Colora WK 5 DS water bath (± 0.1 °C) was used.External measurements under matched load and short circuit conditions: The exposure chamber was made of rectangular waveguides (248 mm x 124 mm; SAIREM), the two sample-holders first tested were rectangular plastic flasks (91 mm x 83 mm x 37 mm, inner dimensions), the samples were a 15 ml (tap water, or D-mem) liquid layer (»2 mm thick) in each flask, and the flasks were kept in place by means of polystyrene foam blocks. The waveguide chamber and the flasks inside were kept in such a way that the E field was either horizontal (parallel to the liquid layer) or vertical (perpendicular to the layer). Under matched load conditions the overall power absorption efficiency of the applicator, (absorbed power) / (incident power), was evaluated by measuring the amplitude of the reflection (s11) and transmission (s21) coefficients of the exposure chamber, under different loading conditions. Measurements were carried out over the band 0.8 – 1.0 GHz, by means of a microwave vector network analyzer (Wiltron-Anritsu 37269B). As expected it was found that a maximum of absorbed power occurs when the E-field is horizontal (parallel to the liquid layer) and the samples are both kept where the incident electric field E = Ey and the transverse magnetic field ( Hx ) are maximum. Also four-flask (8 ml each) configurations were examined. Under short circuit loading conditions the absorption efficiency evaluations were based on the measurement of the reflection coefficient (s11) alone. Thermal evaluations of the Specific Absorption Rate (W/kg): Experimental evaluations of the Specific Absorption Rate (SAR) were carried out at high (1 W) incident power level, by measuring (fiber-optic probes FISO, and computer controlled thermometer, FISO UMI 4) the heating curves at nine points in the liquid sample (15 ml). NUMERICAL EVALUATIONS AND CONCLUSIONS: Numerical evaluations were performed by using a commercial code, based on the Finite Integration Technique, and the comparison with the experimental SAR pattern was found satisfactory. Both a two-flask loading (15 ml each), and a four-flask loading (8 ml each) were analized. The best trade-off between efficiency (SAR per 1 W incident power) and SAR uniformity, was found under horizontal E-field polarization and matched load conditions. Power efficiency was found to be 13.6 W/kg/W in the two-flask case, and 5.6 W/kg/W in the four-flask case; SAR standard deviation over the mean value was found to be sligthly higher than 30% in the former case and 15% in the latter. Statistical analysis of the SAR distribution was also performed.
Complete article: http://www.bioelectromagnetics.org/doc/bems2002-abstracts.pdf
Application of High Amplitude Alternating Magnetic Fields for Heat Induction of Nanoparticles Localized in Cancer
Objective: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of high-amplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles.
Methods: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100%), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals.
Results: No adverse effects were observed for AMF amplitudes of ≤700 Oe, even at continuous power application (100% duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50%.
Conclusion: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination. These results suggest that it is possible to apply high-amplitude AMF (>500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded.
Complete article: http://clincancerres.aacrjournals.org/content/11/19/7093s.full
Development of Tumor Targeting Bioprobes (111In-Chimeric L6 Monoclonal Antibody Nanoparticles) for Alternating Magnetic Field Cancer Therapy
Objectives:111In-chimeric L6 (ChL6) monoclonal antibody (mAb)–linked iron oxide nanoparticle (bioprobes) pharmacokinetics, tumor uptake, and the therapeutic effect of inductively heating these bioprobes by externally applied alternating magnetic field (AMF) were studied in athymic mice bearing human breast cancer HBT 3477 xenografts. Tumor cell radioimmunotargeting of the bioprobes and therapeutic and toxic responses were determined.
Methods: Using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide HCl, 111In-7,10-tetra-azacyclododecane-N, N′,N″,N?-tetraacetic acid-ChL6 was conjugated to the carboxylated polyethylene glycol on dextran-coated iron oxide 20 nm particles, one to two mAbs per nanoparticle. After magnetic purification and sterile filtration, pharmacokinetics, histopathology, and AMF/bioprobe therapy were done using 111In-ChL6 bioprobe doses (20 ng/2.2 mg ChL6/ bioprobe), i.v. with 50 μg ChL6 in athymic mice bearing HBT 3477; a 153 kHz AMF was given 72 hours postinjection for therapy with amplitudes of 1,300, 1,000, or 700 Oe. Weights, blood counts, and tumor size were monitored and compared with control mice receiving nothing, or AMF or bioprobes alone.
Results:111In-ChL6 bioprobe binding in vitro to HBT 3477 cells was 50% to 70% of that of 111In-ChL6. At 48 hours, tumor, lung, kidney, and marrow uptakes of the 111In-ChL6 bioprobes were not different from that observed in prior studies of 111In-ChL6. Significant therapeutic responses from AMF/bioprobe therapy were shown with up to eight times longer mean time to quintuple tumor volume with therapy compared with no treatment (P = 0.0013). Toxicity was only seen in the 1,300 Oe AMF cohort, with 4 of 12 immediate deaths and skin erythema. Electron micrographs showed bioprobes on the surfaces of the HBT 3477 cells of excised tumors and tumor necrosis 24 hours after AMF/bioprobe therapy.
Conclusion: This study shows that mAb-conjugated nanoparticles (bioprobes), when given i.v., escape into the extravascular space and bind to cancer cell membrane antigen, so that bioprobes can be used in concert with externally applied AMF to deliver thermoablative cancer therapy.
Complete article: http://clincancerres.aacrjournals.org/content/11/19/7087s.full
Thermal Dosimetry Predictive of Efficacy of 111In-ChL6 Nanoparticle AMF–Induced Thermoablative Therapy for Human Breast Cancer in Mice
Antibody (mAb)-linked iron oxide nanoparticles (bioprobes) provide the opportunity to develop tumor specific thermal therapy (Rx) for metastatic cancer when inductively heated by an externally applied alternating magnetic field (AMF). To evaluate the potential of this Rx, in vivo tumor targeting, efficacy, and predictive radionuclide-based heat dosimetry were studied using 111In-ChL6 bioprobes (ChL6 is chimeric L6) in a human breast cancer xenograft model.
Methods: Using carbodiimide, 111In-DOTA-ChL6 (DOTA is dodecanetetraacetic acid) was conjugated to polyethylene glycol-iron oxide–impregnated dextran 20-nm particles and purified as 111In-bioprobes. 111In doses of 740–1,110 kBq (20–30 µCi) (2.2 mg of bioprobes) were injected intravenously into mice bearing HBT3477 human breast cancer xenografts. Pharmacokinetic (PK) data were obtained at 1, 2, 3, and 5 d. AMF was delivered 72 h after bioprobe injection at amplitudes of 1,410 (113 kA/m), 1,300 (104 kA/m), and 700 (56 kA/m) oersteds (Oe) at 30%, 60%, and 90% "on" time (duty), respectively, and at 1,050 Oe (84 kA/m) at 50% and 70% duty over the 20-min treatment. Treated and control mice were monitored for 90 d. Tumor total heat dose (THD) from activated tumor bioprobes was calculated for each Rx group using 111In-bioprobe tumor concentration and premeasured particle heat response to AMF amplitudes. Tumor growth delay was analyzed by Wilcoxon rank sum comparison of time to double, triple, and quintuple tumor volume in each group, and all groups were compared with the controls.
Results: Mean tumor concentration of 111In-bioprobes at 48 h was 14 ± 2 percentage injected dose per gram; this concentration 24 h before AMF treatment was used to calculate THD. No particle-related toxicity was observed. Toxicity was observed at the highest AMF amplitude–duty combination of 1,300 Oe and 60% over 20 min; 6 of 10 mice died acutely. Tumor growth delay occurred in all of the other groups, correlated with heat dose and, except for the lowest heat dose group, was statistically significant when compared with the untreated group. Electron microscopy showed 111In-bioprobes on tumor cells and cell death by necrosis at 24 and 48 h after AMF.
Conclusion: mAb-guided bioprobes (iron oxide nanoparticles) effectively targeted human breast cancer xenografts in mice. THD, calculated using empirically observed 111In-bioprobe tumor concentration and in vitro nanoparticle heat induction by AMF, correlated with tumor growth delay.
Complete article: http://jnm.snmjournals.org/cgi/content/full/48/3/437
Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment
Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (P<0.05). The nsPEF-treated tumor volume was reduced significantly compared with the control group (P<0.01). Hematoxylin and eosin stain and transmission electron microscopy showed morphological changes and nuclear shrinkage in the tumor. Fontana-Masson stain indicates that nsPEF can externalize the melanin. Iron stain suggested nsPEF caused slight hemorrhage in the treated tissue. Histology confirmed that repeated applications of nsPEF disrupted the vascular network. nsPEF treatment can significantly disrupt the vasculature, reduce subcutaneous murine melanoma development, and produce tumor cell contraction and nuclear shrinkage while concurrently, but not permanently, damaging peripheral healthy skin tissue in the treated area, which we attribute to the highly localized electric fields surrounding the needle electrodes.
Bacterial inactivation using atmospheric pressure single pin electrode microplasma jet with a ground ring
Bacterial inactivation experiment was performed using atmospheric pressure microplasma jets driven by radio-frequency wave of 13.56 MHz and by low frequency wave of several kilohertz. With addition of a ground ring electrode, the discharge current, the optical emission intensities from reactive radicals, and the sterilization efficiency were enhanced significantly. When oxygen gas was added to helium at the flow rate of 5 SCCM, the sterilization efficiency was enhanced. From the survival curve of Escherichia coli, the primary role in the inactivation was played by reactive species with minor aid from heat, UV photons, charged particles, and electric fields.
Complete article: http://apl.aip.org/applab/v94/i14/p141502_s1?isAuthorized=no
FIBER PRESSURE SENSOR FOR THE POLVAD PROSTHESIS
Heart problems are more and more common in human population. Living with diseased heart is difficult and sometimes impossible. In these cases the only way to cure heart muscle is mechanical support [1-4]. For this purpose POLVAD heart supporting devices are used. The main purpose of the ventricular assist device (VAD) is to aid the human circulatory system by external blood pump connected directly to the human vascular system. Artificial heart support relieves the human heart from a large part of its burden, what accelerates healing process. The POLVAD device (Fig 1) is driven by a pneumatic driving unit (PDU) of the POLPDU-401 type. Both prosthesis and driver form the Polish Cardiac Assist System (POLCAS) [5,6]. Presently PDU gives possibility of setting both the volume and the rate of blood pumped during one cycle. The main problem to be solved is feedback, so the driving unit could provide information about the current status of prosthesis, which is impossible now. The main purpose of this work is to research possible real time pressure measurement systems, and choose one method for future incorporation in prosthesis. This paper includes recent researches on fiber pressure sensor.
Complete article: http://ogpta.polsl.pl/mqa/files/29/pdf/135-141.pdf
Radiation hardness of fiber-optic sensors for monitoring and remote handling applications in nuclear environments
We report on our irradiation experiments on different types of fiber-optic sensors, including three types of commercially available temperature sensors, a multimode extrinsic Fabry-Perot cavity strain sensor and fiber Bragg-gratings. For the temperature sensors, results show that gamma radiation does not interfere with the basic sensing mechanism and that the most critical component turns out to be the optical fiber itself. Semiconductor absorption temperature sensors showed no degradation up to total doses of 250 kGy, whereas the specifications of Fabry-Perot type sensors and fluorescence temperature sensors were already dramatically influenced below the kGy-level. Replacing the optical fiber by a more radiation resistant version allowed to increase the radiation hardness of the fluorescence sensor system by orders of magnitude. The use of fiber-optic sensors in the presence of neutron radiation remains compromised. Similar conclusions are valid for the Fabry-Perot type fiber-optic strain sensors. We finally show that the Bragg-grating resonance wavelength can shift with radiation dose, but that the temperature sensitivity remains unaltered.
Complete article: http://chandlermonitoring.net/PDF/radiation.pdf
Quantification of tumor tissue populations by multispectral analysis
Tumor heterogeneity complicates the quantification of a therapeutic response by MRI. To address this issue, a novel approach has been developed that combines MR diffusion imaging with multispectral (MS) analysis to quantify tumor tissue populations. K-means (KM) clustering of the apparent diffusion coefficient (ADC), T2, and proton density (M0) was employed to estimate the volumes of viable tumor tissue, necrosis, and neighboring subcutaneous adipose tissue in a human colorectal tumor xenograft mouse model. In a second set of experiments, the temporal evolution of the MS tissue classes in response to therapeutic intervention Apo2L/TRAIL and CPT-11 was observed. The multiple parameters played complementary roles in identifying the various tissues. The ADC was the dominant parameter for identifying regions of necrosis, whereas T2 identified two necrotic subpopulations, and M0 contributed to the differentiation of viable tumor from subcutaneous adipose tissue. MS viable tumor estimates (mean volume = 275 ± 147 mm3) were highly correlated (r = 0.81, P < 0.01) with histological estimates (117 ± 51 mm3). In the treatment study, MS viable tumor volume (at day 10) was 77 ± 67 mm3 for the Apo2L/TRAIL+CPT-11 group, and was significantly reduced relative to the control group (292 ± 127 mm3, P < 0.01). This method shows promise as a means of detecting an early therapeutic response in vivo. Magn Reson Med 51:542-551, 2004. © 2004 Wiley-Liss, Inc.
Complete article: http://www3.interscience.wiley.com/journal/107629487/abstract
Measuring Local RF Heating in MRI: Simulating Perfusion in a Perfusionless Phantom
In the MR literature on the evaluation of RF heating safety, conflicting methods for measuring local RF heating are proposed. Each method suffers from some non-ideality. In vivo temperature measurements are difficult to conduct reproducibly. Measurements conducted using fluid phantoms introduce convection, which is not physiological. Gel phantom measurements lack the cooling effect of physiological perfusion. Earlier, we proposed a Green’s function averaging technique , but this method requires extensive computer simulations. In this study, we propose a method for predicting in vivo temperature increase by using a straightforward gel phantom experiment.
Measurement of Specific Absorption Rate and Thermal Simulation for Arterial Embolization Hyperthermia in the Maghemite-Gelled Model
Theoretical models are designed to be applied in hyperthermia treatment planning and to help optimize the surgical treatment procedures. However, it is difficult to obtain every physical parameter of the magnetic field in the living tissue in detail, which is necessary for the calculation. We therefore investigated the simulation of thermal distribution in arterial embolization hyperthermia (AEH) stimulated by the external ferrite-core applicator, and measured specific absorption rate (SAR) of magnetic nanoparticles in the maghemtite-gelled composite model. We used fiber optic temperature sensors (FOTS) to measure the values of SAR, which depend on the microstructure and sizes of particles and the intensity and frequency of external ac magnetic field. Detailed tests indicated that the attenuation of magnetic field was mainly focused on the vertical distance in the aperture of the apparatus. We built a simplified cylindrical phantom containing maghemite particles of 20 nm for thermal field simulation on the basis of SAR measurement. The results of simulation indicated that temperature elevation, induced by nanoparticles inside tumors under ac magnetic field, was dose-dependent. The temperature data acquired from the experiment were compatible with the theoretical results, which demonstrated that the current model considering the inhomogenous heat generation could provide accurate and reliable simulation results and a theoretical and technical basis for controlling temperature during AEH therapy
Effects of Shape and Size of Cobalt Ferrite Nanostructures on Their MRI Contrast and Thermal Activation
Cobalt ferrite magnetic nanostructures were synthesized via a high temperature solution phase method. Spherical nanostructures of various sizes were synthesized with the help of seed mediated growth of the nanostructures in the organic phase, while faceted irregular (FI) cobalt ferrite nanostructures were synthesized via the same method but in the presence of a magnetic field. Magnetic properties were characterized by superconducting quantum interference device (SQUID) magnetometry, relaxivity measurements, and thermal activation under RF field, as a function of size and shape. The results show that the saturation magnetization of the nanostructures increases with an increase in size, and the FI nanostructures exhibit lower saturation magnetization than their spherical counterparts. The relaxivity coefficient of cobalt ferrite nanostructures increases with an increase in size, while FI nanostructures show a higher relaxivity coefficient than spherical nanostructures with respect to their saturation magnetization. In the case of RF thermal activation, the specific absorption rate (SAR) of nanostructures increases with an increase in the size. The contribution sheds light on the role of size and shape on important magnetic properties of the nanostructures in relation to their biomedical applications.
Complete article: http://pubs.acs.org/doi/abs/10.1021/jp905776g
Magnetically Sensitive Alginate-Templated Polyelectrolyte Multilayer Microcapsules for Controlled Release of Doxorubicin
Magnetically sensitive alginate-templated polyelectrolyte multilayer microcapsules were successfully synthesized by a novel process combining emulsification and layer-by-layer self-assembly techniques. The as-synthesized microcapsules (2.67 μm in diameter) were superparamagnetic with a saturation magnetization of 14.2 emu·g−1, which contained approximately 30 wt % maghemite nanoparticles. The drug (doxorubicin) encapsulation efficiency was 56.4% and loading content was 3.5%. The in vitro release behavior under a high-frequency magnetic field (HFMF) indicated that the applied HFMF accelerated significantly the drug release from the microcapsules, which might be related to the microcapsules’ magnetic properties. Moreover, the in vitro cytotoxicity of doxorubicin-loaded alginate-templated polyelectrolyte multilayer microcapsules and the doxorubicin released from the microcapsules were investigated.
Complete article: http://pubs.acs.org/doi/abs/10.1021/jp911933b
Effects of hyperthermia with dextran magnetic fluid on the growth of grafted H22 tumor in mice
Objective: To study the effect of dextran magnetic fluid hyperthermia on growth, vascular endothelial growth factor (VEGF) expression and apoptosis of the grafted H22 tumors in mice.
Methods: Mice with grafted H22 tumor were randomly divided into four groups. The treatment group was intratumorally injected with dextran magnetic fluid and subsequently exposed to a 55 kHz 20 kA/m alternating magnetic field for 10 min. The three control groups were respectively injected with physiological saline and no magnetic field; with physiological saline and exposed to 55 kHz 20 kA/m alternating magnetic field for 10 min; and with dextran magnetic fluid only. The inhibitive ratios were calculated. Other mice with grafted tumor were randomly divided into two groups, respectively injected with dextran magnetic fluid or physiological saline and exposed to a 55 kHz 20 kA/m alternating magnetic field for 10 min. The VEGF expression and apoptosis in tumor tissues were analyzed at 1 h, 5 h, 24 h, 48 h and 336 h after treatment.
Results: The inhibitive ratio of treated group was 59.74%, 52.51% and 40.35% respectively. Necrotic areas in tumor tissue were mainly distributing around the magnetic fluid and became larger with the lengthening of treatment. The VEGF expression and apoptosis of the treated group did not show obvious difference from that of the control group at different time points.
Conclusion: Single time magnetic fluid hyperthermia significantly inhibited growth of grafted H22 tumor in mice, which mainly resulted from inducing necrosis while not inhibiting VEGF expression or inducing apoptosis.
Effect of Different Preparation Methods on Physicochemical Properties of Salidroside Liposomes
Salidroside liposomes were prepared by using five different methods: thin film evaporation, sonication, reverse phase evaporation, melting, and freezing−thawing. The effect of different preparation methods and salidroside loading capacity on the formation of liposomes and their physicochemical properties were evaluated by means of encapsulating efficiency, particle size, morphology, and ζ potential. Results showed that the encapsulating efficiency of liposomes was highest when prepared by freezing−thawing, followed by thin film evaporation, then reverse phase evaporation and the lowest with melting and sonication. Loading capacity of salidroside had a significant effect on encapsulating efficiency, average diameter, and ζ potential of liposomes. Liposomal systems prepared by sonication, melting, and reverse phase evaporation displayed better dispersivity. Determination of leakage of salidroside from different liposomal systems revealed that the melting method had the lowest leakage of 10% and 15%, at 4 and 30 °C after 1 month of storage, respectively. In all cases, a straight-line leakage behavior of salidroside was found. This revealed that the leakage of salidroside was a diffusion process from the membrane of liposomes. Furthermore, the storage stability of different liposomal systems showed that salidroside liposomes prepared by melting had a better physicochemical stability. Instability in the systems was exacerbated when temperature increased. Salidroside liposomes showed the slower increase in particle size than liposomes without salidroside. This could indicate that salidroside played an important role in preventing the aggregation and fusion of liposomes.
Complete article: http://pubs.acs.org/doi/abs/10.1021/jf062935q
Preparation of salidroside nano-liposomes by ethanol injection method and in vitro release study
The purpose of this work was to prepare salidroside nano-liposomes by the ethanol injection method. To obtain the higher encapsulating efficiency of salidroside nano-liposomes, several factors including salidroside-loading capacity, cholesterol, Tween 80, ion strength and lipid concentration were investigated. The higher encapsulating efficiency of salidroside, 45%, was obtained with cholesterol to lipid mass ratio of 1:4, Tween 80 and lipid to the molar ratio of 1:2, and ion strength in a range 20–50 mmol/L. With the optimization operation, the particles of nano-liposomes were below 100 nm and zeta potential was in the range of −10 and −20 mV. The release study of salidroside in vitro from nano-liposomes exhibited a prolonged release profile as studied over a period of 24 h.
Complete article: http://www.springerlink.com/content/r826ttw180624883/
Transient temperature rise in a mouse due to low-frequency regional hyperthermia
A refined nonlinear heat transfer model of a mouse has been developed to simulate the transient temperature rise in a neoplastic tumour and neighbouring tissue during regional hyperthermia using a 150 kHz inductive coil. In this study, we incorporate various bio-energetic enhancements to the heat transfer equation and numerical validations based on experimental findings for the mouse, in terms of nonlinear metabolic heat production, homeothermy, blood perfusion parameters, thermoregulation, psychological and physiological effects. The discretized bio-heat transfer equation has been validated with the commercial software FEMLAB on a canonical multi-sphere object before applying the scheme to the inhomogeneous mouse voxel phantom. The time-dependent numerical results of regional hyperthermia of mouse thigh have been compared with the available experimental temperature results with only a few small disparities. During the first 20 min of local unfocused heating, the temperature in the tumour and the surrounding tissue increased by around 7.5 degrees C. The objective of this preliminary study was to develop a validated electrothermal numerical scheme for inductive hyperthermia of a small mammal with the intention of expanding the model into a complete numerical solution involving ferromagnetic nanoparticles for targeted heating of tumours at low frequencies. In addition, the numerical scheme herein could assist in optimizing and tailoring of focused electromagnetic fields for hyperthermia.
Complete article: http://www.ncbi.nlm.nih.gov/pubmed/16552097
This section displays a list of papers that have been published in various journals and magazines.
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