Initial in vivo experience with EIT as a thermal estimator during hyperthermia

Thermal imaging experiments using electrical impedance tomography (EIT) have been conducted during hyperthermia treatments delivered to two human patients and one animal subject. Coplanar and circumferential arrays of 16 and 32 tin-plated copper electrodes etched on a 0.005″ polyimide sheet were used to inject 12.5 KHz current patterns of increasing sinusoidal spatial frequencies and subsequent potential distributions were recorded at each electrode site. Image reconstruction was achieved with a finite element method and difference images of conductivity changes during the course of treatment were formed. An assumed linear relationship (2%/d`C increase) between tissue impedance change and temperature change was used to produce thermal images of the treatment field in patients whereas an empirically measured nonlinear relationship obtained from excised tissue samples was applied retrospectively in the animal subject case. Reconstructed conductivity changes are shown to be possible given electrical data measured in vivo during hyperthermia delivery with conventional equipment (spiral microstrip applicator at 433 MHz). These correlated well with direct temperature measurements and demonstrated quantitative levels of agreeement to the extent that estimated temperature accuracies were approximately 1.5d`C; although large errors (> 5d`C) did exist. This work suggests that EIT is a potentially useful tool for hyperthermia treatment monitoring and assessment. The relationship between tissue impedance and temperature is complex and confounds the ability to make simple correlations between conductivity and temperature changes. Further, study is required to discern whether this will ultimately limit EIT as a thermal estimator or whether it will lead to more fundamental uses of impedance as an indicator of thermal effect.     

Quantitative assessment of impedance tomography for temperature measurements in hyperthermia.

The objective of this study is a non-invasive assessment of the thermal dose in hyperthermia. Electrical impedance tomography (EIT) has previously been given a first trial as a temperature monitoring method together with microwave-induced hyperthermia treatment, but it has not been thoroughly investigated. In the present work we have examined this method in order to investigate the correlation in vitro between the true spatial temperature distribution and the corresponding measured relative resistivity changes. Different hyperthermia techniques, such as interstitial water tubings, microwave-induced, laser-induced and ferromagnetic seeds have been used. The results show that it is possible to find a correlation between the measured temperature values and the tomographically measured relative resistivity changes in tissue-equivalent phantoms. But the uncertainty of the temperature coefficients, which has been observed, shows that the method has to be improved before it can be applied to clinical in vivo applications.     

Quantification of the heterogeneity in breast cancer cell lines using whole-cell impedance spectroscopy.

PURPOSE: Quantification of the heterogeneity of tumor cell populations is of interest for many diagnostic and therapeutic applications, including determining the cancerous stage of tumors. We attempted to differentiate human breast cancer cell lines from different pathologic stages and compare that with a normal human breast tissue cell line by characterizing the impedance properties of each cell line. EXPERIMENTAL DESIGN: A microelectrical impedance spectroscopy system has been developed that can trap a single cell into an analysis cavity and measure the electrical impedance of the captured cell over a frequency range from 100 Hz to 3.0 MHz. Normal human breast tissue cell line MCF-10A, early-stage breast cancer cell line MCF-7, invasive human breast cancer cell line MDA-MB-231, and metastasized human breast cancer cell line MDA-MB-435 were used. RESULTS: The whole-cell impedance signatures show a clear difference between each cell line in both magnitude and phase of the electrical impedance. The membrane capacitance calculated from the impedance data was 1.94 +/- 0.14, 1.86 +/- 0.11, 1.63 +/- 0.17, and 1.57 +/- 0.12 muF/cm(2) at 100 kHz for MCF-10A, MCF-7, MDA-MB-231, and MDA-MB-435, respectively. The calculated resistance for each cancer cell line at 100 kHz was 24.8 +/- 1.05, 24.8 +/- 0.93, 24.9 +/- 1.12, and 26.2 +/- 1.07 MOhm, respectively. The decrease in capacitances of the cancer cell lines compared with that of the normal cell line MCF-10A was 4.1%, 16.0%, and 19.1%, respectively, at 100 kHz. CONCLUSIONS: These findings suggest that microelectrical impedance spectroscopy might find application as a method for quantifying progression of cancer cells without the need for tagging or modifying the sampled cells.     

Temperature field estimation using electrical impedance profiling methods. II. Experimental system description and phantom results

An electrical impedance tomography system has been developed and tested for the purpose of thermal imaging. Since impedance changes with temperature, images of impedance subtracted from normothermic baselines will provide a map of temperature data. A system was designed to be operational at 10–50 kHz and to utilize 16 external electrodes around the periphery of a tissue-equivalent phantom encompassing the region of interest. These electrodes serve as current sources for the 5 mA constant-current inputs and are also used for reading differential voltages. Hyperthermia treatments for cancer require that internal thermometry probes be inserted into the tumour volume. Linear arrays of electrodes with thermometry tracks for micro-dimension thermometry serve this function, as well as providing localized voltage measurements in the region of interest. The embedded temperature sensors provide a quality assurance and calibration standard for the linear arrays in reconstruction of impedance profiles. Results of transient heating experiments with conductive and ultrasound heating are shown where image reconstruction is performed using a finite element model. Temperature predictions in these studies were accurate to better than 1°C on average when using information from surface electrodes combined with internal linear arrays. Maximum temperature errors, however, was found to be > 5°C which suggests that further noise reduction during data acquisition and improvements in the reconstructions algorithms are needed.     

B型超声诊断肝癌假阳性,假阴性分析

本文分析了70例肝脏B超检查中产生的假阳性和假阴性各5例的原因。如慢性肝病伴肝血管瘤时因损害的肝组织与肝血管瘤间声阻抗差减少;结节型肝硬化时,很多纤维结缔组织在再生结节周围产生强大声衰减及早期肝脓疡因组织间声阻抗不同形成的回声团,B超检查时易误诊为肝癌,出现假阳性。而肝表面粟粒样的转移灶及卵巢癌囊性肝转移易漏诊。本文对如何提高B超诊断的准确性作了简要说明。     

Technology review: the use of electrical impedance scanning in the detection of breast cancer

The present paper focuses on electrical impedance scanning. The basic science behind the new modality, measurements of breast tissue impedance in vivo and in vitro, and the studies performed with a newly available commercial machine are discussed. Electrical impedance scanning has been generating interest for several reasons, including comfort to the patient, the relatively low cost, and studies suggest that it may be effective in detecting disease in mammographically dense breasts.     

Technology review: The use of electrical impedance scanning in the detection of breast cancer

The present paper focuses on electrical impedance scanning. The basic science behind the new modality, measurements of breast tissue impedance in vivo and in vitro, and the studies performed with a newly available commercial machine are discussed. Electrical impedance scanning has been generating interest for several reasons, including comfort to the patient, the relatively low cost, and studies suggest that it may be effective in detecting disease in mammographically dense breasts.     

Changes in the noninvasive, in vivo electrical impedance of three xenografts during the necrotic cell-response sequence

PURPOSE: To investigate the noninvasive, in vivo use of electrical impedance spectroscopy (EIS) as a method for observing the real-time, cellular-level responses of a volume of tissue to therapies. Here, we studied the EIS response during the development and progression of hyperthermia-induced coagulative necrosis in three diverse human xenografts. METHODS AND MATERIALS: A necrotic cell response sequence was selectively induced in three types of subcutaneously-grown human tumor xenografts by applying hyperthermia at 44.5 degrees C. The electrical impedance of the tumors was measured from 100 Hz to 10 MHZ, noninvasively, in vivo during the treatments. From the full spectrum EIS, ratios between resistivities at selected frequencies (p-ratios) were used as indicators of the changes in the electrical impedance spectra of each tumor's cell population. RESULTS: The rho-ratios consistently demonstrated characteristic, early, rapid increases which coincided with cell and organelle swelling typical of early necrosis. These increases subsequently slowed, but no decrease began before the end of treatment, unlike previous, similarly treated, thermo-sensitive EMT6 mouse tumors. This was consistent with the xenograft histology, which revealed ubiquitous, early-stage coagulative necrosis, with no gross plasma membrane damage at the end of treatment. The extent of both the necrosis and p-ratio changes were similar to those seen early in the EMT6 tumor treatment. Within several days after treatment, the xenograft volumes regressed nearly completely, suggesting completion of the cell populations' necrotic response (lysing) during this period. Consistent with this, extended EIS measurements over a 24-h posttreatment period allowed tracking of the necrotic response sequence through this lysing phase for one type of xenograft. CONCLUSION: The change in the electrical impedance of a volume of tumor tissue which occurs during and/or after a hyperthermia treatment can be correlated with the extent of necrosis observed histologically in the cell population.     

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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.     

Breast Imaging Using Electrical Impedance Tomography: Correlation of Quantitative Assessment with Visual Interpretation

Background: Electrical impedance tomography (EIT) is a new non-invasive, mobile screening method whichdoes not use ionizing radiation to the human breast; allows conducting quantitative assessment of the imagesbesides the visual interpretation. The aim of this study was to correlate the quantitative assessment and visualinterpretation of breast electrical impedance tomographs and associated factors. Materials and Methods: Onehundred and fifty mammography patients above 40 years and undergoing EIT were chosen using convenientsampling. Visual interpretation of the images was carried out by a radiologist with minimum of three yearsexperience using the breast imaging - electrical impedance (BI-EIM) classification for detection of abnormalities.A set of thirty blinded EIT images were reinterpreted to determine the intra-rater reliability using kappa.Quantitative assessment was by comparison of the breast average electric conductivity with the norm andcorrelations with visual interpretation of the images were determined using Chi-square. One-way ANOVA wasused to compare the mean electrical conductivity between groups and t-test was used for comparisons withpre-existing Caucasians statistics. Independent t-tests were applied to compare the mean electrical conductivityof women with factors like exogenous hormone use and family history of breast cancer. Results: The meanelectrical conductivity of Malaysian women was significantly lower than that of Caucasians (p<0.05). Quantitativeassessment of electrical impedance tomography was significantly related with visual interpretation of imagesof the breast (p<0.05). Conclusions: Quantitative assessment of electrical impedance tomography images wassignificantly related with visual interpretation.     

Resolution and contrast in magnetic resonance electrical impedance tomography (MREIT) and its application to cancer imaging

It has been reported that the electrical impedance of malignancies could be 20-40 times lower than healthy tissues and benign formations. Therefore, in vivo impedance imaging of suspicious lesions may prove to be helpful in improving the sensitivity and specificity of detecting malignant tumors. Several systems have been developed to map the conductivity distribution inside a volume of tissue, however they suffer from poor spatial resolution because the measurements are taken only from surface electrodes. MRI based impedance imaging (MREIT) is a novel method, in which weak electrical currents are injected into the tissue and the resulting perturbations in the magnetic field are measured using MRI. This method has been shown to provide better resolution compared to previous techniques of impedance imaging because the measurements are taken from inside the object on a uniform grid. Thus, it has the potential to be a useful modality that may detect malignancies earlier. Several phantom imaging experiments were performed to investigate the spatial resolution and dynamic range of contrast of this technique. The method was also applied to a live rat bearing a R3230 AC tumor. Tumor location was identified by contrast enhanced imaging.     

Quantitative Ultraschallrastermikroskopie zur Bestimmung der akustischen Impedanz von kortikalem Knochengewebe

An in vitro scanning acoustic microscopy measurement technique is described to assess the elastomechanical properties of human bone tissue at the level of cellular organizational structures. The technique allows to measure the acoustic impedance as a material describing parameter. Contrast influences caused by defocus, surface edges and inclinations, respectively are separated or eliminated and the microscopic acoustic impedances of the remaining data points are determined by a dynamic calibration method. Cortical bone samples of the human femur embedded in polymethylmethacrylate (PMMA) were investigated at a frequency of 900 MHz. The resulting impedance maps showed a strong structural dependence and the mean values were found to be in the range from 2 to 6 Mrayl, which is significantly lower than macroscopic bulk values of the bone compound measured by acoustic low frequency methods.     

Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood–brain-barrier: in vitro investigation of CD15 and CD15s in lung-to-brain metastasis

Purpose

Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types of brain metastasis. The mechanisms involved in how circulating cancer cells transmigrate into brain parenchyma are not fully understood. The aim of this work was to investigate the role of fucosylated carbohydrate epitopes CD15 and sialyated CD15s in cancer adhesion to brain-derived endothelial cells and determine their influence in blood–brain barrier (BBB) disruption

Methods

Three distinct, independent methods were used to measure brain endothelial integrity and include voltohmmeter (EVOM?), impedance spectroscopy (CellZscope®) and electric cell-substrate impedance sensing system (ECIS?). Two fucosyltransferases (FUT4 and 7) responsible for CD15 and CD15s synthesis were modulated in four human cancer cell lines (three lung cancer and one glioma).

Results

Overexpression of CD15 or CD15s epitopes led to increase in adhesion of cancer cells to cerebral endothelial cells compared with wild-type and cells with silenced CD15 or CD15s (p?<?0.01). This overexpression led to the disruption of cerebral endothelial cell monolayers (p?<?0.01). Knockdown of FUT4 and FUT7 in metastatic cancer cells prevented disruption of an in vitro BBB model. Surprisingly, although the cells characterised as ‘non-metastatic’, they became ‘metastatic’ -like when cells were forced to over-express either FUT4 or FUT7.

Conclusions

Results from these studies suggest that overexpression of CD15 and CD15s could potentiate the transmigration of circulating NSCLC cells into the brain. The clinical significance of these studies includes the possible use of these epitopes as biomarkers for metastasis.

     

Microphysiological testing for chemosensitivity of living tumor cells with multiparametric microsensor chips

A constraint in the reliability of predictive chemosensitivity assays is linked to the fact that they analyze only a single cellular or biochemical parameter. A multiparametric test system using microsensor chips has been developed which can detect online microphysiological changes in living cells. Tumor cells were grown directly on glass- or silicon-based electronic sensor chips. Changes in extracellular pH and pO(2), reflecting metabolic activities, and changes in impedance, reflecting morphological properties, were monitored. In this study, colon and breast cancer cells as well as doxorubicin-sensitive and doxorubicin-resistant sarcoma cell lines were exposed to cytochalasin B, chloroacetaldehyde, or doxorubicin. Results show (1) reduction in medium acidification, (2) marked and rapid changes in O(2) consumption, and (3) modulations in impedance correlating with morphological changes observed in the microscope. Drug-resistant cells do not show these changes. Therefore, this microphysiological monitoring is a versatile tool for chemosensitivity testing of tumor cells.     

99mTc-DTPA uptake and electrical impedance measurements in verification of in vivo electropermeabilization efficiency in rat muscle

OBJECTIVE: In vivo electropermeabilization of cell membranes in rat muscle tissue cause a significant decrease of the electrical impedance, in the frequency region of 1-10 kHz. We aimed to study how the 99mTc-DTPA uptake in the electropermeabilized region correlates to the change of admittance Y = 1/absZ, where Z is the measured impedance. METHODS: The electropermeabilization was performed in vivo by applying high-voltage (0.5-2 kV) short (0.1-2 ms) pulses through gold-plated needle electrodes in skeletal muscle. The impedance was measured before and after each electropermeabilization pulse. The uptake of 99mTc-DTPA uptake in the electropermeabilized region was measured after 6 and 24 hours with a gamma camera. RESULTS: The pulse shape (square and exponential), duration, and amplitude of the applied electric field were varied, and electropermeabilization efficiency was evaluated using the various measurement modalities. Good correlations were found (correlation coefficient approximately 0.9) between the 99mTc-DTPA uptake in the electropermeabilized and control "region of interest" the admittance ratio Y (post-treatment)/Y (pretreatment), and charge displacement parameter Q. CONCLUSION: The electrical impedance measurements method can be utilized in clinical settings to verify the efficiency of electropermeabilization applied to chemotherapy and to power RNAi (RNA-interference) and DNA-plasmid transfection in vaccination, immunization, and gene-therapy.     

Bioelectrical impedance phase angle as a prognostic indicator in breast cancer

Background  

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive, and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by bioelectrical impedance analysis (BIA), detects changes in tissue electrical properties and has been hypothesized to be a marker of malnutrition. Since malnutrition can be found in patients with breast cancer, we investigated the prognostic role of phase angle in breast cancer.     

Dual-antenna applicator for hyperthermia of tumours at intermediate depth

A dual-antenna applicator with 21 x 26 cm2 aperture, that is fully loaded and operates at 74 MHz, was developed at the Mallinckrodt Institute of Radiology. By placing two antennas into an applicator capable of propagating TE10 mode, a significant enlargement of heating pattern was achieved without an increase in applicator dimensions. When antennas are placed symmetrically about a parallel to the antenna axis of symmetry, the sensitivity of the applicator input impedance to variations of load impedance reduces. Stable coupling of the RF power to the treatment area may be provided. Twenty patients with eccentrically located tumours were treated using this device.     

Secretory otitis media: A school health survey

The present study was carried out to find out prevalence of secretory otitis media in 200 school going children between the age group of 5–7 years by impedance audiometry besides clinical evaluation. 100 children were taken from two different schools catering to higher and lower socioeconomic strata of society. The overall prevalence of secretory otitis media came out to be 20.75%. It was 28.5% in lower socioeconomic group and, 13% in the other group. This high prevalence warrants routine screening for secretory otitis media. Further impedance audiometry was found to be very good method of screening secretory otitis media.     

Electrical Impedance Tomography as a Primary Screening Technique for Breast Cancer Detection

Electrical impedance tomography (EIT) is a new non-invasive, mobile screening method which does not useionizing radiation to the human breast. It is based on the theory that cancer cells display altered local dielectricproperties, thus demonstrating measurably higher conductivity values. This article reviews the utilisation ofEIT in breast cancer detection. It could be used as an adjunct to mammography and ultrasonography for breastcancer screening.     

鼻咽癌3-D计划放射治疗后放射性中耳炎的临床分析

背景与目的:中耳咽鼓管损害高峰发生在放疗后半年,并且在很多病例可持续终身,至今为止临床上尚无有效的治疗方法,寻求放射治疗中中耳鼓室及咽鼓管更好的保护仍是放射治疗医师面临的责任,在精确放疗技术应用逐渐普遍的今天,肿瘤周围正常组织和器官的保护受到越来越多的重视,但到目前为止,有关中耳放射损伤的研究报道极少。我们采用回顾性分析的方法,通过比较鼓室腔及骨性段咽鼓管剂量分布与放疗后分泌性中耳炎的发生率,评价在鼻咽癌3-D计划放射治疗中中耳功能保护的可能性,同时了解放疗后时间、化疗、T分期等因素对结果的影响。方法:40例80耳有完整听力学检查材料的鼻咽癌3-D计划放射治疗的患者进入此项研究。所有病例放疗前后均经耳部检查,电测听及声阻抗测听,放疗后随访时间为6~24个月。电测听以500,1 000,2 000,4 000 Hz听阈平均值计算气骨导差,声阻抗根据鼓室图分为A、B、C 3型,A型为正常鼓室图,B型为中耳鼓室积液,C型为咽鼓管功能不良。结果:79耳符合声阻抗分析条件。放疗后62%耳与放疗前保持不变,13%耳得到改善,25%耳恶化。鼓室腔及骨性段咽鼓管剂量分布在恶化耳与其他各组耳之间比较差异有显著性。80耳电测听分析结果,放疗后无变化耳58%,改善耳12%,恶化耳30%。分析剂量因素对声阻抗结果的影响,恶化组的鼓室腔及骨性段咽鼓管平均受照剂量为(5379.81±706.01)cGy,不变组的平均受照剂量为(4735.72±812.30)cGy,改善组的平均剂量为(4652.86±809.78)cGy;分析剂量因素对电测听结果的影响,恶化组的中耳及骨性咽鼓管平均受量为(5229.38±778.11)cGy,不变组的平均受量为(4719.64±744.82)cGy,改善组的平均剂量为(4702.38±922.21)cGy。统计分析发现3组的剂量差异有显著性。T分期变化及1年内或1年后时间分组对听力测试结果的影响差异有显著性,而化疗对听力测试结果的影响不明显。结论:在鼻咽癌3-D放射治疗中,如将鼓室腔及骨性段咽鼓管剂量控制在4700 cGy以下,则可明显减少延迟性放射性中耳炎的发生率。对中耳鼓室腔及骨性段的保护随着肿瘤体积的增大可能性减少。放射性中耳功能损伤发病高峰在1年内,在放疗前具有正常听觉功能者,放疗1年后有更多的机会从放射损伤中恢复。