Increased detection of high grade CIN, when using electrical impedance spectroscopy as an adjunct to routine colposcopy, is maintained when used across international boundaries: Prospective data from nine European countries.

OBJECTIVE: To evaluate the performance of EIS (ZedScan) with colposcopy in the detection of high grade CIN (HG-CIN) in different health care settings. METHOD: Pooled analysis of data from 26 colposcopy centres in 9 countries. All women underwent colposcopy and ZedScan examination. Data was recorded prospectively via a proforma. Indications for referral to colposcopy were according to national guidelines. Pathology was reported according to national guidelines. RESULTS: 5257 women were examined by 82 colposcopists, median 93 women per centre (range 41 - 2684), 3 users per centre (range 1-8). Referral indications were; 19.3% high grade cytology, 50.4% low grade, 30.3% clinical or HPV positive / cytology negative. The prevalence of HG-CIN was 26.5%; 79.1% in high grade referrals, 16.7% low grade, 9.4% clinical or HPV positive / cytology negative. The use of ZedScan detected an extra 269 cases of high grade CIN (24% increase) (7.5% increase for high grade referrals, 57.9% for low grade and 52% for clinical or HPV positive/cytology negative). Based upon colposcopic impression (CI), the sensitivity of colposcopy for CIN2 + was 74.1% compared with 91.6% for colposcopy with ZedScan (Chi2 p < 0.0001). The PPV for a ZedScan directed biopsy varied according to referral cytology and colposcopic impression (19.5% to 85.7%). 489 women underwent treatment at first visit, when ZedScan suggested treatment, 95.1% had HG-CIN/HG-CGIN or cervical cancer. The pooled results for the whole 26 centres were consistent with the results obtained for the largest centre (Sheffield) alone and also with the results with this largest centre excluded. CONCLUSIONS: The addition of EIS (ZedScan) increases detection of HG-CIN with the PPV for a ZedScan directed biopsy consistent with the published literature. Results were similar in multiple healthcare settings. With more women being referred to colposcopy at low risk of HG-CIN, due to HPV vaccination and primary HPV screening, this study confirms the value of a real time adjunctive technology.

Use of Electrical Impedance Spectroscopy for Intraoperative Tissue Differentiation During Thyroid and Parathyroid Surgery.

BACKGROUND: Electrical impedance (EI) measures tissue resistance to alternating current across several frequencies and may help identify tissue type. A recent rabbit model demonstrated that electrical impedance spectroscopy (EIS) may facilitate identification of parathyroid glands and potentially improve outcomes following surgery. This study looks at the EI patterns of soft tissues in the human neck to determine whether parathyroid tissue can be accurately identified. METHODS: This was a phase 1, single-arm interventional study involving 56 patients undergoing thyroid and/or parathyroid surgery. Up to 12 EI readings were taken from in vivo and ex vivo thyroid and parathyroid glands, adipose tissue and muscle of each patient. Each reading consists of a series of measurements over 14 frequencies from each tissue. EI patterns were analysed. Two patients were excluded due to data loss due to device malfunction. RESULTS: The median age of participants was 53.5 (range 20-85) years. Thirty-five participants had surgery for thyroid pathology, 17 for parathyroid pathology and four for both. Six hundred and six EIS spectra were reviewed for suitability. One hundred and eighty-four spectra were rejected leaving 422 spectra for analysis. The impedance patterns of the soft tissues differed by histological type. The EI ratio of low (152 Hz) to high (312 kHz) frequencies demonstrated a significant difference between the soft tissues (p = 0.006). Using appropriate thresholds, parathyroid tissue can be distinguished from thyroid tissue with a sensitivity of 76% and specificity of 60%. CONCLUSIONS: This study demonstrates the feasibility of using EIS to aid parathyroid identification and preservation. Further changes to the device and modelling of the EI patterns across the range of frequencies may improve accuracy and facilitate intraoperative use. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02901873).

Influence of high risk HPV genotype on colposcopic performance: A large prospective study demonstrates improved detection of disease with ZedScan I, particularly in non-HPV 16 patients.

OBJECTIVE: To assess the influence of high-risk Human Papilloma Virus (hrHPV) genotyping on the detection of high-grade disease (CIN2+) using colposcopic impression both with and without electrical impedance spectroscopy (ZedScan I) as an adjunct. STUDY DESIGN: A prospective cohort of women with a known hrHPV genotype referred to a single colposcopy service. RESULTS: 839 women underwent colposcopy and ZedScan I examination. 613 women were referred with abnormal cytology; 411 (67%) with low-grade dyskaryosis (67%) and 202 (33%) with high-grade dyskaryosis. 187 were referred with persistent hrHPV but negative cytology. 35 were attended for follow up and 4 for a clinical indication. 159 (19%) women were positive for HPV16 only; 54 (6%) with HPV18 only, 443 (53%) women were positive for hrHPV other types (HPV O). 183 (22%) were positive for multiple hrHPV genotypes. CIN2+ was present in 170 (84.2%) of high-grade and 69 (16.7%) of low-grade cytology referrals. Colposcopy was better at detecting HPV16 associated CIN2+ than that associated with HPV18 or HPV O (86.9% vs 79.7%, p=0.0191). ZedScan I increased the detection of CIN2+ from 85.6% to 96% irrespective of hrHPV genotype status (p<0.0001). CONCLUSION: The use of an electrical impedance spectroscopic device (ZedScan I) increases detection of CIN2+ irrespective of hrHPV genotype.

Electrical Impedance Spectroscopy to Aid Parathyroid Identification and Preservation in Central Compartment Neck Surgery: A Proof of Concept in a Rabbit Model.

BACKGROUND: Accurate identification of parathyroid glands during thyroid surgery is crucial to avoid postthyroidectomy hypocalcemia. Electrical impedance spectroscopy has the potential to differentiate between tissues of different morphology. The aim of this study was to determine the electrical impedance patterns of the thyroid, parathyroid, and other soft tissue structures in the rabbit neck. METHODS: The central compartments were exposed in 9 freshly culled New Zealand White rabbits. In situ and ex vivo electrical impedance was measured from thyroid lobes, external parathyroid glands, adipose tissue, and strap muscle using the APX100 device. Specimens of all identified glands were sent for histopathology examination. RESULTS: Histology confirmed correct identification of all excised thyroid and parathyroid glands. The impedance was higher for thyroid tissue at lower frequencies and for parathyroid tissue at higher frequencies. Ex vivo electrical impedance spectra were significantly higher compared with the in situ spectra across all frequencies for thyroid and parathyroid tissues (P < .001). The ratio of low to high frequency in situ impedance of thyroid, parathyroid, and muscle was significantly different (P < .001), allowing for differentiation between these tissues. CONCLUSION: The electrical impedance spectra of rabbit thyroid and parathyroid glands are distinct and different from each other and from skeletal muscle. If these results are replicated in human tissue, they have the potential to improve patient outcomes by achieving early identification and preservation of parathyroid glands.

Feasibility of using 'lung density' values estimated from EIT images for clinical diagnosis of lung abnormalities in mechanically ventilated ICU patients.

This paper reports on the results of a study which compares lung density values obtained from electrical impedance tomography (EIT), clinical diagnosis and CT values (HU) within a region of interest in the lung. The purpose was to assess the clinical use of lung density estimation using EIT data. In 11 patients supported by a mechanical ventilator, the consistency of regional lung density measurements as estimated by EIT was validated to assess the feasibility of its use in intensive care medicine. There were significant differences in regional lung densities recorded in the supine position between normal lungs and diseased lungs associated with pneumonia, atelectasis and pleural effusion (normal; 240 ± 71.7 kg m(-3), pneumonia; 306 ± 38.6 kg m(-3), atelectasis; 497 ± 130 kg m(-3), pleural effusion; 467 ± 113 kg m(-3): Steel-Dwass test, p < 0.05). In addition, in order to compare lung density with CT image pixels, the image resolution of CT images, which was originally 512 × 512 pixels, was changed to 16 × 16 pixels to match that of the EIT images. The results of CT and EIT images from five patients in an intensive care unit showed a correlation coefficient of 0.66 ± 0.13 between the CT values (HU) and the lung density values (kg m(-3)) obtained from EIT. These results indicate that it may be possible to obtain a quantitative value for regional lung density using EIT.

Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions.

The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool.

Whither lung EIT: where are we, where do we want to go and what do we need to get there?

Breathing moves volumes of electrically insulating air into and out of the lungs, producing conductivity changes which can be seen by electrical impedance tomography (EIT). It has thus been apparent, since the early days of EIT research, that imaging of ventilation could become a key clinical application of EIT. In this paper, we review the current state and future prospects for lung EIT, by a synthesis of the presentations of the authors at the 'special lung sessions' of the annual biomedical EIT conferences in 2009-2011. We argue that lung EIT research has arrived at an important transition. It is now clear that valid and reproducible physiological information is available from EIT lung images. We must now ask the question: How can these data be used to help improve patient outcomes? To answer this question, we develop a classification of possible clinical scenarios in which EIT could play an important role, and we identify clinical and experimental research programmes and engineering developments required to turn EIT into a clinically useful tool for lung monitoring.

Indirect measurement of lung density and air volume from electrical impedance tomography (EIT) data.

This paper describes a method for estimating lung density, air volume and changes in fluid content from a non-invasive measurement of the electrical resistivity of the lungs. Resistivity in Ω m was found by fitting measured electrical impedance tomography (EIT) data to a finite difference model of the thorax. Lung density was determined by comparing the resistivity of the lungs, measured at a relatively high frequency, with values predicted from a published model of lung structure. Lung air volume can then be calculated if total lung weight is also known. Temporal changes in lung fluid content will produce proportional changes in lung density. The method was implemented on EIT data, collected using eight electrodes placed in a single plane around the thorax, from 46 adult male subjects and 36 adult female subjects. Mean lung densities (±SD) of 246 ± 67 and 239 ± 64 kg m(-3), respectively, were obtained. In seven adult male subjects estimates of 1.68 ± 0.30, 3.42 ± 0.49 and 4.40 ± 0.53 l in residual volume, functional residual capacity and vital capacity, respectively, were obtained. Sources of error are discussed. It is concluded that absolute differences in lung density of about 30% and changes over time of less than 30% should be detected using the current technology in normal subjects. These changes would result from approximately 300 ml increase in lung fluid. The method proposed could be used for non-invasive monitoring of total lung air and fluid content in normal subjects but needs to be assessed in patients with lung disease.

Effect of varying phase between frequency and amplitude modulation on bone conduction auditory steady state responses.

OBJECTIVES: Auditory steady state response (ASSR) testing provides a means to objectively estimate hearing levels in newborns and adults for whom behavioral tests prove difficult. When testing these patient groups, it is preferable that clear responses to both air and bone conduction stimuli are obtained in a short amount of time. Much of the literature addressing ASSRs, such as investigations of stimulus and recording parameters, have focused on air conduction ASSRs. The aim of this investigation was to study the amplitudes, latencies, and test times of bone conduction ASSRs elicited using amplitude- (AM), frequency- (FM), and mixed-modulated (MM) stimuli and provide suggestions for optimum recording parameters. DESIGN: Bone and air conduction multiple ASSRs were recorded from two groups of 20 normal-hearing adults using the Multiple Auditory Steady State Response research system. AM, FM, and MM sinusoidal tones were used (0.5-, 1-, 2-, and 4-kHz carrier frequencies), which were modulated between 78 and 92 Hz. AM depth was 100% and FM depth was 20%. ASSR amplitudes and latencies (calculated using the "preceding cycles" technique) were analyzed for MM phase settings across the cycle from 0° at 45° intervals and compared with AM responses. Optimum phase settings for bone and air conduction ASSRs were calculated using a sinusoidal model based on the amplitude data. RESULTS: Similar effects of stimulus type and carrier frequency were observed for bone and air conduction ASSRs. AM responses were larger in amplitude compared with FM responses. MM (at all phase settings tested) and AM response latencies increased with decreasing carrier frequency. MM phase setting had a significant (p < 0.01) sinusoidal effect on ASSR amplitudes, compared with AM responses, at 1, 2, and 4 kHz but not 0.5 kHz for air conduction and 1 and 2 kHz but not 0.5 and 4 kHz for bone conduction. Using a sinusoidal function to model this effect, MM phase settings (±95% confidence intervals) of 318° (295 to 350°) and 295° (290 to 310°) are predicted to evoke the largest responses for bone conduction ASSRs at 1 and 2 kHz, respectively. Phase settings of 293° (285 to 310°), 300° (280 to 310°), and 280° (255 to 330°) are predicted for air conduction ASSRs at 1, 2, and 4 kHz, respectively. MM phase setting had little effect on estimated latency. Test times were significantly (p < 0.01) affected by phase setting with both increases and decreases being observed. Test times for ASSRs at 1, 2, and 4 kHz could be significantly reduced if the estimated optimum phase settings are used. CONCLUSIONS: Different stimuli can significantly affect the amplitudes of bone conduction ASSRs. These effects are similar to those observed for air conduction ASSRs. MM stimuli with specific phase settings evoke larger bone conduction ASSRs compared with AM and FM stimuli alone, and calculations show that the time taken to obtain these responses is reduced. Implementation of the suggested optimum settings will promote efficient collection of bone conduction, and indeed air conduction, ASSR data.

Absolute electrical impedance tomography (aEIT) guided ventilation therapy in critical care patients: simulations and future trends.

Thoracic electrical impedance tomography (EIT) is a noninvasive, radiation-free monitoring technique whose aim is to reconstruct a cross-sectional image of the internal spatial distribution of conductivity from electrical measurements made by injecting small alternating currents via an electrode array placed on the surface of the thorax. The purpose of this paper is to discuss the fundamentals of EIT and demonstrate the principles of mechanical ventilation, lung recruitment, and EIT imaging on a comprehensive physiological model, which combines a model of respiratory mechanics, a model of the human lung absolute resistivity as a function of air content, and a 2-D finite-element mesh of the thorax to simulate EIT image reconstruction during mechanical ventilation. The overall model gives a good understanding of respiratory physiology and EIT monitoring techniques in mechanically ventilated patients. The model proposed here was able to reproduce consistent images of ventilation distribution in simulated acutely injured and collapsed lung conditions. A new advisory system architecture integrating a previously developed data-driven physiological model for continuous and noninvasive predictions of blood gas parameters with the regional lung function data/information generated from absolute EIT (aEIT) is proposed for monitoring and ventilator therapy management of critical care patients.

The role of cervical Electrical Impedance Spectroscopy in the prediction of the course and outcome of induced labour.

BACKGROUND: Previous work by us and others had suggested that cervical electrical impedance spectroscopy (EIS) may be predictive of the outcome of induced labour. We sought to determine which probe configuration of the EIS device is predictive of the outcome of induced labour and compare this to digital assessment by the Bishop score. METHODS: In a prospective cohort of 205 women admitted for induction of labour, we used four probes of diameter 3, 6, 9 and 12 mm connected to an impedance meter to measure cervical resistivity (CR) in Ohm.meters at 14 electrical frequencies and compared their values to digital assessment of the cervix by the Bishop score for the prediction of the outcome of induced labour. We tested the association of labour characteristics and outcomes with CR and Bishop score by stepwise multilinear regression analyses, and the accuracy of prediction of categorical clinical outcomes by analysis of the area under the curves (AUC) of derived Receiver Operator Characteristic (ROC) curves. RESULTS: Of the four CR probe dimensions studied, only the 12 mm probe was predictive of any labour indices. In the frequency range 19 - 156 kHz, CR obtained with this probe was higher in women who delivered by caesarean section (CS) than those who delivered vaginally, and in labours lasting > 24 hrs. Cervical resistivity at 78.1 kHz best predicted vaginal delivery [optimal cut-off <2.25 Ohm.meter, AUC 0.66 (95% CI 0.59-0.72), sensitivity 71.0%, specificity 56.5%, LR+ 1.63, LR- 0.51, P < 0.01] and labour duration >24 hrs [optimal cut-off 2.27 Omega.m, AUC 0.65 (95% CI 0.58, 0.72), sensitivity 71%, specificity 59%, LR+ 1.72, LR- 0.50, P < 0.05]. In contrast digital assessment by the Bishop score neither predicted vaginal delivery nor the duration of labour. However, Bishop score predicted time to onset of labour > 12 hours and induction-delivery interval < 24 hrs [optimal cut-off

The detection of cervical intraepithelial neoplasia by electrical impedance spectroscopy: the effects of acetic acid and tissue homogeneity.

OBJECTIVE: To evaluate the efficacy of an electrical impedance probe (Epitheliometer) in the diagnosis of high grade cervical intraepithelial neoplasia (CIN) in women referred with cervical smear abnormalities and to assess the effect of acetic acid (AA) and tissue boundaries on the measurements. METHODS: A prospective observational study was undertaken in the colposcopy clinic. One hundred and sixty-five women, either with a clinical indication or abnormal cervical cytology, were recruited into the study. A pencil type probe was used to record impedance spectra from 12 points on the cervix before and after the application of 5% AA. Spectra were also recorded from tissue boundaries. Colposcopic examinations, including probe positioning, were video recorded to allow for correlations between histopathological diagnosis of colposcopically directed biopsies, colposcopic impression and the diagnosis based on impedance measurements. RESULTS: Receiver operating characteristic (ROC) curves were derived. The areas under the curves (AUCs) to discriminate original squamous from high grade CIN were 0.80 (pre AA) and 0.79 (post AA). Comparison of these curves showed no significant difference, indicating that application of AA does not produce a large change in spectra. The probe could distinguish tissue boundaries from homogeneous tissue points. CONCLUSION: The Epitheliometer has the potential to be used as an adjunct to colposcopy in the diagnosis of high grade CIN. It has the advantage of real time results, decreasing the need for diagnostic cervical biopsies, and facilitates a wider use of the 'see and treat' policy without the risk of overtreatment.

Reproducibility and repeatability of measuring the electrical impedance of the pregnant human cervix-the effect of probe size and applied pressure.

BACKGROUND: The utility of cervical electrical impedance spectroscopy (EIS) as a diagnostic tool is being investigated in clinical trials. We sought to assess the reliability of two different sizes of tetrapolar probes used in measuring cervical impedance. METHODS: Cervical transfer impedance was measured at 14 frequencies between 76 and 625 000 Hz from 11 pregnant subjects at term. Repeated measurements were taken with two probes (3 mm and 12 mm diameter) applied softly (approximately 0.7 Newton of force), and firmly (approximately 2.2 Newton) to the surface of the cervix by two observers. The intra-class correlation coefficient (ICC), coefficient of variation (CV) and repeatability standard deviations (SD) were derived from these measurements and compared. RESULTS: Measurements taken by one observer were highly repeatable for both probes as demonstrated by high ICC and low CV values. Probe performance was improved further by firm application. Firm application of the 3 mm probe resulted in ICC values that ranged from 0.936 to 0.986 (p = 0.0001) and CV values between 1.0 and 3.4%. Firm pressure with the 12 mm probe resulted in ICC values that ranged between 0.914 and 0.988 (p = 0.0001) with CV values between 0.7 and 2.1%. In addition, the repeatability SD was low across all frequencies implying that there was low intra-observer variability. Measurements taken by 2 observers with firm application of the 12 mm probe demonstrated moderate reproducibility between 9.8 and 156 kHz, the frequency range in which previous clinical studies have shown predictive association between high cervical resistivity and vaginal delivery: ICC values ranged between 0.528 and 0.638 (p < 0.05), CV values were between 3.3 and 5.2% and reproducibility SD values were also low. In contrast the 3 mm probe demonstrated poor reproducibility at all study frequencies. CONCLUSION: Measuring cervical resistivity by a single observer with both the 3 and 12 mm probes is highly repeatable whilst inter-observer reproducibility is poor with the 3 mm probe but moderately good when the 12 mm probe is firmly applied to the cervix in the frequency range 9.8 to 156 kHz, consistent with our observations of probe performance in clinical trials.

Impedance spectral measurements made through a membrane infection barrier.

Impedance spectra of superficial tissues can be used to detect pre-malignant changes in the cervix but require electrical contact to be made between a probe and the tissue. Using a membrane which is permeable to ions but forms a barrier to agents of infection should enable impedance spectra to be measured without causing an infection risk to the patient. The properties required of such a membrane are considered and measurements on two suitable membranes are presented. It is shown that impedance spectra can be measured through a thin natural cellulose based membrane (Cuprophan) and that these are not significantly different from directly measured spectra. The ability of the membranes to block a virus is tested using expired polio virus vaccine.

Comparison of human uterine cervical electrical impedance measurements derived using two tetrapolar probes of different sizes.

BACKGROUND: We sought to compare uterine cervical electrical impedance spectroscopy measurements employing two probes of different sizes, and to employ a finite element model to predict and compare the fraction of electrical current derived from subepithelial stromal tissue. METHODS: Cervical impedance was measured in 12 subjects during early pregnancy using 2 different sizes of the probes on each subject. RESULTS: Mean cervical resistivity was significantly higher (5.4 vs. 2.8 Omegam; p < 0.001) with the smaller probe in the frequency rage of 4-819 kHz. There was no difference in the short-term intra-observer variability between the two probes. The cervical impedance measurements derived in vivo followed the pattern predicted by the finite element model. CONCLUSION: Inter-electrode distance on the probes for measuring cervical impedance influences the tissue resistivity values obtained. Determining the appropriate probe size is necessary when conducting clinical studies of resistivity of the cervix and other human tissues.

Electrical impedance spectroscopy of the cervix in non-pregnant and pregnant women.

OBJECTIVES: We sought to validate and measure the electrical impedance of the uterine cervix in non-pregnant and pregnant women by spectroscopy. STUDY DESIGN: Cervical stromal impedance (CSI) was measured in 50 non-pregnant, 20 1st, 20 2nd and 50 3rd trimester pregnant women. The technique was also validated by comparing in vivo data to a finite element (FE) model of cervical tissue. RESULTS: CSI agreed well with the FE model and was highly reproducible in all study groups. Mean (S.E.) CSI at 4-819 kHz was higher in pregnant (2.78 +/- 0.09 Omega m) compared to non-pregnant (2.38 +/- 0.07, p < 0.01) women, and in the 3rd trimester (3.08 +/- 0.13) compared to non-pregnant (p < 0.01), 1st trimester (2.42 +/- 0.12, p < 0.001) and 2nd trimester (2.20 +/- 0.05, p < 0.001) pregnant women. CONCLUSION: Measurement of CSI provides a non-invasive method of assessing cervical tissue characteristics. Cervical extracellular matrix synthesis and leukocyte infiltration may account for the increased tissue impedance noted in the 3rd trimester.

Tactile information transfer: a comparison of two stimulation sites.

Two experiments on the discrimination of time-varying tactile stimuli were performed, with comparison of stimulus delivery to the distal pad of the right index finger and to the right wrist (palmar surface). Subjects were required to perceive differences in short sequences of computer-generated stimulus elements (experiment 1) or differences in short tactile stimuli derived from a speech signal (experiment 2). The pulse-train stimuli were distinguished by differences in frequency (i.e., pulse repetition rate) and amplitude, and by the presence/absence of gaps (approximately 100-ms duration). Stimulation levels were 10 dB higher at the wrist than at the fingertip, to compensate for the lower vibration sensitivity at the wrist. Results indicate similar gap detection at wrist and fingertip and similar perception of frequency differences. However, perception of amplitude differences was found to be better at the wrist than at the fingertip. Maximum information transfer rates for the stimuli in experiment 1 were estimated at 7 bits s(-1) at the wrist and 5 bits s(-1) at the fingertip.

Detection of cervical intraepithelial neoplasia using impedance spectroscopy: a prospective study.

OBJECTIVE: To compare cervical impedance spectrometry in the cervical epithelium of women with cervical intraepithelial neoplasia (CIN) and normal epithelium. DESIGN: Prospective observational study. SETTING: Colposcopy clinic, Jessop Wing, Royal Hallamshire Hospital, Sheffield, UK. POPULATION: Eighty-seven women referred to colposcopy with a moderate or severely dyskaryotic smear. METHODS: A pencil probe incorporating four gold electrodes was used to measure an electrical impedance spectrum from cervical epithelium. Colposcopy examinations, including probe positioning, were recorded by video to allow for correlation between results obtained from colposcopic impression, histopathological examination of colposcopically directed punch biopsies and the impedance measurements. MAIN OUTCOME MEASURES: Cervical impedance derived parameters R, S and C were assessed to see if there was a significant difference in values obtained in CIN and normal squamous epithelium. Analysis was based upon matching the electrical components measured to those identified by cellular modelling as being most sensitive for premalignancy. RESULTS: From normal epithelium through CIN 1 to CIN 2/3, R decreased by a factor of 4.5, S increased by a factor of 2.5 but C remained unchanged. CONCLUSIONS: Cervical impedance spectrometry provides a potentially promising screening tool with similar sensitivity and specificity to currently used screening tests, but with the potential advantage of providing instant results. Further work is currently being undertaken to improve the probe in its clinical use.

Stand-off electrode (SoE): a new method for improving the sensitivity distribution of a tetrapolar probe.

Tetrapolar probes have been widely used for measuring the impedance spectra of tissues. However, the non-uniform sensitivity distribution of these probes limits the ability to identify conductivity changes in tissue. This paper presents a novel method for improving the sensitivity distribution beneath a tetrapolar probe. The method consists of placing a hydrogel layer between the probe and the tissue in order to make the sensitivity positive everywhere within the tissue. Theoretical and measured sensitivity distributions are compared. A good agreement between theoretical and measured data from an electrolytic tank was obtained with a maximum error of 1.3%. In vivo forearm measurements showed that the use of a conductive layer does enable tissue conductivity spectra to be determined. A smaller variation between subjects was obtained when using the stand-off. It was not possible to assess the absolute accuracy of the method due to the absence of a 'gold standard' for the measurement of tissue conductivity spectra.

Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude.

Recent work suggests that treatment with inhaled beta(2)-agonists reduces the incidence of high-altitude pulmonary edema in susceptible subjects by increasing respiratory epithelial sodium transport. We estimated respiratory epithelial ion transport by transepithelial nasal potential difference (NPD) measurements in 20 normal male subjects before, during, and after a stay at 3,800 m. NPD hyperpolarized on ascent to 3,800 m (P < 0.05), but the change in potential difference with superperfusion of amiloride or isoprenaline was unaffected. Vital capacity (VC) fell on ascent to 3,800 m (P < 0.05), as did the normalized change in electrical impedance (NCI) measured over the right lung parenchyma (P < 0.05) suggestive of an increase in extravascular lung water. Echo-Doppler-estimated pulmonary artery pressure increases were insufficient to cause clinical pulmonary edema. There was a positive correlation between VC and NCI (R(2) = 0.633) and between NPD and both VC and NCI (R(2) = 0.267 and 0.418). These changes suggest that altered respiratory epithelial ion transport might play a role in the development of subclinical pulmonary edema at high altitude in normal subjects.