Accuracy of surrogate methods to estimate skeletal muscle mass in non-dialysis dependent patients with chronic kidney disease and in kidney transplant recipients.

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) and anthropometric predictive equations have been proposed to estimate whole-body (SMM) and appendicular skeletal muscle mass (ASM) as surrogate for dual energy X-ray absorptiometry (DXA) in distinct population groups. However, their accuracy in estimating body composition in non-dialysis dependent patients with chronic kidney disease (NDD-CKD) and kidney transplant recipients (KTR) is unknown. The aim of this study was to investigate the accuracy and reproducibility of BIA and anthropometric predictive equations in estimating SMM and ASM compared to DXA, in NDD-CKD patients and KTR. METHODS: A cross-sectional study including adult NDD-CKD patients and KTR, with body mass index (BMI) ≥18.5 kg/m2. ASM and estimated SMM were evaluated by DXA, BIA (Janssen, Kyle and MacDonald equations) and anthropometry (Lee and Baumgartner equations). Low muscle mass (LowMM) was defined according to cutoffs proposed by guidelines for ASM, ASM/height2 and ASM/BMI. The best performing equation as surrogate for DXA, considering both groups of studied patients, was defined based in the highest Lin's concordance correlation coefficient (CCC) value, the lowest Bland-Altman bias (<1.5 kg) combined with the narrowest upper and lower limits of agreement (LoA), and the highest Cohen's kappa values for the low muscle mass diagnosis. RESULTS: Studied groups comprised NDD-CKD patients (n = 321: males = 55.1%; 65.4 ± 13.1 years; eGFR = 28.8 ± 12.7 ml/min) and KTR (n = 200: males = 57.7%; 47.5 ± 11.3 years; eGFR = 54.7 ± 20.7 ml/min). In both groups, the predictive equations presenting the best accuracy compared to DXA were SMM-BIA-Janssen (NDD-CKD patients: CCC = 0.88, 95%CI = 0.83-0.92; bias = 0.0 kg; KTR: CCC = 0.89, 95%CI = 0.86-0.92, bias = -1.2 kg) and ASM-BIA-Kyle (NDD-CKD patients: CCC = 0.87, 95%CI = 0.82-0.90, bias = 0.7 kg; KTR: CCC = 0.89, 95%CI = 0.86-0.92, bias = -0.8 kg). In NDD-CKD patients and KTR, LowMM frequency was similar according to ASM-BIA-Kyle versus ASM-DXA. The reproducibility and inter-agreement to diagnose LowMM using ASM/height2 and ASM/BMI estimated by BIA-Kyle equation versus DXA was moderate (kappa: 0.41-0.60), in both groups. Whereas female patients showed higher inter-agreement (AUC>80%) when ASM/BMI index was used, male patients presented higher AUC (70-74%; slightly <80%) for ASM/height2 index. CONCLUSIONS: The predictive equations with best performance to assess muscle mass in both NDD-CKD patients and KTR was SMM-BIA by Janssen and ASM-BIA by Kyle. The reproducibility to diagnose low muscle mass, comparing BIA with DXA, was high using ASM/BMI in females and ASM/height2 in males in both groups.

Bioimpedance Spectroscopy for Assessment of Breast Cancer-Related Lymphedema: A Systematic Review.

Bioimpedance spectroscopy is currently used to evaluate patients with breast cancer-related lymphedema (BCRL). We aimed to describe published studies on the use of bioimpedance spectroscopy for assessment for BCRL. We queried the PubMed, Ovid Medline, and Embase databases to identify studies that evaluated the use of bioimpedance spectroscopy as an assessment tool. We searched for the keywords "bioimpedance" AND ("lymphedema" OR "lymphoedema"). We included English-language studies that reported the use of bioimpedance spectroscopy for assessment of BCRL. Out of 152, 116, and 235 articles identified in each database, respectively, only a total of 11 articles were included. Bioimpedance spectroscopy was studied as a method to assess and predict response to BCRL treatment, assess volume changes, and calibrate L-Dex scores for conversion to units of volume. All studies reported that bioimpedance spectroscopy is a promising tool for predicting response to BCRL treatment and measuring volume changes. Bioimpedance spectroscopy can be used for assessment of BCRL. However, the accuracy of bioimpedance spectroscopy for BCRL assessment has not been determined, and consequently further studies are needed.

Electrochemical impedance spectroscopy characterization of beverages.

This paper compares the results of standard chemical analytical processes and electrochemical impedance spectroscopy (EIS) in the characterization of different beverages, namely ground coffee, soluble coffee, coffee substitutes, barley, cow milk, vegetable drinks, tea, plant infusions and plant mixtures. For the two approaches, the similarities between the experimental data are assessed by means of the Euclidean and Canberra distances. The resulting information is processed by means of the multidimensional scaling (MDS) clustering and visualization algorithm. The results of the chemical analytical processes and EIS reveal identical clusters for the two adopted distances. Furthermore, the robustness of the experimental and computational scheme are assessed by means of the Procrustes technique. The results confirm the effectiveness of combining the EIS and MDS.

Towards mm-wave spectroscopy for dielectric characterization of breast surgical margins.

PURPOSE: The evaluation of the surgical margin in breast conservative surgery is a matter of general interest as such treatments are subject to the critical issue of margin status as positive surgical margins can undermine the effectiveness of the procedure. The relatively unexplored ability of millimeter-wave (mm-wave) spectroscopy to provide insight into the dielectric properties of breast tissues was investigated as a precursor to their possible use in assessment of surgical margins. METHODS: We assessed the ability of a mm-wave system with a roughly hemispherical sensitive volume of ∼3 mm radius to distinguish malignant breast lesions in prospectively and consecutively collected tumoral and non-tumoral ex-vivo breast tissue samples from 91 patients. We characterized the dielectric properties of 346 sites in these samples, encompassing malignant, fibrocystic disease and normal breast tissues. An expert pathologist subsequently evaluated all measurement sites. RESULTS: At multivariate analysis, mm-wave dielectric properties were significantly correlated to histologic diagnosis and fat content. Further, using 5-fold cross-validation in a Bayesian logistic mixed model that considered the patient as a random effect, the mm-wave dielectric properties of neoplastic tissues were significantly different from normal breast tissues, but not from fibrocystic tissue. CONCLUSION: Reliable discrimination of malignant from normal, fat-rich breast tissue to a depth compatible with surgical margin assessment requirements was achieved with mm-wave spectroscopy.

Changes in serum osmotic pressure following haemodialysis treatments lead to changes in bioimpedance spectroscopy estimates of lean and adipose tissue.

Haemodialysis (HD) patients are at risk of sarcopenia. Newer bioimpedance devices (BIS) using a three-compartmental body composition model, separate extracellular water overhydration from normo-hydrated lean tissue mass (LTM) and adipose tissue mass (ATM). During HD hydration status changes, along with changes in electrolytes and solutes, and may alter body composition measurements. As such, we measured BIS and serum osmotic pressure (sOP) pre- and post dialysis in 43 patients. There were no significant changes in LTM (39.5±15.1 vs 39.3±15.2 kg) or sOP (33.2±8.3 vs 35.9±9.7 mm Hg). Higher post-dialysis sOP was associated with a greater percentage fall in LTM (r=0.43, P=0.08) and increase in ATM (r=-0.43, P=0.017). Increased sOP post dialysis was associated with a reduction in LTM (r=0.36, P=0.033) and increased ATM (r=-0.44, P=0.013). Changes in sOP with HD are associated with changes in BIS body composition measurements. BIS measurements should preferably be made when patients are least overhydrated.

Factors affecting the use of impedance spectroscopy in the characterisation of the freezing stage of the lyophilisation process: the impact of liquid fill height in relation to electrode geometry.

This study aims to investigate the application of impedance spectroscopy using fixed electrode geometries on a standard glass vial in the characterisation of the freezing process of solutions at different fill liquid volumes. Impedance spectra (between 10 and 10(6) Hz) were recorded every 3 min, during the freezing cycle on a solution of 30 mg/mL sucrose contained within 10 mL glass vials having an electrode system (two thin copper foils: w, 18 mm; h, 5 mm) affixed to the external surface of the vial. A fill factor (Φ) was defined in terms of the relative height of the solution volume to the height of the electrodes from the base of the vial. Solution volumes of 1.5 to 5 mL (corresponding to Φ= 0.5-1.6) were investigated to establish the applicability of having a fixed electrode geometry for a range of solution volumes. A linear relationship between the time duration of the ice formation/solidification phase and the fill factor suggests that fixed electrode geometries may be used to investigate a range of fill volumes. The benefit of this approach is that it does not invade the solution and hence records the freezing process without providing additional nucleation sites and in a manner which is representative of the entire fill volume.

Electrical impedance spectroscopy as a potential adjunct diagnostic tool for cutaneous melanoma.

BACKGROUND: Previous studies have shown statistically significant differences in electrical impedance between various cutaneous lesions. Electrical impedance spectroscopy (EIS) may therefore be able to aid clinicians in differentiating between benign and malignant skin lesions. OBJECTIVES: The aim of the study was to develop a classification algorithm to distinguish between melanoma and benign lesions of the skin with a sensitivity of at least 98% and a specificity approximately 20 per cent higher than the diagnostic accuracy of dermatologists. PATIENTS/METHODS: A total of 1300 lesions were collected in a multicentre, prospective, non-randomized clinical trial from 19 centres around Europe. All lesions were excised and subsequently evaluated independently by a panel of three expert dermatopathologists. From the data two classification algorithms were developed and verified. RESULTS: For the first classification algorithm, approximately 40% of the data were used for calibration and 60% for testing. The observed sensitivity for melanoma was 98.1% (101/103), non-melanoma skin cancer 100% (25/25) and dysplastic nevus with severe atypia 84.2% (32/38). The overall observed specificity was 23.6% (66/280). For the second classification algorithm, approximately 55% of the data were used for calibration. The observed sensitivity for melanoma was 99.4% (161/162), for non-melanoma skin cancer was 98.0% (49/50) and dysplastic nevus with severe atypia was 93.8% (60/64). The overall observed specificity was 24.5% (116/474). CONCLUSION: EIS has the potential to be an adjunct diagnostic tool to help clinicians differentiate between benign and malignant (melanocytic and non-melanocytic) skin lesions. Further studies are needed to confirm the validity of the automatic assessment algorithm.

Analysis of concordance between the bioelectrical impedance vector analysis and the bioelectrical impedance spectroscopy in haemodialysis patients.

INTRODUCTION: The values of body composition provided by the two most commonly used bioelectrical impedance systems in Spain, single-frequency bioelectrical impedance vector analysis (SF-BIVA) and multi-frequency bioelectrical impedance spectroscopy (MF-BIS) are different and not comparable. OBJECTIVE: Analyse whether the inter-method variability is due to bioelectrical variables measured by the different monitors, or rather due to the equations used to calculate body volume and mass. Another objective was to determine whether, despite the inter-method variability, the classification of hydration status by the two methods is consistent. MATERIAL AND METHODS: Bioelectrical impedance was measured by SF-BIVA and MF-BIS immediately before a dialysis session in 54 patients on haemodialysis. In 38 patients, the study was repeated by SF-BIVA at the end of the same dialysis session. RESULTS: Resistance and phase angle values provided by the two monitors at a frequency of 50kHz were consistent. For resistance, variability was 1.3% and the intra-class correlation coefficient was 0.99. For phase angle, variability and the intra-class correlation coefficient were 11.5% and 0.92, respectively. The volume values for total body water, extracellular water, fat mass and body cell mass were biased, with a level of variability that would not be acceptable in clinical practice. The intra-class correlation coefficient also suggested a poor level of agreement. SF-BIVA systems define overhydration or dehydration as a vector below or above the tolerance ellipse of 75% on the longitudinal axis. MF-BIS uses two criteria for pre-dialysis hyper-hydration: overhydration (OH) greater than 2.5 litres, or greater than 15% of extracellular water. The degree of equivalence with the results of the SF-BIVA monitor was better with the second criterion (kappa: 0.81, excellent agreement) than with the first one (kappa: 0.71, acceptable agreement). The MF-BIS system defines post-dialysis normal hydration as a difference between OH and ultrafiltratation volume between ­1.1 and 1.1 litres and agreement with the SF-BIVA system for this parameter was acceptable (weighted kappa index: 0.64). CONCLUSIONS: The MF-BIS and SF-BIVA systems provide similar readings for bioelectrical parameters, and the wide variation in the quantification of volume and body mass must be attributed to the different equations used for calculation. Furthermore, the criteria used by both systems to define both pre- and post-dialysis hydration have an acceptable level of equivalence.

Adaptive frequency distribution for electrical bioimpedance spectroscopy measurements.

This paper presents a novel frequency distribution scheme intended to provide more accurate estimations of Cole parameters. Nowadays a logarithmic frequency distribution is mostly used in Electrical Bioimpedance Spectroscopy (EBIS) applications. However it is not optimized following any criterion. Our hypothesis is that an EBIS signal contains more information where the variation of the measurement regarding the frequency is larger; and that there ought to be more measuring frequencies where there is more information. Results show that for EBIS data with characteristic frequencies up to 200 kHz the error obtained with both frequency distribution schemes is similar. However, for EBIS data with higher values of characteristic frequency the error produced when estimating the values from EBIS measurements using an adaptive frequency distribution is smaller. Thus it may useful for EBIS applications with high values of characteristic frequency, e.g. cerebral bioimpedance.

Characterization of interdigitated electrode structures for water contaminant detection using a hybrid voltage divider and a vector network analyzer.

Interdigitated capacitive electrode structures have been used to monitor or actuate over organic and electrochemical media in efforts to characterize biochemical properties. This article describes a method to perform a pre-characterization of interdigitated electrode structures using two methods: a hybrid voltage divider (HVD) and a vector network analyzer (VNA). Both methodologies develop some tests under two different conditions: free air and bi-distilled water media. Also, the HVD methodology is used for other two conditions: phosphate buffer with laccase (polyphenoloxidase; EC 1.10.3.2) and contaminated media composed by a mix of phosphate buffer and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The purpose of this study is to develop and validate a characterization methodology using both, a hybrid voltage divider and VNA T-# network impedance models of the interdigitated capacitive electrode structure that will provide a shunt RC network of particular interest in detecting the amount of contamination existing in the water solution for the media conditions. This methodology should provide us with the best possible sensitivity in monitoring water contaminant media characteristics. The results show that both methods, the hybrid voltage divider and the VNA methodology, are feasible in determining impedance modeling parameters. These parameters can be used to develop electric interrogation procedures and devices such as dielectric characteristics to identify contaminant substances in water solutions.

Body fat and fat-free mass measured by bioelectric impedance spectroscopy and dual-energy X-ray absorptiometry in obese and non-obese adults.

The aim of the present study was to compare body fat mass (FM) and fat-free mass (FFM) estimates by bioelectric impedance spectroscopy (BIS), with respective estimates by dual-energy X-ray absorptiometry (DXA), in obese and non-obese subjects. Body composition was measured in ninety-three obese and non-obese men and women by BIS device, BodyScout (Fresenius Kabi, Bad Homburg, Germany) and DXA device, Lunar iDXA (GE Healthcare, Madison, WI, USA). Mean difference between the methods was analysed by t tests, and Bland-Altman plots were generated to further examine the differences between the methods. Mean difference between the estimates by DXA and BIS (ΔDXA - BIS and Bland-Altman 95 % limits of agreement) were as follows: FM 4·1 ( - 2·9, 11·2) kg and 4·5 ( - 2·9, 11·8) %, FFM - 4·1 ( - 11·2, 2·9) kg and - 4·5 ( - 11·9, 2·9) %, indicating large inter-individual variation and statistically significant underestimation of FM and overestimation of FFM by BIS, as compared to DXA. The underestimation of FMkg (FM measured in kg) and overestimation of FFMkg (FFM measured in kg) were more pronounced in men than in women, and the underestimation of FM% (FM measured in percent) and overestimation of FFM% (FFM measured in percent) were more pronounced in normal weight (BMI = 20·0-24·9 kg/m2) than in overweight and obese (BMI ≥ 25·0 kg/m2) subjects. BIS may be suitable for classification of a population into groups according to FM and FFM. However, the large inter-individual variation suggests that this BIS device with the proprietary software is insufficient for estimation of single individual body FM and FFM.

16-channel CMOS impedance spectroscopy DNA analyzer with dual-slope multiplying ADCs.

We present a 16-channel, mixed-signal CMOS DNA analyzer that utilizes frequency response analysis (FRA) to extract the real and imaginary impedance components of the biosensor. Two computationally intensive operations, the multiplication and integration required by the FRA algorithm, are performed by an in-channel dual-slope multiplying ADC in the mixed-signal domain resulting in minimal area and power consumption. Multiplication of the input current by a digital coefficient is implemented by modulating the counter-controlled duration of the charging phase of the ADC. Integration is implemented by accumulating output digital bits in the ADC counter over multiple input samples. The 1.05 mm×1.6 mm prototype fabricated in a 0.13 µm standard CMOS technology has been validated in prostate cancer DNA detection. Each channel occupies an area of only 0.06 mm² and consumes 42 µW of power from a 1.2 V supply.

Multichannel bipotentiostat integrated with a microfluidic platform for electrochemical real-time monitoring of cell cultures.

An electrochemical detection system specifically designed for multi-parameter real-time monitoring of stem cell culturing/differentiation in a microfluidic system is presented. It is composed of a very compact 24-channel electronic board, compatible with arrays of microelectrodes and coupled to a microfluidic cell culture system. A versatile data acquisition software enables performing amperometry, cyclic voltammetry and impedance spectroscopy in each of the 12 independent chambers over a 100 kHz bandwidth with current resolution down to 5 pA for 100 ms measuring time. The design of the platform, its realization and experimental characterization are reported, with emphasis on the analysis of impact of input capacitance (i.e., microelectrode size) and microfluidic pump operation on current noise. Programmable sequences of successive injections of analytes (ferricyanide and dopamine) and rinsing buffer solution as well as the impedimetric continuous tracking for seven days of the proliferation of a colony of PC12 cells are successfully demonstrated.

Electrochemical impedance spectroscopy in label-free biosensor applications: multivariate data analysis for an objective interpretation.

Electrochemical impedance spectroscopy plays an important role in biosensor science thanks to the possibility of finding specific information from processes with different kinetics at a chosen electrode potential in one experiment. In this paper we briefly discuss label-free impedimetric biosensors described in the literature. A novel method for neutral interpretation of impedance data is presented that includes complex number chemometrics. Three examples are given based on impedance measurements on synthetic biomembranes, in this case a lipid monolayer deposited on a mercury electrode. The interaction of various compounds with the monomolecular lipid layer is illustrated with the following: (1) different concentrations of magainin (Geladi et al. in Proc. Int. Fed. Med. Biomed. Eng. 9:219-220, 2005); (2) different derivatives of gramicidin A (Lindholm-Sethson et al. in Langmuir 24:5029-5032, 2007), and (3) an antimicrobial peptide (Ringstad et al. in Langmuir 24:208-216, 2008).