|Year : 2005 | Volume
| Issue : 1 | Page : 6-16
|Bioimpedance and Its Application
Thawee Chanchairujira1, Ravindra L Mehta2
1 Department of Medicine, Division of Nephrology, Siriraj Hospital, Mahidol University, Thailand
2 Department of Medicine, Division of Nephrology, University of California, San Diego, California, USA
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|How to cite this article:|
Chanchairujira T, Mehta RL. Bioimpedance and Its Application. Saudi J Kidney Dis Transpl 2005;16:6-16
| Introduction|| |
Body composition assessment is useful in a variety of clinical settings for obtaining information about nutritional condition and the status of body fluid compartments. ,,,,, Bioimpedance analysis (BIA) is an attractive technique for the purpose because it is safe, non-invasive, inexpensive and easy to use. BIA was first applied to determine total body water (TBW) by Hoffer et al. in 1969.  He proposed using the value of whole body impedance measured between hand and foot to determine total body water. The principle underlying this application is that biological conductivity is primarily within fat-free tissue as it contains virtually all of the water and conducting electrolytes in the body; impedance is inversely related to the volume of this tissue, and volume changes produce impedance changes. BIA was subsequently used to determine nutritional status by Luskaski in 1985.  The extension of TBW determination to fatfree mass (FFM) estimation relies on the assumption that TBW is a constant fraction of FFM, usually given as 73 %. ,,, Once total body water is known, the lean body mass (LBM) or fat-free mass can be calculated according to the following formula: LBM = TBW/0.73. According to the two-compartment body composition model, body fat can then be determined as follows: body fat = body weightLBM [Figure - 1]. Recently, BIA has been applied to determine nutritional parameters, ,,,, determine urea distribution volume,  assess "dry weight", ,,, and monitor body fluids in dialysis patients. , Many studies have applied the basic technique of BIA to estimate body composition in various clinical and research settings.
Bioimpedance analysis (BIA) measures the opposition of body cells and tissues to the flow of a small (less than 1 m Ampere) radiofrequency alternating electric current. The voltage drop between electrodes provides a measure of impedance (Z), which is the vector sum of the resistance (R) and the reactance (X).  Resistance is relatively low in lean tissue that contains large amounts of water and electrolytes, and relatively high in adipose tissue and bone. Reactance is the opposition to the flow of electric current due to capacitance of cell membranes. These parameters are linked mathematically as Z 2 = R 2 + X 2 .  In the human body, more than 90% of the measured impedance is composed of resistance, so the magnitude of Z is similar to that of R. 6 For this reason, most BIA applications use resistance, rather than impedance, to predict body composition. This review will focus on current bioelectrical theory and methods of impedance data analysis for the prediction and assessment of body fluid compartment volume [Table - 1], [Table - 2].
| Current Bioelectrical Impedance Analysis Theory and Technique|| |
Two types of BIA systems are currently available: single frequency and multiple frequencies. The single-frequency system uses 50 kHz single-frequency impedance as a surrogate measurement of TBW and fat-free mass. There are two types of multiple frequency systems, dual-frequency (low-high frequency) and multifrequency bioimpedance analysis or bioelectrical impedance spectroscopy (BIS), which theoretically can provide estimation of extracellular water (ECW), intracellular water (ICW) and TBW. 
Application of the BIA technique for whole body impedance measurement uses a tetrapolar surface electrode arrangement, consisting of two measurement electrodes (or voltage sensing electrodes) and two distally positioned drive electrodes (injecting current electrodes) [Figure - 2]. The bioimpedance machine introduces an alternating electric current (I) of about 800 pA into the body through the injecting electrodes placed on the hand and foot, and measures the voltage from sensing electrodes placed on the ipsilateral wrist and ankle. The current passes between the two sensing electrodes and generates voltages between different points in the body volume according to Ohm's law. The actual parameter measured with BIA is the voltage (Vo) that is produced between two voltage sensing electrodes. The measurement normally is expressed as a ratio, Vo/I, which is also called impedance (Z). Some BIA machines may also provide reactance and phase angle values.
| Series Resistance Model|| |
The series resistance model assumes that the body represents resistors in series. A number of biophysical assumptions are necessary to translate the resistance value to TBW, which include the assumption that the human body tissue can be represented as a single uniformly shaped cylinder with a constant intracellular/ extracellular water ratio (thus providing uniform conductance) and that a 50 kHz frequency will penetrate all cells equally. The electrical characteristics are linked to the geometry of the conductor. Therefore, the measurement of resistance permits one to determine the volume of a conductor. The resistance of a cylindrical volume conductor characterized by resistivity (ρ), cross-sectional area (A), and length (L) is R = ρL/A. The volume of a cylinder (V) is L x A. Hence V = ρL 2 /R.
Application of the formula to human subjects requires the assumption that the human body physically approximates a cylinder and uses subject height (H) as a surrogate measure of the conducting path length. Therefore, the basic relationship becomes TBW ~ H 2 /R. Historically, many single-frequency equations are calibrated against TBW measured by the isotopic dilution techniques, with empirical algorithms relating whole body impedance measurement to TBW as the following relationship: TBW = aH 2 /R + c, where H is the subject's height, R is the resistance (or whole body impedance) obtained by single-frequency BIA (usually 50 kHz), a is a proportionality constant specific for a given subject population, and c is a constant. In many of these algorithms other subject parameters such as weight, age, and sex have been included to improve the predictive power of the numerical relationship. This simplified approach results in correlation coefficients of 0.8 or greater attained in most studies. ,
| Parallel Resistance and Multi-Frequency BIA Model|| |
The parallel resistance model assumes that the body represents resistors in parallel. The resistance of ECW is an independent resistive component in parallel with the intracellular water (ICW) compartment [Figure - 3]. In the low frequency range (1-5 kHz), there is minimal conduction through the cells because of the high Z of the cell membrane capacitance (Cm), and the impedance is governed primarily by the properties of the ECW. At high frequency (100-500 kHz) the ICW becomes fully conductive, and the impedance is a function of both ECW and ICW. Estimation of ECW and TBW are obtained from the body impedance measurement at low and high frequency, respectively. The ICW compartment can then be obtained from the difference between TBW and ECW.
The parallel model is more consistent with human physiology than with the older series model.  Parallel single-frequency BIA appears to be useful for body cell mass (BCM) monitoring.  Fat-free mass estimates seem to be acceptable only when fluid status is normal. A recent review recommended that the single-frequency BIA be limited to studies in healthy subjects and some clinical populations in which ECW/ICW ratio is normal. 
| Multifrequency BIA and Cole-Cole Models|| |
Bioelectrical impedance spectroscopy (BIS), using multiple frequency scanning (10-50 frequencies, between 1 kHz and 1 MHz), may be more useful in assessing fluid compartments in patients with altered fluid distribution. , Since measured impedance is frequency dependent, using only two fixed frequencies (dual-frequencies, low-high frequencies) may provide an incomplete picture of the underlying physiologic response and can result in an erroneous estimate of fluid volume and distribution, especially in those with altered fluid status. In addition, there is a problem of deciding what pair of frequencies to use that would work accurately in all cases.
The Cole-Cole model can be computed graphically or mathematically using nonlinear curve fitting to extrapolate the impedance spectrum data to identify theoretical values of resistance at zero frequency (Ro) and at infinite frequency (R∞) for use as predictors of ECW and TBW, respectively. Resistance ICW (Ri) is then computed as 1/Ri = 1/R∞ - 1/Ro. The impedance locus in the curve, which is formed by plotting the complex Z plane (R and X) and the frequency varying from low to high, produces a semicircular relationship between R and X, with a depressed center [Figure - 4]. 
| Hanai's Mixture Theory|| |
Hanai's mixture theory treats the body as a concentrated nonconductive suspension of cells suspended in a conductive medium. The volume of extracellular compartment (Ve) can be estimated by the following formula:
Ve = 10 -3 k e (W 1/2 H 2 /Re) 2/3
k E = (KB 2/3ρe 2/3 /D 1/3 )
where Re is whole body extracellular resistance, W is body weight (in Kg), H is body height (in cm), k E is a function of resistivity of ECW (ρe, in Ω. cm), D body density (in kg/m 3 ), and K B is a dimensionless factor relating H to limb and trunk size.
The volume of intracellular compartment (Vi) is derived as follows:
where Kp = (ρe/ρi); ρi is the resistivity of ICW and Ri is whole body intracellular resistance.
This model attempts to relate impedance data more closely to biological reality rather than to a simple electrical model. The model has been validated with tracer dilution technique for TBW (deuterium dilution) and for ECW (Na bromide space).  However this model requires, in the absence of definitive data, assumed values for body density and tissue resistivities.
| Segmental vs Whole Body Bioimpedance|| |
Whole body resistance (also called wristto-ankle impedance) gives little information about alterations in trunk fluid content, since more than 90% of whole body resistance is caused by resistance in the limbs, while the limbs contribute only about 30% of total ECW.  This problem was attributed to different cross-sectional areas of arm, trunk, and leg segments. It has been observed that ECW estimated from whole body bioimpedance measurements is susceptible to changes in body position such as an apparent increase in ECW with orthostasis and a decrease with supine body position. , These changes can be explained by changes in regional fluid distribution in different parts of the body, which lead to changes in whole body bioimpedance and hence to spurious estimations of ECW. The change from a standing to a supine body position causes regional fluid shift from peripheral (legs) compartments to the central compartment (trunk) and leads to a marked increase in whole body impedance. Therefore the standardization procedures for measuring whole body impedance are essential. The optimal method for obtaining impedance measurements-though not always practical in a clinical setting-involves having the subject (preferably having fasted) lie supine for at least 10 minutes. Some investigators have used bioimpedance measured from one segment with well-characterized geometry, such as the lower leg or the forearm, and related changes in segmental measurement to changes in body hydration in dialysis patients; however, because extracellular fluid may shift between segments without being removed from the body, measurements in one segment will be subject to the same inaccuracies as measurement using the whole body technique.
The sum of segmental bioimpedance (SBIA) technique has been introduced to account for fluid shifts between segments. , This technique assumes that the body can be considered as five interconnecting segments or cylinders: two legs, two arms and the trunk. Body segmental impedance is obtained by standard tetrapolar electrodes and two additional sensing electrodes at acromion and upper anterior iliac spine to measure the resistance of the arm, trunk and leg segments separately [Figure - 2]. The compartmental distribution of fluid in each segment is estimated from the segmental resistance, which are summed to derive the total body fluid compartment. Recent studies have shown that SBIA may be more accurate in measuring ECW changes than whole body impedance, as SBIA is less affected by change of body position. 
| Phase Angle|| |
Phase angle is an alternate approach for bioelectrical impedance analysis, without the need to know the subject's height.  The phase angle is the arc tangent of the X/R ratio, which is the phase difference between voltage and current and is determined by the reactive component of Z. Phase angle can range in theory from 0 to 90 degrees; 0 degrees if the circuit is only resistive (a system with no cell membranes) and 90 degrees if the circuit is only capacitive (a system of membranes with no fluid). The phase angle may be clinically useful because it should respond to changes in the ICW/ECW ratio, which is a more sensitive measurement of malnutrition and illness than either ICW or ECW alone [Figure - 4]. 
Chertow et al., in a study of 3009 hemodialysis patients, reported direct correlation among phase angle and BCM and traditional biochemical nutritional surrogates, including creatinine, albumin and prealbumin. , The range of the mean phase angle (determined at 50 kHz) in these hemodialysis patients was much narrower than that of a healthy population. After adjusting for age, sex, race, and several biochemical indicators of nutritional status, dialysis patients with a phase angle <3 0 had a threefold increase in mortality. Phase angle has been reported as an independent predictor of survival in hemodialysis , and peritoneal dialysis patients,  and as a more powerful predictor of survival than the usual nutritional indexes in HIV patients.  Changes in phase angle may reflect the derangement in the electrical charge in the cell membrane. The relation between phase angle and mortality in dialysis patients could be explained by a reduction in body cell mass or overhydration or both.  However, it is not clear physiologically what phase angle means. More studies are needed to understand the exact biological meaning of this parameter and its abnormalities in various disease conditions.
| R-X Plots|| |
The R-X plot, a graphical method for analyzing single frequency impedance data, was introduced by Piccoli et al. for use as an operational clue to assess dry weight in hemodialysis patients.  The vector of R and X are standardized for the subject's height and expressed as R/H and X/H in Ohm/m. The bivariate 95% confidence limits for the impedance vectors are calculated and plotted as their confidence ellipses. The confidence ellipses for different subject groups may then be compared with each other and with the healthy reference population. The method maybe useful as a screening or monitoring tool, but is unsuitable for evaluating absolute value of body fluid compartments.
| Ri/Re Ratio or ECW/ICW (E/I) Ratio|| |
Total body water contains ICW, which reflects the water content of the BCM, which is assumed to be stable in the steady state, and changes of TBW will reflect the changes in volume status [Figure - 5]. However in some clinical situations, BCM may change in subtle amounts over short periods of time, or dramatically over longer periods (in response to nutritional status change or illness). Using TBW as an index for assessing volume status or muscle mass, without considering body composition (muscle vs. fat vs. edema), will result in under- or overestimation of volume status in some patients. This limitation may be particularly important in persons with end-stage renal disease, given extracellular fluid retention due to impaired salt and water excretion, and diminished muscle mass secondary to limited exercise tolerance, insufficient dietary protein intake, and frequent catabolic stresses. E/I ratio may be advantageous in detecting body composition changes, since either increase in ECW or decrease in ICW will give higher E/I ratio [Figure - 5].  The E/I ratio may be a good parameter for tracing fluid compartment changes, especially in patients with altered fluid distribution.
The Ri/Re ratio is the ratio of impedances measured at a high and a low frequency, and it may be used as an index of the relative sizes of ICW and ECW. , The change in this ratio may be clinically informative in the absence of the need for absolute values for TBW and ECW, thus avoiding errors inherent in the use of any prediction equation. 
| Accuracy and Limitations|| |
All models of BIA measurement require the following conditions: 1) constancy of temperature; 2) constancy of body fluid conductivities; and 3) defined body posture during measurements. For accuracy, well-stan dar dized conditions are needed, such as fasting condition, posture, and timing of measurement after supine position or after hemodialysis. , The subject should have abstained from strenuous exercise, excess alcohol consumption, and use of diuretic substances prior to exam. Accurate measurement of the subject's height and weight is essential, because these parameters are commonly included in formulas used to estimate body composition from BIA measurements. Over- or underestimation of height by 2.5 cm has been shown to cause an error of 1.0 liters of TBW. Over-or underestimation of weight by 1 kg can cause an error of 0.2 liters of TBW. Thus, subjects should have stature measured to the nearest 0.5 cm and weight determined to the nearest 0.1 kg. The electrodes must be accurately placed since displacement by as little as 1.0 cm can easily result in a 2% or greater change in the resistance value. 
Although all BIA equations have been derived and validated against other reference body composition techniques, only a few have been cross-validated in independent target populations. The single-frequency (series and parallel models), the multifrequency or Cole-Cole model, and the Hanai mixture model have not been rigorously evaluated in large population studies for accuracy and sensitivity. Since series BIA requires the use of prediction equations to estimate body composition, its fat is very limited. In contrast, serial BIA measurement using the single-frequency parallel transformed model and the multifrequency BIA approach may provide more acceptable estimates of BCM and FFM, even for those patients undergoing significant weight loss.
Both the whole body BIA and the sum of segmental BIA technique can be used to track relative extracellular fluid (ECF) volume changes in hemodialysis patients; , however, they are not accurate in quantifying change of the absolute ECF volume.  Segmental measurements may be more useful in certain clinical settings, such as in patients with significantly abnormal fluid distributions such as burns, liver disease with ascites or amputated limbs. In the hospital setting, particularly among the acutely or critically ill, the role of BIA has not been clearly defined.  Disturbances of ICW and ECW, for example, often accompany organ dysfunction, severe malnutrition, injury and/or inflammation. Use of multifrequency BIA to monitor changes in ECW or the ECW/BCM ratio may prove useful in these situations, but more clinical research is clearly needed to clarify and validate the appropriate applications.
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Department of Medicine, Division of Nephrology, Siriraj Hospital, Mahidol University
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2]
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