principles of bioelectrical impedance analysis--by rudolph j. liedtke

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Principles of Bioelectrical Impedance Analysis Rudolph J. Liedtke (1-Apr-1997) History In 1940, clinically induced changes in hydration status were first correlated with total body changes in resistance and capacitive reactance (1). Also in 1940, Dr. Jan Nyboer pioneered work relating bioelectri- cal impedance changes to dynamic changes in pulsatile blood flow to organs, arterial pulse waveforms and respiration (19). The applications of impedance plethysmography, (the term given to the measure- ment of electrical impedance changes across limbs, organs and other body sites to detect dynamic blood volume changes), have been extensively validated by numerous investigators (9, 21, 24). A relationship between TBW and electrical impedance was first reported by Thomasett in 1962 (24) and further delineated by Hoffer, et.al. in 1969 (7). There were no subsequent attempts for over a decade to determine the usefulness of impedance for the analysis of human body composition. In 1983, Nyboer applied the electrical volume resistivity principals of impedance plethysmography to the study of body composition using static total body impedance measurements (15). Since that time, when RJL Systems pioneered BIA sciences, with the help of Dr. Jan Nyboer, until today (4/97) the utility and reliability of whole body impedance measurements to assess body water and composition has been reported by hun- dreds of peer review papers and thousands of abstracts. This brief essay will try to explain the physics and electrical nature of BIA. Resistance, Reactance and Phase Angle Resistance All substances have resistance to the flow of an electric direct current (DC). For example, metal conduc- tors such as copper have resistance in millions where as insulators have resistances in mega-mega ohms (1 X 10 12 ). Ohm’s law states that the resistance of a substance is proportional to the voltage drop of an applied current as it passes through a resistive substance, or Resistance(ohms) = appied voltage drop ( volts) current ( amps ) An ohm is a unit of electrical resistance equal to the resistance of a circuit in which an electromotive force of one volt maintains a current of one ampere. An ampere is a unit representing the rate of charge flow in a conducting medium, whereas a volt is a practical unit of electrical work. Pure electrical resis- tance (resistors with no reactance) is the same when applying direct current and alternating current at any frequency. In the body, highly conductive lean tissues contain large amounts of water and conducting electrolytes, and represent a low resistance electrical pathway. Fat and bone, on the other hand, are poor conductors or a high resistance electrical pathway with low amounts of fluid and conducting electrolytes.

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Bioelectrical impedance measurement

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Page 1: Principles of Bioelectrical Impedance Analysis--by Rudolph J. Liedtke

Principles of Bioelectrical Impedance Analysis

Rudolph J. Liedtke (1-Apr-1997)

History

In 1940, clinically induced changes in hydration status were first correlated with total body changes inresistance and capacitive reactance (1). Also in 1940, Dr. Jan Nyboer pioneered work relating bioelectri-cal impedance changes to dynamic changes in pulsatile blood flow to org ans, arterial pulse wav eformsand respiration (19). The applications of impedance plethysmography, (the term given to the measure-ment of electrical impedance changes across limbs, organs and other body sites to detect dynamic bloodvolume changes), have been extensively validated by numerous investigators (9, 21, 24).

A relationship between TBW and electrical impedance was first reported by Thomasett in 1962 (24) andfurther delineated by Hoffer, et.al. in 1969 (7). There were no subsequent attempts for over a decade todetermine the usefulness of impedance for the analysis of human body composition. In 1983, Nyboerapplied the electrical volume resistivity principals of impedance plethysmography to the study of bodycomposition using static total body impedance measurements (15). Since that time, when RJL Systemspioneered BIA sciences, with the help of Dr. Jan Nyboer, until today (4/97) the utility and reliability ofwhole body impedance measurements to assess body water and composition has been reported by hun-dreds of peer review papers and thousands of abstracts. This brief essay will try to explain the physicsand electrical nature of BIA.

Resistance, Reactance and Phase Angle

Resistance

All substances have resistance to the flow of an electric direct current (DC). For example, metal conduc-tors such as copper have resistance in millions where as insulators have resistances in mega-mega ohms(1 X 1012). Ohm’s law states that the resistance of a substance is proportional to the voltage drop of anapplied current as it passes through a resistive substance, or

Resistance(ohms) =appied voltage drop (volts)

current (amps)

An ohm is a unit of electrical resistance equal to the resistance of a circuit in which an electromotiveforce of one volt maintains a current of one ampere. An ampere is a unit representing the rate of chargeflow in a conducting medium, whereas a volt is a practical unit of electrical work. Pure electrical resis-tance (resistors with no reactance) is the same when applying direct current and alternating current atany frequency.

In the body, highly conductive lean tissues contain large amounts of water and conducting electrolytes,and represent a low resistance electrical pathway. Fat and bone, on the other hand, are poor conductorsor a high resistance electrical pathway with low amounts of fluid and conducting electrolytes.

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Reactance

Reactance, also known as capacitive reactance when describing biological tissues, is the opposition tothe instantaneous flow of electric current caused by capacitance. Mathematically reactance is expressedby the following equation in alternating current (AC) circuits:

Reactance(ohms) =1. 0

2 • π • frequency • capacitance

Where:

Reactance is expressed in OhmsFrequency is expressed in HertzCapacitance is expressed in FaradsPI = 3.1428

Farads are large units of measurement and are usually expressed in smaller fractions, such as micro-Farads (1 X 10-6) or pico-Farads (1 x 10-12). The above equation demonstrates that reactance is thereciprocal of frequency and capacitance, therefore, reactance decreases as frequency increases. Atextremely low frequencies reactance is virtually infinite. A capacitor consisting of two plates separatedby a thin air wafer to insulate the plates, would have less reactance than if the plates where larger in sur-face area. In addition, if the plates where further separated by the air wafer the reactance would increase.In biological conductors for example, the smaller the semi-permeable membrane volume or the smallerquantity of membranes the greater the reactance. This is the opposite of what one would expect. Gener-ally, high reactance values from a bioelectrical impedance measurement indicate better health and cellmembrane integrity. The reason for this paradox is in visualizing the proper model of a single resistorand capacitor in a series or parallel combination. Ideally reactance should be expressed in capacitance ata giv en frequency. Capacitance is independent of frequency and indirectly defines cell membrane vol-ume. The mathematical transformations to resolve this problem will be discussed later.

By definition, a capacitor consists of two or more conducting plates separated from one another by aninsulating, or non-conductive material known as a dielectric. Capacitors will store a charge of electronsfor a period of time depending on the resistance of the dielectric. The amount of charge a capacitor willhold is determined by:

C =Q

E=

W 2

E2

Where:

Q = Quantity of electricityC = Capacitance in FaradsE = Applied voltage drop (volts)W = Energy in Joules (Watt seconds)

In the healthy living body, the cell membrane consists of a layer of non-conductive lipid material sand-wiched between two layers of conductive protein molecules. The structure of cell membranes makesthem capacitive reactive elements which behave as capacitors when exposed to an alternating current(See image below). Biologically, the cell membrane functions as a selectively permeable barrier separat-ing the intracellular and extracellular fluid compartments. It protects the interior of the cell while

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allowing passage of some materials to which it is permeable. The cell membrane maintains a fluidosmotic pressure and ion concentration gradient between the intracellular and extracellular compart-ments. This gradient creates an electrical potential difference across the membrane which is essential tocell survival. Damage to the cell membrane, and its functions, is as lethal to the cell as direct damage tothe nucleus itself.

Theoretically, reactance is a measure of the volume of cell membrane capacitance and an indirect mea-sure of the intracellular volume or body cell mass. Whereas, body fat, total body water and extracellularwater offer resistance to electrical current, only cell membranes offer capacitive reactance. Since fat tis-sue cells ARE NOT SURROUNDED BY CELL MEMBRANES, reactance is not affected by the quan-tity of body fat.

bilayer

lipid

and extracellular volume.

bilayer

lipid

��������������������

��������������������

converted to their PARALLEL

equivalent of impedancemeasure the SERIES

directly. These values are

All RJL instruments

dielectric

Capacitor

pumpprotein

Electrical capacitor in PARALLEL with a resistor.

Capacitance is analogous to intracellular volumeand resistance is analogous to extracellular volume.

protein

channel

protein

The outer boundary of the cell is a plasma membrane ofphospholipid molecules which become a dielectric to forman electrical capacitor when a radio frequency signal is introduced to the cells environment.

Resistor

equivalent to predict intracellular

extracellular space

The Plasma Membrane of a Cell and its Electrical Equivalent

Cytoplasmintracellular space

Phase Angle

Phase angle is a linear method of measuring the relationship between resistance and reactance in seriesor parallel circuits. Phase angle can range from 0 to 90 degrees; 0 degrees if the circuit is only resistive(as in a system with no cell membranes) and 90 degrees if the circuit is only capacitive (all membraneswith no fluid). A phase angle of 45 degrees would reflect a circuit (or body) with an equal amount ofcapacitive reactance and resistance, such as in fresh vegetables.

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Normal statistics

The National Health and Nutrition Examination Survey (NHANES) is a periodic survey conducted byNCHS. The third National Health and Nutrition Examination Survey (NHANES III), conducted from1988 through 1994, was the seventh in a series of these surveys based on a complex, multi-stage sampleplan. It was designed to provide national estimates of the health and nutritional status of the UnitedStates civilian, noninstitutionalized population aged two months and older.

Normal Phase Angle from NHANES III

Males (n = 8545) Females (n = 9115)Parameter Phase Angle Age Phase Angle Age

Mean 7.80 42.56 7.23 42.76± SD 1.25 21.16 1.07 21.06Range 6.19 - 8.83 12 - 90 5.98 - 8.04 12 - 90

Phase angle of a resistorand capacitor in series

Resistance

Rea

ctan

ce Impedance

Phase angle ( )φ

ReactanceResistance

Phase angle ( ) = arctanφ

The average phase angle for a healthy individual is approximately 6 to 9 degrees, depending on gender.Lower phase angles appear to be consistent with low reactance and either cell death or a breakdown inthe selective permeability of the cell membrane. Higher phase angles appear to be consistent with highreactance and large quantities of intact cell membranes and body cell mass.

Resistance and Capacitance in Parallel and Series

The human body consists of resistance and capacitance connected in parallel and in series. A circuitmodel will be used to illustrate this point. When two or more resistors and capacitors are connected inseries, they hav e an orientation to each other as seen in the series frame. In the series pathway, two ormore resistors and capacitors are equal to impedance (Z) as the vector sum of their individual resistanceand reactance since both are expressed in Ohms. When two or more resistors and capacitors are con-nected in parallel, they hav e an orientation to each other as seen in the parallel frame.

In the parallel pathway, two or more resistors and capacitors are equal to impedance as the vector sum oftheir individual RECIPROCAL resistances and reactance.

Series impedance2 = resistance2 + reactance2

Parallel1

impedance2=

1

resistance2+

1

reactance2

Converting a series model to a parallel model

Resistanceparallel = Resistanceseries +Reactance2

series

Resistanceseries

Reactanceparallel = Reactanceseries +Resistance2

series

Reactanceseries

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In vivo, the human body is a mixture of resistance and reactance in both parallel and series orientations.Bioelectrical impedance models which assume the human body consist only of resistance and capaci-tance in series and would invalidate sciences which depend upon direct current conduction, such as elec-trocardiography and galvanic skin response (direct current will not flow through a capacitor). With therealization that the human body consists of resistance and capacitance both in parallel and series orienta-tions, the knowledge of reactance quantities becomes essential for the accurate determination of cellularbody composition compartments.

The simplest biological equivalent model is a single resistor and capacitor in parallel. This network maybe analyzed with a single frequency of 50 Khz. There is some degree of validity to this model since itcan be conceived that cells and their supporting mechanisms are not a series of extracellular and intracel-lular components but reside in parallel with a small series effect from the nucleolus of the cells. There isa major effect contributed by electrode length (or stature height) and must always be a variable to correctresistance and/or reactance independent variables used in prediction equations.

Typical total body bioelectrical impedance (BIA) measurements display the vectors of resistance andreactance which are intrinsically based on a series network (resistor and capacitor in series). Resistanceis indirectly related to the extracellular mass and reactance is indirectly related to the intracellular mass.These measured resistance and reactance values are highly interactive with each other in a simple paral-lel network, and are obscure when not mathematically transformed to an equivalent parallel model. AllBIA measurements assume an equivalent series model and must be transformed to their parallel equiv-alent. The transformation is shown in the series to parallel transformation frame.

The transformed parallel equivalent of Xc and R are the close approximations of the real electrical val-ues of the biological tissue assuming an equivalent parallel model of a single resistor and capacitor.

Total Body Measurements

The measurement of total body impedance (resistance and reactance) from a macroscopic perspective isthe vector sum of resistance and reactance in the limbs and torso. The limbs, because of the smaller cir-cumference and greater length, contribute to most of the impedance. The torso impedance ranges from15 to 30 ohms depending on the physical size of the subject. This is approximately 5.5 % of the totalbody when compared to a typical total body impedance of 450 ohms for males.

The impedance of a geometrical system, in this case the human body, is related to conductor length andgeometrical size, its cross-sectional area and signal frequency (18). Using a constant signal frequencyand fairly constant configuration, the body’s impedance to current flow can be related to its volume,since conductor volume equals the cross-sectional area x length or height.

Resistance = ρLength

AreaMultipling by

Length

Lengthor 1. 0

Then

Resistance = ρLength2

VolumeVolume = ρ

Length2

Resistance

ρ (rho) is determined statistically when applied to whole body prediction equations.

Determining body composition using any method, volume or TBW must be known. Electrically deter-mined TBW is equal to the L2/R, multiplied by a coefficient and constant (y intercept). This coefficientis the relative volume resistivity per cubic liter of ionic water distributed in organized tissues for males

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and females (23). It is numerically less in adult males as a group. When measuring TBW withimpedance the mathematical coefficients of length (or height) L2/R, weight and the associated constantsfor males and females are the only variables subject to change.

A complex impedance measurement assesses both resistance and reactance, including phase shift, orphase angle Ø which develops between the alternating current being passed through the body and thevoltage drop across the body. At a fixed frequency, such as in the RJL BIA 50 Khz instruments, anincrease in the phase angle and reactance represents an increase in the ratio of charge stored per potentialdifference, or voltage drop across the body.

Whole body impedance and muscle resistivity measured by Settle contralaterally (using the tetrapolarmethod) were both found to have a frequency of approximately 50 KHz. For this reason, muscle, as alarge portion of body volume, is considered primarily responsible for the total body impedance measure-ment (23).

Static impedance measurement of any homogeneous conductor describe its absolute electrical volume.When the resistivity of the conductive material is known then the electrical volume equals the physicalvolume. This general principle is easily applied to simple geometric shapes. When applied to the com-plex geometry of the human body, some difficulties arise. Total body resistance and reactance measuredby Settle from the wrist to the contralateral ankle was found to closely resemble the complex impedanceproperties of muscle tissue (23). In earlier studies by Hoffer (1970), (using a tetrapolar electrode tech-nique), TBW was measured using tritium oxide dilution and total body impedance with a Hewlett-Packard Model 200CD oscillator at 100 KHz with a vacuum tube volt meter (7) (Impedance not resis-tance and reactance). A significant correlation coefficient of -.70 was found between subject height2/Z.This correlation improved to .92 in healthy subjects and .93 in patients with various diseases when a lin-ear regression of TBW versus subject height2/Z was performed. Despite this strong correlation in agroup of patients (some with hydration disorders), there was a large standard deviation of 11% or 3.84liters between predicted TBW and observed TBW (7).

In 1996 Kotler reported: "Predictive equations for body cell mass (BCM), fat free mass (FFM), and totalbody water (TBW) were derived from direct measurements through use of single-frequency bioelectricalimpedance analysis (BIA) in 322 subjects, including white, black, and Hispanic men and women, whowere both healthy control subjects and patients infected with the human immune deficiency virus (HIV).Preliminary studies showed more accurate predictions of BCM when parallel-transformed values ofreactance were used rather than the values reported by the bioelectrical impedance analyzer. Modelingequations derived after logarithmic transformation of height, reactance, and impedance were more accu-rate predictors than equations using height2/resistance, and the use of sex-specific equations furtherimproved accuracy. The effect of adding weight to the modeling equation was less important than theBIA measurements. The resulting equations were validated internally, and race and disease (HIV infec-tion) were shown not to affect predictions. The equation for FFM was validated externally againstresults derived from hydrodensitometry in 440 healthy individuals; the SEE was < 5%. These resultsindicate that body composition can be estimated with simple and easily applied techniques, and that theestimates are sufficiently precise for use in clinical investigation and practice". Am J Clin Nutr1996;64(suppl):489S-97S.

Reproducibility

Electrical impedance prediction equations for assessing TBW and LBM are based on the variables oftotal body resistance, height and to weight. The variable height is the standing height of the subject andweight is the mass of the subject measured by a medically accepted weight scale. The resistance variable

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is the resistance measured by the impedance analyzer’s detecting electrodes in ohms. When protocolsare followed, the reproducibility in measuring total body water and lean body mass will approximate the.99 test-retest correlation coefficient as reported by Lukaski, et.al. (14) of the United States Departmentof Agriculture, Human Nutrition Research Center, in numerous studies using the RJL BIA instruments(12,13,14).

"No significant difference (p > 0.05) was found among resistance values determined on five successivedays. The individual coefficients of variation for these resistance values ranged from 0.9 to 3.4%, andthe average precision was 2%. Test-retest correlation coefficient was .99 for a single resistance measure-ment and the reliability coefficient for a single resistance measurement over 5 days was .99" (13).

Dr. Karen R. Segal, et.al. of the Department of Medicine, College of Physicians and Surgeons, ColumbiaUniversity at St. Luke’s-Roosevelt Hospital Center also reported:

"The Biological Impedance Analyzer resistance readings were extremely stable. Theyexhibited virtually no change within the five measurements when the electrodes were keptin place. The accuracy of the measurement of resistance was checked using 250, 400, 500and 750 ohm precision resistors. The measured resistance did not deviate from the expectedvalues by more than ± 2%"(22).

BIA is the most reproducible technique available to assess body composition, assuming electrode proto-cols are followed. It is this characteristic that allows BIA to track change, both long term (days, months)and short term (minutes, hours). If any method of evaluation does not have repeatability, it can not havesensitivity to change. The specificity of BIA has been proven by hundreds of validation studies through-out the world over the past ten years (see abstracts). Recently, the sensitivity of BIA (TBW, FFM,BCM) has been positively shown with long term studies of Kotler (HIV wasting disorders) and Lukaski(controlled weight loss). (papers in publication) These studies had remarkable correlations to criterionmethods of dual X-Ray absorptiometry (DEXA) and K40 total body isotope counting (K40).

Measurement Technique

Whole body electrical impedance is measured by passing a small constant alternating current (I) throughthe body and measuring the voltage drop (V) produced as a product of R X I, since I is constant V isdirectly proportional to R. A shift in the phase angle between the current and voltage defines reactanceor a complex impedance measurement including the dielectric nonconducting space attributed to cellmembrane capacitance.

Electrode placement, measurement frequency and skin impedance are the primary procedural specifica-tions that must accompany impedance data. Skin impedance ranges from approximately 300 to one mil-lion ohm/cm. To accurately assess body volume electrically, skin impedance must be bypassed usingeither the two electrode or four electrode techniques. The two electrode technique used by Thomasetthas several limitations (24). Results from this technique are often irreproducible due to excessive inter-ference by electrochemical reactions at the subcutaneous needle electrode surface causing additionalelectrode polarization anomalies. In addition, the small diameter of the electrode needles results in amuch greater current density near the electrodes than in the rest of the body. Therefore, the integrity oftissue near the electrodes and electrode size can effect the impedance measurement between electrodes,and confuse desired data (23).

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current source

electrodeCurrent source

Sinusoidal constant

DetectingelectrodeDetecting

electrodeelectrodeCurrent source

Constantcurrentsource

Phase sensitivevoltmeter

Measured biologicalresistance and

reactance

High inputimpedance

The four electrode techniques used by RJL Systems largely avoids these difficulties. Four surface elec-trodes are used situated either ipsilaterally or contralaterally on the dorsal surfaces of the right hand andfoot at the distal metacarpals and metatarsals, respectively, and the distal prominences of the radius andulnar and between the medial and lateral malleoli at the ankle. The RJL System delivers 800 uA at 50KHz which is passed between the outer two electrodes. The voltage drop between the inner two is mea-sured with a high input impedance amplifier. The impedance of the skin and the electrode polarizationimpedance does not effect the measurement of total body impedance with the four surface electrodetechnique since negligible current is drawn through the skin by the passively coupled input circuits. Thefour surface electrode technique utilizing a constant deep homogeneous electrical field in the variableconductor of the human body also minimizes problems with field distribution and electrode irregulari-ties. The constant current source is regulated to ± 1% accuracy from 0 to 8,000 ohms. The detectingelectrodes have input characteristics that do not require complex electrodes or conductive bands.

Safety

The safety of bioelectrical instrumentation is assessed by two parameters. One is the aspect of electricalisolation from ground potentials for the subject. The second is the definition of what is a harmless cur-rent vs. frequency that can be deliberately introduced into the subject. There are few references that haveexplicitly established the standards for what is a safe subject current and frequency. Dr. L.A. Geddes andL.E. Baker in Applied Biomedical Instrumentation describe the threshold of electrical perception ofalternating currents of varying frequency (4). At frequencies of 50 to 60 Hz (those used in power lines),nerve and muscle cells are stimulated. The sensation threshold is a few uA while pain and involuntarymuscle contractions occur with much higher currents (80). Due to the large magnitude of cell mem-brane capacitance, the sensation and pain thresholds increases an order of magnitude as frequenciesincrease (4). The RJL Systems impedance analyzers have a precision oscillator tuned to 50 KHz. Thisoscillator is connected to a network of transformer coupled feedback circuits to generate a constant cur-rent at the subject source electrodes. The constant current supply has an accuracy of 1% from 1 to 8,000

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ohms at 800 microamps RMS maximum. Geddes and Baker determined that the pain threshold at thisfrequency would be approximately 40 milliamps (4). This is 50 times the nominal current of these twoinstruments. Therefore the high frequency currents used by RJL BIA products present no hazard to thesubject. There have been many applications of electrical impedance plethysmography at frequenciesfrom 10 KHz to 5 MHz that have been introduced to critical human organs. Nyboer and Kornmesser(20) applied an impedance plethysmograph (designed and built by Rudolph J. Liedtke) to the area of theuterus to monitor pregnancy labor movements. There were no reported abnormalities after these obser-vations using this method. The instruments that were used had a frequency of 100 KHz (crystal con-trolled) at approximately 3 milliamps. Bishop and Nyboer (2) applied the same instrument directly to theeye with an electrode array configured in a contact lens with no ill effects at this frequency and current(100 KHz at 3 milliamps). In addition, Nyboer (21) applied this equipment to many areas of the humanbody to pioneer the clinical application of electrical impedance plethysmography. In a personal commu-nication to the author "we never hav e had any ill effects from the application of this equipment."

The National Aeronautics and Space Administration (NASA) published an extensive book titled Devel-opment and Evaluation of an Impedance Cardiographic System to Measure Cardiac Output and OtherCardiac Parameters by W.G. Kubicek (9). In this publication an electrical impedance plethysmograph isapplied directly to the thorax to predict cardiac output. The source electrode frequency is 100 KHz at 4milliamps. There were no published hazards at this frequency and current.

There are several institutions that are able to evaluate medical electronic instruments for electrical isola-tion standards of safety. Underwriters Laboratories (UL) has had the most experience in specifying elec-trical safety standards. In addition, most cities or states have their own standards and companies to makethese determinations. The RJL Systems instruments has been approved by the ITT Research Institute ofChicago, Illinois for electrical isolation safety. In addition, many international safety institutes haveapproved all RJL products for safety. The never been a rejection of a IRB approval based on BIA sci-ences.

References

1. Barnett, A.: Electrical method for studying water metabolism and translocation in body segments. Proc. Soc. Exp.Biol. Med. 44: 142, 1940.

2. Bishop, S., Nyboer, J.: Electrical impedance of the anterior eye chamber. Annals of the New York Academy of Sci-ence. Vol 170, (2): 793-800, 1970.

3. Durnin, J.U.G.A., and Womersly, J.: Body fat assessed from total body density and its estimation from skinfold thick-ness: measurement on 481 men and women aged 16-72. British Journal of Nutrition, 32: 77-97, 1974.

4. Geddes, L.A. and Baker, L.E.: Principles of Applied Biomedical Instrumentation, 2nd Edition, John Wiley and Sons,New York, pp. 616, 1975.

5. Geddes, L.A., Baker, L.E.: Applied Biomedical Instrumentation. Second Edition. John Wiley and Sons, New York, pp.276-300, 1975.

6. Geddes, L.A. and Sadler, C.: The specific resistance of blood at body temperature. Med. Biol. Eng., 11: 336, 1973.

7. Hoffer, E.C., Meador, C.K. and Simpson, D.C.: Correlation of whole body impedance with total body water volume. J.Appl. Physiol., 27: 531, 1969.

8. Hoffer, E.C., Meador, C.K. and Simpson, D.C.: A relationship between whole body impedance and total body watervolume. Annals N.Y. Acad. of Sciences, 197: 452-469, 1970.

9. Kubicek, W.G.: Development and Evaluation of an Impedance Cardiographic System to Measure Cardiac Output andOther Cardiac Parameters. National Aeronautics and Space Administration (NASA). July 1, 1968 to June 30, 1969.Contract No. NAS 9-4500.

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10. Kushner, R.F. and Schoeller, D.A.: Estimation of total body water by bioelectrical impedance analysis. Am. J. ClinNutr., 44: 417-424, 1986.

11. Kushner, R.F. and Schoeller: Estimation of total body water by bioelectrical Impedance analysis. Am. J. Clin. Nutr.,44: 417-424, 1986.

12. Lukaski, H.C. and Bolonchuk, W.W.: Theory and validation of the tetrapolar bioelectrical impedance method to assesshuman body composition. Int. Symp. on In Viv o Body Composition Studies, Sept. 28 - Oct. 1, 1986, BrookhavenNational Laboratory.

13. Lukaski, H.C., Johnson, P.E., Bolonchuk, W.W., Lykken, G.I.: Assessment of fat free mass using bio-electricalimpedance measurements of the human body. Am. J. Clin. Nutr., 41: 810-817, 1985.

14. Lukaski, H.C., Bolonchuk, W.W., Hall, C.B., and Siders, W.: Validation of tetrapolar bioelectrical impedance methodto assess human body composition. Journal of Applied Physiology. 60 (4): 1327-1332, 1986.

15. Nyboer, J., Liedtke, R.J., Reid, K.A. and Gessert, W.A.: Nontraumatic electrical detection of total body water and den-sity in man. Proceedings of VIth ICEBI, 381-384, 1983.

16. Nyboer, J., Polasek, P. and Giliard, R.: Bioelectric impedance analyzer. Proc. Second Int. Conf. of Bioelec.Impedance, p. 5 1976.

17. Nyboer, J.: Electrorheometric properties of tissues. Ann. N.Y. Acad. of Sciences, 170 (2): 410-420, 1970.

18. Nyboer, J.: Workable volume and flow concepts of biosegments by electrical impedance plethysmography. T.I.T. Jour-nal of Life Sciences (2): 1-13, 1972.

19. Nyboer, J., Bango, S., Barnett, A. and Halsey, R.H.: Radiocardiograms - the electrical impedance changes of the heartin relation to electrocardiograms and heart sounds. J. Clin. Invest., 19: 963, 1940.

20. Nyboer, J., Kornmesser, J.G.: Electrical impedance of the abdomen during maternal labor. Annals of the New YorkAcademy of Science, Vol. 170, art. 2: 801-803, June 1970.

21. Nyboer, J.: Electrical Impedance Plethysmography. Second Edition. Charles C. Thomas, Springfield, IL, 1970.

22. Segal, K.R., Gutin, B., Presta, E., Wang, J., Van Itallie, T.: Estimation of human body composition by electricalimpedance methods: a comparative study. Journal of Applied Physiology, 58 (5): 1565-1571, 1985.

23. Settle, R.G., Foster, K.R., Epstein, B.R. and Mullen, J.L.: Nutritional assessment: whole body impedance and fluidcompartments. Nutrition and Cancer, 2 (1): 72-80, 1980.

24. Thomasett, A.: Bioelectrical properties of tissue impedance. Lyon Med. 207: 107-118, 1962.