Technical Articles - Bioelectrical Impedance Analysis in Clinical Disease Monitoring and Diagnosis

The electrical properties of biological tissues can be divided into two categories, active and passive, depending on the source of the electrical signal. If the electrical current of biological tissues is generated by ions inside the cells, we call it an active response. These electrical signals are called biopotentials, and the best known examples are electrocardiogram and electroencephalogram signals. If biological tissues respond to external electrical stimuli (such as current or voltage generators), the response is passive. In this case, we need to consider bioelectrical impedance.

Bioelectrical Impedance Analysis

Bioelectrical impedance analysis is a low-cost, non-invasive technique used to measure body composition and assess clinical conditions. Bioimpedance is a complex number consisting of a resistance value R (real part) that is mainly due to the amount of water in the body and a reactance value Xc (imaginary part) that is mainly due to the capacitance generated by the cell membrane. The impedance can also be represented by a vector with magnitude |Z| and phase angle φ. The phase angle plays a major role in determining body composition.

(1)

(2)

(3)

The resistance R of a conductor of cross-sectional area S and length l, and the capacitance C of a parallel plate capacitor of surface area S and distance d are given by the following formulas:

(4)

(5)

As can be seen from Equation 4 and Equation 5, resistance and capacitance depend on geometric parameters (length, distance, and surface area), which means that they are related to the measurement system and physical parameters adopted; that is, the resistivity ρ and the dielectric constant ε are closely related to the type of material to be measured (in this case, biological tissue). Figure 1 shows a simplified model of the electrical characteristics of a bioimpedance and its measurement instrument. RE considers the resistance of the extracellular fluid, RI represents the resistance of the intracellular fluid, and Cm is the capacitance of the cell membrane. The connection between the instrument and the human body is achieved through electrodes placed on the skin. The instrument provides an excitation voltage to the electrodes and measures the resulting current. The excitation signal is generated by a digital-to-analog converter (DAC) connected to a back-end driver. The DAC is programmed by a microcontroller, which allows the signal amplitude and frequency to be set. For current measurement, a transimpedance amplifier (TIA) is used, which is connected to a high-resolution analog-to-digital converter (ADC) for accurate measurement. The acquired data is processed using a system microcontroller to extract the information required for analysis.

Figure 1. Block diagram of the bioimpedance measurement system.

In bioimpedance measurement, the human body is divided into five sections: two upper limbs, two lower limbs, and the trunk. This distinction is important to understand the measurement method used. The most common are hand to foot, foot to foot, and hand to hand.

During the Bioelectrical Impedance Analysis (BIA) test, several factors are considered, including anthropometric parameters; namely height, weight, skin thickness and body shape. Other factors include gender, age, ethnicity and, especially, the patient's health status; namely, any malnutrition or dehydration. If these factors are not taken into account, the test results may be distorted. The interpretation of the measurement results is based on statistical data and formulas that take into account the various factors mentioned above.

Human body composition

When studying the body composition, we refer to the three-compartment model, which includes:

Fat body mass

Cell quality

Extracellular mass

Figure 2 explains these concepts, starting with the well-known two-compartment model of lean body mass (fat-free body mass) and fat body mass. Fat body mass has two components, essential fat and storage fat. Lean body mass is divided into body cellular mass (composed of protein mass and intracellular water) and extracellular mass (composed of extracellular water and bone mass). The last parameter is the basis for determining water content and is the total body water obtained by the sum of intracellular and extracellular water.

From an electrical properties perspective, the intracellular and extracellular electrolyte solutions behave like good conductors, while fat and bone tissue are poor conductors.

Figure 2. Human body composition

Bioimpedance Measurement Technology

The various bioimpedance measurement techniques in widespread use differ in the frequency of the excitation signal used. The simplest instruments are based on fixed-frequency measurements (single-frequency bioimpedance analysis or SF-BIA), some use multi-frequency systems (multi-frequency bioimpedance analysis or MF-BIA), while the most sophisticated instruments perform actual spectrum measurements over a range of frequencies (bioimpedance spectroscopy or BIS). There are also many techniques for evaluating the results, the most important of which are bioimpedance vector analysis and real-time analysis.

In the SF-BIA instrument, the frequency of the current injected into the body is 50 kHz; this is based on the inverse relationship between the measured impedance and the total body water (TBW) (the conductive part of the impedance), which is composed of intracellular water (ICW) and extracellular water (ECW). This technology provides good results for test subjects with normal hydration, but loses its effectiveness in test subjects with drastic changes in hydration due to the limited ability to evaluate changes in ICW.

The MF-BIA technique overcomes the limitations of SF-BIA by performing measurements at both low and high frequencies. Low-frequency measurements allow for a more accurate estimate of ECW, while high frequencies provide an estimate of TBW. The difference between the two estimates yields the ICW. However, the technique is not perfect and has shown limitations in estimating body fluid in elderly populations with medical conditions.

Finally, BIS is based on the measurement of impedance, which, according to the model of Figure 1, is the resistance RE generated by the extracellular fluid at zero frequency and the parallel connection of RE and RI at infinite frequency. At these two frequency extremes, the capacitance generated by the cell membrane behaves as an open circuit or a short circuit. Intermediate frequency measurements provide information about the capacitance value. BIS provides more detailed information than other techniques, but in this case the measurement takes longer.

Bioimpedance vector analysis (bioelectrical impedance vector analysis or BIVA) is a human health assessment technique based on the measurement of the absolute value of bioimpedance. It uses a graph to display a vector representation of impedance, where the horizontal axis shows the resistance value and the vertical axis shows the capacitive impedance value, both of which are benchmarked to the patient's height. The method is based on the formula of 3 tolerance ellipses: 50%, 75% and 95%. The 50% tolerance ellipse defines a population with an average body composition. Moving along the horizontal axis of the ellipse, individuals with a low percentage of lean body mass are identified on the right and vice versa; that is, individuals with a high percentage of lean body mass are identified on the left. Moving along the vertical axis determines the water content, with tendencies towards the upper half of the ellipse representing levels below the norm and towards the lower half of the ellipse above the norm.

Figure 3. Bioelectrical impedance vector-analysis tolerance ellipse.

Observing fluctuations in body composition (e.g., deviations from normal values ​​for lean body mass, fat body mass, and total body water) is a key factor in determining a patient's health status. Significant loss of lean body mass and fluid imbalances are both primary parameters used in diagnosing disease. Currently, bioelectrical impedance analysis is used to diagnose diseases of the following human systems:

Pulmonary system

Lung cancer

Pulmonary Edema

Cardiovascular System

Postoperative effusion

Circulatory system

Intravascular volume

Hyponatremia

Hydration

Renal system

Hemodialysis

Estimated dry weight

nervous system

Alzheimer's disease

Anorexia nervosa

Muscular system

Changes in body composition during training

Immune system

Assessment of HIV-infected patients

Cancer patient assessment

dengue

AD5940, a flexible and high precision analog front end

Analog Devices has a broad portfolio of impedance analysis products, including devices such as the ADuCM35x, which is a highly integrated system-on-chip (SoC) designed for impedance spectroscopy. The recently launched AD5940 is a high-precision, low-power analog front end that is ideal for portable applications. Designed for measuring bioimpedance and skin conductivity, the AD5940 consists of two excitation loops and a general-purpose measurement channel. The first excitation loop is capable of generating signals with a maximum frequency of 200 Hz and can be configured as a potentiostat for measuring different types of electrochemical cells. Its basic components include a dual-output DAC, a precision amplifier that provides the excitation signal, and a transimpedance amplifier for measuring the current. This loop operates at low frequency and consumes low power, so it is also called a low-power loop. The second excitation loop has a similar configuration, but is capable of processing signals up to 200 kHz, so it is called a high-speed loop. The device is equipped with an acquisition channel with a built-in 16-bit, 800 kSPS SAR-type ADC and the converter analog signal processing chain front end, which includes a buffer, a programmable gain amplifier (PGA), and a programmable anti-aliasing filter. To complete the architecture, a switch matrix multiplexer is implemented that allows multiple signals from multiple sources internal to the device or external to the ADC to be connected. This allows accurate system diagnostics to be performed to verify the full functionality of the instrument in addition to the main impedance measurement function.

Figure 4 shows the connections for the AD5940 for absolute human body impedance measurement in a four-wire configuration. For this type of measurement, a high frequency loop is used; a programmable ac voltage generator provides the excitation signal. A second generator provides the common-mode voltage for proper measurement. The current resulting from the body impedance is measured by a transimpedance amplifier and converted using a 16-bit ADC. The system is capable of measuring at frequencies up to 200 kHz and provides a signal-to-noise ratio (SNR) of 100 dB at 50 kHz. The digital data is sent to a hardware accelerator to extract the desired values; namely, the real and imaginary parts of the impedance.

As a medical device, the bioimpedance analyzer must comply with the IEC 60601 standard. This standard sets limits on the voltage and current that can be applied to the human body. To this end, this device provides a resistor Rlimit to limit the maximum current and four coupling capacitors CisoX to prevent the DC component from being applied to the human body.

Figure 4. Four-wire connection of the AD5940 for bioelectrical impedance analysis.

in conclusion

Bioimpedance measurement is a low-cost, versatile method for quickly and noninvasively assessing body composition and diagnosing certain types of diseases. With the use of devices such as the AD5940, current technology allows compact, high-performance, low-power bioimpedance analyzers that can be battery powered. The high level of integration, small size, and low power consumption of the AD5940 also make it particularly suitable for wearable applications.