Biopotentials and Electrophysiology Measurement

Agenda 1 st half Introduction to biopotentials Measurement methods Traditional: ECG, EEG, EMG, EOG Novell: VCG 2 nd half Measurement considerations Electronics Electrodes Practices Q&A

1 st half

Introduction to biopotentials

Measurement methods

Traditional: ECG, EEG, EMG, EOG

Novell: VCG

2 nd half

Measurement considerations

Electronics

Electrodes

Practices

Q&A

What are biopotentials Biopotential: An electric potential that is measured between points in living cells, tissues, and organisms, and which accompanies all biochemical processes. Also describes the transfer of information between and within cells This book focuses strictly on the measurement of potentials

Biopotential: An electric potential that is measured between points in living cells, tissues, and organisms, and which accompanies all biochemical processes.

Also describes the transfer of information between and within cells

This book focuses strictly on the measurement of potentials

Mechanism behind biopotentials 1/2 Concentration of potassium (K + ) ions is 30-50 times higher inside as compared to outside Sodium ion (Na + ) concentration is 10 times higher outside the membrane than inside In resting state the member is permeable only for potassium ions Potassium flows outwards leaving an equal number of negative ions inside Electrostatic attraction pulls potassium and chloride ions close to the membrane Electric field directed inward forms Electrostatic force vs. diffusional force Nernst equation: Goldman-Hodgkin-Katz equation:

Concentration of potassium (K + ) ions is 30-50 times higher inside as compared to outside

Sodium ion (Na + ) concentration is 10 times higher outside the membrane than inside

In resting state the member is permeable only for potassium ions

Potassium flows outwards leaving an equal number of negative ions inside

Electrostatic attraction pulls potassium and chloride ions close to the membrane

Electric field directed inward forms

Electrostatic force vs. diffusional force

Nernst equation:

Goldman-Hodgkin-Katz equation:

Mechanism behind biopotentials 2/2 When membrane stimulation exceeds a threshold level of about 20 mV, so called action potential occurs: Sodium and potassium ionic permeabilities of the membrane change Sodium ion permeability increases very rapidly at first, allowing sodium ions to flow from outside to inside, making the inside more positive The more slowly increasing potassium ion permeability allows potassium ions to flow from inside to outside, thus returning membrane potential to its resting value While at rest, the Na-K pump restores the ion concentrations to their original values The number of ions flowing through an open channel >10 6 /sec Body is an inhomogeneous volume conductor and these ion fluxes create measurable potentials on body surface

When membrane stimulation exceeds a threshold level of about 20 mV, so called action potential occurs:

Sodium and potassium ionic permeabilities of the membrane change

Sodium ion permeability increases very rapidly at first, allowing sodium ions to flow from outside to inside, making the inside more positive

The more slowly increasing potassium ion permeability allows potassium ions to flow from inside to outside, thus returning membrane potential to its resting value

While at rest, the Na-K pump restores the ion concentrations to their original values

The number of ions flowing through an open channel >10 6 /sec

Body is an inhomogeneous volume conductor and these ion fluxes create measurable potentials on body surface

Electrocardiography (ECG) Measures galvanically the electric activity of the heart Well known and traditional, first measurements by Augustus Waller using capillary electrometer (year 1887) Very widely used method in clinical environment Very high diagnostic value 1. Atrial depolarization 2. Ventricular depolarization 3. Ventricular repolarization

Measures galvanically the electric activity of the heart

Well known and traditional, first measurements by Augustus Waller using capillary electrometer (year 1887)

Very widely used method in clinical environment

Very high diagnostic value

ECG basics Amplitude: 1-5 mV Bandwidth: 0.05-100 Hz Largest measurement error sources: Motion artifacts 50/60 Hz powerline interference Typical applications: Diagnosis of ischemia Arrhythmia Conduction defects

Amplitude: 1-5 mV

Bandwidth: 0.05-100 Hz

Largest measurement error sources:

Motion artifacts

50/60 Hz powerline interference

Typical applications:

Diagnosis of ischemia

Arrhythmia

Conduction defects

12-Lead ECG measurement Most widely used ECG measurement setup in clinical environment Signal is measured non-invasively with 9 electrodes Lots of measurement data and international reference databases Well-known measurement and diagnosis practices This particular method was adopted due to historical reasons, now it is already rather obsolete Einthoven leads: I, II & III Goldberger augmented leads: V R , V L & V F Precordial leads: V 1 -V 6

Most widely used ECG measurement setup in clinical environment

Signal is measured non-invasively with 9 electrodes

Lots of measurement data and international reference databases

Well-known measurement and diagnosis practices

This particular method was adopted due to historical reasons, now it is already rather obsolete

Why is 12-lead system obsolete? Over 90% of the heart’s electric activity can be explained with a dipole source model Only 3 orthogonal components need to be measured, which makes 9 of the leads redundant The remaining percentage, i.e. nondipolar components, may have some clinical value This makes 8 truly independent and 4 redundant leads 12-lead system does, to some extend, enhance pattern recognition and gives the clinician a few more projections to choose from … but…. If there was no legacy problem with current systems, 12-lead system would’ve been discarded ages ago

Over 90% of the heart’s electric activity can be explained with a dipole source model

Only 3 orthogonal components need to be measured, which makes 9 of the leads redundant

The remaining percentage, i.e. nondipolar components, may have some clinical value

This makes 8 truly independent and 4 redundant leads

12-lead system does, to some extend, enhance pattern recognition and gives the clinician a few more projections to choose from

… but….

If there was no legacy problem with current systems, 12-lead system would’ve been discarded ages ago

Electroencephalography (EEG) Measures the brain’s electric activity from the scalp Measured signal results from the activity of billions of neurons Amplitude: 0.001-0.01 mV Bandwidth: 0.5-40 Hz Errors: Thermal RF noise 50/60 Hz power lines Blink artifacts and similar Typical applications: Sleep studies Seizure detection Cortical mapping

Measures the brain’s electric activity from the scalp

Measured signal results from the activity of billions of neurons

Amplitude: 0.001-0.01 mV

Bandwidth: 0.5-40 Hz

Errors:

Thermal RF noise

50/60 Hz power lines

Blink artifacts and similar

Typical applications:

Sleep studies

Seizure detection

Cortical mapping

EEG measurement setup 10-20 Lead system is most widely clinically accepted Certain physiological features are used as reference points Allow localization of diagnostic features in the vicinity of the electrode Often a readily available wire or rubber mesh is used Brain research utilizes even 256 or 512 channel EEG hats

10-20 Lead system is most widely clinically accepted

Certain physiological features are used as reference points

Allow localization of diagnostic features in the vicinity of the electrode

Often a readily available wire or rubber mesh is used

Brain research utilizes even 256 or 512 channel EEG hats

Electromyography (EMG) Measures the electric activity of active muscle fibers Electrodes are always connected very close to the muscle group being measured Rectified and integrated EMG signal gives rough indication of the muscle activity Needle electrodes can be used to measure individual muscle fibers Amplitude: 1-10 mV Bandwidth: 20-2000 Hz Main sources of errors are 50/60 Hz and RF interference Applications: muscle function, neuromuscular disease, prosthesis

Measures the electric activity of active muscle fibers

Electrodes are always connected very close to the muscle group being measured

Rectified and integrated EMG signal gives rough indication of the muscle activity

Needle electrodes can be used to measure individual muscle fibers

Amplitude: 1-10 mV

Bandwidth: 20-2000 Hz

Main sources of errors are 50/60 Hz and RF interference

Applications: muscle function, neuromuscular disease, prosthesis

Electrooculography (EOG) Electric potentials are created as a result of the movement of the eyeballs Potential varies in proportion to the amplitude of the movement In many ways a challenging measurement with some clinical value Amplitude: 0.01-0.1 mV Bandwidth: DC-10 Hz Primary sources of error include skin potential and motion Applications: eye position, sleep state, vestibulo-ocular reflex

Electric potentials are created as a result of the movement of the eyeballs

Potential varies in proportion to the amplitude of the movement

In many ways a challenging measurement with some clinical value

Amplitude: 0.01-0.1 mV

Bandwidth: DC-10 Hz

Primary sources of error include skin potential and motion

Applications: eye position, sleep state, vestibulo-ocular reflex

Vectorcardiogram (VCG or EVCG) Instead of displaying the scalar amplitude (ECG curve) the electric activation front is measured and displayed as a vector (dipole model, remember?)  It has amplitude and direction Diagnosis is based on the curve that the point of this vector draws in 2 or 3 dimensions The information content of the VCG signal is roughly the same as 12-lead ECG system. The advantage comes from the way how this information is displayed A normal, scalar ECG curve can be formed from this vectro representation, although (for practical reasons) transformation can be quite complicated Plenty of different types of VCG systems are in use  No legacy problem as such

Instead of displaying the scalar amplitude (ECG curve) the electric activation front is measured and displayed as a vector (dipole model, remember?)

 It has amplitude and direction

Diagnosis is based on the curve that the point of this vector draws in 2 or 3 dimensions

The information content of the VCG signal is roughly the same as 12-lead ECG system. The advantage comes from the way how this information is displayed

A normal, scalar ECG curve can be formed from this vectro representation, although (for practical reasons) transformation can be quite complicated

Plenty of different types of VCG systems are in use

 No legacy problem as such

The biopotential amplifier Small amplitudes, low frequencies, environmental and biological sources of interference etc. Essential requirements for measurement equipment: High amplification High differential gain, low common mode gain  high CMRR High input impedance Low Noise Stability against temperature and voltage fluctuations Electrical safety, isolation and defibrillation protection

Small amplitudes, low frequencies, environmental and biological sources of interference etc.

Essential requirements for measurement equipment:

High amplification

High differential gain, low common mode gain  high CMRR

High input impedance

Low Noise

Stability against temperature and voltage fluctuations

Electrical safety, isolation and defibrillation protection

The Instrumentation Amplifier Potentially combines the best features desirable for biopotential measurements High differential gain, low common mode gain, high CMRR, high input resistance A key design component to almost all biopotential measurements! Simple and cheap, although high-quality OpAmps with high CMRR should be used CMRR fine tuning

Potentially combines the best features desirable for biopotential measurements

High differential gain, low common mode gain, high CMRR, high input resistance

A key design component to almost all biopotential measurements!

Simple and cheap, although high-quality OpAmps with high CMRR should be used

Application-specific requirements ECG amplifier Lower corner frequency 0.05 Hz, upper 100Hz Safety and protection: leakage current below safety standard limit of 10 uA Electrical isolation from the power line and the earth ground Protection against high defibrillation voltages EEG amplifier Gain must deal with microvolt or lower levels of signals Components must have low thermal and electronic noise @ the front end Otherwise similar to ECG EMG amplifier Slightly enhanced amplifier BW suffices Post-processing circuits are almost always needed (e.g. rectifier + integrator) EOG amplifier High gain with very good low frequency (or even DC) response DC-drifting  electrodes should be selected with great care Often active DC or drift cancellation or correction circuit may be necessary

ECG amplifier

Lower corner frequency 0.05 Hz, upper 100Hz

Safety and protection: leakage current below safety standard limit of 10 uA

Electrical isolation from the power line and the earth ground

Protection against high defibrillation voltages

EEG amplifier

Gain must deal with microvolt or lower levels of signals

Components must have low thermal and electronic noise @ the front end

Otherwise similar to ECG

EMG amplifier

Slightly enhanced amplifier BW suffices

Post-processing circuits are almost always needed (e.g. rectifier + integrator)

EOG amplifier

High gain with very good low frequency (or even DC) response

DC-drifting  electrodes should be selected with great care

Often active DC or drift cancellation or correction circuit may be necessary

Electrical Interference Reduction Power line interference (50 or 60 Hz) is always around us Connects capacitively and causes common mode interference The common mode interference would be completely rejected by the instrumentation amplifier if the matching would be ideal Often a clever “driven right leg circuit” is used to further enhance CMRR  Average of the V CM is inverted and driven back to the body via reference electrode

Power line interference (50 or 60 Hz) is always around us

Connects capacitively and causes common mode interference

The common mode interference would be completely rejected by the instrumentation amplifier if the matching would be ideal

Often a clever “driven right leg circuit” is used to further enhance CMRR

 Average of the V CM is inverted and driven back to the body via reference electrode

Filtering Filtering should be included in the front end of the InstrAmp Transmitters, motors etc. cause also RF interference Small inductors or ferrite beads in the lead wires block HF frequency EM interference RF filtering with small capacitors High-pass filter to reject DC drifting Low-pass filtering at several stages is recommended to attenuate residual RF interference

Filtering should be included in the front end of the InstrAmp

Transmitters, motors etc. cause also RF interference

50 or 60 Hz notch filter Sometimes it may be desirable to remove the power line interference Overlaps with the measurement bandwidth May distort the measurement result and have an affect on the diagnosis! Option often available with EEG & EOG measuring instruments Twin T notch filter Determines notch frequency Notch tuning

Sometimes it may be desirable to remove the power line interference

Overlaps with the measurement bandwidth

May distort the measurement result and have an affect on the diagnosis!

Option often available with EEG & EOG measuring instruments

Artifact reduction Electrode-skin interface is a major source of artifact Changes in the junction potential causes slow changes in the baseline Movement artifacts cause more sudden changes and artifacts Drifting in the baseline can be detected by discharging the high-pass capacitor in the amplifier to restore the baseline

Electrode-skin interface is a major source of artifact

Changes in the junction potential causes slow changes in the baseline

Movement artifacts cause more sudden changes and artifacts

Drifting in the baseline can be detected by discharging the high-pass capacitor in the amplifier to restore the baseline

Electrical isolation Electrical isolation limits the possibility of passage of any leakage current from the instrument in use to the patient Such passage would be harmful if not fatal! Transformer Transformers are inherently high frequency AC devices Modulation and demodulation needed Optical isolation Optical signal is modulated in proportion to the electric signal and transmitted to the detector Typically pulse code modulated to circumvent the inherent nonlinearity of the LED-phototransistor combination

Electrical isolation limits the possibility of passage of any leakage current from the instrument in use to the patient

Such passage would be harmful if not fatal!

Transformer

Transformers are inherently high frequency AC devices

Modulation and demodulation needed

Optical isolation

Optical signal is modulated in proportion to the electric signal and transmitted to the detector

Typically pulse code modulated to circumvent the inherent nonlinearity of the LED-phototransistor combination

Defibrillation Protection Measuring instruments can encounter very high voltages E.g. 1500…5000V shocks from defibrillator Front-end must be designed to withstand these high voltages 1. Resistors in the input leads limit the current 3. Protection against much higher voltages is achieved with low-pressure gas discharge tubes (e.g. neon lamps) (note: even isolation components such as transformers and optical isolators need these spark gaps) Discharge @ ~100V 2. Diodes or Zener diodes protect against high voltages Discharge @ 0.7-15V

Measuring instruments can encounter very high voltages

E.g. 1500…5000V shocks from defibrillator

Front-end must be designed to withstand these high voltages

Electrodes – Basics High-quality biopotential measurements require Good amplifier design Use of good electrodes and their proper placement on the patient Good laboratory and clinical practices Electrodes should be chosen according to the application Basic electrode structure includes: The body and casing Electrode made of high-conductivity material Wire connector Cavity or similar for electrolytic gel Adhesive rim The complexity of electrode design often neglected

High-quality biopotential measurements require

Good amplifier design

Use of good electrodes and their proper placement on the patient

Good laboratory and clinical practices

Electrodes should be chosen according to the application

Basic electrode structure includes:

The body and casing

Electrode made of high-conductivity material

Wire connector

Cavity or similar for electrolytic gel

Adhesive rim

The complexity of electrode design often neglected

Electrodes - Basics Skin preparation by abrasion or cleansing Placement close to the source being measured Placement above bony structures where there is less muscle mass Distinguishing features of different electrodes: How secure? The structure and the use of strong but less irritant adhesives How conductive? Use of noble metals vs. cheaper materials How prone to artifact? Use of low-junction-potential materials such as Ag-AgCl If electrolytic gel is used, how is it applied? High conductivity gels can help reduce the junction potentials and resistance but tend to be more allergenic or irritating Baseline drift due to the changes in junction potential or motion artifacts  Choice of electrodes Muscle signal interference  Placement Electromagnetic interference  Shielding

Skin preparation by abrasion or cleansing

Placement close to the source being measured

Placement above bony structures where there is less muscle mass

Distinguishing features of different electrodes:

How secure? The structure and the use of strong but less irritant adhesives

How conductive? Use of noble metals vs. cheaper materials

How prone to artifact? Use of low-junction-potential materials such as Ag-AgCl

If electrolytic gel is used, how is it applied? High conductivity gels can help reduce the junction potentials and resistance but tend to be more allergenic or irritating

Ag-AgCl, Silver-Silver Chloride Electrodes The most commonly used electrode type Silver is interfaced with its salt silver-chloride Choice of materials helps to reduce junction potentials Junction potentials are the result of the dissimilar electrolytic interfaces Electrolytic gel enhances conductivity and also reduces junction potentials Typically based on sodium or potassium chloride, concentration in the order of 0.1 M weak enough to not irritate the skin The gel is typically soaked into a foam pad or applied directly in a pocket produced by electrode housing Relatively low-cost and general purpose electrode Particularly suited for ambulatory or long term use

The most commonly used electrode type

Silver is interfaced with its salt silver-chloride

Choice of materials helps to reduce junction potentials

Junction potentials are the result of the dissimilar electrolytic interfaces

Electrolytic gel enhances conductivity and also reduces junction potentials

Typically based on sodium or potassium chloride, concentration in the order of 0.1 M weak enough to not irritate the skin

The gel is typically soaked into a foam pad or applied directly in a pocket produced by electrode housing

Relatively low-cost and general purpose electrode

Particularly suited for ambulatory or long term use

Gold Electrodes Very high conductivity  suitable for low-noise meas. Inertness  suitable for reusable electrodes Body forms cavity which is filled with electrolytic gel Compared to Ag-AgCL: greater expense, higher junction potentials and motion artifacts Often used in EEG, sometimes in EMG Conductive polymer electrodes Made out of material that is simultaneously conductive and adhesive Polymer is made conductive by adding monovalent metallic ions Aluminum foil allows contact to external instrumentation No need for gel or other adhesive substance High resistivity makes unsuitable for low-noise meas. Not as good connection as with traditional electrodes

Very high conductivity  suitable for low-noise meas.

Inertness  suitable for reusable electrodes

Body forms cavity which is filled with electrolytic gel

Compared to Ag-AgCL: greater expense, higher junction potentials and motion artifacts

Often used in EEG, sometimes in EMG

Made out of material that is simultaneously conductive and adhesive

Polymer is made conductive by adding monovalent metallic ions

Aluminum foil allows contact to external instrumentation

No need for gel or other adhesive substance

High resistivity makes unsuitable for low-noise meas.

Not as good connection as with traditional electrodes

Metal or carbon electrodes Other metals are seldom used as high-quality noble metal electrodes or low-cost carbon or polymeric electrodes are so readily available Historical value. Bulky and awkward to use Carbon electrodes have high resistivity and are noisier but they are also flexibleand reusable Applications in electrical stimulation and impedance plethysmography Needle electrodes Obviously invasive electrodes Used when measurements have to be taken from the organ itself Small signals such as motor unit potentials can be measured Needle is often a steel wire with hooked tip

Other metals are seldom used as high-quality noble metal electrodes or low-cost carbon or polymeric electrodes are so readily available

Historical value. Bulky and awkward to use

Carbon electrodes have high resistivity and are noisier but they are also flexibleand reusable

Applications in electrical stimulation and impedance plethysmography

Obviously invasive electrodes

Used when measurements have to be taken from the organ itself

Small signals such as motor unit potentials can be measured

Needle is often a steel wire with hooked tip

That’s it, Now for Q&A SQUID = Superconducting Quantum Interference Device