Medical Instrumentation

Design of instrument must match

Measurement needs (environmental conditions, safety, reliability, etc) Instrument performance (speed, power, resolution, range, etc)

A medical device is
any item promoted for a medical purpose that does not rely on chemical action to achieve its intended effect
[Medical Device Amendments (Public law 94-295)]

i.e., any electrical or mechanical device for medical applications

this class will focus on electrical (including electromechanical and electrochemical)

Difference from any conventional instrument

source of signals is living tissue energy is applied to the living tissue

Impact on biomedical instrumentation (BI) design requirements?

Reliability and Safety

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 1

Generalized Medical Instrumentation System

actuator sensor measurand electronic instrumentation feedback

signal conditioning
basic advanced

signal processing

output display storage transmission

Measurand: Physical quantity, property or condition that the system measures Types of biomedical measurands
Internal Blood pressure Body surface ECG or EEG potentials Peripheral Infrared radiation Offline Extract tissue sample, blood analysis, or biopsy

Typical biomedical measurand quantities

Biopotential, pressure, flow, dimensions (imaging), displacement (velocity, acceleration and force), impedance, temperature and chemical concentration
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 2

Medical and Physiological Parameters

Parameter Blood flow Arterial blood pressure ECG EEG EMG Respiratory rate Range 1-300 ml/s 25-400mm Hg 0.5 4 mV 5 300 microV 0.1 5 mV 2 50 breaths/min Frequency dc 20 Hz dc 50 Hz 0.01 250 Hz dc 150 Hz dc 10,000 Hz 0.1 10 Hz Sensor Flowmeter (ultrasonic) Cuff, strain-gage Skin electrodes Scalp electrodes Needle electrodes Strain-gage, nasal thermistor
Ch1 Basics. p. 3

ECE 445: Biomedical Instrumentation

Sensor
actuator sensor measurand electronic instrumentation feedback

signal conditioning
basic advanced

signal processing

output display storage transmission

A sensor converts physical measurand to an electrical output Sensor requirements

Selective should respond to a specific form of energy in the measurand Minimally invasive (invasive = requiring entry into a part of the body)
sensor should not affect the response of the living tissue

Most common types of sensors in biomedical systems

displacement pressure
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 4

Signal Conditioning
actuator sensor measurand electronic instrumentation feedback

signal conditioning
basic advanced

signal processing

output display storage transmission

Signal Conditioning: Amplification and filtering of the signal acquired from the sensor to make it suitable for display General categories
Analog, digital or mixed-signal signal conditioning Time/frequency/spatial domain processing (e.g., filtering) Calibration (adjustment of output to match parameter measured) Compensation (remove of undesirable secondary sensitivities)
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 5

Units of Measurement
Fundamental SI units
SI = Systemes Internationales dUnites

Derived SI units

source: A. Morris, Principles of Instrumentation and Measurement, 3rd Ed., Butterworth-Heinemann, 2001. ECE 445: Biomedical Instrumentation Ch1 Basics. p. 6

Units of Measurement
Unit Definitions

source: A. Morris, Principles of Instrumentation and Measurement, 3rd Ed., Butterworth-Heinemann, 2001. ECE 445: Biomedical Instrumentation Ch1 Basics. p. 7

BI = biomedical instrumentation

BI Operational Modes

Direct vs. Indirect

Direct mode: measure desired measurand directly
if the sensor is invasive, direct contact with the measurand is possible but expensive, risky and least acceptable

Indirect mode: measure a quantity that is accessible and related to the desired measurand
assumption: the relationship between the measurands is already known often chosen when the measurand requires invasive procedures to measure directly

Example indirect mode

Cardiac output (volume of blood pumped per minute by the heart)

can be determined from measurement of respiration, blood gas concentration & dye dilution

Organ morphology
can be determined from x-ray shadows
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 8

BI Operational Modes
Sampling vs. Continuous mode
Sampling: for slow varying measurands that are sensed infrequently
like body temperature & ion concentrations

Continuous: for critical measurements requiring constant monitoring

like electro-cardiogram and respiratory gas flow

Generating vs. Modulating

Generating: also known as self-powered mode
derive their operational energy from the measurand itself Example: piezoelectric sensors, solar cells

Modulating: measurand modulates the electrical signal which is supplied externally

modulation affects output of the sensor Example: photoconductive or piezoresistive sensor

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 9

BI Operational Modes
Analog vs. digital modes
most sensors are inherently analog
(some optical sensors are exceptions)

require analog-to-digital converters before any DSP techniques could be applied for filtering

Real-time vs. Delayed-time mode

Real-time
Example: ECG signals need to measured in real-time to determine an impending cardiac arrest

Delayed-time
Example: cell cultures which requires several days before any output is acquired

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 10

Measurement Constraints
The signal to be measured imposes constraints on how it should be acquired and processed Signal/frequency ranges
Most medical measurands parameters are typically much lower than conventional sensing parameters (microvolts, mm Hg, low frequency)

Interference and cross-talk

Noise from environment, instruments, etc. Other measurands affect measurement (and cant be isolated)
e.g., Cannot measure EEG without interference from EMG

Require filtering and/or compensation

Placement of sensor(s) in/on/near the body plays a key role in any bio-instrumentation design
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 11

Measurement Constraints
Measurement variability is inherent at molecular, organ and body level
Primary cause
interaction between different physiological systems existence of numerous feedback loops whose properties are poorly understood

Therefore evaluation of biomedical devices rely on probabilistic/statistical methods (biostatistics) SAFETY

Due to interaction of sensor with living tissue, safety is a primary consideration in all phases of the design & testing process
the damage caused could be irreversible

In many cases, safe levels of energy is difficult to establish Safety of medical personnel also must be considered

Operator constraints
Reliable, easy to operate, rugged and durable

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 12

Classification of biomedical instruments

Quantity being sensed
pressure, flow or temperature makes comparison of different technologies easy resistive, inductive, capacitive, ultrasonic or electrochemical makes development of new applications easy cardiovascular, pulmonary, nervous, endocrine isolates all important measurements for specialists who need to know about a specific area

Principle of transduction

Organ systems

Clinical specialties

pediatrics, obstetrics, cardiology or radiology easy for medical personnel interested in specialized equipment.
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 13

Measurement Input Sources

Desired inputs Interfering inputs
measurands that the instrument is designed to isolate quantities that inadvertently affect the instrument as a consequence of the principles used to acquire and process the desired inputs undesired quantities that indirectly affect the output by altering the performance of the instrument itself

Interfering Inputs Instrument Measurand

Modifying inputs

ECG example Desired input ECG voltage Interfering input 60 Hz noise voltage, displacement currents Modifying input orientation of the patient cables

Modifying Inputs

when the plane of the cable is perpendicular to the magnetic field the magnetic interference is maximal

Interfering inputs generally not correlated to measurand Modifying inputs may be correlated to the measurand
more difficult to remove often easy to remove/cancel

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 14

Design Criteria and Process

Signal Factors
Sensitivity Range Differential or single ended Input Impedance Transient and frequency response Accuracy Linearity Reliability Specificity Signal-to-noise ratio stability: temperature, Humidity, pressure, Shock, vibration, Radiation Power requirements, Mounting size, shape Invasive or non-invasive Tissue-sensor Interface requirements Material toxicity Electrical safety, Radiation and heat dissipation, Patient discomfort Cost, Availability, Warranty, Consumable requirements, Compatibility with Existing equipment Initial Instrument Design

Prototype Tests

Environmental Factors Measurand

Final Instrument Design

Medical Factors

FDA approval

Production

Economic Factors

Regulation of Medical Devices <OPTIONAL>

Regulatory division of medical devices: class I, II and III
more regulation for devices that pose greater risk

Class I (General controls)

Manufacturers are required to perform registration, premarketing notification, record keeping, labeling, reporting of adverse experiences and good manufacturing practices

Class II (Performance standards)

800 standards needed to be met

Class III (Premarketing approval )

Manufacturers have to prove the safety of these devices prior to market release

Implanted devices (pacemakers etc.) are typically designated class III Investigational devices are typically exempt
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 16

Compensation Techniques
Compensation: elimination or reduction of interfering and modifying inputs Techniques
Altering the design of essential instrument components
simple to implement

Adding new components to offset the undesired inputs

Methods
Reduce sensitivity to interfering and modifying inputs
Example: use twisted cables and reduce number of electrical loops

Signal Filtering
temporal, frequency and spatial separation of signal from noise

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 17

Compensation: Negative Feedback

When modifying input cannot be avoided, negative feedback is used to make the output less dependent on the transfer function of the device
Amplifier

Vin
Feedback

Vout

Feedback devices must be accurate and linear

ECE 445: Biomedical Instrumentation Ch1 Basics. p. 18

Feedback
Open loop amplifiers are seldom used for precise amplification Using feedback generates precision amplifiers

R2
VX

R1
-

Vin VX VX Vout = R1 R2

Vin

Vout = A(Vref VX )
Vout
Vout R2 Vin R1 = 1 R2 [1 + (1 + )] A R1

Vref

For a large open-loop gain

R2 A >> (1 + ) R1

Vout =

R2 Vin R1

closed-loop gain
Ch1 Basics. p. 19

ECE 445: Biomedical Instrumentation

Feedback II
Large open loop gain criterion
easy to satisfy

R2 A >> (1 + ) R1
Vout = Vin

Irrespective of the open loop gain A, closed loop gain can be set to almost any value R2
e.g., 100, 200 or 1000

R1

Easy to design amplifiers with high gain

precision not required

Linearity and precision of closed loop amp

determined by ratio of resistors

R2
-

R1

Vin

Vref
ECE 445: Biomedical Instrumentation

Vout
Ch1 Basics. p. 20

Other Compensation Techniques

Opposing inputs or noise cancellation When interfering and modifying inputs cannot be filtered

additional inputs can be used to cancel undesired output components similar to differential signal representation

Next Lecture Topics Biostatistics

statistics terms and definitions biomedical studies

Instrumentation characteristics
static dynamic
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 21

Biostatistics
Used to design experiments and clinical studies:
To summarize, explore, analyze and present data To draw inferences from data by estimation or by hypothesis testing To evaluate diagnostic procedures To assist clinical decision making

Medical research studies can be classified as:

Observational studies: Characteristics of one or more groups of patients are observed and recorded. Experimental intervention studies: Effect of a medical procedure or treatment is investigated.

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 22

Biostatistics Studies
Observational studies case-series studies
Case-control studies
use of individuals selected because they have some outcome or disease then look backward to determine possible causes

Cross-sectional studies:
Analyze characteristics of patients at one particular time to determine the status of a disease or condition.

Cohort observational studies:

A particular characteristics is a precursor for an outcome or disease

Controlled studies:
If procedures compared to the outcome for patients given a placebo or other accepted treatment
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 23

Biostatistics Studies II
Concurrent control:
Patients are selected in the same way and for the same duration

Double-blind study:
Randomized selection of patients to treatment options to minimize investigator or patient bias

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 24

Biostatistics: Data Analysis

Distributions of data reflect the values of a variable/characteristic and frequency of occurrence of those values

Mean: (X )average of N values (arithmetic or geometric mean) Xi Median: middle of ranked values GM = N X 1 X 2 ... X N X = i Mode: most frequent value N Standard deviation: (s) spread of data
75% of values lie between X 2 s
s=

(X
i

N 1

Coefficient of Variation: (CV)

permits comparison of different scales

s CV = 100% X

Percentile
Percentage of distribution that is less than or equal to the percentile number
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 25

More Biostatistics
Correlation coefficient (r)
r= Measure of the relationship between two Xi X numerical variables for paired observations values between +1 and -1 (+1 means strong correlation)

(X

X Yi Y

)(

(Y Y )
i

Estimation and Hypothesis Testing

Confidence intervals Hypothesis testing P-value:
indicates the degree of confidence that data contains the true mean reveals whether the sample gives enough evidence for us to reject the null hypothesis (statement expressing the opposite of what we think is true) how often the observed difference would occur by chance alone

Methods for measuring the accuracy of a diagnostic procedure:

opposite: false-negative rate opposite: false-positive rate

Sensitivity: probability of the test yielding positive results in patients who actually have the disease Specificity: probability of the test yielding negative results in patients who do not have the disease
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 26

Instrument Characterization
Enable comparison of available instruments Permit evaluation of new instrument designs Generalized static characteristics Static characteristics:
performance of instruments for dc or very low frequency inputs some sensors respond only to time-varying inputs and have no static characteristics

Dynamic characteristics:
require temporal relationships to describe the quality of measurements

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 27

Static Characteristics
Accuracy
Difference between the true value and the measured value normalized by the magnitude of the true value Several ways to express accuracy
most popular is in terms of percentage of full-scale measurement

Precision

Expresses number of distinguishable alternatives from which a given result is selected High-precision does not mean high accuracy. Smallest incremental quantity that can be measured with certainty Ability of an instrument to give the same output for equal inputs applied over some period of time
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 28

Resolution

Reproducibility

Statistical Control and Static Sensitivity

Measurement conditions have to take into account randomness introduced by environmental conditions Statistic sensitivity (dc-gain)
To perform calibration between output and input For linear calibration If the source of variation can not be removed, then use averaging

n xd y xd y d d m= d 2 2 xd n xd d d

2 y xd xd y xd d d b = d d 2 2 xd n xd d d

y = mxd + b
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 29

Static Characteristics
static sensitivity curves

Zero drift (offset error)

Sensitivity drift (gain error)

When all measurements increases or decrease by the same absolute amount Causes: manufacturing misalignment, variations in ambient temperature, hysteresis vibration, shock, dc-offset voltage at electrodes When the slope of the calibration curve changes as a result of interfering or modifying input Causes: manufacturing tolerances, variations in power supply, non-linearity Example: ECG amplifier gain changes due to dc power-supply variation

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 30

Linearity
Linearity (formally) : A system that demonstrates superposition principle
If system inputs x1, x2 generate outputs y1, y2,
i.e., (x1 y1 AND x2 y2)

Then system is linear if (x1 + x2 y1 + y2) AND (Kx1 Ky1)

Linearity (informally): Output is linearly proportional to measurand quantity

data is fit to linear curve, generally using least-squares technique
outputs, yi linear fit, zi minimize (zi yi)2

Non-linearity defined as maximum deviation of any output reading from linear fit line
Non-linearity is usually expressed as a percentage of full-scale reading
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 31

Dynamic Characteristics <OPTIONAL>

Quantify response of medical equipment with respect to timevarying inputs Many engineering instruments can be described by ordinary linear differential equations

dx dny dy d mx an n + ... + a1 + a0 y (t ) = bm m + ... + b1 + b0 x(t ) dt dt dt dt

Most practical instruments have a first or second order response Practical evaluation of a system
Apply input as a unit-step function, sinusoidal function or white noise

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 32

Dynamic Characteristics
Operational transfer function:

bn s n + ... + b1s + b0 Y (s) = H (s) = X ( s ) am s m + ... + a1s + a0

Frequency response of a system For a sinusoidal input
the output is a sinusoid with different magnitude and phase

s = j

H ( s ) = K H1 ( s )...H m ( s )
Magnitude: Phase:

| H ( s ) |= K | H1 ( s ) | ... | H m ( s ) | H ( s ) = H1 ( s ) + ... + H m ( s )
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 33

Zero-order Instrument
a0 y (t ) = b0 x(t )
Y ( s ) b0 H (s) = = X ( s ) a0
Linear potentiometer is an example of a zero order instrument In practice, at high frequencies parasitic capacitance and inductance will cause distortion Step response is proportional to the input amplitude; no variation with frequency
ECE 445: Biomedical Instrumentation Ch1 Basics. p. 34

First-order Instrument
First-order instrument contains a single energy-storage element

dy a1 + a0 y (t ) = b0 x(t ) dt

Y (s) K = H (s) = X ( s ) (1 + s )

K = b 0 / a 0 is the static sensitivity (dc-gain) = a1 / a 0 is the time-constant of the system

Step response is characterized by a single time constant

A frequency transfer function is given by

| H ( j ) |=

K 1 + 2 2

H ( j ) = arctan( )
Ch1 Basics. p. 35

ECE 445: Biomedical Instrumentation

Second-order Instrument
Second-order instrument contains a minimum of two energy-storage element.

dy d y a2 2 + a1 + a0 y (t ) = b0 x(t ) dt dt
where

H (s) = (1 +

K 2s

s2

2 0

K = b0 / a 0

is the static sensitivity (dc-gain) Step response is characterized by

a0 0 = a2
=
a1 2 a0 a 2

is the undamped natural frequency

undamped natural frequency and the damping ratio

is the damping ratio

ECE 445: Biomedical Instrumentation Ch1 Basics. p. 36

1st & 2nd order Instruments

ECE 445: Biomedical Instrumentation

Ch1 Basics. p. 37