Biomedical Instrumentation

Winter 1393

Bonab University

Introduction

Course information

Lecturer: Dr. Fariborz Rahimi• Email: frahimi@bonabu.ac.ir

Prerequisites:• Electronic Measurements

Recommended Books and Notes:• J.G. Webster, “Medical Instrumentation Application and Design”, John Wiley & Sons, 2010

• J. Aston, “Principles of Biomedical Instrumentation and Measurement”, Merrill Publishing Company, 1990.

• J.D. Enderle, J.D.Bronzino, “Introduction to Biomedical Engineering”, Wiley, 3rd Ed. 2008

Tentative Grading:• Project (including in-class presentation) 35%

• Oral Presentation in class 20%

• Review paper (2-3 pages, IEEE conference format) 15%

• Final Exam 65%

2

Intro

The main Course book

3

J.G. Webster, “Medical

Instrumentation Application and

Design”, John Wiley & Sons, 4th

ED., 2010

Describes:

-principles

-applications

-design

Medical instruments commonly

Used in hospitals

Just fundamentals (details

change with time)

Intro

About John G Webster’s book

4

Intro

سرفصل مصوب وزارت

5

Intro

Examples: Cochlear Implant

6

Intro

• A surgically implanted electronic device that provides a sense of sound to a person who is profoundly deaf

• The quality of sound is different from natural hearing, with less sound information

• Each sensory fiber of the cochlear nerve handles a specific frequency (electively sensitive to a very narrow

frequency band) stimulate all fibers

Examples: Advances in Vision (Retinal Stimulation)

7

Intro

• A retinal implant is a biomedical implant

technology currently being developed

• Meant to partially restore useful vision to

people who have lost their vision due to

degenerative eye conditions

• Provide the user with low resolution images

by electrically stimulating surviving retinal

cells

• Sufficient for restoring specific visual

abilities, such as light perception and

object recognition

Examples: Mini Gastric Imaging

• It is considered to be a very safe method to determine an unknown cause of a gastrointestinal bleed

• to examine parts of the gastrointestinal tract that cannot be seen with other types of endoscopy

• capsule usually passes through feces within 24–48 hours

8

Intro

A success story: The AutoAnalyzer (Technicon, 35 years)

• New medical instrument: invention-prototype-development-clinical testing-regulatory approval-manufacturing-marketing-sale of new instrument…

• An automated analyzer using a flow technique called continuous flow analysis (CFA)

• The design is based on separating a continuously flowing stream with air bubbles

• A continuous stream of material is divided by air bubbles into discrete segments in which chemical reactions occur

• Was used: determine levels of albumin, alkaline phosphatase, blood urea nitrogen, bilirubin, calcium, cholesterol,… but now is replaced by discrete systems

• Now mainly in industrial processes: Water, soil extracts

9

CH-1

Generalized Medical instrumentation system

10

Figure 1.1 The sensor converts energy or information from the measurand

to another form (usually electric). This signal is then processed and

displayed so that humans can perceive the information. Elements and

connections shown by dashed lines are optional for some applications.

Perceptible

outputOutput

display

Control

And

feedback

Signal

processing

Data

transmissionData

storage

Variable

Conversion

element

Sensor

Primary

Sensing

element

Measurand

Calibration

signal

Radiation,

electric current,

or other applied

energy

Power

source

CH-1

Medical System

Measurand (quantity the system measures): Physical quantity

• Measurand accessibility:• Internal (blood pressure), on the body surface

(electrocardiogram potential), emanate from body

(infrared radiation), derived from a sample (blood, biopsy)

• Biopotential

• Pressure

• Flow

• Dimensions (imaging)

• Displacement (velocity, acceleration, force)

• Impedance

• Temperature

• Chemical Concentration

11

CH-1

Medical System

Sensor and Transducer

• Transducer• Converts one form of energy to another

• Sensor• Converts a physical measurand to an electrical output

• Interface with living system

• Minimize the energy extracted

• Minimally invasive

12

diaphragm Strain gagepressure

displacement electric voltage

CH-1

Pulse Oximetry

Medical System

Signal Conditioning

• Amplification

• Filtering

• Impedance matching

• Analog/Digital for signal processing

• Signal form (time and frequency domains)

13

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Medical System

Output Display

• Numerical

• Graphical

• Discrete or continuous

• Visual

• Hearing

14

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Beeps

Medical System

Auxiliary Element

• Calibration Signal (as early in signal processing chain

as possible)

• Control and Feedback (auto or manual)• Adjust sensor and signal conditioning

15

CH-1

Medical System

1.3 Alternative Operational Modes

• Direct Mode: Measurand is readily accessible• Temperature

• Heart Beat

• Indirect Mode: desired measurand is measured by measuring accessible measurand.• Morphology of internal organ: X-ray shadows

• Volume of blood pumped per minute by the heart: respiration and blood gas concentration

• Pulmonary volumes: variation in thoracic impedance

(Breathing out = Low impedance)

16

CH-1

Medical System

1.3 Sampling and Continuous Modes

• Sampling and collecting data will depend on the following:• The rate of change in the measurand (temp., ion concentration = slow

sampling vs. ECG or respiratory gas continuous)

• Condition of the patient

• Generating and Modulating Sensors• Generating sensors produce their outputs from energy taken from

measurand (Photovoltaic cell)

• Modulating Sensors uses the measurand to alter the flow of energy from an external source (Photoconductive cell)

• Analog and Digital Modes

• Real-Time and Delayed-Time Modes

17

CH-1

Medical System

1.4 Medical Measurement Constraints

• Magnitude and frequency range of medical measurand are very low

• Proper measurand-sensor interface cannot be obtained (without damage)

• Medical variables are seldom deterministic

• External energy must be minimized to avoid any damage

• Equipment must be reliable

18

CH-1Medical System

Ballistocardiograph

19

A person lies down on a flat board set on rollers. A laser beam is

directed at a tiny mirror positioned on one of the rollers. The laser

beam is projected onto the ceiling or wall. The beating of the

person's heart causes a slight movement in the body as indicated by

the laser. This upward movement of the body is due to the 3rd Law

reaction force of the blood being pumped to the lower body. The

left ventricle of the heart squeezes blood upward into the aorta

shown below. At the peak of the contraction, about 80 grams of

blood is moving upward at 30 cm/s. The aorta does a U-turn forcing

most of the blood to flow down to the lower body. The aorta and

body force the blood down and in turn the body is forced up. The

amount is too small to be seen by eye but can be seen when

"amplified" by the laser-mirror arrangement used in the

demonstration. It can also be seen when standing quietly on a

weight scale if the scale is sensitive enough and the vibration is not

damped by the scale mechanism. Your weight decreases slightly

when the blood slams into the top of the aorta.

CH-1

Medical System

1.5 Classification of Medical Instrument

• Quantity that is sensed• pressure, flow, temp

• Principle of transduction• resistive, capacitive, electrochemical, ultrasound

• Organ system• Cardiovascular

• Pulmonary

• Nervous

• Medicine specialties• pediatrics, cardiology, radiology

20

CH-1Medical System

1.6 Interfering and Modifying Inputs

• Desired Inputs: measurands that the instrument is designed to isolate.

• Interfering Inputs: quantities that unintentionally affect the instrument as a consequence of the principles used to acquire and process the desired inputs.

• Modifying Inputs: undesired quantities that indirectly affect the output by altering the performance of the instrument itself.

21

CH-1

Effect of a burst or ESD (Electrostatic discharge)

disturbance on an electronic board.http://incompliancemag.com/article/emc-design-in-the-ic-

environment-with-respect-to-esd-and-burst/

Interference

1.6 Interfering and Modifying Inputs

22

Electrodes

60-Hz

ac magnetic

field

Displacement

currents

Differential

amplifier

+

-

+Vcc

-Vcc

Z1

ZbodyZ2

vo

vecg

Desired input: Electrocardiographic voltage Vecg

Interfering input: voltage due to 60-Hz

Figure 1.2 Simplified electrocardiographic recording system Two possible interferinginputs are stray magnetic fields and capacitively coupled noise. Orientation of patient cables and changes in electrode-skin impedance are two possible modifying inputs. Z1 and Z2represent the electrode-skin interface impedances.

CH-1

Interference

1.7 Compensation Techniques

To eliminate interfering and modifying input:

1.Alter the design of essential instrument components to be less sensitive to interference. (preferred)

2.Adding new components designed to offset the undesired inputs.

23

CH-1

The four

electromagnetic

interference (EMI)

coupling modes

Interference

1.7 Compensation Techniques

•Inherent Insensitive (twist electrode wires in ECG)

•Negative Feedback to minimize Gd which is effected by the modifying inputs

• (xd – Hfy)Gd = y (1.1)

• xdGd = y(1 + HfGd) (1.2)

• (1.3)

•Signal Filtering (electric, mechanical, magnetic)• At the input, output, inside the device (many designers use non-electric at input)

•Opposing Inputs (additional interfering inputs to cancel undesired)

24

d

df

d

1x

GH

Gy

CH-1

Interference

Compensation Techniques- Example

An amplifier with gain 10 that has 20% fluctuation due to temperature and environmental change. How to compensate the system to minimize the fluctuation?

• Solution: (say, for when gain decreases by 20%)• Use a thermistor (temperature dependent resistor)

• Adjust characteristics of active

system elements

(say, amplification factor)

25

CH-1

Interference

1.8 Biostatistics

• Applications of Statistics to medical data

- Design experiment

- Clinical Study: summarize, explore, analyze

- Draw inference from data: estimation, hypothesis

- Evaluate diagnostic procedures: assist clinical decision making

26

CH-1

Biostatistics

Medical Research Studies

• - Observational: Characteristics of patients are observed and recorded

- Case-series: describe characteristic of group

- Case-control: observe group that have some disease

- Cross-sectional: Analyze characteristics of patients (1 particular time)

- Cohort: determine if a particular characteristic is a precursor for a disease.

- Experimental Intervention: Effect of a medical procedure or treatment is investigated

- Controlled: Comparing outcomes to drug and placebo

- Uncontrolled: No placebo and no comparison

- Concurrent controls: patient are selected the same way and for the same time.

- Double-blind: Patients random to treatments and investigator does not know which

27

CH-1

Biostatistics

Statistical Measurements

• Measures of the mean and central tendency

- Mean

- Median: Middle value (used for skewed data)

- Mode: is the observation that occurs most frequently

- Geometric Mean: used with data on a logarithmic scale

28

CH-1

nnXXXXGM 321

n

XX

i

Biostatistics

Statistical Measurements

Measure of spread or dispersion of data• Range: Difference between the largest

and smallest observation

• Standard deviation: is a measure of the

spread of data about the mean

• For symmetric distribution 75% of the data lies between (mean - 2s) and (mean + 2s)

• Coefficient of variation: standardize the variation to compare data measured in different scales.

29

CH-1

1

2

-

-

n

XXs

i

%100

X

sCV

Biostatistics

Statistical Measurements

• Percentile: gives the percentage of a distribution that is less than or equal to the percentile number.

• Standard error of the mean (SEM): Express the variability to be expected among the mean in future samples.

• Correlation Coefficient r: is a measure of a linear relationship between numerical variables x and y for paired observations

30

CH-1

--

--

22

YYXX

YYXXr

ii

ii

Biostatistics

Methods for inference

Methods for inference about a value in a population of subjects from a set of observations.

• Estimation and confidence interval:

are used to estimate specific parameters such as

the mean and the variance.

• Hypothesis testing and P-value:

reveals whether the sample gives enough evidence for us to reject the null hypothesis. P-value indicates how often the observed difference would occur by chance alone.

31

CH-1

Biostatistics

Methods for measuring the accuracy of a diagnostic procedure

•Sensitivity of a test:

Probability of its yielding positive results in patients who actually have the disease.

•Specificity of a test:

Probability of its yielding negative results in patients who do not have the disease

•Prior Probability:

the prevalence of the condition prior to the test.

32

CH-1

Biostatistics

Characteristics of Instrument Performance

• Two classes of characteristics are used to evaluated and compare new instrument

• Static Characteristics:

describe the performance for dc or very low frequency input.

• Dynamic Characteristics:

describe the performance for ac and high frequency input.

33

CH-1

Characteristic

1.9 Generalized Static Characteristics

Parameters used to evaluate medical instrument:

• Accuracy:

The difference between the true value and the measured value divided by the true value

• Precision:

The number of distinguishable alternatives from which a given results is selected {2.434v or 2.43v}

• Resolution:

The smallest increment quantity that can be measured with certainty

• Reproducibility:

The ability to give the same output for equal inputs applied over some period of time.

34

CH-1Static Char.

1.9 Generalized Static Characteristics

Parameters used to evaluate medical instrument:

• Statistical Control:

Accuracy is meaningful if all environmental factors are known Ensures:Systematic errors or bias are tolerable or can be removed by calibration.

Systematic error / bias can be removed by calibration / correction factors , but random variation more difficult

• Statistical Sensitivity:

Static calibration = hold all inputs constant except one incrementally increase that input

The ratio of the incremental output quantity to the incremental input quantity, Gd.

35

CH-1

Static Char.

Finding static sensitivity Gd using line equation with the minimal sum of the squared difference between data points and the line

36

CH-1

-

-

2

d

2

d

dd

xxn

yxyxnm

-

-

2

d

2

d

dd

2

d

xxn

xyxxyb

bmxy d

n: Total number

of points

Static Char.

1.9 Generalized Static Characteristics

37

CH-1

Figure 1.3 (b) Static sensitivity: zero drift and sensitivity drift. Dotted lines indicate that zero drift and sensitivity drift can be negative.

Zero Drift: all output values increase or decrease by

the same amount due to manufacturing misalignment,

variation in ambient temperature, vibration,….

Sensitivity Drift: Output change in

proportion to the magnitude of the input.

Change in the slope of the calibration curve.

Static Char.

38

CH-1

Figure 1.4 (a) Basic definition of linearity for a system or element. The same linear system or element is shown four times for different inputs. (b) A graphical illustration of independent nonlinearity equals A% of the reading, or B% of full scale, whichever is greater (whichever permits the largererror). xd (Input)

B% of full scale

A% of reading

Overall tolerance band

Least-squares

straight line

(b)

Point at whichA% of reading = B% of full scale

y (Output)

(a)

x1 (x1 + x2)y1

x2 Kx1 Ky1y2Linearsystem

Linearsystem

Linearsystem

Linearsystem

and and

(y1 + y2)

Linearity

Independent nonlinearity- A% deviation of the reading

- B% deviation of the full scale

Input Ranges (I): Minimum resolvable input < I < normal linear operating range

Static Char.

Example

A linear system described by the following equation y=2x+3. Find the overall tolerance band for the system if the input range is 0 to 10 and its independent nonlinearity is 0.5% deviation of the full scale and 1.5% deviation of the reading.

39

CH-1

y

x

3

0 10

0.5% FSD = .0523

1.5% Rdng = .15

Static Char.

Input Impedance

40

CH-1

variableflow

iableeffort var

d2

d1 X

XZ x

2

d2

2

d1d2d1 XZ

Z

XXXP x

x

• Disturb the quantity being measured.

• Xd1 : desired input (voltage, force, pressure)

• Xd2 : implicit input (current, velocity, flow)

• P = Xd1.Xd2 :Power transferred across the tissue-sensor interface

• Generalized input impedance Zx

•Goal: Minimize P, when measuring effort variable Xd1, by

maximizing Zx which in return will minimize the flow

variable Xd2.

•Loading effect is minimized when source impedance Zs is

much smaller then the Zx

Static Char.

1.10 Generalized Dynamic Characteristics

41

CH-1

)()( 0101 txbdt

dxb

dt

xdbtya

dt

dya

dt

yda

m

m

mn

n

n

)()( 0101 txbDbDbtyaDaDa m

m

n

n

01

01

)(

)(

aDaDa

bDbDb

Dx

Dyn

n

m

m

Most medical instrument process signals that are functions

of time. The input x(t) is related to the output y(t) by

ai and bi depend on the physical and electrical parameters

of the system.

Transfer FunctionsThe output can be predicted for any input (transient,

periodic, or random)

Dynamic Char.

Frequency Transfer FunctionCan be found by replacing D by j

42

CH-1

01

01

)(

)(

aDaDa

bDbDb

Dx

Dyn

n

m

m

01

01

)()(

)()(

)(

)()(

ajωajωa

bjωbjωb

jωX

jωYjH

n

n

m

m

Example:If x(t) = Ax sin ( t)

then y(t) = |H()| Ax sin ( t + /_H())

Dynamic Char.

Zero-Order Instrument

43

CH-1

Figure 1.5 (a) A linear potentiometer, an example of a zero-order system. (b) Linear static characteristic for this system. (c) Step response is proportional to input. (d) Sinusoidal frequency response is constant with zero phase shift.

a0 y(t) = b0 x(t)

Ka

b

jX

jωY

Dx

Dy

0

0

)(

)(

)(

)(

K: static sensitivity

Dynamic Char.

First-Order Instrument

44

CH-1

)()()(

001 txbtyadt

tdya

)()(1τD tKxty

τD

K

Dx

Dy

1)(

)(

1τ/arctan1

τ1

22ω

τω

K

jωX

jωY

jω

K

jωX

jωY

-

0

0

0

1

a

bK

a

a Where is the time constant

/1 teKty --

Dynamic Char.

First-Order Instrument

45

CH-1

t

1

(c)

(a)

C

+

-

+

-

y(t)

Output y(t)

Input x(t)

Slope = K = 1

(b)

Y (j

X (j

Log

scale

1.0

0.707

Log scale

(d)

0°

- 45°

-90°

Log scale

t

1

0.63

LS

L

S

SL

L

S

x(t)

x(t)

y(t)

R

τD

K

Dx

Dy

1)(

)(

/1 teKty --

Example 1.1:

Low-pass filter

)()()(

txtydt

tdyRC

1)(1 txKRC

Dynamic Char.

Second-Order Instrument Many medical instrument are 2nd order or higher

46

CH-1

txbtya

dt

tdya

dt

tyda 0012

2

2 tKxtyω

ζD

ω

D

nn

1

22

2

unitsinput by defined unitsoutput y,sensitivit static0

0 a

bK

rad/s frequency, natural undamped 2

0 a

aωn

essdimensionl ratio, damping 2

ζ20

1 aa

a

12

2

2

nn ω

ζD

ω

D

K

Dx

DyOperational Transfer Function

ωωωω

ζ

ωωζωω

K

jωX

jωY

ωζjωωjω

K

jωX

jωY

nnnn

nn

//

2arctan

/4/1

1/2/

22222

2

-

-

Frequency Transfer Function

Dynamic Char.

2nd order mechanical force-measuring Instrument

47

CH-1

Figure 1.7 (a) Force-measuring spring scale, an example of a second-order instrument. (b) Static sensitivity. (c) Step response for overdamped case = 2, critically damped case = 1, underdamped case = 0.5. (d) Sinusoidal steady-state frequency response, = 2, = 1, = 0.5.

Output y(t)

(b)

(d)(c)

1

Ks

x(t)

y(t)yn yn + 1

Resonance

2

Logscale

1

2

-90°

0.51

2 -180°

1

0.5

0.5

Log scale

Log scale

K1

t

t

Input x(t)

Slope K =1

Ks

0°

n

n

Y (j

X (j

Output

displacement

(a)

Input

Force x(t)0

y(t)

2

2

dt

tydMtyK

dt

tdyBtx s --

sKK /1

M

Kω s

n

MK

Bζ

s2

B = viscosity constant

Ks = spring constant

Natural freq.

Damping ratio

Dynamic Char.

Overdamped

48

CH-1

KKeζ

ζζKe

ζ

ζζty

tωζζtωζζ nn

-

--

-

--

---

-- 1

2

21

2

2 22

12

1

12

1

:1ζ

KKetωty tω

nn - -1

:1ζ

2

2

2

1arcsin

1sin1

ζ

KtωζKζ

ety n

tζωn

-

--

--

Underdamped

Critically damped

1

Ks

y(t)

0.5

t

21 - nd Damped natural freq.

:1ζDynamic Char.

Example 1.2: for underdamped second-order instruments, find the damping ratio from the step response

49

CH-1

21

2/3

ζω

πt

n

n

-

-

2

1

1

2/7

ζω

πt

n

n

-

-

21

2

22

22

1

1

2ln

1

2exp

1

2/7exp

1

1

2/3exp

1

ζ

πζ

y

y

ζ

πζ

ζω

πζω

ζ

K

ζω

πζω

ζ

K

y

y

n

n

n

n

n

n

n

n

-

-

-

--

-

-

--

-

224

πζ

and

Logarithmic decrement

KtωζKζ

ety n

tζωn

--

--

2

21sin

1

Dynamic Char.

Time Delay System

50

CH-1

dτtKxty -dτt

djωKejωX

jωY -

Logscale

Log scale

Log scale

K

0°

Y (j

X (j

dτ

Output is exactly as input,

only delayed

Dynamic Char.

Design Criteria

51

CH-1

Figure 1.8 Design process for medical instruments

Choice and design of instruments are affected by signal factors, and also by environmental,

medical, and economic factors.

Device Design

Commercial Medical Instrumentation Development Process

52

CH-1

•Ideas: come from people working in the health care

•Detailed evaluation and signed disclosure

•Feasibility analysis and product description

•Medical need

•Technical feasibility

•Brief business plan (financial, sales, patents, standards, competition)

•Product Specification (interface, size, weight, color)

“What” is required but nothing about “how”

•Design and development (software and hardware)

Device Design

Commercial Medical Instrumentation Development Process

53

CH-1

•Prototype development

•Testing on animals or human subjects

•Final design review (test results for, specifications, subject feedback, cost)

•Production (packaging, manual and documents)

•Technical support

Device Design

Regulation of Medical Devices

54

CH-1

Medical devices is “any item promoted for a medical

purpose that does not rely on chemical action to achieve its

intended effect”

2 Ways for Medical Devices Classification

First Method: (based on potential hazards)

Class I: general controls

Class II: performance standards

Class III: premarketing approval

Second Method: (see Table 1.2 in textbook)

preamendment, postamendment, substantially equivalent,

implant, custom, investigational, transitional

Device Design

Regulation of Medical Devices

55

CH-1

Second Way of classifications: ( Table 1.2 )

Preamendment: Devices on the market before 5/28/1976

Postamendment: Devices on the market after 5/28/1976

Substantially equivalent: Equivalent to preamendment devices

Implant: devices inserted in human body and intended to remain there for >30 days.

Custom: Devices not available to other licensed and not in finished form

Investigational: Unapproved devices undergoing clinical investigation

Transitional: devices that were regulated as drugs and now defined as

medical devices

Device Design