INTRODUCTION TO BIOMEDICAL ENGINEERING

PART III: Biomedical Signal Processing: An Introduction.

Instructor: Prof. Ju-Hong Lee.

Office: Room 517,

Tel: 23635251 ext. 517,

Email: [email protected]

Textbook: Eugene N. Bruce, Biomedical Signal Processing

and Signal Modeling,

John Wiley & Sons, Inc., New York, 2001.

Reference: Robert B. Northrop, Signals and Systems

Analysis in Biomedical

Engineering,

CRC Press LLC, 2003.

1
 COURSE OUTLINE

(I) Introduction to Biomedical Signals:

Signals from Physiological Systems

ECG, EEG, EGG, EMG, ERG, etc.

Signals from Man-Made Instruments

CW Doppler Ultrasound signals, MRI signals,

Positron Emission Tomography (PET) signals, etc.

Continuous-Time (CT) and Discrete-Time (DT)

Signals.

Purposes of Processing Biomedical Signals.

(II) Introduction to Linear System Theory:

Properties of Operators and Transformations.

The Impulse Response of a Linear System.

Convolution Form of a linear shift-invariant (LSI)

System.

Relation to Signal Processing.

Frequency Response of Discrete-Time Systems.

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 (III) Modeling CT Signals as Sum of Sine Waves.

Orthogonal Functions and Sinusoidal Basis

Functions.

Relationship of CT Fourier Transform (CTFT) to

Frequency Response.

(IV) Modeling DT Signals as Sum of DT Sine Waves.

The DT Fourier Series.

Fourier Transform of DT signals.

Sampling Process and Sampling Theorem.

(V) Noise Removal and Signal Compensation.

Linear Digital Filters.

Digital Filtering of Biomedical Signals.

Information for Further Reference:

(1)

10/27 cchen3@uchi
-Imaging of Life: Positron Emission
4:305:20 R143 cago.edu
Tomography (PET)

3
A Biomedical Signal is generally acquired by a sensor, a

transducer, or an electrode, and is converted to a proportional

voltage or current for processing or storage.

Electrocardiogram (ECG) The electrical potential at the

electrode or the potential difference between two electrodes

induced by the presence of time-varying electrical activity in

cardiac muscle. ECG is useful for a physician to obtain

considerable insight about whether the contractions of the

heart are occurring normally.

Electroencephalogram (EEG) The recording of brain

electrical activity from electrodes on the scalp. EEG is used to

determine if a person is asleep and to identity the sleep state.

Electrogastrogram (EGG) An electrogastrogram is

similar to an electrocardiogram (EKG) of the heart. It is a

recording of the electrical signals that travel through the

muscles of the stomach and control the muscles contraction.

4
Electromyogram (EMG) The signal recorded by placing
electrodes in, on, or near a muscle and amplifying the

electrical potential or the potential difference between two

electrodes induced by the generation and propagation of

action potentials along muscle fibers.

Electroretinogram (ERG) The electroretinogram (ERG)

is a retinal signal that is evoked by visual stimuli, but which is

not necessarily a part of the visual cascade. But, similar to the

visual cascade it is evoked by light absorption in the

photoreceptors and therefore is an epi-phenomenon of the

visual cascade. We measure the ERG non-invasively in human

subjects by positioning a small thread (DTL electrode) on the

cornea of the subject. The DTL electrode is not disturbing and

is conducts electrical currents, so that the ERG can be

measured. The visual stimulator is a computer controlled color

monitor.

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 Continuous-Time (CT) and Discrete-Time (DT) Signals
The signals resulting from these measurements are generally
continuous-time (CT) signals denoted by x(t). (Figure 1)
The signals taken from the sampling the values of a continuous-time
signal at integer multiples of some fundamental time increment
represent the discrete-time (DT) signals denoted by x(n). (Figure 2)
Mathematically, we write

x(n) =
n =0
x(t)(tnT), where T is the sampling period.

Example 1.2 of Text:

PURPOSES OF PROCESSING BIOMEDICAL SIGNALS

Why biomedical signals are Processed ?
(1) To remove unwanted signal components that are corrupting the
signal of interest.
(2) To extract information by rendering it in a more obvious or more
useful form.
(3) To predict future values of the signal in order to anticipate the
behavior of its source.
Signal Processing can be viewed as the manipulation of a signal (input)
for the purpose of either extracting information from the input signal
or producing an alternative representation of the input signal.
(Figures 1.8, 1.9 of Text)
Example: Example 1.6 of Text.

INTRODUCTION TO LINEAR SYSTEM THEORY

6
A linear system can be viewed as any physical device or set of rules
which transforms one variable (i.e., signal) x(t) into another variable
(or signal) y(t) linearly. (Figure 1.5 of Text) In equation form:
y(t) = T[ x(t) ]
(1) Linearity: T[ ] is a linear transformation if it is both additive
and homogeneous. That is, T[ ax1(t) + bx2(t) ] = aT[ x1(t) ] +
bT[ x2(t) ].
(2) Causality: T[ ] is a causal transformation if its output at any
time depends on the input at that time or at earlier times but not
on the input at future times. That is, y(t) = T[ x(t) ] for any time
instant t0, y(t0) depends on x(t), for t t0 only.
(3) Time-Invariant Property: T[ ] is a time-invariant transformation
if shifting of the input in time by an amount t0 only has the effect
of shifting the output in time by the same amount. That is, y(t) =

T[ x(t) ], then y(tt0) = T[ x(tt0) ]. So, we can say that T[ ] is

independent of the chosen time origin.

The Impulse Response of A Linear Time-Invariant System

Consider a unit impulse (n) called a delta function with
(n) = 1, n=0 and (n) = 0, otherwise.
A linear time-invariant (LTI) system T[ ] with input (n) produces
the output y(n) as follows:
y(n) = T[ (n) ] = h(n)
which is defined as the impulse response of the LTI system.
A Discrete-Time (DT) system is called a finite impulse response (FIR)

7
system if its h(n) =0, for all n > K, where K < . Otherwise, the LTI
system is called infinite impulse response (IIR) system.

Convolution Form of a linear shift-invariant (LSI) System

For a given discrete input signal x(n), we can express it as follows:
x(n) = +x(-2)(n+2)+x(-1)(n+1)+x(0)(n)+x(1)(n-1)+x(2)(n-2)++

= x(i )(n i ) .
i =

Then, y(n) = T[ x(n) ] = x(i )T[(n i )] =
i =
x(i )h(n i ) .
i =

This represents a fundamental expression of the input-output

relationship of an LTI DT system known as the convolution sum. In
general, it is symbolized as
y(n) = x(n) h(n).
By a change of variables, the convolution sum also can be written as

y(n) = x(n i )h(i ) .
i =

Figures 3.6 ~ 3.7.

Relation to Signal Processing

Applying a signal to the input of an LTI system produces an output
that is a modified form of the input signal as shown by the convolution
sum equation.
Low-Pass Filters attenuate rapid changes in the input more than slow
ones.
High-Pass Filters relatively unattenuate the rapid changes but its
output for a slowly varying input will be close to zero.
(Figure 3.10 of Text)
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The process of convolving the impulse response of an LTI system with
an input signal is the time-domain representation of filtering. Hence,
convolution is a key concept for understanding the modification of
signals by filters.
(Example 3.10 of Text)

Frequency Response of Discrete-Time Systems

In many applications, we may be interested in knowing the response of
an LTI system to an input signal in terms of quantitative description of
the transformation properties of the LTI system.
Moreover, in many physical systems, frequency-dependent behavior is
a universal phenomenon which is another indication of the filtering
properties of a system.
(Example of Figure 4.1 of Text)

Generalized Frequency Response:

Consider the LTI system with impulse response h(n), input x(n), and
output y(n). Let x(n) = a exp(jn), n. The output is found by
convolution to be

y(n) =
k =
h(k)x(n-k) =
k =
h(k)a exp[j(n-k)]

= a exp(jn) h(k) exp[-jk]
k =

= x(n)H(ej),

9

where H(ej) =
k =
h(k) exp[-jk] is called the generalized frequency

response of the LTI system. y(n) is a scaled version of the input. Any
input signal for which the output of an LTI system is simply a scaled
version of the input is known as an eigenfunction of an LTI system.
So, exp(jn) is an eigenfunction of an LTI system.
Magnitude (or Gain) Response: | H(ej) |
Phase Shift Response: arg(H(ej))
(Example 4.4 of Text The Frequency response of a DT lowpass filter)
Biomedical Example: The Frequency Response of an Auditory System
in Figure 4.15 of Text.

Modeling CT Signals as Sum of Sine Waves

Example: Figure 5.1 of Text
In this case, we use sinusoidal waves with different periods to model
the measured signal data. First, we use the sine wave with period
equal to 24 hours for approximation (Figure 5.2(a)). The
corresponding error curve can be approximated by a sinusoidal wave
with period equal to 8 hours (Figure 5.2(b)). Finally, these two
sinusoidal waves are added to model the original data. A better
approximation of the original data can be obtained. Hence, in this
way, it would be possible to model the noisy periodic signal as a sum
of sine waves.
Orthogonal Functions and Sinusoidal Basis Functions
Define an operator Q[] and a set of functions P = {pi(t), i =
1 ,2, ..K}. The functions in P are said to be orthogonal under the

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 0 i j
operator Q[] if Q[ pi(t)pj(t) ] = ,
i = j
where is a constant. This indicates that we can express a function
x(t) as a weighted sum of pi(t), i = 1, 2, ., K. For example, let x(t) = a
p1(t). Then, we have
1
Q[ x(t)pj(t) ] = a

if j = 1 and the result is zero if j 1. That is, the operation of x(t)
with each function pj(t) in the set P is a scalar that expresses how
much of each function pj(t) is present in x(t). The set of orthogonal
functions is termed a basis set. Any function x(t) can be expressed as
K
x(t) =
i =0
ai pi(t) .

Sinusoidal Basis Functions:

Consider the basis functions given by a set of orthogonal
trigonometric functions: sin(nt), cos(mt), for m, n.
T
Let the operator Q[ ] =
0
[ ] dt , where T = 2/.

Then, a periodic function x(t) with period = T can be expressed as the

Fourier series:

x(t) = n =0
[ an cos(nt) + bn sin(nt) ],

where the coefficients an and bn can be obtained as follows:\

2 T
an =
T 0
x(t) cos(nt) dt , n > 0

1 T 1 T
a0 =
T 0
x(t) cos(0) dt =
T 0
x(t) dt,

2 T
bn =
T 0
x(t) sin(nt) dt , n 0 .

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Hence,

x(t) = a0 +
n =1
[ an cos(nt) + bn sin(nt) ]

we can see that x(t) is represented as the sum of its mean value over a
cycle plus deviations from that mean value.

Complex Exponential Form of the Fourier Series:

We can rewrite x(t) as follows:

x(t) = a0 +
n =1
[ an cos(nt) + bn sin(nt) ]

exp( jnt ) exp( jnt )
= a0 + [ an exp( jnt ) + exp( jnt ) + bn ]
n =1 2 2j

a jbn a + jbn
= a0 + [ n exp(jnt)+ n exp(-jnt) ]
n =1 2 2

=
n =
cn exp(jnt) .

an jbn a + jbn
where cn = , c-n = n , c0 = a0,
2 2

Relationship of Continuous-Time Fourier Transform (CTFT) To

Frequency Response

From x(t) =
n =
cn exp(jnt), we can write

1
cn =
T
x(t)exp(-jnt) dt.
1
Let X() =
x(t)exp(-jt) dt, then cn =
T
X(n)

1
Hence, x(t) =
n =
cn exp(jnt) =
T

n =
X(n) exp(jnt)

1
=
2

n =
X(n) exp(jnt) .

Consider T , then d, and n .

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 1
We get x(t) =
2
X() exp(jt) d.

This describes the reconstruction of x(t) from a function of frequency

X(). As a result, X() is termed the Fourier transform (FT) of x(t)
while x(t) is termed the inverse Fourier transform (IFT) of X().
Utilizing the FT of any signal, we are able to investigate the
frequency contents of the signal. So, X() can also be called the
frequency response of x(t).
(Example 5.10 of Text)

The frequency response of a general LTI system is given by

H() =
h(t)exp(-jt) dt

which is the FT of the impulse response of the LTI system.

Fourier Transform of DT signals

Based on the FT relationship, we can write the FT of a DT signal x(n)
as follows:

X(ej) =
n =
x(n) exp(-jn)

And the IFT of X(ej) is given by

1
x(n) = X(ej) exp(jn) d.
2

This leads to the following important relationship describing the

input/output of an LTI system:
Consider the case: Let x(n) = exp(jn) = an eigenfunction of any LTI
system. So, y(n) = H(ej) exp(jn).

13
 1
Next, let x(n) = X(ej) exp(jn) d.
2

1
Then, y(n) = H(ej)X(ej) exp(jn) d.
2

1
= Y(ej) exp(jn) d.
2

Hence, Y(ej) = H(ej)X(ej) = Fourier transform of y(n) = h(n) * x(n).

Fourier transform of h(n) * x(n) = H(ej)X(ej).

Sampling Process and Sampling Theorem

To sample a continuous-time signal x(t) is to represent x(t) at a

discrete number of points, t = nT, where T is the sampling period,
which is the time between samples, and n is an integer that
establishes the time position of each sample. This process is
illustrated in the following figure. For the sampling process to be
useful, we must be able to show that it is possible to sample in such a
way that the signal x(t) can be reconstructed from the samples. The
easiest way is to discuss in the frequency domain.
(I) First, the sampled x(t), denoted xs(t), is written as
xs(t) = x(t) p(t),
where p(t), called the sampling function, models the action of the
sampling switch in the figure. In general, the sampling function p(t) is
assumed to be the periodic pulse train of period T illustrated in the
figure.
(II) Next, we derive the spectrum or the Fourier transform of xs(t),
and form this spectrum we are able to choose appropriate values T.
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Since p(t) is a periodic, it can be represented by a Fourier series as
follows:

p(t) =
n =
Cn exp(jn2fst),

where s = 2fs = 2/T and Cn is the nth Fourier coefficient of p(t),

given by
1 T /2
Cn =
T T / 2
p(t )exp( j 2nf st )dt

xs(t) =
n =
Cnx(t) exp(jn2fst)

Now the Fourier transform of xs(t) is defined by

Xs(f) =
xs(t) exp(-j2ft) dt

Xs(f) =

n =
Cnx(t) exp(jn2fst) exp(-j2ft) dt

Xs(f) =
n =
Cn

x(t) exp(jn2fst) exp(-j2ft) dt

Xs(f) =
n =
Cn

x(t) exp{ -j2[f-nfs]t } dt

Since the Fourier transform

X(f-nfs) =
x(t) exp{ -j2[f - nfs]t } dt

Thus the Fourier transform of the sampled signal can be written

Xs(f) =
n =
Cn X(f - nfs)

which shows the spectrum of the sampled continuous-time signal, x(t),

is composed of the spectrum of x(t) plus the spectrum of x(t)
translated to each harmonic of the sampling frequency. Each of the
translated spectra is multiplied by a constant, given by the
corresponding term in the Fourier series expansion of p(t).
In theory, we shall assume p(t) to be composed of an infinite train of
impulse functions of period T. Thus,
15

p(t) =
n =
(t-nT)

1 T /2
Cn =
T T / 2
(t) exp(-jn2fst) dt

1
Cn = = fs for all n.
T

Xs(f) = fs
n =
X(f - nfs)

(III) Finally, we can reconstruct the original CT signal x(t) from xs(t)
perfectly as follows: Using a low-pass filter (called a reconstruction
filter) to pick up the frequency content C0X(f).
(IV) Sampling Theorem:
We can see that the original CT signal x(t) from xs(t) perfectly if x(t) is
bandlimited, i.e., X(f) is zero for |f| fh and

fs fh fh

i. e., fs 2fh (Hertz)

Hence, the minimum sampling frequency is 2fh, where fh is the
highest frequency in x(t). In general, 2fh is known as the Nyquist Rate.

(V) The effect of sampling at too low a rate:

If x(t) is sampled below the Nyquist Rate, i. e.,

fs fh fh

then the adjacent spectra overlap making it impossible to recover x(t)

by filtering as shown by the following figure. This effect is known as
aliasing.
(V) Noise Removal and Signal Compensation
Removing noise from a signal probably is the most frequent
16
application for processing biomedical signals.
Example 1: Reducing the ECG artifact in an EMG recording. (Figure
8.1 of Text)
To record an EMG from muscles on the torso, the ECG is commonly
superimposed on the EMG signal because of the physical proximity
of the heart and the large electrical amplitude of the ECG compared
to many EMG signals. From the figure, we observe that the
frequency contents of the EMG and ECG signals seem to overlap
below about 30 Hertz. So, removal of the ECG signal by filtering the
EMG recording with a high-pass filter will necessarily remove some
EMG signal component also. However, the ECG can be reduced in
some degree through the high-pass filtering.

Example 2: Removing noise from an Ultrasound signal. (Figure 8.22

of Text)
To obtain the velocity of movement of red blood cells in a vessel may
be measured by oassing an ultrasound beam through the vessel wall
and determining the Doppler shift of frequency of the reflected beam.
Now using a 2-MHz ultrasound wave passes through the temporal
region of the skull without excessive attenuation, we are able to
measure blood flow velocity in arteries of the brain of humans.
Usually, blood flow velocity in the middle cerebral artery (VMCA) is
measured in Figure 8.22(c).
The signal was sampled at fs = 100 and it is desired to remove the
high-frequency noise using a digital filter. We use a low-pass digital
filter with cutoff frequency = 10 Hz to achieve this purpose. Two
17
types of digital filters, i. e., Hamming window filter and Equiripple
filter, are employed.
Figure 8.22 (a) plots the impulse response for each of these two filters.
Figure 8.22(b) plots the frequency response for each of these two
filters.
The Hamming window filter has a smaller stopband gain but its
transition band is about twice the width of that of the Equiripple
filter.

Example 3: The biomedical signal to be processed is the pressure in

the left ventricle of the heart (PLV). The maximum derivative of this
signal (during a given heart beat) is often considered as index of
myocardial contractility. We use a digital differentiator to achieve
this goal.
Figure 8.23(a) shows a sample of PLV.
Figure 8.23(b) and (c) plot the impulse response and the frequency
response of the digital differentiator.
Figure 8.23(d) depicts a portion of the original signal and its
derivative signal which appears to reflect the maximum derivative
occurs during the upstroke of the ventricular pressure.

18
ECG Signals

The Electrocardiogram

How the Electrocardiograph Works

Correlation of the ECG with Heart Sounds

Glossary Terms

A pair of surface electrodes placed directly on the heart will

record a repeating pattern of changes in electrical action

potential. As action potentials spread from the atria to the

ventricles, the voltage measured between these two electrodes

will vary in a way that provides a picture of the electrical

activity of the heart. The nature of this picture can be varied by

changing the position of the recording electrodes; different

positions provide different perspectives, enabling an observer to

gain a more complete picture of the electrical events.

Summary The body is a good conductor of

electricity because tissue fluids contain

a high concentration of ions that move

(creating a current) in response to

19
potential differences. Potential

differences generated by the heart are

thus conducted to the body surface

where they can be recorded by surface

electrodes placed on the skin. The

recording thus obtained is called an

electrocardiogram (ECG or EKG).

The electrocardiogram indicates

the conduction of electrical

impulses through the heart,

measures and records both the

20
 intensity of this electrical activity

(in milivolts), and the time

intervals involved.

How the There are two types of ECG recording

Electrocardiograph electrodes, or leads. The bipolar limb

Works leads record the voltage between

electrodes placed on the wrists and

legs. These bipolar leads include lead I

(right arm to left arm), lead II (right

arm to left leg), and lead III (left arm to

left leg). In the unipolar leads, voltage

is recorded between a single

exploratory electrode placed on the

body and an electrode that is built into

the electrocardiograph and maintained

at zero potential (ground).

The unipolar limb leads are placed on

the right arm, left arm, and left leg;

21
 these are abbreviated AVR, AVL, and

AVF, respectively. The unipolar chest

leads are labeled one through six,

starting from the midline position (see

below). There are thus a total of twelve

standard ECG leads that view the

changing pattern of the hearts

electrical activity from different

perspectives. This is important because

certain abnormalities are best seen with

particular leads and may not be visible

at all with other leads.

The unipolar limb

leads are placed on

the right arm, left

arm, and left leg;

these are

abbreviated AVR,

AVL, and AVF,

22
respectively. The

unipolar chest leads

are labeled one

through six, starting

from the midline

position (see

below). There are

thus a total of

twelve standard

ECG leads that

view the changing

pattern of the

hearts electrical

activity from

different

perspectives. This is

important because

certain

abnormalities are

23
best seen with

particular leads and

may not be visible

at all with other

leads.

The placement of the bipolar leads and the exploratory

electrode for the unipolar chest leads in an

electrocardiogram (ECG); (RA = right arm, LA = Left

arm, LL = left leg.)

Each cardiac cycle produces three distinct

ECG waves, designated P, QRS, and T. It

24
should be noted that these waves are not

action potentials; they represent changes

in potential between two regions on the

surface of the heart which are produced by

the composite effects of action potentials

in many myocardial cells. For example, the

spread of depolarization through the atria

causes a potential difference that is

indicated by an upward deflection of the

ECG line. When about half the mass of the

atria is depolarized, this upward deflection

reaches a maximum value, because the

potential difference between the

depolarized and unstimulated portions of

the atria is at a maximum. When the entire

mass of the atria is depolarized, the ECG

returns to baseline because all regions of

the atria have the same polarity. The

spread of atrial depolarization thus creates

25
the P wave.

Conduction of the impulse into the

ventricles similarly creates a potential

difference that results in a sharp upward

deflection of the ECG line, which then

returns to the baseline as the entire mass

of the ventricles becomes depolarized. The

spread of the depolarization into the

ventricles is thus represented by the QRS

wave. During this time the atria repolarize,

but this event is hidden by the greater

depolarization occurring in the ventricles.

Finally, repolarization of the ventricles

produces the T wave (see illustration

below).

26
The conduction of electrical impulses in the heart, as

indicated by the electrocardiogram (ECG). The direction

of the arrows in (e) indicates that depolarization of the

ventricles occurs from the inside (endocardium) out (to

the epicardium), whereas the arrows in (g) indicate

that repolarization of the ventricles occurs in the

opposite direction.

27
Correlation of the Depolarization of the ventricles, as

ECG with Heart indicated by the QRS wave, stimulates

Sounds contraction by promoting the uptake of

Ca++ into the regions of the sarcomeres.

The QRS wave is thus seen to occur at the

beginning systole. The rise in

intraventricular pressure that results

causes the AV valves to close so that the

first heart sound (S1, or lub) is produced

immediately after the QRS wave (see

following illustration).

28
The relationship between changes in

intraventricular pressure and the

electrocardiogram during the cardiac

cycle. The QRS wave (representing

depolarization of the ventricles)

occurs at the beginning of systole,

whereas the T wave (representing

repolarization of the ventricles)

29
occurs at the beginning of diastole.

Repolarization of the ventricles, as

indicated by the T wave, occurs at the

same time that the ventricles relax at the

beginning of diastole. The resulting fall in

intraventricular pressure causes the aortic

and pulmonary semilunar valves to close

so that the second heart sound (S2, or

dub) is produced shortly after the T wave

in an electrocardiogram begins.

30
 EEG Signals

The History

of the

Electroencep

halogram

In 1929, a German

psychiatrist named

Hans Berger, who

worked in the city of

Jena, announced to the

world that:

it was possible to record the feeble electric currents

generated on the brain, without opening the skull, and

to depict them graphically onto a strip of paper.

31
 Berger named this new form of recording as the

electroencephalogram (EEG, for short);

that this activity changed according to the functional

status of the brain, such as in sleep, anesthesia,

hypoxia (lack of oxygen) and in certain nervous

diseases, such as in epilepsy.

First EEG recorded by Hans Berger, circa 1928.

These were revolutionary discoveries, and, in fact, Berger

founded an entirely new and very important branch of

medical science, named clinical neurophysiology.

Berger electrodes were too large to made detailed

topographycal studies of the EEG (in other words, to use

electrical activity recorded from the brain to pinpoint areas

of sensory projection, the localization of tumors or of

epileptic foci, etc.).

32
This was left to W.

Gray Walter, a

remarkable British

scientist, who, in

1936, proved that,

by using a larger

number of

electrodes pasted to the scalp, each one having a small

size, it was possible to identify abnormal electrical activity

in the brain areas around a tumor, and diminished activity

inside it.

Impressed with the possibilities of building bidimensional

maps of the EEG activity over the brain surface, W. Gray

Walter invented the toposcope in 1957.

This was a remarkably complex device and showed Grey

Walter's inventiveness (besides being a physician, he was

also an engineer). It had 22 cathode ray tubes (similar to a

TV tube), each of them connected to a pair of electrodes

33
attached to the skull. The electrodes (and their

corresponding tubes) were arranged in a bidimensional

geometrical array, such as that each tube was able to

depict the intensity of the several rhythms which compose

the EEG in a particular area of the brain (the frontal ,

parietal and occipital lobes, etc.). This array of CRT tubes,

were photographed face up, so that a kind of

phosphorescent spiral display showed simultaneously

which kind of rhythm was present in a particular part of the

brain.

Gray Walter asked his subjects to perform several mental

tasks, with the result that the EEG rhythms were altered in

different ways, times and parts of the brain. He was the

first to prove, for instance, that the so-called alpha rhythm

(present during a resting state) disappears from almost all

the brain during a mental task which demands awareness,

being substituted by a faster rhythm, the beta waves.

34
It was immediately apparent to neurologists that the

toposcope could be a great help to locate epileptic foci (the

points where a convulsion originates in the brain, due to a

local lesion, tumor or functional alteration). However, it was

very complex and expensive and it did not achieve

commercial success or widespread use.

The topographic study of brain electrical activity was born

again only when fast desktop computers became available

in the 80s. Thus, EEG brain topography was developed

and is widely in use today. It is also called Color Brain

Mapping.

The Brain is Electric...

Technical developments in the field of electrical

measurement and recording in the last quarter of the 19th

century made possible one of the greatest triumphs of

modern neuroscience: the discovery, made by a German

35
psychiatrist named Hans Berger, that the human brain has

a continuous electrical activity, and that it can be recorded

(see the History of the Electroencephalogram).

The electroencephalographic recording is usually taken

by electrodes (small metallic discs) pasted by an electricity

conducting gel to the surface of the skull's skin (scalp). A

powerful electronic amplifier increases several hundreds or

thousands of times the amplitude of the weak signal (less

than a few microvolts) which is generated in this place. A

device called galvanometer, which has a inkpen attached

to its pointer, writes on the surface of a paper strip, which

moves continuously at a fixed speed past it. The result is a

wiggly "wave" like the picture above. One pair of

electrodes usually make up a channel. EEG recordings,

depending on its use, can have from 8 to 40 channels

36
recorded in parallel. This is called multichannel EEG

recording.

Since the times of Berger, it is know that the characteristics

of EEG activity change in many different situations,

particularly with the level of vigilance: alertness, rest,

sleep and dreaming. The frequency and the amplitudes of

waves change, and they have been labelled with names

such as alpha, beta, theta and delta. Particular mental

tasks also alter the pattern of the waves in different parts of

the brain (See the article on the physiological basis of

dreaming, in the last issue of Brain & Mind).

Electroencephalograms are also used in neurology and

psychiatry, mainly to help diagnose diseases of the brain,

such as epilepsy (convulsions caused by a chaotic activity

of neurons), sleep disorders and brain tumors.

37
 Building Maps of the Mind

An important application of multichannel EEG is to try to

find the location of a epileptic focus (a small spot in the

brain where the abnormal activity originates and then

spreads to other parts of the brain) or of a tumor, even

when they are not visible in a x-ray or CT scan of the head.

38
 A 32-channel EEG using a modern recorder.

Each horizontal tracing corresponds to an

electrode pair placed on a particular area of the

patient's scalp, forming a regular grid-like pattern.

By noting the set of channels where abnormal waves

occurr (such as those marked in red), the neurologist is

able to infer the parts of the brain where the abnormality is

located. This is very difficult to scan and to interpret, and

subject to many errors, however, when the number of

abnormal channels is large, or the nature of changes is

complex. A precise bidimensional location of a focus or

tumor is impossible to achieve.

So, what is the solution ? The computer, of course.

Computers and Brain Waves

39
 In order to use the superior

power and flexibility of the

computer to store and to

analyze the EEG and other

biosignals, an invention was of fundamental importance:

the so-called analog-digital converter (or DAC).

Essentially, it is an electronic device that takes a

continuously variable wave and transform it to a list of

numbers (each number being a measurement of the

wave's amplitude at regular time intervals. These

measurements are called samples, so the whole process is

also named sampling). Sampling is performed at a high

speed (100 to 200 times per second), and the resulting

numbers are stored onto the computer's disk. Each

channel of EEG has its own separate DAC process, in

parallel with the others, and this proceeds in real time.

Once all the numbers which were recorded along a period

of time are inside the computer, special software programs

are used to display the waves in the video screen, print it

40
 out, etc. Mathematical

techniques working with these

large arrays of numbers are

used to do filtering, frequency

and amplitude analysis and color

mapping. This approach is called quantitative EEG,

because it's different from the traditional approach, which

doesn't make any measurements on the tracings; instead,

it relies on qualitative assessment or overall apperance of

the patterns of waves.

EEG Brain Topography

With the possibility of recording simultaneously a great

number of digitized channels of EEG, a new technique was

born: EEG brain topography, at the end of the 80s. In this

41
technique a large number of electrodes is placed onto the

head, following a geometrical array of even-spaced

points. A special software inside the apparatus' computer,

plots the activity on a color screen or printer, by coding the

amount of activity in several tones of color (for example,

black and blue might depict low EEG amplitude, while

yellow and red might depict larger amplitudes). The spatial

points lying between electrodes are calculated by

mathematical techniques of interpolation (calculating

intermediary values on the basis on the value of its

neighbors), and thus a smooth gradation of colors is

achieved.

This approach gives a much more accurate and

representative view of the location of alterations of rhythm,

amplitude, etc., in relation to i the surface of the skull.

Neurologists working with the EEG brain topographic

system were soon able to differentiate several kinds of

diagnoses (including some mental diseases whose

biological origin, or ethiology, was previously unknown).

42
Pinpointing the exact location of EEG alterations was also

made much more easier. In addition, the use of the cin

mode (animations using several sequential pictures taken

from the brain maps) made possible the dynamic study of

brain function in action.

What For ?

EEG brain topography is not performed in all cases

requiring a recording of the brain activity. Its main

indication is to determine the presence of tumors and focal

disease of the brain (including epilepsy, arteriovenous

mal-formations and stroke). It is also appropriate when

disturbances in consciousness and vigilance are present,

such as narcolepsy (the abrupt onset of sleep), coma, etc..

In addition, EEG brain topography is being increasingly

used to monitor the effects of withdrawal of psychoactive

drugs, and in infectious diseases of the braim, such as

43
 meningites, as well as to follow up patients

who where subjected to brain operations. In

psychiatry, EEG brain topography has been

of value in identifying disorders of biological

origin, such as schizophrenia, dementias,

hyperactivity and depression, brain atrophy and attention

deficit disorders in children.

Today, there are many

commercial EEG brain

topography systems in use.

They are generally installed in

PC- or Macintosh-based

microcomputer platforms, and can be easily operated by

technicians or physicians, due to the Windows-based

software which comes with the package. This software is

highly flexible, permitting the programming of many

recording configurations and parameters, as well as to

44
build a reference database of images, composed of typical

patient cases in several pathologies. Usually, the

multichannel records can be shown side by side with the

reconstructed topographical brain map. In addition, several

maps taken in different epochs can be displayed side by

side.

45
EGG Signals

Electrogastrogram (EGG)

What is an electrogastrogram?

An electrogastrogram is similar to an electrocardiogram

(EKG) of the heart. It is a recording of the electrical signals

that travel through the muscles of the stomach and control

the muscles contraction.

When is an electrogastrogram used?

An electrogastrogram is used when there is a suspicion

that the muscles of the stomach or the nerves controlling

the muscles are not working normally. Usually this

suspicion arises when there is a problem with recurrent

nausea and vomiting, signs that the stomach is not

emptying food normally. If the electrogastrogram is

abnormal, it confirms that the problem probably is with the

46
stomachs muscles or the nerves that control the muscles.

The electrogastrogram can be considered an experimental

procedure since its exact role in the diagnosis of diseases

of the stomach has not been defined yet.

How is an electrogastrogram done?

For an electrogastrogram, several electrodes are taped

onto the abdomen over the stomach in the same manner

as electrodes on the chest for an electrocardiogram. The

electrodes sense the electrical signals coming from the

stomachs muscles, and the signals are recorded on a

computer for analysis. Recordings are made both fasting

and after a meal with the patient lying quietly. The study

takes two or three hours.

How are the results of the electrogastrogram

evaluated?

In normal individuals there is a regular electrical rhythm

47
generated by the muscles of the stomach--just as in the

heart--and the power (voltage) of the electrical current

increases after the meal. In patients with abnormalities of

the muscles or nerves of the stomach, the rhythm often is

irregular or there is no post-meal increase in electrical

power.

Are there any side effects of an electrogastrogram?

There are no side effects. The study is painless.

Are there alternatives to the electrogastrogram?

No, there are no alternatives; however, other studies, for

example, antro-duodenal motility studies or gastric

emptying studies may give additional information since

abnormal electrical activity of the stomach often results in

abnormal muscular activity and reduced emptying of food

from the stomach.

48
 Fig. 1. EGG tracings during the

baseline period and during the

shock and dive stimuli. The

View larger version segments shown are 1 minute in

duration and are from the same

subject. Notice the change in

frequency during the shock stimulus

compared with the baseline period

and the relative lack of change in

frequency during the dive stimulus

compared with the baseline period.

Effects of Shock and Dive Stimuli on Emotions

49
EMG Signals

The Electromyogram (EMG) records the electrical activity

in muscles. It can diagnose diseases of the nerves and

muscles. This test can help determine the cause of muscle

weakness, spasms, paralysis, pain in the arms, hands, legs or

face. It can detect conditions such as pinched nerves,

inflamed muscles and carpal tunnel syndrome. The electrode,

a tiny needle, is inserted into a muscle to record its electrical

activity. It records activity during the insertion, while the

50
muscle is at rest, and while the muscle contracts. An

amplifier increases the strength of the electrical signal from

the muscle. An oscilloscope, which resembles a television or

computer screen, displays the image. Speakers are used so

the sounds produced by the electrical signals can be

analyzed. After the first muscle is tested, the electrode may

be inserted into another muscle. The total testing time may

range from just a few minutes to more than an hour,

depending upon how many muscles are tested. After the

exam, you may feel tenderness in the tested muscles. There is

a slight risk of minor, localized inflammation in muscles

during the test. This usually lasts only a few hours.

An EMG Application

Deriving an activity index from an EMG waveform is a

specific application of the integral. The following example

illustrates how the rectification and integration functions of

Advanced CODAS are applied to an EMG channel to

51
derive an activity index. The EMG signal shown in Figure 2

was obtained from a bioelectric amplifier connected to a

pair of surface electrodes placed several centimeters apart

over the biceps muscle. The signal was acquired with a

WINDAQ data acquisition system installed in a Toshiba

Portable personal computer. The output of the bioelectric

amplifier was connected to the input of the WINDAQ board

through an option 01 module and a total gain of 1000 was

applied using the live, interactive program capabilities of

WinDaq acquisition software. A sample rate of 1000

samples per second provided better than 100Hz response.

This is similar to the best response that could be achieved

with a pen-type oscillographic chart recorder. Figure 2

shows the acquired EMG signal with a compression factor

of 16 applied, equivalent to slowing down a chart

recorder's paper speed by a factor of 16.

52
Figure 2 The original EMG signal acquired by skin

surface electrodes placed several centimeters apart over

the biceps muscle. Other than the duration and intensity of

the muscular contraction, the waveform conveys little

meaningful information in this state.

53
Figure 3 Channels 2 and 3 illustrate the activity index

waveform. The Channel 2 shows the activity index with

sample/hold enabled, while Channel 3 shows the activity

index with sample/hold disabled.

54
ERG Signals

As early as 1865 Holmgren found that a light stimulus could

cause a change in the electrical potential of the amphibian

eye. Shortly afterwards, similar findings were reported by

Dewar from Scotland. He showed that light illumination

through the pupil, which had previously been covered,

caused a slight movement of a galvanometer, suggestive of a

positive electrical change in the cornea relative to the back

of the eye (Armington, 1974). This light-induced electrical

activity of the eye was called the electroretinogram.

Nowadays the electroretinogram response is commonly

abbreviated to the ERG.

Gotch (1903) was the first to report that the response of the

eye to a light flash consisted of two waves; first the cornea

became negative and then a positive wave of larger

amplitude appeared. Later Einthoven and Jolly (1908)

separated the ERG response into three waves. The first wave

to appear immediately after turning on a light stimulus was

55
negative on the cornea. It was followed by a positive wave

and a final slower wave that was also positive. Einthoven

and Jolly (1908) suggested that the light stimulus triggered a

chain of reactions leading to the formation of products A, B

and C, and that every electrical wave indicated a change in a

'relevant' product. These authors' work was the foundation

for the form of analysis of the ERG used to the present day.

The waves are called a-, b- and c-waves. An additional

corneal-positive wave, that is more rarely recorded at the

termination of the light flash, is called the d-wave.

Figure 1 shows ERG responses from different species. These

responses are to bright light stimuli applied in the

dark-adapted state. The ERG of the turtle eye (Fig. 1A) as

elicited by a long (900ms) step of light, shows an a-wave and

b-wave complex separated from the d-wave which is

generated at stimulus offset. A bright light stimulus of 40sec

duration is used to record the ERG of the bullfrog in figure

1B (Oakley, 1977). The a-wave and b-wave are followed by

the slow corneal-positive c-wave. After termination of the

56
stimulus, a d-wave develops. The ERG responses of the

rabbit (Fig. 1C) and the human (Fig. 1D) are elicited by fast

bright flashes (50 or 100ms in duration) and therefore, only

the a-wave and b-wave are seen. In the human response (Fig.

1D), fast oscillations can also be seen on the ascending limb

of the b-wave. These ERGs in the different species clearly

differ in amplitude and pattern. Some of this variability is

due to species differences, particularly, the relative densities

of rods and cones, while technical factors such as duration

and intensity of photostimulation and method of recording

also affect the waveform. Nevertheless, ERG responses of

turtle, bullfrog, rabbit and human (Fig. 1), in addition to

those recorded from other vertebrate species, are

characterized by the basic features of a negative a-wave

followed by a positive b-wave.

57
Fig. 1. (A) ERG response of turtle Pseudemys scripta elegans

elicited by a 900ms light stimulus in order to separate the

a-wave and b-wave from the d-wave. (B) The ERG of the

bullfrog elicited by a long (40sec) light stimulus in order to

show the c-wave in addition to the a-, b- and d-waves

(Oakley, 1977). (C) The ERG response of a rabbit to a flash

(20_s) flash of white light. (D) The ERG response from a

human as typically recorded in the clinic. Note the fast

oscillations on the ascending limb of the b-wave. Calibration

bars are denoted separately for each ERG response. (59 K

jpeg image)

58
CW Doppler Ultrasound Signals
Diagnostic Ultrasound
is an important tool in
today's sophisticated
medical diagnostics.
Nearly every medical
discipline benefits
from this relatively
inexpensive method
providing an accurate
view of the inner
organs of the human
body without
exposing any
radiation to the
patient.

Continuous
improvements in
technology are
leading to higher
resolution images and
thus to new
applications, which is
also an important
contribution to cost
reduction by
replacing more
expensive and
harmful diagnostics.

Diagnostic ultrasound
is the most innovative
sector of the
diagnostic imaging
market today and
constitutes the
largest imaging
59
 modality worldwide.

As an independent
supplier, sonoTECH
provides research
and development
services to the
worldwide ultrasound
community.
sonoTECH is uniquely
positioned to serve as
an extension to the
customer's research
and development
operations by
providing state of the
art ultrasound
know-how.

sonoTECHs
technical expertise
covers every item
throughout
ultrasound imaging
and Doppler
technology from low
noise front ends, high
performance analog
or digital beam
formers, spectral and
color Doppler
processing modules
to digital scan
converters and cine
loop subsystems.

60
Ultrasound

Know-how

sonoTECH's
engineering
department has
developed a
number of
successful
technologies
including:

Analogue
Beam Forming
for linear and
curved array
transducers in
the frequency
range from 1.0
MHz to 10.0
MHz. Our
sophisticated
analogue beam
forming
technology with
32 or more
channels
achieves an
outstanding
image quality at
a very
competitive cost
level. The high
dynamic range in
combination with
the low noise
levels results in
61
sharp, clear and
crisp 2D,
Spectral Doppler
and Color Flow
images.

The Imaging
System for
Mechanical
Probes (2 MHz
to 15 MHz),
including
digitally
controlled servo
module for
mechanical
probes, which
supports
transducer
geometries up to
360 degrees.

Digital Beam
Forming allows
finer delay
quantization,
higher phase
accuracy and
more versatility
for linear-curved
and phased
array high end
ultrasound
systems.
Our CW and
interleave
(duplex) PW
highly sensitive
Spectral
62
Doppler
Modules with FFT
Spectrum
Analyzer and
Oversampling
Digital Audio
Processing.

The Digital
Scan Converter
performs
continuous
zooming of living
and even frozen
images, with
cine loop
capabilities of up
to 256 images
for linear and
sector
geometries with
scan angles up to
360 degrees.

The
Physiological
Channels
Module including
ECG.
The Color Flow
Processing
Module uses a
second
generation,
highly advanced
multi gate
autocorrelation
technique in
combination with
63
an improved
(lossless)
stationary echo
canceller for
higher flow
sensitivity and
resolution even
at lowest blood
velocities.
This is achieved
by using the
paralleled
processing
power of ten
high speed signal
processors.

All Color
Doppler modes
like velocity
mode,
velocity-variance
mode, intensity
mode,
directional
intensity mode,
tissue doppler
mode and
B-Flow are
supported at
fundamental and
harmonic
frequencies.

64
MRI Signals

Medical Applications

Multiple Sclerosis

MRI is providing scientists with a clear view of the circuitry

of the brain, and it is showing them how the brain works, as

well as how disease causes it to malfunction. For example,

multiple sclerosis (MS) is a chronic, progressive disease that

afflicts roughly a quarter-million Americans. Typical

symptoms include loss of balance, paralysis, numbness,

visual disturbances, incontinence, and even dementia. These

symptoms, resulting when components of the immune

system misguidedly attack specialized sheaths

that insulate connections between nerve cells, vary greatly,

making diagnosis difficult. But MRI can overcome such

diagnostic uncertainties because it readily shows those

damaged sheaths as small, whitish spots.

65
MRI also can help doctors determine whether or when a

patient with early-stage MS needs treatment. Even when a

patient appears clinically stable, the disease can be stealthily

ravaging the brain, and such early-stage MS patients usually

should be treated, whereas those whose MRIs show few

active lesions may safely delay treatment.

Researchers are developing other, potentially more accurate

ways to monitor MS with MRI. Dr. Richard Rudick and Dr.

Elizabeth Fisher of the Cleveland Clinic Foundation use

MRI to measure brain volumes with precision. Among

healthy men and women 20-50 years old, 87 percent of the

brain volume is tissue and the remaining 13 percent is water,

with less than one percent variability. However, among

individuals with MS, the tissue fraction declines by about 0.7

percent

annually. Measuring these declining tissue volumes may

enable physicians to determine how long individual patients

have had MS and to more accurately predict the course of

the disease. "It looks as if the atrophy severity and the

66
change in atrophy score predict the patient's status 6-8 years

down the line," says Dr. Rudick. This use of MRI also might

help determine whether a patient's treatment is working, as

well as the effectiveness of new drugs being tested in clinical

trials.

Stroke

Another devastating brain disease, stroke, is the third

leading cause of death in the U.S. About 550,000 strokes

occur annually, killing roughly 100,000 people and leaving

many others severely disabled. One such patient, a retired

college professor who was writing a book when stricken, was

left paralyzed and with so little short-term memory that she

was usually unable to recall which close friend had visited

her as recently as an hour earlier.

Most strokes occur when a brain artery is blocked, either by

a clot growing on the vessel wall, or, as in the case of this

college professor, by one that the blood swept into the brain

from elsewhere in the body. Less often, in about 20-25

67
percent of cases, a stroke may result from a ruptured blood

vessel. In both cases, brain tissue that becomes deprived of

oxygen quickly dies. However, knowing the cause of stroke is

critical for determining how stroke patients are treated.

Strokes caused by clots are treated with clot-busting

thrombolytic drugs, provided the patient reaches the

hospital within three to six hours of onset. However, if the

stroke arises from a hemorrhage such drugs need to be

resolutely avoided because they can make matters worse.

Most patients with an acute stroke receive a CT scan before

MRI, because CT is particularly sensitive to bleeding in the

brain and also because such instruments are cheaper and

thus more widely available than MRI. While CT shows

bleeding, MRI can reveal the size and location of the stroke

far more accurately and precisely than CT. This more

detailed information can be vital when making treatment

decisions.

68
A recently developed MRI technique, called diffusion

imaging (Fig.2), can diagnose strokes within minutes,

revealing the location and size of damage. Diffusion imaging

highlights the random movement, or diffusion, of water,

which decreases when a stroke kills nerve cells. Thus, where

neurons are dying, there is a net flow of water from the

extracellular spaces into the cells. Since water diffuses

relatively freely outside cells, while its movement is

constrained inside cells by all the cellular machinery, there is

less than ordinary diffusion in the vicinity of the stroke, and

this difference shows up clearly on diffusion MRI. That

movement of water from the extracellular spaces into the

dying neurons takes place because normal, healthy cells,

including neurons have a lower concentration of salt than

the surrounding extracellular fluids. Therefore salt leaks

into the neurons, like water seeping into a boat through tiny

holes in the gunwales, and so the neurons have to bail it.

They have special pumps just for this task. But as a clot

chokes off the blood, the bailing pumps lose their energy

69
supply and stop working, and the cell dies. Salt flows inward

and water follows.

Figure 2. Three different MRI imaging protocols of a

patient 20 min after a stroke event. The T2 weighted

image in the first panel shows some structural

information about the patient's brain but no evidence

of the site of the stroke. The diffusion weighted image,

which monitors the random movement of water,

shows a distinct lesion on the right side of the patient

(right side of middle panel). This is representative of

decreased water diffusion in the area of the stroke,

where there are dead neurons. The third panel shows

a perfusion image, which demonstrates regions of the

brain where there is reduced blood flow. The region

of reduced blood flow in this patient (dark areas) is

70
identifiable by the lower contrast and structural

detail. This is larger than the area highlighted in the

diffusion-weighted image, which may indicate that

there may be additional neuronal cell loss. Courtesy

of Drs. Steven Warach and Lawrence Lautor,

National Institutes of Neurological Disorders and

Stroke, National Institutes of Health, MD.

One challenge in treating strokes is that most victims do not

reach the hospital quickly enough to be candidates for

thrombolytic drugs, which ordinarily are effective only when

used within about three hours of onset. But Dr. Chelsea S.

Kidwell of the University of California, Los Angeles and her

colleagues are developing a means for using MRI imaging

information to predict whether particular patients might

benefit from such thrombolytic treatments at times

following that usual three-hour window. "We believe that

the information we are obtaining from the MRI will indicate

if there is still salvageable tissue beyond these absolute time

71
windows, and that this information could then be used to

make treatment decisions," says Dr. Kidwell.

The central area of the stroke, where the blood supply is

choked off, may be surrounded by an area where the blood

flow is merely restricted, stressing the still-undamaged nerve

cells. A recently developed technique called

perfusion-weighted MRI can measure this blood flow (Fig.

2). Combined with diffusion-weighted images, it can provide

valuable information about how the stroke may progress. If

an area of low blood flow surrounds the central area of the

stroke, the stroke is likely to spread, unless normal blood

flow is quickly restored. But if not, doctors can be pretty

sure that the stroke has run its course and that further

treatment with thrombolytic drugs offers no benefit.

Within hours following a stroke, the brain begins adapting

to its new limitations, marshalling regions that normally

have nothing to do with the tasks that the damaged region

had been performing. Sometimes, however, the damage

72
overwhelms this limited ability of other brain segments to

adapt to performing new activities. Using functional MRI

(see box previous page), Dr. Marcel Just of Carnegie Mellon

University is developing therapies that aim at improving the

damaged brain's capacity to deal with its changed

circumstances. For instance, patients whose language

networks are damaged by stroke often can no longer

understand complex sentences. Based on functional MRI

studies, Dr. Just learned that the undamaged brain

sometimes enlists the prefrontal cortex to reason through

unfamiliar tasks. To engage the prefrontal cortex to help

language-impaired stroke patients overcome some of their

speech-associated difficulties, Dr. Just has presented them

with sentences, asking them to find the verb, and to explain

the action. He finds that, over a month, some patients

improve so much that they could again analyze complex

sentences as quickly as subjects with normal brains.

Functional MRI studies indicate that the patients' prefrontal

cortices again are active when the patients converse.

73
Brain Surgery

It is no accident that brain surgeons use many, if not all, the

MRI tools that are available. Operating on the brain is

delicate and complex for many reasons. The skull is difficult

to penetrate, nerve cells are easily damaged and slow or

impossible to repair, and anatomic landmarks are difficult

to discern. Even with MRI to help in visualizing the

functional anatomy of the brain, brain surgeons are

afforded a view that is more like that from a tiny porthole

rather than a picture window.

Thus, despite their value, conventional MRI maps of the

brain have shortcomings. When tumors or otherwise

diseased tissues are extracted, the brain undergoes

seismic-like shifts, rendering the original map inaccurate.

"When the tumor comes out, it leaves this hole," says Dr.

Jolesz of Brigham and Women's Hospital. "The remaining

cortex is falling in, and so there are deformations.

74
You can't use the original image to guide the surgery."

Edema, or swelling that occurs during surgery may also shift

the terrain. At Brigham and Women's, however, recent

improvements being made to conventional MRI mapping

procedures are changing all that.

Before surgeons ever scrub for surgery, they review

three-dimensional composites of various MRI images of

their patients' respective brains to plan the best path to a

particular damaged area and to avoid causing incidental

damage, such as "big bleeds." First, conventional MRI

provides a structural map, pinpointing the tumor and major

arteries in its vicinity. Additionally, functional MRI maps

help to locate centers of speech, movement, and other

critical functions.

Typically during MRI-guided brain surgery, a patient lies

upon a platform that spans two magnets shaped like huge

tires that are spaced far enough apart for members of the

surgical team to stand between them. Initially, a monitor

75
above the surgical field displays the same image that the

surgeon studied, but aligned precisely with the patient's

brain, providing the surgeon with the virtual equivalent of

X-ray vision. Throughout the operation, the MRI system

provides a series of fresh images, each new one overlaying its

predecessor on the screen, thereby updating any shifts

within the anatomic terrain. Moreover, a special probe

enables the surgeon to monitor specific sites along the

incision within the brain, providing fresh images that appear

immediately upon the screen above.

Not only does this MRI-based technology reduce the danger

of damaging the brain, it also enables surgeons to remove

more of each tumor that they encounter. Before this

image-guided surgery became available, up to 80 percent of

operations ultimately failed because they left bits of

low-grade tumor behind.

76
 PET Signals

Welcome Page Research Areas

What is PET?

The name "PET" comes from Positron Emission

Tomography. It is a new scanning technique in medical

research. PET allows us, for the first time, to measure in

detail the functioning of distinct areas of the human brain

while the patient is comfortable, conscious and alert. We can

now study the chemical process involved in the working of

healthy or diseased human brains in a way previously

impossible. Before the advent of the PET scanner, we could

only infer what went on within the brain from post-mortems

(dissections after death) or animal studies.

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 PET represents a new step forward in the

way scientists and doctors look at the brain

and how it functions. An X-ray or a CT scan

shows only structural details within the brain.

The PET scanner gives us a picture of the brain at work.

Positron: Antimatter equivalent of the electron

A positron is an anti-electron. Positrons are given off during

the decay of the nuclei of specific radioisotopes. A type of

radioactive fluorine produced at TRIUMF for the PET

programme is a positron emitter. When matter collides with

its corresponding antimatter, both are annihilated. When a

positron meets an electron, the collision produces two

gamma rays having the same energy, but going in opposite

directions. The gamma rays leave the patient body and

are detected by the PET scanner. The information is then

fed into a computer to be converted into a complex picture

of the patient working brain.

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How does it work?

A conventional "X-ray" is taken by firing X-rays through a

person and onto a film. This "shadow" image shows some

structures in the body, such as cartilage and bone. A CT

scanner uses fine streams of X-rays. By firing them through

the body from several directions, the CT scanner is able to

build up a composite picture of anatomical details within a

"slice" through the person. Magnetic Resonance Imaging

(MRI) does much the same thing, but using magnetic and

radiowave fields. In contrast, the PET scanner utilizes

radiation emitted from the patient to develop images. Each

patient is given a minute amount of a radioactive

pharmaceutical that closely resembles a natural substance

used by the body. One example of such a pharmaceutical

produced at TRIUMF is 2-fluoro-2-deoxy-D-glucose (FDG),

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which is similar to a naturally occurring sugar, glucose, with

the addition of a radioactive fluorine atom. Gamma

radiation produced from the positron-emitting fluorine is

detected by the PET scanner and shows in fine detail the

metabolism of glucose in the brain.

How does it feel to have a PET

scan?

During a scan the patient

reclines on a comfortable

couch with his or her head

inside the large,

doughnut-shaped Positron Emission Tomograph. While the

patient head must be kept very still, the only real

discomfort involved may be the pinprick of a hypodermic

needle as a minute amount of radiopharmaceutical is

injected. The radiopharmaceutical could be administered as

an intravenous injection or inhaled as a gas. How it is

administered depends on the radiopharmaceutical. Which

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one is chosen depends on what function the scientist wants to

study.

What does a PET scan show?

The brain function being studied during a PET scan

determines which radiopharmaceutical is used. Oxygen-15

can be used to label oxygen gas for the study of oxygen

metabolism, carbon monoxide for the study of blood volume,

or water for the study of blood flow in the brain. Similarly,

fluorine-18 is attached to a glucose molecule to produce

FDG for use in the observation of the brain sugar

metabolism. Many more PET radiopharmaceuticals exist,

and research is under way to develop still more to assist in

the exploration of the working human brain. For example,

dopa, a chemical active in brain cells, is labelled with

positron-emitting fluorine or carbon and applied in research

on the communication between certain brain cells which are

diseased, as in dystonia, Parkinson disease, or

schizophrenia.

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How much radiation does a patient get?

PET scans using radioactive fluorine in FDG would result in

patients receiving exposures comparable to (or less than)

those from other medical procedures, such as the taking of

X-rays. Other scanning agents - for instance, 6-F-dopa or

radioactive water -

normally cause

even less exposure.

cyclotrons and

radiochemistry

laboratories at the

TRIUMF project

that are the source

of the PET scanning agents. The laboratories are linked to

the UBC Health Sciences Centre Hospital by the world

longest "pea shooter", a 2.4 km pneumatic pipeline used for

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the PET: Research tool of the future

The PET programme at TRIUMF and UBC is in a unique

position among world medical research centres in having

many of the expensive major facilities required to mount a

powerful PET programme. These include the delivery of

PET scanning agents in the shortest possible time. These

facilities have a capacity that has not been equaled by any

other university/health sciences centre in the world.

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