Biomagnetism: An application of squid sensors to medicine and physiology

70

l'hysica 126 B ( 1984 ) 70-81 North-ttolla,d. Amsterdam

BIOMAGNETISM:

Clan

AN A P P L I C A T I O N

OF SQUID

SENSORS

i'O M E D I C I N E

AN]] PHYS[,)b)(?f ~

Luca ROMANI

Istituto

The

di E l e t t r o n i c a

unrivaled

ability

physiological is g a i n i n g

of

significant is

SQUID

are

approach

proved

has

interest

being

to primary

both

in laboratory

even

for

to ensure

be

particnlarly

to

of s p o n t a n e o u s

Via C]neto

measure

in the human

made

and higher

t,o

magnetometers

activity

satisfactory

improvements

the study

Stato Solido - C.N.R.,

and p a t h o l o g i c a l

instrumentation

related

dello

the

higher

brain activity

demandin~

feasibility in

functions,

magnetic

started

~oma -

associated

1~elds

applica~ion~,.

in practical

loca]izin~

.*'Li:il

cerebra]

,,,'h[cl

state o~ ~rt <)I"

Nevertheless

operslion.

lr;ipmess~ve results

and in t h r e e - d i m e n s i o n a l

[+al,,

~ ne'~
in cli.~]~ca~ llse. The presenL

most

successful

level brain

weak

body has

and

Roman{) 42 - ] < { :

fast

The Piomaw
~ources,

like

those,

have oeen ~Jchieved also

locniLzat~m

of epilepti<

ili

for1.

10 9 i. I N T R O D U C T I O N Almost

fifteen

Superconducting (SQUID)

was

signals

initiated only

first

generated

h u m a n body

years

(i).

used

has

gained

for what c o n c e r n s

last few years, should

not

excitable

only

define

but

the

magnetic

in

an

applied

field.

biomagnetic

fields:

strengths,

reported frequency

about low

five

orders

as a few tens

of

the

fields action

fibers, (2).

potential

along

susceptibility

the

we should

can

supported

cardloorom

o

oeuIoqrarn

c-

myogrom fetal cardiogram encephaloqram

(.3 ,4- 10 3' ~3

his- pur klnje

cE3

E evoked

over be

propagation and

mention of

SQUID

that

,

I 0 -I

of

I_

overload serious by the

Finalizzato

0 3 7 8 - 4 3 6 3 / 8 4 / $ 0 3 . 0 0 © Elsevier Science Publishers B.V. (North-Holland Physics Publishing Division)

,

I

1

,

I01

I

,

102

I

10 3

frequency (Hz)

one

"in vivo"

iron

noise

For

conducting cardiac

by P r o g e t t o

rellnogrom cortical activlly

i0 u

as

take into account

or deficiency in patients a f f e c t e d by hematic pathologies became possible Work partially

currents

typical

(IO-15T).

isolated

measurements

a

studied

span

and

the

origin

obdomlnol

approximative

magnitude,

with

due

tissues shows

bandwidths,

of neural

Finally,

i

of the most

we should

by

those

some

versus

associated

both

of

t--

from

outside

lung and

of f e m t o T e s l a s

sake of c o m p l e t e n e s s also

we

produced

their

experimental

ma{Jnetlzed lung contaminants

c-

and

Figure

representation

in the

fields

those

in the

i0 e

not

originating

susceptibility

J

investigation

inside

also

contaminants

to

was thus

side.

those

flow

=a"

f

in the

especially

biomagnetic

consider

current

comprehensive

magnetic

interest

fundamental

,o

a

Device

activity

growing

but also,

cells,

magnetic

since

measure

on the c l i n i c a l

to

biochemical

to

by b i o e l e c t r i c

of human p h y s i o l o g y we

passed

Interference

A new field of r e s e a r c h

which

Were

have

QUantum

FI(]IIRE 1 rl'ypical amplitudes

and

main

f~elds.

b iomagnetic

£req~lency The

schematically represents ~he d i s t u r b i n g fields amp] ] tude~. "Tecno~ogie

BiomedJche

e ~an~tarie"

ranges

o[" the

shaded

lower

- !£H,.

range

area ot

G.L. Romani / Biomagnetism

biomagnetic

approach

and are

proving

to

be one

of the most promising clinical applications

investigation have

been

so far achieved.

illustrated

Proceedings (4).

milestones

in

of an Advanced

detail

of investigation

shall

consulted briefly

Nato Study Institute

by

modeling

the

interested

describe

can

fields

(6-8) and i n s t r u m e n t a t i o n

instrumentation, approach

the

(5) and several review articles

on specific topics can be

They

in

A comprehensive survey of the main

and

the

how

yield

a simple

significant

experimental

reader.

state

field

of

2. INSTRUMENTATION

(3).

Space l i m i t a t i o n s force us to s t r o n g l y limit the description of the general principles of the biomagnetic method as well as of the

art

(9)

71

2.1. Single channel systems As far people are

as instrumentation about to switch from

systems to multi-sensors ones.

is concerned, single channel

Indeed, for about

a decade e x p e r i m e n t a l i s t s have tried performances of systems like schematically

depicted

superconducting tail

of

a

assembly

in is

superinsulated

to improve the one Fig.2.

located

the

dewar

and

fiberglass

kept cold at liquid He temperature.

The SQUID -

We

either rf- or de-biased - is c o n n e c t e d

of

external

theoretical results

in

distributions

and

"flux

world

by

means

transformer".

loop,

of

This

a

A

inside

with the

superconducting

consists

of

a closed

one end of which - the "detection" coil -

senses the external field, while the other - the

l o c a l i z i n g active sources inside the body. Last,

"input" coil - is tightly coupled to the SQUID.

we

recently

A magnetic

study

of

produces

want

to

through

shall

focus

on

the

Rome

physiology

and

collected brain

by

some

results

group,

in the

pathology.

We

field applied an

induced

the

input

to the

current

coil,

detection coil

which,

in

turn

flowing

generates

remark that these are only few examples

of what

magnetic flux which is sensed by the SQUID.

is

and

is

the

in

the

going

on

demonstrating

all that

over

the

important

world progress

frequency

range

of

interest

flux

transporting is independent of frequency,

being

u n d e r s t a n d i n g of physioloy=~v and pathology of the

the circuitry all superconducting.

human body approach.

flux-to-voltage

can

be

achieved

by

the

biomagnetic

a In

conversion

SQUID provide,

after

and detection, the

The unrivaled

properties

appropriate

of

the

amplification

a voltage signal proportional to

magnetic

field

applied

to

the

detection

coil. The reason why people prefer to use a flux transformer be

lies

shaped

to

requirements following.

in that the detection coil can best

- as Under

suit

the

will appear optimization

experimental clear in the of the flux

t r a n s f e r r i n g conditions a significant portion of the

signal

energy

can

be

transferred

to

the

SQUID (9). The use of large diameter detection coils provides high field sensitivity: figures as

low

as

3

literature magnitude

lower

alternative point

out

are to is

fT

(9).

been

This

value

than

magnetic that

investigation

typical

is

other

diameter if high

and of

any

reported

detectors.

small

be preferred

required,

cases,

have

of for

However, detection

we coils

spatial r e s o l u t i o n

sources

sensitivities

the

reported

particularly

shallow

in

orders

of

for

(9). SQUID

are adequate to the task of measuring weakest biomagnetic fields.

In

the all

systems even the

2.2. Ambient noise A FIGURE 2 Schematic

of

the

cryogenic

deeper

glance

at

Figure

i points

out the

two-fold problem experimentalists are to cope when trying to perform biomagnetic measurements: assembly

typical b i o m a g n e t i c instrumentation.

for

a

to measure extremely weak fields in a very noisy environment. The shaded area in the upper part

G,L. Romani / Biomagptetism

72

of the

figure

range

of

noise

schematically

amplitude

of"

- which more

undesired

They

we

decreasing l Hz

(9)); at

harmonies, total

plus

frequencies,

due

Shielded solution the

density the

was

first

of

view

(i)

noise

prevent

and

of

the

used

other

electrical

four of these

SQUID

"spatial than

highly

principle

second-order insensitive

sometimes - probably

of

shielded

rejection (i0)

of

and

its

for

(Ii).

configurations detection

mass

Figure which

coil

The

splitting

single

the

generally

referred

sub-coils

having

of

a

depicts be

basic to

turns

based

coil as

mutual

and

this

in

3a)

magnetometer combination

(N)-sense

of

winding

-

coils

are

they

sense

field

and

gradiometers

named only

in space.

first-order the

higher

first orders.

(W-+/-)

back-to-back

shown for

gradiometers, Two

of

as the

first-order

arranged

assllmpt i(m

form

a

in the

coils,

the tabs

reduction. are

~econd-

is

unwanted

is

not

-

thal i ( enough

the to

Gradient

baseline

that

of

significantly

reduce

low-frequency

range

of

]he the

be the

i abricatin} for

adequate

super'conduct, ins in

intrinsic

proxJrrl[t'~

"balance"

m]

obtained

bv

balance, one

can

a constant

in

positioned

the

to its planes of

conditions

sufficient

Consequently,

is

Far

signal

or h a v i n g

achievable

appropriately

adjusting

or

rurl in

sati s ['actori Ly

practice

practical

to improve

the gradiometer. respect

the

accuracy

gradiometer

of coils

-

Pields

being c o n s t a n t Under

mechanical noise

is negligible,

grad1 ometer, relatively i.e. the dLstanee between

as

roo~s,

['or ren<)te

of" g r a d i o m e t e r s

experimental

of" d i s t u r b i n g

from the "baseline",

gradient.

a !lagnetor!letep shielded

and clinics.

the

source

~*pat~ ~l

third-order"

ar'e snccessl'uily

principle

adjacent

~

environiLents;

upon

-

These d e t e c t i o n

derivative

based

by

the urban noise

shielded

i~ aad

Lb{ ~uitable

operating

regarded

into

grad]crueler

where

vhici

de~_~ree of

('onsequenl ly,

laboratories

The

in

area(A)-

such that ~ A i x N i x W i = O . The c o n f i g u r a t i o n in 3b) provides zero n e t induced c ~ r e n t fields u n i f o r m

the

consists

shown

many

the

fields

ilLghe~' pro,,ided

third-order' g r a d i o m e t e r s

verified

to

lhi form

inside m a g n e t i c a l l y

IDeations,

olin]ca]

some of" the

even is

(3d).

or in weakly


f'ields

~c I,

i~otb

An

gradiometer

for

:i !'.tin I [) system

discrirnin~l:ion.

discrimiua tior~

hospital

spurious idea

also

on

given

achieve

cancellation.

gained

,:onfigurat lors

,,'i tln

gradiometer

gradients.

present,

in u n s h i e l d e d

can

to

has At

screening 3

proposed

feasibility

conditions.

are in use even

procedure,

was

used

to

must be used

instrumentations

assessment

spatial

used

use.

ago

because

environments,

achieve

possible

soils

cost and

problems

a noise

noisy

biomagnetic

detection

a first-order

years

large c o n s e n s u s

the

equal

space - which

discrimination",

ten

of

level

Gradiometers

Alternatively,

applied

and

},'lGI}R} Some

systems

the high

widespreading

a in

laboratories

hand,

for clinical

from

of multiple

high

a noise

the

claustrophobic

environments

to

consisted

Nowadays,

of "living"

serious

large

proximity

by means

guarantee

that

the

the exiguity

-

rooms

materials.

On

of

_

SZ

its

to Lhe

isolated

presence

permeability

than

therein.

and

at

which

-

at

featuring

contributions

close

their p e r f o r m a n c e s

number

noise,

in use in b i o m a g n e t i c

lower

which

roughly

frequency

in

ambient

conductivity rooms are

line

to

point

layers of high

in

interaction

area.

2.3.

more

to

"urban"

facilities

The

historical

c

as

in one Hz b a n d w i d t h

additional

the e x p e r i m e n t a l

namely

define

and a m p l i t u d e

spectral

instrumental

reducing

the

power

noise

2.4.

due

(~lOpT

iii) the

a

c o n s i s t of: i) -5 (~Sx]O T); ii)

field

variations,

as I/f

peaks

poses

should

the solar wind and the ionosphere,

show c i r c a d i a n

or

lower

magnetic

typically

"mieropulsations",

between

the

ambient

properly

signals.

the e a r t h steady m a g n e t i c its

indicates

the

gmadiometer

other, measured

has

prover]

noise

(12} and p e p m i t t e d

with

in

to the

operation

G.L. Romani / Biomagnetism

73

even in an unshielded hospital environment (ii). Practical putting close

measurements

the

as

source

possible

gradiometer, substantially

of to

are

performed

biomagnetic

the

lowest

by

fields

coil

as

of

the "pickup" coil, reducing the subtraction

the

thus effect

due to the other coils. The penalty we pay is a progressive reduction of sensitivity when using higher and higher order configurations.

This is

due to the sharing of the detected signal energy among all

the

inductive

elements

of

the

transformer:

not Only

the

input

coil

pickup coil,

but also

the

other coils

flux

and

the

of

the

gradiometer. To partially compensate this effect an

asymmetrical

used

(13).

inductance the

configuration

It -

pickup

and

tends

to

(3e,3f)

consequently

coil,

while

can

concentrate

the

be the

the energy appropriate

in

flux

balance condition is satisfied by enlarging the area of the compensating coils. 2.4. System performances Performances

of unshielded systems

based

on

rf-SQUIDs are generally satisfactory, being only a

factor

3-5

worse

than

those

achieved

in

magnetically shielded rooms. DcSQUID systems are still not so widespread,

but show noise figures

of i0 to 20 fT/~-~z (14).

It must be pointed out

that an "intrinsic" subject noise, many experimentalists, level

to

the

observed by

probably sets a minimum

sensitivity

required

is

for

instance the

standard

noise

level

measured in presence of a subject in the Berlin magnetically

shielded

instrumental noise The i/f behavior in typical

of

represents the

all

room

(15)

is about

the noise problem,

experiment demands

the

the

lower.

spectral density

biomagnetic

a serious

although

three times

instrumentations particularly

if

maximum sensitivity

in the very low-frequency range. The adoption of more

sophisticated

balancing techniques

multi-channel

system

operating

at

the

Neuromagnetism Laboratory at the NYU.

for

biomagnetic purposes at approximately i0 fT/H~z. This

FIGURE 4 The

should

probably overcome this drawback.

dewar at successive recording sites. Such a long duration

is

certainly

unpractical

and

becomes

unbearable with specific patients.

Furthermore,

the

measurements

non-simultaneity

costitutes

a

dramatic

spontaneous brain

of

magnetic

problem

activity,

in the study

which has

far only partially overcome (16). greatest efforts

have been

of

been so

Consequently,

devoted in the last

time to develop multi-channel instrumentation. At present few multi-probe systems are being tested in different laboratories.

Fig.

4 shows

an overall view of the dcSQUID system operating

2.5. Multi-channel systems

at the Neuromagnetism Laboratory of the New York

As

University (17). Five parallel signal channels 2nd-orders gradiometers appropriately positioned

mentioned before,

the importance of the

results obtained during the last three years has gathered

increasing interest from a

larger and

larger number of researchers and members of the medical

class.

One

of

the

most

serious

limitations of the technique when operating in the clinical field, is the overlengthy duration of a recording session. Typical runs require from 2 to 4 hours to get appropriate field mapping. This time is spent not only for data acquisition, but primarily in positioning the

to cover a portion of a spherical surface provide a sensitivity of 15-20 fT/H~z, above approximately 1 H z .

This performance is achieved

by means of electronic noise subtraction:

four

additional rfSQUID channels are located inside the same dewar and provide outputs proportional to the x, y, z component of the ambient field, and to the first gradient z. An appropriate mixing of these signals is subtracted from each

G.L. Romaui / Biomagnetism

74

standard

electroencephalo}Lraphy,

sensors order

a Ii

distributed

to

cover

the

a

to

devoted

to

These

data

of a "functional as

fast

as

reasonable

to

or

and

]f things

expect

~ast that

should facili

analMs~s the

to

_~ in

possibly

system

computer

image".

in

[5

dewars

of',

~Qpge

appropriate

s}~y

adequate

lar~
scalp.

coupled

inside

be

ties,

to r e c o n s t r u c t i n u few

these

will

proceed

years goals

]t are

ts riot

far-away . 3.

MODELING 3.1.

AN[) SOURCE

Source

The problem

of

in the human body The

forward

F]GUHE Close

up

view

under test Stato

a

four

gradiometric vector

one

5

rooms.

(19-2!)

-V/IW-

delln

systems

are

They use either (18)

with

the field

shows

a

system

Istituto

di

the

(18,20)

close-up

presently

Elettronica

This instrument,

unshielded 2rid-order

purpose the

of

the

2 cm

a

or

or

the

improved

performance

uses

oi

field

By s u b s t i t u t i o n a figure on

measurements similar

of

on

a

gradiometer

The

basis

of

final t a r g e t of

in

40

to the

10 fT/fH~z is preliminary with

a

(22).

being the setup

channels

of this new era, of systems

comparable

b

to

about

connected

We are just at the b e g i n n i n g number

coupled is

of four dcSQUIDs

dcSQUID

in

sensitivity,

approximately

the

the

8olido

four p r e - b a l a n c e d

rfSQUIDs,

fT/H~z.

four

at

for o p e r a t i o n

gradiometers

rfSQUIDs expected,

test

Stato

designed

gradiometers. with

view

under

dello

environments,

measured

a

conductor

(19,21).

channels

the

of a volume

balancing.

configuration

either

Fig.

Rome.

at the surface

the

electric

sysuem

Elettronica

multi-channel

shielded

magnetometer

meastming

di

to get optimal

least

in calculating,

f'lelds and/or

5

fo~'-gradiometer

istituto

o p e r a t i n 8 inside

source~

in two ways.

of" m a g n e t i c

in Rome.

channel

At

the

at the

8olido

signal

of

[dentifyin},~ electrical can be approached

pz-oblem consists

distribution potentials

¿,~)CALIZAT]ON

modelin[.

with

with that of

FIGURE a) The c u r r e n t generated

by a current

the

component

the

sphere

dipolar

flow and oF

source

dipole,

field

lines

b)Distributiom

off

the

magnetic

field

norma~

as

produced

by

tangential

surface

head s i l h o u e t t e

b

the magnetic

0.3

units

i.s added

of

radius

a

deep.

for clearness.

to the

G.L. Romani / Biomagnetism

as

generated

by

a configuration

known strength and position. tries

to

identify

the

of

sources

of

The inverse problem

sources

in

the

volume

conductor from the e x p e r i m e n t a l d i s t r i b u t i o n of fields and potentials at the surface. It is well known

that

solution,

the

latter

problem

has

no

unique

as infinite source c o n f i g u r a t i o n s can

what

75

happens

to

of the

component

scalp the

normal provides

intracellular

structure of the generators,

the

number

and

and on the physical

properties of the volume c o n d u c t o r are made,

an

approximate solution can be achieved. One of has

been

the simplest widely

used

modeling to

source,

account

for

which

excitable

volume

currents by

Fig.

current

flow

whereas

the

to

scalp

and

may

electrical

depicts

the

be

significantly

properties

of

the

distribution

of

the

the surface of a spherical medium,

as generated radius

a

current

dipole

below the surface. comparison.

a

the

by

posterior

i.e.

the

6b

the

dipole,

over

related

component of the magnetic field p e r p e n d i c u l a r to

cell activity and particularly for neural one is current

field

distribution of electric potentials depends also on

intervening tissue.

on

the

directly

currents,

if

hypotheses

of

information

affected

specific

potentials.

a m e a s u r e m e n t of the d i s t r i b u t i o n

account for the measured patterns. Nevertheless, some

electric

Consequently,

part

0.3

unit

of

deep

The sphere is inserted in the

of

The

a

head

silhouette,

calculated

pattern

for

shows

two

c o n c e n t r a t e d in an e l e m e n t a r y volume dV. Fig. 6a

regions of maximum field with opposite polarity.

shows

This

this

source

and

the

current

lines

a s s o c i a t e d with it, when immersed in an infinite medium with h o m o g e n e o u s conductivity. intracellular

ionic

the

currents

"volume"

flow.

s u r r o u n d i n g medium, printed

The outer

which,

black

Indeed

no

i.e. the

dipole

lines are

flowing

close the loop,

transverse

oriented

The

a r r o w represents the "primary" current,

circles

distribution

dipole

in

the

The heavy-

represent

the

magnetic

normal

positioned important is

at

the

magnetic field lines. It should be remarked that

depicted

in Fig.

the use

is

however, of

does

not

to oversimplify the problem:

schematically

population

representing

of

"equivalent"

neurons

dipole

mathematically

provides

derivable described only

the idea

activity

the

above

the

primary

For

diminished. shows

tool

which

is

only

sufficiently for

equations

Biot-Savart currents

radial one,

of

interest

the

from

an

in

the

configuration law

guarantees

contribute

to

the

sphere.

of

a one

This

technique by

the

the

pattern

tangential

direction

to

a

whereas the relative amplitudes are The

electric

potentials

pattern

similar symmetry - but for 90 ° rotation for

a tangentially

In conclusion, may

be

oriented

dipole,

the

relatively minor difficulties

expected

when

bioeleetrical sources by

trying

to

localize

magnetic measurements.

3.2. Source localization The i n t e r p r e t a t i o n of experimental magnetic patterns in terms of a simple model like the one described

above

hypotheses

concerning

currents being zero. This favorable situation is

and substantial measured and the

when more realistic geometries provided that some symmetry

by

by

6b is mantained as the dipole the

magnetic field, the n e t c o n t r i b u t i o n from volume partially saved are studied,

or

however,

symmetry

a

symmetry being lost when the dipole o r i e n t a t i o n is modified (23).

all

is limited to few KHz.

Maxwell

limit.

tilted

of

e l e c t r o m a g n e t i c relationships are

from

quasi-static

a

mean,

means and

of

biomagnetic measurements Consequently,

the

by

accessible

realistic as well. The frequency range

that

model

the

generated

the

to

surface.

magnetic

compensated,

that

a simple

of the

due

the

surface

center of

as

to

is

the

limitation

partially

calculated field

to

advantage

of such

is

tangentially

-

provided the

the

model

fundamental

are

satisfied

similarities between theoretical distributions

the are

c o n d i t i o n s are s a t i s f i e d (5, 23). Infact, if the dipole is immersed in a half-space with

observed - yields t h r e e - d i m e n s i o n a l localization of the e q u i v a l e n t generator. Generally the procedure consists in a five parameters fit -

h o m o g e n e o u s conductivity,

three for the c o o r d i n a t e s

or in

a

sphere

with

for the intensity

of the dipole and two

of its tangential

component -

h o m o g e n e o u s conductivity, or even a sphere with a r a d i a l l y varying conductivity, only the dipole

which

is

performed

itself c o n t r i b u t e s to the c o m p o n e n t of the field

numerical

procedures.

perpendicular

position is provided, together with the appropriate uncertainty region and a level of

to

the

surface

separating

the

medium from the air. By contrast, the tangential component of the field is determined by both the dipole

and the

volume

currents, similarly

to

by

means

of

As a result,

iterative the dipole

significance, which indicates the r e l i a b i l t y o f the localization.

G, L. Romani / Biomagnetism

76

IF

i 2 e~ !

v

i "\ \

"

\

theor.

exp.

{ d

e F [GUHE '7

a-c)

Example

of 3-D l o c a l i z a t i o n

of" the equivalent, source

the auditory

system

i KHz

sites.

experimental

The

localization

by means

of

and

of the source

tone bursts

theoretical

elicited

(0).

distributions

by 4 KHz

for ~ field pattern Crosses are

tone bursts

represent

shown

in

d)

is also shown

evoked

by s t i m u l a t i o n

tile experimental and

e~

the

A

el

recordJn~

respectively.

?he

(1). P

An

example

procedure

is

cent our

depicted

map

by

of

means

each r e c o r d i n g field.

The

site,

correspondance the

evoked

of

field.

the r e c o r d i n g and

was

the

scalp,

The

of

in the of

previous approach

by

distribution source,

as

localization elicited above

of"

but

component

of

the t r a n s v e r s e

of

-

in a-c)

( ),

In

source

than

that

this

region

of"

provided

auditory

cortex

is

95% c o n f i d e n c e

the skull

was

used

generator by

filled

which

cortical is

in

-

for

the centra[

localization.

identified circles

region

the also

- is localized

a r e a and good

in

which at

a depth

agreement

with

findings o b t a i n e d by the n e u r o m a g n e t i c (24). Indeed, the s i g n i f i c a n c e level

the

two

by

interval

(squares}

experiment

described

bursts.

The

location

backward

in

and deeper" - b=-'.b r, to i KHz stimulation.

oi" T2 mm g u a r a n t e e s

are

ef'fectiveiy

locations,

evaluated

for

with

tonotopic (2A) .

shows th(~

sotlrce

slight].'? shifted

direction,

sources

different agrees

equivalent

atso

case the level off si£sliftoan(:e .,o the ~ " flit: was l a r g e r t h a n 2q%. :{

temporal fitting

the

correspondin?

the

sphere,

equivalent

]so-field

the

7a-c)

i

{ulppoi't

second

the

best

is

t
i'i~!.

the

distribHtion

U~rthep

produced

with I KHz tone

of" the

comfit'ms

theoretica[

by r e p l i c a t i n g

in

distribution

one.

e). the

test

experimental

the

shown i n

which

appropriate cm,

an "evoked"

the

theoretical

calculated

is reported

the 95% c o n f i d e n c e

2.]

fop

the

provided

cover

sections

include

qO ms

200 times

NIO0

spatial

in

auditory

and

bs'

between

to

equivalent

three

measured

bursts,

was

large

The

agreement

the

provided

below The

portion

tone

map

positions

chosen

located.

as

thus p r o d u c i n g

the

iso-Eield

of" his

was r e p e a t e d

iso-field

>~15%

represents

subject

i KHz

The s t i m u l a t i o n

described

field p e r p e n d i c u l a r

stimulation of

The

d)

scalp of" a normal

system, long.

in

of the m a g n e t i c

correspondance

the

in Fig.7.

shown

distribution to the

illustrating

the

what

is

i'he higher

organization Also

tangential

the

component

larger

of

on t h e the

estimated of

the

depth

frequency

expected

tt,,at

positioned

ir~

value

~enerator basis

o]" t h e

auditory

(optex

values equivalent

Qt=3.8 A.m and Ot=4.] A.u r e s p e c t i v e l y with typical amplitudes of" cortical

ol

lhe

source- a~ree current

G.L. Romani / Biornagnetism

density available in the literature (24). We

have

dwelt

on

the

example

brain and develops into an incredible number

illustrated

above as it well focuses advantages and limits of the procedure and which kind of results one can

expect

when

localization. of

the

geometry

neuromagnetic

regions

of

the

for

head.

convolutions and fissures.

The

cortical

is

and

width

cells - is preferentially aligned in a direction

Furthermore,

it is expectable that the most active areas from a

inside fissures,

as they probably become essential for signals

functions.

like

related

for

instance

Nevertheless,

to

complex

higher

for

the present state of and

point

of

view

are

those

located

rather than those distributed

from

of

the

"primary"

the first

peripheral

areas,

analysis of

sensory

which

are

input signals

systems.

A

typical

procedure for investigating these areas consists

in the study of human physiology and pathology.

in "bombarding" the chosen system by repetitive stimulation and detecting fields which are time-locked to the stimulus over the appropriate

BRAIN MEASUREMENTS. the most

many

devoted to

has permitted achieving of significant progress

5.

magnetic

As a consequence,

along convolutions. This is fortunately the case

brain

art is satisfactory for many investigators,

Many of

constant

normal to the cortex surface.

more complicated source configurations should be interpreting

approximately

representing

studied, phenomena,

of

folds - namely,

within this 5 mm of grey matter at least one population of neurons - the so-called pyramidal

A crucial point is the inadequacy

spherical

particular

facing

77

important results

achieved

region of the scalp.

The neuromagnetic study of

so far by the

biomagnetic approach concern the

cerebral activity evoked by sensory stimuli has

investigation

of

marked several

brain

activity.

Although

cerebral magnetic fields are extremely weak, the interpretation probably the

of

scalp

favored by

skull,

represented

posterior and cortex covers

a

is

important

the particular geometry of

which by

distributions

can

sphere,

be at

milestones

the

achievements

investigation

of

satisfactorily

functions (6,25,26).

least

on

in

in the

understanding

of brain organization and functioning (6). Other

its

central portion. The cerebral all the basic structures of the

the

study

of

spontaneous brain

are

being

higher

collected

levels

of

in

brain

Our accent will be placed

magnetic

fields

activity which

related

to

is proving

to

be one of the most interesting research areas also from a clinical point of view.

v

a

b

Sub: R I (28y)

Sub: RI (28y)

-50

0

50

'"~°"

FIGURE 8 a)Relative Covariance pattern over the scalp of a normal subject reflecting the measured distribution of the magnetic alpha rhythm. The shaded area represents negative RC values, b)localization of the equivalent generators: the shaded circles represent the equivalent cortical area possibly involved.

G.L. Roma~H / Biomagtwtism

78

4.1.

Normal

The

alpha

strongest

spontaneous rhythm,

bioeleetrioal

arising

in

the

investigated,

(EEG)

electroencephalogram Hz

electric is

region

everybody.

The alpha waves

keeps

reduced

by

of

however,

experimentalists

the

simple

mental

possible

and

almost

At

and

or

by

present,

still

structure

the

generally

input

uncertain

location

of"

their source(s). The this

is

approach

from

relative

phase

possible

solution

of" m a g n e t i c

problem

consists

in

to

the

correlation this

between

procedure,

to as the Relative calculates and

around

the

electric is d i v i d e d

these

which

Covariance

covariance

the f r e q u e n c y

The e o v a r i a n c e

the

the EEG and the MEG and

method

filtering

recordings on

has (RC)

between

channels of" interest

which

or

The to

magnetic

stimu]ating

be

typical

values

of neural

c o m p a r.eod The

with

~-

['it provided

hypothesis

that

occipital

alpha

rhythm

by

two

produced approximately indicated

one

by

the

the

buring

measured

finding

the

been

we

FIGURE EEG

different signals

and MEG

9

focal

tracings

subjects.

RM

as r e c o r d e d

shows

in both MEG and EEG,

a quasi-rhythmic

activity

at about

clear while 2 Hz.

from

spike-

IE shows

the

and

those

are

s ti i l

of" the

epilepsies.

successfully

investigated

< '!,

sisera i

affected

the

neural

activity

is

source ett<)r't~

ppocednpe~

confront

-

i'his

relatively

gneatesL the

I:'}

intervals

distribution,

the

ot

'esu] ts

avail able

t?roll other

it should

be emphasized

iar

From

On the basis of

we can

o!" view.

studies

magnetic

pathological

Far achieved

research,

point

patients

refine

to

r(p~"esent~;

o~

[ntericLai

consequently, to


several

that

measured

devoted

localization

like

yeal-s

For sake of c l e a r n e s s that

and

cortex

['(><'i

method

clinical

- during

obtained with techniques.

Mr6

',Pa,

of"

area

a dipolar-like

localization

two

!athoiogica[

the scaIi~ of

concentrated:

Real-time

eptlel tic

thai

suggests

underlying have

ot

few

focal e p i l e p s i e s often display

FLK.

area

of

the

shown

over

the

for ~s

generat,ors

shown i n

promisLn~

from last

have

t:he

be a c c o u n t e d

neuromagrletic

rlost

the

to oi"

circle::.

Loca[izatien

of

3;2 )

as

i m~

currcnt~ .

portion

equivalent

h,y t h e

i.?.


o£

Large

~'qui v a l e n t

located the

too

suppor't

major

oi"

t ie[(~

strength

further

the

sides

visual

would

( ~ }~)

150 ffV

~qght


suppressed

dipole

deep

particularly

SUB. LE.

two

single

involving

M[6

the

~he

td)

The

l)asi

Jn

}'urthermore,

after

I1 pT

the

par't.icl)lar,

separately.

by the v a r i a n c e

I-~

on

In

and

is

or'

sourcet{.

wer'e seLective]y

]eft

a~

descr/bed

dipole,

shallower

alpha

scalp

ihe

pattern

interpr'eLed

sil%{le

(YS).

and

from

the

was

deep,

was prefferred

activity

R.M.

by

latter h y p o t h e s i s

'The i n v e s t i g a t i o n

SUB.

Lhe iso-RC

distribution

arguments

correspond

ma~ne t[c

riley come

actinp

by

reference

o!" the rlagnetic

sNbject

a quite

,

or" ~he IR:

R~; v a l u e s

8a shows

For

i t,, .

recor'din S

same

that

two s y n c h r o n o u s l y

af

[he

im-phase

fft'om s n o r m a l

either

all

the

pruvided

Fig.

procedure. due

to

positive

signals,

obtained

intens

r'ef]ects

or

out-of-phase

same source.

compensate

a spati~ I list:r/bution

Negative

electric

Io source for

respect

provides

coefficient

in repeated

with

lead,

the o e c [ p i [ a l

A

been r e f e r r e d

Hz).

positions

amounts

signals.

effect

magnetic

analysis,

in

measured

the

the

the

similar

to

signal

variations

off

of

in

(28),

study

information

recording

In

the

difficult,

getting

simultaneously signals.

to

particularly

that the n o n - s i m u l t a n e i t y prevents

studying

electric

several

neuromagnetic

phenomenon

the

possible

ffield.

the

when

are

tasks. are

A

over o1"

visual

execution

an

approximately

are s t r o n g e r

closed

[on~ ol

(f'/).

1929 -

scalp

the

the eyes

significantly

about

in

detectable

occipital subject

of

been

recording

signal

-

frequency

has

first

the

spontaneously

brain,

the

of

represents

activity

human

since

quasi-periodic i0

activity

which

classify

the

achieving,

source

in

all

the l'esults c] LnLcal

according

to

two

so

cases main

categories, d e p e n d i n g or not on the presence the EEGs of" repetitive spike-like si~nals

in oi"

G.L. Romani / Biomagnetism

Y

79

2 cm

Y

L~

A

R

l

L C FIGURE i0

a-c) 3-D localization of the equivalent source for subject RM

(frontal

lobe epilepsy).

The open and

the solid circles identify sources as obtained by the RC and the averaging method respectively. scan picture is shown in d). em

The CT

~v

l i

i' i

A

C FIGURE ii The RC method for subject EI (right motor epilepsy). approximative locations of the Sylvian and Rolandic fissures, as derived by a standard anatomical textbook are also shown, d) The spatial d i s t r i b u t i o n o f the RC over the r o l a n d i c area (units in cm).

a-c)

3-D

localization

achieved

by

the

G.L. Romani / Biomagnetism

80

large amplitude: procedure

can

i) those

be

distl-ibution o v e r can

be

studied

for which an a v e r a g i n g

parasitical

to get

localization

applied by

the

field

[n order to clarify the

in d) and well m a t c h e s

Covariance

category.

this s t a t e m e n t

belong

Fig.9

to

shows

the

first

simultaneous

EEG and MEG tracings,

two patients

affected

case

figure

-

-

present quite

in

RM,

subject

both

occurring

in the

E E G can

source

producing

provides

the

further

signals

Theiz" spatial

iso-field

elaboration. can

Covariance

procedure.

of

the

RC

be

analyzed The

coefficient

mentioned,

reflects

can as well serve

source. lower

quite

different

clearcut rhythmic

in

the

we

Fig.

achieve

affected should

by

be

lobe c l e a r l y between

by

circles)

and

excellent

can

history

sensory-motor

permit

Covariance

be

evaluated used

Subject

of

be checked

of

the

and

]nvolvin}{ surgical

f'of ~J] 1

(33)

approach ']o

The

has proved

the

these

we

by

the

experience

e n c o u r a ~ lng

important

ot

results

investigated overall

fo

source

and

t,'~

~
achievements.

(EI).

has

been

to

~ives Zn this of" the

who

the r i g h t removal

presentation

hint

about

research.

unavoidably

Few

examples.

limited

important

achievements

which

in

study

the

upon in

we

spaee

cardiomagnetic

least

mention

the

heart

study and

The

ul

of

activation state

the

space

reasons on

lhe

levels

enough

,i<~st toil('h

we

should

progress

conduction

bra in

of

to

aL

achieved

sjstem

of

the

ventriculsr

(/}.

of

the

fiiven

uniquenesses

irk

method.

field of map

o£ an in

drawback

unsurmountable development therefore

a

fundamental

that

fhe

advances

tc~ the and

approprJ atn

torso

r-equires ~ complete

epileptic

patient

}fours.

can

step }ikely

['his

prove

specific

are

of

recordin$,

the

t:o

<~ be

ih(,

systems

thanks

is

~~

patients,

multi-channel

decisive

serve

instance,

[hr'ee

which

with uP

or bur

in case

recorded

should

over

scalp

the even

local i z] n£

] Jm i t a t i o n s

We r e m a r k

sessions,

and and

3

slid

patterns

the

overlengthy

section

instrumental

/,

modeling

['ocus

biomagnetic

the

[rl section

procedures the

of

description

survey

region

in

dwelt

measurements,

of" aft; given

mapping

to

on

are being tulle< ted

fundamental the

been

L,oin[-

the abnorm~Jll,'¢ d e l a y e d

brief

shorter

for not

hi ~4}ler'

of"

Had

is

]'he survey' of" resnlts

have

functions.

has

what

We

to

is whi
to he gained.

ACKNOWLEDGEMENT:]

result

neuromagnetic basis

this

a

the b i o m a g n e t i c

serious

that

off

(solid

(open circles)

on the

~o tar

and

(29,3l).

just

is

which

procedure

patient,

been

others

l?he aim provide

typ[call,y

A comparison

the

iH

£roup

loea li zin,~,

of further

of

[n that

The same e n c o u r a g i n g

of

to

(RM)

epilepsy

patient

in

particularly

magnetic

localization

method

seizures

consequence

not

the results

lobe

averaging

validity

the

of the

calci['icatJon

for the second

localization

a

the

the RC

the

clinical

the

region

D. CONCLUS [©NS

a

quasiin

moment,

above.

"anatomical" both

(E:I),

localization.

frontal to

agreement.

is a c h i e v e d

can

a

shown by the CT scan.

this

provided

does

ii illustrate

right

related

a

appreciable

in

described

of"

depicts

the R e l a t i v e

source

]0 and Fig.

the p r o c e d u r e s

as

see

example

The m o r p h o l o g y

bandwidth

will

field -

localization

rather

signals

appropriate

eventually

case

(,v2 Hz)

Nevertheless,

as

alread,y

The EEG does n o t show

as well.

electric

averaging.

same

Relative

distribution

Fig.9,

signals,

activity tracing

pathologic

and,

situation.

for"

the

as

The second of

then

needed

which,

part

spike-like

magnetic

are saved

the

spatial

-

[lq

repot'ted

caser; have

several

group

promise

the

imp]ies

that of the magnetic

the e q u i v a l e n t the

using

for a t t e m p t i n g

shown

in

spikes

Alternatively,

recordings

therefore

by the same

maps

m~

ollr own

activity.

add

UCLA

in

distribution

contour

pathological

the a

a dozen by

successful

should

map

the a p p r o p r i a t e

but one the n e u r o m a g n e t ] c be

tso-RC

'he

showl]

spikes

This

generated

than

are

shows

signals

to them.

the e l e c t r i c a l

by the average.

EEG

the

area.

source

cortex,

investigated

for trigger[n~l

corresponding

magnetic

of

signals

ratio,

be used

Prom

in the

par~

the

noise

MEG which are t i m e - l o c k e d that: only

upper as

to

of" the

recorded

spike-like

channels:

signal

the average

second

of" r e a l - t i m e

by focal epilepsy,

simultaneous

~ood

which

and

four p o r t i o n s

More

we want to

examples,

rolandic

equiva]ent

Relative

following

respectively

the

the

is based on

the sensory

discuss

in

of

Fi~.]] ,a-c)

method.

first

cyst

and ii) those which

the scalp,

only

magnetic

shows hand

o1'

a

'}'he author help

in

the

particularly on m o d e l i n g due ~

is indebted preparation

author

wants

or" this

for his c o n t r i b u t i o n and source

to Dr'. S.N.Erng, critical

to llr. H.Leoni

revision to

thank

For hi~;

paper,

localization.

L~hanks are

['or helpl'lll s u g g e s t i o n s of all

the

and

to the section

manuscript.

the other

members

and 'r'he of"

G.L. Romani / Biomagnetism

the biomagnetic group of Rome, and in particular Prof. I.Modena for daily collaboration and useful discussions. Finally, special thanks are due to Prof. A. Paoletti, whose continous encouragements and guidance have helped to achieve the described results.

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REFERENCES E.Edelsack and J.E.Zimmerman, (i) D.Cohen, Appl. Phys. Lett. 16 ((1970) 278. (2) J.P.Wikswo, J.P.Barach, S.C.Gundersen, J.D.Palmer and J.A.Freeman, Ii Nuovo Cimento 2D (1983) 512. -J.P.Wikswo, J.P.Barach, S.C.Gundersen, M.J.McLean and J.A.Freeman, I1 Nuovo Cimento 2D (1983) 368. (3) G.M.Brittenham, D.E.Farrell, J.W.Harris, E.S.Feldman, E.H.Danish, W.A.Muir, J.H.Tripp, J.N.Brennan and E.M.Bellon, Ii Nuovo Cimento 2D (1983) 569. (4) Biomagnetism an interdisciplinary approach, eds. S.J.Williamson, G.L.Romani, L.Kaufman and I.Modena (Plenum Press, New York and London, 1983). (5) S.J.Williamson and L.Kaufman, J. Magn. Magn. Mat. 22 (1981) 129. (6) S.J.Williamson and L.Kaufman, IEEE Trans. Magn. MAG-19 (1983) 835. (7) S.N.Ern@ and R.R.Fenici, Proc. ICEC i0 Conference, Helsinki 1984, in press. (8) T.Varpula, Ii Nuovo Cimento 2D (1983) 624. (9) G.L.Romani, S.J.Williamson and L.Kaufman, Rev. Sci. Instrum. 53 (1982) 1815. (i0) J.E.Zimmerman and N.V.Frederick, Appl. Phys. Lett. 19 (1971) 16. (ii) R.R.Fenici, M.Masselli, S.N.Ern& and H.D.Hahlbohm, Proc. 5th World Conference on Biomagnetism, Vancouver 1984, in press. (12) S.Barbanera, P.Carelli, R.Fenici, R.Leoni, I.Modena and G.L.Romani, IEEE Trans. Magn. MAG-17 (1981) 849. (13) J.E.Zimmerman, J. Appl. Phys. 48 (1977) 702. (14) S.J.Williamson and L.Kaufman, Proc. ICEC i0 Conference, Helsinki 1984, in press. (15) S.N.Ern@, personal communication. (16) G.L.Romani and R.Leoni, Proc. 5th World Conference on Biomagnetism, Vancouver 1984, in press. (17) S.J.Williamson, personal communication. The system is manufactured by S.H.E. Co. San Diego, CA, USA. (18) P.T.B. Institut Berlin. Three-channel magnetometer developed as a joint project

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81

between the P.T.B Institut Berlin and the I.E.S.S.-CNR, Rome. J.Lekkala and J.Malmivuo, Proc. ICEC i0 Conference, Helsinki 1984, in press. R.Ilmoniemi, Proc. ICEC i0 Conference, Helsinki 1984, in press. M.Seppanen, T.Katila, T.Tuomisto, T.Varpula, D.Duret and P.Karp, Ii Nuovo Cimento 2D (1983) 166. P.Carelli, personal communication. S.J.Williamson and L.Kaufman, in: Biomagnetism, eds. S.N.Ern6, H.D.Hahlbohm and H.L5bbig (Walter de Gruyter, Berlin, New York, 1981) 353. G.L.Romani, S.J.Williamson and L.Kaufman, Science 216 (1982) 1339. H.Weinberg, P.A.Brickett, J.Vrba, A.A.Fife and M.B.Burbank, Annals of New York Academy of Sciences (1984) in press. R.Fiumara, F.Campitelli, G.L.Romani, R.Leoni, M.Caporali, M.Zanasi, A.Cappiello, G.Fioriti and I.Modena, Proc. 5th World Conference on Biomagnetism, Vancouver 1984, in press. H.Berger, Arch. ?sychiat. 87 (1929) 527. R.M.Chapman, R.Ilmoniemi, S.Barbanera and G.L.Romani, Electroencephalogr. Clin. Neurophysiol. (1984), in press. D.S.Barth, W.H.Sutherling, J.Engel and J.Beatty, Science 218 (1982) 891. R.M.Chapman, G.L.Romani, S.Barbanera, R.Leoni, I.Modena, G.B.Ricci and F.Campitelli, Lett. Nuovo Cimento 38 (1983)

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D.S.Barth, W.Sutherling, J.Engel and J.Beatty, Science 223 (1984) 293. G.B.Ricci, I.Modena, S.Barbanera, F.Campitelli and G.L.Romani, Acta Neurochirurgica, Suppl.33 (1984) 85. G.B.Ricci, R.Leoni, G.L.Romani, F.Campitelli, S.Buonomo and I.Modena, Proc. 5th World Conference on Biomagnetism, Vancouver 1984, in press.