NMR Imaging in Medicine

Nuclear magnetic resonance, or NMR, can reveal the distribution

ofatoms in a sample ofmaterial. It can do the same in the body,
generating images ofinternal structure without the use ofX rays

by Ian L. Pykett

T
he medical need to see inside the NMR spectroscopy were laid by Felix This direction conventionally defines the
human body from the outside has Bloch of Stanford University and Ed­ z axis.
been met for many decades by re­ ward M. Purcell of Harvard University Spinning nuclei behave rather like
cording the differential absorption of X more than three decades ago, work for tiny tops or gyroscopes. If the axis of a
rays. A major deficiency of the standard which they were awarded a Nobel prize spinning gyroscope is tipped away from
method of radiography is its inability to in 1952. It had been known since the the vertical, the gyroscope will rotate
discriminate among overlapping struc­ 1920's that many atomic nuclei have an about its former axis in a motion de­
tures. This deficiency has been remedied angular momentum arising from their scribing the wall of a cone. It is the mo­
in recent years by the development of X­ inherent property of rotation, or spin. tion called precession. Similarly, if the
ray computerized tomography, or CT Since nuclei are electrically charged, the bulk magnetization M, corresponding
scanning, a technique in which X-ray spin corresponds to a current flowing to an assembly of spinning nuclei in a
data recorded from many different di­ about the spin axis, which in turn gener­ magnetic field, is tipped away from the
rections are reconstructed mathemati­ ates a small magnetic field. Each nucle­ z direction, M will precess about the z
cally to yield cross-sectional views of us of nonzero spin therefore has a mag­ axis. Such a tipping can be achieved by
selected regions of any part of the body. netic moment, or dipole, associated with applying a much smaller magnetic field
Although CT scanning has proved to be it. Only nuclei with an odd number of that is rotating in the x-y plane, at right
an extremely useful diagnostic tool, the nucleons (protons or neutrons) exhibit a angles to the static (nonrotating) field.
information its images provide is basi­ net spin and therefore lend themselves In practice the rotating magnetic field
cally anatomical; they tell little about to NMR spectroscopy. is applied by surrounding the sample
the functional or physiological state of In general the magnetic dipoles of the with a coil connected to a source of ra­
the internal organs. Moreover, some nuclei with spin will be pointing in ran­ dio-frequency power. In order to tip the
pathological lesions have X-ray absorp­ dom directions. When they are placed in macroscopic spin vector away from the
tion properties so similar to those of the a magnetic field, however, they will ori­ z axis the frequency of the applied elec­
surrounding tissues that the lesions can ent themselves with the field's lines of tromagnetic radiation must match the
go undetected in a CT scan unless they induction, or lines of force. For nuclei of natural precessional frequency of the
are large enough to change the size or the spin designated 1/2, such as protons nuclei of the sample, hence the term nu­
shape of the organ. Beyond that X rays, (hydrogen nuclei, IH), the only allowed clear magnetic resonance.
even in small doses, carry a finite risk of orientations of the dipoles are parallel A simple mathematical relation links
doing physiological harm. to the field or antiparallel to it (in the the resonance frequency, often called
A new technique for obtaining cross­ opposite direction). The two orienta­ the Larmor frequency, to the value of
sectional pictures through the human tions have slightly different energies, de­ the externally applied static magnetic
body without exposing the patient to scribed as a Zeeman splitting of the en­ field. The' frequency is equal to the
ionizing radiation is on the threshold of ergy levels. In the case of protons the strength of the field multiplied by the
clinical application: nuclear-magnetic­ difference between the number of pro­ "gyromagnetic ratio," which is unique
resonance imaging. NMR imaging not tons with spin "up" (parallel) and spin for each nuclear species of nonzero spin.
only yields anatomical information com­ "down" (antiparallel) is very small: only For hydrogen nuclei (protons) in a mag­
parable in many ways to the informa­ about one part in 108, with a slight ex­ netic field of one tesla ( 10,000 gauss) the
tion supplied by a CT scan but also cess in the lower energy state (spin up). resonance frequency is 42.57 megahertz
promises to discriminate more sensitive­ (MHz), or 42.57 million cycles per sec­
ly between healthy and diseased tissue. he magnetic behavior of the entire ond. For nuclei of the isotope phos­
The latter prospect is founded on the T population of nuclei can be predict­ phorus 3 1 (3IP) in the same field the
well-established ability of NMR spec­ ed by defining a macroscopic, or bulk, resonance frequency is 17.24 MHz; for
troscopy to elucidate the intricate con­ magnetization vector, M, that represents nuclei of sodium 23 (23Na) it is 1 1.26
formation of organic molecules and to the net effect of all the magnetic mo­ MHz. These frequencies are in the ra­
provide insight into dynamic chemical ments of the nuclei of a given nuclear dio-frequency band of the electromag­
processes. For several years biochem­ species in the sample of material being netic spectrum. Such frequencies, far
ists have exploited NMR techniques to examined. In the absence of an exter­ below those of X rays or even visible
monitor metabolic reactions in experi­ nal magnetic field the bulk magnetiza­ light, are powerless to disrupt the mole­
mental animals and human beings. It is tion is of course zero. When a magnetic cules of living systems.
the recent development of methods for field is imposed on the sample, however, It is evident, therefore, that by the
presenting NMR information in pictori­ the nuclear dipoles become oriented to proper choice of frequency one can
al form that is now providing clinicians yield a finite equilibrium bulk mag­ "tune in" to specific nuclear species and
with a powerful new diagnostic tool. netization that will point in a direction observe their response in isolation. All
The experimental foundations of parallel to the applied magnetic field. medical NMR images produced so far,

78

© 1982 SCIENTIFIC AMERICAN, INC

however, have been obtained with the point the tipping of the bulk magnetiza­ cy field exactly equals the difference in
resonances only of hydrogen nuclei. tion vector of an assembly of nuclei magnetic energy between the two ener­
Other nuclei not only have a lower away from its equilibrium position is gy states. The fact that medical NMR
intrinsic NMR sensitivity but also are equivalent to a transition from a lower images can be most easily generated
found in much lower concentrations in energy state to a higher one. The transi­ from the resonance of hydrogen nuclei
biological material. tion is effected only when the energy of is fortunate, because the human body
From the quantum-mechanical view- the quanta carried by the radio-frequen- is 75 percent water, each molecule of

NMR IMAGES are cross-sectional pictures of thin slices through containing water and lipid molecules in blood and tissue. The three
the body obtained by using radio waves to interrogate susceptible transverse images at the left show sections at three levels: through
atomic nuclei that have been precisely oriented in a magnetic field. the center of the brain (top), at eye level (middle) and just below eye
The susceptible nuclei are those that have an odd number of nucle­ level(bottom). The three images in the middle show a section at the
ons (protons or neutrons) and therefore exhibit a net spin. Hydrogen midline (center ) and parallel sections about three centimeters to the
nuclei (protons) are the most Ubiquitous in living matter. After radio left and right. The three images at the right show the head from the
excitation the nuclei reveal their location by emitting a signal of pre­ front at the brain's widest point (top) and at two regions farther to
cise frequency for a brief period. With computer techniques pictorial the rear. The images, which were made in the NMR research labo­
images can be reconstructed from the emitted signals. Here are nine ratory of the Massachusetts General Hospital, were generated with
images of a human head, reconstructed from a single three-dimen­ NMR apparatus built by the Technicare Corporation of Solon, Ohio.
sional data collection, showing primarily the distribution of proton- The apparatus had a magnet operating at .15 tesla (1,500 gauss).

79

© 1982 SCIENTIFIC AMERICAN, INC

which has two hydrogen nuclei. More­ magnetization vector continues to ro­ relaxation time. Spin-spin relaxation
over, the distribution of water, togeth­ tate freely in the x-y plane, and in so do­ phenomena influence the natural life­
er with that of various other small, ing it generates a small electromotive time of the free induction signal, during
hydrogen-rich molecules (for example force that can be detected either by the which the various components of mag­
lipids), is known to be altered by many same coil that transmitted the pulse or netization in the x-y plane remain more
disease states. by a separate receiver coil. The emit­ or less in phase. When the excitation
ted signal is called the free induction pulse ends, each nucleus continues to
he displacement angle between the signal or free induction decay. In quan­ "feel" not only the external static field
T nuclear magnetization vector M and tum-mechanical terms the signal is gen­ but also local fields associated with the
the direction of the static magnetic field erated as the nuclei drop back from the magnetic properties of neighboring nu­
continues to increase for as long as the excited energy level to the ground state, clei. The nuclei will therefore acquire a
rotating field is applied to the sample, the lowest energy level. range of slightly different precessional
and the rate of increase depends on the After the excitation pulse ends, the frequencies, causing the free induction
power of the field. A pulse long and magnetization vector of the nuclei even­ signal to go out of phase. In a liquid,
strong enough to tip M from its ini­ tually returns to its original position where the atoms and their nuclei are
tial position until it is just rotating in the directed along the z axis. The return continuously in motion, the internuclear
x-y plane is termed a 90-degree pulse. to equilibrium is characterized by two magnetic fields responsible for spin-spin
But how does one know that there has principal "relaxation" times, Tl and T2• relaxation tend to average out. As a re­
been any tipping? Immediately after the To discuss T2 first, it is called the spin­ sult the signal decays much more slowly
application of a 90-degree pulse the spin relaxation time or the transverse than it would in a solid, where the nuclei

MAGNET x MAGNET
(SOUTH POLE) (SOUTH POLE)
z

i
Bo

t
RADIO-FREQUENCY
GENERATOR

MAGNET MAGNET
(NORTH POLE) (NORTH POLE)

Bo
PULs �4
RADIO-FREQUENCY

Bo

/
/
/
/
'
1111
-----« ----« I
, " \
,

'" \i t t t t t
,

tttttt
,
,

NO EXTERNAL EXTERNAL NET MAGNETIC ADDITION OF FIELD B 1 NET MAGNETIC

MAGNETIC MAGNETIC MOMENT (M) AT RIGHT ANGLES TO Bo MOMENT (M)
FIELD FIELD = Bo

IN THE PRESENCE OF A MAGNETIC FIELD, Bo, nuclei with This is done (right) by applying a second magnetic field, B 10 which
nonzero spin orient themselves with the magnetic field lines, which has a rotating component in the plane x-y at right angles to the static
point in the z direction (left). A net magnetic moment M, aligned par­ (nonrotating) field. Only' when the frequency of the rotating field ex­
allel to the field, is therefore generated within the sample. In quan­ actly matches the Larmor frequency (the natural resonance frequen­
tum-mechanical terms the alignment corresponds to the creation of cy) of the nuclei is M tipped toward the x-y plane. B 1 is generated by
multiple magnetic energy levels. For nuclei with the spin designated placing around the sample a coil that applies radio-frequency ener­
1/2, which include protons, two levels are established, with a small ex­ gy to the spin system. In quantum-mechanical terms quanta of radio
cess of nuclei in the lower energy state. The vector M can be made to energy that exactly match the gap between energy levels will cause
precess about the magnetic field direction as if it were a falling top. some nuclei to "flip" from the lower energy state to the higher one.

80

© 1982 SCIENTIFIC AMERICAN, INC

 z
remain essentially fixed in space. In a
pure liquid T2 can be as long as several t z

seconds. In a solid it is usually only a few 80

microseconds; indeed, the signal decays
so fast that it is generally undetectable.
If the static magnetic field were per­
fectly uniform, T2 could be determined
simply by measuring the rate of decay of
the free induction signal. The fields gen­
erated by real magnets, however, are al­
ways less than perfect. Even though the ---�>� X
�
J-�L-
imperfections in the best magnets used
for NMR spectroscopy are extremely
small, they cause the free induction sig­
nal to decay faster than it would if the
magnetic field were perfectly homoge­
neous. The time constant defining the
I
C\= 15 DEGREES
actual rate of signal decay in an im­ 15·DEGREE R.F. PULSE
perfect field is designated Ti ("T two­ y
y
star") to distinguish it from the true re­
laxation time T2. z

z
t is nonetheless possible to determine
I the intrinsic T2 value for a sample of
material even when it is in an imperfect
,
field, because the nonuniformities in the "-
"-
magnetic field are constant and can in "

effect be identified and canceled. For �\

this purpose one can recall the signal in \
the form of a "spin echo," or a series of \
echoes, by applying a special pattern of \
I
radio-frequency pulses called the Carr­ I-_J...___
... ��'� x
Purcell pulse sequence. In such a se­ M
quence the initial free induction decay
signal and each of the individual spin
echoes decay with a time constant Ti,
but the peak heights of successive spin
echoes decay with a time constant equal
= 90 DEGREES

I
C\
to the intrinsic T2 value of the sample. 90-DEGREE R.F. PULSE
The other relaxation time, Tb is y
y
known as the spin-lattice relaxation time
or longitudinal relaxation time. Tl is z

characteristic of the time required for t z

the spin system to return to thermal 80

equilibrium with its surroundings (the
"lattice") after the excitation pulse ends.
In quantum-mechanical terms the fluc­
tuating magnetic fields of the nuclei
making up the lattice must have appro­
priate frequency components to stimu­
late transitions from the upper magnetic
energy level back down to the ground
state. In solids or in samples of materi­ j---t----T--7 x
I
al at low temperatures, where the at­
/
oms and molecules move about very /
little, there will be few components at /
/
the right frequency, and Tl can last for /
hours. For protons in pure, simple liq­ I?
/
uids, such as distilled water, Tl and T2 ...­
.... /
are approximately equal (a few sec­ -
-
, ;
180 DEGREES
=

onds), an indication of the mutual de­ 180-DEGREE RF PULSE

pendence of the relaxation times on the
fluctuating, internal magnetic fields. PRECESSIONAL ANGLE, a, continues to increase as long as tbe rotating magnetic field, B1>
In liquid and liquidlike materials, is applied. The precessional frequency, however, remains constant, being fixed by the inherent
then, the ratio of T2 to Tl tends to properties of the nuclei and the strength of the static field, Bo. The radio-frequency pulse need­
ed to tip the vector of the net magnetic moment M through an angle of 15 degrees is described
approach unity, but in solid materials
as a 15-degree pulse. Pulses of 90 and 180 degrees cause corresponding increases in the preces­
the ratio is very small. The internuclear
sional angle. To an imaginary observer rotating with the magnetization vector at the Larmor
("dipole-dipole") magnetic interactions frequency (right) the increase in the precessional angle would appear to be a simple rotation of
that cause T2 to be extremely short in M about the applied field B 1> which would appear to be stationary. Whenever a net compo­
solids can be effectively canceled by re­ nent of M exists in the x-y plane, an electromotive force is generated that can be detected
sorting to complex multiple-pulse cy- by a coil surrounding tbe sample. This electromotive force is the origin of the NMR signal.

81

© 1982 SCIENTIFIC AMERICAN, INC

 z

�
/ pu�
z x z

e
y
a-DEGREE R.F.

b
I

-
�.b�--- X '-----�-X

z z

d c

�---
TIME

7------r- X �------��--- X

y y
a-DEGREE
RADIO- FREQUENCY
PULSE
NMR SIGNAL
a-DEGREE
RADIO­ "/ / DECAY CONSTANT
EXPONENTIAL
T2
�
FREQUENCY --_ =

PULSE --
EX PONENTIAL GROWTH
CONSTANT = T,
TIME� COM PONENT
I OF M IN z
I DIRECTION
I
I
I TIME�
I I I I I
I I I I I I
a c d e 0 a b c d e

IN A PULSED NMR EXPERIMENT the emitted signal is observed formities in the magnetic field. The net component of M in the x-y
after the radio-frequency energy that induces precession is turned plane therefore diminishes, and the signal amplitude decays exponen­
off. In these diagrams the frame of reference is assumed to be rotat­ tially with a time constant 12 (c, d ). If the magnetic field Bo is per­
ing at the average Larmor frequency. After a radio-frequency pulse fectly uniform, the signal decay time is longer, and the time constant
tips the vector of net magnetic moment M through some angle, a, is T2, called the spin-spin relaxation time. Simultaneously the longitu­
there will be a component of M in the x-y plane (b). For a brief in­ dinal component of magnetization increases as M returns to its equi­
stant the NMR signal is at a maximum (curve at bottom left). Nuclei librium position, aligned with the z axis (e). This relaxation, designat­
immediately begin to precess, however, at slightly different rates be­ ed T1 (spin-lattice relaxation time), measures the time needed for the
cause of magnetic interactions between nuclei and slight nonuni- spin system to return to thermal equilibrium (curve at bottom right).

82

© 1982 SCIENTIFIC AMERICAN, INC

cles. Such cycles, however, have not yet a a-DEGREE R.F. PULSE NMR SIGNAL = Ti
been employed for medical NMR imag­
ing; only liquidlike regions in biological
materials yield any appreciable signal.
/
We have seen that it is possible to de­
termine the material's intrinsic relaxa­
tion time T2. It is also possible to deter­ ,/
mine the intrinsic value of Tj• This is
done by applying a second pulse after 1< >1 TIME --7
the signal has decayed but before there t - T,
has been full spin-lattice relaxation. The
second pulse will evoke another free
b /' a-DEGREE R.F. PULSE STEADY-STATE NMR SIGNAL
induction signal, but the amplitude in
this case will be smaller. The explana­
tion is that the strength of the evoked
signal is proportional to the longitudi­
/
nal component of magnetization along
the field direction z just before the pulse ,/
is applied. Before the initial pulse all the
nuclei are aligned with the field, and 1< )1 TIME --7

�
the evoked signal is therefore maximal.
The second pulse, however, is applied
while the component of magnetization 180-DEGREE gO-DEGREE
c T;
is still in the process of returning to the
aligned position, so that the evoked sig­
/
R.F. PULSE
� gO-DEGREE 180-DEGREE-
R.F. PULSE
"'--..
NMR SIGNAL =

nal is not as strong as the original one.

.F. PULSE R.F. PULSE "'--..
Since the component of magnetization
returns to its equilibrium value expo­
nentially with a time constant Tj, the
respective amplitude of the two signals ,/
is a measure of that constant.
k--- t -,»+EI<�---- - 3 T, ----->�I TIME--7
T,
Variations in the value of Tj can be
exploited in NMRimaging to in­
t -

crease the contrast between different re­ TRUE DECAY CONSTANT = T2

gions in samples of soft tissue. Differ­ d gO-DEGREE R.F. PULSE
ences in Tj values can be brought out by
means of special pulse sequences, for / /
180-DEGREE
R.F. PULSE
example the "saturation-recovery" se­
quence. Here the sample is exposed to a
train of radio-frequency pulses with a
constant spacing between pulses. Pro­
�L
vided that complete spin-spin relaxation
(T2) occurs in each pulse interval, the
amplitude of free induction decay sig­ � t -)'l>IIIE<-- 2t -----';l>okl<�-2t--�)k'I('----2t -->l TIME-----::'
nals will reach a steady-state value that
is dependent on both the value of Tj and
the density of liquidlike nuclei contrib­ VARIOUS PULSE PATTERNS that emphasize different aspects of the evoked NMR signal
uting to the signal. The relation to-signal can be exploited to alter the contrast of NMR images. In a "saturation-recovery" pulse se­
strength is such that for areas in the im­ quence (a) a series of 90-degree pulses is applied with an interpulse spacing, I, longer than the
age where Tj is long compared with the decay time T2 and roughly the same length as T1• When the value of I is changed, variations in
interval between pulses the image inten­ Tl in different parts of a sample will show up as differences in image intensity and a "T1 map"
sity is weak. can be generated. If I is much shorter than T2, the signal will not decay to zero between succe�­
This imaging procedure yields images sive pulses, creating a condition known as steady-state free precession, or SSFP (b). Now im­
that are said to be Trweighted. If two or age contrast can be altered by changing the pulse angle a. In the "inversion-recovery" pulse se­
quence (c) the magnetization vector is inverted by first applying a IS0-degree pulse and then a
more images are obtained with different
90-degree "read" pulse. This sequence also emphasizes Tl variations in the sample. The "Carr­
spacings between pulses, it is possible to
Purcell spin echo" sequence ( d ) consists of a 90-degree pulse followed by a series of ISO-degree
calculate from the data a Tj value for pulses. Here the resulting images are strongly depeudent on the spin-spin relaxation time T2•
each pixel, or picture element, in the im­
age, independent of spin density. The
result is a "Tj map." The Tj differences the signal intensity is dependent on T2 as recovery sequence in that Tj variations
identified in this way are extremely use­ well as Tj• This pulse sequence is called in the sample are emphasized. In this
ful in proton NMR imaging because steady-state free precession, or SSFP. pattern the bulk magnetization vector
proton Tj differences among various Although images of very high quality is first completely inverted by applying
soft tissues are much greater than cor­ have been generated with the SSFP se­ a I80-degree pulse to the sample. Tj
responding differences in mobile pro­ quence, it is not easy to separate the in­ relaxation proceeds during a selected
ton density. dividual contributions of Tj and T2 to pulse interval, after which a 90-degree
If the pulses are applied so rapidly the resulting image intensity. "read" pulse is applied. The free induc­
that the signal does not decay to zero Another 'frequently adopted pulse tion signal that follows the read pulse
between successive pulses, a different pattern is the "inversion-recovery" se­ serves to generate the image.
steady-state condition arises in which quence, which resembles the saturation- The inversion-recovery sequence gives

83

© 1982 SCIENTIFIC AMERICAN, INC

 --------')0)0 80 --------�)o 80 an image of higher contrast than the
--------�>)o G saturation-recovery sequence, but a
penalty is paid in the form of either
longer imaging time or reduced spatial
resolution. The reason is that if errors in
Tj determinations are to be avoided, a
delay time equal to at least three times
the value of Tl should be allowed to
elapse before repetition of the 180- and
90-degree pair of pulses. Tl maps can
also be derived from inversion-recovery
pulse patterns. The spin-echo pulse se­
RADIO-FREQUENCY PULSE quence mentioned above is useful for

\
creating images that are primarily or
NMR SIGNAL solely dependent on the spin-spin relax­
ation time, T2.
Therefore by choosing an appropriate
TIME ------7 TIME� pulse sequence, the intensity of an NMR
image can be made to reflect one or
more of several NMR parameters inher­
ent to the tissue being examined. Such
parameters in turn are sensitive to the
FOURIER TRANSFORMATION FOURIER TRANSFORMATION
..... I ..... / physicochemical environment of the
Y Y nuclei and underlie the conviction that
NMR imaging holds promise for de­

!
tecting disease early and for monitor­
ing its progress.

--------
he foregoing methods for manipu­
T lating the NMR response apply not
only to NMR imaging but also to NMR
LARMOR FREQUENCY LARMOR FREQUENCY
spectroscopy, in which the signal elicit­
METHODS OF CREATING NMR IMAGE call for spatial "encoding" of the NMR sig­ ed represents a summation of the NMR
nal. Here the sample is water in two cylinders, viewed from above. The hydrogen NMR signal response from the entire sample of ma­
obtained in NMR spectroscopy (left) appears as a single tall spike after Fourier transforma­ terial. But if the nuclear signal comes
tion, a mathematical process that converts a curve representing signal strength v. time into one from the entire sample, how can it be
representing signal strength v. frequency. If a linear magnetic field gradient, G, is now added encoded with spatial information? As
to the original static field, Bo, the evoked signal, after Fourier transformation, takes the form of long ago as 195 1 Robert Gabillard of
a curve that is representative of the shape of the sample (right). The area under the curves
the E cole Normale Superieure in Paris
represents the total number of protons in the sample, and therefore the area is equal for both.
was puzzled by the reverse question: he
noted that the NMR signal could be dis­
torted according to the shape and size of
the sample. This was correctly attribut­
--------�) 80 ed to nonuniformities in the static mag­
netic field. The degree of distortion de­
pends on how much of the sample is in
nonuniform parts of the field and on the
magnitude of the nonuniformities.
A continuing effort in NMR instru­
mentation has therefore been to remove
the influence of sample shape on the
NMR signal by making magnets with
g
fields of ever increasing homo eneity
and stability. The quest may conceiv­
ably have delayed the advent of NMR
imaging, because in imaging it is neces­
sary to make the field nonuniform delib­
erately, albeit in a controlled manner,
usually by superimposing on it a linear
magnetic field gradient.
The primary motivation for perfect­
ing the static field of magnets has come
from the desire of NMR spectroscopists
to measure the subtle "chemical shift"

o
RECONSTRUCTED IMAGE
in samples incorporating molecules of
complex structure. One might expect all
nuclei of the same species in a homoge­
IN PROJECTION-RECONSTRUCTION IMAGING a magnetic field gradient is rotated to neous magnetic field to have the same
obtain "snapshots" of the sample at many different angles covering an arc of at least 180 de­ resonant frequency; that is to say, one
grees. From such a set of data a computer can reconstruct a cross-sectional image of the sam­ would expect to observe a single, nar­
ple. The method is analogous to the one in X-ray computerized tomography (CT scanning). row peak in the NMR frequency spec-

84

© 1982 SCIENTIFIC AMERICAN, INC

trum. For nuclei in samples consisting ten precludes the extraction of such in­ Most of the two- and three-dimen­
of very simple molecules (such as for the formation. sional methods call for the application
hydrogen nuclei of pure water) this is The first published NMR image can of a linear magnetic field gradient to
indeed so. For more complex molecules, be credited to Paul C. Lauterbur of supply one dimension of spatial infor­
however, the magnetic field is subtly al­ the State University of New York at mation. Resolution in the second and
tered around some nuclei as a result of Stony Brook. In a 1973 article he pre­ third dimensions can be achieved by
"shielding currents" that are associated sented images of two water-filled capil­ sequentially stepping gradient magni­
with the distribution of electrons around lary tubes, obtained with a modified tudes or directions through a predeter­
adjacent atoms. Such alterations cause NMR spectrometer. The sample can be mined set of values. There are other ap­
shifts in the resonance frequency that regarded as a medium that couples the proaches. Rotating-frame zeugmatogra­
are representative of particular molecu­ radio-frequency field to the gradient phy, first reported by David Hoult of the
lar conformations and therefore direct­ of the magnetic field, and so Lauter­ National Institute of Dental Research, is
ly aid in the determination of chemical bur called his imaging method zeugma­ unique in that it exploits a gradient in
structure. tography, from the Greek zeugma, that the radio-frequency field as well as one
which joins together. in the static magnetic field. Peter Mans­
hese chemical shifts are very small, NMR imaging systems can be de­ field of the University of Nottingham
T being measured in parts per million signed to receive data from a single has devised a very high-speed method,
with respect to the strength of the static point in the sample, from a line, from echo-planar imaging, that generates a
magnetic field, and this explains why a plane or from the complete three-di­ complete, spatially resolved image fol­
such emphasis has been placed on the mensional volume all at once. In point­ lowing a single radio-frequency pulse.
construction of magnets with a highly or line-scanning methods images can be The first images produced by Lau­
uniform field. In the current genera­ generated by electronically moving the terbur borrowed image-reconstruction
tion of NMR imaging systems the static selected point or line through the sam­ computer algorithms, used also in CT
magnetic field is not uniform enough to ple in a raster, or sequential pattern. scanning. If a sample of water is placed
show chemical shifts with a useful de­ Such methods, however, have been al­ in a homogeneous magnetic field, the
gree of accuracy. In any case the im­ most entirely superseded by two- and NMR frequency spectrum of the hydro­
aging procedure itself (specifically the three-dimensional methods, which are gen nuclei in the water molecules is a
application of the field gradients) of- much more efficient. single narrow line. If the magnetic field

--------,O)� 80
)G

012 3 456
PHASE-ENCODING
GRADIENT

0 -

5--
SECOND FOURIER

INCREASING
/ TRANSFORMATION

PHASE· ENCODING
GRADIENT

IN FOURIER ZEUGMATOGRAPHY another magnetic field gra­ a series of increasingly "phase-distorted" projections are generated.
dient is applied for a short time just before the usual gradient, G, is Corresponding points from each of the projections (brokell lilies ill
turned on. This new gradient, termed a phase-encoding gradient, is color) are then subjected to a second Fourier transformation to gen­
applied at right angles to the original one, and its magnitude is raised erate the final image. The term zeugmatography is from the Greek
from zero in a series of many small steps. The effect of the two gra­ zeugmD, that which joins together. It alludes here to the way the sam­
dients on the NMR signal is such that after Fourier transformation ple couples the radio-frequency field and the magnetic-gradient field.

85

© 1982 SCIENTIFIC AMERICAN, INC

 is perfectly uniform, the shape of the
line is independent of the geometry of
the sample. If a linear magnetic field
gradient is now superimposed, resonant
nuclei at one side of the sample will feel
a weaker total magnetic field than those
at the other side. There will thus be a
linear distribution of Larmor frequen­
cies across the sample. Then the free
induction decay signal can be subject­
ed to Fourier transformation, a mathe­
matical procedure that transforms the
data from a curve representing signal
strength v. time into one representing
signal strength v. frequency.
The result is a spectrum that is
broadened to a shape corresponding to
the one-dimensional projection of the
LUMBAR REGION OF THE HUMAN SPINE is depicted in two reconstructions from strength of the NMR signal onto the fre­
three-dimensional NMR data set. The image at the left shows the spinal cord within the spinal
quency axis. By rotating the magnetic
canal. In the image at the right the plane of the image has been moved a few centimeters to re­
field gradient electronically one can get
veal the intervertebral disks. It is difficult to obtain clear pictures of the spine over such a large
area with a CT scan or any other imaging method. The images were provided by Technicare. a projection from a slightly different an­
gle. Computer analysis of many such
projections reconstructs the sample's ge­
ometry. In the two-dimensional applica­
tion of the technique the direction of
the gradient is rotated within a single
plane. In the three-dimensional exten­
sion of the method the gradient is rotat­
ed in three-dimensional space through
at least half a sphere.
Two-dimensional Fourier-transfor­
mation imaging, or Fourier zeugmatog­
raphy, was first demonstrated in 1975 by
A. Kumar, D. Welti and R. R. Ernst of
the Swiss Federal Institute of Technolo­
gy. Their method owes more to NMR
spectroscopy than to CT reconstruction
algorithms, because both amplitude in­
formation and phase information are
acquired to spatially encode the signal.
The first step again calls for generating a
"GATED" IMAGES OF THE HEART are shown in NMR cross sections of the human chest. one-dimensional projection, but here a
(The two smaller shapes at each side of the chest are the arms.) The image at the left shows the phase-encoding gradient is applied just
heart at the end of systole, when the chambers are being emptied. The image at the right shows
before the original gradient is turned on.
the end of diastole, when the chambers are filled. The images, supplied by Technicare, were
The phase-encoding gradient is applied
made by gating, or synchronizing, the recording of data to match the stage of the cardiac cycle.
at right angles to the original gradient,
and its duration (or amplitude) is succes­
sively increased from zero, rather than
the gradient's being progressively rotat­
ed, as was done in the original form
of zeugmatography. The phase-encoded
projections are stacked in increasing or­
der of magnitude of the phase-encoding
gradient, and the corresponding points
from each projection are Fourier-trans­
formed a second time to generate the
final image [see illustration on preced­
ing page].

uclear magnetic resonance is inher­

N ently a three-dimensional phenom­
enon. Since NMR signals are normally
obtained from the total volume of mate­
rial enclosed within the transmitter and
receiver coils, considerable ingenuity
NMR IMAGE AND X-RAY CT-SCAN IMAGE can be compared in these two transverse is required to reduce the volume from
views of the brain of a patient with a brain tumor. In the NMR image (left), reconstructed which signals come to defined points,
from three-dimensional data, the tumor is a dark circular area at the right side of the brain. In lines or planes. In one method, called
the CT scan (right) the tumor is all but invisible. The pictures, made at the Massachusetts Gen­ selective irradiation, a radio-frequency
eral Hospital, are reproduced with permission of Journal of Computerized Axial Tomography. pulse is applied that is specially tailored

86

© 1982 SCIENTIFIC AMERICAN, INC

MIDSECTION OF A CANCER PATIENT appears in two NMR the pulse sequence to discriminate among tissues on the basis of their
images made by James M. S. Hutchison, Francis Smith and John R. Tl relaxation-time differences. Color coding was then introduced to
Mallard and their co-workers in the Faculty of Medicine at the Uni­ enhance the discrimination. The patient had a cancer of the rectum
versity of Aberdeen, using a .04-tesla imaging system. The black­ that had spread to the liver. The normal liver tissue appears light
and-white image is a simple record of proton density. The colored im­ blue. The cancerous regions are yellow-brown. The spinal cord and
age is a computer synthesis of a series of images obtained by altering the spinal canal are more clearly seen in the proton-density image.

to consist of only a very narrow band than a true three-dimensional image, the such attenuation may become a limit­
of frequencies. Only those nuclei lying three-dimensional one can be "dissect­ ing factor when the frequency exceeds
within a single slice perpendicular to the ed" at leisure into a great many slices, so about 15 megahertz, which for proton
direction of a plane-selection gradient that the imaging time per plane is much imaging corresponds to a field strength
will exhibit resonant frequencies corre­ reduced. of .35 tesla (3,500 gauss). This field
sponding to those in the radio-frequency The spatial resolution of a three-di­ strength would be regarded as a low
pulse. Hence only a thin, isolated slab of mensional set of data is usually isotrop­ one in NMR spectroscopy, but in NMR
material is irradiated. The thickness or ic, or equal in all three dimensions. imaging the large working volume in
position of the plane can be altered by Therefore two-dimensional slices of se­ which uniformity of magnetic field is
changing the width or the frequency lected thickness, with any position or needed has called for novel approaches
offset of the irradiation spectrum elec­ orientation, can be generated at any to magnet design.
tronically. time after the primary data have been At present the two commonest mag­
A second method, devised by Waldo acquired. With three-dimensional data net designs are the four-coil air-core
S. Hinshaw, who was then working at in hand, surfaces can be detected math­ ambient-temperature magnet and the
the University of Nottingham, imposes ematically, enabling the clinician to de­ large-bore, helium-cooled supercon­
an oscillating magnetic field to select a termine the volume of organs or of ducting magnet. NMR systems with
particular plane. In this method the di­ pathological lesions. conventional nonsuperconducting mag­
rection of the plane-selection field gradi­ In medical practice many factors nets are less costly and are entirely satis­
ent is periodically reversed, often sinu­ must be considered when a particular factory for whole-body proton imaging
soidally. There is then just one plane at imaging method is being chosen, par­ at field strengths below about .2 tes­
the fulcrum of oscillation within which ticularly the time scale of involuntary la, for which the power consumption is
the magnetic field remains time-inde­ movements of the tissue being studied. about 50 kilowatts and cooling require­
pendent; signals from outside this plane The head, for example, is particularly ments are not prohibitive. Supercon­
vary in, such a way that they do not con­ amenable to true three-dimensional im­ ducting magnets, although they are ini­
tribute to the intensity of the image. aging because it can be held still for tially much more expensive, may have
These are just two of several possible the duration of the scan. The heart, on lower operating costs and are able to
methods for selecting planes. the other hand, which beats incessantly, generate magnetic fields that are both
Although whole-volume methods of­ requires either a high-speed imaging stronger and stabler than those attain­
fer important advantages, they also method or one that can "gate," or syn­ able with nonsuperconducting magnets.
have some technical drawbacks. The chronize, the data collected over a series Superconducting magnets are therefore
sheer mass of data acquired calls for of cardiac cycles. preferred if it is intended to image nuclei
a computer with a large data-handling other than hydrogen, which demand sig­
and storage capacity. For example, gen­ he apparatus needed for NMR im­ nificantly stronger fields. For example,
erating a three-dimensional image that T aging exploits the same basic tech­ the observation of phosphorus 31 at 15
shows 256 data points in each dimen­ nology developed for NMR spectrosco­ megahertz calls for a field strength of
sion, with 256 levels of signal intensity py. Indeed, many of the early imaging .87 tesla. One critical component of an
(equal to eight bits) per data point, calls experiments were conducted with modi­ NMR imaging apparatus not usually
for a system with more than 134 million fied NMR spectrometers. The signal­ found in an NMR spectroscopy appara­
bits of memory (2563 X 8). Moreover, to-noise ratio of an NMR image can be tus is the gradient coil system, which
many sequential values of field-gradient improved by increasing the strength of is needed to create linear field gradi­
magnitude or direction are needed to the static magnetic field of the appara­ ents whose magnitude must sometimes
uniquely define all the points in such tus. As the field strength is increased the be altered very rapidly. The conflicting
a three-dimensional data matrix. This Larmor-precession frequency of the nu­ requirements of large-magnitude gradi­
lengthens the data-collection time, par­ clei in the sample of material being ex­ ents and fast switching times have given
ticularly if Tl maps are desired. For amined increases linearly, and a higher rise to many original designs.
such reasons it is sometimes preferable radio frequency is needed. The draw­ It should be emphasized that the spa­
to generate a small number of selected back is that both the transmitted and tial resolution of an NMR image is not
two-dimensional images. Although it is the emitted signals are more strongly dictated by the wavelength of radiation
true that a single two-dimensional im­ absorbed as the frequency is increased. that yields the image, as it is in many
age can usually be acquired in less time For imaging the whole human body imaging systems. (The wavelength of

87

© 1982 SCIENTIFIC AMERICAN, INC

1S-megahertz radiation in free space is good at detecting necrotic (dead) tissue, blood flows through the major vessels,
20 meters.) In NMR imaging spatial res­ ischemia (local anemia caused by me­ and recent experiments show that the
olution depends rather on the uniform­ chanical obstruction of the blood sup­ action of the heart in various parts of its
ity of the static magnetic field and on ply), malignancies and degenerative dis­ cycle can be "frozen" by high-speed or
the strength of the gradient fields. The ease of various kinds. The soft-tissue stroboscopic NMR imaging.
T2 relaxation time of the free induction contrast is inherently superior to that of Perhaps the greatest potential of all
signal is usually the dominant decay X-ray techniques, and the sensitivity for lies in the imaging of nuclei other than
process in current NMR imaging sys­ the detection of lesions in general ap­ hydrogen, particularly the phosphorus
tems, and therefore T2 sets a minimum pears to be very high. nucleus. Phosphorus is a major constitu­
line width of the NMR spectrum. The One promising idea is to adminis­ ent of the high-energy molecules adeno­
strength of the gradient fields must be ter NMR "tracers," or contrast materi­ sine triphosphate (ATP) and phospho­
high enough for the frequency incre­ als, orally or by injection. For example, creatine, which mediate the transfer of
ments from pixel to pixel in the final paramagnetic ions such as those of man­ energy in the living cell. NMR spectros­
image to dominate the T2 line width. ganese (Mn + + ) have unpaired electrons, copy of phosphorus in localized vol­
Some spatial encoding methods, how­ so that they have a magnetic moment umes within the body clearly reveals
ever, require that this condition be satis­ and tend to align themselves in the static several chemically shifted resonance
fied less rigorously than others. magnetic field of an NMR system. They peaks whose heights correspond to the
increase the local magnetic field slightly concentration of the individual phos­
MR imaging in medicine is still at and substantially modify the relaxation phorus compounds. From knowledge of
N an early stage. A systematic body time of NMR-sensitive nuclei. The re­ such concentrations it is possible to infer
of data must be built up so that the ef­ sulting change in image intensity would the metabolic status of internal organs,
ficacy of the technique for detecting allow the distribution of the paramag­ and it may eventually be possible to add
pathological lesions in various parts of netic species to be mapped. Such tracers this capability to an imaging instrument.
the body can be established. Early clin­ could play a role analogous to that of The next few years will undoubtedly see
ical results at the Massachusetts Gen­ the radioactive tracers administered in both an improvement in the quality of
eral Hospital with two imaging systems nuclear medicine. Several laboratories NMR images and a growing diversity of
made by the Technicare Corporation are investigating the feasibility of using applications for nuclear magnetic reso­
suggest that NMR may be particularly NMR to measure the velocity at which nance in clinical practice.

MAGNET RINGS

RADIO-FREQUENCY COIL

NMR IMAGING MAGNET is depicted schematically. The four panels. The NMR signals evoked by the radio-frequency pulses are
rings hold windings that generate a static magnetic field (Bo). The ra­ detected by the same coil and forwarded to a computer. Costlier sys­
dio-frequency pulse is generated by a coil in the form of two curved tems with higher magnetic fields employ superconducting magnets.

88

© 1982 SCIENTIFIC AMERICAN, INC

I t 's difficult to ask a blood chemis­ representative to isolate and correct maintenance options. A n d , most
important, backed by the Kodak

A
try analyzer to say "Aah." O r have the problem, quickly.
a microfilmer take a deep breath and co mmitment t o respond t o the
hold it. O r get the pulse of a color nother is a unique telephonic link­ market 's needs for productivity.
print processor. up that enables the equipment
Difficult. But not impossible.
Rapid , precise diagnosis is essential
to "call in" its vital signs to a sophisti­
cated d iagnostic computer that
W e know that you evaluate
capital expenditure by R O J .
to the productivity of capital equip­ responds instantly to the ESR on site.
Equipment R O I depends largely on
ment. A nd it's the foundation of our And once d iagnosis is made, the
maximum uptime. And that uptime
service philoso phy. treatment is equally rapid because
often hinges on service. Timely, thor­
The field maintenance p rocessor Kodak designs serviceability into its
ough service.
shown here is j u st one example of the equipment from the very first blue­
If you'd like to know more about
extra dimension of serviceability that p rint . . . with d rop-in subassemblies
the ways we can get a machine to stick
you can expect in Kodak equipment. and built-in ease of access.
out its tongue, send for a copy of our
Linked into the controls of a custom­ Of course, all this lead ing-edge
technology is backed by extensive Brochure A-3000, " Performance
er's machine, this portable, state-of­
Plus." W rite t o Eastman Kodak
the-art microcomputer swiftly checks training of our technicians (and , if
Company, Dept. G B- S A- l , 343 S tate
internal fu nctions (s oftware drive, desired , of your people). Backed by a
S treet, Rochester, NY 14650.
electrical and l or mechanical) , allow­ computerized global network of parts
ing the Kodak equipment service stocks and a variety of service and

© Eastman Kod a k Company. 1982

© 1982 SCIENTIFIC AMERICAN, INC

Before you look under the he
At Honda, we believe the car that of painstaking preparation throughout.
goes together better stays together Lift the hood and you'll see the pains
better. So we're very precise when we our engineers have taken to make
assemble Honda automobiles. servicing less troublesome. The engine
Hood , doors, trunk and hatch fit the compartment is well organized .
body with close tolerances all around. Open the door and look inside. .
Body panels and moldings align. There's not an unfinished area or rough
Run your hand along the edges and edge in sight. Carpets fit snugly. No
down the seams. The whole car feels wrinkles or loose threads in the headliner.
smooth to your touch . That's the result The upholstery seams are neat.
© IYHl American ( InnLl;] \ Imor Co" I nc.

© 1982 SCIENTIFIC AMERICAN, INC

od,look at how the hood fits.
Sit behind the wheel and feel the And Honda cars have traditionally
controls. They work the way they were retained a high resale value, among the
designed to work. Try the smooth action best in the automotive industry.
of the front seat adjustment. It's all done To understand why, you only have
right. It meets Honda quality. to look at how the hood fits.
Honda quality is an important "Source: R. L. Iblk and Co. 1981 model year New CorBuyerAllolysis.

reason why Honda owners are so loyal.

:Why they continue to buy more Hondas.
Honda is number one in owner loyalty mm�mm
among all leading import cars� We make it simple.

© 1982 SCIENTIFIC AMERICAN, INC