Note: Descriptions are shown in the official language in which they were submitted.
- 1 - lZ~8~
liOD F0~ ~rilll~NCII~G l~r~ ~GII~G; AND DIAGI~OSTIC USE
This invention relates to ~edical imaging and more
5 particularly to a method for enhancing nuclear magnetic
resonailce imaging.
Although it had been known since the 1920's that
many atomic nuclei have angular momentum arising from their
lO inherent property of rotation, or spin and that each nucleus
of nonzero spin has a magnetic moment or dipole associated
with it, it wasn't until 194~ that the first nuclear magnetic
resonance method was developed as a tool applied to studies
of structural chemistry ~nd it was not until the late 1970's
15 that the method found application in clinical diagnosis.
Nuclear magnetic resonance imaying is based on the
manipulation of an entire population of nuclei by the
e~posure of the nuclei -to an external magnetic field,
altering the characteristics of said ield and n~easuring the
20 response of the nuclei thereto.
The magnetic behavior of the entire population of
nuclei can be defined by the macroscopic or bulk
magnetization vector, which represents the net effect of all
of the mag~etic moments o all of the nuclei of a given
25 species in the sample being analyzed. In the absence of an
e~ternal magnetic field, the maanetic dipoles will be
pointing in random directions hence the bulk maynetization
~ill be zero. However, when the population of nuclei is
e~;posed to an e~ternal magnetic field the dipoles become
30 oriented, pointing in a direction parallel to the applied
- field.
~244~
1 Once the external rlagnetic ficld has been applied
and the bulk magnetic moment of the population has been
e~tablished, the next phase of the analysis involves
perturbing the oriented nuclei. The perturbation is
5 accomplished by the application of a second magnetic field at
right angles to the first and alternating in polarity. The
analogy of a spinning top or gyroscope has been applied to
illustrate the effect of this second magnetic field. The
spinning nuclei are represented as spinning tops or
10 syroscopes and because of the influence of the initial
r.)agnetic field all of the axes of the gyroscopes are pointed
vertically. If the axis of a spinning gyroscope is tipped
away from the vertical, the gyroscope will continue to rotate
about the former vertical axis in a motion describing the
15 ~all of an inverted cone. This motion is ~nown as
precession. Similarly, the bulk magnetization vector can be
caused to precess about its original axis under the "tipping"
influence of a second magnetic field. It should be
understood that in order to tip the macroscopic spin vector
20 a~ay from its original axis, the applied electro~agnetic
radiation must match (i.e. be in resonance with) the natural
precessional fre~uency of the nuclei of the sample, hence the
term nuc]ear magnetic resonal-ce (N~tR).
A simple mathematical relation links the resonance
25 frequency, often called the Larmor frequency, to the value of
the externally applied static magnetic field. The frequency
is equal to the strength of the field multiplied by the
"gyromagnetic ratio," which is unique for each nuclear
s~ecies of nonzero spin. For hydrogen nuclei (protons) in a
30 magnetic field of one testa tlO,OOO gauss) the resonance
requency is 42.57 megahertz (~5Hz), or 42.57 million cycles
per second. For nuclei of the isotope phosphorus 31(31P)
--3--
1 in the same field the resonance frequency is 17.24 Ç~Hz; for
nuclei of sodium 23( ~'a) it is 11.26 ~IKz. These
frequencies are far below those of x-rays or even visible
light and as such are powerless to disrupt the molecules of
5 living systems, hcnce providing one of the major desirable
features of this type of analysis when applied to diagnostic
scanning.
During the perturbation caused by the application
of the second field many of the nuclei which are in a low
10 energy state (i.e. their magnetic moments are aligned with
the first (static) magnetic field) undergo a transition to a
higher energy state (i.e. their magnetic moments tend to be
aligned with the second (rotating or alternating) field. The
displacement angle between the nuclear magnetization ~-ector
15 and the direction of the static magnetic field continues to
increase as long as the competing rotating field is applied
and the rate of increase depends on the power of the field.
A pulse long and strong enough to tip the bulk vector`from
its origina7 position tv one ~hich is parallel to the
20 rotating field is known as a 90 pulse owing to the
perpendicular arrangement of the two magnetic fields.
Precession pattern of nuclei under these conditions resemble
a flattened disc rather than a cone.
Once the external energy source of alternating
25 frequency is removed, the nuclei in the excited (high energy)
state tend to revert to the more stable (low energy) state.
This is accomplished by a remission of the energy at the same
frequency ~Larmor frequency) at which it was absorbed. It is
the detection and analysis of this decay signal which forms
30 the basis or the NMR imaging technology.
~ _4~ 8~
1 The return to equilibrium of the nuclei is
characteriz~d by two principal "rela,:ation timcs", Tl and
T2. The relaxation times Tl (spin - lattice or
longitudinal rela~ation time) and T2 (spin-spin or
5 transverse relaxation time) are parameters ~hich describe ~he
e~ponential return to equilibrium of the nuclear magnetism of
the sample nuclei in directions parallel or perpendicular,
respectively, to the applied (i.e. rotating~ magnetic field.
The rate at which nuclei assume the ground state depends on
10 how readily they can dispose of their e~cess energy. T
represents a time constant describing one route for the
dissipation of said energy, specifically the loss of energy
to the local molecular environment ~i.e. the lattice). T2,
on the other hand, is a rate constant which describes a
15 second route of dissipation, namely the loss of energy to
other protons. This latter disposition of energy has ,he
effect of dephasing many of the excited nuclei ~ithout loss
o~ energy to the surrounding environment.
A variety of methods e~ist for converting the N~R
20 signal resulting from free induction clecay into an image.
Damadian (Philos. Trans. R. soc. Lond. Biol. 289~ 121
(19~01) has taken the approach of displaying the intensity of
the ~MR signal from discrete points in the human anatomy on a
coordinate grid. This ~ethod depends on the shape of the
25 magnetic field produced by the particular magnet
configuration employed to focus on a given point ~7ithin the
body. The magnetic field used has been descxibed as "saddle
shaped", and its strength is said to vary appreciably ~ithin
very small distances along the sloping surface of this
3
" ` 5 ~L2~
.
1 con'iguration. The field center (or "saddle point") is used
as the refer~nce to choose an exciting RF frequency to
achieve the resonance condition. Using this technique, an
image is created by moving the body area to be examined
5 through the saddle point in an ordered fashion so that a
recognizable structure tlill be achieved from the cignal
determinations at each location of interest.
Lauterbur and Lai (I.E.E.E. Trans. Nucl. Sci.
27:1227-31 (1980)) have described a method of imaye
10 reconstruction involving the analysis of many planes of NMR
signals in a manner similar to x-ray compu~ed tomographic
(CT) images. In this technique, known as zeugmatography,
signals from the sample v-olume are contained in each
one-dimensional projection. Imaging may be achieved by
15 superimposing a linear magnetic field gradient on the area of
interest (e.g., human anatomic area or oryan) that has been
placed in a uniform magnetic field. The resonance
fre~uencies of the precessing nuclei will depend on their
position along the direction of the magnetic yradient. If
20 one obtains a series of one-dimensional projections at
different gradient orientations, two- and three-dimensional
images of the structure or organ of interest can be obtained
by this technique.
other techniques may isolate a point, line, or
25 plane ~ithin the human body by use of oscillating magnetic
field gradients, as for example described by Y.inshaw et al.
(Br. J. Radiol. 51:273-2P,0 (197~)).
3o
~ -6~ 8~
l Althou~h a poten'lally useful system, NrlR imaging
is plagued with several problems. Firstly, ~ R is much lecs
sensitive than other forms of spectroscopy and secondly, its
use is restricted to certain atomic nuclei. Three nuclei
5 have been used almost exclusively in biological N~IR imaging
studies, the hydrogcn atom or ?roton (1~I), 31phosphorus
(31p~, and 13carbon (13C). Of the three the proton
gives the strongest sicJnal but is so ubiquitous in living
tissue that special techniques are necessary to resolve
10 individual signals from a multitude of overlapping peaks.
The most abundant isotope of carbon is l2C, which possesses
- no nuclear spin. Only 1~ of natural carbon is 13C ~hich
~ields a much weaker signal than the proton Most M~R work
on intact biological systems has cen~ered on 31p, the
15 naturally occurring isotope of phosphorus, but this nucleus
only gives a signal one~sixth the strength of the proton.
Several attempts have been made to try to overcome
the low sensitivity of NMR. For example a system whereby
many spectra are summed (overlayed) has been employed. For
20 biological work, the procedure is best caxried out with
pulsed N~IR, in which short, powerful bursts of radiation at
rany frequencies are given to the sample. Each resultant
signal contains all tlle information required to yenerate an
entire spectrum by the mathematical process of Fourier
25 transformation but in practice it is usual to add together
many signals before transforming them in order to obtain a
sufficient sisnal/noise ratio.
One furtIler aspect of N~;R spectroscopy must be
mentioned: the time taken for the nuclei per~urbed by the
3o radiofrequency signal to relax back to their unperturbed
state. This obvicu~ly limits the rate at which pulses can
usefully be administered to the sample.
~24~8'~
7--
Investigations by Brady, T.J. et al. (Radiology
143:343-347 (1982)) and Ujeno, Y. (Physiol. Chem. &
Physics 12:271-275 (1980)) have sought to enhance proton
signals by the addition of substances which affect the
Tl and T2 relaxation times of the NMR-sensitive nuclei.
As will be apparent from the discussion to follow, an
object of one aspect of the instant invention is to
enhance NMR-imaging, not by affecting Tl/T2 per se, but
rather to focus and concentrate the magnetic field which
is applied to the sample, so that the sharpness of the
signal is augmented (i.e., less dispersion in the peaks)
whereby the resol~tion or clarity of the mapped signals,
i~e., the image is enhanced.
In accordance with one particular aspect of
the present invention, there is provided, in a method
for nuclear magnetic resonance imaging through the
application of a frequency oscillating field, the
improvement comprising (a) imparting a high frequency
oscillating magnetic field of predetermined frequency to
an area which is to be imaged; (b) introducing
ferromagnetic, paramagnetic or diamagnetic particles to
the area; (c) imparting a high frequency oscillating
magnetic Eield at a specific frequency thereto so as to
enhance the image intensity produced by the nuclear
magnetic resonance-sensitive nuclei within the area; (d)
and comparing the images obtained before and subsequent
to the introduction of the particles to obtain a measure
in the change of the magnetic properties of the
particles.
In accordance with another particular aspect
of the present invention, there is provided, in a method
for nuclear magnetic resonance imaging through the
application of a frequency oscillating field, the
3~,i,
~24~8~Z
-7a-
improvement comprising (a) imparting a high frequency
oscillating magnetic field of predetermined frequency to
an area which is to be imaged; (b) introducing
metabolizable ferromagnetic, paramagnetic or diamagnetic
particles to the area; (c) imparting a high frequency
oscillating magnetic field at a specific frequency
thereto so as to enhance the image intensity produced by
the nuclear magnetic resonance-sensitive nuclei within
the area; (d) and comparing the images obtained before
and subsequent to the introduction of the particles to
obtain a measure in the change of the magnetic
properties of the particles.
In accordance with a still further particular
aspect of the present invention, there is provided, in a
method for nuclear magnetic resonance imaging, the
improvement comprising introducing metabolizable
ferromagnetic, diamagnetic or paramagnetic particles to
an area to be imaged, imaging the area under a high
frequency magnetic field at one Erequency and after the
passage o a su:Eicient period of metabolic time,
reimaging the area under a magnetic field oE a second
frequency thereby detecting metabolic changes w:ithin the
area.
In accordance with still another particular
aspect of the present invention, there is provided, in a
method for nuclear magnetic resonance imaging, the
improvement comprising the introduction of
ferromagnetic, paramagnetic or diamagnetic particles to
an area to be imaged, thereby enhancing the image
intensity produced by the nuclear magnetic resonance-
sensitive nuclei within the area.
`S
8'h
-7b-
ln accordance with yet another particular
aspect of the present invention, there is provided a
nuclear magnetic resonance imaging apparatus including
means for rendering a first image under a first set of
functional apparatus parameters, means for rendering a
second image under a second set of functional apparatus
parameters, and means for comparing the first and second
sets of images; at least one of the means for rendering
a first image and the means for rendering a second image
including means for the sensing of paramagnetic,
ferromagnetic or diamagnetic particles in the viewing
field.
In accordance with yet a still further
particular aspect of the present invention, there is
provided in a nuclear magnetic resonance imaging
apparatus including means for providing correlative
images over the passage oE time, the improvement wherein
the apparatus includes means for the sensing of
paramagnetic, Eerromagnetic or diamagnetic particles in
the viewing Eield, to thereby augment at least one of
the images.
Another particular aspect of the present
invention provides, in an apparatus for nuclear magnetic
resonance imaging through the application of frequency
oscillating field, including means for imparting a high
frequency oscillating magnetic field of predetermined
frequency to an area which is to be imaged; means for
introducing ferramagnetic, paramagnetic or diamagnetic
particles to the area; the means for imparting the
magnetic field further imparting the field at a specific
frequency subsequent to the particles introduction so as
to enhance the image intensity produced by the nuclear
magnetic resonance-sensitive nuclei within the area; the
~ ~g~8'~
improvement comprising means for comparing the images
obtained before and subsequent to the introduction of
the particles to obtain a measure in the change of the
magnetic properties of the particles.
Still another particular aspect of the present
invention provides in an apparatus for nuclear magnetic
resonance imaging through the application of a frequency
oscillating field, including means for imparting a high
frequency oscillating magnetic field of predetermined
frequency to an area which is to be imaged; means for
introducing metabolizable ferromagnetic, paramagnetic or
diamagnetic particles to the area; the means for
imparting the magnetic field further imparting the field
at a specific frequency subsequent to the particle
introduction so as to enhance the image intensity
produced by the nuclear magnetic resonance-sensitive
nuclei within the area; the improvement comprising
means for comparing the images obtained beEore and
subsequent to the introduction of the particles to
~0 obtain a measure in the change of the magnetic
properties of the particles.
An additional particular aspect of the present
invention provides in an apparatus for nuclear magnetic
resonance imaging, the improvement comprising: means
introducing metabolizable ferromagnetic, diamagnetic or
paramagnetic particles to an area to be imaged, means
for imaging the area under a high frequency magnetic
ield at one frequency and after the passage of a
sufficient period of metabolic time, and for reimaging
the area under a magnetic field of a second frequency
thereby detecting metabolic changes within the area.
Still another particular aspect of the present
invention provides in a method for nuclear magnetic
resonance imaging, the improvemen-t comprising the
8'~
-7d-
introduction of metabolizable ferromagnetic,
paramagnetic or diam~gnetic particles to an area to be
imaged, thereby enhancing the image produced by -the
nuclear magnetic resonance-sensitive nuclei within the
area.
In accordance with yet a further particular
aspect of the present invention, there is provided in a
method for nuclear magnetic resonance imaging, the
improvement comprising: introducing metabolizable
ferromagnetic, diamagnetic or paramagnetic particles to
an area to be imaged, imaging said area, and aEter the
passage of a sufficient period of metabolic time,
reimaging the area thereby detecting metabolic changes
within the area.
In still another particl~lar aspect oE the
prèsent invention, there is provided a method for
improving resolution in NMR medical imaging of an area
comprising, prior to the NMR imaging, providing to the
area a population of particles having a magnetic moment,
the population in size and density being suEEicient to
enhance the clarity of the mapped NMR signals.
In greater detail of specific aspects, the
introduction oE ferromagnetic, diamagnetic or
paramagnetic particles act to focus and concentrate the
magnetic field in the area to be imaged, thereby
improving image in-tensity due to NMR-sensitive nuclei
within the sample area. Further, by comparing the
images before and after addition of the particles, the
changes therein can be related to the spatial density
and distribution of the particles themselves.
The increased resolution and sensitivity
resulting from the application of the instant invention
will permit, not only structural evaluations, but
metabolic monitoring as well.
1 The lattcr is particularly true if the
ferromagnetic diamagnetic a paramaynetic particles are
themselves subject to metaholism by the cells of the sample
to be analyzed. The particles then serve as sensitive
5 metabolic "probes" of the extracellular and/or intracellular
environment of the cells ~ithin the area to be imaged.
This invention relates to the area of medical
imaging and more specifically to the enhancement of nuclear
10 m~snetic resonance imaging. Although the subject invention
may be employed with any of many imaging systems currently
available, a zeugmatography system ~lill be used for ease of
discussion.
The conceptual problem which plagued all early
15 attempts at NMR imaging was the manner in which the
relatively uniform NMR signal emanating from the sample would
be encoded with spatial in~ormation. The breakthrough
occur-ed with the appreciation that the signal ~as not
completely uniform, that is to say the NIIR could be distorted
20 according to the sh~pe and size of the sample. The
distortion is due to nonuniformities in the static magnetic
field. This particular feature, long considered to be an
imperfection to be removed by l~5~ spectroscopists, was to be
fostered by scientists concerned with the imaging problem.
25 Since the de~ree of distortion depends on how much of the
sample was located in nonuniform parts of the field and on
tlle magnitude of the distortion, it was necessary for imaging
to be successful to deliberately make the field nonuniform.
The controlled nonuniformity is achieved by superimposing
30 upon the static magnetic rield a linear magnetic field
~ gradient.
~ ~9~ $8~
1 The first images produced by Lauterbur borrowed
image-reconstruction computer algorithms, used in
computerized tomography scanning. If a sample of ~ater is
placed in a homogeneous m2snetic field, the NMR frequency
5 spectruM of the hydrogen nuclei in the water molecules is a
single narrow line. If the magnetic field is perfectly
uniform, the shape of the line is independent of the gecmetry
of the sample. If a 3inear magnetic field gradient is no~
superimposed, resonant nuclei at one side of the sample will
10 feel a wea]cer total magnetic field than those at the other
side. There will thus be a linear distribution of Larmor
~requencies across the sample. Then the free induction decay
signal can be subjected to Fourier transformation, a
mathematical procedure that transforms the data from a curve
15 representing signal strength v. time into one represen.ing
- signal strength v. frequency.
The result is a spectrum that is broadened to a
shape corresponding to the one-dimensional projecting ot- the
strength of the N~IR signal onto the frequency axis. By
20 rotating the magnetic field gradient electronically one can
s~cure a projection from a slightly diffelent angle.
Computer analysis of many such projections reconstructs the
sample's geometry. In the tt/o-d;imensional application of the
technique the direction of the gradient is l~otated within a
25 single plane. In the three-dimensional extension of the
method the gradient is rotated in three-dimensional space
through at least half a sphere.
This method of imaging, as well as the others
mentioned previously, is not without some r.egative aspects.
30 Chiefly, among them is a loss of resolution. Spatial
resolution of an NMR image is dictated by the uniformity of
the s~atic field and by the strength of the field gradients.
- 1 o- ~ 8'~
. ~ .
1 Thus the modification of the uniformity of the static field
~hich permits spatial analysis of structures, limits the
resolution of those very structures. It is the object of the
instant invention to increase the resolution of NMR images by
5 the use of accessory materials to focus and concentrate the
magnetic fields applied to the sample to be imaged.
Accessory materials particular useful in the liyht
of the subject invention are those described by Gordon in
U.S. Patent Nos. 4,303,636 and 4,136,683. Although the
10 particles so described do not contain ~I~R-sensitive nuclei
(i.e. an odd number of protons or neutrons) they do possess
unpaired electrons and hence display a magnetic moment. The
particles ~ill thus influence the magnetic fields of an l~iR
system and therefore, the images resulting from the signals
15 generated by nuclei which are NMR-sensitive tiill be enhanced~
(The obverse is also true, whereby the intensification of
e.Ytant NIIR sensitive nuclei is used as an indicator of the
spatial density and distribution of the particles. This
application is particular uceful when the enhancing particles
20 are to be used ultimately in ~ treatment reSimen as described
by Gordon in U.S~ Patent No. 4,106,488.) ~ore specifically,
these fine particles; responsive to and interactive ~ith the
imposed magnetic field (provide more local anomalies) in the
field and enhance the mapped signal image in much the manner
25 of the enhancement of a television image by increasing tlle
number of "lines" transmitted and displayed. Less dispersion
is seen in individual peaks, i.e., they are sharper whereby
the image is better resolved, offering enllanced cl~rity. The
particles serve a "shadowing" unction, intensifying and
30 contrasting an image yenerated by the NMR sensitive nuclei.
- More specifically the particles affect p~rticularly spin-spin
interactions related to the dephasing of nuclei and the
4~
. ~ . .,;
1 transfer of energy between adjacent nuclei, hence T2 values
are influenced by the presence of the particles. That is,
the presence of a substance having a certain magnetie
susceptibility in a high frequency oscillating field causes a
5 change in frequency as a consequence of a "heterodyning"
phenomenon relative to a fi~;ed frequency signal. ~ach
magnetieally susceptible nucleus when dephased acts as a high
frequency oscillator; and the presence of the ferromagnètic,
diamagnetic or paramagnetic particles thus dampens or
10 reinforces the phased precession of the magnetically
susceptible muclei, affeeting the observed frequencies
directly and therefore sharpening ~he resultant NMR peaks
reflected in individual plots of signal vs fre~uency, or
mapped sample regions collecting sueh peaks. The result is a
15 clearer image, of enhanced resolution, by reason of the
controlled perturbation of the field in a requency related
manner, in turn governing the width of the plotted NMR peaks.
In con-tradistinction to the above effect, the use of
paramagnetie salts or radio protective substances as
20 diselosed by Brady, et al. or Ujeno su~ merely influences
diffusional Brownian motion, provid;.ng an "ordering" to the
system (i.e., lattice) reflected primarily in changes in
spin-lattiee relaxation times, or Tl.
As aforesaid, the particles employed are those
25 generically disclosed in Gordon U.S. Patent Nos. 4,303,636
and 4,136,683. These fine particles, unlike macro-
particulate materials intended merely to modi~y Tl T2, by
reason of their size (and shape), provide a multiplicity of
anomalies to the magnetic field in a localized area. Where
30 the particles are selectively absorbed or collected through
bioprocesses, the particle spatial distribution or density
itself further enhances resolution of the i~ages in the
3~
-12- ~4~8~
1 localized region of interest. Then, the pattern of
distributioll itself evidences the underlying bioprocess as
for e~ample malignancy requiring treatment such as that of
Gordon U.S. Patent No. 4,1~6,488.
The particles may be supplied to the sy tem, e.g.,
tissue, ~rgan or organism in a selective manner to provide
intracellular absorption or more generally, are selected to
have a fine particle size sufficient to enhance the NMR
imas~e. Generally; the particles lie in the micron range, and
10 preferably are of no more -than 1 micron in dimension. Shape
selection may be of importance in a given system, and will be
chosen in relation to use and performance.
According to one form of the invention
metabolically susceptible ferromagnetic, diamagnetic, or
15 paramagnetic particles may be employed. Particularly useful
materials in this regard include iron de,ctrans,
metal-containing hematoporphyrins, such as rare-earth
metal-containing porphyrins and the like.
Although attempts to measure cellular metabolism by
20 means of NI~R have been made (P~oberts and Jardetzky, ~iochem.
Biophys. ~cta. 639:53-76 (1981)), they have been hampered by
low sensitivity thus limiting ln vivo observations to largely
low molecular weight. metabolites that are present in
relatively high concentration.
The application of the instant application removes
such limitations. gy providing an image-enhancing
environment any or all of the ~MR-sensitive nuclei within ~he
sample area may be eY.amined. Furthermore, since it is the
image-enhancing environment that is the target of cellular
3 metabolism, changes in image intensity and or sensitivity
- will result even ir the NMR sensitive nuclei ~hich gererate
the image are met~bolically inert.
-13--
When the sample area to be monitored is "perfused"
with a known metabolically reactive imaye-enhancing
particle, a general picture of the metabolic state of
the sample area will emerge. Alternatively, a specific
location with the sample area may be examined by
employing metabolically susceptible image enhancing
particles which will specifically localize in the area
of interest. This specific targeting may be achieved by
judicious selection of the metabolically susceptible
particles. For example, selection based upon particle
size, charge and composition can be used to ensure
intracellular localization or, iE desired, cellular
exclusion of the particle~ Specific cell types or
cellular locations may be monitored by specifically
targeting the particles by means of antigens,
antibodies, enzymes or specific prosthetic groups. In
the latter case, porphyrins containing ferromagnetic,
diamagnetic or paramagnetic particles are employed, for
example, to ensure localization within specific
intracellular compartments such as mitoch~ndria or
chloroplasts.
If intracellular localization is desired, the
particles may be constructed and delivered to the same
area as described by Gordon in U.5. Patent Nos.
4,303,636; 4,136,683, or 4,106,488. In accordance with
preferred embodiments, a metabolizable form of particle
is employed. Particularly useful material for such a
formulation is an iron dextran as described by Cox et
al. (J. Pharmacy and Pharacol. 24(7):513-17 (1971)).
The image-enhancing particles thus become sensitive
probes of the metabolic environment and are therefore
useful for the diagnosis of various metabolic diseases
1~4~ 3Z
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1 as well as malignancies. All that is necessary for such
a determination to be made ~s to image a sample area
con-taining the metabolically susceptible image enhancing
particlesr wait for a sufficient period of metabolic
time, e.g. that amount of time required for a
significant, measurable change to occur in the magnekic
properties of -the susceptible particles due to the
action of cellular metabolism, then reimage the area of
interest. A comparison of the images resolvable at the
beginning and the end of said time span is then
correlated with various metabolic disease or malignant
states.
An apparatus which may be inventively employed for
the implemen-tation of the inventive method for nuclear
ma~netic resonance imaging, is fully described in
Raymond V. Damadian U.S. Patent No. 4,411,270, issued
October 25, 1983.
