U.S. patent number RE32,619 [Application Number 06/661,718] was granted by the patent office on 1988-03-08 for apparatus and method for nuclear magnetic resonance scanning and mapping.
Invention is credited to Raymond V. Damadian.
United States Patent |
RE32,619 |
Damadian |
March 8, 1988 |
**Please see images for:
( Certificate of Correction ) ** |
Apparatus and method for nuclear magnetic resonance scanning and
mapping
Abstract
An improved apparatus and method for analyzing the chemical and
structural composition of a specimen including whole-body specimens
which may include, for example, living mammals, utilizing nuclear
magnetic resonance (NMR) techniques. A magnetic field space
necessary to obtain an NMR signal characteristic of the chemical
structure of the specimen is focused to provide a resonance domain
of selectable size, which may then be moved in a pattern with
respect to the specimen to scan the specimen.
Inventors: |
Damadian; Raymond V. (Woodbury,
NY) |
Family
ID: |
27098371 |
Appl.
No.: |
06/661,718 |
Filed: |
October 17, 1984 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
Reissue of: |
961858 |
Nov 20, 1978 |
04354499 |
Oct 19, 1982 |
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Current U.S.
Class: |
600/410; 324/309;
600/415 |
Current CPC
Class: |
A61B
5/055 (20130101) |
Current International
Class: |
A61B
5/055 (20060101); A61B 005/05 () |
Field of
Search: |
;128/653
;324/309,307 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Other References
Physiological Chem. & Physics, vol. 9, No. 1, 1977, pp. 97-108.
.
Hospital Practice, Jul. 1977, pp. 63-70. .
Lauterbur, P. C., Paper Pres. at 5th Intern. Symp. on Mag.
Resonance, Bombay, India, Jan. 1974, pp. 1-10. .
Kumar, A. et al., Journ. of Mag. Resonance, vol. 18, No. 1, Apr.
1975, pp. 69-83. .
Damadian, R. et al., Physiol. Chem. & Physics, No. 8, 1976, pp.
61-65. .
Grannell, P. K. et al., Phys. Med. Biol. 1975, vol. 20, No. 3, pp.
477-482..
|
Primary Examiner: Howell; Kyle L.
Assistant Examiner: Smith; Ruth S.
Attorney, Agent or Firm: Conover; Richard C.
Claims
I claim:
1. A method of detecting selected nuclei within a specimen
utilizing nuclear magnetic resonance phenomenon comprising:
(a) providing a .[.nonuniform.]. primary .[.static.]. magnetic
field .[.space.]. .Iadd.oriented in a direction H.sub.o
.Iaddend.;
(b) focusing the primary .[.static.]. magnetic field .[.space by a
time-independent shaping of the primary static magnetic field
space.]. to provide a .Iadd.resultant magnetic field oriented in
the Ho direction and having .Iaddend.a three dimensional resonance
domain of selectable size .[.wherein.]. .Iadd.within which
.Iaddend.the field strength .Iadd.in the direction Ho .Iaddend.is
substantially uniform .Iadd.and wherein there are points in the
resultant magnetic field not in the resonance domain but having the
same field strength in the Ho direction, all said points being in
regions of non-uniform field intensity having sufficiently large
gradients so as not to generate substantial resonance signals;
(c) maintaining the configuration of the resultant field within the
resonance domain during generation of a nuclear magnetic resonance
signal; .Iaddend.
.[.(c).]. .Iadd.(d) .Iaddend.positioning the specimen such that the
resonance domain impinges on the specimen;
.[.(d).]. .Iadd.(e) .Iaddend.directing oscillating magnetic
radiation to the resonance domain such that the magnetic field
orientation of the oscillating magnetic radiation is orthogonal to
the magnetic field orientation of the primary .[.static.]. magnetic
field to cause a nuclear magnetic resonance signal to be generated
by selected nuclei within the resonance domain;
.[.(e).]. (.Iadd.f) .Iaddend.receiving the nuclear magnetic
resonance signal generated; and
.[.(f).]. .Iadd.(g) .Iaddend.processing the nuclear magnetic
resonance signal to determine a nuclear magnetic resonance value
directly which nuclear magnetic resonance valve represents the
selected nuclei extant in the resonance domain .[.impringing.].
.Iadd.impinging .Iaddend.on the specimen.
2. A method of detecting selected nuclei within a specimen
utilizing nuclear magnetic resonance phenomenon comprising:
(a) providing a .[.nonuniform.]. primary .[.static.]. magnetic
field .Iadd.oriented in a direction Ho and .Iaddend.having a known
field configuration with a region of uniformity where the field
strength is substantially uniform;
(b) providing a .[.time-independent.]. focusing .[.static.].
magnetic field having a selectable field configuration with a
region of uniformity where the field strength is substantially
uniform;
(c) superimposing the .[.time-independent.]. focusing .[.static.].
magnetic field on the primary .[.static.]. magnetic field such that
the respective regions of uniformity coincide to produce a
resulting .[.static.]. magnetic field having a three-dimensional
resonance domain located within a region where the regions of
uniformity coincide, the field strength of the resulting
.[.static.]. magnetic field within the resonance domain being
substantially uniform .Iadd.and wherein all points in the resulting
magnetic field not in the resonance domain but having the same
field strength are in regions of non-uniform field intensity having
sufficiently large gradients so as not to generate a nuclear
resonance signal; .Iaddend.
(d) maintaining the configuration of the resulting magnetic field
within the resonance domain during generation of a nuclear
resonance signal;
.[.(d) selecting.]. .Iadd.(e) adjusting .Iaddend.the field
configuration of the .[.time-independent.]. focusing .[.static.].
magnetic field to .[.adjust.]. .Iadd.select .Iaddend.the size of
the resonance domain;
.[.(e).]. .Iadd.(f) .Iaddend.positioning the specimen such that the
resonance domain impinges on the specimen;
.[.(f).]. .Iadd.(g) .Iaddend.directing oscillating magnetic
radiation to the resonance domain such that the magnetic field
orientation of the oscillating magnetic radiation is orthogonal to
the magnetic field orientation of the resulting .[.static.].
magnetic field to cause a nuclear magnetic resonance signal to be
generated;
.[.(g).]. .Iadd.(h) .Iaddend.receiving the nuclear magnetic
resonance signal generated; and
.[.(h).]. .Iadd.(i) .Iaddend.processing the signal to determine a
nuclear magnetic resonance value directly which nuclear magnetic
resonance valve represents the selected nuclei extant in the
resonance domain within the specimen.
3. The method according to claim 2 wherein the field configuration
of the primary static magnetic field has a saddle shaped gradient
with the region of uniformity at the saddle point and the focusing
static magnetic field has an adjustable saddle shaped gradient with
the region of uniformity at the saddle point and wherein the size
of the resonance domain is adjusted by changing the gradient of the
focusing static magnetic field as it approaches its saddle
point.
4. The method according to claim 2 wherein the oscillating magnetic
radiation is directed to the resonance domain on a periodic basis
and further including the step of repositioning the specimen after
a nuclear magnetic resonance signal has been received such that a
different portion of the specimen coincides with the resonance
domain whereby scanning of the specimen may be accomplished.
5. The method according to claim 4 wherein the specimen is moved in
a planar grid pattern across a cross section of the specimen such
that a grid of nuclear magnetic resonance values is obtained for
the cross section of the specimen.
6. The method according to claim 5 further including the step of
displaying the grid of nuclear resonance values to provide a visual
image of the grid.
7. The method according to claim 2 wherein a doughnut shaped
superconducting magnet is utilized for providing the primary static
magnetic field space and wherein the specimen is positioned within
the interior space of the doughnut shaped superconducting
magnet.
8. The method according to claim 7 wherein field focusing coils are
used to provide the focusing static magnetic field.
9. The method according to claim 2 wherein the specimen includes a
live mammal and the nuclear magnetic values may include intensities
of nuclear magnetic resonance signals received, spin-spin
relaxation time, spin-lattice relaxation times, spin-mapping
values, and amplitude versus frequency spectra.
10. The method according to claim 2 wherein the selected nuclei may
be selected from P.sup.31, K.sup.39, Na.sup.23, H.sup.1, C.sup.13,
N.sup.15, N.sup.14 or O.sup.17.
11. Nuclear magnetic induction apparatus for detecting selected
nuclei within a specimen comprising:
(a) means for providing a .[.nonuniform.]. primary .[.static.].
magnetic field .[.space.]. .Iadd.oriented in a direction Ho;
.Iaddend.
(b) means for focusing the primary .[.static.]. magnetic field
.[.space by a time-independent shaping of the primary magnetic
field space.]. to provide a .Iadd.resultant magnetic field oriented
in the Ho direction and having a .Iaddend.three dimensional
resonance domain of selectable size wherein the field strength
.Iadd.in the direction Ho .Iaddend.is substantially uniform
.Iadd.and wherein there are points in the resultant magnetic field
is not in the resonance domain but having the same field strength
in the Ho direction, all said points being in regions of
non-uniform field intensity having sufficiently large gradients so
as not to generate substantial resonance signals.Iaddend.;
i (.Iadd.c) means for maintaining the configuration of the
resultant field within the resonance domain during generation of a
nuclear magnetic resonance signal.Iaddend.;
.[.(c).]. .Iadd.(d) .Iaddend.means for positioning the specimen
such that the resonance domain impinges on the specimen;
.[.(d).]. .Iadd.(e) .Iaddend.means for directing oscillating
magnetic radiation to the resonance domain such that the magnetic
field orientation of the oscillating magnetic radiation is
orthogonal to the magnetic field orientation of the primary
.[.static.]. magnetic field to cause a nuclear magnetic
.Iadd.resonance .Iaddend.signal to be generated by selected nuclei
within the resonance domain;
.[.(e).]. .Iadd.(f) .Iaddend.means for receiving the nuclear
magnetic resonance signal generated; and
.[.(f).]. .Iadd.(g) .Iaddend.means for processing the nuclear
magnetic resonance signal to determine a nuclear magnetic resonance
value directly which nuclear magnetic resonance value represents
the selected nuclei extant in the resonance domain impinging on the
specimen.
12. Nuclear magnetic induction apparatus for detecting the selected
nuclei within a specimen comprising:
(a) means for providing a .[.nonuniform.]. primary .[.static.].
magnetic field .Iadd.oriented in a direction Ho and .Iaddend.having
a known field configuration with a region of uniformity where the
field strength is substantially uniform;
(b) means for providing a .[.time-independent.]. focusing
.[.static.]. magnetic field .Iadd.oriented in the Ho direction
.Iaddend.having a selectable field configuration with a region of
uniformity where the field strength is substantially uniform;
(c) .Iadd.means for .Iaddend.superimposing the
.[.time-independent.]. focusing .[.static.]. magnetic field upon
the primary .[.static.]. magnetic field such that the respective
regions of uniformity coincide to produce a resulting .[.static.].
magnetic field having a three dimensional resonance domain located
within a region where the regions of uniformity coincide, the field
strength of the resulting .[.static.]. magnetic field within the
resonance domain being substantially uniform .Iadd.and wherein all
points in the resulting magnetic field not in the resonance domain
but having the same field strength are in regions of non-uniform
field intensity having sufficiently large gradients so as not to
generate resonance signals.Iaddend.;
(d) means for maintaining the configuration of the resultant field
within the resonance domain during generation of a nuclear magnetic
resonance signal;
.[.(d).]. .Iadd.(e) .Iaddend.means for .[.selecting.].
.Iadd.adjusting .Iaddend.the field configuration of the
.[.time-independent.]. focusing .Iadd.static .Iaddend.magnetic
field to .[.adjust.]. .Iadd.select .Iaddend.the size of the
resonance domain;
.[.(e).]. .Iadd.(f) .Iaddend.means for positioning the specimen
such that the resonance domain impinges on the specimen;
.[.(f).]. .Iadd.(g) .Iaddend.means for directing oscillating
magnetic radiation to the resonance domain such that the magnetic
field orientation of the oscillating magnetic radiation is
orthogonal to the magnetic field orientation of the resulting
magnetic field to cause a nuclear magnetic resonance signal to be
generated;
.[.(g).]. .Iadd.(h) means for .Iaddend.receiving the nuclear
magnetic signal generated; and
.[.(h).]. .Iadd.(i) means for .Iaddend.processing the signal to
determine a nuclear magnetic resonance value directly which nuclear
magnetic resonance value represents the selected nuclei extant in
the resonance domain within the specimen.
13. The apparatus according to claim 12 wherein the means for
providing oscillating magnetic radiation is actuated on a periodic
basis and further includes means for repositioning the specimen
with respect to the resonance domain after a nuclear magnetic
resonance signal has been received such that a different portion of
the specimen coincides with the resonance domain whereby scanning
of the specimen may be accomplished.
14. The apparatus according to claim 12 wherein the means for
providing a primary static magnetic field comprises a doughnut
shaped superconducting magnet.
15. The apparatus according to claim 12 wherein the means for
providing a focusing static magnetic field comprises field focusing
coils.
Description
BACKGROUND OF INVENTION
This invention relates to an improved apparatus and method of
analyzing the chemical structure of a specimen utilizing nuclear
magnetic resonance ("NMR") techniques. A resonance domain having a
selectable size is moved in a discrete cross sectional grid pattern
with respect to the specimen to scan the specimen. NMR signals are
generated at discrete grid locations during scanning which signals
are detected and processed to form a map showing the location and
an indication of the quantitative amount of selected nuclei present
at such location. By suitable rearrangement of the apparatus,
sagittal and frontal sectional maps may also be produced.
This invention is an improvement of the apparatus and method
described in U.S. Pat. No. 3,789,832 to Raymond V. Damadian (the
'832 patent). As described in the '832 patent, it was discovered
that cancerous cells had chemical structures different from normal
cells. A method and apparatus were described in the '832 patent of
measuring certain NMR signals produced from a specimen and
comparing these signals with the NMR signals obtained from normal
tissue to obtain an indication of the presence, location and degree
of malignancy of cancerous tissue within the specimen.
The use of NMR techniques to analyze materials including living
tissue has been an active field since the issuance of the '832
patent. For example, see "Medical Imaging by NMR" by P. Mansfield
and A. A. Maudsley, British Journal of Radiology, Vol. 50, pages
188-194 (1977); "Image Formation by Nuclear Magnetic Resonance: The
Sensitive-Point Method" by Waldo S. Hinshaw, Journal of Applied
Physics, Vol. 47, No. 8, August, 1976; "Magnetic Resonance
Zeugmatography" by Paul C. Lauterbur, Pure and Applied Chemistry,
Vol. 40, No. 1-2 (1974); U.S. Pat. No. 4,015,196 to Moore et al.;
and U.S. Pat. No. 3,932,805 to Abe et al.
These references include discussion of various methods of analyzing
a specimen utilizing NMR techniques. All of these methods, however,
have a major disadvantage in that the magnetic field for generating
NMR signals cannot be focused to adjust the size of the resonance
domain depending on the particular user requirements which might
occur, for example, when a macroscopic scan of a specimen is
desired instead of a microscopic scan.
The inventor here has published several articles on the general
subject of utilizing field focusing NMR techniques. See "Tumor
Imaging In A Live Animal By Field Focusing NMR (FONAR)",
Physiological Chemistry and Physics, Vol. 8, pages 61-65, (1976);
"Field Focusing Nuclear Magnetic Resonance (FONAR): Visualization
of a Tumor in a Live Animal", Science, Vol. 194, pages 1430-1432
(Dec. 27, 1976); "Nuclear Magnetic Resonance: A Noninvasive
Approach to Cancer", Hospital Practice, pages 63-70 (July, 1977)
and "NMR in Cancer: XVI. Fonar Image of the Live Human Body" by R.
Damadian et al., Physiological Chemistry and Physics, Vol. 9, No. 1
(1977). There has also appeared an article "Damadian's Super Magnet
and How He Hopes To Use It To Detect Cancer" by Susan Renner-Smith
in Popular Science, pages 76-79, 120 (December, 1977).
SUMMARY OF THE INVENTION
In its broad aspects, the present invention overcomes the
disadvantages of the prior art by providing a method and apparatus
for producing a resonance domain of selectable size, which may be
utilized in whole body scanning of a live specimen such as a human.
When oscillating magnetic radiation is directed to the resonance
domain NMR signals are generated characteristic of the structure of
selected nuclei within the resonance domain. These NMR signals are
detected, processed and displayed to provide a user with
information for analyzing the chemical structure of the specimen
within the resonance domain. Apparatus is provided to move the
resonance domain in a cross sectional grid pattern with respect to
the specimen to obtain an indication of the composition of a cross
section of the specimen. Thus an improved method and apparatus are
provided for noninvasively analyzing the chemical structure of a
cross section of a specimen including, for example, a live mammal
such as a human.
The present invention is particularly useful in cancer detection,
though its use is not limited to cancer. The invention expected to
be used effectively whenever diseased tissue is chemically
different from normal tissue.
BRIEF DESCRIPTION OF THE DRAWINGS
In order that the invention may be clearly understood and readily
carried into effect, several preferred embodiments will now be
described, by way of example only, with reference to the
accompanying drawings wherein:
FIG. 1 is a schematic diagram of one embodiment for analyzing the
chemical structure of a specimen, which as shown here may include a
human;
FIG. 2 is a schematic diagram of field focusing coils used in the
embodiment shown in FIG. 1;
FIG. 3 is a schematic diagram of the field focusing coils shown in
FIG. 2 mounted on a cylindrical form;
FIG. 4 is a schematic cross section of a human chest;
FIG. 5 is a schematic diagram showing the location of the cross
section shown in FIG. 4;
FIG. 6 is a NMR map obtained according to the principles of this
invention of a cross section of a chest corresponding to the cross
section shown in FIG. 4;
FIG. 7 is a NMR map obtained according to the principles of this
invention of a cross section of a chest having a diseased left
lung;
FIG. 8 is a schematic diagram of second perspective for analyzing
the composition of a specimen which again may include a human as
shown here;
FIG. 8A is a sectional schematic diagram of transmitter coils
utilized in the embodiment shown in FIG. 8 along the section line
A--A in FIG. 8.
FIG. 9 is a schematic diagram useful in describing the principle of
operation of the perspective shown in FIG. 8.
FIG. 10 is a schematic perspective diagram of a third embodiment
for analyzing the composition of a specimen utilizing permanent
magnets;
FIG. 11 is a schematic front view of the embodiment shown in FIG.
10;
FIG. 12 is a schematic side view of the embodiment shown in FIG. 10
with one permanent magnet removed;
FIG. 13 is a schematic diagram of the embodiment shown in FIG. 10
showing the location of the various coils utilized in this
embodiment;
FIG. 14A is a NMR spectrum obtained from normal muscle tissue,
and
FIG. 14B is a NMR spectrum obtained from cancerous muscle
tissue.
DESCRIPTION OF PREFERRED EMBODIMENT
Apparatus for analyzing the chemical structure of a cross section
of a live specimen is shown in FIG. 1. A doughnut shaped magnet 30
preferably superconducting, but which may be a copper wound ambient
temperature electromagnet, having a frame 31 provides a primary
static magnetic field for aligning the nuclei in specimen 32, in
the direction H.sub.o as shown in FIG. 1. The specimen 32 may be a
human as shown in FIG. 1. Two pairs of field focusing coils 34,
34a, and 36, 36a provide a focusing static magnetic field used to
adjust the primary static magnetic field configuration within the
interior of the doughnut shaped magnet 30.
Field focusing coils 34, 34a, and 36, 36a are formed as shown in
FIGS. 2 and 3. The coils are wound on a planar surface as shown
schematically in FIG. 2. The dimensions of the field focusing coils
34, 34a, and 36, 36a are shown in FIG. 2 where "a" is the interior
radius of the doughnut shaped magnet 30. The field focusing coils
34, 34a, and 36, 36a are then placed on a cylindrical form 38 which
may for example be constituted of a transparent material as shown
in FIG. 3. The form 38 is then placed in the interior of the
doughnut shaped magnet 30 as shown in FIG. 1 and secured to the
frame 31 by brackets 39.
The primary static magnetic field configuration within the doughnut
shaped magnet 30 alone is well known in the art. The amplitude of
the static magnetic field in the H.sub.o direction is saddle shaped
with a saddle point at the origin of magnet 30. The field focusing
coils 34, 34a, and 36, 36a were chosen so that when D.C. current is
applied to the four field focusing coils 34, 34a, and 36, 36a in
the direction as shown in FIG. 2, by D.C. sources 40, 40a, a saddle
shaped static magnetic field in the direction H.sub.o is
superimposed upon the saddle shaped static magnetic field provided
by magnet 30 with the saddle points coinciding at the origin of
magnet 30 to form a resulting static magnetic field space in the
interior of magnet 30. The current level of the two D.C. sources,
40 and 40a, may be varied to adjust the sharpness of the saddle
point provided by the field focusing coils 34, 34a, and 36,
36a.
The region surrounding the coincident saddle points at the origin
of magnet 30 is a region of relatively uniform field strength in
the direction H.sub.o. Since the sharpness of the peak at the
saddle point provided by field focusing coils 34, 34a, and 36, 36a
is adjustable, the region of substantially uniform field strength
is also adjustable. Thus when this peak is broadened, the region of
relatively uniform field strength is made larger and when the peak
is made sharper the region is made smaller. This region is the
resonance domain 44 in which NMR conditions will be satisfied for
selected nuclei as will be described later. This region of
substantially uniform field strength, the resonance domain 44, is
defined as that volume where the magnetic field gradient is less
than 3.9 gauss/cm.
In equipment which has been built for analyzing mammals, the
strength of the static magnetic field in the direction H.sub.o at
the origin of the magnet 30 is approximately 500 gauss where the
operating frequency is 10 MHz for protons and the D.C. sources 40
and 40a are each providing approximately 20 amperes. The size of
the resonance domain 44 is dependent upon the current supplied by
D.C. sources 40 and 40a. With each of the D.C. sources 40 and 40a
providing 20 amperes of current, the resonance domain 44 has a
volume of approximately 1 mm.sup.3. In this example, the resonance
domain is relatively small. By decreasing the current from D.C.
sources 40 and 40a to 10 amperes, the size of the measuring volume
is increased to approximately 6 mm.sup.3.
Nuclear magnetic resonance conditions must exist before NMR signals
are generated. The nuclear magnetic resonance conditions are
described according to the well known equation:
where:
.omega..sub.o =resonance angular frequency of the selected
nuclei
.gamma.=gyromagnetic ratio for the selected nuclei and is a
constant for the selected nuclei
.vertline.H.sub.o .vertline.=magnitude of static magnetic field in
direction H.sub.o
The static magnetic field in the H.sub.o direction is provided by
the superconducting magnet 30 and field focusing coils 34, 34a, and
36, 36a. The resonance frequency .omega..sub.o is supplied by a
conventional adjustable radio frequency oscillator such as included
in the nuclear induction apparatus or NMR spectrometer 42 which was
described in the '832 patent. The oscillator provides a radio
frequency signal at its output terminal having a frequency which
can be adjusted manually by a frequency selector. The radio
frequency signal is directed to radio frequency coil 46 as shown in
FIG. 1 via transmitter and receiver line 43 and conventional
capacitor divider network 41. The capacitor divider network 41
includes two capacitors 41a and 41b for impedence matching the coil
46 to line 43 as is well known in the art. The coil 46 is
positioned to surround the resonance domain 44 and is of a size to
surround a cross section of specimen 32. In FIG. 1, a human is
shown in a sitting position with the coil 46 positioned to surround
the chest. The coil 46 is placed on a form (not shown) and mounted
to a frame 45, shown schematically in FIG. 1, which is anchored to
a translator beam 48 that will be described later.
For NMR conditions to exist the coil 46 must be positioned so that
the direction of the oscillating magnetic field provided by coil 46
is orthogonal to H.sub.o. Since the direction of the radio
frequency magnetic field provided by coil 46 is along the
longitudinal axis of the 46, the coil 46 must be positioned such
that the longitudinal axis is along the "Y" axis when the patient
is sitting as shown in FIG. 1. (For purposes of explanation only,
throughout this specification a three dimensional space has been
assigned a conventional "X", "Y" and "Z" dimensional frame of
reference as shown in the drawings.) If the patient is to lie prone
on the translator beam 48, in the "Z" direction, a circular coil 46
could not be used and would need to be replaced with, for example,
a pair of cylindrical Helmholtz radio frequency coils, each located
on opposite sides of the chest and positioned so that the direction
of the radio frequency field would be in the "X" or "Y"
direction.
In practice, the value of .vertline.H.sub.o .vertline. at the
location of the resonance domain 44 is determined by direct
measurement prior to placing a specimen or patient within the
magnet 30. Since two of the variables of equation (1) are now
known--namely, .gamma. for the selected nuclei and
.vertline.H.sub.o .vertline.--a user may obtain a NMR signal for
selected nuclei present in the resonance domain 44 if radio
frequency radiation of the proper .omega..sub.o frequency to
satisfy equation (1) is directed to the resonance domain 44 in a
direction orthogonal to H.sub.o.
The apparatus shown in FIG. 1 is used in a pulse mode of operation
to analyze a specimen. In this embodiment a pulse of radio
frequency energy from the oscillator in the NMR spectrometer 42 is
directed to the resonance domain 44 through the coil 46. The coil
46 is then switched to a receiver mode to detect the NMR signal, if
any, produced. The detected signal is transmitted to the NMR
spectrometer 42 via transmitter and receiver line 43. The NMR
spectrometer 42 includes a computer and memory means for storing
NMR signal parameters such as intensities and relaxation times
together with the spatial coordinates of the translator beam
48.
In the analytical apparatus described in the '832 patent, the
detector and transmitting coils in the '832 patent were separate
coils and were positioned orthogonal to one another. In the
embodiment shown in FIG. 1, the receiver coil is the same physical
coil as the transmitting coil. This is another way of accomplishing
the same result. The reason for this is that when radio frequency
radiation is injected into the resonance domain, the magnetic
moment of the selected nuclei are energized from their equilibrium
states parallel to the direction of H.sub.o to a higher energy
state through nuclear magnetic resonance absorption to a direction
orthogonal to the direction H.sub.o when viewed in the rotating
frame. When the radio frequency radiation is turned off, the
energized nuclei emit a radio frequency signal as they return to
their equilibrium states according to a well known equation
described in the '832 patent. The orientation of the receiver or
detector coil relative to the transmitter coil is immaterial so
long as they are orthogonal to the H.sub.o direction. In fact, the
transmitter coil and the receiver coil may be the same physical
coil as is the case of the above described embodiment shown in FIG.
1. When a single coil is used a pulsed mode of operation is
necessary. It should be realized, however, that a continuous mode
of operation would be possible by separating the transmitter and
receiving coils and orienting them orthogonal to one another and
orthogonal to H.sub.o.
In FIG. 1, H.sub.T designates the direction of the transmission
axis and the H.sub.R designates the direction of the receiving
axis.
Scanning of a cross section of the specimen 32 in the embodiment
shown in FIG. 1 is accomplished by using a translator beam 48 on
which the specimen 32 is placed. Drive box 49 includes motors and
gears for moving the translator beam 48 in a conventional manner in
an "X" direction and "Z" direction as shown in FIG. 1. The drive
box 49 is automatically activated by control unit 50 in a
conventional manner to move the specimen 32 with respect to the
stationary resonance domain 44 in a grid pattern in a "X-Z" plane
through the specimen 32. The spatial coordinates of the translator
beam 48 are transmitted to the NMR spectrometer 42 as previously
discussed via lead 51 connecting the control unit 50 with the NMR
spectrometer 42. Thus in scanning a human specimen 32 as shown in
FIG. 1, the human is moved with respect to the stationary resonance
domain 44 in a grid pattern through a cross section of the human's
chest. Although FIG. 1 shows apparatus for moving the specimen 32
with respect to a stationary resonance domain 44, moving the
resonance domain 44 with respect to a stationary specimen 32 is
also considered to be within the scope of the present
invention.
EXAMPLE 1
An experiment was performed to map a cross section of a live human
chest. The human was placed in the position shown in FIG. 1 with
coils 46 surrounding the chest. In this measurement, hydrogen
nuclei were selected to be detected. The magnet 30 was adjusted to
produce 500 gauss at the origin thereof. The translator beam 48 was
moved in a grid pattern so that the human was moved with respect to
the resonance domain 44 in a cross sectional pattern through the
8th thoracic vertebra as shown in FIG. 5. A pictorial depiction of
this cross section is shown in FIG. 4.
The frequency of the radio frequency oscillator in NMR spectrometer
42 was set to 2.18 MHz and the oscillator adjusted to provide a 10
watt pulse of radio frequency magnetic radiation over 60
microseconds and to repeat the pulse every 800 microseconds. The
control unit 50 was set to move the human patient in a grid pattern
in the "X-Z", plane with movement to a new grid location
accomplished just prior to the transmission of the pulse of radio
frequency radiation. The NMR signals generated were detected by
coil 46 and transmitted via line 43 to the NMR spectrometer 42.
The NMR spectrometer 42 processed the NMR signals utilizing a Data
General computer which was programmed to store values of NMR signal
intensities received corresponding to each location on the grid.
The Data General computer was also programmed so that upon
completion of a cross sectional scan, a map was generated showing
the NMR signal intensities for each location on the grid which map
was then displayed on a video display tube in 16 colors. Each color
corresponded to a different intensity, ranging from white to yellow
to red to blue to black with white corresponding to maximum
intensity. FIG. 6 shows a black and white photograph of the
original 16 color video display. The top of the image is the
anterior boundary of the chest wall. The left area is the left side
of the chest looking downward. The hydrogen atom NMR signal
intensity is coded with black assigned to zero signal amplitude,
white assigned to signals of strongest intensities and intermediate
grey scales assigned to intermediate intensities. Proceeding from
the anterior to the posterior along the midline, the principal
structure is the heart seen encroaching on the left full lung
(black cavity). The left lung is diminished in size relative to the
right lung (black cavity to right of midline), as it should be (see
schematic of the human chest in FIG. 4 at the 8th thoracic level
shown in FIG. 5). More posteriorly and slightly left of midline is
a grey circular structure corresponding to the descending
aorta.
In the body wall, beginning at the sternum (anterior midline) and
proceeding around the ellipse, alternation of high intensity
(white) with intermediate intensity (grey) could correspond to
alternation of intercostal muscles (high intensity) with ribs (low
intensity) as shown in FIG. 4.
EXAMPLE 2
With the apparatus of FIG. 1 set up as with Experiment 1 a map was
created of a cross section through the chest of a human patient
havig a known cancerous left lung. The black and white photograph
of an original 16 color video display showing infiltration of
disease into the left lung is shown in FIG. 6.
The top portion of the image in FIG. 6 is the anterior chest wall
and the left side is the left side of the chest looking downward.
The cancerous left lung is clearly visible.
In a second embodiment a resonance domain 44a of selectable size is
formed by the apparatus as shown in FIG. 8. In this embodiment two
identical doughout shaped magnets 51 and 52, which may again be
super-conducting or copper wound ambient temperature magnets, are
axially aligned and separated by a Helmholtz distance which
distance is the radius of the magnets 51 and 52. It is well known
that with this configuration, the magnetic field strength within
the space between the two magnets 51 and 52 is substantially
uniform. This field is the primary static magnetic field and the
direction of this field H.sub.o is parallel to the "Z" axis of the
magnet pair 51 and 52.
Field focusing coils 54, 54a, and 56, 56a provide the focusing
static magnetic field and are used to adjust the size of measuring
volume 44a as field focusing coils 34, 34a, and 36, 36a did with
the first described embodiment. The field focusing coils 34, 34a,
and 36, 36a respectively are as shown in FIGS. 2 and 3 except that
the current in coils 54, 54a are reversed from the current in coils
34, and 34a respectively. These coils are placed on cylindrical
form 58 which is attached to the frames of magnets 51 and 52 by
brackets 59. It is known that when these coils are positioned in
this manner, the direction of the magnetic field is along the "Z"
axis and the gradient of the magnetic field strength between the
field focusing coils 54, 54a, and 56, 56a along the "Y" axis is
linear. Thus when the cylindrical form 58 is placed as shown in
FIG. 8 coaxially aligned with the axes of the two magnets 51 and 52
the magnetic field produced by field focusing coils 34, 34a, and
36, 36a is in the H.sub.o direction with a linear gradient
orthogonal to the "Z" axis.
The resulting static magnetic field produced by magnets 51 and 52
and field focusing coils 34, 34a, and 36, 36a in the direction
H.sub.o is substantially uniform in the "X-Z" plane and has a
linear gradient in the "Y" direction. This static magnetic field in
the direction H.sub.o is in the static magnetic field necessary to
establish NMR conditions according to equation (1).
Two transmitter radio frequency coils 60 and 62 are mounted to form
58 by brackets 59 and provide the radio frequency signal necessary
for NMR conditions. These coils may be rectangular but are
preferably circular as shown in FIG. 8 and are arranged orthogonal
to one another with the line of intersection in the "Y" direction
and intersecting the axes of the two magnets 51 and 52. The planes
of each radio frequency coil 60 and 62 is tilted 45.degree. with
respect to the "X-Y" plane as shown in FIG. 8A which is a cross
sectional top view of these coils along the section line A--A shown
in FIG. 8. Radio frequency coils 60 and 62 are connected to radio
frequency current sources 64 and 66 through conventional capacitor
divider networks 61 and 63 and transmission lines 65 and 67. The
capacitor divider networks 61 and 63 are provided to match the
impedance of the coils 60 and 62 with the transmission lines 65 and
64, respectively. The alternating current in the two coils 60 and
62 are phased so that the rsultant of the magnetic field vectors
for the coils is orthogonal to the main magnet axis (i.e.
orthogonal to "Z") and lies in the illustration shown in FIG. 8
along the "X" axis. With this arrangement the maximum amplitude of
the radio frequency magnetic field is along the "Y" axis with an
exponential amplitude drop off from the "Y" axis. The coils 60 and
62 thus focus the oscillating magnetic energy in a pencil beam
along the "Y" axis. This pencil beam will be the source of the
.omega..sub.o in equation (1) above. A separate cylindrical
Helmholtz coil 68 operates as the receiver coil and has its
magnetic axis perpendicular to "X" and "Z", that is along the "Y"
axis in the illustration shown in FIG. 8. The receiver coil 68 is
supported by supports (not shown) on a translator beam 48 and will
move with the patient during scanning.
Reference is now made to the schematic diagram shown in FIG. 9 to
illustrate the method of operation. Scanning along the "Y" axis is
accomplished by merely changing the frequency of the radio
frequency magnetic field. This is possible because the
.vertline.H.sub.o .vertline. value changes linearly along the "Y"
axis between the two pairs of field focusing coils 54, 54a, and 56,
56a. In this embodiment, the superimposed field varies, for
example, from -0.50 to +0.50 gauss between the field focusing coils
54, 54a, and 56, 56a, but the range and therefore the gradient can
be made larger or smaller by varying the current in the field
focusing coils 54, 54a, and 56, 56a. For a particular value
.vertline.H.sub.o .vertline., for example H.sub.oi in FIG. 9, there
is a particular frequency .omega..sub.oi to satisfy NMR conditions
for the selected nuclei. Thus to obtain a measurement at the
location where the value of .vertline.H.sub.o .vertline. is
H.sub.oi+1, the frequency of the transmitter coil is adjusted to be
.omega..sub.oi+1. By varying the frequency directed to transmitter
radio frequency coils 60 and 62, means are provided for scanning a
specimen along a pencil beam through the specimen. The range of
.vertline.H.sub.o .vertline. values established by the field
focusing coils 54, 54a, and 56, 56a along the "Y" axis is
sufficiently small so that only the selected nuclei are energized
when the frequency sources 64 and 66 are changed. Thus a user can
be sure that when a particular .omega..sub.oi is used only the
selected nuclei at the location H.sub.oi are being resonated.
The steepness of the gradient provided by field focusing coils 54,
54a, and 56, 56a determines the size of the measuring volume 44a
because with a smaller gradient there is a larger region with
substantially the same magnetic field strength than with a larger
gradient.
To obtain a cross sectional scan of a specimen, for example a
human, the human is placed on a translator beam 48a as shown in
FIG. 5. The pencil scanning beam provided by transmitter coils 60
and 62 is along "Y" axis. The beam and specimen are moved
incrementally along the "X" axis by a conventional drive box 48a
and drive control unit 50a after a complete scan along the pencil
beam along the "Y" axis is completed. Thus a cross sectional scan
of a slice perpendicular to the "Z" axis in this illustration may
be achieved. At each point on the cross sectional grid the detector
or receiver coil 68 will detect any NMR signal generated. The
intensity or any other parameter of the signal together with the
corresponding position of the resonance domain 44a is stored in a
computer memory located in the NMR spectrometer 42 connected to the
receiver coil 68 through a transmission line 70 and capacitor
divider network 71. These intensity values are later processed to
form a cross sectional grid of values in an "X-Y" plane through the
specimen to provide a map showing the location and intensity of the
signal received at each location on the grid.
Although structure is shown in FIG. 8 for moving the specimen 32
with respect to a stationary pencil of transmitted radio frequency
energy, it is considered that structure may be incorporated for
rotating the field focusing coils 54, 54a, and 56, 56a; the
transmitter coils 60 and 62; and the receiver coil 68 about the "Z"
axis on a stepped bases after a complete scan along the pencil beam
to complete a map of values utilizing a radial sweep pattern. The
pencil beam would be rotated through 180.degree. to obtain a
complete cross sectional scan of a specimen. This is also
considered to be within the scope of the present invention.
In addition, depending on the geometry of the specimen to be
analyzed the direction of the magnetic axis of transmitter coils 60
and 62 (H.sub.T) and direction of the magnetic axis of receiver
coil 68 (H.sub.R) in FIG. 8 may be reversed by repositioning the
transmitting coils 60 and 62 and the receiving coil 68 so long as
H.sub.T, H.sub.R and H.sub.o are mutually orthogonal. In the
particular configuration shown in FIG. 8, it is preferred that the
human patient be positioned to lie on his back, since the length of
the pencil beam provided by transmitter coils 60 and 62 which
extends through the specimen is minimized. However, other
variations are contemplated and considered to be within the scope
of the invention.
A third embodiment embodying the principles of this invention is
shown in FIGS. 10-13. In this embodiment the static magnetic field
in the H.sub.o direction is provided by permanent magnets 76 and
78. Pole faces 72 and 74 are mounted on the magnets 76 and 78 to
concentrate flux. The configuration of the static magnetic field
between permanent magnets 76 and 78 is well known to be
substantially uniform.
The specimen 32 to be analyzed which again may be, for example, a
human is positioned on a translator beam 48c associated again with
drive box 49c and control unit 50c within the space between magnets
76 and 78. Field focusing coils 80, 80a, and 82, 82a correspond to
field focusing coils 54, 54a, and 56, 56a of the second embodiment
shown in FIG. 8 and provide a linear gradient of the static field
in the H.sub.o direction along the "Y" axis.
Transmitter coils 86 and 88 correspond to transmitter coils 60 and
62 of the embodiment shown in FIG. 8. In this embodiment, the line
of intersection of the transmitter coils 86 and 88 is along the "Y"
axis and each of the transmitter coils 86 and 88 are orthogonal to
the other and tilted 45.degree. to the "Y-Z" plane. The receiver
coil 90 corresponds to receiver coil 68 in the embodiment shown in
FIG. 8. In FIGS. 11-14, the connection of these coils to sources
and the NMR spectrometer are not shown since they are the same as
the embodiment shown in FIG. 8.
The apparatus shown in FIGS. 10-13 functions in the same manner as
the apparatus shown in FIG. 8 and is similar to such apparatus with
the exception that here permanent magnets 76 and 78 replace the
Helmholtz pair of magnets 51 and 52 as was the case with the
embodiment shown in FIG. 8. The magnetic directions of transmitter
coils 86 and 88 (H.sub.T) and the receiver coil 90 (H.sub.R) are
still orthogonal and both are still orthogonal to H.sub.o. To
accommodate a human patient, the coils had to be rearranged;
however, the principle of operation in both embodiments is
identical.
The direction of H.sub.o in this third embodiment is along the "X"
axis instead of the "Z" axis. H.sub.R is in the "Y" direction, and
H.sub.T is in the "Z" direction, thus H.sub.o, H.sub.R and H.sub.T
are all orthogonal to one another. A resonance domain 92 is located
on a pencil beam provided by the transmitter coils 86 and 88 as was
the case with the embodiment shown in FIG. 8. Since the pencil beam
is located on the line of intersection of the planes of the two
transmitter coils 86 and 88, the pencil beam lies along the "Y"
axis.
Scanning is accomplished as with the embodiment shown in FIG. 8 by
scanning along the pencil beam in the "Y" direction and translating
the specimen or patient 32 in the "X" direction. This provides
scanning in the "X-Y" plane. The NMR signal intensity is measured
at each point on the pencil beam at each discrete position of the
pencil beam with respect to the specimen. Again, the values
detected are stored, processed and displayed to show a cross
sectional map of the specimen showing intensities of NMR signal at
each location on the cross section of the specimen.
With any of the three embodiments above described, a user may
process the NMR signal obtained and determine a nuclear magnetic
value which may be, for example, the intensity of the NMR signal
obtained representing the degree of presence of the selected nuclei
within the resonance domain, an amplitude versus frequency spectrum
indicative of the atomic combinations of the selected nuclei within
the resonance volume; the spin-lattice relaxation time; the
spin-spin relaxation time; spin-mapping values of selected nuclei
indicative of the degree of organization of the selected nuclei
within the resonance domain. All of these nuclear magnetic
resonance values obtained may be displayed for analysis by a user
and cross sectional maps may be made. In detecting cancerous tissue
in mammals it is preferred that the selected nuclei be, for
example, P.sup.31, K.sup.39, Na.sup.23, H.sup.1, C.sup.13,
N.sup.15, N.sup.14 and O.sup.17. However, this apparatus may be
used in detecting and analyzing other diseases in tissue when
selected nuclei in the diseased tissue has a different chemical
organizational structure from the selected nuclei of normal
non-diseased tissue.
In forming NMR amplitude versus frequency spectra, a pulse mode of
operation may be used with the above described three embodiments
wherein the transmitted pulse injected into the resonance domain
has a band of frequencies. The resulting amplitude versus time NMR
signal detected by the receiver coils is directed to NMR
spectrometer 42 having a computer programmed to perform a Fast
Fourier Transform on the data received to develop an amplitude
versus frequency spectrum.
Examples of such amplitude versus frequency spectra which were
obtained using the first embodiment are shown in FIGS. 14A and
14B.
EXAMPLE 3
FIG. 14A shows a P.sup.31 NMR spectrum obtained non-invasively for
normal muscle tissue and FIG. 14B shows on P.sup.31 NMR spectrum
obtained non-invasively for malignant muscle. The operating
frequency of the radio frequency oscillator was 100 MHz and the
bandwidth of the transmitted pulse was 5,000 Hz and from 100
MHz-1000 Hz to 100 MHz+4,000 Hz and the pulse interval was 10
seconds. The resulting spectrum was the 256 averaged free induction
decay peak positions based on the mean positions of 8 separate
experiments. Each peak is the resonance from phosphorus for a
different phosphorus containing molecule except in the case of
adenoisine tri-phosphate (ATP) where three resonances (Peaks D, E
and F in FIG. 15A) are seen for the molecule, one for each of three
phosphates. Peak A in FIGS. 14A and 14B is the phosphorus resonance
of a sugar phosphate positioned at -3.9 ppm in normal muscle and
-4.3 ppm in malignant muscle (a difference of 40 Hz at the
operating frequency of 100 MHz). Ppm is an abbreviation for parts
per million and here is used to locate the frequency positions of
peaks with respect to the operating frequency. One ppm corresponds
to a frequency 100 Hz above the operating frequency of 100 MHz and
-1 ppm corresponds to a frequency 100 Hz less than the operating
frequency 100 MHz. Peak B in FIGS. 14A and 14B is the phosphorus
resonance for the inorganic salts of phosphorus positioned at -1.7
ppm in normal muscle and -2.4 ppm in malignant muscle (a difference
of 70 Hz). Peak C in FIG. 14A is creatine phosphate (absent in
cancer), and Peaks D, E, F in FIG. 14A are the three phosphates of
ATP (absent in cancer). Thus by noting the absence of certain peaks
and the shift of certain peaks in a NMR spectrum obtained for
tissue located within the resonance domain as compared with a NMR
spectrum for malignant tissue, malignant tissue may be detected and
located non-invasively.
Depending on the physical constraints caused by the geometry of the
specimen to be measured, the receiver coil in all three embodiments
may be a circular type coil if it can surround the specimen or be a
split cylindrical Helmholtz coil if it is not practical to
physically position the coil around the specimen.
Furthermore, in all three embodiments, the tranmitter and receiver
coils may be combined provided a pulse mode of operation is
utilized as explained above in conjunction with the first
embodiment.
All such variations are considered to be within the scope of the
present invention.
A continuous mode of operation could also be used with the three
embodiments described. However, in this mode of operation, separate
transmitter and receiver coils are required which by necessity must
be orthogonal to the direction H.sub.o of the static magnetic
field. In the continuous mode or high resolution mode, the
transmitter operates continuously as either its frequency is
gradually varied or the strength of the static magnetic field in
the H.sub.o direction is varied. Under these conditions and in a
specimen where the selected nuclei (for example, hydrogen) exist in
a variety of combinations with other atoms, the different
combinations would be seen as resonance peaks. See for example
FIGS. 14A and 14B. Each resonance peak represents a different
wavelength for NMR absorption and is caused by the fact that
different atomic combinations with the selected nuclei alter the
configuration of the electron cloud surrounding the nucleus and
consequently the net magnetic moment of the electron cloud. Thus,
the frequency at which resonance occurs also varies with the
various combinations of other nuclei with the selected nuclei. The
different resonant frequencies appear as resonance peaks on an
amplitude versus frequency spectrum.
As described above in conjunction with Example 3, an amplitude
versus frequency spectrum can also be obtained in the pulse mode by
transmitting a pulse of a predetermined bandwidth to the resonance
domain; detecting the resulting NMR signal; and using a Fast
Fourier Transform to generate the spectrum. The continuous mode
obtained by varying the frequency of the transmitter with time
provides a method of obtaining an amplitude versus frequency
spectrum directly without the need of using a Fast Fourier
Transform.
It should be understood that the above three embodiments could be
adapted to measure NMR signals for multiple selected nuclei by, for
example, mounting multiple receiver coils, one for each of the
separate types of selected nuclei on top of one another. The
transmitter coil would be pulsed in a timed sequence providing the
necessary radio frequency signal required for NMR conditions for
the first selected nuclei then the second selected nuclei, etc.
Other variations such as providing electronic circuitry for
detecting the transmitted signal and which would eliminate the need
for multiple receiver coils is contemplated by and is within the
scope of this invention. The detected NMR signals could then be
processed and displayed on multiple video displays.
The present invention provides a much needed method and apparatus
for determining the chemical structure of a specimen including
apparatus for making a macroscopic scan or microscopic scan of the
specimen. It is understood that many modifications of the structure
of the preferred embodiments will occur to those skilled in the
art, and it is understood that this invention is to be limited only
by the scope of the following claims.
* * * * *