Method for the imaging of intra-voxel movements by NMR in a body

Movements within volume elements or voxels of a body are depicted by subjecting this body to sequences of electro-magnetic excitation of the SSFP type during an NMR experiment. It is shown that by performing two series of excitation/reading sequences with different sensitization characteristics, it is possible to obtain images of molecular diffusion and/or perfusions in a far quicker and in a far more differentiated way than with standard types of excitation methods, of the spin-echo type for example.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
An object of the present invention is a method for the imaging of 
intra-voxel movements by nuclear magnetic resonance (NMR) in a body. It 
can be applied more particularly in medicine where NMR imaging is an 
indispensable diagnostic tool. 
2. Description of the Prior Art 
A known method of NMR imaging is described in the European patent No. 86 
401 423.8. In this method, it is explained that the depiction of standard 
images by highlighting the spin-lattice relaxation times T.sub.1 and the 
spin-spin relaxation times T.sub.2 of the magnetic moments of the 
particles of a body being examined is not always enough to differentiate 
certain healthy tissues from neighboring tumors and to identify lesions. 
For improved differentiation, it was proposed to measure and depict the 
distribution of the molecular diffusion coefficients of the imaged 
tissues. In the development and perfecting of this invention, it emerged 
that the method used to reveal the molecular diffusion coefficients did 
not circumvent the effect of the more comprehensive molecular movements 
within the volume elements taken into account, corresponding to the 
necessary discretization of an image to enable the computation of this 
image. These volume elements are called voxels. For, group movements such 
as movements of blood molecules create micro-circulation motions which 
become identified with the molecular diffusion characteristics of the 
tissues examined. 
In the above-mentioned patent application, it was shown that, by repeating 
an imaging experiment with different experimental characteristics and by 
comparing the results obtained at the end of the first experiment with 
those obtained at the end of the second experiment, it was possible to 
depict two images. With these two images, it was possible to present the 
molecular diffusion coefficients independently of the coefficients of 
blood perfusion of the tissues and vice versa. 
In practice, the first experiment comprises two series of radiofrequency 
excitations of the body under NMR examination: a first series known as a 
series with little diffusion and a second series known as a diffusive 
series. The second experiment has only a third series of radiofrequency 
excitations, also called diffusive but having characteristics of 
sensitization to molecular diffusion which are different from the 
characteristics of sensitization to the molecular diffusion of the second 
series of excitations. For, in the second experiment, it is unnecessary to 
reiterate the series of excitations with little diffusion. A series of 
radiofrequency excitations more precisely comprises a series of 
excitation/measurement sequences. In each sequence, the body to be 
examined is made to undergo an excitation, at the end of which the NMR 
signal resulting from this excitation is measured. During the excitation, 
magnetic encodings of space are additionally applied to the body so as to 
cause encodings of the measured signal in order to extract therefrom, by 
decoding, information directly representing luminosity values to be 
assigned to the different pixels of the image. These encoding/decoding 
operations constitute imaging methods. These encodings are applied in the 
form of magnetic field gradient pulses. A preferred imaging method 
described in the above-mentioned patent application is the 2DFT method. 
The essential feature of the invention which wa the object of the 
above-mentioned patent application resides in the fact that there is a 
common duration to all the sequences of every series of experimental 
sequences. 
In the excitation-measuring sequences, the NMR signal resulting from the 
excitation is known to fade away very quickly after excitation, namely 
before the additional magnetic encodings can be efficiently applied to the 
regions to be imaged, prior to the measurement. This fading away is due to 
non-homogeneity in the orienting magnetic field in the body examined. This 
non-homogeneity causes a corresponding dispersal in the phase of the NMR 
signals emitted by the different particles distributed in space. It has 
become customary to cause this phase dispersal to be reflected by applying 
an additional excitation pulse, called a spin-echo pulse or, again, a 
180.degree. pulse because it causes the orientation of the magnetic 
moments of the particles to be imaged to flip by 180.degree.. At the end 
of a period which is twice the interval between the initial excitation and 
the application of this 180.degree. excitation pulse, the signal is 
revived and can be measured. Typically, each excitation-measurement 
sequence of this type is separated from the following one by 400 to 1000 
milliseconds (repetition time). 
The greater the number of excitation-measurement sequences of each series 
of excitations, the more precise is the definition of the images 
presented. Ultimately, the images determined at the end of each series are 
all the more precise if the time taken to acquire them is long. Since it 
is necessary to acquire three series of excitations, the total period 
during which a patient is subjected to an NMR excitation of this type may 
rule out this kind of examination. This approach entails examination 
periods of about 20 minutes. In general, to resolve problems related to 
the duration of the experiment, the excitation method currently used is 
the so-called SSFP (steady state free precession) method. In this method, 
the excitations are very close to one another in time and cause the 
magnetic moments of the nuclear particles of the body to flip each time by 
a relatively small angle depending on the period between the excitations. 
It has been shown that this method, although it has no 180.degree. 
spin-echo excitation pulse, causes the revival of composite NMR signals 
formed by echos of free precession signals. These revived signals can be 
used as measurable NMR signals. It has thus been shown that a state of 
dynamic equilibrium can be created between a longitudinal magnetization 
M.sub.z of the magnetic moments of the particles and the transversal 
magnetization M.sub.xy of these magnetic moments by choosing a 
radiofrequency pulse corresponding to a flip-over angle known as the angle 
of Ernst, the value of which depends on the repetitivity of the excitation 
pulses of the sequence and on the average spin-lattice relaxation time of 
the particles sought to be represented. 
When no gradient pulse is applied, the phenomenon occurs simply. On the 
contrary, for imaging, space encoding pulses must be applied during each 
sequence in order to differentiate between the contributions of the 
different particles in the NMR signal. It has been shown that the dynamic 
equilibrium of the transversal magnetization M.sub.xy is got by re-phasing 
the transversal magnetization of the moment of each pulse. The re-phasing 
is got by reversing the direction of the gradient at the origin of the 
phase shift: by compensating, at the end of each sequence, for the phase 
shift effects due to the encoding gradients of the image. The reappearance 
of the NMR signal due to this re-phasing is called the "gradient echo". 
This notion of phase-shifting/rephasing concerns only the immobile 
particles placed at different positions in the magnetic field of the 
machine. 
After a number of excitation pulses have been applied, it may be assumed 
that dynamic equilibrium has been set up. In this mode, a fall is observed 
in the NMR signal, after each pulse, as well as a rise in this signal, 
before each pulse. The fall (evanescent) may be considered to be the 
equivalent of a free precession signal of a standard sequence. The rise 
(echo) may also be considered to be the equivalent of a spin-echo signal. 
The NMR signal can be measured in advance of the measurement of this 
rising signal in the sequence. This can be got by applying additional 
gradient pulses which destroy the component of the NMR signal, related to 
the free precession signal, by phase-shifting. The effect of these 
additional gradient pulses, therefore, is firstly, to separate the reading 
signals according to their origin: namely, those coming from the free 
precession signal and those coming from the rising signal. They also have 
the effect, secondly, of advancing, in the excitation-reading sequence, 
the period during which the reading is done so that this reading of the 
NMR signal does not take place precisely when the excitation is applied. 
In the invention, advantage has been taken of the existence of fast methods 
of the SSFP type to produce apparent molecular diffusion images or, by 
once again reiterating the series of excitations, true molecular diffusion 
and micro-circulation images. In principle, SSFP type methods are not 
indicated for these images because the sensitizing of the NMR signal to 
the molecular diffusion effect requires the application of strong 
diffusing gradient pulses, i.e. pulses with high amplitudes and long 
periods. Now, in an SSFP sequence, the period for which these pulses are 
applied is necessarily short since the sequence is itself short. The 
principle of the invention is based, nonetheless, on the reiteration of an 
SSFP sequence, with a diffusing gradient pulse force designed to remove 
the free precession component and to sensitize the sequence to diffusion 
and micro-circulation movements, which is different, in a second series of 
sequences, from a first series. By contrast, for the different series of 
sequences, the same excitation-reading characteristics are retained (in 
particular, the same repetition time) as also the same imaging 
characteristics (preferably, the depiction of comparable images is sought, 
with one and the same definition, hence with one and the same number of 
sequences in the series of sequences). It has been shown that there is an 
integration effect of these pulses of this diffusing gradient which then 
leads to a paradoxically high level of sensitivity. 
SUMMARY OF THE INVENTION 
Consequently, an object of the invention is a method for the imaging of 
intra-voxel movements by NMR in a body, comprising the following steps: 
a) the body to be examined is subjected to an orienting magnetic field; 
b) the body is subjected to a first series of SSFP type radiofrequency 
electro-magnetic excitation sequences in the presence of image encoding 
magnetic field gradients; 
c) the magnetic resonance signal emitted in return by the body, at the end 
of each sequence of the first series, is measured and the characteristics 
of a so-called standard first image are extracted therefrom; 
d) the body is subjected to a second series of SSFP type radiofrequency 
electro-magnetic sequences having the same characteristics as the 
sequences of the first series, in the presence of image encoding magnetic 
field gradients and in the presence of first, sensitizing magnetic field 
gradients, 
e) the magnetic resonance signal emitted in return by the body at the end 
of each sequence of the second series is measured and the characteristics 
of a second image, called a sensitized image, are extracted therefrom; 
f) the characteristics of the first normal image are compared with the 
characteristics of the second sensitized image and the characteristics of 
a third image corresponding to the intra-voxel movement in the body are 
deduced therefrom.

DESCRIPTION OF PREFERRED EMBODIMENTS 
FIG. 1 shows an NMR machine to implement the method of the invention. This 
machine has means symbolized by a coil 1 to subject a body 2 to a high and 
constant magnetic field B.sub.O. This device further has generators 3 and 
coils 4 to subject the body thus placed to excitation sequences of the 
SSFP type in the presence of field gradient sequences (FIG. 2b, 2c). The 
coils 4 represent the radiofrequency coils and the field gradient coils. 
The machine also has reception means 5 connected to the coils 4 to receive 
the magnetic resonance signal, and means 6 to compute and memorize a first 
normal image I.sub.1 and a second sensitized image I.sub.2 relating to two 
experiments put into effect by commands, marked C.sub.1 and C.sub.2, from 
the generating means 3. In processing circuits 7, the images I.sub.1 and 
I.sub.2 are compared dot by dot by computing the logarithm of the ratio of 
the values representing the magnetic resonance signals assigned to each 
picture element (pixel) of the images. 
The processing circuit 7 then prepares a third image I.sub.3, representing 
intra-voxel movements in which two regions 8 and 9 of the body 2, on an 
imaged section, have different responses in value of molecular diffusion 
and/or perfusion whereas they would have identical responses in standard 
magnetic resonance images. These images I.sub.1 to I.sub.3 can be 
displayed on a display device 50. The method for computing the images 
I.sub.1 or I.sub.2 is a standard one. In one example, the imaging method 
used by the means 6 is a 2D method, preferably a so-called 2DFT method. 
This 2DFT imaging method currently enables the obtaining of the best 
quality images. In one 2D imaging method, only one sectional plane is 
excited at a time by means of radiofrequency excitations applied in the 
presence of a so-called selection gradient. Thus, to simplify the 
explanation, in FIG. 1, the selection gradient may be oriented along the 
axis Z to select a cross-section (along a plane XY). The 2DFT (or 3DFT) 
imaging principle entails phase encoding of the different signals to be 
acquired. This is got by one (or more) pulses of a so-called 
phase-shifting gradient, the axis of which is perpendicular to a reading 
gradient with a constant direction. For example, for a cross section, the 
reading gradient could be the gradient X and the phase-shifting gradient 
could be the gradient Y. The image is reconstructed through a 
two-dimensional Fourier transform, whence the name of the method. Although 
the invention is described herein with a 2DFT type imaging method, it is 
nonetheless applicable to other imaging methods, especially methods of the 
3DFT type which are deduced from the above method by generalization. 
In the case of the invention, the radiofrequency excitations are of the 
SSFP type. They are shown in FIG. 2a. This figure shows a typical 
representation of the excitation pulses and signals corresponding to NMR 
in response to these excitations. In an SSFP type of method, the dynamic 
equilibrium of the longitudinal magnetization M.sub.Z and the transversal 
magnetization M.sub.XY was got for excitations E which cause the 
orientation of the magnetic moments of the particles in a body to flip by 
an angle .alpha. pre-determined by the spin-lattice relaxation time 
T.sub.1 of the body's particles, on the one hand, and by the repetition 
time TR between different excitations on the other hand. If the angle 
.alpha. is accurately adjusted, the presence of two NMR signals S is 
noted, a first free precession signal 10 and a second so-called rising 
signal 11. In one sequence, the signal 11 is presented just before the 
application of an excitation pulse 12 of a following sequence. The signal 
11 is weaker than the signal 10, firstly because of the combined effects 
of the non-homogeneity of the orienting field B.sub.O and, secondly, 
because of the effects of differences in precession speed due to chemical 
shift and to spin-spin relaxation (T.sub.2). 
FIGS. 2b and 2c show the special features of the method of the invention. 
In each sequence, with a period TR, of two series of sequences, an 
excitation 13 is applied in the presence of a pulse 14 of a slice select 
gradient. A selection pulse 14 is conventionally followed by a pulse 15 
for the rephasing of the NMR signals related to a phase shift imposed by 
the duration of the pulse 14. Immediately after the selection of the 
section, a pulse 16 of a phase encoding gradient is applied therein with a 
value that varies from one sequence to another. For this reason, the phase 
encoding gradient 16 is shown with a slanted variation arrow. A pulse 17 
of a read encoder gradient is applied at the instant when it is desired to 
pick up the NMR signal. After the reading, and so that a following 
excitation pulse 18 is applied to the particles under the same conditions, 
each of these pulses 14 to 17 is compensated for by gradient pulses, 19 to 
22 respectively, on the same axes. If simple action were to be taken in 
this way, the rise 11 of the NMR signal and, therefore, its reading would 
have to be just before the application of the excitation 18. It is known 
that, by the application of a pulse 23 to the reading axis prior to the 
reading, it is possible, firstly, to cause the phase dispersal of the NMR 
signal connected to the free precession signal and, secondly, to advance 
the instant at which a rising signal S can be measured efficiently in the 
sequence to an instant T which can be used. 
In the invention (FIG. 2c), the radiofrequency excitations and the 
measurements are repeated with the same characteristics in the course of a 
second series of sequences during which the efficiency of the dispersal 
pulse 23 is increased. For example, an additional gradient pulse 24 is 
imposed on the read axis with an amplitude G and a period d. If a standard 
computation (FIG. 3) is made of a first normal image I.sub.1 at the end of 
the series of sequences of FIG. 2b, and if a computation is made, under 
the same conditions, of a second so-called sensitized image I.sub.2 at the 
end of the sequences shown in FIG. 2c, by making a dot by dot comparison 
of the pixels of these images (in computing the logarithm of the ratio of 
luminosities assigned to each of these pixels) it is possible to deduce 
therefrom a third image I.sub.3 representing intra-voxel movements. It is 
then discovered that this additional gradient pulse G.d, which has the 
effect of reducing the amplitude of the NMR signal S.sub.1 in proportion 
to the movements inside the voxels, is, in this SSFP type sequence, far 
more efficient than an equivalent gradient pulse (G.d) applied in the 
previous spin-echo method. For, to obtain the same results, it is 
necessary in the prior art referred to, to choose far longer intervals d' 
of the diffusing gradients than those that can now be chosen. In practice, 
the spin-echo sequences, used in the prior art referred to, have 
repetition times (TR) of about 500 to 1000 milliseconds whereas the period 
TR of an SSFP type sequence is about 100 milliseconds at most. Whereas the 
diffusing, dispersive gradient pulses capable of being applied in 
sequences of this type ought to be ten times less efficient because of 
their duration, they are actually four times more efficient. In the 
invention, it has been realized, by maintaining the instants T at which 
the resulting NMR signals were read, that the efficiency of the pulses 24 
was paradoxically far greater. 
The far greater efficiency of the pulse 24, which in principle should be 
lower than that of the pulse that could be applied under the same 
conditions in a standard spin-echo sequence, is attributed to the phase 
shift integration undergone by the NMR signals of the magnetic moments of 
the particles, the echoes of which are caused by the sequence of 
excitations. In simplifying the explanation, it can be assumed that the 
signal S measured in an SSFP type sequence, is the composite result of the 
contributions of the number of echos of free precession signals. Thus, if 
particular instants of application of excitation are chosen (for example, 
so as to cause flipping, before each excitation, only in magnetic moments 
which have been brought, by their precession into phase opposition with 
respect to a coherent signal), it can be shown that, for the fixed 
particles in the body, the effect of the gradient pulse 24 like that of 
the pulse 23 is inverted every other time and, ultimately, only has 
compensated effects. On the contrary, for particles driven by movements in 
the body from one sequence to the next one, the compensation for the phase 
shifts does not occur. So much so that their contribution to the rising 
signal is dispersed: the greater the number of these particles driven by 
movements, the weaker the rising signal becomes. 
In view of the fact that the SSFP type sequences deliver NMR signals with a 
signal-to-noise ratio smaller than that of signals from standard type 
sequences (because the measuring period is also smaller) and because the 
efficiency of the gradient pulse 24 located therein is increased tenfold, 
the computations of differentiation needed to arrive at the third image 
I.sub.3, representing movements inside the volume elements, thus lead to 
far better results. 
FIG. 3 shows a preferred mode of implementation of the invention. For, with 
a repetition time of about 100 milliseconds, each of the normal images 
I.sub.1 and I.sub.2 can be acquired in a period close to one minute. 
Knowing then that the patience of patients being examined in NMR machine 
is not excessively tried at this stage, a third series of sequences, also 
lasting about one minute, can be initiated by modifying the value of the 
gradient G and/or the period d of the additional gradient pulse 24. Let G' 
and d' be the conditions of acquisition of a fourth image I.sub.4 which is 
also said to be sensitized and for which the other conditions of 
acquisition (imaging method) are, besides, identical to those of the 
images I.sub.1 and I.sub.2. The NMR signal received in this third series 
is called S'.sub.1. By comparing, in the comparison circuit 7, the image 
I.sub.1 with the image I.sub.4 in the same way as the image I.sub.1 was 
compared with the image I.sub.2, it is possible to produce an other image 
I.sub.5 of movements within voxels. In principle, this image can also be 
used to differentiate between two regions 8 and 9 of the body, on the 
imaged section, having different intra-voxel movement characteristics from 
each other. By then comparing the third image I.sub.3 with the fifth image 
I.sub.5 pixel by pixel, it is possible to compute a sixth image I.sub.6 
representing true characteristics of molecular diffusion inside each of 
the excited voxels and/or a seventh image I.sub.7 representing the 
perfusion within the tissues studied. This second comparison may, as 
described in the above-mentioned prior art, amount to finding the solution 
to a system of two equations with two unknown quantities. For, it can be 
assumed that the two apparent coefficients of molecular diffusion, ADC and 
ADC' (obtained point by point respectively in each of the third and sixth 
images), can be written: 
EQU ADC=D+{Log[((1-f)+fF.sub.0)/((1-f)+fF.sub.1)]}/(b.sub.1 -b.sub.0) 
EQU ADC'=D+{Log[((1-f)+fF.sub.0)/((1-f)+fF'.sub.1)]}/(b'.sub.1 -b.sub.0) 
In this expression D is the coefficient of true molecular diffusion inside 
a voxel in the body, f is the volume fraction of this voxel occupied by a 
fluid (blood) flowing in this voxel, F.sub.0 and F.sub.1 (or F'.sub.1) are 
factors of attenuation due to the micro-circulation movements and relating 
to the non-diffusing and diffusing sequences respectively, wherein the 
signals S.sub.0 (and S.sub.1 or S'.sub.1) are measured and wherein b.sub.0 
and b.sub.1 (or b'.sub.1) are factors depending on the gradient sequence 
used. In the above-mentioned patent application, an indication was given 
of how to compute these factors F.sub.0, F.sub.1 and F'.sub.1. In 
particular, it was indicated that F.sub.0 was substantially equal to 1 and 
had therefore had a negligible effect during the standard sequence: herein 
the sequences shown by FIG. 2b. And, in particular, if the gradients added 
to prepare S.sub.1 and S'.sub.1 are sufficiently efficient, F.sub.1 and 
F'.sub.1 may be considered to be substantially equal to zero. This notably 
simplifies the computations where the expressions of ADC and ADC' become: 
EQU ADC=D-(Log (1-f))/(b.sub.1 -b.sub.0) 
EQU ADC'=D-(Log (1-f))/(b'.sub.1 -b.sub.0) 
These latter formulations of ADC and ADC' actually comprise two unknown 
quantities D and f. These two unknown quantities can be found by resolving 
the system of equations thus formed. D and Log (1-f) are sought. Then, 
knowing Log(1-f), f is found. The first image I.sub.3 represents 
coefficients ADC, the second image I.sub.5 represents coefficients ADC'. 
Knowing b.sub.1 and b'.sub.1 to be different for the computation of the 
images I.sub.2 and I.sub.4, this system can be resolved. In practice, 
three sequences are therefore needed to separate the true diffusion 
information D and the perfusion information f in each volume element. This 
comparison (the resolution of the equations system) can also be performed 
by comparison means 7 which, in a preferred way, comprise a standard 
processing unit. 
Starting from the fact that, in the sensitized sequences, F.sub.1 and 
F'.sub.1, are 0, we can write: 
EQU D={Log (S.sub.1 /S'.sub.1)}/(b'.sub.1 -b.sub.1) 
This enables the determination of the sixth image of pure diffusion by 
direct comparison of the second and fourth sensitized images. From the 
comparison of this sixth image, obtained directly, with the third image 
representing intra-voxel movements, it then becomes possible to determine 
the seventh pure perfusion image. FIG. 4 illustrates this process.