Method of magnetic resonance imaging for the production of rare images with additional preparation of the magnetization for contrast variation

An improved rapid acquisition relaxation enhanced (RARE) imaging method for measuring nuclear magnetic resonance in selected regions of a body is disclosed. The improved RARE imaging method includes introducing an evolution phase of time duration t.sub.2 between the excitation pulse and the first refocusing pulse of the multi-echo train. The evolution phase is introduced to influence the magnetization of the observed nuclei in such a fashion that the intensity and/or phase of the subsequent signals are influenced as a function of this evolution phase. This allows the effects of flow, motion, diffusion and local magnetic field inhomogenities to be measured.

BACKGROUND OF THE INVENTION 
The invention concerns a method for the measurement of nuclear magnetic 
resonance in selected regions of a body for the purpose of imaging body 
cross sections with which the body is exposed to both a homogeneous 
magnetic field as well as to a selection gradient and is excited with a 
selective excitation impulse and, subsequently, the selection gradient is 
replaced by time-limited phase encoding and read gradients which are 
perpendicular to the selection gradient and to each other and the body is 
irradiated with a sequence of refocussing pulses through which a plurality 
of nuclear magnetic resonance signals are excited in the form of so-called 
spin echoes, whereby the switching-in time and strength of the gradients 
is adjusted to the pulse sequence in such a fashion that, at the time of 
occurrence of each refocussing pulse relative to the effect of the 
gradient, the nuclear spins have the same phase state as that at the point 
of time of the preceding refocussing pulse, whereby the read gradient is 
switched-in during the occurrence of the spin echo to be symmetric to same 
and the phase encoding gradients are switched-in following each 
refocussing pulse and are terminated before the appearance of the spin 
echo, switched-in again, with opposite directional influence, after the 
appearance of the spin echo and terminated once more before the next 
refocussing pulse, whereby the strength and/or duration of the phase 
encoding gradient is changed after every refocussing pulse and the spin 
echoes are computed into imaging signals taking into consideration the 
change in the phase encoding gradient in accordance with the 
two-dimensional Fourier transformation method. 
This so-called RARE method is known in the art from U.S. Pat. No. 
4,818,940. 
The RARE method is a rapid imaging method with which spin echoes are 
produced following one excitation pulse through a plurality of refocussing 
pulses which are differently phase encoded through the application of 
suitable magnetic field gradients. In this fashion the number of differing 
phase encoding steps is significantly greater than the number of 
excitation pulses. In extreme cases all phase encoding steps which are 
necessary for image reconstruction can be obtained following one single 
excitation through production of correspondingly long echo trains. Due to 
the behaviour of transverse magnetization under the influence of such a 
sequence of equally spaced refocussing pulses, the sequence is extremely 
stable with regard to flow, motion, diffusion and magnetic field 
inhomogeneties which can occur in biological tissue due to, for example, 
changes in susceptibility. 
A number of magnetic resonance imaging applications are precisely intended 
to measure or image these above mentioned effects. The purpose of the 
present invention is therefore to modify the known RARE method sequence in 
such a fashion that RARE is sensitive to such effects while maintaining 
the otherwise advantageous properties of rapid imaging and high stability 
of the Carr-Purcell-Meiboom-Gill-echo train. 
SUMMARY OF THE INVENTION 
This purpose is achieved in the accordance with the invention in that an 
evolution phase of time duration t.sub.e is introduced between the 
excitation pulse and the first refocussing pulse of the multi-echo train 
in such a fashion that the time difference between the excitation pulse 
and the first refocussing pulse is larger or smaller than the time 
duration .tau. between the first refocussing pulse of the multi-echo train 
and the first spin echo. 
The introduction of the evolution phase of the method in accordance with 
the invention influences the magnetization of the observed nuclei in such 
a fashion that the intensity and/or phase of the subsequent signals are 
influenced as a function of this evolution phase. In this manner it is 
also possible to measure the above mentioned effects of flow, motion, 
diffusion and local magnetic field inhomogeneties using the modified RARE 
sequence based on the influence of the signals due to the evolution phase. 
An embodiment of the method in accordance with the invention is preferred 
with which the time duration t.sub.e differs by 1 msec to 100 msec, 
preferentially by 10 msec, from the time duration .tau.. The T.sub.2 
relaxation time can be taken to be the upper limit for t.sub.e which can 
not be substantially exceeded whereas the lower limit for t.sub.e is an 
evolution phase time duration with which the effects to be observed are 
just barely noticeable in the signal. 
In most applications of the modified RARE method in accordance with the 
invention, the time duration .tau. assumes a value between 5 msec and 20 
msec. The time duration of the entire pulse sequence is usually smaller 
than 20 sec but is usually larger than 1 sec. 
In a particularly preferred embodiment the time duration t.sub.e is chosen 
to be larger than the time duration .tau.. The time duration t.sub.e of 
the evolution phase can, however, also be shorter than the time duration 
.tau. between the refocussing pulse and the spin echo of the multi-echo 
train. In any event, the time duration .tau. is determined by the 
refocussing conditions of the modified RARE sequence and, in accordance 
with the invention, must be different than the time duration of the 
evolution phase. 
An embodiment of the method in accordance with the invention is preferred 
in which the refocussing pulse of the multi-echo train is chosen in such a 
fashion that it causes the magnetization flip angle .beta. to differ from 
180.degree. so that spin echoes are produced which occur at the same times 
but, however, have differing phases -.alpha. or +.alpha. depending on 
their differing refocussing path formations. The dephasing effect can be 
transferred into an amplitude modulation of the signals through 
destructive superposition of the signals. 
In a preferred variation of this embodiment, additional magnetic gradient 
impulses are switched-in in the direction of the read, phase encoding, or 
slice selection gradients symmetrically with respect to every other 
refocussing pulse of the multi-echo train. In this fashion the sensitivity 
of the signals to motion in the plane of the additionally switched-in 
gradients is amplified. 
An improvement of this variation is preferred in which the magnetic 
gradient pulses are chosen in such a fashion that the signal portion of 
the spin echo from one of the possible signal groups having the dephasing 
-.alpha. or +.alpha. is eradicated. In this manner only one of the two 
possible signal groups is observed. 
In another improvement of the above mentioned variation of the method the 
magnetic field gradient pulses are chosen in such a fashion that the 
signal portions of the spin echoes from both possible signal groups with 
the dephasing -.alpha. or +.alpha. occur shifted in time. In this case the 
signal portions of both signal groups can each be separately reconstructed 
into images of opposite dephasing. 
An embodiment of the method in accordance with the invention is 
particularly preferred in which neither radio frequency (HF) pulses are 
irradiated nor gradients applied or switched during the evolution phase. 
In this embodiment, the evolution phase occurs in an additional time 
interval between the excitation pulse and the first refocussing pulse, 
whereby due to the difference between evolution phase time duration 
t.sub.e and the time interval .tau. between the subsequent refocussing 
pulse and the first spin echo, this echo and all subsequent echoes 
experience a dephasing and/or amplitude modulation which depends on the 
differing time intervals and on all mechanisms causing a time dependent 
dephasing of the transverse magnetization. When changing the time duration 
t.sub.e of the evolution interval the gradient effects are refocussed 
during the echo formation, whereas the time independent static effects of 
field inhomogeneties are not. In this fashion the local field 
inhomogeneties can therefore be rendered visible. 
An embodiment of the method in accordance of the invention is particularly 
preferred in which, during the evolution phase and following a time 
interval of duration t.sub.e1 after the excitation pulse, an additional 
refocussing pulse is irradiated to produce an additional spin echo after 
an echo time t.sub.e1, whereby the timing of the first refocussing pulse 
of the multi-echo train is so chosen that the time interval between the 
additional spin echo and the first refocussing pulse of the multi-echo 
train is equal to the time interval .tau. between the first refocussing 
pulse of the multi echo train and the first spin echo thereby produced and 
whereby t.sub.e1 &gt;&gt;.tau.. The multi-echo train following the additional 
spin echo thereby experiences an additional T.sub.2 weighting as well as a 
signal damping due to diffusion in the strong local magnetic fields. In 
this fashion effects of local field inhomogeneties can be suppressed, 
whereas the sensitivity of the method in accordance with the invention to 
motion and diffusion effects remains. 
In a preferred variation, additional magnetic gradient pulses are switched 
during the evolution phase symmetric to the additional refocussing pulse 
to cause a dephasing of spins which move in the direction of the 
additional gradients. In this fashion an additional diffusion dependent 
signal damping is caused when diffusion is present. 
An embodiment of the method in accordance with the invention is 
particularly preferred in which a pair of additional excitation pulses, 
separated by time an interval of duration t.sub.m, are irradiated during 
the evolution phase following a time interval of duration t.sub.e2 after 
the excitation pulse to produce a stimulated echo after a time duration 
t.sub.2 following the second pulse of the pair and with which the timing 
of the first refocussing pulse of the multi-echo train is chosen in such a 
fashion that the time interval between the stimulated echo and the first 
refocussing pulse of the multi-echo train is equal to the time interval 
.tau. between the first refocussing pulse of the multi-echo train and the 
first spin echo thereby produced. The stimulated echo experiences a 
T.sub.1 variation during the t.sub.m interval corresponding to the 
evolution of the magnetization, whereby a signal damping due to the 
diffusion of the magnetization in local magnetic field gradients also 
occurs. 
In a preferred variation of this embodiment, additional magnetic gradient 
pulses are switched symmetrically during the evolution phase before the 
first excitation pulse of the pair and after the second excitation pulse 
of the pair to cause a dephasing of spins, the spins moving in the 
direction of the additional gradients. This leads to an additional signal 
damping due to diffusion in consequence of the dephasing. 
In order to observe the above mentioned effects of field inhomogeneties, 
motion sensitivity, flow and diffusion in an image recorded with the 
method of the invention, a preferred embodiment provides for the recording 
of a image slice of the object under observation in a second measuring 
step using the unmodified RARE method and forming a difference of signal 
amplitudes relative to the first measurement step. For images of largely 
homogeneous tissue, a simple comparison of the inhomogeneties visible in 
the method according to the invention can, however, provide an indication 
of the above mentioned effects without requiring a difference measurement. 
The invention is described and explained in greater detail below with the 
embodiments in connection with the drawing. The features which can be 
extracted from the description and the drawing can be utilized in other 
embodiments of the invention individually or collectively in arbitrary 
combination.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
FIG. 1 shows the manner in which the method in accordance with the 
invention modifies the RARE sequence in such a fashion that an evolution 
phase is introduced between the excitation pulse (generally a 90.degree. 
RF pulse) and the production of the CPMG echo train during which the spin 
system develops as a function of the parameters to be observed. The 
magnetization prepared in this fashion is subsequently read-out with a 
multi-echo train and phase encoded in the manner known through the RARE 
method so that the information required for image reconstruction can be 
collected after one or more of such excitation cycles. 
In FIG. 1, and in the following figures, Rf indicates the sequence of high 
frequency pulses and signals, G.sub.S the slice selection gradient, 
G.sub.R the read gradient and G.sub.P the phase encoding gradient. A 
plurality of possible methods for configuring the evolution phase in order 
to achieve the desired sensitivity to different parameters, will be 
presented below. 
In addition to the utilization of the actual RARE sequence it is also 
possible to read-out the data using a sequence with which a plurality of 
signals can be produced within each spin echo refocussing by means of 
gradient inversion (GRASE method). 
1. Susceptibility sensitive RARE 
1.1. Static susceptibility 
In this case two different susceptibility effects can be separately 
observed. The static susceptibility is due to the time dependent dephasing 
of spins in differing local magnetic fields and the dynamic susceptibility 
effect is caused by diffusion of spins in strong local magnetic field 
gradients. 
The first effect which is completely suppressed by refocussing in the 
normal RARE sequence, can be introduced into the RARE sequence by having 
the evolution phase transpire within a time interval during which the 
described effects develop. The magnetization prepared in this fashion is 
then read-out by multi-echo imaging. 
Since the magnetic fields gradients are applied in accordance with the 
basic sequence, the high stability of the RARE sequence with regard to 
gradient independent dephasing is maintained. Thereby all signal portions 
contributing to a single echo always contribute coherently independent of 
the refocussing path. The signal coherence is therefore not destroyed by 
deviation of the refocussing flip angle from the ideal value of 
180.degree.. 
As shown in the phase diagram of FIG. 2, this coherence is not present with 
regard to magnetic field inhomogeneties due to the additional preparation 
phase. FIG. 2 shows the time development of the phase .PHI. of a spin 
under the influence of the magnetic field inhomogeneties. The high 
frequency pulses are indicated as vertical lines. The diagonal lines 
correspond to the respective transverse magnetizations and the dashed 
horizontal lines to coherent z-magnetization which later leads to the 
formation of stimulated echoes. Signal formation always occurs in the 
middle between two refocussing pulses. In the standard RARE method this 
phase which is caused by inhomogeneties is equal to zero at the echo time. 
If one assumes a susceptibility dependent dephasing under change of the 
evolution period for the first echo formed by an amount .alpha. it can be 
shown that the subsequent signals are dephased by +.alpha. or -.alpha. 
depending on the refocussing path. The overlapping of the differing signal 
portions then leads to an incoherent overlapping and, in the extreme case, 
for .alpha.=90.degree. and for equal distributions of magnetization in 
both signal groups, to the eradication of the signal. 
As shown in FIG. 3, it is possible to vary the method through the 
application of additional gradient pulses in such a fashion that both 
signal groups appear separately. In FIG. 3 both signal groups are 
separately produced between two refocussing pulses by introducing an 
additional gradient into the refocussing interval. This additional 
gradient is alternately switched from echo to echo before and after the 
signal which is to be read out since a signal with dephasing +.alpha. and 
in the next echo with dephasing -.alpha. would otherwise alternately occur 
in each case. This additional gradient is indicated in FIG. 3 as a shaded 
gradient in the direction of the slice selection gradient. In this case 
the signal portions which are not to be measured are dephased and 
therefore not observed. 
As shown in FIG. 4, the additional gradient can also be applied in another 
direction, for example, in the direction of the read gradient. By 
utilizing this read gradient it is possible to observe both signal groups 
next to one another. It should be noted that the order of the sequence of 
correspondence of the echoes of both signal groups alternates from echo to 
echo, as indicated by the numbering of the echoes in FIG. 4. 
Selection by means of additional gradients in the direction of the phase 
gradients is also possible. One should, however hereby observe that the 
additional gradient must exhibit an amplitude which is larger than the 
maximum size of the gradients used for spatial encoding since otherwise 
imaging artifacts could occur due to signal portions which are not 
completely dephased. 
1.2 Dynamic susceptibility 
The dynamic susceptibility effect occurs due to the diffusion of free by 
moving molecules in strong magnetic fields. A substantial difference 
compared to the static susceptibility effect is due to the fact that the 
coherence loss in transverse magnetization caused hereby can not be 
reversed by rephasing using spin echo formation. An experiment is 
consequently suitable for measuring this effect in which the corresponding 
evolution phase containing the effect exhibits a refocussing interval. 
As shown in FIG. 5, the formation of a normal spin echo can be initially 
utilized for this purpose. The RARE sequence which results therefore 
comprises a first refocussing interval with a long echo time 
2.multidot.t.sub.e1 in contrast to which, the signal production is 
effected by means of a rapid sequence of spin echoes with generally 
shorter echo time. 
As shown in FIG. 6, the utilization of a stimulated echo through the 
introduction of two 90.degree. pulses in the evolution time is likewise 
sensitive to dynamic susceptibility. This is particularly the case when 
very long preparation times are to be utilized for the measurement of 
small effects since the slower signal decay during the t.sub.m interval 
with the longitudinal relaxation time T.sub.1 compensates by 50% for the 
inherent signal loss in comparison to the spin echo, since the latter 
decays in biological tissue with the often drastically shorter T.sub.2 
relaxation time. 
2. Motion and diffusion measurements 
As shown in FIGS. 7a and 7b, the macroscopic motion as well as the 
diffusion of spins which also occurs in homogeneous fields, can be 
measured with the methods described in section 1.2 if additional magnetic 
field gradients are introduced in the evolution phase. The corresponding 
sequences are shown in FIGS. 7a and 7b whereby, in comparison to the 
sequences described in the preceding section, added gradients are drawn as 
shaded. 
The motion of the spins in the evolution phase leads to a phase change in 
the subsequently measured signals which can be determined either by direct 
measurement or through a reference experiment having differing motion 
encoding gradients, whereby such reference experiments are preferentially 
carried out either through the removal or inversion of the motion encoding 
gradient. In the case of microscopic diffusion, the stochastic dephasing 
of the spins within a voxel leads to a signal reduction. 
Through variation of the strength of these gradients in sequential 
experiments it is possible to quantitatively precisely determine the 
diffusion constants. 
In all methods described in sections 1.2 and 2 it is, for completeness, to 
be noted that the additional diffusion effects during the formation of the 
multi-echo train are small even though these, in their totality, last 
longer than the preparation interval since the diffusion effects with 
rapid refocussing in a multi-echo train are small. 
One additionally notes that, in the sequences shown in FIGS. 5 to 7, 
additional signals can occur during the formation of the echoes due to the 
application of non-ideal pulses analogous to the splitting of the signal 
into two groups shown in FIG. 2. These can be suppressed, analogously to 
the manner of FIGS. 4 and 5, by additional gradients.