Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
  • G01R33/48—NMR imaging systems
  • G01R33/483—NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
  • G01R33/4838—NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy using spatially selective suppression or saturation of MR signals

Definitions

• This invention concerns nuclear magnetic resonance and is particularly concerned with method and apparatus for selecting regions of interest from a volume which is considerably greater in size than the region of interest.
• volume selective nuclear magnetic resonance As the use of volume selective nuclear magnetic resonance has become more widespread, both for "high resolution spectroscopy” and for “zoom-imaging”, so techniques for extracting signal from a reduced volume of spins within an extended sample have proliferated.
• the most versatile and generally applicable are those involving magnetic field B gradients in conjunction with selective Rf pulses and they fall broadly into two groups: techniques which achieve localisation by selectively exciting spins inside the volume of interest and those which saturate all the magnetisation except that within the volume of interest.
• DRESS (2) achieves good sensitivity with surface coils but also suffers from 2 limitations
• OSIRI (3) technique is useful for observing fast relaxing magnetisation although its suffers from pulse bandwidth limitations and unlike STEAM, it is not feasible to shim on the selected volume.
• New techniques have recently been developed (4,5) which achieve 2D selective excitation in the single radiofrequency/gradient pulse and are much less limited by 2 relaxation. However they also suffer from problems such as poor outer volume suppression, difficulty in moving the selected volume under computer control and off resonance effects.
• the present invention has as its object a new technique for selective saturation, involving noise modulated RF pulses, which overcomes many of the problems outlined above while producing a well defined, non-rectilinear, volume of interest which can be moved anywhere within the sample and which is variable over a wide range of shapes and sizes.
• Random noise generation algorithms are now available for many computer systems,- and it is easy to generate a frequency response function which is random except for a small region of zero amplitude (see Figure 7a).
• Fourier transforma ion of this yields a pseud ⁇ -random modulation function (see Figure 7b), which may be used to modulate an RF signal so as to produce a modulation envelope similar to Figure 7(b) (see Reference 10).
• an Rf pulse having such an envelope is applied to a homogenous sample located in a magnetic field gradient, (which alters the magnetic resonance frequency of the material forming the sample profile in the direction of the gradient) the nuclear spins will be rotated through random angles about random axes except for nucieii within any region along the gradient at which the nuclear magnetic resonance frequency of the material has no corresponding energy component in the RF pulse.
• Noise pulses have been used previously in volume selection, in OSIRIS, where they are used to reduce the subtraction errors in the ISIS experiment (see Reference 11). In that case however the same noise pulse is used, in order to give the same frequency response, for each stage in the subtraction cycle.
• a single noise pulse cannot achieve complete saturation of the required magnetisation, for, whilst an ideal noise pulse may distribute the magnetisation vectors evenly over a sphere, (with random phase and flip-angle over the whole bandwidth) it will do so reproducibly; the pseudo-random pattern of magnetisation produced relates directly to the particular noise pulse used. This is why such pulses work with the ISIS subtraction experiment (see Reference 11).
• a small volume within a large object be defined by using a small radio frequency coil to limit the volume of the object which is influenced by the radiofrequency field.
• the radiofrequency field is not always homogeneous, nor is it always closely matched in shape to the region of interst.
• the invention also has as an object a new technique for selective saturation, involving noise modulated RF pulses, which overcomes many of the problems outlined above while producing a well defined volume of interest which can be moved anywhere within the sample and which is variable over a wide range of shapes and sizes.
• a method of selecting a region of interest within an object whose nuclear magnetic resonance is to be investigated in which the object is located within a zone within a generally uniform intense magnetic field, which zone is influenced not only by the intense field but also by two or more local magnetic fields, so that within the zone a magnetic field gradient exists so that different regions of the object are influenced by different magnetic field intensities to therefore possess differing magnetic resonance frequencies characterised in that the local magnetic fields are varied so that the direction of the magnetic field gradient across the zone is incrementally rotated through a number of discrete positions and an RF signal having a broad spectrum of finite energy frequency components and a defined band of zero or very low energy frequency components, is applied after each incremental step, so as* to cause random nuclear spin orientations of nucleii in the object material located in those parts of the zone for which the RF signal contains energy at the appropriate frequency, but no changes in the orientation of the nuclear spins of nucleii located in those parts of the object material for which the RF signal does not contain energy at the appropriate
• each RF signal is only required to achieve partial saturation of the magnetisation so that much less RF power is required amp-1-i-fier than if saturation is required to be obtained from one burst of RF signal. This is an important factor in clinical applications of the invention where RF power must usually be limited.
• a surface coil may be employed to give increased sensitivity.
• the invention thus provides a method o ⁇ single shot localisation by selective saturation, using a pre-pulse which may be placed at the start of any pulse sequence.
• This method uses "rotating" field gradients and noise modulated RF pulses, the latter with a low power and RF field homogeneity requirement which should allow its use with surface cells.
• the method appears to be applicable to work on both protons and phosphorus.
• Movement of the selected volume by altering the field gradient and/or the RF signal zero energy components may be under computer control and the fact that the non- rectilinear shape is variable over a wide range, generally allows much closer tailoring of the selected region to the region of interest in the sample.
• the invention can be further understood by considering two tubes of water. If the magnetic field (B ) is homogeneous over the entire sample, then all the water protons will resonate at the same frequency. Spatial information can be encoded by applying a linear variation of magnetic field across the sample (a field gradient), so that
• “Slice-selection” in accordance with the invention is achieved by using a frequency-selective RF signal (ie one in which some of the frequency components in the Rf signal are at zero (or very low) energy so that protons having those resonant frequencies are not energised and their spin axes remain aligned). Such a signal will only influence part of the sample.
• the slice position can be varied by changing the band of frequencies within the RF signal.
• the slice thickness depends on the bandwidth of the zero (or very low) energy frequency components in the RF signal.
• an RF carrier is modulated using noise pulses which are optimised by in every case having zero energy components over the same part of their frequency spectrum and a random selection of high energy frequency components outside that part of their spectrum.
• the method isolates a volume of spins in 2 or 3 dimensions, within a larger sample, by selectively saturating spins outside the said volume.
• Selective saturation is relatively common for removing resonance lines in spectroscopy [J.Chem.Phys. vol59, number 4, p1775 1973] and has been used in an early imaging procedure [J.Phys C. vol17, L457 1974]. It has been used for volume selective spectroscopy such as in [J.Mag.Res. 70 319-326 1986] where saturation outside the volume of interest is achieved by creating coherent magnetisation and then dephasing it with gradients. This requires both good RF homogeneity and a high power amplifier.
• OSIRIS J.Mag.Res 78 519-527 1988
• OSIRIS uses noise pulses in volume localisaton but not for saturation and can only inspect rectilinear regions of interest.
• the present invention allows arbitrary regions to be defined by superimposing multiple projections.
• Such methods include; VSE(6),SPARS(7),SPACE(8) and DIGGER (9). All of these selectively create transverse magnetisation outside the volume of interest at some point in the pulse-sequence which is then dephased by the applied field gradients, while magnetisation inside the volume of interest is stored along the Z axis.
• a problem common to all these existing techniques is the high RF power level required to saturate all the spins in the outer volume.
• Other problems associated with pulse bandwidth and pulse imperfections mean that spins near the edge of the sample are not fully saturated while some magnetisation is excited inside the volume of interest. Also, since these techniques all depend on accurate pulse flip angles, good B ⁇ field homogeneity is required which rules out their implementation with surface coils.
• a noise window pulse applied with a constant magnetic field gradient may produce points along the gradient axis, away from the central window, where magnetisation is hardly excited at all and others where it is flipped about 180 degrees, so that even multiple applications of this pulse will leave some Z magnetisation outside the selected volume.
• a "rod" of unperturbed spins can be selected by using the same noise pulse successively, but with the field gradient applied in a different direction each time.
• the cross section of the "rod” is dependant on the variation of the magnetic field (ie the gradient) which can be kept constant or varied between incremental repositioning thereof.
• the invention is of particular merit in the following applications:
• This invention enables any arbitrarily shaped region of interest to be defined within an object. Thereafter, that volume can be studied by magnetic resonance (MR) in a variety of different ways, of which examples are specified below.
• MR magnetic resonance
• the invention can be added as a "module" ahead of, during, or after, any other MR sequence already in use.
• the method selectively saturates the magnetisation of all the spins outside the volume of interest whose MR- signals are thereby suppressed, leaving that of the spins within the volume available for study. Saturation is achieved by use of optimised, pseudo-noise, modulated radiofrequency pulses applied in the presence of tailored gradient waveforms.
• the volume of interest can be interrogated by any class of NMR spectroscopic measurement, whether one-dimensional, two-dimensional or three-dimensional.
• the region defined by the volume of interest can be subjected to imaging by any known method.
• MR can be used to measure quantitatively the movement of liquids - either flow, diffusion or perfusion.
• the invention can be used to saturate all spins except those of a small volume, and then to monitor the movement of those spins from that small volume. (This is known as saturation transfer).
• the invention can be used to define and sample the magnetisation of the region of interest, by saturation of other regions.
• a column of spins can be defined which is either perpendicular, parallel or oblique, with respect to the plane of a surface coil, and then studied using rotating frame zeugmatography, or gradient phase encoding.
• the invention makes feasible a variety of measurements that would otherwise be either impossible, or very difficult.
• the following are given by way of example:
• the B -field is arranged to be homogeneous over the entire diameter of the object, although the homogeneity may fall off along the length.
• the choice of magnets means that this relationship cannot be achieved and the static magnetic field (B Q ) is inhomogeneous. This will mean that MR signals from the region of interest will be degraded by those from those portions of the object which experience the low-grade field.
• all signals can be saturated except those from a defined region of interest which can be "tuned” and positioned to coincide with either the appropriate region within the object, or within the magnet. Importantly, this relationship can be varied from one study to the next.
• the defined region of interest can have any arbitrary shape defined by convex surfaces. (This is to be compared with most available methods which are restricted solely to rectilinear shapes).
• the NMR technique in accordance with the invention, is a method for defining a reduced region within an object under investigation so as to reduce or eliminate the signal from other areas. It involves applying a series of slice selective RF pulses in conjunction with a magnetic field gradient which changes direction after each pulse. Each of these pulses acts to randomise the spins in the sample except within a plane of well defined width and orientation (determined by the gradient direction) where spins are undisturbed. The region of coincidence of all these null slices defines a volume of intact magnetisation which may be interrogated without interference from spins outside this region all of which are saturated.
• STEAM Selective excitation sequences
• T 2 relaxation which is not the case for the invention as it leaves the region unperturbed and is sensitive to T- relaxation
• Rectilinear regions are not always ideal, particularly in-vivo, although conformal versions of the technique are being developed in conjunction. ith d).
• the invention can easily define conformal (non-rectilinear) regions.
• 2D K-space pulses can excite non-rectilinear regions without the need for a spin-echo. They still cannot be used for the shorter 2 species and have some chemical shift sensitivity.
• the invention can define 3D as well as 2D regions and has a more useful chemical shift artefact (see below).
• DIGGER Selective saturation sequences
• each slice is shifted an amount in the gradient direction. This results in a blurring of the region of interest (ROD for the other species, and for narrow bandwidth pulses could be eliminated altogether.
• Remnant coherence in the transverse magnetisation produced by the method of the invention can appear in an FID or simulated echo as contamination. Including side lobes on the cosine gradient waveform can dephase this and avoid the problem. Other gradients in the succeeding sequence may have the same effect.
• Arbitrary convex volumes may be optimised by varying the angle between successive gradient steps according to the shape being selected.
• the invention may be performing using a surface coil to receive, and possibly to transmit also, if the noise pulses are capable of exciting magnetisation to sufficient depth without nulls.
• Optimum use of receiver bandwidth, in imaging may be obtained by following the method of the invention with an imaging sequence, thus potentially improving signal to noise by just collecting signal from the ROI.
• Zoomed images of the ROI, without aliassing, can be obtained by following the method of the invention with an imaging sequence with increased gradients or reduced sweep width.
• a multislice imaging sequence can then follow.
• the tendency of the nucleii in the material surrounding the region of interest to revert to their initial spin state during the multislice imaging sequence can cause contaimination in later ones of the multislice images.
• One way to avoid this is to use a 2 shot process. This involves waiting after the first multislice imaging sequence for the system to fully revert to its initial spin state and then repeat the selection process of the invention before repeating the multislice imaging sequence, applying an RF inversion pulse so as to rotate the spin axis of all nucleii (both inside the reion of interest a well as outside) though 180°.
• the results of the subsequent multislice imaging sequence may then be subtracted from those of the first multislice imaging sequence to eliminate contamination effects due to the previously mentioned reversion (relaxation) of the nucleii in the surrounding material.
• Volume selective snapshot images can be obtained by following the method of the invention with a fast imaging technique.
• EPI is favourable because its low RF power dissipation makes up for the power dissipated by the invention.
• Other possibilities include FLASH or CEFAST.
• a 3D image of the selected volume can be made by following the method of the invention with a suitable imaging sequence.
• Volume selective maps can be made of Chemical shift/Perfusion/Diffusion/relaxation/flow.
• Motion artefacts in vivo can be reduced by suppressing regions most responsible for the artefact, e.g. fat layers with respiratory motion or the heart in upper spine studies.
• a spectra from an FID may be obtained by applying a hard or soft excitation pulse immediately after the inventive selection method to avoid the need for a spin echo.
• a prefocussed pulse can be used for excitation so that the slice gradient also acts as a crusher for unwanted transverse magnetisation.
• Signal-to-noise can be optimised by making the selected region conformal to the ROI using a conformal method according to the invention in 2 and 3 dimensions.
• Diffusion/perfusion/flow can also be measured selectively.
• Figure 1(a) shows a simple three-step saturation sequence
• Figure 1(b) illustrates the idealised 2D response to the sequence of Figure 1(a);
• Figure 2 illustrates an example of a selective saturation prepulse
• Figure 3 shows a simulated 2D effect using a 32 step version of a pre-pulse, and is a profile along the diameter of the selected region;
• Figure 4(a) and (b) show the amplitude and phase of the response to a simple noise-window pulse when (c) and (d) show the response to the optimised pulse used in the experimental work; (a) and (c) are thus the frequency spectra obtained by Fourier transformation, whilst (b) and (d) show the transverse magnetisation of a uniform spin system, obtained by integration of the Bloch equation;
• Figure 5A shows a slice through an agar phantom described in the text, with no selective pre-saturation pulse
• Figure 5B shows the same slice as Figure 5A acquired using the pre-pulse but with no RF power in the noise pulses so that any loss is due solely to eddy current.
• Figure 5C shows the same line as in 5(b) but using the noise pulses to select a small circular region in the centre by saturating all the magnetisation outside;
• Figure 5 also contains a profile through the centre of the three images, and it is to be noted that any variation in intensity from left to right across the image is due to B * inhomogeniety in the probe;
• Figure 6 illustrates how a volume of interest selected from a phantom may be moved around the sample
• Figure 7(a) shows the Fourier transform of the frequency response of a typical noise pulse
• Figure 7(b) shows the response of a uniform spin system to such a pulse.
• the invention lies in a method of using Nuclear Magnetic Resonance equipment and in such equipment when programmed to operate in accordance with the invention.
• NMR apparatus For a general discussion of NMR apparatus, reference is made to the textbook by E. Fukushima, S.B.W. Roeder, "Experimental Pulse NMR”. Addison-Wesley, (1981).
• the B field gradient vector is incrementally rotated so as typically to describe a circle, in a number of discrete steps, while the RF is pulsed after each adjustment of the magnetic field gradient vector direction.
• Figure 1a shows a simple three-step case
• Figure 1b illustrates the ideal response from a uniform plane of spins; the shading represents partial saturation, the darker the shading the greater the degree of saturation.
• this technique is conceptually analogous to the back-projection (12,13) method for image reconstructions.
• Figure 2 shows a typical presaturation pulse where the gradient vector describes a circle and Figure 3 shows the simulated idealized response to such a prepulse with 32 gradient steps.
• the RF power is set so that 99% saturation occurs away from the circular region of interest, when each individual pulse reduces the Z magnetisation by only 14%.
• Figure 5 this simulation is in excellent agreement with experimental results and also illustrates one of the advantages of this technique in that since each RF pulse is only required to achieve partial saturation of the magnetisation, much less RF power is required than if saturation is required every one RF burst.
• Figure 4b shows the transverse response of a uniform spin system to this pulse, calculated to the same resolution as in the frequency spectrum by iterative integration of the Bloch equation using rotation matrices, with the pulse scaled to give zero average Z magnetisation outside the selected region.
• a significant amount of magnetisation is excited within the central region due to a combination of the effects of pulse truncation (giving the high frequency oscillations) and spin system nonlinearity. Since this reduction in longitudinal magnetisation will cause signal loss from the volume of interest when several noise pulses are applied successively, some pulse optimisation is clearly necessary.
• Previous work on noise-modulated RF pulses (14) has concentrated on improving "randomisation" and bandwidth, whereas the invention aims to improve the excitation null in the central window.
• the pulse truncation effect can be reduced by multiplying the noise function used by a Gaussian envelope so that the convolving function in the frequency domain is another smooth Gaussian. However this takes no account of the nonlinearities.
• a simple iterative process may therefore be used by which integration of the Bloch equation yields the response of a uniform spin-system to an initial RF pulse shaped as shown in Figure 7(b).
• the response is first modified by setting all points within the 5% central window to zero, this being the most desired feature of the response, and then Fourier transformed to give an approximate RF pulse shape. This can be inserted into the Bloch equation integration routine and the process repeated.
• This algorithm gives pulse optimisation which is oscillatory.
• Figure 4c shows the much improved excitation null within the central window.
• Figure 4(d) shows the transverse response to the same pulse but with the scaling set to reduce the averge Z magnetisation by 14%, as used in the simulation, and illustrates the corresponding reduction in excited magnetisation with the central window.
• the magnitude of the transverse magnetisation created by this optimised pulse is more uniform than that created by the un- optimised pulse but the phase is still quite random and there is no problem with the creation of unwanted coherence.
• FIG. 5A shows a proton image of an 8 mm slice through this phantom, acquired in one scan using a standard spin-echo imaging sequence with no RF gradient pre-pulse, while Figure 5B shows an image acquired using the same sequence but with selective saturation pre-pulse and zero RF power for the noise pulses.
• the suppression ratio for signal from the outer volume can only be reliably measured by spectroscopy.
• the pulse sequence used for Figures 5b and 5c consisted of a selective pre-pulse with 32 gradient steps (an upper limit dictated by the spectrometer, due to memory constraints), followed by a standard slice-selected spin- echo imaging sequence of echo time 21ms. A stabilisation delay is left between the pre-pulse and the imaging sequence, in this case
• T 1 relaxation during the selection sequence may be a problem for some faster relaxing species, however, preliminary calculations indicate that this effect may be counteracted by increasing the RF power, although possibly at the expense of some signal loss from the region of interest.
• Pre-emphasis may be obviated by greatly increasing the number of. steps defining the gradient shape, so that the length of each step roughly corresponds to the gradient rise time.
• shielded gradient coils may be particularly advantageous to reduce the effect of eddy currents.
• a useful feature of the method of the invention is that non-rectilinear regions of interest may easily be defined by changing the field gradient producing waveforms in the pre-pulse from simple sine/cosine shapes.
• any non-reentrant shape may be defined with- 100% of the magnetisation available from within the selected region, introducing potential signal-to-noise ratio enhancements over the application of rectilinear sampling windows.
• the region of interest can be moved easily to any part of the sample by changing the frequency offsets for each of the noise pulses, according to the distance and direction of movement required and the strength of the field gradient.
• Figure 6(a) shows the image of a whole phantom with no volume selection.
• Figure 6(b) shows an elliptical volume of interest of elliptical section removed from the centre of the sample.
• a further change in the transmitter offset for each of the noise pulses in the selective saturation sequence was changed so as to move the selected volume to the edge of the sample as shown in Figure 6(c).
• the gradient waveforms were modified as well, to rotate the selected volume by 45° in the slice plane.

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