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Volume-selective excitation. A novel approach to topical NMR
JOURNAL
OF MAGNETIC
RESONANCE
%,
350-354 (1984)
Volume-SelectiveExcitation. A Novel Approach to Topical NMR W. P. AUE, S. MULLER, T. A. CROSS, AND J. SEELIG Department ofBiophysica1 Chemistry, Biocenter of the University of Base!, CH-4056 Base/, Switzerland
ReceivedNovember 1, 1983
Topical nuclear magnetic resonance (TNMR) is a noninvasive and nonhazardous new technique to obtain high-resolution NMR spectra from a restricted region within a living system. It allows the collection of detailed information about molecular structure, concentration, kinetics, and metabolism in vivo. For detailed TNMR studies of a complex three-dimensional sample such as that of an animal, a precise method for volume selection is crucial. To give the rationale for the development of a new technique, the methods which are presently available to select a sensitive volume are compared briefly. In principle, TNMR spectra can be obtained indirectly via chemical-shift imaging (l-6), a method to investigate the distribution of various chemical compounds throughout the sample, although at significantly reduced sensitivity. To optimize sensitivity, as well as to simplify the experiment and data handling, it is advantageous to use a one-dimensional method to measure a TNMR spectrum. A number of different techniques have been described to restrict the size of the sensitive volume to a predetermined region of interest. They alI rely either on focusing the static magnetic field B0 or on localizing the rf field Br . The methods with static focusing of B0 (7, 8) make use of the fact that highresolution NMR spectra can be obtained only in a volume with high B0 homogeneity. Outside this region, the spectral lines are very much broadened and therefore do not contribute much signal. At the present time, the position of the focused Bo is restricted to the center of the magnet system, which then requires the object under investigation to be moved for every new volume element of interest. Dynamic focusing of BO has also been proposed (9, 10). In this, a steady-state free-precession experiment is performed under the influence of slowly varying linear BO gradients, which eliminate signal contributions from volumes with time dependent Bo. Although this approach allows the selective volume to be moved easily, it su8ers from ill defined boundaries of the sensitive volume and corresponding lineshape problems. The most common method to localize the rf field is the use of a surface rf coil (II). As the name implies, its application is normally restricted to the surface of samples, although efforts have been taken to push the sensitive volume deeper inside the sample by means of special pulse sequences (12, 13). The inherent drawbacks of the methods mentioned above provided the impetus to develop volume-selective excitation (VSE) to localize the sensitive volume. VSE, for which a possible pulse and gradient sequence is given in Fig. 1, is actually a 0022-2X4/84 $3.00 Copyright @I 1964 by Academic hs, Inc. All rights of reproduction in any form reserved.
350
351
COMMUNICATIONS
I GX
GY
Acq.
Gz
FIG. 1. Radiofrequency pulse and 8, gradient sequence for volume-selective excitation. The one-dimensional process consists of a 45” selective, a 90” broadband, and a 45” selective rf pulse, all about the same axis, in the presence of a & gradient. This preserves z-axis magnetization in the selected plane orthogonal to the direction of the B,, gradient and produces transverse magnetization elsewhere. AtIer three such steps, the volume element common to the three orthogonal selected planes contains negative z magnetization which is then observed with a normal broadband pulse under high-resolution conditions.
straightforward extension of a technique to excite selectively a plane in an object for NMR tomography (24). The effect of a single 45”,,~,,-90”-45”,~“~ pulse sandwich in the presence of a &, gradient is to preserve z-axis magnetization in the plane of interest and generate transverse magnetization elsewhere. After the application of three pulse sandwiches with orthogonal gradients, negative z magnetization is left in the sensitive volume, which can be detected with an additional nonselective observation pulse in the absence of any B0 gradients in the same way as a conventional highresolution NMR spectrum. The magnetization outside the volume of interest will dephase under the influence of the B0 gradients and therefore will not contribute any observable signal. Since VSE depends on flip angles, it requires high rf homogeneity over the whole object under investigation. With the spectrometer frequency on resonance in the absence of B0 gradients, the position of the sensitive volume will be at the center of the magnet system. It can be moved to different positions by switching the frequency between the different pulse sandwiches. Furthermore, the size of the sensitive volume can be adjusted separately in the three directions with appropriate combinations of B0 gradient strength and width of the selective pulse. To demonstrate the performance of VSE, we choose the following procedure: First, we record NMR proton images of the object under investigation in order to define the region of interest. Next, we adjust the sensitive volume to the region of interest, and finally, we measure its high-resolution spectrum. We believe, that this procedure will be typical for many medical and biological applications. The object of our preliminary investigations is a phantom, which consists of a plexiglass cube containing 27 polyethylene spheres of 20 mm outer diameter arranged in a simple cubic lattice. The center sphere contains cyclohexane, whereas 18 surrounding spheres are filled with benzene. The arrangement of the filled spheres is given in Fig. 2 by means of three NMR tomograms showing three consecutive planes within the phantom. The tomograms were obtained with the projection reconstruction technique (15) and yield a resolution which is sufficient to clearly recognize the plastic stoppers and small air bubbles in the spheres. We now focus our attention on the region of interest, namely the cyclohexane sphere, and measure its high-resolution spectrum applying the experiment shown in
352
COMMUNICATIONS
FIG. 2. bstration of the phantom used in our preliminary VSE experiments. A plexigh cube is packed with 27 polyethylene spheres of20 mm o.d. in a simple cubiclattitice. The a%er sphere contains cyctohexane, I8 neighboring spheres benzene. The arrangement of the fuIl spheres (open circles) is given schematically and atso by means of thaw NMR tomograms representing cfosc sections through three consecutive planes within the phantom as indicated by the dotted lks.
Fig. 1. The sptzctra resulting from the stepwise selection pare given in Fig. 3: In (a), the normal ‘H spectrum of the whole phantom is shown with 18 spheres contributing to the benzene signal and a single sphere yielding the cyclohexane peak. Because of the considerable dimensions of the phantom (2 16 cm3), the benzene signals from the outer spheres are broadened somewhat by BO inhomogeneity. In (b), the contributions from the 12 benzene spheres in the left and right planes of the phantom have been eliminated by a onedmensional: selection process. In (c), a twadimensianal selection eliminated 4 more spheres above and below the cyclohexane. In (d), the
4
b)
4
d)
FIG. 3. I-I@-resulutioa ‘H NMR spectra of a thretdimensional phantom demonstrating the stepwise sleetion of a wnsitive volume with VW See text for exphnatkns.
COMMUNICATIONS
353
cyclohexane peak is observed exclusively with the contributions from the 18 benzene spheres suppressed. The expansion emphasizes both the better than loo-fold suppression of the signals from the surrounding spheres and the good lineshape of the cyclohexane peak. The full width at half height of the cyclohexane line is about 0.7 ppm at the present time and wiIl be significantly reduced after the software is modified to allow shimming B,-, on the selected volume. In summary, VSE has the following advantages: (i) The sensitive volume can be moved to any position in the magnet system and is clearly defined, Most important for biological applications, it is not restricted to the surface of the sample. (ii) Since the spectrum is acquired in the absence of any B,-,gradient, the homogeneity in the selected volume can be optimized and the TNMR spectra are obtained with good lineshape and resolution. (iii) The method is one-dimensional and therefore features good sensitivity, a simple experimental design and easy data handling. With all these advantages, VSE has only two restrictions of minor practical importance. First, since B. gradients and frequency selective rf pulses are applied, there is an ambiguity between the influence of the chemical shift and the B. gradient on the Larmor frequency of the spins during the selection process. With weak B. gradients, chemical compounds with very different chemical shifts would be excited at different positions in the sample. This restricts the application of VSE for very accurate localization to conditions where the linear B. gradients are strong compared to the chemical-shift dispersion of the spin system under investigation. On the spectrometer used, the linear x, y, and z gradients measure approximately 12 ppm/mm. This means, that for protons the inaccuracy in localization of the selective volume is
354 der Schweiz, postdoctoral
COMMUNICATIONS and the Fritz fellowship.
Ho&nann-La
Roche
Foundation.
T.A.C.
is a recipient
of a 1983 NATO
REFERENCES
1. A. KUMAR,
D. WELTI, AND R. R. ERNST, J. Magn. Reson. 18, 69 (1975). 2. T. R. BROWN, B. M. KINCAID, AND K. UGURBIL, Proc. Nut. Acud. Sci. USA 79, 3523 (1982). 3. A. A. MAUDSLEY, S. K. HILAL, W. H. PERMAN, AND H. E. SIMON, J. Mu@. Reson. 51, 147 (1983). 4. P. C. LAUTEREIUR, D. M. KRAMER, W. V. HOUSE, AND C.-N. CHEN, J. Am. Chem. Sot. 97, 6866 (1975); P. BENDEL, C.-M. LAI, AND P. C. LAUTERBUR, J. Magn. Reson. 38, 343 (1980). 5. L. D. HALL AND S. SUKUMAR, J. Magn. Reson. 50, 16 1 (1982). 6. S. J. Cox AND P. STYLES, J. Mugn. Reson. 40, 209 (1980). 7. R. DAMADIAN, L. MINKOFF, M. GOLDSMITH, M. STANFORD, AND J. KOUTCHER, Science 194, 1430 (1976). 8. R. E. GORDON, P. E. HANLEY, D. SHAW, D. G. GADIAN. G. K. RADDA, P. STOLES, P. J. BORE, ANLI L. CHAN, Nature (London) 287, 736 (1980). 9. W. S. HINSHAW, J. Appf. Phys. 47, 3709 (1976). 10. K. N. Scorn, H. R. BROOKER, J. R. RTZSIMMONS, H. F. BENNETT, AND R. C. MICK, J. Mugn. Reson. 50, 339 (1982). 11. J. J. H. ACKERMAN, T. H. GROVE, G. C. WONG, D. G. GADIAN, AND G. K. RADDA, Nature (London) 283, 167 (1980). 12. M. R. BENDALL AND R. E. GORDON, J. Magn. Reson. 53, 365 (1983). 13. M. R. BENDALL AND W. P. AUE, J. Mugn. Reson. 54, 149 (1983). 14. A. N. GARROWAY, P. K. GRANNELL, AND P. MANSFIELD, J. Phys. C 7, L457 (1974). 15. P. C. LAUTERBUR, Nature (London) 242, 190 (1973).
OF MAGNETIC
RESONANCE
%,
350-354 (1984)
Volume-SelectiveExcitation. A Novel Approach to Topical NMR W. P. AUE, S. MULLER, T. A. CROSS, AND J. SEELIG Department ofBiophysica1 Chemistry, Biocenter of the University of Base!, CH-4056 Base/, Switzerland
ReceivedNovember 1, 1983
Topical nuclear magnetic resonance (TNMR) is a noninvasive and nonhazardous new technique to obtain high-resolution NMR spectra from a restricted region within a living system. It allows the collection of detailed information about molecular structure, concentration, kinetics, and metabolism in vivo. For detailed TNMR studies of a complex three-dimensional sample such as that of an animal, a precise method for volume selection is crucial. To give the rationale for the development of a new technique, the methods which are presently available to select a sensitive volume are compared briefly. In principle, TNMR spectra can be obtained indirectly via chemical-shift imaging (l-6), a method to investigate the distribution of various chemical compounds throughout the sample, although at significantly reduced sensitivity. To optimize sensitivity, as well as to simplify the experiment and data handling, it is advantageous to use a one-dimensional method to measure a TNMR spectrum. A number of different techniques have been described to restrict the size of the sensitive volume to a predetermined region of interest. They alI rely either on focusing the static magnetic field B0 or on localizing the rf field Br . The methods with static focusing of B0 (7, 8) make use of the fact that highresolution NMR spectra can be obtained only in a volume with high B0 homogeneity. Outside this region, the spectral lines are very much broadened and therefore do not contribute much signal. At the present time, the position of the focused Bo is restricted to the center of the magnet system, which then requires the object under investigation to be moved for every new volume element of interest. Dynamic focusing of BO has also been proposed (9, 10). In this, a steady-state free-precession experiment is performed under the influence of slowly varying linear BO gradients, which eliminate signal contributions from volumes with time dependent Bo. Although this approach allows the selective volume to be moved easily, it su8ers from ill defined boundaries of the sensitive volume and corresponding lineshape problems. The most common method to localize the rf field is the use of a surface rf coil (II). As the name implies, its application is normally restricted to the surface of samples, although efforts have been taken to push the sensitive volume deeper inside the sample by means of special pulse sequences (12, 13). The inherent drawbacks of the methods mentioned above provided the impetus to develop volume-selective excitation (VSE) to localize the sensitive volume. VSE, for which a possible pulse and gradient sequence is given in Fig. 1, is actually a 0022-2X4/84 $3.00 Copyright @I 1964 by Academic hs, Inc. All rights of reproduction in any form reserved.
350
351
COMMUNICATIONS
I GX
GY
Acq.
Gz
FIG. 1. Radiofrequency pulse and 8, gradient sequence for volume-selective excitation. The one-dimensional process consists of a 45” selective, a 90” broadband, and a 45” selective rf pulse, all about the same axis, in the presence of a & gradient. This preserves z-axis magnetization in the selected plane orthogonal to the direction of the B,, gradient and produces transverse magnetization elsewhere. AtIer three such steps, the volume element common to the three orthogonal selected planes contains negative z magnetization which is then observed with a normal broadband pulse under high-resolution conditions.
straightforward extension of a technique to excite selectively a plane in an object for NMR tomography (24). The effect of a single 45”,,~,,-90”-45”,~“~ pulse sandwich in the presence of a &, gradient is to preserve z-axis magnetization in the plane of interest and generate transverse magnetization elsewhere. After the application of three pulse sandwiches with orthogonal gradients, negative z magnetization is left in the sensitive volume, which can be detected with an additional nonselective observation pulse in the absence of any B0 gradients in the same way as a conventional highresolution NMR spectrum. The magnetization outside the volume of interest will dephase under the influence of the B0 gradients and therefore will not contribute any observable signal. Since VSE depends on flip angles, it requires high rf homogeneity over the whole object under investigation. With the spectrometer frequency on resonance in the absence of B0 gradients, the position of the sensitive volume will be at the center of the magnet system. It can be moved to different positions by switching the frequency between the different pulse sandwiches. Furthermore, the size of the sensitive volume can be adjusted separately in the three directions with appropriate combinations of B0 gradient strength and width of the selective pulse. To demonstrate the performance of VSE, we choose the following procedure: First, we record NMR proton images of the object under investigation in order to define the region of interest. Next, we adjust the sensitive volume to the region of interest, and finally, we measure its high-resolution spectrum. We believe, that this procedure will be typical for many medical and biological applications. The object of our preliminary investigations is a phantom, which consists of a plexiglass cube containing 27 polyethylene spheres of 20 mm outer diameter arranged in a simple cubic lattice. The center sphere contains cyclohexane, whereas 18 surrounding spheres are filled with benzene. The arrangement of the filled spheres is given in Fig. 2 by means of three NMR tomograms showing three consecutive planes within the phantom. The tomograms were obtained with the projection reconstruction technique (15) and yield a resolution which is sufficient to clearly recognize the plastic stoppers and small air bubbles in the spheres. We now focus our attention on the region of interest, namely the cyclohexane sphere, and measure its high-resolution spectrum applying the experiment shown in
352
COMMUNICATIONS
FIG. 2. bstration of the phantom used in our preliminary VSE experiments. A plexigh cube is packed with 27 polyethylene spheres of20 mm o.d. in a simple cubiclattitice. The a%er sphere contains cyctohexane, I8 neighboring spheres benzene. The arrangement of the fuIl spheres (open circles) is given schematically and atso by means of thaw NMR tomograms representing cfosc sections through three consecutive planes within the phantom as indicated by the dotted lks.
Fig. 1. The sptzctra resulting from the stepwise selection pare given in Fig. 3: In (a), the normal ‘H spectrum of the whole phantom is shown with 18 spheres contributing to the benzene signal and a single sphere yielding the cyclohexane peak. Because of the considerable dimensions of the phantom (2 16 cm3), the benzene signals from the outer spheres are broadened somewhat by BO inhomogeneity. In (b), the contributions from the 12 benzene spheres in the left and right planes of the phantom have been eliminated by a onedmensional: selection process. In (c), a twadimensianal selection eliminated 4 more spheres above and below the cyclohexane. In (d), the
4
b)
4
d)
FIG. 3. I-I@-resulutioa ‘H NMR spectra of a thretdimensional phantom demonstrating the stepwise sleetion of a wnsitive volume with VW See text for exphnatkns.
COMMUNICATIONS
353
cyclohexane peak is observed exclusively with the contributions from the 18 benzene spheres suppressed. The expansion emphasizes both the better than loo-fold suppression of the signals from the surrounding spheres and the good lineshape of the cyclohexane peak. The full width at half height of the cyclohexane line is about 0.7 ppm at the present time and wiIl be significantly reduced after the software is modified to allow shimming B,-, on the selected volume. In summary, VSE has the following advantages: (i) The sensitive volume can be moved to any position in the magnet system and is clearly defined, Most important for biological applications, it is not restricted to the surface of the sample. (ii) Since the spectrum is acquired in the absence of any B,-,gradient, the homogeneity in the selected volume can be optimized and the TNMR spectra are obtained with good lineshape and resolution. (iii) The method is one-dimensional and therefore features good sensitivity, a simple experimental design and easy data handling. With all these advantages, VSE has only two restrictions of minor practical importance. First, since B. gradients and frequency selective rf pulses are applied, there is an ambiguity between the influence of the chemical shift and the B. gradient on the Larmor frequency of the spins during the selection process. With weak B. gradients, chemical compounds with very different chemical shifts would be excited at different positions in the sample. This restricts the application of VSE for very accurate localization to conditions where the linear B. gradients are strong compared to the chemical-shift dispersion of the spin system under investigation. On the spectrometer used, the linear x, y, and z gradients measure approximately 12 ppm/mm. This means, that for protons the inaccuracy in localization of the selective volume is
354 der Schweiz, postdoctoral
COMMUNICATIONS and the Fritz fellowship.
Ho&nann-La
Roche
Foundation.
T.A.C.
is a recipient
of a 1983 NATO
REFERENCES
1. A. KUMAR,
D. WELTI, AND R. R. ERNST, J. Magn. Reson. 18, 69 (1975). 2. T. R. BROWN, B. M. KINCAID, AND K. UGURBIL, Proc. Nut. Acud. Sci. USA 79, 3523 (1982). 3. A. A. MAUDSLEY, S. K. HILAL, W. H. PERMAN, AND H. E. SIMON, J. Mu@. Reson. 51, 147 (1983). 4. P. C. LAUTEREIUR, D. M. KRAMER, W. V. HOUSE, AND C.-N. CHEN, J. Am. Chem. Sot. 97, 6866 (1975); P. BENDEL, C.-M. LAI, AND P. C. LAUTERBUR, J. Magn. Reson. 38, 343 (1980). 5. L. D. HALL AND S. SUKUMAR, J. Magn. Reson. 50, 16 1 (1982). 6. S. J. Cox AND P. STYLES, J. Mugn. Reson. 40, 209 (1980). 7. R. DAMADIAN, L. MINKOFF, M. GOLDSMITH, M. STANFORD, AND J. KOUTCHER, Science 194, 1430 (1976). 8. R. E. GORDON, P. E. HANLEY, D. SHAW, D. G. GADIAN. G. K. RADDA, P. STOLES, P. J. BORE, ANLI L. CHAN, Nature (London) 287, 736 (1980). 9. W. S. HINSHAW, J. Appf. Phys. 47, 3709 (1976). 10. K. N. Scorn, H. R. BROOKER, J. R. RTZSIMMONS, H. F. BENNETT, AND R. C. MICK, J. Mugn. Reson. 50, 339 (1982). 11. J. J. H. ACKERMAN, T. H. GROVE, G. C. WONG, D. G. GADIAN, AND G. K. RADDA, Nature (London) 283, 167 (1980). 12. M. R. BENDALL AND R. E. GORDON, J. Magn. Reson. 53, 365 (1983). 13. M. R. BENDALL AND W. P. AUE, J. Mugn. Reson. 54, 149 (1983). 14. A. N. GARROWAY, P. K. GRANNELL, AND P. MANSFIELD, J. Phys. C 7, L457 (1974). 15. P. C. LAUTERBUR, Nature (London) 242, 190 (1973).