JOURNAL

OF MAGNETIC

RESONANCE

s&442-457

(1984)

Gaussian Pulses
CHRISTOPHER BAUER, RAY FREEMAN, TOM FRENIUEL,* JAMES REELER, AND A. J. SHAKA
Physical Chemistry Laboratory, Oxford University, Oxford, England Received December 15. 1983 An analysis is made of frequency-selective radiofrequency pulses used for high-resolution NMR studies of liquids. If the pulse envelope is rectangular, there are extensive sidelobes in the frequency-domain excitation pattern, whereas a Gaussian envelope gives a frequencydomain pattern (for the absolute-value mode) that is a slightly distorted Gaussian with no sidelobes. This affords much better selectivity. Furthermore the Gaussian pulse excites a signal with a phase angle which is almost a linear function of offset. The calculations are based on magnetization trajectories predicted by the Bloch equations, neglecting relaxation. It is shown that at appreciable olfsets from resonance the Gaussian pulse produces a characteristic teardrop trajectory which always terminates near the +Z axis, irrespective of offset AB. Examples of applications of Gaussian-shaped pulses include the investigation of the fine structure on carbon-13 resonances, selective coherence transfer experiments between protons, and nuclear Overhauser effect measurements in crowded proton spectra. INTRODUCTION

Several NMR experiments require the application of radiofrequency pulses that are selective in the frequency domain. Such soft pulses may be generated as a single burst of weak irradiation of relatively long duration (I) or as a train of repeated hard pulses with intervening periods of free precession (2). Selectivity is measured by the ability to excite a chosen resonance (or group of resonances) without appreciably affecting near neighbors. For a given net flip angle, selectivity is determined by the duration of the soft pulse or the total duration of the pulse train; it can be made very high, as demonstrated by experiments which burn a hole in an inhomogeneously broadened line (3). Normally the envelope of the pulse (or pulses) is rectangular since this is the simplest scheme to implement. Unfortunately this entails the existence of side lobes in the frequency-domain excitation function, approximating the form of a sin x/x function, since to a first approximation the time- and frequency-domain profiles form a Fourier transform pair. In some applications excitation by a side lobe could lead to ambiguous results. This article examines methods for suppressing these unwanted side lobes by shaping the pulse envelope to eliminate the step-function discontinuities as the pulse is switched on and off. Similar ideas have been used in NMR imaging experiments (4, 5) but not, apparently, in high-resolution spectroscopy. For simplicity the case of the single soft pulse is considered here; the extension to
* Present address: National Institute for Medical Research, Mill Hill, London, England OO22-2364184 $3.00
Copyright 0 1984 by Academic Press, Inc. All rights of reproduction in any form rescrxd.

442

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finite-length pulse trains of the DANTE type (2) should be straightforward. As for the problem of apodization of a truncated free induction signal, a plethora of possible shaping functions is available. It was decided to adopt a pulse envelope which is Gaussian in form, giving (in the linear response region) an excitation function in the frequency domain which is another Gaussian. Because the nuclear spin response to a pulse is not exactly linear, the Fourier transform relationship is only approximate and the actual excitation is somewhat flattened in the central region. A Gaussian curve has the useful property that the amplitude falls off quite rapidly in the tails.
THEORY

The form of the excitation as a function of frequency may be calculated from the transient solutions of the Bloch equations in the rotating reference frame. A radiofrequency pulse B,(t) is applied to a nuclear magnetization vector M = MO initially at equilibrium along the +Z axis of the rotating frame. For any arbitrary timedependence of B,(t) the exact trajectory of M during the pulse can be calculated for any offset from exact resonance AB. This gives the absorption and dispersion components of the signal at the end of the shaped pulse, as a function of AB. In these calculations relaxation during the pulse is assumed to be negligible; it could be included if necessary. For example, the excitation spectrum resulting from a rectangular pulse of amplitude B1 applied for a period zP, and of nominal flip angle a0 = yB,t, = 7r/2 rad, is easily shown analytically to give an absorption mode signal which varies with frequency according to My = Moao sinc[ao/7r sin 81 ill where tan 6 = B,/AB. This may be rewritten MY = Moao sinc[yB,t&r].

L4

where Bz = Bf + AB2. This excitation function is illustrated in Fig. 1, where it is compared with the approximate excitation function predicted by assuming a Fourier transform relationship, M, = Moao sinc[yABt,/a]. [31 Only near the exact resonance condition do the two curves differ significantly since at large offsets, B, z AB. Comparison qf Rectangular and Gaussian Pulses A Gaussian pulse envelope has the inherent problem that the tails must be truncated at some suitably low level in order to extinguish the radiofrequency field before signal acquisition or the application of subsequent pulses. In the present work this truncation is performed when the radiofrequency intensity falls below 1% of the maximum, ensuring that the step discontinuities are small. The pulse width is thus defined as the width between 1% points. An equivalent rectangular pulse is defined as one with the same width and the same integrated area, so both types of pulse have the same flip angle at exact resonance. In all that follows, comparisons between the two pulse shapes assume this condition of equivalence.

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OHz 300 FIG. 1. Absorption-mode signal excited by a 10 ms rectangular pulse of intensity yB,/Z?r = 25 Hz as a function of resonance offset. Curve (a) is obtained by calculating individual trajectories according to the Bloch equations, while curve (b) assumes a Fourier relationship between time- and frequency-domain functions. At exact resonance, curve (a) has unit intensity while curve (b) has intensity ?r/2. The two curves are nearly coincident for appreciable offsets AB 9 B, .

-300

For a pulse where the amplitude is time-dependent the calculation of the excitation spectrum must be performed numerically, the envelope being split into a series of short rectangular pulses of constant B, . Assuming a Gaussian envelope

B,(t) = B': exp[-a(t - tO)2],

the magnetization trajectories (Figs. 2 and 3) and the signal components after the pulse can be calculated. Figure 2 shows a family of trajectories near to resonance. The transverse signal components after the pulse are large and pass from pure ab-

FIG. 2. Trajectories computed according to the Bloch equations for a 10 ms Gaussian-shaped pulse of mean intensity yB,/2rr = 25 Hz acting on a magnetization vector initially along the +Z axis. All relaxation effects are neglected. The normalized offset parameters @B/B,) are (a) zero (a 90 pulse at exact resonance) (b) 2, (c) 4, (d) 6, (e) 8, and (f) 10. At larger offsets the curves approach the shape of the teardrop trajectories illustrated in Fig. 3.

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sorption at exact resonance (a) through dispersion (b), negative absorption (c), and negative dispersion (d), the intensity diminishing until for curve (f) it is almost negligible. Figure 3 shows trajectories for two much larger offsets. These stay close to the +Z axis and may thus be represented in projection on the XY plane. It is these trajectories which emphasize the difference between Gaussian and rectangular pulses. Offsets have been chosen where the excitation after the rectangular pulse is at the peak of a sidelobe. Note that at these offsets the Gaussian pulse (G) returns the nuclear magnetization vector to a point very close to the +Z axis. The trajectory is almost exactly symmetrical about the X2 plane and takes the form of a teardrop where the beginning and end of the trajectory correspond to slow nutation about a weak effective field (B, E AI?) while the center region corresponds to faster nutation (B, > As), The rectangular pulse (R) generates trajectories which are necessarily circular, and which leave the magnetization vector some significant distance from the +Z axis. The clue to the effectiveness of the shaped pulse at appreciable offsets is that the effective field direction moves gradually away from the 2 axis, accelerating until it reaches a maximum inclination 13 and then decelerates as it returns gradually to the Z axis. This motion of the effective field direction is symmetrical in time, with the magnetization vector at a maximum excursion from the Z axis at the center point of the pulse; the return half of the trajectory is a mirror image of the first half (with

a
-0.1 0 -0.1

b
0 0.1 Y

RI

I I \ G 1, ,/ \ G. .,

-0.2

-0.2

FIG. 3. Comparison of trajectories for a 10 ms rectangular pulse (R) and an equivalent Gaussian pulse (G) of intensity yB,/Zn = 25 Hz. The offsets (a) AB = 18B, and (b) AB = 268, were chosen so as to leave a maximum transverse signal (MJ at the end of the rectangular pulse (the last half revolution is shown as a full curve). The excursions are small compared with the radius of the unit sphere and are therefore shown in projection on the XY plane. Although the teardrop trajectory of the equivalent Gaussian pulse exhibits a larger excursion, it returns the magnetization to a point very close to the +Z axis, leaving a negligible detected signal. The dashes represent equal time increments during the pulse to illustrate the acceleration and deceleration stages of the Gaussian excitation.

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respect to the X2 plane) and the magnetization vector is thus returned to the +Z axis. This is a property of symmetrical pulses which rise and fall sufficiently slowly; the Gaussian-shaped pulse is but one example. The frequency-domain excitation pattern for a 10 ms rectangular pulse of intensity yB,/2?r = 25 Hz is illustrated in Fig. 4. This computer simulation of the absorptionmode signal (M,) and the relative phase angle (4) is based on the calculation of magnetization trajectories. Note in particular that after a whole number of complete revolutions about the effective field (where the transverse magnetization passes through zero) there is a ?r rad discontinuity in the phase angle. In Fig. 4 the choice of the sense of this phase jump is arbitrary. The excitation spectrum from a Gaussian-shaped selective pulse may be simulated by calculating trajectories for a range of possible offsets from resonance (Fig. 5). The relative phase of the signal varies almost linearly across the region of interest and may be simply corrected by existing phase-adjustment routines. When the excitation spectrum is displayed in terms of the absolute-value mode signal (Mz + M$*, there are no side lobes at all-the curve is a Guassian slightly distorted so as to have a somewhat flattened top. The advantage of a Gaussian over a rectangular pulse is emphasized when the absolute-value NMR signal is displayed as a function of offset (Fig. 6). After a Gaussian pulse of 10 ms duration, there is negligible excitation beyond AB = 300 Hz whereas after the equivalent rectangular pulse there are appreciable side lobes out beyond 1000 Hz. Choice of Shaping Function At appreciable offsets from resonance the Gaussian pulse excitation is negligible because the magnetization trajectory reduces to a single teardrop loop which returns MO to the +Z axis. This property is not unique to Gaussian pulses, but, as indicated

-l&~-l5 0 Hz

300

rod

FIG. 4. The absorption-mode response (a) and the relative phase shift (b) after a rectangular 10 ms pulse of intensity yB,/2n = 25 Hz, obtained by calculating magnetization trajectories. Note that whenever the magnetization vector completes a full revolution about the effective field, there is a x rad discontinuity in the phase angle.

GAUSSIAN

PULSES -15 rod

447

MCI

-MO ,300

I 0 Hz

.-I5 rod 300

FIG. 5. The absorption-mode response (a) and the relative phaseshift (b) after a GaussianIO ms pulse of mean amplitude yB,/2?r = 25 Hz, obtained by calculating trajectories similar to those of Figs. 2 and 3. Note the almost linear phase gradient across the region where there is finite excitation.

by the Fourier transform argument, requires that the pulse amplitude rise and fall smoothly. It is possible to demonstrate that a Gaussian pulse is one of the best choices for restricting the excitation spectrum. For a given duration of the time-domain function f(t), the most compact frequency-domain excitation is obtained when f(t) can be repeatedly differentiated without introducing discontinuities (6). If a function can be differentiated k times before the derivative becomes impulsive, then at large displacements AR the Fourier transform of this function falls off as aB@. Thus a rectangular pulse, which has a discontinuous first derivative, has an excitation function which falls off only as AK, as does a sine function. All the derivatives of a Gaussian are continuous, so the excitation falls off at the fastest possible rate. (Another function with this property is the hyperbolic secant, which has already been mentioned in a magnetic resonance context (7, 8).) The above conclusions are based on Fourier transform arguments, and are only approximate for a nonlinear NMR response. A simple experimental test of the offset dependence of the excitation after rectangular and Gaussian pulses of 10 ms duration is illustrated for a lightly doped water sample (T, = 3 s) in Fig. 7. The signal amplitude represents the absolute-value mode (44: + Ms)2 and is recorded at frequency offset increments of 30 Hz. At exact resonance the flip angle is 90. Note that beyond an offset of 300 Hz, the response

G:: f-7
-1000

- 500

\/\/\/I^.,\/ I

0 Hz

500

1000

FIG. 6. The frequency-domain response (absolute-value mode) after a 10 ms 90 rectangular pulse (R) and the equivalent Gaussian pulse(G). Note that whereas the excitation after the Gaussian pulse is negligible beyond k300 Hz, the rectangular pulse gives significant excitation lobes at offsets of the order of 1000 Hz.

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Rectangular pulse

Gaussian pulse

LLL-L-------OHz 240 360 400

Resonance

offset

FIG. 7. Experimental offset-dependence of the absolute-value NMR response after a 10 ms rectangular pulse with yE,/2a = 25 Hz and an equivalent Gaussian pulse. The offset increments are 30 Hz. Note that the excitation by the rectangular pulse exhibits sidelobes out to quite large offsets, whereas the excitation by the Gaussian pulse falls off monotonically.

from the Gaussian pulse is negligible whereas the excitation after the rectangular pulse continues beyond the range of this diagram. Very High Selectivity An interesting new effect becomes apparent if a highly selective pulse is employed, that is to say, when the pulse width is set long in comparison with Tz, the inverse of the inhomogeneous linewidth. Under these conditions it is necessary to take into account the spatial distribution of the effective field B,, At appreciable offsets AB the spatial inhomogeneity of the BO field dominates that of the radiofrequency field B, , and the latter may be neglected for a spinning sample. Consider first the case of a rectangular selective pulse with AB $ B, and t, 9 Tt . The overall detected signal is obtained by summation of the signals excited in each small volume element of the sample, represented by individual vectors (isochromats), each with a slightly different value of B, and therefore a different trajectory in the rotating frame. (The extremely small variations in tilt angle 8 may be neglected for the present purposes.) At the end of a long pulse, these isochromats are distributed almost uniformly about a cone of axis B, and with the 2 axis as generator. When the resultant magnetization is evaluated, the components perpendicular to the cone axis cancel to a good approximation, leaving a net magnetization MO cos 6 locked along B,. This removes the oscillatory component of the signal as a function of resonance offset; instead the signal falls slowly and monotonically with offset according to M, = &,B,AB/(Bf + AB) = MO sin 19cos 0.
151

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Note that in this approximation the detected signal is in the dispersion mode. Not only does the signal fall slowly with offset, but the apparent loss in selectivity is aggravated by the fact that the signal intensity at resonance is significantly weaker than normal (Fig. 8). This arises because signals generated in sample regions above and below resonance are only weakly excited, and the dispersion-mode components are in antiphase and thus cancel. It is important to realize that under these conditions, the response to the pulse is very far from linear and the usual Fourier transform arguments do not apply; the excitation spectrum shows no sine function character at all. There is a quite different behavior with the equivalent Gaussian pulse. At appreciable offsets from resonance, each isochromat follows its characteristic teardrop trajectory and is returned to the 2 axis irrespective of small changes in offset due to B0 inhomogeneity. The net signal is vanishingly small. The Gaussian pulse therefore shows to much better advantage than the equivalent rectangular pulse as can be appreciated from the offset dependence illustrated in Fig. 8.
EXPERIMENTAL

An evaluation of the use of Gaussian pulses was made on a Varian XL-200 spectrometer. The shaping function is stored digitally in an ultraviolet-erasable programmable read-only memory (UVEPROM) which forms part of an Intel 8748 singlechip microcomputer. This table of 32 words (of 8 bits each) when fed to an &bit digital-to-analog converter (DAC) provides an amplitude resolution of 1 part in 256 and 64 steps in the time domain (making use of the fact that the envelope is symmetrical

II

Rectangular

pulse

Gaussian pulse 1 -I-------------0 Hz

4 Resonance offset

FIG. 8. Experimental offset-dependence of the absolute-value NMR response after a 1.28 s rectangular pulse with -yB,/27r s 0.2 Hz, compared with an equivalent Gaussian pulse. For pulses of such long duration, the static field inhomogeneity completely obscures the expected sidelobes in the excitation spectrum of the rectangular pulse, but the excitation extends to quite large offsets ABIB,. The Gaussian pulse is far more selective.

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in time). The duration of each step is controlled by counting clock pulses of a 15 MHz crystal in the central processing unit. A low-pass filter smooths out the raw output from the DAC, removing the stepped appearance of the shaping function. This shaping function passes through an operational amplifier to a pair of doublebalanced diode ring mixers arranged in cascade (in order to improve the isolation); these control the low-level radiofrequency output. When the response of this stage was calibrated, it was found to be appreciably nonlinear. Compensation is therefore made in the look-up table defining the pulse shape so that the pulse envelope is a true Gaussian. For experiments on the selective excitation of carbon-l 3 resonances the shaped radiofrequency pulses are amplified in a linear high-power broadband amplifier. Noise generated in this radiofrequency amplifier is excluded from the receiver by means of a gate controlled by the XL-200 pulse programmer. The variable attenuator on the XL-200 is used to control the mean power of the pulse, allowing some flexibility in choosing pulse durations and flip angles. For proton experiments a somewhat different scheme is employed. At 200 MHz the double-balanced mixers used to modulate the pulse envelope suffer from leakage problems. A way around this problem is to use the double-balanced mixers to shape a low-frequency signal and then mix this with another source to give 200 MHz. On the Varian XL-200 spectrometer this is simply achieved by shaping the 10.5 MHz signal and then mixing this with the 210.5 MHz local oscillator frequency (on the proton decoupler board). The phase of the 10.5 MHz signal is controlled by the pulse programmer, which makes this a convenient arrangement. In experiments where it is essential that the absolute phases of the Gaussian selective pulse and the normal hard transmitter pulse are the same, a single offset synthesizer is used to drive both transmitter and decoupler, and the two phases are equalized by adjusting the length of cable between the decoupler and the probe.
APPLICATIONS OF GAUSSIAN PULSES

Fine Structure of Individual

Carbon-13 Resonances

Proton-coupled carbon- 13 spectra are often very crowded, with considerable overlap between adjacent multiplets, making it difficult to interpret the fine structure. Since there is a wide range of carbon- 13 shifts and data storage is limited, the long-range CH couplings are often poorly digitized in the frequency domain. Recording a twodimensional J spectrum circumvents the problem of overlap between multiplets and employs only a restricted spectral width in the F, dimension where the multiplet structure is displayed. Unfortunately, if very fine digitization is required, the number of t, increments becomes very large and the total experimental time may become prohibitive. These drawbacks can be overcome by a simple selective pulse experiment where a chosen carbon- 13 resonance is excited while decoupled from protons but the resulting free induction signal is acquired under proton-coupled conditions. The requisite decoupler gating is a straightforward matter in a Fourier transform spectrometer. Very fine digitization can be used since the spectral width is only a few hundred hertz. These experiments are of inherently lower sensitivity than conventional decoupled

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carbon- 13 spectroscopy and, if several sites are examined, are also more time-consuming. However, for many applications there is only a limited number of longrange CH couplings of interest, and they may be investigated by selective excitation of a very small number of carbon-13 sites one after another. In principle the entire array of carbon- 13 subspectra could be examined, but in this situation the corresponding two-dimensional J spectrum may prove to be a more economical experiment. The original implementation of this idea (2, 3) employed the DANTE method of selective excitation where the effective pulse envelope was rectangular. Clearly a Gaussian shape should be advantageous in crowded carbon- 13 spectra. The Gaussian pulse technique was tested by selectively exciting the C2, C4, and C6 resonances of I-bromo-3-nitrobenzene with a single soft pulse with the proton decoupler switched on, followed by acquisition of the free induction decay with the decoupler switched off. The resulting spin multiplets all show a large direct CH coupling together with fine structure due to long-range coupling. In Fig. 9 the direct coupling has been suppressed in order to focus attention on the long-range couplings. The total experimental time for each subspectrum, including the time averaging of 256 transients, was 50 min, which compares favorably with the 5 h required to obtain the corresponding two-dimensional spectrum, even though the latter showed much poorer resolution of the fine structure due to coarser digitization. The long-range CH couplings were extracted from an iterative least-squares fit of calculated and experimental subspectra, and are reproduced in Table 1. Selective Coherence Transfer between Protons Spectra from complex networks of coupled protons may be assigned by doubleresonance methods such as selective decoupling (9) spin tickling (IO), or selective population inversion (II). More recently, the elegant two-dimensional Fourier transform experiment introduced by Jeener (12, 13) has been applied to this problem, providing the complete pattern of interproton couplings in a single spectrum (1416). The excitation scheme is a simple 90-tl-90-acquire sequence. Lines of the conventional NMR spectrum appear along the principal diagonal of the two-dimensional spectrum and coupling is indicated by the presence of cross-peaks lying off

cza
c4m +95 +85 +75

nn
n -75 -85 -95 Hz

FIG. 9. Fine structure on the carbon-13 resonances decoupler technique. The individual decoupled carbon pulse of mean intensity yB,/2n z 6.3 Hz and duration acquired with the decoupler switched off. A large part order to emphasize the long-range CH couplings.

of I-bromo-3nitrobenzene observed with a gated resonances were excited with a selective Gaussian 40 ms. The carbon-13 free induction decays were of the direct CH coupling has been suppressed in

452
COUPLING

BAUER TABLE

ET
1

AL.

CONSTANTS J(CH) NITROBENZENE

FOR i-BROMD~(Hz)

H2 c2 c4 C6 173.5 4.4 5.5

H4 4.8 170.9 8.0

sign gives a better

HS -1.4 1.6 2.0

H6 5.8 7.9 169.1

The negative spectrum.

fit to the observed

the principal diagonal. The technique is very effective except in cases where the proton shifts are closely crowded together so that many cross-peaks overlap. In this section a frequency-selective version of the Jeener experiment is proposed, giving the same proton coupling information one site at a time, without involving two-dimensional Fourier transformation. It should prove useful for probing regions of the spectrum where the proton shifts are densely packed provided that some proton resonances are sufficiently well separated that they can be picked out for selective irradiation. The high frequency-selectivity of Gaussian-shaped pulses is the key to the technique. A related spin-echo technique for mapping out proton-proton coupling has been described earlier (I 7). Selective pulses have also been used by Brondeau and Canet (18) for studying homonuclear coupling in a rather different context. The experiment described by Jeener is modified to make the initial 90 excitation pulse frequency selective, the second (coherence transfer) pulse remaining a hard 90 pulse. This final pulse converts any longitudinal magnetization into transverse magnetization, and the resulting signals will be intense for all proton sites other than the one excited by the selective pulse. These undesirable signals are suppressed by the same phase-cycling procedure that is used in the nonselective (two-dimensional) coherence transfer experiment where the corresponding signals are much weaker. The variable evolution period ti of the twodimensional experiment is replaced by a fixed period T s (measured from the center of the Gaussian envelope). The frequency of this selective pulse is adjusted to the chemical shift wk of a chosen proton spin muhiplet, with the effective bandwidth calculated so that any excitation of adjacent multiplets can be neglected. As a result the B, field is in general comparable with the J couplings of nucleus k with its neighbors. The various components of the multiplet are therefore excited with different amplitudes and with significant relative phase shifts. In fact the nonuniformity of the initial excitation is not a limitation on the experiment. It may be preferable to operate with high selectivity, perturbing only part of the chosen multiplet, if this avoids excitation of neighboring resonances. This is where a Gaussian pulse shows to good advantage. In a coherence transfer experiment the intensity of the transferred signal depends on the magnitude of the appropriate coupling constant and on the length of the precession interval T, varying in a sinusoidal fashion (Z6). There is thus a slight chance that a particular transfer may fall accidentally at a null condition, so that a coupling path might be overlooked. This risk can be minimized by choosing a value of T that is short compared with the reciprocal of the largest expected coupling

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constant. In practice T was set at its minimum value, half the width of the Gaussian envelope, so that the second pulse followed immediately after the trailing edge of the initial Gaussian selective pulse. A molecule which has been thoroughly investigated by the two-dimensional coherence transfer method (14, 1.5) is that of 9-hydroxytricyclodecan-2,5-dione (I). The two-dimensional spectrum indicates a complex pattern of proton-proton couplings (at least 24 couplings connecting the 11 nonequivalent protons) but it does contain a crowded central region where the assignment of cross-peaks is not immediately obvious (25). This is just the kind of situation where selective coherence transfer methods are most powerful, since a relatively isolated proton can be chosen for irradiation in order to probe its couplings to protons in the crowded region of the spectrum. This method is analogous to the use of double resonance to investigate proton-proton coupling, but it affords some practical advantages; for example, the identification of the coupling partners is more straightforward and there are no BlochSiegert shifts (9). Figure 10 shows the results of selective coherence transfer experiments on this molecule. In each case the transmitter offset is set at the chemical-shift frequency of the selected proton. This resonance therefore appears at the zero point of the frequency scale; however, in Fig. 10, for the purposes of clarity, a common frequency scale is used for all the spectra. Quadrature detection must be used, with a spectral width large enough to cover the entire chemical-shift range whatever the transmitter offset. Five spectra are shown to illustrate selective coherence transfer; they were obtained by selective irradiation of protons K, A, D, G, and C in turn. An absolute-valuemode presentation is employed since the individual components of a spin multiplet have different relative phases. This leads to some distortion of the exact form of these multiplets compared with the conventional spectrum, owing to interference effects between adjacent lines. In general this does not affect the identification of the coherence transfer signals. Note that although resonances C, D, and G fall in the crowded central region of the spectrum, there is little evidence of spillover from the Gaussian pulse to a close neighbor, leading to spurious coherence transfer peaks. The weak responses which appear in trace (f) probably arise from inefficient direct transfer through the couplings JcI and JCJrather than accidental excitation of resonance B by the Gaussian pulse. Trace (g) corresponds to a repetition of this experiment with a conventional rectangular pulse of the same width. Here there is clearly some direct excitation of the neighboring resonances B and D, with concomitant excitation of E which is strongly coupled to D, and some spurious coherence transfer to sites K and A. This highlights the danger of using rectangular selective pulses in crowded spectra.

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b
+ c K *

HZ

600

400

200

FIG. 10. Selective coherence transfer between protons in a tricyclodecanone derivative. The initial 90 excitation pulse was a selective Gaussian of 80 ms duration (b and c) or 160 ms duration (d-f). The second (mixing) pulse was nonselective. The top spectrum is the conventional proton spectrum showing the assignment. In the lower spectra the broad arrows indicate the selectively excited protons, the remaining responses arise from coherence transfer through scalar coupling. Spectrum (g) shows the same coherence transfer experiment as spectrum (f) except that a 160 ms rectangular pulse was used instead of a Gaussian; spurious responses appear at the frequencies of protons A, B, D, E, and K.

Nuclear Overhauser Eflects Measurements of the proton-proton Overhauser effect [( 19) and references therein] are widely used to derive proximity information in large molecules, since for a slowly tumbling system the proton dipole-dipole interaction tends to dominate other relaxation mechanisms. The enhancements can be very small, of the order of a few percent of the parent peak, and hence in a crowded molecule there is always a danger of spurious effects if the excitation spectrum of the selective pulse possessesside lobes in the frequency domain. Recently transient nuclear Overhauser measurements have been advocated (20) on the grounds that spin-diffusion effects (21) are more readily discriminated in transient experiments than in steady-state determinations. This involves the application of a 180 pulse to the selected proton resonance, followed by the measurement of the initial rate of growth of the nuclear Overhauser enhancement. Spin diffusion is expected to proceed on a longer time scale. Clearly there should be some advantage in employing a Gaussian-shaped 180 pulse rather than a conventional rectangular pulse in these situations. An experimental illustration of the use of a Gaussian population inversion pulse is provided by the proton spectrum of sucrose (II). The selectivity was made quite

GAUSSIAN

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HO

OH

H4

II

high by setting the pulse duration to 320 ms (at the 1% points). Although this does not excite a given spin multiplet uniformly, the relative nuclear Overhauser enhancements are unaffected by this shortcoming. Under these conditions there are differential population pumping effects if the irradiation frequency is not exactly centered, analogous to the well known selective population transfer experiments (II). Although these positive and negative intensity perturbations integrate to zero over the entire observed multiplet, they seriously interfere with the observation of the net intensity change due to the nuclear Overhauser effect. Fortunately these perturbations are easily suppressed by making use of the flip angle effect (22) of the final read pulse. If this is set accurately to 90 the population pumping effects are eliminated, so it is sufficient to employ an intense transmitter field (in practice yB,/27r z 20 kHz) and a composite 90 read pulse. Good compensation for both resonance offset and pulse length error was achieved by a new composite sequence 9O(+Y) 270(-X) 36O(+X) analyzed in detail elsewhere. After the selective Gaussian pulse, a 0.6 s delay was introduced to allow for the build-up of the nuclear Overhauser effect. The spectrum of sucrose was then examined in the difference mode, which emphasizes the intensity changes due to cross relaxation. It is seen from Fig. 11 that irradiation of protons Fl (fructose ring) enhances F3 and Gl (in the adjacent glucose ring), while irradiation of Gl enhances Fl and G2, as expected on proximity arguments.
CONCLUSIONS

Evidence has been presented that properly shaped radiofrequency pulses give a more selective excitation pattern than the equivalent rectangular pulses. A Gaussian is a good choice of shaping function since it provides a particularly compact frequencydomain excitation spectrum. In general the improvement stems from the elimination of the broad pattern of side lobes characteristic of a rectangular pulse, which extends to a surprisingly large distance from the centre frequency of the excitation. However, it has been observed that when the selectivity is set high in comparison with the inhomogeneous linewidth, the side lobes normally associated with a rectangular pulse disappear, leaving a broad, monotonically decreasing excitation. Under such conditions, the Gaussian pulse shows to particular advantage. Another idea which has been widely discussed is the use of a sine function for the time-domain envelope of a selective pulse. In the linear approximation this should provide a frequency-domain excitation spectrum which is rectangular, which appears to be an attractive option. Unfortunately this entails a pulse envelope that has a

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a b

HDO

GI

F3

I FI G2

500

400

300

200

100

0 Hz

FIG. 11. Nuclear Overhauser enhancement experiments in the proton NMR spectrum of sucrose. The unperturbed proton spectrum is shown in the top trace after partial suppression of the residual HDO peak by a selective 90 pulse. The broad arrows in the two lower traces indicate where a 320 ms selective Gaussian population inversion pulse has been applied. These difference spectra exhibit Overhauser enhancements between Fl and F3 and Gl. and between Gl and Fl and G2.

relatively long duration (and, incidentally, several phase inversions). A Gaussian pulse of the same total duration would in fact be more selective in the frequency domain. Gaussian pulses should prove useful for the majority of applications of frequencyselective excitation. Only three such experiments are described here, but others include solvent peak suppression, selective relaxation measurements, magnetization transfer by chemical exchange, and selective population transfer (II). The additional pulseshaping hardware (based on a microchip) is not difficult to construct and incorporate into an existing high-resolution spectrometer.
ACKNOWLEDGMENTS This research was supported by an equipment grant and research studentship (C.J.B.) from the Science and Engineering Research Council. James Keeler is the recipient of a Domus Senior Scholarship at Met-ton College, Oxford. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Il. R. FREEMAN AND S. WII-TEKOEK, J. Mum. Reson. 1,238 (1969). G. BODENHAUSEN,R. FREEMAN, ANI) G. A. MORRIS, J. Mugn. Reson. 23, 17 1 (1976). G. A. MORRIS AND R. FREEMAN, J. Magn. Reson. 29,433 (1978). R. J. SUTHERLAND AND J. M. S. HUTCHINSON, J. Phys. E 11, 79 (1978). J. M. S. HUTCHINSON, R. J. SUTHERLAND, AND J. R. MALLARD, J. Whys. E. II,21 7 (1978). R. N. BRACEWELL, The Fourier Transform and Its Applications, Chap. 8, 2nd ed., McGraw-Hill, New York, 1978. J. BAUM, R. TYCKO, AND A. PINES, J. Chem. Phys. 79,4643 (1983). S. L. MCCALL AND E. L. HAHN, Phys. Rev. 183,457 (1969). W. A. ANDERSON AND R. FREEMAN, J. Chem. Phys. 37,85 (1962). R. FREEMAN AND W. A. ANDERSON, J. Chem. Phys. 37,2053 (1962). K. G. R. PACHLER AND P. L. WESSELS,J. Magn. Reson. 12, 337 (1973).

GAUSSIAN

PULSES

457

12. J. JEENER, Ampere International Summer School, Basko Polje, Yugoslavia, 1971. 13. W. P. AUE, E. BARTHOLDI, AND R. R. ERNST, J. Chem. Phys. 64, 2229 (1976). 14. A. BAX, R. FREEMAN, AND G. A. MORRIS, J. Mu@. Reson. 42, 164 ( 198 1). 15. A. BAX AND R. FREEMAN, J. Magn. Reson. 44, 542 (1981). 16. A. BAX, Two-Dimensional Nuclear Magnetic Resonance in Liquids, Reidel, Boston, 17. FENG-KUI PEI AND R. FREEMAN, J. Magn. Reson. 48, 5 19 (1982). 18. D. CANET, J. BRONDEAU, J-P. MARCHAL, AND H. NERY, J. Magn. Reson. 36,35 (1979); AND D. CANET, J. Mugn. Resort 47, 159 (1982). 19. J. K. M. SANDERS AND J. D. MERSH, in Progress in NMR Spectroscopy (J. Emsley, L. Sutcliffe, Ed%), Vol. 55, Pergamon, Oxford, 1983. 20. S. L. GARDEN AND K. WQTHRICH, J. Am. Chem. Sot. 100,1094 (1978). 21. A. KALK AND H. J. C. BERENLISEN, .I. Magn. Reson. 24, 343 (1976). 22. S. SCHAUBLIN, A. HOHENER, AND R. R. ERNST, .I. Mugn. Reson. 13, 196 (1974). 23. A. J. SHAKA AND R. FREEMAN, J. Magn. Reson. 55,487 (1983).

1982. J. BRONDEAU J. Feeney and