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Slice-interleaved depth-resolved surface-coil spectroscopy (SLIT DRESS) for rapid 31P NMR in Vivo
JOURNAL OF MAGNETIC RESONANCE 64347-35
1
(1985)
Slice-Interleaved Depth-Resolved Surface-Coil Spectroscopy (SLIT DRESS) for Rapid 31PNMR in Viva PAUL A. BOTTOMLEY,L. SCOTTSMITH, WILLIAM M. LEUE, AND CECIL CHARLES* General Electric Corporate Research and Development Center, P.O. Box 8, Schenectady, New York 12301. and *General Electric Medical Systems Business Group, P.O. Box 414, Milwaukee, Wisconsin 53201
Received May
21, 1985
Spatially localized “P NMR signals have been recorded in vivo using surface coils (I, 2) topical magnetic resonance (3), depth-resolved surface-coil spectroscopy (DRESS) (4, 5), and two-dimensional Fourier transform (2D FT) techniques that employ either phase-encodingmagnetic field gradients (6) or rf magnetic field gradients (7). The first three of thesetechniques sharethe disadvantageof sequential point NMR imaging methods (8) that long data acquisition periods are necessaryfor clinical applications when spectra from multiple sites are desired. Multiple spectra are useful for comparing normal and pathological tissues in situ. While spectra from multiple locations can be acquired simultaneously via the 2D FT techniques,a number of technical problems arise. These include (i) the loss of adenosinetriphosphate (ATP) peaks due to their short T2 (- 10 ms) when echo times + 10 ms are employed in the phaseencoding gradient method (6); (ii) variable spectral line-broadening effects due to the different eddy currents induced when varying the amplitude of phase-encodinggradients; (iii) the loss of sensitivity due to the use of flip angles # n/2 in the rf field gradient technique (9); and (iv) the loss of spatial resolution when the FT in the spatial dimension contains few points as in 31PNMR (10). The efficiency of all of the techniques is further compromised by the need for long repetition periods to minimize spectral distortion associatedwith the longer T, (-4 s) of phosphocreatine(PCr) (I 1). We describe and demonstrate here a variation of the DRESS method that enables simultaneous acquisition of multiple spatially resolved spectra in essentially the same time as required for a single spectral acquisition, without using 2D FT. The original DRESS technique used a narrow bandwidth 7r/2 rf pulse in the presenceof a linear magnetic field gradient applied perpendicular to the plane of a surface detection coil to confine the NMR signal to a selected plane lying parallel to the surface coil (4). The lateral extent of the selectedvolume was determined by the sensitivity profile of the surface coil. Now, multiple spectracan be acquired by interleaving slice excitations at different depths during the saturation-recovery period, in a manner analogous to multislice NMR imaging. Since the amplitudes of neither rf nor gradient pulses vary during the slice-interleavingprocedure,the technique overcomesthe sensitivity, variable line broadening, and resolution problems associatedwith the 2D FT methods while making efficient use of the long interpulse delay. 341
0022-2364185 $3.00 Copyright 0 1985 by Academic Press. Inc. All rig& of reproduction in any form reserved.
348
COMMUNICATIBNS
The NMR pulse sequence employed for slice-interleaved DRESS (SLIT DRESS) is the same as for conventional DRESS (4), but the sequence is repeated n times faster at intervals of 7&z, where T, is the saturation-recovery interval and n is the number of slices. Successiveapplications of the sequenceexcite the n different slices by offsetting the NMR frequency of the 7r/2 pulse in a single sideband transmitter. The location of the ith slice relative to the center of the gradient field is yi = 271-f/yG, where A is the offset frequency, y is the gyromagnetic ratio of the observed nucleus, and G is the strength of the gradient applied during the rf pulse. f; can be varied either by incorporating the offset frequency in the selective excitation pulse profile provided under computer control in a high-field imaging/spectroscopy system, or by rapidly switching the frequency of a digitally controlled frequency synthesizer, or, possibly, by rapid adjustment of the main static magnetic field. The slice thickness is Ay = 2?rAflyG where Afis the spectral width of the selective excitation pulse. Ideally, selective pulses have sharp excitation profiles (e.g., sine-function modulation), but in practice the edges of adjacent slices may partially saturate due to overlapping slice profiles. Consequently it is prudent to order the offset frequencies or slices nonsequentially. Figure 1 shows applications of the technique to the calf (a) and head (b) of two normal human volunteers. Each “P spectral series was recorded at 25.1 MHz on a 1.5 T imaging/spectroscopy research system (12, 4) in just 5 and 10 min, respectively. A 6 cm diameter surface detection coil and 27 cm diameter transmitter coil were used. The spectra (n = 6) span 6 cm at 1 cm intervals and represent Ay = 1 cm thick slices. The order of excitation of sequential interleaved slices was 1, 4, 2, 5, 3, 6, where numbers represent depths in centimeters (yJ. A truncated sine-modulated rf pulse with the offset frequency incorporated in the modulation profile was used for excitation at 0.333 s intervals for a total T, of 2 s. The maximum slice-selectivegradient amplitude was 140 rT/cm generated, as previously (4), by the whole-body imaging gradient coil set. Data was acquired as free induction decays 4 ms after the cessation of the rfpulse at the end of the negative gradient rephasing lobe. ‘H images (Fig. 2) recorded with a 6 cm diameter ‘H surface coil and a transmitter coil wound on the 3’P coil structure denote the anatomy corresponding to the spectra. As in conventional DRESS, ‘H spectra from the various interleaved slices are used for shimming the magnet homogeneity prior to switching to 31Pwith the same pulsed gradient amplitude. A successful ‘H shim strategy is to optimize the center slice first, and then make minor adjustments until the extreme slicesexhibit acceptablelinewidths. In switching from ‘H to 3’P, both the slice thickness and depth range are increased by the ratio y (‘H)/y (3’P), assuming that the gradient amplitude and rf pulse width are kept constant. The location of the central slice is unchanged by the switchover providing that it is set exactly on resonance. Of course this is not possible for 3’P NMR where chemical-shift dispersions occur, so in practice, different resonances derive from slightly different depths located about the selected slice (4). The spread in depths due to the dispersion is 6y = 27r X lO%+-Jp/~G where Sp is the range in parts per million of chemical shifts present in the sample and v. is the Larmor frequency in hertz. For Sp = 20 ppm and G = 140 pT/cm, S,, = 0.2 cm which is much less than the slice thickness. In any case, since this displacement is directly proportional to the chemical shift, it can be accurately and easily represented by rotating the chemical shift axis of spectra relative to the depth axis in 2D plots such. as Fig. 1, by an angle (Y = arctan
349
COMMUNICATIONS
(a)
/PCr
(4
PCr, y-ATP Pi
pD
A PM
\
\I
1 cm
2cm 9 3cm 4
wm
I 0
’ ’ ’ I -20
’
L
I pm
I
! 0
1
I -20
FIG. 1. In viva “P SLIT DRESS. Spectra were recorded with the lower leg draped over the surface coil showing the calf muscle (a), and with the head lying sidewayson the coil above the left ear(b). Each complete spectral series was recorded in 5 and 10 min, respectively, with 7, = 2 s, and n = 6. Depths relative to the surface are indicated. 8 and 12 Hz exponential filters were applied to the spectra in (a) and (b), respectively. Spectra are baseline flattened. Spectrometer gains are the same within each series ((Y-, @-,y-ATP = (Y-,&, and y-phosphates of adenosine triphosphates; (Y-, y-ATP include other nucleoside phosphate resonances; PCr = phosphocreatine; PD = phosphodiester; PM = phosphomonoester; Pi = inorganic phosphate).
(Q/S&. If Sy 2 Ay, a rectilinear 2D plot can be reconstructedby interpolating reoriented spectra onto a rectangular data array. The calf spectra (Fig. la) resemble normal unsaturated muscle spectra as indicated by the image (Fig. 2a). Inorganic phosphate (Pi) is slightly elevated in the top three slices, possibly reflecting some ischemia in the outer muscle which was compressed onto the surface coil by the weight of the leg. Loss of signal in the deepestslice is due to the presence of bone (Fig. 2a). In the head series (Figs. 1b), brain spectra are characterized by phosphodiester (PD) concentrations that are comparable to ATP (12, 4) and phosphomonoesters(PM) at about half this concentration at depths of y 3 2 cm. The surface spectrum (y = 1 cm) has less PD and a higher PCr/ATP ratio, but differs significantly from the muscle spectra suggestingother contributions (Fig. 2b). Peak amplitudes decrease with increasing depths as the surface coil sensitivity fades (Fig. 2). Some distortion of the PCr/ATP ratio is evident in brain due to saturation of the PCr. Conventional DRESS experiments on nine normal adult brains with T, = 8 s gave PCr/&ATP = 1.1 f 0.1 compared to 0.6 + 0.1 observed here. This difference
350
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FIG. 2. ‘H transverse NMR images corresponding to Fig. 1: (a) the calf muscle; (b) the brain. Image arrays consist of 256 X 256 0.5 X 0.5 X 5 mm pixels obtained with 7, = I s using a 6 cm surface receiver coil and 27 cm diameter transmitter coil. White lines delineate slices represented by the depth resolved spectra in Fig. 1.
can be completely accounted for by saturation ehkcts that do not involve overlapping slices if one assumes T,(PCr) - 4 s and Ti(ATP) - 1 s for brain. Thus the saturation effect due to irradiation of overlapping adjacent slices has been minimized by the slice shuIIling procedure. Some signal is also lost due to TZ relaxation during the 4 ms delay required for the rephasing gradient after cessation of the 7r/2 pulse. This signal loss is negligible for PCr since T#Cr) 2 50 ms, but could be about 30% for ATP if it were assumed that T@ATP) - 10 ms from the unfiltered ATP linewidths. Because uniform rf excitation fields can be applied to the selected volumes, SLIT DRESS is amenableto conventional techniques for providing spectral relaxation times (13), solvent suppression (13), nuclear Overhauser enhancement (NO DRESS), etc. Should the surface coil be used for both excitation and detection, compensation for the nonuniform excitation field is possible by readjusting the pulse amplitudes under computer control for u/2 flip anglesat each selectedslice, according to the slice depth (5). On axis, the depth dependence of the rf fielld is proportional to (R* + J$‘)-~/*, where R is the surface-coil radius. We have successfully used this single surface-coil excitation/detection technique on the head and body (liver and heart) with similar results and acquisition times. In conclusion, SLIT DRESS alleviatesmuch of the difficulty associatedwith existing in viva localized 31P NMR methods and provides useful, spatially resolved spectra from the body in times of order 5- 10 min at 1.5 T. Since these times are comparable to existing ‘H high-field imaging procedures, implementation of the technique on such systems renders clinical applications technically viable and thereby facilitating clinical evaluation of this new modality. ACKNOWLEDGMENTS We thank d. Vatis for rfengineering contributions and R. W. Redington for scientific support.
COMMUNICATIONS
351
REFERENCES I. J. J. H. ACKERMAN, T. H. GROVE, G. G. WONG, D. G. GADIAN, AND G. K. RADDA, Nature (London)
283,167(1980). 2. R. L. NUNNALLY AND P. A. B~TTOMLEY, Science (Washington, D.C.) 211, 177 (198 1). 3. R. E. GORWN, P. E. HANLEY, D. SHAW, D. G. GADIAN, G. K. RADDA, P. STYLES, P. J. BORE, AND L. CHAN, Nature (London) 287,736 (1980). 4. P. A. B~ITOMLEY, T. H. FOSTER, AND R. D. DARROW, J. Magn. Reson. 59, 338 (1984). 5. P. A. BolTOMLEY, Science (Washington, D.C.)? in press (1985). 6. J. C. HAZELGROVE,V. H. SUBFUMANIAN,J. S. LEIGH, L. Gww, AND B. CHANCE, Science(Washington,
D.C.) 220, 1170 (1983). 7. P. STYLES, C. A. SCOTT, AND G. K. RADDA, Magn. Reson. Med. 2,402 (1985). 8. P. A. B~~OMLEY, Rev. Sci. Instrum. 53, 13 19 ( 1982). 9. S. J. Cox AND P. SOLES, J. Magn. Reson. 40,209 (1980). 10. P. A. B~I-I’OMLEY, “Instrumentation Overview,” presented at the 2nd Annual Meeting of the Society of Magnetic Resonance in Medicine Workshop on patbophysiological studies by NMR in viva spec-
troscopy, San Francisco, CA ( I5 Aug. 1983). Il. P. A. BOTTOMLEY, W. A. EDELSTEIN, H. R. HART, J. F. S~HENCK, AND L. S. SMITH, Magn. Reson. Med. 1,410 (1984). 12. P. A. B~TTOMLEY, H. R. HART, W. A. EDELSTEIN, J. F. S~HENCK, L. S. SMITH, W. M. LEUE, 0. M. MUELLER, AND R. W. REDINGTON, Radiology 150,441 (1984). 13. P. A. BOTTOMLEY, W. A. EDELSTEIN, T. H. FOSTER, AND W. A. ADAMS, Proc. Natl. Acad. Sci. USA
82,2148(1985).
1
(1985)
Slice-Interleaved Depth-Resolved Surface-Coil Spectroscopy (SLIT DRESS) for Rapid 31PNMR in Viva PAUL A. BOTTOMLEY,L. SCOTTSMITH, WILLIAM M. LEUE, AND CECIL CHARLES* General Electric Corporate Research and Development Center, P.O. Box 8, Schenectady, New York 12301. and *General Electric Medical Systems Business Group, P.O. Box 414, Milwaukee, Wisconsin 53201
Received May
21, 1985
Spatially localized “P NMR signals have been recorded in vivo using surface coils (I, 2) topical magnetic resonance (3), depth-resolved surface-coil spectroscopy (DRESS) (4, 5), and two-dimensional Fourier transform (2D FT) techniques that employ either phase-encodingmagnetic field gradients (6) or rf magnetic field gradients (7). The first three of thesetechniques sharethe disadvantageof sequential point NMR imaging methods (8) that long data acquisition periods are necessaryfor clinical applications when spectra from multiple sites are desired. Multiple spectra are useful for comparing normal and pathological tissues in situ. While spectra from multiple locations can be acquired simultaneously via the 2D FT techniques,a number of technical problems arise. These include (i) the loss of adenosinetriphosphate (ATP) peaks due to their short T2 (- 10 ms) when echo times + 10 ms are employed in the phaseencoding gradient method (6); (ii) variable spectral line-broadening effects due to the different eddy currents induced when varying the amplitude of phase-encodinggradients; (iii) the loss of sensitivity due to the use of flip angles # n/2 in the rf field gradient technique (9); and (iv) the loss of spatial resolution when the FT in the spatial dimension contains few points as in 31PNMR (10). The efficiency of all of the techniques is further compromised by the need for long repetition periods to minimize spectral distortion associatedwith the longer T, (-4 s) of phosphocreatine(PCr) (I 1). We describe and demonstrate here a variation of the DRESS method that enables simultaneous acquisition of multiple spatially resolved spectra in essentially the same time as required for a single spectral acquisition, without using 2D FT. The original DRESS technique used a narrow bandwidth 7r/2 rf pulse in the presenceof a linear magnetic field gradient applied perpendicular to the plane of a surface detection coil to confine the NMR signal to a selected plane lying parallel to the surface coil (4). The lateral extent of the selectedvolume was determined by the sensitivity profile of the surface coil. Now, multiple spectracan be acquired by interleaving slice excitations at different depths during the saturation-recovery period, in a manner analogous to multislice NMR imaging. Since the amplitudes of neither rf nor gradient pulses vary during the slice-interleavingprocedure,the technique overcomesthe sensitivity, variable line broadening, and resolution problems associatedwith the 2D FT methods while making efficient use of the long interpulse delay. 341
0022-2364185 $3.00 Copyright 0 1985 by Academic Press. Inc. All rig& of reproduction in any form reserved.
348
COMMUNICATIBNS
The NMR pulse sequence employed for slice-interleaved DRESS (SLIT DRESS) is the same as for conventional DRESS (4), but the sequence is repeated n times faster at intervals of 7&z, where T, is the saturation-recovery interval and n is the number of slices. Successiveapplications of the sequenceexcite the n different slices by offsetting the NMR frequency of the 7r/2 pulse in a single sideband transmitter. The location of the ith slice relative to the center of the gradient field is yi = 271-f/yG, where A is the offset frequency, y is the gyromagnetic ratio of the observed nucleus, and G is the strength of the gradient applied during the rf pulse. f; can be varied either by incorporating the offset frequency in the selective excitation pulse profile provided under computer control in a high-field imaging/spectroscopy system, or by rapidly switching the frequency of a digitally controlled frequency synthesizer, or, possibly, by rapid adjustment of the main static magnetic field. The slice thickness is Ay = 2?rAflyG where Afis the spectral width of the selective excitation pulse. Ideally, selective pulses have sharp excitation profiles (e.g., sine-function modulation), but in practice the edges of adjacent slices may partially saturate due to overlapping slice profiles. Consequently it is prudent to order the offset frequencies or slices nonsequentially. Figure 1 shows applications of the technique to the calf (a) and head (b) of two normal human volunteers. Each “P spectral series was recorded at 25.1 MHz on a 1.5 T imaging/spectroscopy research system (12, 4) in just 5 and 10 min, respectively. A 6 cm diameter surface detection coil and 27 cm diameter transmitter coil were used. The spectra (n = 6) span 6 cm at 1 cm intervals and represent Ay = 1 cm thick slices. The order of excitation of sequential interleaved slices was 1, 4, 2, 5, 3, 6, where numbers represent depths in centimeters (yJ. A truncated sine-modulated rf pulse with the offset frequency incorporated in the modulation profile was used for excitation at 0.333 s intervals for a total T, of 2 s. The maximum slice-selectivegradient amplitude was 140 rT/cm generated, as previously (4), by the whole-body imaging gradient coil set. Data was acquired as free induction decays 4 ms after the cessation of the rfpulse at the end of the negative gradient rephasing lobe. ‘H images (Fig. 2) recorded with a 6 cm diameter ‘H surface coil and a transmitter coil wound on the 3’P coil structure denote the anatomy corresponding to the spectra. As in conventional DRESS, ‘H spectra from the various interleaved slices are used for shimming the magnet homogeneity prior to switching to 31Pwith the same pulsed gradient amplitude. A successful ‘H shim strategy is to optimize the center slice first, and then make minor adjustments until the extreme slicesexhibit acceptablelinewidths. In switching from ‘H to 3’P, both the slice thickness and depth range are increased by the ratio y (‘H)/y (3’P), assuming that the gradient amplitude and rf pulse width are kept constant. The location of the central slice is unchanged by the switchover providing that it is set exactly on resonance. Of course this is not possible for 3’P NMR where chemical-shift dispersions occur, so in practice, different resonances derive from slightly different depths located about the selected slice (4). The spread in depths due to the dispersion is 6y = 27r X lO%+-Jp/~G where Sp is the range in parts per million of chemical shifts present in the sample and v. is the Larmor frequency in hertz. For Sp = 20 ppm and G = 140 pT/cm, S,, = 0.2 cm which is much less than the slice thickness. In any case, since this displacement is directly proportional to the chemical shift, it can be accurately and easily represented by rotating the chemical shift axis of spectra relative to the depth axis in 2D plots such. as Fig. 1, by an angle (Y = arctan
349
COMMUNICATIONS
(a)
/PCr
(4
PCr, y-ATP Pi
pD
A PM
\
\I
1 cm
2cm 9 3cm 4
wm
I 0
’ ’ ’ I -20
’
L
I pm
I
! 0
1
I -20
FIG. 1. In viva “P SLIT DRESS. Spectra were recorded with the lower leg draped over the surface coil showing the calf muscle (a), and with the head lying sidewayson the coil above the left ear(b). Each complete spectral series was recorded in 5 and 10 min, respectively, with 7, = 2 s, and n = 6. Depths relative to the surface are indicated. 8 and 12 Hz exponential filters were applied to the spectra in (a) and (b), respectively. Spectra are baseline flattened. Spectrometer gains are the same within each series ((Y-, @-,y-ATP = (Y-,&, and y-phosphates of adenosine triphosphates; (Y-, y-ATP include other nucleoside phosphate resonances; PCr = phosphocreatine; PD = phosphodiester; PM = phosphomonoester; Pi = inorganic phosphate).
(Q/S&. If Sy 2 Ay, a rectilinear 2D plot can be reconstructedby interpolating reoriented spectra onto a rectangular data array. The calf spectra (Fig. la) resemble normal unsaturated muscle spectra as indicated by the image (Fig. 2a). Inorganic phosphate (Pi) is slightly elevated in the top three slices, possibly reflecting some ischemia in the outer muscle which was compressed onto the surface coil by the weight of the leg. Loss of signal in the deepestslice is due to the presence of bone (Fig. 2a). In the head series (Figs. 1b), brain spectra are characterized by phosphodiester (PD) concentrations that are comparable to ATP (12, 4) and phosphomonoesters(PM) at about half this concentration at depths of y 3 2 cm. The surface spectrum (y = 1 cm) has less PD and a higher PCr/ATP ratio, but differs significantly from the muscle spectra suggestingother contributions (Fig. 2b). Peak amplitudes decrease with increasing depths as the surface coil sensitivity fades (Fig. 2). Some distortion of the PCr/ATP ratio is evident in brain due to saturation of the PCr. Conventional DRESS experiments on nine normal adult brains with T, = 8 s gave PCr/&ATP = 1.1 f 0.1 compared to 0.6 + 0.1 observed here. This difference
350
COMMUNICATIONS
FIG. 2. ‘H transverse NMR images corresponding to Fig. 1: (a) the calf muscle; (b) the brain. Image arrays consist of 256 X 256 0.5 X 0.5 X 5 mm pixels obtained with 7, = I s using a 6 cm surface receiver coil and 27 cm diameter transmitter coil. White lines delineate slices represented by the depth resolved spectra in Fig. 1.
can be completely accounted for by saturation ehkcts that do not involve overlapping slices if one assumes T,(PCr) - 4 s and Ti(ATP) - 1 s for brain. Thus the saturation effect due to irradiation of overlapping adjacent slices has been minimized by the slice shuIIling procedure. Some signal is also lost due to TZ relaxation during the 4 ms delay required for the rephasing gradient after cessation of the 7r/2 pulse. This signal loss is negligible for PCr since T#Cr) 2 50 ms, but could be about 30% for ATP if it were assumed that T@ATP) - 10 ms from the unfiltered ATP linewidths. Because uniform rf excitation fields can be applied to the selected volumes, SLIT DRESS is amenableto conventional techniques for providing spectral relaxation times (13), solvent suppression (13), nuclear Overhauser enhancement (NO DRESS), etc. Should the surface coil be used for both excitation and detection, compensation for the nonuniform excitation field is possible by readjusting the pulse amplitudes under computer control for u/2 flip anglesat each selectedslice, according to the slice depth (5). On axis, the depth dependence of the rf fielld is proportional to (R* + J$‘)-~/*, where R is the surface-coil radius. We have successfully used this single surface-coil excitation/detection technique on the head and body (liver and heart) with similar results and acquisition times. In conclusion, SLIT DRESS alleviatesmuch of the difficulty associatedwith existing in viva localized 31P NMR methods and provides useful, spatially resolved spectra from the body in times of order 5- 10 min at 1.5 T. Since these times are comparable to existing ‘H high-field imaging procedures, implementation of the technique on such systems renders clinical applications technically viable and thereby facilitating clinical evaluation of this new modality. ACKNOWLEDGMENTS We thank d. Vatis for rfengineering contributions and R. W. Redington for scientific support.
COMMUNICATIONS
351
REFERENCES I. J. J. H. ACKERMAN, T. H. GROVE, G. G. WONG, D. G. GADIAN, AND G. K. RADDA, Nature (London)
283,167(1980). 2. R. L. NUNNALLY AND P. A. B~TTOMLEY, Science (Washington, D.C.) 211, 177 (198 1). 3. R. E. GORWN, P. E. HANLEY, D. SHAW, D. G. GADIAN, G. K. RADDA, P. STYLES, P. J. BORE, AND L. CHAN, Nature (London) 287,736 (1980). 4. P. A. B~ITOMLEY, T. H. FOSTER, AND R. D. DARROW, J. Magn. Reson. 59, 338 (1984). 5. P. A. BolTOMLEY, Science (Washington, D.C.)? in press (1985). 6. J. C. HAZELGROVE,V. H. SUBFUMANIAN,J. S. LEIGH, L. Gww, AND B. CHANCE, Science(Washington,
D.C.) 220, 1170 (1983). 7. P. STYLES, C. A. SCOTT, AND G. K. RADDA, Magn. Reson. Med. 2,402 (1985). 8. P. A. B~~OMLEY, Rev. Sci. Instrum. 53, 13 19 ( 1982). 9. S. J. Cox AND P. SOLES, J. Magn. Reson. 40,209 (1980). 10. P. A. B~I-I’OMLEY, “Instrumentation Overview,” presented at the 2nd Annual Meeting of the Society of Magnetic Resonance in Medicine Workshop on patbophysiological studies by NMR in viva spec-
troscopy, San Francisco, CA ( I5 Aug. 1983). Il. P. A. BOTTOMLEY, W. A. EDELSTEIN, H. R. HART, J. F. S~HENCK, AND L. S. SMITH, Magn. Reson. Med. 1,410 (1984). 12. P. A. B~TTOMLEY, H. R. HART, W. A. EDELSTEIN, J. F. S~HENCK, L. S. SMITH, W. M. LEUE, 0. M. MUELLER, AND R. W. REDINGTON, Radiology 150,441 (1984). 13. P. A. BOTTOMLEY, W. A. EDELSTEIN, T. H. FOSTER, AND W. A. ADAMS, Proc. Natl. Acad. Sci. USA
82,2148(1985).