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Resonators for in Vivo 31P NMR at 1.5 T
JOURNAL
OF MAGNETIC
RESONANCE
61, 571-578
(1985)
Resonators for in Vivo 31P NMR THOMAS
at 1.5 T
M. GRIST AND JAMES S. HYDE
National Biomedical ESR Center, Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226 Received
October
10. 1984
Phosphorus nuclear magnetic resonance of naturally occurring compounds such as adenosine triphosphate, phosphocreatine, inorganic phosphate, phosphodiesters, and sugar phosphates in biological tissues is a subject of current interest in many laboratories. Tissue metabolism was first observed with 31P NMR in 1974 (1). Subsequently, isolated perfused organs (2) and organs in intact animals using surface coils were studied (3). Changes in phosphorus compound metabolism have been observed noninvasively in pathological states such as ischemia and cancer (4, 5). Clinical applications began by observing forearm muscle metabolism in patients with McCardle’s disease, human kidney viability, and cerebral metabolism in infants (6-8). Finally, studies indicate that 3’P spectroscopy is feasible in a 1 m bore 1.5 T superconducting magnet (9). Quite generally, these studies have used surface coils (3), which are flat, multipleturn loops of wire wound into a “pancake” configuration. These structures (which serve as both NMR transmitter and receiver coils) are placed over the tissue or organ of interest. Methods to increase the sensitivity are of critical importance in the future development of in vivo “P NMR. In this paper an improved surface-coil design is described, together with bench and phantom studies of its characteristics. A spectrum of the thigh muscle of a healthy adult male is shown. The signal-to-noise ratio (SNR) of the NMR experiment has been discussed by Shaw (10) who gives pertinent references. For a series of resonators with identical relative radiofrequency magnetic-field distributions but differing Q’s, the signal intensity will vary as Q ‘I2 . This assumes that the incident power is adjusted such that the same excitation pulse (in angular units) is delivered to a given volume element. The Q depends on coil geometry, and our efforts have been to improve 3’P NMR sensitivity through improved coil geometry, thereby achieving a higher value of Q iI2. Transmission-line concepts developed in connection with the electron spin loop-gap resonator (LGR) (II, 12) were applied to the design of the NMR surface coil. The radiofrequency magnetic field Bi interacts with the sample by two mechanisms: first, by inducing signals from the nuclei of interest within the sample; and second, by giving rise to resistive losses within the sample. Hoult and Richards (13) describe the effects of (B,),, on the signal-to-noise ratio of the NMR experiment, where (B,), is the component of the magnetic field in a plane perpendicular to the static 571
0022-2364185
$3.00
Copyright Q 1985 by Academic Press, Inc. All rights of reproduction in any form resewed.
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field. Ackerman (3) summarized these effects with respect to the signal intensity in surface-coil experiments. The field distribution of Bi is critical, and homogeneous fields are desired. A rapid decrease in the magnitude of B, outside the volume of interest is desired for accurate localization to tissues of interest. The second mechanism of interaction between the magnetic field B, and the sample is a result of the conductivity of the sample. B, induces eddy currents that result in resistive losses within the sample. Hoult and Lauterbur (14) expressed the power dissipated in a spherical sample as
where p is the resistivity of the medium, and b is the radius of the sphere. The power dissipated lowers the Q of the coil and decreases the overall signal-to-noise ratio. This unavoidable decrease in Q provides a measurement of the fraction of the magnetic field energy in the sample volume. The electric lines of force interact with the sample to cause a resonant frequency shift and “dielectric losses.” These losses arise from the dielectric properties of water molecules and from charge transport in the ionicly conductive medium. The losses (t”) are proportional to the conductivity of the medium (15)
where t” is the imaginary part of the dielectric constant that is associated with loss in the nonconducting medium (i.e., pure H20), u is the tissue conductivity (mho cm-‘), and f0 the frequency. The electric lines of force pass through the sample because they are associated with the distributed capacitance of the coil. This capacitance exists for all coils, but its distribution is dependent upon coil geometry (16). Bringing all sources of loss together, one can write an expression for the effective Q: Qeir = stored energy/[(energy lost per cycle in Joulean heating of the coil) + (energy lost per cycle due to magnetic interactions in sample) + (energy lost per cycle due to electric interactions in sample)]. Improved coil design can reduce the first and third types of loss in the denominator of this equation, but not the second. One can define Q,,, as the stored energy/(energy lost per cycle due to magnetic interaction in the sample) and Q, as the stored energy/energy lost per cycle due to electric interactions in the sample. Then l/an = l/Qoii + l/Q,,, + l/Qe . In this notation our design objective is to make Qcoii and Q, high. Loop-gap resonators (LGR) (Fig. 1) designed in accordance with principles developed for ESR spectroscopy (II, 12) but scaled to dimensions for NMR of “P at 1.5 T (25.8 MHz) were fabricated from copper and formed on a coil former. One resonator was formed by silver electroplating a machined Plexiglas structure in a two-step process: (1) chemical deposition followed by (2) silver electroplating to depth three times the skin depth. Teflon and polyethylene dielectric films were inserted into the gap to form the capacitance C. (Resonator dimensions are given in Table 1.)
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TRANSMISSION
FIG. 1. The NMR loop-gap resonator. R = radius, Z = resonator height, t = gap thickness, I = capacitor length, and W = capacitor width.
The standard surface coil was formed by winding two turns of 3 mm diameter copper wire in a flat “pancake” configuration. The outside diameter was 6.5 cm while the inside diameter was 4.5 cm. The tuning capacitor was an Oxley nonmagnetic O-29 pf variable capacitor soldered to a printed circuit board connecting the inductor leads. A Faraday shield (efficiency unknown) was placed between the coil and sample. Physiological equivalent phantoms were made by placing solutions in 9 cm diameter X 20 cm tall polyethylene 1 liter bottles. Solutions of 100 rniV NaCl, 500 mA4 H3P04, and 20 mM H3P04 + 100 mit4 NaCl were mixed. Inductive coupling of the resonator with a coupling loop (Fig. 1) and a Teflon supporting structure was used. The coupling coefficient K is altered by changing the distance between the coupling loop and the resonator. At critical coupling K = 1 and the resonator will be matched for maximum power transfer. Information about the resonant frequency and quality factor of each resonator was obtained by loosely coupling transmit and pickup coils to the resonator. The frequency spectrum was displayed, f0 directly measured with a frequency counter, and the unloaded Q0 calculated by finding the 3 dB points on the curve, using Q = fo/A f and A f = fi - fi. Qes was found in the same manner, except that the sample medium (H20, 100 m/t4 NaCl, human arm) was placed adjacent to the coil. Homogeneity was determined by measuring the relative strength of B,, magnetic field at different distances with respect to the resonator. The pickup loop in this case was a small (6 mm diam) loop made of rigid coaxial line. NMR spectra were acquired from 500 mM H3P04 and 20 mM HJP04 + 100 m/U NaCl phantoms and human thigh muscle at 1.5 T (25.8 MHz) in order to compare the signal intensity for the standard two-turn surface coil and the LGR. The 31P NMR receiver coils were placed directly over the phantoms or human muscle tissue, and a specific calibration procedure was performed as follows: (1) Find 31P resonant frequency at center of magnet using 13 M H3P04 phantom. (2) Tune and match resonator to 50 D transmission line with coil positioned on sample (phantom or tissue) using a vector impedance meter. (3) Measure B,, field homogeneity (‘H spectrum linewidth) using 3’P coil at ‘H frequency. (4) Shim & to obtain as narrow a ‘H line as possible (0.25 ppm). (5) Switch frequencies to 3’P at 1.5 T (25.8 MHz). (6) Acquire spectra using 31P data acquisition package. Table 1 shows the radiofrequency characteristics of 10 versions of the single-loop single-gap resonator. The resonant frequency f0 and Q were measured as a function of the loop radius, capacitor area, dielectric thickness, and loop height.
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No. 1 2 3 4 5
6 7
8 9
10
r (cm)
W (cm)
4.5 2.5 2.5 2.5 2.5 2.5 2.5 3.2 3.2 3.7
7.6 7.6 5.0 5.0 5.0 3.8 5.0 5.0 5.0 5.0
1 (cm) 1.6 7.6 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
f (cm) 0.015 0.015 0.005 0.005 0.005 0.0013 0.0025 0.015 0.015 0.005
Resonators
Z (cm)
/O
1.2 1.2 0.6 2.5 5.0 1.2 2.5 1.2 1.2 1.9
16.7 24.6 43.8 51.8 61.0 25.9 25.4 26.2 25.6 40.9
Dielectric
Qo
Teflon a Teflon Teflon Teflon Teflon Polyethylene b Polyethylene c d Y
308 372 527 718 570 520 590 436 388 850
’ 2 mil Teflon film. b 0.5 mil polyethylene film. ’ 6 mil microwave Teflon substrate. d Resonator No. 8 with O-30 pf Oxley tuning capacitor. ‘Silver-plated (a = 0.015 mm) Plexiglas resonator with 0.015 cm Teflon dielectric.
The only difference between resonators 3, 4, and 5 was the height 2. As it decreased, the resonant frequency decreased in agreement with the increased inductance of the loop, L = P&Z, where puo = permeability, and A = crosssectional area of coil. Since the capacitance C is not altered by changing the height of the resonator, the frequency changes proportional to (L)-“2. The Q of the loopgap resonator is not significantly lowered even as the resonator height approaches 12% of its diameter. This is in general agreement with predictions for Q based on the semiempirical equations describing the loop-gap resonator (8). Resonator number 9 was used for the experiments described here. Table 2 compares the radiofrequency characteristics of the loop-gap resonator to those of the standard surface coil defined earlier. The resonators have the same diameters and are tuned to similar resonant frequencies. The LGR has a higher “unloaded” Q. (388 vs 118) which is the Q measured without coupling and without sample effects. In a matched coil, Q. = 2Q,-,il. The higher Q of the loop-gap TABLE 2 Radiofrequency Characteristics of Loop-Gap Resonator vs Standard Surface Coil r (cm) Standard coil Resonator No. 9
3.2 3.2
f(MHd 25.8 25.6
Qo=
QeRb
118 388
21 134
Qw,
SNRd
SNR=
35 205
3.5 8.0
2.8 5.5
a “Unloaded” Q. * Average effective Q calculated by applying resonators to three human forearms. c Calculated body Q. d 500 mM HgP04 phantom. e 20 mM H,P04 + 100 mJ4 NaCl phantom.
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resonator is attributed to (1) lower intrinsic resistance of the loop, and (2) elimination of losses in the transmission line that connects the surface coil and its resonating capacitor network. The effects of sample losses on Q were measured by placing the loop-gap resonator and the standard surface coil on the surface of physiologically equivalent phantoms and on human muscle tissue, and then measuring Qeff. Tissue data (Table 2) show that the Q of each structure was indeed lowered by the sample. However, the relative decrease in Q was not equal for both structures; Q of the standard surface coil decreased by 79%, while Q of the loop-gap resonator decreased 65%. Most importantly, the calculated “sample Q’s” (Qbody)were quite different: 1 1 -zz1 L+--=L+L where QEd Qcoil Qb~dy Qbody Qm Qe’ High values of Qe are desirable, as previously noted, but performance cannot be improved by increasing Q,,, (which would only indicate that there is no radiofrequency magnetic field in the sample). The intensity of the electric lines of force passing through the sample can be estimated by positioning the receivers on a pure water phantom, which has a high dielectric constant (-75 at 25 MHz) but a low loss tangent (t”/~’ = 0.008 at 25 MHz). In addition, the phantom has a low conductivity (5.4 X 1O-8 mho/cm at pH = 7 and 25°C) which makes inductive losses negligible. The high dielectric constant of water allows the frequency shift to be measured with good sensitivity. The relative frequency shifts can be used to study the distributed capacitance C, of each receiver in an equivalent circuit model. The frequency shift with the phantom adjacent to the receivers is greater for the two-turn surface coil (130 vs 28 kHz). In addition, the resonant frequency of the two-turn surface coil is significantly altered by the water phantom at greater distances (4 vs 2 cm) than the loop-gap resonator. Figure 2 shows the effect of sample loading on Q as a function of distance between the NMR receivers and phantoms containing pure Hz0 and 100 rnA4 NaCl. In both cases the Q’s of the coils are not affected by the pure HZ0 phantoms which have a low conductivity and a low dielectric loss tangent. On the other hand, the 100 mA4 NaCl has a much higher conductivity (120 mho/cm) and higher inductive and dielectric losses. The data in Fig. 2 suggest that the field distributions of the two resonators are different. Since the Q of the loop-gap resonator is lowered more and at greater distances and the dielectric losses are less compared with the standard surface coil, it is concluded that the inductive losses are greater for the loop-gap resonator. This corresponds to greater magnetic field energy stored in the sample volume. Figure 3 shows the dependence of B ix upon the depth below the resonator (x) and the distance along the radial axis (y). These data show less variation in the intensity of B,, for a given x and, therefore, a more homogeneous B,, distribution for the loop-gap resonator. In addition, the boundaries of B1, tend toward a cylindrical shape, as opposed to a conical shape in the two-turn surface coil. This is evidenced by less variation in the magnitude of B1, for values of x less than the radius of the resonator, in addition to a more rapid decrease in BI, field intensity for values of x greater than the resonator radius.
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360 320
240
a 160
0
1
Distance
2
3
of Resonator (cm)
4
5
6
from
Object
7
FIG. 2. Effect of phantoms on quality factor (Q) of the loop-gap resonator and the two-turn standard surface coil. edf is measured while varying the distance lktween the receivers and phantoms containing pure water (closed symbols) and 100 mM NaCl (open symbols). A, loop-gap resonator; 0, standard twoturn surface coil.
Table 2 compares the results of signal-to-noise measurements obtained from phantom studies. The twofold increase in SNR for the loop-gap resonator using a physiological equivalent (100 mA4 NaCl + 20 mM H3P04) phantom is in general agreement with Qeff measurements in Table 2 since SNR a Q$. Naturally, one would expect the 500 nGt4 H3P04 phantom to yield a higher SNR because of the high concentration of 31P nuclei. However, this solution also has a high conductivity. Therefore Q,,, is low for both coils, and the Q’s tend to be dominated by these losses. Finally, the loop-gap resonator was used as a transmitter and receiver to acquire a “P NMR spectrum from the skeletal muscle of a 43-year-old healthy adult male volunteer, Fig. 4. The resonator was placed on the medial aspect of the right thigh 25 cm above the knee, thus acquiring signal from the adductor magnus, adductor brevis, adductor longus, and gracilis muscles, in addition to subcutaneous fat, tissue, and skin. A phase-alternated repeated 90” pulse sequence was used with a repetition time of 1 s, a pulse width of 100 ps, and input power of 12 W. The spectrum was accumulated in 100 s, yielding a phosphocreatine (PCr) signal-to-noise ratio of 4O:l.
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Standard Surface Coil
3
2
1
0 Y (cm)
1
2
3
FIG. 3. The spatial dependence of (BJ, as a function of y, the radial coordinate, for different positions along the x axis. (B,), is normalized to 1.0 at the center of the coil (x, y = 0, 0). The figure shows the magnitude of (B,), for the loop-gap resonator on the right and the standard surface coil on the left.
The peaks appear somewhat broadened. Since no exponential line broadening filters were used, we feel that the linewidth is due in part to inhomogeneities in the static field over the sensitive volume. It has thus been shown that the magnetic-field distributions using the loop-gap resonator are similar to those using a conventional surface coil. Homogeneity in the region of interest and fall-off of field intensity outside this region tend to favor the loop-gap resonator. Improved 31P NMR signals from phantoms and from in vivo muscle have been obtained with signals of comparable quality obtained in three to four times reduced total measurement time using the loop-gap resonator. In this comparison the actual volumes of sampled material were similar, and it appears that the filling factors also were similar. A key question is: To what coil characteristics can this improved performance be attributed? In part, this is certainly due to higher Qaii. Resistances in the loop-gap resonator are much less than in the surface coil because of the absence of a transmission line and capacitive coupling network. We further hypothesize that dielectric losses in the sample are reduced with the loop-gap resonator, leading to an increased Qe. Since QbodY(LGR) % hY (surface coil), and our good NMR results indicate that Q,,, (surface coil) N Q, (LGR), this hypothesis-namely that Q, (surface coil) + Qe (LGR)-gives an internally consistent explanation of our experiments.
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m
FIG. 4. “P NMR spectrum acquired from human calf muscle tissue using loop-gap resonator 9. This spectrum was acquired in 13 min. (Repetition rate = 4.0 s, pulse width = 210 ps, FWHM = 0.755 ppm, N = 200 averages.) Peak assignments are as follows: (I) (u-ATP = -7.54 ppm, (II) fi-ATP = - 16.1 ppm, (III) y-ATP = -2.97 ppm, (IV) PCr = 0.0 ppm by definition, (V) Pi = 4.90 ppm. ACKNOWLEDGMENTS We thank General Electric Medical Systems Group as a whole for their encouragement and support of this research and access to a 1.5 T 3’P spectroscopy system. We are indebted to Dr. J. R. MacFall for providing assistance in initial setup and shimming the 1.5 T system, to Dr. C. E. Hayes for advice in the design and testing of rf coils, and to Dr. F. W. Wehrli for providing advice and encouragement. We thank Dr. G. A. Johnson and Dr. R. J. Hetfkens of the Duke University Department of Radiology for assistance in acquiring the “P muscle spectrum. This work was supported in part by NIH Research Resources Grant RR-01008 and by an NIH Medical Student Summer Research Fellowship. REFERENCES 1. D. I. HOULT,
S. J. W. BUSBY,
D. G. GADIAN,
G. K. RADDA,
R. E. RICHARDS,
AND P. J. SEELEY,
Nature (London) 252, 285 (1974). 2. P. B. GARLICK, G. K. RADDA, P. J. SEELEY, AND B. CHANCE, Biochem. Biophys. Res. Commun. 74, 1256 (1977). 3. J. J. H. ACKERMAN, G. H. GROVE, G. G. WONG, D. G. GADIAN, AND G. K. RADDA, Nature
(London) 283, 167 (1980). NUNNALLY AND P. A. BOTTOMLEY, Science 211, 177 (1981). NG, W. T. EVANOCHRO, R. N. HIRAMOTO, V. K. GHANTA, M. B. LILLY, A. J. LAWSON, H. CORBETT, J. R. DURANT, AND J. D. GLICKSON, J. Magn. Reson. 49,231 (1982). Ross, G. K. RADDA, D. G. GADIAN, G. ROCKER, M. ESIRI, AND J. FALCONER-SMITH, N. Engl. J. Med. 304, 1338 (1981). P. J. BORE, L. CHAN, M. E. FRENCH, D. G. GADIAN, G. K. RADDA, B. D. Ross, AND P. STYLES, Kidney Int. 20, 686 (1981). E. B. CADY, M. J. DAWSON, P. L. HOPE, P. S. TOFTS, A. M. DE L. COSTELLO, D. T. DELPY, E. 0. R. REYNOLDS, AND D. R. WILKIE, Lancet I, 1059 (1983). P. A. B~~OMLEY, H. R. HART, W. A. EDELSTEIN, J. F. SHENK, L. S. SMITH, W. M. LEUE, 0. M. MUELLER, AND R. W. -DINGTON, Lancet 2, 273 (1983). D. SHAW, “Fourier Transform NMR Spectroscopy,” pp. 162-169, Elsevier, Amsterdam, 1976. W. FRONCISZ AND J. S. HYDE, J. Mugn. Reson. 47, 5 15 (1982). J. S. HYDE, W. FRONCISZ, AND A. KLJSUMI, Rev. Sci. Instrum. 53, 1934 (1982). D. I. HOULT AND R. E. RICHARDS, J. Magn. Reson. 24, 71 (1976). D. I. HOULT AND P. C. LAUTERBUR, J. Magn. Reson. 34, 425 (1979). J. B. HASTED, “Aqueous Dielectrics,” pp. 28-29, Chapman & Hill, London, 198 1. F. E. TERMAN, “Radio Engineer’s Handbook,” pp. 73-90, McGraw-Hill, New York, 1943.
4. R. L. 5. T. C. T. 6. B. D. 7. 8. 9. 10.
Il. 12. 13. 14.
15. 16.
OF MAGNETIC
RESONANCE
61, 571-578
(1985)
Resonators for in Vivo 31P NMR THOMAS
at 1.5 T
M. GRIST AND JAMES S. HYDE
National Biomedical ESR Center, Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226 Received
October
10. 1984
Phosphorus nuclear magnetic resonance of naturally occurring compounds such as adenosine triphosphate, phosphocreatine, inorganic phosphate, phosphodiesters, and sugar phosphates in biological tissues is a subject of current interest in many laboratories. Tissue metabolism was first observed with 31P NMR in 1974 (1). Subsequently, isolated perfused organs (2) and organs in intact animals using surface coils were studied (3). Changes in phosphorus compound metabolism have been observed noninvasively in pathological states such as ischemia and cancer (4, 5). Clinical applications began by observing forearm muscle metabolism in patients with McCardle’s disease, human kidney viability, and cerebral metabolism in infants (6-8). Finally, studies indicate that 3’P spectroscopy is feasible in a 1 m bore 1.5 T superconducting magnet (9). Quite generally, these studies have used surface coils (3), which are flat, multipleturn loops of wire wound into a “pancake” configuration. These structures (which serve as both NMR transmitter and receiver coils) are placed over the tissue or organ of interest. Methods to increase the sensitivity are of critical importance in the future development of in vivo “P NMR. In this paper an improved surface-coil design is described, together with bench and phantom studies of its characteristics. A spectrum of the thigh muscle of a healthy adult male is shown. The signal-to-noise ratio (SNR) of the NMR experiment has been discussed by Shaw (10) who gives pertinent references. For a series of resonators with identical relative radiofrequency magnetic-field distributions but differing Q’s, the signal intensity will vary as Q ‘I2 . This assumes that the incident power is adjusted such that the same excitation pulse (in angular units) is delivered to a given volume element. The Q depends on coil geometry, and our efforts have been to improve 3’P NMR sensitivity through improved coil geometry, thereby achieving a higher value of Q iI2. Transmission-line concepts developed in connection with the electron spin loop-gap resonator (LGR) (II, 12) were applied to the design of the NMR surface coil. The radiofrequency magnetic field Bi interacts with the sample by two mechanisms: first, by inducing signals from the nuclei of interest within the sample; and second, by giving rise to resistive losses within the sample. Hoult and Richards (13) describe the effects of (B,),, on the signal-to-noise ratio of the NMR experiment, where (B,), is the component of the magnetic field in a plane perpendicular to the static 571
0022-2364185
$3.00
Copyright Q 1985 by Academic Press, Inc. All rights of reproduction in any form resewed.
572
COMMUNICATIONS
field. Ackerman (3) summarized these effects with respect to the signal intensity in surface-coil experiments. The field distribution of Bi is critical, and homogeneous fields are desired. A rapid decrease in the magnitude of B, outside the volume of interest is desired for accurate localization to tissues of interest. The second mechanism of interaction between the magnetic field B, and the sample is a result of the conductivity of the sample. B, induces eddy currents that result in resistive losses within the sample. Hoult and Lauterbur (14) expressed the power dissipated in a spherical sample as
where p is the resistivity of the medium, and b is the radius of the sphere. The power dissipated lowers the Q of the coil and decreases the overall signal-to-noise ratio. This unavoidable decrease in Q provides a measurement of the fraction of the magnetic field energy in the sample volume. The electric lines of force interact with the sample to cause a resonant frequency shift and “dielectric losses.” These losses arise from the dielectric properties of water molecules and from charge transport in the ionicly conductive medium. The losses (t”) are proportional to the conductivity of the medium (15)
where t” is the imaginary part of the dielectric constant that is associated with loss in the nonconducting medium (i.e., pure H20), u is the tissue conductivity (mho cm-‘), and f0 the frequency. The electric lines of force pass through the sample because they are associated with the distributed capacitance of the coil. This capacitance exists for all coils, but its distribution is dependent upon coil geometry (16). Bringing all sources of loss together, one can write an expression for the effective Q: Qeir = stored energy/[(energy lost per cycle in Joulean heating of the coil) + (energy lost per cycle due to magnetic interactions in sample) + (energy lost per cycle due to electric interactions in sample)]. Improved coil design can reduce the first and third types of loss in the denominator of this equation, but not the second. One can define Q,,, as the stored energy/(energy lost per cycle due to magnetic interaction in the sample) and Q, as the stored energy/energy lost per cycle due to electric interactions in the sample. Then l/an = l/Qoii + l/Q,,, + l/Qe . In this notation our design objective is to make Qcoii and Q, high. Loop-gap resonators (LGR) (Fig. 1) designed in accordance with principles developed for ESR spectroscopy (II, 12) but scaled to dimensions for NMR of “P at 1.5 T (25.8 MHz) were fabricated from copper and formed on a coil former. One resonator was formed by silver electroplating a machined Plexiglas structure in a two-step process: (1) chemical deposition followed by (2) silver electroplating to depth three times the skin depth. Teflon and polyethylene dielectric films were inserted into the gap to form the capacitance C. (Resonator dimensions are given in Table 1.)
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DIELECTRIC
TRANSMISSION
FIG. 1. The NMR loop-gap resonator. R = radius, Z = resonator height, t = gap thickness, I = capacitor length, and W = capacitor width.
The standard surface coil was formed by winding two turns of 3 mm diameter copper wire in a flat “pancake” configuration. The outside diameter was 6.5 cm while the inside diameter was 4.5 cm. The tuning capacitor was an Oxley nonmagnetic O-29 pf variable capacitor soldered to a printed circuit board connecting the inductor leads. A Faraday shield (efficiency unknown) was placed between the coil and sample. Physiological equivalent phantoms were made by placing solutions in 9 cm diameter X 20 cm tall polyethylene 1 liter bottles. Solutions of 100 rniV NaCl, 500 mA4 H3P04, and 20 mM H3P04 + 100 mit4 NaCl were mixed. Inductive coupling of the resonator with a coupling loop (Fig. 1) and a Teflon supporting structure was used. The coupling coefficient K is altered by changing the distance between the coupling loop and the resonator. At critical coupling K = 1 and the resonator will be matched for maximum power transfer. Information about the resonant frequency and quality factor of each resonator was obtained by loosely coupling transmit and pickup coils to the resonator. The frequency spectrum was displayed, f0 directly measured with a frequency counter, and the unloaded Q0 calculated by finding the 3 dB points on the curve, using Q = fo/A f and A f = fi - fi. Qes was found in the same manner, except that the sample medium (H20, 100 m/t4 NaCl, human arm) was placed adjacent to the coil. Homogeneity was determined by measuring the relative strength of B,, magnetic field at different distances with respect to the resonator. The pickup loop in this case was a small (6 mm diam) loop made of rigid coaxial line. NMR spectra were acquired from 500 mM H3P04 and 20 mM HJP04 + 100 m/U NaCl phantoms and human thigh muscle at 1.5 T (25.8 MHz) in order to compare the signal intensity for the standard two-turn surface coil and the LGR. The 31P NMR receiver coils were placed directly over the phantoms or human muscle tissue, and a specific calibration procedure was performed as follows: (1) Find 31P resonant frequency at center of magnet using 13 M H3P04 phantom. (2) Tune and match resonator to 50 D transmission line with coil positioned on sample (phantom or tissue) using a vector impedance meter. (3) Measure B,, field homogeneity (‘H spectrum linewidth) using 3’P coil at ‘H frequency. (4) Shim & to obtain as narrow a ‘H line as possible (0.25 ppm). (5) Switch frequencies to 3’P at 1.5 T (25.8 MHz). (6) Acquire spectra using 31P data acquisition package. Table 1 shows the radiofrequency characteristics of 10 versions of the single-loop single-gap resonator. The resonant frequency f0 and Q were measured as a function of the loop radius, capacitor area, dielectric thickness, and loop height.
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COMMUNICATIONS TABLE I Radiofrequency Characteristics of Loop-Gap
No. 1 2 3 4 5
6 7
8 9
10
r (cm)
W (cm)
4.5 2.5 2.5 2.5 2.5 2.5 2.5 3.2 3.2 3.7
7.6 7.6 5.0 5.0 5.0 3.8 5.0 5.0 5.0 5.0
1 (cm) 1.6 7.6 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
f (cm) 0.015 0.015 0.005 0.005 0.005 0.0013 0.0025 0.015 0.015 0.005
Resonators
Z (cm)
/O
1.2 1.2 0.6 2.5 5.0 1.2 2.5 1.2 1.2 1.9
16.7 24.6 43.8 51.8 61.0 25.9 25.4 26.2 25.6 40.9
Dielectric
Qo
Teflon a Teflon Teflon Teflon Teflon Polyethylene b Polyethylene c d Y
308 372 527 718 570 520 590 436 388 850
’ 2 mil Teflon film. b 0.5 mil polyethylene film. ’ 6 mil microwave Teflon substrate. d Resonator No. 8 with O-30 pf Oxley tuning capacitor. ‘Silver-plated (a = 0.015 mm) Plexiglas resonator with 0.015 cm Teflon dielectric.
The only difference between resonators 3, 4, and 5 was the height 2. As it decreased, the resonant frequency decreased in agreement with the increased inductance of the loop, L = P&Z, where puo = permeability, and A = crosssectional area of coil. Since the capacitance C is not altered by changing the height of the resonator, the frequency changes proportional to (L)-“2. The Q of the loopgap resonator is not significantly lowered even as the resonator height approaches 12% of its diameter. This is in general agreement with predictions for Q based on the semiempirical equations describing the loop-gap resonator (8). Resonator number 9 was used for the experiments described here. Table 2 compares the radiofrequency characteristics of the loop-gap resonator to those of the standard surface coil defined earlier. The resonators have the same diameters and are tuned to similar resonant frequencies. The LGR has a higher “unloaded” Q. (388 vs 118) which is the Q measured without coupling and without sample effects. In a matched coil, Q. = 2Q,-,il. The higher Q of the loop-gap TABLE 2 Radiofrequency Characteristics of Loop-Gap Resonator vs Standard Surface Coil r (cm) Standard coil Resonator No. 9
3.2 3.2
f(MHd 25.8 25.6
Qo=
QeRb
118 388
21 134
Qw,
SNRd
SNR=
35 205
3.5 8.0
2.8 5.5
a “Unloaded” Q. * Average effective Q calculated by applying resonators to three human forearms. c Calculated body Q. d 500 mM HgP04 phantom. e 20 mM H,P04 + 100 mJ4 NaCl phantom.
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resonator is attributed to (1) lower intrinsic resistance of the loop, and (2) elimination of losses in the transmission line that connects the surface coil and its resonating capacitor network. The effects of sample losses on Q were measured by placing the loop-gap resonator and the standard surface coil on the surface of physiologically equivalent phantoms and on human muscle tissue, and then measuring Qeff. Tissue data (Table 2) show that the Q of each structure was indeed lowered by the sample. However, the relative decrease in Q was not equal for both structures; Q of the standard surface coil decreased by 79%, while Q of the loop-gap resonator decreased 65%. Most importantly, the calculated “sample Q’s” (Qbody)were quite different: 1 1 -zz1 L+--=L+L where QEd Qcoil Qb~dy Qbody Qm Qe’ High values of Qe are desirable, as previously noted, but performance cannot be improved by increasing Q,,, (which would only indicate that there is no radiofrequency magnetic field in the sample). The intensity of the electric lines of force passing through the sample can be estimated by positioning the receivers on a pure water phantom, which has a high dielectric constant (-75 at 25 MHz) but a low loss tangent (t”/~’ = 0.008 at 25 MHz). In addition, the phantom has a low conductivity (5.4 X 1O-8 mho/cm at pH = 7 and 25°C) which makes inductive losses negligible. The high dielectric constant of water allows the frequency shift to be measured with good sensitivity. The relative frequency shifts can be used to study the distributed capacitance C, of each receiver in an equivalent circuit model. The frequency shift with the phantom adjacent to the receivers is greater for the two-turn surface coil (130 vs 28 kHz). In addition, the resonant frequency of the two-turn surface coil is significantly altered by the water phantom at greater distances (4 vs 2 cm) than the loop-gap resonator. Figure 2 shows the effect of sample loading on Q as a function of distance between the NMR receivers and phantoms containing pure Hz0 and 100 rnA4 NaCl. In both cases the Q’s of the coils are not affected by the pure HZ0 phantoms which have a low conductivity and a low dielectric loss tangent. On the other hand, the 100 mA4 NaCl has a much higher conductivity (120 mho/cm) and higher inductive and dielectric losses. The data in Fig. 2 suggest that the field distributions of the two resonators are different. Since the Q of the loop-gap resonator is lowered more and at greater distances and the dielectric losses are less compared with the standard surface coil, it is concluded that the inductive losses are greater for the loop-gap resonator. This corresponds to greater magnetic field energy stored in the sample volume. Figure 3 shows the dependence of B ix upon the depth below the resonator (x) and the distance along the radial axis (y). These data show less variation in the intensity of B,, for a given x and, therefore, a more homogeneous B,, distribution for the loop-gap resonator. In addition, the boundaries of B1, tend toward a cylindrical shape, as opposed to a conical shape in the two-turn surface coil. This is evidenced by less variation in the magnitude of B1, for values of x less than the radius of the resonator, in addition to a more rapid decrease in BI, field intensity for values of x greater than the resonator radius.
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FIG. 2. Effect of phantoms on quality factor (Q) of the loop-gap resonator and the two-turn standard surface coil. edf is measured while varying the distance lktween the receivers and phantoms containing pure water (closed symbols) and 100 mM NaCl (open symbols). A, loop-gap resonator; 0, standard twoturn surface coil.
Table 2 compares the results of signal-to-noise measurements obtained from phantom studies. The twofold increase in SNR for the loop-gap resonator using a physiological equivalent (100 mA4 NaCl + 20 mM H3P04) phantom is in general agreement with Qeff measurements in Table 2 since SNR a Q$. Naturally, one would expect the 500 nGt4 H3P04 phantom to yield a higher SNR because of the high concentration of 31P nuclei. However, this solution also has a high conductivity. Therefore Q,,, is low for both coils, and the Q’s tend to be dominated by these losses. Finally, the loop-gap resonator was used as a transmitter and receiver to acquire a “P NMR spectrum from the skeletal muscle of a 43-year-old healthy adult male volunteer, Fig. 4. The resonator was placed on the medial aspect of the right thigh 25 cm above the knee, thus acquiring signal from the adductor magnus, adductor brevis, adductor longus, and gracilis muscles, in addition to subcutaneous fat, tissue, and skin. A phase-alternated repeated 90” pulse sequence was used with a repetition time of 1 s, a pulse width of 100 ps, and input power of 12 W. The spectrum was accumulated in 100 s, yielding a phosphocreatine (PCr) signal-to-noise ratio of 4O:l.
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2
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FIG. 3. The spatial dependence of (BJ, as a function of y, the radial coordinate, for different positions along the x axis. (B,), is normalized to 1.0 at the center of the coil (x, y = 0, 0). The figure shows the magnitude of (B,), for the loop-gap resonator on the right and the standard surface coil on the left.
The peaks appear somewhat broadened. Since no exponential line broadening filters were used, we feel that the linewidth is due in part to inhomogeneities in the static field over the sensitive volume. It has thus been shown that the magnetic-field distributions using the loop-gap resonator are similar to those using a conventional surface coil. Homogeneity in the region of interest and fall-off of field intensity outside this region tend to favor the loop-gap resonator. Improved 31P NMR signals from phantoms and from in vivo muscle have been obtained with signals of comparable quality obtained in three to four times reduced total measurement time using the loop-gap resonator. In this comparison the actual volumes of sampled material were similar, and it appears that the filling factors also were similar. A key question is: To what coil characteristics can this improved performance be attributed? In part, this is certainly due to higher Qaii. Resistances in the loop-gap resonator are much less than in the surface coil because of the absence of a transmission line and capacitive coupling network. We further hypothesize that dielectric losses in the sample are reduced with the loop-gap resonator, leading to an increased Qe. Since QbodY(LGR) % hY (surface coil), and our good NMR results indicate that Q,,, (surface coil) N Q, (LGR), this hypothesis-namely that Q, (surface coil) + Qe (LGR)-gives an internally consistent explanation of our experiments.
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FIG. 4. “P NMR spectrum acquired from human calf muscle tissue using loop-gap resonator 9. This spectrum was acquired in 13 min. (Repetition rate = 4.0 s, pulse width = 210 ps, FWHM = 0.755 ppm, N = 200 averages.) Peak assignments are as follows: (I) (u-ATP = -7.54 ppm, (II) fi-ATP = - 16.1 ppm, (III) y-ATP = -2.97 ppm, (IV) PCr = 0.0 ppm by definition, (V) Pi = 4.90 ppm. ACKNOWLEDGMENTS We thank General Electric Medical Systems Group as a whole for their encouragement and support of this research and access to a 1.5 T 3’P spectroscopy system. We are indebted to Dr. J. R. MacFall for providing assistance in initial setup and shimming the 1.5 T system, to Dr. C. E. Hayes for advice in the design and testing of rf coils, and to Dr. F. W. Wehrli for providing advice and encouragement. We thank Dr. G. A. Johnson and Dr. R. J. Hetfkens of the Duke University Department of Radiology for assistance in acquiring the “P muscle spectrum. This work was supported in part by NIH Research Resources Grant RR-01008 and by an NIH Medical Student Summer Research Fellowship. REFERENCES 1. D. I. HOULT,
S. J. W. BUSBY,
D. G. GADIAN,
G. K. RADDA,
R. E. RICHARDS,
AND P. J. SEELEY,
Nature (London) 252, 285 (1974). 2. P. B. GARLICK, G. K. RADDA, P. J. SEELEY, AND B. CHANCE, Biochem. Biophys. Res. Commun. 74, 1256 (1977). 3. J. J. H. ACKERMAN, G. H. GROVE, G. G. WONG, D. G. GADIAN, AND G. K. RADDA, Nature
(London) 283, 167 (1980). NUNNALLY AND P. A. BOTTOMLEY, Science 211, 177 (1981). NG, W. T. EVANOCHRO, R. N. HIRAMOTO, V. K. GHANTA, M. B. LILLY, A. J. LAWSON, H. CORBETT, J. R. DURANT, AND J. D. GLICKSON, J. Magn. Reson. 49,231 (1982). Ross, G. K. RADDA, D. G. GADIAN, G. ROCKER, M. ESIRI, AND J. FALCONER-SMITH, N. Engl. J. Med. 304, 1338 (1981). P. J. BORE, L. CHAN, M. E. FRENCH, D. G. GADIAN, G. K. RADDA, B. D. Ross, AND P. STYLES, Kidney Int. 20, 686 (1981). E. B. CADY, M. J. DAWSON, P. L. HOPE, P. S. TOFTS, A. M. DE L. COSTELLO, D. T. DELPY, E. 0. R. REYNOLDS, AND D. R. WILKIE, Lancet I, 1059 (1983). P. A. B~~OMLEY, H. R. HART, W. A. EDELSTEIN, J. F. SHENK, L. S. SMITH, W. M. LEUE, 0. M. MUELLER, AND R. W. -DINGTON, Lancet 2, 273 (1983). D. SHAW, “Fourier Transform NMR Spectroscopy,” pp. 162-169, Elsevier, Amsterdam, 1976. W. FRONCISZ AND J. S. HYDE, J. Mugn. Reson. 47, 5 15 (1982). J. S. HYDE, W. FRONCISZ, AND A. KLJSUMI, Rev. Sci. Instrum. 53, 1934 (1982). D. I. HOULT AND R. E. RICHARDS, J. Magn. Reson. 24, 71 (1976). D. I. HOULT AND P. C. LAUTERBUR, J. Magn. Reson. 34, 425 (1979). J. B. HASTED, “Aqueous Dielectrics,” pp. 28-29, Chapman & Hill, London, 198 1. F. E. TERMAN, “Radio Engineer’s Handbook,” pp. 73-90, McGraw-Hill, New York, 1943.
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