Magnetic Resonance Imaging, Vol. 14, No. 9, pp. 1073-1078, 1996 Copyright 0 1996 Elsevier Science Inc.

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ELSEVIER

l Original Contribution

PI1 SO730-725X( 96) 00227-l

“O-DECOUPLED ‘H DETECTION USING A DOUBLE-TUNED COIL

RAVINDER REDDY, ALAN H. STOLPEN, SRIDHAR R. CHARAGUNDLA, E.K. INSKO, AND JOHN S. LEIGH

MMRRCC, Department of Radiology, University of Pennsylvania, Philadelphia, PA

“O-decoupled proton MR spectroscopy and imaging with a double-tuned radiofrequency (RF) coil at 2 T was used to detect and quantify Hz “0 in tissue phantoms containing various concentrations of “O-enriched water in 5 % gelatin. The pulse sequence used in these experiments consisted of a conventional proton spin- echo sequence with RF irradiation at the “0 resonance frequency applied between the proton 90” pulse and the signal acquisition window. The double-tuned coil provided several advantages over systems using separate RF coils for “0 decoupling and proton excitation/detection, including ensuring that the same (or similar) sample volumes are excited and decoupled and permitting accurate calibration of the “0 decoupling pulse amplitude. The efficiency of “0 decoupling as a function of decoupling RF amplitude, decoupling duration, and decoupling resonance offset was investigated. Finally, the specific absorption rate of the “0 decoupled pulse sequence was investigated and found to lie within federal guidelines at 1.5 T. Copyright 0 1996 Elsevier Science Inc.

Keywords: “0; Decoupling; Double-tuned coil; Proton NMR; Gelatin.

INTRODUCTION

Oxygen-17 ( 170) has been used in MR spectroscopy and imaging experiments to quantify cerebral blood flow and oxidative metabolism.1-9 The nonradioactive spin 5/2 170 nucleus can be detected directly by NMR or indirectly through its interaction with other magnetic nuclei, including protons. Unfortunately, direct 170 de- tection methods suffer from poor signal-to-noise ratio. Spatial localization of the 170 MR is made difficult by its very short T2 ( <6 ms) . Finally, direct pulse-acquire measurements using “0 NMR are prone to underesti- mating the true H2 170 concentration. The underestima- tion arises from the tri.ple exponential T2 relaxation of spin 5/2 nuclei (such as “0) for molecular motions outside the extreme narrowing condition (i.e., for wo~c 2 1, where w,, is the Larmor frequency and Q-~ is the correlation time). “zll ‘Under these conditions, it is also possible to create and detect multiple quantum coher- ences, which further confounds direct I70 quantitation.

The many disadvantages of direct 170 NMR stimu- lated a search for suitable indirect detection methods.

The basis for one such method was established by Meiboom, ‘* who, in his study of proton chemical ex- change in 170-enriched water at neutral pH, showed that scalar coupling (i.e., J-coupling or spin-spin cou- pling) between ‘H and 170 caused an increase in proton T,, and T2 relaxation rates with a corresponding line broadening of proton NMR spectra. Furthermore, it was shown that proton chemical exchange between I60 and I70 nuclei (i.e., scalar relaxation of the first kind; 7 - 1 ms) and “0 spin-lattice relaxation (i.e., scalar relaxation of the second kind; “T, - 6 ms) act in concert to modulate the scalar coupling.‘2,13 Burnett and Zeltmann have reported a [“O- ‘H] J-coupling constant of 91 Hz for 170-enriched water.14

H2 170-mediated enhancement of proton T2 and T1, relaxation rates, which is analogous to the behavior of T,-type MR contrast agents, has been exploited in the development of several indirect H2 170 quantitation methods.15-‘7 Ronen and Navon I5 developed a highly sensitive and specific indirect method whose essential feature is 170 decoupling in a T,-weighted proton spin- echo acquisition. Briefly, the 170 resonance frequency

RECEIVED 811195; ACCEPTED 614196. Stellar-Chance Laboratory, 422 Curie Blvd., Philadelphia, Address correspondence to Ravinder Reddy, Ph.D.; PA 19104-6100.

Department of Radiology, University of Pennsylvania, Bl, 1073

1074 Magnetic Resonance Imaging 0 Volume 14, Number 9, 1996

was irradiated during evolution of the proton spin- echo, in a manner not specified by the authors. The decoupling pulse effectively eliminates J-coupling be- tween “0 and ‘H, thereby decreasing proton Tz and T,, relaxation rates and increasing proton signal intensity. HZ1’O concentration was calculated from an equation whose terms include the proton signal intensities in the absence and presence of “0 decoupling.15

Ronen and Navon l5 performed their decoupling ex- periment on a high resolution NMR spectrometer equipped with separate RF coils and transmitters for “0 decoupling and proton excitation. This hardware configuration does not permit direct calibration of the “0 decoupling power, does not facilitate the accurate determination of the specific absorption rate (SAR), and is therefore not useful for quantifying optimal ex- perimental parameters. The two-coil system is also dif- ficult to implement on a standard clinical MR scanner. In this article, we propose strategies for improving implementation of “0 decoupling of a tissue phantom by using a double-tuned coil in a 2-T whole body MRI scanner. In particular, we demonstrate the advantages of using a double-tuned RF coil for “0 decoupling and proton excitation, we describe a strategy for opti- mizing the efficiency of “0 decoupling, and we eval- uate the safety of the decoupling method in terms of estimated SAR.

MATERIALS AND METHODS

“O-enriched water (25.7% atom fraction) was ob- tained from Isotec (Miamisburg, OH) and gelatin from Sigma (St. Louis, MO). NMR phantoms containing 5% gelatin in deionized water (non- “O-enriched) at pH 7.2 in 6 X 50-mm borosilicate tubes were used to mimic the protein content and rigidity of a semisolid tissue. The phantoms were doped with various amounts of “O-enriched water to yield final “0 atom fractions of 0.037 (natural abundance), 0.2,0.4, and 2.0 atom%.

All spectroscopy and imaging experiments were performed on an Oxford 2-T whole body supercon- ducting magnet interfaced to a custom-built spectrome- ter. An eight-turn solenoidal RF coil was custom-built and double-tuned to the I70 ( 11.7 MHz) and proton (86.3 MHz) resonance frequencies, according to the method of Schnall et al.‘* Proton spectra were acquired with a bandwidth of 5 kHz and 2048 data points. The duration of a typical 90” pulse for ‘H was 40 pus. Proton spin-lattice (T,) and spin-spin (T2) relaxation times for the phantoms were determined using 20-point spec- troscopic inversion recovery and conventional spin echo sequences, respectively. Direct detection of the “0 NMR signal was performed using a simple pulse- acquire sequence.

“0 decoupling was performed during a proton spin- echo pulse sequence with a repetition time (TR) of 12 s and an echo-time (TE) of 600 ms. The decoupling pulse(s) consisted of a single, low power, rectangular RF pulse or a train of small flip angle RF pulses at the “0 resonance frequency. Decoupling was applied between the 90” and 180” proton RF pulses and then again between the 180” RF pulse and the signal acquisi- tion window but was not applied during the proton 180” pulse, signal acquisition, or gradient activation. The width of a typical 90” pulse (rgO) for “0 was approximately 12 ps, from which we calculated a max- imum decoupling power equal to (4~~~) -’ or 20.8 kHz. The maximum decoupling power was attenuated, as indicated, in all experiments. Figure 1 depicts the pulse sequence used for ‘70-decoupled proton imaging. The imaging parameters were TR = 3 s, TE = 400 ms, slice thickness = 1 mm, matrix = 256 X 128, and FOV = 2 X 2 cm. A 7-cm-diameter gradient set was used in these imaging experiments. In the spectro- scopic “O-decoupled pulse sequence, the truncated sine pulses were replaced by nonselective RF pulses. A passive switch triggered by a computer-controlled signal (Fig. 2) was used to select the transmitter output frequency (‘H or “0) to the double-tuned coil. This hardware configuration allowed transmission of two RF frequencies to a double-tuned coil with a single input port.

17-o -I-ull

ACQ I I

Fig. 1. Pulse sequence used for “O-decoupled proton im- aging with a double-tuned coil. ‘H and “0 lines represent proton and I70 RF channels, respectively; ACQ line repre- sents proton signal acquisition. Gradient lines show the slice selection, frequency, and phase encoding gradients. “0 de- coupling was applied during the 90- 180” pulse interval and again during the 180” pulse-acquisition window interval us- ing either a single, low power, rectangular pulse or a train of small flip angle pulses. In some experiments, the duration of the I70 decoupling pulse in each interval was reduced by equal amounts without changing TE. Truncated sine pulses ( 1 ms duration) were used for slice selection. In the spectros- copy experiments, the gradients were turned off and hard RF pulses were used.

“O-decoupled ‘H detection l R. REODY ET AL. 1075

t RF2 22 PROBE

Fig. 2. Block diagram of a passive switch. RF1 and RF2 represent synthesized RF at the proton and “0 frequencies respectively. A DC pulse from the computer enables the switch to pass either RF1 or RF2. The output from the switch is then modulated by a computer-generated waveform through the use of a pulse programmer (PPG). Finally, the RF pulse is amplified and coupled to the probe through a transmit-receive switch.

RESULTS Optimization and Sensitivity

A 5% gelatin phantom doped with 2 atom% HZ”0 was used in a series of experiments designed to opti- mize “0 decoupling efficiency. A direct “0 NMR spectrum of this phantom is shown in Fig. 3. For this phantom, the proton T, was 2.9 s and T2 was 120 ms. In comparison, T2 of the phantom containing natural abundance HZ”0 was 590 ms, whereas the T1 was roughly the same for both phantoms. Absolute and fractional change in proton signal intensity (AS and M/S, respectively, where S is the nondecoupled sig- nal intensity and AS is the change in signal intensity

1 F”““‘“““‘!“““““““~

0.6

0.6

-1500 -1000 -600 0 500 1000 1500

FREQUENCY (Hz)

Fig. 3. “0 spectrum at 2 T of a 5% gelatin phantom con- taining 2.0 atom% “0-.enriched water. The spectrum was obtained using a 90” pulse-acquire sequence and 1000 signal averages with a TR of 40 ms; 512 points were collected at a 20-kHz spectral width. The 90” pulse duration was 15 /.Ls. The spectrum was processed with a 30-Hz line broadening.

upon decoupling) was used as a measure of “0 decou- pling efficiency.

With decoupling pulse duration and echo-time fixed at 600 ms, proton signal intensity increased monotoni- cally for decoupling powers between 0 and 2.5 kHz and reached a plateau between 2.5 and 4 kHz (Fig. 4). A single, low power, rectangular decoupling pulse and a train of small flip angle decoupling pulses pro- duced identical increases in proton signal intensity (data not shown). The variation of decoupling effi- ciency with decoupling duration was investigated for a fixed echo-time of 600 ms and decoupling powers between 0 and 2.5 kHz. Proton signal intensity in- creased exponentially for decoupling durations be- tween 0 and 600 ms with a maximum increase of 5800% at the maximum decoupling duration (Fig. 5).

In the usual hardware configuration for a decoupling experiment, a separate RF coil and transmitter are used for decoupling. This configuration frequently lacks a separate detecting system for the decoupled nucleus. Thus, accurate calibration of the frequency and power of the decoupling pulse may be cumbersome. We ex- amined the effect of offsetting the frequency of the “0 decoupling pulse in a 5% gelatin phantom doped with 2 atom% H*“O. Decoupling frequency offsets of less than 100 Hz had little effect on decoupling effi- ciency, whereas offsets greater than 2 kHz completely abrogated the decoupling effect (Fig. 6).

The sensitivity of the decoupling method for low concentrations of HZ”0 was examined using 5% gela- tin phantoms containing natural abundance (0.037

7000

3 4000 k

3000

8 07 2000 Q

1000

0

-1000

-1 0 Deco:pling 2Power ‘(KHz)

4 6

Fig. 4. Effect of I70 decoupling power on proton signal intensity. Data were obtained (from 5% gelatin containing 2 atom% HZ “0) with TR = 12 s, TE = 600 ms, and “0 decoupling durations of 4-600 m s (see symbol legend). The vertical axis represents the percent increase in proton signal intensity produced by 170 decoupling. S represents the proton signal intensity obtained without decoupling and LU represents the difference of proton signal intensities ob- tained with and without decoupling.

1076 Magnetic Resonance Imaging l Volume 14, Number 9, 1996

8 4000 1 0.0 KHz

e 3000

3 2000

1000

-1000

0 100 200 300 400 500 600 700 Decoupling Period (ms)

Fig. 5. Effect of “0 decoupling duration on proton signal intensity. Data were obtained (from 5% gelatin containing 2 atom% H2 “0) with TR = 12 s, TE = 600 ms, and “0 decoupling powers of 0.0, 1.0, 1.5, 2.0, and 2.5 kHz (see symbol legend). The vertical axis represents the percent increase in proton signal intensity produced by “0 decou- pling. S and AS are as described in Fig. 4.

atom%) and 0.2 atom% Hzl’O (Fig. 7). At optimal decoupling power and duration, the percent increase in proton signal intensity was 12% for natural abun- dance “0 and 60% for 0.2 atom% “0. These results demonstrate that the decoupling method possesses suf- ficient sensitivity to detect the low concentrations of Hz”0 likely to be encountered in vivo.

‘70-Decoupled Proton Imaging The feasibility of “O-decoupled proton MR im-

aging was demonstrated with a cluster of three vials

1.2

3 1

cd

- 0.6 4

-z 0.6

E 4 0.4

z .F 0.2 cn

0

-15 -10 ReAance &feet ~Kl-lz)

10 15

Fig. 6. Effect of “O-resonance offset on decoupling effi- ciency. Data were obtained for a 5% gelatin phantom con- taining 2 atom% Hz “0 with TR = 12 s, TE = 500 ms, and a spectral width of 5 kHz. The 90” flip angle was 14 /.Ls. Each point on the plot represents the absolute change in proton signal intensity produced by “0 decoupling.

60

50

s 3 40

e 30

!J 20

10

0

0 1 2 3

I7 0 Decoupling Amplitude (kHz)

Fig. 7. Sensitivity of “O-decoupled ‘H NMR. Decoupling was performed on two 5% gelatin phantoms containing 0.037 and 0.2 atom% H2 “0. The vertical axis represents the per- cent increase in proton signal intensity (AS/S) produced by “0 decoupling, where S and AS are as described in Fig. 4.

containing 5% gelatin variously doped with 0.037,0.2, and 0.4 atom% Hzl’O. Interleaved “O-decoupled and nondecoupled images were acquired, and a “log-ra- tio” image was produced by taking the natural loga- rithm of the ratio of the magnitude images (Fig. 8). The Hzl’O concentration in each vial was derived di- rectly from the pixel intensity of the log-ratio image, according to the following equation19:

f= TE . R2 * d ’

where f is the Hzl’O concentration, the numerator rep- resents the pixel value of the log-ratio image; S,, and S are the “O-decoupled and nondecoupled proton signal intensities, respectively; R2 is the transverse relaxivity of Hzl’O in 5% gelatin (3.3 [atom%]-’ SC’); and d is the decoupling efficiency ( 100%). Table 1 demon- strates excellent agreement between the actual Hz*‘0 concentrations in the vials and those calculated from “O-decoupled proton imaging.

SAR To obtain efficient “0 decoupling, the applied RF

power must satisfy the condition y& B J, where y is the “0 gyromagnetic ratio, B1 is the magnetic field asso- ciated with the RF pulse, and J is the J-coupling con- stant.13 Figure 4 shows that “0 decoupling at 2 T was maximally efficient at an RF power of 2.5 kHz, which easily satisfies the above inequality (i.e., 2.5 kHz + 92 Hz). The long duration of the decoupling pulse raises

‘70-decoupled ‘H detection 0 R. REDDY ET AL. 1077

Fig. 8. “O-decoupled proton MR imaging. This image rep- resents the natural logarithm of the ratio of proton spin-echo images obtained with and without decoupling. The vials A, B, and C correspond to 5% gelatin phantoms with 0.4, 0.2 and 0.037 atom% H2 170, respectively. The imaging parame- ters were TR = 3 s, TE = 400 ms, slice thickness = 1 mm, FOV = 2.0 X 2.0 cm, 256 X 128, one signal average.

concerns about clinical safety-in particular, the SAR. According to published tables, 2o an RF power of 2.5 kHz falls within the range of permissible SAR at 8.8 MHz (the “0 resonance frequency at 1.5 T). Therefore, a decoupling power of 2.5 kHz at 1.5 T is both large enough to produce maximally efficient “0 decoupling and small enough to satisfy SAR limitations.

DISCUSSION

Double-tuned coils are uniquely adapted for quanti- tative heteronuclear NMR experiments, and their use has been amply demonstrated in the literature. We show here the utility of double-tuned coils for the indi- rect detection of I70 through ‘70-decoupled proton MRI. The standard I70 decoupling experiment, as de- scribed by Ronen and Navon, I5 makes use of two or- thogonal RF coils and two separate RF transmission channels. Using a double-tuned coil simplifies the hardware requirements of I70 decoupling by eliminat- ing the need for complex RF circuitry and a second RF channel-neither of which are available on most clinical MR scanners. However, a broad-band transmit- ter/receiver remains necessary in either experimental setup. The double-tuned coil also permits simple and direct calibration of I70 decoupling power and fre-

quency and allows rapid acquisition of interleaved “0 and ‘H spectra. Finally, the double-tuned coil, in marked contrast to the two-coil system, produces the same B, profile for both “0 and ‘H frequencies, assum- ing similar tissue penetration.

Using the double-tuned coil and the relatively sim- ple RF circuitry described herein, it is impossible to decouple I70 during proton signal acquisition. Al- though the lack of decoupling during acquisition re- sults in slightly decreased decoupling efficiency and, therefore, slightly decreased proton signal intensity, we believe this represents a reasonable tradeoff for the more complex circuitry needed to circumvent decou- pling “dead time.” Nonetheless, we are currently de- signing a double-tuned coil system with two input ports and appropriate filters that will permit decoupling dur- ing signal acquisition. The details of this modified dou- ble-tuned coil and the associated RF circuitry will be published elsewhere.

Our data concerning off-resonance decoupling have important implications for the design of 170-decoupled imaging pulse sequences. The simultaneous activation of a gradient and a decoupling pulse will cause off- resonance excitation of some I70 nuclei, resulting in marked spatial variation in decoupling efficiency. Thus, “0 decoupling pulses should not be activated when a gradient is on. This limitation will result in a small loss in decoupling efficiency, probably less than a few percent.

In summary, we described a novel implementation of 170-decoupled proton spectroscopy and imaging us- ing a double-tuned coil and a single broadband trans- mitter. We investigated the relationship between “0 decoupling efficiency and power, duration, and fre- quency offset of the I70 decoupling pulse. We demon- strated that the decoupling method is highly sensitive for the detection of HZ”0 and suggest that ultralow H,170 concentrations can be detected in vivo. Finally, we showed that RF power deposition in the I70 decou- pling experiment at 1.5 T satisfies federal guidelines for SAR. Our laboratory is currently using ‘70-decou- pled localized proton spectroscopy and imaging with a double-tuned coil to quantify cerebral metabolic rate of oxygen consumption in rat brain in vivo.

Table 1. Comparison of actual and experimental concentrations of I70 (atom %) (calculated

from image, Fig. 8)

Vial

Actual Experimental

A B C

0.40 0.20 0.037 0.42 0.21 0.024

1078 Magnetic Resonance Imaging 0 Volume 14, Number 9, 1996

Acknowledgments-We thank Dr. Lizann Bolinger for helpful dis- Moonen, C.T.W.; McLaughlin, A.C. In vivo “0 NMR cussions. This work was supported by National Institutes of Health study of rat brain during “02 inhalation. Magn. Reson. grant RRO2305. Med. 24~370-374; 1992.

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