Original Research

Pulsed Magnetization Transfer versus Continuous Wave Irradiation for Tissue Contrast Enhancement'

Erika Schneider, PhD Robert W. Prost, MS Gary H. Glover, PhD

Pulsed magnetization transfer and continuous wave irradiation techniques are analyzed and compared for saturation efficiency and radio-frequency (RF) power requirements at 1.5 and 0.5 T. Binomial RF pulses transmitted on resonance are a more power- emcient method of exciting saturation transfer and are easily implemented with any pulse sequence. Binomial pulses selectively excite all short T2 spe- cies and behave as 0" pulses for on-resonance, long T2 species.

Index terms: contrast - Pulse sequrnces

JMRI 1993; 3:417-423

Conti-as1 enhancement - Magnetization transfer

From the Applied S( iencc Laboratory. W-875. G E Medical Systems. 3200 N Grandvvlrw Waukesha. Wl53188 IE S ); the 1)epartment oiRa- <lioloiy Medical Colleqe of Wisconsin. Milwaukee. Wis ( R W.P 1: and the Ilepartment of Diagnosrir Radiology. Stanford University School of Med wine. Stanford. C'a1iflG.H.G.). Received April 13. 1992. revision re- quested June 16 final ievlsion received and arcepted November 9 Address reprint requests to E.S.

SMRI. 1993

NONINVASIVE ALTERATION OF tissue contrast in magnetic resonance (MR) imaging is possible by using magnetization transfer techniques. Such methods saturate bound spins invisible with conventional whole-body MR imaging that are coupled by magneti- zation exchange to mobile, observable species. This exchange affects the relaxation rates of the observable spins, allowing indirect observation of the macromo- lecular protons with short T2 values. Magnetization transfer imaging, first described by Balaban et a1 (1-5). alters contrast in MR images by saturating the short T2. species present in tissue (eg, phospholipids, cholesterol). Spins neighboring or coupled to these saturated species then acquire decreased T2 and T1 values. 'Ityo mechanisms for the relaxation time changes have been proposed (1-6). The first model hypothesizes that saturation eliminates cross relax- ation (or spin diffusion) caused by direct dipole-di- pole coupling. The second model hypothesizes ex- change of the saturated species with more mobile components. Both mechanisms can be modeled by first-order exchange calculations (7).

Balaban et al ( 1-5) and others (6) have measured the magnetization transfer effect by applying low- intensity (0.16-0.44 kHz B]), off-resonance (0.5-10 kHz) continuous wave (cw) irradiation. At 1.5 T, an additional radio-frequency (RF) transmitter, com- biner, and control channel are required to produce cw excitation. More important, the RF power needed for off-resonance saturation is substantial for applica- tion at mid-to-high field strengths, and specific ab- sorption rate limitations may preclude achieving com- plete saturation of the bound spins.

In an attempt to implement magnetization transfer on conventional imagers, several investigators have begun using frequency-selective saturation pulses (as in fat suppression) applied several kilohertz off reso- nance (8.9). Although these methods can be used on unmodified imagers, they still deposit relatively large amounts of RF power due to the intrinsically ineffi- cient off-resonance excitation. Recently, an efficient method of magnetization transfer excitation that uses a selective binomial saturation pulse (eg, 90,90-,, 90,90~,90-,90,, 90,90y90y90~,) applied at the mobile

41 7

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C.

-low.o 0.0 1m.o 2OW.O -t.o

- 2 X O . O Fnquenol (W

~. . . . .

-2ooflo -loflo.o 00 10000 2000 0

Fiequency (Hz)

b.

-10: ' 1 J 2000 0 -2000 0 -10000 00 loo00

Frequency (H2)

d. Figure 1. long1'2 species near the water resonance, this pulse has an effective flip angle of 0". Because of this spectral response. the pulse is not transparent for long T2 spins substantially off resonance. (b) An aqueous solution of 0.0 1 mol/L copper sulfate was used to measure response to the above binomial pulse and also to the sequence excitation pulse at 1.5 T. (c, d) Calculated frequency response of spins with longT2 values to 0.624-msec 90,90-, (c) and 1.248-nisec 90,90,90,90~, (d) binomial pulses. A s antici- patsed. the excitation pulse rotates all the spins to +M,. whereas the binomial saturation pulses do not substantially affect the transverse magnetization of the on-resonance spins.

(a) Calculated response of longT2 species to 1.248-msec 90,90 .,90-,90, binomial saturation pulse. Note that for

wai:er resonance was developed by Hu et al [ 10.1 1 ). These pulses excite the bound species with higher effi- ciency than do cw techniques and are transparent to mobile species with long T2. Thus, on-resonance bi- nomial pulses promise RF power reduction relative to previous techniques. The purpose of the present study is to examine the advantages of this technique and to present a theoretical and experimental com- parison of cw versus on-resonance pulsed methods.

THEORY

On-Resonance Binomial Pulses Elinomial pulses of the form 90,90-,, 90,90-,90-,90,,

or 90,90,90,90_ , behave as 0" pulses for long T2 spe- cies when transmitted close to the water resonance. The spectral response of binomial pulses depends on the phase-cycling scheme selected, pulse duration, and transmitter frequency offset, as shown in Figure 1. The 90,90_,90 .,go, pulse is the shortest binomial pulse that is transparent at 0.5 and 1.5 T for both ali-

phatic lipid and mobile water resonances and is not sensitive: to small amounts of in vivo magnetic field inhomogeneity. The two other simple binomial pulses, 90,90-, and 90,90,90,90~,. are not suitable for magnetization transfer applications in regions with even small amounts of magnetic susceptibility or morphol ogy-induced Bo inhomogeneity because they are transparent over only a narrow frequency range.

a standard Euler rotation matrices formulation [ 12). All calculations assumed an isolated spin 112. When T2 decay occurred during the RF pulse, the pulse was divided into small-enough segments so that no decay occurred during any one segment.

pulses with phase differences of either 0 or -IT are inde- pendent of flip angle for spins on resonance. The lim- ited sensitivity to RF field strength (B,) off resonance is demonstrated in Figure 2a and 2b for the 90,90-, and 90,90~,90~,90, binomial pulses. These symniet- ric binomial pulses have superior B, behavior at both the water [on resonance) and lipid (200 Hz off reso-

The Bloch equation simulations were done by using

In general, the spectral response of composite

418 JMRl March/Aprill993

00 500 1000 1500 2000 2500 1000 1500

IIip onq91e (deq)

b.

71 = 1000 ms M I ' O I . - . . . . .

M v

M2 1 0 -- , . . - Mxy _ -

0 5

00 0 0

-0 5 -0 5

0 80

0 70

1 1 = 1000 rns -.--- ,.

/ '

/'

I '

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i I'

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c 060

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Figure 2. (a). 90,90-,90-,90, (b). and 90,90,90,90-, (c) binomial pulses. The plots in a and b were calculated 200 Hz off reso- nance to demonstrate the flip angle sensitivity for the f. .it reso- nance. The plot in c was calculated on resonance, demonstrat- ing its difficulty with nonuniform RF field strength. Binomial pulses with phase differences of 0 or T are not sensitivc to flip angle adjustments for spins on resonance. making the 90,90-, or the 90,90~,90~,90, pulse better suited for magne- tization transfer excitation.

Calculated flip angle dependence of the 90,90-,

0 5c

0 20

0 i c

0 OC 00 500 1000 1500 2000 2500 3000 3500

(imp onqle (deq)

C .

nance) frequencies relative to binomial pulses with quadratic phase, such as the 90,90,90,90~, pulse transmitted on resonance (Fig 2c).

The spectra in Figure 1 are valid only for spins with T:2 values greater than about 50 times longer than the pulse duration. For spins with shorter TZs, the bino- mial pulses saturate the z magnetization (Fig 3a). This

progressive saturation behavior is contrasted with that of a ~ / 2 pulse (Fig 3b), which partially excites spins undergoing T2 relaxation during the pulse

Ofl-Resonance Pulses The cause of high-power requirements for all off-

resonaiice pulses is demonstrated by the behavior of

- Volume3 Number2 JMRl 419

60 0 ““lolion mgle -rf olgle

40 0

20 0

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Figure 4. effective magnetic field rotation angle in the rotating reference frame (rrf ) (dashed line). (b) Signal amplitude (Mxy) calculated as a function of resonance offset frequency. The off-resonance signal decrease demonstrates why higher RF power is required to achieve the same magnetization as for on-resonance excitation.

(a) Calculated magnetization nutation angle as a function of resonance offset frequency (dotted line) and calculated

the nutation angle ( a ) as a function of transmit fre- quency. The nutation angle traversed by the magneti- zal ion ( a ) increases as the transmission frequency moves off resonance (Eq [ 1 I , Fig 4a). Concurrently, the effective magnetic field in the rotating reference frame tilts because of off-resonance irradiation (Eq [ 2 ] , Fig 4a). The nutation angle is calculated from the pulse field strength (B,) and the transmit frequency difference (oo - qransmlt), as described by Ernst et al ( 12), with the following equation:

where y is the gyromagnetic ratio. The angle 8 through which the effective magnetic field vector rotates as a function of the off-resonance frequency is determined by

Thus, the nutation angle and the axis about which the magnetization vector rotates change simultaneously and in opposite directions. These two effects partially cancel, resulting in a slow decrease in signal ampli- tude with increasing off-resonance frequency (Fig 4b). To maintain a constant flip angle under conditions of off .resonance transmission, the RF field strength must therefore increase. A substantial reduction in required RF power can be realized by transmitting on or [close to resonance; therefore, the most RF-efficient magnetization transfer preparation should occur with the on-resonance binomial saturation pulses.

MATERIALS AND METHODS F’ulsed and cw saturation transfer imaging experi-

ments have been performed on 0.5- and 1.5-T Signa Adgantage MR imaging systems (GE Medical Systems, Milwaukee, Wis). Both Hahn spin-echo and gradient- echo pulse sequences were examined. The cw method at I, .5 T used an additional RF exciter, transmitter (4 kW peak power at 64 MHz), multiplexer, and indepen- dently tunable frequency synthesizer. The pulse se-

d saturation pulse

n

Figure 5. Gradient-echo pulse sequence used for satura- tion transfer experiments. The saturation pulse is eithei- a 1.248-msec binomial pulse (90,90~x90~x90,) at a 8, of ap- proximately 0.65-0.96 kHz or a long (200-4.000 msec). low-power (B, = 0.3-0.46 kHz) off-resonance (5-20 kHz) pulse. The saturation pulse is followed by large crusher gra- dients to remove residual magnetization in the x-y plan?. An additional R F transmitter was used for cw experiments at 1.5T.

quence gated the entire auxiliary channel as desired. Figure 5 shows a simplified pulse sequence indicating the location of the saturation pulse. The binomial pulse was applied for a total duration of 1.248 msec by using either amplitude (90,-90,-90,90,) or phase (90,90-,90~,90,) modulation. At 1.5 T, the cw method required an additional transmitter to produce in vivo power levels sufficiently high to saturate spins several kilohertz from the mobile water resonance.

The RIF intensity required for binomial pulsed and cw saturation transfer was measured by comparison of square-pulse rrl2 durations. By using a square RF pulse, the time required for a ~ r / 2 pulse was deter- mined experimentally at each field strength at the RF power level required by the binomial pulse. The rda-

420 JMRl March/Aprill993

Table 1 RF' Amplitude Required to Obtain about 50% Saturation of Muscle Magnetization for Pulsed and cw Saturation Transfer at 0.5 and 1.5 T

Field Pulsed cw Strength Voltage Amplitude Amplitude

Location (T) Ratio* (kHz1 (kHz)+

Head 1.5 2.32 0.704 0.342'

Head 0.5 10.0 0.864 0.405 Body 0.5 3.33 0.959 0.455

Note.-TR was 20 msec for the pulsed experiment and 1 second for the cw experiment. RF coil dimensions and polarizations were identical at 0.5 and 1.5 T. The volun- teer weighed 83 kg. * Forward-to-reverse voltage ratios are an approximate peasure of RF transfer efficiency.

Body 1.5 3.48 0.646 . . .

5 kHz off resonance. *At 1.5 T. this was the maximum RF amplitude that could he used without volunteer heating:

Table 2 Experimental Considerations for cw and Pulsed Saturation Transfer

Pulsed cw

Advantages Transmit on reso- nance (suhstan- tially reduces av- erage RF power)

Allows use of con- ventional imager

Excites all short T2 species

Disadvan- Sensitive to Bc, inho- tages rnogeneity (water

and fat signals can be suppressed)

Transmit off reso- nance (water and fat signals not ex- cited)

Insensitive to Bo in- homogeneity

Deposits relatively large amount of energy due to off- resonance irradia- tion (high average RF power)

Needs separate RF transmitter

Does not excite all short T2 species

tive RF intensities were then measured for the cw technique. This indirect method is preferable for measuring B1 in cw experiments because T2 decay occurs during the pulse and prevents accurate deter- mination of the flip angle. By measuring T or ~ r / 2 du- rations at high pulse intensities and subsequently comparing amplitudes, the most accurate determina- tion of B, is possible. In this manner, BI was calcu- lated without directly measuring transmission losses and without requiring corrections for T2 losses dur- ing the pulse. Amplitude comparisons for the supple- mentary transmitter used for 1.5-T cw saturation were made with a pickup loop. Saturation powers were compared (Table 1) relative to a 50% signal de- crease in calf muscle by using RF coils with identical dimensions and polarizations at 0.5 and 1.5 T.

RESULTS

similar saturation effects and transfer rates. When We found that the pulsed and cw methods yielded

100.0

50 0

0 0 I.! 150 20 0 25 0 30 0 (8 0 5 0 100

Number 01 Saluiotion PuIPes

Figure 6. Progressive saturation of calf muscle magnetiza- tion at 1.5 T as a function of the number of binomial satura- tion pulses (90,90-,90~,90,). The center of the saturation pulses are 7.248 msec apart ( 1.248-msec pulse, 6-msec de- lay, including the gradient crushers); thus, approximately 140 rnsec are required to reach steady state. Additional pulses could not be applied to volunteers because of patient heating. The observed pulse flip angle is n/2. Experiments using cw excitation showed similar time scales. The pulse sequence TR was kept constant at 1.000 msec.

not limited by the specific absorption rate, the cw method saturates the tissue more completely. How- ever, binomial pulses offer a more RF power-efficient approach for saturation transfer. When the duty cycle difference is accounted for (6.5% for pulsed vs 95% for cu'), the average saturation power in the pulsed experiment was 3.3 times less at 0.5 T and 3.6 times less ar 1.5 T than the saturation power used with the cw method. At 1.5 T, patient heating limited the am- plitude and duration of the cw pulse for magnetiza- tion transfer in calf muscle in both gradient-echo and Hahn spin-echo sequences ( 100-4.000 msec TRs). Even with the decreased RF absorption at 0.5 T, com- plete saturation of muscle was impossible. Typical 0.5-T cw transmission duty cycles were 90% (the RF pulse was transmitted for 500 msec at 50% of maxi- mum amplifier output), at amplitude levels of 0.34 kHz in a quadrature-drive extremity coil.

Table 2 compares experimental considerations for off-resonance cw and on-resonance binomial pulse saturation transfer techniques. The two advantages of on-resonance saturation are lower RF power require- ments, allowing use of a conventional imager and ex- citation of all short T2 species. The two main disad- vantages are pulse bandwidth sensitivity to magnetic field irihomogeneities (lipid signal can be suppressed because of chemical shift, and in severe cases of Bo inhomogeneity, water signal can also be suppressed) and that species with T2 values 50 times the pulse duration and less are excited. This latter effect can supprt:ss signal intensity in fluids containing pro- teins.

A steady state is reached after 10-20 binomial pulses have been applied (Fig6). The mean time of magnetization exchange determines when steady state is reached: however, no difference in progressive sat- uration time was measured between 0.5 and 1.5 T.

I Volume3 Number2 JMRl 421

Figure 8. (a) Fast spin- echo sagittal image of knee obtained with a TR of 4,000 msec. effective TE of 80 msec. and 16 echoes. (b) Three-dimensional gra- dient-echo axial image ob- tained with binomial sat- uration pulses. Note the synovial fluid-articular car- tilaige contrast. Both a and b were acquired at 1.5 1’.

Following this preparation, one binomial pulse per TR period (Fig 7) is sufficient to keep the spin system at equilibrium in a short TR (18-50 msec) gradient- echo sequence or an interleaved multisection Hahn spin-echo sequence. However, in a single-section Ha:hn spin-echo sequence, 10-20 binomial pulses per TR period (200-2.000 msec) are required to keep the spin system saturated. Strong gradient crushers are req,uired after application of either the cw or the bino- mial saturation pulses; otherwise, residual transverse coherences are observed.

To demonstrate the effectiveness of pulsed satura- tion transfer, a three-dimensional gradient-echo se- quence was used to examine a knee (Fig 8). In addi- tion to suppressing muscle signal, pulsed saturation tra.nsfer suppressed signal from the articular carti- lage, resulting in enhanced contrast between cartilage, bone, and synovial fluid. However, because species with T2 values in the range of the pulse duration expe- rience progressive saturation, suppression of synovial fluid and blood has been observed. This undesired suppression has been reduced (to a maximum of 10‘5- 12%) by decreasing the saturation pulse length to 0.6 msec. Signal from spins with longT2 values that are not in contact with magnetization transfer- affected proteins is suppressed by less than 3% with the binomial saturation transfer pulses.

0 DISCUSSION A.pplication of on-resonance binomial pulses for

saturation transfer reduces RF power requirements without markedly changing the transfer rate or per- cent saturation relative to cw pulses. Off-resonance cw pulses can saturate tissue more completely than either off- or on-resonance pulsed techniques. How- ever, use of cw pulses is limited to the torso and to multisection acquisitions because of high RF power requirements. On-resonance selective saturation with binomial pulses. as proposed by Hu et al ( 10.1 1). efi- ciently saturates muscle and other tissue with short T2 components, as demonstrated by Equation ( 1 ) and Figure 6.

9Ox9O-x9O-x9Ox Pulsed MTC

r

.d-_ - 1 0 0 2000 4000 6000 8000 10000 12000 14003 16000

lime (mr)

Figure 7. response after saturation with binomial pulses as a function of delay time. The delay time is the time ailowed for magneti- zation recovery after the series of magnetization transfer pulses, before “readout” by the excitation pulse. TR was con- stant at 2,000 msec.

Recovery at 0.5 T of calf muscle magnetization

The 90,90~,90~,90, pulse is the most useful bino- mial pulse because it is of short duration, has a spec- tral response independent of RF field strength, and has an el’fective flip angle of 0” for long T2 species over a relatively large frequency range. This binomial satu- ration pulse may be used on conventional MR imagers with any type of pulse sequence, with only modest in- creases in average power deposition and without the use of an auxiliary cw RF transmitter/exciter. How- ever, if this saturation pulse is applied for durations greater tlhan 1.25 msec at 1.5 T, artifacts resulting from Bo iinhomogeneities may result and may require in vivo shimming. Also, binomial pulses have been found to partially saturate both blood and synovial fluid because of their protein content. Pulsed satura- tion transfer methods will allow magnetization trans- fer to become a routine clinical tool, because inter- leaved section acquisition is allowed and only rarely is

422 JMRl M a r c h / A p r i l 1 9 9 3

the number of sections limited by RF power deposi- tion. 0

Acknowledgments: The authors are grateful to Scott Yohe for help with the 0.5-T images and to Bob Hu. MD, for a preliminary copy of his manuscript.

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IMTC) and tissue water proton relaxation in VIVO. Magn Re- son Med 1989: 10:135-140.

2. Wolff SD, Balaban RS. change. Magri Reson Med 1990: 86: 164-169.

3. Eng J. Ceckler TL. Balaban RS. Quantitative ‘H magneti- zation transfer imaging in vivo. Magn Reson Med 1990; 17:

4. Wolff SD, Eng J. Balaban RS. Magnetization transfer con-

NMR imaging of labile proton ex-

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trast: method for improving contrast in gradient-recalled- echo images. Radiology 1991: 179:133-137. Balaban RS, Chesnick S. Hedges K. Samaha F. Heineman FW. heart. Radiology 1991; 180:671-675.

of nuclear magnetic cross-relaxation spectroscopy to tis- sues. Magn Reson Med 1991: 17:452-459.

5. Magnetization transfer contrast in MR imaging of the

6. Grad J, Mendelson D. Hyder F, Bryant RG. Applications

7. Forsen S. Hoffman RA. Study of moderately rapid chemi- cal exchange reactions by means of nuclear magnetic dou- ble resonance. J Chem Phys 1963: 39:2892-2901.

8. Schnall MD. Dougherty L. Outwater E, Dousset V. Tech- nique for magnetization transfer imaging at 1.5 T using steady state pulsed saturation (abstrl. In: Book of ab- stracts: Society of Magnetic Resonance in Medicine 1991. Berkeley. Calif: Society of Magnetic Resonance in Medicine, 1991; 175. Outwater E. Schnall MD. Bratiman LE, Dinsmore G J . Kressel HY. evaluation of a novel contrast technique in the abdomen. Radiology 1992: 182:535-540.

10. Hi1 BS. Nishimura DG, Macovski A. Pulsed magnetization transfer contrast (abstrl. In: Book of abstracts: Society of Magnetic Resonance in Medicine 1990. Berkeley, Calif So- ciety of Magnetic Resonance in Medicine, 1990; 352. Hu BS. Conolly SM, Wright GA, Nishimura DG. Macovski A. Pulsed saturation transfer contrast. Magn Reson Med 1992: 26:231-240.

12. Ernst RR, Bodenhauser G. Wokaun A. Principles of nu- clear magnetic resonance in one and two dimensions. In- ternational series of monographs on chemistry- 14. New York, NY: Oxford University Press, 1987: 115-137.

9. Magnetization transfer of hepatic lesions:

1 1.

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