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Magnetization transfer contrast imaging of the human leg at 0.1 T: A preliminary study
Magnelic Resonance Imaging, Vol. 10, pp. 361-364, Printed in the USA. All righfs reserved.
1992 Copyright 0
0730-725X/92 $5.00 + .Ml 1992 Pergamon Pres Ltd.
0 Original Con tribution MAGNETIZATION TRANSFER CONTRAST IMAGING OF THE HUMAN LEG AT 0.1 T: A PRELIMINARY STUDY CHARLES E. SWALLOW,*
CHARLES E. KAHN, JR.,*?
JUKKA 1. TANTTU,~
RICHARD E. HALBACH,~
AND RAIMO E. SEPPONEN~
*Department of Radiology, The University of Chicago, Chicago, IL 60637, USA $Instrumentarium Imaging, Milwaukee, WI, USA; 5Instrumentarium Imaging, Helsinki, Finland Magnetization transfer contrast imaging is an MR technique that capitalizes on interactions between the protons of mobile and macromolecularly bound water molecules. Studies to date, conducted prlmarily on 4.7 T and 1.5 T MR systems, have yielded results unique from conventional Ti- and T,-weighted imaglng studies. In this study, performed on a 0.1 T device, a section of lower leg was imaged in 20 normal human subjects and one patient with muscular dystrophy, using both a standard 500/22 gradient-echo sequence and a NO/22 gradient-echo sequence combined with off-resonance radio frequency irradiation designed to elicit magnetization transfer contrast. Results of the two techniques were compared. Our findings suggest that magnetization transfer contrast imaging is feasible at 0.1 T, and that this technique allows reproducible tissue characterization and improves contrast between certain tissues. Keywords: Magnetic resonance imaging; Human studies; Magaetization transfer contrast.
Our study, performed on a O.l-T MR system, was initiated to assess the feasibility and potential usefulness of MT contrast imaging at low magnetic field strengths. To achieve maximum MT contrast, studies done on animal models with field strengths of 4.7 T and 1.5 T have required rates of radio-frequency absorption which approached or exceeded U.S. Food and Drug Administration (FDA) suggested safety guidelines . 5,7 Studies by Tanttu and Sepponen have shown that in O.l-T MT imaging of the abdomen, the specific absorption rate is approximately 0.3 W/kg, wel1 below the 3.2 W/kg and 8 W/kg suggested allowances for head and body/extremity imaging, respectively.’ Because power requirements vary with the square of the field strength, MT sequences can be run on low-field-strength systems with less radio-frequency energy absorption in the patient.
INTRODUCTION Magnetization transfer (MT) is a tissue-dependent characteristic caused by interactions between mobile water protons and molecularly bound or restricted water protons.’ Although its clinical usefulness has not been explored until recently, the MT effect has been recognized for some time. lm3Recent studies have demonstrated the effectiveness of MT at improving image contrast in vivo at 4.7 T and 1.5 T, and have shown that MT provides images unique from traditional MR studies.4*5 The MT technique depends on the selective saturation of macromolecularly restricted protons with off-resonance radio-frequency irradiation. These protons normally have a very short T2 and therefore are not usually imaged with conventional MR sequences. There is a tissue-dependent rate of saturation transfer from bound water protons to free water protons. The reduction in restricted proton saturation is proportional to the macromolecular concentration in the tissue and the strength of the interactions between bound and free water protons.4-6 RECEIVED7/22/9 1; ACCEPTED1 1/ 19/9 1. Address correspondence to Dr. Kahn. tCurrent address: Department of Radiology,
METHODS The study protocol was approved by the institution’s MRI research committee, and informed consent
College of Wisconsin, 8700 West Wisconsin Avenue, MCMC Box 151, Milwaukee, WI 53226, USA. Medical 361
Magnetic Resonance Imaging 0 Volume 10, Number 3, 1992
362
Table 1. Signal-intensity values (mean f standard deviation) and MT contrast ratios in the lower leg of 20 normal human volunteers Gradient echo (ZGE)
Bone marrow Subcutaneous fat Skeletal muscle Fibrous connective tissue
62.81 60.58 38.63 11.40
f 19.09 f 17.51 f 9.28 f 3.69
RESULTS The signal-intensity values for the 20 normal study samples are shown in Table 1. The variations in signal intensity between patients are due to coil loading and auto-gain effects; the paired GE and MT images for each patient have the same coil loading and gain, so the ratio of their signal intensities is a valid measureincreased
the differente
Table 2. Mean signal-intensity
in signal
tissue 1 2 3
MT contrast ratio
60.68 58.18 15.23 6.40
(ZMT/I,E)
+ 18.33 f 16.99 f 3.45 f 2.33
0.967 0.959 0.397 0.581
f f f f
0.030 0.034 0.029 0.155
intensity between fat and muscle, but decreased contrast between muscle and dense fibrous connective tissue. The ratios of the MT signal intensities to those of the GE images were computed separately for each subject; a ratio of 1.OOindicates that the tissue showed no MT effect. Thus, skeletal muscle demonstrated significant MT effect, fibrous connective tissue showed less MT effect, and subcutaneous fat and bone marrow demonstrated almost none. Figure 1 shows the MT and GE images of one normal subject. Similar computations were performed on the data from the volunteer with muscular dystrophy (Table 2). Muscular dystrophy muscle sample no. 1 was taken from a relatively normal area of muscle, no. 2 from a region of intermediate involvement, and no. 3 from a markedly abnormal region. Although the absolute intensity values of the three muscle samples were al1 greater than the average for the normal studies, al1 are within two standard deviations of the mean. The ZMT/Iou ratios, however, showed a marked differente from the normal mean; even the most normal-appearing sample displayed a ratio nearly three standard deviations above the mean. Samples no. 2 and no. 3 had MT contrast ratios which were approximately 4 and 19 standard deviations above the normal mean. Although the absolute intensity value of the sample voxels was about 23 points less than that of subcutaneous fat, muscle section no. 3 behaved more like fatty tissue
values in the lower leg of one volunteer with muscular dystrophy
Gradient echo Bone marrow Subcutaneous fat Fibrous connective Muscle sample no. Muscle sample no. Muscle sample no.
transfer
(ZMT)
was obtained from al1 subjects. The study was performed on 20 normal volunteers and on one patient with muscular dystrophy, using a O.l-T clinical MR imaging system (Mega 4, Instrumentarium Imaging, Helsinki, Finland). A single lO-mm slice through the mid-calf was studied with an MT sequence consisting of an off-resonance radio-frequency pulse (Rff) applied immediately before a gradient echo (GE) XW22 pulse sequence. The off-resonance pulse had an amplitude of 0.25 Gauss, duration of 300 msec, and frequency offset of 7.2 kHz. For comparison, a separate gradient-echo NO/22 sequence was interleaved with the MT sequence at the same level. The signal-intensity values of bone marrow, subcutaneous fat, skeletal muscle, and dense fibrous connective tissue were measured in identical regions on the MT and control GE images. These signal intensities are termed r,T and Ioc, respectively.
ment. MT technique
Magnetization
Magnetization
transfer
MT contrast ratio
(IGE)
(ZMT)
(zMT/zGE)
71.7 72.4 10.0 38.2 47.0 49.1
70.3 70.9 7.0 18.5 23.9 47.1
0.98 0.98 0.70 0.48 0.51 0.96
Magnetization transfer contrast imaging 0 C.E. SWALLOW ET
A
363
AL.
B
Fig. 1. Left lower leg of normal human volunteer: (A) magnetization-transfer
contrast image, (B) gradient-echo
image.
than muscle, as seen by its ZMT/ZoE ratio of 0.96, identical to that of normal fat. In addition, the contrast (i.e., the differente in signal intensities between two tissues) between muscle no. 3, subcutaneous fat, and fibrous connective tissue was essentially unchanged between GE and MT images. Figure 2 displays the images of this volunteer.
The purpose of this study was to determine the effectiveness of MT imaging on low-field MR systems. The results indicate that MT improves contrast between certain tissues and allows characterization of tissues based on the ZMT/ZoEratios. These findings are
A
B
DISCUSSION
Fig. 2. Left lower leg of patient with muscular dystrophy: (A) magnetization-transfer
contrast image, (B) gradient-echo image.
364
Magnetic Resonance Imaging 0 Volume 10, Number 3, 1992
possible using a O. l-T magnetic field, where power deposition in tissues is wel1 within safety levels suggested by the FDA; imaging at a magnetic field strength of 1.5 T or greater may cause energy deposition which exceeds these safety limits. The values for MT contrast appear to be reproducible as well, since studies at 0.1 T with identical off-resonance radiation conditions have provided ZMT/ZoEratios similar to ours for skeletal muscle (0.46) and subcutaneous fat (0.97).9 Although the normal range of absolute signal-intensity values was quite broad in al1 tissues we assessed, in part due to coil loading and auto-gain effects on the images, the Z,,/Zo, ratios were quite consistent for each normal patient, as manifest by the relatively smal1 standard deviations. MT imaging may be especially useful in demonstrating processes of fatty infiltration because of the large MT contrast effect between fatty tissues and muscle. Similar findings have been demonstrated in higher magnetic fields as well, where fat and bone marrow were found to possess almost no MT effect, but skeletal muscle showed substantially more.4*5,10 This is born out clinically in the patient with muscular dystrophy, where the most affected muscles show much less decrease in MT signal intensity, as manifested by abnormal ZMT/ZoEratios, than normal or less involved muscle. Muscle tissue, with a high protein content, exhibited the greatest reduction in signal intensity (ZM,/ZoE = 0.397). Bone marrow and subcutaneous fat changed little with the MT sequence, because of the paucity of free water protons in these tissues which are available for exchange with macromolecularly bound water protons. In summary, MT techniques can increase contrast between certain tissues and allow for reproducible tissue characterization. At 0.1 T the technique can be used safely in humans, and provides data that may prove clinically relevant in evaluation of disease states. Fur-
ther investigation is required to assess the full potential of MT contrast imaging. REFERENCES 1. Dixon, W.T. Use of magnetization transfer contrast in gradient-recalled echo images. Radiology 179: 15-16; 1991. 2. Koenig, S.H.; Bryant, R.G.; Hallenga, K.; Jacob, G.S. Magnetic cross-relaxation among protons in protein solutions. Biochemistry 17:4348-4358; 1978. 3. Muller, R.N.; Marsh, M.J.; Bernardo, M.L.; Lauterbur, P.C. True 3-D imaging of limbs by NMR zeugmatography with off-resonance irradiation. Europ. J. Radiol. 3:286-290;
1983.
4. Wolff, S.D.; Balaban, R.S. Magnetization transfer contrast and tissue water proton relaxation in vivo. Magn. Reson. Med. 10: 135-144; 1989. 5. Wolff, S.D.; Eng, J.; Balaban, R.S. Magnetization transfer contrast: Method for improving contrast in gradient-recalled-echo images. Radiology 179:133-137; 1991.
6. Grad, J.; Bryant, R.G. Nuclear magnetic cross-relaxation spectroscopy. J. Magn. Reson. 90:1-8; 1990. 7. U.S. Food and Drug Administration. Guidance for content and review of a magnetic resonance diagnostic device 510(k) application. Publication number HFZ-401, Washington, DC: Center for Devices and Radiological Health, U.S. Food and Drug Administration; August 2, 1988. 8. Tanttu, J.I.; Sepponen, R.I. Imaging methods for whole-body MR imaging applications of magnetization transfer contrast at 0.1 T. Radiology 177(P):245; 1990. Abstract. 9. Tanttu, J.I.; Kahn, C.E. Jr.; Sepponen, R.E.; Holland, E.A.; Tierala, E.; Lipton, M.J. Magnetization transfer contrast of body tissues in vivo in MR imaging. Radiology 177(P):245; 1990. Abstract. 10. Dixon, W.T.; Engles, H.; Sardashti, M.; Castillo, M. Incidental magnetization transfer contrast affects multislice imaging. Magn. Reson. Imaging 8:417-422; 1990.
1992 Copyright 0
0730-725X/92 $5.00 + .Ml 1992 Pergamon Pres Ltd.
0 Original Con tribution MAGNETIZATION TRANSFER CONTRAST IMAGING OF THE HUMAN LEG AT 0.1 T: A PRELIMINARY STUDY CHARLES E. SWALLOW,*
CHARLES E. KAHN, JR.,*?
JUKKA 1. TANTTU,~
RICHARD E. HALBACH,~
AND RAIMO E. SEPPONEN~
*Department of Radiology, The University of Chicago, Chicago, IL 60637, USA $Instrumentarium Imaging, Milwaukee, WI, USA; 5Instrumentarium Imaging, Helsinki, Finland Magnetization transfer contrast imaging is an MR technique that capitalizes on interactions between the protons of mobile and macromolecularly bound water molecules. Studies to date, conducted prlmarily on 4.7 T and 1.5 T MR systems, have yielded results unique from conventional Ti- and T,-weighted imaglng studies. In this study, performed on a 0.1 T device, a section of lower leg was imaged in 20 normal human subjects and one patient with muscular dystrophy, using both a standard 500/22 gradient-echo sequence and a NO/22 gradient-echo sequence combined with off-resonance radio frequency irradiation designed to elicit magnetization transfer contrast. Results of the two techniques were compared. Our findings suggest that magnetization transfer contrast imaging is feasible at 0.1 T, and that this technique allows reproducible tissue characterization and improves contrast between certain tissues. Keywords: Magnetic resonance imaging; Human studies; Magaetization transfer contrast.
Our study, performed on a O.l-T MR system, was initiated to assess the feasibility and potential usefulness of MT contrast imaging at low magnetic field strengths. To achieve maximum MT contrast, studies done on animal models with field strengths of 4.7 T and 1.5 T have required rates of radio-frequency absorption which approached or exceeded U.S. Food and Drug Administration (FDA) suggested safety guidelines . 5,7 Studies by Tanttu and Sepponen have shown that in O.l-T MT imaging of the abdomen, the specific absorption rate is approximately 0.3 W/kg, wel1 below the 3.2 W/kg and 8 W/kg suggested allowances for head and body/extremity imaging, respectively.’ Because power requirements vary with the square of the field strength, MT sequences can be run on low-field-strength systems with less radio-frequency energy absorption in the patient.
INTRODUCTION Magnetization transfer (MT) is a tissue-dependent characteristic caused by interactions between mobile water protons and molecularly bound or restricted water protons.’ Although its clinical usefulness has not been explored until recently, the MT effect has been recognized for some time. lm3Recent studies have demonstrated the effectiveness of MT at improving image contrast in vivo at 4.7 T and 1.5 T, and have shown that MT provides images unique from traditional MR studies.4*5 The MT technique depends on the selective saturation of macromolecularly restricted protons with off-resonance radio-frequency irradiation. These protons normally have a very short T2 and therefore are not usually imaged with conventional MR sequences. There is a tissue-dependent rate of saturation transfer from bound water protons to free water protons. The reduction in restricted proton saturation is proportional to the macromolecular concentration in the tissue and the strength of the interactions between bound and free water protons.4-6 RECEIVED7/22/9 1; ACCEPTED1 1/ 19/9 1. Address correspondence to Dr. Kahn. tCurrent address: Department of Radiology,
METHODS The study protocol was approved by the institution’s MRI research committee, and informed consent
College of Wisconsin, 8700 West Wisconsin Avenue, MCMC Box 151, Milwaukee, WI 53226, USA. Medical 361
Magnetic Resonance Imaging 0 Volume 10, Number 3, 1992
362
Table 1. Signal-intensity values (mean f standard deviation) and MT contrast ratios in the lower leg of 20 normal human volunteers Gradient echo (ZGE)
Bone marrow Subcutaneous fat Skeletal muscle Fibrous connective tissue
62.81 60.58 38.63 11.40
f 19.09 f 17.51 f 9.28 f 3.69
RESULTS The signal-intensity values for the 20 normal study samples are shown in Table 1. The variations in signal intensity between patients are due to coil loading and auto-gain effects; the paired GE and MT images for each patient have the same coil loading and gain, so the ratio of their signal intensities is a valid measureincreased
the differente
Table 2. Mean signal-intensity
in signal
tissue 1 2 3
MT contrast ratio
60.68 58.18 15.23 6.40
(ZMT/I,E)
+ 18.33 f 16.99 f 3.45 f 2.33
0.967 0.959 0.397 0.581
f f f f
0.030 0.034 0.029 0.155
intensity between fat and muscle, but decreased contrast between muscle and dense fibrous connective tissue. The ratios of the MT signal intensities to those of the GE images were computed separately for each subject; a ratio of 1.OOindicates that the tissue showed no MT effect. Thus, skeletal muscle demonstrated significant MT effect, fibrous connective tissue showed less MT effect, and subcutaneous fat and bone marrow demonstrated almost none. Figure 1 shows the MT and GE images of one normal subject. Similar computations were performed on the data from the volunteer with muscular dystrophy (Table 2). Muscular dystrophy muscle sample no. 1 was taken from a relatively normal area of muscle, no. 2 from a region of intermediate involvement, and no. 3 from a markedly abnormal region. Although the absolute intensity values of the three muscle samples were al1 greater than the average for the normal studies, al1 are within two standard deviations of the mean. The ZMT/Iou ratios, however, showed a marked differente from the normal mean; even the most normal-appearing sample displayed a ratio nearly three standard deviations above the mean. Samples no. 2 and no. 3 had MT contrast ratios which were approximately 4 and 19 standard deviations above the normal mean. Although the absolute intensity value of the sample voxels was about 23 points less than that of subcutaneous fat, muscle section no. 3 behaved more like fatty tissue
values in the lower leg of one volunteer with muscular dystrophy
Gradient echo Bone marrow Subcutaneous fat Fibrous connective Muscle sample no. Muscle sample no. Muscle sample no.
transfer
(ZMT)
was obtained from al1 subjects. The study was performed on 20 normal volunteers and on one patient with muscular dystrophy, using a O.l-T clinical MR imaging system (Mega 4, Instrumentarium Imaging, Helsinki, Finland). A single lO-mm slice through the mid-calf was studied with an MT sequence consisting of an off-resonance radio-frequency pulse (Rff) applied immediately before a gradient echo (GE) XW22 pulse sequence. The off-resonance pulse had an amplitude of 0.25 Gauss, duration of 300 msec, and frequency offset of 7.2 kHz. For comparison, a separate gradient-echo NO/22 sequence was interleaved with the MT sequence at the same level. The signal-intensity values of bone marrow, subcutaneous fat, skeletal muscle, and dense fibrous connective tissue were measured in identical regions on the MT and control GE images. These signal intensities are termed r,T and Ioc, respectively.
ment. MT technique
Magnetization
Magnetization
transfer
MT contrast ratio
(IGE)
(ZMT)
(zMT/zGE)
71.7 72.4 10.0 38.2 47.0 49.1
70.3 70.9 7.0 18.5 23.9 47.1
0.98 0.98 0.70 0.48 0.51 0.96
Magnetization transfer contrast imaging 0 C.E. SWALLOW ET
A
363
AL.
B
Fig. 1. Left lower leg of normal human volunteer: (A) magnetization-transfer
contrast image, (B) gradient-echo
image.
than muscle, as seen by its ZMT/ZoE ratio of 0.96, identical to that of normal fat. In addition, the contrast (i.e., the differente in signal intensities between two tissues) between muscle no. 3, subcutaneous fat, and fibrous connective tissue was essentially unchanged between GE and MT images. Figure 2 displays the images of this volunteer.
The purpose of this study was to determine the effectiveness of MT imaging on low-field MR systems. The results indicate that MT improves contrast between certain tissues and allows characterization of tissues based on the ZMT/ZoEratios. These findings are
A
B
DISCUSSION
Fig. 2. Left lower leg of patient with muscular dystrophy: (A) magnetization-transfer
contrast image, (B) gradient-echo image.
364
Magnetic Resonance Imaging 0 Volume 10, Number 3, 1992
possible using a O. l-T magnetic field, where power deposition in tissues is wel1 within safety levels suggested by the FDA; imaging at a magnetic field strength of 1.5 T or greater may cause energy deposition which exceeds these safety limits. The values for MT contrast appear to be reproducible as well, since studies at 0.1 T with identical off-resonance radiation conditions have provided ZMT/ZoEratios similar to ours for skeletal muscle (0.46) and subcutaneous fat (0.97).9 Although the normal range of absolute signal-intensity values was quite broad in al1 tissues we assessed, in part due to coil loading and auto-gain effects on the images, the Z,,/Zo, ratios were quite consistent for each normal patient, as manifest by the relatively smal1 standard deviations. MT imaging may be especially useful in demonstrating processes of fatty infiltration because of the large MT contrast effect between fatty tissues and muscle. Similar findings have been demonstrated in higher magnetic fields as well, where fat and bone marrow were found to possess almost no MT effect, but skeletal muscle showed substantially more.4*5,10 This is born out clinically in the patient with muscular dystrophy, where the most affected muscles show much less decrease in MT signal intensity, as manifested by abnormal ZMT/ZoEratios, than normal or less involved muscle. Muscle tissue, with a high protein content, exhibited the greatest reduction in signal intensity (ZM,/ZoE = 0.397). Bone marrow and subcutaneous fat changed little with the MT sequence, because of the paucity of free water protons in these tissues which are available for exchange with macromolecularly bound water protons. In summary, MT techniques can increase contrast between certain tissues and allow for reproducible tissue characterization. At 0.1 T the technique can be used safely in humans, and provides data that may prove clinically relevant in evaluation of disease states. Fur-
ther investigation is required to assess the full potential of MT contrast imaging. REFERENCES 1. Dixon, W.T. Use of magnetization transfer contrast in gradient-recalled echo images. Radiology 179: 15-16; 1991. 2. Koenig, S.H.; Bryant, R.G.; Hallenga, K.; Jacob, G.S. Magnetic cross-relaxation among protons in protein solutions. Biochemistry 17:4348-4358; 1978. 3. Muller, R.N.; Marsh, M.J.; Bernardo, M.L.; Lauterbur, P.C. True 3-D imaging of limbs by NMR zeugmatography with off-resonance irradiation. Europ. J. Radiol. 3:286-290;
1983.
4. Wolff, S.D.; Balaban, R.S. Magnetization transfer contrast and tissue water proton relaxation in vivo. Magn. Reson. Med. 10: 135-144; 1989. 5. Wolff, S.D.; Eng, J.; Balaban, R.S. Magnetization transfer contrast: Method for improving contrast in gradient-recalled-echo images. Radiology 179:133-137; 1991.
6. Grad, J.; Bryant, R.G. Nuclear magnetic cross-relaxation spectroscopy. J. Magn. Reson. 90:1-8; 1990. 7. U.S. Food and Drug Administration. Guidance for content and review of a magnetic resonance diagnostic device 510(k) application. Publication number HFZ-401, Washington, DC: Center for Devices and Radiological Health, U.S. Food and Drug Administration; August 2, 1988. 8. Tanttu, J.I.; Sepponen, R.I. Imaging methods for whole-body MR imaging applications of magnetization transfer contrast at 0.1 T. Radiology 177(P):245; 1990. Abstract. 9. Tanttu, J.I.; Kahn, C.E. Jr.; Sepponen, R.E.; Holland, E.A.; Tierala, E.; Lipton, M.J. Magnetization transfer contrast of body tissues in vivo in MR imaging. Radiology 177(P):245; 1990. Abstract. 10. Dixon, W.T.; Engles, H.; Sardashti, M.; Castillo, M. Incidental magnetization transfer contrast affects multislice imaging. Magn. Reson. Imaging 8:417-422; 1990.