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NMR images by the multiple sensitive point method: application to larger biological systems
This content has been downloaded from IOPscience. Please scroll down to see the full text. 1977 Phys. Med. Biol. 22 971 (http://iopscience.iop.org/0031-9155/22/5/016) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 142.103.160.110 This content was downloaded on 06/09/2015 at 21:58
Please note that terms and conditions apply.
PHYS. MED. BIOL.,
1977,
VOL.
22, NO. 5 , 971-974.
@
1977
Xcienti$c Note
NMR Images by the Multiple Sensitive Point Method: Application to Larger Biological Systems E. R. ANDREW, P. A. BOTTOMLEY, W. S. HINSHAW, G. N. HOLLAND, W. S. MOORE and C . SIMAROJ Department of Physics, University of Nottingham, University Park, Nottingham NG7 2RD, England
Received 2 M a y 1977
Image formation by nuclear magnetic resonance? was initially restricted to objects of order 1 cm in size in order to be accommodated within the magnet gap of conventional NMR spectrometers (Lauterbur 1973, Garroway, Grannell and Mansfield 1974, Hinshaw 1974a, b, Grannell and Mansfield 1975, Kumar, Welti and Ernst 1975). With a view to applying the method to problems in medicine and biology we have recently developed and constructed an NMR imaging system capable of examining objects of order 10 cm in size, and in this note we report first examplesof images obtained with this instrument. Features of this system are its successful exploitation of a new fast multisensitive point method, the use of a steady-state free precession NMR mode of operation to optimize sensitivity and the generation of truly three-dimensional images. Inthe earlier single sensitivepointmethod(Hinshaw 1974a, b, 1976) alternating magnetic field gradients were applied to theobject along orthogonal X, Y and Z directions at three different non-conjugate low frequencies. The intersection of the threenull planes of these three alternating gradientsdefined a small sensitive volume element whose NMR signal was filtered and detected. By traversing this element in place a by raster, theNMR signal could scan thin slices in the object yielding an NMR image of proton density, or spin map, of the slice. A stack of images of such slices constitutes a 3D image of the object characterizing its structure in three dimensions. I n order to accelerate the collection of NMR information and the more rapid production of NMR images the multisensitive point method has been devised, full details of which will be published later. Briefly, in this method a column of N sensitive points scans all N raster lines simultaneously, achieving an N-fold reductioninpicture acquisition time. This column of N sensitive points forms a sensitive line. In themultiple sensitive point method, two alternating gradients,one along each of the X and Z directions, define the sensitive line in the Y direction, along ~
tA
~~
general introductiontothesubject of image formationbynuclearmagnetic resonance (NMR), sometimes called Zeugmatography(Lauterbur 1973), is given by Andrew (1976), where other references to work in the subject are cited.
972
E. R.Andrews et al.
which a static gradient is superimposed. A string of coherent, equally-spaced phase-alternated resonant radiofrequencypulses applied to theobject provides a steady-state free precession (SFP) mode of NMR detection (Hinshaw 1976). Viewed in the frequency domain this periodically-pulsed radiation represents a comb of equally-spaced discrete frequencies which generate NMR signals from discrete volume elements along the sensitive line. Discrete Fourier transformation of the signal received between pulses yields the proton density along the sensitive line. This line of sensitive points may be traversed through the null YZ plane defined by thetwo alternating gradients,so yielding a proton density image in this plane of the object. A Varian V7300 electromagnet with 127 mm gap and 380 mm pole diameter provides a field of 0.7 T in a working volume of order 10 cm diameter. Proton NMR signals from a home-built pulsed NMR spectrometer operating in the SFP mode a t 30 MHz are signal averaged and then processed by a Data General Kova 2-10 minicomputer,ready for displayona Hewlett-Packard 13358 variable persistence monochrome oscilloscope. Window levels may be selected a t will and colour images are generated t o a predetermined attribution scheme by a variety of techniques, oneof which uses selected colour filters (Holland and Bottomley 1977). Images currently produced consist of 128 x 128 independent picture elements and are obtained in typically two minutes. Two examples of proton density images of medical and biological interest are shown in figs 1 and 2 based on a 16 colour attribution scheme. An in vivo section, a few mm thick, through the right hand of one of us (G N H) is shown in fig. 1 clearly revealing the thumb andfour fingers and some detail of internal structure. I n fig. 2 is shown a section through the abdominal region of an intact rat, 6 cm width, a few hours after death. This is one of a number of such cross-section scans taken at intervals along the length of the rat. It should be noted that these images are not 2D projections of proton density from thick slices whose width is determined by the radiofrequency coil system, but are thin slices whose width is controlled by the effective thickness of the null plane of the alternating gradient normal to the slice. These images should be seen asfirst examples which will be improved upon astechniques develop and artefacts are removed. There remains much to learn concerning the detailed correlation of the proton density image with the actual biological structure. There is no evidence of significant attenuation of the radiofrequency signal within the animal, consistent with our earlier estimate, ba’sed on conductivity data, of a ‘skin’ depth of order 10 cm. This gives some confidence that the electromagnetic radiation would penetrate sufficiently far into living tissue for human whole-body applications. For medical imaging NMR has the potential advantage over X-rays of being devoid of known human hazard, the radiofrequency photons having an energy of 10-7 eV, several orders below ionization levels, and the radiofrequency mean power levels being well below those used in diathermic therapy; there is moreover the added possibility of discrimination of cancerous tissue through longer proton relaxation times (see for example Damadian 1971, Hazelwood, Cleveland and Medina 1974, Hutchinson, Nallard and Go11 1974,Coles 1976). With the present instrument investigations Of
N M R Images
973
Fig. 1. Proton N M R image of a live human hand. Using a 16 level colour display the proton density is shown in a thin cross-sectionof the right hand passing through the head of the proximal phalanx of the middle fmger. The dorsal surface of the hand is uppermost.
Fig. 2. Proton NMR image of an abdominal section of a female rat 6 cm across, a few hours after death. The animal was placed horizontallyon its back inthe apparatus. Comparison with a section cut from the ratshortly afterwards shows that thedeep red region (upper left quadrant) is associated with the intestines, the blue region (upper right hand quadrant) with the stomach, the red region (far upper right) with the spleen and the white regions (bottom left) with fatty tissue.
974
N M R Images
animals and human limbs are possible with a view to assessment of prospects of the usefulness of NMR imaging in medicine and other fields.
We wish to express our gratitude to the Medical Research Council fora research grant to support this project, to Dr. M. R. Price of the Nottingham University Cancer Research Campaign Laboratories for provision of the rat and t o Dr. P. S. Allen and Dr. R. H. Brooker for helpful discussions. REFERENCES ANDREW, E. R., 1976, in 4th AMPERE International Summer School, Pula, Yugoslavia, in press. COLES, B. A., 1976, J . Nutn Cancer Inst., 57, 389. DAMADIAN, R., 1971, Science N . Y . , 171, 1151. GARROWAY, A. N., GRANNELL,P. K., and MANSFIELD,P., 1974, J . Phys. C : Solid State Phys., 7, L457. GRANKELL,P. K., and MANSFIELD, P., 1975, Phys. Med. Biol., 20, 477. HAZLEWOOD, C. F., CLEVELAND,G., and MEDINA,D., 1974, J . Nutn Cancer Inst., 52,1849. HINSHAW, W. S.,1974a, Phys. Lett., 48A, 87. HINSHAW,W. S.,197413, in Proc. 18th A M P E R E Congress, Nottingham, p. 433. HINSHAW, W. S.,1976, J . Appl. Phys., 47, 3709. HOLLAKD, G. N., and BOTTOMLEY, P. A., 1977, J . Phys. E : Sci. Instrum., in press. HUTCHINSON, J. M. S.,MALLARD,J. R., and GOLL,C. C., 1974, in Proc. 18th A M P E R E Congress, Nottingham, p. 283. KUMAR, A., WELTI,D., and ERNST,R. R., 1975, J . Mug. Res., 18, 69. LAUTERBUR, P. C., 1973, Nature, Lond., 242, 190.
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My IOPscience
NMR images by the multiple sensitive point method: application to larger biological systems
This content has been downloaded from IOPscience. Please scroll down to see the full text. 1977 Phys. Med. Biol. 22 971 (http://iopscience.iop.org/0031-9155/22/5/016) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 142.103.160.110 This content was downloaded on 06/09/2015 at 21:58
Please note that terms and conditions apply.
PHYS. MED. BIOL.,
1977,
VOL.
22, NO. 5 , 971-974.
@
1977
Xcienti$c Note
NMR Images by the Multiple Sensitive Point Method: Application to Larger Biological Systems E. R. ANDREW, P. A. BOTTOMLEY, W. S. HINSHAW, G. N. HOLLAND, W. S. MOORE and C . SIMAROJ Department of Physics, University of Nottingham, University Park, Nottingham NG7 2RD, England
Received 2 M a y 1977
Image formation by nuclear magnetic resonance? was initially restricted to objects of order 1 cm in size in order to be accommodated within the magnet gap of conventional NMR spectrometers (Lauterbur 1973, Garroway, Grannell and Mansfield 1974, Hinshaw 1974a, b, Grannell and Mansfield 1975, Kumar, Welti and Ernst 1975). With a view to applying the method to problems in medicine and biology we have recently developed and constructed an NMR imaging system capable of examining objects of order 10 cm in size, and in this note we report first examplesof images obtained with this instrument. Features of this system are its successful exploitation of a new fast multisensitive point method, the use of a steady-state free precession NMR mode of operation to optimize sensitivity and the generation of truly three-dimensional images. Inthe earlier single sensitivepointmethod(Hinshaw 1974a, b, 1976) alternating magnetic field gradients were applied to theobject along orthogonal X, Y and Z directions at three different non-conjugate low frequencies. The intersection of the threenull planes of these three alternating gradientsdefined a small sensitive volume element whose NMR signal was filtered and detected. By traversing this element in place a by raster, theNMR signal could scan thin slices in the object yielding an NMR image of proton density, or spin map, of the slice. A stack of images of such slices constitutes a 3D image of the object characterizing its structure in three dimensions. I n order to accelerate the collection of NMR information and the more rapid production of NMR images the multisensitive point method has been devised, full details of which will be published later. Briefly, in this method a column of N sensitive points scans all N raster lines simultaneously, achieving an N-fold reductioninpicture acquisition time. This column of N sensitive points forms a sensitive line. In themultiple sensitive point method, two alternating gradients,one along each of the X and Z directions, define the sensitive line in the Y direction, along ~
tA
~~
general introductiontothesubject of image formationbynuclearmagnetic resonance (NMR), sometimes called Zeugmatography(Lauterbur 1973), is given by Andrew (1976), where other references to work in the subject are cited.
972
E. R.Andrews et al.
which a static gradient is superimposed. A string of coherent, equally-spaced phase-alternated resonant radiofrequencypulses applied to theobject provides a steady-state free precession (SFP) mode of NMR detection (Hinshaw 1976). Viewed in the frequency domain this periodically-pulsed radiation represents a comb of equally-spaced discrete frequencies which generate NMR signals from discrete volume elements along the sensitive line. Discrete Fourier transformation of the signal received between pulses yields the proton density along the sensitive line. This line of sensitive points may be traversed through the null YZ plane defined by thetwo alternating gradients,so yielding a proton density image in this plane of the object. A Varian V7300 electromagnet with 127 mm gap and 380 mm pole diameter provides a field of 0.7 T in a working volume of order 10 cm diameter. Proton NMR signals from a home-built pulsed NMR spectrometer operating in the SFP mode a t 30 MHz are signal averaged and then processed by a Data General Kova 2-10 minicomputer,ready for displayona Hewlett-Packard 13358 variable persistence monochrome oscilloscope. Window levels may be selected a t will and colour images are generated t o a predetermined attribution scheme by a variety of techniques, oneof which uses selected colour filters (Holland and Bottomley 1977). Images currently produced consist of 128 x 128 independent picture elements and are obtained in typically two minutes. Two examples of proton density images of medical and biological interest are shown in figs 1 and 2 based on a 16 colour attribution scheme. An in vivo section, a few mm thick, through the right hand of one of us (G N H) is shown in fig. 1 clearly revealing the thumb andfour fingers and some detail of internal structure. I n fig. 2 is shown a section through the abdominal region of an intact rat, 6 cm width, a few hours after death. This is one of a number of such cross-section scans taken at intervals along the length of the rat. It should be noted that these images are not 2D projections of proton density from thick slices whose width is determined by the radiofrequency coil system, but are thin slices whose width is controlled by the effective thickness of the null plane of the alternating gradient normal to the slice. These images should be seen asfirst examples which will be improved upon astechniques develop and artefacts are removed. There remains much to learn concerning the detailed correlation of the proton density image with the actual biological structure. There is no evidence of significant attenuation of the radiofrequency signal within the animal, consistent with our earlier estimate, ba’sed on conductivity data, of a ‘skin’ depth of order 10 cm. This gives some confidence that the electromagnetic radiation would penetrate sufficiently far into living tissue for human whole-body applications. For medical imaging NMR has the potential advantage over X-rays of being devoid of known human hazard, the radiofrequency photons having an energy of 10-7 eV, several orders below ionization levels, and the radiofrequency mean power levels being well below those used in diathermic therapy; there is moreover the added possibility of discrimination of cancerous tissue through longer proton relaxation times (see for example Damadian 1971, Hazelwood, Cleveland and Medina 1974, Hutchinson, Nallard and Go11 1974,Coles 1976). With the present instrument investigations Of
N M R Images
973
Fig. 1. Proton N M R image of a live human hand. Using a 16 level colour display the proton density is shown in a thin cross-sectionof the right hand passing through the head of the proximal phalanx of the middle fmger. The dorsal surface of the hand is uppermost.
Fig. 2. Proton NMR image of an abdominal section of a female rat 6 cm across, a few hours after death. The animal was placed horizontallyon its back inthe apparatus. Comparison with a section cut from the ratshortly afterwards shows that thedeep red region (upper left quadrant) is associated with the intestines, the blue region (upper right hand quadrant) with the stomach, the red region (far upper right) with the spleen and the white regions (bottom left) with fatty tissue.
974
N M R Images
animals and human limbs are possible with a view to assessment of prospects of the usefulness of NMR imaging in medicine and other fields.
We wish to express our gratitude to the Medical Research Council fora research grant to support this project, to Dr. M. R. Price of the Nottingham University Cancer Research Campaign Laboratories for provision of the rat and t o Dr. P. S. Allen and Dr. R. H. Brooker for helpful discussions. REFERENCES ANDREW, E. R., 1976, in 4th AMPERE International Summer School, Pula, Yugoslavia, in press. COLES, B. A., 1976, J . Nutn Cancer Inst., 57, 389. DAMADIAN, R., 1971, Science N . Y . , 171, 1151. GARROWAY, A. N., GRANNELL,P. K., and MANSFIELD,P., 1974, J . Phys. C : Solid State Phys., 7, L457. GRANKELL,P. K., and MANSFIELD, P., 1975, Phys. Med. Biol., 20, 477. HAZLEWOOD, C. F., CLEVELAND,G., and MEDINA,D., 1974, J . Nutn Cancer Inst., 52,1849. HINSHAW, W. S.,1974a, Phys. Lett., 48A, 87. HINSHAW,W. S.,197413, in Proc. 18th A M P E R E Congress, Nottingham, p. 433. HINSHAW, W. S.,1976, J . Appl. Phys., 47, 3709. HOLLAKD, G. N., and BOTTOMLEY, P. A., 1977, J . Phys. E : Sci. Instrum., in press. HUTCHINSON, J. M. S.,MALLARD,J. R., and GOLL,C. C., 1974, in Proc. 18th A M P E R E Congress, Nottingham, p. 283. KUMAR, A., WELTI,D., and ERNST,R. R., 1975, J . Mug. Res., 18, 69. LAUTERBUR, P. C., 1973, Nature, Lond., 242, 190.
