1979, British Journal of Radiology, 52, 242-243
Short communication Carcinoma of the breast imaged by nuclear magnetic resonance (NMR) By P. Mansfield, B.Sc, Ph.D., P. G. Morris, M.A., Ph.D., R. Ordidge, B.Sc, Department of Physics, University of Nottingham R. E. Coupland, M.D., Ph.D., D.Sc, F.R.S.E., Department of Human Morphology, University of Nottingham H. M. Bishop, F.R.C.S., and R. W. Blarney, M.D., F.R.C.S., Department of Surgery, University of Nottingham {Received October, 1978) NMR has shown promise as a non-invasive and nonhazardous method of imaging the mobile proton distributtion (mainly water) on a small scale in both animal and human tissues (Mansfield and Maudsley, 1977) and more recently on a much larger whole-body scale (Mansfield, et ah, 1978; Damadian et ah, 1977). In this paper we report the first localization of a breast cancer by this technique in a simple mastectomy specimen from a 47-year-old woman. Following mastectomy the specimen was rapidly transferred from the City Hospital to the Physics Department and the NMR scan started about 1J hours following operation. The specimen measured some 15 cm in the long axis, one end of which was the axillary tail; it had a maximum thickness of about 4 cm at the centre tapering off to about 1 cm at the periphery. The surface of the specimen was marked with waterproof ink for identification purposes and placed flat in a plastic container. The slice thickness scanned included the whole of the breast; the images produced correspond to coronal scan projections of water and fat distributed in the whole breast. METHOD
The NMR line scanning technique used here has been largely described elsewhere (Mansfield, et al., 1976). The principle of operation is: mobile protons contained in the water, fat or oil distributed throughout biological material are first aligned in a large static magnetic field. A weak nuclear magnetization results due to the small magnetic moment possessed by each proton or hydrogen nucleus. The weak polarization produced is proportional to the localized proton density (water content, etc.); this is read out line by line across the specimen by applying switched magnetic field gradients to define position within the specimen, and weak radiofrequency (rf) pulses tuned to the nuclear resonance frequency. The rf pulses perturb the nuclear magnetization from alignment and transient nuclear free-induction decay (FID) signals are recorded and Fourier analysed to yield the effective proton density of the specimen along a particular line. The static field used was approximately 1 kG corresponding to a resonance frequency of 4.0 MHz. In addition to distributed content of water and fat etc., the spatial distribution of spin lattice relaxation times T\ (x, y) can be measured. Ti is the time for disturbed protons to realign in the large polarizing field. Changes in T\ reflect differences in mobility of the water and also differences in metabolic activity and dissolved salts contained in the cytoplasmic and extra-cellular water. Immediately after scanning, the tissue was immersed in 20% formalin in which it remained for four days. It was then deep frozen and horizontal slices of about 8 mm thickness prepared and photographed. Paraffin sections of selected parts confirmed the presence of malignant tissue.
The distribution of the carcinoma was reconstructed from the sections. RESULTS AND DISCUSSION
The NMR images (Fig. 1A and B) reflect the general outline of the specimen. This correlates well with the outline of the fixed specimen (Fig. 2). In Fig. 1A each line of the picture was averaged 512 times with a delay of 0.15 sec. The dark zone to the right corresponds with the nipple region and underlying carcinoma and the larger dark central and left image corresponds to the main mass of the tumour (a scirrhous carcinoma). Bright zones on the scan correspond to normal breast tissue and the general gradation of the image intensity towards the periphery reflects the progressively reduced thickness of sample towards the edges. In normal tissue the thickest part of the specimen (the centre) would be expected to yield the brightest zone in the image. Figure 1B is the same specimen scanned immediately after producing Fig 1 A but with the delay time doubled to 0.3 sec. The dark nipple region remains but contrast in the tumourous region is reduced as a result of a somewhat longer Ti compared with that of surrounding normal tissues (Damadian, 1971). The image intensity of the nipple region does not change so significantly with decrease in repetition period and indicates that in the excized specimen this region has a lower water and/or fat content in keeping with known histological structures. A second breast containing a large circumscribed fibroadenoma about 4 cm in diameter taken from a 73-year-old woman has also been examined and shows an image consistent with the tumour position. Further study of breast tumours by NMR is continuing and we hope soon to be able to use the whole body imaging capability of the machine which allows examination of breasts in vivo before operation. ACKNOWLEDGMENTS
We are grateful to the MRC for a project grant to support this work. We are especially indebted to T. Baines for the design and construction of the electronic apparatus and V. Bangert for his assistance in the design of the gradient coils. REFERENCES DAMADIAN, R. 1971. Tumour detection by nuclear magnetic resonance. Science, N. Y., 171, 1151 -1153. DAMADIAN, R., GOLDSMITH, M. and MINKOFF, L.
1977.
NMR in cancer: XVI. Fonar image of the live human body. Physiological Chemistry and Physics, 9, 97. MANSFIELD, P. and MAUDSLEY, A. A. 1977. Medical imaging
242
by NMR. British Journal of Radiology, 50, 188-194.
MARCH
1979
Short communication FIG.1.
NMR line scan images of excised breast: (A) Delay time 0.15 sec. Dark region to right corresponds with nipple. Dark central region corresponds to tumour site. (B) Delay time is increased to 0.30 sec thus generally lowering picture contrast so that only the main mass of the tumour in the centre is revealed. Dark region to left of each picture corresponds to a notch in the tissue mass.
FIG. 2. Reconstruction of position of scirrhous carcinoma which was thickest centrally and tapered towards left and right margins. Position of nipple indicated by black circle. Axillary tail is at the top of the specimen.
MANSFIELD, P., MAUDSLEY, A. A. and BAINES, T. 1976. Fast
scan proton density imaging by NMR. Journal of Physics, E,9, 271-278. MANSFIELD, P., PYKETT, I. L., MORRIS, P. G. and COUP-
LAND, R. E. 1978. Human whole body line scan imaging by NMR. British Journal of Radiology, 51, 921-922.
243
Short communication Carcinoma of the breast imaged by nuclear magnetic resonance (NMR) By P. Mansfield, B.Sc, Ph.D., P. G. Morris, M.A., Ph.D., R. Ordidge, B.Sc, Department of Physics, University of Nottingham R. E. Coupland, M.D., Ph.D., D.Sc, F.R.S.E., Department of Human Morphology, University of Nottingham H. M. Bishop, F.R.C.S., and R. W. Blarney, M.D., F.R.C.S., Department of Surgery, University of Nottingham {Received October, 1978) NMR has shown promise as a non-invasive and nonhazardous method of imaging the mobile proton distributtion (mainly water) on a small scale in both animal and human tissues (Mansfield and Maudsley, 1977) and more recently on a much larger whole-body scale (Mansfield, et ah, 1978; Damadian et ah, 1977). In this paper we report the first localization of a breast cancer by this technique in a simple mastectomy specimen from a 47-year-old woman. Following mastectomy the specimen was rapidly transferred from the City Hospital to the Physics Department and the NMR scan started about 1J hours following operation. The specimen measured some 15 cm in the long axis, one end of which was the axillary tail; it had a maximum thickness of about 4 cm at the centre tapering off to about 1 cm at the periphery. The surface of the specimen was marked with waterproof ink for identification purposes and placed flat in a plastic container. The slice thickness scanned included the whole of the breast; the images produced correspond to coronal scan projections of water and fat distributed in the whole breast. METHOD
The NMR line scanning technique used here has been largely described elsewhere (Mansfield, et al., 1976). The principle of operation is: mobile protons contained in the water, fat or oil distributed throughout biological material are first aligned in a large static magnetic field. A weak nuclear magnetization results due to the small magnetic moment possessed by each proton or hydrogen nucleus. The weak polarization produced is proportional to the localized proton density (water content, etc.); this is read out line by line across the specimen by applying switched magnetic field gradients to define position within the specimen, and weak radiofrequency (rf) pulses tuned to the nuclear resonance frequency. The rf pulses perturb the nuclear magnetization from alignment and transient nuclear free-induction decay (FID) signals are recorded and Fourier analysed to yield the effective proton density of the specimen along a particular line. The static field used was approximately 1 kG corresponding to a resonance frequency of 4.0 MHz. In addition to distributed content of water and fat etc., the spatial distribution of spin lattice relaxation times T\ (x, y) can be measured. Ti is the time for disturbed protons to realign in the large polarizing field. Changes in T\ reflect differences in mobility of the water and also differences in metabolic activity and dissolved salts contained in the cytoplasmic and extra-cellular water. Immediately after scanning, the tissue was immersed in 20% formalin in which it remained for four days. It was then deep frozen and horizontal slices of about 8 mm thickness prepared and photographed. Paraffin sections of selected parts confirmed the presence of malignant tissue.
The distribution of the carcinoma was reconstructed from the sections. RESULTS AND DISCUSSION
The NMR images (Fig. 1A and B) reflect the general outline of the specimen. This correlates well with the outline of the fixed specimen (Fig. 2). In Fig. 1A each line of the picture was averaged 512 times with a delay of 0.15 sec. The dark zone to the right corresponds with the nipple region and underlying carcinoma and the larger dark central and left image corresponds to the main mass of the tumour (a scirrhous carcinoma). Bright zones on the scan correspond to normal breast tissue and the general gradation of the image intensity towards the periphery reflects the progressively reduced thickness of sample towards the edges. In normal tissue the thickest part of the specimen (the centre) would be expected to yield the brightest zone in the image. Figure 1B is the same specimen scanned immediately after producing Fig 1 A but with the delay time doubled to 0.3 sec. The dark nipple region remains but contrast in the tumourous region is reduced as a result of a somewhat longer Ti compared with that of surrounding normal tissues (Damadian, 1971). The image intensity of the nipple region does not change so significantly with decrease in repetition period and indicates that in the excized specimen this region has a lower water and/or fat content in keeping with known histological structures. A second breast containing a large circumscribed fibroadenoma about 4 cm in diameter taken from a 73-year-old woman has also been examined and shows an image consistent with the tumour position. Further study of breast tumours by NMR is continuing and we hope soon to be able to use the whole body imaging capability of the machine which allows examination of breasts in vivo before operation. ACKNOWLEDGMENTS
We are grateful to the MRC for a project grant to support this work. We are especially indebted to T. Baines for the design and construction of the electronic apparatus and V. Bangert for his assistance in the design of the gradient coils. REFERENCES DAMADIAN, R. 1971. Tumour detection by nuclear magnetic resonance. Science, N. Y., 171, 1151 -1153. DAMADIAN, R., GOLDSMITH, M. and MINKOFF, L.
1977.
NMR in cancer: XVI. Fonar image of the live human body. Physiological Chemistry and Physics, 9, 97. MANSFIELD, P. and MAUDSLEY, A. A. 1977. Medical imaging
242
by NMR. British Journal of Radiology, 50, 188-194.
MARCH
1979
Short communication FIG.1.
NMR line scan images of excised breast: (A) Delay time 0.15 sec. Dark region to right corresponds with nipple. Dark central region corresponds to tumour site. (B) Delay time is increased to 0.30 sec thus generally lowering picture contrast so that only the main mass of the tumour in the centre is revealed. Dark region to left of each picture corresponds to a notch in the tissue mass.
FIG. 2. Reconstruction of position of scirrhous carcinoma which was thickest centrally and tapered towards left and right margins. Position of nipple indicated by black circle. Axillary tail is at the top of the specimen.
MANSFIELD, P., MAUDSLEY, A. A. and BAINES, T. 1976. Fast
scan proton density imaging by NMR. Journal of Physics, E,9, 271-278. MANSFIELD, P., PYKETT, I. L., MORRIS, P. G. and COUP-
LAND, R. E. 1978. Human whole body line scan imaging by NMR. British Journal of Radiology, 51, 921-922.
243
