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Biomagnetic activity in breast lesions
Biomagnetic activity in breast lesions P. Anastasiadis,
Ph. Anninos
and E. Sivridis
Departments of Obstetrics and Gynaecology, Alexandroupolis, Greece
Medical Physics and Ptrthnlogy, Democritean
Uni\wsity
of‘ Thrwc.
S U MM A H Y. The spontaneous magnetic activity generated from 24 palpable breast lumps was measured by means of a superconducting quantum interference device (SQUID). The magnetic fields recorded in the 2-7 Hz frequency range were of high amplitudes in malignant breast neoplasms (754 + 305 fI’/t/Hz) and of low amplitudes in benign breast disease (274 f 49 ff/dHz). It is suggested that the differences detected by SQUID may provide the basis for new diagnostic or prognostic procedures.
Table
INTRODUCTION
diagnosis
of the 24 palpable breast lesions
Benign lesions Fibrocystic diseaae Fibroadenoma Duct ectasia
Breast cancer mortality rates have not changed during the past 60 years despite significant advances in screening mammography.’ It is tempting, therefore, to use novel technology in order to achieve a better understanding of breast oncology. The female breast, like any other living tissue, emits spontaneous magnetic activity caused by ionic movements across the plasma membrane.2 This activity, although exceedingly weak? (it is about 10-x of the earth’s magnetic field which is equivalent to 50 pT), can be measured by means of a superconducting quantum interference device (SQUID). Over the last few years we have explored the potential value of this method in investigating normal, benign and malignant breast lesions.’
PATIENTS
Histological
Malignant disease Invasive duct carcinoma of no special type (NST) Medullary carcinoma Mutinous carcinoma Invasive lobular carcinoma
3
I I Ih
I I
I
invasive procedure might increase biomagnetic activity. Informed consent for the study was obtained from all patients prior to the procedures. The method used for the recording of magnetic activity has been described in detail elsewhere.ti In brief, we used a single channel SQUID second ordergradiometer (DC SQUID model 601 of the Biomagnetic Technologies). The gradiometer operates at low liquid helium temperatures (4 “K) on the basis of the Josephson effect of superconductivity,’ with a sensitivity of 95 pTesla/Volt at 100 Hz. Recordings were taken in an electrically shielded room with the patient lying supine on a wooden bed, free of any metallic object (Fig. 1). She was asked to relax and close her eyes to avoid artifacts from eye flickering. In all patients five points were selected for examination. Point 5 (PS) was located at the very centre of the breast lump, whereas points l-4 (Pl-P4) were located at the periphery of the examined area. For each point 32 recordings of 1 second duration each were taken with the SQUID detector placed 3 mm above the recording position. This allows the maximum magnetic flux to pass through the coil with little deviation from the vertical direction. The sampling frequency was 256 Hz with a bandwidth of between 1 and 100 Hz. Using an AD converter. the analog signals were con-
AND METHODS
Magnetic recordings were obtained from 24 patients with palpable breast lumps: of these 19 were invasive carcinomas and 5 were benign breast lesions. The exact nature of these lumps was determined histologically (Table). The age of the patients with malignant tumours ranged from 42 to 64 compared with a range of 33-43 for patients with benign breast disease. Only patients with lesions in the right breast were included in this investigation. This was considered necessary if any interference from the heart’s magnetic activity was to be eliminated. Similarly. no patient in this series was subjected to fine needle aspiration cytology, as such an Address correspondence to: Professor P. Anastasiadis, MD, FIAC. Department of Obstetrics and Gynaecology, Democritean University of Thrace. Alexandroupolis 68 100. Greece
171
17X
The Breast
Fig. l-The SQUID and the patient during magnetomammographic measurements.
verted to digital ones and, after Fourier statistical analysis, the average spectral densities from the 32 records of magnetic field strength were obtained from each one of the five points measured in the frequency range 2-7 Hz. By convention, the maximum value was used when assessing the breast lesions. In all patients measurements from areas of interest (signals) were related to measurements of background magnetic activity (noise). Operators were blinded to clinical and mammographic findings.
Fig. 2-The wave form (raw data) of the magnetic field emitted from a fibrocystic disease of the breast: low amplitudes (250 fT/dHz) are distributed in the frequency of 3 Hz.
RESULTS The results are shown in Figures 2 and 7. The magnetic fields recorded in the 2-7 Hz frequency range were of high aplitudes in malignant breast neoplasms (754 + 305 ff/dHz) and of low amplitudes in benign breast disease (274 + 49 ff/dHz). These measurements represent the maximum values obtained from points 1 to 5, after Fourier statistical analysis. Values were more or less indifferent, although values from point 5 tended to be somewhat higher than those from point 1 to 4. In all cases the results were reproducible and the signal to noise ratio was very high. Figure 2 demonstrates the wave form (raw data) recorded from a benign breast lesion. The corresponding spectral amplitudes after statistical Fourier analysis are shown in Figure 3. The maximum total average of the spectral amplitude emitted ‘by benign breast lesions was 270.8 fT/dHz) (range 198-312 ff/dHz) in the 2-7 Hz frenquency band (Fig. 4). The wave forms recorded from malignant breast lesions and the corresponding spectral amplitudes are shown in Figures 5 and 6, respectively. The maximum total average of spectral amplitudes emitted by malignant breast tumours was 720.15 fT/dHz (range 365-l 100 ff/ ~Hz) in the 2-7 frequency band (Fig. 7). This difference between benign and malignant lesions was of statistical significance (Student’s t-test P < 0.005) and there was no overlap between the values obtained from the two types of breast lesions. None of the patients experienced side effects during or after the procedure.
Fig. %-The corresponding spectral densities of the magnetic field strength of the fibrocystic disease of breast: low spectral amplitudes (250 fI’/dHz) are distributed in the frequency of 3 Hz. (Analysis Fourier in a logarithmic scale.)
1 5
Fig. 4-The spontaneous magnetic activity generated palpable benign breast lesions.
from the 5
DISCUSSION The data presented in this study, although preliminary, justify an enthusiastic approach to the magnetomammogram (MMG) and suggest that this method of measuring the breast’s magnetic activity can be potentially exploited in differentiating benign and malignant breast
Biomagnetic
Fig. S-The wave form (raw data) of the magnetic field emitted from an invasive duct carcinoma: high amplitudes (1800 ff/dHz) are distributed in the frequency of 3 Hz.
Fig. &-The spectral densities of the wave form illustrated in Figure 5. High spectral amplitudes ( 1800 fT/dHz) are distributed in the frequency of 3(T)Hz. (Analysis Fourier in a logarithmic scale.)
activity in breast lesions
179
to any extent by other factors such as the size of the tumour, the proportion of fat to glandular tissue, or the depth of the lesion within the mammary gland. The size of the lesion per se seems to have very little influence on the recordings obtained and, indeed. the largest lesion in the series was a benign fibroadenoma with a low value. Equally, if there was to be any interference from the fat tissue surrounding the lesions, this should have an adverse effect on the magnitude of values obtained for the group of older patients, i.e. those with malignancies. since the proportion of fat to glandular tissue increases with advancing age. Undoubtedly, the closer the lesion to the skin surface the greater the values recorded, but there was no evidence that malignant lesions were lying more superficially than benign abnormalities. In addition. deep-seated tumours are suitable for biomagnetic measurements as the probe used is sensitive to a depth of 4 cm. Artifacts that could affect results include patients’ slight motions, but these, if any, would affect both groups of patients equally. It has to be mentioned, however, that these results relate exclusively to palpable breast lumps and not to early impalpable lesions. Furthermore, a much larger sample of patients is required before more firm conclusions can be drawn. Despite these limitations, it appears that biomagnetometry may be useful in identifying patients with malignant breast tumours and a further refinement of the method, together with the use of a more sensitive and multiple channel SQUID, may provide valuable adjunctive information in evaluating nonpalpable breast lesions. The same improvements may be useful in overcoming the interference from the heart’s magnetic activity which is of the order of SO pT. Measurements are unaffected by blood flow in the internal mammary artery as this vessel is well away from the points of measurement. It would be also of interest to correlate the data obtained from the MMG with other measurements of vascularity, e.g. colour flow Doppler and dynamic MRI. The method described is simple, effective, completely non-invasive and safe.J ‘J.’
References
Fig. 7-The spontaneous magnetic palpable malignant breast lesions.
activity generated
from the 19
lesions. This is not unexpected as malignant tissues, by virtue of their rapid expansion, vascularity and, therefore, increased ionic movements produce magnetic fields of higher intensity than slower growing benign breast tissues.? This is in line with previously published work which compares malignant versus normal breast tissues.j The differences reported in these studies are apparently due to malignancy itself and are not influenced
McLelland R. Pisano E D. Issues in mammography. Cancer 1990: 66: 1341-1344. Rose D F. Smith P D. Sato S. Magnetoencephalography and epilepsy research. Science 1987; 238: 329-335. Anastasiadis P, Anninos Ph. Sivridis E. Biomagnetic measurements in normal and malignant breast tissues using SQUID. In: Heine H (ed). Matrixforschung in der Praventivmedizin. Stuttgart - New York Gustav Fischer Verlag. 1989: pp 117-122. 4. Anninos P A, Anogianakis G. Lehnertz K. Pantev C H. Hoke M. Biomagnetic measurements using SQUID. Int J Neuroscience 1987: 37: 149-168. s. Elger C H. Hoke M. Lehnertz K et al. Mapping of MEG amplitude spectra: its significance for the diagnosis of focal epilepsy. In: K. Maurer (ed.). Topographic brain mapping of EEG and evoked potentials. Berlin: Springer Verlag, pp. 567-570. 6. Anninos P A. Tsagas N. Sandyk R. Derpapas K. Magnetic stimulation in the treatment of partial seizures. Int J Neuroscience 1991: 60: 141-171.
180
The Breast
7. Josephson B D. Possible effects in superconducting tunnelling. Phys lett 1962; 1: 252-256. 8. Barth D S. Sutherling W, Engel J, Beatty J. Neuromagnetic evidence of spatially distributed sources underlying epileptiform
spikes in the human brain. Science 1984; 223: 293-296. 9. Cohen D, Cuffin N, Yonokuchi K et al. MEG versus EEG localization test using implanted sources in the human brain. Ann Neurology 1990; 28: 81 l-817.
4th NOTTINGHAM INTERNATIONAL BREAST CANCER CONFERENCE 20 - 22 September 1995 Conference Secretary: Mrs Wendy Bartlam Professorial Unit of Surgery, City Hospital, Nottingham NG5 lPB, UK Telephone (0602) 625707, Fax (0602) 627765 Abstracts from the conference will appear in The Breast. Papers can be submitted to the Journal during the meeting, whereby prompt refereeing will aim for rapid publication of articles.
Ph. Anninos
and E. Sivridis
Departments of Obstetrics and Gynaecology, Alexandroupolis, Greece
Medical Physics and Ptrthnlogy, Democritean
Uni\wsity
of‘ Thrwc.
S U MM A H Y. The spontaneous magnetic activity generated from 24 palpable breast lumps was measured by means of a superconducting quantum interference device (SQUID). The magnetic fields recorded in the 2-7 Hz frequency range were of high amplitudes in malignant breast neoplasms (754 + 305 fI’/t/Hz) and of low amplitudes in benign breast disease (274 f 49 ff/dHz). It is suggested that the differences detected by SQUID may provide the basis for new diagnostic or prognostic procedures.
Table
INTRODUCTION
diagnosis
of the 24 palpable breast lesions
Benign lesions Fibrocystic diseaae Fibroadenoma Duct ectasia
Breast cancer mortality rates have not changed during the past 60 years despite significant advances in screening mammography.’ It is tempting, therefore, to use novel technology in order to achieve a better understanding of breast oncology. The female breast, like any other living tissue, emits spontaneous magnetic activity caused by ionic movements across the plasma membrane.2 This activity, although exceedingly weak? (it is about 10-x of the earth’s magnetic field which is equivalent to 50 pT), can be measured by means of a superconducting quantum interference device (SQUID). Over the last few years we have explored the potential value of this method in investigating normal, benign and malignant breast lesions.’
PATIENTS
Histological
Malignant disease Invasive duct carcinoma of no special type (NST) Medullary carcinoma Mutinous carcinoma Invasive lobular carcinoma
3
I I Ih
I I
I
invasive procedure might increase biomagnetic activity. Informed consent for the study was obtained from all patients prior to the procedures. The method used for the recording of magnetic activity has been described in detail elsewhere.ti In brief, we used a single channel SQUID second ordergradiometer (DC SQUID model 601 of the Biomagnetic Technologies). The gradiometer operates at low liquid helium temperatures (4 “K) on the basis of the Josephson effect of superconductivity,’ with a sensitivity of 95 pTesla/Volt at 100 Hz. Recordings were taken in an electrically shielded room with the patient lying supine on a wooden bed, free of any metallic object (Fig. 1). She was asked to relax and close her eyes to avoid artifacts from eye flickering. In all patients five points were selected for examination. Point 5 (PS) was located at the very centre of the breast lump, whereas points l-4 (Pl-P4) were located at the periphery of the examined area. For each point 32 recordings of 1 second duration each were taken with the SQUID detector placed 3 mm above the recording position. This allows the maximum magnetic flux to pass through the coil with little deviation from the vertical direction. The sampling frequency was 256 Hz with a bandwidth of between 1 and 100 Hz. Using an AD converter. the analog signals were con-
AND METHODS
Magnetic recordings were obtained from 24 patients with palpable breast lumps: of these 19 were invasive carcinomas and 5 were benign breast lesions. The exact nature of these lumps was determined histologically (Table). The age of the patients with malignant tumours ranged from 42 to 64 compared with a range of 33-43 for patients with benign breast disease. Only patients with lesions in the right breast were included in this investigation. This was considered necessary if any interference from the heart’s magnetic activity was to be eliminated. Similarly. no patient in this series was subjected to fine needle aspiration cytology, as such an Address correspondence to: Professor P. Anastasiadis, MD, FIAC. Department of Obstetrics and Gynaecology, Democritean University of Thrace. Alexandroupolis 68 100. Greece
171
17X
The Breast
Fig. l-The SQUID and the patient during magnetomammographic measurements.
verted to digital ones and, after Fourier statistical analysis, the average spectral densities from the 32 records of magnetic field strength were obtained from each one of the five points measured in the frequency range 2-7 Hz. By convention, the maximum value was used when assessing the breast lesions. In all patients measurements from areas of interest (signals) were related to measurements of background magnetic activity (noise). Operators were blinded to clinical and mammographic findings.
Fig. 2-The wave form (raw data) of the magnetic field emitted from a fibrocystic disease of the breast: low amplitudes (250 fT/dHz) are distributed in the frequency of 3 Hz.
RESULTS The results are shown in Figures 2 and 7. The magnetic fields recorded in the 2-7 Hz frequency range were of high aplitudes in malignant breast neoplasms (754 + 305 ff/dHz) and of low amplitudes in benign breast disease (274 + 49 ff/dHz). These measurements represent the maximum values obtained from points 1 to 5, after Fourier statistical analysis. Values were more or less indifferent, although values from point 5 tended to be somewhat higher than those from point 1 to 4. In all cases the results were reproducible and the signal to noise ratio was very high. Figure 2 demonstrates the wave form (raw data) recorded from a benign breast lesion. The corresponding spectral amplitudes after statistical Fourier analysis are shown in Figure 3. The maximum total average of the spectral amplitude emitted ‘by benign breast lesions was 270.8 fT/dHz) (range 198-312 ff/dHz) in the 2-7 Hz frenquency band (Fig. 4). The wave forms recorded from malignant breast lesions and the corresponding spectral amplitudes are shown in Figures 5 and 6, respectively. The maximum total average of spectral amplitudes emitted by malignant breast tumours was 720.15 fT/dHz (range 365-l 100 ff/ ~Hz) in the 2-7 frequency band (Fig. 7). This difference between benign and malignant lesions was of statistical significance (Student’s t-test P < 0.005) and there was no overlap between the values obtained from the two types of breast lesions. None of the patients experienced side effects during or after the procedure.
Fig. %-The corresponding spectral densities of the magnetic field strength of the fibrocystic disease of breast: low spectral amplitudes (250 fI’/dHz) are distributed in the frequency of 3 Hz. (Analysis Fourier in a logarithmic scale.)
1 5
Fig. 4-The spontaneous magnetic activity generated palpable benign breast lesions.
from the 5
DISCUSSION The data presented in this study, although preliminary, justify an enthusiastic approach to the magnetomammogram (MMG) and suggest that this method of measuring the breast’s magnetic activity can be potentially exploited in differentiating benign and malignant breast
Biomagnetic
Fig. S-The wave form (raw data) of the magnetic field emitted from an invasive duct carcinoma: high amplitudes (1800 ff/dHz) are distributed in the frequency of 3 Hz.
Fig. &-The spectral densities of the wave form illustrated in Figure 5. High spectral amplitudes ( 1800 fT/dHz) are distributed in the frequency of 3(T)Hz. (Analysis Fourier in a logarithmic scale.)
activity in breast lesions
179
to any extent by other factors such as the size of the tumour, the proportion of fat to glandular tissue, or the depth of the lesion within the mammary gland. The size of the lesion per se seems to have very little influence on the recordings obtained and, indeed. the largest lesion in the series was a benign fibroadenoma with a low value. Equally, if there was to be any interference from the fat tissue surrounding the lesions, this should have an adverse effect on the magnitude of values obtained for the group of older patients, i.e. those with malignancies. since the proportion of fat to glandular tissue increases with advancing age. Undoubtedly, the closer the lesion to the skin surface the greater the values recorded, but there was no evidence that malignant lesions were lying more superficially than benign abnormalities. In addition. deep-seated tumours are suitable for biomagnetic measurements as the probe used is sensitive to a depth of 4 cm. Artifacts that could affect results include patients’ slight motions, but these, if any, would affect both groups of patients equally. It has to be mentioned, however, that these results relate exclusively to palpable breast lumps and not to early impalpable lesions. Furthermore, a much larger sample of patients is required before more firm conclusions can be drawn. Despite these limitations, it appears that biomagnetometry may be useful in identifying patients with malignant breast tumours and a further refinement of the method, together with the use of a more sensitive and multiple channel SQUID, may provide valuable adjunctive information in evaluating nonpalpable breast lesions. The same improvements may be useful in overcoming the interference from the heart’s magnetic activity which is of the order of SO pT. Measurements are unaffected by blood flow in the internal mammary artery as this vessel is well away from the points of measurement. It would be also of interest to correlate the data obtained from the MMG with other measurements of vascularity, e.g. colour flow Doppler and dynamic MRI. The method described is simple, effective, completely non-invasive and safe.J ‘J.’
References
Fig. 7-The spontaneous magnetic palpable malignant breast lesions.
activity generated
from the 19
lesions. This is not unexpected as malignant tissues, by virtue of their rapid expansion, vascularity and, therefore, increased ionic movements produce magnetic fields of higher intensity than slower growing benign breast tissues.? This is in line with previously published work which compares malignant versus normal breast tissues.j The differences reported in these studies are apparently due to malignancy itself and are not influenced
McLelland R. Pisano E D. Issues in mammography. Cancer 1990: 66: 1341-1344. Rose D F. Smith P D. Sato S. Magnetoencephalography and epilepsy research. Science 1987; 238: 329-335. Anastasiadis P, Anninos Ph. Sivridis E. Biomagnetic measurements in normal and malignant breast tissues using SQUID. In: Heine H (ed). Matrixforschung in der Praventivmedizin. Stuttgart - New York Gustav Fischer Verlag. 1989: pp 117-122. 4. Anninos P A, Anogianakis G. Lehnertz K. Pantev C H. Hoke M. Biomagnetic measurements using SQUID. Int J Neuroscience 1987: 37: 149-168. s. Elger C H. Hoke M. Lehnertz K et al. Mapping of MEG amplitude spectra: its significance for the diagnosis of focal epilepsy. In: K. Maurer (ed.). Topographic brain mapping of EEG and evoked potentials. Berlin: Springer Verlag, pp. 567-570. 6. Anninos P A. Tsagas N. Sandyk R. Derpapas K. Magnetic stimulation in the treatment of partial seizures. Int J Neuroscience 1991: 60: 141-171.
180
The Breast
7. Josephson B D. Possible effects in superconducting tunnelling. Phys lett 1962; 1: 252-256. 8. Barth D S. Sutherling W, Engel J, Beatty J. Neuromagnetic evidence of spatially distributed sources underlying epileptiform
spikes in the human brain. Science 1984; 223: 293-296. 9. Cohen D, Cuffin N, Yonokuchi K et al. MEG versus EEG localization test using implanted sources in the human brain. Ann Neurology 1990; 28: 81 l-817.
4th NOTTINGHAM INTERNATIONAL BREAST CANCER CONFERENCE 20 - 22 September 1995 Conference Secretary: Mrs Wendy Bartlam Professorial Unit of Surgery, City Hospital, Nottingham NG5 lPB, UK Telephone (0602) 625707, Fax (0602) 627765 Abstracts from the conference will appear in The Breast. Papers can be submitted to the Journal during the meeting, whereby prompt refereeing will aim for rapid publication of articles.