Biomagnetic Measurements Research Articles

Non-invasive assessment of the heart function in unshielded clinical environment by SQUID gradiometry

Bioelectrical activity of the heart produces minute magnetic fields that may be measured above the torso with superconducting quantum interference device (SQUID) sensors. A new application has been developed which permits noninvasive assessment of the heart function in unshielded magnetically harsh clinical environment. The system incorporates a multichannel SQUID system, a supine nonmagnetic ergometer, a peripheral data interface and software tools for processing magnetocardiographic data. To demonstrate the performance of the method, biomagnetic measurements have been performed both at rest and during physical exercise. Signal processing, signal-to-noise ratio and artifact rejection procedures have been discussed.

Active magnetic shielding for biomagnetic measurement using spatial gradient fields

Biomagnetic measurement performed outside a magnetically shielded room is subject to distortion by strong magnetic fields. Reducing such disturbances can enhance and stabilize biomagnetic measurement conditions in the absence of passive shielding. We have developed an active magnetic shielding system that produces both homogeneous and spatial gradient magnetic fields. The system is composed of anisotropic magnetoresistive sensors, a digital signal processor controller and two different coil systems. In order to improve the measurement environment for a first-order gradient coil SQUID system, the disturbing vertical magnetic fields and vertical field gradients are reduced, thus achieving a shielding factor of approximately 6 at 100 Hz. Our system provides a more flexible and less costly alternative to magnetically shielded rooms.

Differential diagnosis of prostate lesions with the use of biomagnetic measurements and non-linear analysis.

The purpose of this study was to investigate the biomagnetic activity emitted from the prostate gland and to differentiate cancerous from benign prostate lesions with the use of biomagnetic measurement and non-linear analysis. Magnetic recordings were obtained from 47 patients with palpable prostate lesions. Histology revealed 24 prostate cancer patients and 23 benign prostate hyperplasia (BPH) patients. The superconducting quantum interference device (SQUID) biomagnetometer was used to measure the prostate's magnetic field by placing the SQUID detector 3 mm above the symphysis pubis. The magnetic field recorded in the 2-7 Hz frequency range was of high amplitude in most malignant lesions whereas all benign cases were of low amplitude. According to our results, the sensitivity, specificity, positive predictive value and negative predictive value were 83.33%, 100%, 100% and 85.18%, respectively. By applying the Grassberger-Procaccia algorithm to the magnetoprostatogram time series in malignant and benign prostate lesions we found clear saturation in malignant prostate lesions with m>7 whereas in the benign lesions there was not clear saturation. Prostate cancer emits higher biomagnetic activity than the BPH. This confirms a higher angiogenic activity in prostate cancer than the BPH lesions. Furthermore, the saturation value in the estimation of the correlation dimension of the attractor for the cancer lesions confirms the lower complexity of the system in comparison to the BPH, which is characterized by higher complexity.

Research and some applications of high-Tc SQUIDS

In the work, we studied the noise characteristics of electronic gradiometers in unshielded environments. In the off-axis electronic gradiometers for biomagnetic measurements, we optimized low frequency noise and performed two-dimensional magnetic mapping of magnetic signal from human heart. The measured magnetocardiography (MCG) signal was averaged according to the simultaneously recorded electrocardiography signal to further enhance the signal-to-noise ratio. The off-axis configuration in our gradiometer system offers the flexibility for multichannel SQUID-based MCG applications. In the study of the SQUID microscope for circuit detection in unshielded environment, we fabricated SQUIDS, considered the design of cryostat, and used the lock-in technique to examine the circuit board. We also examined the magnetic field pattern from the magnetized magnetic thin film.

Fetal magnetoencephalography in intrauterine growth retarded pregnancies.

To investigate the fetal brain activity in pre-eclamptic and normal pregnancies. Biomagnetic measurements were performed by means of a superconducting quantum interference device (SQUID) in an electrically shielded room of low magnetic noise. The study population included 28 pre-eclamptic (34-37 weeks' gestation) and 19 normal pregnancies (34-37 weeks' gestation). The pre-eclamptic group consisted of 11 cases with birth weight below the 10th percentile (1969 +/- 129 g) and 17 cases above the 10th percentile (2496 +/- 257 g). Biomagnetic signals (waveforms) recorded from fetal brains were expressed in terms of magnetic power spectral amplitudes. The total corresponding spectral amplitudes in the frequency range 2-7 Hz were high (719 +/- 69 Ft/ radical Hz in neonates <10th percentile and 537 +/- 105 Ft/ radical Hz in neonates >10th percentile) in most (82%) pre-eclamptic pregnancies and low (382 +/- 35 Ft/ radical Hz) in most normal pregnancies (95%). The difference between normal and all pre-eclamptic pregnancies was highly significant (Student's t-test: p < 0.0001). Comparing the two groups of pre-eclampsia we found also a highly significant difference (Student's t-test: p < 0.0001). Biomagnetic measurements of fetal brain activity could be useful in the assessment of fetal central nervous system development.

Operation of high-temperature superconductor magnetometer with submicrometer bicrystal junctions

We investigated the noise properties of dc superconducting quantum interference device flip-chip magnetometers with submicrometer-wide bicrystal junctions operating at 77.4 K. The noise of the magnetometers with electronics was about 6 fT/√Hz at frequencies above 100 Hz increasing up to about 20 fT/√Hz at 1 Hz. The operation of the magnetometers was characterized in an electronic axial first order gradiometer system, which was employed for biomagnetic measurements. The system demonstrated a gradient resolution of about 1 fT/cm√Hz at 77.4 K and stable operation in a standard magnetically shielded room under clinical conditions.

Entwicklung eines nichtmagnetischen Winkel-Encoders zur aktiven Abschirmung bei biomagnetischen Messungen / Development of a Non-magnetic Angle Encoder for Active Shielding during Biomagnetic Measurements

Biomagnetic fields--in particular in the low-frequency range--are subject to environmental interference, which cannot be adequately reduced by most passive shielding methods. However, the signal-to-noise ratio can be increased by active compensation. For this purpose, the interference is detected by reference sensors and fed back through integrated compensation coils. To establish deviation of normal directions between reference sensors and compensation coils, an angle encoder was developed. The rotation of the reference sensors about two axes at right angles to each other, is converted into voltage pulses by means of codewheels and photoelectric beams. The pulses are counted by incremental encoders, and represent a measure of the angles. A cardanic suspension and a plumb-line act as a reference system. The pulses counted are converted into binary angle values, which are used for coordinate transformation of the interfering fields. The angle encoder can determine the tilt of the reference sensors with an accuracy of 1 degree within a range between -45 and +45 degrees. The noise level of the system remains unaffected during a biomagnetic measurement. Magnetic signals of up to 5 pT arising during the oscillation of the plumb-line can be neglected because of the static nature of the angular measurement.

Investigation of gastrointestinal transport by magnetic marker localization.

The method of magnetic marker monitoring MMM with a biomagnetic measurement system allows the tracking of the transport of solid drug forms with high spatiotemporal resolution. This technique enables to display the path and the disintegration of the magnetic marked pharmaceutical dosage form via the decrease of its magnetic moment. The method was used to assess exogenous factor on the esophageal transport of orally administered solid drug forms in five healthy volunteers. In a drug delivery study we have applied the MMM to monitor the path of a tablet during the gastrointestinal passage and to visualize the disintegration in the small intestine by the magnetic moment of the tablet. The signal to noise ratio of the measurement data was improved by ICA filtering.

ベクトル脳磁界計測における信号部分空間法によるノイズ軽減の一手法

In the biomagnetic measurement performed in laboratory, the biomagnetic signal is extremely weak compared with environmental magnetic noise. We propose the noise reduction method of estimating the subspace spanned by the sensor outputs. It is estimated from the lead-field vectors for the uniformly distributed lattice points in the head. It has been shown by simulation that projection of the measurement to the signal subspace reduces the noise effectively. By applying this method to vector AEF data (averaging: 10, 20, 50), the effect of noise reduction with 30 % was obtained to each data. And, it has been shown this method is more effectively vector MEG than not vector MEG.

Determination of the disintegration behavior of magnetically marked tablets

The disintegration behavior of different tablets that were marked as magnetic dipoles by the incorporation of ferromagnetic black iron oxide and subsequent magnetization was studied using a specially developed measurement setup. This novel apparatus records the magnetic induction generated by the magnetic dipole moment of the tablets during their disintegration. It was found that the observed decrease of the magnetic induction can be used for a quantitative determination of the disintegration of tablets. In particular, it could be shown that the magnetic data provide information about the disintegration mechanism. For tablets with a minor influence of swelling on the disintegration mechanism a linear decline of the magnetic fluxes was observed. After addition of swelling disintegrants (crospovidone) the decline of the magnetic flux could be fitted by an exponential function, indicating the involvement of a disintegration force. Furthermore, the data demonstrate that using modern multichannel biomagnetic measurement equipment the monitoring of the disintegration behavior of magnetically marked tablets in humans will be possible.

Characteristics and prediction of magnetic noise due to DC electric railcars for biomagnetic measurements

A magnetically shielded room for biomagnetism should be designed taking account of the S/N ratio of the biomagnetic signal to the environmental magnetic noise generated mainly by dc electric railcars at an installed location. This paper describes the characteristics of the fluctuation of magnetic noise and a method of prediction of its amplitude. The distance dependence of the magnetic noise is measured at three locations near railroad by using fluxgate-magnetometers. A decay factor of the magnetic noise vs. the distance from a railroad can be obtained from such a measurement. The decay factors measured are in fairly good agreement with those calculated. The amplitude of the fluctuation of magnetic noise at any distance from the railroad can be easily predicted if the decay factor is measured.

Improved system for measurement of the magnetization characteristics of high-temperature superconductors by the compensation method in weak magnetic fields

This article follows the previous publication (1999) of the author where the theoretical sensitivity limits and the basic analysis of the parameters of the superconducting quantum interference device systems for measurement of the magnetization characteristics of high-temperature (HTc) superconductors in ac low-frequency magnetic field with the help of a compensation method were given. It contains the theoretical base for the optimization of such systems and the results achieved by its application in an experimental model of the measuring system. The article deals with the dependence of the spectral sensitivity and the signal-to-noise ratio of the electronic unit of superconducting quantum gradiometer (EU SQG) output on the volume and the susceptibility of the HTc superconducting material sample. It concluded that the chosen dimensions of the pellet shaped sample (diameter 12 mm, thickness 2.5 mm) were optimum for the given measuring system in magnetically unshielded ambient. A method is presented of how to reduce the magnetization current source noise component influence on the sensitivity of the measuring system using a resistance current divider. The concept of spectral sensitivity components of the measuring system has been introduced. These components correspond to the noise spectral densities of three considered noise sources (magnetization current noise component, magnetic noise of the environment, and the EU SQG intrinsic noise). Derived theoretical relations have been applied in the computation and optimization of the experimental system with the standard EU SQG with the input energy sensitivity 1×10−28 J/Hz. In the magnetically unshielded Faraday chamber originally intended for biomagnetic fields measurement, it achieves the spectral sensitivity 8×10−10 Am2 Hz−1/2. Examples of typical magnetization characteristics measured using the triangle alternating magnetization field with a frequency of 0.1 Hz are given. The method and the system are basically also suitable for nonsuperconducting materials.

Low-noise biomagnetic measurements with a multichannel dc-SQUID system at 77 K

Directly coupled dc-SQUID magnetometers made from the high-temperature superconductor (HTS) YBa/sub 2/Cu/sub 3/O/sub 7/ on symmetric 24/spl deg/ and 30/spl deg/ SrTiO/sub 3/-bicrystals have been optimized for low-noise operation in static magnetic fields. These magnetometers are encapsulated, for reliable operation in liquid nitrogen. In our small glass cryostat, allowing even mobile applications, up to 24 magnetometers can be mounted in three levels for gradiometer arrangements. With first-order gradiometers an external noise suppression of more than a factor of 100 is achieved. In a magnetically shielded chamber we find a typical noise /spl radic/S/sub B/ (77 K, 10 Hz) of less than 50 fT//spl radic/Hz and low-noise magnetocardiograms are recorded. Due to the low noise of the dc-SQUID sensors also electrically stimulated magnetoencephalography measurements were possible.

Integrated LTc-SQUID magnetometers for multichannel systems

A reliable procedure based on the niobium technology has been developed to fabricate low intrinsic noise Josephson devices. Results concerning both the design and the characterization of fully integrated DC-SQUID magnetometers are reported. Such devices well meet the requirements of multichannel systems for biomagnetic measurements.

生体磁気計測のための低磁場空間の生成

生体磁気計測のための低磁場空間の生成

High Tc superconducting asymmetric gradiometer for biomagnetic applications

We describe a high transition temperature superconducting, first-order gradiometer intended for biomagnetic measurements in an unshielded environment. The gradiometer involves a single-layer, planar flux transformer with two loops of unequal size, the smaller of which is inductively coupled to the pickup loop of a directly coupled magnetometer. In this configuration, the presence of the flux transformer reduces the sensitivity of the magnetometer by only about 5%. The flux transformer is patterned in a thin film of YBa2Cu3O7−δ deposited on a 100 mm diam wafer, and has a baseline of 48 mm. The flux transformer and magnetometer substrates are permanently bonded together in a flipchip arrangement. The common mode rejection of uniform magnetic field fluctuations in any direction is better than 1 part per 100. The outputs of two such gradiometers are subtracted to form a second-order gradiometer, which rejects first-order gradient fluctuations to about 1 part in 100. With the aid of three orthogonally mounted magnetometers, one can reduce the response of the gradiometers to uniform field fluctuations to below 100 ppm. This system is used to detect magnetic signals from the human heart in an unshielded environment.

Cancellation technique of external noise inside a magnetically shielded room used for biomagnetic measurements

First-order gradiometers inside a magnetically shielded room (MSR) were used to cancel magnetic-field noise. However, the magnetic field inside a MSR is distorted when the amount of external noise is large. This distortion is caused by the low-pass filter property of the MSR. Therefore, the time constants of the frequency-dependent attenuation of the MSR vary spatially and this variation must be taken into account. To investigate noise cancellation, we used a multichannel superconducting quantum interference device consisting of four gradiometers measuring a source signal and two gradiometers as a reference. To compensate for the different magnitudes of the gradiometer wave forms, which differed because of slight differences in their pickup-coil cancel rates, we calculated a fitting parameter. The noise-cancellation method consisted of two processes: reduction of ambient noise caused by the differences in the cancel rate of the gradiometers and a gradient magnetic field inside the MSR, and cancellation of wave-form distortion caused by the spatial variation of the time constants inside the MSR. This cancellation method provides additional attenuation of over 20–30 dB in addition to the balance (&amp;gt;46 dB) of a first-order gradiometer. However, the remaining noise, especially a spike (&amp;lt;2 pT) at the beginning of a large ambient noise step, could not be completely canceled. This noise was caused by the slight difference between the time constants at the reference sensor position and at the signal sensor position. Except for this noise spike, however, the noise cancellation enabled clear magnetocardiogram wave forms to be measured without being affected by strong external noise.

Biomagnetic systems for clinical use

We present two multichannel systems based on a superconducting quantum interference device (SQUID) for biomagnetic measurements, installed at the University of Chieti. Both systems have been designed for clinical and routine use and have been developed owing to an international cooperation. The main issues in the instrument implementation were field sensitivity and spatial resolution, as well as flexibility and stability during operation. The first system is a planar system and is devised for magnetocardiographic measurements. This system is composed of 74 dc SQUID integrated magnetometers contained in a low-noise dewar: 55 sensors are measurement channels and 21 are placed far from the subject and are used as reference channels to create software gradiometers. The second system is a helmet system and consists of 165 de SQUID integrated magnetometers to perform magnetoencephalographic recordings; 153 channels are distributed over a surface covering the whole scalp and 12 channels are used as references. The field noise of the SQUID magnetometers is about 5 fT Hz -1/2 . Each system is placed in a magnetically shielded room for eddy current shielding and magnetic shielding. The magnetic field is recorded with sampling frequencies up to 10 kHz. The analogue-to-digital converted data are processed on line by means of an array of digital signal processors, allowing bandpass filtering, decimation and noise compensation.

Design of a large-scale vertical open-structure cylindrical shield employing magnetic shaking

The shield developed consists of four concentric magnetic shells positioned on the outer surfaces of paper pipes of ∼2.7 m length, ∼1 cm thickness, and with outer diameters of 67, 72, 82.2, and 97.4 cm, respectively. The first (innermost) shell is a Permalloy shell of 2.1 mm thickness and 1.8 m length. The second, third, and fourth shells are made of ∼50 mm wide, ∼22 μm thick Metglas 2705M amorphous ribbons. The second shell, which is a 2.2 m long helical structure, consists of 48 layers of Metglas ribbon divided into four equal sections by ∼1 cm thick flexible Styrofoam sheets. The third shell, 2.43 m in length, and fourth shell, 2.7 m in length, consist of 26 and 30 layers, respectively. A thin polyethylene film is tightly wound on each section of the second shell as well as on the third and fourth shells. It increases the friction between the Metglas ribbons and prevents them from sliding down; there is no foreign material in between the layers of the ribbon. All shells are enclosed by toroidal coils which are used to demagnetize the Permalloy shell and to apply magnetic shaking to the amorphous magnetic shells. The gross weight of the shield is ∼400 kg including ∼65 kg of Permalloy and ∼110 kg of Metglas. An ∼105 transverse shielding factor and a relatively large ∼380 axial shielding factor, despite the effect of the openings, are achieved for a 10 μT external field in the extremely low frequency region. The measured shaking leakage and magnetic noise field strengths at the shield’s center are less than 1 nT. As these low field strengths, it is possible to operate highly sensitive SQUID magnetometers for biomagnetic measurements.

簡易磁気シールド環境下の生体磁気計測におけるオフライン処理による商用電源ノイズ低減の検討

In biomagnetic measurement in a magnetically moderately shielded room, the dominant environmental field noise is the line-frequency (50 Hz) noise. We have studied off-line processing to reduce the line-frquency noise that is included in the raw data measured with a multichannel SQUID magnetometer. Our method utilizes digital filtering and averaging to obtain exclusively the magnetic field unit vectors, which represent the spatial distribution of the noise field. The results for the magnetic field waveform, after subtraction of line-frequency noise components, indicated the effectiveness of our method in reducing the noise. Further, localization of a single equivalent current dipole in a simulation showed that the noise-reduced data decreased the error of the dipole location and increased the goodness-of-fit values.