Optimization of a Magnetometric System for Investigation of Magnetic Signals of Biological Objects

As sensitive magnetic sensors, superconducting quantum interference devices (SQUIDs) can be applied to measure weak magnetic field signals. Biomagnetism, measurement of magnetic signals from human body, especially at low frequency range below few kHz, is one of the important applications of SQUIDs, and biomagnetic technology can be applied for the functional study of human brain and heart. KRISS has been developing both low-noise SQUIDs and biomagnetic measurement technology. The SQUIDs are low-temperature Nb double relaxation oscillation SQUID, and high-temperature YBCO SQUID. We are applying SQUID technology for measuring magnetoencephalography signals and magnetocardiography signals. Using the high sensitivity of SQUID, we are developing nuclear magnetic resonance technology for imaging of brain anatomy at very low magnetic field, and direct imaging of brain electrical activity.

Globally, the demand for improved health care delivery while managing escalating costs is a major challenge. Measuring the biomagnetic fields that emanate from the human brain already impacts the treatment of epilepsy, brain tumours and other brain disorders. This roadmap explores how superconducting technologies are poised to impact health care. Biomagnetism is the study of magnetic fields of biological origin. Biomagnetic fields are typically very weak, often in the femtotesla range, making their measurement challenging. The earliest in vivo human measurements were made with room-temperature coils. In 1963, Baule and McFee (1963 Am. Heart J. 55 95-6) reported the magnetic field produced by electric currents in the heart ('magnetocardiography'), and in 1968, Cohen (1968 Science 161 784-6) described the magnetic field generated by alpha-rhythm currents in the brain ('magnetoencephalography'). Subsequently, in 1970, Cohen et al (1970 Appl. Phys. Lett. 16 278-80) reported the recording of a magnetocardiogram using a Superconducting QUantum Interference Device (SQUID). Just two years later, in 1972, Cohen (1972 Science 175 664-6) described the use of a SQUID in magnetoencephalography. These last two papers set the scene for applications of SQUIDs in biomagnetism, the subject of this roadmap. The SQUID is a combination of two fundamental properties of superconductors. The first is flux quantization - the fact that the magnetic flux ? in a closed superconducting loop is quantized in units of the magnetic flux quantum, ?0 ? h/2e, ? 2.07 × 10-15 Tm2 (Deaver and Fairbank 1961 Phys. Rev. Lett. 7 43-6, Doll R and Nabauer M 1961 Phys. Rev. Lett. 7 51-2). Here, h is the Planck constant and e the elementary charge. The second property is the Josephson effect, predicted in 1962 by Josephson (1962 Phys. Lett. 1 251-3) and observed by Anderson and Rowell (1963 Phys. Rev. Lett. 10 230-2) in 1963. The Josephson junction consists of two weakly coupled superconductors separated by a tunnel barrier or other weak link. A tiny electric current is able to flow between the superconductors as a supercurrent, without developing a voltage across them. At currents above the 'critical current' (maximum supercurrent), however, a voltage is developed. In 1964, Jaklevic et al (1964 Phys. Rev. Lett. 12 159-60) observed quantum interference between two Josephson junctions connected in series on a superconducting loop, giving birth to the dc SQUID. The essential property of the SQUID is that a steady increase in the magnetic flux threading the loop causes the critical current to oscillate with a period of one flux quantum. In today's SQUIDs, using conventional semiconductor readout electronics, one can typically detect a change in ? corresponding to 10-6 ?0 in one second. Although early practical SQUIDs were usually made from bulk superconductors, for example, niobium or Pb-Sn solder blobs, today's devices are invariably made from thin superconducting films patterned with photolithography or even electron lithography. An extensive description of SQUIDs and their applications can be found in the SQUID Handbooks (Clarke and Braginski 2004 Fundamentals and Technology of SQUIDs and SQUID Systems vol I (Weinheim, Germany: Wiley-VCH), Clarke and Braginski 2006 Applications of SQUIDs and SQUID Systems vol II (Weinheim, Germany: Wiley-VCH)). The roadmap begins (chapter 1) with a brief review of the state-of-the-art of SQUID-based magnetometers and gradiometers for biomagnetic measurements. The magnetic field noise referred to the pick-up loop is typically a few fT Hz-1/2, often limited by noise in the metallized thermal insulation of the dewar rather than by intrinsic SQUID noise. The authors describe a pathway to achieve an intrinsic magnetic field noise as low as 0.1 fT Hz-1/2, approximately the Nyquist noise of the human body. They also descibe a technology to defeat dewar noise. Chapter 2 reviews the neuroscientific and clinical use of magnetoencephalography (MEG), by far the most widespread application of biomagnetism with systems containing typically 300 sensors cooled to liquid-helium temperature, 4.2 K. Two important clinical applications are presurgical mapping of focal epilepsy and of eloquent cortex in brain-tumor patients. Reducing the sensor-to-brain separation and the system noise level would both improve spatial resolution. The very recent commercial innovation that replaces the need for frequent manual transfer of liquid helium with an automated system that collects and liquefies the gas and transfers the liquid to the dewar will make MEG systems more accessible. [...]

Introduction. Superconducting magnetometers based on SQUIDs (SQUID- Superconducting QUantum Interference Device) are currently used to register weak magnetic fields generated in various human organs and measured outside the body (in the environment). The creation of information technology, which is a set of methods and software tools combined into a technological chain that ensures registration, storage, pre-processing, analysis of measurement data and automatic diagnostic output, is an essential science-intensive component that determines the possibilities and success of the applied use of non-contact diagnostic systems of the human heart The purpose. Article presents new algorithms for spatial analysis of cardiomagnetic signal measurement results. The algorithms are based on the inverse problem solution, when the magnetic field source is matched to the spatial distribution of the magnetic signal and the parameters and spatial configuration of the source are determined. A model of the cardiomagnetic source was used in the form of a system of current density vectors, which are distributed in a plane that is parallel to the measurement plane and crosses the volume of the heart. Results. The inverse problem is solved using the apparatus of two-dimensional integral Fourier transformations. The data transformation algorithm allows to correctly take into account the design of the magnetic flux transformer (the dimensions of the pickup coils, their spatial location and the electrical connection scheme). Algorithm modifications have been developed for most of the known (implemented in existing magnetocardiographs) designs of magnetic flux transformers of the first and second order gradientometers. The operation of the algorithm is modeled on real data of magnetometric investigations of the human heart. Investigations have shown that the application of the proposed algorithms allows obtaining new information about the spatial configuration of the magnetic signal source in the human heart, which can be used in the future for the diagnosis of human heart diseases. Keywords: magnetocardiography, inverse problem of magnetostatics, Fourier transform, SQUID gradientometer.

A prototype of gradiometer for detection and analysis of magnetic signals that are generated by defects in metal structures and materials in the presence of external magnetic bias is based on dc-current superconducting quantum interference device (SQUID). A prototype of single-channel SQUID gradiometer that contains a fiberglass nonmagnetic cryostat, measurement probe with the SQUID sensor and magnetic flux transformer (second-order axial gradiometer), SQUID electronics, and software for control of SQUID gradiometer is studied. The prototype exhibits stable operation under laboratory conditions in the absence of additional magnetic shielding. Upgrade of the SQUID sensors and remaining elements of the prototype of magnetometer is planned for application in nondestructive testing.

Iron excess in tissues can lead to toxicity and organ disease. The liver, as the primary site of body iron deposition, is also a principal target for its toxicity. Heavy iron overload in humans is usually associated with a genetically determined disturbance of iron homeostasis (i.e. hereditary hemochromatosis, HH) or with intensive transfusion regimens associated with hereditary anemia (i.e. bthalassemia). Liver biopsy is the most accurate method for assessing hepatic iron burden and provides important information on underlying liver damage and diseases. However, it entails the risk for potential complications while accurate iron measurements may be biased by sampling variability in advanced chronic disease. Therefore, at least within a diagnostic workup, costs and benefits of liver biopsy should be carefully considered. In hereditary hemochromatosis, a positive genetic test for HFE or other hemochromatosis gene mutations (transferrin receptor 2, hemojuvelin, hepcidin) may allow to avoid liver biopsy in most symptomatic patients, whereas histology remains essential in homozygotes with abnormal transaminases, hepatomegaly or serum ferritin higher than 1000 ng/ml [1]. In recent years, the potential role of mild iron overload as factor of comorbidity in the progression of several hepatic disorders (e.g. viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, porphyria cutanea tarda) has been increasingly recognized. In fact, accurate evaluation of hepatic iron content is now regarded as an important clinical manoeuvre in the management of chronic non-HH liver disease. Due to safety concerns of liver biopsy, non-invasive methods to measure hepatic iron content have been, therefore, devised. Serum ferritin may be a good surrogate marker for evaluating iron stores but suffers from low specificity. High sensitivity has been reported for the superconducting quantum interference device (SQUID) that measures magnetic susceptibilities [2]. SQUID, however, is not widely available and requires experienced operators. Computed tomography shows attenuation of the liver in the presence of excess iron, but seems to suffer of low sensitivity and specificity particular at mild iron overload grades and in the presence of fat [3]. Magnetic resonance has been intensively exploited, until recently, as a sensitive and specific tool for assessing hepatic iron overload [4‐9]. Due to the paramagnetic properties of iron, its increased hepatic content decreases both the T2 relaxation time and the liver signal’s intensity (SI): this gives the typical dark liver at MRI. Gradient-recalled-echo (GRE) techniques have been shown to be more accurate in quantifying mild iron overload states than spin-echo sequences due to higher sensitivity to field inhomogeneities induced by paramagnetic substances. Most published studies agree on the fact that MRI is accurate in assessing a moderate-severe iron overload but a validated and cost effective method for taking advantage of MRI in quantifying also low grades of iron stores was still missing. In addition, an ideal method should also be simple and easy to be standardized in order to be transferred and applied to different machines. Gandon and coworkers seem to have taken a fundamental step toward this end [7]. They studied 174 patients by both percutaneous liver biopsy with biochemical assessment of hepatic iron concentration and MRI of the liver with various GRE sequences on a 1.5 T magnet. They calculated liver iron concentration by evaluating the correlation between liver to muscle (L/M) signal intensity ratio and developed an algorithm to calculate magnetic resonance hepatic iron concentration. Data obtained in a study group (nZ139) that included patients with suspected iron overload or patients managed for hepatitis C, were then applied to a validation group (nZ35). A highly

A low noise superconducting quantum interference device (SQUID) readout scheme is developed to detect the small magnetic field signal at frequency up to MHz. It consists of a low noise small signal amplifier and a direct-coupled flux-locked loop. The flux-locked loop keeps the working point stable by cancelling the low frequency flux interference from environment. Around the working point with the maximal flux-to-voltage transfer coefficient, the SQUID is operated as high frequency small signal flux-to-voltage converter and read out by a high frequency low noise matching amplifier using a step-up transformer and a junction field-effect transistor (JFET). Experimental tests of the readout on a conventional SQUID at 4.2 K show that the equivalent flux noise is below 5 μΦ0/√Hz with frequency up to MHz.

We mounted a vector-scanning superconducting quantum interference device (SQUID) sensor on a commercial SQUID microscope and successfully improved the sensitivity and spatial resolution of the sensor. Our proposed vector 3D SQUID sensor used multilayered niobium (Nb)-based technology; we realized three SQUID sensors in the structure of a vector pickup coil system on a single chip. The vector pickup coil system was built with three pickup coils that were orthogonal to one another to obtain the X, Y, and Z components of a magnetic field vector. To improve both sensitivity and spatial resolution, we attempted to reduce the inner diameter by increasing the number of windings of the pickup coils using the multilayered Nb process. The design value for the dc SQUID sensors was either the critical current density Jc = 320 A cm−2 for two Josephson junctions (JJs) or the critical current Ic = 12.8 μA for the 2 μm × 2 μm JJs. To measure the current–voltage (I–V) and voltage–flux (V–Φ) characteristics of a sensor, we constructed a homemade measurement system. The fundamental characteristics of our SQUID sensors were in good agreement with the design parameters. We mounted our vector SQUID sensor on a commercial scanning SQUID microscope (SQM2000, Seiko Instrument Inc.) with a single flux-locked loop channel to test one of the three channels. We repeated the measurements three times to obtain the X, Y, and Z componential images of the magnetic field from a single vortex, and we synthesized the 3D mapping of the magnetic field vectors from a single vortex. We proved that our sensor mounted on a SQUID microscope was suitable for measuring the X, Y, and Z components of a vector magnetic field.

In this paper, we propose a new method for imaging the distribution of electric currents; this method involves a combination of ultrasonography and SQUID magnetometry. To evaluate this new method, we used a block of gelatin pierced through by a lead wire as a model of a biological object. An electric current was applied to the wire and the magnetic signal generated around the wire was measured by a superconducting quantum interference device (SQUID). At the same time, an ultrasound image of the wire was taken by means of an ultrasound imaging machine. Subsequently, the magnetic field image was aligned with the ultrasound image with respect to the position of marker coils relative to the ultrasound probe. The source of the magnetic signal was localized by solving the inverse problem and visualized on the ultrasound image of the wire. The position error was 2.9 mm. The results demonstrated the applicability of the new technique combining SQUID magnetometry with ultrasound imaging.

Superconducting quantum interference devices (SQUIDs) are sensitive detectors of magnetic flux. A SQUID consists of a superconducting loop interrupted by either one or two Josephson junctions for the RF or dc SQUID, respectively. Low transition temperature (T/sub c/) SQUIDs are fabricated from thin films of niobium. Immersed in liquid helium at 4.2 K, their flux noise is typically 10/sup -6//spl Phi//sub 0/ Hz/sup -1/2/, where /spl Phi//sub 0//spl equiv/h/2e is the flux quantum. High-T/sub c/ SQUIDs are fabricated from thin films of YBa/sub 2/Cu/sub 3/O/sub 7-x/, and are generally operated in liquid nitrogen at 77 K. Inductively coupled to an appropriate input circuit, SQUIDs measure a variety of physical quantities, including magnetic field, magnetic field gradient, voltage, and magnetic susceptibility. Systems are available for detecting magnetic signals from the brain, measuring the magnetic susceptibility of materials and geophysical core samples, magnetocardiography and nondestructive evaluation. SQUID "microscopes" detect magnetic nanoparticles attached to pathogens in an immunoassay technique and locate faults in semiconductor packages. A SQUID amplifier with an integrated resonant microstrip is within a factor of two of the quantum limit at 0.5 GHz and will be used in a search for axions. High-resolution magnetic resonance images are obtained at frequencies of a few kilohertz with a SQUID-based detector.

Magnetic Coupling between SQUID and Probe of STM-SQUID

The excess low-frequency flux noise in dc superconducting quantum interference devices (SQUIDs) operated at ultra-low temperatures was studied. A large number of single SQUIDs as well as SQUID arrays from 16 wafers fabricated over a period of six years were characterized at 4.2 K and <;320 mK. Considering the large spread in the low-frequency noise at 4.2 K, there was no observable dependence of the low-frequency energy resolution ε <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/f</sub> on the SQUID design or fabrication parameters. In contrast, below 4.2 K the low-frequency noise changed moderately or increased strongly depending on whether the bottom Nb or the insulation layer were fabricated in our newer sputter system instead of the older one. The corresponding excess noise levels ε <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/f</sub> at <;320 mK and f=10 Hz are typically 40 h and 300 h, respectively (h is Planck's constant). The excess noise scales as ε <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/f</sub> ∝ f <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-α</sup> with α typically around 0.6 for good devices. For devices with strong low-frequency excess noise, α increases up to about 0.9. The best energy resolution ε achieved so far with a 50 pH test SQUID operated at 16 mK is 0.62 h at 100 kHz, increasing to 1.64 h at 1 kHz and 14 h at 10 Hz.

Improving the design of superconducting quantum interference devices (SQUIDs) for quantum sensing applications can involve a compromise between competing device parameters. For SQUIDs made from high-temperature superconductors (HTS), accurate modelling for optimization should include the device geometry, material properties and their temperature dependences, as well as thermal noise. We outline here a lumped element model that calculates the voltage response to magnetic flux of a hairpin SQUID and use it to explore the effect of these parameters on optimizing the SQUID voltage output. We first validate our model by showing close agreement with current-voltage and voltage-flux measurements performed on Yttrium Barium Copper Oxide hairpin SQUIDs with different geometries by including structures such as the bias leads. We show the effect of track width on the kinetic to geometric inductance ratios ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\kappa$</tex-math></inline-formula> ) for a range of film thicknesses and temperatures, to aid researchers how to optimize SQUID designs. Then, through numerical simulations, we show on how (i) the voltage modulation depth decreases exponentially with the total inductance, independent of the asymmetry ratio; (ii) narrower superconducting tracks lead to a broader temperature operation range, <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\Delta T \sim 30$</tex-math></inline-formula> K, while wider tracks operate in a narrower temperature range, <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\Delta T \sim 10$</tex-math></inline-formula> K, but are more sensitive to temperature changes; and (iv) the optimal bias current, which maximises the device performance, depends on the operating temperature.

We have developed two methods of compensating environmental disturbances applicable to high- and low-temperature superconducting quantum interference device (SQUID) systems, operating in a magnetically unshielded environment. For testing, we used first- and second-order axial electronic gradiometer setups with rf SQUID magnetometers operating at 77 K, with different baselines between 1.8 and 8 cm. The magnetometers were single-layer washer rf SQUIDs, with bulk or thin-film magnetic flux concentrators and transformers in flip-chip geometry. The tested methods resulted in disturbance compensation levels comparable with those attained using electronically formed gradiometers. The white noise of the compensated magnetometers resulted in maximum gradiometric sensitivities of 13.5 fT/cm √Hz for first-order and 22 fT/cm2 √Hz for second-order compensation, with baselines between 7 and 8 cm down to 10 Hz. Common mode rejection was balanced to, better than 104 for homogeneous fields, and better than 200 for gradient fields, with second-order compensation. Magnetically unshielded measurements of biomagnetic signals with different baselines were demonstrated.

A new generation of astronomical detectors has recently been developed, on the basis of superconducting tunnel junctions (STJs). STJs are capable of detecting photons in a wide range of wavelengths, from X-rays to infrared; also the counting of single photons in the optical range has been demonstrated. Since these detectors operate at very low temperature (down to 100 mK), a natural candidate for the read-out electronics is the dc superconducting quantum interference device (SQUID), an extremely sensitive magnetometer that is fabricated with a similar technology to the STJ junctions. Biasing the STJ at a constant voltage, the current pulse caused by the incoming radiation is passed through the tightly coupled input coil of the SQUID and converted into a magnetic flux signal which can be detected. In this paper we present measurements on a home-made dc SQUID, showing the response of the device to current pulses, which simulate the real signals from a STJ. We show how the SQUID performance can be i...

CAT and MRI dramatically changed modern medicine by its excellent anatomical resolution. For functional analysis of central nervous system, however, good old EEG (electro-encephalo-graphy) is still the main weapon. Although computer topography brought some improvement in this field, poor spatial resolution has been the main shortcoming for EEG. This is because voltage distribution of neuron activity over the skull is easily influenced by the complicated human head structure. It is known that magnetic field is emitted from the brain together with electrical neuron activity. Distribution of magnetic field over the skull is less sensitive to the complicated head structure. Thus it is theoretically possible to calculate the accurate location of neuron activity by recording magnetic field over the skull. The magnetic field, however, is too weak for conventional magnetic sensors to detect. Recently SQUID (superconducting quantum interference device) has been introduced as an extremely sensitive magnetic sensor. With SQUID system, it is possible to record weak magnetic field from the brain. Multi-channel SQUID system is the main concern since accuracy of neuron activity localization and time needed for recording are dramatically improved. Study of tonotopic and amplitopic organization of human auditory cortex is presented as an example of SQUID application. Multi-channel DC-SQUID system, installed at the Center for Neuromagnetism of New York University Medical Center, was used. Auditory stimulus of various frequency and intensity was applied to the right ear in randomized order with randomized interstimulus interval. The magnetic response was recorded from left hemisphere with one probe fixed at maxima and the other probe at minima of the magnetic field. Signals were then averaged and dipole location was calculated using spherical model method. The location of auditory response was in primary auditory cortex (Area 41). The location of neuron activity shifted medially as auditory stimulus frequency increased. On the other hand, location of neuron activity tended to shift anterioly in the main as auditory stimulus intensity increased. Thus, SQUID system made it possible to analyze minute neuron network function and its location without any invasion and anesthesia to human. SQUID system has been mainly used to study auditory, visual and somatosensory response of the human brain. Magnetic signal during motor activity is also analyzed to elucidate the mechanism of motor initiation, The main current interest of SQUID application is the diagnosis of epilepsy. Magnetic signal emitted during epilepsy is large and distinctive. With SQUID system, location of epilepsy focus and its modality of spreading can be detected. Once the focus is found, it may be possible to treat epilepsy with minor surgery such as electrical cauterization without opening the skull. From the technical point of view, however, the current SQUID system is still under development. The number of channel and complicated structure may be renovated by utilizing recent IC production technology.