NMR of room temperature samples with a flux-locked dc SQUID

Superconducting quantum interference devices (SQUIDs) are the most sensitive detectors of magnetic fields. Since SQUIDs detect the magnetic flux rather than its rate of change, they can be used to great advantage to measure nuclear magnetic resonance (NMR) signals at low fields and frequencies. We have used a dc (direct-current) SQUID operated in flux-locked mode to significantly improve upon our previous low-field NMR results performed using an RF (radio-frequency) SQUID. The increase in sensitivity gained by using the dc SQUID has helped in reducing the signal acquisition time by a factor of more than 100 compared with our earlier measurements using an RP SQUID. We have also obtained a simple one-dimensional T₁-contrasted NMR image of a two-component sample consisting of mineral oil and tap water at room temperature. Our results highlight the sensitivity of the SQUID as an NMR detector and the promise of using SQUIDs in NMR imaging at low fields for both medical applications and for materials' nondestructive evaluation     

Neurofeedback using functional spectroscopy

Neurofeedback based on real‐time measurement of the blood oxygenation level‐dependent (BOLD) signal has potential for treatment of neurological disorders and behavioral enhancement. Commonly used methods are based on functional magnetic resonance imaging (fMRI) sequences that sacrifice speed and accuracy for whole‐brain coverage, which is unnecessary in most applications. We present multivoxel functional spectroscopy (MVFS): a system for computing the BOLD signal from multiple volumes of interest (VOI) in real‐time that improves speed and accuracy of neurofeedback. MVFS consists of a FS pulse sequence, a BOLD reconstruction component, a neural activation estimator, and a stimulus system. The FS pulse sequence is a single‐voxel, magnetic resonance spectroscopy sequence without water suppression that has been extended to allow acquisition of a different VOI at each repetition and real‐time subject head motion compensation. The BOLD reconstruction component determines the T2* decay rate, which is directly related to BOLD signal strength. The neural activation estimator discounts nuisance signals and scales the activation relative to the amount of ROI noise. Finally, the neurofeedback system presents neural activation‐dependent stimuli to experimental subjects with an overall delay of less than 1 s. Here, we present the MVFS system, validation of certain components, examples of its usage in a practical application, and a direct comparison of FS and echo‐planar imaging BOLD measurements. We conclude that in the context of realtime BOLD imaging, MVFS can provide superior accuracy and temporal resolution compared with standard fMRI methods. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 138–148, 2014     

Solving the MEG Inverse Problem: A Robust Two-Way Regularization Method

Magnetoencephalography (MEG) is a common noninvasive imaging modality for instantly measuring whole brain activities. One challenge in MEG data analysis is how to minimize the impact of the outliers that commonly exist in the images. In this article, we propose a robust two-way regularization approach to solve the important MEG inverse problem, that is, reconstructing neuronal activities using the measured MEG signals. The proposed method is based on the distributed source model and produces a spatio-temporal solution for all the dipoles simultaneously. Unlike the traditional methods that use the squared error loss function, our proposal uses a robust loss function, which improves the robustness of the results against outliers. To impose desirable spatial focality and temporal smoothness, we then penalize the robust loss through appropriate spatial–temporal two-way regularization. Furthermore, an alternating reweighted least-squares algorithm is developed to optimize the penalized model fitting criterion. Extensive simulation studies and a real-world MEG study clearly demonstrate the advantages of the proposed method over three nonrobust methods.     

Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging

Although most current diffuse optical brain imaging systems use only nearest- neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.     

Superconducting instrumentation for biomagnetism

Magnetic fields generated by the human body have been studied in the last ten years thanks to superconducting magnetometers or SQUIDs.

So far, signals connected to the activity of the heart, brain, muscles and those due to the presence of magnetic impurities in the lungs have been studied. Because of the extremely small amplitude of the signals to be detected (down ro 10⁻¹⁰ Gs with respect to a magentic background of the order of 1 Gs), the greatest part of the efforts during the early 70s was devoted to the construction and optimization of sophisticated instrumentation. Two main ways have been followed: the former consists in the construction of magnetically shielded environments to lower the magnetic background by several orders of magnitudes: the letter consists of the use of magnetic sensors employing an appropriate geometrical configuation. This allows a rejection of spurious magnetic fields down to levels compatible with those of biomagnetic signals.

After this first stage, a systematic utilization of this technique has been started in the biomedical field.

At present in many countries and physicians are working together in order to fully exploit the actual power of the method.

In this paper the most remarkable results so far obtained in the physiological and clinical fields are presented.     

Long-term optical imaging of intrinsic signals in anesthetized and awake monkeys

Some exciting new efforts to use intrinsic signal optical imaging methods for long-term studies in anesthetized and awake monkeys are reviewed. The development of such methodologies opens the door for studying behavioral states such as attention, motivation, memory, emotion, and other higher-order cognitive functions. Long-term imaging is also ideal for studying changes in the brain that accompany development, plasticity, and learning. Although intrinsic imaging lacks the temporal resolution offered by dyes, it is a high spatial resolution imaging method that does not require application of any external agents to the brain. The bulk of procedures described here have been developed in the monkey but can be applied to the study of surface structures in any in vivo preparation.     

SQUID-Detected Magnetic Resonance Imaging in Microtesla Magnetic Fields

We describe studies of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) of liquid samples at room temperature in microtesla magnetic fields. The nuclear spins are prepolarized in a strong transient field. The magnetic signals generated by the precessing spins, which range in frequency from tens of Hz to several kHz, are detected by a low-transition temperature dc SQUID (Superconducting QUantum Interference Device) coupled to an untuned, superconducting flux transformer configured as an axial gradiometer. The combination of prepolarization and frequency-independent detector sensitivity results in a high signal-to-noise ratio and high spectral resolution (～1 Hz) even in grossly inhomogeneous magnetic fields. In the NMR experiments, the high spectral resolution enables us to detect the 10-Hz splitting of the spectrum of protons due to their scalar coupling to a ³¹P nucleus. Furthermore, the broadband detection scheme combined with a non-resonant field-reversal spin echo allows the simultaneous observation of signals from protons and ³¹P nuclei, even though their NMR resonance frequencies differ by a factor of 2.5. We extend our methodology to MRI in microtesla fields, where the high spectral resolution translates into high spatial resolution. We demonstrate two-dimensional images of a mineral oil phantom and slices of peppers, with a spatial resolution of about 1 mm. We also image an intact pepper using slice selection, again with 1-mm resolution. In further experiments we demonstrate T₁-contrast imaging of a water phantom, some parts of which were doped with a paramagnetic salt to reduce the longitudinal relaxation time T₁. Possible applications of this MRI technique include screening for tumors and integration with existing multichannel SQUID systems for brain imaging.     

SQUIDs from Physics to Brain Research

Superconducting Quantum Interference Devices (SQUlDs) can be utilized to construct extremely sensitive magnetometers for brain research. Magnetoencephalographic (MEG) arrays of hundreds of individual SQUID sensors are now in use in over 80 laboratories worldwide. This paper describes the development of four multi-channel MEG arrays of increasing complexity and power at the Low Temperature Laboratory (LTL) under the guidance of Academician Olli Lounasmaa. TWe impact of the availability of these multi-channel MEG arrays on our capacity to characterize the dynamics of both normal and abnormal brain activity is discussed through examples drawn from research conducted at LTL.     

Space applications of superconductivity: Low frequency superconducting sensors

This is the third of a seven part series on the potential applications of superconductivity in space. Superconducting quantum interference devices (SQUIDs) are used in highly-sensitive magnetometers and gradiometers. They are superior to all other magnetic sensors in sensitivity, frequency response, range, and linearity. They are potentially useful for measuring low-level magnetic field variations in space, such as fluctuations in the solar wind and small- or large-scale spacial anomalies of planetary fields. They are useful also as galvanometers and amplifiers, particularly for applications requiring extreme voltage sensitivity such as, for example, low-impedance bolometer amplifiers. In connection with low-frequency sensors, superconductivity provides some adjunct devices, namely perfect magnetic shields and flux transformers, the latter being used for a number of purposes including construction of fairly elaborate gradiometer pickup-loop arrays.     

Design, Fabrication, and Multiplexing of Magnetic Calorimeter X-ray Detectors with High-Efficiency SQUID Readout

Metallic magnetic calorimeters, where deposited energy is detected by measuring a temperature-dependent magnetization with a low-noise SQUID, remain a promising potential route to X-ray spectrometers with energy resolution approaching 1 eV. In this paper we describe our recent work toward array-compatible, high-resolution MMCs fabricated entirely using thin-film techniques. We describe a meander-style pickup loop designed for good coupling to high-efficiency, low noise SQUIDs, as well as considering various routes to a thin-film paramagnetic sensor. We also briefly overview the most promising technology for multiplexing arrays of non-dissipative metallic magnetic calorimeters.      

Integrated niobium DC SQUID gradiometers for non-destructive evaluation and biomagnetism

We describe the design and fabrication of thin-film Nb gradiometers with integrated DC SQUIDs for use in non-destructive evaluation (NDE) and biomagnetism. Issues of sensitivity, imbalance and field response are considered. Results are presented from eddy-current NDE in an unshielded environment of aluminium plates with sub-surface flaws, and from biomagnetic measurements of spinal and peripheral nerve evoked fields.     

EEG‐based brain source localization using visual stimuli

Electroencephalography (EEG) is widely used in variety of research and clinical applications which includes the localization of active brain sources. Brain source localization provides useful information to understand the brain's behavior and cognitive analysis. Various source localization algorithms have been developed to determine the exact locations of the active brain sources due to which electromagnetic activity is generated in brain. These algorithms are based on digital filtering, 3D imaging, array signal processing and Bayesian approaches. According to the spatial resolution provided, the algorithms are categorized as either low resolution methods or high resolution methods. In this research study, EEG data is collected by providing visual stimulus to healthy subjects. FDM is used for head modelling to solve forward problem. The low‐resolution brain electromagnetic tomography (LORETA) and standardized LORETA (sLORETA) have been used as inverse modelling methods to localize the active regions in the brain during the stimulus provided. The results are produced in the form of MRI images. The tables are also provided to describe the intensity levels for estimated current level for the inverse methods used. The higher current value or intensity level shows the higher electromagnetic activity for a particular source at certain time instant. Thus, the results obtained demonstrate that standardized method which is based on second order Laplacian (sLORETA) in conjunction with finite difference method (FDM) as head modelling technique outperforms other methods in terms of source estimation as it has higher current level and thus, current density (J) for an area as compared to others.     

Liquid-crystal tunable filter spectral imaging for brain tumor demarcation

Past studies have demonstrated that combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain. To achieve efficient, real-time surgical resection guidance with optical biopsy, probe-based spectroscopy must be extended to spectral imaging to spatially demarcate the tumor margins. We describe the design and characterization of a combined fluorescence and diffuse reflectance imaging system that uses liquid-crystal tunable filter technology. Experiments were conducted to quantitatively determine the linearity, field of view, spatial and spectral resolution, and wavelength sensitivity of the imaging system. Spectral images were acquired from tissue phantoms, mouse brain in vitro, and human cortex in vivo for functional testing of the system. The spectral imaging system produces measured intensities that are linear with sample emission intensity and integration time and possesses a 1 in. (2.54 cm) field of view for a 7 in. (18 cm) object distance. The spectral resolution is linear with wavelength, and the spatial resolution is pixel-limited. The sensitivity spectra for the imaging system provide a guide for the distribution of total image integration time between wavelengths. Functional tests in vitro demonstrate the capability to spectrally discriminate between brain tissues based on exogenous fluorescence contrast or endogenous tissue composition. In vivo imaging captures adequate fluorescence and diffuse reflectance intensities within a clinically viable 2 min imaging time frame and demonstrates the importance of hemostasis to acquired signal strengths and imaging speed.     

Comparative analysis of algorithms for processing mineral luminescence signals in the task of detecting diamonds in an ore stream

Results are provided for modelling in a Mathcad medium digital algorithms for processing signals obtained in diamond x-ray luminescence separators with continuous excitation. An estimate is given of the effectiveness of these algorithms and they are compared with analog traditional methods of signal processing. The question of temporal resolution of mineral luminescence signals is considered.     

Research and Some Applications of High-T c 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.     

Magnetic soft X-ray transmission microscopy

Recent advances in imaging magnetic microstructures on a nanometer length-scale and their temporal evolution on a sub-nanosecond time-scale have been achieved with magnetic transmission X-ray microscopy. With a lateral resolution down to 20 nm, element-specificity, recording in external magnetic fields and stroboscopic pump-and-probe imaging, insights into fundamental mechanisms of the magnetism in thin films and nanopatterned elements are provided which are also relevant in magnetic storage and sensor technologies.     

Rhesus monkey brain imaging through intact skull with thermoacoustic tomography

Two-dimensional microwave-induced thermoacoustic tomography (TAT) is applied to imaging the Rhesus monkey brain through the intact skull. To reduce the wavefront distortion caused by the skull, only the low-frequency components of the thermoacoustic signals (< 1 MHz) are used to reconstruct the TAT images. The methods of signal processing and image reconstruction are validated by imaging a lamb kidney. The resolution of the system is found to be 4 mm when we image a 1-month-old monkey head containing inserted needles. We also image the coronal and axial sections of a 7-month-old monkey head. Brain features that are 3 cm deep in the head are imaged clearly. Our results demonstrate that TAT has potential for use in portable, cost-effective imagers for pediatric brains.     

Spectral Doppler estimation utilizing 2-D spatial information and adaptive signal processing

The trade-off between temporal and spectral resolution in conventional pulsed wave (PW) Doppler may limit duplex/triplex quality and the depiction of rapid flow events. It is therefore desirable to reduce the required observation window (OW) of the Doppler signal while preserving the frequency resolution. This work investigates how the required observation time can be reduced by adaptive spectral estimation utilizing 2-D spatial information obtained by parallel receive beamforming. Four adaptive estimation techniques were investigated, the power spectral Capon (PSC) method, the amplitude and phase estimation (APES) technique, multiple signal classification (MUSIC), and a projection-based version of the Capon technique. By averaging radially and laterally, the required covariance matrix could successfully be estimated without temporal averaging. Useful PW spectra of high resolution and contrast could be generated from ensembles corresponding to those used in color flow imaging (CFI; OW = 10). For a given OW, the frequency resolution could be increased compared with the Welch approach, in cases in which the transit time was higher or comparable to the observation time. In such cases, using short or long pulses with unfocused or focused transmit, an increase in temporal resolution of up to 4 to 6 times could be obtained in in vivo examples. It was further shown that by using adaptive signal processing, velocity spectra may be generated without high-pass filtering the Doppler signal. With the proposed approach, spectra retrospectively calculated from CFI may become useful for unfocused as well as focused imaging. This application may provide new clinical information by inspection of velocity spectra simultaneously from several spatial locations.     

Transformers to Readout Arrays of Microcalorimeters

We investigated the possibility of using transformers to replace SQUIDs for the readout of microcalorimeters. This simple scheme has been used in the past for bolometers, however it was discarded for the use with TES microcalorimeters because of the inadequate performance. Our work shows that, with a few simple changes, the performance of transformers as current transducers, while still not comparable to that of SQUIDs, is sufficient to read out the signal from TES microcalorimeters without any degradation in speed or energy resolution. In contrast to SQUIDs, transformers do not dissipate any power and their working principle makes them natural candidates for frequency multiplexing. Their extension to several channels is therefore straightforward.