Toward direct neural current imaging by resonant mechanisms at ultra-low field.

A variety of techniques have been developed to noninvasively image human brain function that are central to research and clinical applications endeavoring to understand how the brain works and to detect pathology (e.g. epilepsy, schizophrenia, etc.). Current methods can be broadly divided into those that rely on hemodynamic responses as indicators of neural activity (e.g. fMRI, optical, and PET) and methods that measure neural activity directly (e.g. MEG and EEG). The approaches all suffer from poor temporal resolution, poor spatial localization, or indirectly measuring neural activity. It has been suggested that the proton spin population will be altered by neural activity resulting in a measurable effect on the NMR signal that can be imaged by MRI methods. We present here the physical basis and experimental evidence for the resonant interaction between magnetic fields such as those arising from neural activity, with the spin population in ultra-low field (microT) NMR experiments. We demonstrate through the use of current phantoms that, in the case of correlated zero-mean current distributions such as those one might expect to result from neural activity, resonant interactions will produce larger changes in the observed NMR signal than dephasing. The observed resonant interactions reported here might one day form the foundation of a new functional neuroimaging modality ultimately capable of simultaneous direct neural activity and brain anatomy tomography.

Ultra-low field NMR measurements of liquids and gases with short relaxation times.

Interest in nuclear magnetic resonance measurements at ultra-low magnetic fields (ULF, approximately microT fields) has been motivated by various benefits and novel applications including narrow NMR peak-width, negligible susceptibility artifacts, imaging of samples inside metal containers, and possibility of directly imaging neuronal currents. ULF NMR/MRI is also compatible with simultaneous measurements of biomagnetic signals. However the most widely used technique in ULF NMR-prepolarization at high field and measurement at lower field-results in large transient signals which distort the free induction decay signal. This is especially severe for the measurement of signals from samples and materials with short T1 time. We have devised an approach that largely cancels the transient signals. The technique was successfully used to measure NMR signals from liquids and gases with T1 in the range 1-4 ms.

Noise-free magnetoencephalography recordings of brain function.

Perhaps the greatest impediment to acquiring high-quality magnetoencephalography (MEG) recordings is the ubiquitous ambient magnetic field noise. We have designed and built a whole-head MEG system using a helmet-like superconducting imaging surface (SIS) surrounding the array of superconducting quantum interference device (SQUID) magnetometers used to measure the MEG signal. We previously demonstrated that the SIS passively shields the SQUID array from ambient magnetic field noise, independent of frequency, by 25-60 dB depending on sensor location. SQUID 'reference sensors' located on the outside of the SIS helmet measure ambient magnetic fields in very close proximity to the MEG magnetometers while being nearly perfectly shielded from all sources in the brain. The fact that the reference sensors measure no brain signal yet are located in close proximity to the MEG sensors enables very accurate estimation and subtraction of the ambient field noise contribution to the MEG sensors using an adaptive algorithm. We have demonstrated total ambient noise reduction factors in excess of 10(6) (> 120 dB). The residual noise for most MEG SQUID channels is at or near the intrinsic SQUID noise floor, typically 2-3 fT Hz-1/2. We are recording MEG signals with greater signal-to-noise than equivalent EEG measurements.

Simultaneously detected biomagnetic signals and NMR.

We have obtained 1H NMR spectra simultaneously with high temporal resolution biomagnetic signals such as the magnetocardiogram (MCG) and magnetomyogram (MMG). The NMR spectra are acquired at measurement fields of 2-50 microT, with corresponding proton Larmor frequencies of 80-2000 Hz. Our measurements demonstrate a method suitable for MR imaging with concurrent measurement of biomagnetic signals that can provide sub-millisecond temporal resolution. The narrow line widths, reduction in susceptibility noise and enhanced spectral resolution at ultra low fields provide a new and extremely sensitive measurement method that may enable direct imaging of biological currents by detecting the phase or frequency shifts produced by magnetic fields arising from those currents. The results of our simultaneous measurements of NMR with MCG and MMG are compared to results from a current phantom to investigate the exciting potential of direct MRI of bioelectric currents.

A model for frequency dependence of conductivities of the live human skull.

A mathematical model (sigma(omega) approximately equal to A omega alpha, where, sigma is identical with conductivity, omega = 2 pi f is identical with applied frequency (Hz), A (amplitude) and alpha (unit less) is identical with search parameters) was used to fit the frequency dependence of electrical conductivities of compact, spongiosum, and bulk layers of the live and, subsequently, dead human skull samples. The results indicate that the fit of this model to the experimental data is excellent. The ranges of values of A and alpha were, spongiform (12.0-36.5, 0.0083-0.0549), the top compact (5.02-7.76, -0.137-0.0144), the lower compact (2.31-10.6, 0.0267-0.0452), and the bulk (7.46-10.6, 0.0133-0.0239). The respective values A and alpha for the respective layers of the dead skull samples were (40.1-89.7, -0.0017-0.0287), (5.53-14.5, -0.0296 - -0.0061), (4.58-15.9, -0.0226-0.0268), and (12.7-25.3, -0.0158-0.0132).

Conductivities of three-layer live human skull.

Electrical conductivities of compact, spongiosum, and bulk layers of the live human skull were determined at varying frequencies and electric fields at room temperature using the four-electrode method. Current, at higher densities that occur in human cranium, was applied and withdrawn over the top and bottom surfaces of each sample and potential drop across different layers was measured. We used a model that considers variations in skull thicknesses to determine the conductivity of the tri-layer skull and its individual anatomical structures. The results indicate that the conductivities of the spongiform (16.2-41.1 milliS/m), the top compact (5.4-7.2 milliS/m) and lower compact (2.8-10.2 milliS/m) layers of the skull have significantly different and inhomogeneous conductivities. The conductivities of the skull layers are frequency dependent in the 10-90 Hz region and are non-ohmic in the 0.45-2.07 A/m2 region. These current densities are much higher than those occurring in human brain.

Conductivities of three-layer human skull.

In this study, electrical conductivities of compact, spongiosum, and bulk layers of cadaver skull were determined at varying electric fields at room temperature. Current was applied and withdrawn over the top and bottom surfaces of each sample and potential drop across different layers was measured using the four-electrode method. We developed a model, which considers of variations in skull thicknesses, to determine the conductivity of the tri-layer skull and its individual anatomical structures. The results indicate that the spongiform and the two compact layers of the skull have significantly different and inhomogeneous conductivities ranging from 0.76 +/- .14 to 11.5 +/- 1.8 milliS/m.