All existing superconducting instrumentation for measuring the concentration of iron stored in the human liver requires liquid helium for its operation. We report the mathematical modeling, optimization, and instrumental performance of an instrument that uses high-transition-temperature (high-Tc) superconductors. Requiring only liquid nitrogen to operate, the susceptometer represents the first medical application of the phenomenon of high-temperature superconductivity with the potential for widespread clinical utility.

We describe a new approach to the magnetic measurement of liver iron stores, using an instrument that incorporates a combination of permanent magnets and superconducting flux transformers. Instead of traditional low-transition-temperature superconductor (LTS) transformers, the susceptometer employs their high-transition-temperature (HTS) counterparts. This innovation substantially reduces the size and weight of the instrument, allowing the whole assembly to be scanned in a horizontal plane. We report engineering details of the HTS flux transformers, magnet assembly, field sensing, and scan mechanism, and present experimental data to show that scanning susceptometer can determine not only the susceptibility of cylindrical phantom models but also their diameters. We conjecture that further refinements of scanning susceptometer could lead to a form of susceptibility imaging that would enhance the accuracy of measurements of liver iron stores and also lead to new medical applications of the method.

We have studied the magnetic field produced by the brain when attending to a variety of rare events. The temporal character of the response to a rare auditory stimulus is reported. The magnetic field appears to offer a useful new probe of endogeneous activity in the human brain.

This paper describes a new computer-enhanced dual-channel SQUID susceptometer designed to achieve accuratein vivo estimates of tissue storage iron concentrations. We discuss the practical design considerations, instrumental noise performance and anticipated clinical resolution of the new system.

We have exploited the spatial resolution of the magnetic sensor to provide numerical estimates of the atrial contribution to magnetic fields recorded just prior to ventricular depolarization. The contribution is found to be small, strenghening our original interpretation that such fields originate mostly in the conduction system of the heart.

A magnetic method for direct noninvasive measurements of human hepatic storage iron with a SQUID susceptometer has been developed.In vivo magnetic andin vitro chemical determinations of liver nonheme iron are closely correlated. Magnetic measurements of iron stores are clinically useful in the diagnosis of disorders of iron metabolism.

We made direct noninvasive magnetic measurements of hepatic iron stores with a specially designed superconducting quantum-interference-device (SQUID) susceptometer in 20 normal subjects and in 110 patients with liver disease, iron deficiency, hereditary hemochromatosis, or transfusional iron overload. Magnetic in vivo measurements of liver non-heme iron were closely correlated with chemical in vitro measurements in liver-biopsy specimens (r = 0.98, P less than 10(-5) up to 115 mumol per gram of liver tissue (wet weight) or more. Magnetically determined storage-iron concentrations were below 6.0 mumol per gram in iron-deficient patients and normal men and premenopausal women, but they were raised (9.7 to 31.4 mumol) in 12 of 67 patients with liver disease and were greatly increased (22.9 to 117.7 mumol) in patients with untreated hereditary hemochromatosis or transfusional iron overload. Magnetic measurements of iron stores provide a new quantitative technique for early detection of hereditary hemochromatosis and for rapid evaluation of treatment regimens for transfusional iron overload.

An overview is given of recent progress in our understanding of the magnetic field of the human cardiac conduction system. This field, of the order of 0.5 pT, has been mapped with a first-order SQUID gradiometer in a rural location having the very low overall noise level of 6×10−3 pT/√Hz. Measurements of similar sensitivity in an ordinary clinical environment have not yet been attempted but we discuss a new approach to noise reduction which should permit this to be achieved. A theoretical model, based on an electrophysiological description of the nerve fibers of the cardiac conduction system accounts quantitatively for the principal features of the existing observations. This constitutes a first step toward the extraction of clinically useful information from magnetic measurements of the conduction system. An extension of this approach is discussed, which promises to supply useful information on abnormal as well as normal subjects.

This communication discusses a development in medical diagnostics, made possible by the application of a SQUID magnetic susceptometer to in vivo measurement of the iron stored in human tissue. Some new results are reported which indicate that a carefully designed susceptometer can provide the clinician with a useful non-invasive measure of excess iron in the human liver. Extension of this technique to other important iron storage problems is discussed.

This paper provides a review of the principles and practice of biomagnetic susceptometry, with particular reference to magnetic susceptibility measurements of the human liver. A novel SQUID biomagnetic susceptometer is described consisting of a second-order gradiometer combined with a superconducting field coil assembly. We report the first clinical non-invasive diagnosis of liver iron overload achieved with this susceptometer at the Metropolitan General Hospital in Cleveland. Estimates are provided for the limiting resolution of the method. Ongoing efforts to apply the same principles to the determination of iron overload in the heart are briefly described. Our work represents the first clinical diagnostic procedure to utilize the recently developed superconducting technology of weak field measurement.

Small but reproducible and consistent auditory evoked magnetic fields have been obtained for 6 male subjects. These fields exhibit features with a clear spatial symmetry which can be accounted for by assuming that their source consists of two vertically oriented neuronal complexes symmetrically located deep in the temporal lobes. This assignment, which is also consistent with the available electrical data, places the sources within the auditory cortex near the sylvian fissure. Our results suggest that auditory evoked magnetic fields may provide assistance in unravelling the source structure that produces the auditory evoked response, both electrical and magnetic.

It has recently been suggested that depolarization of the entire His-Purkinje conduction system of the heart produces a characteristic waveform in the surface electrocardiogram. The magnetic probe offers a different and, in some respects, advantageous means of observing such waveforms, and extensive records of the surface magnetic field generated by the human heart have been obtained for four normal subjects. A first-order SQUID gradiometer was employed havinAthe lowest noise level yet reported in any biomagnetic study (6 X 10-15 T/√Hz). Using an on-line computer, 100 beat averages were taken at 49 positions over the chest on a 1 in square grid. The fields observed have a characteristic symmetry and provide support for the suggestion that events associated with depolarization of the conduction system may be observed at the surface of the torso.

Reliable non-invasive information on the P-R segment of the cardiac cycle would be of great clinical value for the analysis of conduction disturbances in the heart. Considerable recent effort has centered on obtaining such information from the ECG. However, practical difficulties are encountered which, so far at least, have prevented a widespread application of the method. The magnetic field of the heart offers an alternative probe which appears in principle to be better suited for recording conduction processes. Accordingly, we have obtained preliminary magnetic records using SQUID instrumentation. A very simple averaging scheme was used, employing an on-line 8 bit microprocessor. Our preliminary results confirm that the magnetic record contains clear structure, qualitatively and quantitatively consistent with conduction activity. A biphasic deflection has been observed whose onset is sharply localized in time about 40 msec prior to the onset of ventricular activity and additional activity of interest has also been noted just prior to ventricular activation. The electrical and magnetic approaches to the recording of conduction activity are assessed and it is concluded that the magnetic technique has significant advantages for this purpose.

Calculations of the effect of torso geometry on the extracorporeal magnetic field produced by a simple cardiac source have been carried out. Contrary to the results at present in the literature, it is found that the field solution is stable under perturbations of geometry in the sense that small relative changes in geometry produce comparably small changes in the magnetic field. Thus, simplified torso models may have a wider range of validity and usefulness than was previously thought.

New residual-resistivity data are presented for all solutes which show an appreciable solubility in zinc (Cu, Ag, Au, Cd, Hg, Al). In contrast with some previous work for zinc, the residual resistivity per atomic percent impurity is found to be a well-defined experimental quantity. The results are discussed within the framework of Blatt's lattice-distortion model for impurity resistivity, and clear evidence is obtained for significant lattice-distortion screening effects. Some systematic departures from the model predictions are correlated with solute position in the Periodic Table.