Biyomagnetik olaylar

Abstract

îkinci bölümde, Bir akımın magnetik alanının ve maddenin magnetik özellikleri anlatılıyor. Bu kısmın anlatılmasındaki ana amaç daha sonra ileriki hesaplamalarda kullanılan Ampere Yasası, Biot-Savvart kanunu ve diğer formüllerin anlaşılmasında kolaylık sağlamasıdır. Üçüncü bölümde Biyomagnetik akımlar ve onların modellerinden bahsediliyor. Akımların ve onların modellerinin anlaşılması maksadıyla bazı örnekler veriliyor. Ayrıca bir hücrenin membranmın dinlenme halindeki potensiyeli, Aksiyon potensiyeli anlatılıyor. Dördüncü bölümde, SQUID sensörlerinin prensiplerini anlayabilmek için Süper iletkenlikteki bir takım teorilerden bahsediliyor. Daha sonra RF SQUID, DC SQUID magnetometre'lar, Manyetiksel Shield'li odalar, yüksek Tc süperiletkenlikten yapılmış DC SQUID'lann şimdiki ve gelecekteki durumlarından bahsediliyor. Beşinci bölümde, özel hacim iletken şekillerindeki dipolün magnetik alanı ele alınıyor. Burada dört hacim iletken şekli inceleniyor. Bunların üçü yaklaşım olarak insan başı şeklinde ve bu yüzden MEG'i analiz etme açısından yararlıdır. Altıncı bölümde, Kardiyomagnetizmin temelleri ele alınıyor ayrıca MCG'deki ters problemin çözümü, kardiyak anormallikleri ile ilgili MCG çalışmaları, Kardiyak kateterleme sırasında MCG pratiklemesi, MCG'deki haritaların önemi, MCG'nin kliniksel önemi ve Elektrokardiolojistlerin MCG'den beklentileri ele almıyor. Yedinci bölümde, MEG sinyali üreteçlerinin doğal yapısı, Hacim akımlarının MEG'e sinyali üreteçlerinin doğal yapısı, Hacim akımlarının MEG'e etkisi ve modellenmesi, MEG'de kaynak lokalizasyonuna ait yeni yaklaşımlar ele alınıyor. Sekizinci bölümde, Hücre organel hareketleri ve sitoplazmik kararlılık ile Manyetopnömografi ele alınıyor. Onuncu bölümde ise Nömogretizmin Temelleri, Nöral biyoelektrik aktiviteyi modelleme, Kliniksel uygulama alanları ele alınıyor.

Over the past twenty-five years the study of biomagnetic phenomena has evolved into an interdisciplinary resarch effort involving individuals whose primary training has most often been in either biology, engineering, medicine, physics, or psychology. The goal of this tutorial is to present to a similarly eclectic audience the essential physics and electrophysiology required to describe the biological sources of magnetic fields, the spatial variation of these fields and how the sources and their fields can be modeled mathematically Asa result, many of us enter biomagnetism with an intuition that is ill-prepared to describe how biological cells produce currents that flow throughout an inhomogeneous body that has a complicated geometry. It is even harder to understand the spatial variation and information content of the magnetic fields associated with these currents. In complex systems such as the human heart or brain, the simple equations presented in an introductory physics course must be written in a more general form, usually involving vector or tensor calculus. Since the discovery of superconductivity by Kamerlingh Onnes in 1911 this physical phenomenon has found several important applications. Superconductive devices work only at low temperatures; such a temperature is usually maintained with the aid of liquid helium. Storage and use of liquid helium requires special thermally isolated dewars. Since 1970, Superconducting Quantum Interference Device ( SQUID ) magnetometers have been used for biomagnetic studies. In the 70's most SQUID magnetometers were single channel devices and they were used at magnetically unshielded measurement sites. Cohen reported in 1979 a two-channel "2-D" planar gradiometer and Seppanen et al. in 1983 a 3-channel first-order vector gradiometer. In 1984, the 3+1 channel system (Ilmoniemi et al. 1984) and finally 1985 the BTi 5- channel system ( Williamson et al. 1985 ) were reported. These were systems finally designed for studies in a magnetically shielded room ( MSR ), and working at sensitivities edequate for biomagnetic studies s 50 f /T \Hz During the last few years, the number of channels has first grow to seven and thereafter to 24 and 37. The sensitivity of 7-channel devices has increased to 5-7 f /T V/fe and one-channel device to 3 f /T \Hz ( Nenonen et al., these proceedings). The discovery by Bednorz in 1986 of a new class of superconductors with higher transition temperatures than known before initiated a search for XVUl superconductivity at liquid nitrogen temeperature and higher. Superconductivity at 90 K was observed in the perovskite type Y-Ba-Cu-0-system in 1987. In the Bi-Sr-Ca- Cu-O system, a phase with the new materials will be suited for magnetometric applications. Systems have also been constructed, where the cryogenic temperatures needed for the use of SQUID's are reached without the use of liquified helium. Superconducting QUantum Interference Devices ( SQUIDs ) have now been fabricated by a number of groups from high temperature ( hig Tc ) superconductors j_ 4. Many reported devices operate at 77 K and noise measurements have been made on a small number of these high Tc SQUIDs. The nature of the junctions forming the SQUIDs, which have been naturally occurring grain boundaries in all but a few of the reported devices, and the physical mechanisms responsible for the noise sources are discussed. At the beginning of the eighties still no demonstration had been given that magnetocardiography could be performed in a noisy unshielded hospital environment. Furthermore, when the first so called " high resolution MCG measurements " were reported, although clearcut and impressively coherent with what experimental measurements on the basis of mathematical models, although clearcut and impressively coherent with what expected from the anatomy and physiology of the heart, were strongly criticized. Few experimental animal investigation had given counterdicting results (Leifer et al 1983). Both cardiac electrophysiologists and cardiologists asked for direct demonstration that magnetocardiography could really provide new information with respect to the less expensive and troubleless electric measurements and that the MCG could be easily recorded in an hospital setting. For this reason at the Clinical Physiology Laboratory of the Catholic University of Rome a perspective project was started in 1980 to set up a Cardiac Catheterization laboratory, without the use of any electromagnetic shielding. First high resolution MCG recordings in this hospital laboratory were carried out in 1982, however only in 1985 first simultaneous magnetocardiographic and invasive electrophysiologic measurements were successful. This provided the first direct clinical validation for the interpretation of high resolution MCG recordings. Furthermore the first demonstration was given of the MCG accuracy for the 3D localization of cardiac accessory pathways, and of an artificial current dipole pacing the human heart. Cellular currents that initiate the periodic muscle contractions of the heart will also generate volume currents in the ionic, conductive medium of the body. These volume, currents create potential differences at the body surface which can be displayed as the electrocardiogram (ECG). Both cellular and volume currents produce small magnetic fields near the body surface. A recording of these periodic magnetic field changes constitute a magnetocordaiogram (MCG). xix While it is now over a hundred years ago that the first ECG was measured, the first MCG was recorded just over 25 years ago by Balue (1963). They used large coils, with two million turns each, in a gradiometer arrangement. The development of the SQUID and the use of a shielded room made high quality (Low noise) MCG's possible. Imporvements in gradiometer designs enabled several groups to operate in an unshielded or moderately shielded environment. These developments made MCG technology accessible to many researchers. Lately the development and use of multirobe sensors makes mass screening not only simple an safe, but also a quick procedure that would be acceptable to the medical community. In addition new high resolution MCG probes provide us with a signal to noise ratio that is essentially the same as that in high resolution ECG. These new developments will stimulate research to explore further the unique capabilities of the MCG. Reviews on MCG have recently written by Siltanen (1989), as well as by Katila (1988). Measurements of electric potential differences in the human ehart, made possible by the electrocardiogram, have established strong underpinnings for researching bioelectric cardiac phenomena and opening the way for its use in clinical diagnosis. The same bioelectric currents in the body that generate electric potentials also generate weak magnetic fields. These biomagnetic fields are extremely low in magnitude (approximately 10 " 14 t0 \q - 10) ^ an(j jt was not until 1963 that the first successful detection of the magnetic field in the human heart was reported. However, it was only after the development of ultrasensitive superconducting quantum interference device (SQUID) detectors in the beginning of 1970's that more accurate detection of biomagnetic signals became possible, advancing the field of magnetocardiography (MCG). Other related fields, such as studies of the magnetic fields in the human brain-magnetoencephalography (MEG)-have also become of increasing interest. Biomagnetic studies offer functional information concerning the electrical activity of various organs, such as the heart or brain, that is difficult to obtain by other methods. Imaging methods such as X-ray, magnetic resonance imaging (MR1), computed tomography (CT), and ultrasound imaging, for instance, provide mainly anatomical and morphological information Functional information about metabolic processes is available by positron emission tomography (PET), but the imaging times are several minutes, and the resolution are to 15 mm. In constrast, biomagnetic methods are suitable for detecting fast transient phenomena; the time scale of the detectable signals ranges from times causes difficulties in corresponding bioelectric potential measurements. The source localization problem is interesting and clinically very important. In recent years, rapid development has taken place in the nonpharmacologic treatment of varios life-threatening cardiac arrhythmias. New methods have been developed, such as arrhythmia surgery and catheter ablation is likely to reduce the need for open-chest surgery, but the essential condition for successful treatments is an accurate localization of the arrhythmogenic region. Thus, these new treatment methods xx increase the need to develop noninvasive methods for more accurate and reliable localization of the arrhythmia sources, in order to shorten the time needed for invasive catheterization. Most localization studies require the solution of the forward problem, i.e., solution of the external potential and magnetic field for a given source configuration and volume conductor. The forward problem is considered for currentdipole sources in different volume conductor medols. Here, we address the inverse problem, i.e., estimating the source current density underlying measured external fields. The solution of this inverse problem is presented in term of equivelent point sources in different volume conductor models Also, we will discuss methods to reconstruct source current patterns from measured magnetic fields. Finally, some instrumentational aspects and validation of the localization results are presented. Electric phenomena in the heart are of low frequency or even quasistatic, so that accompanying magnetic events are at quite low level in insetsity. Nevertheless, recent development of magnetocardiography, enables us to expect a contribution to the solution of several problems in the field of electrocardiography. Limitations of the method are still apparent in certain clinical applications, because of the essential complexity of the phenomenon or of the technical problems. Steady effort on research of the magnetocardiogram (MCG) has been made since the introduction of SQUID gradiometer to measure weak magnetic field of the heart. The isomagnetic map was useful to study instantaneousmagnetic field of ecah phase of cardiac cycle like the isopotential map. However, compared with the isopotential map, few studies on MCG mapping have been made, and previous studies on the MCG did not provide us with a clear answer about whether the MCG is a clinically useful tool. In some conditions the MCG mapping was superior to the ECG mapping. These conditions were: (1) the detection of the opposing dipoles, (2) detection of the current source close to the anterior chest wall, and (3) source localization ( Inverse solution). Initial work on MEG assumed that the head is a sphere, either homogenous or a set of successive concentric layers, and emphasized that if the magnetic field from the spherical head is recorded radially only the impressed current, the cellular current associated with some neural event like an into account (Williamson, 1982). The volume currents, those generated far from the excited cells, over the whole volume of the electrically conducting brain, CSF, skull, and scalp, and due to the electrical potentials generated by the impressed current, give no contribution if thesensors are oriented radially. The magnetic field can then be calculated from the current in a small ragion of space with Biot Savart's Law (Williamson, 1982). For this approximation, scanning around the head should give a symmetric map with two extrema of opposite signs. Recording from the occipital area, for example, offers support of this picture. XXI However, the head is not a sphere. It is a complex structure consisting of the brain, CSF, skull, and scalp. The skull, especially its cortical bone, is a good insulator compared with the other structures. It strongly limits the electrical currents issuing through the skull from electrical sources inside. In simulating the head for MEG studies, as a first approximation, it is appropriate to concentrate on the electrical currents inside the skull, which can be taken as an insulator, and neglect the skull, which can be taken as an insulator, and neglect the scalp. In simulating the intracranial cavity, therefore, the spherical approximation is not very good in the low temporal and frontal areas. Also, near the jaw, if the neuromagnetometer is kept as close as possible to the outer surface of the head in order to get the highest signal-to-noise ratio, it will not be perpendicular to the inner skull surface. This condition is especially difficult to satisfy with multichannel neuromagnetometers. With recording of anterotemporal sharp waves, the MEG maps are in general very asymmetric (Rose et al., 1987) when scanning is done in the usual way, almost parallel to the face. Over the face, the sensors are tilted relative to the inner surface of the skull, and volume current effects should play a role through the tangential component of the head, if the volume current effects are to be taken into account in the spherical approximation, it is necessary to use the equations for a dipole in a sphere (Stok, 1986; Hari, 1987; Sarvas, 1987a), which are available in analytic form. The main concepts emerging from these formulas are as follows: 1. The magnetic field generated by a radiyal dipole in a sphere (homogeneous or a succession of concentric layers with different conductivities) is zero. This is true for both the radial component and the tangential component of the magnetic field. 2. Even if the head is simulated as a set of concentric spheres, each layer with its own conductivity, the volume current contribution to the magnetic field does not depend on the conductivities of the different layers or on their radius. This statement is valid for any component of the magnetic field. The only head parameter that must be specified for this spherical approximation is the coordinates of its center. These coordinates, together with the position, orientation, and magnitude of the dipole, are all that are needed to calculate the magnetic field outside the head for any orientation of the sensors, with inclusion of volume current effects. Neither the radius nor the conductivities are needed for the calculation of the magnetic field for any direction in space. This is a very important point that deserves to be stressed. It is important to determine how much the inclusion of volume cerrent effects can improve the localization and quality of the calculated maps for the dipole that best fits the data, as compared with the experimental ones. This can be accomplished through correct hadling of the tangential component of the magnetic field rather than just considering the field from the impressed current and depends on the area of the head under consideration, the importance of departures from XXll sphericity, and the tilt of the sensors relative to the normal to the skull surface. Since in the National Institute of Neurological Disorders and Stroke (NINDS) and important area of research is temporal lobe epilepsy, we attempted to answer this question by concentrating first on the temporal area. Some of the progress made in recent years toward understanding the nature ot generators of MEG signals. Attempts to rigorously relate cellular currents to an MEG signal have forced us to examine in detail the ways by wich varios currents in the volume conductor can give rise to such a signal. In the hearnt and brain coherent ionic currents flow across appreciable volumes producing detectable magnetic fields * Contaminant magnetic material in the body The body may contain, as contaminants, ferromagnetic or ferrimagnetic material. Magnetite Fe3Û4 is commonly found in dust and is easily inhaled. It is a strong ferrimagnet and as little as a fraction of a gram of magnetite in the lungs is easily detectable. By measuring the field outside the chest it is possible to both monitor the dust burden of the lungs and assess lung function. The measurements are entirely non-invasive. * Intrinsic magnetic material in the body Overall, biological tissue is diamagnetic ( with a susceptibility of order 10"^m"3) though, significantly, it does contain some paramagnetic material. In the Earth's field; the presence of a biological organism changes the local magnetic induction by about 500 pT. SQUID magnetometers have sufficient sensitivity to map the local susceptibility variations of tissues as a way of probing their composition. This idea underlies a method of measuring stored iron levels in the liver. * Quasi de ionic currents Because of the difficulty of making reliable de electrode measurements on biological systems, many potentially significant electrophysiological processes are unexplored. ' Injury current is an example. This may be a simple epiphenomenon, but it has been suggested that the currents have a significant role in the repair process. A linked suggestion is that the ionic currents that accompany development help to ' shape ' the organism.DC magnetic field studies of such phenomena may allow monitoring of hidden injuries and help to elucidate fundamental biological processes. Magnetic particles in the size range of 0,5 to 2m diameter can serve to quantify a number of disparate phenomena when these particles are enmeshed in tissues, cells, or polymer fluids. Proteins (including iron-containing proteins) and other tissue components are not ferromagnetic, but tiny ferromagnetic crystals can xxni be introduced as probe particles. Such partieles can be magnetically aligned by application of a strong magnetic field, after wich they act in unison to produce a remanent magnetic field (RMF) measured at the body surface. The magnitude and time course of the RMF depend, respectively, on the quantity of magnetic material present and on the degree of particle motion. Magnetic particles can be used to examine clearance or dissolution of particulate metarial from the lungs, liver, or other organs. Particle rotation within the body or within cells causes the RMF to decay after magnetization, a phenomenon called relaxation; the initial magnitude of the RMF can be restored by remagnetization, and relaxiton begins again. The decay rate of the RMF is related to the time constants of şartide motions, and relaxation can noninvasively quuantify cell organelle movement. A torque can be applied to magnetic particles by external fields, and the resulting rate of particle rotation depends on the viscoelasticity of the particle environment, e.g, airway mucus, lung surfactant, cytoplasm, or purified protein gels. When magnetic particles are ingested by cells, magnetic elutriation techniques can be used to separet cells info subpopulations according to the quantity of magnetic material they have internalized. Although the first attempt to detect a magnetic signal associated with bioelectric activity in the human brain traces back to the late sixties, and was performed by means of a non-superconducting sensor, it was only four years later than a SQUID was successfully used to record a human magnetic alpha rhytm with a satisfactory signal-to-noise ratio. Some years later, magnetic signals associated with brain activity evoked by peripheral sensory stimulation were also detected. They examined some cases of generalized epilepsy, but the identitication of the most promising application of the neuromagnetic method in the clinical field, namely the sutdy of focal epilepsy, was achieved by the independent work of two groups at the beginning of the nineteeneighties (Barth et al., 1984). During the last decade impressive progress have been achieved in the field of neuromagnetism. Fundamental understanding on the structural organization of primary areas in the human brain has been accompanied by important findings on higher levels of brain functions, such as different sounds processing, or the effect of memory. The generators of some of the natural rhythms, like alpha and mu have been found to be partly localized in specific cortical areas and, even more fascinating, they are likely to be synchronized in an impressive " resonant", macroscopic response. The noninvasive investigation of focal epilepsy has proved to be a new, powerful tool for preoperative diagnosis in a widespread disease (Rose et al., 1987). But also in more complex pathologies, such the photoconvulsive response in generalized epilepsy, the neuromagnetic investigation has provided significant new information. Finally, at least other two major results have been obtained, which have remarkable value for future clinical use: the preoperative evaluation for appropriatness to implant a cochlear prosthesis in deaf patients, and the detection of pathological neural activity associated with tinnitus. The neuromagnetic techique is rapidly establishing its role as a noninvasive tool to explore human auditory function. The supratemporal auditory cortex, embedded within the Sylvian fissure, is optimally situated for XXIV magnetoencephalographic (MEG) recording: the subject can lie comfortably while magnetic field is measured over the lateral aspect of the head. The usefulness of MEG is often compared with that of electric scalp potential recordings. Some auditory evoked potentials, like those originating in the brainstem, are widely applied in clinical assessment of peripheral auditory pathways. However, studies of long latency evoked potentials have not comtributed significantly to neurological diagnostics nor to our understanding about information processing along the auditory pahtways. One important reason is the poor localization accuracy of the electric method, which has prevented interpretation of the recordings in terms of the underlying neural substrate. When sources cannot be separated is not possible to study, for example, effects of different acoustic parameters or tasks on neural activity in specific brain areas. Consequently, too much emphasis has been paid on the peaks and bumps of the electric respones at descriptive level. Many of these problems can be overcome with magnetics recordings which often allow accurate localization of the underlying neural sources. Having started from comparisons of the electric and magnetic response waveforms and distributions, the neuromagnetism community is now increasingly aiming at more functional approaches to probe neurophysiological properties of cortical networks. After the first neuromagnetic measurements with single-SQUID instruments in the eraly 1970's, multi-channel devices were built in several laboratories (for a review, see Ilmoniemi et al., 1989). The number of channels has been rather limited and multiple measurements at different dewar positions are generally needed for locating the neural current sourcess accurately. It consists of a 24-channel dc-SQUID gradiometer signal detection electronics, signal preconditioning and measurement control electronics, data acquisition system, a probe position indicator (PPI) computer hardware, and software for measurement and analysis of data. Will first give an overview of our system and will then concentrate on features of the software which have been the main responsibility of the author.