Eur Respir J 1989,2, 14!H59

REVIEW

Magnetopneumography: a general review

V. Le Gros*, D. Lemaigre*, C. Suon•, J.P. Pozzi**, F. Uot*

Magnetopneumography: a general review. V. Le Gros, D. Lemaigre. C. Suon, J .P. Pozzi, F. Liot.

• Service Central d'Explorations Fonctionnelles, H()pital Ambroise Pare, Boologne Billancourt.

ABSTRACT: Magnetopneumography is the study of the remanent magnetism of foreign intrathoracic ferromagnetlc particles after mag­netization by an external magnetic field. Given knowledge of the magnetic characteristics of the inhaled particles, this highly sensitive and non-Invasive technique allows the measurement of lung dust loads. Many groups or workers have been examined in this way, e.g. welders, coalmlners, asbestos, foundry and steel workers. Mag­netopneumography also allows analysis of the distribution of aerocontaminants in the dltTerent anatomical structures and, when repeated, the study of clearance speeds and migration from site to site of such particles. Emphasis has been laid on the Importance of study of the fading of the remanent magnetic signal as time elapses. This short-term phenomenon, called relaxation, seems highly significant for the study of the dynamic properties of the Immediate environment of extra pulmonary particles and especially for the study of macrophage activity.

•• Director of Research for the CNRS, Ecole Normale Superieure (Geologie), Pa.ris.

Correspondence: Pr. F. Liot, Service Central d'Explorations Fonctionnelles, H()pital Ambroise Pare, 9 avenue Charles de Gaulle, 92104 Boologne Cedex, France.

Keywords: Biomagnetism; magnetopneumograpby; ocx:upational health; pulmonary clearance.

Eur Respir }.,1989, 2,149-159

Magnetopneumography is a highly sensitive and non­invasive technique for the in vivo detection of certain foreign particles in the lungs. It is the study of the re­manent magnetism of intra-thoracic ferromagnetic aero­contaminants after magnetization by an external magnetic field. This technique has been developed from 1973 onwards in the USA, Finland, Denmark, Sweden, West Germany, Italy, Japan, Canada, and more recently in France.

Principles of magnetopneumography

Generalities

The principle of magnetopneumography is simple: when a so-called ferromagnetic body is introduced into a magnetic field H, that body acquires an induced magnetism J. This magnetism results from the align­ment of the elementary magnetic moments of the body in the direction of field H, whereas they were randomly oriented before magnetization. Alignment occurs mainly through displacement of domain boundaries and rotation of multidomained particles (with a diameter greater than about 0.05 IJ.ffi). Induced magnetism J and magnetic field H are linked by the formula J=X·H, where X is the magnetic susceptibility of the body studied, a non­dimensional number. The units used and their meanings may be found in Appendix 1.

Ferromagnetic bodies are uniquely susceptible, and the only ones capable of being strongly magnetized. If

magnetic field H is removed, induced magnetism J disappears, but a weaker remanent magnetism B, remains. It is thus possible to expose the thorax of a subject to a magnetic field, and subsequently to look for the existence of remanent magnetism. Its intensity measured at the surface of the thorax is proportional to the quantity of ferromagnetic aerocontaminants con­tained in the lungs (fig. 1).

Ferromagnetic bodies are composed of iron, nickel, cobalt, and certain of their oxides. They are present in variable proportions in most industrial aerosols, essentially in an oxidised form as a result of the small size of the particles and the high temperatures occas­ionally attained in their production. Iron oxide magnetite (Fep4),which is commonly present in industrial aero­sols, has strong ferromagnetic, (or more accurately ferrimagnetic) properties, and is used as a tracer in studies of lung clearance.

Exposure, generally occupational, to aerocontamin­ants containing ferromagnetic material can cause various illnesses; pneumoconioses, chronic bronchitis, bronchial and pleural cancers. These pathological conditions are connected either with prolonged exposure to a very high concentration of pollutant, or more often with relatively high individual rates of deposition and/ or individual sensitivity to the inhaled-aerosols. Groups most at risk are arc welders, coalminers, asbestos, foundry and steel workers.

In practice th.e first stage of magnetopneumography is the phase of magnetization, in which the thorax of the individual to be studied is subjected to a sufficienlly

150 V. LE GROS ET AI-

A Belore magnetization

Magnotlzlng lleld H (kAim)

No remanent magnetic Held

8 Magnetization

lndueo~cllleld J

c Mer magnetization

Helmoltzcoll

Magnetometer

Rc!msMnt magr>ellc llotd Br (plco ToSIU)

Mag·neUc moments of ferromagneuc Inhaled par11eles In the lungs

Fig. 1.-This figure shows in sum the principle of magnetopneumogra­phy. A: Before magnetization the orientation of the magnetic moments of intrathoracic ferromagnetic contaminants is randomly distributed. No remanent magnetic field is detectable at the surface of the thorax. B: During application of the magnetizing field H (here produced by two Helmholtz electromagnetic coils) the magnetic moments are orientated in the direction of field H and an induced magnetism J appears, equal to xH (X magnetic susceptibility). C: On cessation of the magnetic field, induced magnetism disappears, but a weaker remanent magnetism Br remains. Its intensity measured by magnetometer at the thorax surface is proportional to the quantity of intrathoracic ferromagnetic aerocontaminants.

strong external magnetic field. When the magnetic field is removed, the intensity of the signal produced by remanent magnetism is measured by magnetometer at the surface of the thorax. Certain magnetometers attain a sensitivity of 10'13 Teslas (a tenth of a pico Tesla), which corresponds to extremely weak concentrations of ferromagnetic material, of the order of 10 ng·cm·3• For comparison, the intensity of magnetic fields produced by thoracic remanent magnetism in dust-contaminated subjects is about 10,000 times weaker than that of the continuous constituent of the Earth's magnetic field [1]. We shall hence forth call the signal produced by reman­ent magnetism of the thorax the magnetic field or signal.

Endogenic iron (FeO, Fe20 3 and reserve iron FeOOH), although representing a mass of about 4 g in adults, is not detectable by magnetopneumography, since it is not present in ferromagnetic form and there­fore does not acquire appreciable remanent magnetism [2].

Description of magnetopneumographical techniques

Every team working on magnetopneumographical research has its own techniques of magnetization and measurements. We cannot therefore compare raw fig­ures for remanent magnetic signals, but only deduced dust load values expressed either as absolute values in mg or relative values compared with a signal of ref­erence [3].

Techniques of magnetization. Two techniques of mag­netization have been suggested for the thorax:

1) Global magnetization. In this method, the whole of the thoracic area is magnetized by a uniform magnetic field perpendicular to the frontal plane, by placing the subject between two Helmholtz coils which produce a field with an intensity of the order 25-80 kA·m·•. The remanent magnetic field is measured subsequently. STERN and eo-workers [2] have suggested a technique which synchronizes the phases of global magnetization and measurement, by measuring not remanent but in­duced magnetism. This apparently simple method is in practice very delicate to perform and insufficiently sen­sitive.

2) Local magnetization. This method, suggested by FREEDMAN and eo-workers [4] measures the remanent magnetic field at different points of the thorax after local magnetization by a portable magnet or by a small powered coil. This technique may improve spatial reso­lution but has the disadvantage of very small measured volume by comparison with total lung volume. It does not, therefore, allow measurement of the total pulmo­nary magnetic field.

Measurement techniques. Whatever the system of meas­urement chosen, it is essential to guard against ambi­ent magnetic noise by the use of a magnetically protected chamber. Most of the methods of magnetic insulation use passive attenuation techniques, which place both subject and magnetometer in a polyhedric enclosure with metallic walls. There are also so-called 'active' protection procedures which use tri-axial com­pensation of the external fields.

The instrument normally used for the measurement of the remanent magnetic field is either a SQUID (superconducting quantum interference device) magne­tometer, the most sensitive but the most delicate to use; a second-order fluxgate gradientmeter magnetometer; or a pair of frrst-order gradientrneter magnetometers placed on either side of the thorax [5, 6]. The measurement system is sometimes incorporated into the magneti­zation bank, which avoids moving the subject between the magnetization and measurement phases [6).

After global magnetization, the remanem magnetic field is measured along different horizontal lines of the front and occasionally the rear side of the thorax (fig. 2). After local magnetization, it is measured at the different points of magnetization.

KALuoMAK.I and eo-workers [7, 8] recommended co­mpleting measurement of the remanent magnetic field by recording the coercive pulsed field, applying short magnetizing or demagnetizing pulsed fields with a coil, in order to determine not only the quantity but also the nature of the particles retained in the lungs.

Factors influencing the remanent magnetic signal

Factors specific to the individual studied will be dealt with later; these are the total quantity of intrathoracic

MAGNETOPNEUMOGRAPHY: A GENERAL REVIEW 151

-ANTERIOR SIDE -----POSTERIOR SIDE

Fig. 2.-Remanent magnetic signal measured on five lines oflhe front and rear sides of the thorax of a dust-contaminated welder [17].

ferromagnetic particles, the physicochemical properties of these particles, and the phenomenon of relaxation. We shall mention only directly controllable factors, which must be taken into account since they may give rise to measurement errors.

Configuration and intensity of the magnetizing field. The intensity of the remanent magnetic field diminishes when the magnetizing field is not perpendicular to the frontal plane.

The remanent field increases in roughly linear pro­portion with the intensity of the magnetizing field, when the latter has a strength of between 0 and 48 kA·m·1• The magnetism of most magnetic materials in practice reaches saturation for magnetizing fields of 40-200 kA·m·1 [3, 9].

Magnetization lime. The intensity of the remanent mag­netic field depends upon the length of time of applica­tion of the magnetizing field [10]. This intensity increases rapidly at first as a function of magnetization time, and then more slowly, stabilizing for magneti­zation times of 10-100 s. For magnetization times longer than about one second, the remanent field in­creases approximately logarithmically with magnetiza­tion time. The remanent field may be determined by the following empirical formula: B,=Br~·(l+v·log t.J, where B,1 is the remanent field measured after one second of magnetization, v a parameter of viscosity and tm the magnetization time in seconds. The para­meter of viscosity v, which is 0.5 for weak mag­netizing field, diminishes when the intensity of the magnetizing fields increases. This formula is inappli­cable for times less than one second, since it then gives physically impossible results. [6].

This influence of magnetization time on the remanent field is attributed to the slow speed of rotation of par­ticles towards a position of maximum magnetic moment and minimum energetic configuration [10]. The curve representing the remanent magnetic field as a function of the application time of the magnetizing field (fig. 3) could therefore be influenced by the viscosity of the medium containing the particles; this is why CoHEN [10] called it the 'viscoity curve'. The shape of this curve varies from individual to individual for, as yet, unexplained reasons. It may be the result of several curves with different time constants [6]; the particles' orientation speed probably differs according to their localization, being faster for free intra-alveolar particles

c. 0 ,...

400

0 J!l 200 '2 :I

a:r 0

-o- Subject 1 - •- Subject 2

Normalized at 8.5 secs

0o~--~--~2--~---J4--------6~--~--~s~

Magnetizing pulse on-time sec

Fig. 3.- Thoracic remanent magnetic signal as a function of magnetiza­tion time (magnetizing field of 11 kA·m·1). Subject 1 has inhaled a magnetite tracer five hours before measuremenL Subject 2 is a retired welder exposed for several years. The shape of the curve is probably a function of the viscosity of the ambient medium of the particles, whicJ:! is greater in subject 2 than in subject 1 [10].

than for those in the pulmonary interstitium or in macrophages.

Some authors recommend a short magnetization time, of the order of one second, so that only the relatively free particles can have time to orientate themselves in the direction of the magnetizing field. The remanent field thus obtained is a small fraction of the maximum possible value. This technique allows better comparison of what occurs in vivo and in vitro for certain dry dust samples.

Since the mobility of particles may vary in time with phagocytosis and/or passage into the interstitium, it would be preferable to use a longer magnetization time, from a few seconds to a few tens of seconds. The re­manent field obtained is then maximal and is more reproducible from one measurement to another.

Several studies on men and animals have in fact shown that the influence of magnetization time is im­portant only for magnetizing fields of low intensity [6].

Distance between the thorax and the magnetometer. The measured remanent signal diminishes as the distance between the centre of the thorax and the magnetome­ter increases. Techniques of localized magnetization appear to accentuate this phenomenon [6]. Conversely, risks inher~nt to this parameter would be diminished either by using a SQUID magnetometer placed above the subject, with a non-uniform magnetization systerm consisting of a large coil placed below the subject, or by use of a pair of first-order fluxgate gradientmeter magnetometers placed on either side of the thorax.

Measurement variations due to the influence of respi­ration and cardiac activity. These are quite minimal, being of the order of 2 nT for the former and 0.3 nT for the latter [11].

152 V. LE GROS ET AL.

Variation of the remanent field as a function of time. As soon as magnetization ceases, the remanent magnetic signal diminishes with time due to random redistribution of the magnetic moments of magnetized particles. This phenomenon, known as relaxation, ne­cessitates calculation of the initial remanent field by extrapolation to time zero of the measured field. The formula for this calculation will be studied in the para­graph concerned with relaxation.

The remanent magnetic signal therefore depends on a certain number of technical factors apart from the concentration of ferromagnetic material; these can and must be controlled.

Applications of magnetopneumography

Determination of the total quantity of aerocontaminants in the lungs

General principles. Magnetopneumography is a sensi­tive, non-invasive, and reproducible technique for meas­uring lung dust loads. To date quantitative measurement of these has proved difficult. Methods such as chest X­ray. lung function tests, examination of alveolar lavage fluid, bronchial or transbronchial biopsy or surgical pul­monary biopsy are either nonspecific and late, or too invasive for daily practice practised. Simple knowledge of pollution concentrations of inhaled air allows iden­tification of high-risk groups of workers, but gives no information as to individual lung dust loads due to the considerable variation of lung retention between in­dividuals working in similar conditions. Only post­mortem studies have provided information on total aerocontaminant loads in the lung.

Measurement of the pulmonary remanent magnetic field allows calculation of the quantity of dust contained in the lungs. The intensity of the remanent field pro­duced by a given quantity of ferromagnetic material and the methods of calculating total lung dust loads de­pend on the system of magnetization and measurement adopted. Standardization of the apparatus is indispen­sable in all cases. Such standardization is achieved by use of lung models and dust samples with known char­acteristics.

S1ROINK and eo-workers [5, 12] recommend direct calculation of total remanent dipolar moment from the field measured, using analysis of the data depending on dipolar and quadripolar coefficients for determination of the origin of multi-polar expansion of the field.

Whatever system is used, knowledge of work history and of the magnetic characteristics of dust inhaled is indispensable for precise calculation of total lung dust load. Figure 4 sums up the principle of this calculation.

The magnetic characteristics of a given dust are defined by its maximum specific remanent magnetic moment M ... which represents the remanent field pro­duced by a kg of such dust after magnetization to saturation. M , equal to about 7 Am2·kg-1 for pure magnetite dust, is between 0.05 and 2 Am2·kg-1 for most metallic dusts. M .. is proportional to the prod-

uct of the magnetite concentration cm. in the sample of dust by the dust's coercive field I\ [6]. The coer­cive field is that magnetizing field, the direction of which is opposite to that of the remanent field, which is capable of neutralizing it. M , C and H are rs mag c linked by the following empirical formula: M =A·C ·H, where A is a constant equal to 1.10-3

:f" ID'!f, C m ·kg-1 [bJ. The coercive field He is increased by mechanical distortion of the particles, the smallest hav­ing a stonger coercive field and a larger M... The coercive field therefore depends on the generative proc­ess of the particles and is independent of the mass or the magnetite concentration of the sample. Its measure­ment therefore constitutes a real 'fingerprint' of the dust studied [6]. The coercive field of inhaled dusts ranges from 3-30 kA·m-1•

~~ ~ ~~A MEASURED

~~rt f---. MOMENT '-~E

MEASUREMENT Am 2

4 AMOUNT

OF DUST r+ mg

SPECIFIC DUST PHYSICS f--->

MOMENT -

OCCUPATIONAL DENSITY

f---> Am 21kg HISTORY

Fig. 4. - Principle of calculation of total pulmonary aerocontaminant content of an individual exposed to ferromagnetic dust [6].

Two factors may cause limited under- or over­estimation of dust loads determined by magnetopneu­mography [14]. The first is the viscosity of the medium containing the particles. In vitro the remanent mag­netic moment of ferromagnetic particles diminshes as the viscosity of the ambient medium increases. Intram­acrophagic and intersitial particles are in a medium of greater vicosity than free intra-alveolar particles or those from certain in vitro samples. Their remanent magnetic moment is hence weaker, which can lead to slight un­der estimation of lung dust load. Conversely, solubil­ity in the lung of certain constituents of inhaled dust can lead to some small overestimation of lung dust load, calculation of which supposes that the proportion of ferromagnetic material is the same in intra-thoracic dust as in dust samples from the atmosphere. These two under- and over-estimation factors intervene variably according to the type of dust inhaled [14].

All determinations of lung dust load by magnetopneu­mography have been confirmed by measurements of real dust loads on autopsied lungs [6, 15].

Magnetopneumography is much more sensitive than other techniques. Its detection threshold is at best from 1-5 mg of dust deposited in the lungs, and at worst 20 mg, whilst, for example, 1,000-2,000 mg of arc welding dust deposited uniformly is needed to give

MAGNETOPNEUMOGRAPHY: A GENERAL REVIEW 153

detectable radiological opacification [3, 16]. One month of work exposure as a welder in a shipbuilding yard is enough to produce a measurable magnetic signal [9].

Magnetopneumography has made it possible to study the lung dust loads of several groups of workers, but raises an important question: is it useful to measure the lung dust loads of exposed workers and to detect those showing abnormally high loads at an early stage? Whilst individuals suffering from occupational respiratory illnesses usually have high dust loads, some subjects with very high loads have no pathological conditions at all. Other factors may be involved; smoking, variability of individual response, etc. It is, therefore, essential to compare for each group of exposed workers magnetopneumographical data, clinical data (incidence of pneumoconiosis, chronic bronchitis, pleuro-pulmonary cancer, etc), chest X-ray, lung func­tion tests including the flow-volume curve and if appropriate other parameters such as urinary elimination of chromium for stainless steel welders. To date several studies have found significant correlation between the dust load as determined by magnetopneumography and certain of the above factors [6].

Results obtained by magnetopneumography in occupational clinical medicine. The first results were published in 1973 by D. Cohen. Since then magne­topneumography has been widely used for the study of several groups of workers.

1) Welders. Welders are a large but non-homogeneous group of workers, for the properties of inhaled welding fumes depend both on the welded material and the method of welding. The chemical characteristics of these fumes have been particularly closely studied [6, 17, 18]. The main groups of welders are the following:

a) Mild steel welders, especially MMA/MS workers (manual metal arc/mild steel, i.e. manual arc welding of mild steel with coated metal electrodes).

b) Stainless steel welders, especially MMA/SS workers (manual metal arc/stainless steel, i.e. manual arc welding of stainless steel with coated metal electrodes), and TIG/SS (tungsten inert gas/stainless steel, i.e. welding of stainless steel with tungsten electrodes and inert gas flux).

Whatever the type of metal welded and welding process, welding fumes are made up of toxic gases and particles causing respiratory tract changes, the pathogeny of which is complex and little known. It is therefore important to make programmed obser­vations of welders, including study of lung dustloads by magnetopneumography, precise exposure details, and parameters of respiratory function.

MMA/SS Welders. Welders working in shipyards have been intensely studied because of their relatively homo­geneous exposure. Average lung dust load values vary according to the shipyards studied: 200 mg [19]; 1000 mg [9], 250 mg [20], 230 mg [21], and 220 mg (STERN

et al. 1984 personal communication). Inter-individual variations are considerable, even among welders working in similar conditions.

Comparison of thoracic remanent magnetic signals from shipyard welders with the theoretical signal which should be observed if all the inhaled dust remained in the lungs allows to conclude that only about 0.1% of inhaled fumes are retained by the lungs over continuous long-term exposure [19].

The study by R.M. Stem et al. of 59 nonsmoking heavily exposed shipyard welders found no significant correlation between incidence of chronic bronchitis and self-diagnosed exposure or lung dust loads determined by magnetopneumography. Conversely NA.sLUND and HOGSTEDT [21], who studied 51 Swedish shipyard welders, found significant correlation between incidence of chronic bronchitis and dust loads determined by magnetopneumography. This descrepancy is probably connected with methodological differences and sensitivity of measurement techniques.

From 1976 onwards the lung dust loads of 47 ship­yard welders has been measured every 3-6 months [7]. Yearly alveolar deposition is between 50 and 130 mg. Average retention after 10 yrs of continuous exposure is equal to 1 g and yearly clearance rate measured in retired welders is between 10 and 20%, which corresponds to an average clearance half-time of 3.5 yrs [27]. There are large inter-individual variations. Finally, the average dust load is stable after 10 yrs of continuous exposure. Balance between retention and clearance therefore seems to occur after about ten years of continuous exposure [6].

There is significant correlation between radiological anomalies in the lung and the average remanent magnetic signal of shipyard welders [6,15]. Aero­contaminant cartography made by radiography on anatomical sections of shipyard welders' lungs superimposes well on that made by the magnetic method [23]. To date no significant correlation has been found between conventional spirometric indices and radiological pulmonary anomalies or magneto­pneumographic· data [24]. However, recent results, concerning MMNS shipyard welders, indicate that flow-volume curve anomalies are clearly correlated with lung dust load figures [6]. No significant difference was shown between average dust loads of smokers and nonsmokers, except in a study by HOGsTEDT and eo­workers, who found lower average dust loads in smokers [21, 25, 26].

Stainless steel welders. Alveolar retention of part­icles from MMNSS welding fumes is greater than for those of other metallic aerosols studied. Their average half-clearance time after retirement is 8.7 yrs [22].

Radiological modifications observed in MMNSS welders are small and are not correlated to lung dust load figures. Urinary elemination of chromium by MMNSS welders is, however, significantly correlated to lung dust load determined by the magnetic method [6].

In 1981, 21 TIG/SS and 29 MMNSS welders were

154 V. LE GROS ET AL

examined by magnetopneumography. The average lung dust load of the former was 200 mg and of the latter 4,000 mg [9].

2) Asbestos miners. About 4% of magnetite adheres strongly to asbestos chrysotiles and 0.5% to manu­factured asbestos fibres. This explains the differences in the magnetic properties of the various types of asbestos fibres. These properties are, however, always enough to allow the detection of asbestos by magneto­pneumography.

Asbestos mine workers in Thetford, Quebec, were ex­amined by COHEN: the lung dust load was between 0 and 500 mg with an average of about 100 mg [10]. There is a weak correlation between the remanent magnetic signal and work exposure, which suggests a balance between deposition and clearance in most of these workers. The average dust load in nonsmokers is greater than in smokers, probably due to airways con­striction in the latter [27]. STROINK and eo-workers found equivalent figures: extreme values 0--640 mg, average value 71 mg [28].

The sub-group of miners also exposed to arc weld­ing fumes, even for a relatively short time, shows an average remanent signal 2-5 times greater [10, 28].

Unlike radiological anomalies, those of respiratory function are poorly correlated with magnetopneumogra­phic data [29].

Unfortunately, the results of these studies cannot be compared with measurements performed on autopsied lungs, since the latter are expressed in quantities of fibres per cm3 of pulmonary tissue and there is no di­rect relationship between the quantity of fibres and their weight [10].

3) Coalminers. The percentage of ferromagnetic par­ticles of coal dust is small (0.25% on average) and above all variable according to mines and sampling sites within the same coalfield [15].

In 1974 COHEN found no significant difference be­tween coalminers from Pennsylvania and city dwelling controls [10], but this was not the case for FREEDMAN and eo-workers [15] in 1980. They examined active and retired coalminers and country dwelling controls. Retired miners had a lung dust load of between 152 and 998 mg with a significantly higher average value than ·those of the control group and the group of ac­tive miners. Two sub-groups of active miners were identified: a 'cold' sub-group not significantly different from the control group (dust load between 26 and 118 mg) and a 'hot' sub-group with dust loads significantly greater than both the control and 'cold' sub-groups (dust load between 216 and 1,442 mg). Miners from the 'hot' sub-group could not be differentiated from the others either by their working history or by their lung radiog­raphy. Finally lung dust load values determined by magnetopneumography were comparable to those meas­ured in autopsied lungs from individuals suffering from coalminers' pneumoconiosis.

In 1982 STROINK and eo-workers found in miners a dust load between 0 and 8,000 mg (with an average

of 1,800 mg), uncorrelated with radiological anoma­lies [28].

4) Steelworkers. In 1982 KALLIOMAKI and eo-workers [6] found dust load values between 20 and 200 mg in blast-furnace workers, between 10 and 40 mg in blast roasting workers and between 2 and 20 mg in subjects working near the continuous flow of molten metal. These results agreed with exposure conditions estimated by measurements taken in steelworks [6]. The level of pulmonary contamination in steelworkers is lower than in ironworkers, which is itself lower than in MMNSS welders [6]. In 1981 a study of 55 Japanese steelwork­ers showed a dust load between 56 and 1,000 mg, sig­nificantly correlated with radiological anomalies [29].

5) Foundry workers. Foundry workers are a hetere­geneous group owing to considerable variability of the magnetic properties of samples taken in the various job sites [6]. Numerous studies of the respiratory condition of foundry workers have been carried out, mostly con­cerning silicosis and occasionally chronic bronchitis. However metallic components from foundry dust are not well-known [6].

In 1974 COHEN found a high average dust load cor­responding to about 500 mg of magnetite in seven foundry workers [10]. In 1981 KALLIOMAKI and eo­workers found dust load values between 60 and 4,000 mg, with an average of about 200 mg [9]. Radiologi­cal pulmonary anomalies correlated closely with the remanent magnetic signal [6].

Several studies have shown significant correlation be­tween lung dust loads determined by radiography and certain elements such as clinical data, lung radiography and tests of respiratory function.

Study of the distribution of ferromagnetic particles in the lungs

Measurements performed on shipyard welders allow the following conclusions:

a) ferromagnetic aerocontaminants are distributed ac­cording to distribution of ventilation thus: 48±5% in the left lung, 52±5% in the right lung; b) the main deposition areas are the hilar regions, probably due to preferential lymphatic clearance of par­ticles deposited in non-ciliated zones; c) 40±10% of particles are localized in the front part of the lung, 60±10% in the rear part [6].

Magnetopneumography also permits study of the migration of magnetite particles used as tracers. This as­pect of magnetopneumography is discussed in the fol­lowing paragraph.

Study of the function of pulmonary clearance

This is an essential application of magnetopneu­mography. Until now measurements of pulmonary

MAGNETOPNEUMOGRAPHY: A GENERAL REVIEW 155

clearance speed in animals necessitated the use of ra­dioactive particles. Studies of clearance over several months hence meant using isotopes with long half-life. The magnetic method using magnetite as a tracer al­lows study of long-term clearance in man.

Many studies in animals have validated the magnetic method as opposed to the conventional radioactive method. Such validation has been established by intra­cheat instillation of radioactive magnetite CS9pep

4) in

a dwarf donkey [30], in rats [31], and in rabbits [32]. Results obtained from the donkey and the rats are summed up in the curves of figures 5 and 6. During the initial period of rapid decline, magnetic and radio­active curves superimpose well. Hence the decline of the remanent magnetic signal over time does reflect the clearance of the magnetite and not physico-chemical modifications to it.

A slight paradoxical increase in the remanent mag­netic field was observed in the donkey about 150 days after instillation of magnetite. It is attributed to the migration of particles towards the hilar regions [30]. The same phenomenon has been observed in man a few days after inhalation [4, 10].

Comparison of magnetopneumographical measure­ments, repeated over time, with real pulmonary iron content was made in rabbits after intratracheal instilla­tion of magnetite. Whilst five days after instillation no further remanent magnetic signal was detected, fourteen days were necessary before no iron was detectable in the lungs. Magnetopneumography hence appears less sensitive than spectrophotometric analysis of lung tis­sue. This method has, however, the advantage of being non-invasive and reproducible over time. Similar lack of sensitivity is observed for the radioactive method [33].

At present magnetopneumography is used in an­imals to study the influence of different factors on pul­monary clearance of magnetite particles [34, 35].

Studies of pulmonary clearance by magnetic method in man can be envisaged in two situations: a) after final exposure of an exposed worker: we have already cited the studies performed in such conditions of arc welders in retirement, the average half-clearance time being 3.5 yrs for MMA/MS and 8.7 yrs for MMNSS welders [22]. b) after voluntary inhalation of a small quantity of purified magnetite. In 1979 COHEN and eo-workers studied twelve men, three heavy smokers and nine non­smokers, after inhalation of 1 mg of magnetite particles of 2.8±1.4 J.Un diameter. The average remanent mag­netic field of nonsmokers decline by 90% of its initial value after 11 months, while that of smokers decline by only 50%. This could explain, at least in part, why smoking and exposure to certain aerocontaminants have a synergic action on the incidence of certain bronchial cancers.

In 1981 STERLING questioned the scientific reliabil­ity and safety of the use of magnetic techniques in man, but reached no decisive conclusion [36].

Lung retention % 100

• Fe 59 radioisotope 0 o Fe30 4 remanent field

50 . ... 0

• 0

• 0 0

30 .. ~ ~ y 0 . ~ . 0

? p o ooy 0. t ••

f • l f '·1 ! '

5 l 0 30 60 90 120 150 180 210 240

Time days

Fig. 5. -Pulmonary retention of '9fe30 4 as a function of time. Measure­

ments performed on a dwarf donkey by radioisotopic and magnetic methods [30].

In 1984 FREEDMAN and eo-workers [4] asked four­teen smokers and fifteen nonsmokers to inhale a mag­netite aerosol (with an average diameter equal to 1.1 JJ.m) with a concentration of 60 mg·m-3 for 45 min. The tracheobronchial phase of clearance was not detected in any group owing to preferential alveolar deposition of particles of this size. During the first week, the rema­nent magnetic field tended to increase. After one to two weeks, a slow decline of the remanent field compatible with slow alveolar clearance was observed. Clearance was significantly slower in smokers. The average time of half time clearance was 78 days for nonsmokers and 127 days for smokers. Migration of the magnetite towards proximal structures was also ob­served. In smokers, clearance was significantly slower in all compartments studied (peripheral, central and proximal pulmonary structures), the greatest differences between the two groups occurring in the proximal struc­tures [4].

Study of the phenomenon of relaxation

Relaxation is the decline of the thoracic remanent magnetic field observed upon the cessation of magneti­zation. This phenomenon is secondary to disalignment of the magnetized particles.

Morphology of the relaxation curve. The relaxation curve decreases exponentially during the first three min­utes following the cessation of magnetization. The re­manent field B (t) measured at time t after cessation of magnetization ~md the remanent field B,(O) measured immediately after cessation of magnetization are linked by the following equation:

where A. is a constant of time which is a function of

156 V. lE GROS ET AL.

Percent lung retention of "Fe,O, 100 •

10

OMagnotlc • Radiologic

----:-----.:_-~- ~M o

1.0

0 7 14 21 28 35 Time days

Fig. 6.- Pulmonary retention of S9Fe30

4 as a function of time. Measure­

ments performed on seven rabbits by radioisotopic and magnetic meth­ods [31].

the duration of the ferromagnetic particles in the lungs. It is approximately equal to 0.20 mn-1 when the depo­sition of particles is less than a year old. For longer periods A. decreases with time [10].

Another formula has been suggested to determine the value of the remanent magnetic signal between 0.1 and 10 min after magnetization:

Br (t)=Br (60)-(1-p·log t/60),

where Pis a parameter of relaxation (equal on aver­age to 0.5), t the time in seconds elapsed from cessa­tion of magnetization and Br (60) the remanent field measured 60 s after cessation of magnetization. Unlike the exponential formula, this logarithmic formula can­not be used to extrapolate the remanent signal at time zero [6].

Causes of relaxation. The first hypothesis to explain relaxation was advanced by D. Cohen. Since relaxation speed is diminished when respiratory frequency slows, and relaxation is no longer observed on lung sections, he concluded that the phenomenon is secondary to the mixing of particles by respiratory movements [6].

In fact, the mechanism presently accepted is the mobilization by intracellular organelles of ferromagnetic particles phagocytosed by the macrophages. GEHR and eo-workers hypothesized this mechanism when observ­ing that the remanent field produced by intrahepatic fer­romagnetic particles shows a relaxation curve nearly identical to that observed in the lung. The liver is not subject to the same movements as the lungs and its fer­romagnetic particles are almost exclusively localized in the macrophages, called Kuppfer's cells [37, 38]. Con­firmation of this hypothesis was obtained by instilling magnetite particles into hamster tracheas and gathering the alveolar macrophages 24-36 h later by pulmonary lavage. These magnetite-bearing macrophages were iso-

lated and cultured. The cultures were then magnetized and the remanent magnetic field measured for 20 min. Relaxation similar to that of the living animal was observed. Cultures treated with cytochalasine B, a sub­stance which destroys the actine filament system, had a diminished relaxation speed whilst this speed is prac­tically unchanged by treatment with colchicine, a sub­stance which destroys the microtubules. Relaxation speed is also diminished in cultures exposed to lower temperatures (20• instead of 37") and in cultures treated with p-trifluoromethoxy-carbonyl-cyanide-phenylhydra­zone, which suggests the energy-dependent character of this process. Finally, no relaxation is observed in cul­tures fixed by glutaraldehyde. Relaxation is therefore a phenomenon linked to intracellular forces originating in contractile filaments which randomize the orientation of magnetite-containing organelles [39]. Other experiments have led to the same conclusions [40, 41].

The present tendency is to use magnetic measure­ments after cellular incorporation of magnetite for the study of dynamic aspects of cell physiology. This new technique is known as cytomagnetometry [39].

Factors influencing relaxation speed

Intensity of the magnetizing field. When the intensity of the magnetizing field is less than 8 kA·m-1, relaxa­tion speed increases proportionally as the magnetizing field weakens. Above 8 kA·m- 1

, relaxation speed remains constant. It seems likely that this phenomenon is linked to the fact that different particle populations are concerned according to the intensity of the magnet­izing field [10].

Duration of ferromagnetic particle presence in the lungs. Relaxation speed is proportionally slower as the duration of ferromagnetic particle presence in the lungs lengthens (fig. 7) [10].

The parameter of relaxation p is equal to about 1 in young welders who have been exposed for only a few months, to about 0.5 after ten years' exposure, and to about 0.15 in retired welders after 30 years' exposure (magnetizing field of 40 kA·m-1) [6].

After intratracheal instillation of magnetite in ham­sters, relaxation speed increases rapidly during the first 12 h, then stabilizes and decreases slowly from day 5 to day 30. These variations may be linked to the passage of particles from the extracellular to the intra­cellular sector, and to intracellular movements [38].

Ventilatory parameters. Relaxation speed increases with respiratory frequency and tidal volume. Conversely it falls when respiration stops for several minutes. After death it decreases rapidly and after 20 min is no longer measurable [10].

Smoking. The influence of smoking on relaxation speed has been studied in man after inhalation of a magnetite tracer [4, 42].

Smokers have a relaxation speed higher than overall

MAGNETOPNEUMOGRAPHY: A GENERAL REVIEW 157

Mngn01ic field In arbil~ry units

so • arc-we lder c voluntary Inhalati on

30

20

10 -

OL---~--~----L---~--~~ -----0 10 20 30 40 50 60

Time In minutes

Fig. 7.-Relaxation cmves of an arc welder having inhaled ferromagnetic aerocontaminants some years before measurement and of a volunteer after inhalation of magnetite a few days before. The abscissa indicates time elapsed after cessation of magnetization. These curves are charac­teristic of magnetizing fields stronger than 8 kA ·m -I. For fields of lesser intensity the curves would fall more rapidly [I 0].

nonsmokers. Thus 20 min after magnetization ceases, the remanent magnetic signal decreases on average by 25% of its initial value in smokers and by only 8% in nonsmokers [42].

After initial inhalation of magnetite, FREEDMAN and eo-workers [4] repeated measurements of relaxation speed over time in smokers and nonsmokers. When these measurements are taken shortly after inhalation of magnetite, the initial part of the relaxation curve (from 0-5 min after magnetization ceases) shows no differ­ence between smokers and nonsmokers. With time, however, it becomes slower in smokers than in non­smokers. The latter part of the relaxation curve (from 5 min after magnetization ceases) is much slower for nonsmokers than for smokers and does not modify with time in either group.

The exact mechanism of the influence of smoking on relaxation speed is unknown. It may be explained by an increase in the number and/or activity of macroph­ages in smokers. As of now no study has been under­taken to examine possible negative correlation between relaxation and clearance speeds.

The nature of inhaled dust. There are no significant dif­ferences between the average relaxation speeds of the different groups of workers studied, (welders, foundry workers and iron and steelworkers) [6]. Relaxation speed seems, therefore, not to depend on the nature of inhaled dust.

Conclusion

This concise review of magnetopneumography has recapitulated the principles and applications of what is still an uncommontechnique. Being non-invasive, highly sensitive and reproducible, it allows measurement of lung dust load in individuals who have inhaled aerocontaminants with ferromagnetic content. At the present time the future prospects of magnetopneumato­graphy seem to lie in two fields:

i) Occupational pathology:

- Pursuance of the search for a correlation between magnetopneumographical data and the incidence of res­piratory pathologies by repeated measurements on work­ers from the most exposed groups. These studies will last several years and will allow very early diagnosis of individuals showing abnormally large lung dust loads. - The search for new groups of workers who might be examined by magnetopneumography. The first measure­ments performed by the present authors concerned one of these groups, namely makers of dental prostheses.

The development of such research demands close col­laboration between pneumologists, physiologists, scien­tists specializing in magnetism, and teams specializing in the identification and measurement of aerocontami­nants, the study of the environment, and occupational diseases.

ii) Physiology:

- Study in man and more especially in animals of the evolution in the lung of a magnetite tracer after expo­sure to various substances liable to accelerate or to slow its clearance. - Study of the parameters of relaxation, especially with regard to possible correlation with pulmonary clearance capacity. - Finally, the development of cytomagnetometry for the exploration of certain dynamic aspects of cellular physi­ology.

Appendix 1

Units of measurement used in magnetopneumography

The unit of magnetizing field and induced magneti­zation per unit volume in the international system is the ampere per metre (A·m-1) . Magnetic induction is expressed in Teslas (T) or Webers per m2 (Wb·m-2) ,

while the c.g.s. system's old unit, the gauss, was equal to 104 Teslas. Remanent magnetism may be expressed in amperes·m2 (A·m2), this being a unit of magnetic moment corresponding to the product of magnetic

158 V. LE GROS Ef AL

induction in A·m-1 by the volume of material in m3 •

The product of magnetic induction B by the surface S perpendicular to the field where B has at all points the same intensity as S is termed the magnetic induc­tion flux ~- The Weber (Wb) is the unit of magnetic flux induction in the international system. It is some­times used instead of the Tesla.

References

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La magneto-pneumographie: revue gerliraie. V. Le Gros, D. Lemaigre, C. Suon, J.P. Pozzi, F. Liot. RESUME: La magneto-pneumographie est !'etude du magnetisme remanent de particules ferro-magnetiques etrangeres intra-thoraciques apres magnetisation par un champ magnetique exteme. Vu la connaissance des caracteristiques magnetiques des particules inhalees, cette technique hautement sensible et non invasive permet de mesurer les charges de poussiere pulmonaire. De nombreux groupes de travailleurs ont ete examines de cette f~on, par exemple les soudeurs, les mineurs et les ouvriers de l'asbeste, des fonderies et des acieries. La magneto-pneumographie permet egalement !'analyse de la distribution des aeero-contaminants dans les differentes structures anatomiques et, en cas de repetition, !'etude des vitesses de clearance et de migration de ces par­ticules d'un site a !'autre. L'on a insistee sur !'importance de !'etude de l'affaiblissement du signal magnetique remanent avec le temps. Ce phenomene a court terme, appele relaxa­tion, semble hautement significatif pour !'etude des proprietes dynarniques de I'environnement immediat des particules ex­tra-pulmonaires, et specialement pour !'etude de l'activite macrophagique. Eur Respir J., 1989, 2, 149-159.