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Magnetic resonance imaging: A new window into industrial processing
Magnetic Resonance Imaging, Vol. IO, pp. 713-721, Printed in the USA. All rights reserved.
1992 Copyright
0
0730-725X/92 $5.00 + .Ml 1992 Pergamon Press Ltd.
l Session: Plenary Lecture
MAGNETIC RESONANCE IMAGING: A NEW WINDOW INTO INDUSTRIAL PROCESSING L.D. HALL* AND T.A. CARPENTER University of Cambridge School of Clinical Medicine, Herchel Smith Laboratory for Medicinal Chemistry, University Forvie Site, Robinson Way, Cambridge, CB2 2PZ, UK Although the most important use of nuclear magnetic resonance imaging (MRI) continues to be for diagnostic medicine, recognition is being gained for many nonmedical applications. Examples include the following areas: petrogeology, food, agriculture, polymers and polymer-composites, and pharmaceuticals. These areas all involve studies of species that have short spin-spin relaxation times, and consequently need far fast gradient switching. These technical details are discussed and typical applications given. Keywords: Nuclear magnetic resonance imaging; Nonmedical applications; Gradient switching; Spin-spin relaxation.
At the outset, it is important to make a clear-cut distinction between “academic science” and “industrial engineering” (Table 2). The objectives of the former can frequently be satisfied by demonstrating feasibility of a particular protocol or procedure on a sample carefully selected so that its NMR properties lie within a range easily acceptable and compatible with straightforward NMR measurements. In contrast, the demands of the practical reality of industrially based engineers start with a pre-defined set of materials, questions, or expectations, to which the NMR method has to conform if it is to be accepted. It is our experience that these two goals are hugely different, and can only be made coincident by a great deal of effort; in particular, the NMR-scientist has invariably to accept technical challenges that exceed those of normal academic expectation. Importantly too, industrial colleagues invariably need quantitative data, and protocols
INTRODUCTION The purpose of this article is to provide a global overview of the opportunities which exist for nuclear magnetic resonance (NMR) imaging (MRI) as an industrial tool in general, but with particular emphasis on the visualisation of industrial processes. Table 1 summarises the industrial areas in which we already have an active interest in Cambridge. These include objects which range from soft, wet tissues as in plants, animals and humans which are characterised by spin-spin relaxation times (7”-values) of many 100s of milliseconds (Fig. l), to hard materials containing small quantities of NMR active species that have T2 values of 1 msec or less; the latter provide a considerable challenge to the MRI method, especially if it is required to quantitate measurement of the concentration of the NMRactive species. Furthermore, the physical size of these objects ranges from a few millimetres diameter (plant stems) to many tens of cubic kilometres (as for oil-reservoir rocks in-situ!); hence it is not obvious what sort of magnet should be used, nor what class of MRI method. As a result, industrial applications of MRI pose a far wider range of challenges for the NMR scientist than does clinical MRI with its exclusive concentration on studies of one object (humans); and these opportunities are all the more exciting given that so little data are currently available in the literature.
Table 1. Summary of industrial areas for application of nuclear magnetic resonance imaging Agricultural, environmental, and soil sciences Biomedical and pharmaceutical sciences Food and nutritional sciences Materials and engineering sciences Petrogeological and constructional services 713
714
Magnetic Resonance Imaging 0 Volume 10, Number 5, 1992
Table 4. General interests in biomedical and pharmaceutical sciences Fraction of original magnetisation
20
40
60
80
Biochemistry (animals and humans) Drug-trials (animals and humans) Clinical radiology Patient assessment Veterinary medicine Human and animal nutrition
100
Time after excitation (ms)
Fig. 1. Graphical representation of relationship between plot of magnetisation intensity versus time for spin-spin relaxation times of 1000, 100, and 1 msec.
Table 5. General interests in food and nutritional sciences Authentication
Table 2. Concepts of interest to industry
of raw produce
Storage, ripening, packaging, transportation Food cooking processing (heating, microwave, freezing, mixing) Food texture evaluation
Quantitative information Resolution of spatial inhomogeneities Time resolution of dynamic processes Data for optimisation of new processes of new materials Academic motivations New NMR spin physics Novel data acquisition protocols
Human and animal nutrition Fat/water
ratio of animals and meat
Fat distribution
(animals, humans)
- -
Table 3. General interests in agricultural, environmental, and soil sciences
Table 6. Materals and engineering sciences
Spatial characterisation of pore structure (soil, plants, buildings) Optimisation of plant growth Breeding of low-fat animals Pollution of soil Air pollution damage (plants, buildings)
Polymer formation and processing Polymer morphology Polymer flow, rheology Composite formulation, processing Particulate settling and filtration Mass transport through defined geometries
that are equally applicable to all samples submitted, and not merely a sub-set carefully selected to minimise the technical demand. At first reading, the topics listed in Table 1 and Tables 3-7 may appear to be a bewildering, unrelated ar-
ray. Yet, it is our experience in Cambridge that the majority of them involve just a few intellectual themes, and that technical control of any one of the areas can be immediately adapted to the remainder, important members of those themes include the following:
Table 7. Petrogeological Characterisation Core laboratory Well head Downhole
of rock properties
and construction
services
Process optimisation
Mass transportation
Drilling mud formulation Filtration Cementation Acidisation Enhanced oil recovery
Flow Pefusion/imbibement Diffusion Drying
MRI: A new window into industrial processing 0 L.D. HALL AND T.A. CARPENTER
Visualisation of the NMR-active Component which is also “‘Mobile” The important point here is that the NMR-active species must have a sufficiently long spin relaxation time (T2 value, set) that its magnetisation can be created and detected in an MRI measurement. In practice it is trivially easy to obtain images from water in plant’ and animal tissues2 and in many softer texture foods,3 because it has T2 values of 100-1000 msec; the same is true for water in clean rock that has large pores. However, when the water is tightly bound to the porous matrix as in a grain of dry rice, or when it is located in small sized pores, or when it is in the presence of a paramagnetic species, its T2 value will be short and it will be hard to visualise by MRI. Indeed, bearing in mind that application of a frequency selective radio frequency used for slice-selection can require 10 msec, it may be that none of its magnetisation can be visualised by MRI. Technically, solution to the problems of this area require access to short gradient switching times.4 Additionally, advantage should be taken of all chances to increase the T2 value, either by studying the sample at an elevated temperature,5 or by sophisticated pulse NMR measurements summarised by later speakers in this conference. 6 Making Allowance for Magnetic Susceptibility of the Matrix A simple illustration of the potential image distortion which can be induced by variations in magnetic susceptibility is given in Fig. 2; as can be seen, substantial frequency changes can be induced, which result in image-distortions. Although these can be controlled, at least in principle, by use of appropriate image sequences and gradient strengths, this is a non-trivial task when dealing with materials of unknown composition and structure. In addition to spatial distortions, the internal magnetic field gradients associated with susceptibility variations constitutes an important source of image contrast associated with the effective spinspin relaxation rate. Quantitation of Image Intensity Variations of the concentration of an NMR-active species (C,), of its magnetisation (M,), and of its spinlattice (T, value) and spin-spin (T,-value) relaxation times can all contribute to the distribution of signal intensity of an NMR-image. Hence, for interpretation of image-contrast it is imperative to produce images in which the signal intensity of each voxel reflects just one of those parameters. These are referred to as “quantitative images” and can be achieved by analysis of the intensities of individual voxels from carefully
715
Fig. 2. Image of a 5-mm diameter glass tube filled with water, placed vertically in a dry bed of sand.
designed MRI sequences. Typically, a T, inversion recovery sequence is used as a front end to a series of MRI spin warp sequences; suitable data analysis will then produce an M, and a Tl value for every voxel in the image; similarly, A& and T2values can be mapped.7 We shall demonstrate their use later. An alternative motivation for quantitation is determination of the total concentration of the NMR active content in an object. in principle, this can be achieved by comparing the size of the NMR response obtained from the object, with that from a reference sample which has known content. Although this is trivially easy when the NMR active species has a long TT value, the task becomes increasingly difficult as the TZ+values decrease; indeed it becomes impossible when the loss of magnetisation is fast compared with the time required to sample it. We have developed methods which work to an accuracy of 3% for T; values of 80 psec or greater. Even so, the combination of that technology with rigorously quantitative measurements of relaxation times is not commonly available, and data acquisition is inevitably so time consuming that it is rarely compatible with living systems or those which change with time. Thus far we have discussed MRI as if all of the NMR active spins come from a single chemical species. Admittedly, water-only MRI, is the single most important measurements, yet many applied systems contain substantial quantities of organic molecules. The most important combination is “water-lipid” . . . water/oil
716
Magnetic Resonance Imaging 0 Volume 10, Number 5, 1992
in petro-geology, water/fat in humans or animals, and water/fat in many food systems. Providing that the system of interest has long T2 values, and hence chemical shift-resolved resonances, it is possible to obtain separate images from oil and from water using chemical shift resolved imaging methods.s This can be achieved by frequency-selective excitation of either the oil or the water image, or by saturation of the response from one or other. Alternatively, advantage can be taken of differences in relaxation times between the different species. The first industrial area for discussion is Food, and Table 5 summarises the general interests of those in the food industry. Evaluation of the raw produce itself is relatively easy using the same methodology as that originally developed for clinical MRI, relying on the fact that the magnetically active probe nucleus is water. With regard to “fresh produce,” a major industrial need is for improved methods for transporting the fresh produce so that it reaches the customer at its peak condition; another need is the preparation of “convenience” foods. The pair of slice images taken’ through an apple (Fig. 3) illustrate the problem of bruising of fruit and vegetables and the ease with which that damage can be visualised by MRI. The pair of images shown in Fig. 4 illustrateiO~” the visualisation of the changes induced by freezing, one of the commonly used methods for providing “convenience” vegetables. Neither of these demonstrations, however, sheds any insight as to the mechanism whereby the image contrast is induced, nor its interpretation. The first stage is to acquire images in which the imageintensity is dependent on a single NMR variable. For example, the images in Fig. 3 show that the bruise of
Fig. 4. Slice images taken through courgette: (A) fresh and (B) frozen-thawed. Resolution = 200 pm, TE = 4 set, TE = 35 msec, Slice thickness = 2 mm.
an apple is best visualised by the differences in T2 value compared with the normal tissues. Interpretation of the reasons for this can be based on modelling” the diffusion of the water within the cells of the tissues, and also of the changes in magnetic susceptibility of the sample due to the movement of the bulk water following thawing. The latter occurs because the ice-crystals formed when the water freezes, rupture the cells, thereby releasing some of the intracellular water from the cells into the interstitial space; as this occurs, air is displaced from those spaces and a result, the internal susceptibility differences in thawed courgette are far smaller than those in fresh tissues. Consequently, the diffusional movement of the water occurs against a background of smaller field gradients which are more evenly distributed; overall, this leads to a suppression of image contrast in the thawed tissues. One last example relevant to food storage, shown in Fig. 5, is the slice image through a chocolate bar in which the normal chocolate is clearly distinguishedI from that which has been warmed and then allowed to solidify. This contrast reflects the huge difference in the crystal morphology of the cocoa butter between the normal chocolate which has been prepared under carefully controlled thermal annealing conditions in the factory, compared with the random cooling rate in the
Fig. 3. Slice images taken through an apple. (A) Unbruised, and (B) bruised prior to measurement. TR = 4 set, TE = 35 msec, slice thickness = 2 mm, resolution = 250 pm.
laboratory. It is this sensitivity to changes in physicochemical environment of the probe nuclei which confers so much versatility to the MRI method. Figure 6 shows an experimental cavity for studying the heating (or cooling) of food; it comprises a glass, Dewared vessel approximately 16 cm in outer diameter, con-
MRI: A
new window into industrial processing 0 L.D.
HALL AND T.A.
717
CARPENTER
Fig. 5. Slice images through chocolate: (A) fresh and (B) after heating. TE = 9 msec, TR = 3 set, slice thickness = 3 mm, resolution = 230 pm.
tained inside a sine-spaced NMR resonant cavity, fitted with a source for heated air. This is designed for variable temperature studies of a range of materials including food. The series of six, slice-images taken through small meat pies (Fig. 7) illustrate several of those points. The pairs of images A/B, C/D, and E/F each correspond to the identical physical slice, but with chemical shift selectivity having been used to separate the water-only images A, C, E from the fat-only images B, D, F. In this case the discrimination was achieved using the Dixon pulse sequence but many other alternatives exist. The relatively low signal intensity from the fat in the pie-crust at ambient temperature (B) compared with that from the heated pie-crust (E,F) reflects the enhanced mobility, and hence the longer T2 value at the higher temperature. The ability to separately identify the location of fat and water inside a food, and any changes which occur during either storage or processing has several important implications. Fat is such an important ingredient in most cooked foods that its presence is vital to the acceptability of the product. Yet, with the ever increasing concern in most nations of the western world, with
Fig. 6. Photograph
of variable
temperature
probe.
the mortality and morbidity associated with cardiovascular diseases has come an awareness of the need for lower-fat diets, along with the need to use a greater proportion of unsaturated fat; this concern coincides with increasing demands for high quality foods which have traditional taste and texture, yet which can be obtained in convenient precooked portions that can be rapidly warmed or finished for the table. At present for many foods, these demands verge on total incompatibility. This will remain the case until the food industry develop completely new food formulations, and processes, for which purpose they require new analytical tools to map in space and time the physico-chemical structure and materials-texture of the new products so that they can make the foods have traditional qualities. We believe that MRI has a number of important roles to play in this context; especially, the already demonstrated sensitivity of the NMR parameters of water are extremely encouraging. The availability of hardware for heating large sam-
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Magnetic Resonance Imaging 0 Volume 10, Number 5, 1992
7. Images of meat pies, TR = 3 set, TE = 5 msec, slice thickness = 3 mm, resolutic m = 20( lrn.
ples inside the bore tube of a magnet is also of relevance to the polymer and polymer composite industries; two examples will indicate what can be achieved. The set of images shown14 in Fig. 8 are of the proton resonances of methyl methacrylate (MMA) contained in a mould heated to 65°C. At that temperature, the dibenzoyl peroxide dissolved in the MMA decomposes, and the resultant benzoyl radicals imitate the chain polymerisation reaction. The spin-warp method gives images which show the spatial distribution of the mobile MMA molecules; however, the protons of the polymer have such short T2values that they give zero signal in-
tensity. This image-contrast between “starting material” and “polymeric product” is a general one, which has great utility. For example, it enables pools of unreacted monomer or of only partially polymerised material, to be located whilst the polymerisation reaction is progressing; any such unevenness in the polymerisation process can lead to macroscopic imperfections in the final product; however, since these can often be detected by other means they are of less significance than other more subtle areas in which physical weaknesses or local strain are far more difficult to detect. It is these which are of particular concern to those
MRI:
A new window into industrial processing 0 L.D.
HALL AND T.A.
CARPENTER
719
Fig. 8. PMMA polymerisation through moulds. The time after filling the mould is given. This reaction took place at 60°C usin g Perkadox-16s as the initiator. (TE = 11 msec, TR = 210 msec, 2 averages, 128 x 256 pixels. No slice selection was used, and the thickness of the mould is determined by the O-ring (approximately 4.5 mm).
who have the task of optimising the development of new processes for fabricating high performance articles from the new materials now being invested. The formation of “stealth-bomber” from carbon-fibre reinforced epoxy-resin will serveI to illustrate this point. The images shown in Fig. 9 are from the proton resonance signals of the epoxy resin which are sufficiently mobile at 60°C to give a reasonable signal level in a spin-warp image obtained at a TE value of 8ms. The object is a series of spirals wound from ribbons of “pre preg,” that is carbon-fibre matt which had been impregnated with partially cured epoxyresin. Initially, no signal intensity is observed because the epoxy resin is too viscous; however, as the sample is warmed by a stream of hot air which impinges on the same from the lower left hand corner, the increased mobility of the polymer chains result in longer T2 values and sufficient signal intensity for a complete image to be obtained by the time that the entire sample has become heated. Of course, the enhanced mobility enables the polymerisation reaction to
commence, and the attendant loss of signal intensity indicates the advancing wave of polymerisation as it crosses the sample. At the end of the reaction the only signal intensity visualisable comes from the blocks of polystyrene used to hold the sample firm inside the cavity of the oven. CONCLUSIONS It is clear from even the small amount of work in the literature that MRI has great potential in many industrially important areas; in turn, more areas will challenge the MRI method to achieve new levels of performance and sophistication. Other papers associated with this meeting attest to the rapid progress that is being made in many laboratories; most of those will deal with problems of data acquisition in recognition that this is the first barrier to be overcome. However, if our experiences in Cambridge are as typical as we believe they are, then data management and processing also represent formidable problems which have
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Magnetic Resonance Imaging 0 Volume 10, Number 5, 1992
Fig. 9. Setting of carbon-fibre pre-preg. As the resin warms, the signal increases but then dies away again as the final cure phase results in a solid matrix. (TE = 8 msec, TR = 500 msec, 128 x 128 pixels, 8-mm slice thickness. The object is about 5
cm wide at its widest point).
been addressed by either those who practice MRI or those who manufacture the equipment. For example, using techniques such as SNAPSHOT FLASH it is possible to acquire 16 MBytes of data within 5 min, which represents a total of 2 GBytes in a typical 12-h working day; the logistics of archiving so much data are prodigious. Clearly interrogation and interpretation of the data can only be achieved by off-line data processing, and here it is our good fortune that the scientific workstations are now available at reasonable cost and with sufficient performance to cope with most conceivable tasks. Still lacking at this time is the software necessary for data processing - for image display the situation is satisfactory, but for quantitation, let alone modelling, there is a great need. If this is true for academic research, the situation is even more fraught for many potential industrial users whose real interests lie in the quantitative numerical conclusions from engineering and functional models, rather than the NMR parameters themselves. To give just one example, oil reserbarely
voir engineers wish to know the permeability of a piece of rock, not the Tr value of the brine contained therein. Successful solutions to challenges such as these will ensure that industrially oriented MRI will take its place alongside the already well established clinical MRI method. Acknowledgments-This work could not have been undertaken without a magnificent benefaction from Dr. Herchel Smith. Equally, we are indebted to many colleagues in industry whose technical needs have challenged us to produce new methodology, some of which is reported here.
REFERENCES 1. Sarafis, V.; Rumpel, H.; Pope, J.M.; Kuhn, W. Noninvasive histochemistry of plant materials by magnetic resonance microscopy. Protoplasma 159:70-73; 1990. 2. Moonen, C.T.W.; Van Zijl, P.C.M.; Frank, J.A.; Le Bihan, D.; Becker, E.D. Function magnetic resonance imaging in medicine and physiology. Science 250:53-61; 1990.
MRI: A
new window into industrial processing 0 L.D. HALLANDT.A. CARPENTER
3. McCarthy, M.J.; Kauten, R.J. Magnetic resonance imaging applications in food research. Trends Food Sci. Technol. 134-139; 1990. 4. Carpenter, T.A.; Hall, L.D.; Jezzard, P. Proton Mag-
netic resonance imaging of solid polymers using instrumentation designed for the liquid state. J. Magn. Reson. 84:383-387; 1989. 5. Jezzard, P.; Carpenter,
T.A.; Hall, L.D. Simple NMR imaging of solid polymers at elevated temperatures. Po-
Iym. Commun. 32174-76; 1991. 6. Jezzard, P.; Attard, J.J.; Carpenter,
T.A.; Hall, L.D. Nuclear magnetic resonance imaging in the solid state. Prog. Nucl. Mag. Reson. Spectroscopy 23:1-40;
1991.
7. Attard, J.; Hall, L.D.; Herrod, N.; Duce, S. Materials mapped with NMR. Physics World 4:41-45; 1991. 8. Hall, L.D.; Rajanayagam, V. Thin-slice, chemical-shift
imaging of oil and water in sandstone rock at 80 MHz. J. Magn. Reson. 74:139-146; 1987. 9. Duce, S.L.; Carpenter, T.A.; Hall, L.D. Nuclear magnetic resonance imaging of fresh and frozen courgettes. Journal of Food Engineering. 16165172; 1992. 10. Duce, S.L.; Carpenter, T.A.; Hall, L.D.; Hills, B.P. An
721
investigation of the origins of contrast in NMR spin echo images of plant tissue. Magn. Reson. Imaging lO(2): 289-297;
1992.
11. Hills, B.P.; Duce, S.L. The influence of chemical and diffusive exchange on Water Proton Transverse Relaxation in Plant Tissues. Magn. Reson. Imaging 8:321331; 1990. 12. Duce, S-L.; Carpenter,
T.A.; Hall, L.D. Nuclear magnetic resonance imaging of chocolate confectionery and the spatial detection of polymorphic states of cocoa butter in chocolate. Lebensm- W.&sU-Technol23545549;
1990. 13. Jackson, P.; Clayden, N.J. Magnetic resonance imaging
studies of the polymerisation
of methylmethacrylate.
Polymer International 24:139-143;
1991. 14. Carpenter, T.A.; Hall, L.D.; Jezzard, P.; Wiggins, C. J.
MRI Studies of In-situ polymerisation reactions at elevated temperatures, In: B. Blumich, W. Kuhn (Eds). NMR Microscopy: Methods and Applications in Materials Science, Agriculture and Biomedicine. Weinheim, Germany: VCH Publishers. (In press)
1992 Copyright
0
0730-725X/92 $5.00 + .Ml 1992 Pergamon Press Ltd.
l Session: Plenary Lecture
MAGNETIC RESONANCE IMAGING: A NEW WINDOW INTO INDUSTRIAL PROCESSING L.D. HALL* AND T.A. CARPENTER University of Cambridge School of Clinical Medicine, Herchel Smith Laboratory for Medicinal Chemistry, University Forvie Site, Robinson Way, Cambridge, CB2 2PZ, UK Although the most important use of nuclear magnetic resonance imaging (MRI) continues to be for diagnostic medicine, recognition is being gained for many nonmedical applications. Examples include the following areas: petrogeology, food, agriculture, polymers and polymer-composites, and pharmaceuticals. These areas all involve studies of species that have short spin-spin relaxation times, and consequently need far fast gradient switching. These technical details are discussed and typical applications given. Keywords: Nuclear magnetic resonance imaging; Nonmedical applications; Gradient switching; Spin-spin relaxation.
At the outset, it is important to make a clear-cut distinction between “academic science” and “industrial engineering” (Table 2). The objectives of the former can frequently be satisfied by demonstrating feasibility of a particular protocol or procedure on a sample carefully selected so that its NMR properties lie within a range easily acceptable and compatible with straightforward NMR measurements. In contrast, the demands of the practical reality of industrially based engineers start with a pre-defined set of materials, questions, or expectations, to which the NMR method has to conform if it is to be accepted. It is our experience that these two goals are hugely different, and can only be made coincident by a great deal of effort; in particular, the NMR-scientist has invariably to accept technical challenges that exceed those of normal academic expectation. Importantly too, industrial colleagues invariably need quantitative data, and protocols
INTRODUCTION The purpose of this article is to provide a global overview of the opportunities which exist for nuclear magnetic resonance (NMR) imaging (MRI) as an industrial tool in general, but with particular emphasis on the visualisation of industrial processes. Table 1 summarises the industrial areas in which we already have an active interest in Cambridge. These include objects which range from soft, wet tissues as in plants, animals and humans which are characterised by spin-spin relaxation times (7”-values) of many 100s of milliseconds (Fig. l), to hard materials containing small quantities of NMR active species that have T2 values of 1 msec or less; the latter provide a considerable challenge to the MRI method, especially if it is required to quantitate measurement of the concentration of the NMRactive species. Furthermore, the physical size of these objects ranges from a few millimetres diameter (plant stems) to many tens of cubic kilometres (as for oil-reservoir rocks in-situ!); hence it is not obvious what sort of magnet should be used, nor what class of MRI method. As a result, industrial applications of MRI pose a far wider range of challenges for the NMR scientist than does clinical MRI with its exclusive concentration on studies of one object (humans); and these opportunities are all the more exciting given that so little data are currently available in the literature.
Table 1. Summary of industrial areas for application of nuclear magnetic resonance imaging Agricultural, environmental, and soil sciences Biomedical and pharmaceutical sciences Food and nutritional sciences Materials and engineering sciences Petrogeological and constructional services 713
714
Magnetic Resonance Imaging 0 Volume 10, Number 5, 1992
Table 4. General interests in biomedical and pharmaceutical sciences Fraction of original magnetisation
20
40
60
80
Biochemistry (animals and humans) Drug-trials (animals and humans) Clinical radiology Patient assessment Veterinary medicine Human and animal nutrition
100
Time after excitation (ms)
Fig. 1. Graphical representation of relationship between plot of magnetisation intensity versus time for spin-spin relaxation times of 1000, 100, and 1 msec.
Table 5. General interests in food and nutritional sciences Authentication
Table 2. Concepts of interest to industry
of raw produce
Storage, ripening, packaging, transportation Food cooking processing (heating, microwave, freezing, mixing) Food texture evaluation
Quantitative information Resolution of spatial inhomogeneities Time resolution of dynamic processes Data for optimisation of new processes of new materials Academic motivations New NMR spin physics Novel data acquisition protocols
Human and animal nutrition Fat/water
ratio of animals and meat
Fat distribution
(animals, humans)
- -
Table 3. General interests in agricultural, environmental, and soil sciences
Table 6. Materals and engineering sciences
Spatial characterisation of pore structure (soil, plants, buildings) Optimisation of plant growth Breeding of low-fat animals Pollution of soil Air pollution damage (plants, buildings)
Polymer formation and processing Polymer morphology Polymer flow, rheology Composite formulation, processing Particulate settling and filtration Mass transport through defined geometries
that are equally applicable to all samples submitted, and not merely a sub-set carefully selected to minimise the technical demand. At first reading, the topics listed in Table 1 and Tables 3-7 may appear to be a bewildering, unrelated ar-
ray. Yet, it is our experience in Cambridge that the majority of them involve just a few intellectual themes, and that technical control of any one of the areas can be immediately adapted to the remainder, important members of those themes include the following:
Table 7. Petrogeological Characterisation Core laboratory Well head Downhole
of rock properties
and construction
services
Process optimisation
Mass transportation
Drilling mud formulation Filtration Cementation Acidisation Enhanced oil recovery
Flow Pefusion/imbibement Diffusion Drying
MRI: A new window into industrial processing 0 L.D. HALL AND T.A. CARPENTER
Visualisation of the NMR-active Component which is also “‘Mobile” The important point here is that the NMR-active species must have a sufficiently long spin relaxation time (T2 value, set) that its magnetisation can be created and detected in an MRI measurement. In practice it is trivially easy to obtain images from water in plant’ and animal tissues2 and in many softer texture foods,3 because it has T2 values of 100-1000 msec; the same is true for water in clean rock that has large pores. However, when the water is tightly bound to the porous matrix as in a grain of dry rice, or when it is located in small sized pores, or when it is in the presence of a paramagnetic species, its T2 value will be short and it will be hard to visualise by MRI. Indeed, bearing in mind that application of a frequency selective radio frequency used for slice-selection can require 10 msec, it may be that none of its magnetisation can be visualised by MRI. Technically, solution to the problems of this area require access to short gradient switching times.4 Additionally, advantage should be taken of all chances to increase the T2 value, either by studying the sample at an elevated temperature,5 or by sophisticated pulse NMR measurements summarised by later speakers in this conference. 6 Making Allowance for Magnetic Susceptibility of the Matrix A simple illustration of the potential image distortion which can be induced by variations in magnetic susceptibility is given in Fig. 2; as can be seen, substantial frequency changes can be induced, which result in image-distortions. Although these can be controlled, at least in principle, by use of appropriate image sequences and gradient strengths, this is a non-trivial task when dealing with materials of unknown composition and structure. In addition to spatial distortions, the internal magnetic field gradients associated with susceptibility variations constitutes an important source of image contrast associated with the effective spinspin relaxation rate. Quantitation of Image Intensity Variations of the concentration of an NMR-active species (C,), of its magnetisation (M,), and of its spinlattice (T, value) and spin-spin (T,-value) relaxation times can all contribute to the distribution of signal intensity of an NMR-image. Hence, for interpretation of image-contrast it is imperative to produce images in which the signal intensity of each voxel reflects just one of those parameters. These are referred to as “quantitative images” and can be achieved by analysis of the intensities of individual voxels from carefully
715
Fig. 2. Image of a 5-mm diameter glass tube filled with water, placed vertically in a dry bed of sand.
designed MRI sequences. Typically, a T, inversion recovery sequence is used as a front end to a series of MRI spin warp sequences; suitable data analysis will then produce an M, and a Tl value for every voxel in the image; similarly, A& and T2values can be mapped.7 We shall demonstrate their use later. An alternative motivation for quantitation is determination of the total concentration of the NMR active content in an object. in principle, this can be achieved by comparing the size of the NMR response obtained from the object, with that from a reference sample which has known content. Although this is trivially easy when the NMR active species has a long TT value, the task becomes increasingly difficult as the TZ+values decrease; indeed it becomes impossible when the loss of magnetisation is fast compared with the time required to sample it. We have developed methods which work to an accuracy of 3% for T; values of 80 psec or greater. Even so, the combination of that technology with rigorously quantitative measurements of relaxation times is not commonly available, and data acquisition is inevitably so time consuming that it is rarely compatible with living systems or those which change with time. Thus far we have discussed MRI as if all of the NMR active spins come from a single chemical species. Admittedly, water-only MRI, is the single most important measurements, yet many applied systems contain substantial quantities of organic molecules. The most important combination is “water-lipid” . . . water/oil
716
Magnetic Resonance Imaging 0 Volume 10, Number 5, 1992
in petro-geology, water/fat in humans or animals, and water/fat in many food systems. Providing that the system of interest has long T2 values, and hence chemical shift-resolved resonances, it is possible to obtain separate images from oil and from water using chemical shift resolved imaging methods.s This can be achieved by frequency-selective excitation of either the oil or the water image, or by saturation of the response from one or other. Alternatively, advantage can be taken of differences in relaxation times between the different species. The first industrial area for discussion is Food, and Table 5 summarises the general interests of those in the food industry. Evaluation of the raw produce itself is relatively easy using the same methodology as that originally developed for clinical MRI, relying on the fact that the magnetically active probe nucleus is water. With regard to “fresh produce,” a major industrial need is for improved methods for transporting the fresh produce so that it reaches the customer at its peak condition; another need is the preparation of “convenience” foods. The pair of slice images taken’ through an apple (Fig. 3) illustrate the problem of bruising of fruit and vegetables and the ease with which that damage can be visualised by MRI. The pair of images shown in Fig. 4 illustrateiO~” the visualisation of the changes induced by freezing, one of the commonly used methods for providing “convenience” vegetables. Neither of these demonstrations, however, sheds any insight as to the mechanism whereby the image contrast is induced, nor its interpretation. The first stage is to acquire images in which the imageintensity is dependent on a single NMR variable. For example, the images in Fig. 3 show that the bruise of
Fig. 4. Slice images taken through courgette: (A) fresh and (B) frozen-thawed. Resolution = 200 pm, TE = 4 set, TE = 35 msec, Slice thickness = 2 mm.
an apple is best visualised by the differences in T2 value compared with the normal tissues. Interpretation of the reasons for this can be based on modelling” the diffusion of the water within the cells of the tissues, and also of the changes in magnetic susceptibility of the sample due to the movement of the bulk water following thawing. The latter occurs because the ice-crystals formed when the water freezes, rupture the cells, thereby releasing some of the intracellular water from the cells into the interstitial space; as this occurs, air is displaced from those spaces and a result, the internal susceptibility differences in thawed courgette are far smaller than those in fresh tissues. Consequently, the diffusional movement of the water occurs against a background of smaller field gradients which are more evenly distributed; overall, this leads to a suppression of image contrast in the thawed tissues. One last example relevant to food storage, shown in Fig. 5, is the slice image through a chocolate bar in which the normal chocolate is clearly distinguishedI from that which has been warmed and then allowed to solidify. This contrast reflects the huge difference in the crystal morphology of the cocoa butter between the normal chocolate which has been prepared under carefully controlled thermal annealing conditions in the factory, compared with the random cooling rate in the
Fig. 3. Slice images taken through an apple. (A) Unbruised, and (B) bruised prior to measurement. TR = 4 set, TE = 35 msec, slice thickness = 2 mm, resolution = 250 pm.
laboratory. It is this sensitivity to changes in physicochemical environment of the probe nuclei which confers so much versatility to the MRI method. Figure 6 shows an experimental cavity for studying the heating (or cooling) of food; it comprises a glass, Dewared vessel approximately 16 cm in outer diameter, con-
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Fig. 5. Slice images through chocolate: (A) fresh and (B) after heating. TE = 9 msec, TR = 3 set, slice thickness = 3 mm, resolution = 230 pm.
tained inside a sine-spaced NMR resonant cavity, fitted with a source for heated air. This is designed for variable temperature studies of a range of materials including food. The series of six, slice-images taken through small meat pies (Fig. 7) illustrate several of those points. The pairs of images A/B, C/D, and E/F each correspond to the identical physical slice, but with chemical shift selectivity having been used to separate the water-only images A, C, E from the fat-only images B, D, F. In this case the discrimination was achieved using the Dixon pulse sequence but many other alternatives exist. The relatively low signal intensity from the fat in the pie-crust at ambient temperature (B) compared with that from the heated pie-crust (E,F) reflects the enhanced mobility, and hence the longer T2 value at the higher temperature. The ability to separately identify the location of fat and water inside a food, and any changes which occur during either storage or processing has several important implications. Fat is such an important ingredient in most cooked foods that its presence is vital to the acceptability of the product. Yet, with the ever increasing concern in most nations of the western world, with
Fig. 6. Photograph
of variable
temperature
probe.
the mortality and morbidity associated with cardiovascular diseases has come an awareness of the need for lower-fat diets, along with the need to use a greater proportion of unsaturated fat; this concern coincides with increasing demands for high quality foods which have traditional taste and texture, yet which can be obtained in convenient precooked portions that can be rapidly warmed or finished for the table. At present for many foods, these demands verge on total incompatibility. This will remain the case until the food industry develop completely new food formulations, and processes, for which purpose they require new analytical tools to map in space and time the physico-chemical structure and materials-texture of the new products so that they can make the foods have traditional qualities. We believe that MRI has a number of important roles to play in this context; especially, the already demonstrated sensitivity of the NMR parameters of water are extremely encouraging. The availability of hardware for heating large sam-
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7. Images of meat pies, TR = 3 set, TE = 5 msec, slice thickness = 3 mm, resolutic m = 20( lrn.
ples inside the bore tube of a magnet is also of relevance to the polymer and polymer composite industries; two examples will indicate what can be achieved. The set of images shown14 in Fig. 8 are of the proton resonances of methyl methacrylate (MMA) contained in a mould heated to 65°C. At that temperature, the dibenzoyl peroxide dissolved in the MMA decomposes, and the resultant benzoyl radicals imitate the chain polymerisation reaction. The spin-warp method gives images which show the spatial distribution of the mobile MMA molecules; however, the protons of the polymer have such short T2values that they give zero signal in-
tensity. This image-contrast between “starting material” and “polymeric product” is a general one, which has great utility. For example, it enables pools of unreacted monomer or of only partially polymerised material, to be located whilst the polymerisation reaction is progressing; any such unevenness in the polymerisation process can lead to macroscopic imperfections in the final product; however, since these can often be detected by other means they are of less significance than other more subtle areas in which physical weaknesses or local strain are far more difficult to detect. It is these which are of particular concern to those
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Fig. 8. PMMA polymerisation through moulds. The time after filling the mould is given. This reaction took place at 60°C usin g Perkadox-16s as the initiator. (TE = 11 msec, TR = 210 msec, 2 averages, 128 x 256 pixels. No slice selection was used, and the thickness of the mould is determined by the O-ring (approximately 4.5 mm).
who have the task of optimising the development of new processes for fabricating high performance articles from the new materials now being invested. The formation of “stealth-bomber” from carbon-fibre reinforced epoxy-resin will serveI to illustrate this point. The images shown in Fig. 9 are from the proton resonance signals of the epoxy resin which are sufficiently mobile at 60°C to give a reasonable signal level in a spin-warp image obtained at a TE value of 8ms. The object is a series of spirals wound from ribbons of “pre preg,” that is carbon-fibre matt which had been impregnated with partially cured epoxyresin. Initially, no signal intensity is observed because the epoxy resin is too viscous; however, as the sample is warmed by a stream of hot air which impinges on the same from the lower left hand corner, the increased mobility of the polymer chains result in longer T2 values and sufficient signal intensity for a complete image to be obtained by the time that the entire sample has become heated. Of course, the enhanced mobility enables the polymerisation reaction to
commence, and the attendant loss of signal intensity indicates the advancing wave of polymerisation as it crosses the sample. At the end of the reaction the only signal intensity visualisable comes from the blocks of polystyrene used to hold the sample firm inside the cavity of the oven. CONCLUSIONS It is clear from even the small amount of work in the literature that MRI has great potential in many industrially important areas; in turn, more areas will challenge the MRI method to achieve new levels of performance and sophistication. Other papers associated with this meeting attest to the rapid progress that is being made in many laboratories; most of those will deal with problems of data acquisition in recognition that this is the first barrier to be overcome. However, if our experiences in Cambridge are as typical as we believe they are, then data management and processing also represent formidable problems which have
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Fig. 9. Setting of carbon-fibre pre-preg. As the resin warms, the signal increases but then dies away again as the final cure phase results in a solid matrix. (TE = 8 msec, TR = 500 msec, 128 x 128 pixels, 8-mm slice thickness. The object is about 5
cm wide at its widest point).
been addressed by either those who practice MRI or those who manufacture the equipment. For example, using techniques such as SNAPSHOT FLASH it is possible to acquire 16 MBytes of data within 5 min, which represents a total of 2 GBytes in a typical 12-h working day; the logistics of archiving so much data are prodigious. Clearly interrogation and interpretation of the data can only be achieved by off-line data processing, and here it is our good fortune that the scientific workstations are now available at reasonable cost and with sufficient performance to cope with most conceivable tasks. Still lacking at this time is the software necessary for data processing - for image display the situation is satisfactory, but for quantitation, let alone modelling, there is a great need. If this is true for academic research, the situation is even more fraught for many potential industrial users whose real interests lie in the quantitative numerical conclusions from engineering and functional models, rather than the NMR parameters themselves. To give just one example, oil reserbarely
voir engineers wish to know the permeability of a piece of rock, not the Tr value of the brine contained therein. Successful solutions to challenges such as these will ensure that industrially oriented MRI will take its place alongside the already well established clinical MRI method. Acknowledgments-This work could not have been undertaken without a magnificent benefaction from Dr. Herchel Smith. Equally, we are indebted to many colleagues in industry whose technical needs have challenged us to produce new methodology, some of which is reported here.
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