October 1991, Volume 41, Issue 10

Review Articles

NUCLEAR MAGNETIC RESONANCE IMAGING (MRI)

S. Javaid Khurshid  ( Nuclear Chemistry Division, PINSTECH, P.O. Nilore, Islamabad. )
Amin M. Hussain  ( Head, Biosciences, Pakistan Atomic Energy Commission, Islamabad. )

ABSTRACT

This article discusses the basic concepts of Magnetic Resonance Imaging (MRI) with the intention to introduce the subject to uninitiated. The MRI technique is a powerful noninvasive probe of the body’s internal anatomy. In MAI, the images are produced not by X-rays, but through the use of non-ionizing radio waves that stimulate transitions between spin states of nuclei in a magnetic field when passed through the body. The time required for the nucleus to return to equilibrium gives information about the environment of that nucleus. In this way tissue abnormalities can be determined in vivo. This article covers the basis of MRI phenomena, the concept of magnetic moment of the sample, NMR exalation and emission and the equipment necessary to observe these NMR properties. The primary agents used to increase tissue contrast in MRI are also mentioned. Finally the importance and prospects of this technique in Pakistan have been discussed (JPMA 41: 259, 1991).

INTRODUCTION

Scientists prefer to examine the biochemical ac­tivity of living systems without disturbing its life and growth. MRI has transformed that dream into reality by which scientists can examine the metabolism of an intact cell, organ and even whole organism without disturbing, cutting or damaging the tissues. This new, exciting and non-invasive technique has enabled the diagnosis of a variety of muscular and vascular diseases, to identify cancerous tissues and to monitor the health of the transplant. The MIII also offers a new powerful probe of the body’s internal anatomy and function. There are two major approaches, the first one is the generation of high resolution anatomical images which reflects the nuclear density distribution or spatial variation at the molecular level and chemical environments of the nuclei 1H which is the most abundant in biological tissues and prominent in magnetic qualities. When a non-uniform magnetic field is applied across a section of body, the hydrogen nuclei present in varying concentration in the section are tagged with different frequencies, and are processed to give an image. The second major approach is an analytical. Scientists prefer to examine the biochemical ac­tivity of living systems without disturbing its life and growth. MRI has transformed that dream into reality by which scientists can examine the metabolism of an intact cell, organ and even whole organism without disturbing, cutting or damaging the tissues. This new, exciting and non-invasive technique has enabled the diagnosis of a variety of muscular and vascular diseases, to identify cancerous tissues and to monitor the health of the transplant. The MIII also offers a new powerful probe of the body’s internal anatomy and function. There are two major approaches, the first one is the generation of high resolution anatomical images which reflects the nuclear density distribution or spatial variation at the molecular level and chemical environments of the nuclei ‘H which is the most abundant in biological tissues and prominent in magnetic qualities. When a non-uniform magnetic field is applied across a section of body, the hydrogen nuclei present in varying concentration in the section are tagged with different frequencies, and are processed to give an image. The second major approach is an analytical technique using 31P NMR spectroscopy for identification and quantification of the most abundant metabolites in various tissues. Changes in the levels of these metabolites and intracellular cytoplasmic pH can be followed in various ischaemic and hypoxic conditions to monitor metabolic response to stress situation and to diagnose inborn errors of metabolism, The historical develop­ment, conceptual basis and the application of various MM techniques are discussed.

PERSPECTWE

NMR was first observed by Purcell1 and Bloch2 in 1946 who received the Nobel prize in 1952. They developed NMR studies of liquids and solids that have never been since used as powerful tools to identify and determine the structure, conformational and motional properties of the simplest to the most complex molecules and their phases. The possibility of obtaining pictures or images of spatial distribution of NMR signals was first demonstrated in 19733. Bloch observed a strong NMR signals from his finger placed in the detector coil of the apparatus4. Gabillard investigated one dimensional dis­tribution of NMR signals5,6 Singer conducted blood flow experiment7 using NMR in 1959 and Damadian observed elevated NMR relaxation time in cancerous tissues8 in vitro in 1971. Damadian’s observation and the extensive in vitro studies of tissue relaxation times provided an early basis that MM can provide information of medical and biological importance. It should be noted that the use of pulsed and static magnetic field gradients in NMR is an essential ingredient of all MM techniques9-12. After Lauterbur’s work, in­dividual groups led by Mansfield13-16, Hinshaw17-19, Hutchison20 and Ernst21-22 devised and demonstrated several alternative MRI schemes. One of the first dedicated large scale imaging system was completed by Hinshaw in 1977, yielding promising proton imaging results of human forearm and live mammals upto 8cm in diameter23-28. Mansfield and coworkers also achieved improvements in images of finger in vivo MRI scans29-35, MM scan of human head and body were also produced36-44. Other groups were also actively involved with MRI45-52. The imaging NMR parameters other than nuclear density and relaxation times have also received attention; schemes for imaging or generating chemical shift spectra have also been devised53-57. This technique can also be used to monitor metabolic state of intact biological tissues58 and to image blood flow59. The recent tech­nological advances in MRI have proved it as a promising modality in children due to lack of radiation exposure, superior anatomic resolution and exquisite soft tissue contrast capability60. MM seems to be advantageous over CT in a wide spectrum of central nervous system (CNS), abdomen, heart and urinary tract problems61.
Nuclear Magnetic Resonance Imaging technique
MM relies on atomic nuclei such as hydrogen with an odd number of protons or neutrons, which are electrically charged and act like a small magnet possess­ing a magnetic moment. An externally applied magnetic field rotates this magnetic moment towards the direction of the magnetic field and also aligns them. However, they wobble at a specific rate of frequency. The stronger the magnetic field, the greater the frequency. If a radiofrequency is aimed at these protons, it excites them and changes the alignment of their nuclei. When the radiofrequency is switched off the nuclei spiral back into place and realign themselves within milli seconds transmitting a small electric or radio signal of their own. A computer translates these faint signals into an image of the area scanned. The image reveals varying densities of the hydrogen atom and their interaction with surrounding tissues in a cross section of the body and also relaxation times (T1 = spin-lattice, T2 = spin-spin) which are different for different tissues depending on the biological state. Scientists chose hydrogen as basis for MM scanning because of its abundance in the body and its prominent magnetic qualities. Since hydrogen reflects water con­tents, doctors can use the image to make distinctions between tissues. Lauterbur pioneered3,62,63 the work that produced images from NMR specter by taking a series of projections at different gradient orientations and superimposing them- a two or three dimensional image can thus be produced37,38. This technique is called zeugmatography where zeugma means to join together. A number of other methods of MIIT have been suggested64 some of which place more reliance on NMR spectra and less on computational power. These methods can be roughly grouped in terms of the way they build up cross-sectional images, such as point to point, line by line or a whole cross-section at one time. The point to point technique was explored early in the development of MM by Damadian and asso­ciates35,65,66 who used a static magnetic field distribution that was uniform only over a small, well localized region. The sample in question is moved step by step to cause a small homogeneous region to be scanned. Hinshaw’s single sensitive point technique17,18,67 brought about three orthogonal oscillating field gradients which en­sured that the detected signals came from the spatial region of time dependent field at the intersection of null planes of oscillating ingredients. The point by point technique has a double disadvantage; first it is very slow and dependent on weak signals arising from small volume, and second it requires much bigger detection coil. However, the technique is flexible to provide well localized measurements and it is also possible to obtain images without the help of a computer. The line by line scan technique23,29,46 has an advantage of both time and signal size over point to point method. The common feature of line scan method is that by means of various NMR maneuvers, it arranges for the only detectable signals to originate along unique line with the prescribed cross section of the sample. This will ensure NMR frequency spectrum, representing the den­sity of resonant nuclei at each point along the line. Successive lines then generate the cross section in a manner similar to a television picture. Hutchison68 also proposed an alternative selective irradiation line scan scheme. The construction of an image by this technique reduces the imaging time from the order of hours to several minutes. However, this technique must be differentiated from image reconstruc­tion and projection62, which detects the signals from image generation. The technique of planar spin29-31 imaging, multiple line scan method69 or echo planner70,71 imaging, generate an image from a single shot of the planar response. More than twenty types of imaging techniques have been proposed and tested, some of them are mentioned below, but no method has proved universally acceptable.
1)  Field Focusing Nuclear Magnetic Resonance (FONAR), 2) Image Reconstruction from ID Projections. 3) Direct 2D Projection Imaging, 4) Selective Irradiation, 5) Sensitive Region Method, 6) Inversion Recovery, 7) Echo-planar, 8) Spin Warp, 9) Fourier Zeugmatography, 10) Rotating Frame Zeugmatography, 11) Direct 3D Imaging. The diversity of potential imaging raises many questions for equipment manufacturers as well as for users72. The solution of these problems will involve testing clinical applications and situations and certainly some compromises. It is unlikely that any one machine will be able to provide all these solutions. In spite of this variability, there are some common elements in all Mill scanners which are discussed.
Nuclear Magnetic Resonance Imaging equipment
The imaging system consists of a number of elements and each plays an important role. The principal components are primary magnets, magnetic gradient, radio equipment, computer data storage and display system. In addition other components such as data manipulation systems, amplifiers, AD converter, com­puter memory system, magnetic tape unit, matrix camera and display unit are also involved. A schematic descrip­tion of these major sub-systems of Mill scanners is shown in Figure.

The role of computer data storag and display sub-systems are identical as in CT imaging, therefore, these are familiar to most of the medical imaging personnel. Only the remaining sub-systems are discussed here.
1. Magnetic System - The magnet is definitely the key element in any Mill sub-systems as the specifica­tions required place great demands. The three types of magnets used in clinical Mill machines are electromagnet, permanent magnet and supercon­ducting magnet.
2. Gradient Field Subsystem-The purpose of this sub­system is to create homogeneity and control gradients in the magnet field to allow spatial localization of the NMR signals.
3. Radio equipment subsystem - This consists of a radio transmitter, a power amplifier, transmitter-receiver coil, preamplifier and receiver. It also in­cludes systems of converting the analog radio signal into digital form that can be processed and analyzed by the computer to form the final signal of the size and shape of RE energy from patients body.
Contrast agents In MRI
Contrast agents play an important role as their need arose due to overlapping of relaxation times in different pathological conditions (abscesses, malignant neoplas­ma, benign tumours) which do not provide absolute and specific diagnostic information73,74. This low image inten­sity can be altered by the use of paramagnetic agents and thus increase the needed diagnostic specificity. These paramagnetic contrast agents alter the mag­netic properties of the nuclei being observed in the image without being detected. The effectiveness of Mill con­trast agents depends on its ability to change the NMR properties (nuclear spin density and relaxation time T1, and T2) of the nucleus being studied. The principal proton species used in Mill is H2O, the contrast agents generally reduce T1, and H20. These contrast agents are paramagnetic, mostly metals in nature and usually pos­sessing incomplete d and orbitals. Ions of these metals usually contains 1-7 unpaired electrons (Table)75.

The strength of a magnetic moment is proportional to the number of these unpaired electrons which is one of the factors that determines relaxation time. Water molecules binds directly to these ions, leading to drastic decrease in H2O relaxation time. Other paramagnetic species used include free radicals and oxygen76-77. These contrast agents have been reviewed in detail78-87. Clinical status of Magnetic Resonance Imaging in the world and its prospects in Pakistan. The growing awareness and enthusiasm88 in nuclear magnetic resonance imaging (Mill) led to the most momentous development in diagnostic imaging. Mill reflects on the behaviour of hydrogen atoms and focuses at water molecules, therefore the organs with water density higher than other tissues appear brighter. This allows Mill to do certain things better than CT scanners. This technique provides information at the cellular level and is very successful in the anatomical format and also appears to have appreciable promise in the physiological and metabolic areas. No definite imaging protocols have been estab­lished yet. Performing MR images demand multiple choice of protocols such as acquisition parameters, imaging plane orientation, type of coil, slice thickness, matrix size and number of excitations. These parameters can provide a foundation and practical basis for inter­pretation of Mill which generate a series of slices in the chosen plane (axial, sagittal, posterior). In practice the choice of plane and their order depends on the organ of the body. The examination of spinal cord begins with sagittal sections followed by axial slices. For the ab­dominal organs (liver, spleen, pancreas, kidney, adrenals) and the genitopelvic organs, two planes are often sufficient. In pathology such as an abnormality in craniocervical junction, such as Chiari malformation, can be imaged best in sagittal plane. The extent of a tumor in a long bone can be demonstrated by sections in a plane parallel to the diaphysis. Preoperative brain workup is an indication for assessment in all three orthogonal planes, in order to give the surgeon maximum number of anatomical indications. The fast imaging technique in Mill makes it possible to form primary scans within seconds. The work done and its clinical application to entire spectrum of medical disorders in the world is very exciting. In central nervous system Mill provides struc­tural detail not attained by other modalities. The diagnos­tic significance of Mill is quite clearly evident in neurol­ogy89, the head90-93 and in spinal column94-96. MRI is superior to CT in delineating the cortic such due to lack of beam hardening. Mill provides dramatic discrimina­tion of grey and white matter and is more sensitive in detecting white matter hyperintensities97. MRI provides excellent delineation of brain tumors of many varieties than CT due to better resolution, lack of beam hardening or streak artifacts and multiple imaging capabilities. Inparticular Mill is superior in evaluating cerebellum and brain stem while there may be severe artifacts on CT. Mill can distinctly demonstrate hemorphagic infarcts, which may be missed on CT. MIII technique has proved to be ideally suited due to its ability to depict soft tissues in high contrast such as in spinal cord, thus reducing the painful procedure of injecting a contrast agent into the tissues for X-ray. The Mill also showed its worth in heart media stinum liver , gallbladder , pancreas kidney108, adrenals109-111 and other disorders. In case of mediastinum it offers an advantage over CT in that the major blood vessels are easily identified and the thymus is clearly delineated over non displaced mediastinal structures MRI is also promising modality for pediatric imag­ing112 due to lack of radiation exposure, superior anatomic resolution and exquisite soft tissue contrast capability. Mill seems to be advantageous over CT in a wide spectrum of pediatric brain disorders, with the exception of acute head trauma and herpes en­cephalitis112. MIII is superb for demonstrating Arnold­Chiari and Dandy-Walker malformations112. Recent studies show that Mill may be more sensi­tive than CT for the early detection of avascular ne­crosis112 and in non-invasive measurement of dynamics and elasticity of caratoid artery113. Direct blood flow measurement is also accessible in MRI through variations in signal intensity of blood in the major vessels. The pulsatile nature of blood flow, and indeed the heart, can be observed in images collected synchronously with respect to the cardiac cycle. Sequence of such image show the dynamic function of the heart, potentially providing invaluable assistance in assessment of patients suffering from heart disease. Mifi is very sensitive but has its limitation in not being specific since motion badly degrades the images114. Mill has some reservation in patients with medical prostheses of metal construction, particularly pacemakers whose operation could be affected by the pulses or movements within the static field115. Beside this, neurostimulators and ferromagnetic implants such as (intracranial vasicular clips, metallic foreign bodies in soft tissues etc.) are likely to be displaced. Some metallic implants such as stainless steel dental hardware, hip prosthesis, Harrington rod, etc. also cause image ar­tifacts116. It can be assumed that the role of Mill in diagnostic radiology is very bright in future. This technique has already been adopted by all the big medical institutes in the USA, Canada and Europe. Currently more than 12 companies are building Mill systems and today more than 400 machines have been installed and are operating in the United States. This explosive growth reflects Mill’s wonderful diagnostic results. The other developed and less developed countries are in the process of acquiring this technique. At present it costs more than 2.5 million US dollars for equipment plus half a million dollars for a room completely insulated from external radiofrequen­cy. Mill can play very useful role in the health sector in Pakistan and its benefits would certainly outweigh its high cost. This technique will serve neurologists, on­cologists and rheumatologists as a very powerful diagnos­tic tool.

REFERENCES

1. Purcell, E.M.,Torrey, H.C. and Pound, LV. Resonanceabsorption by nuclearmagnetic resonance in a solid. Pbys. Rev., 1946; 69:37.
2. Bloch, F., Hansen, W.W. and Pakard, M. Nuclear Induction. Phys. Rev., 1946; 69 127.
3. Lauterbur, P.C Image formation by induced local interactions; examples employing nuclear magneticresonsnce. Nature, 1959; 242: 190.
4. Andrew, ER. N.M.R. imaging of intact biological systems. Philos. Trans. R. Soc. Lond. (Biol.), 1980; 289: 471.
5. Gabillard, R. Nuclear resonance: Aaimple apparatus for study of paramagnetic nuclear absorption. comp. Send., 1951; 232:324.
6. Gabillard, LA studystate tecbnique in nuclear resonance. Phys. Rev., 1952; 85:694.
7. Singer, J.R. Blood flow rates by nudest magnetic resonance measurements. Science, 1959; 130: 1652.
8. Damadisn, R. Tumordetection bynuclearmágnetic resonance. Science, 1971; 171:1151.
9. carr, H.Y. and Purcell, E.M. Effects of diffusion on free precession in nuclearmagnetic resonance. Phys. Rev., 1954; 94:630.
10. Stejskal, E.O. and Tanner, J.E. Spin diffusion measurementa; spin echoes in the presence of a time dependent field gradiant. J. Chem. Pbys., 1965; 42: 288.
11. Packer, K.J. Studyofalowcoberent molecular motion bypulsed NMR. Mol. Phys., 1969;17: 355.
12. Grover, T. and Singer, JR. NMR spin echo-flow measurement. J.App. Phys., 1971; 42:938.
13. Msnafield, P. and Gsrnell, P.K NMR "diffraction" in solida? 3. Pbya., 1973; C6: L422.
14. Allen, P.S., Andrew, ER. and Bates, CR. Proceeding of 18th Congress Ampere. North Holland, Amsterdam, 1934, p.431.
15. Garroway, A.N., Garnell, P.K. and Mansfield, P.J. Image formation in NMR by a selective radiation process. J. Phys., 1974; c7: L457.
16. Mansfield, P. and Garnell, P.K Diffraction and microscopy in solids and liquid by NMR. Pbys. Rev., 1975; B. 12:3618.
17. Hinshsw, W.S. Spin mapping; the application of moving gradienta to NMR. Phys. Lett, 1974; A48: 87.
18. Hinshaw, W.S. Image formation by nuclear magnetic resonance; the sensitive point method. I. AppL Physiol., 1976; 47:3709.
19. Proceeding of 18th Congresa Ampere. Edited by Allen, P.S., Andrew, E.R. and Bates, CA. North Holland, Amsterdam, 1975, p. 433.
20. Proceeding of 18th Congress Ampere. Edited by Allen, P.S., Andrew, ER. and Bates, CA. North Holland, Amsterdam, 1975, p.283.
21. Kumar, A., Welti, I. and Ernst, R.R NMR fourier zegumatogrsphy. Nsturwissen Schaften., 1975; 62:34.
22. Kumar, A., Welti, D. and Ernst, R.R. NMR Fourierzeugmatogrsphy. 3. Magn, Reson., 1975; 18:69.
23. Andrew, ER., Bottomly, PA., Hinshaw, W.S., Holland, G.N., Moore, W.S.and Simaroj, C. NMR image by the multiple sensitive point method; application to larger biological systems Phys. Med. Biol., 1977; 22:971.
24. Hinshsw, W.S., Bottomley, PA. and Holland, G.N. Radiographic thin-section image of ihe bumanwrist bynuclear msgneticreaonsnce. Nature, 1977; 270:722.
25. Hinshaw, W.S., Andrew, E.R., Bottomley, PA., Holland, G.N., Moore. W.S. and Worthington, B.S. Display of cross-sectional anatomy by nuclear magnetic resonance imaging,). RadioL, 1978; 51: 273.
26. Hinshaw, W.S., Andrew, R.R., Bottomtey, P.A., Holland, G.N., Moore, W.S. and Worthington, B.S. An invivo study of the fore- arm and hand by thin section NMR imaging. Br.). R.adiol., 1979; 52:36.
27. Bottomley, PA. Invivo tumor discrimination in a rat by proton nuclear magnetic resonance imaging. Cancer Rca., 1979; 39:468.
28. Hinahaw, W.S., Bottomley, PA. and Holland, G.N. A demonstration of the resolution of NMR imaging in biological tystems. Experientia, 1979; 35: 1268
29. Mansfield, P., Maudsley, A.A. and Baines, T. FsstScan proton density imaging byNMR. J. Phya. (E), 1976; 9:271.
30. Mansfield, P. and Maudsley, A.A. Planarspin imaging by NMR.J. Magn. Res., 1977; 27:101-119.
31. Mansfield, P. and Maudaley, A.A. Planar spin imaging by NMR.). Phya(C)., 1976; 9: L409.
32. Proceedingof the X1Xth Congress Ampere. Edited by Brunner, H., Hannser, K.H. sod Schwcitzer, D. Heidelberg, GroupmentAmpere, 1976; p.247.
33. Mansfield, P. and Maudsley, PP. Medical imaging byNMR. Br.). Radiol., 1977;50:188.
34. Damadisn, R., Goldsmith, M. and Minkoff, L NMRin cancer. XVI. FONAR imagingof the live human body. Physiol. Chem. Phys. Med. NML, 1977; 9:97.
35. Damadian, R., Minkoff, L., Goldsmith, M. and Koutcher, ).A. Field-focusing nuclear magnetic resonance (FONAR); formation of images. Naturwissenschaften, 1978; 65:250.
36. Moor,W.S., Holland, G.N. and Kreel, LThe NMRCATscannera newlookatthe brain. J.Comput. Assist Tomogr., 1980; 4: 1-7.
37. Holland, G.N., Moore, W.S. and Hawkea, R.C. Nuclear magnetic resonance tomog­raphy of the brain.). Comput Assist. Tomogr., 1980; 4: 1.
38. Hawkes, R.C., Holland, G.N., Moore, W.S. and Worthington, B-S. Nuclear magnetic resonance (NMR) tomography of the brain; a preliminary clinical assesament with demonstration of pathology.). Comput Assist. Tomogr., 1980;4:577.
39. Hawkes, P_C, Holland, G.N., Moore, W.S. Nuclear magnetic resonance (NMR) tomography of the normal heart. J. Comput Assist Tomogr., 1981;5: 605.
40. Hswkes, R.C, Holland, G.N., Moore, W.S., Roebuck, EJ. and Worthington, B.S. Nuclear magnetic resonance (NMR) tomography of the normal abdomen.). Comput Assist Tomogr., 1981; 5:613.
41. Doyle, RH., Gore, J.C., Pennock, J.M., Bydder, G.M., Orr, 3.5., Steiner, RE., Young, I.R., Burl, M., Clow, H., Gilderdsle, D.J., Bailes, DR. snd Walters, P.R Imaging of the brain by nuclesr magnetic resonance. Lancet, 1981; 2:53.
42. Young, IL, Burl, M., Clark, G.J., Hall, A.S., Patmore,T., Collins, A.). and Smith, D. Magnetic resonance properties of hydrogen. Imaging the posterior fossa. AJR., 1987; 137:895-901.
43. Lai, CM. and Lauterbur, P.C. True three dimensional image reconstruction by nuclear magnetic resonancezeugmatography.). Phys., 1980; E13:747.
44. Lauterbur, P.C. NMR in zeugmatographicimagingoforgans and organisms.). Comput Assist Tomogr., 1981; 5:285.
45. Hansen, G., Crooks, LE., Davis, P., DeGroot, 3., Herfkena, R., Margulis, AR., Gcoding, C., Kaufman, L, Hoenninger, 3., Arakawa, M., McRee, R. and Watts,). Invivo imsging of the rstsnatomy with nuclear magnetic resonance. Radiology, 1980; 136:695.
46. Crooks, L., Hoenninger, 3., Arakawa, M., Kaufman, L., McRee, R., Watts,). and Singer, J.H. Tomography of the hydrogen with nuclear magnetic resonance. Radiology, 1980;136: 701.
47. Hoult, D.L Zeugmatography; a criticism of the concept of a selective pulse in the presence of a field gradiant J. Magn. Res., 1977; 26: 165.
48. Hoult, D.l. Rotating frame zeugmatography. J. Magn. Res., 1979;33:183.
49. Hoult, D.l. NMR imagingrotation frame selective pulses.). Magn. Rca., 1980; 38:369.
50. Tropper, M.M. NMR imaging,). Magn. Rca., 1981; 42:193.
51. Feiner, L.F. and Locker, P.R On NMRapin imaging by magneticfield. App. Phya., 1980:22:257-271.
52. Tanaka, K., Yamada, Y., Yamamoto, E.R.Z., Abe. NMR relaxation data processingand a method for separation of multirelaxation time. Proc. lEE, 1978; 66: 1582.
53. Lauterbur, P.C, Karmer, D.M., House, W.V. and Chen, C.N. Zeugmatography high resolution NMR spectroacopy. Image of chemical inhomogenecity with microscopic objects.). Am. Chem. Soc., 1975; 97:6866.
54. Bendel, P., Lai, CM. and Lauterbur, P.C. Phosphorua-31 apectroacopic zeugmatog­raphy of phosphorus metabolities.). Magn. Rca., 1980; 38:343.
55. Ackerman, J.J.H., Grove, T.H., Wong G.G., Gsdian, D.G. and Rsdda, G.K. Msppingof metsbolitiea inwhole animals by p NMR using surface coils. Nature, 1980; 283: 167.
56. Gordon, RE., Hsnley, P.E., Shaw, D., Gadian, D.G., Radda, G.K Styles P., Bore, P.). and Chsn, L Localization of metabolites in animals using P topical magnetic resonance. Nature, 1980; 287:736.
57. Cox, S.). and Styles, P. Towards biochemical imaging,). Magn. Rca., 1980; 40:209.
58. Nannually, RL and Bottomley, P.A. Assessment of pharmacological treatment of myocardial infarction by phosphorus-31 NMRwith surface coil. Science, 1981;211:177.
59. Singer, JR. IEEE Blood flow measurements of the intact body. Trans. NucI. ScL, 1980; NS-27:       1245-1249.
60. Cohen, M.D. Pediatric magnetic resonance imaging. Philadelphia, Saunders 1986.
61. George, 3.C., Doyle, PH. and Pennock, J.M. Relaxation rate enhancementobserved, in vivo by NMR imaging. Edited by Partain, CL and James, A.E. 2nd ed. Philadelphia. Saunders, 1988, p.194.
62. Lauterbur, P.C Magneticresonance zeugmatography. Pure Appl. Chem., 1974; 40:149.
63. Lauterbur, P.C., Lai, C.M. Zeugmatography by reconstruction from projections. IEEE Trana. NucI. Sci., 1980; NS-27: 1227.
64. Manesfield, P., Morris, PG., Waugh, J.S. Eds. Special Supplement in Adv. Magn. Resonance. New York, AcademiePress, 1983.
65. Damadian, R. Field focussingn.m.r. (FONAR) and the formation of chemical images in man. Philos. Trans. It Soc. Lond. (BioL), 1980; 289:489.
66. Goldsmith, M., Damadian, R., Stanford, M. and Lipkowitz M. NMR in cancer. XVIII. A superconductive NMR magnet fora human sample. 67.Physiol. Chem. Phys.. 1977; 9: 105. Proceeding of 18th Congress Ampere. Allen, PS, Andrew, ER and Bates, CW. North Holland, Amsterdam, 1975; p.433.
68. Hutchison, J.M.S., Edelstein, W.A. and Johson, G. A whole body NMR imaging machine. J. Phys. (E), 1980 13: 947.
69. Maudsley, A.A. Multiple line scanning spin density imaging. J. Magn. Res., 1980; 41:112
70. Mansfield, P. Multiplanar image formation usingNMR spin echoes. 3. Phys., 1977; ClO: L55.
71. Mansfield, P. and Pykett, I.L Biological and medical imaging by NMR. 3. Magn. Rea.. 1978; 29: 355.
72. Brown, P. NMR: Outof R&D and into radiology. Disgn. Imaging. 1981; 32-3K
73. Herficens, It, Davis, P., Crooks, L, Kaufman, L, Price, D., Miller, T., Margullis, A.R., Watts, 3., Hoenninger, 3., Arakaws, M. and Mcree, R. Nuclear magnetic resonance imaging of the abnormal liver rat and correlation with tissue characteristics. Radiology, 1981; 141:211.
74. Brady, Ti., Bunonanno, P.S., Pykett, LL, New, PP., Davis, K. R., Pohost, G.M. and Kistler, J.P. Preliminssy clinical results of proton (1H) imaging of cranial neoplasms; in vivo measurements of TI and mobile proton density. AJNR., 1983; 4:255.
75. Drago, R.S. Physical method in chemistry. Philadelphia, Saunders, 1977.
76. Stone,TJ., Buckman, T., Nordio, P.L et al. Spin-labelled biomolecules. Proc. Acad. Sci. USA., 1965; 54: 1010.
77. Brasch, R.C. Work in progress; methods of contrast enhancement for NMR imaging and potential application. Radiology, 1983; 147: 781.
78. Mendonca-Dias, M.H., Gaggelli, E. and Lauterbur, P. Paramagnetic contrast agents in nuclear magneticresonance medical imaging. Semin. Nuct Med., 1983; 12: 364.
79. Runge, V.M., Clanton, J.A., Lukehart, CM., Partain, CL and James, A. E. Jr. Paramagnetic agents for contrast-enhanced NMR imaging. APR., 1983; 141: 1209.
80. Goldman, M.R., Brady, Ti., Pykett, I.L., Burt, C.T., Buonanno, P.S., Kiatler, J.P., Newhouse, J.H., Hinshaw, W. S. and Pohoat, G.M. Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts. Circulation, 1982; 66: loll
81. Alfidi, R.J., Hasga, JR., Elyovsef, S.J., Bryan, P.3., Fletcher, B.D., Lipuma, J.P., Morrison, S.C, Kaufman, B., Richey, J.B., Hinshaw, W.S., Karanrer, D.M., Yeung. H.N., Cohen, A.M., Butler, HE., Ament, A.E. and Ueberman, J.M. Preliminary experimental results in humans and animalswishasuperconducting. whole-bodynuclear magnetic resonance scanner. Radiology, 1981; 143: 175.
82. Gore, J.C, Doyle, F.H. and Pennock, 3M. In Nuclear Magnetic Resonance Imaging. Psrtain, CL, James,A.E.Jr. snd Rollo, F.D. eda. Philadelphia, W.B. Saunders Co., 1983; pp. 44-106.
83. Young. I.R., Clark, Gi., Bailes, D.R, Pennock, 3M., Doyle, PH. and Bydder, G.M. Enhancement of relaxation rate with paramagnetic contrast agents in NMR imaging. CF., 1981; 5:543.
84. Wesbey, G.E., Braach, ltC, Engelstal, Bt, Moss, A.A., Crooks, LE. and Brito, A.C Nuclear magnetic resonance contrast enhancement studiet of the gastrointestinal tract of rats and a human volunteer using nontoxic oral iron solutions. Radiology, 1983; 149:175.
85. Braseh, R.C., London, D.A., Wesbey, G.E., Tozer, T.N., Nitecki, D. B., Williams, R.D., Doemeny, 3,, Tuck, LD. and Lallemand, D.P. Work in progress; nuclear magnetic resonance study of a paramagnetic nitroxide contrast agent for enhancement of renal structure in experimental animals. Radiology, 1983; 147: 773.
86. Brashch, R.C, Nitecki, D.E., Brant-Zawadzki, M., Enzmann, D.R., Wesbey. G.E., Tozer, T.N., Thck, LD., Cann, CE., Pike, J.R and Shelden, P. Brain nuclear magnetic resonance imaging enhanced by a paramagnetic nitroxide contrast agent; preliminary report. AJR., 1983; 141: 1019.
87. Young. I.R., Bailca,D.R. and Burt, M. Initial clinical evaluation ofa whole body nuclear magnetic resonance (NMR) tomograph.). Comput. Asst. Tomogr., 1982; 6: 1.
88. Stark, D.D. and Bradty, W,W. eda. Magnetic resonance imaging. Saint Louis, Mosby,1988.
89. Anderson, M. Nuclear magnetic resonance imaging and neurology. Br. Med. J., 1982;284:1359.
90. Tishler, J.M. and Partain, CL Nuclear magnetic resonance of the central nervous system. Ala. 3. Med. Sci., 1984; 21: 190.
91. Araki, T., Inouye, T., Suzuki, H., Machida, T. and Lio, M. Magnetic resonance imaging of brain tumors; meaaurementofTl. Radiology, 1984; 150:95.
92. Young, l.R., Bydder, G.M., Hall, A.S., Steiner, R.E., Worthington, B.S., Hawkes, R.C., Holland, G.N. and Moore, W.S. Thc role of NMR imaging in the diagnosis and management of acoustic neuroma. AINR., 1983; 4:233.
93. Young. I.R., Randall, C.P., Kaplan, P.W., James, A., Bydder, G.M., and Steiner, RE. Nuclear magnetic resonance (NMR) imaging in white matter disease of the brain using spin-echo sequences. 3. Compont. Asstt. Tomogr.. 1983; 7:290.
94. Modic, M.T. and Weinstein, MA. Nuclear magnetic resonance of the spine. Br. Med. Bull., 1984; 40: 183.
95. Normon, D. et aL MRI of the spinal cord and canal. AJNR, 1984; 5:9.
96. Smith, F.W., Punge. V., Permezel, M., and Smith, CC Nuclear magnetic resonance imaging in the diagnosis of spinal osteomyelitis. Magn. Resonan. Imag., 1984; 2:53.
97. George, A.E., deLeon, Mi. and Kalnin, A. Leukoencephalopathy in normal and pathological aging. 2. MRI of brain lucencies. AJNR., 1986; 7:567.
98. Lanzer, P., Botvinick, BK., Schiller, N.B., Crooks, LE., Arakswa, M., Kaufman, L, Davis, P.L, Herfkens, It, Lipton, M.J. and Higgins, CB. Cardiac imaging using gated magnetic resonance. Radiology, 1984; 150: 121.
99. Leiberman, J.M., Alfidi, Ri., Nelson, A.D., Botti, R.E., Moir, T.W., Haaga, J.R., Kopiwada, S., Miraldi, PD., Cohen, AM., Butler, H.E. et al. Gated magnetic resonance imagingof the normal and diseased heart. Radiology, 1984; 152:465.
100. Pohost, G.M. and Ratner, A.V. Nuclear magnetic resonance potential applications in clinical cardiology. JAMA., 1984; 251: 1304.
101. Steiner, R.E. Nuclear magnetic resonance imaging of heart and mediastinum. Br. Med. Bull., 1984; 40: 191.
102. Vandijik, P. Direct cardiac NMR imaging of heart wall and blood flow velocity. J. Compuc. Assist. Tomogr., 1984;8:429.
103. Cohen, SM. Application of Nuclear magnetic resonance to thestudy of liverphysiology and disease. Heptalogy, 1983; 3: 738.
104. Moon, K.L. Jr., Hricak, H., Margulis, AR, Bernhoft, R., Way, LW., Filly, R.A, and Crooks, LE. Nuclear magnetic resonance imagingof characteristic of gallstone in vitro. Radiology, 1983; 148: 753.
105. Stark, D.D., Goldberg. UI., Moss, A.A. and Bass, N.M. Chronic liverdisease; evaluation by magnetic resonance. Radiology, 1984; 150: 149.
106. Hirack, H., Filly, RA., Margulis, A.R., Moon, K.L., Crooks, LB. and Kaufman, L Work in progress; nuclear magnetic resonance imaging of the gallbladder. Radiology, 1983; 147: 481.
107. Stark, D.D., Moss, A.A., Goldberg. H.I., Davis, P.L. and Fderle, M.P. Magnetic resonance and CTof the normal and diseased pancreas; acomparacive study. Radiology, 1984; 150:153.
108. Hirack, U., Crooks, L, Sheldon, P. and Kaufman, L Nuclear magnetic resonance imagingof the kidney. Radiology, 1983; 146:425,
109. Smith, F.W., Hutchison, J.M.S., Millard, J.R, Reid, A., Johson, G., Redpath, T.W. and Sebie, RD. Renal cysts or tumors. Differentiation by whole-body nuclear magnetic resonance imaging. Diag. Imaging. 1981; 50:61.
110. Smith, P.W., Reid, A., Mallard, J.R., Hutchison, 3M., Power, D.A. and Catto, G. 111. Nuclear magnetic resonance tomographic imaging in renal disease. Diag. Imaging. 1982; 51: 209.112. Steyn, J.H. and Smith, F.W. Nuclear magnetic resonance imaging of the prostrate. Br. J. Urol., 1982; 54: 726.
113. Grty. I., Delbeke, D. and SandIer, M.P. Correlative pediatric Imaging. 3. NucI. Med., 1989; 30:15.
114. Behling, R.W. and Tubba, U.K. Stroboscopic NMR microscopy of the carotid srtery. Nature, 1989; 341: 321.
115. Bradly, W.G. Magnetic resonance appearance of flowing blood flow and cerebrospinal fluid, in brain magnetic resonance imaging of central nervous system. Edited by Zawadaski, M. and Norman, D. New York, Raven Press, 1987, p.83.
115. Pavlicek, W., Geisinger, M., Castle, L, Borkowski, G.P., Mesney, T.P., Brean, B.L and Gallagher, J.H. The effects of nuclear magnetic resonance on pstients with cardiac pacemakers. Radiology, 1983; 147:149.
116. BeIlon, E.M., Hascke, B. M., Coleman, P.E., Sacco, DC, Steiger, D.A. and Gangarosa, RE. MR. Artifacts; a review. MR., 1986; 147: 1271.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: