Development and clinical application of part body neutron activation analysis using Californium-252

Californium 252 sources were used in a clinical environment for neutron activation analysis studies for a period of 2 1/2 years. During this period changes in part body calcium in bone, in response to different treatment regimes, were measured in patients suffering from primary or secondary bone disease. Measurements were performed on peripheral bone, in 252 particular the forearm, using two sources of Cf, minimum total activity 56 mCi, and a purpose built partial body counter. Optimisation of the irradiation geometry and the patient irradiation programme enabled calcium measurements to be performed with a precision of between 1.5% and 1.8% and a bone dose less than 3 rem. The following clinical studies were undertaken: the effect of 1-oc-hydroxycholecalciferol on 19 patients under going chronic haemodialysis, the use of vitamin D2 or D3 in the treatment of 33 patients with potential anticonvulsant osteomalacia, the effect of lithium carbonate in 15 patients with manic depression and the efficacy of conventional treatments in combating thyrotoxic osteodystrophy. Apparatus was also developed to measure calcium 252 changes in the lumbar spine. Two Cf sources of total activity 200 mCi were used for irradiation and a whole body counter for detection of the induced activity. A precision of 2% was obtained for patient measurements, with a bone dose of 1.3 rem

Physical science techniques for non-invasive, quantitative measurements within the living human body

The research in this thesis focuses on the use of a range of physical science techniques to perform quantitative measurements within the living human body in a non-invasive manner, for the purpose of understanding disease processes, diagnosing abnormality or monitoring therapeutic responses. The research publications cover work which has been undertaken over the last thirty years in the Universities of Edinburgh, London and Leeds. The research has not concentrated on one aspect of the physical sciences but has taken advantage of scientific and technological developments, encompassing neutron, X and y ionising radiation, laser and THz non-ionising radiation, magnetism, radio-waves and a range of mathematical and computing techniques. Clinical applications have encompassed a wide range of diseases and conditions and include osteoporosis and other metabolic bone diseases, cardiac disease, vascular disease, rheumatoid arthritis and cancer.PUBLICATIONS • • BONE MEASUREMENT • 1. Development of apparatus to measure calcium changes in the forearm and spine by neutron activation analysis using Cf-252 (*PhD) MA Smith and P Tothill Physics in Medicine and Biology 24, 319-329, 1979 2. Measurement of spinal calcium by in vivo neutron activation analysis in osteoporosis (*PhD) MA Smith, R Eastell, NSJ Kennedy, LG Mcintosh, JD Simpson, JA Strong and P Tothill Clinical Physics and Physiological Measurement 2, 45-48, 1981 3. Long term effect of dialysate calcuim and 1a -OHD3 on bone calcium in haemodialysis patients as measured by neutron activation analysis of the forearm (*PhD) MA Smith, RJ Winney, JA Strong and P Tothill Nephron 28, 213-217, 1981 4. Total body neutron activation analysis of calcium: calibration and normalisation NSJ Kennedy, R Eastell, CM Ferrington, JD Simpson, MA Smith, JA Strong and P Tothill Physics in Medicine and Biology 27, 697-708, 1982 5. The crossover correction in dual photon absorptiometry with Gd-153 MA Smith and P Tothill Physics in Medicine and Biology 27, 1515-1521, 1982 6. Bone demineralisation in patients with Turner's syndrome MA Smith, J Wilson and WH Price Journal of Medical Genetics 19, 100-103, 1982 7. Total body calcium in rheumatoid arthritis: effects of disease activity and corticosteroid treatment DM Reid, NSJ Kennedy, MA Smith, P Tothill and G Nuki British Medical Journal 285, 330-332 1982 8. Comparison between Gd-153 and Am-241, Cs-137 for dual photon absorptiometry of the spine MA Smith, D Sutton and P Tothill Physics in Medicine and Biology 28, 709-721, 1983 9. Intra-laboratory variations using dual photon absorptiometry MA Smith and P Tothill Physics in Medicine and Biology 28, 748-751, 1983 10. Dual photon absorptiometry of the spine with a low activity source of gadolinium 153 P Tothill, MA Smith and D Sutton British Journal of Radiology 56, 829-835, 1983 11. Normal levels of total body sodium and chlorine by neutron activation analysis NSJ Kennedy, R Eastell, P Tothill and MA Smith Physics in Medicine and Biology 28, 215-222, 1983 12. The assessment of postmenopausal osteoporosis by total body neutron activation analysis R Eastell, NSJ Kennedy, MA Smith, JD Simpson, JA Strong and P Tothill Metabolic Bone Disease and Related Research 5, 65-67, 1983 13. Bone mass in nodal primary generalised osteoarthritis DM Reid, NSJ Kennedy, MA Smith, P Tothill and G Nuki Annals of the Rheumatic Diseases 43, 240-242, 1984 14. Changes in total body calcium after renal transplantation effect of low-dose steroid regime R Eastell, NSJ Kennedy, MA Smith, P Tothill and JL Anderton Nephron 40, 139-142, 1985 15. The seasonal variation of total body calcium P Tothill, NSJ Kennedy, JJ Nicoll, MA Smith, DM Reid and G Nuki Clinical Physics and Physiological Measurement 7, 361-367, 1986 16. Bone mass in ankylosing spondylitis DM Reid, JJ Nicoll, NSJ Kennedy, MA Smith, P Tothill and G Nuki Journal of Rheumatology 13, 932-935, 1986 17. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica DM Reid, JJ Nicoll, MA Smith, B Higgins, P Tothill and G Nuki British Medical Journal 293, 1463-1466, 1986 18. Total and peripheral bone mass in patients with psoriatic arthritis and rheumatoid arthritis DM Reid, NSJ Kennedy, JJ Nicoll, MA Smith, P Tothill and G Nuki Clinical Rheumatology 5, No 3, 372-278, 1986 19. Changes in total body calcium following surgery for primary hyperparathyroidism R Eastell, NSJ Kennedy, MA Smith, P Tothill and CRW Edwards Bone 7, 269-272 1986 20. Bone loss in rheumatoid arthritis and primary generalized osteoarthrosis: effects of corticosteroids, suppressive antirheumatic drugs drugs and calcium supplements DM Reid, NSJ Kennedy, MA Smith, JJ Nicoll, N Brown, P Tothill and G Nuki British Journal of Rheumatology 25, 253-259, 1986 21. Measurement of hand bone mineral content using single-photon absorptiometry JJ Nicoll, MA Smith, DM Reid, E Law, N Brown, P Tothill and G Nuki Physics in Medicine and Biology 32, 697-706, 1987 22. In-vivo precision of total body calcium and sodium measurements by neutron activation analysis JJ Nicoll, P Tothill, MA Smith, DM Reid, NSJ Kennedy and G Nuki Physics in Medicine and Biology 32, 243-246, 1987 23. Prediction of fracture healing in the tibia by quantitative radionuclide imaging MA Smith, E Jones, R Strachan, P Tothill, JJK Best and SPF Hughes Journal of Bone and Joint Surgery 69-B, 441-448, 1987 24. Premenopausal bone loss in the lumbar spine and neck of femur: a study of 225 Caucasian women A Rodin, B Murby, MA Smith, M Caleffi, I Fentiman, MG Chapman and I Fogelman Bone 11, 1-5, 1990 25. Bone ultrasound attenuation in women: reproducibility, normal variation and comparison woth photon absorptiometry JG Truscott, M Simpson, SP Stewart, R Milner, CF Westmacott, B Oldroyd, JA Evans, A Horsman, CM Langton and MA Smith Clinical Physics and Physiological Measurement 13, 29-36, 1992 26. The use of a radiation sensitive CCD camera system to measure bone mineral content in the neonatal forearm: a feasibility study JG Truscott, R Milner, S Metcalfe and MA Smith Physics in Medicine and Biology 37, 1391-1397, 1992 27. Primary Generalised Osteoarthritis and Bone Mass LD Hordon, SP Stewart, PR Troughton, V Wright, A Horsman and MA Smith British Journal of Rheumatology 32, 1059-1061, 1993 28. Variation in lumbar spine and femoral neck bone mineral measured by dual energy X-ray absorption: a study of 329 normal women JG Truscott, B Oldroyd, M Simpson, SP Stewart, CF Westmacott, R Milner, A Horsman and MA Smith British Journal of Radiology 66, 514-521, 1993 29. A phantom for quantitative ultrasound of trabecular bone AJ Clarke, JA Evans, JG Truscott, R Milner and MA Smith Physics in Medicine and Biology 39, 1677-1687, 1994 30. Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation SM Orme, M Simpson, SP Stewart, B Oldroyd, CF Westmacott, MA Smith and PE Belchetz Clinical Endocrinology 41(2), 245-50, 1994 31. A portable system for measuring bone mineral density in the pre-term neonatal forearm JG Truscott, R Milner, PC Holland, C Wood and MA Smith British Journal of Radiology 69, 532-8, 1996 32. Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology S Fletcher, RG Jones, HC Rayner, P Harnden, LD Hordon, JE Aaron, B Oldroyd, AM Brownjohn, JH Turney and MA Smith Nephron 75(4), 412-9, 1997 33. Regional bone mineral density after orthotopic liver transplantation SH Hussaini, B Oldroyd, SP Stewart, F Roman, MA Smith, S Pollard, P Lodge, JG O'Grady and MS Losowsky European Journal of Gastroenterology Hepatology 11(2), 157-63, 1999 • PATENTS (COPIES NOT INCLUDED) • 34. Material to mimic bone and its interaction with ultrasound J Clarke, JA Evans, R Milner and MA Smith 1994 35. Anthropomorphic spinal phantom R Milner, E Berry and MA Smith 1999 • STATISTICS • 36. The comparison of neutron activation analysis and photon absorptiometry at the same part body site MA Smith, RA Elton and P Tothill Clinical Physics and Physiological Measurement 2, 1-7, 1981 37. Survival after peptic ulcer surgery AH McLean Ross, J Anderson, WP Small and MA Smith British Medical Journal 282, 1472, 1981 38. Late mortality after surgery for peptic ulcer AH McLean Ross, MA Smith, JR Anderson and WP Small New England Journal of Medicine 307, 519-522, 1982 39. Survival after surgery WP Small, MA Smith and AH MacLean-Ross British Medical Journal 289, 108-109, 1984 40. Metabolism of sodium pentosan polysulphate in man-catabolism of iodinated derivatives IR MacGregor, J Davies, L Paton, DS Pepper, CV Prowse and MA Smith Thrombosis and Haemostasis 51, 321-325, 1984 41. Correction factors for gravimetric measurement of peritumoural oedema in man BA Bell, MA Smith, JL Tocher and JD Miller British Journal of Neurosurgery 1, 435-440, 1987 42. Inter-individual differences in the pituitary-thyroid axis influence the interpretation of thyroid function tests CA Meier, MN Maisey, A Lowry, J Muller and MA Smith Clinical Endocrinology 39, 101-107, 1993 • MAGNETIC RESONANCE IMAGING • 43. The installation of a commercial resistive NMR imager MA Smith, JJK Best, RHB Douglas and DM Kean British Journal of Radiology 57, 1145-1158, 1984 44. Brain water in chronic alcoholic patients measured by magnetic resonance imaging MA Smith, J Chick, DM Kean, RHB Douglas, A Singer, RE Kendell and JJK Best Lancet i, 1273-1274, 1985 45. Nuclear magnetic resonance imaging in hypertrophic cardiomyopathy M Been, DM Kean, MA Smith, RHB Douglas, JJK Best, and AL Muir British Heart Journal 54, 48-52, 1985 46. Two examples of CNS lipomas demonstrated by CT and low field MRI DM Kean, MA Smith, RHB Douglas, CN Martyn and JJK Best Journal of Computer Assisted Tomography 9(3), 494-496, 1985 47. Characterisation of acute myocardial infarction by gated magnetic resonance imaging M Been, MA Smith, JP Ridgway, JWE Brydon, RHB Douglas, DM Kean, JJK Best and AL Muir Lancet ii, 348-350, 1985 48. Brain water measured in volunteers after alcohol and vasopressin AJ Mander, MA Smith, DM Kean, J Chick, RHB Douglas, AU Rehman, GJ Weppner and JJK Best Lancet, ii, 1075, 1985 49. ECG gated T1 images of the heart MA Smith, JP Ridgway, JWE Brydon, M Been, RHB Douglas, DM Kean, JJK Best and AL Muir Physics in Medicine and Biology 31, 771-778, 1986 50. The absence of tissue specificity in MRI using in-vivo T1 or T2 determination - true biological variation or technical artefact? MA Smith and DG Taylor British Journal of Radiology 59, 82-83, 1986 51. A description of a low field resistive magnetic resonance imaging system and its application in imaging midline central nervous system pathology DM Kean, MA Smith, RHB Douglas and JJK Best Clinical Radiology, 37, 211-217, 1986 52. A technique for velocity imaging using magnetic resonance imaging JP Ridgway and MA Smith British Journal of Radiology 59, 603-607, 1986 53. Correlation of human NMR T1 values measured in vivo and brain water content HL MacDonald, BA Bell, MA Smith, DM Kean, JL Tocher, RHB Douglas, JD Miller and JJK Best British Journal of Radiology 59, 355-357, 1986 54. A surface coil design for a vertical field MRI system and its application in imaging the breast MA Smith and DW Pye Magnetic Resonance Imaging 4, 455-560 1986 55. Cardiac gating in nuclear magnetic resonance imaging MA Smith Journal of Medical Engineering and Technology 10(6), 325-328, 1986 56. Brain water measured by magnetic resonance imaging: correlation with direct estimation and changes after mannitol and dexamethasone BA Bell, MA Smith, DM Kean, CNJ McGhee, HL MacDonald, JD Miller, GH Barnett, JL Tocher, RHB Douglas, JJK Best The Lancet (i), 66-69, 1987 57. Demonstration of pulsatile cerebrospinal-fluid using magnetic resonance phase imaging JP Ridgway, LW Turnbull and MA Smith British Journal of Radiology 60, 423-427, 1987 58. Magnetic resonance flow imaging: a possible method for distinguishing communicating syringomyelia from cystic intraspinal lesions LW Turnbull, JP Ridgway, MA Smith and JJK Best British Journal of Radiology 60, 517-518, 1987 59. Cerebral and brain stem changes after ECT revealed by nuclear magnetic resonance imaging AJ Mander, A Whitfield, DM Kean, MA Smith, RHB Douglas and RE Kendell British Journal of Psychiatry 151, 69-71, 1987 60. Serial changes in the T1 magnetic relaxation parameter after myocardial infarction in man M Been, MA Smith, JP Ridgway, RHB Douglas, DP De Bono, JJK Best and AL Muir British Heart Journal 59, 1-8, 1988 61. Myocardial involvement in systemic lupus erythematosus detected by magnetic resonance imaging M Been, BJ Thompson, MA Smith, JP Ridgway, RHB Douglas, JJK Best and AL Muir European Heart Journal 9 1250-1256, 1988 62. Brain hydration during alcohol withdrawal in alcoholics measured by magnetic resonance imaging MA Smith, JD Chick, HM Engelman, DM Kean, AJ Mander, RHB Douglas and JJK Best Drug and Alcohol Dependence 21, 25, 1988 63. Magnetic resonance spectroscopy in-vivo DA Porter, MA Smith Journal of Biomedical Engineering 10, 562-567, 1988 64. Blood flow imaging by magnetic resonance DJ West, M Tarnawski, MJ Graves, MG Taylor, S Padayachee, VT Ayton and MA Smith Medicamundi 33, 101-111, 1988 65. Magnetic resonance imaging of the infant heart at 15T MA Smith, EJ Baker, VT Ayton, JM Parsons, EJ Ladusans and MN Maisey British Journal of Radiology 62, 367-370, 1989 66. High field strength magnetic resonance imaging of ventricular septal defects in infants EJ Baker, VT Ayton, MA Smith, JM Parsons, EJ Ladusans, RH Anderson, M Tynan and NLK Fagg British Heart Journal 62, 305-310, 1989 67. Magnetic resonance imaging of coarctation of the aorta in infants: use of high field strength EJ Baker, VT Ayton, MA Smith, JM Parsons, EJ Ladusans, RH Anderson, M Tynan, AK Yates and PB Deverall British Heart Journal 62, 97-101, 1989 68. Magnetic resonance imaging of the brain in alcoholics: cerebral atrophy, lifetime alcohol consumption and cognitive defects JD Chick, MA Smith, HM Engleman, DM Kean, AJ Mander, RHB Douglas and JJK Best Alcoholism: Clinical and Experimental Research 13, 512-517, 1989 69. Phospholipids are visible in P-31 NMR spectra of human breast tumours M Lowry, DA Porter, CJJ Twelves, PE Heasley, PB Garlick, MA Smith, RD Rubens, MN Maiseyand MA Richards Biochemical Society Transactions 17, 1053-1054, 1989 70. The measurement and visualisation of vessel blood flow by magnetic resonance imaging MA Smith Clinical Physics and Physiological Measurement 11,2, 101-123, 1990 71. A method for characterising localisation techniques in volume selected nuclear magnetic resonance spectroscopy SF Keevil, DA Porter and MA Smith Physics in Medicine and Biology 35(7), 821-834, 1990 72. The measurement of time-averaged flow by magnetic resonance imaging using continuous acquisition in the carotid arteries and its comparison with Doppler ultrasound M Tarnawski, S Padayachee, DJ West, MJ Graves, V Ayton, MG Taylor and MA Smith Clinical Physics and Physiological Measurement 11(1), 27-36, 1990 73. Measurement of time-averaged flow in the middle cerebral artery by magnetic resonance imaging M Tarnawski, S Padayachee, MJ Graves, V Ayton, MG Taylor and MA Smith British Journal of Radiology 64, 178-181, 1991 74. Visibility of phosholopids in 31P NMR spectra of human breast tumours in-vivo M Lowry, DA Porter, CJ Twelves, PE Heasley, MA Smith and MA Richards NMR in Biomedicine 5, 37-42, 1992 75. Experimental characterisation of the ISIS Technique for volume selected NMR spectroscopy SF Keevil, DA Porter and MA Smith NMR in Biomedicine 5, 200-208, 1992 76. Rapid dynamic contrast-enhanced magnetic resonance imaging of the liver and portal vein J Ward, D Martinez, AG Chalmers, J Ridgway, P Robinson and MA Smith British Journal of Radiology 66, 214-222, 1993 77. Phosphorus-31 metabolism of human breast - an in-vivo magnetic resonance spectroscopy study at 1,5T CJ Twelves, M Lowry, DA Porter, NA Dobbs, PE Graves, MA Smith and MA Richards British Journal of Radiology 67, 36-45, 1994 78. Phosphorus-31 metabolism of post-menopausal breast cancer studied in vivo by magnetic resonance CJ Twelves, DA Porter, M Lowry, NA Dobbs, PE Graves, MA Smith, Rubens RD and MA Richards British Journal of Cancer 69(6), 1151-6, 1994 79. Stepping-table gadolinium-enhanced digital subtraction MR angiography of the aorta and lower extremity arteries: preliminary experience JF Meaney, JP Ridgway, S Chakraverty, I Robertson, D Kessel, A Radjenovic, M Kouwenhoven, A Kassner and MA Smith Radiology 211(1), 59-67, 1999 80. Quantitative comparison of intrabrain diffusion in adults and preterm and term neonates and infants SF Tanner, LA Ramenghi, JP Ridgway, E Berry, MA Saysell, D Martinez, RJ Arthur, MA Smith and Ml Levene American Journal of Roentgenology 174(6), 1643-9, 2000 81. A systematic review of the precision and accuracy of dose measurements in photon radiotherapy using polymer and Fricke MRI gel dosimetry ND MacDougall, WG Pitchford and MA Smith Physics in Medicine and Biology 47, 107-121, 2002 Response to comments: Physics in Medicine and Biology 48, L19 - 22, 2003 82. Cerebral perfusion in infants and neonates: preliminary results obtained using dynamic susceptibility contrast enhanced MRI SF Tanner, LG Cornette, LA Ramenghi, LS Miall, JP Ridgway, MA Smith and Ml Levene Archives for Disease in Childhood 88(6), F525-530, 2003 83. Evaluation of the dosimetric performance of BANG3 polymer gels ND MacDougall, ME Miquel, DJ Wilson, SF Keevil and MA Smith Physics in Medicine and Biology 50, 1717 - 1726, 2005 84. T1 measurement using a short acquisition period for quantitative cardiac applications DM Higgins, JP Ridgway, A Radjenovic, UM Sivananthan, and MA Smith Medical Physics 32, 1738-1746, 2005 85. A method for pharmacokinetic modeling of dynamic contrast enhanced MRI studies of rapidly enhancing lesions acquired in a clinical setting A Radjenovic, JP Ridgway and MA Smith Physics in Medicine and Biology 51, N187-N197, 2006 • PATENTS (COPIES NOT INCLUDED) • 86. Surface coils for magnetic resonance imaging MA Smith 1986 87. Sympathetic resonance in magnetic resonance imaging MA Smith 198

Requirements for Boron Neutron Capture Therapy (BNCT) at a Nuclear Research Reactor

An international workshop, funded by the JRC¿s Enlargement and Integration Action, took place in Prague in 2005 entitled ¿Requirements for BNCT at a Nuclear Research Reactor¿. The intention of the workshop was to exchange knowledge between the EU BNCT programme at the HFR Petten (EC, NL) and other existing clinical and preclinical research programmes on BNCT throughout Europe, with the special aim to transfer information towards groups and places that are preparing their own national BNCT projects. The future of nuclear research institutes will depend on their ability to open research programmes into new areas and to link nuclear technologies with other applications. Medicine is one of the most interesting but also sensitive areas for such multidisciplinary work. Boron Neutron Capture Therapy (BNCT) is a dedicated and well-known topic that demonstrates such a link in an exemplary way. This book expands on some of the topics presented at the workshop. It is intended to support scientists, clinicians and politicians that are interested to develop a local or national BNCT activity.JRC.F.6-Energy systems evaluatio

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