Skip to main content
SpringerLink
Log in

Magnetic Resonance Imaging Techniques to Monitor Phase III Treatment Trials

  • Conference paper
Book cover Magnetic Resonance Techniques in Clinical Trials in Multiple Sclerosis

Part of the book series: Topics in Neuroscience ((TOPNEURO))

Abstract

Since its introduction early in the 1980s, magnetic resonance (MR) has become established as the most important paraclinical tool for monitoring treatment efficacy in phase III multiple sclerosis (MS) trials. MR protocols are now routinely incorporated in such studies, providing powerful evidence of therapeutic effect and extending clinical observations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 33: 1444–1452

    Article  PubMed  CAS  Google Scholar 

  2. Noseworthy JH, Vandervoort MK, Wong CJ, et al. (1990) Interrater variability with the expanded disability status scale (EDSS) and functional systems (FS) in a multiple sclerosis clinical trial. The Canadian Cooperation MS Study Group. Neurology 40:971–975

    Article  PubMed  CAS  Google Scholar 

  3. Rudick RA, Antel J, Confavreux C, et al. (1996) Clinical outcome assessment in multiple sclerosis. Ann Neurol 40: 469–479

    Article  PubMed  CAS  Google Scholar 

  4. Whitaker JN, McFarland HF, Rudge P, et al. (1995) Outcomes assessment in multiple sclerosis clinical trials: A critical analysis. Mult Scler 1: 37–47

    PubMed  CAS  Google Scholar 

  5. Miller DH, Grossman RI, Reingold SC, et al. (1998) The role of magnetic resonance techniques in understanding and managing multiple sclerosis. Brain 121: 3–24

    Article  PubMed  Google Scholar 

  6. Thompson AJ, Kermode AG, Wicks D, et al. (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29: 53–62

    Article  PubMed  CAS  Google Scholar 

  7. Thompson AJ, Miller DH, Youl B, et al. (1992) Serial gadolinium enhanced MRI in relapsing remitting multiple sclerosis of varying disease duration. Neurology 42:60–63

    Article  PubMed  CAS  Google Scholar 

  8. Miller DH, Barkhof F, Nauta JJ (1993) Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis. Brain 116:1077–1094

    Article  PubMed  Google Scholar 

  9. Kidd D, Thorpe JW, Kendall BE, et al. (1996) MRI dynamics of brain and spinal cord in progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 60:15–19

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Paty DW, Li DKB, Oger JJF, et al. (1994) Magnetic resonance imaging in the evaluation of clinical trials in multiple sclerosis. Ann Neurol 36: S95–S96

    Article  PubMed  Google Scholar 

  11. Gass A, Barker GJ, Kidd D, et al. (1994) Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis. Ann Neurol 36: 62–67

    Article  PubMed  CAS  Google Scholar 

  12. IFNB Multiple Sclerosis Study Group, University of British Columbia MS/MRI Analysis Group (1995) Interferon beta-lb in the treatment of multiple sclerosis: Final outcome of the randomised, controlled trial. Neurology 45:1277–1285

    Article  Google Scholar 

  13. Gasperini C, Horsfield MA, Thorpe JW, et al. (1996) Macroscopic and microscopic assessments of disease burden by MRI in multiple sclerosis: Relationship to clinical parameters. J Magn Reson Imaging 6: 580–584

    Article  PubMed  CAS  Google Scholar 

  14. Zhao GJ, Li DKB, Wolinsky JS, et al. (1997) Clinical and magnetic resonance imaging changes correlate in a clinical trial monitoring cyclosporine therapy for multiple sclerosis. J Neuroimaging 7: 1–7

    PubMed  CAS  Google Scholar 

  15. McDonald WI (1992) Multiple sclerosis: Diagnostic optimism [editorial]. BMJ: 1256–1260

    Google Scholar 

  16. Allen IV, McKeown SR (1979) A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci 41: 81–91

    Article  PubMed  CAS  Google Scholar 

  17. Armspach JP, Gounot D, Rumbach L, et al. (1991) In vivo determination of multiexponential T2 relaxation in the brain of patients with multiple sclerosis. Magn Reson Imaging 9: 107–113

    Article  PubMed  CAS  Google Scholar 

  18. Dousset V, Grossman RI, Ramer KN, et al. (1992) Experimental allergic encephalomyelitis and multiple sclerosis: Lesion characterization with magnetization transfer imaging. Radiology 182:483–491

    Article  PubMed  CAS  Google Scholar 

  19. Filippi M, Campi A, Dousset V, et al. (1995) A magnetisation transfer imaging study of normal appearing white matter in multiple sclerosis. Neurology 45: 478–482

    Article  PubMed  CAS  Google Scholar 

  20. Loevner LA, Grossman RI, Cohen JA, et al. (1995) Microscopic disease in normal-appearing white matter on conventional images in patients with multiple sclerosis: Assessment with magnetization-transfer measurements. Radiology 196:511–515

    Article  PubMed  CAS  Google Scholar 

  21. Arnold DL, Matthews PM, Francis G, et al. (1992) Proton magnetic resonance spectroscopic imaging for metabolic characterisation of demyelinating plaques. Ann Neurol 31: 235–241

    Article  PubMed  CAS  Google Scholar 

  22. Husted CA, Goodkin DS, Hugg JW, et al. (1994) Biochemical alterations in multiple sclerosis lesions and normal appearing white matter demonstrated by in vivo 31P and 1H spectroscopic imaging. Ann Neurol 36:157–165

    Article  PubMed  CAS  Google Scholar 

  23. Rooney WD, Goodkin DE, Schuff N, et al. (1997) 1H MRSI of normal appearing white matter in multiple sclerosis. Mult Scler 3: 231–237

    Article  PubMed  CAS  Google Scholar 

  24. Davie CA, Barker GJ, Thompson AJ, et al. (1997) 1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis. J Neurol Neurosurg Psychiatry 63: 736–742

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Fu L, Matthews PM, De Stefano N, et al. (1998) Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain 121:103–113

    Article  PubMed  Google Scholar 

  26. Barbosa S, Blumhardt LD, Roberts N, et al. (1994) Magnetic resonance relaxation time mapping in multiple sclerosis: Normal appearing white matter and the “invisible” lesion load. Magn Reson Imaging 12: 33–42

    Article  PubMed  CAS  Google Scholar 

  27. Miller DH, Barkhof F, Albert PS, et al. (1996) Guidelines for the use of magnetic resonance techniques in monitoring the treatment of MS. Ann Neurol 39: 6–16

    Article  PubMed  CAS  Google Scholar 

  28. Paty DW, Li DKB, the UBC MS/MRI Study Group, the IFNB Multiple Sclerosis Study Group (1993) Interferon beta-1b is effective in relapsing-remitting MS. MRI analysis results of a multcenter, randomised, double blind, placebo controlled trial. Neurology 43: 662–667

    Article  PubMed  CAS  Google Scholar 

  29. Miller DH, Molyneux PD, MacManus DG, et al. (1998) A double-blind, placebo-controlled trial of beta interferon-1b in secondary progressive multiple sclerosis. Neurology (in press)

    Google Scholar 

  30. Polman C, Dahlke F, Thompson AJ, et al. (1995) Interferon beta-1b in secondary progressive multiple sclerosis. Outline of the clinical trial. Mult Scler 1: S51–54

    PubMed  CAS  Google Scholar 

  31. Filippi M, Horsfield MA, Ader HJ, et al. (1998) Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis. Ann Neurol 43: 499–506

    Article  PubMed  CAS  Google Scholar 

  32. Paty DW, Rebif Study Group (1997) Interferon-beta 1A (Rebif) in the treatment of relapsing-remitting multiple sclerosis: The MRI results of a large multicentre study. Mult Scler 3: 269

    Google Scholar 

  33. Molyneux PD, Miller DH, Filippi M, et al. (1998) Sample size requirements for phase III treatment trials based on changes in total brain lesion load on T2 weighted images: A model based approach to power calculations. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2:1320 (abstract)

    Google Scholar 

  34. Cavazzuti M, Merelli E, Tassone G, et al. (1997) Lesion load quantification in serial MR of early relapsing multiple sclerosis patients in azathioprine treatment. A retrospective study. Eur Neurol 38: 284–290

    Article  PubMed  CAS  Google Scholar 

  35. Filippi M, van Waesberghe JH, Horsfield MA, et al. (1997) Interscanner variation in brain MRI lesion load measurements in MS: Implications for clinical trials. Neurology 49: 371–377

    Article  PubMed  CAS  Google Scholar 

  36. Evans AC, Frank JA, Antel J, et al. (1997) The role of MRI in clinical trials of multiple sclerosis: Comparison of image processing techniques. Ann Neurol 41: 125–132

    Article  PubMed  CAS  Google Scholar 

  37. Simon JH, Jacobs LD, Campion M, et al. (1998) Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol 43: 79–87

    Article  PubMed  CAS  Google Scholar 

  38. Rudick RA, Simonian NA, Alam JA, et al. (1998) Incidence and significance of neutralizing antibodies to interferon beta-la in multiple sclerosis. Neurology 50:1266–1272

    Article  PubMed  CAS  Google Scholar 

  39. Tubridy N, Ader HJ, Barkhof F, et al. (1998) Exploratory treatment trials in multiple sclerosis using MRI: Sample size calculations for relapsing-remitting and secondary progressive subgroups using placebo controlled parallel groups. J Neurol Neurosurg Psychiatry 64: 50–55

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Thompson AJ, Kermode AJ, MacManus DG, et al. (1989) Pathogenesis of progressive multiple sclerosis [letter]. Lancet i: 1322–1323

    Article  Google Scholar 

  41. Thompson AJ, Polman C, Miller DH, et al. (1997) Primary progressive multiple sclerosis. Brain 120: 1085–1096

    Article  PubMed  Google Scholar 

  42. Leary SM, Miller DH, Thompson AJ (1997) Design of a study of interferon beta-la in primary progressive multiple sclerosis. J Neurol 244(Suppl 3): 291

    Google Scholar 

  43. Tofts PS, Barker GJ, Filippi M, et al. (1997) An oblique cylinder contrast-adjusted (OCCA) phantom to measure the accuracy of brain lesion estimation schemes in multiple sclerosis. Magn Reson Imaging 15: 183–192

    Article  PubMed  CAS  Google Scholar 

  44. Gawne-Cain ML, Webb S, Tofts P, et al. (1996) Lesion volume measurement in MS: How important is accurate repositioning? J Magn Reson Imaging 6: 705–713

    Article  PubMed  CAS  Google Scholar 

  45. Simon JH, Scherzinger A, Raff U, et al. (1997) Computerized method of lesion volume quantification in multiple sclerosis: Error of serial studies. AJNR Am J Neuroradiol 18: 580–582

    PubMed  CAS  Google Scholar 

  46. Filippi M, Marcianò N, Capra R, et al. (1997) The effect of imprecise repositioning on lesion volume measurements in patients with multiple sclerosis. Neurology 49: 274–276

    Article  PubMed  CAS  Google Scholar 

  47. Rovaris M, Gawne-Cain ML, Sormani MP, et al. (1998) The effect of repositioning on brain MRI lesion load assessment in multiple sclerosis: Reliability of subjective quality criteria. J Neurol 245: 273–275

    Article  PubMed  CAS  Google Scholar 

  48. Gallagher HL, MacManus DG, Webb SL, et al. (1997) A reproducible repositioning method for serial magnetic resonance imaging studies of the brain in treatment trials for multiple sclerosis. J Magn Reson Imaging 7: 439–441

    Article  PubMed  CAS  Google Scholar 

  49. Molyneux PD, Tubridy N, Parker GJM, et al. (1998) The effect of slice thickness between 1 and 5 mm with 3D fast-FLAIR on MRI lesion detection and quantification in multiple sclerosis. AJNR Am J Neuroradiol (in press)

    Google Scholar 

  50. Jacobs LD, Cookfair DL, Rudick RA, et al. (1996) Intramuscular interferon beta-la for disease progression in relapsing multiple sclerosis. Ann Neurol 39: 285–294

    Article  PubMed  CAS  Google Scholar 

  51. Kastrukoff LF, Oger JJ, Hashimoto SA, et al. (1990) Systemic lymphoblastoid interferon therapy in chronic progressive multiple sclerosis. I. Clinical and MRI evaluation. Neurology 40: 479–486

    Article  PubMed  CAS  Google Scholar 

  52. Hennig J, Naureth A, Friedburg H (1986) RARE imaging: A fast imaging method for clinical MR. Magn Reson Med 3: 823–833

    Article  PubMed  CAS  Google Scholar 

  53. Hennig J, Friedburg H (1988) Clinical applications and methodological developments of RARE technique. Magn Reson Imaging 6: 391–395

    Article  PubMed  CAS  Google Scholar 

  54. Bastianello S, Bozzao A, Paolillo A, et al. (1997) Fast spin-echo and fast fluid-attenuated inversion-recovery versus conventional spin-echo sequences for MR quantification of multiple sclerosis lesions. AJNR Am J Neuroradiol 18: 699–704

    PubMed  CAS  Google Scholar 

  55. Thorpe JW, Halpin SF, MacManus DG (1994) A comparison between fast and conventional spin-echo in the detection of multiple sclerosis lesions. Neuroradiology 36:388–392

    Article  PubMed  CAS  Google Scholar 

  56. Constable RT, Gore JC (1992) The loss of small objects in variable TE imaging: Implications for FSE, RARE and EPI. Magn Reson Imaging 28: 9–24

    CAS  Google Scholar 

  57. Rovaris M, Gawne-Cain ML, Wang L, et al. (1997) A comparison of conventional and fast spin-echo sequences for the measurement of lesion load in multiple sclerosis using a semiautomated contour technique. Neuroradiology 39: 161–165

    Article  PubMed  CAS  Google Scholar 

  58. Gawne-Cain ML, O’Riordan JI, Coles A, et al. (1998) MRI lesion volume measurement in MS and its correlation with disability: A comparison of fast FLAIR and spin echo sequences. J Neurol Neurosurg Psychiatry 64:197–203

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Barkhof F, Filippi M, Miller D, et al. (1997) Strategies for optimising MRI techniques aimed at monitoring disease activity in multiple sclerosis treatment trials. J Neurol 244: 76–84

    Article  PubMed  CAS  Google Scholar 

  60. Grossman RI (1996) Magnetic resonance imaging: Current status and strategies for improving multiple sclerosis clinical trial design. In: Goodkin DE, Rudick RA (eds) Treatment of multiple sclerosis: Trial design, results, and future strategies. Springer, Berlin Heidelberg New York, pp 161–186

    Chapter  Google Scholar 

  61. 61. De Coene B, Hajnal JV, Gatehouse P, et al. (1992) MR of the brain using fluid-attenuated inversion recovery (FLAIR) pulse sequences. AJNR Am J Neuroradiol 13:1555–1564

    PubMed  Google Scholar 

  62. Thorpe JW, Halpin SF, MacManus, et al. (1994) Detection of multiple sclerosis by magnetic resonance imaging. Lancet 344:1235

    Article  PubMed  CAS  Google Scholar 

  63. De Coene B, Hajnal JV, Pennock JM, et al. (1993) MR of the brain using fluid-attenuated inversion recovery (FLAIR) pulse sequences. Neuroradiology 35: 327–331

    Article  PubMed  Google Scholar 

  64. Rydberg JN, Hammond CA, Grimm RC, et al. (1994) Initial clinical experience in MR imaging of the brain with a fast fluid-attenuated inversion recovery pulse sequence. Radiology 193: 173–180

    Article  PubMed  CAS  Google Scholar 

  65. Filippi M, Yousry T, Baratti C, et al. (1996) Quantitative assessment of MRI lesion load in multiple sclerosis: A comparison of conventional spin echo with fast fluid attenuated inversion recovery. Brain 119:1349–55

    Article  PubMed  Google Scholar 

  66. Gawne-Cain ML, O’Riordan JI, Thompson AJ, et al. (1997) Multiple sclerosis lesion detection in the brain: a comparison of fast fluid-attenuated inversion recovery and conventional T2-weighted dual spin echo. Neurology 49: 364–370

    Article  PubMed  CAS  Google Scholar 

  67. 67. Hajnal JV, Oatridge J, Murdoch J, et al. (1998) Failure of FLAIR sequences to suppress CSF in the posterior fossa: Diagnosis of a problem and solution with adiabatic inversion pulses. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2:1350 (abstract)

    Google Scholar 

  68. Boggild MD, Williams R, Haq N, et al. (1996) Cortical plaques visualised by fluid-attenuated inversion recovery imaging in multiple sclerosis. Neuroradiology 38(Suppl 1): 10–13

    Article  Google Scholar 

  69. Filippi M, Horsfield MA, Rovaris M, et al. (1998) Intraobserver and interobserver variability in schemes for estimating volume of brain lesions on MR images in multiple sclerosis. AJNR Am J Neuroradiol 19: 239–244

    PubMed  CAS  Google Scholar 

  70. Gawne-Cain ML, Silver NC, Moseley IF, et al. (1997) Fast FLAIR of the brain: The range of appearances in normal subjects and its application to quantification of white matter disease. Neuroradiology 39: 243–249

    Article  PubMed  CAS  Google Scholar 

  71. Bradley WG, Glenn BJ (1987) The effect of variation in slice thickness and interslice gap on MR lesion detection. AJNR Am J Neuroradiol 8:1057–1062

    PubMed  CAS  Google Scholar 

  72. Filippi M, Horsfield MA, Campi A, et al. (1995) Resolution-dependent estimates of lesion volumes in MRI studies of the brain in multiple sclerosis. Ann Neurol 38: 749–754

    Article  PubMed  CAS  Google Scholar 

  73. Filippi M, Yousry T, Horsfield M, et al. (1996) A high-resolution three-dimensional T1-weighted gradient echo sequence improves the detection of disease activity in multiple sclerosis. Ann Neurol 40: 901–907

    Article  PubMed  CAS  Google Scholar 

  74. Barker GJ (1998) 3D Fast FLAIR. A CSF-nulled fast spin echo pulse sequence. Magn Reson Imaging (in press)

    Google Scholar 

  75. Filippi M, Horsfield MA, Tofts PS, et al. (1995) Quantitative assessment of MRI lesion load in monitoring the evolution of multiple sclerosis. Brain 118:1601–1612

    Article  PubMed  Google Scholar 

  76. Erickson BJ, Avula RT (1998) An algorithm for automatic segmentation and classification of magnetic resonance brain images. J Digit Imaging 11: 74–82

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  77. 77. Clarke LP, Velthuizen RP, Camacho MA, et al. (1995) MRI segmentation: Methods and applications. Magn Reson Imaging 13: 343–68

    Article  PubMed  CAS  Google Scholar 

  78. Plante E, Turkstra L (1991) Sources of error in the quantitative analysis of MRI scans. Magn Res Imaging 9: 589–595

    Article  CAS  Google Scholar 

  79. Molyneux PD, Wang L, Lai M, et al. (1998) Quantitative techniques for lesion load measurement in multiple sclerosis: An assessment of the global threshold technique after non-uniformity and histogram matching corrections. Eur J Neurol 5: 55–60

    Article  PubMed  Google Scholar 

  80. Fleiss JL (1985) The design and analysis of clinical experiments. John Wiley and Sons, New York

    Google Scholar 

  81. Streiner DL, Norman GR (1995) Health measurement scales: A practical guide to their development and use. Oxford University, Oxford, pp 104–127

    Google Scholar 

  82. Molyneux PD, Tofts PS, Fletcher A, et al. (1998) Precision and reliability for measurement of MRI lesion volume in multiple sclerosis: A comparison of two computer assisted techniques. J Neurol Neurosurg Psychiatry 65: 42–47

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  83. Koopmans RA, Li DKB, Redekop WK, et al. (1993) The use of magnetic resonance imaging in monitoring interferon therapy of multiple sclerosis. J Neuroimaging 3: 163–168

    PubMed  CAS  Google Scholar 

  84. Filippi M, Gawne-Cain ML, Gasperini C, et al. (1998) Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis. Neurology 50: 238–244

    Article  PubMed  CAS  Google Scholar 

  85. Wicks DAG, Tofts PS, Miller DH, et al. (1992) Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study. Neuroradiology 34: 475–479

    Article  PubMed  CAS  Google Scholar 

  86. Filippi M, Rovaris M, Campi A, et al. (1996) Semi-automated thresholding technique for measuring lesion volumes in multiple sclerosis: Effects of change of the threshold on the computed lesion loads. Acta Neurol Scand 93: 30–34

    Article  PubMed  CAS  Google Scholar 

  87. Filippi M, Horsfield MA, Bressi S, et al. (1995) Intra- and inter-observer variability of brain MRI lesion volume measurements in multiple sclerosis. A comparison of techniques. Brain 118: 1593–1600

    Article  PubMed  Google Scholar 

  88. Grimaud J, Lai M, Thorpe J, et al. (1996) Quantification of MRI lesion load in MS: a comparison of three computer-assisted techniques. Magn Reson Imaging 14: 495–505

    Article  PubMed  CAS  Google Scholar 

  89. van Walderveen MAA, Barkhof F, Hommes OR, et al. (1995) Correlating MRI and clinical disease: Relevance of hypointense lesions on short-TR/short-TE (T1-weighted) spin-echo images. Neurology 45: 1684–1690

    Article  PubMed  Google Scholar 

  90. Kohn M, Tanna M, Herman G (1991) Analysis of brain and cerebrospinal fluid volumes with MR imaging. Radiology 178:115–122

    Article  PubMed  CAS  Google Scholar 

  91. Kikinis R, Shenton M, Jolesz F, et al. (1992) Routine quantitative MRI-based analysis of brain and fluid spaces. J Magn Reson Imaging 2: 619–629

    Article  PubMed  CAS  Google Scholar 

  92. Mitchell JR, Karlik SJ, Lee DH, et al. (1994) Computer-assisted identification and quantification of multiple sclerosis lesions in MR imaging volumes in the brain. J Magn Reson Imaging 4: 197–208

    Article  PubMed  CAS  Google Scholar 

  93. Simmons A, Arridge SR, Barker GJ, et al. (1994) Improvements in the quality of MRI cluster analysis. Magn Reson Imaging 12: 1191–1204

    Article  PubMed  CAS  Google Scholar 

  94. Simmons A, Arridge SR, Barker GJ, et al. (1996) Simulation of MRI cluster plots and application to neurological segmentation. Magn Reson Imaging 14: 73–92

    Article  PubMed  CAS  Google Scholar 

  95. Bedell BJ, Narayana PA, Wolinsky JS (1997) A dual approach for minimising false lesion classification on magnetic resonance images. Magn Reson Med 37: 94–102

    Article  PubMed  CAS  Google Scholar 

  96. Udupa JK, Samarasekera S (1996) Fuzzy connectedness and object definition: Theory, algorithms and applications in image segmentation. Graph Models Image Proc 58: 246–261

    Article  Google Scholar 

  97. Udupa JK, Wei L, Samarasekera S, Miki Y, et al. (1997) Multiple sclerosis lesion quantification using fuzzy connectedness principles. IEEE Trans Med Imaging 16: 598–609

    Article  PubMed  CAS  Google Scholar 

  98. Samaresekera S, Udupa JK, Miki Y, et al. (1997) A new computer-assisted method for the quantification of enhancing lesions in multiple sclerosis. J Comput Assist Tomogr 21:145–151

    Article  Google Scholar 

  99. Edan G, Miller D, Clanet M, et al. (1997) Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: A randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 62:112–118

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  100. Goodkin DE, Ross JS, Medendorp SM, et al. (1992) MRI lesion enlargement in MS. Disease-related activity, chance occurrence, or measurement artifact? Arch Neurol 49: 261–263

    Article  PubMed  CAS  Google Scholar 

  101. Barkhof F, Filippi M, van Waesberghe JH, et al. (1997) Improving interobserver variation in reporting gadolinium-enhanced MRI lesions in multiple sclerosis. Neurology 49: 1682–1688

    Article  PubMed  CAS  Google Scholar 

  102. Molyneux PD, Miller DH, Filippi M, et al. (1998) Intra and inter-observer variation in reporting activity on serial T2 weighted brain MR images in multiple sclerosis. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2:1330 (abstract)

    Google Scholar 

  103. Smith ME, Stone LA, Albert PS, et al. (1993) Clinical worsening in multiple sclerosis is associated with increased number and area of gadopentate dimeglumine-enhancing magnetic resonance imaging lesions. Ann Neurol 33: 480–489

    Article  PubMed  CAS  Google Scholar 

  104. Filippi M, Paty DW, Kappos L (1995) Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: A follow-up study. Neurology 45:255–260

    Article  PubMed  CAS  Google Scholar 

  105. Khoury SJ, Guttman CRG, Orav EJ, et al. (1994) Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden. Neurology 44: 2120–2124

    Article  PubMed  CAS  Google Scholar 

  106. Pozilli C, Bastianello S, Koudriavtseva T, et al. (1996) Magnetic resonance imaging changes with recombinant human interferon-B-la: A short term study in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 61: 251–258

    Article  Google Scholar 

  107. Molyneux PD, Filippi M, Barkhof F, et al. (1998) Correlations between monthly enhanced MRI lesion rate and changes in T2 lesion volume in multiple sclerosis. Ann Neurol 43: 332–339

    Article  PubMed  CAS  Google Scholar 

  108. Frank JA, Stone LA, Smith ME, et al. (1994) Serial contrast-enhanced magnetic resonance imaging in patients with early relapsing-remitting multiple sclerosis: Implications for treatment trials. Ann Neurol 36(Suppl): S86–S90

    Article  PubMed  Google Scholar 

  109. Losseff N, Kingsley DPE, McDonald WI, et al. (1996) Clinical and magnetic resonance predictors of disability in primary and secondary progressive multiple sclerosis. Mult Scler 1:218–222

    PubMed  CAS  Google Scholar 

  110. Koudriavtseva T, Thompson AJ, Fiorelli M, et al. (1997) Gadolinium enhanced MRI disease activity in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 62: 285–287

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  111. Giovannoni G, Lai M, Thorpe J, et al. (1997) Longitudinal study of soluble adhesion molecules in multiple sclerosis: Correlation with gadolinium enhanced magnetic resonance imaging. Neurology 48: 1557–1565

    Article  PubMed  CAS  Google Scholar 

  112. Hiehle JF, Grossman RI, Ramer KN, et al. (1995) Magnetization transfer effects in MR-detected multiple sclerosis lesions: Comparison with gadolinium-enhanced spin echo images and nonenhanced T1-weighted images. AJNR Am J Neuroradiol 16: 69–77

    PubMed  Google Scholar 

  113. van Waesberghe JHTM, Castelijns JA, Scheltens P, et al. (1997) Comparison of four potential parameters of tissue destruction in multiple sclerosis lesions. Magn Reson Imaging 15: 155–162

    Article  PubMed  Google Scholar 

  114. Truyen L, van Waesberghe JH, van Walderveen MA, et al. (1996) Accumulation of hypointense lesions (‘black holes’) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 47: 1469–1476

    Article  PubMed  CAS  Google Scholar 

  115. van Walderveen MAA, Kamphorst W, Scheltens, et al. (1998) Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 50: 1282–1288

    Article  PubMed  Google Scholar 

  116. van Waesberghe JHTM, van der Boom R, Filippi M, et al. (1998) MR outcomes in multiple sclerosis. Comparison of conventional parameters and MTR parameters in association with disability. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2: 1319 (abstract)

    Google Scholar 

  117. Lycklama a Nijeholt GJ, van Walderveen MAA, Castelijns JA, et al. (1998) Brain and spinal cord abnormalities in multiple sclerosis. Correlations between MRI parameters, clinical subtypes and symptoms. Brain 121: 687–697

    Article  Google Scholar 

  118. Filippi M, Rocca MA, Horsfield MA, et al. (1998) Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis. AJNR Am J Neuroradiol 19: 235–238

    PubMed  CAS  Google Scholar 

  119. Sailer M, Losseff N, Wang L, et al. (1998) The relationship between T1 lesion load and cerebral atrophy in multiple sclerosis. J Neurol 245(6/7): 371 (abstract)

    Google Scholar 

  120. O’Riordan JI, Gawne-Cain M, Coles A, et al. (1998) T1 hypointense lesion load assessment in secondary progressive multiple sclerosis. J Neurol 245(6/7): 440 (abstract)

    Google Scholar 

  121. van Waesberghe JHTM, van Walderveen MAA, Castelijns JA, et al. (1998) Patterns of lesion development in multiple sclerosis: Longitudinal observations with T1-weighted spin-echo and magnetisation transfer MR. AJNR Am J Neuroradiol 19: 675–683

    PubMed  Google Scholar 

  122. Wolff SD, Balaban RS (1989) Magnetisation transfer contrast (MTC) and tissue water proton relaxation in vivo. Magn Reson Med 10:135–144

    Article  PubMed  CAS  Google Scholar 

  123. Wolff SD, Balaban RS (1994) Magnetization transfer imaging: Practical aspects and clinical applications. Radiology 192: 593–599

    Article  PubMed  CAS  Google Scholar 

  124. Fralix TA, Ceckler TL, Wolff SD, et al. (1991) Lipid bilayer and water proton magnetization transfer: Effect of cholesterol. Magn Reson Med 18: 214–223

    Article  PubMed  CAS  Google Scholar 

  125. Silver NC, Barker GJ, MacManus, et al. (1996) Decreased magnetisation transfer ratio due to demyelination: A case of central pontine myelinolysis. J Neurol Neurosurg Psychiatry 61: 208–209

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  126. Silver NC, Barker GJ, MacManus DG, et al. (1997) Magnetisation transfer ratio of normal brain white matter: A normative database spanning four decades of life. J Neurol Neurosurg Psychiatry 62: 223–228

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  127. Lexa FJ, Grossman RI, Rosenquist AC (1994) MR of Wallerian degeneration in the feline visual system: Characterization by magnetization transfer rate with histopathologic correlation. AJNR Am J Neuroradiol 15: 201–212

    PubMed  CAS  Google Scholar 

  128. Dousset V, Brochet B, Vital F, et al. (1994) MR Imaging including diffusion and magnetisation transfer of chronic relapsing experimental encepalomyelitis-correlation with immunological and pathological datas. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2:1401 (abstract)

    Google Scholar 

  129. Dousset V, Brochet B, Vital A, et al. (1995) Lysolecithin-induced demyelination in primates: Preliminary in vivo study with MR and magnetisation transfer. AJNR Am J Neuroradiol 16: 225–231

    PubMed  CAS  Google Scholar 

  130. Thorpe JW, Barker GJ, Jones SJ, et al. (1995) Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and elctrophysiology. J Neurol Neurosurg Psychiatry 59: 487–492

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  131. Filippi M, Rocca MA, Rizzo G, et al. (1998) Magnetization transfer ratios in multiple sclerosis lesions enhancing after different doses of gadolinium. Neurology 50: 1289–1293

    Article  PubMed  CAS  Google Scholar 

  132. Lai HM, Davie CA, Gass A, et al. (1997) Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple sclerosis. J Neurol 244: 308–311

    Article  PubMed  CAS  Google Scholar 

  133. van Buchem MA, McGowan JC, Kolson DL, et al. (1996) Quantitative volumetric magnetisation transfer analysis in multiple sclerosis: Estimation of macroscopic and microscopic disease burden. Magn Reson Med 36: 632–636

    Article  PubMed  Google Scholar 

  134. van Buchem MA, Udupa JK, McGowan, et al. (1997) Global volumetric estimation of disease burden in multiple sclerosis based on magnetisation transfer imaging. AJNR Am J Neuroradiol 18:1287–1290

    PubMed  Google Scholar 

  135. Silver NC, Gass A, Barker GJ, et al. (1998) Evaluation of magnetisation transfer ratio histogram analysis methods in multiple sclerosis. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2: 1322 (abstract)

    Google Scholar 

  136. Iannucci G, Rovaris M, Minicucci L, et al. (1998) Assessment of disease severity in multiple sclerosis patients with magnetisation transfer histograms. In: Proceeding of the International Society of Magnetic Resonance in Medicine 1: 120 (abstract)

    Google Scholar 

  137. Berry I, Barker G, Barkhof F, et al. (1996) A multicenter measurement of magnetisation transfer ratio in normal white matter. In: Proceedings of the International Society of Magnetic Resonance in Medicine 1: 536 (abstract)

    Google Scholar 

  138. Barker GJ, Schreiber W, Gass A, et al. (1997) Standardising magnetisation transfer ratio measurements between MR scanners from different manufacturers. In: Proceedings of the International Society of Magnetic Resonance in Medicine 3: 1556 (abstract)

    Google Scholar 

  139. Kidd D, Thorpe JW, Thompson AJ, et al. (1993) Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology 43: 2632–2637

    Article  PubMed  CAS  Google Scholar 

  140. Thorpe JW, Kidd D, Moseley IF, et al. (1996) Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Neurology 46: 373–378

    Article  PubMed  CAS  Google Scholar 

  141. Thorpe JW, Kidd D, Moseley IF, et al. (1996) Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI. Brain 119: 709–714

    Article  PubMed  Google Scholar 

  142. Filippi M, Campi A, Colombo B, et al. (1996) A spinal cord MRI study of benign and secondary progressive multiple sclerosis. J Neurol 243: 502–505

    Article  PubMed  CAS  Google Scholar 

  143. Losseff NA, Webb SL, O’Riordan JI, et al. (1996) Spinal cord atrophy and disability in multiple sclerosis: A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119: 701–708

    Article  PubMed  Google Scholar 

  144. Losseff NA, Stevenson VL, Miller DH, et al. (1996) Spinal cord atrophy and disability in multiple sclerosis: A serial MRI study. Eur J Neurol 3(Suppl 4): 2 (abstract)

    Google Scholar 

  145. Stevenson VL, Leary SM, Losseff NA, et al. (1998) Spinal cord atrophy and disability in multiple sclerosis: A longitudinal study. Neurology (in press)

    Google Scholar 

  146. Silver NC, Barker GJ, Losseff NA, et al. (1997) Magnetisation transfer ratio measurement in the cervical spinal cord: A preliminary study in multiple sclerosis. Neuroradiology 39: 441–445

    Article  PubMed  CAS  Google Scholar 

  147. Mathias JM, Tofts PS, Losseff NA (1998) Quantification of pathological changes within the spinal cord due to multiple sclerosis (MS) using texture analysis. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2:1336 (abstract)

    Google Scholar 

  148. Losseff NA, Wang L, Lai HM, et al. (1996) Progressive cerebral atrophy in multiple sclerosis. A serial study. Brain 119: 2009–2019

    Article  PubMed  Google Scholar 

  149. Fox NC, Freeborough PA (1997) Brain atrophy progression measured from registered serial MRI: Validation and application to Alzheimer’s disease. J Magn Reson Imaging 7: 1069–1075

    Article  PubMed  CAS  Google Scholar 

  150. Mastronardo G, Rocca MA, Comi G, et al. (1998) Quantitative volumetric analysis of brain MRI from patients with multiple sclerosis. In: Proceedings of the International Society of Magnetic Resonance in Medicine 2:1315 (abstract)

    Google Scholar 

  151. Arnold DL, Matthews PM, Francis G, et al. (1990) Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: Assessment of the load of disease. Magn Reson Med 14: 154–159

    Article  PubMed  CAS  Google Scholar 

  152. Davie CA, Barker GJ, Webb S, et al. (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118:1583–1592

    Article  PubMed  Google Scholar 

  153. Davie CA, Hawkins CP, Barker GJ, et al. (1994) Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 117: 49–58

    Article  PubMed  Google Scholar 

  154. De Stefano N, Matthews PM, Antel JP, et al. (1995) Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann Neurol 38: 901–909

    Article  PubMed  Google Scholar 

  155. Narayana PA, Doyle TJ, Lai D, et al. (1998) Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol 43: 56–71

    Article  PubMed  CAS  Google Scholar 

  156. Larsson HBW, Christianson P, Jenson M, et al. (1991) Localized in vivo proton spectroscopy in the brain of patients with multiple sclerosis. Magn Reson Med 22: 23–31

    Article  PubMed  CAS  Google Scholar 

  157. Grossman RI, Lenkinski RE, Ramer KN, et al. (1992) MR proton spectroscopy in multiple sclerosis. AJNR Am J Neuroradiol 13: 1535–1543

    PubMed  CAS  Google Scholar 

  158. Kidd D, Barker GJ, Tofts PS, et al. (1997) The transverse magnetisation decay characteristics of longstanding lesions and normal-appearing white matter in multiple sclerosis. J Neurol 244:125–130

    Article  PubMed  CAS  Google Scholar 

  159. Horsfield MA, Lai M, Webb SL, et al. (1996) Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance. Magn Reson Med 36: 393–400

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. NMR Research Unit, Institute of Neurology, National Hospital, Queen Square, London, UK

    P. D. Molyneux & D. H. Miller

Authors
  1. P. D. Molyneux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. H. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Neuroimaging Research Unit, Department of Neuroscience Scientific Institute Ospedale San Raffaele, University of Milan, Italy

    Massimo Filippi

  2. Department of Radiology, University of Pennsylvania, Philadelphia, USA

    Robert I. Grossman

  3. Clinical Trials Unit, Department of Neuroscience, Scientific Institute Ospedale San Raffaele, University of Milan, Italy

    Giancarlo Comi

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Italia

About this paper

Cite this paper

Molyneux, P.D., Miller, D.H. (1999). Magnetic Resonance Imaging Techniques to Monitor Phase III Treatment Trials. In: Filippi, M., Grossman, R.I., Comi, G. (eds) Magnetic Resonance Techniques in Clinical Trials in Multiple Sclerosis. Topics in Neuroscience. Springer, Milano. https://doi.org/10.1007/978-88-470-2153-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-2153-2_5

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-2180-8

  • Online ISBN: 978-88-470-2153-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation