Characterization of brain tumours with spin–spin relaxation: pilot case study reveals unique T 2 distribution profiles of glioblastoma, oligodendroglioma and meningioma

Journal of Neurology volume 264, pages2205–2214(2017)Cite this article

Abstract

Prolonged spin–spin relaxation times in tumour tissue have been observed since some of the earliest nuclear magnetic resonance investigations of the brain. Over the last three decades, numerous studies have sought to characterize tumour morphology and malignancy using quantitative assessment of T 2 relaxation times, although attempts to categorize and differentiate tumours have had limited success. However, previous work must be interpreted with caution as relaxation data were typically acquired using a variety of multiple echo sequences with a range of echoes and T 2 decay curves and were frequently fit with monoexponential analysis. We defined the distribution of T 2 components in three different human brain tumours (glioblastoma, oligodendroglioma, meningioma) using a multi-echo sequence with a greater number of echoes and a longer acquisition window than previously used (48 echoes, data collection out to 1120 ms) with no a priori assumptions about the number of exponential components contributing to the T 2 decay. T 2 relaxation times were increased in tumour tissue and each tumour showed a distinct T 2 distribution profile. Tumours have complex and unique compartmentalization characteristics. Quantitative assessment of T 2 relaxation in brain cancer may be useful in evaluating different grades of brain tumours on the basis of their T 2 distribution profile, and has the potential to be a non-invasive diagnostic tool which may also be useful in monitoring therapy. Further study with a larger sample size and varying grades of tumours is warranted.

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References

  1. 1.

    Parrish RG, Kurland RJ, Janese WW, Bakay L (1974) Proton relaxation rates of water in brain and brain tumors. Science 183(123):438–439

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Kjaer L, Thomsen C, Gjerris F, Mosdal B, Henriksen O (1991) Tissue characterization of intracranial tumors by MR imaging. In vivo evaluation of T1- and T2-relaxation behavior at 1.5 T. Acta Radiol 32(6):498–504

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Oh J, Cha S, Aiken AH, Han ET, Crane JC, Stainsby JA, Wright GA, Dillon WP, Nelson SJ (2005) Quantitative apparent diffusion coefficients and T2 relaxation times in characterizing contrast enhancing brain tumors and regions of peritumoral edema. J Magn Reson Imaging 21(6):701–708. doi:10.1002/jmri.20335

    Article  PubMed  Google Scholar 

  4. 4.

    Naruse S, Horikawa Y, Tanaka C, Hirakawa K, Nishikawa H, Yoshizaki K (1986) Signifcance of proton relaxation time measurement in brain oedema, cerebral infarction and brain tumors. Magn Reson Med 4:293–304

    CAS  Google Scholar 

  5. 5.

    Martin-Landrove M, Figueroa G, Paluszny M, Torres W (2007) A quasi-analytical method for relaxation rate distribution determination of T2-weighted MRI in brain. Conf Proc IEEE Eng Med Biol Soc 2007:1318–1321. doi:10.1109/iembs.2007.4352540

    PubMed  Google Scholar 

  6. 6.

    Chatel M, Darcel F, de Certaines J, Benoist L, Bernard AM (1986) T1 and T2 proton nuclear magnetic resonance (NMR) relaxation times in vitro and human intracranial tumours. Results from 98 patients. J Neurooncol 3(4):315–321

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Ngo FQ, Bay JW, Kurland RJ, Weinstein MA, Hahn JF, Glassner BJ, Woolley CA, Dudley AW Jr, Ferrario CM, Meaney TF (1985) Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements. Magn Reson Imaging 3(2):145–155

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Rinck PA, Meindl S, Higer HP, Bieler EU, Pfannenstiel P (1985) Brain tumors: detection and typing by use of CPMG sequences and in vivo T2 measurements. Radiology 157(1):103–106

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Just M, Higer HP, Schwarz M, Bohl J, Fries G, Pfannenstiel P, Thelen M (1988) Tissue characterization of benign brain tumors: use of NMR-tissue parameters. Magn Reson Imaging 6(4):463–472

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Wilmes LJ, Hoehn-Berlage M, Els T, Bockhorst K, Eis M, Bonnekoh P, Hossmann KA (1993) In vivo relaxometry of three brain tumors in the rat: effect of Mn-TPPS, a tumor-selective contrast agent. J Magn Reson Imaging 3(1):5–12

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Eis M, Els T, Hoehn-Berlage M (1995) High resolution quantitative relaxation and diffusion MRI of three different experimental brain tumors in rat. Magn Reson Med 34(6):835–844

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Hoehn-Berlage M, Bockhorst K (1994) Quantitative magnetic resonance imaging of rat brain tumors: in vivo NMR relaxometry for the discrimination of normal and pathological tissues. Technol Health Care 2(4):247–254

    CAS  PubMed  Google Scholar 

  13. 13.

    Schad LR, Brix G, Zuna I, Harle W, Lorenz WJ, Semmler W (1989) Multiexponential proton spin–spin relaxation in MR imaging of human brain tumors. J Comput Assist Tomogr 13(4):577–587

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Rajan SS, Rosa L, Francisco J, Muraki A, Carvlin M, Tuturea E (1990) MRI characterization of 9L-glioma in rat brain at 4.7 Tesla. Magn Reson Imaging 8(2):185–190

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Hoehn-Berlage M, Tolxdorff T, Bockhorst K, Okada Y, Ernestus RI (1992) In vivo NMR T2 relaxation of experimental brain tumors in the cat: a multiparameter tissue characterization. Magn Reson Imaging 10(6):935–947

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Bockhorst K, Hoehn-Berlage M, Ernestus RI, Tolxdorf T, Hossmann KA (1993) NMR-contrast enhancement of experimental brain tumors with MnTPPS: qualitative evaluation by in vivo relaxometry. Magn Reson Imaging 11(5):655–663

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Larsson HB, Barker GJ, MacKay A (1998) Nuclear magnetic resonance relaxation in multiple sclerosis. J Neurol Neurosurg Psychiatry 64(Suppl 1):S70–S76

    PubMed  Google Scholar 

  18. 18.

    Does MD, Gore JC (2002) Compartmental study of T(1) and T(2) in rat brain and trigeminal nerve in vivo. Magn Reson Med 47(2):274–283

    Article  PubMed  Google Scholar 

  19. 19.

    Whittall KP, MacKay AL, Li DK (1999) Are mono-exponential fits to a few echoes sufficient to determine T2 relaxation for in vivo human brain? Magn Reson Med 41(6):1255–1257

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Dortch RD, Yankeelov TE, Yue Z, Quarles CC, Gore JC, Does MD (2009) Evidence of multiexponential T2 in rat glioblastoma. NMR Biomed 22(6):609–618. doi:10.1002/nbm.1374

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Ali TS, Bjarnason T, Sun Y, Lun X, Senger D, Forsyth P, Dunn J, Mitchell JR (2009) Is quantitative T2 sensitive to tumor cell infiltration?. International Society for Magnetic Resonance in Medicine, Stockholm, p 3163

    Google Scholar 

  22. 22.

    Laule C, Kolind SH, Bjarnason TA, Li DK, Mackay AL (2007) In vivo multiecho T(2) relaxation measurements using variable TR to decrease scan time. Magn Reson Imaging 25(6):834–839

    Article  PubMed  Google Scholar 

  23. 23.

    Bjarnason TA, Mitchell JR (2010) AnalyzeNNLS: magnetic resonance multiexponential decay image analysis. J Magn Reson 206(2):200–204. doi:10.1016/j.jmr.2010.07.008

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Whittall KP, MacKay AL (1989) Quantitative interpretation of nmr relaxation data. J Magn Reson 84:134–152

    CAS  Google Scholar 

  25. 25.

    Jones CK, Whittall KP, MacKay AL (2003) Robust myelin water quantification: averaging vs. spatial filtering. Magn Reson Med 50(1):206–209

    Article  PubMed  Google Scholar 

  26. 26.

    Efron B, Tibshirani RJ (1986) Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci 1:54–77

    Article  Google Scholar 

  27. 27.

    Skinner MG, Kolind SH, Mackay AL (2007) The effect of varying echo spacing within a multiecho acquisition: better characterization of long T(2) components. Magn Reson Imaging 25(6):834–839

    Article  Google Scholar 

  28. 28.

    MacKay A, Whittall K, Adler J, Li D, Paty D, Graeb D (1994) In vivo visualization of myelin water in brain by magnetic resonance. Magn Reson Med 31(6):673–677

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Russell-Schulz B, Laule C, Li DK, MacKay AL (2013) What causes the hyperintense T2-weighting and increased short T2 signal in the corticospinal tract? Magn Reson Imaging 31(3):329–335. doi:10.1016/j.mri.2012.07.003

    Article  PubMed  Google Scholar 

  30. 30.

    Engelhard HH, Stelea A, Cochran EJ (2002) Oligodendroglioma: pathology and molecular biology. Surg Neurol 58(2):111–117 (discussion 117)

    Article  PubMed  Google Scholar 

  31. 31.

    Manousaki M, Papadaki H, Papavdi A, Kranioti EF, Mylonakis P, Varakis J, Michalodimitrakis M (2011) Sudden unexpected death from oligodendroglioma: a case report and review of the literature. Am J Forensic Med Pathol 32(4):336–340. doi:10.1097/PAF.0b013e3181d3dc86

    Article  PubMed  Google Scholar 

  32. 32.

    Robertson DM, Vogel FS (1962) Concentric lamination of glial processes in oligodendrogliomas. J Cell Biol 15:313–334

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Liberski PP, Kordek R (1997) Ultrastructural pathology of glial brain tumors revisited: a review. Ultrastruct Pathol 21(1):1–31

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Liberski PP (1996) The ultrastructure of oligodendroglioma: personal experience and the review of the literature. Folia Neuropathol 34(4):206–211

    CAS  PubMed  Google Scholar 

  35. 35.

    Kamitani H, Masuzawa H, Sato J, Okada M (1986) Ultrastructure of concentric laminations in primary human brain tumors. Acta Neuropathol 71(1–2):83–87

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Hokama Y, Tanaka J, Nakamura H, Hori T (1986) MBP and GFAP immunohistochemistry of oligodendrogliomas with relationship to myelin-forming glia in cell differentiation. No To Shinkei 38(4):379–386

    CAS  PubMed  Google Scholar 

  37. 37.

    Sirrs SM, Laule C, Maedler B, Brief EE, Tahir SA, Bishop C, MacKay AL (2007) Normal appearing white matter in subjects with phenylketonuria: water content, myelin water fraction, and metabolite concentrations. Radiology 242(1):236–243

    Article  PubMed  Google Scholar 

  38. 38.

    Laule C, Vavasour IM, Madler B, Kolind SH, Sirrs SM, Brief EE, Traboulsee AL, Moore GR, Li DK, Mackay AL (2007) MR evidence of long T(2) water in pathological white matter. J Magn Reson Imaging 26(4):1117–1121

    Article  PubMed  Google Scholar 

  39. 39.

    Crome L (1962) The association of phenylketonuria with leucodystrophy. J Neurol Neurosurg Psychiatry 25:149–153

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Crome L, Pare CMB (1960) Phenylketonuria. J Ment Sci 106:S62

    Google Scholar 

  41. 41.

    Malamud N (1966) Neuropathology of phenylketonuria. J Neuropathol Exp Neurol 25(2):254–268

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Eimoto T, Hashimoto K (1977) Vacuolated meningioma. A light and electron microscopic study. Acta Pathol Jpn 27(4):557–566

    CAS  PubMed  Google Scholar 

  43. 43.

    Yoshida T, Hirato J, Sasaki A, Yokoo H, Nakazato Y, Kurachi H (1999) Intranuclear inclusions of meningioma associated with abnormal cytoskeletal protein expression. Brain Tumor Pathol 16(2):86–91

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Ito H, Kawano N, Yada K, Kameya T (1991) Meningiomas differentiating to arachnoid trabecular cells: a proposal for histological subtype “arachnoid trabecular cell meningioma”. Acta Neuropathol 82(5):327–330

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Yamashima T, Kida S, Yamamoto S (1988) Ultrastructural comparison of arachnoid villi and meningiomas in man. Mod Pathol 1(3):224–234

    CAS  PubMed  Google Scholar 

  46. 46.

    Englund E, Brun A, Larsson EM, Gyorffy-Wagner Z, Persson B (1986) Tumours of the central nervous system. Proton magnetic resonance relaxation times T1 and T2 and histopathologic correlates. Acta Radiol Diagn (Stockh) 27(6):653–659

    CAS  Article  Google Scholar 

  47. 47.

    Menon RS, Rusinko MS, Allen PS (1992) Proton relaxation studies of water compartmentalization in a model neurological system. Magn Reson Med 28(2):264–274

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Does MD, Snyder RE (1995) T2 relaxation of peripheral nerve measured in vivo. Magn Reson Imaging 13(4):575–580

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Does MD, Snyder RE (1996) Multiexponential T2 relaxation in degenerating peripheral nerve. Magn Reson Med 35(2):207–213

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Laule C, Vavasour IM, Kolind SH, Traboulsee AL, Moore GRW, Li DKB, MacKay AL (2007) Long T2 water in multiple sclerosis: what else can we learn from multi-echo T2 relaxation? J Neurol 254(11):1579–1587

    Article  PubMed  Google Scholar 

  51. 51.

    Whittall KP, MacKay AL, Li DK, Vavasour IM, Jones CK, Paty DW (2002) Normal-appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T(2). Magn Reson Med 47(2):403–408

    Article  PubMed  Google Scholar 

  52. 52.

    Jenkinson MD, du Plessis DG, Smith TS, Brodbelt AR, Joyce KA, Walker C (2010) Cellularity and apparent diffusion coefficient in oligodendroglial tumours characterized by genotype. J Neurooncol 96(3):385–392. doi:10.1007/s11060-009-9970-9

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Deng Z, Yan Y, Zhong D, Yang G, Tang W, Lu F, Xie B, Liu B (2010) Quantitative analysis of glioma cell invasion by diffusion tensor imaging. J Clin Neurosci 17(12):1530–1536. doi:10.1016/j.jocn.2010.03.060

    Article  PubMed  Google Scholar 

  54. 54.

    Prasloski T, Rauscher A, MacKay AL, Hodgson M, Vavasour IM, Laule C, Madler B (2012) Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence. Neuroimage 63(1):533–539. doi:10.1016/j.neuroimage.2012.06.064

    Article  PubMed  Google Scholar 

  55. 55.

    Tsolaki E, Kousi E, Svolos P, Kapsalaki E, Theodorou K, Kappas C, Tsougos I (2014) Clinical decision support systems for brain tumor characterization using advanced magnetic resonance imaging techniques. World J Radiol 6(4):72–81. doi:10.4329/wjr.v6.i4.72

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Roy B, Gupta RK, Maudsley AA, Awasthi R, Sheriff S, Gu M, Husain N, Mohakud S, Behari S, Pandey CM, Rathore RK, Spielman DM, Alger JR (2013) Utility of multiparametric 3-T MRI for glioma characterization. Neuroradiology 55(5):603–613. doi:10.1007/s00234-013-1145-x

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Zhang H, Tan Y, Wang XC, Qing JB, Wang L, Wu XF, Zhang L, Liu QW (2013) Susceptibility-weighted imaging: the value in cerebral astrocytomas grading. Neurol India 61(4):389–395. doi:10.4103/0028-3886.117617

    Article  PubMed  Google Scholar 

  58. 58.

    Ma L, Song ZJ (2013) Differentiation between low-grade and high-grade glioma using combined diffusion tensor imaging metrics. Clin Neurol Neurosurg 115(12):2489–2495. doi:10.1016/j.clineuro.2013.10.003

    Article  PubMed  Google Scholar 

  59. 59.

    Einstein DB, Wessels B, Bangert B, Fu P, Nelson AD, Cohen M, Sagar S, Lewin J, Sloan A, Zheng Y, Williams J, Colussi V, Vinkler R, Maciunas R (2012) Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys 84(3):668–674. doi:10.1016/j.ijrobp.2012.01.020

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Sincere thanks to the subjects, MRI technologists, neuropathologists and surgeons and the MS Society of Canada. Thank you to Katy Wyper for assistance with the literature search. CL was the recipient of the Women Against MS (WAMS) endMS Research and Training Network Transitional Career Development Award from the Multiple Sclerosis Society of Canada.

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Affiliations

  1. Radiology, University of British Columbia, Vancouver, Canada

    Cornelia Laule, Thorarin A. Bjarnason, Irene M. Vavasour, David K. B. Li & Alex L. MacKay

  2. Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

    Cornelia Laule & G. R. Wayne Moore

  3. Blusson Spinal Cord Centre/ICORD (International Collaboration on Repair Discoveries), 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada

    Cornelia Laule & G. R. Wayne Moore

  4. Diagnostic Imaging Services, Interior Health, Kelowna, Canada

    Thorarin A. Bjarnason

  5. Physics, University of British Columbia Okanagan, Kelowna, Canada

    Thorarin A. Bjarnason

  6. Medicine, University of British Columbia, Vancouver, Canada

    Anthony L. Traboulsee, G. R. Wayne Moore & David K. B. Li

  7. UBC MRI Research Centre, University of British Columbia, Vancouver, Canada

    David K. B. Li & Alex L. MacKay

  8. Physics and Astronomy, University of British Columbia, Vancouver, Canada

    Alex L. MacKay

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  1. Cornelia Laule
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  2. Thorarin A. Bjarnason
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  4. Anthony L. Traboulsee
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  5. G. R. Wayne Moore
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  7. Alex L. MacKay
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Correspondence to Cornelia Laule.

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This study was approved by the Clinical Research Ethics Board at the University of British Columbia with written informed consent obtained from all subjects in accordance with the Declaration of Helsinki of 1964 and its later amendments.

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Laule, C., Bjarnason, T.A., Vavasour, I.M. et al. Characterization of brain tumours with spin–spin relaxation: pilot case study reveals unique T 2 distribution profiles of glioblastoma, oligodendroglioma and meningioma. J Neurol 264, 2205–2214 (2017). https://doi.org/10.1007/s00415-017-8609-6

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Keywords

  • Tumour
  • MRI
  • T 2 relaxation
  • Edema
  • Glioblastoma
  • Oligodendroglioma
  • Meningioma