Advertisement

European Radiology

, Volume 19, Issue 8, pp 2041–2048 | Cite as

Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation

  • Sonali S. De Silva
  • Geoffrey S. Payne
  • Veronica A. Morgan
  • Thomas E. J. Ind
  • John H. Shepherd
  • Desmond P. J. Barton
  • Nandita M. deSouzaEmail author
Magnetic Resonance

Abstract

To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR = 1,500 ms, TE = 135 ms). tCho, 2 ppm and -CH2 lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. 1H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p = 0.03) and 2 ppm (p = 0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH2 lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH2 lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer.

Keywords

Cervical cancer 1H MR spectroscopy Cervical intraepithelial neoplasia Choline Mobile lipid resonances 

Notes

Acknowledgements

This study was supported by Cancer Research UK (CUK) grant numbers C1353/A5408 and C1060/A808. We thank Mr. Paul Carter, Mr. Norman McWhinney, Mr. Mike Katesmark, Ms. Jane Bridges and Mr. David Milliken for their assistance with patient recruitment and sample collection and Dr. Valerie Thomas for her assistance with histopathology. We are grateful to nurses and medical staff at St George’s Hospital, Epsom and St. Helier Hospitals and at The Royal Marsden Hospital, for their support.

References

  1. 1.
    Sitter B, Bathen T, Hagen B, Arentz C, Skjeldestad FE, Gribbestad IS (2004) Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy. MAGMA 16:174–181PubMedCrossRefGoogle Scholar
  2. 2.
    Bolan PJ, Meisamy S, Baker EH et al (2003) In vivo quantification of choline compounds in the breast with 1H MR spectroscopy. Magn Reson Med 50:1134–1143PubMedCrossRefGoogle Scholar
  3. 3.
    Mueller-Lisse UG, Swanson MG, Vigneron DB, Kurhanewicz J (2007) Magnetic resonance spectroscopy in patients with locally confined prostate cancer: association of prostatic citrate and metabolic atrophy with time on hormone deprivation therapy, PSA level, and biopsy Gleason score. Eur Radiol 17:371–378PubMedCrossRefGoogle Scholar
  4. 4.
    Mahon MM, Williams AD, Soutter WP et al (2004) 1H magnetic resonance spectroscopy of invasive cervical cancer: an in vivo study with ex vivo corroboration. NMR Biomed 17:1–9PubMedCrossRefGoogle Scholar
  5. 5.
    De Silva SS, Payne GS, Thomas V, Carter P, Ind T, deSouza NM (2009) Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using (1)H and (31)P magic angle spinning MRS of intact tissue. NMR Biomed 22(2):191–8PubMedCrossRefGoogle Scholar
  6. 6.
    Gruber S, Stadlbauer A, Mlynarik V, Gatterbauer B, Roessler K, Moser E (2005) Proton magnetic resonance spectroscopic imaging in brain tumor diagnosis. Neurosurg Clin N Am 16:101–14PubMedCrossRefGoogle Scholar
  7. 7.
    Hourani R, Brant LJ, Rizk T, Weingart JD, Barker PB, Horska A (2008) Can proton MR spectroscopic and perfusion imaging differentiate between neoplastic and nonneoplastic brain lesions in adults? AJNR Am J Neuroradiol 29:366–372PubMedCrossRefGoogle Scholar
  8. 8.
    Nelson SJ, Graves E, Pirzkall A et al (2002) In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1H MRSI. J Magn Reson Imaging 16:464–476PubMedCrossRefGoogle Scholar
  9. 9.
    Hu J, Yu Y, Kou Z et al (2008) A high spatial resolution 1H magnetic resonance spectroscopic imaging technique for breast cancer with a short echo time. Magn Reson Imaging 26:360–366PubMedCrossRefGoogle Scholar
  10. 10.
    Hricak H (2005) MR imaging and MR spectroscopic imaging in the pre-treatment evaluation of prostate cancer. Br J Radiol 78(Spec No 2):S103–S111PubMedCrossRefGoogle Scholar
  11. 11.
    Kwock L, Smith JK, Castillo M et al (2006) Clinical role of proton magnetic resonance spectroscopy in oncology: brain, breast, and prostate cancer. Lancet Oncol 7:859–868PubMedCrossRefGoogle Scholar
  12. 12.
    Mueller-Lisse UG, Scherr M (2003) 1H magnetic resonance spectroscopy of the prostate. Radiology 43:481–488CrossRefGoogle Scholar
  13. 13.
    Gilderdale DJ, deSouza NM, Coutts GA et al (1999) Design and use of internal receiver coils for magnetic resonance imaging. Br J Radiol 72:1141–1151PubMedGoogle Scholar
  14. 14.
    Star-Lack J, Nelson SJ, Kurhanewicz J, Huang LR, Vigneron DB (1997) Improved water and lipid suppression for 3D PRESS CSI using RF band selective inversion with gradient dephasing (BASING). Magn Reson Med 38:311–321PubMedCrossRefGoogle Scholar
  15. 15.
    Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14:260–264PubMedCrossRefGoogle Scholar
  16. 16.
    Reinsberg SA, Payne GS, Riches SF et al (2007) Combined use of diffusion-weighted MRI and 1H MR spectroscopy to increase accuracy in prostate cancer detection. AJR Am J Roentgenol 188:91–98PubMedCrossRefGoogle Scholar
  17. 17.
    Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153PubMedCrossRefGoogle Scholar
  18. 18.
    Vanhamme L, van den BA, Van Huffel S (1997) Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 129:35–43PubMedCrossRefGoogle Scholar
  19. 19.
    Armitage P, Berry G, Matthews JNS (2001) Statistical Methods in Medical Research. Blackwell Science Ltd, OxfordGoogle Scholar
  20. 20.
    Pickles M, Boothi S, Manton D et al (2008) Proton Spectrscopy of Gynaecology Lesions at 3.0T in a Routine Clinical Setting. Proc Int Soc Magn Res Med 16:3844Google Scholar
  21. 21.
    Candiota AP, Majos C, Bassols A et al (2004) Assignment of the 2.03 ppm resonance in in vivo 1H MRS of human brain tumour cystic fluid: contribution of macromolecules. MAGMA 17:36–46PubMedCrossRefGoogle Scholar
  22. 22.
    Andre E, Xu M, Yang D et al (2006) MR spectroscopy in sinus mucocele: N-acetyl mimics of brain N-acetylaspartate. AJNR Am J Neuroradiol 27:2210–2213PubMedGoogle Scholar
  23. 23.
    Lee JH, Cho KS, Kim YM et al (1998) Localized in vivo 1H nuclear MR spectroscopy for evaluation of human uterine cervical carcinoma. AJR Am J Roentgenol 170:1279–1282PubMedGoogle Scholar
  24. 24.
    Allen JR, Prost RW, Griffith OW, Erickson SJ, Erickson BA (2001) In vivo proton (H1) magnetic resonance spectroscopy for cervical carcinoma. Am J Clin Oncol 24:522–529PubMedCrossRefGoogle Scholar
  25. 25.
    So P, Krausz T, Soutter W, Williams A, Bell J, deSouza N (1998) Regional biochemical variations in the normal uterine cervix by 1H MRS ex vivo. Proc Int Soc Magn Res Med 7:39Google Scholar
  26. 26.
    Schiebler ML, Miyamoto KK, White M, Maygarden SJ, Mohler JL (1993) In vitro high resolution 1H-spectroscopy of the human prostate: benign prostatic hyperplasia, normal peripheral zone and adenocarcinoma. Magn Reson Med 29:285–291PubMedCrossRefGoogle Scholar
  27. 27.
    Carlstedt I, Lindgren H, Sheehan JK, Ulmsten U, Wingerup L (1983) Isolation and characterization of human cervical-mucus glycoproteins. Biochem J 211:13–22PubMedGoogle Scholar
  28. 28.
    Toida T, Karkinuma N, Toyoda H, Imanari T (1994) 1H- NMR profile of Glycosaminoglycans in Human Urine. Anal Sci 10:537–541CrossRefGoogle Scholar
  29. 29.
    Murray R, Granner D, Mayes P (1996) Glycoproteins. Appleton & Lange, Stanford, ConneticutGoogle Scholar
  30. 30.
    Thornton D, Davies J, Carlstedt I (1997) Structure and biochemistry of human respiratory mucins. In: Rogers D, Lethem M (eds) Airway Mucus Basic Mechanisms and Clinical Perspectives. Birkhäuser Verlag, Basel, SwitzerlandGoogle Scholar
  31. 31.
    Brockhausen I (1999) Pathways of O-glycan biosynthesis in cancer cells. Biochim Biophys Acta 1473:67–95PubMedGoogle Scholar

Copyright information

© European Society of Radiology 2009

Authors and Affiliations

  • Sonali S. De Silva
    • 1
  • Geoffrey S. Payne
    • 1
  • Veronica A. Morgan
    • 1
  • Thomas E. J. Ind
    • 2
  • John H. Shepherd
    • 2
  • Desmond P. J. Barton
    • 2
  • Nandita M. deSouza
    • 1
    • 3
    Email author
  1. 1.Cancer Research UK Clinical Magnetic Resonance Research GroupInstitute of Cancer Research and Royal Marsden NHS Foundation TrustSuttonUK
  2. 2.Department of Gynaecological SurgeryRoyal Marsden NHS Foundation TrustLondonUK
  3. 3.CR UK Clinical Magnetic Resonance Research GroupInstitute of Cancer Research and Royal Marsden NHS Foundation TrustSuttonUK

Personalised recommendations