Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

A decade in prostate cancer: from NMR to metabolomics

Nature Reviews Urology volume 8, pages 301–311 (2011)Cite this article

Subjects

Abstract

Over the past 30 years, continuous progress in the application of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance spectroscopic imaging (MRSI) to the detection, diagnosis and characterization of human prostate cancer has turned what began as scientific curiosity into a useful clinical option. In vivo MRSI technology has been integrated into the daily care of prostate cancer patients, and innovations in ex vivo methods have helped to establish NMR-based prostate cancer metabolomics. Metabolomic and multimodality imaging could be the future of the prostate cancer clinic—particularly given the rationale that more accurate interrogation of a disease as complex as human prostate cancer is most likely to be achieved through paradigms involving multiple, instead of single and isolated, parameters. The research and clinical results achieved through in vivo MRSI and ex vivo NMR investigations during the first 11 years of the 21st century illustrate areas where these technologies can be best translated into clinical practice.

Key Points

  • Magnetic resonance spectroscopy (MRS) measures the concentration of cellular metabolites, and has been incorporated into diagnostic radiology protocols for patients with prostate cancer

  • Analyses of prostate cancer tissue specimens with magnetic resonance spectrometers at high field-strengths can identify cancer-specific metabolites, distinguishing malignant from benign tissue

  • The application of high-resolution magic angle spinning (HRMAS) proton MRS on prostate tissue samples enables quantification of individual metabolites without compromising the evaluation of tissue pathology using histological methods

  • The correlation between tissue metabolites and pathology is the basis of prostate cancer metabolomics

  • Metabolomics and other multiparametric and multimodal imaging techniques, including MRS, are likely to be beneficial for every stage of diagnosis and characterization of prostate cancer in the clinic

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Proton MR spectra of human prostates.
Figure 2: 400 MHz HRMAS proton MR spectra (water-suppressed, T2-filtered) of human prostate tissues.
Figure 3: The progression of MRSI in clinical use.

Similar content being viewed by others

References

  1. Damadian, R. Tumor detection by nuclear magnetic resonance. Science 171, 1151–1153 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. Mansfield, P., Grannell, P. K., Garroway, A. N. & Stalker, D. C. in Proceedings of the 1st Specialized AMPERE Colloquium 16–27 (Krakow, Poland, 1973).

    Google Scholar 

  3. Lauterbur, P. Image formation by induced local interations: examples employing nuclear magnetic resonance. Nature 242, 190–191 (1973).

    Article  CAS  Google Scholar 

  4. Ambrose, J. & Hounsfield, G. Computerized transverse axial tomography. Br. J. Radiol. 46, 148–149 (1973).

    Article  CAS  PubMed  Google Scholar 

  5. Hounsfield, G. N. Computerized transverse axial scanning (tomography). 1. Description of system. Br. J. Radiol. 46, 1016–1022 (1973).

    Article  CAS  PubMed  Google Scholar 

  6. McCook, A. Life after fraud. The Scientist 23, 28 (2009).

    Google Scholar 

  7. Findings of Scientific Misconduct NIH Guide. 25 (1996).

  8. Fossel, E. T., Carr, J. M. & McDonagh, J. Detection of malignant tumors. Water-suppressed proton nuclear magnetic resonance spectroscopy of plasma. N. Engl. J. Med. 315, 1369–1376 (1986).

    Article  CAS  PubMed  Google Scholar 

  9. Andrew, E., Bradbury, A. & Eades, R. Nuclear magnetic resonance spectra from a crystal rotated at high speed. Nature 182, 1695 (1958).

    Article  Google Scholar 

  10. Cheng, L. L. et al. Enhanced resolution of proton NMR spectra of malignant lymph nodes using magic-angle spinning. Magn. Reson. Med. 36, 653–658 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Cheng, L. L. et al. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc. Natl Acad. Sci. USA 94, 6408–6413 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheng, L. L. et al. Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy. Neuro Oncol. 2, 87–95 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cheng, L. L., Wu, C., Smith, M. R. & Gonzalez, R. G. Non-destructive quantitation of spermine in human prostate tissue samples using HRMAS 1H NMR spectroscopy at 9.4 T. FEBS Lett. 494, 112–116 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Cheng, L. L. & Pohl, U. in The Handbook of Metabonomics and Metabolomics (eds Lindon, J. C., Nicholls, J. K. & Holmes, E.) 345–374 (Elsevier, Amsterdam, 2007).

    Book  Google Scholar 

  15. van der Graaf, M. et al. Proton MR spectroscopy of prostatic tissue focused on the detection of spermine, a possible biomarker of malignant behavior in prostate cancer. MAGMA 10, 153–159 (2000).

    CAS  PubMed  Google Scholar 

  16. Smith, R., Litwin, M., Lu, Y. & Zetter, B. Identification of an endogenous inhibitor of prostate carcinoma cell growth. Nat. Med. 1, 1040–1045 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Swindle, P. et al. Pathologic characterization of human prostate tissue with proton MR spectroscopy. Radiology 228, 144–151 (2003).

    Article  PubMed  Google Scholar 

  18. Menard, C. et al. Magnetic resonance spectroscopy of the malignant prostate gland after radiotherapy: a histopathologic study of diagnostic validity. Int. J. Radiat. Oncol. Biol. Phys. 50, 317–323 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Costello, L. C., Franklin, R. B., Feng, P., Tan, M. & Bagasra, O. Zinc and prostate cancer: a critical scientific, medical, and public interest issue (United States). Cancer Causes Control 16, 901–915 (2005).

    Article  PubMed  Google Scholar 

  20. Serkova, N. J. et al. The metabolites citrate, myo-inositol, and spermine are potential age-independent markers of prostate cancer in human expressed prostatic secretions. Prostate 68, 620–628 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Kline, E. E. et al. Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection. J. Urol. 176, 2274–2279 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Averna, T. A., Kline, E. E., Smith, A. Y. & Sillerud, L. O. A decrease in 1H nuclear magnetic resonance spectroscopically determined citrate in human seminal fluid accompanies the development of prostate adenocarcinoma. J. Urol. 173, 433–438 (2005).

    Article  PubMed  Google Scholar 

  23. Swanson, M. G. et al. Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues. Magn. Reson. Med. 50, 944–954 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. van Asten, J. J. et al. High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies. MAGMA 21, 435–442 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Tessem, M. B. et al. Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues. Magn. Reson. Med. 60, 510–516 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stenman, K. et al. Detection of polyunsaturated omega-6 fatty acid in human malignant prostate tissue by 1D and 2D high-resolution magic angle spinning NMR spectroscopy. MAGMA 22, 327–331 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. Swanson, M. G. et al. Quantification of choline and ethanolamine-containing metabolites in human prostate tissues using 1H HR-MAS total correlation spectroscopy. Magn. Reson. Med. 60, 33–40 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Swanson, M. G. et al. Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy. Magn. Reson. Med. 55, 1257–1264 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Komoroski, R. A., Holder, J. C., Pappas, A. A. & Finkbeiner, A. E. (31)P NMR of phospholipid metabolites in prostate cancer and benign prostatic hyperplasia. Magn. Reson. Med. 65, 911–913 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Taylor, J. L. et al. High-resolution magic angle spinning proton NMR analysis of human prostate tissue with slow spinning rates. Magn. Reson. Med. 50, 627–632 (2003).

    Article  PubMed  Google Scholar 

  31. Burns, M. A. et al. Reduction of spinning sidebands in proton NMR of human prostate tissue with slow high-resolution magic angle spinning. Magn. Reson. Med. 54, 34–42 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Jordan, K. W., He, W., Halpern, E. F., Wu, C. L. & Cheng, L. L. Evaluation of tissue metabolites with high resolution magic angle spinning MR spectroscopy human prostate samples after three-year storage at −80°C. Biomark. Insights 2, 147–154 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wu, C. L. et al. Proton high-resolution magic angle spinning NMR analysis of fresh and previously frozen tissue of human prostate. Magn. Reson. Med. 50, 1307–1311 (2003).

    Article  PubMed  Google Scholar 

  34. Zektzer, A. S. et al. Improved signal to noise in high-resolution magic angle spinning total correlation spectroscopy studies of prostate tissues using rotor-synchronized adiabatic pulses. Magn. Reson. Med. 53, 41–48 (2005).

    Article  PubMed  Google Scholar 

  35. Ratiney, H., Albers, M. J., Rabeson, H. & Kurhanewicz, J. Semi-parametric time-domain quantification of HR-MAS data from prostate tissue. NMR Biomed. 23, 1146–1157 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Burns, M. A., He, W., Wu, C. L. & Cheng, L. L. Quantitative pathology in tissue MR spectroscopy based human prostate metabolomics. Technol. Cancer Res. Treat. 3, 591–598 (2004).

    Article  PubMed  Google Scholar 

  37. Cheng, L. L. et al. Metabolic characterization of human prostate cancer with tissue magnetic resonance spectroscopy. Cancer Res. 65, 3030–3034 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Sciarra, A. Words of wisdom. Re: Retrospective analysis of prostate cancer recurrence potential with tissue metabolomic profiles. Maxeiner A, Adkins CB, Zhang Y. et al. Prostate 2010;70, 710–717. Eur. Urol. 58, 315 (2010).

    Google Scholar 

  39. Maxeiner, A. et al. Retrospective analysis of prostate cancer recurrence potential with tissue metabolomic profiles. Prostate 70, 710–717 (2010).

    PubMed  PubMed Central  Google Scholar 

  40. Kurhanewicz, J. et al. Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24–07-cm3) spatial resolution. Radiology 198, 795–805 (1996).

    Article  CAS  PubMed  Google Scholar 

  41. Kurhanewicz, J. et al. Citrate as an in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and normal prostate peripheral zone: detection via localized proton spectroscopy. Urology 45, 459–466 (1995).

    Article  CAS  PubMed  Google Scholar 

  42. Star-Lack, J., Nelson, S., Kurhanewicz, J., Huang, L. & Vigneron, D. Improved water and lipid suppression for 3D PRESS CSI using RF band selective inversion with gradient dephasing (BASING). Magn. Reson. Med. 38, 311–321 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. Star-Lack, J., Vigneron, D. B., Pauly, J., Kurhanewicz, J. & Nelson, S. J. Improved solvent suppression and increased spatial excitation bandwidths for three-dimensional PRESS CSI using phase-compensating spectral/spatial spin-echo pulses. J. Magn. Reson. Imaging 7, 745–757 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Pucar, D. et al. Prostate cancer: correlation of MR imaging and MR spectroscopy with pathologic findings after radiation therapy—initial experience. Radiology 236, 545–553 (2005).

    Article  PubMed  Google Scholar 

  45. Villeirs, G. M. et al. Combined magnetic resonance imaging and spectroscopy in the assessment of high grade prostate carcinoma in patients with elevated PSA: a single-institution experience of 356 patients. Eur. J. Radiol. 77, 340–345 (2011).

    Article  PubMed  Google Scholar 

  46. Villeirs, G. M., Oosterlinck, W., Vanherreweghe, E. & De Meerleer, G. O. A qualitative approach to combined magnetic resonance imaging and spectroscopy in the diagnosis of prostate cancer. Eur. J. Radiol. 73, 352–356 (2008).

    Article  PubMed  Google Scholar 

  47. Mueller-Lisse, U. G. et al. Localized prostate cancer: effect of hormone deprivation therapy measured by using combined three-dimensional 1H MR spectroscopy and MR imaging: clinicopathologic case-controlled study. Radiology 221, 380–390 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Zakian, K. L. et al. Transition zone prostate cancer: metabolic characteristics at 1H MR spectroscopic imaging--initial results. Radiology 229, 241–247 (2003).

    Article  PubMed  Google Scholar 

  49. Fradet, V. et al. Prostate cancer managed with active surveillance: role of anatomic MR imaging and MR spectroscopic imaging. Radiology 256, 176–183 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Zhang, J. et al. Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR spectroscopic imaging. Radiology 253, 425–434 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Jung, J. A. et al. Prostate depiction at endorectal MR spectroscopic imaging: investigation of a standardized evaluation system. Radiology 233, 701–708 (2004).

    Article  PubMed  Google Scholar 

  52. Wetter, A. et al. Combined MRI and MR spectroscopy of the prostate before radical prostatectomy. AJR Am. J. Roentgenol. 187, 724–730 (2006).

    Article  PubMed  Google Scholar 

  53. Portalez, D. et al. Prospective comparison of T2w-MRI and dynamic-contrast-enhanced MRI, 3D-MR spectroscopic imaging or diffusion-weighted MRI in repeat TRUS-guided biopsies. Eur. Radiol. 20, 2781–2790 (2010).

    Article  PubMed  Google Scholar 

  54. Coakley, F. V. et al. Prostate cancer tumor volume: measurement with endorectal MR and MR spectroscopic imaging. Radiology 223, 91–97 (2002).

    Article  PubMed  Google Scholar 

  55. Hasumi, M. et al. The combination of multi-voxel MR spectroscopy with MR imaging improve the diagnostic accuracy for localization of prostate cancer. Anticancer Res. 23, 4223–4227 (2003).

    PubMed  Google Scholar 

  56. Hom, J. J. et al. High-grade prostatic intraepithelial neoplasia in patients with prostate cancer: MR and MR spectroscopic imaging features--initial experience. Radiology 242, 483–489 (2007).

    Article  PubMed  Google Scholar 

  57. Chabanova, E. et al. Prostate cancer: 1.5 T endo-coil dynamic contrast-enhanced MRI and MR spectroscopy-correlation with prostate biopsy and prostatectomy histopathological data. Eur. J. Radiol. doi: 10.1016/j.ejrad.2010.07.004.

    Article  PubMed  Google Scholar 

  58. Xu, S. et al. Real-time MRI–TRUS fusion for guidance of targeted prostate biopsies. Comput. Aided Surg. 13, 255–264 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Testa, C. et al. Accuracy of MRI/MRSI-based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy. NMR Biomed. 23, 1017–1026 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Prando, A., Kurhanewicz, J., Borges, A. P., Oliveira, E. M. Jr & Figueiredo, E. Prostatic biopsy directed with endorectal MR spectroscopic imaging findings in patients with elevated prostate specific antigen levels and prior negative biopsy findings: early experience. Radiology 236, 903–910 (2005).

    Article  PubMed  Google Scholar 

  61. Kumar, V. et al. Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious of malignancy on three-dimensional (1)H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4–10 ng/ml. NMR Biomed. 20, 11–20 (2007).

    Article  PubMed  Google Scholar 

  62. Manenti, G. et al. Magnetic resonance imaging of the prostate with spectroscopic imaging using a surface coil. Initial clinical experience. Radiol. Med. 111, 22–32 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Hata, N. et al. MR imaging-guided prostate biopsy with surgical navigation software: device validation and feasibility. Radiology 220, 263–268 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Lagerburg, V., Moerland, M. A., van Vulpen, M. & Lagendijk, J. J. A new robotic needle insertion method to minimise attendant prostate motion. Radiother. Oncol. 80, 73–77 (2006).

    Article  PubMed  Google Scholar 

  65. Rodriguez, O. et al. Contrast-enhanced in vivo imaging of breast and prostate cancer cells by MRI. Cell Cycle 5, 113–119 (2006).

    Article  CAS  PubMed  Google Scholar 

  66. Krieger, A. et al. Design of a novel MRI compatible manipulator for image guided prostate interventions. IEEE Trans. Biomed. Eng. 52, 306–313 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Mozer, P. C., Partin, A. W. & Stoianovici, D. Robotic image-guided needle interventions of the prostate. Rev. Urol. 11, 7–15 (2009).

    PubMed  PubMed Central  Google Scholar 

  68. Zelefsky, M. J. et al. Intraoperative conformal optimization for transperineal prostate implantation using magnetic resonance spectroscopic imaging. Cancer J. 6, 249–255 (2000).

    CAS  PubMed  Google Scholar 

  69. DiBiase, S. J. et al. Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 52, 429–438 (2002).

    Article  PubMed  Google Scholar 

  70. Kirilova, A. et al. 3D MR-Spectroscopic Imaging assessment of metabolic activity in the prostate during the PSA “bounce” following (125)Iodine brachytherapy. Int. J. Radiat. Oncol. Biol. Phys. 79, 371–378 (2011).

    Article  PubMed  Google Scholar 

  71. Kim, Y. et al. Class solution in inverse planned HDR prostate brachytherapy for dose escalation of DIL defined by combined MRI/MRSI. Radiother. Oncol. 88, 148–155 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kazi, A., Godwin, G., Simpson, J. & Sasso, G. MRS-guided HDR brachytherapy boost to the dominant intraprostatic lesion in high risk localised prostate cancer. BMC Cancer 10, 472 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mueller-Lisse, U. G. et al. Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging. Magn. Reson. Med. 46, 49–57 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Pickett, B. et al. Use of MRI and spectroscopy in evaluation of external beam radiotherapy for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 60, 1047–1055 (2004).

    Article  PubMed  Google Scholar 

  75. Coakley, F. V. et al. Endorectal MR imaging and MR spectroscopic imaging for locally recurrent prostate cancer after external beam radiation therapy: preliminary experience. Radiology 233, 441–448 (2004).

    Article  PubMed  Google Scholar 

  76. Pucar, D. et al. Preliminary assessment of magnetic resonance spectroscopic imaging in predicting treatment outcome in patients with prostate cancer at high risk for relapse. Clin. Prostate Cancer 3, 174–181 (2004).

    Article  PubMed  Google Scholar 

  77. Sciarra, A. et al. Role of dynamic contrast-enhanced magnetic resonance (MR) imaging and proton MR spectroscopic imaging in the detection of local recurrence after radical prostatectomy for prostate cancer. Eur. Urol. 54, 589–600 (2008).

    Article  PubMed  Google Scholar 

  78. Zakian, K. L. et al. An exploratory study of endorectal magnetic resonance imaging and spectroscopy of the prostate as preoperative predictive biomarkers of biochemical relapse after radical prostatectomy. J. Urol. 184, 2320–2327 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Weinreb, J. C. et al. Prostate cancer: sextant localization at MR imaging and MR spectroscopic imaging before prostatectomy—results of ACRIN prospective multi-institutional clinicopathologic study. Radiology 251, 122–133 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Chen, A. P. et al. High-resolution 3D MR spectroscopic imaging of the prostate at 3 T with the MLEV-PRESS sequence. Magn. Reson. Imaging 24, 825–832 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Futterer, J. J. et al. Initial experience of 3 tesla endorectal coil magnetic resonance imaging and 1H-spectroscopic imaging of the prostate. Invest. Radiol. 39, 671–680 (2004).

    Article  PubMed  Google Scholar 

  82. Futterer, J. J. et al. Prostate cancer: local staging at 3-T endorectal MR imaging—early experience. Radiology 238, 184–191 (2006).

    Article  PubMed  Google Scholar 

  83. Crehange, G. et al. Tumor volume and metabolism of prostate cancer determined by proton magnetic resonance spectroscopic imaging at 3T without endorectal coil reveal potential clinical implications in the context of radiation oncology. Int. J. Radiat. Oncol. Biol. Phys. doi:10.1016/j.ijrobp.2010.03.007.

    Article  PubMed  Google Scholar 

  84. McLean, M. A. et al. Prostate cancer metabolite quantification relative to water in (1)H-MRSI in vivo at 3 Tesla. Magn. Reson. Med. 65, 914–919 (2011).

    Article  CAS  PubMed  Google Scholar 

  85. Near, J. et al. High-field MRSI of the prostate using a transmit/receive endorectal coil and gradient modulated adiabatic localization. J. Magn. Reson. Imaging 30, 335–343 (2009).

    Article  PubMed  Google Scholar 

  86. Pinkerton, R. G., Near, J. P., Barberi, E. A., Menon, R. S. & Bartha, R. Transceive surface coil array for MRI of the human prostate at 4T. Magn. Reson. Med. 57, 455–458 (2007).

    Article  PubMed  Google Scholar 

  87. Klomp, D. W., Bitz, A. K., Heerschap, A. & Scheenen, T. W. Proton spectroscopic imaging of the human prostate at 7 T. NMR Biomed. 22, 495–501 (2009).

    Article  CAS  PubMed  Google Scholar 

  88. Choi, H. & Ma, J. Use of perfluorocarbon compound in the endorectal coil to improve MR spectroscopy of the prostate. AJR Am. J. Roentgenol. 190, 1055–1059 (2008).

    Article  PubMed  Google Scholar 

  89. Rosen, Y. et al. 3T MR of the prostate: reducing susceptibility gradients by inflating the endorectal coil with a barium sulfate suspension. Magn. Reson. Med. 57, 898–904 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Scheidler, J., Vogel, M., Gross, P. & Heuck, A. Combined MRI and MRS in prostate cancer: improvement of spectral quality by susceptibility matching. Rofo 181, 531–535 (2009).

    Article  CAS  PubMed  Google Scholar 

  91. Males, R. G. et al. Clinical application of BASING and spectral/spatial water and lipid suppression pulses for prostate cancer staging and localization by in vivo 3D 1H magnetic resonance spectroscopic imaging. Magn. Reson. Med. 43, 17–22 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Pels, P. et al. Quantification of prostate MRSI data by model-based time domain fitting and frequency domain analysis. NMR Biomed. 19, 188–197 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Kelm, B. M., Menze, B. H., Zechmann, C. M., Baudendistel, K. T. & Hamprecht, F. A. Automated estimation of tumor probability in prostate magnetic resonance spectroscopic imaging: pattern recognition vs quantification. Magn. Reson. Med. 57, 150–159 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Tiwari, P., Rosen, M. & Madabhushi, A. A hierarchical spectral clustering and nonlinear dimensionality reduction scheme for detection of prostate cancer from magnetic resonance spectroscopy (MRS). Med. Phys. 36, 3927–3939 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Ahmed, H. U. et al. Is it time to consider a role for MRI before prostate biopsy? Nat. Rev. Clin. Oncol. 6, 197–206 (2009).

    Article  PubMed  Google Scholar 

  96. Wu, C. L. et al. Metabolomic imaging for human prostate cancer detection. Sci. Transl. Med. 2, 16ra8 (2010).

    PubMed  PubMed Central  Google Scholar 

  97. Ackerstaff, E., Pflug, B. R., Nelson, J. B. & Bhujwalla, Z. M. Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. Cancer Res. 61, 3599–3603 (2001).

    CAS  PubMed  Google Scholar 

  98. Ippolito, J. E. et al. Linkage between cellular communications, energy utilization, and proliferation in metastatic neuroendocrine cancers. Proc. Natl Acad. Sci. USA 103, 12505–12510 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Dyke, J. P. et al. Metabolic response of the CWR22 prostate tumor xenograft after 20 Gy of radiation studied by 1H spectroscopic imaging. Clin. Cancer Res. 9, 4529–4536 (2003).

    CAS  PubMed  Google Scholar 

  100. Rantalainen, M. et al. Statistically integrated metabonomic-proteomic studies on a human prostate cancer xenograft model in mice. J. Proteome Res. 5, 2642–2655 (2006).

    Article  CAS  PubMed  Google Scholar 

  101. Milkevitch, M., Jeitner, T. M., Beardsley, N. J. & Delikatny, E. J. Lovastatin enhances phenylbutyrate-induced MR-visible glycerophosphocholine but not apoptosis in DU145 prostate cells. Biochim. Biophys. Acta 1771, 1166–1176 (2007).

    Article  CAS  PubMed  Google Scholar 

  102. Gabellieri, C. et al. Modulation of choline kinase activity in human cancer cells observed by dynamic 31P NMR. NMR Biomed. 22, 456–461 (2009).

    Article  CAS  PubMed  Google Scholar 

  103. Levin, Y. S. et al. Methods for metabolic evaluation of prostate cancer cells using proton and (13)C HR-MAS spectroscopy and [3-(13)C] pyruvate as a metabolic substrate. Magn. Reson. Med. 62, 1091–1098 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Robey, I. F. et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 69, 2260–2268 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ackerstaff, E., Artemov, D., Gillies, R. J. & Bhujwalla, Z. M. Hypoxia and the presence of human vascular endothelial cells affect prostate cancer cell invasion and metabolism. Neoplasia 9, 1138–1151 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Al-Saffar, N. M. et al. The phosphoinositide 3-kinase inhibitor PI-103 downregulates choline kinase alpha leading to phosphocholine and total choline decrease detected by magnetic resonance spectroscopy. Cancer Res. 70, 5507–5517 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Raina, K., Serkova, N. J. & Agarwal, R. Silibinin feeding alters the metabolic profile in TRAMP prostatic tumors: 1H-NMRS-based metabolomics study. Cancer Res. 69, 3731–3735 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Larson, P. E. et al. Investigation of tumor hyperpolarized [1–13C]-pyruvate dynamics using time-resolved multiband RF excitation echo-planar MRSI. Magn. Reson. Med. 63, 582–591 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Albers, M. J. et al. Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Cancer Res. 68, 8607–8615 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Cunningham, C. H. et al. Sequence design for magnetic resonance spectroscopic imaging of prostate cancer at 3 T. Magn. Reson. Med. 53, 1033–1039 (2005).

    Article  PubMed  Google Scholar 

  111. Scheenen, T. W. et al. Optimal timing for in vivo 1H-MR spectroscopic imaging of the human prostate at 3T. Magn. Reson. Med. 53, 1268–1274 (2005).

    Article  CAS  PubMed  Google Scholar 

  112. Trabesinger, A. H., Meier, D., Dydak, U., Lamerichs, R. & Boesiger, P. Optimizing PRESS localized citrate detection at 3 Tesla. Magn. Reson. Med. 54, 51–58 (2005).

    Article  CAS  PubMed  Google Scholar 

  113. Gambarota, G., van der Graaf, M., Klomp, D., Mulkern, R. V. & Heerschap, A. Echo-time independent signal modulations using PRESS sequences: a new approach to spectral editing of strongly coupled AB spin systems. J. Magn. Reson. 177, 299–306 (2005).

    Article  CAS  PubMed  Google Scholar 

  114. Lange, T., Trabesinger, A. H., Schulte, R. F., Dydak, U. & Boesiger, P. Prostate spectroscopy at 3 Tesla using two-dimensional S.-PRESS. Magn. Reson. Med. 56, 1220–1228 (2006).

    Article  CAS  PubMed  Google Scholar 

  115. Chen, A. P. et al. High-speed 3T MR spectroscopic imaging of prostate with flyback echo-planar encoding. J. Magn. Reson. Imaging 25, 1288–1292 (2007).

    Article  PubMed  Google Scholar 

  116. Weis, J. et al. Two-dimensional spectroscopic imaging for pretreatment evaluation of prostate cancer: comparison with the step-section histology after radical prostatectomy. Magn. Reson. Imaging 27, 87–93 (2009).

    Article  PubMed  Google Scholar 

  117. Thomas, M. A. et al. Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo. MAGMA 21, 443–458 (2008).

    Article  CAS  PubMed  Google Scholar 

  118. Near, J., Romagnoli, C. & Bartha, R. Reduced power magnetic resonance spectroscopic imaging of the prostate at 4.0 Tesla. Magn. Reson. Med. 61, 273–281 (2009).

    Article  CAS  PubMed  Google Scholar 

  119. Thakur, S. B., Yaligar, J. & Koutcher, J. A. In vivo lactate signal enhancement using binomial spectral-selective pulses in selective MQ coherence (SS-SelMQC) spectroscopy. Magn. Reson. Med. 62, 591–598 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Bertilsson, H. et al. A new method to provide a fresh frozen prostate slice suitable for gene expression study and MR spectroscopy. Prostate 71, 461–469 (2011).

    Article  CAS  PubMed  Google Scholar 

  121. Lenkinski, R. E. et al. An illustration of the potential for mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer. MAGMA 21, 411–421 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Santos, C. F. et al. Metabolic, pathologic, and genetic analysis of prostate tissues: quantitative evaluation of histopathologic and mRNA integrity after HR-MAS spectroscopy. NMR Biomed. 23, 391–398 (2010).

    CAS  PubMed  Google Scholar 

  123. Shukla-Dave, A. et al. Correlation of MR imaging and MR spectroscopic imaging findings with Ki-67, phospho-Akt, and androgen receptor expression in prostate cancer. Radiology 250, 803–812 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Kaul, D. et al. Assessing prostate cancer growth with mRNA of spermine metabolic enzymes. Cancer Biol. Ther. 9, 736–742 (2010).

    Article  CAS  PubMed  Google Scholar 

  125. Jhavar, S. G. et al. Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique. J. Clin. Pathol. 58, 504–508 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Zhan, Y., Feldman, M., Tomaszeweski, J., Davatzikos, C. & Shen, D. Registering histological and MR images of prostate for image-based cancer detection. Med. Image Comput. Comput. Assist. Interv. 9, 620–628 (2006).

    PubMed  Google Scholar 

  127. Alterovitz, R., Goldberg, K., Kurhanewicz, J., Pouliot, J. & Hsu, I. C. Image registration for prostate MR spectroscopy using modeling and optimization of force and stiffness parameters. Conf. Proc. IEEE Eng. Med. Biol. Soc. 3, 1722–1725 (2004).

    Google Scholar 

  128. Park, H. et al. Registration methodology for histological sections and in vivo imaging of human prostate. Acad. Radiol. 15, 1027–1039 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  129. McGrath, D. M., Vlad, R. M., Foltz, W. D. & Brock, K. K. Technical note: fiducial markers for correlation of whole-specimen histopathology with MR imaging at 7 tesla. Med. Phys. 37, 2321–2328 (2010).

    Article  PubMed  Google Scholar 

  130. Shah, V. et al. A method for correlating in vivo prostate magnetic resonance imaging and histopathology using individualized magnetic resonance-based molds. Rev. Sci. Instrum. 80, 104301 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Mazaheri, Y. et al. Semi-automatic deformable registration of prostate MR images to pathological slices. J. Magn. Reson. Imaging 32, 1149–1157 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Ozer, S. et al. Supervised and unsupervised methods for prostate cancer segmentation with multispectral MRI. Med. Phys. 37, 1873–1883 (2010).

    Article  PubMed  Google Scholar 

  133. Sciarra, A. et al. Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin. Cancer Res. 16, 1875–1883 (2010).

    Article  CAS  PubMed  Google Scholar 

  134. Wang, X. Z. et al. 1H-MRSI of prostate cancer: the relationship between metabolite ratio and tumor proliferation. Eur. J. Radiol. 73, 345–351 (2010).

    Article  PubMed  Google Scholar 

  135. Westphalen, A. C. et al. Peripheral zone prostate cancer: accuracy of different interpretative approaches with MR and MR spectroscopic imaging. Radiology 246, 177–184 (2008).

    Article  PubMed  Google Scholar 

  136. Vilanova, J. C. et al. Peripheral zone prostate cancer in patients with elevated PSA levels and low free-to-total PSA ratio: detection with MR imaging and MR spectroscopy. Radiology 253, 135–143 (2009).

    Article  PubMed  Google Scholar 

  137. Kumar, V. et al. Potential of (1)H MR spectroscopic imaging to segregate patients who are likely to show malignancy of the peripheral zone of the prostate on biopsy. J. Magn. Reson. Imaging 30, 842–848 (2009).

    Article  PubMed  Google Scholar 

  138. Cazares, L. H. et al. Imaging mass spectrometry of a specific fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 discriminates cancer from uninvolved prostate tissue. Clin. Cancer Res. 15, 5541–5551 (2009).

    Article  CAS  PubMed  Google Scholar 

  139. Eberlin, L. S. et al. Cholesterol sulfate imaging in human prostate cancer tissue by desorption electrospray ionization mass spectrometry. Anal. Chem. 82, 3430–3434 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Schwamborn, K. et al. Identifying prostate carcinoma by MALDI-Imaging. Int. J. Mol. Med. 20, 155–159 (2007).

    CAS  PubMed  Google Scholar 

  141. Sreekumar, A. et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457, 910–914 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Jentzmik, F. et al. Sarcosine in prostate cancer tissue is not a differential metabolite for prostate cancer aggressiveness and biochemical progression. J. Urol. 185, 706–711 (2011).

    Article  CAS  PubMed  Google Scholar 

  143. Jiang, Y., Cheng, X., Wang, C. & Ma, Y. Quantitative determination of sarcosine and related compounds in urinary samples by liquid chromatography with tandem mass spectrometry. Anal. Chem. 82, 9022–9027 (2010).

    Article  CAS  PubMed  Google Scholar 

  144. Jentzmik, F. et al. Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur. Urol. 58, 12–18 (2010).

    Article  CAS  PubMed  Google Scholar 

  145. Delongchamps, N. B. et al. Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2-weighted, dynamic contrast-enhanced and diffusion-weighted imaging. BJU Int. doi:10.1111/j.1464-410X.2010.09808.x.

    Article  PubMed  Google Scholar 

  146. Scherr, M. K. et al. MR-perfusion (MRP) and diffusion-weighted imaging (DWI) in prostate cancer: quantitative and model-based gadobenate dimeglumine MRP parameters in detection of prostate cancer. Eur. J. Radiol. 76, 359–366 (2010).

    Article  CAS  PubMed  Google Scholar 

  147. Schmuecking, M. et al. Dynamic MRI and CAD vs. choline MRS: where is the detection level for a lesion characterisation in prostate cancer? Int. J. Radiat. Biol. 85, 814–824 (2009).

    Article  CAS  PubMed  Google Scholar 

  148. Langer, D. L. et al. Prostate cancer detection with multi-parametric MRI: logistic regression analysis of quantitative T2, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. J. Magn. Reson. Imaging 30, 327–334 (2009).

    Article  PubMed  Google Scholar 

  149. Chen, M. et al. Prostate cancer detection: comparison of T2-weighted imaging, diffusion-weighted imaging, proton magnetic resonance spectroscopic imaging, and the three techniques combined. Acta Radiol. 49, 602–610 (2008).

    Article  CAS  PubMed  Google Scholar 

  150. Carlani, M., Mancino, S., Bonanno, E., Finazzi Agro, E. & Simonetti, G. Combined morphological, [1H]-MR spectroscopic and contrast-enhanced imaging of human prostate cancer with a 3-Tesla scanner: preliminary experience. Radiol. Med. 113, 670–688 (2008).

    Article  CAS  PubMed  Google Scholar 

  151. Testa, C. et al. Prostate cancer: sextant localization with MR imaging, MR spectroscopy, and 11C-choline PET/CT. Radiology 244, 797–806 (2007).

    Article  PubMed  Google Scholar 

  152. Yamaguchi, T. et al. Prostate cancer: a comparative study of 11C-choline PET and MR imaging combined with proton MR spectroscopy. Eur. J. Nucl. Med. Mol. Imaging 32, 742–748 (2005).

    Article  CAS  PubMed  Google Scholar 

  153. Schreibmann, E. & Xing, L. Narrow band deformable registration of prostate magnetic resonance imaging, magnetic resonance spectroscopic imaging, and computed tomography studies. Int. J. Radiat. Oncol. Biol. Phys. 62, 595–605 (2005).

    Article  PubMed  Google Scholar 

  154. Grosu, A. L., Wiedenmann, N. & Molls, M. Biological imaging in radiation oncology. Z. Med. Phys. 15, 141–145 (2005).

    Article  PubMed  Google Scholar 

  155. Eggleston, J. C., Saryan, L. A. & Hollis, D. P. Nuclear magnetic resonance investigations of human neoplastic and abnormal nonneoplastic tissues. Cancer Res. 35, 1326–1332 (1975).

    CAS  PubMed  Google Scholar 

  156. Steyn, J. H. & Smith, F. W. Nuclear magnetic resonance imaging of the prostate. Br. J. Urol. 54, 726–728 (1982).

    Article  CAS  PubMed  Google Scholar 

  157. Sillerud, L., Halliday, K., Griffey, R., Fenoglio-Preiser, C. & Sheppard, S. In vivo 13C NMR spectroscopy of the human prostate. Magn. Reson. Med. 8, 224–230 (1988).

    Article  CAS  PubMed  Google Scholar 

  158. Narayan, P. et al. Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report. J. Urol. 146, 66–74 (1991).

    Article  CAS  PubMed  Google Scholar 

  159. Schick, F. et al. Localized proton MR spectroscopy of citrate in vitro and of the human prostate in vivo at 1.5 T. Magn. Reson. Med. 29, 38–43 (1993).

    Article  CAS  PubMed  Google Scholar 

  160. Schiebler, M. L., Miyamoto, K. K., White, M., Maygarden, S. J. & Mohler, J. L. In vitro high resolution 1H-spectroscopy of the human prostate: benign prostatic hyperplasia, normal peripheral zone and adenocarcinoma. Magn. Reson. Med. 29, 285–291 (1993).

    Article  CAS  PubMed  Google Scholar 

  161. Lynch, M. & Nicholson, J. Proton MRS of human prostatic fluid: correlations between citrate, spermine, and myo-inositol levels and changes with disease. Prostate 30, 248–255 (1997).

    Article  CAS  PubMed  Google Scholar 

  162. Hahn, P. et al. The classification of benign and malignant human prostate tissue by multivariate analysis of 1H magnetic resonance spectra. Cancer Res. 57, 3398–3401 (1997).

    CAS  PubMed  Google Scholar 

  163. van Dorsten, F. A. et al. Combined quantitative dynamic contrast-enhanced MR imaging and (1)H MR spectroscopic imaging of human prostate cancer. J. Magn. Reson. Imaging 20, 279–287 (2004).

    Article  PubMed  Google Scholar 

  164. Wang, L. et al. Prediction of organ-confined prostate cancer: incremental value of MR imaging and MR spectroscopic imaging to staging nomograms. Radiology 238, 597–603 (2006).

    Article  PubMed  Google Scholar 

  165. Coakley, F. V. et al. Validity of prostate-specific antigen as a tumour marker in men with prostate cancer managed by watchful-waiting: correlation with findings at serial endorectal magnetic resonance imaging and spectroscopic imaging. BJU Int. 99, 41–45 (2007).

    Article  CAS  PubMed  Google Scholar 

  166. Shukla-Dave, A. et al. Prediction of prostate cancer recurrence using magnetic resonance imaging and molecular profiles. Clin. Cancer Res. 15, 3842–3849 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Ms J. Fordham for editorial assistance. Grant funding support: NIH CA115746, CA115746S2, and CA141139.

Author information

Authors and Affiliations

  1. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02114, MA, USA

    Elita M. DeFeo & Leo L. Cheng

  2. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02114, MA, USA

    Chin-Lee Wu

  3. Department of Urology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02114, MA, USA

    W. Scott McDougal

Authors
  1. Elita M. DeFeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chin-Lee Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Scott McDougal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leo L. Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

E. M. Defeo and L. L. Cheng researched data for the article, took part in discussions of content and wrote the manuscript. All authors contributed to review and editing of the article before submission.

Corresponding author

Correspondence to Leo L. Cheng.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

DeFeo, E., Wu, CL., McDougal, W. et al. A decade in prostate cancer: from NMR to metabolomics. Nat Rev Urol 8, 301–311 (2011). https://doi.org/10.1038/nrurol.2011.53

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2011.53

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research