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Pre-clinical PET/MR: technological advances and new perspectives in biomedical research

  • Hans F. Wehrl
  • Martin S. Judenhofer
  • Stefan Wiehr
  • Bernd J. PichlerEmail author
Article

Abstract

Introduction

Combined PET/MRI allows for multi-parametric imaging and reveals one or more functional processes simultaneously along with high-resolution morphology. Especially in small-animal research, where high soft tissue contrast is required, and the scan time as well as radiation dose are critical factors, the combination of PET and MRI would be beneficial compared with PET/CT.

Development

In the mid-1990’s, several research groups used different approaches to integrate PET detectors into high-field MRI. First, systems were based on optical fibres guiding the scintillation light to the PMT’s, which reside outside the fringe magnetic field. Recent advances in gamma ray detector technology, which were initiated mainly by the advent of avalanche photodiodes (APD’s) as well as the routine availability of fast scintillation materials like lutetium oxyorthosilicate (LSO), paved the way towards the development of fully magnetic-field-insensitive high-performance PET detectors.

Technology

Current animal PET/MR technologies are reviewed and pitfalls when engineering a full integration of a PET and a high-field MRI are discussed. Compact PET detectors can be integrated in small-bore, high-field MRI tomographs. Detailed performance evaluations have shown that the mutual interference between the two imaging systems could be minimized. The performance of all major MR applications, ranging from T1- or T2-weighted imaging up to echo-planar imaging (EPI) for functional MRI (fMRI) or magnetic resonance spectroscopy (MRS), could be maintained, even when the PET insert was built into the MRI and acquiring PET data simultaneously. Similarly, the PET system performance was not influenced by the static magnetic field or applied MRI sequences.

Applications

Initial biomedical research applications range from the combination of functional information from PET with the anatomical information from the MRI to multi-functional imaging combining metabollic PET and MRI data.

Discussion

Compared to other multi-modality approaches PET/MR offers a multitude of complementary function and anatomical information. The ability to obtain simultaneous PET and MRI data with this new imaging modality could have tremendous impact on small animal imaging research.

Keywords

PET MRI Combination Functional imaging Multi-modality Multi-functional imaging 

Notes

Conflict of interest statement

Bernd J Pichler is a consultant for Siemens Medical Solutions.

References

  1. 1.
    Beyer T, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;1 (8):1369–79.Google Scholar
  2. 2.
    Beyer T, Townsend DW, Blodgett TM. Dual-modality PET/CT tomography for clinical oncology. Q J Nucl Med 2002;6 (1):24–34.Google Scholar
  3. 3.
    Antoch G, et al. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J Clin Oncol 2004;2 (21):4357–68.CrossRefGoogle Scholar
  4. 4.
    Townsend DW, et al. PET/CT today and tomorrow. J Nucl Med 2004;45 (Suppl 1):4S–14S.PubMedGoogle Scholar
  5. 5.
    Pfannenberg AC, et al. Value of contrast-enhanced multi-phase CT in combined PET/CT protocols for oncological imaging. Br J Radiol 2007;80 (9154):437–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Czernin J, Schelbert HR. PET/CT in cancer patient management. Introduction. J Nucl Med 2007;48 (Suppl 1):2S, 3S.PubMedGoogle Scholar
  7. 7.
    Schoder H, Gonen M. Screening for cancer with PET and PET/CT: potential and limitations. J Nucl Med 2007;48 (Suppl 1):4S–18S.PubMedGoogle Scholar
  8. 8.
    Cherry SR. The 2006 Henry N. Wagner Lecture: Of mice and men (and positrons)—advances in PET imaging technology. J Nucl Med 2006;47 (11):1735–45.PubMedGoogle Scholar
  9. 9.
    Judenhofer MS, et al. Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med 2008;14 (4):459–65.PubMedCrossRefGoogle Scholar
  10. 10.
    Schlemmer HP, et al. Simultaneous MR/PET imaging of the human brain: feasibility study. Radiology 2008;248 (3):1028–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Catana C, et al. Simultaneous in vivo positron emission tomography and magnetic resonance imaging. Proc Natl Acad Sci USA 2008;105 (10):3705–10.PubMedCrossRefGoogle Scholar
  12. 12.
    Raylman RR, et al. Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and positron emission tomography (PET) images with a prototype MR-compatible, small animal PET imager. J Magn Reson 2007;186 (2):305–10.PubMedCrossRefGoogle Scholar
  13. 13.
    Yamamoto S, Mazumoto K, Senda M. Development of a multi-slice dual layer MR-compatible animal PET system using DOI detectors. Supplement to the Journal of Nuclear Medicine 2007;48:89P.Google Scholar
  14. 14.
    Lucas A, et al. Development of a combined micro-PET-MR system. IEEE Nucl Sci Symp Conf Rec 2006;2345–8.Google Scholar
  15. 15.
    Mackewn JE, et al. Design and development of an MR-compatible PET scanner for imaging small animals. IEEE Trans Nucl Sci 2005;52 (5):1376.CrossRefGoogle Scholar
  16. 16.
    Goetz C, et al. SPECT low-field MRI system for small-animal imaging. J Nucl Med 2008;49 (1):88–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Shao Y, et al. Development of a PET detector system compatible with MRI/NMRsystems. IEEE Trans Nucl Sci 1997;44 (3):1167–71.CrossRefGoogle Scholar
  18. 18.
    Shao Y, et al. Simultaneous PET and MR imaging. Phys Med Biol 1997;42 (10):1965–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Pichler B, et al. Performance Test of a LSO-APD PET Module in a 9.4 Tesla Magnet. IEEE Nucl Sci Symp Med Imaging Conf 1998;1237–39.Google Scholar
  20. 20.
    Ziegler SI, et al. A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals. Eur J Nucl Med 2001;28 (2):136–43.PubMedCrossRefGoogle Scholar
  21. 21.
    Chatziioannou AF, et al. Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging. J Nucl Med 1999;40 (7):1164–75.PubMedGoogle Scholar
  22. 22.
    Weber S, et al. The design of an animal PET: flexible geometry for achieving optimal spatial resolution or high sensitivity. IEEE Trans Med Imaging 1997;16 (5):684–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Marsden PK, et al. Simultaneous PET and NMR. Br J Radiol 2002;75:S53–9.PubMedGoogle Scholar
  24. 24.
    Raylman RR, et al. Simultaneous MRI and PET imaging of a rat brain. Phys Med Biol 2006;51 (24):6371–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Slates RB, et al. A study of artefacts in simultaneous pet and mr imaging using a prototype mr compatible pet scanner. Phys Med Biol 1999;44 (8):2015–27.PubMedCrossRefGoogle Scholar
  26. 26.
    Lecomte R, et al. Performance analysis of phoswich/APD detectors and low-noise CMOS preamplifiers for high-resolution PET systems. IEEE Trans Nucl Sci 2001;48 (3):650–55.CrossRefGoogle Scholar
  27. 27.
    Pichler BJ, et al. A 4 × 8 APD Array, Consisting of two Monolithic Silicon Wafers, Coupled to a 32-Channel LSO Matrix for High-Resolution PET. IEEE Trans Nucl Sci 2001;48 (4):1391–6.CrossRefGoogle Scholar
  28. 28.
    Pichler BJ, et al. Lutetium oxyorthosilicate block detector readout by avalanche photodiode arrays for high resolution animal PET. Phys Med Biol 2004;49 (18):4305–19.PubMedCrossRefGoogle Scholar
  29. 29.
    Grazioso R, et al. APD Performance in Light Sharing PET Applications. IEEE Trans Nucl Sci 2005;52 (5):1413–16.CrossRefGoogle Scholar
  30. 30.
    Schlemmer HP, et al. An integrated MR/PET system: prospective applications. Abdom Imaging 2008 doi: 10.1007/.s00261-008-9450-2.
  31. 31.
    Schenck JF. The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibility of the first and second kinds. Med Phys 1996;23 (6):815–50.PubMedCrossRefGoogle Scholar
  32. 32.
    Yamamoto S, Kuroda K, Senda M. Scintillator selection for MR-compatible gamma detectors. IEEE Trans Nucl Sci 2003;50 (5):1683–5.CrossRefGoogle Scholar
  33. 33.
    Strul D, et al. Gamma shielding materials for MR-compatible PET. IEEE Trans Nucl Sci 2003;50 (1):60.CrossRefGoogle Scholar
  34. 34.
    Schick F. Whole-body MRI at high field: technical limits and clinical potential. Eur Radiol 2005;15 (5):946–59.PubMedCrossRefGoogle Scholar
  35. 35.
    Catana C, et al. Simultaneous Acquisition of Multislice PET and MR Images: Initial Results with a MR-Compatible PET Scanner. J Nucl Med 2006;47 (12):1968–76.PubMedGoogle Scholar
  36. 36.
    Camacho CR, Plewes DB, Henkelman RM. Nonsusceptibility artifacts due to metallic objects in MR imaging. J Magn Reson Imaging 1995;5 (1):75–88.PubMedCrossRefGoogle Scholar
  37. 37.
    Reese TG, et al. Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magn Reson Med 2003;49 (1):177–82.PubMedCrossRefGoogle Scholar
  38. 38.
    Klose U. In vivo proton spectroscopy in presence of eddy currents. Magn Reson Med 1990;14 (1):26–30.PubMedCrossRefGoogle Scholar
  39. 39.
    Friedman L, Glover GH. Report on a multicenter fMRI quality assurance protocol. J Magn Reson Imaging 2006;23 (6):827–39.PubMedCrossRefGoogle Scholar
  40. 40.
    Pichler BJ, et al. Performance test of an LSO-APD detector in a 7T MRI scanner for simultaneous PET/MRI. J Nucl Med 2006;47 (4):639–47.PubMedGoogle Scholar
  41. 41.
    Judenhofer MS, et al. PET/MR images acquired with a compact MR-compatible PET detector in a 7T magnet. Radiology 2007;244 (3):807–14.PubMedCrossRefGoogle Scholar
  42. 42.
    Tai YC, et al. Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging. J Nucl Med 2005;46 (3):455–63.PubMedGoogle Scholar
  43. 43.
    Gilbert KM, et al. Design of field-cycled magnetic resonance systems for small animal imaging. Phys Med Biol 2006;51 (11):2825–41.PubMedCrossRefGoogle Scholar
  44. 44.
    Townsend DW. Multimodality imaging of structure and function. Phys Med Biol 2008;53 (4):R1–R39.PubMedCrossRefGoogle Scholar
  45. 45.
    Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med 2007;48 (6):932–45.PubMedCrossRefGoogle Scholar
  46. 46.
    Willowson K, Bailey DL, Baldock C. Quantitative SPECT reconstruction using CT-derived corrections. Phys Med Biol 2008;53 (12):3099–112.PubMedCrossRefGoogle Scholar
  47. 47.
    Basu S, Alavi A. Feasibility of automated partial-volume correction of SUVs in current PET/CT scanners: can manufacturers provide integrated, ready-to-use software? J Nucl Med 2008;49 (6):1031–2. author reply 1032–3.PubMedCrossRefGoogle Scholar
  48. 48.
    Baete K, et al. Evaluation of anatomy based reconstruction for partial volume correction in brain FDG-PET. Neuroimage 2004;23 (1):305–17.PubMedCrossRefGoogle Scholar
  49. 49.
    Thesen S, et al. Prospective acquisition correction for head motion with image-based tracking for real-time fMRI. Magn Reson Med 2000;44 (3):457–65.PubMedCrossRefGoogle Scholar
  50. 50.
    Brankov JG, et al. Multi-modality tomographic image reconstruction using mesh modeling. Proc IEEE Int Symp Biomedical Imaging 2002;2002:405–8.CrossRefGoogle Scholar
  51. 51.
    Cheon J, Lee JH. Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. Acc Chem Res 2008;41 (12):1630–40.CrossRefPubMedGoogle Scholar
  52. 52.
    Jack CR Jr., et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain 2008;131 (Pt 3):665–80.Google Scholar
  53. 53.
    Ciccarelli O. et al. Diffusion-based tractography in neurological disorders: concepts, applications, and future developments. Lancet Neurol 2008;7 (8):715–27.Google Scholar
  54. 54.
    El Fakhri G, et al. Quantitative simultaneous (99m)Tc-ECD/123I-FP-CIT SPECT in Parkinson’s disease and multiple system atrophy. Eur J Nucl Med Mol Imaging 2006;33 (1):87–92.PubMedCrossRefGoogle Scholar
  55. 55.
    Raichle ME, et al. Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. J Nucl Med 1983;24 (9):790–8.PubMedGoogle Scholar
  56. 56.
    Herscovitch P, Markham J, Raichle ME. Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis. J Nucl Med 1983;24 (9):782–9.PubMedGoogle Scholar
  57. 57.
    Stollfuss JC, et al. Quantitative assessment of myocardial perfusion: is it of clinical relevance? Q J Nucl Med 1996;40 (1):76–84.PubMedGoogle Scholar
  58. 58.
    Parkes LM. Quantification of cerebral perfusion using arterial spin labeling: two-compartment models. J Magn Reson Imaging 2005;22 (6):732–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Ostergaard L. Cerebral perfusion imaging by bolus tracking. Top Magn Reson Imaging 2004;15 (1):3–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Kober F, Duhamel G, Cozzone PJ. Experimental comparison of four FAIR arterial spin labeling techniques for quantification of mouse cerebral blood flow at 4.7 T. NMR Biomed 2008;21 (8):781–92.PubMedCrossRefGoogle Scholar
  61. 61.
    Arbab AS, et al. Brain perfusion measured by flow-sensitive alternating inversion recovery (FAIR) and dynamic susceptibility contrast-enhanced magnetic resonance imaging: comparison with nuclear medicine technique. Eur Radiol 2001;11 (4):635–41.PubMedCrossRefGoogle Scholar
  62. 62.
    Koziak AM, et al. Validation study of a pulsed arterial spin labeling technique by comparison to perfusion computed tomography. Magn Reson Imaging 2008;26 (4):543–53.PubMedCrossRefGoogle Scholar
  63. 63.
    Chen JJ, et al. Cerebral blood flow measurement using fMRI and PET: A cross-validation study. Int J Biomed Imaging 2008;2008:516359.PubMedCrossRefGoogle Scholar
  64. 64.
    Pohmann R, et al. Fast perfusion measurements in rat skeletal muscle at rest and during exercise with single-voxel FAIR (flow-sensitive alternating inversion recovery). Magn Reson Med 2006;55 (1):108–15.PubMedCrossRefGoogle Scholar
  65. 65.
    Diao C, Zhu L. Temperature distribution and blood perfusion response in rat brain during selective brain cooling. Med Phys 2006;33 (7):2565–73.PubMedCrossRefGoogle Scholar
  66. 66.
    Rajendran JG, Krohn KA. Imaging hypoxia and angiogenesis in tumors. Radiol Clin North Am 2005;43 (1):169–87.PubMedCrossRefGoogle Scholar
  67. 67.
    Krohn KA, Link JM, Mason RP. Molecular imaging of hypoxia. J Nucl Med 2008;49 (Suppl 2):129S–48S.PubMedCrossRefGoogle Scholar
  68. 68.
    Al-Hallaq HA, et al. Correlation of magnetic resonance and oxygen microelectrode measurements of carbogen-induced changes in tumor oxygenation. Int J Radiat Oncol Biol Phys 1998;41 (1):151–9.PubMedGoogle Scholar
  69. 69.
    Baudelet C, Gallez B. How does blood oxygen level-dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors? Magn Reson Med 2002;48 (6):980–6.PubMedCrossRefGoogle Scholar
  70. 70.
    Mason RP, Shukla H, Antich PP. In vivo oxygen tension and temperature: simultaneous determination using 19F NMR spectroscopy of perfluorocarbon. Magn Reson Med 1993;29 (3):296–302.PubMedCrossRefGoogle Scholar
  71. 71.
    Morris P, Bachelard H. Reflections on the application of 13C-MRS to research on brain metabolism. NMR Biomed 2003;16 (6, 7):303–12.PubMedCrossRefGoogle Scholar
  72. 72.
    Day SE, et al. Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 2007;13 (11):1382–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Van Zijl PC, et al. Determination of cerebral glucose transport and metabolic kinetics by dynamic MR spectroscopy. Am J Physiol 1997;273 (6 Pt 1):E1216–27.PubMedGoogle Scholar
  74. 74.
    Herholz K, Coope D, Jackson A. Metabolic and molecular imaging in neuro-oncology. Lancet Neurol 2007;6 (8):711–24.PubMedCrossRefGoogle Scholar
  75. 75.
    Volkow ND, et al. PET evaluation of the dopamine system of the human brain. J Nucl Med 1996;37 (7):1242–56.PubMedGoogle Scholar
  76. 76.
    Ungerleider LG, Doyon J, Karni A. Imaging brain plasticity during motor skill learning. Neurobiol Learn Mem 2002;78 (3):553–64.PubMedCrossRefGoogle Scholar
  77. 77.
    Badgaiyan RD, Fischman AJ, Alpert NM. Striatal dopamine release in sequential learning. Neuroimage 2007;38 (3):549–56.PubMedCrossRefGoogle Scholar
  78. 78.
    Kida I, Hyder F. Physiology of functional magnetic resonance imaging: energetics and function. Methods Mol Med 2006;124:175–95.PubMedGoogle Scholar
  79. 79.
    Fox PT, Raichle ME. Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography. J Neurophysiol 1984;51 (5):1109–20.PubMedGoogle Scholar
  80. 80.
    Fox PT, Raichle ME. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 1986;83 (4):1140–4.PubMedCrossRefGoogle Scholar
  81. 81.
    Seitz RJ, Roland PE. Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study. Acta Neurol Scand 1992;86 (1):60–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Davis TL, et al. Calibrated functional MRI: mapping the dynamics of oxidative metabolism. Proc Natl Acad Sci USA 1998;95 (4):1834–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Hoge RD, et al. Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. Proc Natl Acad Sci USA 1999;96 (16):9403–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Kim SG, et al. Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation. Magn Reson Med 1999;41 (6):1152–61.PubMedCrossRefGoogle Scholar
  85. 85.
    Mintun MA, et al. Time-related increase of oxygen utilization in continuously activated human visual cortex. Neuroimage 2002;16 (2):531–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Lin AL, et al. Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI. Neuroimage 2009;44 (1):16–22.PubMedCrossRefGoogle Scholar
  87. 87.
    Jacobs AH, et al. 18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors. J Nucl Med 2005;46 (12):1948–58.PubMedGoogle Scholar
  88. 88.
    Garlick PB, et al. PET and NMR dual acquisition (PANDA): applications to isolated, perfused rat hearts. NMR Biomed 1997;10 (3):138–42.PubMedCrossRefGoogle Scholar
  89. 89.
    Pichler BJ, et al. Positron emission tomography/magnetic resonance imaging: the next generation of multimodality imaging? Semin Nucl Med 2008;38 (3):199–208.PubMedCrossRefGoogle Scholar
  90. 90.
    Handler WB, et al. Simulation of scattering and attenuation of 511 keV photons in a combined PET/field-cycled MRI system. Phys Med Biol 2006;51 (10):2479–91.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hans F. Wehrl
    • 1
  • Martin S. Judenhofer
    • 1
  • Stefan Wiehr
    • 1
  • Bernd J. Pichler
    • 1
    Email author
  1. 1.Department of Radiology, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-FoundationUniversity of TübingenTübingenGermany

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