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Hybrid PET-MRI in Alzheimer’s Disease Research

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Biomarkers for Alzheimer’s Disease Drug Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1750))

Abstract

Multiple factors, namely amyloid, tau, inflammation, metabolic, and perfusion changes, contribute to the cascade of neurodegeneration and functional decline occurring in Alzheimer’s disease (AD). These molecular and cellular processes and related functional and morphological changes can be visualized in vivo by two imaging modalities, namely positron emission tomography (PET) and magnetic resonance imaging (MRI). These imaging biomarkers are now part of the diagnostic algorithm and of particular interest for patient stratification and targeted drug development.

In this field the availability of hybrid PET/MR systems not only offers a comprehensive evaluation in a single imaging session, but also opens new possibilities for the integration of the two imaging information. Here, we cover the clinical protocols and practical details of FDG, amyloid, and tau PET/MR imaging as applied in our institutions.

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References

  1. Fujimoto K, Polimeni JR, van der Kouwe AJ, Reuter M, Kober T, Benner T, Fischl B, Wald LL (2014) Quantitative comparison of cortical surface reconstructions from MP2RAGE and multi-echo MPRAGE data at 3 and 7T. NeuroImage 90:60–73. https://doi.org/10.1016/j.neuroimage.2013.12.012

    Article  PubMed  Google Scholar 

  2. Marques JP, Kober T, Krueger G, van der Zwaag W, Van de Moortele PF, Gruetter R (2010) MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field. NeuroImage 49(2):1271–1281. https://doi.org/10.1016/j.neuroimage.2009.10.002

    Article  PubMed  Google Scholar 

  3. Varrone A, Asenbaum S, Vander Borght T, Booij J, Nobili F, Nagren K, Darcourt J, Kapucu OL, Tatsch K, Bartenstein P, Van Laere K (2009) EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2. Eur J Nucl Med Mol Imaging 36(12):2103–2110. https://doi.org/10.1007/s00259-009-1264-0

    Article  PubMed  Google Scholar 

  4. Xie L, Helmerhorst E, Taddei K, Plewright B, Van Bronswijk W, Martins R (2002) Alzheimer’s beta-amyloid peptides compete for insulin binding to the insulin receptor. J Neurosci 22(10):RC221. 20026383 [pii]

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kantarci K, Lowe VJ, Boeve BF, Senjem ML, Tosakulwong N, Lesnick TG, Spychalla AJ, Gunter JL, Fields JA, Graff-Radford J, Ferman TJ, Jones DT, Murray ME, Knopman DS, Jack CR Jr, Petersen RC (2016) AV-1451 tau and beta-amyloid positron emission tomography imaging in dementia with Lewy bodies. Ann Neurol 81:58. https://doi.org/10.1002/ana.24825

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Hostetler ED, Walji AM, Zeng Z, Miller P, Bennacef I, Salinas C, Connolly B, Gantert L, Haley H, Holahan M, Purcell M, Riffel K, Lohith TG, Coleman P, Soriano A, Ogawa A, Xu S, Zhang X, Joshi E, Della Rocca J, Hesk D, Schenk DJ, Evelhoch JL (2016) Preclinical characterization of 18F-MK-6240, a promising PET tracer for in vivo quantification of human neurofibrillary tangles. J Nucl Med 57(10):1599–1606. https://doi.org/10.2967/jnumed.115.171678

    Article  PubMed  CAS  Google Scholar 

  7. Aleksandar Jovalekic NK, Mueller A, Stephens AW (2016) New protein deposition tracers in the pipeline. EJNMMI Radiopharm Chem 1(11). https://doi.org/10.1186/s41181-016-0015-3

  8. Harada R, Okamura N, Furumoto S, Tago T, Yanai K, Arai H, Kudo Y (2016) Characteristics of tau and its ligands in PET imaging. Biomol Ther 6(1):7. https://doi.org/10.3390/biom6010007. biom6010007 [pii]

    Article  CAS  Google Scholar 

  9. Shah M, Seibyl J, Cartier A, Bhatt R, Catafau AM (2014) Molecular imaging insights into neurodegeneration: focus on alpha-synuclein radiotracers. J Nucl Med 55(9):1397–1400. https://doi.org/10.2967/jnumed.113.136515

    Article  PubMed  CAS  Google Scholar 

  10. Villemagne VL, Okamura N (2014) In vivo tau imaging: obstacles and progress. Alzheimers Dement 10(3 Suppl):S254–S264. https://doi.org/10.1016/j.jalz.2014.04.013

    Article  PubMed  Google Scholar 

  11. Wooten D, Guehl NJ, Verwer EE, Shoup TM, Yokell DL, Zubcevik N, Vasdev N, Zafonte RD, Johnson KA, El Fakhri G, Normandin MD (2016) Pharmacokinetic evaluation of the tau PET radiotracer [18F]T807 ([18F]AV-1451) in human subjects. J Nucl Med, vol 58, p 484. https://doi.org/10.2967/jnumed.115.170910

    Book  Google Scholar 

  12. Rodriguez-Vieitez E, Leuzy A, Chiotis K, Saint-Aubert L, Wall A, Nordberg A (2017) Comparability of [18F]THK5317 and [11C]PIB blood flow proxy images with [18F]FDG positron emission tomography in Alzheimer’s disease. J Cereb Blood Flow Metab 37(2):740–749. https://doi.org/10.1177/0271678X16645593

    Article  PubMed  CAS  Google Scholar 

  13. Mainta IC, Perani D, Delattre BM, Assal F, Haller S, Vargas MI, Zekry DS, Frisoni GB, Zaidi H, Ratib O, Garibotto V (2017) FDG PET/MR imaging in major neurocognitive disorders. Curr Alzheimer Res 14(2):186–197. CAR-EPUB-76693 [pii]

    Article  CAS  PubMed  Google Scholar 

  14. Ladefoged CN, Law I, Anazodo U, St Lawrence K, Izquierdo-Garcia D, Catana C, Burgos N, Cardoso MJ, Ourselin S, Hutton B, Merida I, Costes N, Hammers A, Benoit D, Holm S, Juttukonda M, An H, Cabello J, Lukas M, Nekolla S, Ziegler S, Fenchel M, Jakoby B, Casey ME, Benzinger T, Hojgaard L, Hansen AE, Andersen FL (2016) A multi-centre evaluation of eleven clinically feasible brain PET/MRI attenuation correction techniques using a large cohort of patients. NeuroImage 147:346–359. https://doi.org/10.1016/j.neuroimage.2016.12.010

    Article  PubMed  Google Scholar 

  15. Werner P, Rullmann M, Bresch A, Tiepolt S, Jochimsen T, Lobsien D, Schroeter ML, Sabri O, Barthel H (2016) Impact of attenuation correction on clinical [(18)F]FDG brain PET in combined PET/MRI. EJNMMI Res 6(1):47. https://doi.org/10.1186/s13550-016-0200-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Jochimsen TH, Zeisig V, Schulz J, Werner P, Patt M, Patt J, Dreyer AY, Boltze J, Barthel H, Sabri O, Sattler B (2016) Fully automated calculation of image-derived input function in simultaneous PET/MRI in a sheep model. EJNMMI Phys 3(1):2. https://doi.org/10.1186/s40658-016-0139-2

    Article  PubMed  PubMed Central  Google Scholar 

  17. Loeb R, Navab N, Ziegler SI (2015) Direct parametric reconstruction using anatomical regularization for simultaneous PET/MRI data. IEEE Trans Med Imaging 34(11):2233–2247. https://doi.org/10.1109/TMI.2015.2427777

    Article  PubMed  Google Scholar 

  18. Delso G, Furst S, Jakoby B, Ladebeck R, Ganter C, Nekolla SG, Schwaiger M, Ziegler SI (2011) Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 52(12):1914–1922. https://doi.org/10.2967/jnumed.111.092726

    Article  PubMed  Google Scholar 

  19. Grant AM, Deller TW, Khalighi MM, Maramraju SH, Delso G, Levin CS (2016) NEMA NU 2-2012 performance studies for the SiPM-based ToF-PET component of the GE SIGNA PET/MR system. Med Phys 43(5):2334. https://doi.org/10.1118/1.4945416

    Article  PubMed  Google Scholar 

  20. Juttukonda MR, Mersereau BG, Chen Y, Su Y, Rubin BG, Benzinger TL, Lalush DS, An H (2015) MR-based attenuation correction for PET/MRI neurological studies with continuous-valued attenuation coefficients for bone through a conversion from R2* to CT-Hounsfield units. NeuroImage 112:160–168. https://doi.org/10.1016/j.neuroimage.2015.03.009

    Article  PubMed  Google Scholar 

  21. Khalil MM (ed) (2017) Basic science of PET imaging. Springer, Cham

    Google Scholar 

  22. Vandenberghe S, Mikhaylova E, D'Hoe E, Mollet P, Karp JS (2016) Recent developments in time-of-flight PET. EJNMMI Phys 3(1):3. https://doi.org/10.1186/s40658-016-0138-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Zaidi H, Ojha N, Morich M, Griesmer J, Hu Z, Maniawski P, Ratib O, Izquierdo-Garcia D, Fayad ZA, Shao L (2011) Design and performance evaluation of a whole-body ingenuity TF PET-MRI system. Phys Med Biol 56(10):3091–3106. https://doi.org/10.1088/0031-9155/56/10/013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Drzezga A, Barthel H, Minoshima S, Sabri O (2014) Potential clinical applications of PET/MR imaging in neurodegenerative diseases. J Nucl Med 55(Suppl 2):47S–55S. https://doi.org/10.2967/jnumed.113.129254

    Article  PubMed  Google Scholar 

  25. Damoiseaux JS (2012) Resting-state fMRI as a biomarker for Alzheimer’s disease? Alzheimers Res Ther 4(2):8. https://doi.org/10.1186/alzrt106

    Article  PubMed  PubMed Central  Google Scholar 

  26. Vemuri P, Jones DT, Jack CR Jr (2012) Resting state functional MRI in Alzheimer’s disease. Alzheimers Res Ther 4(1):2. https://doi.org/10.1186/alzrt100

    Article  PubMed  PubMed Central  Google Scholar 

  27. Alan D, Waxman MKH, Lewis DH, Herscovitch P, Minoshima S, Ichise M, Drzezga AE,Devous MD, Mountz JM (2009) Society of Nuclear Medicine Procedure Guideline for FDG PET Brain Imaging Version 1.0, approved February 8, 2009

    Google Scholar 

  28. Surasi DS, Bhambhvani P, Baldwin JA, Almodovar SE, O’Malley JP (2014) (1)(8)F-FDG PET and PET/CT patient preparation: a review of the literature. J Nucl Med Technol 42(1):5–13. https://doi.org/10.2967/jnmt.113.132621

    Article  PubMed  Google Scholar 

  29. Berti V, Mosconi L, Pupi A (2014) Brain: normal variations and benign findings in fluorodeoxyglucose-PET/computed tomography imaging. PET Clin 9(2):129–140. https://doi.org/10.1016/j.cpet.2013.10.006

    Article  PubMed  Google Scholar 

  30. Hsiao IT, Huang CC, Hsieh CJ, Hsu WC, Wey SP, Yen TC, Kung MP, Lin KJ (2012) Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies. Eur J Nucl Med Mol Imaging 39(4):613–620. https://doi.org/10.1007/s00259-011-2051-2

    Article  CAS  PubMed  Google Scholar 

  31. Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, Dannals RF, Nandi A, Brasic JR, Ye W, Hilton J, Lyketsos C, Kung HF, Joshi AD, Skovronsky DM, Pontecorvo MJ (2010) In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med 51(6):913–920. https://doi.org/10.2967/jnumed.109.069088

    Article  PubMed  CAS  Google Scholar 

  32. Camus V, Payoux P, Barre L, Desgranges B, Voisin T, Tauber C, La Joie R, Tafani M, Hommet C, Chetelat G, Mondon K, de La Sayette V, Cottier JP, Beaufils E, Ribeiro MJ, Gissot V, Vierron E, Vercouillie J, Vellas B, Eustache F, Guilloteau D (2012) Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Eur J Nucl Med Mol Imaging 39(4):621–631. https://doi.org/10.1007/s00259-011-2021-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. van Berckel BN, Ossenkoppele R, Tolboom N, Yaqub M, Foster-Dingley JC, Windhorst AD, Scheltens P, Lammertsma AA, Boellaard R (2013) Longitudinal amyloid imaging using 11C-PiB: methodologic considerations. J Nucl Med 54(9):1570–1576. https://doi.org/10.2967/jnumed.112.113654

    Article  PubMed  CAS  Google Scholar 

  34. Schwarz CG, Senjem ML, Gunter JL, Tosakulwong N, Weigand SD, Kemp BJ, Spychalla AJ, Vemuri P, Petersen RC, Lowe VJ, Jack CR Jr (2017) Optimizing PiB-PET SUVR change-over-time measurement by a large-scale analysis of longitudinal reliability, plausibility, separability, and correlation with MMSE. Neuroimage 144(Pt A):113–127. https://doi.org/10.1016/j.neuroimage.2016.08.056

    Article  PubMed  Google Scholar 

  35. Schwarz AJ, Yu P, Miller BB, Shcherbinin S, Dickson J, Navitsky M, Joshi AD, Devous MD Sr, Mintun MS (2016) Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain 139(Pt 5):1539–1550. https://doi.org/10.1093/brain/aww023

    Article  PubMed  Google Scholar 

  36. Shcherbinin S, Schwarz AJ, Joshi A, Navitsky M, Flitter M, Shankle WR, Devous MD Sr, Mintun MA (2016) Kinetics of the tau PET tracer 18F-AV-1451 (T807) in subjects with normal cognitive function, mild cognitive impairment, and Alzheimer disease. J Nucl Med 57(10):1535–1542. https://doi.org/10.2967/jnumed.115.170027

    Article  PubMed  CAS  Google Scholar 

  37. Lowe VJ, Curran G, Fang P, Liesinger AM, Josephs KA, Parisi JE, Kantarci K, Boeve BF, Pandey MK, Bruinsma T, Knopman DS, Jones DT, Petrucelli L, Cook CN, Graff-Radford NR, Dickson DW, Petersen RC, Jack CR Jr, Murray ME (2016) An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 4(1):58. https://doi.org/10.1186/s40478-016-0315-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgment

This work was supported by the Swiss National Science Foundation under grant SNF 320030_169876.

Author information

Authors and Affiliations

  1. Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland

    Ismini C. Mainta & Valentina Garibotto

  2. Faculty of Medicine, Nuclear Medicine Department, Geneva University Medical Center, University of Geneva, Geneva, Switzerland

    Ismini C. Mainta, Maria I. Vargas, Sara Trombella, Giovanni B. Frisoni & Valentina Garibotto

  3. Division of Neuroradiology, Geneva University Hospitals, Geneva, Switzerland

    Maria I. Vargas

  4. Department of Internal Medicine, Geneva University Hospitals, Geneva, Switzerland

    Giovanni B. Frisoni

  5. Institute for Regenerative Medicine and Hospital for Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland

    Paul G. Unschuld

Authors
  1. Ismini C. Mainta
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  2. Maria I. Vargas
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  3. Sara Trombella
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  4. Giovanni B. Frisoni
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  5. Paul G. Unschuld
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  6. Valentina Garibotto
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Corresponding author

Correspondence to Ismini C. Mainta .

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Editors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany

    Robert Perneczky

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Mainta, I.C., Vargas, M.I., Trombella, S., Frisoni, G.B., Unschuld, P.G., Garibotto, V. (2018). Hybrid PET-MRI in Alzheimer’s Disease Research. In: Perneczky, R. (eds) Biomarkers for Alzheimer’s Disease Drug Development. Methods in Molecular Biology, vol 1750. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7704-8_12

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  • DOI: https://doi.org/10.1007/978-1-4939-7704-8_12

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7703-1

  • Online ISBN: 978-1-4939-7704-8

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