Advertisement

18F-FDG-PET/CT (FDG-PET) in Neurodegenerative Disease

  • Selene Capitanio
  • Matteo Bauckneht
  • Dario Arnaldi
  • Federico Massa
  • Riccardo Meli
  • Valentina Ceriani
  • Flavio Nobili
  • Silvia MorbelliEmail author
Chapter
Part of the Clinicians’ Guides to Radionuclide Hybrid Imaging book series (CGRHI)

Abstract

Neurodegenerative diseases are a heterogeneous group of conditions due to different etiologies and different neuropathological and neurochemical alterations leading to different clinical pictures and courses.

With its peculiar ability to noninvasively reflect cerebral synaptic density and activity, FDG-PET plays a major role in evaluating the extent and localization of neuronal dysfunction, thus characterizing the endophenotype of a neuronal injury.

The identification of typical patterns of hypometabolism since the earliest stages of neurodegenerative diseases can support clinicians in differential diagnosis, especially in atypical and challenging cases.

References

  1. 1.
    Nasrallah IM, Wolk DA. Multimodality imaging of Alzheimer disease and other neurodegenerative dementias. J Nucl Med. 2014;55:2003–11.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Kovacs GG. Molecular pathological classification of neurodegenerative diseases: turning towards precision medicine. Int J Mol Sci. 2016;17:189.PubMedCentralGoogle Scholar
  3. 3.
    Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45:358–68.PubMedGoogle Scholar
  4. 4.
    Rocher AB, Chapon F, Blaizot X, Baron JC, Chavoix C. Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons. NeuroImage. 2003;20:1894–8.PubMedGoogle Scholar
  5. 5.
    Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734–46.PubMedGoogle Scholar
  6. 6.
    Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–9.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Ossenkoppele R, Prins ND, Pijnenburg YA, Lemstra AW, van der Flier WM, Adriaanse SF, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement. 2013;9:414–21.PubMedGoogle Scholar
  8. 8.
    Rabinovici GD, Rosen HJ, Alkalay A, Kornak J, Furst AJ, Agarwal N, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011;77:2034–42.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Sorbi S, Hort J, Erkinjuntti T, Fladby T, Gainotti G, Gurvit H, et al. EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol. 2012;19:1159–79.PubMedGoogle Scholar
  10. 10.
    Filippi M, Agosta F, Barkhof F, Dubois B, Fox NC, Frisoni GB, et al. EFNS task force: the use of neuroimaging in the diagnosis of dementia. Eur J Neurol. 2012;19:1487–501.Google Scholar
  11. 11.
    Varrone A, Asenbaum S, Vander Borght T, Booij J, Nobili F, Någren K, et al. EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2. Eur J Nucl Med Mol Imaging. 2009;36:2103–10.PubMedGoogle Scholar
  12. 12.
    Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frölich L, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. NeuroImage. 2002;17:302–16.PubMedGoogle Scholar
  13. 13.
    Herholz K, Carter SF, Jones M. Positron emission tomography imaging in dementia. Br J Radiol. 2007;80:S160–7.PubMedGoogle Scholar
  14. 14.
    Mosconi L, Tsui WH, Herholz K, Pupi A, Drzezga A, Lucignani G, et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med. 2008;49:390–8.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Hellwig S, Amtage F, Kreft A, Buchert R, Winz OH, Vach W, et al. [18F]FDG-PET is superior to [123I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology. 2012;79:1314–22.PubMedGoogle Scholar
  16. 16.
    Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med. 1995;36:1238–48.PubMedGoogle Scholar
  17. 17.
    Gallucci M, Limbucci N, Catalucci A, Caulo M. Neurodegenerative diseases. Radiol Clin N Am. 2008;46:799–817.PubMedGoogle Scholar
  18. 18.
    Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging. 2005;32:486–510.PubMedGoogle Scholar
  19. 19.
    Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42:85–94.PubMedGoogle Scholar
  20. 20.
    Morbelli S, Piccardo A, Villavecchia G, Dessi B, Brugnolo A, Piccini A, et al. Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study. Eur J Nucl Med Mol Imaging. 2010;37:36–45.PubMedGoogle Scholar
  21. 21.
    Ohnishi T, Hoshi H, Nagamachi S, Jinnouchi S, Flores LG II, Futami S, et al. High-resolution SPECT to assess hippocampal perfusion in neuropsychiatric diseases. J Nucl Med. 1995;36:1163–9.PubMedGoogle Scholar
  22. 22.
    Kim EJ, Cho SS, Jeong Y, Park KC, Kang SJ, Kang E, et al. Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients. Brain. 2005;128:1790–801.PubMedGoogle Scholar
  23. 23.
    Morbelli S, Perneczky R, Drzezga A, Frisoni GB, Caroli A, van Berckel BN, et al. Metabolic networks underlying cognitive reserve in prodromal Alzheimer disease: a European Alzheimer disease consortium project. J Nucl Med. 2013;54:894–902.PubMedGoogle Scholar
  24. 24.
    Madhavan A, Whitwell JL, Weigand SD, Duffy JR, Strand EA, Machulda MM, et al. FDG PET and MRI in logopenic primary progressive aphasia versus dementia of the Alzheimer's type. PLoS One. 2013;8:e62471.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Laforce R Jr, Tosun D, Ghosh P, Lehmann M, Madison CM, Weiner MW, et al. Parallel ICA of FDG-PET and PiB-PET in three conditions with underlying Alzheimer’s pathology. Neuroimage Clin. 2014;4:508–16.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Rosenbloom MH, Alkalay A, Agarwal N, Baker SL, O'Neil JP, Janabi M, et al. Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution. Neurology. 2011;76:1789–96.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Woodward MC, Rowe CC, Jones G, Villemagne VL, Varos TA. Differentiating the frontal presentation of Alzheimer’s disease with FDG-PET. J Alzheimers Dis. 2015;44:233–42.PubMedGoogle Scholar
  28. 28.
    Ossenkoppele R, Schonhaut DR, Schöll M, Lockhart SN, Ayakta N, Baker SL, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain. 2016;139:1551–67.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Kerrouche N, Herholz K, Mielke R, Holthoff V, Baron JC. 18FDG PET in vascular dementia: differentiation from Alzheimer’s disease using voxel-based multivariate analysis. J Cereb Blood Flow Metab. 2006;26:1213–21.PubMedGoogle Scholar
  30. 30.
    Seltman RE, Matthews BR. Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs. 2012;26:841–70.PubMedGoogle Scholar
  31. 31.
    Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Whitwell JL, Josephs KA. Neuroimaging in frontotemporal lobar degeneration—predicting molecular pathology. Nat Rev Neurol. 2012;8:131–42.PubMedGoogle Scholar
  33. 33.
    Morbelli S, Ferrara M, Fiz F, Dessi B, Arnaldi D, Picco A, et al. Mapping brain morphological and functional conversion patterns in predementia late-onset bvFTD. Eur J Nucl Med Mol Imaging. 2016;43:1337–47.PubMedGoogle Scholar
  34. 34.
    Mendez MF, Shapira JS, McMurtray A, Licht E, Miller BL. Accuracy of the clinical evaluation for frontotemporal dementia. Arch Neurol. 2007;64:830–5.PubMedGoogle Scholar
  35. 35.
    Chow TW, Miller BL, Boone K, Mishkin F, Cummings JL. Frontotemporal dementia classification and neuropsychiatry. Neurologist. 2002;8:263–9.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Jeong Y, Cho SS, Park JM, Kang SJ, Lee JS, Kang E, et al. 18F-FDG PET findings in frontotemporal dementia: an SPM analysis of 29 patients. J Nucl Med. 2005;46:233–9.PubMedGoogle Scholar
  37. 37.
    Womack KB, Diaz-Arrastia R, Aizenstein HJ, Arnold SE, Barbas NR, Boeve BF, et al. Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors. Arch Neurol. 2011;68:329–37.PubMedGoogle Scholar
  38. 38.
    Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Matías-Guiu JA, Cabrera-Martín MN, Moreno-Ramos T, Valles-Salgado M, Fernandez-Matarrubia M, Carreras JL, et al. Amyloid and FDG-PET study of logopenic primary progressive aphasia: evidence for the existence of two subtypes. J Neurol. 2015;262:1463–72.PubMedGoogle Scholar
  40. 40.
    Rabinovici GD, Jagust WJ, Furst AJ, Ogar JM, Racine CA, Mormino EC, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol. 2008;64:388–401.PubMedPubMedCentralGoogle Scholar
  41. 41.
    McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89:88–100.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Bauckneht M, Arnaldi D, Nobili F, Aarsland D, Morbelli S. New tracers and new perspectives for molecular imaging in Lewy body diseases. Curr Med Chem. 2018;25(26):3105–30.PubMedGoogle Scholar
  43. 43.
    Graff-Radford J, Murray ME, Lowe VJ, Boeve BF, Ferman TJ, Przybelski SA, et al. Dementia with Lewy bodies: basis of cingulate island sign. Neurology. 2014;83:801–9.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Pagani M, Chiò A, Valentini MC, Öberg J, Nobili F, Calvo A, et al. Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis. Neurology. 2014;83:1067–74.PubMedGoogle Scholar
  45. 45.
    Prado LGR, Bicalho ICS, Magalhães D, Caramelli P, Teixeira AL, de Souza LC. C9ORF72 and the FTD-ALS spectrum: A systematic review of neuroimaging studies. Dement Neuropsychol. 2015;9:413–21.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Magistretti PJ. Cellular bases of functional brain imaging: insights from neuron-glia metabolic coupling. Brain Res. 2000;886:108–12.PubMedGoogle Scholar
  47. 47.
    Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29.PubMedGoogle Scholar
  48. 48.
    Morbelli S, Bauckneht M, Arnaldi D, Picco A, Pardini M, Brugnolo A, et al. 18F-FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage. Eur J Nucl Med Mol Imaging. 2017;44:2073–83.PubMedGoogle Scholar
  49. 49.
    Morbelli S, Bauckneht M, Scheltens P. Imaging biomarkers in Alzheimer’s disease: added value in the clinical setting. Q J Nucl Med Mol Imaging. 2017;61:360–71.PubMedGoogle Scholar
  50. 50.
    Perani D, Della Rosa PA, Cerami C, Gallivanone F, Fallanca F, Vanoli EG, et al. Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting. Neuroimage Clin. 2014;6:445–54.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Smailagic N, Vacante M, Hyde C, Martin S, Ukoumunne O, Sachpekidis C. 18F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015;1:CD010632.PubMedGoogle Scholar
  52. 52.
    Morbelli S, Garibotto V, Van De Giessen E, Arbizu J, Chételat G, Drezgza A, et al. A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives. Eur J Nucl Med Mol Imaging. 2015;42:1487–91.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Selene Capitanio
    • 1
  • Matteo Bauckneht
    • 1
  • Dario Arnaldi
    • 2
  • Federico Massa
    • 2
  • Riccardo Meli
    • 2
  • Valentina Ceriani
    • 1
  • Flavio Nobili
    • 2
  • Silvia Morbelli
    • 1
    Email author
  1. 1.Department of Health Sciences (DiSSAL)University of Genoa and Nuclear Medicine Unit, Polyclinic San Martino HospitalGenoaItaly
  2. 2.Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), Clinical Neurology, Polyclinic San Martino HospitalUniversity of GenoaGenoaItaly

Personalised recommendations