Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2016

01-11-2016 | Original Article

Feasibility and acceptance of simultaneous amyloid PET/MRI

Authors: Lisa Schütz, Donald Lobsien, Dominik Fritzsch, Solveig Tiepolt, Peter Werner, Matthias L. Schroeter, Jörg Berrouschot, Dorothee Saur, Swen Hesse, Thies Jochimsen, Michael Rullmann, Bernhard Sattler, Marianne Patt, Hermann-Josef Gertz, Arno Villringer, Joseph Claßen, Karl-Titus Hoffmann, Osama Sabri, Henryk Barthel

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2016

Login to get access

Abstract

Purpose

Established Alzheimer’s disease (AD) biomarker concepts classify into amyloid pathology and neuronal injury biomarkers, while recent alternative concepts classify into diagnostic and progression AD biomarkers. However, combined amyloid positron emission tomography/magnetic resonance imaging (PET/MRI) offers the chance to obtain both biomarker category read-outs within one imaging session, with increased patient as well as referrer convenience. The aim of this pilot study was to investigate this matter for the first time.

Methods

100 subjects (age 70 ± 10 yrs, 46 female), n = 51 with clinically defined mild cognitive impairment (MCI), n = 44 with possible/probable AD dementia, and n = 5 with frontotemporal lobe degeneration, underwent simultaneous [18F]florbetaben or [11C]PIB PET/MRI (3 Tesla Siemens mMR). Brain amyloid load, mesial temporal lobe atrophy (MTLA) by means of the Scheltens scale, and other morphological brain pathologies were scored by respective experts. The patients/caregivers as well as the referrers were asked to assess on a five-point scale the convenience related to the one-stop-shop PET and MRI approach.

Results

In three subjects, MRI revealed temporal lobe abnormalities other than MTLA. According to the National Institute on Aging-Alzheimer’s Association classification, the combined amyloid-beta PET/MRI evaluation resulted in 31 %, 45 %, and 24 % of the MCI subjects being categorized as “MCI-unlikely due to AD”, “MCI due to AD-intermediate likelihood”, and “MCI due to AD-high likelihood”, respectively. 50 % of the probable AD dementia patients were categorized as “High level of evidence of AD pathophysiological process”, and 56 % of the possible AD dementia patients as “Possible AD dementia - with evidence of AD pathophysiological process”. With regard to the International Working Group 2 classification, 36 subjects had both positive diagnostic and progression biomarkers. The patient/caregiver survey revealed a gain of convenience in 88 % of responders as compared to a theoretically separate PET and MR imaging. In the referrer survey, an influence of the combined amyloid-beta PET/MRI on the final diagnosis was reported by 82 % of responders, with a referrer acceptance score of 3.7 ± 1.0 on a 5-point scale.

Conclusion

Simultaneous amyloid PET/MRI is feasible and provides imaging biomarkers of all categories which are able to supplement the clinical diagnosis of MCI due to AD and that of AD dementia. Further, patient and referrer convenience is improved by this one-stop-shop imaging approach.
Literature
1.
go back to reference Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 2007;6(8):734–46.CrossRefPubMed Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 2007;6(8):734–46.CrossRefPubMed
2.
go back to reference Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMed Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMed
3.
go back to reference Albert MS, DeKosky ST, Dickson D, 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(3):270–9.CrossRefPubMedPubMedCentral Albert MS, DeKosky ST, Dickson D, 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(3):270–9.CrossRefPubMedPubMedCentral
4.
go back to reference McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia 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(3):263–9.CrossRefPubMedPubMedCentral McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia 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(3):263–9.CrossRefPubMedPubMedCentral
5.
go back to reference de Leon MJ, Ferris SH, George AE, et al. Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am J Neuroradiol. 1983;4(3):568–71.PubMed de Leon MJ, Ferris SH, George AE, et al. Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am J Neuroradiol. 1983;4(3):568–71.PubMed
6.
go back to reference Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55(10):967–72.CrossRefPubMedPubMedCentral Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55(10):967–72.CrossRefPubMedPubMedCentral
7.
go back to reference Barthel H, Seibyl J, Sabri O. The role of positron emission tomography imaging in understanding Alzheimer’s disease. Expert Rev Neurother. 2015;15(4):395–406.CrossRefPubMed Barthel H, Seibyl J, Sabri O. The role of positron emission tomography imaging in understanding Alzheimer’s disease. Expert Rev Neurother. 2015;15(4):395–406.CrossRefPubMed
8.
go back to reference Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol. 2015;14(1):114–24.CrossRefPubMed Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol. 2015;14(1):114–24.CrossRefPubMed
9.
go back to reference Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83.CrossRefPubMed Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83.CrossRefPubMed
10.
go back to reference Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 2012;11(8):669–78.CrossRefPubMed Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 2012;11(8):669–78.CrossRefPubMed
11.
go back to reference Teipel S, Drzezga A, Grothe MJ, et al. Multimodal imaging in Alzheimer’s disease: validity and usefulness for early detection. Lancet Neurol. 2015;14(10):1037–53.CrossRefPubMed Teipel S, Drzezga A, Grothe MJ, et al. Multimodal imaging in Alzheimer’s disease: validity and usefulness for early detection. Lancet Neurol. 2015;14(10):1037–53.CrossRefPubMed
12.
go back to reference Vercher-Conejero JL, Rubbert C, Kohan AA, Partovi S, O’Donnell JK. Amyloid PET/MRI in the differential diagnosis of dementia. Clin Nucl Med. 2014;39(6):e336–9.CrossRefPubMed Vercher-Conejero JL, Rubbert C, Kohan AA, Partovi S, O’Donnell JK. Amyloid PET/MRI in the differential diagnosis of dementia. Clin Nucl Med. 2014;39(6):e336–9.CrossRefPubMed
13.
go back to reference McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. [Review]. Neurology. 1984;34(7):939–44.CrossRefPubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. [Review]. Neurology. 1984;34(7):939–44.CrossRefPubMed
14.
go back to reference American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR. 4th ed. Washington, D.C.: American Psychiatric Association; 2000. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR. 4th ed. Washington, D.C.: American Psychiatric Association; 2000.
15.
16.
go back to reference Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.CrossRefPubMed Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.CrossRefPubMed
17.
go back to reference Barthel H, Sabri O. Florbetaben to trace amyloid-β in the Alzheimer brain by means of PET. J Alzheimers Dis JAD. 2011;26 Suppl 3:117–21.PubMed Barthel H, Sabri O. Florbetaben to trace amyloid-β in the Alzheimer brain by means of PET. J Alzheimers Dis JAD. 2011;26 Suppl 3:117–21.PubMed
19.
go back to reference Barthel H, Gertz H-J, Dresel S, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.CrossRefPubMed Barthel H, Gertz H-J, Dresel S, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.CrossRefPubMed
20.
go back to reference Villemagne VL, Mulligan RS, Pejoska S, et al. Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39(6):983–9.CrossRefPubMed Villemagne VL, Mulligan RS, Pejoska S, et al. Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39(6):983–9.CrossRefPubMed
21.
go back to reference Drzezga A, Barthel H, Minoshima S, Sabri O. Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Disea. J Nucl Med. 2014;55(Supplement 2):47S–55.CrossRefPubMed Drzezga A, Barthel H, Minoshima S, Sabri O. Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Disea. J Nucl Med. 2014;55(Supplement 2):47S–55.CrossRefPubMed
22.
go back to reference Geroldi C, Rossi R, Calvagna C, et al. Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment. J Neurol Neurosurg Psychiatry. 2006;77(11):1219–22.CrossRefPubMedPubMedCentral Geroldi C, Rossi R, Calvagna C, et al. Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment. J Neurol Neurosurg Psychiatry. 2006;77(11):1219–22.CrossRefPubMedPubMedCentral
23.
24.
25.
go back to reference Schoonenboom NSM, van der Flier WM, Blankenstein MA, et al. CSF and MRI markers independently contribute to the diagnosis of Alzheimer’s disease. Neurobiol Aging. 2008;29(5):669–75.CrossRefPubMed Schoonenboom NSM, van der Flier WM, Blankenstein MA, et al. CSF and MRI markers independently contribute to the diagnosis of Alzheimer’s disease. Neurobiol Aging. 2008;29(5):669–75.CrossRefPubMed
26.
go back to reference Petersen RC, Aisen P, Boeve BF, et al. Criteria for Mild Cognitive Impairment Due to Alzheimer’s Disease in the Community. Ann Neurol. 2013;74(2):199–208.PubMedPubMedCentral Petersen RC, Aisen P, Boeve BF, et al. Criteria for Mild Cognitive Impairment Due to Alzheimer’s Disease in the Community. Ann Neurol. 2013;74(2):199–208.PubMedPubMedCentral
27.
go back to reference Galluzzi S, Geroldi C, Amicucci G, et al. Supporting evidence for using biomarkers in the diagnosis of MCI due to AD. J Neurol. 2013;260(2):640–50.CrossRefPubMed Galluzzi S, Geroldi C, Amicucci G, et al. Supporting evidence for using biomarkers in the diagnosis of MCI due to AD. J Neurol. 2013;260(2):640–50.CrossRefPubMed
28.
go back to reference Lowe VJ, Peller PJ, Weigand SD, et al. Application of the National Institute on Aging-Alzheimer’s Association AD criteria to ADNI. Neurology. 2013;80:2130–7.CrossRefPubMedPubMedCentral Lowe VJ, Peller PJ, Weigand SD, et al. Application of the National Institute on Aging-Alzheimer’s Association AD criteria to ADNI. Neurology. 2013;80:2130–7.CrossRefPubMedPubMedCentral
29.
go back to reference Johnson KA, Minoshima S, Bohnen NI, et al. Update on Appropriate Use Criteria for Amyloid PET Imaging: Dementia Experts, Mild Cognitive Impairment, and Education. J Nucl Med. 2013;54(7):1011–3.CrossRefPubMed Johnson KA, Minoshima S, Bohnen NI, et al. Update on Appropriate Use Criteria for Amyloid PET Imaging: Dementia Experts, Mild Cognitive Impairment, and Education. J Nucl Med. 2013;54(7):1011–3.CrossRefPubMed
30.
go back to reference Jack CR, Knopman DS, Weigand SD, et al. An Operational Approach to NIA-AA Criteria for Preclinical Alzheimer’s Disease. Ann Neurol. 2012;71(6):765–75.CrossRefPubMedPubMedCentral Jack CR, Knopman DS, Weigand SD, et al. An Operational Approach to NIA-AA Criteria for Preclinical Alzheimer’s Disease. Ann Neurol. 2012;71(6):765–75.CrossRefPubMedPubMedCentral
31.
32.
go back to reference Tiepolt S, Patt M, Hoffmann K-T, Schroeter ML, Sabri O, Barthel H, et al. PET Imaging Pattern in an Amyloid-Negative Mild Cognitive Impairment Subject. Zwan M, ed. J Alzheimers Dis. 2015;47(3):539–43.CrossRefPubMed Tiepolt S, Patt M, Hoffmann K-T, Schroeter ML, Sabri O, Barthel H, et al. PET Imaging Pattern in an Amyloid-Negative Mild Cognitive Impairment Subject. Zwan M, ed. J Alzheimers Dis. 2015;47(3):539–43.CrossRefPubMed
33.
go back to reference Jack CR, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9(1):119.CrossRefPubMedPubMedCentral Jack CR, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9(1):119.CrossRefPubMedPubMedCentral
34.
go back to reference Weise D, Tiepolt S, Awissus C, et al. Critical Comparison of Different Biomarkers for Alzheimer’s Disease in a Clinical Setting. J Alzheimers Dis. 2015;48(2):425–32.CrossRefPubMed Weise D, Tiepolt S, Awissus C, et al. Critical Comparison of Different Biomarkers for Alzheimer’s Disease in a Clinical Setting. J Alzheimers Dis. 2015;48(2):425–32.CrossRefPubMed
35.
go back to reference Bowen SL, Byars LG, Michel CJ, Chonde DB, Catana C. Influence of the partial volume correction method on 18F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM. Phys Med Biol. 2013;58(20):7081–106.CrossRefPubMedPubMedCentral Bowen SL, Byars LG, Michel CJ, Chonde DB, Catana C. Influence of the partial volume correction method on 18F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM. Phys Med Biol. 2013;58(20):7081–106.CrossRefPubMedPubMedCentral
36.
go back to reference Rullmann M, Dukart J, Hoffmann K-T, et al. Partial volume effect correction improves quantitative florbetaben beta-amyloid PET scan analysis. J Nucl Med. 2015:jnumed.115.161893. Rullmann M, Dukart J, Hoffmann K-T, et al. Partial volume effect correction improves quantitative florbetaben beta-amyloid PET scan analysis. J Nucl Med. 2015:jnumed.115.161893.
37.
go back to reference Andersen FL, Ladefoged CN, Beyer T, et al. Combined PET/MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone. NeuroImage. 2014;84:206–16.CrossRefPubMed Andersen FL, Ladefoged CN, Beyer T, et al. Combined PET/MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone. NeuroImage. 2014;84:206–16.CrossRefPubMed
38.
go back to reference Su Y, Rubin B, McConathy J, et al. Impact of MR based attenuation correction on neurological PET studies. J Nucl Med. 2016:jnumed.115.164822. Su Y, Rubin B, McConathy J, et al. Impact of MR based attenuation correction on neurological PET studies. J Nucl Med. 2016:jnumed.115.164822.
39.
go back to reference Izquierdo-Garcia D, Hansen AE, Forster S, et al. An SPM8-Based Approach for Attenuation Correction Combining Segmentation and Nonrigid Template Formation: Application to Simultaneous PET/MR Brain Imaging. J Nucl Med. 2014;55(11):1825–30.CrossRefPubMedPubMedCentral Izquierdo-Garcia D, Hansen AE, Forster S, et al. An SPM8-Based Approach for Attenuation Correction Combining Segmentation and Nonrigid Template Formation: Application to Simultaneous PET/MR Brain Imaging. J Nucl Med. 2014;55(11):1825–30.CrossRefPubMedPubMedCentral
40.
go back to reference Gückel B, Gatidis S, Enck P, et al. Patient comfort during positron emission tomography/magnetic resonance and positron emission tomography/computed tomography examinations: subjective assessments with visual analog scales. Investig Radiol. 2015;50(10):726–32.CrossRef Gückel B, Gatidis S, Enck P, et al. Patient comfort during positron emission tomography/magnetic resonance and positron emission tomography/computed tomography examinations: subjective assessments with visual analog scales. Investig Radiol. 2015;50(10):726–32.CrossRef
Metadata
Title
Feasibility and acceptance of simultaneous amyloid PET/MRI
Authors
Lisa Schütz
Donald Lobsien
Dominik Fritzsch
Solveig Tiepolt
Peter Werner
Matthias L. Schroeter
Jörg Berrouschot
Dorothee Saur
Swen Hesse
Thies Jochimsen
Michael Rullmann
Bernhard Sattler
Marianne Patt
Hermann-Josef Gertz
Arno Villringer
Joseph Claßen
Karl-Titus Hoffmann
Osama Sabri
Henryk Barthel
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3462-x

Other articles of this Issue 12/2016

European Journal of Nuclear Medicine and Molecular Imaging 12/2016 Go to the issue