Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18 F-Flutemetamol PET: Comparing Visual Reads and Quantitative Methods

Lyduine E. Collij, Elles Konijnenberg, Juhan Reimand, Mara Ten Kate, Anouk den Braber, Isadora Lopes Alves, Marissa Zwan, Maqsood Yaqub, Daniëlle M.E. van Assema, Alle Meije Wink, Adriaan A. Lammertsma, Philip Scheltens, Pieter Jelle Visser, Frederik Barkhof, Bart N.M. van Berckel

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic 18F-flutemetamol PET scans were acquired using a coffee-break protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60% female). Parametric images were generated from SUV ratio (SUVr) and nondisplaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using κ-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (κ = 0.57) and good for BPND images (κ = 0.77). There was discordance between readers for 35 cases (18%) using SUVr and for 15 cases (8%) using BPND, with 9 overlapping cases. For the total cohort, the mean (±SD) SUVr and BPND were 1.33 (±0.21) and 0.16 (±0.12), respectively. Most of the 35 cases (91%) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of 18F-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semiquantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population.

LanguageEnglish
Pages541-547
Number of pages7
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume60
Issue number5
Early online date12 Oct 2018
DOIs
Publication statusPublished - May 2019

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Amyloid
Pathology
Population
Coffee
ROC Curve
Positron-Emission Tomography
flutemetamol

Keywords

  • 18F-flutemetamol PET
  • amyloid pathology
  • preclinical Alzheimer disease
  • visual assessment

Cite this

Collij, Lyduine E. ; Konijnenberg, Elles ; Reimand, Juhan ; Kate, Mara Ten ; Braber, Anouk den ; Alves, Isadora Lopes ; Zwan, Marissa ; Yaqub, Maqsood ; van Assema, Daniëlle M.E. ; Wink, Alle Meije ; Lammertsma, Adriaan A. ; Scheltens, Philip ; Visser, Pieter Jelle ; Barkhof, Frederik ; van Berckel, Bart N.M. / Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18 F-Flutemetamol PET : Comparing Visual Reads and Quantitative Methods. In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019 ; Vol. 60, No. 5. pp. 541-547.
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abstract = "Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic 18F-flutemetamol PET scans were acquired using a coffee-break protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60{\%} female). Parametric images were generated from SUV ratio (SUVr) and nondisplaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using κ-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (κ = 0.57) and good for BPND images (κ = 0.77). There was discordance between readers for 35 cases (18{\%}) using SUVr and for 15 cases (8{\%}) using BPND, with 9 overlapping cases. For the total cohort, the mean (±SD) SUVr and BPND were 1.33 (±0.21) and 0.16 (±0.12), respectively. Most of the 35 cases (91{\%}) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of 18F-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semiquantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population.",
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author = "Collij, {Lyduine E.} and Elles Konijnenberg and Juhan Reimand and Kate, {Mara Ten} and Braber, {Anouk den} and Alves, {Isadora Lopes} and Marissa Zwan and Maqsood Yaqub and {van Assema}, {Dani{\"e}lle M.E.} and Wink, {Alle Meije} and Lammertsma, {Adriaan A.} and Philip Scheltens and Visser, {Pieter Jelle} and Frederik Barkhof and {van Berckel}, {Bart N.M.}",
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Collij, LE, Konijnenberg, E, Reimand, J, Kate, MT, Braber, AD, Alves, IL, Zwan, M, Yaqub, M, van Assema, DME, Wink, AM, Lammertsma, AA, Scheltens, P, Visser, PJ, Barkhof, F & van Berckel, BNM 2019, 'Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18 F-Flutemetamol PET: Comparing Visual Reads and Quantitative Methods', Journal of nuclear medicine : official publication, Society of Nuclear Medicine, vol. 60, no. 5, pp. 541-547. https://doi.org/10.2967/jnumed.118.211532

Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18 F-Flutemetamol PET : Comparing Visual Reads and Quantitative Methods. / Collij, Lyduine E.; Konijnenberg, Elles; Reimand, Juhan; Kate, Mara Ten; Braber, Anouk den; Alves, Isadora Lopes; Zwan, Marissa; Yaqub, Maqsood; van Assema, Daniëlle M.E.; Wink, Alle Meije; Lammertsma, Adriaan A.; Scheltens, Philip; Visser, Pieter Jelle; Barkhof, Frederik; van Berckel, Bart N.M.

In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Vol. 60, No. 5, 05.2019, p. 541-547.

Research output: Contribution to JournalArticleAcademicpeer-review

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T1 - Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18 F-Flutemetamol PET

T2 - Journal of nuclear medicine : official publication, Society of Nuclear Medicine

AU - Collij, Lyduine E.

AU - Konijnenberg, Elles

AU - Reimand, Juhan

AU - Kate, Mara Ten

AU - Braber, Anouk den

AU - Alves, Isadora Lopes

AU - Zwan, Marissa

AU - Yaqub, Maqsood

AU - van Assema, Daniëlle M.E.

AU - Wink, Alle Meije

AU - Lammertsma, Adriaan A.

AU - Scheltens, Philip

AU - Visser, Pieter Jelle

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N2 - Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic 18F-flutemetamol PET scans were acquired using a coffee-break protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60% female). Parametric images were generated from SUV ratio (SUVr) and nondisplaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using κ-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (κ = 0.57) and good for BPND images (κ = 0.77). There was discordance between readers for 35 cases (18%) using SUVr and for 15 cases (8%) using BPND, with 9 overlapping cases. For the total cohort, the mean (±SD) SUVr and BPND were 1.33 (±0.21) and 0.16 (±0.12), respectively. Most of the 35 cases (91%) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of 18F-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semiquantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population.

AB - Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic 18F-flutemetamol PET scans were acquired using a coffee-break protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60% female). Parametric images were generated from SUV ratio (SUVr) and nondisplaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using κ-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (κ = 0.57) and good for BPND images (κ = 0.77). There was discordance between readers for 35 cases (18%) using SUVr and for 15 cases (8%) using BPND, with 9 overlapping cases. For the total cohort, the mean (±SD) SUVr and BPND were 1.33 (±0.21) and 0.16 (±0.12), respectively. Most of the 35 cases (91%) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of 18F-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semiquantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population.

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KW - preclinical Alzheimer disease

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