Accurate measurement of changes in amyloid-β (Aβ) deposition over time is important in longitudinal studies, particularly in anti-Aβ therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Aβ PET measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Aβ changes using 18F-florbetaben PET. Methods: Forty-five patients with mild cognitive impairment (mean age ± SD, 72.69 ± 6.54 y; 29 men/16 women) who underwent up to 3 18F-florbetaben scans were included. Baseline scans were visually classified as high (Aβ+) or low (Aβ-) amyloid. Six cortical regions were quantified using a standardized region-of-interest atlas applied to the spatially normalized gray matter image obtained from segmentation of the baseline T1-weighted volumetric MRI. Four RRs (cerebellar gray matter [CGM], whole cerebellum [WCER], pons, and subcortical white matter [SWM]) were studied. The SUV ratio (SUVR) for each RR was calculated by dividing cortex activity by RR activity, with a composite SUVR averaged over 6 cortical regions. SUVR increase from baseline to 1 and 2 y, and percentage Aβ deposition per year, were assessed across Aβ+ and Aβ- groups. Results: SUVs for any RR were not significantly different over time. Percentage Aβ accumulation per year derived from composite SUVR was 0.10 ± 1.72 (Aβ-) and 1.36 ± 1.98 (Aβ+) (P = 0.02) for CGM and 0.13 ± 1.47 and 1.32 ± 1.75 (P = 0.01), respectively, for WCER. Compared with baseline, the composite SUVR increase in Aβ+ scans was significantly larger than in Aβ- scans at 1 y (P = 0.04 [CGM]; P = 0.03 [WCER]) and 2 y (P = 0.02 [CGM]; P = 0.01 [WCER]) using these 2 RRs. Significant SUVR changes using the pons as the RR were detected only at 2 y (P = 0.46 [1 y], P = 0.001 [2 y]). SUVR using the SWM as the RR showed no significant differences at either follow-up (P = 0.39 [1 y], P = 0.09 [2 y]). Conclusion: RR selection influences reliable early measurement of Aβ changes over time. Compared with SWM and pons, which do not fulfil the RR requirements and have limited sensitivity to detect Aβ changes, cerebellar RRs are recommended for 18F-florbetaben PET because they allow earlier detection of Aβ accumulation.
Accurate measurement of changes in amyloid-β (Aβ) deposition over time is important in longitudinal studies, particularly in anti-Aβ therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Aβ PET measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Aβ changes using 18F-florbetaben PET. Methods: Forty-five patients with mild cognitive impairment (mean age ± SD, 72.69 ± 6.54 y; 29 men/16 women) who underwent up to 3 18F-florbetaben scans were included. Baseline scans were visually classified as high (Aβ+) or low (Aβ-) amyloid. Six cortical regions were quantified using a standardized region-of-interest atlas applied to the spatially normalized gray matter image obtained from segmentation of the baseline T1-weighted volumetric MRI. Four RRs (cerebellar gray matter [CGM], whole cerebellum [WCER], pons, and subcortical white matter [SWM]) were studied. The SUV ratio (SUVR) for each RR was calculated by dividing cortex activity by RR activity, with a composite SUVR averaged over 6 cortical regions. SUVR increase from baseline to 1 and 2 y, and percentage Aβ deposition per year, were assessed across Aβ+ and Aβ- groups. Results: SUVs for any RR were not significantly different over time. Percentage Aβ accumulation per year derived from composite SUVR was 0.10 ± 1.72 (Aβ-) and 1.36 ± 1.98 (Aβ+) (P = 0.02) for CGM and 0.13 ± 1.47 and 1.32 ± 1.75 (P = 0.01), respectively, for WCER. Compared with baseline, the composite SUVR increase in Aβ+ scans was significantly larger than in Aβ- scans at 1 y (P = 0.04 [CGM]; P = 0.03 [WCER]) and 2 y (P = 0.02 [CGM]; P = 0.01 [WCER]) using these 2 RRs. Significant SUVR changes using the pons as the RR were detected only at 2 y (P = 0.46 [1 y], P = 0.001 [2 y]). SUVR using the SWM as the RR showed no significant differences at either follow-up (P = 0.39 [1 y], P = 0.09 [2 y]). Conclusion: RR selection influences reliable early measurement of Aβ changes over time. Compared with SWM and pons, which do not fulfil the RR requirements and have limited sensitivity to detect Aβ changes, cerebellar RRs are recommended for 18F-florbetaben PET because they allow earlier detection of Aβ accumulation.
Authors: Xiaofan Xiong; Timothy J Linhardt; Weiren Liu; Brian J Smith; Wenqing Sun; Christian Bauer; John J Sunderland; Michael M Graham; John M Buatti; Reinhard R Beichel Journal: Med Phys Date: 2020-01-06 Impact factor: 4.071
Authors: Kunal P Patel; David T Wymer; Vinay K Bhatia; Ranjan Duara; Chetan D Rajadhyaksha Journal: Radiographics Date: 2020 Jan-Feb Impact factor: 5.333
Authors: Bart M de Vries; Tessa Timmers; Emma E Wolters; Rik Ossenkoppele; Sander C J Verfaillie; Robert C Schuit; Philip Scheltens; Wiesje M van der Flier; Albert D Windhorst; Bart N M van Berckel; Ronald Boellaard; Sandeep S V Golla Journal: Mol Imaging Biol Date: 2021-01-14 Impact factor: 3.488
Authors: Binu P Thomas; Takashi Tarumi; Min Sheng; Benjamin Tseng; Kyle B Womack; C Munro Cullum; Bart Rypma; Rong Zhang; Hanzhang Lu Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.160
Authors: Hyuk Jin Yun; Seung Hwan Moon; Hee Jin Kim; Samuel N Lockhart; Yearn Seong Choe; Kyung Han Lee; Duk L Na; Jong-Min Lee; Sang Won Seo Journal: Sci Rep Date: 2017-11-24 Impact factor: 4.379
Authors: Peter N E Young; Mar Estarellas; Emma Coomans; Meera Srikrishna; Helen Beaumont; Anne Maass; Ashwin V Venkataraman; Rikki Lissaman; Daniel Jiménez; Matthew J Betts; Eimear McGlinchey; David Berron; Antoinette O'Connor; Nick C Fox; Joana B Pereira; William Jagust; Stephen F Carter; Ross W Paterson; Michael Schöll Journal: Alzheimers Res Ther Date: 2020-04-27 Impact factor: 6.982
Authors: Sung Woo Kang; Seun Jeon; Young-Gun Lee; Mincheol Park; Kyoungwon Baik; Jin Ho Jung; Seok Jong Chung; Han Soo Yoo; Seong Ho Jeong; Mijin Yun; Phil Hyu Lee; Young H Sohn; Alan C Evans; Byoung Seok Ye Journal: Sci Rep Date: 2021-07-13 Impact factor: 4.379
Authors: Santiago Bullich; John Seibyl; Ana M Catafau; Aleksandar Jovalekic; Norman Koglin; Henryk Barthel; Osama Sabri; Susan De Santi Journal: Neuroimage Clin Date: 2017-05-13 Impact factor: 4.881