Evaluation of PiB visual interpretation with CSF Aβ and longitudinal SUVR in J-ADNI study

Abstract

Objective The objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) reflects quantitative amyloid measurements and the time course of 11 C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer's disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time. Methods From the National Bioscience Database Center Human Database of the Japanese Alzheimer's Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer's disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-β 1-42 (CSF-Ab 42) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab 42 were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive). Results From the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (F = 174.9, p < 0.001). The baseline CSF-Ab 42 level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (F = 37, p < 0.001). Over the 3-year follow-up, annual changes in SUVR were − 0.00 ± 0.02 in the negative group, 0.02 ± 0.02 in the equivocal group, and 0.04 ± 0.07 in the positive group (F = 8.4, p < 0.001). Conclusions Trinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with Data used in preparation of this article were obtained from the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) database deposited in the National Bioscience Database Center Human Database, Japan (Research ID: hum0043.v1, 2016). As such, the investigators within J-ADNI contributed to the design and implementation of J-ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of J-ADNI investigators can be found at: https ://human dbs.biosc ience dbc.jp/en/hum00 43-j-adni-autho rs.

Automated semi-quantitative amyloid PET analysis technique without MR images for Alzheimer’s disease

“…1 3 quantitatively, and classify them as positive or negative depending on the Aβ deposition in the brain. Regarding the positivity/negativity of Aβ deposition in the brain, the inter-rater agreement of visual assessment of 11 C-Pittuberg compound B (PiB) [1][2][3] PET images, the most commonly used amyloid PET tracer worldwide, was higher (κ = 0.9) than those of 18 F-florbetapir [4,5], 18 F-florbetaben [6], and 18 F-flutemetamol [7 − 9] (κ = 0.8 each). Approximately 10% of Aβ-PET images are interpreted as equivocal as a border case between positivity and negativity, causing false-positive/negative results [10 − 12].…”

“…One of the methods to solve this problem is the centiloid (CL) scale developed by Klunk et al [13]. Briefly, CL values are calculated by converting the SUVr of each 18 F-amyloid PET image to the SUVr obtained from images at 50-70 min postinjection of 11 C-PiB and standardizing the semi-quantitative amyloid imaging measures to a scale from 0 to 100. The 0-anchor is intended to represent a definitively non-amyloid brain, while the 100-anchor is intended to represent the amount of global amyloid deposition found in a typical mild-to-moderate AD patient [13].…”

“…Approximately 10% of Aβ-PET images are interpreted as equivocal as a border case between positivity and negativity, causing false-positive/negative results [10 − 12]. There have been reports that a semi-quantitative analysis using cortical standardized uptake value ratio (SUVr) to the cerebellar cortex or pons was useful for the evaluation of equivocal cases [ 3 , 10 , 11 ]. However, the SUVr is influenced by and varies according to differences in tracers, PET scanners, and/or imaging protocol such as radioactivity, time before images are acquired, and scan time, and hence, it is not suitable for quantification analysis of amyloid imaging [ 13 ].…”

Comparison of consistency in centiloid scale among different analytical methods in amyloid PET: the CapAIBL, VIZCalc, and Amyquant methods

“…Considering the benefits of early intervention using disease-modifying therapies, early screening using more objective methods to interpret amyloid PET findings is crucial. There have been reports that semi-quantitative analysis using the SUVR is useful for the interpretation of such equivocal cases [ 18 – 20 ]. Quantitative evaluation, including the SUVR of amyloid PET, is vulnerable to variations arising from differences in tracers, timing of imaging acquisition, PET scanners, and imaging protocols [ 21 ].…”

Longitudinal change in ATN biomarkers in cognitively normal individuals

“…One potential explanation for the five individuals changing from a positive to negative amyloid status by visual rating (positive-negative) could be that these scans were false-positive at baseline. While the quantitative measures might not have changed much over time, scan could be visually assessed differently at the two time points due to an imperfect intra-rater agreement [24][25][26]. This is part of clinical practice, especially in early disease stages.…”