Abstract
Background: In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development.Aims: We aimed to determine cutoffs for positivity in quantitative analysis of 18F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321).Methods: Ninety-three patients suspected of having AD underwent 18F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area.Results: Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ2 = 51.3, p < 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%.Conclusion: Quantitative analysis of amyloid PET using 18F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.
Highlights
One of the pathological features of Alzheimer’s disease (AD) is senile plaques caused by the aggregation and accumulation of amyloid beta (Aβ) in the brain
The CL scaling method has been applied to 18Fflutemetamol Positron emission tomography (PET) [11], this method has not been compared with visual assessments, and its cutoff for amyloid positivity has not been determined
Inclusion criteria were as follows: diagnosis of probable or possible AD according to the National Institute on Aging and the Alzheimer’s Association (NIA-AA) [14] or diagnosis of major or mild neurocognitive disorder according to the Diagnostic and Statistical Manual of Mental Disorders—V [15] and having undergone brain magnetic resonance imaging (MRI; T1-weighted, T2-weighted, and FLAIR imaging) up to 60 days before registration
Summary
One of the pathological features of Alzheimer’s disease (AD) is senile plaques caused by the aggregation and accumulation of amyloid beta (Aβ) in the brain. When using amyloid PET in clinical practice, qualitative determination of whether amyloid PET is positive or negative is performed by visual interpretation alone. SUVR values vary according to the target and reference regions used and according to the particular amyloid tracer used This variation could be resolved through a Centiloid (CL) scaling process that standardizes the quantitative amyloid imaging measures by standardizing the outcome of each analysis method or PET ligand to a scale from 0 to 100 [10]. Equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development
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