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

Abstract

Objective Although beta-amyloid (Aβ) positron emission tomography (PET) images are interpreted visually as positive or negative, approximately 10% are judged as equivocal in Alzheimer’s disease. Therefore, we aimed to develop an automated semi-quantitative analysis technique using 18F-flutemetamol PET images without anatomical images. Methods Overall, 136 cases of patients administered 18F-flutemetamol were enrolled. Of 136 cases, five PET images each with the highest and lowest values of standardized uptake value ratio (SUVr) of cerebral cortex-to-pons were used to create positive and negative templates. Using these templates, PET images of the remaining 126 cases were standardized, and SUVr images were produced with the pons as a reference region. The mean of SUVr values in the volume of interest delineated on the cerebral cortex was compared to those in the CortexID Suite (GE Healthcare). Furthermore, centiloid (CL) values were calculated for the 126 cases using data from the Centiloid Project (http://www.gaain.org/centiloid-project) and both templates. 18F-flutemetamol-PET was interpreted visually as positive/negative based on Aβ deposition in the cortex. However, the criterion "equivocal" was added for cases with focal or mild Aβ accumulation that were difficult to categorize. Optimal cutoff values of SUVr and CL maximizing sensitivity and specificity for Aβ detection were determined by receiver operating characteristic (ROC) analysis using the visual evaluation as a standard of truth. Results SUVr calculated by our method and CortexID were highly correlated (R2 = 0.9657). The 126 PET images comprised 84 negative and 42 positive cases of Aβ deposition by visual evaluation, of which 11 and 10 were classified as equivocal, respectively. ROC analyses determined the optimal cutoff values, sensitivity, and specificity for SUVr as 0.544, 89.3%, and 92.9%, respectively, and for CL as 12.400, 94.0%, and 92.9%, respectively. Both semi-quantitative analyses showed that 12 and 9 of the 21 equivocal cases were negative and positive, respectively, under the optimal cutoff values. Conclusions This semi-quantitative analysis technique using 18F-flutemetamol-PET calculated SUVr and CL automatically without anatomical images. Moreover, it objectively and homogeneously interpreted positive or negative Aβ burden in the brain as a supplemental tool for the visual reading of equivocal cases in routine clinical practice.

Development of software for measuring brain amyloid accumulation using 18F‐florbetapir PET and calculating global Centiloid scale and regional Z‐score values

“…In contrast, several studies (Bourgeat et al, 2018;Edison et al, 2013;Fujishima & Matsuda, 2022;Imabayashi et al, 2022;Saint-Aubert et al, 2014;Tsubaki et al, 2020), including our own research (Fujishima & Matsuda, 2022), have reported anatomic standardization using the amyloid PET template alone without MRI. Out of these studies, the uses of an adaptive template generated from a linear combination of an amyloid-negative and amyloid-positive template with a weight-optimized algorithm have obtained comparable CL scales to those obtained with the standard MRI-guided method (Bourgeat et al, 2018;Fujishima & Matsuda, 2022;Imabayashi et al, 2022).…”

“…In contrast, several studies (Bourgeat et al, 2018;Edison et al, 2013;Fujishima & Matsuda, 2022;Imabayashi et al, 2022;Saint-Aubert et al, 2014;Tsubaki et al, 2020), including our own research (Fujishima & Matsuda, 2022), have reported anatomic standardization using the amyloid PET template alone without MRI. Out of these studies, the uses of an adaptive template generated from a linear combination of an amyloid-negative and amyloid-positive template with a weight-optimized algorithm have obtained comparable CL scales to those obtained with the standard MRI-guided method (Bourgeat et al, 2018;Fujishima & Matsuda, 2022;Imabayashi et al, 2022). However, our correlation analysis (Fujishima & Matsuda, 2022) between this PET-alone method and the standard MRIguided method showed that the CL scales slightly deviated from the validation criteria for 18 F-florbetapir from the Alzheimer's Disease Neuroimaging Initiative dataset (slope, 1.028; intercept, −4.302; R 2 , .974).…”

Quantitative Evaluation of Striatal Uptake Ratios Using an Adaptive Template Registration Method for 123I-Ioflupane Dopamine Transporter SPECT

“…Therefore, conventional morphological standardization based on normal typical examples, as done in FDG-PET or CBF SPECT, may lead to increased errors in individual subjects [17][18][19]. To address this issue, an approach called the adaptive atlas method has been reported, which assumes that amyloid PET images in actual subjects can be linearly approximated from typical amyloid-positive and -negative images [8][9][10][11][12]. This method uses a weighted average image of typical positive and negative images as the template image for morphological standardization.…”

“…However, in amyloid PET, an Adaptive Template Registration (ATR) method has been proposed as a solution, where templates for amyloid-positive and -negative subjects are prepared for analysis of 18F-utemetamol PET image data. Several weighted images are created from these templates, and the most appropriate weighted image is selected as the template for standardizing PET images, with successful outcomes [8][9][10][11][12].…”

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

“…In addition to CapAIBL, two other softwares have been developed to calculate the CL values. First, VIZCalc is a novel automated semiquantitative analysis technique without MRI that is primarily used for processing 18F-flutemetamol PET images [ 10 ]. Its core feature lies in the weighted average image of the positive and negative template methods, which obtains the optimal template and resolves the issue of overestimation of SUVR values encountered in traditional average template-based standardization.…”