Purpose: Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) reveals altered cerebral metabolism in individuals with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). Previous metabolic connectome analyses derive from groups of patients but do not support the prediction of an individual’s risk of conversion from present MCI to AD. We now present an individual metabolic connectome method, namely the Kullback-Leibler Divergence Similarity Estimation (KLSE), to characterize brain-wide metabolic networks that predict an individual’s risk of conversion from MCI to AD. Methods: FDG-PET data consisting of 50 healthy controls, 332 patients with stable MCI, 178 MCI patients progressing to AD, and 50 AD patients were recruited from ADNI database. Each individual’s metabolic brain network was ascertained using the KLSE method. We compared intra- and intergroup similarity and difference between the KLSE matrix and group-level matrix, and then evaluated the network stability and inter-individual variation of KLSE. The multivariate Cox proportional hazards model and Harrell’s concordance index (C-index) were employed to assess the prediction performance of KLSE and other clinical characteristics. Results: The KLSE method captures more pathological connectivity in the parietal and temporal lobes relative to the typical group-level method, and yields detailed individual information, while possessing greater stability of network organization (within-group similarity coefficient, 0.789 for sMCI and 0.731 for pMCI). Metabolic connectome expression was a superior predictor of conversion than were other clinical assessments (hazard ratio (HR) = 3.55; 95% CI, 2.77–4.55; P < 0.001). The predictive performance improved further upon combining clinical variables in the Cox model, i.e., C-indices 0.728 (clinical), 0.730 (group-level pattern model), 0.750 (imaging connectome), and 0.794 (the combined model). Conclusion: The KLSE indicator identifies abnormal brain networks predicting an individual’s risk of conversion from MCI to AD, thus potentially constituting a clinically applicable imaging biomarker.

Background: Parkinson’s disease (PD) is an irreversible neurodegenerative disease. The diagnosis of PD based on neuroimaging is usually with low-level or deep learning features, which results in difficulties in achieving precision classification or interpreting the clinical significance. Herein, we aimed to extract high-order features by using radiomics approach and achieve acceptable diagnosis accuracy in PD. Methods: In this retrospective multicohort study, we collected ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) images and clinical scale [the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn & Yahr scale (H&Y)] from two cohorts. One cohort from Huashan Hospital had 91 normal controls (NC) and 91 PD patients (UPDRS: 22.7±11.7, H&Y: 1.8±0.8), and the other cohort from Wuxi 904 Hospital had 26 NC and 22 PD patients (UPDRS: 20.9±11.6, H&Y: 1.7±0.9). The Huashan cohort was used as the training and test sets by 5-fold cross-validation and the Wuxi cohort was used as another separate test set. After identifying regions of interests (ROIs) based on the atlas-based method, radiomic features were extracted and selected by using autocorrelation and fisher score algorithm. A support vector machine (SVM) was trained to classify PD and NC based on selected radiomic features. In the comparative experiment, we compared our method with the traditional voxel values method. To guarantee the robustness, above processes were repeated in 500 times. Results: Twenty-six brain ROIs were identified. Six thousand one hundred and ten radiomic features were extracted in total. Among them 30 features were remained after feature selection. The accuracies of the proposed method achieved 90.97%±4.66% and 88.08%±5.27% in Huashan and Wuxi test sets, respectively. Conclusions: This study showed that radiomic features and SVM could be used to distinguish between PD and NC based on 18F-FDG PET images.

BACKGROUND: Subjective cognitive decline (SCD) has been recognized as a potential risk stage for progression to Alzheimer's disease (AD), while glymphatic dysfunction is considered an important characteristic of AD. We hypothesize that glymphatic dysfunction occurs during the SCD stage, aiming to discover potential biomarkers for SCD.METHODS: Participants from two independent studies, Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 654) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 650), representing different ethnicities and disease stages, were included to assess glymphatic function using diffusion tensor image analysis along the perivascular space (DTI‐ALPS).RESULTS: Abnormal glymphatic function occurs during the SCD stage, with the ALPS index demonstrating excellent classification performance for SCD and normal controls (area under the receiver operating characteristic curve [AUC]_SILCODE = 0.816, AUC_ADNI = 0.797). Lower ALPS index indicates higher risk of cognitive progression, which is negatively correlated with Subjective Cognitive Decline Questionnaire 9 scores and amyloid positron emission tomography burden.DISSCUSION: Our study suggests the ALPS index has the potential to serve as a biomarker for SCD.Highlights: Glymphatic function characterized by the analysis along the perivascular space (ALPS) index becomes abnormal in subjective cognitive decline (SCD), the earliest symptomatic manifestation and preclinical stage of Alzheimer's disease (AD). The ALPS index demonstrates excellent classification performance for SCD and normal controls in the East Asian and Western cohorts. Participants with a lower ALPS index show a higher risk of clinical progression. The ALPS index is closely associated with serval cognitive scales and amyloid beta burden.

Background: Alzheimer’s disease (AD) is the most common form of progressive and irreversible dementia, and accurate diagnosis of AD at its prodromal stage is clinically important. Currently, computer-aided diagnosis of AD and mild cognitive impairment (MCI) using ¹⁸F-fluorodeoxy-glucose positron emission tomography (¹⁸F-FDG PET) imaging is usually based on low-level imaging features or deep learning methods, which have difficulties in achieving sufficient classification accuracy or lack clinical significance. This research therefore aimed to implement a new feature extraction method known as radiomics, to improve the classification accuracy and discover high-order features that can reveal pathological information. Methods: In this study, ¹⁸F-FDG PET and clinical assessments were collected in a cohort of 422 individuals [including 130 with AD, 130 with MCI, and 162 healthy controls (HCs)] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 44 individuals (including 22 with AD, and 22 HCs) from Huashan Hospital, Shanghai, China. First, we performed a group comparison using a two-sample Student’s t test to determine the regions of interest (ROIs) based on 30 AD patients and 30 HCs from ADNI cohorts. Second, based on two time scans of 32 HCs from ADNI cohorts, we used Cronbach’s alpha coefficient for radiomic feature stability analyses. Pearson’s correlation coefficients were regarded as a feature selection criterion, to select effective features associated with the clinical cognitive scale [clinical dementia rating scale in its sum of boxes (CDRSB); Alzheimer’s disease assessment scale (ADAS)] with 500-times cross-validation. Finally, a support vector machine (SVM) was used to test the ability of the radiomic features to classify HCs, MCI and AD patients. Results: As a result, we identified brain regions which were mainly distributed in the temporal, occipital and frontal areas as ROIs. A total of 168 radiomic features of AD were stable (alpha > 0.8). The classification experiment led to maximal accuracies of 91.5%, 83.1% and 85.9% for classifying AD versus HC, MCI versus HCs and AD versus MCI. Conclusion: The research in this paper proved that the novel approach based on high-order radiomic features extracted from ¹⁸F-FDG PET brain images that can be used for AD and MCI computer-aided diagnosis.

Predicting progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) is clinically important. In this study, we propose a dual-model radiomic analysis with multivariate Cox proportional hazards regression models to investigate promising risk factors associated with MCI conversion to AD. T1 structural magnetic resonance imaging (MRI) and ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) data, from the AD Neuroimaging Initiative database, were collected from 131 patients with MCI who converted to AD within 3 years and 132 patients with MCI without conversion within 3 years. These subjects were randomly partition into 70% training dataset and 30% test dataset with multiple times. We fused MRI and PET images by wavelet method. In a subset of subjects, a group comparison was performed using a two-sample t-test to determine regions of interest (ROIs) associated with MCI conversion. 172 radiomic features from ROIs for each individual were established using a published radiomics tool. Finally, L1-penalized Cox model was constructed and Harrell’s C index (C-index) was used to evaluate prediction accuracy of the model. To evaluate the efficacy of our proposed method, we used a same analysis framework to evaluate MRI and PET data separately. We constructed prognostic Cox models with: clinical data, MRI images, PET images, fused MRI/PET images, and clinical variables and fused MRI/PET images in combination. The experimental results showed that captured ROIs significantly associated with conversion to AD, such as gray matter atrophy in the bilateral hippocampus and hypometabolism in the temporoparietal cortex. Imaging model (MRI/PET/fused) provided significant enhancement in prediction of conversion compared to clinical models, especially the fused-modality Cox model. Moreover, the combination of fused-modality imaging and clinical variables resulted in the greatest accuracy of prediction. The average C-index for the clinical/MRI/PET/fused/combined model in the test dataset was 0.69, 0.73, 0.73 and 0.75, and 0.78, respectively. These results suggested that a combination of radiomic analysis and Cox model analyses could be used successfully in survival analysis and may be powerful tools for personalized precision medicine patients with potential to undergo conversion from MCI to AD.

Introduction: Subjective cognitive decline (SCD) represents a cognitively normal state but at an increased risk for developing Alzheimer’s disease (AD). Recognizing the glucose metabolic biomarkers of SCD could facilitate the location of areas with metabolic changes at an ultra-early stage. The objective of this study was to explore glucose metabolic biomarkers of SCD at the region of interest (ROI) level. Methods: This study was based on cohorts from two tertiary medical centers, and it was part of the SILCODE project (NCT03370744). Twenty-six normal control (NC) cases and 32 SCD cases were in cohort 1; 36 NCs, 23 cases of SCD, 32 cases of amnestic mild cognitive impairment (aMCIs), 32 cases of AD dementia (ADDs), and 22 cases of dementia with Lewy bodies (DLBs) were in cohort 2. Each subject underwent [18F]fluoro-2-deoxyglucose positron emission tomography (PET) imaging and magnetic resonance imaging (MRI), and subjects from cohort 1 additionally underwent amyloid-PET scanning. The ROI analysis was based on the Anatomical Automatic Labeling (AAL) template; multiple permutation tests and repeated cross-validations were conducted to determine the metabolic differences between NC and SCD cases. In addition, receiver operating characteristic curves were used to evaluate the capabilities of potential glucose metabolic biomarkers in distinguishing different groups. Pearson correlation analysis was also performed to explore the correlation between glucose metabolic biomarkers and neuropsychological scales or amyloid deposition. Results: Only the right middle temporal gyrus (RMTG) passed the methodological verification, and its metabolic levels were correlated with the degrees of complaints (R = − 0.239, p = 0.009), depression (R = − 0.200, p = 0.030), and abilities of delayed memory (R = 0.207, p = 0.025), and were weakly correlated with cortical amyloid deposition (R = − 0.246, p = 0.066). Furthermore, RMTG metabolism gradually decreased across the cognitive continuum, and its diagnostic efficiency was comparable (NC vs. ADD, aMCI, or DLB) or even superior (NC vs. SCD) to that of the metabolism of the posterior cingulate cortex or precuneus. Conclusions: These findings suggest that the hypometabolism of RMTG could be a typical feature of SCD, and the large-scale hypometabolism in patients with symptomatic stages of AD may start from the RMTG, which gradually progresses starting in the preclinical stage. The specificity of identifying SCD from the perspective of self-perceived symptoms is likely to be increased by the detection of RMTG metabolism.