Detection of individual brain tau deposition in Alzheimer's disease based on latent feature-enhanced generative adversarial network.

OBJECTIVE: The conventional methods for interpreting tau PET imaging in Alzheimer's disease (AD), including visual assessment and semi-quantitative analysis of fixed hallmark regions, are insensitive to detect individual small lesions because of the spatiotemporal neuropathology's heterogeneity. In this study, we proposed a latent feature-enhanced generative adversarial network model for the automatic extraction of individual brain tau deposition regions. METHODS: The latent feature-enhanced generative adversarial network we propose can learn the distribution characteristics of tau PET images of cognitively normal individuals and output the abnormal distribution regions of patients. This model was trained and validated using 1131 tau PET images from multiple centres (with distinct races, i.e., Caucasian and Mongoloid) with different tau PET ligands. The overall quality of synthetic imaging was evaluated using structural similarity (SSIM), peak signal to noise ratio (PSNR), and mean square error (MSE). The model was compared to the fixed templates method for diagnosing and predicting AD. RESULTS: The reconstructed images archived good quality, with SSIM = 0.967 ± 0.008, PSNR = 31.377 ± 3.633, and MSE = 0.0011 ± 0.0007 in the independent test set. The model showed higher classification accuracy (AUC = 0.843, 95 % CI = 0.796-0.890) and stronger correlation with clinical scales (r = 0.508, P < 0.0001). The model also achieved superior predictive performance in the survival analysis of cognitive decline, with a higher hazard ratio: 3.662, P < 0.001. INTERPRETATION: The LFGAN4Tau model presents a promising new approach for more accurate detection of individualized tau deposition. Its robustness across tracers and races makes it a potentially reliable diagnostic tool for AD in practice.

[Construction and analysis of brain metabolic network in temporal lobe epilepsy patients based on 18F-FDG PET].

The establishment of brain metabolic network is based on 18fluoro-deoxyglucose positron emission computed tomography ( 18F-FDG PET) analysis, which reflect the brain functional network connectivity in normal physiological state or disease state. It is now applied to basic and clinical brain functional network research. In this paper, we constructed a metabolic network for the cerebral cortex firstly according to 18F-FDG PET image data from patients with temporal lobe epilepsy (TLE).Then, a statistical analysis to the network properties of patients with left or right TLE and controls was performed. It is shown that the connectivity of the brain metabolic network is weakened in patients with TLE, the topology of the network is changed and the transmission efficiency of the network is reduced, which means the brain metabolic network connectivity is extensively impaired in patients with TLE. It is confirmed that the brain metabolic network analysis based on 18F-FDG PET can provide a new perspective for the diagnose and therapy of epilepsy by utilizing PET images.

A novel classification model based on cerebral 18F-FDG uptake pattern facilitates the diagnosis of acute/subacute seropositive autoimmune encephalitis.

PURPOSE: To explore the intrinsic alteration of cerebral 18F-FDG metabolism in acute/subacute seropositive autoimmune encephalitis (AE) and to propose a universal classification model based on 18F-FDG metabolic patterns to predict AE. METHODS: Cerebral 18F-FDG PET images of 42 acute/subacute seropositive AE patients and 45 healthy controls (HCs) were compared using voxelwise and region of interest (ROI)-based schemes. The mean standardized uptake value ratios (SUVRs) of 59 subregions according to a modified Automated Anatomical Labeling (AAL) atlas were compared using a t-test. Subjects were randomly divided into a training set (70%) and a testing set (30%). Logistic regression models were built based on the SUVRs and the models were evaluated by determining their predictive value in the training and testing sets. RESULTS: The 18F-FDG uptake pattern in the AE group was characterized by increased SUVRs in the brainstem, cerebellum, basal ganglia, and temporal lobe, and decreased SUVRs in the occipital, and frontal regions with voxelwise analysis (false discovery rate [FDR] p<0.05). Utilizing ROI-based analysis, we identified 15 subareas that exhibited statistically significant changes in SUVRs among AE patients compared to HC (FDR p<0.05). Further, a logistic regression model incorporating SUVRs from the calcarine cortex, putamen, supramarginal gyrus, cerebelum_10, and hippocampus successfully enhanced the positive predictive value from 0.76 to 0.86 when compared to visual assessments. This model also demonstrated potent predictive ability, with AUC values of 0.94 and 0.91 observed for the training and testing sets, respectively. CONCLUSIONS: During the acute/subacute stages of seropositive AE, alterations in SUVRs appear to be concentrated within physiologically significant regions, ultimately defining the general cerebral metabolic pattern. By incorporating these key regions into a new classification model, we have improved the overall diagnostic efficiency of AE.

2-[18F]FDG PET/CT parameters associated with WHO/ISUP grade in clear cell renal cell carcinoma.

PURPOSE: To explore the potential parameters from preoperative 2-[18F]FDG PET/CT that might associate with the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade in clear cell renal cell carcinoma (ccRCC). METHODS: One hundred twenty-five patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery or biopsy were retrospectively reviewed. The metabolic parameters and imaging features obtained from 2-[18F]FDG PET/CT examinations were analyzed in combination with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to identify the predictive factors of WHO/ISUP grade. RESULTS: Metabolic parameters of primary tumor maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), and tumor-to-kidney SUV ratio (TKR) were significantly different between any two of the four different WHO/ISUP grades, except those between the WHO/ISUP grade 3 and grade 4. The optimal cutoff values to predict high WHO/ISUP grade for SUVmax, TLR, and TKR were 4.15, 1.63, and 1.59, respectively. TLR (AUC: 0.841) was superior to TKR (AUC: 0.810) in distinguishing high and low WHO/ISUP grades (P = 0.0042). In univariate analysis, SUVmax, TLR, TKR, primary tumor size, tumor thrombus, distant metastases, and clinical symptoms could discriminate between the high and low WHO/ISUP grades (P < 0.05). In multivariate analysis, TLR (P < 0.001; OR: 1.732; 95%CI: 1.289-2.328) and tumor thrombus (P < 0.001; OR: 6.199; 95%CI: 2.499-15.375) were significant factors for differentiating WHO/ISUP grades. CONCLUSION: Elevated TLR (> 1.63) and presence of tumor thrombus from preoperative 2-[18F]FDG PET/CT can distinguish high WHO/ISUP grade ccRCC effectively. 2-[18F]FDG PET/CT may be a feasible method for noninvasive assessment of WHO/ISUP grade.

Utility of FDG PET/CT in the Characterization of Sinonasal Neoplasms: Analysis of Standardized Uptake Value Parameters.

OBJECTIVE: We aimed to evaluate the contribution of different standardized uptake value (SUV) parameters generated from pretreatment 18F-FDG PET/CT in the characterization of sinonasal neoplasms with histopathologic correlations. MATERIALS AND METHODS: This retrospective study included 97 consecutive patients (58 men, 39 women; age range, 20-93 years; mean age, 62 years) with pathologically proven untreated sinonasal neoplasms who underwent FDG PET/CT from February 2010 to August 2017. Semiquantitative analysis of primary tumors were performed to evaluate the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and the ratio of the SUVmax of the primary tumor to the SUVmean of mediastinal blood pool, which we refer to here as " SUVratio." Various sinonasal tumor histopathologic subgroups (n = 14) were analyzed. The Kruskal-Wallis test was used to compare the SUVmax, SUVmean, and SUVratio with the histopathologic diagnosis. RESULTS: Mean values of SUVmax, SUVmean, and SUVratio for the sinonasal neoplasms were 16.6 ± 9.7 (SD), 8.6 ± 5.1, and 5.9 ± 3.7, respectively, and each parameter was significantly different between histopathologic types (p < 0.05). Mean values of SUVmax, SUVmean, and SUVratio were higher in sinonasal undifferentiated carcinoma (SNUC) than in olfactory neuroblastoma, metastasis, and adenoid cystic carcinoma (p < 0.05). Mean values of SUVmax and SUVmean were higher in squamous cell carcinoma (SCC) than in olfactory neuroblastoma and metastasis (p < 0.05). Also, mean SUVmax was higher in SCC and SNUC than in poorly differentiated carcinoma (p < 0.05). Mean SUVratio was higher in SCC than in small cell carcinoma, olfactory neuroblastoma, and adenoid cystic carcinoma (p < 0.05). CONCLUSION: We conclude that different SUV parameters from FDG PET/CT can be used as so-called "metabolic biopsy" to categorize sinonasal neoplasms into different histopathologic subgroups because it can help in the characterization of some of the more common subgroups of sinonasal neoplasms. However, we found that there is overlap in FDG uptake values among some of the rare histologic subgroups; hence, surgical biopsy is still needed for differentiation of histologic subtypes of aggressive sinonasal masses.

The Precuneus - A Witness for Excessive Aß Gathering in Alzheimer's Disease Pathology.

Evidence of cortical beta-amyloid (Aß) load, assessed by Aß positron emission tomography (Aß-PET), is an established in vivo biomarker of Alzheimer's disease (AD)-related pathophysiology. Qualitative assessment of Aß-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aß burden along the continuum of AD. METHODS: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aß-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αß distribution pattern considering age as a nuisance covariate. RESULTS: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor-betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. CONCLUSIONS: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aß depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aß. We found a positive association between the overall Aß-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aß deposition continuously takes place as the disease progresses.

Multi-instance learning attention model for amyloid quantification of brain sub regions in longitudinal cognitive decline.

Amyloid PET scans help in identifying the beta-amyloid deposition in different brain regions. The purpose of this study is to develop a deep learning model that can automate the task of finding amyloid deposition in different regions of the brain only by using PET scan and without the corresponding MRI scan. 2647 18F-Florbetapir PET scans are collected from Alzheimer's Disease Neuroimaging Initiative (ADNI) from multiple centres taken over a period. A deep learning model based on multi-instance learning and attention is proposed which is trained and validated using 80% of the scans and the remaining 20% of the scans are used for testing the model. The performance of the model is validated using Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE). The proposed model is further tested upon an external dataset consisting of 1413 18F-Florbetapir PET scans from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study. The proposed model achieves MAE of 0.0243 and RMSE of 0.0320 for summary Standardized Uptake Value Ratio (SUVR) based on composite reference region for ADNI test set. When tested on the A4-study dataset, the proposed model achieves MAE of 0.038 and RMSE of 0.0495 for summary SUVR based on the composite region. The results show that the proposed model provides less MAE and RMSE when compared with existing models. A graphical user interface is developed based on the proposed model where the predictions are made by selecting the files of 18F-Florbetapir PET scans.

Alterations in Gut Microbiota and Their Correlation with Brain Beta-Amyloid Burden Measured by 18F-Florbetaben PET in Mild Cognitive Impairment Due to Alzheimer's Disease.

(1) Background: This study investigated changes in the gut microbial composition of individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and their relationship with positron emission tomography (PET) amyloid accumulation. (2) Methods: In total, 17 cognitively normal individuals without amyloid-beta (Aß) accumulation (Aß-NC) and 24 with Aß-positive mild cognitive impairment (Aß+MCI) who underwent 18F-florbetaben PET and fecal bacterial 16S ribosomal RNA gene sequencing were enrolled. The taxonomic compositions of the Aß-NC and Aß+MCI groups were compared. The abundance of taxa was correlated with the standardized uptake value ratio (SUVR), using generalized linear models. (3) Results: There were significant differences in microbiome richness (ACE, p = 0.034 and Chao1, p = 0.024), alpha diversity (Shannon, p = 0.039), and beta diversity (Bray-Curtis, p = 0.018 and Generalized UniFrac, p = 0.034) between the Aß-NC and Aß+MCI groups. The global SUVR was positively correlated with the genus Intestinibacter (q = 0.006) and negatively correlated with the genera Roseburia (q = 0.008) and Agathobaculum (q = 0.029). (4) Conclusions: In this study, we identified significant changes in the gut microbiota composition that occur in individuals with MCI due to AD. In particular, the correlation analysis results between PET amyloid burden and gut microbial abundance showed that amyloid deposition is associated with a reduction in specific taxa involved in butyrate production.

Spectrum of [18F]FDG PET/CT Findings in Primary Central Nervous System Lymphoma - A Pictorial Essay.

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive variant of extranodal non-Hodgkin's lymphoma. Although gadolinium-enhanced magnetic resonance imaging remains the initial imaging modality of choice, a whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is imperative to exclude systemic lymphomatous involvement. Furthermore, the metabolic parameter, maximum standardized uptake value (SUVmax) of the lesion, tumor-to-normal cerebral tissue SUVmax ratio, and FDG uptake patterns help in differentiating intracranial lymphomas from High-grade Glioblastoma Multiforme (HGM) and infectious lesions, and hence, consolidating the diagnosis. In this pictorial essay, we present a series of PCNSL cases, representing the different imaging characteristics and metabolic uptake patterns.

The mediating effect of 18F-FDG metabolism in right caudate between depressive symptoms and cognitive function in Alzheimer's disease.

Purpose: The objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer's disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients. Methods: In this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients. Results: The ADD group exhibited significant cognitive impairment compared to the ADND group (p < 0.001) and healthy controls (p < 0.001). The ADD patients exhibited the reduced SUVR (0.228 ± 0.126) in the right caudate (the voxel level p < 0.005, cluster level p < 0.05, after false discovery rate (FDR) correction) compared to ADND patients (0.459 ± 0.064) and healthy controls (0.706 ± 0.122). The SUVR of the right caudate was correlated with the HAMD scores (r = -0.792, p < 0.001) and mini-mental state examination (MMSE) (r = 0.738, p < 0.01). The relationship between depressive symptoms and the cognitive function in ADD patients is mediated by the right caudate SUVR (total effects = -0.385, direct effects = -0.02, total indirect effects = -0.405). Conclusion: The ADD group exhibited the reduced SUVR in the right caudate compared to the ADND group and healthy controls. The relationship between depressive symptoms and the cognitive ability of AD patients was mediated by the right caudate SUVR. The results contribute to a deeper understanding of the neurobiological mechanisms related to AD with depressive symptoms.

Feasibility evaluation of middle-phase 18F-florbetaben positron emission tomography imaging using centiloid quantification and visual assessment.

Background: 18F-florbetaben (FBB) positron emission tomography (PET) scan has been widely used in research and routine clinical practice. Most studies used late-phase (scanning from 90 to 110 min after injection) FBB scans to generate beta-amyloid accumulation data. The feasibility of middle-phase scan is seldom discussed. Using the middle-phase data can shorten the patients' waiting between the injection and scan, and hospital can acquire more flexible schedule of routine scan. Methods: Paired middle-phase (60-80 min) FBB scans and standard (90-110 min) FBB scans were obtained from 27 subjects (12 neurodegenerative dementia, 8 mild cognitive impairment, 3 normal control, and 4 patients not suffering from neurodegenerative dementia). Standardized uptake value ratios (SUVRs) were calculated and converted to centiloid (CL) scale to investigate the impact on image quantification. CL pipeline validation were performed to build an equation converting the middle-phase data into equivalent standard scans. Cohen's kappa of binary interpretation and brain amyloid plaque load (BAPL) score were also used to evaluate the intrareader agreement of the FBB image from the two protocols. Results: The middle-phase FBB SUVR showed an excellent correlation, which provided a linear regression equation of SUVRFBB60-80 = 0.88 × SUVRFBB90-110 + 0.07, with R2=0.98. The slope of the equation indicated that there was bias between the middle and standard acquisition. This can be converted into the CL scale using CL = 174.68 × SUVR - 166.39. Cohen's kappa of binary interpretation and BAPL score were 1.0 (P<0.0001). Conclusions: Our findings indicate that the middle-phase FBB protocol is feasible in clinical applications for scans that are at either end of beta-amyloid spectrum, which provides comparable semiquantitative results to standard scan. Patient's waiting time between the injection and scan can be shortened.

White matter hyperintensities influence distal cortical ß-amyloid accumulation in default mode network pathways.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid ß (Aß) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults. METHODS: Regional standard uptake value ratios (SUVr) from Aß-PET and white matter hyperintensity (WMH) volumes from three-dimensional magnetic resonance imaging FLAIR images were analyzed across a sample of 72 clinically unimpaired (mini-mental state examination ≥26), older adults (mean age 74.96 and standard deviation 8.13) from the Alzheimer's Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aß-PET SUVr in the connected cortical DMN regions was analyzed using linear regression models adjusted for age, sex, ApoE, and total brain volumes. RESULTS: The regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus were associated with increased regional SUVr in the inferior parietal lobule (p = .011). CONCLUSION: The findings suggest that the relation between Aß in parietal cortex is associated with SVD in downstream white matter (WM) pathways in preclinical AD. The biological relationships and interplay between Aß and WM microstructure alterations that precede overt WMH development across the continuum of AD progression warrant further study.

Predicting diffuse large B-cell lymphoma outcomes with lesion-to-liver maximum standardized uptake value for interim-treatment and end-of-treatment positron emission tomography-computed tomography.

Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been used in response evaluation systems for malignant lymphomas and is an important tool for determining efficacy and prognosis. The Deauville 5-point scale (D-5PS) is an 18F-FDG PET-CT image-interpretation protocol for patients with lymphoma. Nevertheless, a number of limitations in visual image interpretation, such as interobserver disagreement and the increase of false-positive results, suggests that new parameters are needed. In this study, we aimed to evaluate the prognostic values of interim-treatment (I-) and end-of-treatment (EOT) PET-CT by comparing D-5PS to the semiquantitative lesion-to-liver maximum standardized uptake value ratio (RLL). Methods: A total of 90 patients with diffuse large B-cell lymphoma (DLBCL) (45 I-PET and 45 EOT-PET) were analyzed, and the RLL was calculated. Patients were additionally evaluated using the D-5PS system. We determined the optimal cutoff value of RLL using receiver operating characteristic (ROC) analysis. Kaplan-Meier survival analysis was used to compare the outcome predictions, while multivariate Cox regression analysis was used to identify the predictive factors. Results: Among the patients examined, 41 (20 I-PET and 21 EOT-PET) experienced progression, and 49 (25 I-PET, 24 EOT-PET) did not. The optimal cutoff values of the RLL for predicting disease progression were 1.37 for I-PET (sensitivity 75%, specificity 88%) and 2.03 for EOT-PET (sensitivity 45.5%, specificity 100%), while the cutoffs of the D-5PS were scores 4 for I-PET (sensitivity 80%, specificity 72%) and 5 for EOT-PET (sensitivity 40.9%, specificity 100%). The prognostic efficacy was higher for the RLL at interim than for the D-5PS [area under the curve (AUC) =0.848 vs. 0.741]. The EOT prognostic efficacy of both evaluation methods was essentially equivalent (AUC =0.785 vs. 0.725). Univariate and multivariate analyses showed that RLL and D-5PS were independent factors affecting DLBCL outcomes for both interim and EOT assessment. Conclusions: RLL and D-5PS have independent predictive values for the interim and EOT evaluation of outcomes in patients with DLBCL. The RLL has better interim predictive ability than does D-5PS and can optimize D-5PS interpretation, thus improving interim outcome prediction.

Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function.

Co-occurrence of beta amyloid (Aß) and white matter hyperintensities (WMHs) increase the risk of dementia and both are considered biomarkers of preclinical dementia. Moderation and mediation modeling were used to define the interplay between global and regional Aß and WMHs measures in relation to executive function (EF) and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 clinically normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI 2). The moderation regression analysis showed additive effects of Aß and WMHs over baseline memory and EF scores (p = 0.401 and 0.061, respectively) and synergistic effects over follow-up EF (p < 0.05). Through mediation analysis, the data presented demonstrate that WMHs effects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. These findings suggest that Aß and WMHs contribute to baseline cognition independently while WMHs volumes exert effects on baseline cognitive performance directly and through influences on Aß accumulation.

Quantitative comparative analysis of amyloid PET images using three radiopharmaceuticals.

OBJECTIVE: Amyloid positron emission tomography (PET) with F-18 florbetaben (FBB), F-18 flutemetamol (FMM), and F-18 florapronol (FPN) is being used clinically for the evaluation of dementia. These radiopharmaceuticals are commonly used to evaluate the accumulation of beta-amyloid plaques in the brain, but there are structural differences between them. We investigated whether there are any differences in the imaging characteristics. METHODS: A total of 605 subjects were enrolled retrospectively in this study, including healthy subjects (HS) and patients with mild cognitive impairment or Alzheimer's disease. Participants underwent amyloid PET imaging using one of the three radiopharmaceuticals. The PET images were analyzed visually and semi-quantitatively using a standardized uptake value ratio (SUVR). In addition, we calculated and compared the cut-off SUVR of the representative regions for each radiopharmaceutical that can distinguish between positive and negative scans. RESULTS: In the negative images of the HS group, the contrast between the white matter and the gray matter was high in the FMM PET images, while striatal uptake was relatively higher in the FPN PET images. The SUVR showed significant differences across the radiopharmaceuticals in all areas except the temporal lobe, but the range of differences was relatively small. Accuracy levels for the global cut-off SUVR to discriminate between positive and negative images were highest in FMM PET, with a value of 0.989. FBB PET also showed a high value of 0.978, while FPN PET showed a relatively low value of 0.901. CONCLUSIONS: Negative amyloid PET images using the three radiopharmaceuticals showed visually and quantitatively similar imaging characteristics except in the striatum. Binary classification using the cut-off of the global cortex showed high accuracy overall, although there were some differences between the three PET images.

Altered metabolic-functional coupling in the epileptogenic network could predict surgical outcomes of mesial temporal lobe epilepsy.

Objective: To investigate the relationship between glucose metabolism and functional activity in the epileptogenic network of patients with mesial temporal lobe epilepsy (MTLE) and to determine whether this relationship is associated with surgical outcomes. Methods: 18F-FDG PET and resting-state functional MRI (rs-fMRI) scans were performed on a hybrid PET/MR scanner in 38 MTLE patients with hippocampal sclerosis (MR-HS), 35 MR-negative patients and 34 healthy controls (HC). Glucose metabolism was measured using 18F-FDG PET standardized uptake value ratio (SUVR) relative to cerebellum; Functional activity was obtained by fractional amplitude of low-frequency fluctuation (fALFF). The betweenness centrality (BC) of metabolic covariance network and functional network were calculated using graph theoretical analysis. Differences in SUVR, fALFF, BC and the spatial voxel-wise SUVR-fALFF couplings of the epileptogenic network, consisting of default mode network (DMN) and thalamus, were evaluated by Mann-Whitney U test (using the false discovery rate [FDR] for multiple comparison correction). The top ten SUVR-fALFF couplings were selected by Fisher score to predict surgical outcomes using logistic regression model. Results: The results showed decreased SUVR-fALFF coupling in the bilateral middle frontal gyrus (PFDR = 0.0230, PFDR = 0.0296) in MR-HS patients compared to healthy controls. Coupling in the ipsilateral hippocampus was marginally increased (PFDR = 0.0802) in MR-HS patients along with decreased BC of metabolic covariance network and functional network (PFDR = 0.0152; PFDR = 0.0429). With Fisher score ranking, the top ten SUVR-fALFF couplings in regions from DMN and thalamic subnuclei could predict surgical outcomes with the best performance being a combination of ten SUVR-fALFF couplings with an AUC of 0.914. Conclusion: These findings suggest that the altered neuroenergetic coupling in the epileptogenic network is associated with surgical outcomes of MTLE patients, which may provide insight into their pathogenesis and help with preoperative evaluation.

Amyloid-PET Levels in the Precuneus and Posterior Cingulate Cortices Are Associated with Executive Function Scores in Preclinical Alzheimer's Disease Prior to Overt Global Amyloid Positivity.

BACKGROUND: Global amyloid-ß (Aß) deposition in the brain can be quantified by Aß-PET scans to support or refute a diagnosis of preclinical Alzheimer's disease (pAD). Yet, Aß-PET scans enable quantitative evaluation of regional Aß elevations in pAD, potentially allowing even earlier detection of pAD, long before global positivity is achieved. It remains unclear as to whether such regional changes are clinically meaningful. OBJECTIVE: Test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in pAD. METHODS: Global and regional standardized uptake value ratios (SUVr) from 18F-florbetapir PET/CT scanning were determined using the Siemens Syngo.via® Neurology software package across a sample of 99 clinically normal participants with Montreal Cognitive Assessment (MoCA) scores≥23. Relationships between regional SUVr and cognitive test scores were analyzed using linear regression models adjusted for age, sex, and education. Participants were divided into two groups based on SUVr in the posterior cingulate and precuneus gyri (SUVR≥1.17). Between group differences in cognitive test scores were analyzed using ANCOVA models. RESULTS: Executive function performance was associated with increased regional SUVr in the precuneus and posterior cingulate regions only (p < 0.05). There were no significant associations between memory and Aß-PET SUVr in any regions of the brain. CONCLUSION: These data demonstrate that increased Aß deposition in the precuneus and posterior cingulate (the earliest brain regions affected with Aß pathology) is associated with changes in executive function that may precede memory decline in pAD.

Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer's Disease Spectrum: Who Really Deserves an A+?

BACKGROUND: Association between cerebrospinal fluid (CSF)-amyloid-ß (Aß)42 and amyloid-PET measures is inconstant across the Alzheimer's disease (AD) spectrum. However, they are considered interchangeable, along with Aß42/40 ratio, for defining 'Alzheimer's Disease pathologic change' (A+). OBJECTIVE: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients. METHODS: We included 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of Aß42 within a 365-days interval. Thresholds used for dichotomization were: Aß42 < 640 pg/mL (Aß42+); pTau > 61 pg/mL (pTau+); and Aß42/40 < 0.069 (ADratio+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC). RESULTS: Different pipelines gave highly inter-correlated standardized uptake value ratios (SUVRs) (rho = 0.93-0.99). The most significant findings were: pTau positive correlation with SPMCL SUVR (rho = 0.56, p = 0.0063) and Aß42/40 negative correlation with SPMCL and SPMAAL SUVRs (rho = -0.56, p = 0.0058; rho = -0.52, p = 0.0117 respectively). No correlations between CSF-Aß42 and global SUVRs were observed. In subregion analysis, both pTau and Aß42/40 values significantly correlated with cingulate SUVRs from any pipeline (R2 = 0.55-0.59, p < 0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for Aß42/40 ratio were still significant in linear regression models. Moreover, combining pTau with Aß42 or using Aß42/40, instead of Aß42 alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids. CONCLUSION: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-Aß42/40 and secondarily pTau rather than Aß42 levels.

Probing the Role of a Regional Quantitative Assessment of Amyloid PET.

BACKGROUND: In clinical practice, the amy-PET is globally inspected to provide a binary outcome, but the role of a regional assessment has not been fully investigated yet. OBJECTIVE: To deepen the role of regional amyloid burden and its implication on clinical-neuropsychological features. MATERIALS: Amy-PET and a complete neuropsychological assessment (Trail Making Test, Rey Auditory Verbal Learning Test, semantic verbal fluency, Symbol Digit, Stroop, visuoconstruction) were available in 109 patients with clinical suspicion of Alzheimer's disease. By averaging the standardized uptake value ratio and ELBA, a regional quantification was calculated for each scan. Patients were grouped according to their overall amyloid load: correlation maps, based on regional quantification, were calculated and compared. A regression analysis between neuropsychological assessment and the regional amyloid-ß (Aß) load was carried out. RESULTS: Significant differences were observed between the correlation maps of patients at increasing levels of Aß and the overall dataset. The Aß uptake of the subcortical gray matter resulted not related to other brain regions independently of the global Aß level. A significant association of semantic verbal fluency was observed with ratios of cortical and subcortical distribution of Aß which represent a coarse measure of differences in regional distribution of Aß. CONCLUSION: Our observations confirmed the different susceptibility to Aß accumulation among brain regions. The association between cognition and Aß distribution deserves further investigations: it is possibly due to a direct local effect or it represents a proxy marker of a more aggressive disease subtype. Regional Aß assessment represents an available resource on amy-PET scan with possibly clinical and prognostic implications.

18F-fluorodeoxyglucose positron emission tomography-based prediction for splenectomy in patients with suspected splenic lymphoma.

BACKGROUND: Diagnostic splenectomy is often performed on patients with suspected splenic lymphoma. However, unnecessary splenectomy entails more harm than benefit for patients. Therefore, a preliminary screening method for patients with suspected splenic lymphoma that has high sensitivity and specificity is urgently needed. METHODS: From the pathology database at Huadong and Huashan Hospital, we retrospectively identified 60 patients of suspected splenic lymphoma who underwent fluorodeoxyglucose (FDG)-positron emission tomography (PET) before receiving a splenectomy and did not show any increase in FDG uptake except in the spleen. We compared the indicators of PET-CT, such as the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and the SUVmax of 18F-FDG uptake ratios between the spleen/liver, spleen/bone marrow, and liver/bone marrow. RESULTS: No significant differences were detected in SUVmax, TLG, MTV, or the SUVmax ratio of the liver/bone marrow between the lymphoma and benign groups. However, the SUVmax ratios of the spleen/liver and spleen/bone marrow were significantly higher in the lymphoma group than in the benign group (P=0.001; P=0.001). Receiver operating characteristic (ROC) curve analysis determined a spleen/liver SUVmax ratio of >2.42 and a spleen/bone marrow SUVmax ratio of >1.45 to be the indications for requiring a diagnostic splenectomy for lymphoma. Parallel testing increased the specificity and sensitivity of the test. CONCLUSIONS: Patients whose PET-CT results are inconclusive regarding the need for splenectomy may benefit from our prediction model. Future large-scale prospective clinical trials are required to verify these findings.