18F-fluorodeoxyglucose PET Research Articles

Glucose metabolism patterns: A potential index to characterize brain ageing and predict high conversion risk into cognitive impairment.

Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected 18F-fluorodeoxyglucose (18F-FDG) PET brain images from two independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 127) and the Xuanwu Hospital of Capital Medical University, Beijing, China (N = 84). During follow-up (mean 80.60months), 23 participants in the ADNI cohort converted to cognitive impairment. ARGMPs were identified using the scaled subprofile model/principal component analysis method, and cross-validations were conducted in both independent cohorts. A survival analysis was further conducted to calculate the predictive effect of conversion risk by using ARGMPs. The results showed that ARGMPs were characterized by hypometabolism with increasing age primarily in the bilateral medial superior frontal gyrus, anterior cingulate and paracingulate gyri, caudate nucleus, and left supplementary motor area and hypermetabolism in part of the left inferior cerebellum. The expression network scores of ARGMPs were significantly associated with chronological age (R = 0.808, p < 0.001), which was validated in both the ADNI and Xuanwu cohorts. Individuals with higher network scores exhibited a better predictive effect (HR: 0.30, 95% CI: 0.1340 ~ 0.6904, p = 0.0068). These findings indicate that ARGMPs derived from CN participants may represent a novel index for characterizing brain ageing and predicting high conversion risk into cognitive impairment.

18F-fluorodeoxyglucose PET and PET/computed tomography for the evaluation of immunoglobulin G4-related disease: a systematic review.

In the last years, 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) has demonstrated its utility for the evaluation of immunoglobulin G4 (IgG4)-related disease (IgG4RD). The studies are, however, really heterogeneous and different. The aim of this review is, therefore, to analyze the diagnostic performance of 18F-FDG PET and PET/CT for the assessment of IgG4RD. A wide literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane library databases was made to find relevant published articles about the diagnostic performance of 18F-FDG PET or PET/CT for the evaluation of IgG4RD. The comprehensive computer literature search revealed 779 articles. On reviewing the titles and abstracts, 756 articles were excluded because the reported data were not within the field of interest. Twenty-three studies were included in the review. Despite some limitations that affect our review, 18F-FDG PET or PET/CT demonstrated the ability to assess IgG4RD both at initial evaluation and after therapy. In general, no correlation between PET/CT parameters and IgG4 serum levels has been reported. A possible role for 18F-FDG PET/CT to drive differential diagnosis with other disease is starting to emerge.

A computational model of neurodegeneration in Alzheimer\u2019s disease

Disruption of mental functions in Alzheimer’s disease (AD) and related disorders is accompanied by selective degeneration of brain regions. These regions comprise large-scale ensembles of cells organized into systems for mental functioning, however the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and functional systems is not clear. Here we present a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques in two cohorts of patients with AD. This reflected a simple information processing-based functional description of macroscale brain anatomy which we link to AD physiology, functional networks, and mental abilities. We further apply the model to normal aging and seven degenerative diseases of mental functions. We propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology.

Application of a smart 18F-FDG-PET adaptive threshold segmentation algorithm for the biological target volume delineation in head and neck cancer.

The aim of the present study is to evaluate the reliability of a 18F-fluorodeoxyglucose (18F-FDG) PET adaptive threshold segmentation (ATS) algorithm, previously validated in a preclinical setting on several scanners, for the biological target volume (BTV) delineation of head and neck radiotherapy planning. [18F]FDG PET ATS algorithm was studied in treatment plans of head and neck squamous cell carcinoma on a dedicated workstation (iTaRT, Tecnologie Avanzate, Turin, Italy). BTVs segmented by the present ATS algorithm (BTV<inf>ATS</inf>) were compared with those manually segmented for the original radiotherapy treatment planning (BTV<inf>VIS</inf>). We performed a qualitative and quantitative volumetric analysis with a comparison tool within the ImSimQA TM software package (Oncology Systems Limited, Shrewsbury, UK). We reported figures of merit (FOMs) to convey complementary information: Dice Similarity Coefficient, Sensitivity Index, and Inclusiveness Index. The study was conducted on 32 treatment plans. Median BTV<inf>ATS</inf> was 11 cm3 while median BTV<inf>VIS</inf> was 14 cm3. The median Dice Similarity Coefficient, Sensitivity Index, Inclusiveness Index were 0.72, 63%, 88%, respectively. Interestingly, the median volume and the median distance of the voxels that are over contoured by ATS were respectively 1 cm3 and 1 mm. ATS algorithm could be a smart and an independent operator tool when implemented for 18F-FDG-PET-based tumor volume delineation. Furthermore, it might be relevant in case of BTV-based dose painting.

3D Convolutional Neural Network-Based Denoising of Low-Count Whole-Body 18F-Fluorodeoxyglucose and 89Zr-Rituximab PET Scans.

Acquisition time and injected activity of 18F-fluorodeoxyglucose (18F-FDG) PET should ideally be reduced. However, this decreases the signal-to-noise ratio (SNR), which impairs the diagnostic value of these PET scans. In addition, 89Zr-antibody PET is known to have a low SNR. To improve the diagnostic value of these scans, a Convolutional Neural Network (CNN) denoising method is proposed. The aim of this study was therefore to develop CNNs to increase SNR for low-count 18F-FDG and 89Zr-antibody PET. Super-low-count, low-count and full-count 18F-FDG PET scans from 60 primary lung cancer patients and full-count 89Zr-rituximab PET scans from five patients with non-Hodgkin lymphoma were acquired. CNNs were built to capture the features and to denoise the PET scans. Additionally, Gaussian smoothing (GS) and Bilateral filtering (BF) were evaluated. The performance of the denoising approaches was assessed based on the tumour recovery coefficient (TRC), coefficient of variance (COV; level of noise), and a qualitative assessment by two nuclear medicine physicians. The CNNs had a higher TRC and comparable or lower COV to GS and BF and was also the preferred method of the two observers for both 18F-FDG and 89Zr-rituximab PET. The CNNs improved the SNR of low-count 18F-FDG and 89Zr-rituximab PET, with almost similar or better clinical performance than the full-count PET, respectively. Additionally, the CNNs showed better performance than GS and BF.

GPC3-targeted immunoPET imaging of hepatocellular carcinomas.

Early detection of hepatocellular carcinoma (HCC) remains a clinical challenge. Glypican 3 (GPC3) is a proteoglycan highly specific for HCC and is a potential diagnostic and therapeutic target for HCC. This work aims to develop GPC3-targeted immuno-positron emission tomography (immunoPET) imaging strategies and to assess the diagnostic values in preclinical HCC models. Flow cytometry was used to screen GPC3-positive HCC cell lines. The expression of GPC3 in HCCs was detected by immunohistochemistry on tissue microarray. A novel GPC3-specific single domain antibody (sdAb) was produced and labeled with gallium-68 (68Ga, T1/2 = 1.1h) and fluorine-18 (18F, T1/2 = 1.8h) to develop radiotracers with different half-lives. The diagnostic efficacies of the developed probes (i.e., [68Ga]Ga-NOTA-G2, [18F]F-G2, and [68Ga]Ga-NOTA-ABDG2) were interrogated in preclinical HCC models bearing varying GPC3 levels. GPC3 was strongly expressed on HCC cell lines and patients with poorly differentiated HCC. [68Ga]Ga-NOTA-G2 immunoPET imaging specifically delineated the subcutaneous HCC lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. ImmunoPET imaging with [18F]F-G2 also efficiently diagnosed the tumors with clarity. Moreover, the fusion of G2 to an albumin-binding domain (ABD) significantly increased the tumor uptake and decreased kidney accumulation of the radiotracer when compared to [68Ga]Ga-NOTA-G2. In the work, we successfully developed sdAb-derived GPC3-targeted immunoPET imaging strategies and characterized the superior diagnostic accuracies in preclinical HCC models. Furthermore, we synthesized a fusion protein ABDG2 with improved targeting and pharmacokinetic properties, serving as a promising candidate for developing radioimmunotherapy agents.

Precise characterization of a solitary pulmonary nodule using tumor shadow disappearance rate-corrected F-18 FDG PET and enhanced CT.

We aimed to characterize solitary pulmonary nodule (SPN) using imaging parameters for F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) or enhanced CT corrected by tumor shadow disappearance rate (TDR) to reflect the tissue density.We enrolled 51 patients with an SPN who underwent PET/CT and chest CT with enhancement. The FDG uptake of SPN was evaluated using maximum standardized uptake value (SUVmax) on PET/CT. The mean Hounsfield unit (HU) for each SPN was evaluated over the region of interest on nonenhanced and enhanced CT images. The change in mean HU (HUpeak-pre) was quantified by subtracting the mean HU of the preenhanced CT from that of the post-enhanced CT. TDR was defined as the ratio of the tumor area, which disappears at a mediastinal window, to the tumor area of the lung window. We investigated which parameters (SUVmax or HUpeak-pre) could contribute to the characterization of SPN classified by TDR value and whether diagnostic performance could be improved using TDR-corrected imaging parameters.For SPN with higher tissue density (TDR <42%, n = 22), high value of SUVmax (≥3.1) was a significant factor to predict malignancy (P = .006). High value of HUpeak-pre (≥38) was a significant factor to characterize SPN (P = .002) with lower tissue density (TDR ≥42%, n = 29). The combined approach using TDR-corrected parameters had better predictive performance to characterize SPN than SUVmax only (P = .031).Applying imaging parameters such as SUVmax or HUpeak-pre in consideration of tissue density calculated with TDR could contribute to accurate characterization of SPN.

Use of 18F-fluorodeoxyglucose positron emission tomography to standardize clinical trial recruitment in Takayasu's arteritis.

To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu's arteritis (TAK). The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data. In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01]. Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.

Assessment of Takayasu arteritis in routine practice with PETVAS, an 18F-FDG PET quantitative scoring tool.

The aim of this study was to evaluate the value of the PET vascular activity score (PETVAS) during the follow-up of patients with Takayasu arteritis. Takayasu arteritis patients who underwent 18F-Fluorodeoxyglucose (FDG) PET imaging were evaluated retrospectively. In 8 patients both 1 and 2-h imagings were also performed prospectively. For PETVAS, 9 arterial areas were scored between 0-3 according to the FDG uptake. Forty-six images of 34 patients were evaluated. PETVAS was higher in patients with clinically active disease (p = 0.03) and in the C-reactive protein (CRP) elevated group among clinically inactive patients (p = 0.0015). PETVAS correlated with CRP (p = 0.003, r = 0.53) and erythrocyte sedimentation rate (p = 0.005, r = 0.41), whereas age, disease duration, immunosuppressive, and glucocorticoid (GC) treatments were not associated with PETVAS. First vs. 2nd-h PETVAS was similar in patients who had both 1st and 2nd h PET scans (p = 0.67). We observed higher PETVAS in patients with active disease and elevated acute phase reactants. Although scores in our study (performed at one-h) were lower compared to the original PETVAS study performed at two h, PETVAS seems to be a reliable tool to quantify FDG PET scores in routine practice.

Lung adenocarcinoma: development of nomograms based on PET/CT images for prediction of epidermal growth factor receptor mutation status and subtypes.

To develop nomograms that combine clinical characteristics, computed tomographic (CT) features and 18F-fluorodeoxyglucose PET (18F-FDG PET) metabolic parameters for individual prediction of epidermal growth factor receptor (EGFR) mutation status and exon 19 deletion mutation and exon 21 point mutation (21 L858R) subtypes in lung adenocarcinoma. In total 124 lung adenocarcinoma patients who underwent EGFR mutation testing and whole-body 18F-FDG PET/CT were enrolled. Each patient's clinical characteristics (age, sex, smoking history, etc.), CT features (size, location, margins, etc.) and four metabolic parameters (SUVmax, SUVmean, MTV and TLG) were recorded and analyzed. Logistic regression analyses were performed to screen for significant predictors of EGFR mutation status and subtypes, and these predictors were presented as easy-to-use nomograms. According to the results of multiple regression analysis, three nomograms for individualized prediction of EGFR mutation status and subtypes were constructed. The area under curve values of three nomograms were 0.852 (95% CI, 0.783-0.920), 0.857 (95% CI, 0.778-0.937) and 0.893 (95% CI, 0.819-0.968) of EGFR mutation vs. wild-type, 19 deletion mutation vs. wild-type and 21 L858R vs. wild-type, respectively. Only calcification showed significant differences between the EGFR 19 deletion and 21 L858R mutations. EGFR 21 L858R mutation was more likely to be nonsolid texture with air bronchograms and pleural retraction on CT images. And they were more likely to be associated with lower FDG metabolic activity compared with those wild-types. The sex difference was mainly caused by the 19 deletion mutation, and calcification was more frequent in them.

Radiomics model based on preoperative 18F-fluorodeoxyglucose PET predicts N2-3b lymph node metastasis in gastric cancer patients.

The aim of the study was to construct and validate 18F-fluorodeoxyglucose (18F-FDG) PET-based radiomics nomogram and use it to predict N2-3b lymph node metastasis in Chinese patients with gastric cancer (GC). A total of 127 patients with pathologically confirmed GC who underwent preoperative 18F-FDG PET/CT imaging between January 2014 and September 2020 were enrolled as subjects in this study. We use the LIFEx software to extract PET radiomic features. A radiomics signature (Rad-score) was developed with the least absolute shrinkage and selection operator algorithm. Then a prediction model, which incorporated the Rad-score and independent clinical risk factors, was constructed and presented with a radiomics nomogram. Receiver operating characteristic (ROC) analysis was used to assess the performance of Rad-score and the nomogram. Finally, decision curve analysis (DCA) was applied to evaluate the clinical usefulness of the nomogram. The PET Rad-score, which includes four selected features, was significantly related to pN2-3b (all P < 0.05). The prediction model, which comprised the Rad-score and carcinoembryonic antigen (CEA) level, showed good calibration and discrimination [area under the ROC curve: 0.81(95% confidence interval: 0.74-0.89), P < 0.001)]. The DCA also indicated that the prediction model was clinically useful. This study presents a radiomics nomogram consisting of a radiomics signature based on PET images and CEA level that can be conveniently used for personalized prediction of high-risk N2-3b metastasis in Chinese GC patients.

Four-modality imaging of unmedicated subjects with schizophrenia: 18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, and MRI

Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D2/D3 receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia. Integration of data from all four modalities yielded better predictive power than less inclusive combinations, specifically in the thalamus, left dorsolateral prefrontal and temporal regions. Among the modalities, fractional anisotropy showed highest discrimination in white matter whereas 18F-fallypride binding showed highest discrimination in gray matter. Structural and functional modalities displayed comparable discriminative power but different topography, with higher sensitivity of structural modalities in the left prefrontal region. Combination of functional and structural imaging modalities with inclusion of both gray and white matter appears most effective in diagnostic discrimination. The highest sensitivity of 18F-fallypride PET to gray matter changes in schizophrenia supports the primacy of dopaminergic abnormalities in its pathophysiology.

Preserved myocardial viability in patients with chronic total occlusion of a single coronary artery

ObjectiveTo assess the benefits of coronary collateral circulation on myocardial perfusion, viability and function in patients with total occlusion of a single coronary artery using the 99mTc-sestamibi SPECT and 18F-fluorodeoxyglucose PET. Methods164 Consecutive patients were included who underwent coronary angiography results exhibited total occlusion of a single coronary artery and received 99mTc-MIBI SPECT and 18F-FDG PET within 90 days of angiography. Myocardial perfusion and viability in patients with collateral circulation and those without it were compared. Long-term follow-up was performed through a review of patient clinical records. ResultsCollateral circulation was present in 56 patients (34%) and absent in 108 patients (66%). The total perfusion defect size in patients with collateral circulation decreased when compared to those without (30% ± 13% to 35% ± 14%, P < .05). The myocardial viability was 22% ± 12% in patients with collateral circulation, and 12% ± 9% in those without (P < .001). The left ventricular ejection fraction was higher, and the end-diastolic and end-systolic left ventricular volumes were lower in patients with collateral circulation (39% ± 11%, 138 ± 66, 89 ± 57) compared to patients without collateral circulation (31% ± 9%, 177 ± 55, 125 ± 48, all P < .001, respectively). Multi-factor logistic regression identified that concerning the variables of sex, age, viable myocardium, collateral circulation, treatment type and others, only treatment type was significantly associated with therapeutic effects (OR 3.872, 95% CI 1.915-7.830, P < .001). ConclusionCollateral circulation can preserve resting myocardial blood perfusion and myocardial viability, and help maintain the function of the left ventricular myocardium. The appropriate treatment strategy will have a substantial impact on the therapeutic outcome.

Impact of 18F-Fluorodeoxyglucose positron emission tomography on management of cancer of unknown primary: systematic review and meta-analysis

BackgroundCancers of unknown primary (CUP) have traditionally been treated empirically, with a dismal prognosis. Compared with standard diagnostic tests, including CT and MRI, imaging with 18F-fluorodeoxyglucose (FDG) PET or PET/CT has shown the capacity to better identify the primary tumour site and detect additional sites of metastasis. However, its clinical impact is not well established. We performed a systematic review and meta-analysis of prior studies to assess the impact of FDG-PET or PET/CT on the management of patients with CUP. Materials and methodsPubmed and EMBASE databases were searched up to 4th February 2021. Studies that reported the proportion of patients with CUP who experienced a management change after FDG-PET or PET/ computed tomography (CT) were included and the proportions were pooled using the random-effects model. Study quality was assessed using QUADAS-2. Subgroup analysis was conducted to explore heterogeneity. ResultsThirty-eight studies (involving 2795 patients) were included. The pooled proportion of patients with management changes was 35% (95% confidence interval 31%–40%). There was substantial heterogeneity among the studies (Q-test, p < 0.01; I2 = 82%). The specific reason for management change was more commonly detection of the primary site (22% [95% CI 18–28%]) than detection of additional metastatic sites (14% [95% CI 10–19%]). The pooled proportions of patients with management changes were similar among numerous subgroups (range, 32.8%–38.2%). ConclusionFDG-PET or PET/CT had a meaningful impact on the management of patients with CUP. Approximately, a third of patients had their management changed because of FDG-PET or PET/CT results, and this finding was consistent across numerous subgroups.

Mapping covariance in brain FDG uptake to structural connectivity

PurposeInter-subject covariance of regional 18F-fluorodeoxyglucose (FDG) PET measures (FDGcov) as proxy of brain connectivity has been gaining an increasing acceptance in the community. Yet, it is still unclear to what extent FDGcov is underlied by actual structural connectivity via white matter fiber tracts. In this study, we quantified the degree of spatial overlap between FDGcov and structural connectivity networks.MethodsWe retrospectively analyzed neuroimaging data from 303 subjects, both patients with suspected neurodegenerative disorders and healthy individuals. For each subject, structural magnetic resonance, diffusion tensor imaging, and FDG-PET data were available. The images were spatially normalized to a standard space and segmented into 62 anatomical regions using a probabilistic atlas. Sparse inverse covariance estimation was employed to estimate FDGcov. Structural connectivity was measured by streamline tractography through fiber assignment by continuous tracking.ResultsFor the whole brain, 55% of detected connections were found to be convergent, i.e., present in both FDGcov and structural networks. This metric for random networks was significantly lower, i.e., 12%. Convergent were 80% of intralobe connections and only 30% of interhemispheric interlobe connections.ConclusionStructural connectivity via white matter fiber tracts is a relevant substrate of FDGcov, underlying around a half of connections at the whole brain level. Short-range white matter tracts appear to be a major substrate of intralobe FDGcov connections.

Metabolic Brain Network and Surgical Outcome in Temporal Lobe Epilepsy: A Graph Theoretical Study Based on 18F-fluorodeoxyglucose PET

Drug-resistant temporal lobe epilepsy (TLE) is a potential candidate for surgery; however, nearly one-third subjects had a poor surgical prognosis. We studied the underlying neuromechanism related to the surgical prognosis using graph theory based on metabolic brain network. Sixty-four unilateral TLE subjects with preoperative 18F-fluorodeoxyglucose (FDG) PET scanning were retrospectively enrolled and divided into Ia (Engel class Ia, n = 32) and non-Ia (Engel class Ib-IV, n = 32) groups according to more than 3-year follow-up after unilateral anterior temporal lobectomy (ATL). The metabolic brain network was constructed and the changed metabolic connectivity of Ia and non-Ia was detected compared with 15 matched healthy controls (HCs). Further, the network properties, including small-worldness and global efficiency, were calculated and hub nodes were also identified for the 3 groups respectively. Non-Ia group exhibited increased connectivity between contralateral fusiform gyrus and contralateral lingual gyrus; while Ia showed decreased connectivity mainly among bilateral frontal, temporal and parietal cortex. Graph theoretical analysis revealed that non-Ia group showed increased small-worldness (35%<s < 55%, P ≤ 0.05) compared to HCs; and elevated global efficiency (P = 0.05) and decreased Lp (P = 0.05) compared to Ia group. Ia group showed reduced Cp (55%<s < 63%, P < 0.05) and increased small-worldness (35%<s < 37%, P < 0.05) compared to HCs; Furthermore, disrupted hub nodes distribution pattern with the midcingulate gyrus disappeared, was also found in non-Ia group compared with the Ia group. All those results revealed that elevated network integration and metabolic connectivity, redistributed hub nodes pattern is associated with ongoing postoperative seizures in subjects with intractable TLE.

Age, vascular disease, and Alzheimer\u2019s disease pathologies in amyloid negative elderly adults

BackgroundWe recently reported that CSF phosphorylated tau (p-Tau181) relative to Aβ40 (CSF p-Tau/Aβ40 ratio) was less noisy and increased associations with Alzheimer’s disease (AD) biomarkers compared to CSF p-Tau181 alone. While elevations of CSF p-Tau/Aβ40 can occur in amyloid-β (Aβ) negative (Aβ-) individuals, the factors associated with these elevations and their role in neurodegeneration and cognitive decline are unknown. We aim to explore factors associated with elevated tau in CSF, and how these elevated tau are related to neurodegeneration and cognitive decline in the absence of Aβ positivity.MethodsWe examined relationships between CSF p-Tau/Aβ40, and CSF Aβ42/Aβ40, Aβ PET, and white matter hyperintensities (WMH) as well as vascular risk factors in 149 cognitively unimpaired and 52 impaired individuals who were presumably not on the Alzheimer’s disease (AD) pathway due to negative Aβ status on both CSF and PET. Subgroups had 18F-fluorodeoxyglucose (FDG) PET and adjusted hippocampal volume (aHCV), and longitudinal measures of CSF, aHCV, FDG PET, and cognition data, so we examined CSF p-Tau/Aβ40 associations with these measures as well.ResultsElevated CSF p-Tau/Aβ40 was associated with older age, male sex, greater WMH, and hypertension as well as a pattern of hippocampal atrophy and temporoparietal hypometabolism characteristic of AD. Lower CSF Aβ42/Aβ40, higher WMH, and hypertension but not age, sex, Aβ PET, APOE-ε4 status, body mass index, smoking, and hyperlipidemia at baseline predicted CSF p-Tau/Aβ40 increases over approximately 5 years of follow-up. The relationship between CSF p-Tau/Aβ40 and subsequent cognitive decline was partially or fully explained by neurodegenerative measurements.ConclusionsThese data provide surprising clues as to the etiology and significance of tau pathology in the absence of Aβ. It seems likely that, in addition to age, both cerebrovascular disease and subthreshold levels of Aβ are related to this tau accumulation. Crucially, this phenotype of CSF tau elevation in amyloid-negative individuals share features with AD such as a pattern of metabolic decline and regional brain atrophy.

Assessing the qualitative and quantitative impacts of simple two-class vs multiple tissue-class MR-based attenuation correction for cardiac PET/MR

BackgroundHybrid PET/MR imaging has significant potential in cardiology due to its combination of molecular PET imaging and cardiac MR. Multi-tissue-class MR-based attenuation correction (MRAC) is necessary for accurate PET quantification. Moreover, for thoracic PET imaging, respiration is known to lead to misalignments of MRAC and PET data that result in PET artifacts. These factors can be addressed by using multi-echo MR for tissue segmentation and motion-robust or motion-gated acquisitions. However, the combination of these strategies is not routinely available and can be prone to errors. In this study, we examine the qualitative and quantitative impacts of multi-class MRAC compared to a more widely available simple two-class MRAC for cardiac PET/MR. Methods and ResultsIn a cohort of patients with cardiac sarcoidosis, we acquired MRAC data using multi-echo radial gradient-echo MR imaging. Water-fat separation was used to produce attenuation maps with up to 4 tissue classes including water-based soft tissue, fat, lung, and background air. Simultaneously acquired 18F-fluorodeoxyglucose PET data were subsequently reconstructed using each attenuation map separately. PET uptake values were measured in the myocardium and compared between different PET images. The inclusion of lung and subcutaneous fat in the MRAC maps significantly affected the quantification of 18F-fluorodeoxyglucose activity in the myocardium but only moderately altered the appearance of the PET image without introduction of image artifacts. ConclusionOptimal MRAC for cardiac PET/MR applications should include segmentation of all tissues in combination with compensation for the respiratory-related motion of the heart. Simple two-class MRAC is adequate for qualitative clinical assessment.

Mild cognitive impairment and abnormal brain metabolic expression in idiopathic REM sleep behavior disorder

BackgroundMild cognitive impairment (MCI) is a common feature of isolated rapid-eye-movement sleep behavior disorder (iRBD). Here, we assessed cognitive functions and MCI in a prospective iRBD cohort and investigated their association with disease-specific brain metabolic patterns. MethodsForty-four patients with polysomnography-confirmed iRBD performed a standardized battery of neuropsychological examinations every two years. We used previously established spatial covariance patterns from de novo drug-naïve Parkinson's disease with concomitant RBD (denovoPDRBD-RP) and iRBD (iRBD-RP) using 18F-fluorodeoxyglucose PET scan. We compared those expressions between iRBD with normal cognition (iRBD-NC) and with mild cognitive impairment (iRBD-MCI), and evaluated whether they predict progressive cognitive deterioration. ResultsTwenty iRBD patients (45 %) had MCI at baseline and 12 patients (27 %, about 7 % per year) had clinically significant cognitive deterioration after 4 years. The iRBD-MCI and iRBD-NC groups showed similar rates of cognitive change, but iRBD-MCI consistently performed worse in the domains of verbal memory and executive function. Elevated denovoPDRBD-RP expression predicted cognitive deterioration (hazard ratio = 5.98 [1.70–21.06]), whereas iRBD-RP did not. ConclusionsIncreased disease-specific brain metabolic patterns are associated with iRBD-MCI and impending cognitive deterioration with the risk of progression to Lewy body dementia.

Neutrophil extracellular traps in giant cell arteritis biopsies: presentation, localization and co-expression with inflammatory cytokines.

To explore the presence of neutrophil extracellular traps (NETs) in inflamed temporal artery biopsies (TABs) of patients with GCA. Ten patients with GCA [five with limited and five with associated generalized vascular involvement, as defined by 18F-fluorodeoxyglucose PET with CT (PET/CT)] and eight with PMR were studied. The presence, location, quantitation and decoration of NETs with IL-6, IL-1β and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Paired serum levels of IL-6 and IL-17A were also evaluated in all patients. All temporal artery biopsies from GCA, but not PMR, patients had NETs located mainly in the adventitia, adjacent to the vasa vasorum. NETs decorated with IL-6 were present in 8/10 TABs of GCA patients, of whom 5 were PET/CT(+) and 3 PET/CT(-) patients. IL-17A(+) NETs were observed in all GCA patients. IL-1β(+) NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL-17A levels and NETs containing IL-6 and/or IL-17A. NETs bearing pro-inflammatory cytokines are present in inflamed GCA-TABs. Future studies with a larger number of patients from different centres will show whether the findings regarding neutrophils/NETs in the TAB are consistent and disclose their clinical impact.