18F-fluorodeoxyglucose Positron Emission Tomography Imaging Research Articles

Association of 18 F-Fluorodeoxyglucose-Positron Emission Tomography Activity With Angiographic Progression of Disease in Large Vessel Vasculitis.

To assess whether vascular activity seen on 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan is associated with angiographic change in large vessel vasculitis (LVV). Patients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG-PET imaging. Follow-up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow-up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged. A total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow-up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG-PET scan at baseline had no angiographic change over the follow-up period (787 [99%] of 793). Few territories with baseline FDG-PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG-PET activity at baseline. Within the same patient, an arterial territory with baseline FDG-PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG-PET activity (odds ratio 19.49 [95% confidence interval 2.44-156.02]; P < 0.01). Concomitant edema and wall thickening further increased risk for angiographic change. Development of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG-PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG-PET activity.

Stress related neural activity: potential mechanism contributing to benefit of physical activity on heart failure incidence

Abstract Background We previously observed that: 1) physical activity (PA) decreases stress-related neural activity (SNA) in a dose-dependent manner and 2) resting SNA predicts incident heart failure (HF). Thus, we hypothesize that PA may decrease the risk of incident HF in part through its beneficial effect on SNA. Methods Self-reported PA data were acquired from Partners Biobank participants. Metabolic equivalent of task-minutes per week (MET*minutes/week) were calculated and participants were categorized according to their adherence to current PA recommendations (&amp;lt;500 and ≥500 MET-min/wk). In a subset with clinically indicated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging (n=744), SNA was measured as a ratio of amygdalar to ventromedial prefrontal cortical activity. Subsequent HF and baseline CVD risk factor data were obtained using International Classification of Diseases Codes. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between PA vs HF risk. Mediation analysis was used to test whether PA's impact on SNA significantly mediated the association between PA and HF. Results Among 50,363 participants (median age 59 years [IQR 42, 70], 40% male), 13,850 (11.6%) were diagnosed with HF over a median period of 3.1 years. PA within recommendations was associated with lower risk of subsequent HF (hazard ratio (HR) [95% confidence interval (CI)]: 0.849 [0.760, 0.948], p=0.004, Figure 1) in a model adjusted for CVD risk factors and history of myocardial infarction. As noted previously, higher SNA associated with higher risk of subsequent HF (HR [95% CI]: 1.34 [1.08, 1.66], p=0.007); and PA within guideline recommendations (vs.below) associated with lower SNA (Zscore ± SD: −0.14±0.92 vs 0.02±1, p=0.037). Moreover, mediation analysis shows that exercise reduces HF risk in part via reductions in SNA, accounting for 9% of the total relationship between exercise and HF risk (p&amp;lt;0.05, Figure 2). Conclusion PA associates with reductions in: A) stress-associated neural activity and B) subsequent HF risk. Moreover, the mechanism by which PA reduces HF risk may involve salutary effects on stress-related neural pathways. Funding Acknowledgement Type of funding sources: None.

Prognostic value of quantitative parameters for esophageal squamous cell carcinoma determined by preoperative FDG-PET after trimodal therapy

BackgroundAssociations between tumor metabolic and volumetric parameters determined by preoperative 18F-fluorodeoxyglucose–positron emission tomography and survival in patients with esophageal squamous cell carcinoma who underwent trimodal therapy have not been fully investigated. MethodsWe evaluated relationships between reductions in maximal standardized uptake value, metabolic tumor volume, and total lesion glycolysis in primary tumors on 18F-fluorodeoxyglucose–positron emission tomography images between before and after neoadjuvant chemoradiotherapy and the survival of 120 patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy followed by surgery. ResultsThe optimal cutoffs of Δ maximal standardized uptake value, Δ metabolic tumor volume, and Δ total lesion glycolysis were defined to statistically yield the largest differences in recurrence-free survival for good and poor positron emission tomography responders to neoadjuvant chemoradiotherapy (cutoffs: 70%, 85%, and 90%, respectively). These cutoff values significantly stratified overall survival (Δ maximal standardized uptake value, P = .004; Δ metabolic tumor volume, P = .001; Δ total lesion glycolysis, P < .0001). Univariate analysis showed that Δ maximal standardized uptake value (hazard ratio, 0.50; 95% confidence interval, 0.32–0.79; P = .003), Δ metabolic tumor volume (hazard ratio, 0.50; 95% confidence interval, 0.31–0.81; P = .004), and Δ total lesion glycolysis (hazard ratio, 0.37; 95% confidence interval, 0.23–0.61; P < .001) were statistically significant for recurrence-free survival. Furthermore, Δ metabolic tumor volume (hazard ratio, 0.45; 95% confidence interval, 0.27–0.76; P = .003) and Δ total lesion glycolysis (hazard ratio, 0.37; 95% confidence interval, 0.22–0.63; P < .001) were independent factors for recurrence-free survival in multivariate analyses that included preoperative and pathological factors. ConclusionTogether with significant pathological prognostic factors, Δ metabolic tumor volume and Δ total lesion glycolysis were valuable for patients with esophageal squamous cell carcinoma who received trimodal therapy. Thus, preoperative 18F-fluorodeoxyglucose–positron emission tomography is a useful and noninvasive diagnostic tool that might facilitate tailoring optimal therapies for locally advanced esophageal squamous cell carcinoma.

Combining PET with MRI to improve predictions of progression from mild cognitive impairment to Alzheimer's disease: an exploratory radiomic analysis study.

BackgroundThis study aimed to explore the potential of a combination of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging (MRI) to improve predictions of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). The predictive performances and specific associated biomarkers of these imaging techniques used alone (single-modality imaging) and in combination (dual-modality imaging) were compared.MethodsThis study enrolled 377 patients with MCI and 94 healthy control participants from 2 medical centers. Enrolment was based on the patients’ brain MRI and PET images. Radiomic analysis was performed to evaluate the predictive performance of dual-modality 18F-FDG PET and MRI scans. Regions of interest (ROIs) were determined using an a priori brain atlas. Radiomic features in these ROIs were extracted from the MRI and 18F-FDG PET scan data. These features were either concatenated or used separately to select features and construct Cox regression models for prediction in each modality. Harrell’s concordance index (C-index) was then used to assess the predictive accuracies of the resulting models, and correlations between the MRI and 18F-FDG PET features were evaluated.ResultsThe C-indices for the two test datasets were 0.77 and 0.80 for dual-modality 18F-FDG PET/MRI, 0.75 and 0.73 for single-modality 18F-FDG PET, and 0.74 and 0.76 for single-modality MRI. In addition, there was a significant correlation between the crucial image signatures of the different modalities.ConclusionsThese results indicate the value of imaging features in monitoring the progress of MCI in populations at high risk of developing AD. However, the incremental benefit of combining 18F-FDG PET and MRI is limited, and radiomic analysis of a single modality may yield acceptable predictive results.

Differentiating solitary brain metastases from glioblastoma by radiomics features derived from MRI and 18F-FDG-PET and the combined application of multiple models

This study aimed to explore the ability of radiomics derived from both MRI and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) images to differentiate glioblastoma (GBM) from solitary brain metastases (SBM) and to investigate the combined application of multiple models. The imaging data of 100 patients with brain tumours (50 GBMs and 50 SBMs) were retrospectively analysed. Three model sets were built on MRI, 18F-FDG-PET, and MRI combined with 18F-FDG-PET using five feature selection methods and five classification algorithms. The model set with the highest average AUC value was selected, in which some models were selected and divided into Groups A, B, and C. Individual and joint voting predictions were performed in each group for the entire data. The model set based on MRI combined with 18F-FDG-PET had the highest average AUC compared with isolated MRI or 18F-FDG-PET. Joint voting prediction showed better performance than the individual prediction when all models reached an agreement. In conclusion, radiomics derived from MRI and 18F-FDG-PET could help differentiate GBM from SBM preoperatively. The combined application of multiple models can provide greater benefits.

Underdiagnosis of cardiac sarcoidosis by ECG and echocardiography in cases of extracardiac sarcoidosis

BackgroundAlthough screening with 12-lead electrocardiography and transthoracic echocardiography for cardiac involvement has been recommended for patients with biopsy-proven extracardiac sarcoidosis, cardiac sarcoidosis has been reported even in patients with normal electrocardiography and echocardiography findings. We investigated the prevalence and characteristics of these patient cohorts.MethodsWe studied 112 consecutive patients (age, 55±17 years, 64% females) with biopsy-proven extracardiac sarcoidosis who had undergone 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging for cardiac sarcoidosis evaluation. The patients were categorised as those showing normal findings both in electrocardiography and transthoracic echocardiography (normal group) and those showing abnormal findings in one or both examinations (abnormal group).Results33 (29%) and 79 (71%) patients were categorised into the normal and abnormal groups, respectively, of which 6 (18%) and 43 (54%) patients, respectively, were diagnosed with cardiac sarcoidosis (p<0.01). Of these six patients in the normal group, two with multiple-organ sarcoidosis showed clinical deterioration of cardiac involvement and required steroid therapy; three with small cardiac involvement showed natural remission over follow-up assessments; and one underwent steroid therapy and showed an improvement in the left ventricular ejection fraction to within normal limits.ConclusionsThe prevalence of cardiac sarcoidosis in patients with biopsy-proven extracardiac sarcoidosis and normal electrocardiography and transthoracic echocardiography findings was ∼20%. Electrocardiography and transthoracic echocardiography may not detect cardiac sarcoidosis in patients without conduction and morphological abnormalities. However, some of these patients may subsequently show clinically manifested cardiac sarcoidosis. Physicians should be mindful of this population.

Diagnostic utility of fusion 18F-fluorodeoxyglucose positron emission tomography/cardiac magnetic resonance imaging in cardiac sarcoidosis

BackgroundAlthough each 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been used to diagnose cardiac sarcoidosis (CS), active CS is still misdiagnosed. MethodsActive CS, diagnosed by PET alone, was defined as focal or focal on diffuse FDG uptake pattern. In fusion PET/CMR imaging, using a regional analysis with AHA 17-segment model, the patients were categorized into four groups: (1) PET−/LGE−, (2) PET+/LGE−, (3) PET+/LGE+, and (4) PET−/LGE+. PET+/LGE+ was defined as active CS. Results74 Patients with suspected CS were enrolled. Between PET alone and fusion PET/CMR imaging, 20 cases had mismatch evaluations of active CS, and most had diffuse or focal on diffuse FDG uptake pattern on PET alone imaging. 40 Patients fulfilled the 2016 the Japanese Circulation Society diagnostic criteria for CS. The interobserver diagnostic agreement was excellent (κ statistics 0.89) and the overall accuracy for diagnosing CS was 87.8% in fusion PET/CMR imaging, which were superior to those in PET alone imaging (0.57 and 82.4%, respectively). In a sub-analysis of diffuse and focal on diffuse patterns, the agreement (κ statistics 0.86) and overall accuracy (81.8%) in fusion PET/CMR imaging were still better. ConclusionsFusion PET/CMR imaging with regional analysis offered reliable and accurate diagnosis of CS, covering low diagnostic area by FDG-PET alone.

Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer\u2019s disease with an implantable ultrasound device

BackgroundTemporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer’s disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and efficacy of this approach in patients with mild AD using an implantable ultrasound device.MethodsAn implantable, 1-MHz ultrasound device (SonoCloud-1) was implanted under local anesthesia in the skull (extradural) of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB. 18F-florbetapir and 18F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at 4 and 8 months after the initiation of sonications to monitor the brain metabolism and amyloid levels along with cognitive evaluations. The evolution of cognitive and neuroimaging features was compared to that of a matched sample of control participants taken from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).ResultsA total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at 4 months of − 6.6% (SD = 7.2%) on 18F-florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in the longitudinal change in the glucose metabolism were observed compared to the neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison with the ADNI participants as expected due to the small sample size and duration of the trial.ConclusionsThese results demonstrate the safety of ultrasound-based BBB disruption and the potential of this technology to be used as a therapy for AD patients. Research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease-modifying drugs may further enhance the effects observed.Trial registrationClinicalTrials.gov, NCT03119961

Processing speed dysfunction is associated with functional corticostriatal circuit alterations in childhood epilepsy with centrotemporal spikes: a PET and fMRI study

PurposeEpilepsy with centrotemporal spikes (ECTS) is the most common epilepsy syndrome in children and usually presents with cognitive dysfunctions. However, little is known about the processing speed dysfunction and the associated neuroimaging mechanism in ECTS. This study aims to investigate the brain functional abnormality of processing speed dysfunction in ECTS patients by using the 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI).MethodsThis prospective study recruited twenty-eight ECTS patients who underwent the 18F-FDG PET, rs-fMRI, and neuropsychological examinations. Twenty children with extracranial tumors were included as PET controls, and 20 healthy children were recruited as MRI controls. The PET image analysis investigated glucose metabolism by determining standardized uptake value ratio (SUVR). The MRI image analysis explored abnormal functional connectivity (FC) within the cortical–striatal circuit through network-based statistical (NBS) analysis. Correlation analysis was performed to explore the relationship between SUVR, FC, and processing speed index (PSI).ResultsCompared with healthy controls, ECTS patients showed normal intelligence quotient but significantly decreased PSI (P = 0.04). PET analysis showed significantly decreased SUVRs within bilateral caudate, putamen, pallidum, left NAc, right rostral middle frontal gyrus, and frontal pole of ECTS patients (P < 0.05). Rs-fMRI analysis showed absolute values of 20 FCs were significantly decreased in ECTS patients compared with MRI controls, which connected 16 distinct ROIs. The average SUVR of right caudate and the average of 20 FCs were positively correlated with PSI in ECTS patients (P = 0.034 and P = 0.005, respectively).ConclusionThis study indicated that ECTS patients presented significantly reduced PSI, which is closely associated with decreased SUVR and FC of cortical–striatal circuit. Caudate played an important role in processing speed dysfunction.Clinical trial registrationNCT04954729; registered on July 8, 2021, public site, https://clinicaltrials.gov/ct2/show/NCT04954729

The Frontal and Cerebellar Metabolism Related to Cognitive Dysfunction in Multiple System Atrophy.

BackgroundCognitive dysfunctions have been reported in multiple system atrophy (MSA). However the underlying mechanisms remain to be elucidated. This study aimed to explore the possible cerebral metabolism associated with domain-specific cognitive performances in MSA.MethodsA total of 84 patients were diagnosed as probable or possible MSA, comprised of 27 patients as MSA with predominant parkinsonism (MSA-P) and 57 patients as MSA with predominant cerebellar ataxia (MSA-C). The comprehensive neuropsychological tests and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging were performed. Z-score was calculated to non-dimensionalize and unify indicators of different tests in the domains of executive function, attention, language, memory, and visuospatial function. Correlations between specific Z-score and cerebral 18F-FDG uptake were analyzed using statistical parametric mapping. The cognition-related metabolic differences between patients with MSA-P and MSA-C were analyzed using the post-hoc test.ResultsZ-scores of the domains including attention, executive function, and language correlated positively with the metabolism in the superior/inferior frontal gyrus and cerebellum, but negatively with that in the insula and fusiform gyrus (p < 0.001). No significant differences in neuropsychological performances and frontal metabolism were found between patients with MSA-P and MSA-C. Only lower metabolism in the cerebellum was observed in MSA-C.ConclusionMetabolic changes in the frontal lobe and cerebellum may participate in the cognitive impairments of patients with MSA. Nevertheless, cognitive and corresponding metabolic differences between the two subtypes of MSA still need more exploration.

Multimodal Classification of Alzheimer's Disease and Amnestic Mild Cognitive Impairment: Integrated 18F-FDG PET and DTI Study.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and memory impairment. Amnestic mild cognitive impairment (aMCI) is the intermediate stage between normal cognitive aging and early dementia caused by AD. It can be challenging to differentiate aMCI patients from healthy controls (HC) and mild AD patients. To validate whether the combination of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and diffusion tensor imaging (DTI) will improve classification performance compared with that based on a single modality. A total of thirty patients with AD, sixty patients with aMCI, and fifty healthy controls were included. AD was diagnosed according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable. aMCI diagnosis was based on Petersen's criteria. The 18F-FDG PET and DTI measures were each used separately or in combination to evaluate sensitivity, specificity, and accuracy for differentiating HC, aMCI, and AD using receiver operating characteristic analysis together with binary logistic regression. The rate of accuracy was based on the area under the curve (AUC). For classifying AD from HC, we achieve an AUC of 0.96 when combining two modalities of biomarkers and 0.93 when using 18F-FDG PET individually. For classifying aMCI from HC, we achieve an AUC of 0.79 and 0.76 using the best individual modality of biomarkers. Our results show that the combination of two modalities improves classification performance, compared with that using any individual modality.

Systemic Inflammation Index and Tumor Glycolytic Heterogeneity Help Risk Stratify Patients with Advanced Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Treated with Tyrosine Kinase Inhibitor Therapy.

Simple SummaryPatients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma have been known to respond to first-line tyrosine kinase inhibitor (TKI) treatment. However, a subgroup of patients are non-responsive to the treatment, with poor survival outcomes, and those who are initially responsive may still experience resistance. A reliable prognostic tool may provide a valuable direction for tailoring individual treatment strategies in this clinical setting. With this aim, the present study explores the prognostic power of the combination of the systemic inflammation index (portrayed by hematological markers) and tumor glycolytic heterogeneity (characterized by 18F-fluorodeoxyglucose positron emission tomography images). The model integrating these two biomarkers could be used to improve risk stratification, and the subsequent personalized management strategy in patients with advanced EGFR-mutated lung adenocarcinoma.Tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. Over half of patients failed to achieve prolonged survival benefits from TKI therapy. Awareness of a reliable prognostic tool may provide a valuable direction for tailoring individual treatments. We explored the prognostic power of the combination of systemic inflammation markers and tumor glycolytic heterogeneity to stratify patients in this clinical setting. One hundred and five patients with advanced EGFR-mutated lung adenocarcinoma treated with TKIs were retrospectively analyzed. Hematological variables as inflammation-induced biomarkers were collected, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). First-order entropy, as a marker of heterogeneity within the primary lung tumor, was obtained by analyzing 18F-fluorodeoxyglucose positron emission tomography images. In a univariate Cox regression analysis, sex, smoking status, NLR, LMR, PLR, SII, and entropy were associated with progression-free survival (PFS) and overall survival (OS). After adjusting for confounders in the multivariate analysis, smoking status, SII, and entropy, remained independent prognostic factors for PFS and OS. Integrating SII and entropy with smoking status represented a valuable prognostic scoring tool for improving the risk stratification of patients. The integrative model achieved a Harrell’s C-index of 0.687 and 0.721 in predicting PFS and OS, respectively, outperforming the traditional TNM staging system (0.527 for PFS and 0.539 for OS, both p < 0.001). This risk-scoring model may be clinically helpful in tailoring treatment strategies for patients with advanced EGFR-mutated lung adenocarcinoma.

Measuring Heterogeneity in 18F-Fluorodeoxyglucose Positron Emission Tomography Images for Classifying Metastatic and Benign Bone Lesions in Patients with Cervical Cancer

PurposeHeterogeneity assessment can be applied for medical imaging analysis. Here, we evaluated first-order and texture analysis (TA) metrics in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging for classification of metastatic and benign bone lesions in patients with cervical cancer.MethodsThe data of 18F-FDG PET studies performed on a specific PET/CT system from 2016 to 2018 in patients with cervical cancer were retrieved. The data of bone lesions extracted from studies over 2016–2017 and 2018 were used as training and validation datasets, respectively. Metastatic bone lesions were identified in each dataset, with an equal number of benign bone lesions selected. Cuboid volume of interest (VOI) consisting of 3 × 3 × 5 reconstructed voxels was applied for first-order metrics, and cubic VOI consisting of smaller voxels with trilinear interpolation of standardized uptake value (SUV) was adopted for TA metrics. First-order metrics included the maximum SUV (SUVmax) of lesions and the mean voxel SUV and its standard deviation (SUVsd), skewness, and kurtosis in VOI. In total, 4464 TA metrics based on 62 texture features were evaluated. Logistic regression was used for classification with area under the receiver operating characteristic curve (AUC) as the performance measure.ResultsFrom the training and validation datasets, 98 and 42 metastatic bone lesions were identified, respectively. SUVsd demonstrated higher performance than did SUVmax in both the training (AUC .798 vs .732, P = .001) and validation (AUC .786 vs .684, P < .001) datasets. Top-performing TA metrics demonstrated significantly higher performance in the training dataset, but not in the validation dataset.ConclusionA simple first-order measure of heterogeneity, SUVsd, was found to be superior to SUVmax for the classification of metastatic and benign bone lesions. Multiple hypothesis testing can result in false-positive findings in TA with multiple features and parameters; careful validation is required.

Abstract 9057: Anti-inflammatory Effect of Biologic Therapy in Patients With Psoriatic Disease: A Prospective Cohort Fdg-pet Study

Introduction: Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. Hypothesis: Central vascular inflammation (VI) as measured on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta will improve in patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and controls. We also postulate that in patients responding to biologics, there will be an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. Methods: We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and patients with non-inflammatory arthritis). The primary outcome of our study was the change in VI, estimated as the target-to-background ratio by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. Results: 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (change in TBRmax: -0.46±0.55) when compared to the the PsO group treated with non-biologic therapy (change in TBRmax: 0.23±0.67). The group with imaging evidence of a response to biologic agents (i.e. TBRmax drop greater than median value) maintained MFR (change in MFR of 0.05±0.19) when compared to the group with a response on TBRmax that was below the median, which had a drop in MFR (-2.9±0.8) (P=0.03). Conclusions: VI in the thoracic aorta decreased compared to psoriasis patients treated with non-systemic therapies and controls. Psoriasis patients treated with biologics who demonstrated a significant response on FDG PET imaging, maintained their MFR compared to non-responders. There is a positive impact of immune therapies on VI and microvascular disease in patients with chronic inflammation.

Identification of the main components of spontaneous speech in primary progressive aphasia and their neural underpinnings using multimodal MRI and FDG-PET imaging

BackgroundPrimary progressive aphasia (PPA) is a clinical syndrome characterized by gradual loss of language skills. This study aimed to evaluate the diagnostic capacity of a connected speech task for the diagnosis of PPA and its variants, to determine the main components of spontaneous speech, and to examine their neural correlates. MethodsA total of 118 participants (31 patients with nfvPPA, 11 with svPPA, 45 with lvPPA, and 31 healthy controls) were evaluated with the Cookie Theft picture description task and a comprehensive language assessment protocol. Patients also underwent 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging studies. Principal component analysis and machine learning were used to evaluate the main components of connected speech and the accuracy of connected speech parameters for diagnosing PPA. Voxel-based analyses were conducted to evaluate the correlation between spontaneous speech components and brain metabolism, brain volumes, and white matter microstructure. ResultsDiscrimination between patients with PPA and controls was 91.67%, with 77.78% discrimination between PPA variants. Parameters related to speech rate and lexical variables were the most discriminative for classification. Three main components were identified: lexical features, fluency, and syntax. The lexical component was associated with ventrolateral frontal regions, while the fluency component was associated with the medial superior prefrontal cortex. Number of pauses was more related with the left parietotemporal region, while pauses duration with the bilateral frontal lobe. The lexical component was correlated with several tracts in the language network (left frontal aslant tract, left superior longitudinal fasciculus I, II, and III, left arcuate fasciculus, and left uncinate fasciculus), and fluency was linked to the frontal aslant tract. ConclusionSpontaneous speech assessment is a useful, brief approach for the diagnosis of PPA and its variants. Neuroimaging correlates suggested a subspecialization within the left frontal lobe, with ventrolateral regions being more associated with lexical production and the medial superior prefrontal cortex with speech rate.

Deep-Learning Radiomics for Discrimination Conversion of Alzheimer's Disease in Patients With Mild Cognitive Impairment: A Study Based on 18F-FDG PET Imaging.

Objectives: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the older people. Some types of mild cognitive impairment (MCI) are the clinical precursors of AD, while other MCI forms tend to remain stable over time and do not progress to AD. To discriminate MCI patients at risk of AD from stable MCI, we propose a novel deep-learning radiomics (DLR) model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images and combine DLR features with clinical parameters (DLR+C) to improve diagnostic performance.Methods: 18F-fluorodeoxyglucose positron emission tomography (PET) data from the Alzheimer's disease Neuroimaging Initiative database (ADNI) were collected, including 168 patients with MCI who converted to AD within 3 years and 187 patients with MCI without conversion within 3 years. These subjects were randomly partitioned into 90 % for the training/validation group and 10 % for the independent test group. The proposed DLR approach consists of three steps: base DL model pre-training, network features extraction, and integration of DLR+C, where a convolution network serves as a feature encoder, and a support vector machine (SVM) operated as the classifier. In comparative experiments, we compared our DLR+C method with four other methods: the standard uptake value ratio (SUVR) method, Radiomics-ROI method, Clinical method, and SUVR + Clinical method. To guarantee the robustness, 10-fold cross-validation was processed 100 times.Results: Under the DLR model, our proposed DLR+C was advantageous and yielded the best classification performance in the diagnosis of conversion with the accuracy, sensitivity, and specificity of 90.62 ± 1.16, 87.50 ± 0.00, and 93.39 ± 2.19%, respectively. In contrast, the respective accuracy of the other four methods reached 68.38 ± 1.27, 73.31 ± 6.93, 81.09 ± 1.97, and 85.35 ± 0.72 %. These results suggested the DLR approach could be used successfully in the prediction of conversion to AD, and that our proposed DLR-combined clinical information was effective.Conclusions: This study showed DLR+C could provide a novel and valuable method for the computer-assisted diagnosis of conversion to AD from MCI. This DLR+C method provided a quantitative biomarker which could predict conversion to AD in MCI patients.

Moderate alcohol intake associates with a decreased risk of venous thrombosis: mediation through decreased stress-associated brain activity

Abstract Background Prior studies suggest that moderate alcohol intake may associate with a lower incidence of deep venous thrombosis (DVT). However, it is unclear if this association persists after robust adjustment for confounders. Moreover, the mechanisms mediating this potential benefit are unclear. Prior studies show that chronic stress promotes stress-related neural activity (amygdalar activity: AmygA), which in turn triggers inflammation and elevates thrombosis risk. Since moderate alcohol intake decreases AmygA, we hypothesize that this neural effect of alcohol may partially mediate its beneficial impact on DVT risk. Purpose To evaluate whether the association between moderate alcohol intake and decreased DVT risk: A) persists after robustly accounting for potential confounders and B) is mediated by reductions in stress-related neural activity. Methods Data were obtained from the Mass General Brigham Biobank, which included detailed health, lifestyle, and follow-up outcomes information on 53 059 adult participants. Alcohol intake was classified as low (&amp;lt;1 drink/week), moderate (1–14 drinks/week), or high (&amp;gt;14 drinks/week). A subset of 656 study subjects underwent clinical 18F-fluorodeoxyglucose positron emission tomography imaging from which AmygA was measured as the ratio of amygdalar to regulatory (ventromedial pre-frontal cortex) activity. Individuals on anticoagulant therapies for atrial fibrillation prior to enrolment and/or imaging were excluded. Cox analysis were performed wherein patients who developed DVT prior to Biobank enrolment (1064 subjects) were excluded. Mediation analysis was used to examine the role of AmygA in mediating the link between alcohol intake and DVT. Results The median age of the study population was 59 years [interquartile range (IQR) 26] and 51.9% were female. DVT occurred in 573 participants (1.2%) over a median follow up period of 3.4 years (IQR 2.9). Cox regression analysis showed that moderate alcohol intake was associated with lower incident DVT rates after controlling for confounders (hazard ratio [95% confidence intervals (CI)] 0.773 [0.644,0.929], p=0.006, Table 1). In the subset of participants who underwent brain imaging, moderate alcohol intake associated with decreased AmygA activity (standardized β [95% CI]: −0.218 [−0.370, −0.065], p=0.005). Further, AmygA associated with DVT (odds ratio (OR) [95% CI]: 1.374 [1.089, 1.734], p=0.007). Path analysis demonstrated that decreased AmgyA mediated the salutary effect of moderate alcohol on DVT (log OR [95% CI]: −0.0635 [−0.1383, −0.0078], p&amp;lt;0.05, Figure 1). Conclusion Moderate alcohol intake is associated with a decreased risk of DVT via a mechanism that may involve a reduction in stress-related neurobiological activity. Alternative therapies targeting this neural pathway should be identified with the goal of reducing the burden of DVT. Funding Acknowledgement Type of funding sources: None.

Anxiety and depression associate with heightened risk of deep venous thrombosis: mediation through neural pathways

Abstract Background Anxiety disorders and depression associate with an increased risk of deep venous thrombosis (DVT). However, it is unclear if this association persists after robust adjustment for confounders. Further, the mechanism mediating this potential link remains unknown. Prior studies show that anxiety and depression associate with heightened stress-associated neural activity (notably in the amygdala: AmygA), which in turn promotes chronic inflammation, a driver of thrombosis syndromes. Purpose To evaluate whether the association between anxiety/depression and DVT risk: A) persists after robustly accounting for potential confounders, and B) is mediated by upregulated stress-associated neural activity (namely AmygA). Methods Data were obtained from the Mass General Brigham Biobank, which included detailed health information on 118 871 adult participants. A subset of 1520 study subjects underwent clinical 18F-fluorodeoxyglucose positron emission tomography imaging during the follow up period, from which AmygA was measured as the ratio of amygdalar to regulatory (ventromedial pre-frontal cortex) activity. International Classification of Disease (ICD) codes in the medical record were used to define anxiety disorders, depression, and lower extremity DVT. Individuals on anticoagulant therapies for atrial fibrillation prior to enrolment and/or imaging were excluded. Cox analysis were performed wherein patients who developed DVT prior to Biobank enrolment (2599 subjects) were excluded. Mediation analysis was used to examine the role of AmygA in mediating the link between anxiety/depression and DVT. Results The median age of the study population was 57 years [interquartile range (IQR) 28] and 58.4% were female. DVT occurred in 1231 participants (1.2%) over a median follow up period of 3.3 years (IQR 3.0). Cox regression analysis showed that anxiety disorders and depression were independent predictors of incident DVT after controlling for confounders (Table 1; p&amp;lt;0.0001 for all analyses). In the subset of 1383 participants who underwent brain imaging, anxiety disorders and depression associated with increased AmygA activity after controlling for risk factors including age, sex, Charlson index, hormone use and cancer history (standardized β [95% CI]: 0.124 [0.017–0.232], p=0.023 and 0.151 [0.041–0.260], p=0.007 respectively). Further, AmygA associated with DVT (odds ratio (OR) [95% CI]: 1.248 [1.064–1.465], p=0.007). Path analysis demonstrated that increased AmgyA mediated the effect of both anxiety and depression on DVT (log OR [95% CI]: 0.0256 (0.0009–0.0592), p&amp;lt;0.05 and 0.0314 (0.0033 to 0.0718), p&amp;lt;0.05 respectively, Figure 1). Conclusion Anxiety disorders and depression associate with an increased risk of DVT via a mechanism that includes heightened stress-related neurobiological activity. Future studies should evaluate whether modulating this neural pathway could reduce the incidence of DVT. Funding Acknowledgement Type of funding sources: None.

Value of 18F-FDG PET/MR Imaging in the Early Evaluation of Treatment Response following Radiofrequency Ablation of Liver Cancer in a Rabbit Model

PurposeTo test the hypothesis that 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging can detect early residual tumor following radiofrequency (RF) ablation of liver cancer using a VX2 tumor model. Materials and MethodsTwenty-four rabbits with VX2 liver tumors were randomly divided into 3 groups (n = 8/group): Group 1 without RF ablation treatment, Group 2 with complete ablation, and Group 3 with partial ablation. An 18F-FDG PET/MR imaging scan was obtained within 2 hours after RF ablation. The maximum standardized uptake values (SUV) of the nontreated liver tumor, benign periablational enhancement (BPE), residual tumor, ablated tumor, and adjacent liver parenchyma and mean SUV of the normal liver were measured. The ratios of maximum SUV for these targets to the mean SUV of the normal liver (TNR) were calculated and compared. ResultsThe mean TNR of the nontreated liver tumors in Group 1 was significantly greater than that of the adjacent liver parenchyma (8.68 ± 0.71 vs 1.89 ± 0.26, P < .001). In Group 2, the mean TNR of BPE was significantly greater than that of the adjacent liver parenchyma (2.85 ± 0.20 vs 1.86 ± 0.25, P < .001). In Group 3, the mean TNR of the residual tumor was significantly greater than that of BPE (8.64 ± 0.59 vs 2.78 ± 0.23, P < .001), which was significantly greater than that of completely ablated tumor (2.78 ± 0.23 vs 0.50 ± 0.06, P < .001). Conclusions18F-FDG PET/MR imaging may serve as a promising imaging tool for the early detection of viable residual tumors due to incomplete tumor ablation.

ANTI-INFLAMMATORY EFFECT OF BIOLOGIC THERAPY IN PATIENTS WITH PSORIATIC DISEASE COMPARED WITH TREATMENT WITH NON-BIOLOGIC DMARDS: A PROSPECTIVE COHORT FDG-PET STUDY

<h3>BACKGROUND</h3> Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. We hypothesized that central vascular inflammation on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta would improve in these patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and non-inflammatory control patients. We also postulated that in patients responding to biologics, there would an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. <h3>METHODS AND RESULTS</h3> We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and control patients with non-inflammatory arthritis). The primary outcome of our study was the change in vascular inflammation, estimated as the target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. A total of 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). The majority (64.7%) of participants were men and the median age was 62 years (IQR: 48, 69). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (thoracic aorta change in TBRmax: -0.46±0.55) when compared to the change in the thoracic aorta FDG uptake of the PsO group treated with non-biologic therapy (thoracic aorta change in TBRmax: 0.23±0.67). Furthermore, the group with imaging evidence of a response to biologic agents (i.e. TBRmax drop > median value of 7%) maintained MFR (3.40±1.23 MFR to 3.5±1.2 MFR over 6 months) when compared to the group with a below median response on TBRmax which had a drop in MFR (2.9±0.8 MFR to 2.2±0.6 over 6 months) (P=0.03). <h3>CONCLUSION</h3> In a cohort of psoriasis patients treated with biologics, the FDG uptake in the thoracic aorta decreased over the study period compared to psoriasis patients treated with non-systemic therapies as well as controls. Additionally, psoriasis patients treated with biologics who demonstrated a significant anti-inflammatory response on FDG PET imaging, maintained their MFR compared to non-responders. This study supports the notion that there is a positive impact of immune therapies on vascular inflammation and microvascular disease in patients with chronic inflammation.