Dataset Information

Metabolic Changes Precede Radiation-Induced Cardiac Remodeling in Beagles: Using Noninvasive ¹⁸F-FDG (¹⁸F-Fludeoxyglucose) and ¹³N-Ammonia Positron Emission Tomography/Computed Tomography Scans.

ABSTRACT: Background This study was performed to characterize the metabolic, functional, and structural cardiac changes in a canine model of radiation-induced heart disease by serial in vivo imaging and ex vivo analyses. Methods and Results Thirty-six dogs were randomly assigned to control or irradiated groups at 3 time points (months 3, 6, and 12 after radiation; each group comprised 6 dogs). The left anterior myocardium of dogs in irradiated groups was irradiated locally with a single dose of 20-Gy X-ray. The irradiated myocardial regions showed increased myocardial uptake of ¹⁸F-FDG (¹⁸F-fludeoxyglucose) in the irradiated beagles, but the increased uptake area decreased at months 6 and 12 compared with month 3 after radiation. Abnormality of myocardial perfusion and cardiac function were detected at month 6 after radiation. Compared with the control groups, the protein expression of GLUT4 (glucose transporter 4) was upregulated in the irradiated groups, correlating with significantly decreased CPT1 (carnitine acyltransferase 1) expression. Mitochondria degeneration, swelling, and count reduction in the irradiated groups were observed. The difference in CD68 of macrophage markers and the inflammatory cytokines (IL-6 [interleukin 6], TNF-? [tumor necrosis factor ?]) between the irradiation and control groups was not significant. Furthermore, the progressive aggravation of apoptosis and fibrosis was displayed. Conclusions Elevated ¹⁸F-FDG uptake occurred after irradiation and subsequently led to ventricular perfusion defects and dysfunction. The process was associated with myocardial metabolic substrate remodeling, cardiac muscle cell apoptosis, and myocardial fibrosis rather than inflammation.

SUBMITTER: Yan R

PROVIDER: S-EPMC7727013 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Metabolic Changes Precede Radiation-Induced Cardiac Remodeling in Beagles: Using Noninvasive 18F-FDG (18F-Fludeoxyglucose) and 13N-Ammonia Positron Emission Tomography/Computed Tomography Scans.

Yan Rui R Li Xiang X Song Jianbo J Guo Min M Cai Honghong H Wu Zhifang Z Wu Ping P Li Li L Yang Minfu M Wang Yuetao Y Li Sijin S

Journal of the American Heart Association 20200911 18

Background This study was performed to characterize the metabolic, functional, and structural cardiac changes in a canine model of radiation-induced heart disease by serial in vivo imaging and ex vivo analyses. Methods and Results Thirty-six dogs were randomly assigned to control or irradiated groups at 3 time points (months 3, 6, and 12 after radiation; each group comprised 6 dogs). The left anterior myocardium of dogs in irradiated groups was irradiated locally with a single dose of 20-Gy X-ra ...[more]

PMID: 32914660

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Project description:BackgroundCardiac arrest (CA) patients who survived by cardiopulmonary resuscitation (CPR) can present different levels of neurological deficits ranging from minor cognitive impairments to persistent vegetative state and brain death. The pathophysiology of the resulting brain injury is poorly understood, and whether changes in post-CA brain metabolism contribute to the injury are unknown. Here we utilized [18F]fluorodeoxyglucose (FDG)-Positron emission tomography (PET) to study in vivo cerebral glucose metabolism 72 h following CA in a murine CA model.MethodsAnesthetized and ventilated adult C57BL/6 mice underwent 12-min KCl-induced CA followed by CPR. Seventy-two hours following CA, surviving mice were intraperitoneally injected with [18F]FDG (~ 186 µCi/200 µL) and imaged on Molecubes preclinical micro-PET/computed tomography (CT) imaging systems after a 30-min awake uptake period. Brain [18F]FDG uptake was determined by the VivoQuant software on fused PET/CT images with the 3D brain atlas. Upon completion of Positron emission tomography (PET) imaging, remaining [18F]FDG radioactivity in the brain, heart, and liver was determined using a gamma counter.ResultsGlobal increases in brain [18F]FDG uptake in post-CA mice were observed compared to shams and controls. The median standardized uptake value of [18F]FDG for CA animals was 1.79 versus sham 1.25 (p < 0.05) and control animals 0.78 (p < 0.01). This increased uptake was consistent throughout the 60-min imaging period and across all brain regions reaching statistical significance in the midbrain, pons, and medulla. Biodistribution analyses of various key organs yielded similar observations that the median [18F]FDG uptake for brain was 7.04%ID/g tissue for CA mice versus 5.537%ID/g tissue for sham animals, p < 0.05).ConclusionsThis study has successfully applied [18F]FDG-PET/CT to measure changes in brain metabolism in a murine model of asystolic CA. Our results demonstrate increased [18F]FDG uptake in the brain 72 h following CA, suggesting increased metabolic demand in the case of severe neurological injury. Further study is warranted to determine the etiology of these changes.

Project description:ImportanceNo guidelines at present describe when fludeoxyglucose F 18-labeled positron emission tomography and computed tomography (FDG PET-CT) should be used in the initial posttreatment period for evaluation of oropharyngeal squamous cell carcinoma treatment outcome and recurrence.ObjectiveTo compare accuracies of the initial posttreatment PET-CT between primary treatment groups and to define indicators of false-positive findings.Design, setting, and participantsThis retrospective cohort study identified adults with a new diagnosis of oropharyngeal squamous cell carcinoma who received treatment with curative intent from October 1, 2006, through November 30, 2016, using the Alberta Cancer Registry (n?=?380). Patients who underwent PET-CT within 1 year of treatment completion were included (n?=?190). Of these, 103 patients (54.2%) had PET-CT findings positive for residual or recurrent disease, and 61 (32.1%) had false-positive findings. Among the 61 patients, 42 (68.9%) had received chemoradiotherapy (CRT) and 19 (31.1%) had primary surgery. Forty-two patients had true-positive findings, indicating a prevalence rate of disease of 22.1%. Data were analyzed from July through October 2017.ExposuresOne of 2 primary treatment modalities (surgery with or without adjuvant therapy vs CRT). All patients had posttreatment FDG PET-CT.Main outcomes and measuresPrimary outcome measures included the diagnostic odds ratio, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET-CT for detecting residual and/or recurrent disease. A multivariate analysis determined indicators of false-positive findings. Discriminative ability was assessed using receiver operating characteristic curve analysis of maximum standardized uptake value (SUVmax) metabolic data.ResultsOf the 190 participants, 77.9% were men, with a mean (SD) age at diagnosis of 58.5 (8.5) years. The diagnostic odds ratio was 19.3 (95% CI, 5.7-65.1); pooled sensitivity, 93.3% (95% CI, 80.7%-98.3%); and pooled specificity, 57.9% (95% CI, 49.4%-66.0%). The PPV of detecting disease was 54.7% (95% CI, 38.8%-69.8%) for primary surgery and 31.1% (95% CI, 20.2%-44.4%) for CRT. The NPV was 100% (95% CI, 94.7%-100%) for primary surgery and 96.6% (95% CI, 89.5%-99.1%) for CRT. Multivariate analysis identified treatment type, p16 disease, and smoking status as indicative of false-positive findings. In the receiver operating characteristic curve analysis for primary tumors, the optimal cutoff SUVmax for indicating true- vs false-positive results was 5.1 for surgically treated patients (area under the curve,?0.729; 95% CI,?0.570-0.888) and 5.3 for patients treated with CRT (area under the curve,?0.844; 95% CI,?0.700-0.989).Conclusions and relevanceThe results indicate a higher specificity for FDG PET-CT for initial posttreatment surveillance imaging among patients treated with primary surgery compared with nonsurgical management. Both sets of patients with posttreatment FDG PET-CT findings with an SUVmax greater than 5.0 should undergo close evaluation for possible residual or recurrent disease.

Project description:PurposeHead and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury.MethodsData for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3-6 months post-RT (Xero 3-6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0-5 Gy, 5-10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT.Results432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3-6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10-50 Gy (p < 0.05). Kruskal-Wallis test showed a significantly higher mean RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p = 0.03). Multiple logistic regression showed a combined clinical-dosimetric-metabolic imaging model could predict the severity of Xero 3-6mo; AUC = 0.78 (95%CI: 0.66-0.85; p < 0.0001).ConclusionWe sought to quantify pre- and post-RT 18FDG-PET metrics of parotid glands in patients with OPC. Temporal dynamics of PET-derived metrics can potentially serve as MIBs of RT-related xerostomia in concert with clinical and dosimetric variables.

Project description:BackgroundAtrial fibrillation (AF) has been identified to increase stroke risk, even after oral anticoagulants (OACs), and the recurrence rate is high after radiofrequency catheter ablation (RFCA). Inflammation is an essential factor in the occurrence and persistence of AF. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is an established molecular imaging modality to detect local inflammation. We aimed to investigate the relationship between atrial inflammatory activity and poor prognosis of AF based on 18F-FDG PET/CT.MethodsA total of 204 AF patients including 75 with paroxysmal AF (ParAF) and 129 with persistent AF (PerAF) who underwent PET/CT before treatment were enrolled in this prospective cohort study. Clinical data, electrocardiograph (ECG), echocardiography, and cardiac 18F-FDG uptake were collected. Follow-up information was obtained from patient clinical case notes or telephone reviews, with the starting point being the time of PET/CT scan. The follow-up deadline was either the date of AF recurrence after RFCA, new-onset stroke, or May 2023. Cox proportional hazards regression models were used to identify predictors of poor prognosis and hazard ratios (HRs) with 95% confidence intervals (CIs) was calculated.ResultsMedian follow-up time was 29 months [interquartile range (IQR), 22-36 months]. Poor prognosis occurred in 52 patients (25.5%), including 34 new-onset stroke patients and 18 recrudescence after RFCA. The poor prognosis group had higher congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (TIA) or thromboembolism (doubled), vascular disease, age 65-74 years, sex category (female) (CHA2DS2-VASc) score [3.0 (IQR, 1.0-3.75) vs. 2.0 (IQR, 1.0-3.0), P=0.01], right atrial (RA) wall maximum standardized uptake value (SUVmax) (4.13±1.82 vs. 3.74±1.58, P=0.04), higher percentage of PerAF [39 (75.0%) vs. 90 (59.2%), P=0.04], left atrial (LA) enlargement [45 (86.5%) vs. 104 (68.4%), P=0.01], and RA wall positive FDG uptake [40 (76.9%) vs. 79 (52.0%), P=0.002] compared with the non-poor prognosis group. Univariate and multivariate Cox proportional hazard regression analysis concluded that only CHA2DS2-VASc score (HR, 1.29; 95% CI: 1.06-1.57; P=0.01) and RA wall positive FDG uptake (HR, 2.68; 95% CI: 1.10-6.50; P=0.03) were significantly associated with poor prognosis.ConclusionsRA wall FDG positive uptake based on PET/CT is tightly related to AF recurrence after RFCA or new-onset stroke after antiarrhythmic and anticoagulation treatment.

Dataset Information

Metabolic Changes Precede Radiation-Induced Cardiac Remodeling in Beagles: Using Noninvasive ¹⁸F-FDG (¹⁸F-Fludeoxyglucose) and ¹³N-Ammonia Positron Emission Tomography/Computed Tomography Scans.

Publications

Metabolic Changes Precede Radiation-Induced Cardiac Remodeling in Beagles: Using Noninvasive <sup>18</sup>F-FDG (<sup>18</sup>F-Fludeoxyglucose) and <sup>13</sup>N-Ammonia Positron Emission Tomography/Computed Tomography Scans.

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