Metabolic changes in an animal model of amyotrophic lateral sclerosis evaluated by [18F]-FDG positron emission tomography.
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ABSTRACT:
SUBMITTER: Giacobbo BL
PROVIDER: S-EPMC8220836 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection.Methods and resultsThirty patients with suspected CIED infection underwent 18F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related 18F-FDG-PET/CT. 18F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. 18F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. 18F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. 18F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUVmax of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of 18F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%.Conclusions18F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.
| S-EPMC8709812 | biostudies-literature
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.
| S-EPMC7606281 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with limited treatment options. Despite decades of therapeutic development, only two modestly efficacious disease-modifying drugs-riluzole and edaravone-are available to ALS patients. Biomarkers that can facilitate ALS diagnosis, aid in prognosis, and measure drug pharmacodynamics are needed to accelerate therapeutic development for patients with ALS. Positron emission tomography (PET) imaging has promise as a biomarker for ALS because it permits visualization of central nervous system (CNS) pathology in individuals living with ALS. The availability of PET radioligands that target a variety of potential pathophysiological mechanisms-including cerebral metabolism, neuroinflammation, neuronal dysfunction, and oxidative stress-has enabled dynamic interrogation of molecular changes in ALS, in both natural history studies and human clinical trials. PET imaging has potential as a diagnostic biomarker that can establish upper motor neuron (UMN) pathology in ALS patients without overt UMN symptoms, as a prognostic biomarker that might help stratify patients for clinical trials, and as a pharmacodynamic biomarker that measures the biological effect of investigational drugs in the brain and spinal cord. In this Review, we discuss progress made with 30 years of PET imaging studies in ALS and consider future research needed to establish PET imaging biomarkers for ALS therapeutic development.
| S-EPMC6405430 | biostudies-literature
Project description:PurposeTo assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET).MethodsThree hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates.ResultsBrain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3.ConclusionsOur findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.
| S-EPMC8041703 | biostudies-literature
Project description:BackgroundInterstitial lung disease is a common complication of systemic sclerosis (SSc-ILD), and it remains difficult to accurately predict its course. Progressing ILD could be more metabolically active, suggesting that the 18F-FDG tracer could be a tool in the managing of SSc-ILD.MethodsIn our center, SSc patients and controls (non-Hodgkin lymphoma cured after first-line regimen) who had received a PET/CT were screened retrospectively. The FDG uptake (visual intensity, pattern, SUVmax) was systematically recorded in > 30 regions of interest (ROIs) linked to SSc in a blind reviewing by 2 independent nuclear medicine physicians using a standardized form.ResultsAmong the 545 SSc patients followed up in our center, 36, including 22 SSc-ILDs, had a PET/CT, whose indication was cancer screening in most cases. The mean ± SD age was 57.9 ± 13.0 years with 20/36 females. Fourteen patients had a disease duration of less than 2 years. A third had anti-centromere antibodies and 27.8% had anti-topoisomerase antibodies. Pulmonary FDG uptakes were higher in SSc patients than in controls (n = 89), especially in those with ILD compared with those without ILD. Pulmonary FDG uptakes were positively correlated with the ILD severity (fibrosis extent, %FVC, and %DLCO). No significant difference was found in the FDG uptakes from extrathoracic ROIs. Progressing SSc-ILDs within the 2 years after PET/CT (n = 9) had significant higher pulmonary FDG uptakes at baseline than stable SSc-ILDs (n = 13).ConclusionPET/CT could be a useful tool in the assessment of the severity and the prediction of pulmonary function outcome of SSc-ILD.
| S-EPMC7936499 | biostudies-literature
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.
| S-EPMC8239739 | biostudies-literature
Project description: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-α [tumor necrosis factor α]) 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.
| S-EPMC7727013 | biostudies-literature
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.
| S-EPMC10895105 | biostudies-literature
Project description:Solid tumors are hypoxic with altered metabolism, resulting in secretion of acids into the extracellular matrix and lower relative pH, a feature associated with local invasion and metastasis. Therapeutic and diagnostic agents responsive to this microenvironment may improve tumor-specific delivery. Therefore, we pursued a general strategy whereby caged small-molecule drugs or imaging agents liberate their parent compounds in regions of low interstitial pH. In this manuscript, we present a new acid-labile prodrug method based on the glycosylamine linkage, and its application to a class of positron emission tomography (PET) imaging tracers, termed [(18)F]FDG amines. [(18)F]FDG amines operate via a proposed two-step mechanism, in which an acid-labile precursor decomposes to form the common radiotracer 2-deoxy-2-[(18)F]fluoro-d-glucose, which is subsequently accumulated by glucose avid cells. The rate of decomposition of [(18)F]FDG amines is tunable in a systematic fashion, tracking the pKa of the parent amine. In vivo, a 4-phenylbenzylamine [(18)F]FDG amine congener showed greater relative accumulation in tumors over benign tissue, which could be attenuated upon tumor alkalinization using previously validated models, including sodium bicarbonate treatment, or overexpression of carbonic anhydrase. This new class of PET tracer represents a viable approach for imaging acidic interstitial pH with potential for clinical translation.
| S-EPMC4854293 | biostudies-literature
Project description:BackgroundOur previous research investigated the ability of [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging results to predict outcome in patients with sarcoma. Tumor uptake of FDG before and after neoadjuvant chemotherapy was predictive of patient outcome. With this background, a prospective clinical study was designed to assess whether tumor FDG uptake levels in the middle of neoadjuvant chemotherapy added additional prognostic information to pre-therapy imaging data.MethodsSixty-five patients with either bone or soft-tissue sarcoma were treated with neoadjuvant-based chemotherapy according to the standard clinical practice for each tumor group. All patients had FDG PET studies before therapy, mid-therapy (after two cycles of chemotherapy), and before resection. Tumor FDG uptake (SUVmax, the maximum standardized uptake value) at each imaging time point, tumor type (bone or soft-tissue sarcoma), tumor size, and histopathologic grade were recorded for each patient. The time from the pre-therapy FDG PET study to events of local tumor recurrence, metastasis, or death were extracted from the clinical records for comparison with the imaging data. Univariate and multivariate analyses of the imaging and clinical data were performed.ResultsUnivariate and multivariate data analyses showed that the difference (measured as the percentage reduction) between the pre-therapy and mid-therapy maximum tumor uptake values added prognostic value to patient outcome predictions independently of other patient variables.ConclusionsThe utility of a tumor pre-therapy FDG PET scan as a biomarker for the outcome of patients with sarcoma was strengthened by a mid-therapy scan to evaluate the interim treatment response.
| S-EPMC3903137 | biostudies-literature