Fluorodeoxyglucose Positron Emission Tomography Research Articles

Retrosplenial hypometabolism precedes the conversion from mild cognitive impairment to Alzheimer's disease.

Not all individuals who experience mild cognitive impairment (MCI) transition through progressive stages of cognitive decline at the same rate, if at all. Previous observational studies have identified the retrosplenial cortex (RSC) as an early site of hypometabolism in MCI which seems to be predictive of later transition to Alzheimer's disease (AD). We examined N=399 MCI subjects with baseline 18F-fluorodeoxyglucose positron emission tomography. Subjects were classified based on whether their diagnosis converted from MCI to AD. Whole-brain metabolism was decreased in converters (MCI-AD). This effect was more prominent at the RSC, where MCI-AD subjects showed even greater hypometabolism. Observations of RSC hypometabolism and its utility in predicting transition from MCI-AD withstood statistical analyses in a large retrospective study. These results point to the utility of incorporating RSC hypometabolism into predictive models of AD progression risk and call for further examination of mechanisms underlying this relationship. Not all individuals who develop MCI will progress to AD. Individuals with MCI who progress to AD show early whole-brain hypometabolism. Early hypometabolism is particularly prominent at the RSC.

Role of negative transthoracic echocardiography in excluding infective endocarditis

Abstract Background Recent guidelines suggest an extensive role of transesophageal echocardiography (TOE) in the diagnostic work-up for suspected infective endocarditis (IE). However, the negative predictive value of transthoracic echocardiography (TTE) remains poorly investigated. Purpose The purpose of our study was to evaluate the accuracy of TTE in ruling out IE in order to avoid unnecessary TOE, a more invasive and expensive diagnostic exam. Methods We reviewed data of 637 consecutive patients referred to our laboratory of echocardiography with a suspected diagnosis of IE who underwent TOE within 14 days of TTE (median 4.4 days; interquartile range 2.4-7.4). For each patient we obtained age, sex, blood culture results, complete blood count, blood chemistry, evidence of systemic embolism or pulmonary embolism, and presence of moderate/severe heart valve disease, congenital heart disease, valve prostheses and intracardiac devices. Patients with initial doubtful findings at TOE were referred for a follow-up TOE after one week and/or 18F fluorodeoxyglucose positron emission tomography computed tomography to achieve a definitive clinical diagnosis. Patients in whom a clear diagnosis of IE could not be achieved (n=7) were considered to have the disease. Results Of the 637 patients enrolled, 375 had negative TTE for IE (59%). TOE was positive and doubtful for IE in 44 (12%) and 29 (8%) of these patients, respectively. After further assessment, a final diagnosis of IE was achieved in 56 patients (15%). Variables associated with IE at univariable analysis included presence of valve prostheses (p<0.001), systemic or pulmonary embolism (p<0.001), lower platelet count (p=0.003), positive blood culture (p=0.005), aortic valve regurgitation (p=0.02), aortic valve stenosis (p=0.03) and mitral regurgitation (p=0.03). At multivariable logistic regression, independent predictors of IE (OR=odds ratio; CI=confidence interval) included evidence of systemic or pulmonary embolism (OR 17.75, 95% CI 6.66-47.3, p<0.001), bioprosthetic heart valves (OR 2.93, 95% CI 1.31-6.53 p=0.023) and lower platelet count (OR 0.995, 95% CI 0.991-0.998, p=0.003). Among the subgroup of patients (n=183, 49%) with no evidence of embolism, no bioprosthetic valve and platelet count >190,000/mL (median value), IE was diagnosed in 11 patients only (6%). Conclusions In our study, a negative TTE in the subgroup of patients with suspected IE showing platelet count >190,000/mL and absence of embolism and valvular bio-prosthesis, had a negative predictive value for IE of 94%, suggesting that, in this subset of patients, TOE can initially be delayed and performed only if clinical suspicion continues to remain high.

Predictive value of cardiac 18F-fluorodeoxyglucose positron emission tomography for fatal ventricular arrhythmic events in patients with cardiac sarcoidosis

Abstract Background Patients with cardiac sarcoidosis (CS) face an elevated risk of fatal ventricular arrhythmic events (FVAE), including sudden cardiac death. Late gadolinium enhancement (LGE) from contrast-enhanced cardiac magnetic resonance is used for diagnosis of CS and estimation of FVAE risk. However, its application is limited in cases with cardiac devices, renal failure or contrast agent allergies. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) emerges as a diagnostic tool for CS, even in cases where LGE is not feasible. Purpose This study aimed to investigate the potential utility of FDG-PET in predicting FVAE in patients with CS by hypothesizing that higher or lower percent FDG uptake could predict the FVAE risk. Methods Cardiac FDG-PET data from 121 patients with CS, acquired at our university hospital between March 2008 and November 2020, were analyzed. A polar-map model was used to calculate percent uptake relative to maximal cardiac FDG uptake in each of the American Heart Association (AHA) 17 segments (Figure A). Percent uptakes of the AHA 17 segments were compared between groups with and without future FVAE. LGE information was available in 82 patients and was used to assess the presence of LGE in regions where percent FDG uptake differed between the two groups. Results Among enrolled patients (mean age 59.5 ± 10.0 years, 67.8% women), 43 experienced FVAE following FDG-PET image acquisition. The group with future FVAE had a higher history of FVAE (7.7% vs. 37.2%) and beta-blocker administration (38.5% vs. 60.5%), larger left ventricular diastolic diameter (LVDd) (49.3 ± 7.3 mm vs. 57.4 ± 9.5 mm) and lower ejection fraction (LVEF) (56.6 ± 13.6% vs. 42.0 ± 15.2%) compared to the group without it (P < 0.05 all). Percent FDG uptake in the basal interventricular septum part (segment 3) (Figure A) was lower in patients with future FVAE compared to those without it (54.4 ± 13.8% vs. 41.8 ± 15.2%, P < 0.001 corrected for multiple comparisons). Kaplan-Meier analysis with a median split of percent FDG uptake in segment 3 showed that patients with lower uptake (<49%, N= 62) had lower FVAE-free survival compared to those with higher uptake (≥49%, N = 59) (P = 0.007) (Figure B). A Cox hazard model also demonstrated an association between percent FDG uptake in segment 3 and FVAE onset (hazard ratio 0.972 [95% CI 0.951, 0.995], P = 0.015) after adjusting for previous FVAE, beta-blocker administration, LVDd and LVEF. Similarly, analysis within the subgroup with LGE in the septum (N = 58) revealed a higher risk of FVAE in the group with lower percent FDG uptake compared to those with higher uptake (P = 0.020) (Figure C(a)). However, this association was not evident in patients without LGE in the septum (N = 24) (P = 0.821) (Figure C(b)). Conclusions Reduced percent FDG uptake with LGE in the basal intraventricular septum may serve as a valuable predictor of future FVAE occurrence in patients with CS.

Evaluation of 18F FOL a PET tracer targeting folate receptor beta in a rat model of myocardial infarction

Abstract Background Expression of folate receptor-β (FR-β) on the activated macrophages is associated with inflammatory diseases. However, the role of FR-β in the immune response following myocardial infarction (MI) remains unknown. Purpose To investigate FR-β-targeted positron emission tomography (PET) tracer aluminium fluoride-18-labeled 1,4,7,-triazacylononane-1,4,7-triacetic acid conjugated folate ([18F]FOL) for imaging immune response in a rat model of MI. Methods Rats underwent PET scan from 20 to 40 minutes after injection of 50±6 MBq of [18F]FOL on 3 (n=6), 7 (n=21), 15 (n=9), and 90 (n=11) days after surgical ligation of the left coronary artery. As controls, rats were studied on 3 (n=6), 7 (n=14), 15 (n=5), and 90 (n=8) days after sham-operation. [18F]FDG PET was performed a day before [18F]FOL injection in order to localize myocardium and area of MI. After [18F]FOL PET, autoradiography, histology, and staining of CD68 were performed 3 (n=6), 7 (n=6), and 90 (n=11) days after MI in order to detect [18F]FOL uptake and activated macrophages in myocardial tissue sections. A subgroup of rats (n=15) underwent serial [18F]FOL PET 7 and 90 days after MI together with echocardiography in order to evaluate left ventricular function. Results The presence of MI was confirmed by histology in all rats after coronary ligation. PET images showed increased uptake of [18F]FOL in the area of MI. The uptake was significantly higher (p<0.001) in the area of MI than in the myocardium of sham-operated rats on day 3 (SUV 2.04±0.25 vs. 0.74±0.12), and remained increased on day 7 (SUV 1.39±0.33 vs. 0.68±0.12), day 15 (SUV 1.24±0.20 vs. 0.59±0.07), and day 90 (SUV 1.39±0.25 vs. 0.69±0.11). On day 3, pre-treatment with folate glucosamine (n=3) reduced the [18F]FOL signal by 50% in the area of MI indicating specific binding to FR-β. Autoradiography confirmed focally increased uptake of [18F]FOL in the area of MI. A positive correlation was found between uptake of [18F]FOL in PET images and areal percentage of CD68-positivity in the area of MI (r2=0.447, p<0.001). Uptake of [18F]FOL on day 7 after MI was associated with decline in left ventricular ejection fraction (R=-0.665, p<0.01) and increase in left ventricular systolic volume (R=0.561, p=0.02) between 7 and 90 days after MI. Conclusion Cardiac [18F]FOL PET detects increased macrophage-associated FR-β expression after MI in a rat model. FR-β expression peaks early and remains elevated up to 3 months in the infarcted area. Increased FR-β expression early after MI is associated with worsening of left ventricular systolic function late after MI.

Imaging signs of carotid plaque vulnerability predict subclinical neurological events in asymptomatic patients: the carotid artery multi-modality imaging prognostic study

Abstract Background Carotid artery plaques should be considered for invasive treatment if diameter stenoses is ≥60%, in the presence of clinical and/or imaging characteristics associated with an increased risk of ipsilateral stroke, such as intraplaque haemorrhage (IPH) or lipid-rich necrotic core (LRNC). However, little is known about plaque’s characteristics in patients with <60% stenoses. Purpose To evaluate the prevalence and significance of imaging signs of plaque vulnerability in patients with asymptomatic <60% carotid artery stenoses. Methods In the Carotid Artery Multi-modality imaging Prognostic (CAMP) study (granted by Bando Ricerca Salute 2018 - Regione Toscana) we prospectively enrolled 200 patients with asymptomatic, mild/moderate (40-60%) carotid artery stenoses, as assessed at Doppler ultrasound (DUS). All patients were evaluated with multimodality imaging, including computed tomography angiography (CTA), magnetic resonance angiography (MRA) and brain magnetic resonance imaging (MRI), whenever not contraindicated. A subgroup of 75 patients underwent also a 18[F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). A thorough clinical, biochemical, cardiological and neurological evaluation was performed in all patients. Results Imaging signs of plaque vulnerability were frequent (IPH and/or LRNC at MRA were found in 26.3% patients, plaque ulceration at CTA was found in 36.7% of patients). No difference in the prevalence of cardiovascular risk factors was noted in those with and without signs of vulnerability. Subclinical embolic brain infarctions at brain MRI were found in 8.8% of patients at enrollment. These patients had more frequently a LRNC at MRA than patients without subclinical embolic brain infarctions (50% vs 17%, p<0.05), lower estimated glomerular filtration rate (55±8 vs 73±23 mL/min/1.73mq, p<0.001), higher troponin HS values (16±4 vs 12±8 ng/ml, p<0.05). Presence of LRNC at MRA was the only predictor of embolic lesions at MRI (odds ratio 4.86, 95% confidence interval 1.08-21.8, p<0.05). Conclusions Imaging signs of vulnerability are highly prevalent in patients with asymptomatic intermediate carotid artery stenosis. Presence of a LRNC at MRA is associated with subclinical embolic brain infarcts. The use of non-invasive multi-imaging can better characterize carotid plaques, independent of the degree of stenosis, and help identifying a subgroup of patients at higher risk of events.

Evaluation of aortic inflammation in marfan syndrome patients with 18-fluorodeoxyglucose positron emission and computed tomography

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.

Associations Between Testing and Treatment Pathways in a Case of Pediatric Nonlesional Epilepsy: A Census Survey of NAEC Center Directors.

Epilepsy surgery is vital in managing of children with drug-resistant epilepsy. Noninvasive and invasive testing modalities allow for evaluation and treatment of children with drug-resistant epilepsy. Evidence-based algorithms for this process do not exist. This study examines expert response to a vignette of pediatric nonlesional epilepsy to assess associations in evaluation and treatment choices. We analyzed annual report data and an epilepsy practice survey reported in 2020 from 135 pediatric epilepsy center directors in the United States. Characteristics of centers along with noninvasive and invasive testing and surgical treatment strategies were collected. Multivariable logistic regression modeling was performed. The response rate was 100% with 135 responses included in the analyses. Most used noninvasive testing modalities included Neuropsychology evaluation (90%), interictal brain fluorodeoxyglucose-positron emission tomography (85%), and functional magnetic resonance imaging (MRI) (72%) with nearly half obtaining genetic testing. Choosing functional MRI was associated with stereo electroencephalography (EEG) (P = .025) and selecting Wada with subdural grid/strips (P = .038). Directors from pediatric-only centers were more likely to choose stereo EEG as opposed to combined centers (P = .042). Laser interstitial thermal therapy was almost 7 times as likely to be chosen as a treatment modality compared with open resection in dedicated pediatric centers (OR 6.96, P = .002). In a vignette of nonlesional childhood drug-resistant epilepsy, epilepsy center directors' patterns of noninvasive testing, invasive testing, and treatment were examined. Management choices were associated with pediatric versus combined pediatric/adult center characteristics. Expert opinions demonstrated equipoise in evaluation and management of children with drug-resistant epilepsy and the need for evidence-based management strategies.

Plasma phosphorylated tau181 outperforms [18F] fluorodeoxyglucose positron emission tomography in the identification of early Alzheimer disease.

This study was undertaken to compare the performance of plasma p-tau181 with that of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD). We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests. Receiver operating characteristic analyses were used to determine the diagnostic accuracy of plasma p-tau181 and [18F]FDG-PET using clinical diagnosis and core AD biomarkers ([18F]florbetapir-PET and cerebrospinal fluid [CSF] p-tau181) as reference standards. Differences in the diagnostic accuracy between plasma p-tau181 and [18F]FDG-PET were determined by bootstrap-based tests. Correlations of [18F]FDG-PET and plasma p-tau181 with CSF p-tau181, amyloid β (Aβ) PET, and cognitive performance were evaluated to compare associations between measurements. We observed that both plasma p-tau181 and [18F]FDG-PET identified individuals with positive AD biomarkers in CSF or on Aβ-PET. In the MCI group, plasma p-tau181 outperformed [18F]FDG-PET in identifying AD measured by CSF (p = 0.0007) and by Aβ-PET (p = 0.001). We also observed that both plasma p-tau181 and [18F]FDG-PET metabolism were associated with core AD biomarkers. However, [18F]FDG-PET uptake was more closely associated with cognitive outcomes (Montreal Cognitive Assessment, Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, and logical memory delayed recall, p < 0.001) than plasma p-tau181. Overall, although both plasma p-tau181 and [18F]FDG-PET were associated with core AD biomarkers, plasma p-tau181 outperformed [18F]FDG-PET in identifying individuals with early AD pathophysiology. Taken together, our study suggests that plasma p-tau181 may aid in detecting individuals with underlying early AD.

Identification of metabolic progression and subtypes in progressive supranuclear palsy by PET molecular imaging.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with diverse clinical presentations that are linked to tau pathology. Recently, Subtype and Stage Inference (SuStaIn) algorithm, an innovative data-driven method, has been developed to model both the spatial-temporal progression and subtypes of disease. This study explores PSP progression using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging and the SuStaIn algorithm to identify PSP metabolic progression subtypes and understand disease mechanisms. The study included 72 PSP patients and 70 controls, with an additional 24 PSP patients enrolled as a test set, undergoing FDG-PET, dopamine transporter (DAT) PET, and neuropsychological assessments. The SuStaIn algorithm was employed to analyze the FDG-PET data, identifying progression subtypes and sequences. Two PSP subtypes were identified: the cortical subtype with early prefrontal hypometabolism and the brainstem subtype with initial midbrain alterations. The cortical subtype displayed greater cognitive impairment and DAT reduction than the brainstem subtype. The test set demonstrates the robustness and reproducibility of the findings. Pathway analysis indicated that disruptions in dopaminergic cortico-basal ganglia pathways are crucial for elucidating the mechanisms of cognitive and behavioral impairment in PSP, leading to the two metabolic progression subtypes. This study identified two spatiotemporal progression subtypes of PSP based on FDG-PET imaging, revealing significant differences in metabolic patterns, striatal dopaminergic uptake, and clinical profiles, particularly cognitive impairments. The findings highlight the crucial role of dopaminergic cortico-basal ganglia pathways in PSP pathophysiology, especially in the cortical subtype, providing insights into PSP heterogeneity and potential avenues for personalized treatments.

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An invivo microPET study.

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague-Dawley rats were imaged with [11C]UCB-J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB-J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB-J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof-of-concept study shows for the first time that acute taVNS for 30 min can modulate invivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS.

D-[5-11C]-Glutamine Positron Emission Tomography Imaging for Diagnosis and Therapeutic Monitoring of Orthopedic Implant Infections.

Orthopedic implant infections (OIIs) present diagnostic and therapeutic challenges, owing to the lack of methods to distinguish between active infection and sterile inflammation. To address this unmet need, d-amino-acid-based radiotracers with unique metabolic profiles in microorganisms have emerged as a novel class of infection-specific imaging agents. Given the pivotal role of d-glutamine in bacterial biofilm formation and virulence, herein, we explored the potential of positron emission tomography (PET) imaging with d-[5-11C]-Glutamine (d-[5-11C]-Gln) for early detection and treatment monitoring of OIIs. In vitro studies confirmed an active uptake of d-[5-11C]-Gln by Staphylococcus aureus (S. aureus) biofilm commonly associated with OIIs. In vivo evaluations included PET imaging comparisons with d-[5-11C]-Gln vs l-[5-11C]-Gln or 2-deoxy-2-[18F]-fluoroglucose ([18F]-FDG) in a rat OII model with tibial implantation of sterile or S. aureus-colonized stainless-steel screws before and after treatment. These studies demonstrated that the uptake of d-[5-11C]-Gln was significantly higher in the infected screws than that in sterile screws (∼3.4-fold, p = 0.008), which displayed significantly higher infection-to-background muscle uptake ratios (∼2-fold, p = 0.011) with d-[5-11C]-Gln as compared to l-[5-11C]-Gln. Following a 3 week vancomycin treatment, imaging with d-[5-11C]-Gln showed a significant reduction in uptake at the infected sites (∼3-fold, p = 0.0008). Further regression analyses revealed a superior correlation of residual infection-associated radiotracer uptake with the postimaging ex vivo bacterial counts for d-[5-11C]-Gln (k = 0.473, R2 = 0.796) vs [18F]-FDG (k = 0.212, R2 = 0.434), suggesting that d-[5-11C]-Gln PET had higher sensitivity for detecting residual bacterial burden than [18F]-FDG PET. Our results demonstrate the translational potential of d-[5-11C]-Gln PET imaging for noninvasive detection and treatment monitoring of OIIs.

Impaired brain glucose metabolism in glucagon-like peptide-1 receptor knockout mice

BackgroundQuantitative mapping of the brain’s metabolism is a critical tool in studying and diagnosing many conditions, from obesity to neurodegenerative diseases. In particular, noninvasive approaches are urgently required. Recently, there have been promising drug development approaches for the treatment of disorders related to glucose metabolism in the brain and, therefore, against obesity-associated diseases. One of the most important drug targets to emerge has been the Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R). GLP and GLP-1R play an important role in regulating blood sugar and maintaining energy homeostasis. However, the macroscopic effects on brain metabolism and function due to the presence of GLP-1R are unclear.MethodsTo explore the physiological role of GLP-1R in mouse brain glucose metabolism, and its relationship to brain function, we used three methods. We used deuterium magnetic resonance spectroscopy (DMRS) to provide quantitative information about metabolic flux, fluorodeoxyglucose positron emission tomography (FDG-PET) to measure brain glucose metabolism, and resting state-functional MRI (rs-fMRI) to measure brain functional connectivity. We used these methods in both mice with complete GLP-1R knockout (GLP-1R KO) and wild-type C57BL/6N (WT) mice.ResultsThe metabolic rate of GLP-1R KO mice was significantly slower than that of WT mice (p = 0.0345, WT mice 0.02335 ± 0.057 mM/min, GLP-1R KO mice 0.01998 ± 0.07 mM/min). Quantification of the mean [18F]FDG signal in the whole brain also showed significantly reduced glucose uptake in GLP-1R KO mice versus control mice (p = 0.0314). Observing rs-fMRI, the functional brain connectivity in GLP-1R KO mice was significantly lower than that in the WT group (p = 0.0032 for gFCD, p = 0.0002 for whole-brain correlation, p < 0.0001 for ALFF).ConclusionsGLP-1R KO mice exhibit impaired brain glucose metabolism to high doses of exogenous glucose, and they also have reduced functional connectivity. This suggests that the GLP-1R KO mouse model may serve as a model for correlated metabolic and functional connectivity loss.

Characteristics and prognosis of patients with cardiac sarcoidosis presenting with atrioventricular block and ventricular arrhythmias

Cardiac sarcoidosis (CS) may initially present with life-threatening arrhythmias such as atrioventricular block (AVB) and ventricular arrhythmia (VA), including ventricular tachycardia and ventricular fibrillation. Diagnosing CS is challenging due to subtle or absent findings in routine tests and the low sensitivity of the definitive diagnostic tool, endomyocardial biopsy. CS can also mimic other cardiac conditions such as dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy, and it may occur without any systemic involvement. Consequently, delays in presentation, accurate diagnosis, and initiation of appropriate treatment are frequent. Greater awareness of the condition could improve outcomes for patients with CS. Non-invasive advanced imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging are essential for diagnosis, although they may not be accessible in all clinical settings. Management of arrhythmias in CS involves conventional therapies in the utilization of antiarrhythmics and non-pharmacological therapy (e.g., implantable devices), but with notable divergences in the use of immunosuppression and a preference for implantable cardioverter defibrillators over permanent pacemakers. This narrative review aimed to outline the clinical features of patients with CS presenting with AVB or VA and examine diagnostic investigations, imaging techniques, treatment approaches, and prognosis based on current research and international guidelines.

Tracing proliferating potential of lung tumours by [11C]Nicotinamide

Many tumours rely on aerobic glycolysis, known as the Warburg effect, to satisfy energy needs and sustain rapid proliferation [1]. High demands of glucose in tumours can be measured by [18F[fluorodeoxyglucose, [18F]FDG, positron emission tomography (PET). Nicotinamide adenine dinucleotide (NAD) is a coenzyme involved in redox reactions in many metabolic pathways, including glycolysis. To maintain the high rates of glycolysis and proliferation, tumours need increased NAD+ levels and use nicotinamide for the upregulated NAD+ salvage pathway that is the main source of NAD+ in proliferative cancer cells [2]. Herein, we show an improved synthesis method of [11C]Nicotinamide, [11C]NAM, and studied the uptake of [11C]NAM and [18F]FDG to measure proliferating capacity in a lung cancer model. [Carboxyl-11C]nicotinamide was synthesized by a one-pot radiolabeling method [3] on the SYNTHRA synthesizer (Synthra GmbH, Germany) (see Figure 1A). We used a KrasG12D/+ genetically engineered mouse model of lung cancer and evaluated the uptake of [11C]nicotinamide and [18F]FDG with dual-tracer sequential imaging protocol (see Figure 1B) using a NanoScan PET/MRI scanner (Mediso Medical Imaging Systems, Hungary). We obtained [carboxyl-11C]nicotinamide in a radiochemical yield of 15 ± 5 %, volumic activity of 50 ± 10 MBq/ml, and radiochemical purity was &gt; 99 %. We optimized the imaging protocol and found the uptake of [11C]nicotinamide co-localized with the uptake of [18F]FDG in the KrasG12D/+ model of lung cancer as shown in Figure 1C suggesting the higher NAM uptake was associated with high NAD+ production in highly proliferating tumours. We demonstrated that metabolic PET/MRI imaging with [11C]NAM can complement [18F]FDG PET and be useful for probing proliferative potential in lung cancer. This method could be translated and applied in clinical practice to enable visualization of NAD+ metabolism in lung tumours and targeted therapeutically. Please click on the 'PDF' for the full abstract!

Uncommon Pediatric Immune-Mediated Epilepsy: Disease Course, Diagnosis, and Outcome - A Series of Three Cases.

Immune-mediated epilepsy (IME) constitutes a substantial proportion of drug-refractory epilepsies. Rapid diagnosis and prompt immunosuppression are required along with antiseizure medications (ASMs). Here we report three unrelated children who presented with fever, encephalopathy, and refractory epilepsy and subsequently tested positive for rare intraneuronal and surface receptor antibodies, namely, contactin-associated protein like 2 (CASPR2), glutamic acid decarboxylase (GAD65), and paraneoplastic antigen Ma2 (PNMA2). In all of them, brain magnetic resonance imaging (MRI) was noncontributory. Electroencephalography showed nonspecific interictal epileptic discharges. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scan revealed abnormality in metabolic pattern with hypermetabolism in basal ganglia, thalami, frontotemporal cortices, and cerebellar hemispheres, consistent with autoimmune encephalitis. Immunosuppression was initiated along with ASMs. Complete seizure freedom was achieved in GAD65 antibody IME and >50% seizure reduction in CASPR2 and PNMA2 antibody IME. A variable degree of behavioral problems persisted in all. Early immunosuppression is warranted in IME, but does not universally guarantee a complete response.

Chemoradiotherapy treatment increases cardiac and aortic [18F]FDG uptake ratios in lung cancer patients

[18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is an indispensable non-invasive imaging tool to aid diagnosis, prognostication, and therapeutic monitoring in oncology, but it can also evaluate cardiovascular inflammation1,2. Previously, cardiac metabolic changes using [18F]FDG with chemoradiotherapy have been explored3 but changes in the rest of the cardiovascular system remain undetermined. To investigate the cardiovascular metabolic changes pre- and post-chemoradiotherapy in stage 3b non-small cell lung cancer (NSCLC) patients. A retrospective analysis of 26 patients (43-82 years) with stage 3b NSCLC from the American College of Radiology Imaging Network (ACRIN 6668) trial was performed3. All available pre- and post-treatment imaging were retrieved from the Cancer Imaging Archive (TCIA)4 and regions of interest for the left ventricle and calcified large arteries were contoured on all PET-CT scans using PMOD version 4.0 software. The mean, maximum standard uptake value (SUVmean and SUVmax) and target-to-background ratio (TBR) were quantified on PMOD. At approximately 14 weeks post-chemoradiotherapy, there was a higher SUVmean (mean difference 0.81, p=0.01) and SUVmax (mean difference 2.20, p=0.006) in the left ventricle compared with pretreatment scans. TBR for aorta was higher post-treatment (mean difference 0.06, p=0.005). However, SUVmean for carotid arteries and right brachiocephalic artery was reduced post-chemoradiotherapy (mean difference 0.15, p=0.008 and mean difference 0.28, p=0.03). A reduction in SUVmax was also seen for aortic arch (mean difference 0.58, p=0.03) and right brachiocephalic artery (mean difference 0.42, p=0.03 and mean difference 0.42, p=0.03). Cardiovascular glucose metabolism is selectively increased in the left ventricle and aorta post-chemoradiotherapy. Changes in glucose metabolism of atherosclerotic plaques vary across different vessels throughout the body. Please click on the 'PDF' for the full abstract!

Heparin does not improve myocardial glucose metabolism suppression in [18 F]FDG PET/CT in patients with low β-hydroxybutyrate level

BackgroundInadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [18F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [18F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [18F]FDG-PET/CT.Results155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15–20 min before [18F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [18F]FDG uptake pattern was evaluated visually and [18F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1–5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875).ConclusionsWhile high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.

Comparing total-body metabolic PET imaging signatures of lung cancer cachexia to other wasting conditions

Cancer cachexia (CC) is a debilitating wasting condition. While anorexia and muscle wasting are features of cachexia, CC is a distinct and poorly understood metabolic syndrome1. We harnessed preclinical models of lung cancer to study how glucose uptake changes during CC and performed comparative analyses with anorexia and muscle wasting. Lung K-rasG12D/+;Lkb1-/-(KL) mice suffering CC were imaged using [18F]fluorodeoxyglucose (FDG) PET at 15-19% weight loss alongside K-ras wild-type (WT) non-tumour bearing controls. Mice were injected with 12-18MBq of FDG, imaging 80-100 minutes post injection with the Mediso nanoScan® PET/MRI 1T. In non-tumour bearing male animals, we modelled anorexia, muscle wasting, and circulation of cachexia factor GDF15 as follows, respectively: fasted overnight for 20 hr, treated with dexamethasone 21-phosphate (dexa) (2mg/kg, i.p. daily, 21 days) and single injection of recombinant human GDF15 hormone (0.1 mg/kg s.c.). FDG ex vivo biodistribution showed increased uptake in myocardium (p&lt;0.05), brain and liver (both p&lt;0.01) of KL cachexic animals with no significant change in FDG blood pool. Like cachexic KL animals, FDG uptake in fasted animals increased in brain (p&lt;0.0001), perhaps due to increased FDG blood pool. FDG uptake in skeletal muscles and brown adipose tissue decreased (both p&lt;0.05) in fasted state suggesting lower muscle activity and decreased thermogenesis respectively. Dexa-induced muscle atrophy also resulted in decreased FDG uptake in gastrocnemius/soleus muscles (SUVmean 0.63 vehicle vs. 0.45 dexa, p&lt;0.05) but no changes in skeletal muscle FDG uptake were noted in cachexic animals. In contrast to KL animals, GDF15 injection resulted in decreased FDG uptake in myocardium (p&lt;0.05). Overall, the cachexic FDG signature showed differences to other wasting conditions in this mouse model, suggesting different underlying mechanisms. Total-body PET can reveal diverse metabolic wasting states. We aim to elucidate mechanisms of metabolic changes in cachexia to allow metabolic subtyping and personalised treatment options. Please click on the 'PDF' for the full abstract!

18F]FDG PET for mapping the cerebral glucose metabolic characteristics of drug-sensitive and drug-resistant epilepsy in pediatric patients.

This study aimed to investigate [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) mapping for cerebral glucose metabolism in drug-sensitive and drug-resistant pediatric epilepsy patients. This retrospective study enrolled 40 patients and 25 controls. Patients were categorized into drug-sensitive epilepsy (n = 22) and drug-resistant epilepsy (n = 18) according to the seizure frequency at follow-up. All patients underwent two [18F]FDG PET scans separated by a minimum of one year. Absolute asymmetry index (|AI|) was calculated for assessing metabolic differences and changes in epileptic foci. Statistical Parametric Mapping (SPM) was utilized to reveal voxel-wise metabolic characteristics and alterations throughout the brain. Network analysis based on graph theory was used to investigate network-level differences between the two patient groups. The drug-sensitive group showed a lower |AI| at both baseline (P = 0.038) and follow-up (P = 0.003) PET scans than the drug-resistant group. |AI| decreased in the drug-sensitive group and increased in the drug-resistant group across scans, but these trends were not statistically significant (P = 0.240 and P = 0.450, respectively). Both groups exhibited hypometabolism at baseline. The drug-sensitive group showed less hypometabolic brain regions than the drug-resistant group. The drug-sensitive maintained stable level of hypometabolism between the two scans, whereas the drug-resistant group showed an increasing hypometabolism. Network analysis demonstrated that the drug-sensitive group had a higher global efficiency, average degree, and clustering, along with a shorter characteristic path length compared to the drug-resistant group. For the first time, this study revealed in vivo cerebral glucose metabolic pattern of nonsurgical pediatric epilepsy patients treated by antiepileptic drugs. Especially, drug-resistant epilepsy patients represented significantly extensive and progressive hypometabolism with inefficient brain network connectivity compared with drug-sensitive epilepsy. [18F]FDG PET imaging may be a potential visual approach for theranostics of epilepsy patients.

Efficacy of surgery in the management of multiple recurrences of retroperitoneal dedifferentiated liposarcoma.

Retroperitoneal dedifferentiated liposarcoma is associated with a high risk of recurrence; however, treatment strategies that are more effective than surgery remain to be established. This study aimed to determine the optimal number of surgeries that would be effective for patients with recurrent disease. Furthermore, the improvement in prognosis was evaluated according to the malignancy level. The effect of each type of surgery on the prognosis of 118 patients with retroperitoneal dedifferentiated liposarcoma treated at the Osaka International Cancer Institute between 1997 and 2022 was investigated. Among the 118 patients, 103 underwent initial surgery, while 54 and 30 patients underwent second and third surgeries, respectively. The overall and disease-free survival rates of each group were compared using the Kaplan-Meier method, and the log-rank test was used to determine statistical significance in univariate analysis. 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) was used to assess malignancy. Maximum standardized uptake values (SUVmax) of ≥ 4 and < 4 were classified as high and low malignancy, respectively. The first and second surgeries resulted in a significant improvement in the overall survival rate, regardless of the malignancy level (p < 0.001); however, no significant improvement in prognosis was observed after the third surgery (p = 0.077). Low-grade malignancies are associated with a better postoperative prognosis, even in cases of recurrence. In contrast, high-grade malignancies exhibit a reduction in surgical efficacy. This study highlights the importance of considering the tumor malignancy level and the patient's overall condition when deciding whether to perform repeated surgical interventions. Surgical treatment can prolong overall survival, even in patients with recurrence; however, it is advisable to assess malignancy levels when determining the suitability of surgery beyond the second recurrence.