18F-FDG Positron Emission Tomography Scans Research Articles

Impact of different image reconstructions on PET quantification in non-small cell lung cancer: a comparison of adenocarcinoma and squamous cell carcinoma

Positron emission tomography (PET) using 18F-fludeoxyglucose (18F-FDG) is an established imaging modality for tumor staging in patients with non-small cell lung cancer (NSCLC). There is a growing interest in using 18F-FDG PET for therapy response assessment in NSCLC which relies on quantitative PET parameters such as standardized uptake values (SUV). Different reconstruction algorithms in PET may affect SUV. We sought to determine the variation of SUV in patients with NSCLC when using ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) in latest-generation digital PET/CT, including a subanalysis for adenocarcinoma and squamous cell carcinoma. A total of 58 patients (34 = adenocarcinoma, 24 = squamous cell carcinoma) who underwent a clinically indicated 18F-FDG PET/CT for staging were reviewed. PET images were reconstructed with OSEM and BSREM reconstruction with noise penalty strength β-levels of 350, 450, 600, 800 and 1200. Lung tumors maximum standardized uptake value (SUVmax) were compared. Lung tumors SUVmax were significantly lower in adenocarcinomas compared to squamous cell carcinomas in all reconstructions evaluated (all p < 0.01). Comparing BSREM to OSEM, absolute SUVmax differences were highest in lower β-levels of BSREM with + 2.9 ± 1.6 in adenocarcinoma and + 4.0 ± 2.9 in squamous cell carcinoma (difference between histology; p-values > 0.05). There was a statistically significant difference of the relative increase of SUVmax in adenocarcinoma (mean + 34.8%) and squamous cell carcinoma (mean 23.4%), when using BSREM350 instead of OSEMTOF (p < 0.05). In NSCLC the relative change of SUV when using BSREM instead of OSEM is significantly higher in adenocarcinoma as compared to squamous cell carcinoma. The impact of BSREM on SUV may vary in different histological subtypes of NSCLC. This highlights the importance for careful standardization of β-value used for serial 18F-FDG PET scans when following-up NSCLC patients.

The Metabolic Activity of Caudate and Prefrontal Cortex Negatively Correlates with the Severity of Idiopathic Parkinson's Disease.

Positron emission tomography (PET) scan with tracer [18F]-fluorodeoxy-glucose (18F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson’s disease (IPD). Previous studies using 18F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individuals were included as normal controls. Following 18F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hypermetabolism was observed in the cerebellum and vermis. There was a negative correlation (p=0.007, r=-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y (P=0.033, r=-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.

Correlation between the probability of malignancy and maximum standard uptake values of mediastinal lymph nodes on 18F-FDG positron emission tomography scan sampled by endobronchial ultrasound-guided-transbronchial needle aspiration:A retrospective analysis

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is frequently used as an important initial investigation for diagnosing and staging for both suspected malignant and benign mediastinal lesions for the last 10 years. AIM: We aimed to analyze the correlation between probability of malignity by EBUS-TBNA and maximum standard uptake value (SUVmax) obtained by 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET CT). METHODS: This is a retrospective study using hospitals' database records. Demographic features of the patients, characteristics of the biopsied lymph nodes (LNs), PET-CT results, and SUVmax are obtained from hospital database system. RESULTS: A total of 322 patients underwent EBUS-TBNA for a final diagnosis. The mean age was 59.4 years. The most common final diagnosis was nonsmall cell lung cancer. When we compared the average SUVmax, as the SUVmax increased, the probability of malignity increased significantly (P < 0.001). We studied a Youden index for SUVmax and the cutoff point for SUVmax was 9 for 54.39% sensitivity and 79.1% specificity. CONCLUSION: Our study in a real-life setting showed that EBUS-TBNA is effective in diagnosing patients who had mediastinal LNs suspected of malignancy. We also showed that as the SUVmax increased, the probability of malignancy increased. We believe that more data are needed from a larger number of patients from different centers.

Longitudinal effects of aging on 18F-FDG distribution in cognitively normal elderly individuals

Previous studies of aging effects on fluorine-18-labeled fluorodeoxyglucose (18F-FDG) distribution have employed cross-sectional designs. We examined aging effects on 18F-FDG distribution using both cross-sectional and longitudinal assessments. We obtained two 18F-FDG positron emission tomography scans at two different time points from 107 cognitively normal elderly participants. The participants’ mean ages at baseline and second scans were 67.9 and 75.7, respectively. The follow-up period ranged from 4 to 11 years with a mean of 7.8 years. The voxel-wise analysis revealed significant clusters in which 18F-FDG uptake was decreased between baseline and second scans (p < 0.05, family-wise error corrected) in the anterior cingulate cortex (ACC), posterior cingulate cortex/precuneus (PCC/PC), and lateral parietal cortex (LPC). The cross-sectional analysis of 18F-FDG uptake and age showed significant correlations in the ACC (p = 0.016) but not the PCC/PC (p = 0.240) at baseline, and in the ACC (p = 0.004) and PCC/PC (p = 0.002) at the second scan. The results of longitudinal assessments suggested that 18F-FDG uptake in the ACC, PCC/PC, and LPC decreased with advancing age in cognitively normal elderly individuals, and those of the cross-sectional assessments suggested that the trajectories of age-associated 18F-FDG decreases differed between the ACC and PCC/PC.

A combined study of 18F-FDG PET-CT and fMRI for assessing resting cerebral function in patients with major depressive disorder.

The present study investigated changes in the regional cerebral metabolic rates of glucose uptake (rCMRglc) using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and regional homogeneity (ReHo), together with resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients with major depressive disorder (MDD). In total, 18 patients with untreated MDD and 17 healthy control subjects underwent 18F-FDG PET and BOLD-fMRI scanning. The MDD patients' cerebral changes, measured as rCMRglc and ReHo values, were mapped and statistically analyzed. Compared with the control group, the patients with MDD had a decreased rCMRglc in the bilateral superior, middle and inferior frontal gyrus, in the bilateral superior and middle temporal gyrus, in the bilateral anterior cingulate cortex, in the bilateral putamen and caudate, and in the left pallidum, but an increased rCMRglc in the bilateral hippocampus and left thalamus. The ReHo values in the patient group were decreased in the bilateral superior and middle frontal gyrus, left pallidum, bilateral putamen and left anterior cingulate cortex, but increased in the right hippocampus and thalamus. No statistically significant differences were identified between decreased metabolism and ReHo brain regions of MDD patients (χ2=9.16; P=0.90) and between increased metabolism and ReHo brain regions (χ2=3.96; P=0.27), when comparing activated brain regions of PET and MRI. The standardized uptake values (SUV) of the bilateral superior, middle and inferior frontal gyrus, bilateral superior and middle temporal gyrus, bilateral putamen, the left caudate and pallidum, the left anterior cingulate cortex, and the bilateral hippocampus and thalamus were correlated with the ReHo (r=0.51–0.83; P<0.05). However, no correlation was detected between the SUV and ReHo in the right caudate and anterior cingulate cortex (r=0.41 and 0.37, respectively; P>0.05). Taken together, these results demonstrated that patients with MDD displayed characteristic patterns regarding changes of brain glucose uptake and ReHo in the resting state. Furthermore, 18F-FDG PET may be a more sensitive technique compared with BOLD-fMRI for the identification of brain lesions in patients with MDD.

Metabolic and Electrophysiological Changes Associated to Clinical Improvement in Two Severely Traumatized Subjects Treated With EMDR—A Pilot Study

Neuroimaging represents a powerful tool to investigate the neurobiological correlates of Eye Movements Desensitization and Reprocessing (EMDR). The impact of EMDR on cortical and sub-cortical brain regions has been proven by several investigations demonstrating a clear association between symptoms disappearance and changes in cortical structure and functionality. The aim of this study was to assess by electroencephalography (EEG) and for the first time by positron emission tomography (PET) the changes occurring after EMDR therapy in two cases of psychological trauma following brain concussion and comatose state due to traffic accident. A 28 and a 29 years old men underwent extensive neuropsychological examination, which investigated: (i) categorical and phonological verbal fluency; (ii) episodic verbal memory; (iii) executive functions; (iv) visuospatial abilities; (v) attention and working memory as well as clinical assessment by means of psychopathological tests (CAPS, IES, BDI, SCL90R, and DES). They were then treated by eight sessions of EMDR. During the first session EEG monitoring was continuously performed and 18F-FDG PET scans, depicting brain metabolism, were acquired at rest within a week (T0). After the last session, in which the two clients were considered to be symptoms-free, neuropsychological, clinical, and PET assessment were repeated (T1). PET data were semi-quantitatively compared to a group of 18 normal controls, as for EEG the preferential cortical activations were disclosed by thresholding the individual z-score to a p < 0.05. There was a significant improvement in clinical condition for both clients associated with a significant decrease in CAPS scores. IES and BDI were found to be pathological at T0 and improved at T1 in only one subject. Visuo-constructive abilities and abstract reasoning improved after EMDR in both subjects. As for EEG, the most striking changes occurred in fronto-temporal-parietal cortex in subject 1 while subject 2 showed only minor changes. PET showed more pronounced metabolism in orbito-frontal and prefrontal cortex at T1 as compared to T0 in both subjects. In conclusion both clients had a clear clinical improvement in PTSD symptoms associated with metabolic and electrophysiological changes in limbic and associative cortex, respectively, highlighting the value of EMDR also in such extreme pathological conditions.

Optimal transformations leading to normal distributions of positron emission tomography standardized uptake values

The statistical analysis of positron emission tomography (PET) standardized uptake value (SUV) measurements is challenging due to the skewed nature of SUV distributions. This limits utilization of powerful parametric statistical models for analyzing SUV measurements. An ad-hoc approach, which is frequently used in practice, is to blindly use a log transformation, which may or may not result in normal SUV distributions. This study sought to identify optimal transformations leading to normally distributed PET SUVs extracted from tumors and assess the effects of therapy on the optimal transformations. Methods. The optimal transformation for producing normal distributions of tumor SUVs was identified by iterating the Box–Cox transformation parameter (λ) and selecting the parameter that maximized the Shapiro–Wilk P-value. Optimal transformations were identified for tumor SUVmax distributions at both pre and post treatment. This study included 57 patients that underwent 18F-fluorodeoxyglucose (18F-FDG) PET scans (publically available dataset). In addition, to test the generality of our transformation methodology, we included analysis of 27 patients that underwent 18F-Fluorothymidine (18F-FLT) PET scans at our institution. Results. After applying the optimal Box–Cox transformations, neither the pre nor the post treatment 18F-FDG SUV distributions deviated significantly from normality (P > 0.10). Similar results were found for 18F-FLT PET SUV distributions (P > 0.10). For both 18F-FDG and 18F-FLT SUV distributions, the skewness and kurtosis increased from pre to post treatment, leading to a decrease in the optimal Box–Cox transformation parameter from pre to post treatment. There were types of distributions encountered for both 18F-FDG and 18F-FLT where a log transformation was not optimal for providing normal SUV distributions. Conclusion. Optimization of the Box–Cox transformation, offers a solution for identifying normal SUV transformations for when the log transformation is insufficient. The log transformation is not always the appropriate transformation for producing normally distributed PET SUVs.

MRNA Expression of SLC5A5 and SLC2A Family Genes in Papillary Thyroid Cancer: An Analysis of The Cancer Genome Atlas.

PurposeThe present study investigated the dynamics and prognostic role of messenger RNA (mRNA) expression responsible for 18F-fluorodeoxyglucose (FDG) uptake in FDG positron emission tomography (PET) and radioactive iodine (131I) uptake in whole-body radioactive iodine scans (WBS) in papillary thyroid cancer (PTC) patients.Materials and MethodsThe primary and processed data were downloaded from the Genomic Data Commons Data Portal. Expression data for sodium/iodide symporter (solute carrier family 5 member 5, SLC5A5), hexokinase (HK1–3), glucose-6-phosphate dehydrogenase (G6PD), and glucose transporter (solute carrier family 2, SLC2A1–4) mRNA were collected.ResultsExpression of SLC5A5 mRNA were negatively correlated with SLC2A1 mRNA and positively correlated with SLC2A4 mRNA. In PTC with BRAF mutations, expressions of SLC2A1, SLC2A3, HK2, and HK3 mRNA were higher than those in PTC without BRAF mutations. Expression of SLC5A5, SLC2A4, HK1, and G6PD mRNA was lower in PTC without BRAF mutation. PTCs with higher expression of SLC5A5 mRNA had more favorable disease-free survival, but no association with overall survival.ConclusionExpression of SLC5A5 mRNA was negatively correlated with SLC2A1 mRNA. This finding provides a molecular basis for the management of PTC with negative WBS using 18F-FDG PET scans. In addition, higher expression of SLC5A5 mRNA was associated with less PTC recurrence, but not with deaths.

Factors influencing brown fat activation in FDG PET/CT: a retrospective analysis of 15,000+ cases.

Brown fat can exhibit high uptake of fluorine-18 fludeoxyglucose (18F-FDG) on positron emission tomography (PET) and interferes with interpretation of the scan. The goal of this study was to identify factors that may influence brown adipose tissue (BAT) activation. A retrospective study of 18F-FDG PET scans was performed using a database of 15,109 PET/CT reports. BAT activation reported by nuclear medicine physicians and factors influencing BAT activation were gathered. The data were analyzed using in-house software. The total reported BAT activation was 3.6%. BAT activation was reported significantly more often in patients who were female (p < 0.0001), younger (p < 0.0001), with lower body mass index (p < 0.0001), with lower blood glucose levels (p = 0.01), indicated for breast cancer (p = 0.004), not administered chemotherapy recently before the scan (p < 0.0001) and shown to have BAT activation in a previous scan (p < 0.0001). BAT activation was also reported significantly more for lower outdoor temperatures (p < 0.0001) and for late morning scans than for afternoon (p = 0.005) and early morning (p = 0.001) scans. This retrospective study of 15,109 scans highlights multiple factors contributing to BAT activation on 18F-FDG PET. The identification of new factors influencing BAT and confirmation of previously identified factors with a larger data set can be used to more accurately identify patients at risk for BAT activation so that prevention strategies can be implemented. Advances in knowledge: This study presents new factors associated with higher incidence of BAT activation, such as time of day, previous BAT activation and breast cancer. Conversely, recent chemotherapy was associated with reduced incidence of BAT activation.

Assessment of pulmonary 18F-FDG-PET uptake and cytokine profiles in non-small cell lung cancer patients treated with radiotherapy and erlotinib

PurposeTo investigate effects of radiotherapy (RT) and erlotinib on pulmonary glucose uptake using 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) during and after treatment of non-small cell lung cancer (NSCLC) and to identify associations between serum cytokine levels and lung glucose uptake. Material and methodsTwenty-seven patients with advanced NSCLC, receiving RT alone or concomitant RT and erlotinib therapy, were examined by 18F-FDG PET before, during, and after treatment. A total of 57 18F-FDG PET scans were analyzed. Pulmonary 18F-FDG uptake and radiotherapy dose mapping were used to acquire dose-response curves for each patient, where subsequent linear regression gave a glucose uptake level in the un-irradiated parts of the lungs (SUV0) and a response slope (ΔSUV). Serum cytokine levels at corresponding time points were assessed using a multiplex bioassay. Correlations between the most robust cytokines and lung 18F-FDG dose response parameters were further investigated. ResultsFrom the dose response analysis, SUV0 at post-therapy was significantly higher (P<0.001) than at mid- and pre-therapy (45% and 58%, respectively) for the group receiving RT+erlotinib. Also, SUV0 at post-therapy was higher for patients receiving RT+erlotinib compared to RT alone (42%; P<0.001). No differences in ΔSUV were seen with treatments or time. SUV0 was positively associated (r=0.47, P=0.01) with serum levels of the chemokine C–C motif ligand 21 (CCL21) for patients receiving RT+erlotinib. ConclusionsConcomitant RT and erlotinib causes an elevation in pulmonary 18F-FDG uptake post treatment compared to RT alone. Pulmonary glucose uptake is associated with an upregulation of a chemokine (CCL21) involved in inflammatory reactions.

Quantitative analysis of dynamic 18F-FDG PET/CT for measurement of lung inflammation

BackgroundAn inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, is present in some patients with chronic obstructive pulmonary disease (COPD). Thoracic fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been proposed as a promising imaging biomarker to assess this inflammation. We sought to introduce a fully quantitative analysis method and compare this with previously published studies based on the Patlak approach using a dataset comprising 18F-FDG PET scans from COPD subjects with elevated circulating inflammatory markers (fibrinogen) and matched healthy volunteers (HV). Dynamic 18F-FDG PET scans were obtained for high-fibrinogen (>2.8 g/l) COPD subjects (N = 10) and never smoking HV (N = 10). Lungs were segmented using co-registered computed tomography images and subregions (upper, middle and lower) were semi-automatically defined. A quantitative analysis approach was developed, which corrects for the presence of air and blood in the lung (qABL method), enabling direct estimation of the metabolic rate of FDG in lung tissue. A normalised Patlak analysis approach was also performed to enable comparison with previously published results. Effect sizes (Hedge’s g) were used to compare HV and COPD groups.ResultsThe qABL method detected no difference (Hedge’s g = 0.15 [−0.76 1.04]) in the tissue metabolic rate of FDG in the whole lung between HV (μ = 6.0 ± 1.9 × 10−3 ml cm−3 min−1) and COPD (μ = 5.7 ± 1.7 × 10−3 ml cm−3 min−1). However, analysis with the normalised Patlak approach detected a significant difference (Hedge’s g = −1.59 [−2.57 −0.48]) in whole lung between HV (μ = 2.9 ± 0.5 × 10−3 ml cm−3 min−1) and COPD (μ = 3.9 ± 0.7 × 10−3 ml cm−3 min−1). The normalised Patlak endpoint was shown to be a composite measure influenced by air volume, blood volume and actual uptake of 18F-FDG in lung tissue.ConclusionsWe have introduced a quantitative analysis method that provides a direct estimate of the metabolic rate of FDG in lung tissue. This work provides further understanding of the underlying origin of the 18F-FDG signal in the lung in disease groups and helps interpreting changes following standard or novel therapies.

Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma.

Background18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated.MethodsCorrelations between EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients. Molecular causal relationships between EGFR or KRAS mutation status and glucose metabolism were then elucidated in 62 lung adenocarcinomas using cap analysis of gene expression (CAGE), a method to determine and quantify the transcription initiation activities of mRNA across the genome.ResultsEGFR and KRAS mutations were detected in 334 (46%) and 83 (11%) of the 734 lung adenocarcinomas, respectively. The remaining 317 (43%) patients had wild-type tumors for both genes. EGFR mutations were more frequent in tumors with lower SUVmax. In contrast, no relationship was noted between KRAS mutation status and SUVmax. CAGE revealed that 4 genes associated with glucose metabolism (GPI, G6PD, PKM2, and GAPDH) and 5 associated with the cell cycle (ANLN, PTTG1, CIT, KPNA2, and CDC25A) were positively correlated with SUVmax, although expression levels were lower in EGFR-mutated than in wild-type tumors. No similar relationships were noted with KRAS mutations.ConclusionsEGFR-mutated adenocarcinomas are biologically indolent with potentially lower levels of glucose metabolism than wild-type tumors. Several genes associated with glucose metabolism and the cell cycle were specifically down-regulated in EGFR-mutated adenocarcinomas.

Prognostic Implications of the SUVmax of Primary Tumors and Metastatic Lymph Node Measured by 18F-FDG PET in Patients With Uterine Cervical Cancer: A Meta-analysis.

We conducted a meta-analysis to evaluate the prognostic value of the SUVmax measured in pretreatment primary lesions and metastatic lymph nodes (LNs) on 18F-FDG PET scans in patients with uterine cervical cancer. A systematic search of EMBASE and MEDLINE was performed using the keywords "positron emission tomography (PET)," "uterine cervical cancer," and "prognosis." Event-free survival and overall survival were evaluated as outcomes. The impact of SUVmax on survival was measured by the effect size of the hazard ratio (HR). Fourteen eligible studies including 1150 patients were analyzed. Patients with a high primary SUVmax showed a worse prognosis, with an HR of 2.66 (95% confidence interval [CI], 1.90-3.74; P < 0.00001) for adverse events and an HR of 2.45 (95% CI, 1.74-3.45; P < 0.00001) for death. Patients with high SUVmax in metastatic pelvic LN (PLN) showed a worse prognosis, with an HR of 2.92 (95% CI, 1.94-4.39; P < 0.00001) for adverse events and an HR of 2.66 (95% CI, 1.60-4.43; P = 0.0002) for SUVmax in PLN for death. In addition, high SUVmax in metastatic para-aortic LN was associated with a worse prognosis, with an HR of 4.41 (95% CI, 2.32-8.38; P < 0.00001) for death. Patients with uterine cervical cancer and a high SUVmax primary lesion, PLN, or para-aortic LN are at higher risk of adverse events or death.

(18)F-FDG PET scanning of abdominal aortic aneurysms and correlation with molecular characteristics: a systematic review.

PurposeThe purpose of this study is to give an overview of studies investigating the role of fludeoxyglucose F18 (18F-FDG) positron emission tomography (PET) scanning in patients with aortic aneurysms with a focus on molecular characteristics of the aneurysm wall.MethodsMEDLINE, EMBASE, and the Cochrane database were searched for relevant articles. After inclusion and exclusion, we selected 18 relevant articles reporting on 18F-FDG PET scanning of aortic aneurysms.ResultsThe sample size of studies is limited, and there are no standardized imaging protocols and quantification methods. 18F-FDG PET scanning was shown to display molecular characteristics of the aortic wall. Different studies showed contradictory findings of aortic 18F-FDG uptake in aneurysm patients compared to controls.ConclusionsNon-invasively determining molecular characteristics of aortic wall weakening might lead to better rupture and growth prediction. This might influence the decision of the surgeon between conservative and surgical treatment of aneurysms. To date, there is conflicted evidence regarding the use of 18F-FDG PET scanning to predict aneurysm rupture and growth. The role of 18F-FDG PET scanning in rupture risk prediction needs to be further investigated, and standardized imaging protocols and quantification methods need to be implemented.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0153-8) contains supplementary material, which is available to authorized users.

Evaluation of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in rat models with hepatocellular carcinoma with liver cirrhosis.

Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the exact mechanism of the progression from cirrhosis to cancer remains unclear. The uptake of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is widely used as a marker of increased glucose metabolism to monitor the progression of cancer with positron emission tomography (PET)/computed tomography (CT). Here we investigated the feasibility of using (18)F-FDG PET/CT in the diethylnitrosamine (DEN) mediated experimental hepatocellular carcinoma model. Rats received weekly intraperitoneal injections of DEN for 16 weeks for induction of HCC. We recorded starting from 0 days or 0 weeks after the last DEN injection. The weight and survival rate of rats were then measured. Also, an (18)F-FDG PET scan and serum analysis were performed at minus 2, 0, plus 2, and plus 4 weeks after the last DEN injection. The body weight of rats was maintained between 350 g and 370 g during 14 and 20 weeks, and the rats were euthanized at 35 days after the last DEN injection. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphate (ALP) were significantly higher at zero weeks after the last DEN injection. The (18)F-FDG uptake for the quantitative evaluation of HCC was done by measuring the region of interest (ROI). At minus two weeks after the last DEN injection, the ROI of rats had significantly increased compared to the normal group, in a time-dependent manner. These results suggest that FDG uptake serves as a good screening test to evaluate the feasibility of DEN-induced HCC.

In vivo braak staging using 18F-AV1451 Tau PET imaging

Alzheimer's disease (AD) related tau pathology has previously been classified into six consecutive Braak stages describing the gradual regional deposition of hyperphosphorylated tau protein over the course of the disease. Positron emission tomography (PET) using the ligand 18F-AV1451 (previously T807) now renders possible the in vivo assessment and staging of tau pathology and its relationship with cerebral glucose metabolism as measured with 18F-FDG. Nineteen elderly and two young normal controls (NCs), as well as eight AD patients (Table 1), underwent 18F-AV1451 PET scanning (80-100 min tissue ratio, cerebellar gray matter reference). Structural magnetic resonance (MR) images were co-registered to the respective PET images and segmented into regions of interest (ROIs) corresponding anatomically to the transentorhinal (I/II), limbic (III/IV), and isocortical (V/VI) Braak stages using FreeSurfer v5.1 (Figure 1). High AV1451 binding was identified by calculating a ratio of voxels > 2 SD above NC mean over total voxel count within each ROI. In addition, seventeen NCs and five AD patients also received 18F-FDG PET scans (30-60 min tissue ratio, pontine reference). Combined FreeSurfer ROIs We found clear separation of NCs from AD patients throughout all Braak stages (Figure 2). Linear regression identified higher AV1451 uptake in early stage Braak ROIs as being highly predictive of higher uptake in later stage Braak ROIs, independent of ApoE status or age (Figure 3). Furthermore, linear regression of mean 18F-AV1451 uptake in Braak ROIs on 18F-FDG uptake in a predefined set of ROIs covering regions typically susceptible for AD-related hypometabolism yielded significant negative relationships in Braak ROIs I/II and III/IV.

Oncocytic adenomas of thyroid-mimicking benign or metastatic disease on 18F-FDG-PET scan.

The literature is sparse concerning 18F-fluorodeoxyglucose (18F-FDG) accumulation in the Hürthle cell neoplasm (HCN) of the thyroid. Given the difficulty of accurately diagnosing HCN, even with ultrasound (US) and fine needle aspiration biopsy (FNAB), the ability to accurately characterize these lesions by 18F-FDG positron emission tomography (PET) would be of value. To describe six cases of oncocytic proliferation in the thyroid gland that mimics the presence of metastatic disease and was detected incidentally by an 18F-FDG PET scan. We conducted whole-body 18F-FDG PET examinations for cancer staging in 1862 oncological patients from 2012 to 2013. Among them, six subjects (4 women, 2 men; age range, 45-85 years) with focal-enhanced 18F-FDG accumulation in the thyroid gland were selected from the study population. This study group was further investigated using 99 m-Tc-pertechnetate scintigraphy, US, and FNAB. Two experienced nuclear physicians reviewed the images. Gray-scale US and color Doppler (CD) sonographic examinations of the thyroid were undertaken for all subjects using a sonographic device Logiq 5 Expert (GE Medical Systems, Osaka, Japan) equipped with a 7-12 MHz linear array transducer. In all six cases, abnormal 18F-FDG uptake was found locally in the thyroid. The average SUVmax of the HCN was 5.8 (range, 2.6-16). In all six cases, 99 m-Tc-pertechnetate scintigraphy showed a cold spot. Compared with normal parenchymal vascularity, five of the six masses were shown to be hypervascular by CD ultrasonography. On PET scans, oncocytic proliferations of the thyroid may mimic metastases of other malignancies. The focal-enhanced uptake of 18F-FDG PET may be associated with a focal increase in the metabolic activity of the thyroid parenchyma due to the presence of oncocytes. Our study emphasizes the importance of obtaining cytological evidence before making a diagnosis of metastatic disease.

¹⁸F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

¹⁸F-FDFG uptake by brain tissue as measured by positron emission tomography (PET) is a well-established method for assessment of brain function in people with dementia. Certain findings on brain PET scans can potentially predict the decline of mild cognitive Impairment (MCI) to Alzheimer's disease dementia or other dementias. To determine the diagnostic accuracy of the ¹⁸F-FDG PET index test for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease dementia or other forms of dementia at follow-up. We searched the Cochrane Register of Diagnostic Test Accuracy Studies, MEDLINE, EMBASE, Science Citation Index, PsycINFO, BIOSIS previews, LILACS, MEDION, (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases to January 2013. We checked the reference lists of any relevant studies and systematic reviews for additional studies. We included studies that evaluated the diagnostic accuracy of ¹⁸F-FDG PET to determine the conversion from MCI to Alzheimer's disease dementia or to other forms of dementia, i.e. any or all of vascular dementia, dementia with Lewy bodies, and fronto-temporal dementia. These studies necessarily employ delayed verification of conversion to dementia and are sometimes labelled as 'delayed verification cross-sectional studies'. Two blinded review authors independently extracted data, resolving disagreement by discussion, with the option to involve a third review author as arbiter if necessary. We extracted and summarised graphically the data for two-by-two tables. We conducted exploratory analyses by plotting estimates of sensitivity and specificity from each study on forest plots and in receiver operating characteristic (ROC) space. When studies had mixed thresholds, we derived estimates of sensitivity and likelihood ratios at fixed values (lower quartile, median and upper quartile) of specificity from the hierarchical summary ROC (HSROC) models. We included 14 studies (421 participants) in the analysis. The sensitivities for conversion from MCI to Alzheimer's disease dementia were between 25% and 100% while the specificities were between 15% and 100%. From the summary ROC curve we fitted we estimated that the sensitivity was 76% (95% confidence interval (CI): 53.8 to 89.7) at the included study median specificity of 82%. This equates to a positive likelihood ratio of 4.03 (95% CI: 2.97 to 5.47), and a negative likelihood ratio of 0.34 (95% CI: 0.15 to 0.75). Three studies recruited participants from the same Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort but only the largest ADNI study (Herholz 2011) is included in the meta-analysis. In order to demonstrate whether the choice of ADNI study or discriminating brain region (Chételat 2003) or reader assessment (Pardo 2010) make a difference to the pooled estimate, we performed five additional analyses. At the median specificity of 82%, the estimated sensitivity was between 74% and 76%. There was no impact on our findings. In addition to evaluating Alzheimer's disease dementia, five studies evaluated the accuracy of ¹⁸F-FDG PET for all types of dementia. The sensitivities were between 46% and 95% while the specificities were between 29% and 100%; however, we did not conduct a meta-analysis because of too few studies, and those studies which we had found recruited small numbers of participants. Our findings are based on studies with poor reporting, and the majority of included studies had an unclear risk of bias, mainly for the reference standard and participant selection domains. According to the assessment of Index test domain, more than 50% of studies were of poor methodological quality. It is difficult to determine to what extent the findings from the meta-analysis can be applied to clinical practice. Given the considerable variability of specificity values and lack of defined thresholds for determination of test positivity in the included studies, the current evidence does not support the routine use of ¹⁸F-FDG PET scans in clinical practice in people with MCI. The ¹⁸F-FDG PET scan is a high-cost investigation, and it is therefore important to clearly demonstrate its accuracy and to standardise the process of ¹⁸F-FDG PET diagnostic modality prior to its being widely used. Future studies with more uniform approaches to thresholds, analysis and study conduct may provide a more homogeneous estimate than the one available from the included studies we have identified.

PET/CT-guided treatment planning for paediatric cancer patients: a simulation study of proton and conventional photon therapy.

To investigate the impact of including fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) scanning in the planning of paediatric radiotherapy (RT). Target volumes were first delineated without and subsequently re-delineated with access to (18)F-FDG PET scan information, on duplicate CT sets. RT plans were generated for three-dimensional conformal photon RT (3DCRT) and intensity-modulated proton therapy (IMPT). The results were evaluated by comparison of target volumes, target dose coverage parameters, normal tissue complication probability (NTCP) and estimated risk of secondary cancer (SC). Considerable deviations between CT- and PET/CT-guided target volumes were seen in 3 out of the 11 patients studied. However, averaging over the whole cohort, CT or PET/CT guidance introduced no significant difference in the shape or size of the target volumes, target dose coverage, irradiated volumes, estimated NTCP or SC risk, neither for IMPT nor 3DCRT. Our results imply that the inclusion of PET/CT scans in the RT planning process could have considerable impact for individual patients. There were no general trends of increasing or decreasing irradiated volumes, suggesting that the long-term morbidity of RT in childhood would on average remain largely unaffected. (18)F-FDG PET-based RT planning does not systematically change NTCP or SC risk for paediatric cancer patients compared with CT only. 3 out of 11 patients had a distinct change of target volumes when PET-guided planning was introduced. Dice and mismatch metrics are not sufficient to assess the consequences of target volume differences in the context of RT.

Intratumor Textural Heterogeneity on Pretreatment (18)F-FDG PET Images Predicts Response and Survival After Chemoradiotherapy for Hypopharyngeal Cancer.

Increasing evidence suggests that intratumor heterogeneity of solid tumors characterized by textural features on 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) images is associated with response to chemoradiotherapy (CRT) and survival. The current study aimed to determine whether a similar relationship exists in hypopharyngeal squamous cell carcinoma (HPSCC). This study investigated 27 patients with HPSCC who underwent cisplatin-based induction chemotherapy followed by definitive CRT underwent pretreatment (18)F-FDG PET/CT. Standardized uptake value (SUV), metabolic tumor volume (MTV), and textural features (coarseness, busyness, complexity, and contrast) of primary tumors were measured. Patients were classified as nonresponders or responders according to the response evaluation criteria in solid tumors. The capacity of each parameter to classify response was assessed using the Mann-Whitney U test. Cox-proportional hazard models were used to identify variables associated with disease-free survival (DFS) and overall survival (OS). Of 70 patients, 58 (83%) had complete or partial response after CRT. Responders showed lower maximum SUV (P=0.037), lower MTV (P=0.039), lower coarseness (P<0.001), and busyness (P=0.015) compared with nonresponders. Multivariate analysis showed that high coarseness (P=0.001, hazard ratio [HR] 5.65; 95% confidence interval [CI] 2.12-15.07) and busyness (P=0.045; HR 2.56; 95% CI 1.02-6.42) were independently associated with poor DFS, and that high coarseness (P=0.013; HR 2.48; 95% CI 1.21-5.09) was independently associated with poor OS. Abnormal coarseness in baseline (18)F-FDG PET scans may be useful for predicting response and survival after CRT in HPSCC patients.