Underwent 18F-FDG Positron Emission Tomography Research Articles

18F-FDG brain PET: a metabolic predictive factor for gait improvement after cerebrospinal fluid shunting in normal pressure hydrocephalus?

The pathophysiology of normal pressure hydrocephalus (NPH) has not been fully elucidated. Treating NPH with cerebrospinal fluid shunts to improve gait disturbances may have some risks and inconsistent benefits. No clear predictive factor has been identified thus far. This preliminary study aimed to evaluate the predictive value of preoperative brain 18F-FDG positron emission tomography (PET) on overall gait response in patients with NPH. Sixteen patients with NPH who underwent 18F-FDG PET before shunt surgery between 2012 and 2022 were included retrospectively and separated into two groups based on their gait response one year after surgery: responders (R) or nonresponders (NR). Brain glucose metabolism was assessed using visual and semiquantitative analyses using SPM8 software (Welcome Department of Cognitive Neurology, University College, London, UK). Five regions of interest were selected: global cortex, cerebellum, thalamus, striatum, and midbrain. Visual interpretation showed more frequent hypometabolism of the striatum, thalamus and global cortex in NR. None of the patients showing hypometabolism of these regions were R. Based on these results, the visual interpretation allowed us to identify 3/8 NR and 8/8 R. Semiquantitative analysis confirmed significantly lower thalamic metabolism in the NR group (P=0.037) and a trend towards lower metabolism of the striatum (P=0.075) with an area under the curve of 0.77 for thalamic metabolism to discriminate between R and NR. This preliminary study using brain 18F-FDG PET suggests that reduced brain metabolism in the thalamus and striatum along with cortical hypometabolism may be associated with poorer gait response to CSF shunting in normal pressure hydrocephalus (NPH). Although these findings suggest that preoperative brain 18F-FDG PET could potentially aid in selecting appropriate candidates for shunt surgery, further research with larger sample sizes is needed to confirm these results.

Noninvasive monitoring of allograft rejection in a rat lung transplant model: Application of machine learning-based 18F-fluorodeoxyglucose positron emission tomography radiomics.

Standardized uptake values (SUVs) derived from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) are valuable but insufficient for detecting lung allograft rejection (AR). Using a rat lung transplantation (LTx) model, we investigated correlations of AR with the SUVmax and PET-derived radiomics and further evaluated the performance of machine learning (ML)-based radiomics for monitoring AR. LTx was performed on 4 groups of rats: isograft, allograft-cyclosporinecontinuous (CsAcont), allograft-CsAdelayed, and allograft-CsA1week. Each rat underwent 18F-FDG PET at week 3 or 6. The SUVmax and radiomic features were extracted from the PET images. Least absolute shrinkage and selection operator regression was used to construct a radiomics score (Rad-score). Ten modeling algorithms with 7 feature selection methods were performed to develop 70 radiomics models (49 ML models and 21 logistic regression models) for monitoring AR, validated using the bootstrap method. In total, 837 radiomic features were extracted from each PET image. The SUVmax and Rad-score showed significant positive correlations with histopathology (p < .05). The area under the curve (AUC) of SUVmax for detecting AR was 0.783. The median AUC of ML models was 0.921, which was superior to that of logistic regression models (median AUC, 0.721). The optimal ML model using a random forest modeling algorithm with random forest feature selection method exhibited the highest AUC of 0.982 (95% confidence interval, 0.875-1.000) in all models. SUVmax provided a good correlation with AR, but ML-based PET radiomics further strengthened the power of 18F-FDG PET functional imaging for monitoring AR in LTx.

SPDL1 Overexpression Is Associated With the 18F-FDG PET/CT Metabolic Parameters, Prognosis, and Progression of Esophageal Cancer.

Esophageal cancer (ESCA) is one of the common malignant tumors. The roles and signaling mechanisms of spindle apparatus coiled-coil protein 1 (SPDL1) in ESCA progression have not been reported previously. Therefore, the expression levels and potential clinical roles of SPDL1 were investigated using data from multiple databases and tissue samples of 53 ESCA patients who underwent 18F-FDG positron emission tomography (PET)/computed tomography (CT) before therapy. The signaling mechanisms of SPDL1 involved in ESCA progression were investigated via bioinformatics analysis. The effects of SPDL1 on the growth and migration of ESCA cells were investigated using CCK-8, Edu, and transwell assays. SPDL1 was upregulated in ESCA tissues. Increased SPDL1 expression was associated with age, grade, drinking history, cancer stage, lymph node metastasis, TP53 mutation, and poor prognosis in patients with ESCA. SPDL1 overexpression was significantly correlated with SUVmax, SUVmean, and TLG of PET/CT. SPDL1 silencing inhibited cell proliferation, migration, and invasion. SPDL1 was significantly enriched in cell cycle, spliceosome, DNA replication, and other processes. The hub genes of a constructed protein–protein interaction network included CDK1, BUB1, CCNB1, BUB1B, CCNA2, CDC20, MAD2L1, AURKB, NDC80, and PLK1, which were related to SPDL1 expression. The findings of this study suggest that SPDL1 may serve as a biomarker of ESCA prognosis.

Radiomics analysis of [18F]-fluoro-2-deoxyglucose positron emission tomography for the prediction of cervical lymph node metastasis in tongue squamous cell carcinoma.

This study aimed to create a predictive model for cervical lymph node metastasis (CLNM) in patients with tongue squamous cell carcinoma (SCC) based on radiomics features detected by [18F]-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET). A total of 40 patients with tongue SCC who underwent 18F-FDG PET imaging during their first medical examination were enrolled. During the follow-up period (mean 28months), 20 patients had CLNM, including six with late CLNM, whereas the remaining 20 patients did not have CLNM. Radiomics features were extracted from 18F-FDG PET images of all patients irrespective of metal artifact, and clinicopathological factors were obtained from the medical records. Late CLNM was defined as the CLNM that occurred after major treatment. The least absolute shrinkage and selection operator (LASSO) model was used for radiomics feature selection and sequential data fitting. The receiver operating characteristic curve analysis was used to assess the predictive performance of the 18F-FDG PET-based model and clinicopathological factors model (CFM) for CLNM. Six radiomics features were selected from LASSO analysis. The average values of the area under the curve (AUC), accuracy, sensitivity, and specificity of radiomics analysis for predicting CLNM from 18F-FDG PET images were 0.79, 0.68, 0.65, and 0.70, respectively. In contrast, those of the CFM were 0.54, 0.60, 0.60, and 0.60, respectively. The 18F-FDG PET-based model showed significantly higher AUC than that of the CFM. The 18F-FDG PET-based model has better potential for diagnosing CLNM and predicting late CLNM in patients with tongue SCC than the CFM.

Metabolic network as an objective biomarker in monitoring deep brain stimulation for Parkinson\u2019s disease: a longitudinal study

BackgroundWith the advance of subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of Parkinson’s disease (PD), it is desired to identify objective criteria for the monitoring of the therapy outcome.This paper explores the feasibility of metabolic network derived from positron emission tomography (PET) with 18F-fluorodeoxyglucose in monitoring the STN DBS treatment for PD.MethodsAge-matched 33 PD patients, 33 healthy controls (HCs), 9 PD patients with bilateral DBS surgery and 9 controls underwent 18F-FDG PET scans. The DBS patients were followed longitudinally to investigate the alternations of the PD-related metabolic covariance pattern (PDRP) expressions.ResultsThe PDRP expression was abnormally elevated in PD patients compared with HCs (P < 0.001). For DBS patients, a significant decrease in the Unified Parkinson’s Disease Rating Scale (UPDRS, P = 0.001) and PDRP expression (P = 0.004) was observed 3 months after STN DBS treatment, while a rollback was observed in both UPDRS and PDRP expressions (both P < 0.01) 12 months after treatment. The changes in PDRP expression mediated by STN DBS were generally in line with UPDRS improvement. The graphical network analysis shows increased connections at 3 months and a return at 12 months confirmed by small-worldness coefficient.ConclusionsThe preliminary results demonstrate the potential of metabolic network expression as complimentary objective biomarker for the assessment and monitoring of STN DBS treatment in PD patients.Clinical Trial Registration ChiCTR-DOC-16008645. http://www.chictr.org.cn/showproj.aspx?proj=13865.

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma.

The relationship between the local immune status and cancer metabolism regarding 18F‐FDG and 18F‐FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty‐one ESCC patients who underwent 18F‐FDG PET and 18F‐FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD‐1), CD8, Ki‐67, CD34, GLUT1 (18F‐FDG transporter) and LAT1 (18F‐FAMT transporter). ESCC specimens with high tumoral PD‐L1 and high CD8‐positive lymphocytes were considered to have “hot tumor immune status.” High PD‐L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8‐positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki‐67 labelling index (P = 0.009) and CD34‐positive vessel counts (P < 0.001). SUVmax of 18F‐FDG was significantly higher in high PD‐L1 cases than in low PD‐L1 cases (P = 0.009). SUVmax of 18F‐FAMT was significantly higher in high PD‐L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18F‐FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

Assessing the Clinical Value of Myocardial Perfusion SPECT in Cardiac Sarcoidosis with Diffuse Myocardial &lt;sup&gt;18&lt;/sup&gt;F-FDG Uptake

Background: Myocardial 18F-fluorodeoxyglucose (18F-FDG) uptake is a sign of active inflammation in patients with cardiac sarcoidosis (CS) under the correct circumstance. However, even under the proper preparation, diffuse myocardial 18F-FDG uptake is frequently observed in the failing heart and misleads the CS disease activity. The aim of this study was to establish the diagnostic value of resting myocardial perfusion single photon emission computed tomography (SPECT) for assessing CS disease activity in patients with diffuse myocardial 18F-FDG uptake. Methods: We examined 39 patients with either histologically or clinically proven CS. All patients underwent 18F-FDG positron emission tomography (PET) and resting 99mTc-SPECT. The presence of perfusion-metabolic mismatch was evaluated with generating polar maps of 18F-FDG PET and 99mTc-SPECT images. Results: Increased myocardial 18F-FDG uptake was observed in 33 (85%) of 39 patients. Focal 18F-FDG uptake was detected in 16 patients and diffuse 18F-FDG uptake was seen in 17 patients. Brain natriuretic peptide (BNP) levels were significantly higher in patients with diffuse 18F-FDG uptake than those with focal 18F-FDG uptake (p=0.002). With comparing polar maps of 18F-FDG PET and 99mTc-SPECT images, 8 of 16 patients with diffuse 18F-FDG uptake and myocardial perfusion defects demonstrated perfusion-metabolic mismatch which represented active inflammatory lesions in CS. Conclusions: Simultaneous evaluation of myocardial 18F-FDG PET and 99mTc-SPECT by polar map analysis provides more relevant information for assessing disease activity in CS than 18F-FDG PET images alone. Perfusion-metabolic mismatch might indicate latent active inflammation in CS patients with diffuse myocardial 18F-FDG uptake, who had advanced heart failure.

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder

ObjectiveIdiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson’s disease (PD). Positron emission tomography (PET) with 18F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study. Methods19 iRBD patients, 38 PD patients and 19 HC subjects underwent 18F-FDG PET. The images were spatially normalized, scaled to the global mean uptake, and automatically parcellated. We contrasted regional metabolism by group, and allocated the inferred progression to one of several possible trajectories. We further investigated the correlations between 18F-FDG uptake and the disease duration in the iRBD and PD groups, respectively. We also explored relationships between 18F-FDG uptake and the Unified Parkinson’s Disease Rating Scale motor (UPDRS III) scores in the PD group. ResultsPD patients exhibited more extensive relative hyper- and hypo-metabolism than iRBD patients. We identified three dynamic metabolic trajectories, cross-sectional hypo- or hypermetabolism, cross-sectionally unchanged hypo- or hypermetabolism, cross-sectionally late hypo- or hypermetabolism, appearing only in the contrast of PD with iRBD. No correlation was found between relative 18F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores. ConclusionCerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.

Altered Brain Glucose Metabolism Assessed by 18F-FDG PET Imaging Is Associated with the Cognitive Impairment of CADASIL

Recurrent stroke and cognitive impairment are the primary features of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The cognitive deficits in these patients are known to be correlated with structural brain changes, such as white matter lesions and lacunae, and resting-state functional connectivity in brain networks. However, the associations between changes in brain glucose metabolism based on 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging and cognitive scores in CADASIL patients remain unclear. In the present study, 24 CADASIL patients and 24 matched healthy controls underwent 18F-FDG PET imaging. Brain glucose metabolism was measured in all subjects and Pearson's correlation analyses were performed to evaluate relationships between abnormal glucose metabolism in various brain areas and cognitive scores. Compared to controls, CADASIL patients exhibited significantly lower metabolism in the right cerebellar posterior lobe, left cerebellar anterior lobe, bilateral thalamus and left limbic lobe. Additionally, hypermetabolism was observed in the left precentral and postcentral gyri. Importantly, glucose metabolism in the left limbic lobe was positively associated with cognitive scores on the Mini-Mental State Examination (MMSE). Furthermore, glucose metabolism in the left precentral gyri was negatively correlated with cognitive scores on the Montreal Cognitive Assessment (MoCA). The present findings provide strong support for the presence of altered brain glucose metabolism in CADASIL patients as well as the associations between abnormal metabolism and cognitive scales in this population. The present findings suggest that patterns of brain glucose metabolism may become useful markers of cognitive impairment in CADASIL patients.

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.

Preoperative prediction of microvascular invasion of hepatocellular carcinoma using 18F-FDG PET/CT: a multicenter retrospective cohort study.

The aim of this study was to assess the potential of tumor 18F-fluorodeoxyglucose (FDG) avidity as a preoperative imaging biomarker for the prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC). One hundred and fifty-eight patients diagnosed with Barcelona Clinic Liver Cancer stages 0 or A HCC (median age, 57years; interquartile range, 50-64years) who underwent 18F-FDG positron emission tomography with computed tomography (PET/CT) before curative surgery at seven university hospitals were included. Tumor FDG avidity was measured by tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor on FDG PET/CT imaging. Logistic regression analysis was performed to identify significant parameters associated with MVI. The predictive performance of TLR and other clinical variables was assessed using receiver operating characteristic (ROC) curve analysis. MVI was present in 76 of 158 patients with HCCs (48.1%). Multivariable logistic regression analysis revealed that TLR, serum alpha-fetoprotein (AFP) level, and tumor size were significantly associated with the presence of MVI (P < 0.001). Multinodularity was not significantly associated with MVI (P = 0.563). The area under the ROC curve (AUC) for predicting the presence of MVI was best with TLR (AUC = 0.704), followed by tumor size (AUC = 0.685) and AFP (AUC = 0.670). We were able to build an improved prediction model combining TLR, tumor size, and AFP by using multivariable logistic regression modeling (AUC = 0.756). Tumor FDG avidity measured by TLR on FDG PET/CT is a preoperative imaging biomarker for the prediction of MVI in patients with HCC.

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

BackgroundIncreasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images.MethodsFifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated.ResultsPlasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4–5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24).ConclusionThis study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

High Structural Stress and Presence of Intraluminal Thrombus Predict Abdominal Aortic Aneurysm 18F-FDG Uptake: Insights From Biomechanics.

Abdominal aortic aneurysm (AAA) wall inflammation and mechanical structural stress may influence AAA expansion and lead to rupture. We hypothesized a positive correlation between structural stress and fluorine-18-labeled 2-deoxy-2-fluoro-d-glucose (18F-FDG) positron emission tomography-defined inflammation. We also explored the influence of computed tomography-derived aneurysm morphology and composition, including intraluminal thrombus, on both variables. Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent 18F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm 18F-FDG standardized uptake value within aortic wall and wall structural stress, patient clinical characteristics, aneurysm morphology, and compositions was explored using a hierarchical linear mixed-effects model. On univariate analysis, local aneurysm diameter, thrombus burden, extent of calcification, and structural stress were all associated with 18F-FDG uptake (P<0.05). AAA structural stress correlated with 18F-FDG maximum standardized uptake value (slope estimate, 0.552; P<0.0001). Multivariate linear mixed-effects analysis revealed an important interaction between structural stress and intraluminal thrombus in relation to maximum standardized uptake value (fixed effect coefficient, 1.68 [SE, 0.10]; P<0.0001). Compared with other factors, structural stress was the best predictor of inflammation (receiver-operating characteristic curve area under the curve =0.59), with higher accuracy seen in regions with high thrombus burden (area under the curve =0.80). Regions with both high thrombus burden and high structural stress had higher 18F-FDG maximum standardized uptake value compared with regions with high thrombus burdens but low stress (median [interquartile range], 1.93 [1.60-2.14] versus 1.14 [0.90-1.53]; P<0.0001). Increased aortic wall inflammation, demonstrated by 18F-FDG positron emission tomography, was observed in AAA regions with thick intraluminal thrombus subjected to high mechanical stress, suggesting a potential mechanistic link underlying aneurysm inflammation.

Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET. We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUV(max), the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes. A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoV Ca]). The median SUV(max) differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUV(max) of ≥7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUV(max) of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p = .024) than high metabolic group. In multivariate analysis, SUV(max) was a significant prognostic factor for overall survival (OS; p = .047) and progression-free survival (PFS; p = .039). Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC.

The molecular evidence of neural plasticity induced by cerebellar repetitive transcranial magnetic stimulation in the rat brain: A preliminary report

Cerebellar repetitive transcranial magnetic stimulation (rTMS) has been applied to treat several pathological conditions with insufficient evidence of molecular mechanism. Neural plasticity is proposed as one of mechanism. This study aimed to (1) confirm the feasibility of focal stimulation over cerebellar cortex and (2) investigate cerebellar rTMS effects on molecular changes associated with neural plasticity in the rat. For feasibility, six male Sprague–Dawley rats underwent 18F-FDG positron emission tomography (PET) to confirm focal stimulation on the cerebellar cortex after rTMS. For molecular evidence, thirty rats underwent a single (N=15) or 10 sessions (N=15) of rTMS with low-, high-frequency, or sham stimulation. In cerebellar cortex, reverse-transcriptase polymerase chain reaction and western blotting were performed on mRNA and proteins associated with neural plasticity: metabotrophic glutamate receptor 1 (GluR1), 2-amino-5-methyl-4-isoxazole-propionatic acid (AMPA) receptor (GluR2) and protein kinase C (PKC). As a result, 18F-FDG-PET showed an increase of glucose metabolism in the cerebellar cortex. The transcription of mGluR1 decreased following a single session of high-frequency rTMS. Synthesis of mGluR, PKC and GluR2 was reduced after rTMS, especially high frequency stimulation. It is suggested that rTMS could focus on the cerebellar cortex in the rat and induce neural plasticity associated with long-term depression.

Abstract T P85: Restenosis after Carotid Endarterectomy and Preoperative Carotid Plaque Imaging

Introduction: The incidence of restenosis after carotid endarterectomy (CEA) and carotid artery stenting (CAS) was reported to be approximately 6% at two years after the procedure in the CREST study. Restenosis after CEA, rather than CAS, was more likely to be related to a recurrence of stroke. The correlation between the plaque composition and restenosis after CEA has been investigated in previous reports, but the relationship between restenosis after CEA and preoperative plaque imaging is still unclear. Objective: We investigated the relationship between restenosis after CEA based on the preoperative plaque imaging. Methods: One-hundred and eighty-four CEAs were performed from November 2005 to March 2009 in our institution. In this study cohort, we included the 41 cases (40 patients, 37 males, mean age ± SD, 70.7±6.3) who underwent 18F-FDG positron emission tomography (PET) and magnetic resonance (MR) imaging using 3D inversion-recovery -based T1-weighted imaging (magnetization-prepared rapid acquisition gradient-echo [MPRAGE]) before CEA. The signal intensity of the carotid artery plaque on MPRAGE sequences was classified as “high” when the intensity was more than 200% the value of the adjacent muscle. The PET findings were evaluated by the maximum standard uptake value (max SUV) and a high max SUV was defined as &gt;1.74. We included patients who had undergone serial imaging studies (CT angiography; n=36, and/or ultrasonography; n=36) postoperatively. Restenosis was defined as &gt;50% stenosis on a CT angiogram or a &gt;200 cm/sec peak systolic velocity (PSV) on ultrasonography at the treated site. Results: Overall, restenosis occurred in three cases (7.3%). A MPRAGE high signal was recognized in 31 cases (76%) and a high maxSUV was noted in 23 cases (56%). All three patients with restenosis had both high MPRAGE and high maxSUV values. The group with MPRAGE high/maxSUV high (n=18) had a significantly higher incidence of restenosis after CEA than did the other groups (P=0.0420). Conclusions: The incidence of restenosis after CEA is suspected to be higher when the plaque consists of a rich necrotic core/intraplaque hemorrhage and a high degree of inflammation.

Radiobiological Modeling Based on 18F-Fluorodeoxyglucose Positron Emission Tomography Data for Esophageal Cancer.

BackgroundWe investigated the relationship of standardized uptake values (SUVs) to radiobiological parameters, such a 25 s tumor control probability (TCP), to allow for quantitative prediction of tumor response based on SUVs from 18F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after treatment for esophageal cancer.MethodsWe analyzed data from 20 esophageal cancer patients treated with chemoradiotherapy (CRT) followed by surgery. Tumor pathologic response to CRT was assessed in surgical specimens. Patients underwent 18F-FDG PET imaging before and after CRT. Rigid image registration was performed between both images. Because TCP in a heterogeneous tumor is a function of average cell survival, we modeled TCP as a function of <SUVR>, a possible surrogate for average cell survival (<SUVR>=<SUVafter/SUVbefore>). TCP was represented by a sigmoid function with two parameters: SUVR50, the <SUVR> at which TCP=0.5, and γ50, the slope of the curve at SUVR50. The two parameters and their confidence intervals (CIs) were estimated using the maximum-likelihood method. The correlation between SUV before CRT and SUV change <SUVbefore – SUVafter> was also studied.ResultsA TCP model as a function of SUV before and after treatment was developed for esophageal cancer patients. The maximum-likelihood estimate of SUVR50 was 0.47 (90% CI, 0.30-0.61) and for γ50 was 1.62 (90% CI, 0-4.2). High initial SUV and larger metabolic response (larger <SUVbefore –SUVafter>) were correlated, and this correlation was stronger among responders.ConclusionsOur TCP model indicates that <SUVafter/SUVbefore> is a possible surrogate for cell survival in esophageal cancer patients. Although CIs are large as a result of the small patient sample, parameters for a TCP curve can be derived and an individualized TCP can be calculated for future patients. Initial SUV does not predict response, whereas a correlation is found between surrogates for initial tumor burden and cell kill during therapy.

Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer

BackgroundThe aim of this study is to investigate the underlying biologic mechanisms of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake on positron emission tomography (PET) in non-small cell lung cancer (NSCLC). MethodsOne-hundred forty patients with NSCLC who underwent 18F-FDG PET were included in the study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), GLUT3, hypoxia-inducible factor-1 alpha (HIF-1α), hexokinase I, vascular endothelial growth factor (VEGF), microvessels (CD34), epidermal growth factor receptor (EGFR), and molecules relevant to PI3K/Akt/mTOR signaling pathway (PTEN, p-Akt, p-mTOR and p-S6). We also conducted in vitro studies of 18F-FDG uptake and mTOR inhibition in NSCLC cells. ResultsHigh 18F-FDG uptake was significantly associated with poor prognosis in NSCLC patients. 18F-FDG uptake was significantly correlated with GLUT1, hexokinase I, HIF-1α, VEGF, CD34, p-Akt, p-mTOR and EGFR. PTEN expression showed inverse correlation with 18F-FDG uptake. In in vitro study, 18F-FDG uptake was markedly decreased by the inhibition of GLUT1 and GLUT1 upregulation by the induction of HIF-1α increased the 18F-FDG uptake. Inhibition of both mTOR complex1 (mTORC1) and mTORC2 suppressed cell growth, but activity of mTORC1 regulated the 18F-FDG uptake. NCI-H1650 cells with PTEN loss showed the highest 18F-FDG uptake and the least sensitivity to mTOR inhibitors. ConclusionThe amount of 18F-FDG accumulation is associated with molecules relevant to glucose metabolism, hypoxia, angiogenesis and mTOR signaling pathway. Especially, PTEN status may affect not only 18F-FDG uptake but also effect of mTOR inhibitors on the growth of NSCLC.

18F-FDG uptake on PET is a predictive marker of thymidylate synthase expression in patients with thoracic neoplasms

The aim of this study was to investigate the relationship between the expression levels of thymidylate synthase (TS) and 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) uptake on positron emission tomography (PET) in various thoracic neoplasms. In total, 392 patients [non-small cell lung cancer (NSCLC) (n=140), malignant pleural mesothelioma (MPM) (n=21), pulmonary metastatic tumors (PMT) (n=148), thymic epithelial tumors (n=49) and pulmonary neuroendocrine (NE) tumor (n=34)] who underwent ¹⁸F-FDG PET before treatment were included in this study. Tumor sections were stained using immunohistochemistry for determination of TS, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), vascular endothelial growth factor (VEGF), microvessel density (MVD), CD34 and p53. The expression of TS in thoracic neoplasms had a positivity of 58% (230/392), and the positive rates of TS expression in NSCLC, PMT, thymic epithelial tumor, NE tumor and MPM samples were 56, 57, 57, 85 and 47%, respectively. The positivity of TS expression was significantly higher in NE tumors compared to that in other thoracic tumors. A statistically significant correlation between TS expression and ¹⁸F-FDG uptake was observed in thoracic neoplasms, in particular primary lung adenocarcinomas, high-grade NE tumors, thymomas and MPMs. Moreover, TS expression was closely associated with angiogenesis, DPD, OPRT and p53. Our results indicated that SUV(max) by ¹⁸F-FDG uptake may be an alternative biomarker for predicting TS expression in patients with primary lung adenocarcinoma, high-grade NE tumor, thymoma and MPM.

18F-FDG PET Metabolic Parameters and MRI Perfusion and Diffusion Parameters in Hepatocellular Carcinoma: A Preliminary Study

ObjectivesGlucose metabolism, perfusion, and water diffusion may have a relationship or affect each other in the same tumor. The understanding of their relationship could expand the knowledge of tumor characteristics and contribute to the field of oncologic imaging. The purpose of this study was to evaluate the relationships between metabolism, vasculature and cellularity of advanced hepatocellular carcinoma (HCC), using multimodality imaging such as 18F-FDG positron emission tomography (PET), dynamic contrast enhanced (DCE)-MRI, and diffusion weighted imaging(DWI).Materials and MethodsTwenty-one patients with advanced HCC underwent 18F-FDG PET, DCE-MRI, and DWI before treatment. Maximum standard uptake values (SUVmax) from 18F-FDG-PET, variables of the volume transfer constant (Ktrans) from DCE-MRI and apparent diffusion coefficient (ADC) from DWI were obtained for the tumor and their relationships were examined by Spearman’s correlation analysis. The influence of portal vein thrombosis on SUVmax and variables of Ktrans and ADC was evaluated by Mann-Whitney test.ResultsSUVmax showed significant negative correlation with Ktrans max (ρ = −0.622, p = 0.002). However, variables of ADC showed no relationship with variables of Ktrans or SUVmax (p>0.05). Whether portal vein thrombosis was present or not did not influence the SUV max and variables of ADC and Ktrans (p>0.05).ConclusionIn this study, SUV was shown to be correlated with Ktrans in advanced HCCs; the higher the glucose metabolism a tumor had, the lower the perfusion it had, which might help in guiding target therapy.