Fluorodeoxyglucose Positron Emission Tomography Imaging Research Articles

Pattern analysis of glucose metabolic brain data for lateralization of MRI-negative temporal lobe epilepsy

In this paper, we assessed the reliability of glucose metabolic brain data for identifying lateralization of magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE) patients. We designed and developed an efficacious and automatic metabolic-wise lateralization framework. The proposed lateralization framework comprises three main systematic levels. In the first stage of our investigation, we pre-processed interictal fluorodeoxyglucose positron emission tomography images to extract glucose metabolic brain data. In the second stage, we used a voxel selection method involving a feature-ranking strategy to select the most discriminative metabolic voxels. Finally, we used a support vector machine followed by a 10-fold cross-validation strategy to assess the proposed lateralization framework in 27 patients with right MRI-negative TLE and 29 patients with left MRI-negative TLE. The proposed lateralization framework achieved an excellent accuracy of 96.43 % concordance with experienced PET interpreter. Thus, we show that pattern analysis of glucose metabolic brain data can accurately lateralize MRI-negative TLE patients in the clinical setting.

Intranasal anti-caspase-1 therapy preserves myelin and glucose metabolism in a model of progressive multiple sclerosis.

Inflammatory demyelination and axonal injury in the central nervous system (CNS) are cardinal features of progressive multiple sclerosis (MS), and linked to activated brain macrophage-like cells (BMCs) including resident microglia and trafficking macrophages. Caspase-1 is a pivotal mediator of inflammation and cell death in the CNS. We investigated the effects of caspase-1 activation and its regulation in models of MS. Brains from progressive MS and non-MS patients, as well as cultured human oligodendrocytes were examined by transcriptomic and morphological methods. Next generation transcriptional sequencing of progressive MS compared to non-MS patients' normal appearing white matter (NAWM) showed induction of caspase-1 as well as other inflammasome-associated genes with concurrent suppression of neuron-specific genes. Oligodendrocytes exposed to TNFα exhibited upregulation of caspase-1 with myelin gene suppression in a cell differentiation state-dependent manner. Brains from cuprizone-exposed mice treated by intranasal delivery of the caspase-1 inhibitor, VX-765 or its vehicle, were investigated in morphological and molecular studies, as well as by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. Cuprizone exposure resulted in BMC and caspase-1 activation accompanied by demyelination and axonal injury, which was abrogated by intranasal VX-765 treatment. FDG-PET imaging revealed suppressed glucose metabolism in the thalamus, hippocampus and cortex of cuprizone-exposed mice that was restored with VX-765 treatment. These studies highlight the caspase-1 dependent interactions between inflammation, demyelination, and glucose metabolism in progressive MS and associated models. Intranasal delivery of an anti-caspase-1 therapy represents a promising therapeutic approach for progressive MS and other neuro-inflammatory diseases.

GBA Variants in Parkinson's Disease: Clinical, Metabolomic, and Multimodal Neuroimaging Phenotypes.

Alterations in the GBA gene (NM_000157.3) are the most important genetic risk factor for Parkinson's disease (PD). Biallelic GBA mutations cause the lysosomal storage disorder Gaucher's disease. The GBA variants p.E365K and p.T408M are associated with PD but not with Gaucher's disease. The pathophysiological role of these variants needs to be further explored. This study analyzed clinical, neuropsychological, metabolic, and neuroimaging phenotypes of patients with PD carrying the GBA variants p.E365K and p.T408M. GBA was sequenced in 56 patients with mid-stage PD. Carriers of GBA variants were compared with noncarriers regarding clinical history and symptoms, neuropsychological features, metabolomics, and multimodal neuroimaging. Blood plasma gas chromatography coupled to mass spectrometry, 6-[18 F]fluoro-L-Dopa positron emission tomography (PET), [18 F]fluorodeoxyglucose PET, and resting-state functional magnetic resonance imaging were performed. Sequence analysis detected 13 heterozygous GBA variant carriers (7 with p.E365K, 6 with p.T408M). One patient carried a GBA mutation (p.N409S) and was excluded. Clinical history and symptoms were not significantly different between groups. Global cognitive performance was lower in variant carriers. Metabolomic group differences were suggestive of more severe PD-related alterations in carriers versus noncarriers. Both PET scans showed signs of a more advanced disease; [18 F]fluorodeoxyglucose PET and functional magnetic resonance imaging showed similarities with Lewy body dementia and PD dementia in carriers. This is the first study to comprehensively assess (neuro-)biological phenotypes of GBA variants in PD. Metabolomics and neuroimaging detected more significant group differences than clinical and behavioral evaluation. These alterations could be promising to monitor effects of disease-modifying treatments targeting glucocerebrosidase metabolism. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Novel Metabolic Connectome Method to Predict Progression to Mild Cognitive Impairment.

Objective Glucose-based positron emission tomography (PET) imaging has been widely used to predict the progression of mild cognitive impairment (MCI) into Alzheimer's disease (AD) clinically. However, existing discriminant methods are unsubtle to reveal pathophysiological changes. Therefore, we present a novel metabolic connectome-based predictive modeling to predict progression from MCI to AD accurately. Methods In this study, we acquired fluorodeoxyglucose PET images and clinical assessments from 420 MCI patients with 36 months follow-up. Individual metabolic network based on connectome analysis was constructed, and the metabolic connectivity in this network was extracted as predictive features. Three different classification strategies were implemented to interrogate the predictive performance. To verify the effectivity of selected features, specific brain regions associated with MCI conversion were identified based on these features and compared with prior knowledge. Results As a result, 4005 connectome features were obtained, and 153 in which were selected as efficient features. Our proposed feature extraction method had achieved 85.2% accuracy for MCI conversion prediction (sensitivity: 88.1%; specificity: 81.2%; and AUC: 0.933). The discriminative brain regions associated with MCI conversion were mainly located in the precentral gyrus, precuneus, lingual, and inferior frontal gyrus. Conclusion Overall, the results suggest that our proposed individual metabolic connectome method has great potential to predict whether MCI patients will progress to AD. The metabolic connectome may help to identify brain metabolic dysfunction and build a clinically applicable biomarker to predict the MCI progression.

Innervation of supraclavicular adipose tissue: A human cadaveric study.

Functional brown adipose tissue (BAT) was identified in adult humans only in 2007 with the use of fluorodeoxyglucose positron emission tomography imaging. Previous studies have demonstrated a negative correlation between obesity and BAT presence in humans. It is proposed that BAT possesses the capacity to increase metabolism and aid weight loss. In rodents it is well established that BAT is stimulated by the sympathetic nervous system with the interscapular BAT being innervated via branches of intercostal nerves. Whilst there is evidence to suggest that BAT possesses beta-3 adrenoceptors, no studies have identified the specific nerve branch that carries sympathetic innervation to BAT in humans. The aim of this study was to identify and trace the peripheral nerve or nerves that innervate human BAT in the supraclavicular region. The posterior triangle region of the neck of cadaveric specimens were dissected in order to identify any peripheral nerve branches piercing and/or terminating in supraclavicular BAT. A previously undescribed branch of the cervical plexus terminating in a supraclavicular adipose depot was identified in all specimens. This was typically an independent branch of the plexus, from the third cervical spinal nerve, but in one specimen was a branch of the supraclavicular nerve. Histological analysis revealed the supraclavicular adipose depot contained tyrosine hydroxylase immunoreactive structures, which likely represent sympathetic axons. This is the first study that identifies a nerve branch to supraclavicular BAT-like tissue. This finding opens new avenues for the investigation of neural regulation of fat metabolism in humans.

The Molecular Landscape of Hürthle Cell Thyroid Cancer Is Associated with Altered Mitochondrial Function-A Comprehensive Review.

Hürthle cell thyroid carcinoma (HTC) accounts for 3–5% of all thyroid malignancies. Widely invasive HTC is characterized by poor prognosis and limited responsiveness to standard therapy with radioiodine. The molecular landscape of HTC is significantly different from the genetic signature seen in other forms of thyroid cancer. We performed a comprehensive literature review on the association between the molecular features of HTC and cancer metabolism. We searched the Pubmed, Embase, and Medline databases for clinical and translational studies published between 1980 and 2020 in English, coupling “HTC” with the following keywords: “genomic analysis”, “mutations”, “exome sequencing”, “molecular”, “mitochondria”, “metabolism”, “oxidative phosphorylation”, “glycolysis”, “oxidative stress”, “reactive oxygen species”, and “oncogenes”. HTC is characterized by frequent complex I mitochondrial DNA mutations as early clonal events. This genetic signature is associated with the abundance of malfunctioning mitochondria in cancer cells. HTC relies predominantly on aerobic glycolysis as a source of energy production, as oxidative phosphorylation-related genes are downregulated. The enhanced glucose utilization by HTC is used for diagnostic purposes in the clinical setting for the detection of metastases by fluorodeoxyglucose positron emission tomography (FGD-PET/CT) imaging. A comprehensive metabolomic profiling of HTC in association with its molecular landscape might be necessary for the implementation of tumor-specific therapeutic approaches.

Brain Network Segregation and Glucose Energy Utilization: Relevance for Age-Related Differences in Cognitive Function.

The human brain is organized into segregated networks with strong within-network connections and relatively weaker between-network connections. This "small-world" organization may be essential for maintaining an energetically efficient system, crucial to the brain which consumes 20% of the body's energy. Brain network segregation and glucose energy utilization both change throughout the lifespan. However, it remains unclear whether these processes interact to contribute to differences in cognitive performance with age. To address this, we examined fluorodeoxyglucose-positron emission tomography and resting-state functional magnetic resonance imaging from 88 participants aged 18-73 years old. Consistent with prior work, brain network segregation showed a negative association with age across both sensorimotor and association networks. However, relative glucose metabolism demonstrated an interaction with age, showing a negative slope in association networks but a positive slope in sensorimotor networks. Overall, brain networks with lower segregation showed significantly steeper age-related differences in glucose metabolism, compared with highly segregated networks. Sensorimotor network segregation mediated the association between age and poorer spatial cognition performance, and sensorimotor network metabolism mediated the association between age and slower response time. These data provide evidence that sensorimotor segregation and glucose metabolism underlie some age-related changes in cognition. Interventions that stimulate somatosensory networks could be important for treatment of age-related cognitive decline.

Improving MR sequence of 18F-FDG PET/MR for diagnosing and staging gastric Cancer: a comparison study to 18F-FDG PET/CT

PurposeEvaluate the feasibility of fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging in patients with gastric cancer by optimizing the scan protocol and to compare the image quality to 18F FDG PET and computed tomography (CT).MethodsThe PET/CT and PET/MR imaging were sequentially performed in 30 patients with gastric cancer diagnosed by gastroscope using a single-injection-with-dual-imaging protocol. After intravenous injection of 18F-FDG (mean, 249 MBq), PET/CT imaging including low-dose CT was performed (mean uptake time, 47 ± 6 min), and PET/MR imaging including a T1-weighted Dixon sequence for attenuation correction and two different T2-weighted sequences was subsequently acquired (88 ± 15 min after 18F-FDG injection). Four series of images (CT from PET/CT, T1W, T2W Half-Fourier acquisition single-shot turbo spin-echo [T2W-HASTE] and T2W-BLADE from PET/MR) were visually evaluated using a 3–4 points scale for: (1) image artifacts, (2) lesion conspicuity and (3) image fusion quality. The characteristics of the primary lesions were assessed and compared between the PET/CT and PET/MR acquisitions.ResultsThe image quality and lesion conspicuity of the T2W-HASTE images were significantly improved compared to that of the T2W-BLADE images. A significantly higher number of artifacts were seen in the T2W-HASTE images compared with the T1W and CT images (p < 0. 05). No differences in the accuracy of image fusion between PET/MR and PET/CT (p > 0. 05); however, significant difference was seen in the lesion conspicuity measurements (p < 0.05) with T2W-HASTE being superior. For information about the primary lesion characteristics, the T2W-HASTE images provided the most successful identifications compared with those of the T1W and PET/CT (13vs7vs5) images.ConclusionsPET/MR with the T2W-HASTE was better at revealing the details of local stomach lesions compared with PET/CT imaging. Combining the PET/MR with the T2W-HASTE technique is a promising imaging method for diagnosing and staging gastric cancer.

The Additional Value of 18F-FDG PET and MRI in Patients with Glioma: A Review of the Literature from 2015 to 2020.

Aim: Beyond brain computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) hold paramount importance in neuro-oncology. The aim of this narrative review is to discuss the literature from 2015 to 2020, showing advantages or complementary information of fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging to the anatomical and functional data offered by MRI in patients with glioma. Methods: A comprehensive Pubmed/MEDLINE literature search was performed to retrieve original studies, with a minimum of 10 glioma patients, published from 2015 until the end of April 2020, on the use of 18F-FDG PET in conjunction with MRI. Results: Twenty-two articles were selected. Combined use of the two modalities improves the accuracy in predicting prognosis, planning treatments, and evaluating recurrence. Conclusion: According to the recent literature, 18F-FDG PET provides different and complementary information to MRI and may enhance performance in the whole management of gliomas. Therefore, integrated PET/MRI may be particularly useful in gliomas, since it could provide accurate morphological and metabolic information in one-shoot examination and improve the diagnostic value compared to each of procedures.

In-vivo signatures of neurodegeneration in isolated rapid eye movement sleep behaviour disorder.

Isolated rapid eye movement sleep behaviour disorder (iRBD) is a parasomnia, recently recognized as a risk factor for progression to Parkinson's disease, dementia with Lewy body and multiple system atrophy. Biomarker studies in iRBD are relevant due to lack of evidence in this condition. The identification of biomarkers able to predict progression to synucleinopathy diseases is critical for iRBD. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging might provide information about ongoing neurodegenerative processes. In the present study, we tested for presence of brain hypometabolism patterns as biomarkers of neurodegeneration in single iRBD individuals. We recruited 37 subjects with polysomnography-confirmed iRBD, with neuropsychological assessment and available FDG-PET scan. Images were analysed with a validated statistical parametric mapping procedure, providing individual hypometabolism maps. According to the neuropsychological evaluation, 22 subjects with iRBD had normal cognition and 15 subjects showed impairments, particularly in visuoperceptive/visuospatial and memory domains. One-fifth of the cases were impaired on the Qualitative Scoring of Pentagon Test. In 32 iRBD cases, FDG-PET statistical parametric maps revealed significant cerebral hypometabolism, namely in the occipital lobes (n=5), occipital and cerebellar regions (n=13), occipitoparietal regions (n=13) and a selective cerebellar hypometabolism (n=1). Five cases had normal FDG-PET scans. These imaging findings indicate that brain neurodegenerative processes are present and already detectable in iRBD. The different hypometabolism patterns in the single individuals may reflect specific early pathophysiological events due to the underlying synucleinopathy, with a specific neural vulnerability for the occipital cortex that might pre-date a risk of progression towards dementia with Lewy body.

Is there any correlation between HPV and early radioresponse before brachytherapy in cervix uteri carcinoma?

The prognostic effect of human papilloma virus (HPV) on early radioresponse before brachytherapy was evaluated in locally advanced cervix uteri carcinoma patients. Between 2015 and 2018, 150 patients with locally advanced carcinoma of the cervix uteri from University of Health Sciences Okmeydani Training and Research Hospital and Istanbul Oncology Hospital underwent chemotherapy concomitant with external radiotherapy and brachytherapy after performing fluorodeoxyglucose positron emission tomography (FDG PET) and magnetic resonance imaging (MRI) for purposes of staging and treatment planning. The treatment results of patients analyzed retrospectively. The median age of 57 patients was 53years, and the initial tumor volume was 27cm3. The median follow-up period was 22months. The median tumor volume after external radiotherapy was significantly higher in patients without local control than those who responded to external radiotherapy (p = 0.031). The mean tumor diameter and volume in all HPV-negative patients after external radiotherapy were significantly higher than those of HPV-positive patients (p = 0.011 and p = 0.046, respectively). In a group of patients with poor early responses, local disease control could not be achieved despite the use of recommended higher doses of brachytherapy. We could not determine the correlation between HPV contamination and patients who had early response intervention. But residual tumor of more than 2cm in diameter after external radiotherapy may be a predictor of failed local control and development of metastasis within a short time.

Evaluating Positron Emission Tomography-Based Functional Imaging Changes in the Heart After Chemo-Radiation for Patients With Lung Cancer

Studies have noted a link between radiation dose to the heart and overall survival (OS) for patients with lung cancer treated with chemoradiation. The purpose of this study was to characterize pre- to posttreatment cardiac metabolic changes using fluorodeoxyglucose/positron emission tomography (FDG-PET) images and to evaluate whether changes in cardiac metabolism predict for OS. Thirty-nine patients enrolled in a functional avoidance prospective study who had undergone pre- and postchemoradiation FDG-PET imaging were evaluated. For each patient, the pretreatment and posttreatment PET/CTs were rigidly registered to the planning CT, dose, and structure set. PET-based metabolic dose-response was assessed by comparing pretreatment to posttreatment mean standardized uptake values (SUVmean) in the heart as a function of dose-bin. OS analysis was performed by comparing SUVmean changes for patients who were alive or had died at last follow-up and by using a multivariate model to assess whether pre- to posttreatment SUVmean changes were a predictor of OS. The dose-response curve revealed increasing changes in SUV as a function of cardiac dose with an average SUVmean increase of 1.7% per 10 Gy. Patients were followed for a median of 437 days (range, 201-1131 days). SUVmean change was significantly predictive of OS on multivariate analysis with a hazard ratio of 0.541 (95% confidence intervals, 0.312-0.937). Patients alive at follow-up had an average increase of 17.2% in cardiac SUVmean while patients that died had an average decrease in SUVmean decrease of 13.5% (P = .048). Our data demonstrated that posttreatment SUV changes in the heart were significant indicators of dose-response and predictors of OS. The present work is hypothesis generating and must be validated in an independent cohort. If validated, our data show the potential for cardiac metabolic changes to be an early predictor for clinical outcomes.

Flourine-18 fluorodeoxyglucose positron emission tomography imaging exhibits increased SUVmax at the level of the spinal intumescence in normal dogs.

Positron emission tomography (PET) imaging utilizing fluorine-18 labeled fluorodeoxyglucose is a relatively new imaging modality in veterinary medicine that is becoming more common for oncological staging and for musculoskeletal imaging. Thus, it is important to identify the normal variations on PET imaging that may be mistaken for pathology. Variation in standardized uptake values (SUVmax) have been anecdotally identified in the spinal cord of dogs undergoing fluorodeoxyglucose (FDG) PET-CT examinations for oncological staging, with notable increase in SUVmax values identified in the region of the cervical and lumbar spinal intumescences. The aim of this retrospective, analytical study was to compare the SUVmax values at four different locations throughout the spinal cord (C3, C5-T1, T13, and L3-S1) of a group of dogs with no evidence of neurologic disease and compare those findings to histologic specimens from dogs euthanized for unrelated disease. SUVmax values were significantly higher at the cervical and lumbar intumescences in comparison to the control regions (P<.0001 and P<.0001, respectively). Neuronal count and spinal cord gray matter area were also significantly greater at the cervical and lumbar intumescences (neuronal count P=.0025 and P=.0001; area P=.0004 and P=.0009, respectively) while overall neuronal density was lower (P=.003 and P=.028, respectively). We presume the increased SUVmax values at the spinal cord intumescences are the result of overall increased neuron count, increased proportion of gray matter, and increased spinal cord gray matter area. These findings will aid in the interpretation of future PET-CT studies and hopefully prevent the misdiagnosis of spinal cord disease in normal canines.

Contrary effects of coenzyme Q10 and vitamin E after testicular ischemia/reperfusion in a rat model validated with glucose metabolism imaging.

To evaluate the efficacy of antioxidants in cellular-level post-ischemia/reperfusion injury of the testis and to validate these effects with 18F-fluorodeoxyglucose positron emission tomography. Fifty-six adult male rats were randomly divided into seven groups-Group 1: sham; Group 2: ischemia/reperfusion only group; Group 3: ischemia was induced and vitamin E (100 mg/kg) was administered intraperitoneally 30 min before reperfusion; Group 4: vitamin E was given intraperitoneally without ischemia/reperfusion; Group 5: ischemia was induced and coenzyme Q10 (10 mg/body weight) was administered intraperitoneally 30 min before reperfusion; Group 6: coenzyme Q10 was administered intraperitoneally without ischemia/reperfusion; Group 7: ischemia was induced and coenzyme Q10 + vitamin E was administered intraperitoneally 30 min before reperfusion. After detorsion, fluorodeoxyglucose was applied to all groups according to the animals' weight and fluorodeoxyglucose positron emission tomography was performed after 1 h. In pursuit of imaging, orchiectomy was performed for histopathological and biochemical evaluations. A significant effect of group on catalase, maximum standardized uptake value, and seminiferous tubule diameters (p < 0.005) was observed. According to this, combining ischemia/reperfusion with vitamin E increased the maximum standardized uptake value significantly higher than in all other groups; in addition, catalase was significantly higher than in Groups 4-6. Histopathological outcomes revealed that "sham" had significantly larger seminiferous tubule diameter than Groups 2-4. Also, "ischemia/reperfusion" was the only group which had significantly smaller seminiferous tubule diameters than Groups 6 and 7. In contrast to vitamin E, coenzyme Q10 provided remarkable regression of oxidative stress-induced enzymes and revealed consistent effects on histopathological outcomes, which were validated with fluorodeoxyglucose positron emission tomography imaging.

Prediction and Classification of Alzheimer's Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers.

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

P05.06 Phase 2 study to evaluate the safety, pharmacokinetics and clinical activity of PI3K/mTOR inhibitor GDC-0084 given to glioblastoma (GBM) patients with unmethylated O6-methylguanine-methyltransferase (MGMT) promoter status

Abstract BACKGROUND GDC-0084 is a potent, oral, selective small molecule inhibitor of class I phosphoinositide 3-kinase and mammalian target of rapamycin (PI3K/mTOR). The PI3K pathway is activated in ≥ 70% of tumors, making it a compelling target for the treatment of GBM. GDC-0084 crosses the blood-brain barrier and achieves a brain / plasma ratio of approximately 1.0. GDC-0084 was given as once daily oral dosing in a phase 1 study (Wen et al, J Clin Oncol 34, 2016(15) suppl.2012) in 47 patients with recurrent high-grade gliomas. The adverse events were generally consistent with the established PI3K/mTOR inhibitor class-effects. The MTD identified was 45 mg once daily. MATERIAL AND METHODS This study has a 2-part design consisting of an open-label, multicenter dose-escalation study with expansion to assess the safety, tolerability, RP2D, PK, and clinical activity of GDC-0084 at QD dosing in patients with newly-diagnosed GBM with unmethylated MGMT promotor status. In the escalation phase the first cohort is completed without DLT. At the identified MTD, 20 subjects will be recruited in an expansion cohort and patients will be randomized to take GDC-0084 in fed and fasted states. Subjects in the expansion cohort will also have serial fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging.

The accuracy of diagnostic Imaging techniques in patients with a suspected Fracture-related Infection (IFI) trial: study protocol for a prospective multicenter cohort study.

IntroductionThe optimal diagnostic imaging strategy for fracture-related infection (FRI) remains to be established. In this prospective study, the three commonly used advanced imaging techniques for diagnosing FRI will be compared....

Scoring System to Predict pt2 in Gallbladder Cancer Based on Carcinoembryonic Antigen and Tumor Diameter.

T2 gallbladder cancer requires lymph node dissection for curative resection, whereas simple cholecystectomy is adequate to treat T1 gallbladder cancer. Hence, this study aimed to develop an accurate scoring system to preoperatively predict pT2 in gallbladder cancer. We retrospectively assessed data from 57 patients with suspected gallbladder cancer who underwent curative resection between September 2003 and May 2017. Six with apparent invasion of adjacent organs on preoperative images were excluded. We evaluated preoperative computed tomography, magnetic resonance and endoscopic ultrasonographic images, blood biochemistry, and the maximum standard uptake value in fluorodeoxyglucose-positron emission tomography images. We analyzed whether correlations between preoperative findings and the depth of tumor invasion could predict pT2. The pathological diagnosis was gallbladder cancer in 30 (58.8%) patients, of whom 21 (69.9%) had pT2 or worse. Multivariate analyses selected carcinoembryonic antigen and tumor diameter as independent predictors of pT2 or worse (odds ratios = 1.741 and 1.098, respectively; 95% confidence intervals = 1.004-3.020 and 1.008-1.197, respectively). A regression formula was created using carcinoembryonic antigen and tumor diameter to calculate pT2 predictive scores. The area under the receiver operating characteristics curve of the pT2 predictive score was 0.873. We created a scoring system to predict pT2 in gallbladder cancer using carcinoembryonic antigen and tumor diameter. The present findings suggested that carcinoembryonic antigen is important for the preoperative evaluation of gallbladder cancer.

Influence of image noise and object size on segmentation accuracy of FDG-PET imaging: a phantom experiment.

We aimed to evaluate the influence of noise and object size on segmentation accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. The scanned data of spherical phantoms were used. For the gradient method, 40% maximum standardized uptake value (SUVmax) method, and SUV of 2.5 threshold method, we evaluated the correlation between segmentation accuracy and background variability and that between segmentation accuracy and sphere diameters. For the gradient method, background variability did not affect segmentation accuracy, but sphere diameters had a small effect. As for the 40% SUVmax threshold method, both sphere diameters and background variability affected the segmentation accuracy. In the SUV of 2.5 threshold method, segmentation accuracy was affected by sphere diameters but not by background variability. With regard to segmentation accuracy of FDG-PET imaging, the gradient method may be more accurate and reliable compared to threshold methods when applied to images with varying noise or object size.

Metabolic Brain Network Analysis of FDG-PET in Alzheimer's Disease Using Kernel-Based Persistent Features.

Recent research of persistent homology in algebraic topology has shown that the altered network organization of human brain provides a promising indicator of many neuropsychiatric disorders and neurodegenerative diseases. However, the current slope-based approach may not accurately characterize changes of persistent features over graph filtration because such curves are not strictly linear. Moreover, our previous integrated persistent feature (IPF) works well on an rs-fMRI cohort while it has not yet been studied on metabolic brain networks. To address these issues, we propose a novel univariate network measurement, kernel-based IPF (KBI), based on the prior IPF, to quantify the difference between IPF curves. In our experiments, we apply the KBI index to study fluorodeoxyglucose positron emission tomography (FDG-PET) imaging data from 140 subjects with Alzheimer’s disease (AD), 280 subjects with mild cognitive impairment (MCI), and 280 healthy normal controls (NC). The results show the disruption of network integration in the progress of AD. Compared to previous persistent homology-based measures, as well as other standard graph-based measures that characterize small-world organization and modular structure, our proposed network index KBI possesses more significant group difference and better classification performance, suggesting that it may be used as an effective preclinical AD imaging biomarker.