18F FDG Pet imaging

Alzheimer’s disease (AD) is associated with insulin resistance and specific regional declines in cerebral metabolism. The effects of a novel mTOT modulating insulin sensitizer (MSDC-0160) were explored in non-diabetic patients with mild AD to determine whether treatment would impact glucose metabolism measured by FDG-PET in regions that decline in AD. MSDC-0160 (150 mg once daily; N=16) compared to placebo (N=13) for 12 weeks did not result in a significant difference in glucose metabolism in pre-defined regions when referenced to the pons or whole brain. However, glucose metabolism referenced to cerebellum was maintained in MSDC-0160 treated participants while it significantly declined for placebo patients in anterior and posterior cingulate, and parietal, lateral temporal, medial temporal cortices. Voxel-based analyses showed additional differences in FDG-PET related to MSDC-0160 treatment. These exploratory results suggest central effects of MSDC-0160 and provide a basis for further investigation of mTOT modulating insulin sensitizers in AD patients.

Measures of core cognitive processes (fluid abilities) are highly correlated with measures of knowledge (crystallized abilities) in healthy adults. In early stages of Alzheimer's disease (AD), fluid abilities, however, decline more rapidly than crystallized abilities. We hypothesized that cognitively normal older adults who evidenced lower fluid ability compared with crystallized ability (an ability discrepancy) would show evidence of early AD neuropathology indexed via in vivo measures of amyloid-beta (Ab) deposition and cortical thickness in AD-vulnerable regions. A sample of older adults (n = 112) aged 65 to 89 underwent a cognitive battery, structural magnetic resonance imaging, and a subset (n = 75) also completed positron emission tomography scanning to measure Ab deposition using F-18 Florbetapir. Of this sample, 60 older adults (43 with available positron emission tomography scans) evidenced a discrepancy where fluid ability was lower than crystallized ability. The magnitude of the ability discrepancy was independently associated with a greater Ab deposition and thinner cortex in AD-vulnerable regions, as well as age. The data suggest that such a discrepancy may be a marker of preclinical AD.

Background
1 F-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.
Objectives
To determine the diagnostic accuracy of the 1 F-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.
Search methods
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.
Selection criteria
We included studies that evaluated the diagnostic accuracy of 1 F-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’.
Data collection and analysis
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.
Main results
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 1 F-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.
Authors’ conclusions
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 1 F-FDG PET scans in clinical practice in people with MCI. The 1 F-FDG PET scan
is a high-cost investigation, and it is therefore important to clearly demonstrate its accuracy and to standardise the process of 1 F- 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.

(1) Background: Medical imaging provides quantitative and spatial information to evaluate treatment response in the management of patients with non-small cell lung cancer (NSCLC). High throughput extraction of radiomic features on these images can potentially phenotype tumors non-invasively and support risk stratification based on survival outcome prediction. The prognostic value of radiomics from different imaging modalities and time points prior to and during chemoradiation therapy of NSCLC, relative to conventional imaging biomarker or delta radiomics models, remains uncharacterized. We investigated the utility of multitask learning of multi-time point radiomic features, as opposed to single-task learning, for improving survival outcome prediction relative to conventional clinical imaging feature model benchmarks. (2) Methods: Survival outcomes were prospectively collected for 45 patients with unresectable NSCLC enrolled on the FLARE-RT phase II trial of risk-adaptive chemoradiation and optional consolidation PD-L1 checkpoint blockade (NCT02773238). FDG-PET, CT, and perfusion SPECT imaging pretreatment and week 3 mid-treatment was performed and 110 IBSI-compliant pyradiomics shape-/intensity-/texture-based features from the metabolic tumor volume were extracted. Outcome modeling consisted of a fused Laplacian sparse group LASSO with component-wise gradient boosting survival regression in a multitask learning framework. Testing performance under stratified 10-fold cross-validation was evaluated for multitask learning radiomics of different imaging modalities and time points. Multitask learning models were benchmarked against conventional clinical imaging and delta radiomics models and evaluated with the concordance index (c-index) and index of prediction accuracy (IPA). (3) Results: FDG-PET radiomics had higher prognostic value for overall survival in test folds (c-index 0.71 [0.67, 0.75]) than CT radiomics (c-index 0.64 [0.60, 0.71]) or perfusion SPECT radiomics (c-index 0.60 [0.57, 0.63]). Multitask learning of pre-/mid-treatment FDG-PET radiomics (c-index 0.71 [0.67, 0.75]) outperformed benchmark clinical imaging (c-index 0.65 [0.59, 0.71]) and FDG-PET delta radiomics (c-index 0.52 [0.48, 0.58]) models. Similarly, the IPA for multitask learning FDG-PET radiomics (30%) was higher than clinical imaging (26%) and delta radiomics (15%) models. Radiomics models performed consistently under different voxel resampling conditions. (4) Conclusion: Multitask learning radiomics for outcome modeling provides a clinical decision support platform that leverages longitudinal imaging information. This framework can reveal the relative importance of different imaging modalities and time points when designing risk-adaptive cancer treatment strategies.

We report herein two cases of suture granuloma showing focal intense 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-uptake in positron
emission tomography (PET). Follow-up FDG-PET after surgical intervention for head and neck cancer revealed lesions with high FDGuptake,
which were highly suspected of being a recurrent tumor. The lesions were subjected to excisional biopsy for definitive diagnosis.
Histopathological examination proved them to be suture granulomas caused by non-absorbable silk sutures. It should be emphasized that
suture granulomas can show false-positive findings on FDG-PET, thus requiring differential diagnosis from recurrent tumors.
# 2011 Elsevier Ireland Ltd. All rights reserved.

Purpose
Single-pass whole-body (WB) 18F-FDG PET/CT imaging is routinely employed for the clinical assessment of malignant, infectious, and inflammatory diseases. Our aim in this study is the systematic clinical assessment of lesion detectability in multi-pass WB parametric imaging enabling direct imaging of the highly quantitative 18F-FDG influx rate constant Ki, as a complement to standard-of-care standardized uptake value (SUV) imaging for a range of oncologic studies.

Methods
We compared SUV and Ki images of 18 clinical studies of different oncologic indications (lesion characterization and staging) including standard-of-care SUV and dynamic WB PET protocols in a single session. The comparison involved both the visual assessment and the quantitative evaluation of SUVmean, SUVmax, Kimean, Kimax, tumor-to-background ratio (TBRSUV, TBRKi), and contrast-to-noise ratio (CNRSUV, CNRKi) quality metrics.

Results
Overall, both methods provided good-quality images suitable for visual interpretation. A total of 118 lesions were detected, including 40 malignant (proven) and 78 malignant (unproven) lesions. Of those, 111 were detected on SUV and 108 on Ki images. One proven malignant lesion was detected only on Ki images whereas none of the proven malignant lesions was visible only on SUV images. The proven malignant lesions had overall higher Ki TBR and CNR scores. One unproven lesion, which was later confirmed as benign, was detected only on the SUV images (false-positive). Overall, our results from 40 proven malignant lesions suggested improved sensitivity (from 92.5 to 95%) and accuracy (from 90.24 to 95.12%) and potentially enhanced specificity with Ki over SUV imaging.

Conclusion
Oncologic WB Patlak Ki imaging may achieve equivalent or superior lesion detectability with reduced false-positive rates when complementing standard-of-care SUV imaging.

Key Points
• The whole-body spatio-temporal distribution of 18 F-FDG uptake may reveal clinically useful information on oncologic diseases to complement the standard-of-care SUV metric.

• Parametric imaging resulted in less false-positive indications of non-specific 18 F-FDG uptake relative to SUV.

• Parametric imaging may achieve equivalent or superior 18 F-FDG lesion detectability than standard-of-care SUV imaging in oncology.

Keywords
Positron emission tomography Molecular imaging Tumors

Rosai-Dorfman disease (RDD), or sinus histiocy-tosis with massive lymphadenopathy, commonly involves the lymph nodes but may secondarily involve the skin. Purely cutaneous disease without lymphatics or internal organ involvement occurs rarely. The present report detailed a rare case of 18 F-fluoro-2-deoxyglucose positron emission-computed tomography (18 FDG PET-CT) performed in a 33-year-old male soldier with a purely cutaneous form of RDD. Staging with 18 FDG PET-CT was ordered prior to excisional biopsies of the aforedescribed masses and pathology reported RDD. The case demonstrated accurate localization of increased radio-glucose metabolism. The present case was also discussed in light of literature data in terms of clinical features, etiologies, histology, medical imaging, therapy planning and prognosis.

The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence. Pregnant Sprague-Dawley rats were treated in one of four ways: 1) saline; 2) morphine alone; 3) morphine+GVG at 25 mg/kg; 4) morphine+GVG at 50 mg/kg. Morphine was administered throughout gestation, while GVG administration occurred only during the last 5 days of gestation. On post-natal day 1, naloxone-induced withdrawal behaviours were recorded in order to obtain a gross behaviour score. Approximately 28 days following birth, 18 FDG microPET scans were obtained on these same animals (Groups 1, 2, and 4). Morphine-treated neonates demonstrated significantly higher withdrawal scores than saline controls. However, GVG at 50 but not 25 mg/kg/day significantly attenuated them. Upon reaching adolescence, morphine treated animals showed regionally specific changes in 18 FDG uptake. Again, prenatal GVG exposure blocked them. These data demonstrate that low-dose, short-term prenatal GVG administration blocks naloxone-induced withdrawal in neonates. Taken together, these preliminary findings suggest that GVG may provide an alternative and long-lasting pharmacologic approach for the management of neonatal and adolescent symptoms associated with NAS.

ABSTRACT:

Background. The purpose of this study was to determine
whether pretreatment 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) volume-based parameters, such as metabolic tumor volume and total lesion glycolysis, add more prognostic information in patients with oropharyngeal squamous cell carcinoma (SCC).

Methods. The subjects were 47 patients with oropharyngeal SCC who underwent 18F-FDG PET/CT before any treatment and followed by definitive therapy. PET parameters (metabolic tumor volume and total lesion glycolysis) and tumor p16/p53 status were evaluated retrospectively.Univariate and multivariate analyses were performed for disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).

Results. All volume-based PET parameters were found to be significant prognostic factors for DFS, DSS, and OS in univariate analysis. In multivariate analysis, only metabolic tumor volume for total tumor lesions (cutoff 65) retained an independent association with DFS, DSS, and OS.

Conclusion. Metabolic tumor volume for total tumor lesions may be a predictive marker for survival outcomes in patients with oropharyngeal SCC with known p16/p53 status.

OBJECTIVE. The purpose of this study was to determine whether pretreatment quantitative
and visual parameters seen on PET/CT using 18F-FDG add prognostic information for
clinical staging in patients with head and neck cancer.
MATERIALS AND METHODS. We enrolled 108 patients with histologically proven
oral, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who underwent
FDG PET/CT before treatment and, later, definitive therapy in our study. PET/CT parameters—
maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV),
total lesion glycolysis (TLG), and uptake pattern (sphere-shaped or ring-shaped)—were recorded.
The prognostic value of these parameters was evaluated using univariate and multivariate
Cox regression analyses.
RESULTS. In the univariate analysis, all of the FDG PET/CT parameters—SUVmax (> 10
g/mL) of the primary tumor, MTV (> 20 cm3), TLG (> 70 g), and uptake pattern (ringshaped)—
were significantly associated with negative effects on disease-specific survival
(DSS) and disease-free survival (DFS). In the multivariate analysis, the MTV and uptake
pattern remained associated with DSS after corrections for the Union for International Cancer
Control (UICC) stage and definitive therapy (p = 0.023 and < 0.001, respectively). Another
multivariate model that included MTV as a continuous variable, uptake pattern, and UICC
stage showed that the uptake pattern remained significantly associated with DSS, whereas the
association between DSS and MTV was not significant (p < 0.001 and = 0.332, respectively).
CONCLUSION. Our data indicate that the pretreatment PET/CT parameters had prognostic
value. In particular, a qualitative factor, uptake pattern, provided better prognostic information
to the clinical staging of head and neck squamous cell carcinomas than the other
PET/CT parameters.

We report an unusual case of idiopathic internal and external jugular vein thrombosis. Positron
emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG), which was conducted to assess
subclinical malignancy, revealed intense uptake of FDG, corresponding to thrombus within the left internal and
external jugular veins. Although FDG-PET is widely used in differentiating between malignant and benign
diseases, we should bear in mind that this benign entity can demonstrate high accumulation of FDG.

Background: This meta-analysis aims to compare the diagnostic performance of L-3-18 F-α-methyl tyrosine (18 F-FAMT) positron emission tomography (PET) and 2-deoxy-2-[ 18 F]fluoro-D-glucose (18 F-FDG) PET for malignancy detection. Methods: The workflow of this study follows Cochrane Collaboration Guidelines of a systematic review of diagnostic test accuracy studies. An electronic search was performed for clinical diagnostic studies directly comparing 18 F-FAMT and 18 F-FDG PET for malignant tumors. Study quality, the risks of bias and sources of variation among studies were assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) assessment tool. A separate meta-analysis was performed for diagnostic performance based on visual assessment and diagnostic cutoff values. Whenever possible, a bivariate random-effect model was used for analysis and pooling of diagnostic measures across studies.

Bilateral hypermetabolism in the posterior cingulum and the precuneus (p < 0.001) was observed in SIPD patients compared to patients with schizophrenia, with or without cannabis abuse. Conclusions: Our preliminary PET findings suggest that substance abuse may cause increased brain metabolism in patients with induced psychosis but not in those with schizophrenia. These differences in brain metabolism were found in the posterior cingulum and precuneus, which are two core regions of the default mode network in humans .

Statistical comparisons of [(18)F]FDG PET scans between healthy subjects and patients with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) using Statistical Parametric Mapping (SPM) usually require normalization of regional tracer uptake via ROIs defined using additional software. Here, we validate a simple SPM-based method for count normalization. FDG PET scans of 21 mild, 15 very mild AD, 11 aMCI patients and 15 age-matched controls were analyzed. First, we obtained relative increases in the whole patient sample compared to controls (i.e. areas relatively preserved in patients) with proportional scaling to the cerebral global mean (CGM). Next, average absolute counts within the cluster with the highest t-value were extracted. Statistical comparisons of controls versus three patients groups were then performed using count normalization to CGM, sensorimotor cortex (SMC) as standard, and to the cluster-derived counts. Compared to controls, relative metabolism in aMCI patients was reduced by 15%, 20%, and 23% after normalization to CGM, SMC, and cluster-derived counts, respectively, and 11%, 21%, and 25% in mild AD patients. Logistic regression analyses based on normalized values extracted from AD-typical regions showed that the metabolic values obtained using CGM, SMC, and cluster normalization correctly classified 81%, 89% and 92% of aMCI and controls; classification accuracies for AD groups (very mild and mild) were 91%, 97%, and 100%. The proposed algorithm of fully SPM-based count normalization allows for a substantial increase of statistical power in detecting very early AD-associated hypometabolism, and very high accuracy in discriminating mild AD and aMCI from healthy aging.

Abstract A variety of imaging techniques including radiographs, computed tomography, magnetic resonance imaging, ultrasound, bone-, and leukocyte scintigraphy and fluorodeoxyglucose positron emission tomography can contribute in the evaluation of a suspected prosthetic joint infection (PJI). The use of imaging has been intensively investigated and each imaging modality and radiopharmaceutical is characterized by specific diagnostic accuracy, drawbacks, and added value in diagnosing PJI. The choice of the most accurate imaging technique and optimal radiopharmaceutical depends of its effectiveness in each phase of the diagnostic algorithm. The objective of this chapter is to illustrate and describe the most frequently used imaging modalities and radiopharmaceuticals in the assessment of PJI. This chapter will mainly focus on imaging of the most prevalent joint replacements, the knee and hip. Keywords Conventional imaging prosthetic joint infection; Radiography; Ultrasound; CT & MRI; Nuclear imaging prosthetic joint infection; Bone scintigraphy; Leukocyte scintigraphy; FDG-PET; Hybrid imaging prosthetic joint infection

Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [18F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults. Metabolic connectivity was modeled at a group level using sparse inverse covariance estimation. Among 13 WM-relevant Brodmann areas (BAs), 6 appeared to be robustly connected. Connectivity within this network was significantly stronger in subjects with above-median WM performance. In respect to regional intensity, i.e., metabolism, no difference between groups was found. The results encourage examination of covariant patterns in FDG-PET data from non-neurodegenerative populations.

Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (p-tau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer’s disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4+/-3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE >20 points, n=30) and moderate (MMSE <21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [k]=0.34, p=0.016) for t-tau, 68% (k=0.10, n.s.) for p-tau181, and 68% (k=0.04, n.s.) for Aβ1-42. No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, k=0.77, p=0.001) and p-tau181 (88%, k=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer’s dementia, while this is not the case in subjects at an earlier disease stage.

AIMS: In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau(181)) and positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer's disease (AD) under clinical conditions.
METHOD: In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses.
RESULTS: p-tau(181) and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau(181) in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses.
CONCLUSIONS: FDG-PET and CSF p-tau(181) levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau(181) might be somewhat superior for a sensitive detection of patients with MCI.