Fluorodeoxyglucose Uptake Pattern Research Articles

Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers.

Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [18F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called "flip-flop" phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar's Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E- tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E- mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.

Novel Functional Radiomics for Prediction of Cardiac Positron Emission Tomography Avidity in Lung Cancer Radiotherapy.

Traditional methods of evaluating cardiotoxicity focus on radiation doses to the heart. Functional imaging has the potential to provide improved prediction for cardiotoxicity for patients with lung cancer. Fluorine-18 (18F) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging is routinely obtained in a standard cancer staging workup. This work aimed to develop a radiomics model predicting clinical cardiac assessment using 18F-FDG PET/CT scans before thoracic radiation therapy. Pretreatment 18F-FDG PET/CT scans from three study populations (N = 100, N = 39, N = 70) were used, comprising two single-institutional protocols and one publicly available data set. A clinician (V.J.) classified the PET/CT scans per clinical cardiac guidelines as no uptake, diffuse uptake, or focal uptake. The heart was delineated, and 210 novel functional radiomics features were selected to classify cardiac FDG uptake patterns. Training data were divided into training (80%)/validation (20%) sets. Feature reduction was performed using the Wilcoxon test, hierarchical clustering, and recursive feature elimination. Ten-fold cross-validation was carried out for training, and the accuracy of the models to predict clinical cardiac assessment was reported. From 202 of 209 scans, cardiac FDG uptake was scored as no uptake (39.6%), diffuse uptake (25.3%), and focal uptake (35.1%), respectively. Sixty-two independent radiomics features were reduced to nine clinically pertinent features. The best model showed 93% predictive accuracy in the training data set and 80% and 92% predictive accuracy in two external validation data sets. This work used an extensive patient data set to develop a functional cardiac radiomic model from standard-of-care 18F-FDG PET/CT scans, showing good predictive accuracy. The radiomics model has the potential to provide an automated method to predict existing cardiac conditions and provide an early functional biomarker to identify patients at risk of developing cardiac complications after radiotherapy.

Metabolic positron-emission tomography/magnetic resonance imaging in primary progressive aphasia and frontotemporal lobar degeneration subtypes: Reassessment of expected [18F]-fluorodeoxyglucose uptake patterns.

Clinical assessment of frontotemporal lobar degeneration (FTLD)/primary progressive aphasia (PPA) patients is challenging, given that common cognitive assessments rely extensively on language. Since asymmetry in neuroimaging biomarkers is often described as a central finding in these patients, our study evaluated [18F]-fluorodeoxyglucose (FDG) uptake patterns in patients meeting clinical and imaging criteria for FTLD, with emphasis on PPA. Fifty-one subjects underwent brain [18F]-FDG positron-emission tomography/magnetic resonance imaging (PET/MRI) as part of their routine clinical workup for dementia and neurodegenerative disease. Images were obtained using a Siemens Biograph mMR integrated 3T PET/MRI scanner. PET surface maps and fusion fluid-attenuated inversion recovery-PET images were generated utilizing MIMneuro software. Two board-certified neuroradiologists and one nuclear medicine physician blinded to patient history classified each FTLD/PPA subtype and assessed for left- versus right-side dominant hypometabolism. Qualitative and semiquantitative assessment demonstrated 18 cases of PPA, 16 behavioral variant frontotemporal dementia (bvFTD), 12 corticobasal degeneration, and 5 progressive supranuclear palsy. Among the 18 PPA subjects (11 svPPA, 5 lvPPA, and 2 agPPA), 12 (67%) demonstrated left-dominant hypometabolism and 6 (33%) right-dominant hypometabolism. While existing literature stresses left-dominant hypometabolism as a key imaging feature in the PPA subtypes, a third of our cases demonstrated right-dominant hypometabolism, suggesting that emphasis should be placed on the functionality of specific brain regions affected, rather than left versus right sidedness of hypometabolism patterns.

Characteristics of malignant thyroid lesions on [18F] fluorodeoxyglucose (FDG)-Positron emission tomography (PET)/Computed tomography (CT)

ObjectivesTo determine the imaging variables that can best differentiate malignant from benign thyroid lesions incidentally found on F-18 FDG PET/CT scans. MethodsAll F-18 FDG PET/CT studies starting from 2011 to end of 2016 were reviewed for incidental thyroid lesions or metabolic abnormalities. Only patients who were found to have FNAB or histopathology were included. Patients with known thyroid malignancy were excluded. Patients were analyzed for age, sex, SUVmax, non-enhanced CT tissue density in mean Hounsfield units (HU), uptake pattern (focal or diffuse) and gland morphology (MNG or diffuse). A control group of 15 patients with normal thyroid glands were used to assess the tissue density in HU for normal thyroid tissue. Sensitivity, specificity, PPV, NPV and accuracy to detect malignancy were calculated. Pearson Chi-square test was used to compare categorical variables while unpaired T-test and one way ANOVA test were used to compare means of continuous variables. ROC analysis was used to assess the best cut off points for SUVmax and HU. Regression analysis was used to detect the independent predictors for malignant lesions. ResultsBiopsy was unsatisfactory or indeterminate in 4/48 patients (8%). Only 44 patients (mean age 55.2 ± 14.7; 30 females (68 %)) with unequivocal FNAB or histopathology were included for further analysis. MNG was noted in 17/44 patients (38.6 %). Thyroid malignancy was found in 16/44 (36.4 %), benign thyroid lesions in 28/44 (63.6 %). Thyroid malignancies were 12 papillary, 1 follicular, 1 Hurthle cell neoplasm and 2 lymphoma. Benign lesions were 23 benign follicular or colloid nodules and 5 autoimmune thyroiditis. Focal FDG uptake pattern was more frequently associated with malignant lesions compared to benign lesions (75 % vs. 43 %; p = 0.039). The mean SUVmax and tissue density (HU) were both higher in malignant than benign lesions (8.8 ± 8.3 vs. 3.6 ± 1.9, p = 0.024) and (48.9 ± 12.7 vs. 32.9 ± 17.5, p = 0.003) respectively. The mean HU in the control group with normal thyroid tissue was 90 ± 7.4 significantly higher than in both the benign and malignant lesions (p < 0.001). ROC analysis revealed SUVmax cutoff of >4.7 and HU cutoff of >42 to best differentiate malignant from benign lesions. The sensitivity, specificity, PPV, NPV and accuracy to detect malignancy for SUVmax>4.7 were 68.8 %, 78.6 %, 64.8 %, 81.5 & 75.0 % (p = 0.002), for HU > 42 were 81.3.0 %, 75.0 %, 65.0 %, 87.5 & 77.3 % (p = 0.0003) and for both parameters combined were 87.5 %, 60.7 %, 56.0 %, 89.5 % and accuracy of 70.5 % (p = 0.002) respectively. Only HU > 42 and SUVmax>4.7 were independent predictors for malignancy with odd ratios 8.98 and 4.93 respectively. ConclusionA higher tissue density (HU > 42) and SUVmax>4.7 as well as tendency for focal uptake pattern are the most significant characteristics associated with malignant thyroid lesions occasionally detected on PET/CT.

Diagnostic Performance of the Support Vector Machine Model for Breast Cancer on Ring-Shaped Dedicated Breast Positron Emission Tomography Images.

The aim of this study was to evaluate the diagnostic ability of support vector machine (SVM) for early breast cancer (BC) using dedicated breast positron emission tomography (dbPET). We evaluated 116 abnormal fluorodeoxyglucose (FDG) uptakes less than 2 cm on dbPET images in 105 women. Fluorodeoxyglucose uptake patterns and quantitative PET parameters were compared between BC and noncancer groups. Diagnostic accuracy of the SVM model including quantitative parameters was compared with that of visual assessment based on FDG-uptake pattern. Age, maximum standardized uptake value, peak standardized uptake value, total lesion glycolysis, metabolic tumor volume, and lesion-to-contralateral background ratio were significantly different between BC and noncancer groups. Area under the curve, sensitivity, specificity, and accuracy for FDG-uptake pattern of visual assessment were 0.77, 0.57, 0.77, and 0.71, respectively; those of an SVM model including age, maximum standardized uptake value, total lesion glycolysis, and lesion-to-contralateral background ratio were 0.89, 0.94, 0.77, and 0.85, respectively. Support vector machine showed high diagnostic performance for BC using dbPET.

Positron emission tomography-based assessment of metabolic gradient and other prognostic features in sarcoma.

.Intratumoral heterogeneity biomarkers derived from positron emission tomography (PET) imaging with fluorodeoxyglucose (FDG) are of interest for a number of cancers, including sarcoma. A range of radiomic texture variables, adapted from general methodologies for image analysis, has shown promise in the setting. In the context of sarcoma, our group introduced an alternative model-based approach to the measurement of heterogeneity. In this approach, the heterogeneity of a tumor is characterized by the extent to which the 3-D FDG uptake pattern deviates from a simple elliptically contoured structure. By using a nonparametric analysis of the uptake profile obtained from this spatial model, a variable assessing the metabolic gradient of the tumor is developed. The work explores the prognostic potential of this new variable in the context of FDG-PET imaging of sarcoma. A mature clinical series involving 197 patients, 88 of whom have complete time-to-death information, is used. Texture variables based on the imaging data are also evaluated in this series and a range of appropriate machine learning methodologies are then used to explore the complementary prognostic roles for structure and texture variables. We conclude that both texture-based and model-based variables can be combined to achieve enhanced prognostic assessments of outcome for patients with sarcoma based on FDG-PET imaging information.

Does Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography Facilitate Treatment of Medication-Related Osteonecrosis of the Jaw?

There is considerable controversy over the treatment of medication-related osteonecrosis of the jaw (MRONJ) and growing interest and debate related to the timing, type, technique, and goals of surgical intervention. The specific aim was to evaluate the predictive value of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) on healing outcomes in patients undergoing surgery for MRONJ of the mandible. A retrospective cohort study of 31 patients with 33 MRONJ lesions of the mandible who had undergone surgery using FDG PET-CT was conducted. Data were collected on FDG uptake patterns, healing, follow-up, demographics, lesion characteristics, antiresorptive therapy, and adjunctive therapy. Panoramic and/or periapical radiographs were used to identify non-restorable teeth and PET-CT images were used to identify sequestra and FDG uptake. Above the mandibular canal, surgery consisted of marginal resection and/or debridement of clinically involved bone and exposure of clinically uninvolved bone identified by FDG uptake. Below the mandibular canal, mobile segments of bony sequestra were removed, but areas of clinically uninvolved bone with FDG uptake were not. Patients who did not heal underwent segmental resection and reconstruction with rigid fixation and a local or regional soft tissue flap or free fibular flap. The primary predictor variable was the FDG uptake pattern for each patient. The outcome variable was postoperative healing defined by mucosal closure without signs of infection or exposed bone at the time of evaluation. Two risk groups were identified based on FDG uptake pattern. The low-risk group, type A, included 22 patients with activity limited to the alveolus, torus, and/or basal bone superior to the mandibular canal. The high-risk group, type B, included 11 patients with type A FDG activity with extension inferior to the mandibular canal. Treatment of type A MRONJ lesions was more successful than treatment of type B MRONJ lesions (100 vs 27%; P < .001). Seven of the type B failures were successfully retreated by segmental resection and reconstruction (1 patient refused further treatment). These results showed that low-risk FDG PET-CT findings predicted successful healing with surgery above the mandibular canal. In contrast, high-risk FDG findings were associated with a greater than 50% risk of failure for treatment that extended below the mandibular canal. Although these failures suggest that FDG uptake indicates infected tissue, further research is needed to identify which high-risk patients are most likely to benefit from a conservative treatment protocol.

Different Scoring Methods of FDG PET/CT in Giant Cell Arteritis: Need for Standardization.

Giant cell arteritis (GCA) is the most frequent form of vasculitis in persons older than 50 years. Cranial and systemic large vessels can be involved. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is increasingly used to diagnose inflammation of the large arteries in GCA. Unfortunately, no consensus exists on the preferred scoring method. In the present study, we aim to define the optimal FDG PET/CT scoring method for GCA diagnosis using temporal artery biopsy and clinical diagnosis as the reference method.FDG PET/CT scans of GCA patients (12 glucocorticoid-naive, 6 on glucocorticoid treatment) and 3 control groups (inflammatory, atherosclerotic, and normal controls) were evaluated. We compared 2 qualitative visual methods (i.e. (1a) first impression and (1b) vascular uptake versus liver uptake) and 4 semiquantitative methods ((2a) SUVmax aorta, (2b) SUVmax aorta-to-liver ratio, (2c) SUVmax aorta-to-superior-caval-vein ratio, and (2d) SUVmax aorta-to-inferior-caval-vein ratio). FDG uptake pattern (diffuse or focal) and presence of arterial calcifications were also scored.Diagnostic accuracy of the visual method vascular versus liver uptake (1b) was highest when the cut-off point “vascular uptake higher than liver uptake” (sensitivity 83%, specificity 91%) was used. Sensitivity increased to 92% when patients on glucocorticoids were excluded from the analysis. Regarding the semiquantitative methods, the aorta-to-liver ratio (2b) with a cutoff of 1.03 had the highest diagnostic accuracy, with a sensitivity and specificity of 69% and 92%, respectively. Sensitivity increased to 90% when patients on glucocorticoids were excluded. The number of vascular segments with diffuse FDG uptake pattern was significantly higher in GCA patients without glucocorticoid use compared with all control patient groups. CRP was not significantly different between positive and negative FDG PET scans in the GCA group.Visual vascular uptake higher than liver uptake resulted in the highest diagnostic accuracy for the detection of GCA, especially in combination with a diffuse FDG uptake pattern. Of the semiquantitative methods, the aorta-to-liver SUVmax ratio (cutoff point = 1.03) had the highest diagnostic accuracy. The diagnostic accuracy increased when patients using glucocorticoids were excluded from the analyses.

Metabolic signatures of malignant and non-malignant mass-forming lesions in the periampulla and pancreas in FDG PET/CT scan: an atlas with pathologic correlation.

Positron emission tomography (PET) has been used for the characterization of pancreatic and periampullary lesions. Pancreatitis-associated inflammation affecting only a portion of the pancreas gives the appearance of a mass lesion on imaging. Consequently, the differential diagnosis between cancer and pancreatitis becomes a commonly encountered problem. Traditionally, PET was interpreted as positive (to denote malignancy) if fluorodeoxyglucose (FDG) activity in the pancreas exceeded background activity and as negative (to denote benign) if activity was less than or equal to background activity. However, the specificity was limited with this method of interpretation. A relatively wide overlap has been reported between semiquantitative uptake values obtained in cancers and those in inflammatory lesions. Also, the qualitative (metabolic patterns) and quantitative variables (standardized uptake values) have been complementary and at sometimes controversial to each other in various clinical situations. There is paucity of data in the literature highlighting the role of FDG PET/CT in characterization of such mass lesions. The primary aim of this pictorial review is to list the various pathologic processes of pancreas and periampulla that could be studied with FDG PET/CT and recognize the different FDG uptake patterns and apply this information to characterize the different lesions affecting the pancreas and periampulla. We have also discussed the limitations of conventional imaging and advantages of FDG PET/CT for the evaluation mass-forming lesions of the pancreas and periampulla.

Coexistence of atrial myxoma and lung cancer on fluorodeoxyglucose positron emission tomography/computed tomography: The impact of distinct fluorodeoxyglucose uptake pattern on differential diagnosis.

The information regarding fluorodeoxyglucose (FDG) uptake in benign and malignant cardiac tumors is limited in the literature and most of the currrently available data were derived from single case reports. Herein we reported coexistence of atrial myxoma and lung cancer on FDG positron emission tomography/computed tomography with the aim of emphasizing the importance of distinct FDG uptake pattern on differential diagnosis.

Normal patterns of 18F-FDG appendiceal uptake in children

Prior to interpreting PET/CT, it is crucial to understand the normal biodistribution of fluorodeoxyglucose (FDG). It is also important to realize that the normal biodistribution can vary between adults and children. Although many studies have defined normal patterns of pediatric FDG uptake in structures like the thymus, brown fat and bone marrow, patterns of normal pediatric bowel activity, specifically uptake within the appendix, have not been well described. Active lymphoid tissue has increased FDG uptake when compared with inactive tissue. Since children have more active lymphoid tissue than adults, and because the appendix contains aggregated lymphoid tissue, we postulated that appendiceal uptake may be increased in pediatric patients. To define the normal level of appendiceal FDG activity in children by evaluating a series of consecutive FDG PET/CT scans performed for other indications. After obtaining IRB approval, we retrospectively reviewed 128 consecutive whole-body pediatric FDG PET/CT examinations obtained for a variety of clinical indications. CT scans on which the appendix could not be visualized were excluded from analysis. CT scans on which the appendix could be visualized were evaluated for underlying appendiceal pathology. Studies with appendiceal or periappendiceal pathology by CT criteria were excluded. A region of interest (ROI) was placed over a portion of each appendix and appendiceal maximum standardized uptake value (SUVmax) was calculated. If an adjacent loop of bowel activity interfered with accurate measurements of the appendix SUVmax, the scan was excluded from the analysis. A chart review was performed on patients with elevated appendiceal SUVmax values to ensure that the patients did not have clinical symptomatology suggestive of acute appendicitis. When the appendix or a portion of the appendix could be visualized and accurately measured, the SUVmax was determined. SUVmax of the appendix was compared to the SUVmax of normal liver and ratios were recorded. A total of 128 scans were reviewed, patient ages 1 month to 21 years (mean age: 11.6 years). Thirty-one scans were excluded because of inability to visualize the appendix on CT. No scans were excluded for appendiceal/periappendiceal pathology on CT or chart review. No scans had to be excluded for inability to obtain an accurate SUVmax measurement because measurements were calculated on portions of the appendix separate from adjacent bowel using small ROIs. Maximum appendiceal SUVs ranged from 0.5 to 9.4 (mean: 2.2) with an appendix-to-liver background ratio ranging from 0.3 to 3.1 (mean: 1.1). FDG uptake in the appendix is typically similar to that of background activity. However, slight variations in appendiceal FDG uptake do occur, which should not be misinterpreted as pathological.

Role of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography in the characterization of pancreatic masses: Experience from tropics

Early detection and differentiation of malignant from benign pancreatic tumors is very essential as mass-forming pancreatitis is a frequently encountered problem. Positron emission tomography (PET) has a role in establishing the diagnosis of pancreatic carcinoma when the conventional imaging modalities or biopsies are nondiagnostic. In this prospective study, the utility of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in the characterization of mass-forming lesions of the pancreas was reported. (18)F-FDG-PET/CT was prospectively performed in 87 patients diagnosed to have periampullary or pancreatic mass. Lesions with focally increased FDG uptake in PET/CT were considered malignant, whereas those with diffuse or no FDG uptake were considered benign. Semiquantitative analysis with maximum standardized uptake value (SUVmax) was also calculated. The PET/CT results were compared with histopathological results in all patients. Based on the FDG uptake pattern, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for FDG-PET/CT in characterizing the periampullary and pancreatic masses into benign and malignant lesions were 93%, 90%, 95%, 87%, and 92% respectively. Receiver operating characteristics curve analysis of the SUVmax of the lesions yielded a cut-off value of 2.8, with a sensitivity and specificity of 87.5% and 45% respectively. The FDG uptake pattern in PET/CT can differentiate malignant from benign mass-forming lesions of the pancreas with high accuracy and a discrete cut-off value of SUVmax could not be defined for the same as even lesions with pancreatic tuberculosis showed very high FDG uptake. Hence, in patients with a suspicion of malignancy in the pancreas, a focally increase FDG uptake in PET/CT suggests the diagnosis of malignancy.

Multiclass classification of FDG PET scans for the distinction between Parkinson's disease and atypical parkinsonian syndromes

Most available pattern recognition methods in neuroimaging address binary classification problems. Here, we used relevance vector machine (RVM) in combination with booststrap resampling (‘bagging’) for non-hierarchical multiclass classification. The method was tested on 120 cerebral 18fluorodeoxyglucose (FDG) positron emission tomography (PET) scans performed in patients who exhibited parkinsonian clinical features for 3.5 years on average but that were outside the prevailing perception for Parkinson's disease (PD). A radiological diagnosis of PD was suggested for 30 patients at the time of PET imaging. However, at follow-up several years after PET imaging, 42 of them finally received a clinical diagnosis of PD. The remaining 78 APS patients were diagnosed with multiple system atrophy (MSA, N = 31), progressive supranuclear palsy (PSP, N = 26) and corticobasal syndrome (CBS, N = 21), respectively. With respect to this standard of truth, classification sensitivity, specificity, positive and negative predictive values for PD were 93% 83% 75% and 96%, respectively using binary RVM (PD vs. APS) and 90%, 87%, 79% and 94%, respectively, using multiclass RVM (PD vs. MSA vs. PSP vs. CBS). Multiclass RVM achieved 45%, 55% and 62% classification accuracy for, MSA, PSP and CBS, respectively. Finally, a majority confidence ratio was computed for each scan on the basis of class pairs that were the most frequently assigned by RVM. Altogether, the results suggest that automatic multiclass RVM classification of FDG PET scans achieves adequate performance for the early differentiation between PD and APS on the basis of cerebral FDG uptake patterns when the clinical diagnosis is felt uncertain. This approach cannot be recommended yet as an aid for distinction between the three APS classes under consideration.

O4‐09‐02: Diagnostic value of molecular imaging in a memory clinic setting

[11C]Pittsburgh compound-B (PIB) and [18F]fluorodeoxyglucose (FDG) PET measure fibrillar Aß load and glucose metabolism respectively. We assessed the diagnostic value of these tracers in an unselected memory clinic population. Paired dynamic (90 minutes) PIB and static FDG (15 minutes) PET scans were performed in 154 patients, shortly after completing a standard dementia work-up in a memory clinic. PET images were visually assessed by a nuclear medicine physician and results were reported to the cognitive neurologists. Outcome measures were (change in) clinical diagnosis and confidence in that diagnosis after disclosing PET results. At baseline, patients received the following diagnoses: Alzheimer's disease (AD, n = 66), mild cognitive impairment (MCI, n = 30), subjective memory complaints (SMC, n = 15), frontotemporal dementia (FTD, n = 18), dementia with Lewy bodies (DLB, n = 5), other forms of dementia (n = 10), and other psychiatric (n = 6) or neurological diseases (n = 4). PIB scans were positive in 40/66 patients with clinical AD (61%), 5/18 patients with clinical FTD (28%), 4/5 patients with DLB (80%), and 3/10 patients with other dementias (30%). FDG uptake patterns matched the clinical diagnosis in 58% of patients with clinical AD, and in 33% of patients with clinical FTD. PET results led to a change in diagnosis in 35 (23%) patients. A change in clinical diagnosis only occurred when diagnostic certainty was lower than 90% prior to PET. Furthermore, percentage diagnostic alterations after PET increased with decreasing pre-PET diagnostic confidence. Across groups, diagnostic confidence increased from 71±17% before to 87±16% after PET (P<0.001). Two year clinical follow-up in a subsample (n = 39) showed that PIB and FDG predicted progression to AD for patients with MCI, and that the diagnosis of dementia established after PET remained unchanged in 96% of the patients.

Bronchogenic Squamous Cell Carcinoma Mass with Central Photopenia on FDG-PET Scan

A 77-year-old man underwent chest imaging with a hybrid fluoro-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan. The study demonstrated a 5 cm mass on standard CT images (figure 1). The FDG-PET images demonstrated a thick-walled mass characterized by intense FDG uptake with a maximum standardized uptake value of 15.9 (figure 2). A large central region of the mass demonstrated photopenia (ie, normal FDG uptake). Volumetric analysis revealed 30% of the mass showed normal FDG uptake, or photophenia. Biopsy of the mass showed squamous cell carcinoma. The findings were consistent with carcinoma that had outgrown its vascular supply resulting in central tumor necrosis. Figure 1 Thoracic computed tomography image showing right lower lobe mass. Figure 2 Hybrid fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography image showing a thick-walled mass characterized by FDG uptake with a maximum standardized uptake value of 15.9 in the wall of the mass and central photopenia, consistent ... Central necrosis is most commonly observed in primary bronchogenic carcinomas of squamous cell origin, with one series reporting squamous cell origin in 82% of cases of necrotizing lung cancer.1 In an analysis of patterns of FDG uptake in lung cancer based on histologic classification, both large cell and squamous cell carcinomas were significantly more likely to demonstrate central cavitation compared with adenocarcinoma.2 The pathogenesis of cavitary malignancies has not been fully elucidated. It has been postulated that cavity formation in tumors is a consequence of rapid tumor growth which exceeds the supporting blood supply resulting in tumor necrosis and cavitation.3 This hypothesis is supported by reports that have shown tumor-associated vasculature inhibition by antiangiogenesis agents causing central necrosis and cavity formation in patients with squamous cell carcinoma of the lung.4, 5 The development of cavitation may have clinically significant consequences. Cavitating lung tumors may initially simulate an infectious process leading to delayed work up, late diagnosis, and presentation with advanced disease. In previous analyses of patient populations with heterogeneous stages of bronchogenic carcinoma, no difference in survival or response to therapy was found between lung cancers with cavitation and those without cavitation.1,6 However, in a more recent analysis of 72 patients with stage I non-small cell lung cancer, cavitation within the primary tumor was associated with significantly shorter disease-free survival time and overall survival time.7 In this analysis, cavitary lesions were significantly more common in squamous cell carcinomas than in adenocarcinomas and in epidermal growth factor receptor (EGFR)-overexpressing tumors than in tumors that did not overexpress EGFR. Accordingly, the presence of cavitation may have therapeutic implications in helping identify patients likely to benefit from targeted treatment with an anti-EGFR agent. In summary, clinicians should be aware that large bronchogenic carcinomas may develop central cavitation and necrosis, likely resulting from compromised vascular supply, resulting in central photopenia on FDG-PET imaging. This finding may have prognostic and therapeutic implications.

A Statistical Modeling Approach to the Analysis of Spatial Patterns of FDG-PET Uptake in Human Sarcoma

Clinical experience with positron emission tomography (PET) scanning of sarcoma, using fluorodeoxyglucose (FDG), has established spatial heterogeneity in the standardized uptake values within the tumor mass as a key prognostic indicator of patient survival. But it may be that a more detailed quantitation of the tumor FDG uptake pattern could provide additional insights into risk. The present work develops a statistical model for this purpose. The approach is based on a tubular representation of the tumor mass with a simplified radial analysis of uptake, transverse to the tubular axis. The technique provides novel ways of characterizing the overall profile of the tumor, including the introduction of an approach for the measurement of its phase of development. The phase measure can distinguish between early phase tumors, in which the uptake is highest at the core, and later stage masses, in which there can often be central voids in FDG uptake. Biologically, these voids arise from necrosis and fluid, fat or cartilage accumulations. The tumor profiling technique is implemented using open-source software tools and illustrations are provided with clinically representative scans. A series of FDG-PET studies from 185 patients is used to formally evaluate the prognostic benefit. Significant improvements in the prediction of patient survival and progression are obtained from the tumor profiling analysis. After adjustment for other factors including heterogeneity, a typical one standard deviation increase in phase (as determined by the analysis) is associated with close to 20% more risk of progression or death. The work confirms that more detailed quantitative assessments of the spatial pattern of PET imaging data of tumor masses, beyond the maximum FDG uptake (SUV(max)) and previously considered measures of heterogeneity, provide improved prognostic information for potential input to treatment decisions for future patients.

Significance of incidental focal uptake in prostate on 18-fluoro-2-deoxyglucose positron emission tomography CT images

To evaluate the clinical significance of incidental focal prostate fluorodeoxyglucose (FDG) uptake, we reviewed 18-F-FDG positron emission tomography (PET)/CT scans from 2003 to 2007 and selected cases with focal FDG uptake in prostate. Cases of known prostate cancer were excluded. The maximum standardised uptake value (SUV(max)), site (central or peripheral) and pattern (discrete or ill-defined) of FDG uptake, calcification (present or absent) and prostate volume (<30 or ≥30 cc) were recorded. The PET/CT findings were correlated with serum prostate-specific antigen (PSA) levels, imaging studies, clinical follow-up and biopsy. Of a total of 5119 cases, 63 (1.2%) demonstrated focal FDG uptake in prostate. Eight cases were lost to follow-up. Among the 55 cases with follow-up, malignancy was confirmed by biopsy in 3 (5.4%). The three malignant cases had SUV(max) values of 3.3, 3.6 and 2.3, and all were noted in the peripheral portion of prostate; two of these cases had a discrete FDG uptake pattern, none had calcification corresponding to the FDG uptake area and one had a prostatic volume greater than 30 cc. The mean SUV(max) of 52 benign cases was 3.2 ± 1.7 and focal FDG uptake was noted in the peripheral portion in 34 (65%), 20 (38%) cases showed a discrete FDG uptake pattern, 35 (67%) were accompanied by calcification and 32 (62%) had a prostatic volume greater than 30 cc. The majority of cases demonstrating focal FDG uptake in prostate were benign and no PET/CT finding could reliably differentiate benign from malignant lesions; however, when discrete focal FDG uptake without coincidental calcification is seen, particularly in the peripheral zone of the prostate, further clinical evaluation is recommended.

18F]fluorodeoxyglucose Uptake Patterns in Lung Before Radiotherapy Identify Areas More Susceptible to Radiation-Induced Lung Toxicity in Non-Small-Cell Lung Cancer Patients

Our hypothesis was that pretreatment inflammation in the lung makes pulmonary tissue more susceptible to radiation damage. The relationship between pretreatment [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake in the lungs (as a surrogate for inflammation) and the delivered radiation dose and radiation-induced lung toxicity (RILT) was investigated. We retrospectively studied a prospectively obtained cohort of 101 non-small-cell lung cancer patients treated with (chemo)radiation therapy (RT). [(18)F]FDG-positron emission tomography-computed tomography (PET-CT) scans used for treatment planning were studied. Different parameters were used to describe [(18)F]FDG uptake patterns in the lungs, excluding clinical target volumes, and the interaction with radiation dose. An increase in the dyspnea grade of 1 (Common Terminology Criteria for Adverse Events version 3.0) or more points compared to the pre-RT score was used as an endpoint for analysis of RILT. The effect of [(18)F]FDG and CT-based variables, dose, and other patient or treatment characteristics that effected RILT was studied using logistic regression. Increased lung density and pretreatment [(18)F]FDG uptake were related to RILT after RT with univariable logistic regression. The 95th percentile of the [(18)F]FDG uptake in the lungs remained significant in multivariable logistic regression (p = 0.016; odds ratio [OR] = 4.3), together with age (p = 0.029; OR = 1.06), and a pre-RT dyspnea score of ≥1 (p = 0.005; OR = 0.20). Significant interaction effects were demonstrated among the 80th, 90th, and 95th percentiles and the relative lung volume receiving more than 2 and 5 Gy. The risk of RILT increased with the 95th percentile of the [(18)F]FDG uptake in the lungs, excluding clinical tumor volume (OR = 4.3). The effect became more pronounced as the fraction of the 5%, 10%, and 20% highest standardized uptake value voxels that received more than 2 Gy to 5 Gy increased. Therefore, the risk of RILT may be decreased by applying sophisticated radiotherapy techniques to avoid areas in the lung with high [(18)F]FDG uptake.

Significance of incidental fluorodeoxyglucose uptake in the parotid glands and its impact on patient management

Minimal-to-low grade fluorodeoxyglucose (FDG) uptake in the parotid glands is regarded as a normal variant in a whole-body survey with FDG-PET. Not frequently, however, a relatively intense or asymmetric FDG uptake is encountered in the parotid glands. The aim of this study was to determine the causes and characteristics of this 'FDG accumulation of uncertain significance' in the parotid glands in patients without any known or suspected pathologies at the time of whole-body FDG-PET. In addition, we also examined patients in whom there was no documented evidence of parotid pathology before FDG-PET scan and a suspicion of disease involvement was first raised in the reports in view of focal uptake in the FDG-PET images. A total of 25 patients with 49 PET examinations [46 PET and three PET/computed tomography (CT) scans] were identified from the retrospective examination of PET reports and were analyzed in this study. Only those cases with no earlier history of disease involvement of parotid gland or known parotid pathology before FDG-PET were selected for this analysis. These patients were selected from a population of patients with a known malignancy elsewhere who underwent conventional whole-body FDG-PET or PET/CT for staging, disease viability assessment, or treatment monitoring purposes and had demonstrated varying patterns of FDG uptake (unilateral, bilateral, symmetric, or asymmetric) in the parotid glands. FDG uptake in the parotid glands was reported to be of uncertain significance in the majority of these patients and further correlation was suggested in the PET reports. In five patients with asymmetric and focally enhanced FDG uptake, a suspicion of disease involvement was raised in the reports. The results of appropriate correlative investigations with MRI, low-dose nonenhanced attenuation CT images (based on PET/CT scans), and histopathology (in cases in which focal lesions were revealed by the anatomic imaging modalities and biopsy was performed) carried out subsequent to the FDG-PET scans were reviewed for a definitive conclusion with regard to the significance of the FDG uptake in the parotid glands in these patients. In the absence of any focal pathology, clinical and follow-up FDG-PET data were reviewed for a logical conclusion, which were available in a majority of these patients. Standardized uptake values (maximum) were calculated by generating a manual region of interest over FDG activity. The pattern and the intensity of the FDG uptake were correlated with the final diagnosis. In six of the 25 patients with diffuse and symmetrical FDG uptake no clearcut pathology was demonstrated by clinical or radiological examinations. Five patients of this subgroup also demonstrated associated enhanced FDG activity in the submandibular salivary glands. Nineteen patients (76%) demonstrated asymmetric FDG uptake. Among these, focally enhanced uptake was observed in seven patients (28% of the total number of patients and 36.8% of the patients who demonstrated asymmetric FDG uptake in the parotids). Twelve patients (48% of total patients and 63.2% of the patients who demonstrated asymmetric FDG uptake) demonstrated asymmetric and diffuse FDG uptake pattern. No revelation of disease either by the MRI or follow-up clinical and FDG-PET examinations was observed in patients with asymmetric diffuse uptake. Five of the seven patients, who had asymmetric focal uptake in one of the parotids, were found to have focal lesions in either correlative MRI or low-dose nonenhanced CT. The final diagnosis based upon histopathology revealed primary parotid tumors (e.g., Warthin's tumor and pleomorphic adenoma, which presented as FDG-avid parotid incidentaloma) or metastatic disease involvement. Both the pattern and intensity of FDG uptake have important implications for differential diagnosis in the salivary glands in whole-body FDG-PET. A bilaterally symmetrical increased uptake is usually physiological. An asymmetrical uptake, especially when focal, would warrant further radiological and histopathological correlation to rule out disease involvement. At times, this can lead to the detection of an asymptomatic hitherto unknown etiology, which would have been otherwise interpreted as a metastatic disease in the background of an existing malignancy in these patients; this is noteworthy as it may have a bearing on the subsequent management of these patients.

Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies

Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications. Fifty consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.