Intensity Of FDG Uptake Research Articles

Differentiating primary from secondary lung cancer with FDG PET/CT and extra-pulmonary tumor grade

ObjectiveAssess feasibility of differentiating primary from secondary lung cancer in patients with a solid solitary malignant pulmonary lesion (SMPL) and a previously resected extrapulmonary tumor. MethodsPatients with pathology proven primary or secondary lung cancer from a solitary pulmonary lesion and known histopathology of extrapulmonary tumor were included. Patients with a small pulmonary lesion size, multiple malignant pulmonary nodules or an active infectious/inflammatory process were excluded. Extrapulmonary tumor grade was categorized as low, intermediate and high and was matched to FDG uptake intensity of SMPL, with FDG uptake range (SMPL/Liver SUVmax) of <0.9 for low, 0.91–1.99 for intermediate and >2.0 for high extrapulmonary tumor grade. ResultsOf 274 patients, 62 met the study criteria. 46 are primary and 16 are secondary lung cancer. There are 19 low, 27 intermediate and 16 high grade extrapulmonary tumors. Mean SMPL SUVmax is 8.2 ± 4.5 and SMPL/liver SUVmax is 2.4 ± 1.4. There are 37 cases (60%) with mismatched results (e.g., low FDG SMPL with intermediate or high grade extrapulmonary tumor or vice versa) and 25 matched cases (40%) that are inconclusive (e.g., low FDG with low tumor grade or high FDG with high tumor grade). Of the mismatched cases, we correctly predicted 30 cases (81%) as primary lung cancers. ConclusionA mismatch between the SMPL SUVmax and the extrapulmonary tumor grade could be used to differentiate a primary lung cancer from a metastasis with reasonable accuracy. Our preliminary results support the hypothesis that FDG uptake intensity of a metastatic pulmonary lesion mirrors the tumor aggressiveness of its extrapulmonary neoplasm of origin.

Development of a simple standardized scoring system for assessing large vessel vasculitis by 18F-FDG PET-CT and differentiation from atherosclerosis

PurposeThis study is to develop a structured approach to distinguishing large-artery vasculitis from atherosclerosis using 18-fluorodeoxyglucose positron emission tomography combined with low-dose computed tomography (FDG PET/CT).MethodsFDG PET/CT images of 60 patients were evaluated, 30 having biopsy-proven giant cell arteritis (GCA; the most common form of large-artery vasculitis), and 30 with severe atherosclerosis. Images were evaluated by 12 nuclear medicine physicians using 5 criteria: FDG uptake pattern (intensity, distribution, circularity), the degree of calcification, and co-localization of calcifications with FDG-uptake. Criteria that passed agreement, and reliability tests were subsequently analysed for accuracy using receiver operator curve (ROC) analyses. Criteria that showed discriminative ability were then combined in a multi-component scoring system. Both initial and final ‘gestalt’ conclusion were also reported by observers before and after detailed examination of the images.ResultsAgreement and reliability analyses disqualified 3 of the 5 criteria, leaving only FDG uptake intensity compared to liver uptake and arterial wall calcification for potential use in a scoring system. ROC analysis showed an area under the curve (AUC) of 0.90 (95%CI 0.87–0.92) for FDG uptake intensity. Degree of calcification showed poor discriminative ability on its own (AUC of 0.62; 95%CI 0.58–0.66). When combining presence of calcification with FDG uptake intensity into a 6-tiered scoring system, the AUC remained similar at 0.91 (95%CI 0.88–0.93). After exclusion of cases with arterial prostheses, the AUC increased to 0.93 (95%CI 0.91–0.95). The accuracy of the ‘gestalt’ conclusion was initially 89% (95%CI 86–91%) and increased to 93% (95%CI 91–95%) after detailed image examination.ConclusionStandardised assessment of arterial wall FDG uptake intensity, preferably combined with assessment of arterial calcifications into a scoring method, enables accurate, but not perfect, distinction between large artery vasculitis and atherosclerosis.

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

Evaluation of non-stenotic carotid atherosclerotic plaques with combined FDG-PET imaging and CT angiography in patients with ischemic stroke of unknown origin

ObjectivesNon-stenotic plaques are an underestimated cause of ischemic stroke. Imaging aspects of high-risk carotid plaques can be identified on CT angiography (CTA) and 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) imaging. We evaluated in patients with cryptogenic ischemic stroke the usefulness of FDG-PET-CTA. Methods44 patients imaged with CTA and FDG-PET were identified retrospectively. Morphological features were identified on CTA. Intensity of FDG uptake in carotid arteries was quantified on PET. ResultsPatients were imaged 7 ± 8 days after stroke. 44 non-stenotic plaques with increased 18F-FDG uptake were identified in the carotid artery ipsilateral to stroke and 7 contralateral. Most-diseased-segment TBR on FDG-PET was higher in artery ipsilateral vs. contralateral to stroke (2.24 ± 0.80 vs. 1.84 ± 0.50; p < .05). In the carotid region with high FDG uptake, prevalence of hypodense plaques and extent of hypodensity on CTA were higher in artery ipsilateral vs. contralateral to stroke (41% vs. 11%; 0.72 ± 1.2 mm2 vs. 0.13 ± 0.43 mm2; p < .05). ConclusionsIn patients with ischemic stroke of unknown origin and non-stenotic plaques, we found an increased prevalence of high-risk plaques features ipsilateral vs. contralateral to stroke on FDG-PET-CTA imaging suggesting a causal role for these plaques.

Physiologically intense FDG uptake of distal spinal cord on total-body PET/CT.

Physiologically mild-to-moderate FDG uptake of the spinal cord was reported. However, we noticed intense FDG uptake of distal spinal cord in several patients without definite spinal cord lesions on total-body PET/CT. Thus, this study aimed to investigate the frequency, pattern, intensity, and associations of FDG uptake in such cases on total-body PET/CT. The clinical characteristics of age, gender, body mass index (BMI), lower extremity symptom, diabetes, and fasting blood glucose level, and total-body FDG PET/CT metabolic parameters of maximum standard uptake value (SUVmax), SUVmax of lean body mass (SUVlbm), and SUVmax of body surface area (SUVbsa), were retrospectively analyzed in 527 patients without definite spinal cord lesions. Intense FDG uptake was defined as greater than liver glucometabolism on visual analysis, and T5 cord was selected as cord background. Intense FDG uptake of distal spinal cord was observed in 87 out of 527 patients (16.5%) and involved with 2-3 vertebral segments including T11-T12 in 33 cases (38.0%), T12-L1 in 29 (33.3%), and T11-L1 in 25 (28.7%). No lesions were demonstrated on follow-up physical examinations, MRI or contrast-enhanced CT in these 87 cases with intense FDG accumulation in the distal spinal cord. The median SUVmax, SUVlbm, and SUVbsa of distal spinal cord with intense FDG uptake were 3.8 (2.7-5.5), 2.9 (2.2-4.3), and 1.0 (0.7-1.6), respectively. Significant differences in SUVmax, SUVlbm, and SUVbsa of distal cord and cord background were found between the groups with and without intense FDG uptake (P < 0.05). Moreover, significant differences in ratios of distal spinal cord-to-cord background, to mediastinal blood pool, and to liver were observed between two groups (P < 0.05). Intense FDG uptake of distal cord was associated with age, diabetic status, and blood glucose level. Intense FDG uptake of distal spinal cord on total-body PET/CT may be physiological, more common in younger age, patients without diabetes, or lower fasting blood glucose.

Sacral Insufficiency Fracture after Radiotherapy for Cervical Cancer: Appearance and Dynamic Changes on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

Objective With the increasing application of radiotherapy for cervical cancer, the incidence of sacral insufficiency fracture (SIF) is increasing gradually. Incorrect or untimely treatment caused by misdiagnosis may lead to serious adverse clinical consequences. This study retrospectively analyzed SIF caused by radiotherapy regarding the appearance and dynamic changes in 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) positive emission tomography (PET)/computed tomography (CT) images to improve the understanding of SIF. Materials and Methods We retrospectively examined cervical cancer patients who underwent pelvic radiotherapy and 18F-FDG PET/CT between January 2014 and January 2021. Comparative analysis of the imaging performance and follow-up data was conducted. In total, 38 patients with ages ranging from 28 to 81 years (mean age 59.2 ± 10.6 y, median age 56 y) participated in the study. The respective characteristics of the 38 patients were summarized, and diagnosis was confirmed by follow-up changes. Results Twenty-five (65.8%) of the 38 patients suffered from unilateral SIF, and 13 (34.2%) suffered from bilateral SIF. After receiving radiotherapy, SIF first appeared in 3–42 months (median, 13 months). The main 18F-FDG PET/CT manifestations of SIF were increased bone density (35/38, 92.1%), anterior sacral fracture line (28/38, 73.7%), and diffuse or linear uptake patterns parallel to the sacroiliac joint (37/38, 97.3%), with the maximum standard uptake value (SUVmax) ranging from 1.8 to 5.9 (average, 3.1). Follow-up lasted 3–59 months (mean, 14 months). The main changes in SIF were increases in the bone density and high-density range and decreases in the FDG uptake intensity and hypermetabolism range. Three patients had secondary sacral or sacroiliac joint infection (3/38, 7.9%), and 3 patients had secondary fracture and/or pelvic deformation (3/38, 7.9%). Conclusions 18F-FDG PET/CT is an effective technique for diagnosing SIF. A small fracture line in the anterior sacrum and diffuse or linear areas of high density or metabolism parallel to the sacroiliac joint were the characteristic features of SIF. The main changes in SIF were increases in the bone density and high-density range and decreases in the FDG uptake intensity and hypermetabolism range.

Characterizing omental PET/CT findings for differentiating tuberculous peritonitis from peritoneal carcinomatosis.

To characterize and investigate PET/CT findings in the omentum in the differentiation of tuberculous peritonitis (TBP) and peritoneal carcinoma (PC). Thirty-nine patients with TBP and 113 patients with PC who underwent PET/CT were retrospectively enrolled. The omental uptake intensity, distribution characteristics, contracture, size and boundary of soft-tissue lesions, and CT patterns were reviewed. Absent and focal FDG uptake in the lesser omentum was more common in the PC patients (P = 0.034 and P = 0.017, respectively), and diffuse FDG uptake in the lesser omentum was more common in the TBP patients (P < 0.001). An apron-like pattern in the greater omentum commonly occurred in the TBP patients (P = 0.004). Micronodules (< 5mm) were more common in the TBP patients (P < 0.001), and masses (> 3cm) were more common in the PC patients (P = 0.001). Smudged and nodular patterns occurred more frequently in the TBP patients than in the PC patients (P < 0.001 and P = 0.003, respectively), and the caked pattern occurred more frequently in the PC patients (P < 0.001). There was no significant difference in the FDG uptake intensity and the boundary of soft-tissue lesions between the TBP and PC patients (P = 0.191 and P = 0.061, respectively). Diffuse FDG uptake, an apron-like pattern, micronodules, and a smudged and nodular pattern might be significant differential features of TBP. Absent and/or focal FDG uptake, mass, and a caked pattern might be significant differential features of PC.

Head-to-head comparison between 68Ga-PSMA and 18F-FDG-PET/CT in lymphomas: a preliminary analysis.

Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes. Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin's lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin's lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images. FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0-8.2) to 30.9 for FDG and from 1.7 (1.7-1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images. HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas.

Are 18F-fluorodeoxyglucose positron emission tomography results reliable in patients with ascending aortic grafts? A prospective study in non-infected patients.

Our goal was to define characteristic patterns of 18F-fluorodeoxyglucose in non-infected patients with ascending aortic prosthetic grafts during the first year after surgery. 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) was performed at 3, 6 and 12 months postoperatively in 26 uninfected patients. Clinical, analytical and microbiological (blood culture) assessments were performed to confirm the absence of infection. FDG uptake intensity [measured through maximum standardized uptake values (SUVmax) and the target-to-background ratio] and distribution patterns were obtained. Models of generalized estimating equations were used to assess the evolution of the SUVmax over time. The results were compared to those in our endocarditis-over-ascending-aortic-graft series database. The receiver operating characteristic curves of the control group and the 12-month group were assessed. All patients showed increased uptake in all areas. The uptake pattern was heterogeneous in 47.4%, 43.5% and 42.3% at 3, 6 and 12 months. The means and standard deviations of the SUVmax in the graft were 4.80 (±0.99), 4.28 (±0.88) and 4.14 (±0.87) at 3, 6 and 12 months after surgery. A comparison of all values obtained in the 6th and 12th months compared to those from the 3rd month revealed a slow decrease that may persist after the first year. The cut-off value of SUVmax of 4.24 had an overall sensitivity of 84.6% and specificity of 57.7% for patients seen at 12 months. Non-infected ascending aortic grafts showed no predominant uptake pattern; they also showed increased 18F-fluorodeoxyglucose activity that could persist beyond the first year. Caution is therefore recommended when interpreting PET/CT images obtained during the first year after surgery.

Assessment of Therapeutic Response in Pyogenic Vertebral Osteomyelitis Using 18F-FDG-PET/MRI.

Purpose: There is still no definite method to determine therapeutic response in pyogenic vertebral osteomyelitis (PVO). We analyzed the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for assessing therapeutic response in PVO. Methods: This retrospective study included 53 patients (32 men and 21 women) with lumbar PVO. The results of clinical assessments for therapeutic response were divided into “Cured” (group C) and “Non-cured” (group NC). The differences in clinical and radiological features of PVO lesions between the two groups were analyzed using clinical data and simultaneous FDG-PET/magnetic resonance imaging (MRI) obtained at each clinical assessment. Results: Clinical assessments and FDG-PET/MRIs were performed at 41.89 ± 16.08 (21–91) days of parenteral antibiotic therapy. There were 39 patients in group C and 14 in group NC. Diagnostic accuracies (DAs) of FDG uptake intensity-based interpretation and C-reactive protein (CRP) for residual PVO were as follows (p < 0.01): 84.9% of the maximum standardized uptake value of PVO lesion (PvoSUVmax), 86.8% of ΔPvoSUVmax−NmlSUVmax (SUVmax of normal vertebra), 86.8% of ΔPvoSUVmax−NmlSUVmean (SUVmean of normal vertebra), and 71.7% of CRP. DAs were better (92.5–94.3%) when applying FDG uptake intensity-based interpretation and CRP together. Under the FDG uptake distribution-based interpretation, FDG uptake was significantly limited to intervertebral structures in group C (p = 0.026). Conclusion: The interpretations of intensity and distribution of FDG uptake on FDG-PET are useful for detecting residual PVO in the assessment of therapeutic response of PVO. The combination of FDG-PET and CRP is expected to increase DA for detecting residual PVO.

In the evaluation of patients with skull base osteomyelitis, does 18F-FDG PET CT have a role?

To evaluate the diagnostic performance of regional fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET-CT) in patients with skull base osteomyelitis (SBO) and to compare with magnetic resonance imaging (MRI) whenever available. A total of 77 patients (male:female = 56:21; mean age 66.4 ± 9.4 years) with clinically suspected SBO, who underwent regional F-FDG PET-CT were included in this retrospective study. F-FDG PET-CT images were analyzed for presence, localization and intensity of FDG uptake. Diagnostic performance of F-FDG PET-CT was analyzed based on histopathology, culture, and clinical/imaging follow-up. The agreement analysis between F-FDG PET-CT and MRI findings was performed in 56 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of F-FDG PET-CT for diagnosing SBO were 96.7, 93.3, 98.3, 87.5, and 96.1%, respectively. The average SUVmax of the lesions was 5.9 ± 3.5. The SUVmax of the fungal lesions was lower than that of bacterial lesions with P-value of <0.001. On comparing variables like C-reactive protein, erythrocyte sedimentation rate, and SUVmax for prediction of recurrence/progression, by plotting an ROC curve, the SUVmax was found to be an independent prognostic marker. 56 out of 77 patients had undergone both F-FDG PET-CT and MRI. The agreement analysis between the modalities showed almost perfect agreement for delineation of soft tissue and bony involvement with κ values of 0.82 and 0.81, respectively. F-FDG PET-CT is a sensitive tool in evaluation of patients with SBO. It shows a very good agreement with the MRI. It plays a critical role in treatment response evaluation.

507P - In vivo evaluation of cisplatin-loaded PEG-PCL block copolymeric nanoparticles for anticancer drug delivery

BackgroundCisplatin has proved itself an effective therapeutic approach in a variety of solid tumors. However, its therapeutic concentration was limited since the presence of variant inevitable side effects. Nanoparticles (NPs) developed from amphiphilic copolymers have drawn great attention for prolonging drug residency in blood circulation, increasing tumor accumulation, reducing serum protein adherence and preventing uptake by the reticuloendothelial system (RES). Previously, we synthesized polyethylene glycol (PEG)- polycaprolactone (PCL) NPs as anticancer drug and had confirmed its efficacy in vitro. To comprehensively study the influences of cisplatin-loaded PEG-PCL copolymeric NPs, we enlarge the amount of murine models and applied more physical tests to offer a broader view of the impact that cisplatin-loaded PEG-PCL copolymeric NPs brought about. MethodsWe observed the physical alteration of hepatoma-bearing mice and the tumors after administration of cisplatin-loaded PEG-PCL nanoparticles (NPs). Cell uptake and apoptotic rates were measured through fluorescence microscopy and flowcytometry. Murine blood was collected and examined. Positron emission tomography/computed tomography (PET/CT) was utilized for the detection of tumor metabolic status. ResultsThe biopsy and the measurement of tumor volume and murine weights have confirmed the therapeutic efficacy of cisplatin-loaded NPs and was positively related to the dosage of cisplatin. Fluorescence microscope images indicated a better cellular uptake rate of cisplatin-loaded NPs with intracellularly-aggregated, heterogeneous rhodamine B observed in LoVo cells. A decline of apoptotic rates in cisplatin-loaded NPs was measured. Blood tests exhibited less side effects in cisplatin-loaded NPs with higher level of white blood cells and lower aspartate transaminase (AST). PET/CT images revealed less intensity of FDG uptake in murine received higher dosage of cisplatin-loaded NPs. ConclusionsNanoparticles prepared from PEG-PCL/PCL hybrids could be a promising drug carrier for intratumoral delivery with greater efficacy and less side effects. This study provides a theoretical basis for possible clinical application. Legal entity responsible for the studyComprehensive Cancer Center of Drum-Tower Hospital Comprehensive Cancer Center of Drum-Tower Hospital Comprehensive Cancer Center of Drum-Tower Hospital. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

4089Prognostic value of cardiac metabolic activity assessed by 18F-FDG PET in patients with cardiac sarcoidosis

Abstract Background Sarcoidosis is a systemic granulomatous disease that affects multiple organs. Among these,the presenceof cardiac involvementis recognized as a determinant of worse clinical outcomes. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a valuable modality for detecting active inflammatory lesions associated with cardiac sarcoidosis (CS). Generally,the maximum standardized uptake value (SUV) is suitable for evaluating disease activity in CS, but this quantitative method had limitations because it does not integrate both volume and intensity of FDG uptake simultaneously. Cardiac metabolic activity (CMA), which is quantitative measures of FDG volume-intensity, could be a diagnostic tool in the evaluation of CS. However, its prognostic implication in patients with CS is unclear. Purpose We sought to investigate whether CMA assessed by FDG-PET was associated with long-term worse clinical outcomes in patients with CS. Methods A total of 76 consecutive patients suspected CS who underwent FDG-PET between January 2010 and April 2018 in our university hospital were registered. We excluded patients whodid not meet the Japanese Ministry of Health and Welfare 2007 criteria (n=9) and those who received oral corticosteroids at the time of FDG-PET (n=5). Ultimately, 62 CS patients with definitively diagnosed were included in this study.We used a dedicated software to analyze SUV. Cardiac metabolic volume (CMV) was defined as the volume within the boundary determined by the threshold (SUV mean of blood pool × 1.5). CMA was calculated by multiplying CMV by SUV mean. The primary outcome of interest was the composite of advanced atrioventricular block, ventricular tachycardia, ventricular fibrillation, heart failure hospitalization, and all-cause death. Results During a median follow-up period of 1287 (IQR 806–1809) days after the first FDG-PET, the adverse events occurred in 12 patients (19%). Events group had significantly higher CMA compared to no events group (83 [IQR 11–330] vs. 354 [IQR 70–577]) (Figure A). Based on ROC analysis, the optimal cut-off value of CMA for the discrimination of the adverse events was 244 ml, and c-index was 0.71 (95% CI, 0.55–0.87). Patients with high CMA (≥244 ml, n=23) had lower LVEF, and higher prevalence of New York Heart Association functional class III or IV, and higher plasma BNP level compared to those with low CMA (&lt;244 ml, n=39). Kaplan-Meier analysis revealed that composite adverse events more frequently occurred in patients with high CMA compared to those with low CMA (Figure B).Univariable Cox regression analysis showed that higher CMA was associated with increased subsequent risk of adverse events (HR 1.47, 95% CI 1.06–2.24). Conclusions Higher CMA assessed by FDG-PET was associated with worse clinical long-term outcomes in patients with CS, suggesting that measurement of the volume-intensity of abnormal FDG uptake may be useful for risk stratification in patients with CS.

Morpho-metabolic post-surgical patterns of non-infected prosthetic heart valves by [18F]FDG PET/CTA: "normality" is a possible diagnosis.

To define characteristic PET/CTA patterns of FDG uptake and anatomic changes following prosthetic heart valves (PVs) implantation over time, to help not to misdiagnose post-operative inflammation and avoid false-positive cases. Prospective evaluation of 37 post-operative patients without suspected infection that underwent serial cardiac PET/CTA examinations at 1, 6, and 12 months after surgery, in which metabolic features (FDG uptake distribution pattern and intensity) and anatomic changes were evaluated. Standardized uptake values (SUVs) were obtained and a new measure, the valve uptake index (VUI), (SUVmax-SUVmean)/SUVmax, was tested to homogenize SUV results.In total, 111 PET/CTA scans were performed in 37 patients (19 aortic and 18 mitral valves). FDG uptake was visually detectable in 79.3% of patients and showed a diffuse, homogeneous distribution pattern in 93%. Quantitative analysis yielded a mean maximum standardized uptake value (SUVmax) of 4.46 ± 1.50 and VUI of 0.35 ± 0.10. There were no significant differences in FDG distribution or uptake values between 1, 6, or 12 months. No abnormal anatomic changes or endocarditis lesions were detected in any patient during follow-up. FDG uptake, often seen in recently implanted PVs, shows a characteristic pattern of post-operative inflammation and, in the absence of associated anatomic lesions, could be considered a normal finding. These features remain stable for at least 1 year after surgery, so questioning the recommended 3-month safety period. A new measure, the VUI, can be useful for evaluating the FDG distribution pattern.

Nuclear Imaging: Focus on Vascular Probes

Noninvasive imaging technologies offer to identify several anatomic and molecular features of high-risk plaques. For the noninvasive molecular imaging of atherosclerotic plaques, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 18F-fluorodeoxyglucose (FDG) is currently the most widely used radiopharmaceutical for molecular imaging of atherosclerotic plaques with positron emission tomography. The intensity of FDG uptake in the vascular wall correlates closely with the degree of macrophage infiltration in atherosclerotic plaques. FDG positron emission tomographic imaging has become a powerful tool to identify and monitor noninvasively inflammatory activities in atherosclerotic plaques over time. This review examines how FDG positron emission tomographic imaging has given us deeper insight into the role of inflammation in atherosclerotic plaque progression and discusses perspectives for alternative radiopharmaceuticals to FDG that could provide a more specific and simple identification of high-risk lesions and help improve risk stratification of atherosclerotic patients. Visual Overview- An online visual overview is available for this article.

Focal Liver Uptake on FDG PET/CT Without CT Correlate: Utility of MRI in the Evaluation of Patients With Known Malignancy.

OBJECTIVE. The purpose of this study was to determine the significance and utility of MRI in evaluation of focal hepatic uptake on FDG PET/CT without a CT correlate in patients with known malignancy. MATERIALS AND METHODS. In this retrospective study, we identified 36 of 1851 patients between 2005 and 2012 with known malignancy (19 women, 17 men; mean age, 56.1 years old) who had focal hepatic uptake on FDG PET/CT without a CT correlate and follow-up MRI within 100 days for assessment of uptake. Two radiologists reviewed the FDG PET/CT images together, reached consensus about presence of focal hepatic uptake, and measured maximum standardized uptake value (SUVmax) of the focal uptake and background liver. MR images were then reviewed to identify any correlate. Follow-up imaging and histopathologic data were reviewed to confirm or refute metastasis. Statistical correlation between intensity of FDG uptake and presence of focal lesions on MRI was performed. RESULTS. Fifty sites of focal hepatic uptake without CT correlate were identified. The median SUVmax was 4.1 (range, 2.1-10.1), whereas the ratio of median SUVmax of the hepatic lesion to that of normal parenchyma was 1.3 (range, 0.98-2.6). MRI confirmed focal lesions in 26 of 50 sites (52%). Seventy-seven percent of cases of hepatic uptake with an MRI correlate (20/26) were confirmed as metastatic disease (six cases at histopathology). Therefore, 40% of cases of hepatic uptake without a CT correlate (20/50) were metastases. We found no statistically significant difference in the SUVmax of hepatic lesions and SUVmax ratio between the groups with and without an MRI correlate (median SUVmax = 3.85 vs 4.2, p = 0.5; SUVmax ratio = 1.32 vs 1.31, p = 0.97) as well as between the groups with the final diagnosis of benign lesions and metastasis (SUVmax = 4.05 vs 3.95, p = 0.64; SUVmax ratio = 1.31 vs 1.32, p = 0.91). CONCLUSION. More than half of the cases of focal hepatic uptake on PET/CT without a CT correlate had an MRI correlate in our study, and more than 75% of these lesions were metastases, regardless of SUVmax.

FDG atrial uptake is associated with an increased prevalence of stroke in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of stroke. Indeed, silent AF is frequently identified in unexplained ischemic stroke. 18F-FDG-PET/CT is a powerful tool for assessing myocardial metabolic shift and inflammation, both potentially at stake in AF. This case-control study investigated whether AF could promote FDG uptake in atria after physiological myocardial glucose uptake suppression, and the potential relationship between FDG atrial uptake and prevalence of stroke. We retrospectively enrolled 128 patients (64 consecutive patients with AF and 64 without AF as the control group, matched for age and sex) who underwent 18F-FDG-PET/CT after a high-fat low-carbohydrate diet. We analyzed visual and quantitative FDG uptake parameters of the right and left atria (RA/LA) and the right and left appendages (RAA/LAA), and selected clinical features including history of stroke. Diffuse right atrial uptake was present in a third of patients with AF and only two patients in the control group. FDG uptake intensity of both atria was significantly associated with the underlying heart rhythm. The occurrence of stroke was strongly associated with detectable atrial uptake in multivariate analysis, with an odds ratio superior to that of other known risk factors. This study shows a significant correlation between FDG atrial uptake and AF. While inconsistent, this pattern seems to be associated with an increased prevalence of cardioembolic stroke.

Positron Emission Tomography 18F-Fluorodeoxyglucose Uptake Correlates with KRAS and EMT Gene Signatures in Operable Esophageal Adenocarcinoma

Background18F-fluorodeoxyglucose positron emission tomography is an imaging modality critical to the diagnosis and staging of esophageal cancer. Despite this, the genetic abnormalities associated with increased 18F-fluorodeoxyglucose (FDG)-maximum standardized uptake value (SUVmax) have not been previously explored in esophageal adenocarcinoma. Materials and methodsTreatment-naïve patients, for whom frozen tissue and 18F-fluorodeoxyglucose positron emission tomography data were available, undergoing esophagectomy from 2003 to 2012, were identified. Primary tumor FDG-uptake (SUVmax) was quantified as low (<5), moderate, or high (>10). Genome-wide expression analyses (e.g., microarray) were used to examine gene expression differences associated with FDG-uptake. ResultsEighteen patients with stored positron emission tomography data and tissue were reviewed. Overall survival was similar between patients with high (n = 9) and low (n = 6) FDG-uptake tumors (P = 0.71). Differences in gene expression between tumors with high and low FDG-uptake included enriched expression of various matrix metalloproteinases, extracellular-matrix components, oncogenic signaling members, and PD-L1 (fold-change>2.0, P < 0.05) among the high-FDG tumors. Glycolytic gene expression and pathway involvement were similar between the high- and low-FDG tumor subsets (P = 0.126). Gene ontology analysis of the most differentially expressed genes demonstrated significant upregulation of gene sets associated with extracellular matrix organization and vascular development (P < 0.005). Gene set enrichment analysis further demonstrated associations between FDG-uptake intensity and canonical oncogenic processes, including hypoxia, angiogenesis, KRAS signaling, and epithelial-to-mesenchymal transition (P < 0.001). Interestingly, KRAS expression did not predict worse survival in a larger cohort (n = 104) of esophageal adenocarcinomas (P = 0.64). ConclusionsThese results suggest that elevated FDG-uptake is associated with a variety of oncogenic alterations in operable esophageal adenocarcinoma. These pathways present potential therapeutic targets among tumors exhibiting high FDG-uptake.

A novel genomic signature predicting FDG uptake in diverse metastatic tumors

BackgroundBuilding a universal genomic signature predicting the intensity of FDG uptake in diverse metastatic tumors may allow us to understand better the biological processes underlying this phenomenon and their requirements of glucose uptake.MethodsA balanced training set (n = 71) of metastatic tumors including some of the most frequent histologies, with matched PET/CT quantification measurements and whole human genome gene expression microarrays, was used to build the signature. Selection of microarray features was carried out exclusively on the basis of their strong association with FDG uptake (as measured by SUVmean35) by means of univariate linear regression. A thorough bioinformatics study of these genes was performed, and multivariable models were built by fitting several state of the art regression techniques to the training set for comparison.ResultsThe 909 probes with the strongest association with the SUVmean35 (comprising 742 identifiable genes and 62 probes not matched to a symbol) were used to build the signature. Partial least squares using three components (PLS-3) was the best performing model in the training dataset cross-validation (root mean square error, RMSE = 0.443) and was validated further in an independent validation dataset (n = 13) obtaining a performance within the 95% CI of that obtained in the training dataset (RMSE = 0.645). Significantly overrepresented biological processes correlating with the SUVmean35 were identified beyond glycolysis, such as ribosome biogenesis and DNA replication (correlating with a higher SUVmean35) and cytoskeleton reorganization and autophagy (correlating with a lower SUVmean35).ConclusionsPLS-3 is a signature predicting accurately the intensity of FDG uptake in diverse metastatic tumors. FDG-PET might help in the design of specific targeted therapies directed to counteract the identified malignant biological processes more likely activated in a tumor as inferred from the SUVmean35 and also from its variations in response to antineoplastic treatments.

Predictors of unexpected nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC) submitted to thoracoscopic lobectomy.

In the last decades, the use of video-assisted thoracoscopic surgery (VATS) lobectomy for the treatment of early stage non-small cell lung cancer is continuously growing. This is mainly due to the development of more advanced surgical devices, to the rising incidence of peripheral lung tumors and is also favored by the increased reliability of preoperative staging techniques. Despite this progress, postoperative unexpected nodal upstaging is still a relevant issue. Aim of this study is to identify possible predictors of unexpected nodal upstaging in patients affected by cT1-3N0 NSCLC submitted to VATS lobectomy. A total of 231 cases of cT1-3N0 patients submitted to thoracoscopic lobectomy at our centre between June 2012 and October 2016 were retrospectively reviewed. All data regarding clinical staging by means of computed tomography (CT) and positron-emission tomography (PET)/CT were collected and reviewed. The subsequent pathological staging has been analyzed, with special regards to the possible type of nodal involvement, and the number of pathological nodal stations. Most of the patients included in this study were in a clinical stage cT1aN0, cT1bN0 (stage IA) and cT2aN0 (stage IB), 86 (37.2%) patients, 73 (31.6%) patients and 62 (26.8%) patients, respectively. Postoperative histopathological analysis showed that the most frequent tumor histotype was adenocarcinoma (192 patients, 83.1%). Thirty-eight (16.5%) patients had a nodal upstaging; among these, 17 (7.4%) patients had N2 disease (8 patients with isolated mediastinal nodal involvement, 9 patients with N1 + N2 disease) and 21 (9.1%) patients had an isolated hilar nodal involvement (N1). At bivariate analysis, the clinical T (cT)-parameter (P=0.023), the histotype (P=0.029) and the pathological T (pT)-parameter (P=0.003) were identified as statistically significant predictors of nodal upstaging. Concerning the type of nodal upstaging, the pT was found to be statistically significant (P=0.042). At bivariate analysis for the number of involved nodal stations, a statistical significance was highlighted for the parameters cT (P=0.030) and pT (P=0.027). With linear logistic regression, histology as well as pT reached statistical significance (P=0.0275 and P=0.0382, respectively). No correlation was found between nodal upstaging and the intensity of FDG uptake in the primary lung tumor or with the timing between PET and surgery. There is a strong correlation between the clinical staging of the parameter T evaluated with CT and the possible unexpected nodal upstaging. The same correlation with nodal upstaging is found for pT. At equal clinical stage, in patients affected by adenocarcinoma of the lung the relative risk of having a postoperative unexpected nodal upstaging is almost 7 times higher than in patients with squamous cell carcinoma.