Glucose Positron Emission Research Articles

Multimodal imaging measures in the prediction of clinical response to deep brain stimulation for refractory depression: A machine learning approach

Objectives This study compared machine learning models using unimodal imaging measures and combined multi-modal imaging measures for deep brain stimulation (DBS) outcome prediction in treatment resistant depression (TRD). Methods Regional brain glucose metabolism (CMRGlu), cerebral blood flow (CBF), and grey matter volume (GMV) were measured at baseline using 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography (PET), arterial spin labelling (ASL) magnetic resonance imaging (MRI), and T1-weighted MRI, respectively, in 19 patients with TRD receiving subcallosal cingulate (SCC)-DBS. Responders (n = 9) were defined by a 50% reduction in HAMD-17 at 6 months from the baseline. Using an atlas-based approach, values of each measure were determined for pre-selected brain regions. OneR feature selection algorithm and the naïve Bayes model was used for classification. Leave-out-one cross validation was used for classifier evaluation. Results The performance accuracy of the CMRGlu classification model (84%) was greater than CBF (74%) or GMV (74%) models. The classification model using the three image modalities together led to a similar accuracy (84%0 compared to the CMRGlu classification model. Conclusions CMRGlu imaging measures may be useful for the development of multivariate prediction models for SCC-DBS studies for TRD. The future of multivariate methods for multimodal imaging may rest on the selection of complementing features and the developing better models.Clinical Trial Registration: ClinicalTrials.gov (#NCT 01983904)

The Role of Echocardiography in the Contemporary Diagnosis and Prognosis of Cardiac Sarcoidosis: A Comprehensive Review.

Cardiac sarcoidosis (CS) is a rare inflammatory disorder characterised by the presence of non-caseating granulomas within the myocardium. Contemporary studies have revealed that 25-30% of patients with systemic sarcoidosis have cardiac involvement, with detection rates increasing in the era of advanced cardiac imaging. The use of late gadolinium enhancement cardiac magnetic resonance and 18fluorodeoxy glucose positron emission tomography (FDG-PET) imaging has superseded endomyocardial biopsy for the diagnosis of CS. Echocardiography has historically been used as a screening tool with abnormalities triggering the need for advanced imaging, and as a tool to assess cardiac function. Regional wall thinning or aneurysm formation in a noncoronary distribution may indicate granuloma infiltration. Thinning of the basal septum in the setting of extracardiac sarcoidosis carries a high specificity for cardiac involvement. Abnormal myocardial echotexture and eccentric hypertrophy may be suggestive of active myocardial inflammation. The presence of right-ventricular involvement as indicated by free-wall aneurysms can mimic arrhythmogenic right-ventricular cardiomyopathy. More recently, the use of myocardial strain has increased the sensitivity of echocardiography in diagnosing cardiac involvement. Echocardiography is limited in prognostication, with impaired left-ventricular (LV) ejection fraction and LV dilatation being the only established independent predictors of mortality. More research is required to explore how advanced echocardiographic technologies can increase both the diagnostic sensitivity and prognostic ability of this modality in CS.

Evaluation of parametrial infiltration in patients with IB-IIB cervical cancer by a radiomics model integrating features from tumoral and peritumoral regions on 18 F-FDG PET/MRI images.

Parametrial infiltration (PMI) is an essential factor in staging and planning treatment of cervical cancer. The purpose of this study was to develop a radiomics model for accessing PMI in patients with IB-IIB cervical cancer using the features from 18 F-FDG PET/MRI images. In this retrospective study, 66 patients with FIGO stage IB-IIB cervical cancer (22 with PMI and 44 without PMI) underwent 18 F-FDG PET/MRI were divided into a training (n = 46) and a testing dataset (n = 20). Features were extracted from both tumoral and peritumoral regions on 18 F-FDG PET/MRI. Single-modality and multi-modality radiomics models were developed with random forest to predict PMI. The performance of models was evaluated with F1 score, accuracy and AUC. Kappa test was used to observe the differences between pathological results and PMI evaluated by radiomics-based models. Intraclass correlation coefficient for features extracted from each ROI was measured. Three-fold cross-validation was conducted to confirm the diagnostic ability of the features. The radiomics models developed by features from primary tumor on T2 weighted (F1 Score = 0.400, accuracy = 0.700, AUC = 0.708, Kappa = 0.211, P = 0.329) and peritumoral region on PET (F1 Score = 0.533, accuracy = 0.650, AUC = 0.714, Kappa = 0.271, P = 0.202) achieved better performances in the testing dataset among four single-ROI radiomics models. The combined model using the features from primary tumor on T2 weighted and peritumoral region on PET achieved the best performance (F1 Score = 0.727, accuracy = 0.850, AUC = 0.774, Kappa = 0.625, P < 0.05). The results suggest that 18 F-FDG PET/MRI could provide complementary information of cervical cancer. The radiomics-based method integrating the features from tumoral and peritumoral regions on 18 F-FDG PET/MRI had a superior performance on PMI evaluation.

Functional and neuropathological changes induced by injection of distinct alpha-synuclein strains: A pilot study in non-human primates

The role of alpha-synuclein in Parkinson's disease has been heavily investigated since its discovery as a component of Lewy bodies. Recent rodent data demonstrate that alpha-synuclein strain structure is critical for differential propagation and toxicity.Based on these findings, we have compared, for the first time, in this pilot study, the capacity of two alpha-synuclein strains and patient-derived Lewy body extracts to model synucleinopathies after intra-putaminal injection in the non-human primate brain. Functional alterations triggered by these injections were evaluated in vivo using glucose positron emission tomography imaging. Post-mortem immunohistochemical and biochemical analyses were used to detect neuropathological alterations in the dopaminergic system and alpha-synuclein pathology propagation.In vivo results revealed a decrease in glucose metabolism more pronounced in alpha-synuclein strain-injected animals. Histology showed a decreased number of dopaminergic tyrosine hydroxylase-positive cells in the substantia nigra to different extents according to the inoculum used. Biochemistry revealed that alpha-synuclein-induced aggregation, phosphorylation, and propagation in different brain regions are strain-specific.Our findings show that distinct alpha-synuclein strains can induce specific patterns of synucleinopathy in the non-human primate, changes in the nigrostriatal pathway, and functional alterations that resemble early-stage Parkinson's disease.

Imaging Recommendations for Diagnosis, Staging, and Management of Pancreatic Cancer

AbstractPancreatic cancer is the fourth most prevalent cause of cancer-related death worldwide, with a fatality rate equal to its incidence rate. Pancreatic cancer is a rare malignancy with a global incidence and death ranking of 14th and 7th, respectively. Pancreatic cancer cases are divided into three categories without metastatic disease: resectable, borderline resectable, or locally advanced disease. The category is determined by the tumor's location in the pancreas and whether it is abutting or encasing the adjacent arteries and/or vein/s.The stage of disease and the location of the primary tumor determine the clinical presentation: the pancreatic head, neck, or uncinate process, the body or tail, or multifocal disease. Imaging plays a crucial role in the diagnosis and follow-up of pancreatic cancers. Various imaging modalities available for pancreatic imaging are ultrasonography (USG), contrast-enhanced computed tomography (CECT), magnetic resonance imaging (MRI), and 18-fluoro-deoxy glucose positron emission tomography (FDG PET).Even though surgical resection is possible in both resectable and borderline resectable non-metastatic cases, neoadjuvant chemotherapy with or without radiotherapy has become the standard practice for borderline resectable cases as it gives a high yield of R0 resection.

Discrimination of subjective cognitive decline from healthy control based on glucose-oxygen metabolism network coupling features and machine learning.

Our previous studies have proved that preclinical Alzheimer's disease (AD) which including subjective cognitive decline (SCD) stage, can be distinguished from normal control (NC) by glucose-oxygen metabolism coupling at the voxel level, but whether the coupling at the network level worked has not been studied. Therefore, this study aimed to explore the coupling relationship between brain glucose metabolic connectivity network and oxygen functional connectivity network, and whether its feasibility as a biomarker to discriminate SCD from healthy control (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) and glucose positron emission tomography (PET) based on hybrid PET/MRI scans were used to investigate metabolism-oxygen metabolism coupling in 56 SCD individuals and 54 HCs. Network coupling features were selected by logistic regression-recursive feature elimination (LR-RFE), and then a linear support vector machine (SVM) was used to distinguish SCD and HC by using 5-fold cross-validation. The classification average accuracy of network coupling had reached 76.36% with a standard deviation of 9.85% (with a sensitivity of 77.82%±15.13% and a specificity of 75.30%±15.15%). After receiver operating characteristic (ROC) analysis, the average area under curve (AUC) of network coupling was 0.788 (95% confidence interval [Formula: see text]). This study provided a new perspective for exploring network coupling. The proposed classification method highlighted the potential clinical application by combing glucose-oxygen metabolism coupling and machine learning in identifying SCD.

The correlation between metabolic parameters in (18)F-FDG PET-CT and solid and micropapillary histological subtypes in lung adenocarcinoma

Objective: Solid and micropapillary pattern are highly invasive histologic subtypes in lung adenocarcinoma and are associated with poor prognosis while the biopsy sample is not enough for the accurate histological diagnosis. This study aims to assess the correlation and predictive efficacy between metabolic parameters in (18)F-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET-CT), including the maximum SUV (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and solid and micropapillary histological subtypes in lung adenocarcinoma. Methods: A total of 145 resected lung adenocarcinomas were included. The clinical data and preoperative (18)F-FDG PET-CT data were retrospectively analyzed. Mann-Whitney U test was used for the comparison of the metabolic parameters between solid and micropapillary subtype group and other subtypes group. Receiver operating characteristic (ROC) curve and areas under curve (AUC) were used for evaluating the prediction efficacy of metabolic parameters for solid or micropapillary patterns. Univariate and multivariate analyses were conducted to determine the prediction factors of the presence of solid or micropapillary subtypes. Results: Median SUV(max) and TLG in solid and papillary predominant subtypes group (15.07 and 34.98, respectively) were significantly higher than those in other subtypes predominant group (6.03 and 10.16, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for prediction of solid and micropapillary predominant subtypes [AUC=0.811(95% CI: 0.715~0.907) and 0.725(95% CI: 0.610~0.840), P<0.05]. Median SUV(max) and TLG in lung adenocarcinoma with the solid or micropapillary patterns (11.58 and 22.81, respectively) were significantly higher than those in tumors without solid and micropapillary patterns (4.27 and 6.33, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for predicting the presence of solid or micropapillary patterns [AUC=0.757(95% CI: 0.679~0.834) and 0.681(95% CI: 0.595~0.768), P<0.005]. Multivariate logistic analysis showed that the clinical stage (Stage Ⅲ-Ⅳ), SUV(max) ≥10.27 and TLG≥7.12 were the independent predictive factors of the presence of solid or micropapillary patterns (P<0.05). Conclusions: Preoperative SUV(max) and TLG of lung adenocarcinoma have good prediction efficacy for the presence of solid or micropapillary patterns, especially for the solid and micropapillary predominant subtypes and are independent factors of the presence of solid or micropapillary patterns.

C2 STEREOTACTIC ABLATIVE RADIOTHERAPY (STAR) IN PATIENTS WITH ICD AND ARRHYTHMIC STORMS

Abstract Background The current therapy of recurrent ventricular tachycardia (VT) and arrhythmic storms is the radiofrequency catheter ablation (RFCA). The first experiences of stereotaxic radioablation of arrhythmia (STAR) as an alternative in patients (pts) with defibrillator (ICD) and Arrhythmic Storms are emerging. However, a standardized method for STAR is not yet available and many issues are still under discussion. We present the preliminary results of STAR in the pts of our Center. Material and method Pts with ICDs and Arrhythmic Storms, excluded from RFCA, were referred to STAR. Diagnostics performed were Electrophysiological study (EPS) using 3D electroanatomical mapping (3DEAM) using CardioInsightTM vest (Medtronic, Minneapolis, MN), cardio–CT scan and 18F–fluorine–2–deoxy–D–glucose positron emission tomography (18FDG – PET scan) in order to identify the target area of the ventricle. In all pts a sustained monomorphic VT was induced during EPS, and 3DEAM was used to identify the exit point of the VT (Fig. 1). In all cases, a 3 mm thick 4D CT scan was used (Fig. 2) with the aid of an abdominal thermoplastic mask. Each patient was treated with a TrueBeam Linac (Varian Medical Systems, Palo Alto, CA). The prescription of the dose from 21 to 25 Gy in a single delivery. Ethics committee approval was obtained prior to each treatment. Results From January 2020 to March 2021, 6 patients (5 M, 1 F), mean age 78 years (58–80) were treated with STAR. The median delivered dose was 25 Gy (range 21–25 Gy). In follow–up (FU) one patient died from end–stage heart failure after 30 days. At a median FU of 13 months, STAR treatment efficacy was observed in 3/5 patients, in whom no defibrillator activation was recorded. 2/5 patients had recurrence of TV, 2 and 6 months after STAR. No severe acute toxicity was recorded after radiotherapy. Conclusions Arrhythmic stereotaxic radioablation appears to be a safe and effective therapy in PTS with ICDs and arrhythmic storms. Completely non–invasive diagnostics and therapy make it very interesting and ambitious. Additional data is needed to improve the definition of the target zone and to standardize it in patients not eligible for RFCA.

Pretreatment evaluation of 18F-FDG PET-CT in extranodal NK/T-cell lymphoma

Objective: To investigate the clinical value of pretreatment 18F-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET-CT) in extranodal NK/T-cell lymphoma. Methods: Eighty-one patients with pathologically confirmed extranodal NK/T-cell lymphoma and pretreatment with PET-CT scan in Cancer Hospital, Chinese Academy of Medical Sciences from August 2006 to December 2017 were enrolled in the study. The clinical, follow-up and imaging data were analyzed retrospectively. The relationship between maximum standard uptake value (SUVmax) and prognosis were evaluated by Mann-Whitney U test and Spearman rank correlation analysis. Results: Among the 81 patients, 98.8% (80/81) were upper aerodigestive tract (UAT) involved. Lesions at extra-UAT sites were detected in 7 cases, involving parotid gland (n=1), breast (n=1), spleen (n=1), pancreas (n=1), skin and subcutaneous soft tissue (n=1), muscle (n=1), lung (n=2) and bone (n=3). Lymph node involvement were demonstrated in 33 cases. All of the lesions had increased uptake of PET, the median SUVmax was 8.6. PET-CT changed staging in 15 cases, and 12 cases were adjusted treatment methods. 21 cases were changed radiotherapy target because of PET-CT. The 1-, 2-year progression-free survival (PFS) rates were 88.7% and 80.3% while 1-, 2-year overall survival (OS) rates were 97.2% and 94.4% respectively. The median SUVmax of patients with local lymph nodes involvement was significantly higher than those without local lymph nodes involvement (P=0.007). The SUVmax was positively associated with Ann Arbor stage (r=0.366, P=0.001), lactate dehydrogenase (r=0.308, P=0.005) and Ki-67 level (r=0.270, P=0.017). The SUVmax was inversely associated with lymphocyte count (r=-0.324, P=0.003) and hemoglobin content (r=-0.225, P=0.043). Conclusions: Extranodal NK/T-cell lymphoma predominantly occurs in extra-nodal organs, mainly in the upper respiratory and gastrointestinal tracts, with marked FDG-addiction. Compared with conventional imaging, 18F-FDG PET-CT is sensitive and comprehensive in detecting extra-nodal NK/T-cell lymphoma involvement, assisting in accurate clinical staging and treatment planning. Pretreatment SUVmax is potential for prognosis evaluation since it is correlated with prognostic factors.

Quantitative Assessment of Cardiac Hypermetabolism and Perfusion for Diagnosis of Cardiac Sarcoidosis

BackgroundQuantitative assessment of cardiac hypermetabolism from 18Flourodeoxy glucose (FDG) positron emission tomography (PET) may improve diagnosis of cardiac sarcoidosis (CS). We assessed different approaches for quantification of cardiac hypermetabolism and perfusion in patients with suspected CS. Methods and resultsConsecutive patients undergoing 18FDG PET assessment for possible CS between January 2014 and March 2019 were included. Cardiac hypermetabolism was quantified using maximal standardized uptake value (SUVMAX), cardiometabolic activity (CMA) and volume of inflammation, using relative thresholds (1.3× and 1.5× left ventricular blood pool [LVBP] activity), and absolute thresholds (SUVMAX > 2.7 and 4.1). Diagnosis of CS was established using the Japanese Ministry of Health and Wellness criteria. In total, 69 patients were studied, with definite or possible CS in 29(42.0%) patients. CMA above 1.5× LVBP SUVMAX had the highest area under the receiver operating characteristic curve (AUC 0.92). Quantitative parameters using relative thresholds had higher AUC compared to absolute thresholds (p < 0.01). Interobserver variability was low for CMA, with excellent agreement regarding absence of activity (Kappa 0.970). ConclusionsQuantitation with scan-specific thresholds has superior diagnostic accuracy compared to absolute thresholds. Based on the potential clinical benefit, programs should consider quantification of cardiac hypermetabolism when interpreting 18F-FDG PET studies for CS.

Clinical value of routine [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography scans as a decision tool for early immunotherapy discontinuation in advanced melanoma.

Routine [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) may help predict clinical outcomes after response to immunotherapy. With a European Medicines Agency-recommended treatment length until disease progression or unacceptable toxicity, the optimal duration of immunotherapy remains to be defined. In a retrospective study, we retrieved from the Danish Metastatic Melanoma Database (DAMMED), all patients that were annotated as a partial or complete response based on the computed tomography (CT) of serial FDG-PET-CT scans. Patients treated with an anti-Programmed Death (PD)-1-containing regimen for <18 months, and ≥4months without disease progression after halting anti-PD-1 were included. Cases were divided into an "elective" and a "toxicity" group based on the reason for treatment discontinuation. A total of 140 patients were included. At 29.3months of median follow-up, a higher proportion of patients remained alive in the "elective" group (93% vs 75%, P=.0031) with an improved melanoma-specific (HR 0.07, 95% CI 0.02-0.32, P=.0041) survival (MSS). Patients without FDG-avid lesions at the time of treatment discontinuation had an improved MSS (HR 0.03, 95% CI 0.01-0.17, P=.0002), and the absence of FDG-avid lesions was the only independent predictive feature of improved MSS in multivariate analysis. In conclusion, patients with metastatic melanoma who obtain an early response and early discontinue immunotherapy have an excellent prognosis, especially in the absence of FDG-PET avid lesions when discontinuing treatment. These data support the option of early discontinuation, limiting possible overtreatment and thereby toxicity, health and economic expenses and improving logistics.

Diagnosis of cardiac sarcoidosis: a primer for non-imagers.

Sarcoidosis is a multisystem granulomatous disorder that can potentially involve any organ. Cardiac involvement in sarcoidosis has been reported in up to 25% of patients based on autopsy and imaging studies. The gold standard for diagnosing cardiac sarcoidosis is endomyocardial biopsy demonstrating non-caseating granulomas; however, this technique lacks sensitivity due to the patchy nature of myocardial involvement. This, along with the non-specific clinical presentation, renders the diagnosis of cardiac sarcoidosis extremely challenging. Difficulties in obtaining histopathologic diagnosis and the advances in imaging modalities have led to a paradigm shift toward non-invasive imaging in the diagnosis of cardiac sarcoidosis. Advances in cardiac imaging modalities have also allowed unprecedented insights into the prevalence and natural history of cardiac sarcoidosis. This review discusses the role of non-invasive imaging for diagnosis, risk stratification, and monitoring the response to therapies in cardiac sarcoidosis. Echocardiography remains the first-line modality due to widespread availability and affordability. Cardiac magnetic resonance imaging (CMR) can be used to study cardiac structure, function, and most importantly tissue characterization to detect inflammation and fibrosis. Fluoro-deoxy glucose positron emission tomography (FDG PET) is the gold standard for non-invasive detection of cardiac inflammation, and it offers the unique ability to assess response to therapeutic interventions. Hybrid imaging is a promising technique that allows us to combine the unique strengths of CMR and FDG PET. Understanding the advantages and disadvantages of each of these imaging modalities is crucial in order to tailor the diagnostic algorithm and utilize the most appropriate modality for each patient.

Pre-Operative Prediction of Mediastinal Node Metastasis Using Radiomics Model Based on 18F-FDG PET/CT of the Primary Tumor in Non-Small Cell Lung Cancer Patients.

Purpose: We investigated whether a fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics model (RM) could predict the pathological mediastinal lymph node staging (pN staging) in patients with non-small cell lung cancer (NSCLC) undergoing surgery.Methods: A total of 716 patients with a clinicopathological diagnosis of NSCLC were included in this retrospective study. The prediction model was developed in a training cohort that consisted of 501 patients. Radiomics features were extracted from the 18F-FDG PET/CT of the primary tumor. Support vector machine and extremely randomized trees were used to build the RM. Internal validation was assessed. An independent testing cohort contained the remaining 215 patients. The performances of the RM and clinical node staging (cN staging) in predicting pN staging (pN0 vs. pN1 and N2) were compared for each cohort. The area under the curve (AUC) of the receiver operating characteristic curve was applied to assess the model's performance.Results: The AUC of the RM [0.81 (95% CI, 0.771–0.848); sensitivity: 0.794; specificity: 0.704] for the predictive performance of pN1 and N2 was significantly better than that of cN in the training cohort [0.685 (95% CI, 0.644–0.728); sensitivity: 0.804; specificity: 0.568], (P-value = 8.29e-07, as assessed by the Delong test). In the testing cohort, the AUC of the RM [0.766 (95% CI, 0.702–0.830); sensitivity: 0.688; specificity: 0.704] was also significantly higher than that of cN [0.685 (95% CI, 0.619–0.747); sensitivity: 0.799; specificity: 0.568], (P = 0.0371, Delong test).Conclusions: The RM based on 18F-FDG PET/CT has a potential for the pN staging in patients with NSCLC, suggesting that therapeutic planning could be tailored according to the predictions.

The usefulness of fluorodeoxyglucose-positron emission tomography as a preoperative diagnostic tool for thymic epithelial tumors.

To investigate the usefulness of 18F-fluorodeoxy glucose-positron emission tomography (18F-FDG PET) for the preoperative imaging diagnosis of malignant grade in thymic epithelial tumors (TETs) and the correlation between the maximum standardized uptake value (SUVmax) and tumor size in TETs. We retrospectively investigated 51 patients with TETs performed 18F-FDG PET. The SUVmax was compared between thymic carcinomas and thymomas. We also evaluated the difference in the SUVmax limited to small TETs. In addition, the correlation between the SUVmax and the tumor size was evaluated. The mean SUVmax of thymic carcinomas (n=12) and thymomas (n=39) was 5.71±2.6 and 3.08±1.4, respectively. The SUVmax of thymic carcinomas was significantly higher than that of thymomas (P<0.001). The mean SUVmax of these small thymic carcinomas (n=3) and thymomas (n=13) was 2.97±0.24 and 1.79±0.47, respectively. The SUVmax of the small thymic carcinomas was significantly higher than that of the thymomas (P=0.001). We found a positive correlation between the SUVmax and the maximum tumor size of TETs (correlation coefficient: 0.632, P<0.001). 18F-FDG PET might be useful for evaluating the preoperative malignancy of TETs. Of note, the maximum tumor size should be considered when performing assessments by 18F-FDG PET.

Pre-Treatment Myocardial 18FDG Uptake Predicts Response to Immunosuppression in Patients With Cardiac Sarcoidosis

ObjectivesThis study identified predictors of clinical (CR) and echocardiographic response (ER) following immunosuppressive therapy (IST) in patients with cardiac sarcoidosis (CS). BackgroundIST has been the cornerstone of treatment for patients with CS and active myocardial inflammation. However, there are little data to explain the variable response to IST in CS. MethodsData of 96 consecutive patients with CS from the Granulomatous Myocarditis Registry were analyzed. All patients underwent a 18fluorodeoxy glucose positron emission tomography−computed tomography (18FDG-PET-CT) before initiation of IST. Response was assessed after 4 to 6 months of therapy. CR was defined as an improvement in functional class (New York Heart Association functional class ≥I) and freedom from ventricular arrhythmias and heart failure hospitalizations. ER was defined as an improvement in left ventricular ejection fraction (LVEF) ≥10%. ER was assessed only in patients with a LVEF <50%. Complete responders had no residual myocardial FDG uptake and fulfilled both response criteria. Partial responders fulfilled only 1 response criteria or had residual FDG uptake. Nonresponders did not fulfill either CR or ER criteria. The uptake index (UI) was defined as the product of maximum standardized uptake value and the number of LV segments with abnormal uptake on 18FDG-PET-CT. ResultsAmong 91 patients included in the final analysis, 54.9%, 20.9%, and 24.2% of patients were classified as complete and partial responders and nonresponders, respectively. Cox regression analysis (all responders vs. nonresponders) identified the following as independent predictors of response following immunosuppression: LVEF >40% (hazard ratio: 1.61; 95% confidence interval: 1.06 to 7.69; p = 0.031) and myocardial UI >30 (hazard ratio: 1.28; 95% confidence interval: 1.05 to 6.12; p = 0.010). The final model had a good discriminative power (area under the curve [AUC]: 0.85) and predictive accuracy (sensitivity: 85.5%; specificity: 86.4%). Pre-treatment myocardial UI had a strong positive correlation with change in LVEF following immunosuppression. ConclusionsPre-treatment 18FDG myocardial uptake was a predictor of CR and ER response to immunosuppression in patients with CS.

Gallium citrate-67 single-photon emission computed tomography/computed tomography for localizing the foci of classic fever and inflammation of unknown origin: A retrospective study of diagnostic yield.

Only few studies have assessed the use of gallium citrate-67 single-photon emission computed tomography/computed tomography (67Ga-SPECT/CT) for localizing the foci of classic fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Hence, the current study aimed to assess the diagnostic contribution of 67Ga-SPECT/CT in a tertiary referral setting where nuclear imaging tests are performed after an unsuccessful comprehensive primary diagnostic workup. We retrospectively assessed the medical records of 27 adult patients with FUO/IUO who had an unsuccessful diagnostic workup and who underwent 67Ga-SPECT/CT for the localization of FUO/IUO foci in our university hospital between 2013 and 2019. The primary outcome was diagnostic yield. The secondary outcomes were overall clinical efficacy and spontaneous remission of FUO/IUO symptoms in patients with a negative 67Ga-SPECT/CT finding. Almost all patients completed the recommended diagnostic workup, except for urine culture and abdominal ultrasonography. Moreover, prior to 67Ga-SPECT/CT, all patients underwent thoraco-abdominopelvic CT scan, which was a non-diagnostic procedure. After a median follow-up of 843 days, the cause was identified in 16 (59%) patients. 67Ga-SPECT/CT successfully localized the FUO/IUO foci in eight patients (diagnostic yield = 30%; 95% confidence interval [CI]: 14%-50%). However, the causes remained unknown during follow-up in 11 (41%) patients. Among them, five experienced spontaneous regression of symptoms. 67Ga-SPECT/CT was negative in four of the five patients with spontaneous regression in symptoms without a definite cause. Considering this an important event, the overall clinical efficacy of 67Ga-SPECT/CT increased to 44% (95% CI: 25%-65%). 67Ga-SPECT/CT had an acceptable diagnostic yield for the localization of FUO/IUO foci, which are challenging to diagnose, in a contemporary tertiary referral care setting. In patients who experienced spontaneous regression in symptoms with an unexplained cause, the absence of abnormal uptake might indicate prospective spontaneous remission. Thus, 67Ga-SPECT/CT could be an active first-line nuclear imaging modality in settings where fluorine-18-fluorodeoxy glucose positron emission tomography and computed tomography is not available for the assessment of FUO/IUO causes.

Different positron emission tomography findings in schizophrenia and narcolepsy type 1 in adolescents and young adults: a preliminary study.

The association between schizophrenia and narcolepsy has been controversial. We conducted a prospective case control study of schizophrenia and comorbid narcolepsy type 1 in adolescents compared with patients with either diagnosis alone and healthy controls using 18F-fluorodeoxy glucose positron emission tomography, sleep studies, and neurocognitive tests. We included 11 patients (9-20 years old) with schizophrenia and comorbid narcolepsy type 1, 11 with narcolepsy type 1, 11 with schizophrenia, and 11 controls. All groups were matched for age and sex. Participants were required to submit to clinical interviews for sleep and psychiatric disorders, sleep questionnaires, continuous performance test, Wisconsin card sorting test, sleep studies including polysomnography, multiple sleep latency test and actigraphy, and positron emission tomography studies. All data were analyzed to compare the differences between the 4 groups. The positron emission tomography results demonstrated significant differences in the dual diagnoses group compared with the 3 other groups. Compared with the controls, the dual diagnoses group had a significant presence of hypometabolism in the right mid-frontal, right orbital inferior frontal, and right posterior cingulum and a significant presence of hypermetabolism in the left amygdala, bilateral striatum, bilateral substantia nigra, bilateral basal ganglia, and bilateral thalamus. Continuous performance tests and Wisconsin card sorting tests showed that the dual diagnoses group had the worst performance. Patients with schizophrenia and comorbid narcolepsy type 1 had different positron emission tomography findings than those with either schizophrenia or narcolepsy type 1 alone. They also had more neurocognitive impairments and required additional interventions.

Obesity Is Associated With Increased Basal and Postprandial β-Cell Insulin Secretion Even in the Absence of Insulin Resistance.

We tested the hypothesis that obesity, independent of insulin resistance, is associated with increased insulin secretion. We compared insulin kinetics before and after glucose ingestion in lean healthy people and people with obesity who were matched on multiorgan insulin sensitivity (inhibition of adipose tissue lipolysis and glucose production and stimulation of muscle glucose uptake) as assessed by using a two-stage hyperinsulinemic-euglycemic pancreatic clamp procedure in conjunction with glucose and palmitate tracer infusions and positron emission tomography. We also evaluated the effect of diet-induced weight loss on insulin secretion in people with obesity who did not improve insulin sensitivity despite marked (∼20%) weight loss. Basal and postprandial insulin secretion rates were >50% greater in people with obesity than lean people even though insulin sensitivity was not different between groups. Weight loss in people with obesity decreased insulin secretion by 35% even though insulin sensitivity did not change. These results demonstrate that increased insulin secretion in people with obesity is associated with excess adiposity itself and is not simply a compensatory response to insulin resistance. These findings have important implications regarding the pathogenesis of diabetes because hyperinsulinemia causes insulin resistance and insulin hypersecretion is an independent risk factor for developing diabetes.

Can FDG-PET replace biopsy for the evaluation of residual tumor in pediatric mature B-cell non-Hodgkin lymphoma?

The aim of our study is to evaluate the role of 18 F-labeled fluorodeoxy glucose positron emission tomography (18 FDG-PET) scan for the detection of viable residual mass in pediatric mature B-cell non-Hodgkin lymphoma (NHL). This study also aims to detect the negative predictive value, positive predictive value (PPV), sensitivity, and specificity of 18 FDG-PET. A retrospective, cross-sectional nonrandomized study was carried out. We included all patients with newly diagnosed mature B-cell NHL treated at the Children Cancer Hospital Egypt during the period between July 2007 and the end of May 2018. Patients were included in the study if they (a) had a residual tumor mass, (b) underwent an 18 FDG-PET scan, and (c) had a pathologic documentation of this residual tumor. Patients were followed up till June 2019. Thirty-six patients were included, for whom 39 biopsies were performed. Mean age was 7.7 years. Median follow-up period was 52.8, range 6.1 to 117 months.18 FDG-PET scan was positive (Deauville score 3, 4, or 5) in 24 of 39 patients (61.5%), while it was negative (Deauville score 1 or 2) in 15 patients (38.5%). Positive 18 FDG-PET scan and biopsy were performed in 15 of 39 samples (38.4%; true positive, TP), while they were both negative in 13 samples (33.3%; true negative). Nine patients (23%) had positive scan and a negative biopsy (false positive), while 2 patients had negative uptake and a positive biopsy (false negative, FN)). Sensitivity of the 18 FDG-PET scan was 88.2% and specificity was 59.1%. PPV was 62.5% and NPPV was 86.6%. Changing therapy on the basis of a positive finding alone at the time of evaluation is not recommended. FN results exist, so biopsy confirmation is required to avoid the missing refractory disease. If negative, 18 FDG- PET can replace a biopsy if the latter is inaccessible or carries an unnecessary risk.

2-Deoxy-2-[18 F]fluoro-d-glucose positron emission tomography, cortical thickness and white matter graph network abnormalities in brains of patients with amyotrophic lateral sclerosis and frontotemporal dementia suggest early neuronopathy rather than axonopathy.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disorder, although extra-motor degeneration is well recognized, especially in frontotemporal regions manifested as ALS with frontotemporal dementia (ALS-FTD). Previous neuroimaging studies of the brains of ALS-FTD patients have measured abnormalities of either grey matter (GM) or white matter (WM) structures but not of both together. Therefore, the aim was to evaluate both GM and WM in the same ALS-FTD patient using functional and structural neuroimaging. By doing so, insights could be gained into whether neurodegeneration in ALS-FTD is primarily a neuronopathy or axonopathy. After high-resolution brain 2-deoxy-2-[18 F]fluoro-D-glucose (18 F-FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) scans were obtained in ALS-FTD patients and in age- and sex-matched neurological controls, changes in metabolic rate, cortical thickness (CT) and WM network analysis using graph theory were analyzed. Significant reductions in 18 F-FDG PET metabolism, CT and WM connections were observed in motor and extra-motor brain regions of ALS-FTD patients compared to controls. Both CT and underlying WM networks were abnormal in frontal, temporal, parietal and occipital lobes of ALS-FTD patients with 86 of 90 brain regions showing reductions of CT. Abnormalities in significantly fewer WM networks underlying the affected cortical regions suggest that neurodegeneration in brains of ALS-FTD patients is primarily a 'neuronopathy' rather than an 'axonopathy.'