scholarly journals ARVC specific autoantibody identifies cardiac sarcoidosis and correlates with inflammation activity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Suna ◽  
A Kolios ◽  
D Chatterjee ◽  
M Fatah ◽  
A Gasperetti ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Fdg Pet ◽  
Cardiac Sarcoidosis ◽  
Pearson Correlation ◽  
Standardized Uptake Value ◽  
Pathophysiological Mechanism ◽  
Western Blots ◽  
Control Subjects ◽  
Increased Risk ◽  
Antibody Levels

Abstract Introduction Cardiac sarcoidosis (CS) is an inflammatory granulomatous disease of unknown origin. CS and arrhythmogenic right ventricular cardiomyopathy (ARVC) are overlapping syndromes. With both, patients are at increased risk of ventricular arrhythmias and sudden cardiac death. However, the diagnosis of CS is challenging, especially in patients with no extracardiac involvement, but correct diagnosis has large therapeutic impact. Recently, a novel diagnostic autoantibody (anti-DSG2 Ab) was identified in ARVC. We sought to identify this antibody in CS patients and correlate its levels with inflammation activity using cardiac positron-emission-tomography (18-FDG-PET). Methods Recombinant human desmoglein-2 (DSG2) proteins on western blots were exposed to sera as well as purified IgG of 14 patients with sarcoidosis (all confirmed by histology) and 6 controls (1 ARVC patient (positive control) and 5 healthy control subjects (negative control)). Clinical patient characteristics were correlated to detected antibody intensity levels. Results The sarcoidosis cohort comprised 43% (6/14) male patients and the average age was 50±12 years. Anti-DSG2 Abs were identified in 43% (6/14) and were detected faintly (below cut off level) in 21% (3/14) of all sarcoidosis patients. Antibody was also present in the ARVC patient (1/1) and was absent in all control subjects (5/5). Myocardial inflammation was present in 18-FDG PET imaging in all CS patients with positive anti-DSG2 Abs, corresponding to an average SUV (standardized uptake value) of 8.1±4.2. In patients with faint or no antibody, the SUV values were significantly lower with 1.2±2.1 and 3.2±4.0, respectively (P=0.044, one-way ANOVA). The Pearson correlation coefficient (R) was 0.6 (P=0.037) for SUV vs. higher antibody levels assessed by pixel count of the western blot bands for purified IgG. Conclusions Anti-DSG2 Abs are not only a specific biomarker for ARVC, but are also found in CS, suggesting a similar pathophysiological mechanism in these overlapping syndromes, both involving cardiac inflammation and myocyte cell death. Moreover, antibody levels correlate with disease activity on cardiac PET imaging. Larger cohorts are necessary to confirm these findings. Funding Acknowledgement Type of funding source: None

Anti-desmoglein2 autoantibodies are present in patients with cardiac sarcoidosis and correlate with cardiac inflammation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
G Suna ◽  
A Kolios ◽  
D Chatterjee ◽  
M Fatah ◽  
A Gasperetti ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Cardiac Sarcoidosis ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Pearson Correlation ◽  
Standardized Uptake Value ◽  
Western Blots ◽  
Cardiac Inflammation ◽  
Funding Sources ◽  
Positron Emission ◽  
18F Fdg

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Zurich ACM Program is supported by generous grants from the Georg and Bertha Schwyzer-Winniker Foundation, the Baugarten Foundation, Swiss National Science Foundation, Swiss Heart Foundation and Wild Foundation. This work is also supported by a Canadian Institutes of Health Research grant (FRN: 162402) and the Labatt Heart Centre and Waugh Family Innovation Funds, Caitlin Elizabeth Morris Memorial Fund, Alex Corrance Memorial Foundation and Meredith Cartwright. BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) has several phenocopies such as cardiac sarcoidosis (CS), idiopathic outflow tract ventricular tachycardia (OT-VT) and myocarditis. Differentiation between these entities can be challenging. Recently, we have identified diagnostic anti-desmoglein-2 autoantibodies (anti-DSG2 Abs) in patients with ARVC. PURPOSE We sought to examine whether anti-DSG2 Abs are also present in clinical phenocopies of ARVC. METHODS Anti-DSG2 Abs in sera of 25, 19 and 22 patients with sarcoidosis, OT-VT and myocarditis, respectively, were assessed by western blots and ELISA. Clinical and imaging parameters, as well as conventional biomarkers were correlated to detected anti-DSG2 Ab intensity levels. RESULTS Anti-DSG2 Abs, at various intensities, were identified in 6/25 (24%) patients with sarcoidosis, all presenting with CS, but were absent in patients with OT-VT and myocarditis. Cardiac 18F- fluorodeoxyglucose positron emission tomography (18F-FDG PET) was positive in all sarcoidosis patients with positive anti-DSG2 Abs, corresponding to a median PET maximum standardized uptake value (SUVmax) of 5.65 [IQR: 5.15 – 10.9]. In sarcoidosis patients without anti-DSG2 Abs, the SUVmax values were significantly lower with a median of 0 [IQR: 0 – 4] (p = 0.011). The Pearson correlation coefficient (R) was 0.188 (p = 0.039) indicating a positive correlation between cardiac 18F-FDG uptake and anti-DSG2 Abs. No significant correlation was detected for any of the other clinical parameters and biomarkers. CONCLUSIONS In addition to being present in ARVC, anti-DSG2 Abs are also found in CS, a common phenocopy of ARVC; conversely, anti-DSG2 Abs are absent in idiopathic OT-VT and myocarditis. Anti-DSG2 Ab levels positively correlate with myocardial disease activity in CS as indicated by cardiac 18F-FDG PET scanning. Abstract Figure. Central illustration

Crossed Cerebellar Diaschisis in Alzheimer’s Disease

2018 ◽  
Vol 15 (13) ◽  
pp. 1267-1275 ◽  
Author(s):  
F.E. Reesink ◽  
D. Vállez García ◽  
C.A. Sánchez-Catasús ◽  
D.E. Peretti ◽  
A.T. Willemsen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Left Hemisphere ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Pathophysiological Mechanism ◽  
Crossed Cerebellar Diaschisis ◽  
Amyloid Accumulation ◽  
Cerebellar Diaschisis ◽  
18F Fdg

Background: We describe the phenomenon of crossed cerebellar diaschisis (CCD) in four subjects diagnosed with Alzheimer’s disease (AD) according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with 18F-FDG PET and 11C-PiB PET imaging. Methods: 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease most prominent in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer delivery (a surrogate of relative cerebral blood flow) in the left hemisphere. CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. The mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The pathophysiology is thought to have a functional or reversible basis but can also reflect in secondary morphologic change. CCD is a well-recognized phenomenon, since the development of new imaging techniques, although scarcely described in neurodegenerative dementias. Results: To our knowledge this is the first report describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB PET imaging. CCD in our subjects was explained on a functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment. Conclusion: This suggests that CCD might be caused by non-amyloid neurodegeneration. The pathophysiological mechanism, clinical relevance and therapeutic implications of CCD and the role of the cerebellum in AD need further investigation.

Prognostic value of positron emission tomography and preoperative CA19-9 in patients treated on a prospective phase II trial of neoadjuvant therapy and surgery.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15766-e15766
Author(s):  
Chad Barnes ◽  
Mohammed Aldakkak ◽  
Kathleen K. Christians ◽  
Parag Tolat ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Neoadjuvant Therapy ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Prognostic Value ◽  
Prospective Trial ◽  
Standardized Uptake Value ◽  
Carbohydrate Antigen ◽  
Emission Tomography ◽  
Positron Emission

e15766 Background: The role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging of pancreatic cancer (PC) has not been well defined. We evaluated the prognostic value of FDG-PET imaging in patients with localized PC enrolled in a prospective trial of personalized molecular-directed neoadjuvant therapy. Methods: Pretreatment FDG-PET was classified as high or low based on a standardized uptake value (SUV) cutpoint of 7.2 (population median). Carbohydrate antigen 19-9 (CA19-9) was measured after the completion of neoadjuvant therapy (preoperative) and classified as normal (≤35 U/mL) or elevated. Results: Pretreatment FDG-PET imaging was performed on 100 consecutive patients; SUV was high in 50 and low in 50. Preoperative CA19-9 values were available in 99 of 100 patients; 54 (55%) were elevated and 45 (45%) were normal. Of the 100 patients, 81 completed neoadjuvant therapy and surgery, and 19 were not resected. Among the 81 resected patients, SUV was high in 37 (46%) and low in 44 (54%); preoperative CA19-9 was elevated in 40 (49%) and normal in 41 (51%). The median overall survival (OS) for all patients was 39 months; 45 months for who completed all intended neoadjuvant therapy and surgery and 9 months for patients who were not resected. The median OS for patients with normal CA19-9/low SUV, normal CA19-9/high SUV, elevated CA19-9/low SUV, and elevated CA19-9/high SUV were not reached, 35, 24, and 18 months, respectively (p = 0.0001). Conclusions: Pretreatment FDG-PET avidity and preoperative CA19-9 are important prognostic markers and may be used to estimate the anticipated benefit of surgery; information of immediate clinical significance for both treatment sequencing and the application of surgery to patients who are frequently of advanced age or high-risk.

scholarly journals Cytokine Signaling and Matrix Remodeling Pathways Associated with Cardiac Sarcoidosis Disease Activity Defined Using FDG PET Imaging

2021 ◽  
Author(s):  
Bryan D. Young ◽  
Hannah Moreland ◽  
Kelsie E. Oatmen ◽  
Lisa A. Freeburg ◽  
Zartashia Shahab ◽  
...  
Keyword(s):  
Disease Activity ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Cardiac Sarcoidosis ◽  
Cytokine Signaling ◽  
Matrix Remodeling

scholarly journals Cardiac Tuberculosis on 18F-FDG PET Imaging—A Great Masquerader of Cardiac Sarcoidosis

2021 ◽  
Author(s):  
Sumati Sundaraiya ◽  
Abubacker Sulaiman ◽  
Adhithyan Rajendran
Keyword(s):  
Pet Imaging ◽  
Fdg Pet ◽  
Cardiac Sarcoidosis ◽  
Granulomatous Inflammation ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Whole Body ◽  
Left Ventricular Myocardium ◽  
Fdg Uptake ◽  
18F Fdg

AbstractA young gentleman with suspected cardiac sarcoidosis and LV dysfunction whose CMR revealed multifocal subepicardial to mid myocardial linear enhancement in the left ventricular myocardium underwent cardiac 18F-FDG PET imaging. The images revealed patchy regions of increased FDG uptake involving the apical to mid anterolateral, mid to basal anteroseptal/ right ventricular and mildly increased FDG uptake in apical inferior segments of the LV myocardium concordant with CMR findings. Whole body PET CT imaging showed multiple hypermetabolic supra and infra diaphragmatic lymphadenopathy, with no pulmonary lesion identified. Biopsy from the left para aortic lymph node revealed necrotizing granulomatous inflammation consistent with tuberculosis. Based on the histopathological findings of the lymph nodes, diagnosis of cardiac tuberculosis was made, given the similar imaging appearances in both sarcoidosis and TB. This case highlights that cardiac TB although rare, should be included in the differential diagnosis in patients with suspected infiltrative cardiomyopathy, particularly in TB endemic regions.

scholarly journals Maximum Standardized Uptake Value of 18F-deoxyglucose PET Imaging Increases the Effectiveness of CT Radiomics in Differentiating Benign and Malignant Pulmonary Ground-Glass Nodules

2021 ◽  
Vol 11 ◽  
Author(s):  
Rong Niu ◽  
Jianxiong Gao ◽  
Xiaoliang Shao ◽  
Jianfeng Wang ◽  
Zhenxing Jiang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Fdg Pet ◽  
Standardized Uptake Value ◽  
Ground Glass ◽  
Semantic Features ◽  
Diagnostic Efficiency ◽  
Maximum Standardized Uptake Value ◽  
Pet Ct ◽  
Significant Difference ◽  
Ground Glass Nodules

To investigate whether the maximum standardized uptake value (SUVmax) of 18F-deoxyglucose (FDG) PET imaging can increase the diagnostic efficiency of CT radiomics-based prediction model in differentiating benign and malignant pulmonary ground-glass nodules (GGNs). We retrospectively collected 190 GGNs from 165 patients who underwent 18F-FDG PET/CT examination from January 2012 to March 2020. Propensity score matching (PSM) was performed to select GGNs with similar baseline characteristics. LIFEx software was used to extract 49 CT radiomic features, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to select parameters and establish the Rad-score. Logistic regression analysis was performed combined with semantic features to construct a CT radiomics model, which was combined with SUVmax to establish the PET + CT radiomics model. Receiver operating characteristic (ROC) was used to compare the diagnostic efficacy of different models. After PSM at 1:4, 190 GGNs were divided into benign group (n = 23) and adenocarcinoma group (n = 92). After texture analysis, the Rad-score with three CT texture features was constructed for each nodule. Compared with the Rad-score and CT radiomics model (AUC: 0.704 (95%CI: 0.562-0.845) and 0.908 (95%CI: 0.842-0.975), respectively), PET + CT radiomics model had the best diagnostic efficiency (AUC: 0.940, 95%CI: 0.889-0.990), and there was significant difference between each two of them (P = 0.001-0.030). SUVmax can effectively improve CT radiomics model performance in the differential diagnosis of benign and malignant GGNs. PET + CT radiomics might become a noninvasive and reliable method for differentiating of GGNs.

64Cu-DOTA-trastuzumab PET/CT to predict response to ado-trastuzumab emtansine (TDM1) in HER2-positive metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12525-e12525
Author(s):  
Joanne E. Mortimer ◽  
James R. Bading ◽  
Paul Henry Frankel ◽  
Rita Gidwaney ◽  
John Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Standardized Uptake Value ◽  
Response To Therapy ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Pet Ct ◽  
Fdg Pet Ct

e12525 Background: Having demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive (HER2+) breast cancer, we now evaluate the methodology for prediction of response and benefit from TDM1 in women with metastatic disease. Methods: Patients eligible to receive TDM1 as therapy were chosen on the basis of biopsy confirmed HER2+ disease, and at least 1 site of metastasis ≥ 2.0 cm outside the biopsy site. Pretreatment staging included 18F-FDG PET/CT. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 16-28 h (Day1) and 39-49 h (Day 2) over fields of view chosen in reference to the 18F-FDG scans. TDM1 (3.6 mg/kg) was administered every 3 weeks. Restaging 18F-FDG PET/CT was performed every 2 cycles, and response to therapy was determined by PERCIST (solid tumor) criteria. Radiolabel uptake was measured in terms of maximum voxel, standardized uptake value (SUVmax). Results: Ten women between the ages of 48-83 years old (median 55 years) qualified for study, and have been evaluated for response; 4 continue on TDM1 with treatment durations of 3-27 months.Three were trastuzumab-naïve, while 7 had received trastuzumab-containing chemotherapy 3 wks to 55 mo prior to study entry. HER2 was positive by ImmunoHistoChemistry, IHC (3+) in 5 patients, and by FISH testing in the other 5 (3 were 2+ by IHC; 1 was 1+, and 1 was indeterminate). Complete or partial metabolic response was observed in 5 patients. Median Day 2 SUVmax for 64Cu-DOTA trastuzumab was 9.3 g/ml in responding patients, and 4.6 g/ml in non-responders ( P= 0.03). Progression-free survival was longer for patients with higher SUVmax, with a hazard ratio of 0.73 (95% confidence interval 0.46-1.16) for each 1 unit increase in SUVmax. This was not statistically significant, although we can select a threshold SUVmaxfor which the effect is significant even for this small study. Further data is required to confirm such a threshold effect. Conclusions: 64Cu-DOTA-trastuzumab PET imaging predicts benefit from TDM1 in women with biopsy-confirmed HER2+ metastatic disease. Supported by NCI Clinical trial information: NCT02827877.

scholarly journals REGIONAL ABNORMALITIES ON RUBIDIUM-FDG PET IMAGING PREDICT VENTRICULAR TACHYCARDIA AND CONDUCTION DISEASE IN PATIENTS WITH CARDIAC SARCOIDOSIS

2012 ◽  
Vol 59 (13) ◽  
pp. E1307 ◽  
Author(s):  
Roy Chung ◽  
Gian Novaro ◽  
Edmond Cronin ◽  
Patrick Tchou ◽  
Richard Brunken ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Cardiac Sarcoidosis
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