NIMG-02. 18F-FLUCICLOVINE POSITRON EMISSION TOMOGRAPHY TO DISTINGUISH TUMOR PROGRESSION FROM RADIATION NECROSIS FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASIS: A QUALITATIVE ANALYSIS

PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) in a prospective pilot study. MATERIALS/METHODS Adults with post-SRS BM presenting with follow-up brain MRI equivocal for RN versus TP underwent 18F-Fluciclovine PET/CT within 30 days of equivocal MRI. PET images were reconstructed using a point-spread-function algorithm. Three physician reviewers independently performed qualitative analyses of each lesion using a three-point visual score relative to PET-avidity of blood pool and parotid. Quantitative metrics for each lesion were documented. Reference standard was clinical follow-up with brain MRI until tumor board consensus or tissue confirmation. Nonparametric estimates of area under the receiver operating characteristic curve (AUC) for clustered data were estimated, with diagnostic performance based on visual score. RESULTS In 15 subjects with 20 lesions, final diagnosis was RN in 16 (80%) lesions and TP in 4 (20%). Visual score significantly correlated with final diagnosis (AUC range 0.836-0.906 [p≤0.037]). A threshold score of 2 (lesion 18F-fluciclovine uptake above blood pool to parotid) and higher produced sensitivities and specificities of 75-100% and 38-56% respectively among the reviewer majority. Conversely, a threshold of 3 (uptake higher than parotid) produced sensitivities and specificities of 50-75% and 100% respectively. CONCLUSION In this prospective pilot, basic visual analysis of 18F-Fluciclovine PET/CT provided high sensitivity and specificity in detection of TP in post-SRS BM based on different threshold scores, suggesting room for visual threshold optimization. A low TP event rate limited the ability to estimate sensitivity/specificity and to perform combined qualitative/quantitative analyses. Further study to refine interpretation criteria is ongoing.

PSXI-4 Genome-Wide association study for muscle visual score in Nellore cattle raised in pasture-based systems

Visual scoring traits have been proposed as an alternative to evaluate body composition of Zebu cattle near the slaughter season when phenotyping technologies are not available. Considering the increased demand for high-quality animal protein in developing countries, there is a need to genetically improve body muscle (MUSC) in Zebu cattle (Bos taurus indicus), especially in animals raised in pasture-based systems. Therefore, our main objectives were to estimate genetic parameters, perform a genome-wide association study based on the single-step GBLUP approach (ssGWAS), and identify candidate genes and metabolic pathways related to MUSC in Nellore cattle. A total of 20,808 Nellore animals born between 2009 and 2018 were visually score at 18 months of age and 2,775 of these animals were also genotyped using the GGP-Indicus 35K SNP panel (33,247 SNPs after quality control). Heritability was estimated based on the REML approach and the model included the effects of age at measurement as covariable and the contemporary group (farm, birth season, management group and sex). The ssGWAS was performed using the BLUPF90 family programs. The identification of candidate genes was performed through the Ensembl database incorporated in the BioMart tool. MUSC is heritable (0.38) and can be improved through selection. Nineteen genomic regions (explaining 38.12% of the total additive genetic variance) located on BTA1, BTA7, BTA9, BTA16, and BTA21 and harboring 19 candidate genes were identified. The main genes identified were SEMA6A, TIAM2, UNC5A, and UIMC1, which are related to the metabolism of energy, growth, homeostasis and axonogenesis, and therefore, muscle development. These findings contribute to a better understanding of the molecular mechanisms over the gene expression of muscle visual score in Nellore cattle, and the polymorphisms located in these genes can be incorporated in commercial genotyping platforms to improve the accuracy of imputation and genomic evaluations for body and carcass traits.

Visual estimate of coronary artery calcium predicts prevalent coronary artery disease in patients with respiratory disease

Background Coronary artery calcification (CAC) measured using ECG-triggered coronary computed tomography correlates strongly with overt cardiovascular disease risk. Evidence is emerging to suggest CAC measured on non-gated thoracic CT scans may also correlate with cardiovascular disease. Herein, we sought to ascertain the utility of Weston scoring (visual score for CAC) in predicting prevalent coronary artery disease (CAD) and incident cardiovascular disease (CVD) for patients undergoing lung cancer screening or follow-up for interstitial lung disease with a non-triggered high-resolution CT (HRCT) thorax. Methods The Computerised Radiology Information Service (CRIS) database was manually searched to determine all HRCT scans performed in a single UK trust from 01/05/2016 to 01/05/2017 for the aforementioned indications. Radiology reports and images of selected studies were reviewed. For patients with evidence of CAC, we calculated the calcium score using the Agatston and Weston methods. Clinical events were determined from the electronic medical record without knowledge of patients' CAC findings. At baseline, significant CAC was defined as Agatston >400 and Weston >7. Results 2152 scans were analysed. Data at follow up was available for 100% of patients, with a median duration of follow up of 3.6 years. A history of CAD was reported by 8% (172) of subjects at baseline, who were subsequently excluded from analysis. Significant CAC was found in 450 (22.5%) and 650 (32.5%) by Weston and Agatston scores respectively, with a significant correlation between the two scores (r-0.71, p<0.01). During follow up 7.4% (160) of patients developed incident CVD. Patients with low Weston scores of ≤7 and Agatston scores of ≤400 had a lower incidence of CVD compared to those with Weston >7 and Agatston >400 (31 [19.3%] vs 129 [80.6%]; P=0.003 for Weston scores; 37 [23.1%] vs 123 [76.9%] for Agatston scores; P<0.001). Conclusion In this retrospective study of patients with respiratory disease attending for HRCT scanning, the Weston visual score for CAC performs well in predicting prevalent CAD and future CVD events. With previous data demonstrating excellent inter- and intra- observer agreement, our study demonstrates Weston scoring is a valid tool in reporting non-gated CT scans, removing the need for dedicated software analysis as required with the Agatston score, and has a high overall positive and negative predictive value for future CVD. Further multi-centre prospective studies of this strategy, should be conducted to clarify the utility of Weston CAC scoring in non-gated CTs as a prediction tool which may be used to modify cardiac risk and reduce the risk of incident cardiovascular events. FUNDunding Acknowledgement Type of funding sources: None.

Bone scintigraphy in the diagnosis of transthyretin amyloidosis: a different performance in Portuguese hereditary variant?

Introduction Bone scintigraphy using radioactive technetium-99m and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) has been increasingly used to diagnose myocardial involvement of mutated or wild-type transthyretin amyloidosis (ATTR). However, most studies that proved a high sensitivity and specificity of the technique were not in patients with the “Portuguese variant” (Val30Met) mutation in transthyretin (TTR). Other authors had already suggested that in these patients the DPD scan could be less accurate. Methods Observational study of patients referred to Cardiology clinic with suspicion of ATTR cardiomyopathy. We only included patients with data from echocardiogram and DPD scan. For statistical analyses, SPSS was used, p<0.05 for statistical significance. Logistic regressions were used to test an association between DPD result and different covariates. Results Of 273 patients referred with suspicion of cardiac ATTR, we studied 97 patients that did an echocardiogram and a DPD scan. Among the 75 cases with mutated TTR (Val30Met), median age was 36 (IQR 34) and 60% were males. 60 had increased ventricular wall thickness (IVWT) >12 mm, but only 24 had a positive DPD (defined as a visual score >2). Even though a higher wall thickness was associated with a positive DPD (p=0.004), 18 patients with a negative scan had IVWT >14 mm. The DPD results was significantly associated with prior liver transplantation (LT) – p<0.001; 95% CI (7.1; 503.6) – and age at first symptoms – p<0.001; 95% CI (1.036; 1.113); 66.7±10.5 versus 34.8±10.2 years-old for those with and without a positive scan, respectively. Interestingly, fewer patients with a positive scan had neurologic symptoms (74% versus 96%, p=0.009), ophthalmologic, urologic or renal involvement, even though creatinine clearance was on average lower (p=0.01). We did not find a significant association between DPD result and sex, conduction disorders, NT-proBNP, troponin T or treatment with tafamidis. Patients on tafamidis had on average lower IVWT, independent of age (median of 13 versus 14 mm; p=0.020). 4 patients with negative DPD did an endomyocardial biopsy, that was positive for amyloid in 3 cases. In comparison, in the 22 cases with wild-type TTR, there were significantly more males (86%) and patients were older (median age was 81 (IQR 9)). All patients had IVWT (that was significantly higher than in mutated ATTR) and DPD scan was negative in only 2 patients (that had a visual score of 1). Systolic dysfunction was significantly more frequent (59% versus 8%). The occurrence of death or hospitalization for heart failure was significantly higher. Conclusions DPD-scintigraphy seems more sensitive in patients with late onset mutated ATTR or with wild-type ATTR. It is less accurate in early onset patients with Val30Met mutation and particularly if they underwent LT. In those patients, further investigation is needed before excluding myocardial involvement. FUNDunding Acknowledgement Type of funding sources: None.

Viability and DNA Damage of Buccal Mucosa Cells in Patients Exposed to Panoramic X-ray

Panoramic X-ray is well known to cause DNA damage and induces cellular death. The aim of the present study was to evaluate the cytotoxicity of radiation exposure from panoramic radiography on human buccal mucosa cells by assessing the cell viability using the simple-trypan blue exclusion test. The genotoxicity effect was evaluated by assessing comet assay score. This research included a total of 20 healthy patients who had panoramic radiography for a routine dental examination. Buccal mucosa cells were collected from all participants before X-ray exposure and at 30 min or 24 h after exposure in Groups 1 and 2, respectively, and subjected to a comet assay and trypan blue exclusion test to assess cell viability and DNA damage. Cell viability was calculated as the ratio of live (translucent) to total counted cells. Comet assay output images were analysed using OpenComet software and a visual score by measuring the percentages of tail DNA and summing the visual score, respectively. A statistically significant (p < 0.05) reduce in cell viability was observed at 30 min after exposure, furthermore there is no more reduction after 24 h. Both comet assay measurements showed a significant (p < 0.05) increase in the percentage of tail DNA and visual score at 30 min after exposure, then tend to decrease after 24 h of exposure, although it was not significant (p > 0.05). The results showed that panoramic radiography interfered cell viability and induced DNA damage in buccal mucosa cells within 30 min after exposure, but these effects were ceased after 24 h.

Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency

The broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. We developed a multianalyte VISUAL score (variable immunodeficiency score upfront analytical link) aimed to predict severity using individual CVID patient data at baseline of a cohort of 50 CVID patients from two different centers in Portugal and Spain. We retrospectively applied VISUAL to the CVID clinical severity scores proposed by Ameratunga and Grimbacher after 15 years follow-up of our cohort. VISUAL score at CVID diagnosis showed adequate performance for predicting infectious and non-infectious severe complications (Cluster B). Compared to switched memory B lymphocyte phenotype alone, VISUAL provided a more accurate identification of clinically meaningful outcome, with significantly higher sensitivity (85% vs 55%, p = 0.01), and negative predictive value (77% vs 58%) and AUC of the ROC curves (0.72 vs 0.64), with optimal cut-off level of 10. For every increase of 1 point in the VISUAL scale, the odds of being in the higher risk category (Cluster B) increased in 1.3 (p = 0.005) for Ameratunga’s severity score and 1.26 (p = 0.004) for Grimbacher’s severity score. At diagnosis of CVID, VISUAL score ≥ 10 showed 8.94-fold higher odds of severe prognosis than below this threshold. Kaplan–Meier estimates for the VISUAL ≥ 10 points showed significantly earlier progression to Cluster B than those with VISUAL < 10 (p = 0.0002). This prognostic laboratory score might allow close monitoring and more aggressive treatment in patients with scores ≥ 10 on a personalized basis approach. Further studies are needed to prospectively validate VISUAL score.

The use of a novel method for SPECT/CT quantification of 99m-Tc-PYP uptake in the evaluation of ATTR cardiac amyloidosis

Funding Acknowledgements Type of funding sources: None. Background/Introduction: Bone scintigraphy with 99m-Technecium-Pyrophosphate (99m-Tc-PYP) with planar and SPECT imaging is now commonplace for the non-invasive diagnosis of ATTR cardiac amyloidosis. However, the quantification of 99m-Tc-PYP uptake is based on a semi-quantitative visual score and a heart to contralateral lung ratio which suffer from poor reproducibility. A more robust method of quantifying uptake and reporting results would be beneficial and may be possible using volumetric assessment with fused SPECT/CT acquisition. Purpose The aim of this study was to evaluate the performance of a novel semi-automated quantitative software to diagnose ATTR cardiac amyloidosis in patients with a clinical suspicion of cardiac amyloidosis who underwent 99m-Tc-PYP SPECT/CT imaging. Methods This was a retrospective, single-center study of consecutive patients who underwent 99m-Tc-PYP SPECT/CT imaging from September to December 2020. Quantification software was used to obtain standardized uptake values (SUVs) of 99m-Tc-PYP activity in the whole heart using SPECT/CT data. The total SUVs, mean SUVs, and percentage of injected tracer dose in the heart, as well as two other sets of these measurements adjusted for residual blood pool activity were obtained. Activity in the lung and bone was used to calculate heart to bone and heart to right lung ratios. The results from the software quantification were compared to the results from planar imaging as well as to the final clinical diagnosis of amyloidosis. Results A total of 59 patients were imaged during this time with an average age of 74.1 ± 11.8, and 32 (54.2%) were male. After excluding 8 patients for technical issues, 12 patients were found to be positive for amyloid, 39 were negative, and the average imaging delay time was 75.0 ± 15.2 minutes. 13 methods of assessment were evaluated with the metric of the percentage of injected tracer dose found in the heart that was adjusted for the mean residual blood pool activity having the best discrimination between abnormal and normal studies. The mean percentage of injected dose in positive patients was 2.87% vs 0.98% in the patients without amyloidosis (p &lt; 0.0001). Using a cutoff of 2% to ensure that no patients with amyloid would be missed by screening, there was 100% sensitivity, 94.9% specificity, and 96.1% accuracy. There was a significant difference in the percentage injected dose based on gradations of planar heart to contralateral lung ratio and planar visual score. Conclusion Volumetric software quantification may be a superior method of evaluating 99m-Tc-PYP cardiac amyloidosis studies. This methodology may allow for a quantitative definition of a normal or abnormal 99m-Tc-PYP cardiac amyloid study and provide for the potential of following response to therapy.

Quantitation vs visual assessment of 99mTc-DPD cardiac uptake in patients with suspected cardiac amyloidosis

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Universitary Clinic Hospital of Valencia Aim Cardiac uptake of 99mTc-DPD has proved its diagnostic efficacy in transthyretin cardiac amyloidosis(ATTR). We compared the usual visual assessment with two quantitative methods to evaluate cardiac activity and its possible relation with clinical follow-up. Methods We have studied 37 successive patients(p):32 men, 52-90 y/o (79.6 ± 9.3), submitted by suspected cardiac amyloidosis TTR by echo/cardiac MRI. After IV administration of 21.5 ± 3.4mCi of 99mTc-DPD, we obtained early (at 5min) and late (at 3h) whole body(WB) planar images and late SPECT. We assessed cardiac uptake in planar images by visual score (0-absent, 1-cardiac uptake lower than bone uptake, 2-equal, 3- higher than bone uptake), considering 2-3 score compatible with ATTR in absence of abnormal light chains on serum-urine. We obtained quantitative evaluation by heart/contralateral thoracic activity ratio (H/CL) in late images and from early and late WB images the heart retention(HR) ratio and heart/whole body(HWB) activity ratio. Clinical follow-up (12.4 ± 8.3 months) considering as cardiac events(CE): cardiac death and heart failure(HF) admissions. Results Visual score 0(11p), 1(2p), 2(4p) and 3(20p), considering group1(0-1) not suggestive of ATTR and group2(2-3) compatible with ATTR. SPECT showed biventricular uptake with septal predominance in group2. H/CL index was 2.23 ± 0.54(group2) vs 1.05 ± 0.10(group1) p &lt; 0.001), according to published(≥1.5 compatible with ATTR). HR and HWB ratios were also significantly higher in group2 vs group1, respectively 6 ± 3.14vs2.17 ± 0.4(p &lt; 0.001) and 6.51 ± 1.97vs2.65 ± 0.49(p &lt; 0.001). There were a trend to higher values in p with visual score3 than 2, not reaching statistically significant(only 4p with visual score2). There were significant correlation between H/CL-HR(r:0.66,p &lt; 0.01), H/CL-HWB(r:0.85,p &lt; 0.001) and HR-HWB(r:0.85,p &lt; 0.001). After follow-up we detected 6 CE(3p with HF admission, 3p cardiac death): 5p with visual score3 and one with 2, all 6p with high mean values of H/CL: 2.28 ± 0.76, HR: 6.02 ± 3.4 and HWB:5.97 ± 1.69. Conclusion We have found excellent correlation between visual score and the evaluated methods of quantitation of 99mTc-DPD cardiac uptake in our patients referred by suspected cardiac amyloidosis. These quantitative methods could be a helpful tool to correctly identify some patients with doubtful activity and could be useful in the follow-up evaluation, although it is necessary to study a greater number of patients.

Assessment of cerebrovascular disease with computed tomography in COVID-19 patients: correlation of a novel specific visual score with increased mortality risk

Purpose Cerebrovascular disease (CVD) is considered a major risk factor for fatal outcome in COVID-19. We aimed to evaluate the possible association between computed tomography (CT) signs of chronic CVD and mortality in infected patients. Materials and methods We performed a double-blind retrospective evaluation of the cerebral CT scans of 83 COVID-19 patients looking for CT signs of chronic CVD. We developed a rapid visual score, named CVD-CT, which summarized the possible presence of parietal calcifications and dolichosis, with or without ectasia, of intracranial arteries, areas of chronic infarction and leukoaraiosis. Statistical analysis was carried out with weighted Cohen’s K test for inter-reader agreement and logistic regression to evaluate the association of in-hospital mortality with CVD-CT, chest X-ray (CXR) severity score (Radiographic Assessment of Lung Edema-RALE) for radiological assessment of pulmonary disease, sex and age. Results CVD-CT (odds ratio 1.6, 95% C.I. 1.2-2.1, p = 0.001) was associated with increased risk of mortality. RALE showed an almost significant association (odds ratio 1.05, 95% C.I. 1-1.1, p 0.06), whereas age and sex did not. Conclusion CVD-CT is associated with risk of mortality in COVID-19 patients. The presence of CT signs of chronic CVD may be correlated to a condition of fragility of the circulatory system, which constitutes a key risk factor for death in infected patients.