Siemens Healthcare Research Articles

Effect of Season on Hematologic, Biochemical, and Hormonal Analytes in Rams of Two Breeds

Abstract Clinicopathological investigations are essential for the evaluation of the health status of ruminants. Apart from species-specific reference intervals, the effect of common biological factors should be considered for an accurate interpretation of laboratory data. The aim of this study was to evaluate the effect of season on hematologic and biochemical analytes, and serum total thyroxine and cortisol in adult rams of two breeds. Four blood samples (one every season) were collected from each ram. Complete blood count was performed on the Advia 120 (Siemens Healthcare Diagnostics, USA), while the differential leukocyte count was manually conducted. Biochemical and hormonal analyses were performed on Flexor E (Vital Scientific, The Netherlands), AVL 9180 (Roche Diagnostics, Belgium), and Immulite 1000 (Siemens Healthcare Diagnostics, USA), respectively. Linear mixed effects models (R language) were employed for statistical analyses. Forty-three (26 Chios, 17 Florina), adult, clinically healthy rams were included. Statistically significant (p<0.05), mostly breed-independent seasonal differences were observed in almost all of the analytes. However, when assessing these differences in view of the respective reference intervals, only a few of them were considered biologically important. Specifically, mild hyperglycemia and mild decrease in the concentration of total calcium and inorganic phosphorus were detected in winter, while a mild increase in thyroxine concentration (autumn) and creatine kinase activity (spring and summer) was also noted. In conclusion, seasonal effects should be considered when evaluating laboratory results in rams; however, season does not appear to have an essential effect on the clinicopathological profile of rams reared in the Mediterranean region.

Factor VIII Levels in Blood Group O and Non-O in Patients with Non-Severe Haemophilia a

Introduction ABO blood group affects levels of von Willebrand Factor (VWF) and Factor (F) VIII, as individuals with blood group non-O have higher levels of VWF and FVIII. To the best of our knowledge there is no data available regarding the association between blood group and FVIII in non-severe haemophilia. Aim We aimed to explore the influence of ABO blood group on VWF and FVIII levels in patients with non-severe haemophilia A (HA). Methods We recruited persons with non-severe HA (FVIII levels of 1-40%). Adult patients (age ≥ 18 years), with platelet count > 105 /µl, without impaired renal and hepatic function, active cancer, surgery within the last 6 weeks, or overt infection within the last 2 weeks, who gave their informed consent were included. A blood sample was collected for laboratory analysis. The diagnosis of haemophilia was confirmed by molecular analysis of the FVIII gene in all patients. None of the patients had inhibitors against FVIII at the time of sample collection. The lowest FVIII level ever measured in each patient's history served as basis for the assessment of severity. Healthy male persons with a median age comparable to the patient group served as controls. We determined the following parameters: ABO blood group, FVIII, VWF activity (VWF:Act), and VWF antigen (VWF:Ag). FVIII was measured with a one-stage assay (Sysmex-CA7000 - Sysmex, Kobe, Japan, in multi-dilution mode with native FVIII-deficient plasma - Technoclone, Vienna, Austria and Aktin FS activator - Siemens, Marburg, Germany), VWF:Act (BC von Willebrand Reagent or Innovance VWF Ac - Siemens Healthcare, Marburg, Germany) and VWF:Ag levels with a latex agglutination assay (STA LIATEST VWF, Diagnostica Stago). Comparison of VWF and FVIII levels between blood group O and non-O was calculated with Mann-Whitney-U test, correlation between FVIII and VWF levels was calculated with Spearman's correlation, association of FVIII and VWF separated for blood group was calculated with univariable linear regression. Association of FVIII with VWF and blood group was calculated using multivariable linear regression. All calculations were performed with SPSS (IBM Version 25.0). Results A total of 89 persons with HA (71 with mild and 18 with moderate haemophilia) and 82 healthy controls were included. Patient characteristics are listed in Table 1. Median levels of VWF were significantly higher both in patients (p=0.002 for both VWF:Ag and VWF:Act) and healthy controls (p<0.001 for both VWF:Ag and VWF:Act) with blood group non-O compared to individuals with blood group O. FVIII levels were not significantly different between blood group non-O and O in HA patients (15% vs. 14.1%, p=0.716) but significantly higher in healthy controls with blood group non-O versus O (150.0% vs. 109.5%, p<0.001; Table 2). In HA there was no correlation between FVIII and VWF:Act (rho=0.180, p=0.095) or between FVIII and VWF:Ag (rho=0.028, p=0.795, Table 3). In univariable linear regression there was no significant association between VWF and FVIII in HA, neither in those with blood group non-O nor in those with blood group O (Figure 1). Also in multivariable linear regression there was no significant association between VWF (p=0.632) and blood group (p=0.929) with FVIII in patients with HA. In healthy controls, there was a strong positive correlation between FVIII and VWF:Act (rho=0.751, p<0.001) and between FVIII and VWF:Ag (rho=0.790, p<0.001) (Table 3). In the healthy controls with blood group non-O 1% elevation in the VWF:Ag was associated with 0.63% of elevation in the FVIII:Act and in blood group O 1% elevation in the VWF:Ag was associated with 0.66% of elevation in the FVIII:Act (Figure 2). Conclusions Neither the blood group nor the VWF had an influence on FVIII levels in non-severe HA patients. We conclude that the impact of the genetic mutation of the FVIII gene by far outweighs the influence of VWF levels and the blood group. Thus, for the diagnosis of HA and for determination of HA severity, the blood group needs not to be taken into account. Disclosures Pabinger: Roche: Honoraria; Sobi: Research Funding; Novo Nordisk: Research Funding; CSL Behring: Research Funding; Pfizer: Honoraria; Shire: Honoraria; Bayer: Honoraria; Sobi: Honoraria.

Pre-Transplant Hepatic Steatosis (fatty liver) Predicts Chronic Graft-Vs-Host Disease but Does Not Affect Mortality

Introduction: Allogeneic hematopoietic stem cell transplant (allo-HCT) remains the only curative treatment for many hematologic conditions. However, significant mortality risk and risk of severe graft-vs-host disease (GvHD) limit its usefulness. Some patient characteristics such as performance status are used routinely as prognostic markers for poor outcomes after transplant. Steatohepatitis is a metabolic dysfunction manifesting as increased hepatic adiposity and resulting inflammation. A pre-clinical murine study suggests steatohepatitis is associated with GvHD. We assessed whether pre-HCT hepatic steatosis was associated with risk of developing GvHD and post transplant mortality. Methods: This retrospective study reviewed adult patients who underwent allogeneic stem cell transplants at Duke University over a 10-year period between 2008 and 2017 and had a computed tomography scan (CT) of the abdomen and pelvis with contrast within a 1-year period preceding the transplant. Patients with an acute illness as the indication for CT were excluded. We measured the attenuation of the liver vs. spleen as an estimate of hepatic steatosis. We used the widely accepted definition of hepatic steatosis as present when the difference in average attenuation between the spleen and liver was greater than or equal to 10 Hounsfield units and as absent when the difference was less than 10 Hounsfield units. Baseline pre-HCT factors as well as post-HCT outcomes were abstracted from the medical record. Results: We identified 80 patients with pre-HCT CT scans; of those, 59 (74%) had hepatic steatosis as defined above. Patients with hepatic steatosis tended to be older (median 52 vs. 38 years, p=0.0522); there were no statistically significant differences in gender, race, ethnicity, height, weight, Karnofsky Performance Status, HCT Comorbidity Index, history of diabetes, history of coronary artery disease, history of elevated liver function tests, primary disease, conditioning regimen, or stem cell source. Hepatic steatosis did not predict acute GvHD grade II-IV (OR 1.003, 95% CI 0.259 - 3.888, p=0.997). However, it was significantly associated with chronic GvHD on both univariate as well as multivariate analysis (Table 1, multivariate OR 3.83, 95% CI 1.11 - 13.28, p=0.023). There was no difference in overall survival or non-relapse mortality between the two groups. Conclusions: This study suggests that hepatic steatosis may predict chronic GvHD but does not predict acute GvHD or overall/non-relapse mortality. This study can be improved by using other imaging techniques such as a noncontrast CT, which is more accurate for assessment of hepatic steatosis. It is also important to note that imaging can only be used to predict the existence of hepatic steatosis; lobular inflammation, which is required to diagnose steatohepatitis, can only be proven on biopsy. Larger studies with liver biopsy or other noninvasive imaging measures of liver stiffness and steatosis will be needed to confirm the above results. Disclosures Gasparetto: Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Rizzieri:Gilead Sciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy; Millennium: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau; AbbVie: Consultancy; Spectrum: Consultancy; Kite Pharma: Consultancy; Incyte: Consultancy, Speakers Bureau; TEVA: Consultancy; Seattle Genetics: Consultancy, Speakers Bureau; Amgen: Consultancy. Bashir:Metacrine, Inc.: Research Funding; ProSciento, Inc.: Research Funding; Pinnacle Clinical Research: Research Funding; CymaBay Therapeutics: Research Funding; Siemens Healthcare: Research Funding; NGM Biopharmaceuticals: Research Funding; Madrigal Pharmaceulticals: Research Funding. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

An Increased Bone Mineral Density As an Adverse Prognostic Factor in Patients with Systemic Mastocytosis

Systemic mastocytosis (SM) is characterized by expansion of clonal mast cells that infiltrate various organ systems. The extent of organ infiltration and subsequent organ damage distinguishes between indolent SM (ISM) and advanced SM (AdvSM). ISM patients usually present with a low mast cell burden and have a nearly normal life expectancy while AdvSM patients have a high disease burden, multiple organ damage and poor prognosis. In ISM patients, measurement of the bone mineral density (BMD) frequently reveals osteopenia and osteoporosis (lumbar spine BMD T-score of ≤ −2.5 standard deviation [SD]). In contrast, the association between increased BMD and osteosclerosis, respectively, and the various SM subtypes is unclear. We therefore sought to evaluate the BMD in 61 patients (ISM, n = 29, 48%; AdvSM, n = 32, 52%) and correlated the prevalence of osteoporosis, increased BMD and osteosclerosis with clinical parameters and prognosis. All patients were scanned on the same 16 row CT Scanner (SOMATOM Emotion 16, Siemens Healthcare Sector, Forchheim, Germany). The results were expressed as T-score (SD below the mean of young healthy adults) and as Z-score (SD below the age- and gender-matched mean reference value). According to established WHO criteria, osteoporosis was defined as a lumbar spine BMD T-score of ≤ −2.5 SD. Increased BMD and osteosclerosis were defined as Z-score > 1 SD and > 2 SD, respectively. Osteoporosis was detected in 11/29 (38%) patients with ISM and 2/32 (6%) patients with AdvSM (p = 0.004). Bone marrow mast cell infiltration (median 10% versus 20%, p=0.035) and serum tryptase levels (median 31 µg/L versus 58 µg/L, p = 0.047) were significantly lower in ISM patients with osteoporosis as compared to those without osteoporosis (n=18, 62%). No significant differences were seen regarding age, gender, blood counts, and overall survival. An elevated BMD was detected in 1/29 (3%) patient with ISM and 24/32 (75%) patients with AdvSM (p < 0.001) while osteosclerosis was only detected in AdvSM patients (16/32, 50%). AdvSM patients with increased BMD were older (median 77 years versus 68 years, p = 0.0043), had lower platelet counts (median 111 x 109/L versus 238 x 109/L, p = 0.041) and higher levels of bone marrow mast cell infiltration (50% versus 10%, p=0.002), serum tryptase (median 262 µg/L versus 62 µg/L, p = 0.003) and alkaline phosphatase (238 U/L versus 74 U/L, p < 0.0001). In consequence, prognosis of AdvSM patients with increased BMD was significantly inferior as compared to those without increased BMD (median overall survival 3.6 years versus not reached, p = 0.031). In conclusion, i) osteoporosis is a common feature in ISM but not in AdvSM patients, ii) an increased BMD is frequent in AdvSM but not in ISM patients, iii) osteosclerosis is restricted to AdvSM patients, and iv) an elevated BMD is associated with a more aggressive phenotype and inferior survival (Figure A-B). Disclosures Fabarius: Novartis: Research Funding. Reiter:Novartis: Consultancy, Honoraria, Other: Travel reimbursement, Research Funding; Blueprint: Consultancy, Honoraria, Other: Travel reimbursement; Deciphera: Consultancy, Honoraria, Other: Travel reimbursement.

Association of Endothelial Biomarkers with Cerebral MRI Perfusion Analysis in Patients with Sickle Cell Disease

Introduction Sickle cell disease (SCD) is associated with silent cerebral infarcts (SCI) which are related to neurocognitive damage. One of the major causes of SCI is the impaired cerebral oxygenation, which makes cerebral blood flow (CBF) an essential parameter to measure. Previous hemodynamic studies have shown elevated CBF and reduced cerebrovascular reserve (CVR) in patients with SCD (Helton 2015; Václavů 2018). CVR is known as the increase of CBF in response to vasoactive stimulus, relative to the baseline. The reduced CVR renders SCD patients susceptible to cerebral ischemia, especially under hypotensive or hypoxic conditions. Possible factors contributing to microvascular damage and thus reduced CVR include hemoglobin S polymerization, neutrophil activation and endothelial activation and adhesion. Previous studies examined the role of these factors in patients with SCD (Sins 2017; Al Najjar 2017). However, the association between the endothelial biomarkers and hemodynamic parameters is unknown in adult patients with SCD. In this study, we investigated the correlation between CBF and CVR and the adhesion molecules including sVCAM-1, sP-selectin, VWF-Ag and ADAMTS13. Additionally, we studied the association of these endothelial biomarkers with standard laboratory parameters. Methods This study was performed in accordance with the Declaration of Helsinki and was approved by the Review Board of Amsterdam UMC. For this study, 33 steady state patients with SCD (mean age 32.1 ± 10.7, 64% male, 29 HbSS, 4 HbSß) and 10 healthy volunteers (mean age 36,4 ± 15.9, 60% male, 2 HbAS, 8 HbAA) were included. Hematologic laboratory parameters were assessed using standard laboratory procedures. Plasma levels of sVCAM-1 and sP-selectin were determined using ELISA (R&D Systems, USA) and ADAMTS13 and VWF-Ag were measured with the INNOVANCE assay (Siemens Healthcare Diagnostics). For the CBF measurements, pseudo-continuous arterial spin labelling (pCASL) was acquired at 3T MRI (Philips Healthcare, The Netherlands). CBF was measured before and after acetazolamide (vasoactive stimulus) administration and subsequently CVR was calculated using the following equation: CVR = (CBFafter - CBFbefore) / CBFbefore x 100% Plasma levels of endothelial biomarkers were compared between groups using ANOVA test. Correlation between the parameters were measured using single regression model where p<0.05 was considered as statistically significant. Results sVCAM-1 levels and VWF-Ag were significantly higher in SCD patients compared to healthy controls (p < 0.01 and p = 0.01). ADAMTS13 and sP-selectin were not significantly different between the two groups (p = 0.06 and p = 0.33). sVCAM-1 was significantly associated with CBF, and parameters of hemolysis LDH and bilirubin in SCD patients (Fig. 1A and 2C). Negative correlation was observed between sVCAM-1 and hemoglobin (Fig. 1B). The relationship between sVCAM-1 and hemodynamic and laboratory parameters are shown in Table 1. No significant correlation was found between sVCAM-1, hemodynamic and standard laboratory parameters in healthy controls. VWF-Ag, ADAMTS13 and sP-selectin were not significantly associated with hemodynamic MRI parameters. Discussion Our results show elevated sVCAM-1 levels in sickle cell patients, strongly related to CBF. sVCAM-1 is an adhesion molecule and elevated plasma levels are found in patients with endothelial activation due to inflammation or atherosclerosis (Cook-Mills 2013; Cybulsky 2001). Previous studies showed elevated levels in sickle cell disease but no correlation with parameters of cerebral perfusion have been demonstrated yet (Antwi-Boasiako 2018; Kato 2005). The strong correlation with CBF is mostly related to the chronic hemolysis given the association found with hemoglobin levels and markers of hemolysis like LDH and bilirubin. In contrast to sVCAM-1, no such relation was found with other markers of endothelial activation such as VWF activity and sP-selectin levels. No correlation between endothelial markers and the CVR was demonstrated, suggesting that endothelial damage itself may not related to the impaired cerebral vasodilatation in response to a vasoactive stimulus. Conclusion Endothelial adhesion molecule sVCAM-1 showed a strong correlation with CBF and parameters of hemolysis, suggesting a relation between the hemolytic damage of endothelial cells and impaired cerebral perfusion. Disclosures Nur: Novartis Pharmaceuticals: Consultancy.

Rheological Effects of L-Glutamine in Patients with Sickle Cell Disease

Background: ENDARITM (oral pharmaceutical L-glutamine powder) received FDA approval in 2017 as a treatment for sickle cell disease (SCD). A pivotal phase 3 clinical study conducted by Emmaus Medical, Inc. showed that L-glutamine resulted in a lower incidence of vaso-occlusive crises (VOC) as well as a lower rate of hospitalizations and shorter hospital stays. No changes in standard clinical laboratory values were noted. The clinical improvements associated with sickle cell complications are believed to be due to an increase in the proportion of the reduced form of nicotinamide adenine dinucleotides in the red blood cells (RBC) of patients with SCD, reducing the oxidative stress. While the endpoints in the phase 3 study are clinically important, it is essential that we identify biomarkers or measurable laboratory changes that can serve as endpoints for future clinical trials assessing dose optimization and the efficacy and safety of L-glutamine in SCD individuals, including those with hepatic and renal dysfunction. RBC rheology is markedly abnormal in SCD; blood is more viscous for a given hematocrit than normal individuals, dense red blood cells (DRBC) are packed with HbS, potentiating sickling, and RBCs are less deformable than those of HbAA or HbAS individuals. High whole blood viscosity, high DRBCs, and poor RBC deformability are associated with higher rates of VOC. Given the demonstrated reduction in pain events, we hypothesized that L-glutamine might improve RBC rheology and sought to test this in vitro and in vivo using a battery of rheological tests. Methods: For the in vitro study, 6 mL of whole blood was drawn into an EDTA vacutainer from ten pediatric patients with sickle cell anemia (HbSS or HbSβ0) during routine clinical checkups under an IRB approved protocol. The cohort included 3 female and 7 male patients, ages 2-19 years old. All patients were on a steady dose of hydroxyurea and did not receive a transfusion within the 3 months prior to sample collection. A 200 mM stock solution of L-glutamine and water was mixed and filtered under light-protected conditions. Aliquots were stored at -20°C to avoid multiple freeze/thaw cycles. L-glutamine was added to 3 mL of whole blood for a final concentration of 1 mM (average in vivo L-glutamine plasma concentration in patients with SCD treated with L-glutamine); 3 mL of the same patient sample with water added served as a control. After a 24-hour incubation period at 4°C, whole blood viscosity was measured using a cone and plate viscometer at 37°C (DV3T Rheometer, AMETEK Brookfield, USA), %DRBCs were measured on an ADVIA 120 Hematology System (Siemens Healthcare Diagnostics, Inc., USA), and deformability measured using a Laser Optical Rotational Red Cell Analyzer (Lorrca®) (RR Mechatronics, the Netherlands) with the Oxygenscan module. The Oxygenscan measures RBC deformability at normoxia (Elmax), deformability upon deoxygenation (EImin), and point of sickling (PoS), the oxygen tension at which deformability begins to decline, reflecting the patient-specific pO2 at which sickling begins. Paired samples (with and without added L-glutamine) were analyzed using Student's t-test. For the in vivo study, rheological tests were performed on peripheral blood from one patient (18-year-old male on hydroxyurea) at baseline and treated with L-glutamine as part of his routine clinical care. Results and conclusions: Addition of L-glutamine in vitro significantly reduced the PoS, meaning RBCs incubated with L-glutamine could tolerate a lower pO2 before sickling compared to the control. RBCs incubated with L-glutamine also had significantly higher EImin, meaning deoxygenated RBCs were more flexible and deformable. Whole blood viscosity at 45s-1 and 225s-1 did not change significantly following incubation with L-glutamine; %DRBCs also did not change significantly (Table 1). The in vivo patient sample tested exhibited a similar improvement in PoS and EImin (Figure 1). We therefore propose to further test the performance of the PoS and EImin as possible biomarkers of response to L-glutamine in vivo. If validated, these biomarkers may also help further elucidate the mechanisms of action of L-glutamine in SCD. Disclosures No relevant conflicts of interest to declare.

Multicenter Assessment of Radiation Exposure during Pediatric Cardiac Catheterizations Using a Novel Imaging System.

Objectives To quantify radiation exposure during pediatric cardiac catheterizations performed by multiple operators on a new imaging platform, the Artis Q.zen (Siemens Healthcare, Forchheim, Germany), and to compare these data to contemporary benchmark values. Background The Artis Q.zen has been shown to achieve significant radiation reduction during select types of pediatric cardiac catheterizations in small single-center studies. No large multicenter study exists quantifying patient dose exposure for a broad spectrum of procedures. Methods Retrospective collection of Air Kerma (AK) and dose area product (DAP) for all pediatric cardiac catheterizations performed on this new imaging platform at four institutions over a two-year time period. Results A total of 1,127 pediatric cardiac catheterizations were analyzed. Compared to dose data from earlier generation Artis Zee imaging systems, this study demonstrates 70–80% dose reduction (AK and DAP) for similar patient and procedure types. Compared to contemporary benchmark data for common interventional procedures, this study demonstrates an average percent reduction in AK and DAP from the lowest dose saving per intervention of 39% for AK and 27% for DAP for transcatheter pulmonary valve implantation up to 77% reduction in AK and 70% reduction in DAP for atrial septal defect closure. Conclusion Use of next-generation imaging platforms for pediatric cardiac catheterizations can substantially decrease patient radiation exposure. This multicenter study defines new low-dose radiation measures achievable on a novel imaging system.

Accuracy, precision, and consistency of methods for pathogen-specific cerebrospinal fluid/serum Q-value calculation

For a CSF/serum samples pair the specific Q-value is the ratio of antibody concentrations and proportional to the pathogen-specific antibody index. It is usually extracted from optical density (OD) measurements by applying appropriate evaluation methods. Six different methods for Q-value determination, partly using parameter variation, were assessed with respect to accuracy, precision, and the methods' parameter consistency. The methods are based on the Four Parameters Logistic (4PL) equation or the α-method; one method is a polygonal line composed of calibration data. We tested on OD data of 51 CSF/serum sample pairs, measured with EUROIMMUN AG (Lübeck, Germany) ELISA tests for antibody determination in CSF, as part of INSTAND e.V. proficiency survey tests for the MRZH reaction (Measles, Rubella, Varicella zoster, Herpes simplex virus).Each method was tested with four ODs, standard curve methods additionally with only two ODs, identified by a selection rule. We found all methods to be of comparable accuracy and precision. With the standard curve methods, there were no differences between two ODs and four ODs evaluations.Consistency between method parameters and measured OD values is a key property of standard curve methods with a strong impact on accuracy and precision. We found a statistically significant difference with parameter consistency between a 4PL standard curve evaluation of this study and an α-method evaluation of data, measured with ELISAs of Siemens Healthcare GmbH (Marburg, Germany).General considerations show Q-values obtained by parameter variation to be more reliable than those resulting from selection rule application with standard curves.

Effect of hemoglobin F and A2 on hemoglobin A1c determined by cation exchange high-performance liquid chromatography

AbstractBackgroundThe potential effect of increase in hemoglobin (Hb) A2and HbF on glycated hemoglobin (HbA1c) measurements were investigated using a high-performance liquid chromatography (HPLC) method compared with an immunoturbimetric assay.MethodsSamples producing abnormal chromatograms during the measurement of routine HbA1ctesting with HPLC were further analyzed to characterize abnormal Hb variants. Patients were divided into three groups that had only high HbF (group 1), only high HbA2(group 2), and both high HbA2and HbF (group 3). HbA1cvalues of patients were re-assayed using the immunoturbidimetric method (Advia, Siemens Healthcare, Germany).ResultsHbA1clevels were significantly higher in all groups measured by immunoassay than in HPLC. We found a positive correlation between HPLC and immunoturbidimetry in the group 2 and a slight correlation in the group 1. There was no correlation between the two methods in group 3.ConclusionsHbA1cmeasurement by HPLC method interfering with elevated HbA2and HbF, especially HbF, should be verified by an immunoturbidimetric method.

Technical Note: Increased photon starvation artifacts at low helical pitch in ultra-low-dose CT.

The aim of this study was to demonstrate that a low helical pitch causes increased photon starvation artifacts at ultra-low-dose CT. A cylindrical water phantom with a diameter of 30cm was scanned on two different generation CT scanners: a 64-slice scanner (Sensation 64, Siemens Healthcare) and a 192-slice scanner (Somatom Force, Siemens Healthcare) at multiple effective mAs levels (mAs/pitch=200, 100, 50, 25, and 12). The corresponding CTDIvol values were 4.1, 2.0, 1.0, 0.5mGy, on the 64-slice scanner and 3.8, 1.9, 1.0, 0.5mGy on the 192-slice scanner, for the selected effective mAs values. For each dose setting, the scan was repeated at four helical pitches: 1.2, 0.9, 0.6, and the lowest achievable pitch on each scanner. The tube current was automatically adjusted by the scanner so that the effective mAs, and thus CTDIvol , were kept the same for different pitches. All CT data sets were reconstructed with a slice thickness of 3mm and a medium smooth kernel. Images acquired at the same dose level but different helical pitches were visually inspected to assess photon starvation artifacts and noise levels. At the same radiation dose, image noise increased with the decreasing helical pitch. The increase was more severe on the old-generation 64-slice scanner. Photon starvation artifacts were evident at 200 effective mAs on the 64-slice scanner at 80kV. On the 192-slice scanner there was no visible photon starvation artifacts at both 200 and 50 effective mAs (CTDIvol =4.1mGy and 1.0mGy, respectively); nor was there a visible impact from the lower helical pitch. Only when the dose was lowered to be extremely low (~0.26mGy, achievable at 70kV), did photon starvation artifacts become evident. A low helical pitch may increase image noise and photon starvation artifacts compared to a higher pitch for the same dose level, particularly at ultra-low dose CT.

The temperature dependence of gradient system response characteristics.

The gradient system transfer function (GSTF) characterizes the frequency transfer behavior of a dynamic gradient system and can be used to correct non-Cartesian k-space trajectories. This study analyzes the impact of the gradient coil temperature of a 3T scanner on the GSTF. GSTF self- and B0 -cross-terms were acquired for a 3T Siemens scanner (Siemens Healthcare, Erlangen, Germany) using a phantom-based measurement technique. The GSTF terms were measured for various temperature states up to 45°C. The gradient coil temperatures were measured continuously utilizing 12 temperature sensors which are integrated by the vendor. Different modeling approaches were applied and compared. The self-terms depend linearly on temperature, whereas the B0 -cross-term does not. Effects induced by thermal variation are negligible for the phase response. The self-terms are best represented by a linear model including the three gradient coil sensors that showed the maximum temperature dependence for the three axes. The use of time derivatives of the temperature did not lead to an improvement of the model. The B0 -cross-terms can be modeled by a convolution model which considers coil-specific heat transportation. The temperature dependency of the GSTF was analyzed for a 3T Siemens scanner. The self- and B0 -cross-terms can be modeled using a linear and convolution modeling approach based on the threemain temperature sensor elements.

P2673Challenging time limits: Using a single high-sensitive troponin I to rule-out acute myocardial infarction in early presenters

Abstract Introduction According to ESC guidelines, an acute myocardial infarction (MI) can be excluded without serial troponin measurements in patients presenting with a single high-sensitive troponin below the 99th percentile and chest pain starting >6 hours prior to admission. However, it is unclear if single-testing of high-sensitive troponin can rule-out MI in early presenters. Purpose To investigate the diagnostic performance of a single value of high-sensitive cardiac troponin I (hs-cTnI) at presentation for ruling-out MI in patients presenting with chest pain to the Emergency Department irrespective of chest pain onset. Methods We conducted a substudy of preliminary data from the RACING-MI trial. We included patients presenting with chest pain suggestive of MI to the Emergency Department of a Regional Hospital. We used the Siemens hs-cTnI (Siemens Healthcare, TNIH, Limit of detection: 2.21 ng/L) and a diagnostic cut-off value <3 ng/L to rule-out MI at presentation. Two physicians independently adjudicated the final diagnosis based on all clinical information. Patients were stratified based on time from chest pain onset to hospital admission as very early (0–3 hours), early (3–6 hours) and late presenters (>6 hours). Results We included 989 patients with available hs-cTnI results at admission. MI was confirmed in 82 (8.3%) patients. Using hs-cTnI <3 ng/L as diagnostic cut-off value at presentation, 302 (30.5%) patients without MI were classified as rule-out. Overall, the negative predictive value (NPV) for MI was 100% (95% CI 98.7–100). Based on chest pain onset, 33.8% of patients were classified as very early, 12.8% as early, and 42.7% as late presenters, with 10.7% patients with unreported/unknown onset. NPV was 100% (95% CI 96.5–100) for very early, 100% (95% CI 88.3–100) for early and 100% (95% CI 97.3–100) for late presenters. Conclusions Using a single hs-cTnI value <3ng/L as diagnostic cut-off to rule-out MI seems to be safe and to allow rapid rule-out of MI in patients presenting with chest pain to the emergency department, even in very early presenters. ClinicalTrials.gov Identifier: NCT03634384. Acknowledgement/Funding Randers Regional Hospital, A.P Møller Foundation, Boserup Foundation, Korning Foundation, Højmosegård Grant, Siemens Healthcare (TNIH assays), etc.

P1215Non-invasive angiogenesis assessment with PET/CT in a rabbit model of myocardial infarction: feasibility and comparison with molecular markers

Abstract Background Translational molecular imaging using Positron Emission Tomography/Computed Tomography (PET/CT) and Transesophageal Echocardiography (TEE) are powerful non-invasive tools for investigation and monitoring of cardiovascular functions. Following myocardial infarction (MI), formation of new blood vessels (angiogenesis) is of importance in the healing process and can be assessed with the PET tracer 68Ga-NODAGA-E[(cRGDyK)]2 (68Ga-RGD). Purpose The purpose of the study was to assess angiogenesis in a rabbit model of myocardial infarction using molecular imaging (PET/CT) and furthermore to validate the findings using TEE, immunohistochemistry (IHC) and quantitative PCR (qPCR). Methods Ten NZW rabbits were used (MI: n=5, SHAM: n=5). Angiogenesis was assessed with 68Ga-RGD before, 1 and 3 weeks after interventions using PET/CT (Inveon System, Siemens Health Care). TEE was used per-operatively and at termination for assessment of the MI (S8–3T probe, iE33 System, Phillips). Following the final scans, hearts were harvested for ex vivo analyses. Short axis slides were stained for collagen deposition and myocardial differentiation (H&E and Masson's trichrome), endothelial cells (CD31), and macrophage infiltration (RAM11). Gene expression alterations related to wound healing response (inflammation, granulation, and tissue remodeling) were measured using qPCR arrays (84 genes analyzed). Results One week after the interventions, 68Ga-RGD uptake, as assessed with PET was increased in the infarct area when compared to the remote zone of the same rabbit as well as compared to the SHAM group. Three weeks after intervention, there was no difference in 68Ga-RGD uptake between groups. High quality TEE images were obtained in all rabbits. Ex vivo analyses at 3 weeks after intervention revealed moderate vessel formation (CD31) in the infarct zone, none in the border zone, whereas surrounding viable myocardium had visible CD31 positive vessels comparable to the SHAM group. Macrophage infiltration (RAM11) and collagenous scaring (Masson's trichrome) was pronounced in the infarcted area. Gene expression alterations in the infarct area (30 of 84 genes upregulated) were dominated by increased expression of collagens (COL1A2, COL5A1, COL5A4), inflammatory chemokines and cytokines (CCL2, IL1A, IL1B, IL6, IL10) and ECM remodeling enzymes (uPAR, TPA, TIMP1, SERPINE1, MMP9) in the MI group compared to the SHAM group, whereas integrins involved in the angiogenesis response (ITGA4, ITGAV) were only moderately changed in the infarction at termination, confirming the in vivo PET findings. Study outline Conclusions In this rabbit MI model, we demonstrate the feasibility of monitoring angiogenesis in the healing process non-invasively with PET. The imaging results were confirmed by IHC and gene expression analysis. Moreover, TEE using a dedicated pediatric probe is feasible in the rabbit model, making this a robust and translational medium-sized animal model of myocardial infarction.

Potentials and limits of a novel CT reconstruction algorithm (DirectDensity™) developed for radiotherapy treatment planning

Purpose: Computed tomography (CT) represents the standard of treatment planning in radiotherapy. Calculation of dose distribution requires proper energy-dependent curves to convert Hounsfield Units into relative to water electron densities (rED). To possibly reduce the patient dose while maintaining optimal image quality, it could be useful to modulate x-ray tube potential (kVp) based on patient size, but this practice requires the use of several conversion curves in the treatment planning system (TPS). The DirectDensityTM (DD) algorithm, recently developed by Siemens Healthcare, uses projection data to reconstruct images directly proportional to rEDs, regardless of the used kVp. The purpose of this study was to evaluate this algorithm for clinical use in radiotherapy. Methods: Image quality was evaluated on Catphan images reconstructed with standard and DD algorithms. The CIRS Electron Density Phantom, with its several tissue-equivalent inserts, was then used to assess the accuracy of reconstructed rEDs against those certified at different tube voltages. Finally, the treatment plans calculated on clinical images reconstructed with standard and DD algorithms were compared. Results: DD showed an image quality comparable to standard algorithms except for the contrast: DD causes a loss in contrast (up to 69%) for materials densities greater than 1.1 g cm−3. CIRS images analysis proved the rEDs reconstruction accuracy except for the metal inserts: titanium rED was underestimated up to 40% when kVp was reduced. Nevertheless, minimal dosimetric differences were found between treatment plans calculated in different body regions. Conclusions: The DD algorithm allows to plan radiotherapy treatments on CT images acquired at tube potentials optimized both for the anatomical region and patient size, without complicating the clinical workflow with tube potential specific calibration procedures. However, the presence of contrast medium and metal implants can limit the applications of this algorithm in clinical practice.

Quantitative ultrasound in obstetrics and perinatal care

This talk will present recent results from our multi-institutional effort to advance the application of Quantitative Ultrasound in obstetrics and in perinatal care. In the field of obstetrics, we are investigating the use of shear wave elasticity imaging (SWEI) to predict the risk of preterm birth based on assessing the viscoelastic properties of the uterine cervix. Longitudinal studies in non-human primates (NHP) and humans showed a similar rate of decrease of the shear wave speed, SWS (1.6% and 1.5%/% gestational age, respectively), validating the animal model and indicating the value of SWS change as a biomarker for cervical softening. We are currently optimizing the analysis of shear wave dispersion to assess changes in viscosity. In the field of perinatal care, results from a pilot study in NHP neonates suggest that the effective size of diffuse scatterers can be used as a biomarker for thalamic apoptosis induced by long exposures to anesthesia. We are currently investigating the use of coherent scattering features to increase the sensitivity and specificity to neuroapoptosis and to improve attenuation and backscatter coefficient estimations in complex tissues such as the cervix and the neonate brain. [Acknowledgments: All protocols have been IRB- and/or IACUC-approved, and are HIPAA compliant. Equipment loan and technical support from Siemens Healthcare. Funded by: NIH Grant Nos. T32CA009206, F31HD082911, R01HD072077, UL1TR000427, P51OD011106, and R01HD083001; NSERC Grant No. RGPIN-2015-04136; and UNAM-PAPIIT IA104518 and IN107916.This talk will present recent results from our multi-institutional effort to advance the application of Quantitative Ultrasound in obstetrics and in perinatal care. In the field of obstetrics, we are investigating the use of shear wave elasticity imaging (SWEI) to predict the risk of preterm birth based on assessing the viscoelastic properties of the uterine cervix. Longitudinal studies in non-human primates (NHP) and humans showed a similar rate of decrease of the shear wave speed, SWS (1.6% and 1.5%/% gestational age, respectively), validating the animal model and indicating the value of SWS change as a biomarker for cervical softening. We are currently optimizing the analysis of shear wave dispersion to assess changes in viscosity. In the field of perinatal care, results from a pilot study in NHP neonates suggest that the effective size of diffuse scatterers can be used as a biomarker for thalamic apoptosis induced by long exposures to anesthesia. We are currently investigating the use of coherent scat...

3304High sensitive cardiac troponin i at admission and 30 minutes later to rule-in or rule-out acute myocardial infarction - Preliminary results from the RACING-MI trial

Abstract Introduction Current ESC guidelines have introduced a 0h/1h algorithm for accelerated rule-in or rule-out of acute myocardial infarction (MI) when using assay specific high-sensitive cardiac troponin I (hs-cTnI). Several studies have investigated the diagnostic performance and safety of this approach using different hs-cTnI assays. However, little is known of the diagnostic performance of a 0h/30min algorithm. Purpose To evaluate the diagnostic accuracy of early rule-in or rule-out of MI after 30 minutes by applying assay specific hs-cTnI cut-off values from a recently validated 0h/1h algorithm. Methods We prospectively enrolled chest pain patients suggestive of MI admitted to the Emergency Department. Patients underwent serial hs-cTnI measurements at admission (0 hour) and after 3 hours according to clinical practice. In addition, hs-cTnI measurements were performed after 30 minutes. The assay specific cut-off values from the 0h/1h algorithm were applied to the 30 minute cohort (figure 1). Final diagnosis was adjudicated independently by two physicians. Results In total, 943 patients were included. MI was the final diagnosis in 67 (7.1%) patients. Overall, absolute hs-cTnI values after 30 minutes were significantly higher in the MI group than in the non-MI group (19.2 (Q1:Q3) 2.7–75.3) ng/L versus 0.1 (0.2–0.7) ng/L, p<0.001). When applying the assay-specific hs-cTnI cut-off valuesfor the 0h/1h algorithmto the 30 minute patient cohort, 52.4% of patients were classified as rule-out with a negative predictive value of 100% (95% CI: 99.2–100). In total, 8.5% were classified as rule-in with a positive predictive value of 83.8% (95% CI: 74.2–90.3). Sensitivity was 100% (95% CI: 94.6–100) and specificity was 97.4% (95% CI: 95.7–98.6). Overall, 39.1% were assigned to the observational zone with a 3.5% prevalence of MI. Conclusions The use of assay specific hs-cTnI measurement at admission (0h) and 30 min later can be used to safely rule-out MI. This indicates that it might be safe to develop a 0h/30min algorithm and hereby reduce time to diagnosis even further. NCT03634384. Acknowledgement/Funding Randers Regional Hospital, A.P Møller Foundation, Boserup Foundation, Korning Foundation, Højmosegård Grant, Siemens Healthcare (TNIH assays), etc.

P2680Changes in body fat distribution after intensive dietary intervention in patients with stable coronary artery disease

Abstract Introduction Contradictory reports are available on the role of adipose tissue in the pathophysiology and progression of coronary artery disease (CAD). It seems accepted that local fat distribution is more relevant than the general amount of body fat. As in the case of visceral fat, pericardial adipose tissue (PEAT) has been postulated an important mediator of metabolic risk, with a special role attributed to epicardial adipose tissue (EAT). Purpose To study the effect of intensive dietary and lifestyle modification on the distribution of body fat in patients diagnosed with stable CAD qualified to conservative treatment. Methods Total body fat mass (TBF), visceral fat area (VFA), PEAT volume, and EAT volume were measured in 67 participants (43% women) of the DISCO-CT trial (Dietary Intervention to Stop COronary Atherosclerosis in Computed Tomography, NCT02571803) who completed the study by the end of 2018. All patients, randomly assigned to either experimental or control arm in a 1:1 fashion, were regularly followed-up at our site, with those in the experimental arm being strictly supervised by a dietitian to stick to Dietary Approaches to Stop Hypertension (DASH) diet and encouraged to lifestyle changes atop optimal medical therapy. Contrast-enhanced coronary computed tomography was performed at baseline and after the median time of 59 weeks (2x192-multislice scanner, temporal resolution 66 ms, Somatom Force, Siemens). PEAT and EAT volumes, expressed in mm3, were measured with a dedicated offline workstation (syngo.via Frontier, Siemens Healthcare) using a semiautomatic segmentation technique (window width range −195 to −45 Hounsfield units). TBF, expressed in kg, and VFA, expressed in cm2, were measured using the InBody S10 Body Water Analyser at baseline and completion of the study. 57% of subjects included into the analysis represented the experimental arm. Results There were no significant between-arm differences in baseline TBF, VFA, PEAT, and EAT volumes. A significant reduction by 3.7±5.0 kg in TBF (p<0.001; 95% CI 2.1, 5.3) and by 19.7±30.1 cm2 in VFA (p<0.001; 95% CI 9.8, 29.6) was observed in the experimental arm, while in the control group both TBF and VFA irrelevantly increased, by 0.6±4.7 kg (p=0.53; 95% CI −2.4, 1.3) and 2.2±27.0 cm2 (p=0.67; 95% CI −12.7, 8.2), respectively. A significant decrease in PEAT volume, by 19.9±43.0 mm3 (p=0.007; 95% CI 5.8, 34.1), was observed in the experimental group, compared to a non-significant PEAT volume reduction by 5.8±3.5.0 mm3 (p=0.38, 95% CI −7.5; 19.2) in the control group. Contrarily, no significant changes in EAT volumes were observed in either experimental (reduction by 3.8±15.2 mm3; p=0.13, 95% CI −1.2, 8.8) or control arm (reduction by 5.1±17.2 mm3; p=0.13, 95% CI −1.5, 11.6). Conclusion Intensive dietary intervention in patients with stable CAD can lead to a significant reduction in total body fat, visceral fat and pericardial fat, this effect, however, may not apply to epicardial fat. Acknowledgement/Funding This study was founded by a grant (2.15/III/15) from the Institute of Cardiology in Warsaw, Poland

The spectrum of brain MRI findings of methanol intoxication after the methanol affair in the Czech Republic

To demonstrate the variability of brain magnetic resonance imaging (MRI) findings in patients of acute methanol poisoning. A total of 51 patients were scanned an a 3T MAGNETOM Skyra scanner (Siemens Healthcare, Erlangen, Germany) with the same protocol. The MR protocol included 3D T1-weighted, 2D T2-weighted, fluid-attenuated inversion recovery, susceptibility-weighted imaging as well as coronal T2-weighted images with fat sat for visualization of the optic nerves. 3D T1-weighted images were processed using the MorphoBox prototype software yielding estimation of regional brain volumes. Imaging methods revealed a positive finding associated with methanol intoxication in 24 patients (47.1%), mostly seen as symmetrical lesions in the putamen, which afflicted 16 patients (31.4%) (Fig. 1). Haemorrhage was detected in 16 cases (31.4%), deposits in white matter with localisation primarily subcortically in 5 cases (9.8%), and lesions in the region of the pallidum in 7 cases (13.7%) (Fig. 2). There were lesions in the brainstem in 7 patients (13.7%), and lesions in the cerebellum were found in one case. Compared to a control group, survivors of methanol poisoning had smaller putamina, caudates and pallida (p < 0.01). The most common finding showed damage of the putamen, which is a predilection area of methanol poisoning. An interesting finding was the relatively frequent occurrence of selective lesions of the pallidum, which is found more often in other types of intoxication. Atrophy of basal ganglia was prominent in patients after intoxication.

177PD - Prospective, multicenter registry trial to evaluate the clinical feasibility of targeted axillary dissection (TAD) in patients (pts) with breast cancer (BC) and core biopsy proven axillary involvement (cN+)

BackgroundAs part of de-escalating strategies of the axillary treatment in lymph node (LN) positive BC pts, TAD was introduced (Caudle et al., JCO 2016). Despite this very interesting approach, some important aspects regarding the clinical feasibility after neoadjuvant chemotherapy (NACT) were missing if a safe procedure was to be guaranteed. The correct evaluation of pathologic complete response (pCR) has a prognostic impact in high risk BC pts (Katherine, CreATE X). This study aimed to investigate the clinical feasibility of clip placement in positive axillary LNs followed by NACT and TAD in BC patients. MethodsThe Senta trial is a prospective, multicentric registry study (N=598). Prior to NACT, pts with invasive BC received an ultrasound guided core biopsy with clip insertion into the suspicious axillary LN. After NACT, pts underwent axillary surgery according to the investigators discretion, with or without sentinel LN (SLN) biopsy. TAD included removal of the clipped LN and SLN biopsy (SLNB). The pathology of the clipped LN before and after NACT, other LNs, and the SLN were compared. The primary endpoint (EP) was the detection rate (DR) of the clipped LN after NACT. Secondary EP was the false negative rate (FNR) of TAD. ResultsBetween January 2017 and October 2018, 598 cN+ BC pts from 50 different German breast units had biopsy proven axillary LN involvement and received clip insertion into the affected LN. The complete data set from 378 pts was available. After NACT, the clipped N was detected in 78.6% of the patients (target lymph node biopsy = TLNB), and 58.9% of the whole cohort received SLNB as well. The SLN and TLN were identical in 48.0%. An axillary dissection was performed overall in 68%. The FNR of TLNB was 8.0% (CI 95%, 3.0–12.0) for the whole cohort. TAD followed by axillary LN dissection had a FNR of 4.4% (2 of 45, CI 95%, 0.02–9.0). ConclusionsPreliminary results demonstrated a high DR supporting the feasibility of this approach, however, the FNR of TAD (4.4%) was higher than reported earlier (FNR = 2.0%, Caudle et al.). This is of great importance for postneoadjuvant treatment decisions in case of non-pCR and should be discussed. Clinical trial identificationNCT03102307; release date: April 5, 2017. Legal entity responsible for the studyKliniken Essen-Mitte. FundingHas not received any funding. DisclosureM. Reinisch: Honoraria (self): Pfizer, Novartis, Eli Lilly, Roche; Advisory / Consultancy: Roche, Daiichi Sankyo, Hexal, Eli Lilly, Novartis; Travel / Accommodation / Expenses: Pfizer, Celgene, Novartis. J. Heil: Advisory / Consultancy: Roche, Siemens Healthcare Diagnostics; Research grant / Funding (self): BARD; Honoraria (self): Roche, Siemens Healthcare Diagnostics, BARD; Travel / Accommodation / Expenses: Celgene. C. Seiberling: Travel / Accommodation / Expenses: Teva. C. Ankel: Advisory / Consultancy, Travel / Accommodation / Expenses: PFM medicals. V. Hanf: Honoraria (self): Novartis. J. Holtschmidt: Travel / Accommodation / Expenses: Roche. S. Kuemmel: Advisory / Consultancy: Genentech, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex, Daiichi Sankyo, Puma Biotechnology, PFM Medical, Pfizer, MSD Oncology; Travel / Accommodation / Expenses: Roche, Daiichi Sankyo. All other authors have declared no conflicts of interest.

4087Functional assessment of the myocardium in non-ischaemic cardiomyopathy using manganese-enhanced T1 mapping

Abstract Background Delayed-enhancement magnetic resonance imaging (DEMRI) with gadolinium detects macroscopic myocardial fibrosis, but does not directly assess myocardial function. Manganese, a paramagnetic calcium-analogue, enables direct dynamic assessment myocyte calcium handling and is a potential early marker of myocardial dysfunction. We have previously demonstrated manganese-enhanced MRI (MEMRI) can detect altered calcium-handling in remote remodelling myocardium in a rodent infarct model. Purpose To evaluate MEMRI as a marker of altered myocardial calcium handling in patients with non-ischaemic cardiomyopathy (NCT03607669). Methods Healthy volunteers (HV, n=20, 13 male, 42±11 years) and patients with hypertrophic (HCM, n=11, 5 male, 57±15 years) or dilated (DCM, n=5, 3 male, 56±14 years) cardiomyopathies underwent both DEMRI and MEMRI. Myocardial T1 was measured for 40 min after intravenous manganese dipyridoxyl diphosphate (Mn-DPDP, 5 μmol/kg) administration. Images were acquired at 3T with T1 imaging performed using Shortened Modified Look-Locker Inversion recovery [Figure A] (WIP #1048 Siemens Healthcare Ltd). Results No adverse effects were observed. In HV, the myocardialT1 profile following Mn-DPDP administration demonstrated a rapid initial descent (perfusion phase) followed by a slower, more gradual decrease which continued throughout the 40 min imaging period (mean reduction 25.2%, 283±9ms). In patients with HCM, T1 values followed a different pattern following Mn-DPDP administration. In areas of focal myocardial fibrosis (defined by DEMRI) there was again a sharp initial shortening of T1 but this was followed by a steady increase towards baseline, which eventually recovered to &gt;40% of its initial value at 40 minutes. In areas of diffuse myocardial fibrosis, the initial shortening in the perfusion phase was followed by a more gradual recovery which then plateaued, remaining stable at 21% of native T1 by 40 min [Figure B]. Hypertrophied non-fibrosed myocardium had higher native T1 than HV (1178±45 vs 1133±36 ms P=0.005) and the rate of T1 reduction following the perfusion phase was slower (P=0.0005), leading to less overall T1 shortening at 40 min (880±40 vs 841±28 ms, P=0.004, [Figure C]). No patient with DCM had fibrosis by DEMRI. Native T1 was higher than HV (1234±26 vs 1133±36 ms, P&lt;0.0001) and the rate of T1 reduction following the perfusion phase was lower in DCM myocardium (P&lt;0.0001) resulting in less overall T1 shortening at 40 min (914±60 vs 841±28 ms, P=0.0006, [Figure D]). MEMRI in non-ischaemic cardiomyopathy Conclusion MEMRI identifies altered calcium-handling in pathological myocardium of non-ischaemic cardiomyopathy, irrespective of fibrosis by DEMRI. This feasible, safe and novel method of functional myocardial tissue characterisation has exciting potential for future diagnostic, functional and clinical applications. Acknowledgement/Funding British Heart Foundation