1. Conclusion Analysis of the repeatability/variability of RNVG measurement of LVEF using single and dual region of interest techniques was investigated on a small subset of 20 studies were repeat LAO40 projectional data was acquired. This analysis highlighted that a single region of interest approach gives the most reproducible approach, with interoperator variability of ~2% (1σ). This is at the expense of systematically underestimating LVEF due to the overestimation of end systolic counts. Ideally, a single region-of-interest approach should be used for longitudinal monitoring of LVEF as it is most reproducible. However, a dual-region of interest approach is more usually adopted due to the higher normal range. NICE guidelines Herceptin use in the treatment of early-stage HER2-positive breast cancer states that no women who have an LVEF < 55% should commence treatment. The lower limit of the normal range for the single region of interest technique used routinely at GRI is 40%. The variability in LVEF was then assessed for a larger subset of 70 patients covering a wide range in LVEF. Data was processed using 5 RNVG analysis packages and the results between vendors assessed. Although good correlation between software packages was observed, there existed gross differences in individual patients. Bland- Altman analysis shows wide 95% confidence intervals in pairwise differences which indicates that these software packages are not interchangeable. It is therefore essential that the same analysis software is used for longitudinal monitoring of LVEF. Furthermore, the normal range for that software should be established before clinical use. J.Robinson a, J. Prosser b, G.S.M. Cheung c, A. Tarbuck b,S, Allan a, G.McMaster a, S. Reid a and W.Martin a Dept Nuclear Cardiology, Glasgow Royal Infirmary a ; University of Aberdeen b ;Dept Nuclear Medicine Raigmore Hospital, Inverness c ; Introduction and Aims Herceptin is a human epidermal growth factor 2 (HER2) targeted monoclonal antibody with proven efficacy in the treatment of HER2+ metastatic breast cancers, when combined with chemotherapy. Unfortunately, therapy also carries an associated cardiotoxicity risk which can manifest as an asymmetric decrease in left ventricular ejection fraction (LVEF) and heart failure. For this reason, it is essential that LV function is monitored during therapy in a reliable and robust manner. Radionuclide Ventriculography (RNVG) offers such a tool with the National Institute for Health and Clinical Excellence (NICE) Guidelines recommending RNVG for the pre-assessment and monitoring of patients undergoing Herceptin therapy, based on LVEF. The aim of this work is 2 fold. Firstly, the repeatability and operator variability of single and dual region-of-interest (ROI) approaches to LVEF measurement is assessed on a subset of 20 patient acquisitions. Secondly, 70 patient studies covering the full range of LVEF experienced clinically were processed on 5 software applications: Odyssey (Picker/Philips), MAPS 10000 (Link Medical), Xeleris TM (GE), FUGA TM (HERMES Medical Solutions) and Syngo® MI Workspace (Siemens). Each application use differing algorithms in their determination of LVEF. Correlation and Bland-Altman analysis is used to assess the clinical significance between the systems and whether the different software applications can be used interchangeably. Results: Variability between Software Applications A further 70 studies covering the full range of LVEF experienced clinically were processed using 5 software applications provided by the major Nuclear Medicine Vendors. All patient data was anonymised and each operator blinded to the results from the other applications. Assessment of the variability of left ventricular ejection fraction (LVEF) between software algorithms in radionuclide ventriculography (RNVG) Method RNVG imaging is performed by in vivo labelling of red blood cells via administration of 600MBq of 99m Tc-pertechnetate 20 minutes following an initial injection of pyrophosphate. Imaging is carried out in the left anterior oblique (LAO40) position for best septal separation and a 3-lead monitoring ECG placed on the patient to allow triggering on the upslope of R wave. Data is acquired over multiple cardiac cycles until 5x10 6 counts are acquired, with the data binned into 24 frames per cardiac cycle. Results: RNVG Repeatability A subset of 20 patient studies carried out at the Western Infirmary General (WIG) had an additional LAO40 dataset acquired to allow assessment of RNVG repeatability. Each dataset was analysed by two experienced clinical technologists (J and S) using both a dual (2ROI) and single ROI (1ROI) technique. The 1ROI technique uses the end-diastolic ROI to determine ventricular counts at ED and ES. This method will yield systematically lower ejection fractions due to the overestimation of ESc. However this method will be more reproducible as it is not sensitive to the error introduced by drawing a second ROI over the smaller area ES ventricle which has a lower count density. The superior reproducibility of the 1ROI technique is highlighted in the Bland-Altman heatmap below. Interoperability (green boundary) is ~2% (1σ) for 1ROI compared with ~3.3% for 2ROI. Repeatability is ~5% for 1ROI and varies between 4.3 and 7.2% for 2ROI. Also of note, is the non-zero bias (mean difference between analyses) when comparing LVEF between acquisitions and operator for the 2ROI method. However, the small sample size makes these parameters susceptible to outliers and a larger sample size is desirable before making more definitive conclusions. A dual ROI analysis is most commonly used to determine LVEF. ROIs are drawn around the left ventricle at end diastole (ED) and end systole (ES). An inferolateral background ROI is also drawn to account for non-ventricular counts within the LV ROI. LVEF is determined from the background corrected counts within the LV at ED and ES Figure 1: Typical time activity curve highlighting the variation in left ventricular counts throughout the cardiac cycle Figure 2: Heatmaps showing mean bias +/- standard deviation from Bland Altman analysis of all permutations (2 LAO40 datasets [1:2], 2 operators: [J/S]) for dual and single ROI approaches. Eg the lower red box (0.4 +/- 4.9) compares LVEF measurements using a 1ROI technique with operator J analysing dataset 1 and dataset 2 for all 20 patients. VendorsMeanStandard Deviation MinimumMaximum Odyssey 61.8 18.42191 Link Medical 60.011.82786 Xeleris58.112.22376 Hermes57.114.71779 Syngo63.216.02491 Table 1: Summary statistics of LVEF from the 5 software vendors. Figure 3: Scatter plot highlighting the correlation between LVEF measured clinically using Odyssey and the other vendors Figure 3 plots the LVEF measured clinically (Odyssey) against that obtained using alternative software. A strong positive correlation ranging from r = 0.85 (Link) to r = 0.94 (Hermes and Syngo) was observed. Despite this correlation, there were some marked differences in LVEF between software applications given the same raw input. Figure 4: Bland-Altman plot of LVEF difference (Link – Odyssey) vs Mean LVEF Bland-Altman analyses provides a means to measure the level of agreement between methods. Figure 4 highlights the lack of interchangeability between Odyssey and Link Medical software despite the good correlation. There exists a small but significant bias of -1.8% between packages. Of more concern is the large standard deviation of the difference (10.4%) which translates to a 95% confidence interval from -22.6 – 19.4%. Furthermore, there seems to be a trend in the Bland-Altman plot with the difference becoming more pronounced at higher mean LVEF values. Similar correlation and levels of agreement were observed for possible software pairings (Figure 5). Widest 95% confidence intervals in the Bland-Altman plots were observed for the Odyssey-Link, Odyssey-Xeleris and Link-Syngo. Figure 5: Correlation and Bland-Altman heatmaps which depict the correlation and levels of agreement for all pairwise comparisons of software applications.