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Introduction Our aim was to estimate the probability of obstructive CAD (oCAD) for an individual patient as a function of the myocardial flow reserve (MFR) measured with Rubidium-82 (Rb-82) PET in patients with a visually normal or abnormal scan. Materials and Methods We included 1519 consecutive patients without a prior history of CAD referred for rest-stress Rb-82 PET/CT. All images were visually assessed by two experts and classified as normal or abnormal. We estimated the probability of oCAD for visually normal scans and scans with small (5%–10%) or larger defects (> 10%) as function of MFR. The primary endpoint was oCAD on invasive coronary angiography, when available. Results 1259 scans were classified as normal, 136 with a small defect and 136 with a larger defect. For the normal scans, the probability of oCAD increased exponentially from 1% to 10% when segmental MFR decreased from 2.1 to 1.3. For scans with small defects, the probability increased from 13% to 40% and for larger defects from 45% to > 70% when segmental MFR decreased from 2.1 to 0.7. Conclusion Patients with > 10% risk of oCAD can be distinguished from patients with

Background A variety of temporal sampling protocols is used worldwide to measure myocardial blood flow (MBF). Both the length and number of time frames in these protocols may alter MBF and myocardial flow reserve (MFR) measurements. We aimed to assess the effect of different clinically used temporal sampling protocols on MBF and MFR quantification in Rubidium-82 (Rb-82) PET imaging. Methods We retrospectively included 20 patients referred for myocardial perfusion imaging using Rb-82 PET. A literature search was performed to identify appropriate sampling protocols. PET data were reconstructed using 14 selected temporal sampling protocols with time frames of 5-10 seconds in the first-pass phase and 30-120 seconds in the tissue phase. Rest and stress MBF and MFR were calculated for all protocols and compared to the reference protocol with 26 time frames. Results MBF measurements differed (P ≤ 0.003) in six (43%) protocols in comparison to the reference protocol, with mean absolute relative differences up to 16% (range 5%-31%). Statistically significant differences were most frequently found for protocols with tissue phase time frames P ≥ 0.11) for any of the protocols. Conclusions Various temporal sampling protocols result in different MBF values using Rb-82 PET. MFR measurements were more robust to different temporal sampling protocols.

Accurate risk stratification in patients with suspected stable coronary artery disease is essential for choosing an appropriate treatment strategy. Our aim was to develop and validate a machine learning (ML) based model to diagnose obstructive CAD (oCAD).We retrospectively have included 1007 patients without a prior history of CAD who underwent CT-based calcium scoring (CACS) and a Rubidium-82 PET scan. The entire dataset was split 4:1 into a training and test dataset. An ML model was developed on the training set using fivefold stratified cross-validation. The test dataset was used to compare the performance of expert readers to the model. The primary endpoint was oCAD on invasive coronary angiography (ICA).ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.94) for the training dataset and 0.89 (95% CI 0.84-0.93) for the test dataset. The ML model showed no significant differences as compared to the expert readers (p ≥ 0.03) in accuracy (89% vs. 88%), sensitivity (68% vs. 69%), and specificity (92% vs. 90%).The ML model resulted in a similar diagnostic performance as compared to expert readers, and may be deployed as a risk stratification tool for obstructive CAD. This study showed that utilization of ML is promising in the diagnosis of obstructive CAD.

Funding Acknowledgements Type of funding sources: None. Background and purpose Myocardial blood flow (MBF) measurements using PET are increasingly used to guide the management of patients with (suspected) coronary artery disease (CAD). Day-to-day variability of these measurements is poor with a 21% standard deviation or 40% 95%-confidence interval [Reference: JACC Cardiovasc Imaging, 2017;10(5):565]. This limits clinical applicability in diagnosis, risk stratification and follow-up as these all depend on comparison of flow values with fixed cut-off values. We expect that reproducibility can be improved by combining flow measurements with the variation of flow values within the myocardium. As entropy is a measure of variability of the associated distribution, we compared the reproducibility of an entropy-based flow parameter with that of conventional myocardial flow reserve (MFR) measurements. Methods We performed a study using intra-individual comparison in 24 patients who underwent rest and regadenoson-induced stress myocardial perfusion imaging using Rubidium-82 on two different PET systems (PET1: Discovery 690, GE Healthcare, and PET2: Vereos, Philips Healthcare) within 3 weeks. MBF for both rest and stress was calculated using Lortie’s one-tissue compartment model (Corridor4DM, INVIA). MFR (ratio of MBF stress/rest) was determined for the myocardial as a whole (MFRglobal), for the three vascular territories: LAD, LCX and RCA (MFRregional) and for the 17 segments. Next, we calculated Shannon’s entropy to measure the variation of the 17 MFR segmental values. We multiplied Shannon’s entropy by the mean of the MFR segmental values resulting in an entropy-based MFR (MFRentropy). For each patient MFRglobal, MFRregional and MRFentropy were compared between both PET systems. For each of the three parameters the test-retest precision was calculated as the SD of the relative difference between measurements. Results The mean difference in MFR measurements between both cameras did not differ from zero (p > 0.05). Mean values for PET1 were MFRglobal = 2.4, MFRregional = 2.4 (LAD), 2.4 (LCX) and 2.5 (RCA), and MFRentropy = 2.4. For PET2 we found MFRglobal = 2.5, MFRregional = 2.5 (LAD), 2.4 (LCX) and 2.6 (RCA), and MFRentropy = 2.5. Test-retest precision was lower for MFRentropy with 11% compared to that of MFRglobal (21%), MFRregional LAD (22%), MFRregional LCX (23%) and MFRregional RCA (24%) (p Conclusion The reproducibility of myocardial flow reserve measurements using Rubidium-82 PET improved by a factor of 2 when an entropy-based flow parameter instead of global or regional MFR parameters is used. This entropy-based flow-parameter may be used to better discriminate ischemia from non-ischemia and may therefore improve CAD management.

Funding Acknowledgements Type of funding sources: None. Introduction The combination of myocardial blood flow (MBF) measurements using Rubidium-82 (Rb-82) PET and visual assessment of the PET images is increasingly used due to its high diagnostic and prognostic value. Typically, flow measurements are calculated and used for the myocardium as a whole (global). However, small regional flow deficits may go unnoticed when only looking at global flow values. Purpose To compare the diagnostic value of regional and global myocardial flow measurements using Rb-82 PET in the detection of obstructive CAD. Methods We retrospectively included 1034 patients with no history of coronary artery disease (CAD) referred for rest and regadenoson-induced stress Rb-82 PET/CT. MBFs were calculated using Lortie’s one-tissue compartment model. Myocardial flow reserve (MFR) was calculated as the ratio of MBF during stress and rest. Regional flow was determined per vessel and per segment. Vessel MFR was defined as the lowest flow reserve of LAD, LCX and RCA territories and segmental MFR as the lowest flow reserve in all 17 segments. Follow-up data were obtained from medical records. Patients were classified to have obstructive CAD if follow-up included a positive invasive coronary angiography (ICA), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or all cause death. Receiver-operating characteristic (ROC) analyses were constructed to compare the diagnostic value of global and regional flow values. Results Follow-up was obtained in all 1034 patients and the median follow-up time was 2.1 years. Myocardial flow reserve values were significantly lower (p Conclusion The diagnostic value improved with the use of regional MFR instead of global MFR measurements in the detection of obstructive CAD. Therefore, it seems that visual assessment of PET images can best be combined with regional flow measurements either on a per vessel or a per segment basis in Rubidium-82 PET myocardial perfusion imaging.

Background PET scanners using silicon photomultipliers with digital readout (SiPM PET) have an improved temporal and spatial resolution compared to PET scanners using conventional photomultiplier tubes (PMT PET). However, the effect on image quality and visibility of perfusion defects in myocardial perfusion imaging (MPI) is unknown. Our aim was to determine the value of a SiPM PET scanner in MPI. Methods We prospectively included 30 patients who underwent rest and regadenoson-induced stress Rubidium-82 (Rb-82) MPI on the D690 PMT PET (GE Healthcare) and within three weeks on the Vereos SiPM PET (Philips Healthcare). Two expert readers scored the image quality and assessed the existence of possible defects. In addition, interpreter’s confidence, myocardial blood flow (MBF), and myocardial flow reserve (MFR) values were compared. Results Image quality improved (P = 0.03) using the Vereos as compared to the D690. Image quality of the Vereos and the D690 was graded fair in 20% and 10%, good in 60% and 50%, and excellent in 20% and 40%, respectively. Defect interpretation and interpreter’s confidence did not differ between the D690 and the Vereos (P > 0.50). There were no significant differences in rest MBF (P ≥ 0.29), stress MBF (P ≥ 0.11), and MFR (P ≥ 0.51). Conclusion SiPM PET provides an improved image quality in comparison with PMT PET. Defect interpretation, interpreter’s confidence, and absolute blood flow measurements were comparable between both systems. SiPM PET is therefore a reliable technique for MPI using Rb-82. Trial registration ToetsingOnline NL63853.075.17. Registered 13 November, 2017.

Reliability of myocardial blood flow (MBF) quantification in myocardial perfusion imaging (MPI) using PET can majorly be affected by the occurrence of myocardial creep when using pharmacologically induced stress. In this paper, we provide instructions on how to detect and correct for myocardial creep. For example, in each time frame of the PET images the myocardium contour and the observed activity have to be compared to check for misalignments. In addition, we provide an overview of the functionality of commonly used software packages to perform this quality control step as not all software packages currently provide this functionality. Furthermore, important clinical considerations to obtain accurate MBF measurements are given.

Background: Repositioning of the heart during myocardial perfusion imaging (MPI) using Rubidium-82 (Rb-82) PET may occur when using regadenoson. Our aim was to determine the prevalence and the effect of correcting for this myocardial creep on myocardial blood flow (MBF) quantification. Methods: We retrospectively included 119 consecutive patients who underwent dynamic rest- and regadenoson-induced stress MPI using Rb-82 PET. The presence of myocardial creep was visually assessed in the dynamic stress PET series by identifying differences between the automatically drawn myocardium contour and the activity. Uncorrected and corrected stress MBFs were compared for the three vascular territories (LAD, LCX, and RCA) and for the whole myocardium. Results: Myocardial creep was observed in 52% of the patients during stress. Mean MBF values decreased after correction in the RCA from 4.0 to 2.7 mL/min/g (P < 0.001), in the whole myocardium from 2.7 to 2.6 mL/min/g (P = 0.01), and increased in the LAD from 2.5 to 2.6 mL/min/g (P = 0.03) and remained comparable in the LCX (P = 0.3). Conclusions: Myocardial creep is a frequent phenomenon when performing regadenoson-induced stress Rb-82 PET and has a significant impact on MBF values, especially in the RCA territory. As this may hamper diagnostic accuracy, myocardial creep correction seems necessary for reliable quantification.