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Background: Normal stress-only (SO) myocardial perfusion imaging (MPI) using SPECT reduces imaging time and radiation dose with a good prognosis. However, the long-term prognostic value of combining coronary artery calcium score (CACS) with SO MPI to determine the warranty period remains unknown. Hence, we assessed the incremental prognostic value of CACS and its impact on the warranty period of normal SO MPI using SPECT., Methods: We retrospectively included 1375 symptomatic patients without a history of coronary artery disease (CAD) and a normal SO MPI using adenosine who underwent simultaneous CAC scoring. Annual major adverse cardiac events (MACE) rates were calculated for CACS categories: 0, 1-399, 400-999, and ≥1000., Results: The mean age was 60.0 ± 11.8 years (66.9% female) with a median follow-up of 10.3 [IQR 9.6-10.9] years. The warranty period for annual MACE rate for normal SO SPECT extended the total follow-up time in years. MACE rate categorized by CAC categories demonstrated an increase in MACE rates with increasing CACS; CACS 0 and CACS 1-399 were associated with a 10-year warranty period, CACS 400-999 had a warranty period of 4 years and no warranty period could be given for CACS≥1000 (5.9 % at 1 year)., Conclusions: CACS as an adjunct to normal pharmacological SO MPI provides additional prognostic information and aids in determining a warranty period., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

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 < 10% risk based on visual PET interpretation only. However, there is a strong dependence of MFR on patient's individual risk of oCAD. Hence, combining both visual interpretation and MFR results in a better individual risk assessment which may impact treatment strategy., (© 2023. The Author(s).)

Introduction: 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)., Method: 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)., Results: 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%)., Conclusion: 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., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Purpose: Semi-quantitative scores can be used as an adjunct to visual assessment in rubidium-82 positron emission tomography ( 82 Rb PET). The semi-quantitative cut-off values used in 82 Rb PET are derived from single-photon emission computed tomography (SPECT). It is unknown whether these cut-off values can be extrapolated to 82 Rb PET. We compared the semi-quantitative with the visual assessment of ischemia and determined which summed difference score (SDS) score predicts ischemia best., Methods: We included 108 patients who underwent 82 Rb PET imaging and performed visual and semi-quantitative assessment. A scan with a SDS ≥ 2 and a summed stress score (SSS) ≥ 4 was considered to demonstrate ischemia. We compared the semi-quantitative with the visual assessment., Results: 41 (38%) Normal scans, and 67 (62%) scans with ischemia and/or an irreversible defect were included. The semi-quantitative assessment showed ischemia more often than the visual assessment (51% vs 29%, P < .001). Patients with a low or intermediate pre-test probability of coronary artery disease (CAD) and a SDS < 4 did not demonstrate ischemia by visual assessment., Conclusion: Semi-quantitative assessment in 82 Rb PET imaging clearly demonstrates the presence of ischemia. Ischemia is unlikely in patients with low and intermediate pre-test probability of CAD and a SDS < 4., (© 2021. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Purpose: Visual assessment of Rubidium (Rb-82) PET myocardial perfusion images is usually combined with global myocardial flow reserve (MFR) measurements. However, small regional blood flow deficits may go unnoticed. Our aim was to compare the diagnostic value of regional with global MFR in the detection of obstructive coronary artery disease (oCAD)., Methods: We retrospectively included 1519 patients referred for rest and regadenoson-induced stress Rb-82 PET/CT without prior history of oCAD. MFR was determined globally, per vessel territory and per myocardial segment and compared using receiver-operating characteristic analysis. Vessel MFR was defined as the lowest MFR of the coronary territories and segmental MFR as the lowest MFR of the 17-segments. The primary endpoint was oCAD on invasive coronary angiography., Results: The 148 patients classified as having oCAD had a lower global MFR (median 1.9, interquartile range [1.5-2.4] vs. 2.4 [2.0-2.9]), lower vessel MFR (1.6 [1.2-2.1] vs. 2.2 [1.9-2.6]) and lower segmental MFR (1.3 [ 0.9-1.6] vs. 1.8 [1.5-2.2]) as compared to the non-oCAD patients (p < 0.001). The area under the curve for segmental MFR (0.81) was larger (p ≤ 0.005) than of global MFR (0.74) and vessel MFR (0.78)., Conclusions: The use of regional MFR instead of global MFR is recommended as it improves the diagnostic value of Rb-82 PET in the detection of oCAD., (© 2022. The Author(s).)

Background: Knowledge of coronary artery calcium score (CACS) influences the interpretation of myocardial perfusion imaging (MPI) with SPECT; however, the impact on PET interpretation remains unclear. We compared the added value of CACS to reporting MPI using SPECT vs PET., Methods: We retrospectively included 412 patients. 206 patients who underwent Rb-82 PET were propensity-based matched to a cohort of 4018 patients who underwent cadmium-zinc-telluride SPECT MPI to obtain a comparable group of 206 SPECT patients. Next, we created four image sets: SPECT MPI-only, PET-only, SPECT + CACS, and PET + CACS. Two physicians interpreted the 824 images as normal, equivocal, or abnormal for ischemia or irreversible defects. Additionally, event rates were compared between PET and SPECT groups during 30-month follow-up., Results: PET yielded more scans interpreted as normal than SPECT (88% vs 80%, respectively, P = 0.015). Adding CACS to SPECT increased the percentage of normal scans to 86% (P = 0.014), whereas this effect was absent for PET (90%, P = 0.77). Annualized event rates for images interpreted as normal did not differ and varied between 0.7 and 2.0% (P &gt; 0.084)., Conclusion: Adding CACS correctly increased the percentage of normal scans for SPECT MPI but not for PET, possibly limiting the effect of adding CACS to reporting PET., (© 2021. American Society of Nuclear Cardiology.)

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 < 90 seconds. MFR did not differ (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., (© 2021. The Author(s).)

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., (© 2020. The Author(s).)

Background: Clinical practice shows degrading image quality in heavier patients who undergo myocardial perfusion imaging (MPI) with Rubidium-82 (Rb-82) PET when using a fixed tracer activity. Our aim was to derive and validate a patient-specific activity protocol resulting in a constant image quality in PET MPI., Methods: We included 251 patients who underwent rest MPI with Rb-82 PET (Discovery 670, GE Healthcare). 132 patients were included retrospectively and were scanned using a fixed activity of 740 MBq. The total number of measured prompts was normalized to activity and correlated to body weight, mass per body length and body mass index to find the best predicting parameter. Next, a patient-specific activity was derived and subsequently validated in 119 additional patients. Image quality was scored by three experts on a four-point scale., Results: Both image quality and prompts decreased in heavier patients when using a fixed activity (p < .005). Body weight was used to derive a new activity formula: Activity = 8.3 MBq/kg. When applying this formula, both measured prompts and scored image quality became independent of body weight (p > .60)., Conclusion: Administrating a Rb-82 activity that linearly depends on body weight resulted in a constant image quality across all patients and is recommended., (© 2019. American Society of Nuclear Cardiology.)

Background: Regadenoson-induced stress causes a repositioning of the heart, myocardial creep, in half of the patients undergoing Rubidium-82 (Rb-82) positron emission tomography (PET). As a result, misalignment of dynamic PET and computer tomography (CT) may occur, possibly affecting CT-based attenuation correction (AC) and thereby PET-based myocardial blood flow (MBF) quantification. Our aim was to determine the need for frame-wise PET-CT AC to obtain reliable MBF measurements., Methods: 31 Out of 64 consecutive patients had myocardial creep during regadenoson-induced stress Rb-82 PET-CT and were included. Prior to PET image reconstruction, we applied two AC methods; single PET-CT alignment and frame-wise alignment in which PET time-frames with myocardial creep were individually co-registered with CT. The PET-CT misalignment was then quantified and MBFs for the three vascular territories and whole myocardium were calculated and compared between both methods., Results: The magnitude of misalignment due to myocardial creep was 13.8 ± 4.5 mm in caudal-cranial direction, 1.8 ± 2.1 mm in medial-lateral and 2.5 ± 1.8 mm in anterior-posterior direction. Frame-wise PET-CT registration did not result in different MBF measurements (P ≥ .07) and the magnitude of misalignment and MBF differences did not correlate (P ≥ .58)., Conclusion: There is no need for frame-wise AC in dynamic Rb-82 PET for MBF quantification. Single alignment seems sufficient in patients with myocardial creep.

Objective: The presence of extensive coronary artery calcifications (CAC) influences treatment decisions, particularly for revascularization. However, important CAC might be missed with invasive coronary angiography (ICA). Our aim was to determine the accuracy of ICA in the identification of CAC using computed tomography (CT) as reference standard., Patients and Methods: Overall, 349 consecutive patients who underwent both CT-based CAC-scoring and invasive coronary angiography within 60 days were retrospectively included. Two experienced operators classified CAC on ICA, without knowledge of CT-based CAC scoring, for each of the four main vessels as (0) absent, (1) mild, (2) moderate, or (3) dense calcifications. These scores were correlated with the CT-based Agatston CAC-scores, the noninvasive reference standard. The sensitivity, specificity, and accuracy of identified CAC using ICA were derived. Calcifications identified as moderate or dense on ICA or with a vessel-based Agatston score of more than 100 were considered important., Results: CT classified 671 (48%) of the 1396 vessels as having moderately or densely calcified vessels (Agatston score >100), whereas this was 137 (9.8%) using ICA (P<0.001). A significant correlation was found between the CT-based and ICA-based CAC-scores for all vessels (P<0.001). The sensitivity in detecting any CAC by means of ICA was 43% with a specificity of 92% and an accuracy of 55%. The sensitivity of important CAC identification by ICA was 19%, the specificity 99%, and the accuracy 61%., Conclusion: The accuracy of ICA for the identification of calcifications is very low as only 19% of the relevant calcifications was identified. Preprocedural assessment of CAC with CT could be considered to improve the treatment approach.

To derive and validate a practical patient-specific dose protocol to obtain an image quality, expressed by the image noise, independent of patients' size and a better radiation dose justification in coronary CT angiography (CCTA) using prospective ECG triggering. 43 patients underwent clinically indicated CCTA. The image noise, defined as the standard deviation of pixel attenuation values in a homogeneous region in the liver, was determined in all scans. Subsequently, this noise was normalized to the radiation exposure. Next, three patient-specific parameters, body weight, body mass index and mass per length (MPL), were tested for the best correlation with normalized image noise. From these data, a new dose protocol to provide a less variable image noise was derived and subsequently validated in 84 new patients. The normalized image noise increased for heavier patients for all patients' specific parameters (p < 0.001). MPL correlated best with the normalized image noise and was selected for dose protocol optimization. This new protocol resulted in image noise levels independent of patients' MPL (p = 0.28). A practical method to obtain CCTA images with noise levels independent of patients' MPL was derived and validated. It results in a less variable image quality and better radiation exposure justification and can also be used for CT scanners from other vendors.

Background: The decreasing image quality in heavier patients can be compensated by administration of a patient-specific dose in myocardial perfusion imaging (MPI) using a cadmium zinc telluride-based SPECT camera. Our aim was to determine if the same can be achieved when using a conventional SPECT camera., Methods: 148 patients underwent SPECT stress MPI using a fixed Tc-99m tetrofosmin tracer dose. Measured photon counts were normalized to administered tracer dose and scan time and were correlated with body weight, body mass index, and mass per length to find the best predicting parameter. From these data, a protocol to provide constant image quality was derived, and subsequently validated in 125 new patients., Results: Body weight was found to be the best predicting parameter for image quality and was used to derive a new dose formula; A admin (MBq) = 223·body weight (kg)(0.65)/T scan (min). The measured photon counts decreased in heavier patients when using a fixed dose (P < .01) but this was no longer observed after applying a body-weight-dependent protocol (P = .20)., Conclusions: Application of a patient-specific protocol resulted in an image quality less depending on patient's weight. The results are most likely independent of the type of SPECT camera used, and, hence, adoption of patient-specific dose and scan time protocols is recommended.