Patient-tailored risk assessment of obstructive coronary artery disease using Rubidium-82 PET-based myocardial flow quantification with visual interpretation.

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.

Machine learning based model to diagnose obstructive coronary artery disease using calcium scoring, PET imaging, and clinical data.

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.

Value of SiPM PET in myocardial perfusion imaging using Rubidium-82.

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.

Effect of temporal sampling protocols on myocardial blood flow measurements using Rubidium-82 PET.

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.

Impact of regadenoson-induced myocardial creep on dynamic Rubidium-82 PET myocardial blood flow quantification.

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.

How to detect and correct myocardial creep in myocardial perfusion imaging using Rubidium-82 PET?

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.

The relationships between nasal hyperreactivity, quality of life, and nasal symptoms in patients with perennial allergic rhinitis.

BACKGROUND: A clinical test that could inform the clinician about the severity of a patient's nasal symptoms and health-related quality of life (QOL) would be very useful. OBJECTIVE: We attempted to determine whether, in patients with perennial allergic rhinitis, nasal challenge with histamine could be used to estimate daily symptoms and QOL. METHODS: Forty-eight patients with perennial allergic rhinitis were challenged with histamine to determine nasal hyperreactivity. Nasal response was monitored by the number of sneezes, the amount of secretion, and a symptom score. Daily nasal symptoms were recorded during the 2 preceding weeks. Patients also completed a rhinitis QOL questionnaire. RESULTS: Responsiveness to histamine and total daily nasal symptoms were moderately correlated (r = 0.51, p = 0.001). Comparison of total daily nasal symptoms with the overall QOL score showed a moderate correlation (r = 0.59, p < 0.001). Nasal response to histamine and overall QOL score were also correlated (r = 0.43, p = 0.002). However, overall QOL and daily nasal symptoms could be predicted by wide 95% confidence intervals only for each decade of nasal responsiveness to histamine (expressed as a composite symptom score). CONCLUSION: In patients with perennial allergic rhinitis nasal hyperreactivity as determined by histamine challenge, QOL, and daily nasal symptoms are moderately correlated. Therefore nasal histamine challenge can be used as a tool for estimating the severity of daily nasal symptoms and QOL, although it cannot predict nasal symptoms and QOL very accurately.

Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls.

BACKGROUND: In perennial allergic rhinitis, patients are almost daily exposed to aeroallergens. This ongoing allergic reaction results in increased sensitivity to allergens and non-specific stimuli. It is generally known that inflammatory cells and mediators are involved in the pathogenesis of the allergic reaction. OBJECTIVES: To study the relationship between nasal hyperreactivity and nasal inflammation during natural allergen exposure. METHODS: In 48 patients with perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage and a histamine challenge were performed. Nasal inflammation was estimated by the number of eosinophils, levels of albumin, tryptase, prostaglandin D2 (PGD2), eosinophil cationic protein (ECP) and leukotriene C4/D4/E4 (LTC4/D4/E4). RESULTS: In contrast to PGD2 and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC4/ D4/E4 (17.51 vs 1.43 pg/mL, P < 0.0001) and albumin (8.61 vs 2.37 mg/mL, P = 0.0008) were significantly increased in rhinitis patients as compared with controls. Patients also showed increased responses to nasal histamine challenge assessed using a composite symptom score (21.5 vs 4 points, P < 0.0001). The nasal response to histamine was weakly correlated with the total number of eosinophils in the cytospin (correlation coefficient r = 0.38, P = 0.009). CONCLUSION: Nasal hyperreactivity is correlated with the percentage of eosinophils in patients with perennial rhinitis. The patients' mediator profiles suggest that eosinophils are important in the ongoing allergic reaction and nasal hyperreactivity.