Measurement Of Myocardial Flow Reserve Research Articles

Advances in Single-Photon Emission Computed Tomography

The clinical presentation of coronary artery disease (CAD) has changed during the last 20years with less ischemia on stress testing and more nonobstructive CAD on coronary angiography. Single-photon emission computed tomography (SPECT) myocardial perfusion imaging should include the measurement of myocardial flow reserve and assessment of coronary calcium for the diagnosis of nonobstructive CAD and coronary microvascular disease. SPECT/CT systems provide reliable attenuation correction for better specificity and low-dose CT for coronary calcium evaluation. SPECT MFR measurement is accurate, well validated, and repeatable.

Myocardial flow reserve estimation with contemporary CZT-SPECT and 99mTc-tracers lacks precision for routine clinical application

BackgroundPET myocardial flow reserve (MFR) has established diagnostic and prognostic value. Technological advances have now enabled SPECT MFR quantification. We investigated whether SPECT MFR precision is sufficient for clinical categorization of patients. MethodsValidation studies vs invasive flow measurements and PET MFR were reviewed to determine global SPECT MFR thresholds. Studies vs PET and a SPECT MFR repeatability study were used to establish imprecision in SPECT MFR measurements as the standard deviation of the difference between SPECT and PET MFR, or test-retest SPECT MFR. Simulations were used to evaluate the impact of SPECT MFR imprecision on confidence of clinically relevant categorization. ResultsBased on validation studies, the typical PET MFR categories were used for SPECT MFR classification (< 1.5, 1.5-2.0, > 2.0). Imprecision vs PET MFR ranged from 0.556 to 0.829, and test-retest imprecision was 0.781-0.878. Simulations showed correct classification of up to only 34% of patients when 1.5 ≤ true MFR ≤ 2.0. Categorization with high confidence (> 80%) was only achieved for extreme MFR values (< 1.0 or > 2.5), with correct classification in only 15% of patients in a typical lab with MFR of 1.8 ± 0.5. ConclusionsCurrent SPECT-derived estimates of MFR lack precision and require further optimization for clinical risk stratification.

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

BackgroundA 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. MethodsWe 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. ResultsMBF 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. ConclusionsVarious temporal sampling protocols result in different MBF values using Rb-82 PET. MFR measurements were more robust to different temporal sampling protocols.

Correlation of SPECT myocardial blood flow with coronary angiography results

Dedicated CZT cardiac cameras enable dynamic stress and rest SPECT acquisitions and provide accurate measurements of absolute myocardial flow reserve (MFR). MFR have been shown to improve diagnostic performances of coronary artery disease (CAD) in cardiac positron emission tomography. We evaluated the results of SPECT global MFR measurement with the results of invasive coronary angiography (ICA). Patients referred for dynamic SPECT between September 2018 and March 2020 with ICA performed within 3 months were included. Dynamic SPECT were acquired on CZT-based pinhole cardiac cameras in listmode using a stress/rest one-day Tc-99m-tetrofosmin protocol. Kinetic analysis was done with Corridor4DMTMsoftware using a 1-tissue-compartment model and converted to MBF using a previously determined extraction fraction correction. ICA was visually assessed by the experienced interventional cardiologist responsible for the procedure and considered normal if no significant coronary artery plaque (> 10–20%) according to the angiographer conclusion. Sixty-five patients (37 male, 28 female) were included. Thirty-seven patients had already-known CAD. Mean age was 67.8 ± 10.6%; mean BMI was 29.8 ± 5.6%. Mean global MFR was 2.27 ± 1.03. Thirty-one patients had impaired MFR (using a threshold of 2); among them, 3 patients had normal ICA, but had history of diabetes with potential microvascular dysfunction. 34 patients had preserved MFR: 17 with normal ICA, 17 with history of revascularization and/or optimal medical therapy. Considering patients with 1-vessel disease successfully revascularized before SPECT as “normal”, area under curve (ROC) was 0.92 for global MFR. Using the same threshold of 2, sensitivity and specificity were respectively 100% and 85.71%. Global MFR measured during dynamic SPECT is significantly correlated to ICA results. This parameter significantly enhances SPECT diagnostic performances and could help physician decision to perform ICA.

Impact of attenuation correction for CZT-SPECT measurement of myocardial blood flow

ObjectivesMost of cardiac dedicated CZT-SPECT systems are not equipped with CT, whereas PET systems are. We evaluated the impact of AC correction on CZT-SPECT myocardial blood flow (MBF) and myocardial flow reserve (MFR) measurements. Methods104 patients were included. SPECT data were acquired on cadmium zinc telluride (CZT)-based pinhole cardiac camera in listmode using a stress (250 ± 17 MBq)/rest (511 ± 23 MBq) 1-day Tc-99m-tetrofosmin protocol. Low-dose CT was acquired on another SPECT/CT camera in the same position. All analysis was performed using Corridor4DM. ResultsStress and rest MBF were significantly lower when AC was applied (P < 0.001). For regional and global MFR, there was no significant difference between AC and NAC measurements (P > 0.25 at least). Mean global LV MFR was 2.43 ± 0.87 and 2.33 ± 0.89, respectively, for NAC and AC measurements. Using a threshold of 2, 86 patients (83%) remained classified as normal and abnormal regarding global LV MFR whether AC was applied or not. Mean difference between NAC and AC values for the 18 other patients was 0.3. ConclusionAC correction does not significantly affect MFR measurement both in regional and global LV analyses.

Entropy-based myocardial blood flow measurements using PET: a way to improve reproducibility

Abstract 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 &amp;gt; 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 &amp;lt; 0.01). 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.

Value of regional myocardial flow measurements using Rubidium-82 PET

Abstract 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 &amp;lt; 0.001) in the 128 patients classified with obstructive CAD than in the 906 patients without obstructive CAD: global MFR (median 1.9 [interquartile range 1.6-2.4] vs. 2.5 [2.1-2.9]); vessel MFR (1.6 [1.3-2.1] vs. 2.3 [1.9-2.6]); Segmental MFR (1.3 [0.9-1.7] vs. 1.9 [1.6-2.2]). The area under the curve of vessel MFR (0.79 ± 0.02) and segmental MFR (0.81 ± 0.02) were similar but significantly (p &amp;lt; 0.001) larger than the area of global MFR (0.75 ± 0.03), as shown in the Figure. 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.

Myocardial Flow Reserve Measurement During CZT-SPECT Perfusion Imaging for Coronary Artery Disease Screening: Correlation With Clinical Findings and Invasive Coronary Angiography-The CFR-OR Study.

Purpose: The aim of this study was to assess the results of cadmium zinc telluride (CZT)- single-photon emission computed tomography (SPECT) myocardial flow reserve (MFR) in coronary artery disease (CAD) screening regarding clinical risk and its correlation to invasive coronary angiography (ICA).Methods: A total of 137 patients (61 male and 76 female) referred for CAD screening myocardial perfusion imaging (MPI) between November 2018 and April 2020 were included in the CFR-OR prospective trial. The 10-year risk of cardiovascular death according to the European Society of Cardiology (SCORE) was calculated. SPECT 1-day 99mTc-tetrofosmin protocol was acquired on CZT cardiac-dedicated pinhole cameras. Low-dose thoracic CT was used for coronary calcium score (CCS) evaluation. ICA, when performed within 3 months, was also analyzed.Results: Mean SCORE and mean global MFR were, respectively, 4 ± 3.1% and 2.50 ± 0.74; 34 patients had impaired CFR (using a threshold of 2). There was a significant inverse correlation between MFR and SCORE (p = 0.006), gender (p = 0.019), and number of cardiovascular risk factors (p = 0.01). MFR was significantly reduced in patients with CCS above 1 (p = 0.01). No significant correlation was found between MFR and individual cardiovascular risk factors (dyslipidemia, hypertension, diabetes, or family history of CAD). A total of 23 patients underwent ICA. Global MFR SPECT sensitivity and specificity were 83.3 and 100 %, respectively, with an area under the curve of 0.94.Conclusion: Adding MFR to SPECT MPI for CAD screening on CZT camera may contribute to high-risk patient identification and enhance diagnostic performances. MFR could help physician decision to perform ICA.

Myocardial flow reserve measurement in cardiac SPECT: A strong predictor of lesions at invasive coronary angiography

Myocardial flow reserve (MFR) measurement is predictive of major adverse cardiovascular (CV) events (MACE) and has been shown to improve diagnostic performances of coronary artery disease (CAD) in cardiac positron emission tomography. MFR can now be assessed during dynamic myocardial perfusion imaging (MPI) in SPECT, but its correlation with the patient's risk of coronary artery disease (CAD) remains to be investigated. We evaluated the results of SPECT MFR measurement in patients referred for CAD screening. In total, 137 patients (61 male, 76 female) referred for CAD screening MPI between November 2018 and March 2020 were included in a prospective trial (CFR-OR). 10 years risk of cardiovascular death according to the European Society of Cardiology (SCORE) was calculated. SPECT data were acquired on a CZT-cardiac camera using a stress/rest one-day Tc-99m-tetrofosmin protocol. Low dose thoracic CT was used for coronary calcium score (CCS) evaluation. Invasive Coronary Angiography (ICA) was performed upon decision of the referring cardiologist. Mean SCORE was 4 ± 3.1%. Mean global MFR was 2.50 ± 0.74. There was a significant inverse correlation between MFR and SCORE ( P = 0.006), gender ( P = 0.019), and the number of cardiovascular risk factors ( P = 0.01). MFR was significantly reduced in patients with CCS above 1 ( P = 0.01). Twenty-three patients underwent ICA. Eighteen showed coronary plaques qualifying for high-risk patients; among them, 16 patients had impaired MFR (the 2 other patients had moderate stenosis, < 50%, with negative FFR), whereas only 4 had abnormal visual MPI. Based on global MFR, and with a threshold of 2, sensitivity and specificity were respectively 83.3% and 100%, and Area Under Curve (AUC) was 0.94. Global MFR measured during MPI SPECT for CAD screening may contribute to high-risk patient identification. It significantly enhances SPECT diagnostic performances and could help physician decision to perform ICA.

Dependency of cardiac rubidium-82 imaging quantitative measures on age, gender, vascular territory, and software in a cardiovascular normal population

ObjectivesRecent technological improvements to PET imaging equipment combined with the availability of software optimized to calculate regional myocardial blood flow (MBF) and myocardial flow reserve (MFR) create a paradigm shifting opportunity to provide new clinically relevant quantitative information to cardiologists. However, clinical interpretation of the MBF and MFR is entirely dependent upon knowledge of MBF and MFR values in normal populations and subpopulations. This work reports Rb-82-based MBF and MFR measurements for a series of 49 verified cardiovascularly normal subjects as a preliminary baseline for future clinical studies. MethodsForty-nine subjects (24F/25M, ages 41-69) with low probability for coronary artery disease and with normal exercise stress test were included. These subjects underwent rest/dipyridamole stress Rb-82 myocardial perfusion imaging using standard clinical techniques (40 mCi injection, 6-minute acquisition) using a Siemens Biograph 40 PET/CT scanner with high count rate detector option. List mode data was rehistogrammed into 26 dynamic frames (12 × 5 seconds, 6 × 10 seconds, 4 × 20 seconds, 4 × 40 seconds). Cardiac images were processed, and MBF and MFR calculated using Siemens syngo MBF, PMOD, and FlowQuant software using a single compartment Rb-82 model. ResultsGlobal myocardial blood flow under pharmacological stress for the 24 females as measured by PMOD, syngo MBF, and FlowQuant were 3.10 ± 0.72, 2.80 ± 0.66, and 2.60 ± 0.63 mL·minute−1·g−1, and for the 25 males was 2.60 ± 0.84, 2.33 ± 0.75, 2.15 ± 0.62 mL·minute−1·g−1, respectively. Rest flows for PMOD, syngo MBF, and FlowQuant averaged 1.32 ± 0.42, 1.20 ± 0.33, and 1.06 ± 0.38 mL·minute−1·g−1 for the female subjects, and 1.12 ± 0.29, 0.90 ± 0.26, and 0.85 ± 0.24 mL·minute−1·g−1 for the males. Myocardial flow reserves for PMOD, syngo MBF, and FlowQuant for the female normals were calculated to be 2.50 ± 0.80, 2.53 ± 0.67, 2.71 ± 0.90, and 2.50 ± 1.19, 2.85 ± 1.19, 2.94 ± 1.31 mL·minute−1·g−1 for males. ConclusionQuantitative normal MBF and MFR values averaged for age and sex have been compiled for three commercial pharmacokinetic software packages. The current collection of data consisting of 49 subjects resulted in several statistically significant conclusions that support the need for a software specific, age, and sex-matched database to aid in interpretation of quantitative clinical myocardial perfusion studies.

Feasibility and operator variability of myocardial blood flow and reserve measurements with 99mTc-sestamibi quantitative dynamic SPECT/CT imaging

PurposeMyocardial blood flow (MBF) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging. This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with 99mTc-sestamibi (MIBI) dynamic SPECT imaging using a standard dual-head SPECT camera. MethodsTwenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition. Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest (ROI) were defined semi-automatically. A compartmental model was fitted to these ROI-sampled time-activity-curves, and flow-dependent MIBI extraction correction was applied to derive regional MBF values. Myocardial flow reserve (MFR) was estimated as stress/rest MBF ratio. MBF and MFR in low and high risk populations were evaluated for ability to detect disease. Images were each processed twice (≥7 days apart) by one expert and one novice operator to evaluate intra- and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories. ResultsMean rest flow, stress flow, and MFR values were 0.83, 1.82 mL·minute−1·g−1, and 2.45, respectively. For stress/rest MFR, the inter-operator reproducibility was r2 = 0.86 with RPC = 1.1. Stress MBF and MFR were significantly reduced (P < .05) in high risk (n = 9) vs low risk populations (n = 19), indicating ability to detect disease. For expert and novice operators very good intra-operator correlations of r2 = 0.98 and 0.95 (n = 168, P < .001) were observed for combined rest and stress regional flow values. Bland-Altman reproducibility coefficients (RPC) were 0.25 and 0.47 mL·minute−1·g−1 for the expert and novice operators, respectively (P < .001). Inter-operator correlation was r2 = 0.91 and Bland-Altman RPC = 0.58 mL·minute−1·g−1 (n = 336). ConclusionsMBF and reserve measurements using 99mTc-sestamibi on a traditional, two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible, warranting further investigation.

Evaluation of vascular function by modern non-invasive methods

Vascular functional alterations frequently precede morphological changes and, therefore, their recognition may theoretically improve early detection of vascular injury. The aim of this review is to demonstrate recently available non-invasive clinical methods including vascular stiffness examinations, flow-mediated vasodilatation, coronary flow reserve and myocardial flow reserve measurements.

Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 pet and a highly automated analysis program

BackgroundChanges in myocardial blood flow between rest and stress states are commonly used to diagnose coronary artery disease. Relative myocardial perfusion imaging (MPI) is used routinely while myocardial blood flow quantification (MBF) may improve the sensitivity for detection of early disease. The ratio of flow at stress and rest (S/R) and their difference (S-R) have both been proposed as a means to detect regions with reduced myocardial flow reserve (MFR). In this study, we describe a highly automated method to calculate regional and global rest, stress, S/R, and S-R polar maps of the left ventricle myocardium. MethodsWe measured the inter- and intra-operator variability using two randomized datasets (n = 30 each) for each of two operators (novice and expert) with correlation and Bland-Altman reproducibility coefficient (RPC%) analyses. ResultsS-R MBF had less inter-operator dependent variability than S/R (RPC% = 5.0% vs 12.6%, P < .001). While there was no difference in intra-operator variability with S-R MBF (novice vs expert RPC% = 6.4% vs 5.9%, P = ns), variability was higher in the novice-operator for S/R (RPC% = 16.8% vs 8.5% respectively, P < .001), suggesting that S-R may be preferred for detecting small changes in MFR. The novice operator’s intervention pattern became more similar to that of the expert in the later dataset, emphasizing the need for adequate training and quality assurance. ConclusionThe proposed method results in low operator-dependent variability, suitable for routine use.

Dynamic estimation of the myocardial oxygen extraction ratio during dipyridamole stress by MRI: a preliminary study in canines.

The myocardial oxygen extraction fraction (OEF) reflects the balance between myocardial oxygen supply and demand. The feasibility of quantifying myocardial OEF was demonstrated with MRI during pharmacologic vasodilation in dogs. Dipyridamole was infused intravenously to increase blood flow and change in myocardial oxygen content. Arterial and coronary sinus blood sampling was performed during dipyridamole-induced vasodilation to measure the myocardial blood oxygen content. Myocardial T(2) was measured dynamically during the vasodilation, and quantified with a simplified diffusion model as a function of myocardial OEF and blood volume. The results showed a strong correlation (R(2) = 0.89) between myocardial OEF values measured by MRI and those measured by blood sampling. Regional differences in the OEF were demonstrated by direct infusion of dipyridamole into coronary arteries in dogs. Combined with vasodilator stress, dynamic assessments of the OEF may provide a putative measurement of myocardial flow reserve and allow consecutive monitoring of myocardial dose and response.