Measurement Of Myocardial Blood Flow Research Articles

Compact MR-compatible ergometer and its application in cardiac MR under exercise stress: A preliminary study.

PurposeTo develop a compact MR‐compatible ergometer for exercise stress and to initially evaluate the reproducibility of myocardial native T1 and myocardial blood flow (MBF) measurements during exercise stress performed on this ergometer.MethodsThe compact ergometer consists of exercise, workload, and data processing components. The exercise stress can be achieved by pedaling on a pair of cylinders at a predefined frequency with adjustable resistances. Ten healthy subjects were recruited to perform cardiac MRI scans twice in a 3.0T MR scanner, at different days to assess reproducibility. Myocardial native T1 and MBF were acquired at rest and during a moderate exercise. The reproducibility of the two tests was determined by the intra‐group correlation coefficient (ICC) and coefficient of variation (CoV).ResultsThe mean exercise intensity in this pilot study was 45 Watts (W), with an exercise duration of 5 min. Stress induced a significant increase in systolic blood pressure (from 113 ± 11 mmHg to 141 ± 12, P < 0.05) and maximal increase in heart rate by 74 ± 19%. The rate pressure product increased two‐fold (P < 0.001). Excellent reproducibility was demonstrated in native T1 during the exercise (CoV = 3.0%), whereas the reproducibility of MBF and myocardial perfusion reserve during the exercise was also good (CoV = 10.7% and 8.8%, respectively).ConclusionThis pilot study demonstrated that it is possible to acquire reproducible measurements of myocardial native T1 and MBF during the exercise stress in healthy volunteers using our new compact ergometer.

Diagnostic efficiency and incremental value of myocardial blood flow quantification by CZT SPECT for patients with coronary artery disease

Objective: To investigate the diagnostic efficiency and incremental value of quantitative myocardial blood flow measurements by Cadmium-Zine-Telluride (CZT) single photon emission computed tomography (SPECT) dynamic myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) compared with traditional semi-quantitative measurements by MPI. Methods: This is a retrospective, cross-sectional study. We retrospectively analyzed clinical data of patients with suspected or known CAD, who underwent the dynamic MPI quantitative blood flow measurement of CZT SPECT in TEDA International Cardiovascular Hospital from October 2018 to December 2020. Clinical data, semi-quantitative parameters (stress score (SS), rest score (RS) and different score (DS)) and myocardial quantitative blood flow parameters (rest myocardial blood flow (rMBF), stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR)) were analyzed. According to the results of coronary angiography, patients were divided into the stenosis group and the control group with coronary artery stenosis ≥50% or ≥75% as the diagnosis criteria. The differences of quantitative and semi-quantitative parameters between the two groups were compared, and the diagnostic efficacy was compared by receiver operating characteristic(ROC) curve. Results: A total of 98 patients with a mean age of (62.1±8.7) years were included in the study, including 66 males (67%). At the patient level, with the positive standard of coronary artery stenosis≥50%, the left ventricle (LV) stress MBF (LV-sMBF) ((1.36±0.45) ml·min-1·g-1) and LV-MFR (1.45±0.43) of the stenosis group were lower than the LV-sMBF ((2.09±0.64) ml·min-1·g-1) and LV-MFR (2.17±0.54) of control group; summed SS and summed DS were higher than control group (all P<0.05). With the positive standard of coronary artery stenosis ≥75%, the LV-sMBF ((1.19±0.34) ml·min-1·g-1) and LV-MFR (1.34±0.35) of stenosis group were lower than the LV-sMBF ((1.94±0.63) ml·min-1·g-1) and MFR (2.00±0.58) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). At the vascular level, with coronary artery stenosis ≥50% as the diagnosis criteria, the sMBF ((1.26±0.49) ml·min-1·g-1) and MFR (1.35±0.46) of stenosis group were lower than the sMBF ((1.95±0.70) ml·min-1·g-1) and MFR (2.05±0.65) of control group; SS and DS were higher than control group (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the sMBF ((1.12±0.41) ml·min-1·g-1) and MFR (1.25±0.38) of stenosis group were lower than the sMBF ((1.84±0.70) ml·min-1·g-1) and MFR (1.93±0.66) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). With coronary artery stenosis≥50% as the diagnosis criteria and CAG as the reference standard, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.830 (0.783-0.877). The sensitivity (86.1% vs. 61.5%), specificity (82.6% vs. 73.8%), positive predictive value (77.8% vs. 62.5%), negative predictive value (89.3% vs. 73.0%) and accuracy (84.0% vs. 68.7%) were all higher than the semi-quantitative parameters (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.832(0.785-0.879). The sensitivity (89.2% vs. 67.6%), negative predictive value (95.5% vs. 86.2%) and accuracy (80.6% vs. 68.0%) were all higher than semi-quantitative parameters (all P<0.05). Conclusion: Compared with traditional SPECT MPI derived semi-quantitative parameters, diagnostic efficacy for CAD is higher using CZT SPECT quantitative myocardial blood flow parameters, this strategy thus has additional diagnostic benefits and incremental value on the diagnosis of CAD.

Effects of passive heat exposure on myocardial blood flow in healthy young and older adults

INTRODUCTIONExtreme heat is associated with a greater risk of cardiovascular mortality in older adults (≥60 years). However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. One possibility is that myocardial oxygen requirements during heat exposure cannot be met by sufficient increased in myocardial blood flow (MBF) thereby predisposing to ischemia. However, the extent to which MBF increases during heat exposure, and whether age alters this increase, is unknown. The objective of this study was to test the hypothesis that passive heat exposure increases MBF and that this increase is attenuated in healthy older adults.METHODSMBF was measured during passive heat exposure (water‐perfused suit) in 15 young (27 years, range: 24‐30) and 14 older (68 years, range: 64‐72) healthy adults with 82‐Rubidium positron emission tomography. Four MBF measurements were performed: prior to heat exposure (baseline) and at an increase in rectal temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate (ECG) and blood pressure (automated auscultation) were also measured to calculate rate pressure product (RPP; heart rate x systolic blood pressure). MBF reserve (MFR) was calculated by dividing the MBF at 1.5°C by baseline MBF.RESULTSBaseline MBF was 0.76 ± 0.19 mL/min/g in young adults and 0.88 ± 0.21 mL/min/g in older adults (p=0.14). MBF increased similarly in both groups during heat exposure (interaction, p=0.31). Nonetheless, older adults displayed a lower MFR at an increase in rectal temperature of 1.5°C (young: 2.3 ± 0.7 vs. older: 1.8 ± 0.4, p=0.03). The lower MFR in older adults was paralleled by an attenuated increase in RPP during passive heating (at + 1.5°C, young: 6.8 ± 1.7vs. older: 3.6 ± 2.2 bpm·mmHg·103, p&lt;0.01), due to a blunted increase in heart rate (young: 50 ± 12vs. older: 34 ± 14 bpm, p&lt;0.01). When the change in MBF was plotted against the change in RPP, the slope of the regression lines did not differ between young (0.11 [95% CI; 0.07, 0.15]) and older (0.08 [95% CI; 0.04, 0.11] mL/g/min/ bpm·mmHg·103,p=0.24) adults.CONCLUSIONThese results show that passive heat exposure roughly doubles MBF in healthy young and older adults. Furthermore, the results demonstrate that the increase in MBF during passive heat exposure is not altered by age and is proportional to the increase in RPP.

Dose Reduction of Dynamic Computed Tomography Myocardial Perfusion Imaging by Tube Voltage Change: Investigation in a Swine Model.

BackgroundIt is unclear whether tube voltage influences the measurement of perfusion parameters. The present study sought to evaluate the influence of tube voltage change on myocardial blood flow (MBF) measurements in dynamic computed tomography myocardial perfusion imaging (CTP).Methods and ResultsSeven swine [mean weight 55.8 kg ± 1.6 (standard deviation)] underwent rest and stress dynamic CTP with tube voltages of 100 and 70 kV. The image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), radiation dose and MBF value were compared. The 70 kV images had higher CT attenuation and higher image noise (27.9 ± 2.4 vs. 21.5 ± 1.9, P < 0.001) than the 100 kV images, resulting in a higher SNR (20.5 ± 1.6 vs. 15.6 ± 1.8, P < 0.001) and CNR (17.6 ± 1.5 vs. 12.4 ± 1.7, P < 0.001). Compared to the use of conventional 100 kV, 70 kV yielded an approximately 64.6% radiation dose reduction while generating comparable MBF values, both at rest (88.3 ± 14.9 ml/100 g/min vs. 85.6 ± 17.4 ml/100 g/min, P = 0.21) and stress (101.4 ± 21.5 ml/100 g/min vs. 99.6 ± 21.4 ml/100 g/min, P = 0.58) states.ConclusionDynamic CTP using 70 kV instead of 100 kV does not substantially influence the MBF value but significantly reduces the radiation dose. Additional research is required to investigate the clinical significance of this change.

Clinically viable myocardial CCTA segmentation for measuring vessel-specific myocardial blood flow from dynamic PET/CCTA hybrid fusion

BackgroundPositron emission tomography (PET)-derived LV MBF quantification is usually measured in standard anatomical vascular territories potentially averaging flow from normally perfused tissue with those from areas with abnormal flow supply. Previously we reported on an image-based tool to noninvasively measure absolute myocardial blood flow at locations just below individual epicardial vessel to help guide revascularization. The aim of this work is to determine the robustness of vessel-specific flow measurements (MBFvs) extracted from the fusion of dynamic PET (dPET) with coronary computed tomography angiography (CCTA) myocardial segmentations, using flow measured from the fusion with CCTA manual segmentation as the reference standard.MethodsForty-three patients’ 13NH3 dPET, CCTA image datasets were used to measure the agreement of the MBFvs profiles after the fusion of dPET data with three CCTA anatomical models: (1) a manual model, (2) a fully automated segmented model and (3) a corrected model, where major inaccuracies in the automated segmentation were briefly edited. Pairwise accuracy of the normality/abnormality agreement of flow values along differently extracted vessels was determined by comparing, on a point-by-point basis, each vessel’s flow to corresponding vessels’ normal limits using Dice coefficients (DC) as the metric.ResultsOf the 43 patients CCTA fully automated mask models, 27 patients’ borders required manual correction before dPET/CCTA image fusion, but this editing process was brief (2–3 min) allowing a 100% success rate of extracting MBFvs in clinically acceptable times. In total, 124 vessels were analyzed after dPET fusion with the manual and corrected CCTA mask models yielding 2225 stress and 2122 rest flow values. Forty-seven vessels were analyzed after fusion with the fully automatic masks producing 840 stress and 825 rest flow samples. All DC coefficients computed globally or by territory were ≥ 0.93. No statistical differences were found in the normal/abnormal flow classifications between manual and corrected or manual and fully automated CCTA masks.ConclusionFully automated and manually corrected myocardial CCTA segmentation provides anatomical masks in clinically acceptable times for vessel-specific myocardial blood flow measurements using dynamic PET/CCTA image fusion which are not significantly different in flow accuracy and within clinically acceptable processing times compared to fully manually segmented CCTA myocardial masks.

The Application of Conditional Probability to Harmonize Nuclear Cardiology Test Results.

Both exercise single photon emission computed tomography (SPECT) imaging and myocardial perfusion imaging with positron emission tomography produce multiple outcome variables. These include the stress electrocardiogram (ECG), visual perfusion assessment and quantitative myocardial blood flow. Bayes' analysis using conditional probability allows the distillation of multiple test results into a single probability of disease for individual patients. This paper examines the application of conditional probability analysis to two noninvasive modalities that generate multiple outcome results: exercise ECG combined with SPECT imaging and vasodilator RB-82 positron emission tomography perfusion imaging combined with quantitative measure of absolute myocardial blood flow. In this manner, a single probability of disease incorporating all the available data is generated for an individual patient.

Quantification of myocardial perfusion reserve by CZT-SPECT: A head to head comparison with 82Rubidium PET imaging

BackgroundWe measured myocardial blood flow (MBF) and perfusion reserve (MPR) by dynamic CZT-SPECT and 82Rb-PET in patients with suspected or known coronary artery disease (CAD) and compared the accuracy of the two methods in predicting obstructive CAD. MethodsTwenty-five patients with available coronary angiography data underwent 99mTc-sestamibi CZT-SPECT and 82Rb-PET cardiac imaging. Stress and rest MBF and MPR were calculated by both methods and compared. Diagnostic accuracies of CZT-SPECT and PET were also assessed using a receiver-operator-characteristic curve. ResultsCZT-SPECT yielded similar baseline MBF, but higher hyperemic MBF and MPR values compared to PET. There was a modest correlation between the two methods for MPR (r = 0.56, P < .01). MPR by CZT-SPECT showed a good ability in identify a reduced MPR by PET, with an area under the curve of 0.85. A MPR cut-off of 2.5 was identified by CZT-SPECT for detection of abnormal MPR by PET, with a sensitivity, specificity and accuracy of 86%, 73% and 80%. The area under the curve for the identification of obstructive CAD by regional MPR were 0.83 for CZT-SPECT and 0.84 for PET (P = .90). At CZT-SPECT, a regional MPR of 2.1 provided the best trade-off between sensitivity and specificity for identifying obstructive CAD. Diagnostic accuracy of CZT-SPECT and PET using respective cut-off values was comparable (P = .62). ConclusionHyperemic MBF and MPR values obtained by CZT-SPECT are higher than those measured by 82Rb-PET imaging, with a moderate correlation between the two methods. CZT-SPECT shows good diagnostic accuracy for the identification of obstructive CAD. These findings may encourage the use of this new technique to a better risk stratification and patient management.

Reduced acquisition times for measurement of myocardial blood flow with 99mTc-tetrofosmin and solid-state detector SPECT

BackgroundMeasurement of myocardial blood flow (MBF) is feasible using SPECT imaging but the acquisition requires more time than usual. Our study assessed the impact of reducing acquisition times on the accuracy and repeatability of the uptake rate constant (K1). MethodsTwenty-nine patients underwent two rest/stress studies with Tc-99m-tetrofosmin 18 ± 13 days apart, using a one-day rest/stress dynamic SPECT imaging protocol with a solid-state cardiac camera. A 5-minute static image was acquired prior to tracer injection for subtraction of residual activity, followed immediately by 11-minute of list-mode data collection. Static image acquisition times of 0.5, 1, and 3 minutes and dynamic imaging times of 5, 7, and 9 minutes were simulated by truncating list-mode data. Images were reconstructed with/without attenuation correction and with/without motion correction. Kinetic parameters were calculated using a 1-tissue-compartment model. ResultsK1 increased with reduced dynamic but not static imaging time (P < 0.001). The increase in K1 for a 9-minute scan was small (4.7 ± 5.3%) compared with full-length studies. The repeatability of K1 did not change significantly (13 ± 12%, P > 0.17). ConclusionsA shortened imaging protocol of 3-minute (rest) or 30-second (stress) static image acquisition and 9 minutes of dynamic image acquisition altered K1 by less than 5% compared to a previously validated 11-minute acquisition.

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.

Abstract 12183: Multi-Center Evaluation of Inter-Site Variability in SPECT Myocardial Blood Flow Measurement

Introduction: Myocardial blood flow (MBF) imaging with SPECT is possible using cardiac-specific cameras. Single-center studies have shown that SPECT MBF is accurate compared with PET MBF and angiography. Clinical implementation requires consistency of SPECT MBF measurements across multiple sites. This study is the first multi-center evaluation of the inter-site processing variability of SPECT MBF. Objective: To compare SPECT MBF obtained locally to MBF calculated at the core lab in Ottawa, Canada. Methods: Six sites (2 in Canada and one each from Japan, Singapore, Italy, and Germany) each acquired 25 rest/stress MBF studies using Tc99m-tetrofosmin (377 MBq at rest; 1060 MBq at stress) on a pinhole-collimated cadmium-zinc-telluride(CZT)-based cardiac SPECT camera. Patients had intermediate to high pre-test probability of coronary artery disease. MBF was analyzed locally and at a core lab using commercially available software. The time that a room was occupied for a MBF study was compared to that for a standard rest/stress myocardial perfusion study. Results: Preliminary results from 4 sites showed a correlation in MBF between the core lab and the local site of an average of 0.96 (range 0.95 to 0.97) at rest and 0.89 (range 0.77 to 0.96) at stress. From Bland-Altman analysis, the mean bias from zero in global MBF between local and core-lab analysis was 3.3% +/- 13.4% at rest and 3.0 % +/- 18.6% at stress. Between the 4 sites, the bias ranged from -4.1% to 9.9% at rest and from -6.3% to 12.8% at stress; the standard deviation (SD) ranged from 10.5% to 14.0% at rest and from 12.0% to 24.5% at stress. There was no significant difference between sites in the SD. The SD of the local-to-core-lab MBF differences is less than the SD of the test-retest difference of 30%, measured in a previous single-center study. The average additional time to perform a MBF study acquisition varied between sites from 45 to 76 min. This additional time includes the time needed to pharmacologically stress the patient which is normally done outside the camera room. Conclusions: This multi-center evaluation supports the feasibility of consistently measuring MBF using CZT-based cardiac SPECT cameras, as has been suggested from previous single-center studies.

Abstract 14144: Reproducibility of Myocardial Blood Flow Quantification With Low-Dose CT

Introduction: Dynamic CT perfusion can be used for physiological assessment of coronary artery disease. However, it is limited by its high radiation dose and limited reproducibility. Hypothesis: A single-volume myocardial CT perfusion technique can reproducibly measure myocardial blood flow in mL/min/g at a low radiation dose. Methods: The reproducibility of a single-volume myocardial CT perfusion technique was assessed in 4 swine (54.5 ± 1.9 kg) under rest and stress (IV adenosine: 240 μg/mg/kg/min) conditions. Thirteen pairs of repeated CT measurements were made, with a 20-minute delay between each acquisition. Contrast (0.7 mL/kg; 370 mgI/mL) and saline chaser (0.35 mL/kg) were injected peripherally, each at 5 mL/s, followed by bolus tracking and acquisition of a single volume scan at 100 kVp and 200 mA with a 320-slice CT scanner. The timing for acquisition of the single volume scan was determined based on the contrast injection time. The bolus tracking and single volume scan data were then used as analytical inputs into a novel first-pass analysis model to derive perfusion in mL/min/g. The coronary artery centerlines from the volume scan were used for automatic assignment of the left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA) perfusion territories. The reproducibility of myocardial blood flow measurement in each territory was then assessed via regression analysis. Results: The first (P PRO1 ) and second (P PRO2 ) prospective single-volume CT perfusion measurements were related by P PRO2 = 1.04 P PRO1 - 0.05 (Pearson’s r = 0.99; RMSE = 0.24 mL/min/g). The average CT dose index of the technique was only 140.3 mGy. Conclusions: The single-volume quantitative CT perfusion technique provides low-dose, reproducible, myocardial perfusion measurement in mL/min/g using only bolus tracking data and a single whole-heart volume scan. The technique can also provide simultaneous CT angiogram when acquired with appropriate radiation dose.

Reduction of motion effects in myocardial arterial spin labeling.

To evaluate the accuracy and reproducibility of myocardial blood flow measurements obtained under different breathing strategies and motion correction techniques with arterial spin labeling. A prospective cardiac arterial spin labeling study was performed in 12 volunteers at 3 Tesla. Perfusion images were acquired twice under breath-hold, synchronized-breathing, and free-breathing. Motion detection based on the temporal intensity variation of a myocardial voxel, as well as image registration based on pairwise and groupwise approaches, were applied and evaluated in synthetic and in vivo data. A region of interest was drawn over the mean perfusion-weighted image for quantification. Original breath-hold datasets, analyzed with individual regions of interest for each perfusion-weighted image, were considered as reference values. Perfusion measurements in the reference breath-hold datasets were in line with those reported in literature. In original datasets, prior to motion correction, myocardial blood flow quantification was significantly overestimated due to contamination of the myocardial perfusion with the high intensity signal of blood pool. These effects were minimized with motion detection or registration. Synthetic data showed that accuracy of the perfusion measurements was higher with the use of registration, in particular after the pairwise approach, which probed to be more robust to motion. Satisfactory results were obtained for the free-breathing strategy after pairwise registration, with higher accuracy and robustness (in synthetic datasets) and higher intrasession reproducibility together with lower myocardial blood flow variability across subjects (in in vivo datasets). Breath-hold and synchronized-breathing after motion correction provided similar results, but these breathing strategies can be difficult to perform by patients.

Clinical Validation of the Accuracy of Absolute Myocardial Blood Flow Quantification with Dual-Source CT Using 15O-Water PET.

To determine the fitting equation that can correct for the underestimation of myocardial blood flow (MBF) measurement by using dynamic CT perfusion (CTP) with dual-source CT (MBFCT), using MBF with oxygen 15-labeled water (15O-water) PET (MBFPET) as a reference, and to determine the accuracy of corrected MBFCT (MBFCT-corrected) compared with MBFPET in a separate set of participants. In this prospective study (reference no. 2466), 34 participants (mean age, 70 years ± 8 [standard deviation]; 27 men) known or suspected to have coronary artery disease underwent dynamic stress CTP and stress 15O-water PET between January 2014 and December 2018. The participants were randomly assigned to either a pilot group (n = 17), to determine the fitting equation on the basis of the generalized Renkin-Crone model that can explain the relation between MBFCT and MBFPET, or to a validation group (n = 17), to validate MBFCT-corrected compared with MBFPET. The agreement between MBFCT-corrected and MBFPET was evaluated by intraclass correlation and Bland-Altman analysis. In the pilot group, MBFCT was lower than MBFPET (1.24 mL/min/g ± 0.28 vs 2.51 mL/min/g ± 0.89, P < .001) at the segment level. The relationship between MBFCT and MBFCT-corrected was represented as MBFCT = MBFCT-corrected × {1-exp[-(0.11 × MBFCT-corrected + 1.54)/MBFCT-corrected]}. In the validation group, MBFCT-corrected was 2.66 mL/min/g ± 1.93, and MBFPET was 2.68 mL/min/g ± 1.87 at the vessel level. MBFCT-corrected showed an excellent agreement with MBFPET (intraclass correlation coefficient = 0.93 [95% CI: 0.87, 0.96]). The measurement bias of MBFCT-corrected and MBFPET was -0.02 mL/min/g ± 0.74. Underestimation of MBF by CT was successfully corrected with a correction method that was based on contrast kinetics in the myocardium.Keywords: CT, CT-Perfusion, PET, Cardiac, Heart Supplemental material is available for this article. © RSNA, 2021.

A new cardiac phantom for dynamic SPECT

BackgroundIn recent years, with the advance of myocardial blood flow (MBF) measurement capability in dynamic single photon emission computerized tomography (SPECT) systems, significant effort has been devoted to validation of the new capability. Unfortunately, the mechanical phantoms available for the validation process lack essential features—they either have a constant radiotracer concentration or they have rigid (static) walls unable to simulate cardiac beating. Methods and ResultsWe have developed a mechanical cardiac phantom that is able to mimic physiological radiotracer variation in the left ventricle (LV) cavity and in the myocardium (M), while performing beating-like motion. We have also developed a mathematical model of the phantom, allowing a description of the radiotracer concentrations in both regions (LV, M) as a function of time, which served as a tool for experiment planning and to accurately mimic physiological-like time-activity curves (TACs). A net retention model for the phantom was also developed, which served to compute the theoretical (i.e., expected) MBF of the phantom from measured quantities only, and thus validate the MBF reported by the SPECT system. In this paper, phantom experiments were performed on a GE Discovery NM 530c SPECT system. ConclusionsA novel dynamic cardiac phantom for emission tomography has been developed. The new phantom is capable of producing a wide range of TACs that can mimic physiological (and potentially in the future, pathological) curves, similar to those observed in dynamic SPECT systems. SPECT-reported MBF values were validated against known (measured) activity of the injected radiotracer from phantom experiments, which allowed to determine the accuracy of the GE Discovery 530c SPECT system.

Comparison between N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve

BackgroundPET/CT is the standard for quantitative assessments of myocardial blood flow (MBF), but it requires short-lived-tracers, costly, and not widely available. SPECT with Cadmium Zinc Telluride (CZT) detectors allows dynamic acquisition and quantitation of MBF. The study aims were to compare MBF measurements by 99mTc-tetrofosmin-CZT to N13NH3 PET/CT after regadenoson-induced coronary hyperemia and to evaluate the effect of attenuation correction (AC). Methods54 patients were evaluated at rest and during vasodilation by 99mTc-tetrofosmin-CZT and N13NH3 PET/CT within 2 weeks. MBF and MBF reserve (MFR) were measured by CZT with or without AC (NAC). ResultsThe global rest MBF was 0.76 ± 0.19 mL/min/gr by PET and 0.76 ± 0.24 by AC-CZT (P = NS) and 1.14 ± 0.4 by NAC-CZT (P < 0.001 vs PET and AC-CZT). Stress MBF was higher when measured by PET than AC-CZT (1.87 ± 0.45 vs 1.62 ± 0.68 mL/min/gr, P < 0.0008), but lower than NAC-CZT (2.36 ± 1.1, P < 0.0003). The MBF reserve ratio (MFR) was higher by PET than AC-CZT (2.52 ± 0.56 vs 2.22 ± 1 (P < 0.009) and NAC-CZT (2.18 ± 1.0, P < 0.004). Linear regression was better between PET (MFR and stress MBF) and AC-CZT than between PET and NAC-CZT. ROC curve analysis showed the significant ability of AC-CZT to predict MFR < 2 and stress MBF < 1.7 (AUC = 0.75 and 0.82 respectively) and to differentiate between normal and CAD patients (AUC = 0.747 and 0.892 for MFR and stress MBF, respectively). ConclusionsOur data show a reasonable correlation between MBF and MFR measured by N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT. NAC-CZT overestimates MBF. AC is recommended when using CZT for measuring MBF.

Added value of myocardial blood flow using 18F-flurpiridaz PET to diagnose coronary artery disease: The flurpiridaz 301 trial

Background18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography. MethodsWe retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis. ResultsStress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without CAD; 1.92 ± 0.49 in non-obstructed territories of CAD patients; and 1.54 ± 0.50 in diseased territories, P < 0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P < 0.05). In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis. ConclusionsClinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.

The feasibility of SPECT CZT measurement of myocardial blood flow and reserve in patients with acute coronary syndrome: comparison with cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is currently of interest in terms of diagnostic and treatment strategy. The diagnosis of MINOCA has been included in the STEMI guidelines of the European Society of Cardiology. However, there is lack of data regarding the relationship between myocardial damage according to cardiac magnetic resonance (CMR) and myocardial blood flow (MBF), myocardial flow reserve (MFR) obtained by dynamic SPECT. Purpose. To elucidate impairment of myocardial perfusion, MBF and MFR in patients with MINOCA. Methods. The study included 31 patients (21 men, age 62(56;70) years) with ASC. According to electrocardiography, cardiac biomarkers, invasive coronary angiography two groups were identified: with non-obstructive coronary arteries MINOCA (n = 10); MICAD (n = 21). Within 7-14 days after admission to the hospital all patients underwent dynamic SPECT on CZT gamma-camera with the assessment of standard indices of myocardial perfusion (SSS, SRS, SDS) and quantitative parameters (stress/rest myocardial blood flow (s/r MBF), myocardial flow reserve (MFR)). All patients underwent CMR with late gadolinium enhancement as well. Infarct size (IS), microvascular obstruction (MVO) and myocardial edema size (ME) were evaluated. Results. SSS and SRS differed significantly (p &amp;lt; 0.05) in MINOCA and MICAD patients: MINOCA: SSS 5.0(3.0;5.0), SRS 2.0(1.0;3.0); MICAD: SSS 9.0(5.0;13.0), SRS 6.0(3.0;11.0). However, SDS did not differ significantly in these two groups 2.5(1.0;4.0) vs 4.0(2.0;5.0). Moreover MINOCA patients in comparison with those with MIACD had higher values of quantitative parameters (p &amp;lt; 0.05): sMBF 2.02 (1.71;2.37) vs 0.86 (0.72;1.02) ml/min/g, rMBF 0.68 (0.66;0.86) vs 0.49 (0.4;0.57) ml/min/g, MFR 2.61 (2.23;3.14) vs 1.67 (1.1;1.9), respectively. Based on CMR, a total of 93 left ventricular vessel territories were analyzed. A total of 36(39%) vessel territories were considered as having acute myocardial injury (5 in MICAD, 31 in MINOCA). In patients with MICAD the values of IS, ME were significantly higher as compared to those with MINOCA (IS: 19.4(10.4;29.7)% vs1.8(0.0;6.9)%, ME: 19.5(12.0;30.0)% vs 3.0(0.0;12.0)% - p &amp;lt; 0.01). Based on regional analysis sMBF and MFR were significantly lower in vessel territories considering as CMR positive compared to those without MR signs of myocardial injury: regional sMBF 0.98(0.73;1.79) vs 1.33(0.94;2.08); regional MFR 0.58(0.43;0.9) vs 0.71(0.57;0.88), respectively. Conclusion. SPECT CZT is feasible in identifying both global and regional disturbances of myocardial blood flow and reserve in patients with acute coronary syndrome. MINOCA patients are characterized by mild reduction of myocardial blood flow and perfusion assessed visually and quantitatively. Therefore despite the absence of obstructive coronary artery lesion this group of patients has more pronounced risk of cardiac events and need more aggressive observation and treatment.

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 blood flow values based on 15O-water PET are insensitive to image reconstruction settings

Abstract Funding Acknowledgements Type of funding sources: None. Background For 15O-water PET, a cutoff hyperemic myocardial blood flow (MBF) value of 2.3 mL/g/min for significant ischemia has been established (1). For other tracers, different studies show a wide range of proposed cutoff values. The use of uniform absolute cutoff values for pathological hyperemic MBF or flow reserve in clinical decision making requires robust quantification of MBF, with comparable values across scanners, centres, and reconstruction methods. Purpose The aim of the present work was to assess the effect of different reconstruction methods on quantitative MBF values based on 15O-water PET. Methods 20 patients referred for assessment of ischemia underwent 4 min dynamic stress PET scans starting simultaneously with automated bolus injection of 400 MBq 15O-water on a digital PET/CT scanner. Images were reconstructed using 17 different reconstruction methods, with the clinical reconstruction used as reference: time-of-flight (TOF) ordered subsets expectation maximization (OSEM) with 3 iterations and 16 subsets, including point spread function recovery (PSF) and a 5 mm gaussian post-filter. Parameters that were varied were number of iterations (1-6), filter (3, 5 or 8 mm), exclusion of TOF and PSF, and using regularized reconstruction with 7 different values of the regularization parameter beta. Images were analyzed fully automatically using aQuant software, resulting in parametric MBF images and polar maps as well as regional MBF values. Correlation and agreement of MBF values based on each reconstruction were compared using regression and Bland-Altman analysis as well as Wilcoxon tests. Results Whole left ventricle MBF values ranged from 1.1 to 3.9 mL/g/min. Visually, there were only small differences in MBF images or polar maps between methods (Figure 1). Correlation between whole left ventricle MBF values based on the various reconstruction algorithms was high (r &amp;gt; 0.99). At the regional level, correlation coefficients were always &amp;gt; 0.94 (Figure 2). No significant bias was found between any of the reconstruction methods and the standard method (p &amp;gt; 0.65). Regression slopes relative to the standard method ranged from 0.993 to 1.080. Changes in reconstruction settings did not alter diagnosis in any patient. Conclusion Changes in reconstruction settings such as filter size, number of iterations, inclusion of time-of-flight or resolution recovery, and regularization, have negligible impact on MBF values based on 15O-water PET analyzed using the automated software. This is likely due to the fact that MBF is determined by the clearance rate of 15O-water rather than its uptake rate such as for other PET tracers, in addition to the used segmentation routines. These results also indicate that quantitative MBF measurements using 15O-water are likely to be robust across different types of PET scanners and hospitals, which is highly important for reliable clinical use of cut-off values for ischemia.

Effects of two patient-specific dosing protocols on measurement of myocardial blood flow with 3D 82Rb cardiac PET

Clinical measurement of myocardial blood flow (MBF) has emerged as an important component of routine PET-CT assessment of myocardial perfusion in patients with known or suspected coronary artery disease. Although multiple society guidelines recommend patient-specific dosing, there is a lack of studies evaluating the efficacy of patient-specific dosing for quantitative MBF accuracy. Two patient-specific dosing protocols (weight- and BMI-adjusted) were retrospectively evaluated in 435 consecutive clinical patients referred for PET myocardial perfusion assessment. MBF was estimated at rest and after regadenoson-induced hyperemia. The effect of dosing protocol on dose reduction, PET scanner saturation, relative perfusion, and image quality was compared. The effect of PET saturation on the accuracy of MBF and myocardial flow reserve (MFR) in remote myocardium was assessed with multivariable linear regression. BMI-adjusted dosing was associated with lower administered 82Rb activities (1036.0 ± 274 vs. 1147 ± 274MBq, p = 0.003) and lower PET scanner saturation incidence (28 vs. 38%, p = 0.006) and severity (median saturation severity index 0.219 ± 0.33 vs. 0.397 ± 0.59%, p = 0.018) compared to weight-adjusted dosing. PET saturation that occurred with either dosing protocol was moderate and resulted in modest remote MBF and MFR biases ranging from 2 to 9% after adjusting for patient age, sex, BMI, rate-pressure product, and LV ejection fraction. No adverse effects of BMI dose adjustment were observed in relative perfusion assessment or image quality. Patient-specific dosing according to BMI is an effective method for guideline-directed dose reduction while maintaining image quality and accuracy for routine MBF and MFR quantification.