Relative Myocardial Blood Flow Research Articles

Quantitative perfusion by cardiac magnetic resonance analysis reveals compromised myocardial perfusion in patients with angina with non-obstructive coronary artery disease

Abstract Introduction Stress perfusion cardiac magnetic resonance (CMR) visually detects myocardial ischemia through first-pass contrast-enhanced imaging by identifying perfusion defects. However, in generalized myocardial diseases like angina with non-obstructed coronary arteries (ANOCA), visual assessment becomes challenging due to diffuse sub-endocardial perfusion defects, or the findings may even falsely appear normal. Fully automated quantitative perfusion (QP), allowing absolute quantification of myocardial blood flow (MBF) and deriving myocardial perfusion reserve (MPR), might increase diagnostic accuracy in ANOCA patients. Therefore, the purpose of this study is to test the use of QP in detecting ANOCA diagnosed by the invasive golden standard. Methods This study is a cross-sectional cohort study assessing the use of fully automated QP CMR in patients with ANOCA compared with age- and sex-matched healthy controls. All participants underwent adenosine stress perfusion CMR, including visual assessment and quantification of MBF and MPR. Furthermore, all ANOCA patients underwent intracoronary function testing (ICFT) to idenity vasospasm and/or coronary microvascular dysfunction. Results This study included 24 ANOCA patients (83% women, 56.8±8.9 years) and 25 healthy controls (80% women, 56.2±7.2 years). Visual perfusion assessment showed no group differences in terms of perfusion defects (p=0.536). However, in QP, ANOCA patients had higher relative MBF than healthy controls (0.83±0.15 vs 0.74±0.17, p=0.046), while global perfusion was significantly lower during stress (2.43±0.72 vs 2.99±0.65 ml/g/min, p=0.006). Moreover, ANOCA patients had significantly lower MPR than healthy controls (2.24 ±0.79 vs 2.68 ±0.64, respectively p=0.036), with a higher prevalence of an impared MPR (50% vs. 20%, p=0.027). MPR was not significantly different between the various ANOCA entities as stratified during ICFT (p=0.766). Conclusions ANOCA patients displayed significantly reduced MPR, indicating impaired perfusion. The prevalence of diminished MPR was higher in the ANOCA group compared to the healthy controls, constrasting with no differences in visual assessment. These results are promising and underscores the possibilities of the use of QP in detecting vasomotor dysfunction non-invasively in ANOCA patients.Quantitative Perfusion by CMR results

Relationship between microvascular status and diagnostic performance of stress dynamic CT perfusion imaging.

This study aimed to investigate the relationship between microvascular status in the non-ischemic myocardium and the diagnostic performance of stress dynamic CT perfusion imaging (CTP) in detecting hemodynamically significant stenosis. This study included 157 patients who underwent coronary computed tomography angiography (CTA), CTP, and invasive coronary angiography (ICA), including fractional flow reserve (FFR). Hemodynamically significant stenosis was defined by FFR and ICA. A relative myocardial blood flow (MBF) for each myocardial segment was normalized to the highest MBF (remote MBF) among 16 segments. The receiver operating characteristic curve analysis for detecting hemodynamically significant stenosis at the vessel level indicated that patients with lower, intermediate, and higher remote MBF had areas under the curve (AUC) of 0.66, 0.70, and 0.80, respectively, for absolute MBF and AUCs of 0.63, 0.70, and 0.83, respectively, for relative MBF. The optimal cut-off values for absolute MBF were proportional to the levels of remote MBFs, while the ones for relative MBF were more consistent across lower to higher remote MBFs. For the patients with high remote MBF, the relative MBF demonstrated a sensitivity of 69%, specificity of 88%, and accuracy of 85% in detecting hemodynamically significant stenosis. The microvascular status in the non-ischemic myocardium influenced the diagnostic performance of dynamic CTP and threshold values of absolute MBFs, suggesting the potential preference for relative MBF over absolute MBF in clinical settings. Dynamic CTP's quantification of MBF offers the benefit of indicating reliability in ischemia detection relative to microvascular status. Question The relationship between microvascular status and diagnostic performance of dynamic CTP imaging has not been fully investigated. Findings The diagnostic performance of dynamic CTP and threshold values of absolute MBF were impacted by microvascular status. Clinical relevance The differences in diagnostic accuracy of dynamic CTP related to varying remote MBF values necessitate a personalized evaluation of myocardial perfusion in dynamic CTP images.

Diagnosing myocardial ischemia of obstructive coronary artery disease using dynamic computed tomography myocardial perfusion imaging: optimization of relative myocardial blood flow ratio.

To compare the diagnostic efficacy of different relative myocardial blood flow (MBF) ratios in computed tomography perfusion (CTP) for myocardial ischemia in patients with obstructive coronary artery disease (CAD). Between October 2020 and March 2024, patients with suspected or known obstructive CAD who underwent CTP + coronary computed tomography angiography and invasive coronary angiography/fractional flow reserve were retrospectively selected. Patients and vessels were categorized into ischemia and non-ischemia groups. The diagnostic efficacies of the three relative MBF ratios were compared in patients with obstructive CAD. This study included 48 patients (144 vessels). Notably, 34 of the 48 patients (70.83%) and 49 of the 144 vessels (34.03%) were considered to have myocardial ischemia. The area under the curve of Ratio-hi (0.944, 95% confidence interval: 0.893-0.976) was higher than those of Ratio-av, Ratio-Q3, and MBF-lowest; However, no statistical differences were found (P>0.005). The cutoff value for detecting Ratio-hi was 0.667, and the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 91.8%, 83.2%, 75%, 95.24%, and 86.81%, respectively. Relative MBF ratios, especially Ratio-hi, demonstrated excellent performance and exhibited greater robustness in diagnosing myocardial ischemia in patients with obstructive CAD.

Diagnostic efficacy of absolute and relative myocardial blood flow of stress dynamic CT myocardial perfusion for detecting myocardial ischemia in patients with hemodynamically significant coronary artery disease.

Stress dynamic computed tomography myocardial perfusion imaging (CT-MPI) is an accurate quantitative method for diagnosing myocardial ischemia in coronary artery disease (CAD). However, its clinical application has been limited, partly due to the varied cutoff values for absolute myocardial blood flow (MBFa) and the uncertain value of the relative myocardial blood flow ratio (MBF-ratio). This study aimed to compare the diagnostic efficacy of and investigate the optimal cutoff values for MBFa and the MBF-ratio in CT-MPI for diagnosing myocardial ischemia in patients with hemodynamically significant CAD. Patients with suspected or known hemodynamically significant CAD who underwent CT-MPI + CT angiography and invasive coronary angiography (ICA)/fractional flow reserve (FFR) between October 2020 and December 2023 were retrospectively evaluated. ICA ≥80% or FFR ≤0.8 were set as the diagnostic standards for functional ischemia. The patients and vessels were categorized into ischemic and non-ischemic groups, and differences in MBFa and the MBF-ratio were compared between the groups. The area under the curve (AUC) and optimal cutoff values were calculated. Diagnostic efficacy parameters, such as sensitivity, specificity, and accuracy, were also compared. In addition, a consistency test was performed. A total of 46 patients (mean age: 65.37 ± 8.25 years; 120 vessels) were evaluated. Hemodynamically significant stenosis was detected in 30/46 patients (48%) and 81/120 vessels (67.5%). The MBFa and MBF-ratio values were significantly lower in the ischemic than in the non-ischemic group; in the per-vessel analysis, the MBFa values were 73 vs. 128 (P < 0.001) and the MBF-ratio values were 0.781 vs. 0.856 (P < 0.001), respectively. The optimal cutoff values for MBFa and the MBF-ratio were 117.71 and 0.67, respectively. MBFa demonstrated a sensitivity, specificity, accuracy, AUC, positive predictive value, negative predictive value, and kappa value of 97.44%, 74.07%, 81.66%, 0.936 [95% confidence interval (CI): 0.876-0.973, P < 0.001], 63.33%, 98.36%, and 0.631 (95% CI: 0.500-0.762), respectively. The corresponding values for the MBF-ratio were 92.31%, 85.19%, 87.5%, 0.962 (95% CI: 0.911-0.989, P < 0.001), 75%, 95.83%, and 0.731 (95% CI: 0.606-0.857, P < 0.001), with no significant difference (P = 0.1225). Both MBFa and the MBF-ratio exhibit excellent diagnostic performance for myocardial ischemia in patients with hemodynamically significant CAD. The MBF-ratio is more robust than MBFa for interpreting CT-MPI findings in clinical practice, which is useful for radiologists and clinicians implementing CT-MPI.

The incremental value of CCTA-derived myocardial radiomics signature for ischemia diagnosis with reference to CT myocardial perfusion imaging.

To explore the incremental value of myocardial radiomics signature derived from static coronary computed tomography angiography (CCTA) for identifying myocardial ischemia based on stress dynamic CT myocardial perfusion imaging (CT-MPI). Patients who underwent CT-MPI and CCTA were retrospectively enrolled from two independent institutions, one used as training and the other as testing. Based on CT-MPI, coronary artery supplying area with relative myocardial blood flow (rMBF) value <0.8 was considered ischemia. Conventional imaging features of target plaques which caused the most severe narrowing of the vessel included area stenosis, lesion length (LL), total plaque burden, calcification burden, non-calcification burden, high-risk plaque (HRP) score, and CT fractional flow reserve (CT-FFR). Myocardial radiomics features were extracted at three vascular supply areas from CCTA images. The optimized radiomics signature was added to the conventional CCTA features to build the combined model (radiomics + conventional). There were 168 vessels from 56 patients enrolled in the training set, and the testing set consisted of 135 vessels from 45 patients. From either cohort, HRP score, LL, stenosis ≥50% and CT-FFR ≤0.80 were associated with ischemia. The optimal myocardial radiomics signature consisted of nine features. The detection of ischemia using the combined model was significantly improved compared with conventional model in both training and testing set (AUC 0.789 vs 0.608, p < 0.001; 0.726 vs 0.637, p = 0.045). Myocardial radiomics signature extracted from static CCTA combining with conventional features could provide incremental value to diagnose specific ischemia. Myocardial radiomics signature extracted from CCTA may capture myocardial characteristics and provide incremental value to detect specific ischemia when combined with conventional features.

The Impact of Left Ventricle Ejection Fraction Reduction and Transient Ischemic Dilation in Patients With Normal Single-Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging.

Coronary artery disease (CAD) is a leading cause of death in developed countries. Non-invasive functional imaging modalities are currently recommended as initial diagnostic tests in patients with an intermediate-high pretest probability of CAD. Single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) creates images of regional myocardial tracer uptake, reflecting relative myocardial blood flow. However, there are other non-perfusion predictors of CAD, such as transient ischemic dilatation (TID) and reduced post-stress left ventricle ejection fraction (LVEF). Available data regarding these parameters is controversial. The aim of our study was to evaluate the incidence of significant CAD in patients with non-perfusion high-risk markers of ischemia despite a normal SPECT-MPI. Single-center, observational, retrospective, and longitudinal study. Inclusion criteria were age ≥18 years, normal SPECT-MPI, and availability of gated study for LVEF and volume analysis. Exclusion criteria were any known cardiomyopathy or congenital heart disease and known CAD. Non-perfusion high-risk markers: LVEF reduction ≥5% on post-stress images; TID (defined as a stress/rest left ventricle volume ratio ≥ 1.15), including end-systolic, end-diastolic, and mean volumes. The primary endpoint was the identification of significant CAD (stenosis >70% on an epicardial coronary artery or >50% on the left main artery) on invasive coronary angiography. A total of 197 patients met the inclusion criteria. Mean age was 64 ± 12.6 years and 59.4% (n = 117) of patients were male.Overall, 26% of patients had LVEF reduction ≥5% on stress study; 24.9% had a stress/rest end-systolic volume ratio ≥ 1.15; 7.1% had a stress/rest mean volume ratio ≥ 1.15; 7.1% had a stress/rest end-diastolic volume ratio ≥ 1.15. Time-to-primary endpoint was significantly lower in patients with LVEF reduction ≥5% on stress study (67.99 (95% CI 60.49-75.49) vs. 77.56 months (95% CI 75.14-79.99); p = 0.003) and in patients with stress/rest end-systolic volume ratio ≥ 1.15 (68.39 (95% CI 60.69-76.10) vs. 77.31 months (95% ICCI 74.68-79.76); p = 0.013). In patients with normal perfusion on SPECT-MPI, the incidence of significant CAD was significantly higher in those with LVEF reduction ≥ 5% on stress study and in those with a stress/rest end-systolic volume ratio ≥ 1.15, during a follow-up period of five years.

Effect of iterations and time of flight on normal distributions of 82Rb PET relative perfusion and myocardial blood flow

BackgroundAs clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification. MethodsFifty-nine rest/stress dynamic 82Rb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations. ResultsTOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions. ConclusionOptimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution.

Association between coronary plaque volume and myocardial ischemia detected by dynamic perfusion CT imaging

IntroductionWe aimed to evaluate the relationship between quantitative plaque metrics derived from coronary CT angiography (CTA) and segmental myocardial ischemia using dynamic perfusion CT (DPCT).MethodsIn a prospective single-center study, patients with > 30% stenosis on rest CTA underwent regadenoson stress DPCT. 480 myocardium segments of 30 patients were analyzed. Quantitative plaque assessment included total plaque volume (PV), area stenosis, and remodeling index (RI). High-risk plaque (HRP) was defined as low-attenuation plaque burden > 4% or RI > 1.1. Absolute myocardial blood flow (MBF) and relative MBF (MBFi: MBF/75th percentile of all MBF values) were quantified. Linear and logistic mixed models correcting for intra-patient clustering and clinical factors were used to evaluate the association between total PV, area stenosis, HRP and MBF or myocardial ischemia (MBF < 101 ml/100 g/min).ResultsMedian MBF and MBFi were 111 ml/100 g/min and 0.94, respectively. The number of ischemic segments were 164/480 (34.2%). Total PV of all feeding vessels of a given myocardial territory differed significantly between ischemic and non-ischemic myocardial segments (p = 0.001). Area stenosis and HRP features were not linked to MBF or MBFi (all p > 0.05). Increase in PV led to reduced MBF and MBFi after adjusting for risk factors including hypertension, diabetes, and statin use (per 10 mm3; β = −0.035, p < 0.01 for MBF; β = −0.0002, p < 0.01 for MBFi). Similarly, using multivariate logistic regression total PV was associated with ischemia (OR = 1.01, p = 0.033; per 10 mm3) after adjustments for clinical risk factors, area stenosis and HRP.ConclusionTotal PV was independently associated with myocardial ischemia based on MBF, while area stenosis and HRP were not.

Free-breathing motion-informed locally low-rank quantitative 3D myocardial perfusion imaging.

PurposeTo propose respiratory motion‐informed locally low‐rank reconstruction (MI‐LLR) for robust free‐breathing single‐bolus quantitative 3D myocardial perfusion CMR imaging. Simulation and in‐vivo results are compared to locally low‐rank (LLR) and compressed sensing reconstructions (CS) for reference.MethodsData were acquired using a 3D Cartesian pseudo‐spiral in‐out k‐t undersampling scheme (R = 10) and reconstructed using MI‐LLR, which encompasses two stages. In the first stage, approximate displacement fields are derived from an initial LLR reconstruction to feed a motion‐compensated reference system to a second reconstruction stage, which reduces the rank of the inverse problem. For comparison, data were also reconstructed with LLR and frame‐by‐frame CS using wavelets as sparsifying transform (ℓ1‐wavelet).Reconstruction accuracy relative to ground truth was assessed using synthetic data for realistic ranges of breathing motion, heart rates, and SNRs. In‐vivo experiments were conducted in healthy subjects at rest and during adenosine stress. Myocardial blood flow (MBF) maps were derived using a Fermi model.ResultsImproved uniformity of MBF maps with reduced local variations was achieved with MI‐LLR. For rest and stress, intra‐volunteer variation of absolute and relative MBF was lower in MI‐LLR (±0.17 mL/g/min [26%] and ±1.07 mL/g/min [33%]) versus LLR (±0.19 mL/g/min [28%] and ±1.22 mL/g/min [36%]) and versus ℓ1‐wavelet (±1.17 mL/g/min [113%] and ±6.87 mL/g/min [115%]). At rest, intra‐subject MBF variation was reduced significantly with MI‐LLR.ConclusionThe combination of pseudo‐spiral Cartesian undersampling and dual‐stage MI‐LLR reconstruction improves free‐breathing quantitative 3D myocardial perfusion CMR imaging under rest and stress condition.

Imaging Coronary Allograft Vasculopathy with Cardiac PET and Cardiac MRI.

Coronary allograft vasculopathy (CAV) is a leading cause of morbidity and mortality in heart transplant patients. It presents a diagnostic challenge as early CAV is often clinically silent, and it affects both epicardial coronary arteries and microvasculature. This review outlines the role of cardiac positron emission tomography (PET) and cardiac magnetic resonance imaging (CMR) in the diagnosis and prognosis of CAV. Relative myocardial perfusion imaging (MPI) and quantitative myocardial blood flow using cardiac PET are useful in the diagnosis and prognosis of CAV. Late gadolinium enhancement (LGE) and quantitative measures including myocardial perfusion reserve and mean diastolic rate using CMR are useful in the diagnosis and prognosis of CAV. Cardiac PET is now established as a non-invasive imaging modality for screening and monitoring for CAV, and CMR has demonstrated promise in this application. Further investigation of these modalities is needed with larger, multicenter studies that follow patients serially to demonstrate the clinical implications of using these modalities to detect early CAV and alter therapies to improve patient outcomes.

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease

ObjectivesIn this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR). BackgroundCT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies. MethodsAt 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics. ResultsICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively. ConclusionsDynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795)

Extensive and balanced reduction of myocardial blood flow in patients with suspected obstructive coronary artery disease: 15O-water PET study

BackgroundDetection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD. Methods and resultsAmong 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%). ConclusionsAmong symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis.

Stress myocardial perfusion with qualitative magnetic resonance and quantitative dynamic computed tomography: comparison of diagnostic performance and incremental value over coronary computed tomography angiography.

Assessment of haemodynamically significant coronary artery disease (CAD) using cardiovascular magnetic resonance (CMR) imaging perfusion or dynamic stress myocardial perfusion imaging by computed tomography (CT perfusion) may aid patient selection for invasive coronary angiography (ICA). We evaluated the diagnostic performance and incremental value of qualitative CMR perfusion and quantitative CT perfusion complementary to cardiac computed tomography angiography (CCTA) for the diagnosis of haemodynamically significant CAD using fractional flow reserve (FFR) and quantitative coronary angiography (QCA) as reference standard. CCTA, qualitative visual CMR perfusion, visual CT perfusion, and quantitative relative myocardial blood flow (CT-MBF) were performed in patients with stable angina pectoris. FFR was measured in coronary vessels with stenosis visually estimated between 30% and 90% diameter reduction on ICA. Haemodynamically significant CAD was defined as FFR <0.80, or QCA ≥80% in those cases where FFR could not be performed. A total of 218 vessels from 93 patients were assessed. An optimal cut-off of 0.72 for relative CT-MBF was determined. The diagnostic performances (area under the receiver-operating characteristics curves, 95% CI) of visual CMR perfusion (0.84, 0.77-0.90) and relative CT-MBF (0.86, 0.81-0.92) were comparable and outperformed visual CT perfusion (0.64, 0.57-0.71). In combination with CCTA ≥50%, CCTA + visual CMR perfusion (0.91, 0.86-0.96), CCTA + relative CT-MBF (0.92, 0.88-0.96), and CCTA + visual CT perfusion (0.82, 0.75-0.90) improved discrimination compared with CCTA alone (all P < 0.05). Visual CMR perfusion and relative CT-MBF outperformed visual CT perfusion and provided incremental discrimination compared with CCTA alone for the diagnosis of haemodynamically significant CAD.

Stress dynamic myocardial CT perfusion for symptomatic patients with intermediate- or high-risk of coronary artery disease: Optimization and incremental improvement between the absolute and relative myocardial blood flow analysis

BackgroundThe optimization of myocardial CT perfusion (CTP) assessment remains inconsistent and uncertain. Our aim was to explore the superior analysis selection and incremental improvement of myocardial blood flow (MBF) assessment on CTP in diagnosing hemodynamically significant coronary artery disease (CAD). MethodsSixty patients (43 men and 17 women; 61.38 ± 8.01 years) were prospectively recruited and underwent stress dynamic myocardial CTP examinations. Absolute and relative MBF was used for ischemia evaluation with the invasive coronary angiography and fractional flow reserve were used as the reference standard. Areas under the receiver operating characteristic curves (AUCs) and cutoff values were calculated and compared. ResultsThere were 151 vessels in 60 patients finally enrolled for analysis. The sensitivity, specificity, PPV, NPV and diagnostic accuracy for the absolute MBF value and relative MBF ratio were 82.76%, 98.92%, 97.96%, 90.20%, and 92.72% and 74.14%, 93.56%, 87.76%, 85.29%, and 86.09%, respectively. The absolute MBF value was superior than the relative MBF ratio in detecting ischemia (AUC, 0.955 [95%CI: 0.919–0.990] vs.0.906 [95%CI:0.857–0.954])(P = 0.02). For territories with both sensitivity and specificity ≤90%, the diagnostic accuracy increased from 79.1% to 88.4% when the specific data were assessed using the absolute MBF value instead of the relative MBF ratio. ConclusionsThe absolute MBF value from the endocardial myocardium on stress dynamic myocardial CTP showed superior diagnostic performance compared to the relative MBF ratio for the detection of myocardial ischemia in intermediate-to-high risk patients. The absolute MBF value provides an incremental benefit toward diagnostic performance for the relative MBF ratio evaluation.

Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic 201Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.

The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with 99mTc-RP805 and dynamic 201Tl for determination of myocardial blood flow, to quantify the effects of intracoronary delivery of recombinant TIMP-3 (rTIMP-3) on I/R injury. Studies were performed in control pigs (n=5) and pigs following 90-minute balloon occlusion-induced ischemia/reperfusion (I/R) of left anterior descending artery (n=9). Before reperfusion, pigs with I/R were randomly assigned to intracoronary infusion of rTIMP-3 (1.0 mg/kg; n=5) or saline (n=4). Three days post-I/R, dual isotope imaging was performed with 99mTc-RP805 and 201Tl along with contrast cineCT to assess left ventricular function. The ischemic to nonischemic ratio of 99mTc-RP805 was significantly increased following I/R in saline group (4.03±1.40), and this ratio was significantly reduced with rTIMP-3 treatment (2.22±0.57; P=0.03). This reduction in MMP activity in the MI-rTIMP-3 treatment group was associated with an improvement in relative MI region myocardial blood flow compared with the MI-saline group and improved myocardial strain in the MI region. We have established a novel hybrid single-photon emission computed tomography/computed tomography imaging approach for the quantitative assessment of regional MMP activation, myocardial blood flow, and cardiac function post-I/R that can be used to evaluate therapeutic interventions such as intracoronary delivery of rTIMP-3 for reduction of I/R injury in the early phases of post-MI remodeling.

Myocardial blood flow analysis of stress dynamic myocardial CT perfusion for hemodynamically significant coronary artery disease diagnosis: The clinical value of relative parameter optimization

BackgroundThe methods for calculating the optimal myocardial blood flow (MBF) relative parameters in stress dynamic myocardial CT perfusion (CTP) in the detection of hemodynamically significant coronary artery disease (CAD) are non-uniform and lack standards. MethodsA total of 86 patients who were prospectively recruited underwent APT stress dynamic myocardial CTP. The relative MBF perfusion parameters were calculated as av_Ratio, Q3av_Ratio and hi_Ratio according to the three types of reference MBF values, respectively: (1) average segmental MBF value, (2) the third quartile of the average segmental MBF value, and (3) highest segmental MBF value. All the data were derived from both the endocardial and transmural layers of the myocardium. Invasive coronary angiography and fractional flow reserve (ICA/FFR) were used as the reference standards for myocardial ischemia evaluation. ResultsA total of 151 vessels of 60 patients (43 men and 17 women; 61.38 ± 8.01 years) were enrolled in the analysis. The performance of the endocardial layer was superior to that of the transmural layer (all P < 0.05). The hi_Ratio of the endocardial myocardium (AUC = 0.906, 95% CI: 0.857–0.954), for which the highest segmental value was selected as the reference MBF, was superior to both av_Ratio and Q3av_Ratio for ischemia detection (AUC, 0.906 vs.0.879, P < 0.05; 0.906 vs.0.891, P = 0.18), and the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 74.1%, 93.6%, 87.8%, 85.3% and 86.1%, respectively. The cutoff value of hi_Ratio was 0.675. ConclusionsThe relative MBF parameter of the endocardial myocardium using the highest segmental MBF value as a reference provided optimal diagnostic accuracy for the detection of hemodynamically significant CAD.

Variable temporal sampling and tube current modulation for myocardial blood flow estimation from dose-reduced dynamic computed tomography.

Quantification of myocardial blood flow (MBF) can aid in the diagnosis and treatment of coronary artery disease. However, there are no widely accepted clinical methods for estimating MBF. Dynamic cardiac perfusion computed tomography (CT) holds the promise of providing a quick and easy method to measure MBF quantitatively. However, the need for repeated scans can potentially result in a high patient radiation dose, limiting the clinical acceptance of this approach. In our previous work, we explored techniques to reduce the patient dose by either uniformly reducing the tube current or by uniformly reducing the number of temporal frames in the dynamic CT sequence. These dose reduction techniques result in noisy time-attenuation curves (TACs), which can give rise to significant errors in MBF estimation. We seek to investigate whether nonuniformly varying the tube current and/or sampling intervals can yield more accurate MBF estimates for a given dose. Specifically, we try to minimize the dose and obtain the most accurate MBF estimate by addressing the following questions: when in the TAC should the CT data be collected and at what tube current(s)? We hypothesize that increasing the sampling rate and/or tube current during the time frames when the myocardial CT number is most sensitive to the flow rate, while reducing them elsewhere, can achieve better estimation accuracy for the same dose. We perform simulations of contrast agent kinetics and CT acquisitions to evaluate the relative MBF estimation performance of several clinically viable variable acquisition methods. We find that variable temporal and tube current sequences can be performed that impart an effective dose of 5.5mSv and allow for reductions in MBF estimation root-mean-square error on the order of 20% compared to uniform acquisition sequences with comparable or higher radiation doses.

Absolute Versus Relative Myocardial Blood Flow by Dynamic CT Myocardial Perfusion Imaging in Patients With Anatomic Coronary Artery Disease.

The purpose of this study was to evaluate differences in the diagnostic accuracy of absolute and relative territorial myocardial blood flow (MBF) derived from stress dynamic CT myocardial perfusion imaging (MPI) for the detection of significant coronary artery stenosis. Dynamic CT MPI and coronary CT angiography (CTA) datasets from a multicenter registry of 137 patients (mean age, 60.9 ± 8.4 years; 88 men) with suspected or known coronary artery disease were retrospectively analyzed. For each coronary territory, absolute MBF and the MBF relative to remote myocardium (MBF ratio) were calculated. Coronary CTA datasets were visually assessed for significant stenosis (≥ 50% luminal narrowing) in consensus by two observers. Significant stenosis was detected in 137 of 411 (33.3%) vessels. Mean absolute MBF and MBF ratio were statistically significantly lower in territories supplied by arteries with stenosis (80.7 ± 33.7 vs 140.0 ± 38.4 mL/100 mL/min and 0.52 vs 0.89, respectively; both p < 0.0001). ROC analysis showed better discrimination by MBF ratio than by absolute MBF (AUC, 0.925 vs 0.882; p = 0.0022) and increased sensitivity (90.7% vs 82.4%; p < 0.04) and specificity (93.1% vs 80.5%; p < 0.03) for MBF ratio and absolute MBF cutoff values of 0.71 or less and 103 mL/100 mL/min or less, respectively. In stress dynamic CT MPI, relative MBF provides superior diagnostic accuracy compared with absolute territorial MBF values for coronary CTA-detected significant coronary artery stenosis.

Relative myocardial blood flow by dynamic computed tomographic perfusion imaging predicts hemodynamic significance of coronary stenosis better than absolute blood flow.

Quantitative myocardial perfusion imaging by computed tomography (CT) was recently introduced to calculate myocardial blood flow (MBF). Because absolute MBF thresholds may be affected by technique, methodology, and the microvasculature, we investigated whether a relative measure of MBF improves accuracy to identify hemodynamically significant coronary stenosis. In this prospective study, 42 patients (mean [SD] age, 62.3[8.7] years; 8 women) with suspected or known coronary disease underwent dynamic CT myocardial perfusion imaging using adenosine vasodilation, before invasive angiography (coronary angiography) with fractional flow reserve (FFR). Within each myocardial territory MBF, the MBF relative to remote myocardium (MBFratio) was calculated and compared with coronary angiography and FFR. Of the 91 vessels interrogated by FFR (median, 0.81; interquartile range, 0.73-0.94), 45 vessels (49%) had an FFR value lower than 0.8 and were considered hemodynamically significant. Hyperemic MBF was lower in ischemic territories: 75.6 ± 22.5 mL per 100 mL/min versus 98.3 ± 23.1 mL per 100 mL/min (P < 0.0001). The MBFratio correlated better with FFR (P = 0.76) than the absolute MBF did (P = 0.52). Receiver operating curve analysis showed better discrimination by MBFratio: area under the curve of 0.85 versus 0.75 (P = 0.02). The MBF of remote myocardium varied between 60.7 and 167.2 mL per 100 mL/min and was lower in patients without heart rate acceleration (P = 0.0035). The MBFratio seems to better identify hemodynamically significant coronary artery disease than does the absolute MBF determined by dynamic CT perfusion imaging. This may be caused by microvascular status or related to the methodology.

Atorvastatin Treatment Improves Myocardial and Peripheral Blood Flow in Familial Hypercholesterolemia Subjects without Evidence of Coronary Atherosclerosis

Hypercholesterolemia induces early microcirculatory functional and structural alterations that are reversible by cholesterol reduction. Real time myocardial contrast echocardiography (RTMCE) and vascular ultrasound evaluate the effects of hyperlipidemia on peripheral and central blood flow reserve. This study investigated the effects of lipid-lowering therapy on coronary and peripheral artery circulation in patients with familial hypercholesterolemia (FH). RTMCE and vascular ultrasound were performed in 10 healthy volunteers (validation group) at baseline and after 12-week clinical observation, and in 16 age- and sex-matched FH patients without obstructive coronary artery disease (CAD) by computed tomography angiography at baseline and after 12-week atorvastatin treatment. Indexes of relative myocardial blood flow (MBF) were obtained at rest and during adenosine infusion. In validation group, there was no significant difference between flow-mediated dilation (FMD) at baseline and after 12 weeks (0.15 ± 0.02 vs. 0.14 ± 0.03; P = 0.39). Similarly, no differences were observed in MBF reserve at baseline and after 12 weeks (3.31 ± 0.63 vs. 3.48 ± 0.89; P = 0.89). FMD was blunted in FH patients, at baseline, as compared with validation group (0.08 ± 0.04 vs. 0.15 ± 0.02; P < 0.001) and became similar to that group (0.13 ± 0.05 vs. 0.14 ± 0.03; P = 0.07) after treatment. MBF reserve was blunted at baseline in FH patients in comparison with the validation group (2.78 ± 0.71 vs. 3.31 ± 0.63; P = 0.003). After treatment, MBF reserve values were no longer different (3.43 ± 0.66 and 3.48 ± 0.89; P = 0.84, respectively, for FH and validation groups). Patients with FH and no obstructive CAD have blunted MBF reserve and lower FMD values as compared with healthy volunteers. Both FMD and MBF reserve were normalized after atorvastatin treatment.