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Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees.

ABSTRACT: Computational simulations of coronary artery blood flow, using anatomical models based on clinical imaging, are an emerging non-invasive tool for personalized treatment planning. However, current simulations contend with two related challenges - incomplete anatomies in image-based models due to the exclusion of arteries smaller than the imaging resolution, and the lack of personalized flow distributions informed by patient-specific imaging. We introduce a data-enabled, personalized and multi-scale flow simulation framework spanning large coronary arteries to myocardial microvasculature. It includes image-based coronary models combined with synthetic vasculature for arteries below the imaging resolution, myocardial blood flow simulated using Darcy models, and systemic circulation represented as lumped-parameter networks. Personalized flow distributions and model parameters are informed by clinical CT myocardial perfusion imaging and cardiac function using surrogate-based optimization. We reveal substantial differences in flow distributions and clinical diagnosis metrics between the proposed personalized framework and empirical methods based on anatomy; these errors cannot be predicted a priori. This suggests virtual treatment planning tools would benefit from increased personalization informed by emerging imaging methods.

SUBMITTER: Menon K

PROVIDER: S-EPMC10462196 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees.

Menon Karthik K Khan Muhammed Owais MO Sexton Zachary A ZA Richter Jakob J Nieman Koen K Marsden Alison L AL

medRxiv : the preprint server for health sciences 20230823

Computational simulations of coronary artery blood flow, using anatomical models based on clinical imaging, are an emerging non-invasive tool for personalized treatment planning. However, current simulations contend with two related challenges - incomplete anatomies in image-based models due to the exclusion of arteries smaller than the imaging resolution, and the lack of personalized flow distributions informed by patient-specific imaging. We introduce a data-enabled, personalized and multi-sca ...[more]

PMID: 37645850

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Project description:BackgroundCardiac imaging by means of myocardial Positron Emission Tomography/Computed Tomography (PET/CT) is being used increasingly to assess coronary artery disease, to guide revascularization decisions with more accuracy, and it allows robust quantitative analysis of both regional myocardial blood flow (MBF) and myocardial flow reserve (MFR).Recently, a more time-efficient protocol has been developed in combination with a residual activity correction algorithm in which a stress acquisition is performed directly after completion of the rest acquisition to subtract remaining myocardial radioactivity.The objective of this study is to define flow values of myocardial blood flow (MBF) and Myocardial Flow Reserve (MFR) with 13N-ammonia (13NH3) myocardial perfusion PET/CT on patients without coronary artery disease using a time-efficient protocol, since reference values for this particular type of study are lacking in literature. In addition, we aim to determine the effect of the residual activity correction algorithm in this time-efficient protocol.ResultsA mean MBF in rest of 1.02 ± 0.22 ml/g/min, a mean MBF in stress of 2.54 ± 0.41 ml/g/min with a mean MFR of 2.60 ± 0.61 were measured. Female patients had a significant higher MBF in rest and stress, but lower MFR; a small but significant negative correlation was measured between age and MBF in stress and MFR. Residual activity correction had a significant effect resulting in a difference in global stress MBF before and after correction of 0.39 ± 0.13 ml/g/min.ConclusionsThis study established flow values for 13NH3 myocardial PET/CT with a time-efficient protocol, and established that MBF in stress corrected for residual activity is comparable with known reference values in normal studies without temporal overlap. Further validation of the technique could be of value, e.g. by comparison to standard imaging without temporal overlap, or validation against catheterization results.

Project description:BackgroundA growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR.MethodsRest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [18F]flurpiridaz in a total of 56 mice (7-8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [18F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFRApp) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging.ResultsOrchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFRApp was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFRApp (r = -0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females.ConclusionOur experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients.

Project description: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).

Project description:Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that there is no particular advantage between quantitative estimation methods nor to performing dose reduction via tube current reduction compared to temporal sampling reduction. These data are important for optimizing implementation of cardiac dynamic CT in clinical practice and in prospective CT MBF trials.

Project description:ObjectiveTo investigate the diagnostic performance of CT fractional flow reserve (CT-FFR) for myocardial bridging-related ischemia using dynamic CT myocardial perfusion imaging (CT-MPI) as a reference standard.Materials and methodsDynamic CT-MPI and coronary CT angiography (CCTA) data obtained from 498 symptomatic patients were retrospectively reviewed. Seventy-five patients (mean age ± standard deviation, 62.7 ± 13.2 years; 48 males) who showed myocardial bridging in the left anterior descending artery without concomitant obstructive stenosis on the imaging were included. The change in CT-FFR across myocardial bridging (ΔCT-FFR, defined as the difference in CT-FFR values between the proximal and distal ends of the myocardial bridging) in different cardiac phases, as well as other anatomical parameters, were measured to evaluate their performance for diagnosing myocardial bridging-related myocardial ischemia using dynamic CT-MPI as the reference standard (myocardial blood flow < 100 mL/100 mL/min or myocardial blood flow ratio ≤ 0.8).ResultsΔCT-FFRsystolic (ΔCT-FFR calculated in the best systolic phase) was higher in patients with vs. without myocardial bridging-related myocardial ischemia (median [interquartile range], 0.12 [0.08-0.17] vs. 0.04 [0.01-0.07], p < 0.001), while CT-FFRsystolic (CT-FFR distal to the myocardial bridging calculated in the best systolic phase) was lower (0.85 [0.81-0.89] vs. 0.91 [0.88-0.96], p = 0.043). In contrast, ΔCT-FFRdiastolic (ΔCT-FFR calculated in the best diastolic phase) and CT-FFRdiastolic (CT-FFR distal to the myocardial bridging calculated in the best diastolic phase) did not differ significantly. Receiver operating characteristic curve analysis showed that ΔCT-FFRsystolic had largest area under the curve (0.822; 95% confidence interval, 0.717-0.901) for identifying myocardial bridging-related ischemia. ΔCT-FFRsystolic had the highest sensitivity (91.7%) and negative predictive value (NPV) (97.8%). ΔCT-FFRdiastolic had the highest specificity (85.7%) for diagnosing myocardial bridging-related ischemia. The positive predictive values of all CT-related parameters were low.ConclusionΔCT-FFRsystolic reliably excluded myocardial bridging-related ischemia with high sensitivity and NPV. Myocardial bridging showing positive CT-FFR results requires further evaluation.

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Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees.

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Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees.

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