A modified method of noninvasive computed tomography derived fractional flow reserve based on the microvascular growth space

doi:10.1016/j.cmpb.2022.106926

Computer Methods and Programs in Biomedicine

Volume 221, June 2022, 106926

https://doi.org/10.1016/j.cmpb.2022.106926 Get rights and content

Highlights

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We proposed that the space downstream microvascular tree grows in was correlated with the whole heart volume instead of the left ventricular myocardium mass.
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We modified the power-law so that the exponent (γ) could be related to the diameter of vessels to predict the downstream resistance boundary conditions according to the heart's volume and the outlets’ diameter.
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We verified the stability of BCs by taking the circadian fluctuation of inlet boundary conditions into account and found that circadian fluctuation in BAP was negligible when it was used as the inlet BC.

Abstract

Objective

To establish a modified method for optimizing outlet boundary conditions (BC) of computed tomography-derived fractional flow reserve (CT-FFR), considering the myocardium as a growth space for microcirculation. The feasibility and diagnostic performance of the modified method in stable coronary artery disease (CAD) were compared with invasive fractional flow reserve (FFR).

Methods

Nineteen patients (19 lesions) underwent coronary computed tomography angiography (CCTA) and following invasive FFR were included. The microcirculation resistance model generated based on patient-specific anatomical structures and physiological principles was used as the outlet BC, considering the myocardium as a growth space. Brachial artery pressure (BAP) plus or minus 10 mmHg was used as the inlet pressure BC to investigate the effect of the circadian rhythm. After simulation, CT-FFR was compared with invasive FFR with a threshold of 0.80.

Results

Compared with invasive FFR, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CT-FFR with an optimal threshold of 0.80 were 100%, 100%, 100%, 100%, 100%, respectively. There were a good correlation and consistency between CT-FFR and invasive FFR. Little effect of the circadian fluctuation of BAP was found on the simulation.

Conclusions

A modified method for CT-FFR with high diagnostic accuracy compared with invasive FFR was established, considering the whole myocardial as the growth space for microcirculation. Circadian fluctuations in BAP could be ignored when it was used as the inlet BC.

Introduction

Epicardial coronary artery stenosis may lead to myocardial ischemia, and obstructive coronary artery disease (CAD) caused by this is one of the primary causes of death globally [1], [2], [3], [4]. Currently, fractional flow reserve (FFR) is an effective technique to functionally evaluate the significance of coronary artery stenosis, but its clinical application was limited by its invasive operation, high cost, and requirement for the drug-induced hyperemic state [5], [6], [7], [8]. To overcome these limitations, computational fluid dynamics (CFD) has been employed for analyzing hemodynamics [9,10].

Notably, non-invasive computed tomography-derived FFR (CT-FFR) has shown great diagnostic accuracy in quantitatively assessing the severity of coronary artery stenosis [11], [12], [13], [14], [15]. There are three main steps to derive hemodynamics of coronary arteries in CFD simulation [16,17]: (1) Reconstruction of patient-individualized 3D model of coronary artery tree[10]; (2) Determination of personalized inlet and outlet boundary conditions (BC) [18,19]; (3) Numerical solver for Navier-Stokes equation and continuity equation [20]. Thus, the determination of BCs is critical for hemodynamics simulation, and the accurate BCs following physiological laws seriously affect the accuracy of calculated FFR [21].

In previous studies, Taylor et al. determined the unique resistance value of each outlet according to the left ventricular myocardium mass, the allometric scaling laws, and the morphometry laws [20]. They simulated the adenosine-induced hyperemia state by reducing the downstream microcirculation resistance. Moreover, Lo et al. connected a two-element Windkessel model at each outlet to represent the downstream vascular system, providing pressure BCs [17]. In Tesche et al.’s study, the outlet BCs were provided by the coronary microvascular model and estimated based on static state conditions including systolic and diastolic blood pressure, heart rate and ventricular size [22]. However, the resistance of microcirculation assumed according to physiological laws and hypotheses in aforementioned researches may not reflect the real microvascular resistance, and more accurate methods warrant exploration. In addition, previous studies used brachial artery pressure (BAP) as the inlet BC. However, BAP has diurnal fluctuations that may have an impact on the simulation results, but was ignored in the above studies [23].

Previous studies demonstrated that the growth of downstream microcirculation is related to the left ventricular myocardium. In our study, our purpose was to optimize the CT-FFR simulation from the perspective of outlet BCs. Moreover, we verified the stability of BCs by taking the circadian fluctuation of inlet boundary conditions into account. The feasibility of this calculation method has also been verified in this study.

Section snippets

Study population

All study procedures were approved by the Ethics Committee of Zhongshan Hospital, Fudan University. Symptomatic consecutive adult patients with clinically suspected stable CAD in the Department of Cardiovascular Medicine, Zhongshan Hospital, Fudan University underwent preoperative CCTA with standard protocol and following invasive coronary angiography (ICA) and invasive FFR measurement within fifteen days if CCTA suggested the presence of stenosis in the main branch coronary arteries (greater

Patient and lesion characteristics

Patients’ demographics and clinical characteristics are summarized in Table 1. Nineteen patients (male/female: 11/8; age: 60.8 ± 8.1) with coronary artery stenosis (10 lesions) were retrospectively studied. Among these patients, 10.5% have diabetes, 5.3% have a family history, 5.3% have hyperlipidemia, 47.4% have hypertension, and 26.3% have current smoking. Of 19 coronary arteries with an average stenosis degree of 71.3%, 17 are left anterior descending arteries (LAD), 1 is right coronary

Discussion

In this retrospective study, we established a modified method to optimize the outlet BC, considering the whole myocardial as the growth space for microcirculation. The effect of circadian fluctuation of BAP on CT-FFR simulation was also investigated. It was demonstrated that the modified CT-FFR method was feasible and stable with high diagnostic accuracy, suggesting the potential of CT-FFR as a benefit assessment for discrimination of myocardial ischemia.

Accurate BC reflecting patient-specific

Conclusions

This study established a modified method for more accurate CT-FFR, considering the whole myocardial as the growth space for microcirculation. Circadian fluctuations in BAP were found to be negligible when it was used as the inlet BC. The results suggest high diagnostic accuracy and short time consumption for diagnosing myocardium ischemia compared with invasive FFR.

Declaration of Competing Interest

It should be understood that none of the authors have any financial or scientific conflicts of interest about the research described in this manuscript.

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Cited by (3)

A simplified coronary model for diagnosis of ischemia-causing coronary stenosis
2023, Computer Methods and Programs in Biomedicine
The functional assessment of the severity of coronary stenosis from coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR) has recently attracted interest. However, existing algorithms run at high computational cost. Therefore, this study proposes a fast calculation method of FFR for the diagnosis of ischemia-causing coronary stenosis.
We combined CCTA and machine learning to develop a simplified single-vessel coronary model for rapid calculation of FFR. First, a zero-dimensional model of single-vessel coronary was established based on CCTA, and microcirculation resistance was determined through the relationship between coronary pressure and flow. In addition, a coronary stenosis model based on machine learning was introduced to determine stenosis resistance. Computational FFR (cFFR) was then obtained by combining the zero-dimensional model and the stenosis model with inlet boundary conditions for resting (cFFR_r) and hyperemic (cFFR_h) aortic pressure, respectively. We retrospectively analyzed 75 patients who underwent clinically invasive FFR (iFFR), and verified the model accuracy by comparison of cFFR with iFFR.
The average computing time of cFFR was less than 2 s. The correlations between cFFR_r and cFFR_h with iFFR were r = 0.89 (p < 0.001) and r = 0.90 (p < 0.001), respectively. Diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio for cFFR_r and cFFR_h were 90.7%, 95.0%, 89.1%, 76.0%, 98.0%, 8.7, 0.1 and 92.0%, 95.0%, 90.9%, 79.2%, 98.0%, 10.5, 0.1, respectively.
The proposed model enables rapid prediction of cFFR and exhibits high diagnostic performance in selected patient cohorts. The model thus provides an accurate and time-efficient computational tool to detect ischemia-causing stenosis and assist with clinical decision-making.
Research on individualized distribution approach of coronary resting blood flow for noninvasive calculation of fractional flow reserve
2023, Computer Methods and Programs in Biomedicine
The distribution of coronary resting blood flow is critical for accurately calculating the computed tomography (CT) angiography-derived fractional flow reserve (FFR_CT). However, the diagnostic accuracy of FFR_CT calculated by the fixed exponents between two risk factors and coronary resting blood flow, including myocardial mass and diameter of the coronary artery branch, was insufficient compared with invasive fractional flow reserve (FFR). In this study, we proposed the individualized distribution of coronary resting blood flow based on coronary ultrasound blood flow measurement, to improve the diagnostic accuracy of FFR_CT calculation.
Five risk factors and an unknown coefficient K were integrated to calculate the individualized distribution of coronary resting blood flow. The K value was fit using the least square method based on coronary ultrasound blood flow measurement results of 30 volunteers. We developed a novel approach for calculating the individualized distribution of coronary resting blood flow and applied it to calculate FFR_CT (FFR_CTI). Then, we tested the performance of the individualized distribution approach by comparing it with the approach proposed by Taylor based on coronary ultrasound blood flow measurement results of 13 volunteers. Finally, we tested the diagnostic accuracy of FFR_CT calculated by two approaches in invasive FFR of 121 vessels with coronary stenosis.
We identified five risk factors and 6.83×10⁻⁵ for K value, including cardiac output, mean arterial pressure, myocardial mass, coronary artery volume, and diameter of the coronary artery branch, to calculate the individualized distribution of coronary resting blood flow. The mean square error of the individualized distribution approach (0.0088) was significantly less than that of the approach proposed by Taylor (0.0799). The diagnostic accuracy of FFR_CTI calculated by the individualized distribution approach (91.74%) was higher than that of the approach proposed by Taylor (FFR_CTT) (82.64%).
The individualized distribution approach of coronary resting blood flow can significantly improve the diagnostic accuracy of FFR_CT calculation compared with invasive FFR, and support its wide clinical application for diagnosing myocardial ischemia caused by coronary stenosis.
A novel method for calculating CTFFR based on the flow ratio between stenotic coronary and healthy coronary
2023, Computer Methods and Programs in Biomedicine
Epicardial coronary stenosis may lead to myocardial ischaemia, and the resulting obstructive coronary artery disease is one of the leading causes of death. CT-derived fractional flow reserve (CT-FFR) has been clinically shown to be an effective method for the noninvasive assessment of coronary artery stenosis. However, this method has the problem that the measurement result is affected by the selected measurement position.
This study was to obtain a novel flow-based approach to coronary CTFFR (CTQFFR), which was not affected by the measurement location.
This study established healthy-assumed coronary arteries based on narrowed coronary arteries. Based on the assumption that the microvascular resistance remains unchanged in the short term after coronary stenosis treatment, the blood flow in the stenotic coronary artery and the healthy-assumed coronary artery was obtained by numerical simulation, and the CTQFFR based on the blood flow ratio was calculated. The functional relationship between CTQFFR and FFR was fitted by the results of 20 cases.
In this study, the functional relationship between CTQFFR and FFR was fitted by a quadratic curve, and the variance was 0.8744; the functional relationship between CTQFFR and pressure-based approach to coronary CTFFR (CTPFFR) was fitted by a primary curve, and the variance was 0.9971. There was coronary artery growth in all 20 cases. Preliminary validation results using 10 cases showed 100% accuracy in determining whether coronary artery stenosis required for clinical intervention. The relative error of the coefficient with the results proposed in a previous study was 0.316%.
This study proposes a new method for calculating coronary CTFFR, namely, coronary CTQFFR, which is the flow ratio between stenotic coronary and healthy-assumed coronary. This method solves the problem that the downstream CTFFR of coronary stenosis is related to the selected location, which effectively improves the CTFFR at the critical value (CTFFR= 0.8) near reliability. Preliminary research results show that the method obtained in this study has a high accuracy for determining whether there is significant coronary stenosis. However, large multi-centre validation for the feasibility of this method was necessary in our future work.

¹: These authors contributed equally to this work.

View full text

A modified method of noninvasive computed tomography derived fractional flow reserve based on the microvascular growth space

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Patient and lesion characteristics

Discussion

Conclusions

Declaration of Competing Interest

Comput. Methods Prog. Biomed.

Int. J. Cardiol.

Comput. Methods Prog. Biomed.

JACC Cardiovasc. Imaging

Med. Eng. Phys.

J. Am. Coll. Cardiol.

Biophys. J.

Comput. Biol. Med.

J. Biomech.

Heart Lung Circ.

Yoga-based cardiac rehabilitation: current perspectives from randomized controlled trials in coronary artery disease

Vasc. Health Risk Manage

Epidemiology and the magnitude of coronary artery disease and acute coronary syndrome: a narrative review

J. Epidemiol. Glob. Health

Coronary artery disease: from mechanism to clinical practice

Adv. Exp. Med. Biol.

Fractional flow reserve versus angiography for guiding percutaneous coronary intervention

N. Engl. J. Med.

Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial

Circulation

Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease

N. Engl. J. Med.

Numerical analysis of the pressure drop across highly-eccentric coronary stenoses: application to the calculation of the fractional flow reserve

Biomed. Eng. Online