A new method to quantify coronary flow conditions using dynamically scaled in vitro phase contrast magnetic resonance imaging

Blood flow metrics obtained with four-dimensional (4D) flow phase contrast (PC) magnetic resonance imaging (MRI) can be of great value in clinical and experimental cerebrovascular analysis. However, limitations in both quantitative and qualitative analyses can result from errors inherent to PC MRI. One method that excels in creating low-error, physics-based, velocity fields is computational fluid dynamics (CFD). Augmentation of cerebral 4D flow MRI data with CFD-informed neural networks may provide a method to produce highly accurate physiological flow fields. In this preliminary study, the potential utility of such a method was demonstrated by using high resolution patient-specific CFD data to train a convolutional neural network, and then using the trained network to enhance MRI-derived velocity fields in cerebral blood vessel data sets. Through testing on simulated images, phantom data, and cerebrovascular 4D flow data from 20 patients, the trained network successfully de-noised flow images, decreased velocity error, and enhanced near-vessel-wall velocity quantification and visualization. Such image enhancement can improve experimental and clinical qualitative and quantitative cerebrovascular PC MRI analysis.

Quantitative coronary angiography remains the reference standard for assessing coronary anatomy, measuring anatomic severity of the stenotic lesion and assisting in the process of intracoronary interventions. Thus, treatment of coronary artery disease (CAD) is performed primarily on the basis of anatomic measurements of stenosis severity, although the disease severity correlates better with physiologic disturbances which can be revealed by the analysis of coronary artery flow and coronary flow reserve (CFR). Direct invasive measurements of coronary flow signal using Doppler flow wires and catheters provide a lot of information on the pathophysiology of coronary flow dynamics (Chamuleau et al, 2001; Bax et al, 2006; Braden, 2006; Werner et al., 2006; Kaul & Jayaweera, 2008; Courtis et al., 2009). But in clinical practice, these invasive techniques are rarely applied because of the time and expense required. Alternative methodology in detecting coronary flow and CFR is positron emission tomography which is feasible but expensive and scarcely available (West & Kramer, 2009). In fact, a large-scale assessment of such important functional parameters is hampered by the lack of a reliable, low-cost, noninvasive method that might be used for this purpose (Pellikka, 2004). Some years ago transesophageal echocardiography was proposed for evaluation of coronary flow and CFR in man. However, this method demonstrates some important limitations: it is semiinvasive, and has optimal feasibility in visualizing the flow in only very proximal part of the left anterior descending coronary artery (LAD) (ranging from 69% to 97%) and right coronary artery (RCA) (ranging from 66% to 83%) which allowes the assessment of transstenotic or prestenotic CFR but not poststenotic CFR (Vrublevsky et al., 2001, 2004). Until recently, transthoracic echocardiography (TTE) evaluation of the CAD was aimed at the assessment of regional and global left ventricular function (Youn & Foster, 2004). Direct transthoracic visualization of the coronary arteries was attempted in children and occasionally in adults with coronary artery anomalies, arteriovenous fistulas, and aneurysms (Harada et al., 1999; Hiraishi et al, 2000; P.C. Frommelt & M.A. Frommelt, 2004). However, with the advent of harmonic imaging, contrast agents and high-frequency transducers, direct transthoracic Doppler visualization of non-dilated arteries and measurement of coronary artery flow is now relevant in the majority of patients. The aims of this review are to outline the technical aspects of coronary artery visualization and flow measurements both at rest and with pharmacological stress, to demonstrate pathologic coronary artery flow patterns by TTE and to discuss clinical implications of TTE for patients with suspected or confirmed CAD.

Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

<h3>Background</h3> Coronary revascularisation guided by physiological assessment with fractional flow reserve (FFR) improves outcomes and expenditure. However, due to practical limitations, FFR is only used in &lt;10% of percutaneous coronary interventions (PCI) and almost none of the 250,000 diagnostic coronary angiograms performed every year in the UK. We aimed to develop an <i>in silico</i> model of coronary physiology which computes FFR using computational fluid dynamics (CFD) with data from coronary angiography (CAG), which also computes real-time coronary flow. <h3>Methods</h3> We studied 40 patients with stable coronary artery disease undergoing PCI. The <i>in silico</i> workflow reconstructed coronary geometry from CAG images into 3-D geometries using image registration and segmentation protocols. The 3-D domain was coupled to an algebraically encoded zero-D model representing coronary microvascular resistance. CFD simulated pressure and flow. Computed pressures were validated against patient data. Flow was computed from those pressures and validated in a benchtop flow circuit constructed from patient-specific 3-D printed coronary arterial models, a blood analogue, and patient-specific coronary flow patterns using a programmable pump. Pressure and flow were measured with clinical pressure and flow sensitive wires. To reduce computation time, a novel pseudo-transient CFD method was developed and investigated. <h3>Results</h3> Using generic boundary conditions, the initial model computed ‘virtual’ FFR (vFFR) with ±0.06 error and diagnosed physiological lesion significance (FFR &lt;0.80) with 97% accuracy. Ultra-precise, transient CFD took 24 h to compute, whereas the novel ‘pseudo-transient’ method reduced computation to &lt;4 mins on a standard PC with no significant loss of accuracy. Using case-specific boundary conditions (based on invasive measurements) error was reduced to ±0.004 and more useful, artery-specific, patient averaged values yielded ±0.01 error. Coronary flow was computed in all cases and, with the 3-D printed arteries, we demonstrated that the <i>in silico</i> model computed reliable coronary flow with 5.3% error in 3 min. <h3>Conclusions</h3> Our <i>in silico</i> model computes reliable intra-coronary physiology, including pressure and flow, in timescales that are practical for clinical use in the catheter laboratory. Virtual modelling of FFR and hyperaemic stenosis resistance (HSR) is now feasible, which may facilitate increased uptake and impact of physiologically-guided revascularisation planning for every patient undergoing CAG, rather than a small minority undergoing selective PCI. Improved accuracy will follow from better characterisation of the individual’s microvascular resistance. coronary stenosis.

Hypertrophy is considered one of the major mechanisms of the myocardium for adapting to hemodynamic overload. More muscle mass provides more contractile elements for generating the extra work required by the overload. In pressure overload of aortic valve stenosis, concentric left ventricular hypertrophy (LVH) normalizes wall stress, a key determinant of ejection performance.1 Afterload is often expressed as wall stress (pressure×radius/thickness). As the pressure term in the numerator increases, it is offset by an increase in the thickness term of the denominator. In this way, the high systolic pressure required to drive blood through even a very stenotic aortic valve can be consistent with normal afterload and normal ejection fraction. See p 3170 Unfortunately, hypertrophy not only provides benefits but also has many pathological consequences. One of these is myocardial ischemia and the attendant angina reported by patients with aortic stenosis despite normal epicardial coronary arteries. The onset of angina greatly increases the risk of sudden death compared with the risk in asymptomatic patients with aortic valve stenosis.2,3 Angina occurs when myocardial oxygen demand exceeds supply. Demand is proportional to heart rate and wall stress, and the latter can be elevated in cases of aortic stenosis when hypertrophy is inadequate to normalize stress.1 After aortic valve replacement, there is marked regression of hypertrophy that may occur over the next several months to years,4 but angina is relieved immediately. Relief of angina immediately after surgery is probably due to the combination of sudden decreased oxygen demand after removal of pressure overload and increased oxygen supply of improved perfusion. However, there are remaining questions about the physiological mechanisms for reduced myocardial oxygen supply (coronary blood flow) in aortic stenosis and its improvement after relief of pressure overload. Specifically, what is it about critical aortic stenosis that is “critical” …

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

An angiographic method for measurement of absolute coronary blood flow in patients was developed. It is based on 3D-reconstruction of the left or right coronary tree from digitized biplane coronary cineangiograms. The apparatus is presently composed of a 35 mm cinefilm projector with a video camera and a 512 x 512 x 8 bits image array processor controlled by a VAX-11/750 computer. First, the parameters of the two angiographic projections are determined in form of two 4 x 3 matrices from a pair of cineframes showing a 4 cm cube bearing markers. The cube is filmed after the coronary injection, with unchanged geometric configuration. The coronary arteries of interest are then 3D-reconstructed from a pair of cineframes showing them fully opacified. This allows to compute the intravascular volumes needed for flow determination. In vitro experiments showed that the obtained volume are reasonably accurate. For the measurement of coronary flow, the concentration of contrast medium along the involved arteries is computed (in arbitrary units) from two cineframes taken one (or two) cardiac cycle after onset of the injection. This yields a 'concentration-distance' curve per artery. The volume of fluid (contrast medium mixed with blood) which flows into the arteries during this (or these two) cardiac cycle is determined by applying a concentration threshold to the obtained concentration-distance curves. Measurements performed on a constant flow model were satisfying. Preliminary measurements in 12 patients showed that flow values obtained angiographically into the left anterior descending coronary artery correlate well with the values measured simultaneously by thermodilution in the great cardiac vein (Qangio = 0.83 x Qthermo + 16.1 ml, r = 0.87, n = 29).

Background In patients with aortic stenosis (AS), increased systolic wall stress due to increased afterload reduces systolic coronary flow, often leading to systolic coronary flow reversal (SFR) in epicardial coronary arteries. Purpose We used transthoracic echocardiography (TTE) to evaluate severity of AS, left ventricular function, and coronary flow, and investigated echocardiographic indicators associated with SFR. Methods We prospectively evaluated consecutively presenting patients who visited our valvular heart disease outpatient clinic or were admitted to our hospital for investigation of AS (July 2023 to February 2024). Based on ESC guidelines, severity of AS and the left ventricular function were assessed with TTE. At the same time, TTE was used to measure distal left anterior descending coronary artery flow. SFR was defined as the presence of a reversal coronary flow component in systole. Based on the presence or absence of SFR in coronary flow measurements, patients were classified into SFR+ or SFR− groups. The inclusion criteria were AS of moderate or greater severity, and the exclusion criteria were known coronary stenosis and the inability to assess coronary flow. Results Enrolled 28 patients were classified into SFR+ (7 patients) and SFR − (21 patients) groups. Comparing baseline characteristics between the SFR+ and SFR− groups, although there were no significant differences in left ventricular indicators such as left ventricular mass index, left ventricular ejection fraction, stroke volume index, and E/e’ between the two groups, left ventricular global longitudinal strain was significantly lower in the SFR+ group (12.0±3.1%, 14.9±3.0%, p=0.026) (Table 1). Regarding indexes of AS assessment, aortic valve peak velocity and aortic valve mean pressure gradient values were significantly higher in the SFR+ group than in the SFR − group ([475±68 cm/s, 379±55 cm/s, p&amp;lt;0.001] and [56.2±16.5 mm Hg, 34.8±10.5 mm Hg, p&amp;lt;0.001], respectively) (Table 1). Representative cases show Figure 1. Conclusion The presence of SFR in patients with AS assessed using TTE may be a simple echocardiographic index that may be associated with potential decline in left ventricular function and progression of AS.

Fast cine phase contrast magnetic resonance imaging (fast cine phase contrast MRI) can measure phasic coronary flow velocity in humans.The purpose of this study was to compare the coronary flow velocity reserves measured by MR IMAGING with those obtained by Doppler guide wire.Nineteen patients with ischemic or valvular heart disease were studied.Fast cine phase contrast MR images of the left anterior descending (LAD) artery were acquired during breath-hold time in the basal state and after administration of dipyridamole.Flow velocity in the LAD artery was also measured with Doppler guide wire before and after venous injection of dipyridamole in all subjects.Flow velocity in the coronary artery measured with MR IMAG-ING in the basal state (12.5 ؎ 4.9 cm/sec) was significantly lower than that obtained with Doppler guide wire (32.4 ؎ 12.1 cm/sec, P F 0.01).However, MR assessments of coronary flow velocity reserve showed a good linear correlation with those measured by Doppler guide wire (r ‫؍‬ 0.91).In conclusion, fast cine phase contrast MR imaging is a useful technique, which can provide a noninvasive assessment of flow reserve ratios in patients with coronary artery disease.

Purpose: To evaluate aortic pulse wave velocities obtained by real-time phase-contrast (PC) MRI in comparison to cine PC MRI. Methods: Real-time PC MRI of eight healthy volunteers employed highly undersampled radial FLASH sequences and phase-sensitive image reconstructions by regularized nonlinear inversion (NLINV) at 40 ms temporal resolution and 1.3 mm in-plane resolution. Pulse wave velocities were analyzed for combinations of 2, 3 and 4 locations of aortic flow using time-to-upslope and cross-correlation methods. Results: For the time-to-upslope analysis mean pulse wave velocities ranged from 3.5 to 3.9 m s-1 for real-time PC MRI and from 3.5 to 3.8 m s-1 for cine PC MRI. A cross-correlation analysis of the same data resulted in 2.9 to 3.3 m s-1 and 3.3 to 3.7 m s-1, respectively. Conclusion: Real-time PC MRI determined aortic pulse wave velocities from single cardiac cycles in close correspondence to values obtained by cine PC MRI.

HighlightsWhat are the main findings?Cine phase contrast MRI for time-resolved assessment of leg muscle function during voluntary and electrically evoked motion was feasible in typically developing children.The success rates of cine phase contrast MRI during both voluntary and electrically evoked leg motion were reduced in pediatric patients with cerebral palsy.What is the implication of the main finding?Further optimization of the electrical muscle stimulation protocol, the voluntary motion task, and the MRI acquisition—particularly with regard to scan acceleration—is required.These improvements would enable cine phase-contrast MRI to serve as a feasible method for studying muscle dynamics and assessing treatment effects in pediatric patients with neuromuscular diseases.Background/Objectives: Magnetic resonance imaging (MRI) can be used to assess muscle function while performing a motion task within the scanner. Quantitative measures such as contraction velocity and strain can be derived from the images. Cine phase contrast (PC) MRI for time-resolved imaging of muscle function relies on the consistently repeated execution of the motion task for several minutes until data acquisition is complete. This may be difficult for patients with neuromuscular dysfunctions. To date, this approach has been applied only in adults, but not pediatric populations. The aim of this pilot study was to investigate the feasibility of PC MRI for assessing calf muscle function during electrically evoked and voluntary motion in children with cerebral palsy (CP) using open-source hardware and software. Methods: Cine PC MRI was performed at 3T in ambulatory pediatric patients with CP and typically developing children under electrical muscle stimulation (EMS) (n = 14/13) and during voluntary plantarflexion (n = 4/4) using a home-built pedal with a force sensor. A visual feedback software was developed to enable synchronized imaging of voluntary muscle contractions. Muscle contraction velocity and strain were calculated from the MRI data. Data quality was rated by two readers. Results: During EMS, the velocity data quality was rated as sufficient in 21% of scans in patients compared with 82% of scans in controls. During the voluntary task, all patients demonstrated increased compliance and greater generated force output than during EMS. Voluntary motion imaging was successful in all controls but none of the patients, as motion periodicity in patients was worse during voluntary than during stimulated contraction. Conclusions: Cine phase-contrast MRI combined with EMS or voluntary motion proved challenging in pediatric patients with CP, particularly in those with more severe baseline muscle dysfunction or reduced tolerance to stimulation. In contrast, the approach was successfully implemented in typically developing children. Although the scope of the patient-based findings is limited by data heterogeneity, the method demonstrates considerable potential as a tool for monitoring treatment-related changes in muscle function, particularly in less severely affected patients. Further refinement of the EMS and voluntary motion protocols, together with a reduction in MRI acquisition time, is required to improve motion periodicity, tolerability, and consequently the overall success rate in the intended pediatric patient cohort.

The functional significance of coronary arterial stenosis can be evaluated by measuring the pharmacological flow reserve. Magnetic resonance (MR) imaging has a unique potential for noninvasive measurement of coronary blood flow and flow reserve in the native coronary artery and bypass graft. Restenosis after coronary balloon angioplasty and stenting in the left anterior descending artery can be detected noninvasively with serial MR measurements of the coronary flow reserve. Further refinement of the MR pulse sequences to improve spatial and temporal resolutions may permit accurate quantification of blood flow volume and flow reserve in all major coronary arterial branches. MR assessments of blood flow volume and flow pattern allow noninvasive detection of significant stenosis in the coronary artery bypass graft as well. By integrating MR blood flow measurement in the coronary sinus and cine MR assessment of left ventricular myocardial mass, altered myocardial micro-circulation in patients with diffuse myocardial diseases, such as hypertrophic cardiomyopathy and cardiac transplant, has been documented. J. Magn. Reson. Imaging 1999;10:728-733.

Background: Fractional flow reserve (FFR) is used to evaluate the need for percutaneous coronary intervention (PCI) in cases of moderate stenosis of the coronary artery. Recently, diagnostic imaging support with computational fluid dynamics (CFD) analysis has been garnering attention. This study defines the relationship between FFR conducted for cardiac catheterization and CFD analyses conducted using coronary computed tomography (CT) for moderate stenosis, in addition to considering whether wall pressure (WP) and wall shear stress (WSS) can be used to evaluate ischemia.Methods and Results: Cases in which FFR was measured via coronary CT and cardiac catheterization was performed within 3 months were collected retrospectively. In the CFD analysis, WP and WSS were calculated and compared with FFR. Three groups were created to compare results of CFD analysis and FFR values according to the location of the stenosis: the right coronary artery, the left anterior descending artery, and the left circumflex artery. There was a correlation between FFR and WSS according to CFD analysis for moderate stenosis of the coronary artery, with a cut-off value for treatment able to be calculated.Conclusions: The results of this study suggest that ischemia can be evaluated by conducting CFD analysis (WSS) using coronary CT.

Peak blood flow measurement of coronary sinus by cine phase contrast MR imagings: Comparison between breath-hold and respiratory compensation techniques

The Western Washington Intracoronary Streptokinase randomized trial1 first demonstrated that intracoronary thrombolytic therapy improved survival for patients presenting within 12 hours of symptom onset of acute myocardial infarction (MI). Perhaps equally important, this invasive study demonstrated that in-hospital and long-term survival was greatly improved in patients with patent infarct-related arteries.2 These observations ushered in the modern era of reperfusion therapy, and they also firmly established the concept that achieving arterial patency was the predominant mechanism for the prognostic benefit of thrombolytic agents. Numerous trials since then have validated this open-artery hypothesis.3 4 5 In the early 1990s, Ross et al6 definitively established the relationship between prompt reinstitution of flow, improved myocardial salvage, and survival. Anderson et al7 clearly demonstrated that antegrade flow, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria, can differentiate different levels of antegrade flow, with different prognostic implications. Although TIMI flow grades seem to segregate effective from ineffective flow, this analysis is only a qualitative measure that can be subject to bias and interlaboratory variability. Gibson et al8 further refined angiographic flow quantitation using corrected TIMI frame counts. This method of analysis quantitates angiographic contrast velocity measures and decreases variability. Currently, arterial patency is the gold standard for assessing the efficacy of different reperfusion protocols. Refinements in the quantitation of degrees of arterial patency have led to improvements in the prognostic value of this measure. It has, however, become increasingly apparent that contrast velocity alone does not adequately define the level of microvascular perfusion or predict the extent of return of myocardial function after successful reperfusion therapy. Coronary angiography remains a crude means to assess myocardial perfusion after infarction, and it is clear that infarct artery patency is not equivalent to the reestablishment of myocardial tissue perfusion. With the …