Background: Magnetic Resonance Imaging (MRI) 2D phase-contrast flow measurement has been regarded as the gold standard in blood flow measurements and can be performed with free breathing or breath held techniques. We hypothesized that the accuracy of flow measurements obtained with segmented phase-contrast during breath holding, and in particular higher number of k-space segments, would be non-inferior compared to navigator phase-contrast. Volumes obtained from anatomic segmentation of cine MRI and Doppler echocardiography were used for additional reference. Methods: Forty patients, five women and 35 men, mean age 65 years (range 53-80), were randomly selected and consented to the study. All underwent EKG-gated cardiac MRI including breath hold cine, navigator based free-breathing phase-contrast MRI and breath hold phase-contrast MRI using k-space segmentation factors 3 and 5, as well as transthoracic echocardiography within 2 days. Results: In navigator based free-breathing phase-contrast flow, mean stroke volume and cardiac output were 79.7 +/- 17.1 ml and 5071 +/- 1192 ml/min, respectively. The duration of the acquisition was 50 +/- 6 s. With k-space segmentation factor 3, the corresponding values were 77.7 ml +/- 17.5 ml and 4979 +/- 1211 ml/min (p = 0.15 vs navigator). The duration of the breath hold was 17 +/- 2 s. K-space segmentation factor 5 gave mean stroke volume 77.9 +/- 16.4 ml, cardiac output 5142 +/- 1197 ml/min (p = 0.33 vs navigator), and breath hold time 11 +/- 1 s. Anatomical segmentation of cine gave mean stroke volume and cardiac output 91.2 +/- 20.8 ml and 5963 +/- 1452 ml/min, respectively. Echocardiography was reliable in 20 of the 40 patients. The mean diameter of the left ventricular outflow tract was 20.7 +/- 1.5 mm, stroke volume 78.3 ml +/- 15.2 ml and cardiac output 5164 +/- 1249 ml/min. Conclusions: In forty consecutive patients with coronary heart disease, breath holding and segmented k-space sampling techniques for phase-contrast flow produced stroke volumes and cardiac outputs similar to those obtained with free-breathing navigator based phase-contrast MRI, using less time. The values obtained agreed fairly well with Doppler echocardiography while there was a larger difference when compared with anatomical volume determinations using SSFP (steady state free precession) cine MRI.

BACKGROUND:

The transit of blood through the beating heart is a basic aspect of cardiovascular physiology which remains incompletely studied. Quantification of the components of multidirectional flow in the normal left ventricle (LV) is lacking, making it difficult to put the changes observed with LV dysfunction and cardiac surgery into context.

METHODS:

Three dimensional, three directional, time resolved magnetic resonance phase-contrast velocity mapping was performed at 1.5 Tesla in 17 normal subjects, 6 female, aged 44+/-14 years (mean+/-SD). We visualized and measured the relative volumes of LV flow components and the diastolic changes in inflowing kinetic energy (KE). Of total diastolic inflow volume, 44+/-11% followed a direct, albeit curved route to systolic ejection (videos 1 and 2), in contrast to 11% in a subject with mildly dilated cardiomyopathy (DCM), who was included for preliminary comparison (video 3). In normals, 16+/-8% of the KE of inflow was conserved to the end of diastole, compared with 5% in the DCM patient. Blood following the direct route lost or transferred less of its KE during diastole than blood that was retained until the next beat (1.6+/-1.0 millijoules vs 8.2+/-1.9 millijoules, p<0.05); whereas, in the DCM patient, the reduction in KE of retained inflow was 18-fold greater than that of the blood tracing the direct route.

CONCLUSION:

Multidimensional flow mapping can measure the paths, compartmentalization and kinetic energy changes of blood flowing into the LV, demonstrating differences of KE loss between compartments, and potentially between the flows in normal and dilated left ventricles.

Background and aim of the study

Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics was quantified along the entire valvular coaptation line in an ovine model of acute IMR.

Methods

Ten radiopaque markers were sutured in pairs on the anterior (A₁-E₁) and corresponding posterior (A₂-E₂) leaflet edges from the anterior (A₁/A₂) to the posterior (E₁/E₂) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings.

Results

Hemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 ± 0.3 versus 2.3 ± 0.7, p <0.05), decreased contractility (dP/dt_max: 1,948 ± 598 versus 1,119 ± 293 mmHg/s, p <0.05), and slower left ventricular relaxation rate (dP/dt_min: −1,079 ± 188 versus −538 ± 147 mmHg/s, p <0.05). During ischemia, valve opening occurred earlier (A₁/A₂: 112 ± 28 versus 83 ± 43 ms, B₁/B₂: 105 ± 32 versus 68 ± 35 ms, C₁/C₂: 126 ± 25 versus 74 ± 37 ms, D₁/D₂: 114 ± 28 versus 71 ± 34 ms, E₁/E₂: 125 ± 29 versus 105 ± 33 ms; all p <0.05) and was slower (A₁/A₂: 16.8 ± 9.6 versus 14.2 ± 9.4 cm/s, B₁/B₂: 40.4 ± 9.9 versus 32.2 ± 10.0 cm/s, C₁/C₂: 59.0 ± 14.9 versus 50.4 ± 18.1 cm/s, D₁/D₂: 34.4 ± 10.4 versus 25.5 ± 10.9 cm/s; all p <0.05), except at the posterior edge (E₁/E₂: 13.3 ± 8.7 versus 10.6 ± 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia.

Conclusion

Acute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.

Background: Improved quantitative understanding of in vivo leaflet geometry in ischemic mitral regurgitation (IMR) is needed to improve reparative techniques, yet few data are available due to current imaging limitations. Using marker technology we tested the hypotheses that IMR (1) occurs chiefly during early systole; (2) affects primarily the valve region contiguous with the myocardial ischemic insult; and (3) results in systolic leaflet edge restriction. Methods: Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A₁–E₁) and posterior (A₂–E₂) mitral leaflet free edges from the anterior commissure (A₁–A₂) to the posterior commissure (E₁–E₂). Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D marker coordinates before and during acute proximal left circumflex artery occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant-MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was the distance of the midpoint of paired markers to the mitral annular plane at EndS. Results: Acute ischemia increased echocardiographic MR grade (0.5 ± 0.3 vs 2.3 ± 0.7, p < 0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7 ± 10 vs 22 ± 19 mm², 1 ± 2 vs18 ± 16 mm², 0 vs 17 ± 15 mm²); Mid-MOA (9 ± 13 vs 25 ± 17 mm², 3 ± 6 vs 21 ± 19 mm², 0 vs 25 ± 17 mm²); and Post-MOA (8 ± 10 vs 25 ± 16, 2 ± 4 vs 22 ± 13 mm², 0 vs 23 ± 13 mm²), all p < 0.05. There was no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline conditions or ischemia. Tenting height increased with ischemia near the central and the anterior commissure leaflet edges (B₁–B₂: 7.1 ± 1.8 mm vs 7.9 ± 1.7 mm, C₁–C₂: 6.9 ± 1.3 mm vs 8.0 ± 1.5 mm, both p < 0.05). Conclusions: MOA during ischemia was larger throughout systole, indicating that acute IMR in this setting is a holosystolic phenomenon. Despite discrete postero-lateral myocardial ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was associated with leaflet restriction near the central and the anterior commissure leaflet edges. This entire constellation of annular, valvular, and subvalvular ischemic alterations should be considered in the approach to mitral repair for IMR.

Magnetic Resonance Angiography (MRA) and Phase-Contrast MRA (PC-MRA) approaches used for assessment of cardiovascular morphology typically result in data containing information from the entire cardiac cycle combined into one 2D or 3D image. Information specific to each timeframe of the cardiac cycle is, however, lost in this process. This study proposes a novel technique, called Phase-Contrast Magnetic Resonance CardioAngiography (4D PC-MRCA), that utilizes the full potential of 4D Flow CMR when generating temporally resolved PC-MRA data to improve visualization of the heart and major vessels throughout the cardiac cycle. Using non-rigid registration between the timeframes of the 4D Flow CMR acquisition, the technique concentrates information from the entire cardiac cycle into an angiographic dataset at one specific timeframe, taking movement over the cardiac cycle into account. Registration between the timeframes is used once more to generate a time-resolved angiography. The method was evaluated in ten healthy volunteers. Visual comparison of the 4D PC-MRCAs versus PC-MRAs generated from 4D Flow CMR using the traditional approach was performed by two observers using Maximum Intensity Projections (MIPs). The 4D PC-MRCAs resulted in better visibility of the main anatomical regions of the cardiovascular system, especially where cardiac or vessel motion was present. The proposed method represents an improvement over previous PC-MRA generation techniques that rely on 4D Flow CMR, as it effectively utilizes all the information available in the acquisition. The 4D PC-MRCA can be used to visualize the motion of the heart and major vessels throughout the entire cardiac cycle.

Four-dimensional (4D) flow magnetic resonance imaging (4D Flow MRI) enables acquisition of time-resolved three-directional velocity data in the entire heart and all major thoracic vessels. The segmentation of these tissues is typically performed using semi-automatic methods. Some of which primarily rely on the velocity data and result in a segmentation of the vessels only during the systolic phases. Other methods, mostly applied on the heart, rely on separately acquired balanced Steady State Free Precession (b-SSFP) MR images, after which the segmentations are superimposed on the 4D Flow MRI. While b-SSFP images typically cover the whole cardiac cycle and have good contrast, they suffer from a number of problems, such as large slice thickness, limited coverage of the cardiac anatomy, and being prone to displacement errors caused by respiratory motion. To address these limitations we propose a multi-atlas segmentation method, which relies only on 4D Flow MRI data, to automatically generate four-dimensional segmentations that include the entire thoracic cardiovascular system present in these datasets. The approach was evaluated on 4D Flow MR datasets from a cohort of 27 healthy volunteers and 83 patients with mildly impaired systolic left-ventricular function. Comparison of manual and automatic segmentations of the cardiac chambers at end-systolic and end-diastolic timeframes showed agreements comparable to those previously reported for automatic segmentation methods of b-SSFP MR images. Furthermore, automatic segmentation of the entire thoracic cardiovascular system improves visualization of 4D Flow MRI and facilitates computation of hemodynamic parameters.

Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. Methods: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at locations of interest. The method was applied on 4D flow CMR datasets obtained from 11 healthy volunteers and 10 patients with heart failure. Evaluation of the method was performed visually, and by comparison of net flow volumes in the ascending aorta obtained automatically (using the proposed method), and semi-automatically. Further evaluation was done by comparison of net flow volumes obtained automatically at different locations in the aorta, pulmonary artery, and caval veins. Results: Visual evaluation of the generated segmentations resulted in good outcomes for all the major vessels in all but one dataset. The comparison between automatically and semi-automatically obtained net flow volumes in the ascending aorta resulted in very high correlation (r(2) = 0.926). Moreover, comparison of the net flow volumes obtained automatically in other vessel locations also produced high correlations where expected: pulmonary trunk vs. proximal ascending aorta (r(2) = 0.955), pulmonary trunk vs. pulmonary branches (r(2) = 0.808), and pulmonary trunk vs. caval veins (r(2) = 0.906). Conclusions: The proposed method allows for automatic analysis of 4D flow CMR data, including vessel segmentation, assessment of flow volumes at locations of interest, and 4D flow visualization. This constitutes an important step towards facilitating the clinical utility of 4D flow CMR.

The complex myocardial fiber architecture of the left ventricle (LV) enables long-axis motion (annular excursion), short-axis motion and also a small torsional deformation throughout the cardiac cycle. The contribution of the long-axis motion has proven to be important in generating ventricular filling and emptying, and the analysis of annular excursion has become a well established diagnostic tool for the assessment of ventricular function. Cardiac motion can be accurately described with modem non-invasive imaging teclmiques, and this is important ground for deeper understanding and more reliable diagnosis of cardiovascular disease. The focus of this thesis was to provide new insights into cardiac pump function using variables originating from the annular excursion and dynamic changes in shape, applying both established and novel echocardiographic imaging approaches.

The traditional method of evaluating systolic ventricular fimction according to the total annular excursion overestimates the excursion amplitude in relation to true systolic fimction. A novel method presented here, measurement of the systolic annular excursion, more accurately reflects the timing of true systole, and was applied both in patients with heart disease and in healthy subjects. To date, the form of asynchronous myocardial motion called postsystolic shortening (PSS) has mainly been observed in the setting of myocardial ischemia. The significance of PSS in hypertensive heart disease remains incompletely described. We found that a subgroup of hypertensive patients with PSS along the LV long-axis had signs of more severe cardiac involvement unrelated to the level of blood pressure. Endurance trained subjects showed a larger LV long-axis motion as compared to strength trained and untrained controls. Mitral annular (MA) excursion correlated strongly to LV stroke volume, end-diastolic volume and maximal oxygen consumption per body weight, but weakly to LV ejection fraction. These findings provide further evidence of the importance of annular excursion to normal cardiac performance. In order to assess the contribution of MA excursion and shape dynamics to total LV volume change in humans, a novel 4-dimensional transesophageal echocardiography teclmique was developed. The excursion of the annulus accounted for an important portion (19±3%) of the total LV filling and emptying in healthy human subjects. Furthermore, our findings elucidate an atrial influence on MA physiology in humans, as well as a sphincter-like action of the MA. These temporal changes may facilitate ventricular filling by annular expansion during early and mid diastole, and aid competent valve closure during the marked decrease in annular area during late diastole and early systole.

n/a

Analysis of atrioventricular plane displacement (AVPD) is a well established method for assessment of both systolic and diastolic ventricular function. For several years, AVPD has been a clinical tool and there are many current, as well as potential, areas of application. However, clinical work has shown that the traditional method for evaluation of systolic ventricular function, called total AVPD, does not temporally reflect true systole. Systolic AVPD is a new approach for measuring AVPD to assess ventricular systolic function. We wished to apply this new model in healthy subjects and in patients with different common heart diseases. Twenty-eight young healthy males and 30 patients (aortic stenosis, left sided regurgitant lesions, postmyocardial infarction) were enrolled. AVPD was obtained at the four standard sites by M-mode. Total AVPD was measured in the conventional way and systolic AVPD by identifying true systole, by means of mitral- and aortic valve closure respectively. Ventricular volumes were calculated according to biplane Simpson's rule. The systolic AVPD measurements were significantly lower than the total measurements, at both atrioventricular planes in all groups (P<0·001). This discrepancy was greater at the mitral than at the tricuspid annulus in the patients 24·2% vs. 15·5% (P<0·001), but did not differ in the healthy subjects. At the mitral annulus, this discrepancy also seemed to be more pronounced in the patients than in the healthy subjects 24·2% vs. 10·7%. When assessing ventricular systolic function by AVPD, the conventional method overestimates the amplitude in relation to true systolic function in both patients with heart disease and in young healthy males. Thus, there are uncertainties regarding earlier estimations of AVPD in terms of expression of systolic function and regarding previously presented reference values. We recommend the proposed methodology.

Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7–10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution to LVFV increased from 18 ± 4 to 45 ± 13% (P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important.

Aims Mitral atrioventricular plane displacement (AVPD) provides information about left ventricular systolic function. M-mode of systolic annulus amplitude or tissue Doppler imaging of systolic annulus velocity are the current methods of evaluating AVPD. A correlation to ejection fraction (EF) has been demonstrated in patients with coronary artery disease and left ventricular dysfunction. Our aim was (i) to investigate the mitral AVPD of normal subjects with different physical work capacities and (ii) to further evaluate AVPD as an index of left ventricular systolic function.

Methods and results Twenty-eight healthy men mean age 28 years (20–39) were included: endurance trained (ET) (n=10), strength trained (ST) (n=9) and untrained (UT) (n=9). The systolic AVPD was recorded at four sites, septal, lateral, anterior and posterior, using M-mode. Left ventricular volumes were calculated according to Simpson’s rule. Systolic AVPD was higher in endurance trained, 16·9 ± 1·5 mm, as compared with both strength trained, 13 ± 1·6 (P<0·001) and untrained, 14 ± 1·6 (P<0·001). Left ventricular systolic AVPD correlated strongly with end-diastolic volume (r=0·82), stroke volume (r=0·80) and maximal oxygen consumption per body weight (r=0·72). The correlation between AVPD and EF was poor (r=0·22).

Conclusion  In the subjects studied, with a range of normal cardiac dimensions, AVPD correlated to stroke volume, end-diastolic volume and maximal oxygen consumption per body weight, but not to EF. On theoretical grounds, it also seems reasonable that a dimension like AVPD is related to other cardiac dimensions and volumes, rather than to a fraction, like EF. AVPD is one parameter that is useful for evaluation of left ventricular systolic function but is not interchangeable with other measurements such as EF.

Background-In asymptomatic patients with severe isolated mitral regurgitation (MR), identifying the onset of early left ventricular (LV) dysfunction can guide the timing of surgical intervention. We hypothesized that changes in LV transmural myocardial strain represent an early marker of LV dysfunction in an ovine chronic MR model. Methods and Results-Sheep were randomized to control (CTRL, n = 8) or experimental (EXP, n = 12) groups. In EXP, a 3.5-or 4.8-mm hole was created in the posterior mitral leaflet to generate "pure" MR. Transmural beadsets were inserted into the lateral and anterior LV wall to radiographically measure 3-dimensional transmural strains during systole and diastolic filling, at 1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12 weeks (3.0 [2-4] versus 0.5 [0-2], 3.0 [1-4] versus 0.5 [0-1], respectively, both P < 0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201 +/- 18 versus 173 +/- 17 g/m(2), P < 0.01). LVEDVI increased in EXP from 1 to 12 weeks (P = 0.015). Between the 1 and 12 week values, the change in BNP (-4.5 +/- 4.4 versus-3.0 +/- 3.6 pmol/L), PRSW (9 +/- 13 versus 23 +/- 18 mm Hg), tau (-3 +/- 11 versus-4 +/- 7 ms), and systolic strains was similar between EXP and CTRL. The changes in longitudinal diastolic filling strains between 1 and 12 weeks, however, were greater in EXP versus CTRL in the subendocardium (lateral:-0.08 +/- 0.05 versus 0.02 +/- 0.14, anterior:-0.10 +/- 0.05 versus-0.02 +/- 0.07, both P < 0.01). Conclusions-Twelve weeks of ovine "pure" MR caused LV remodeling with early changes in LV function detected by alterations in transmural myocardial strain, but not by changes in BNP, PRSW, or tau.

The mitral annulus (MA) has a complex shape and motion, and its excursion has been correlated to left ventricular (LV) function. During the cardiac cycle the annulus’ excursion encompasses a volume that is part of the total LV volume change during both filling and emptying. Our objective was to evaluate the contribution of MA excursion and shape variation to total LV volume change. Nine healthy subjects aged 56 ± 11 (means ± SD) years underwent transesophageal echocardiography (TEE). The MA was outlined in all time frames, and a four-dimensional (4-D) Fourier series was fitted to the MA coordinates (3-D+time) and divided into segments. The annular excursion volume (AEV) was calculated based on the temporally integrated product of the segments’ area and their incremental excursion. The 3-D LV volumes were calculated by tracing the endocardial border in six coaxial planes. The AEV (10 ± 2 ml) represented 19 ± 3% of the total LV stroke volume (52 ± 12 ml). The AEV correlated strongly with LV stroke volume (r = 0.73; P < 0.05). Peak MA area occurred during middiastole, and 91 ± 7% of reduction in area from peak to minimum occurred before the onset of LV systole. The excursion of the MA accounts for an important portion of the total LV filling and emptying in humans. These data suggest an atriogenic influence on MA physiology and also a sphincter-like action of the MA that may facilitate ventricular filling and aid competent valve closure. This 4-D TEE method is the first to allow noninvasive measurement of AEV and may be used to investigate the impact of physiological and pathological conditions on this important aspect of LV performance.

No abstract available.

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics of pathophysiology that are otherwise difficult to obtain non-invasively in clinical practice.

Background: RFA is a well-established treatment for symptomatic patients with AF. However, the success rate of a single procedure is low. We aimed to investigate the association between the risk of recurrence of atrial fibrillation (AF) after a single radiofrequency ablation (RFA) procedure and cardiac neurohormonal function, left atrial (LA) mechanical function as well as proteins related to inflammation, fibrosis, and apoptosis. Methods and Results: We studied 189 patients undergoing RFA between January 2012 and April 2014, with a follow-up period of 12 months. A logistic regression analysis was performed to investigate the association between pre-ablation LA emptying fraction (LAEF), MR-proANP, Caspase-8 (CASP8), Neurotrophin-3 (NT3), and the risk for recurrence of AF after a single RFA procedure. 119 (63.0%) patients had a recurrence during a mean follow-up of 402 +/- 73 days. An increased risk of recurrence was associated with: Elevated MR-proANP (fourth quartile vs. first quartile: HR, 2.80 (95% CI, 1.14-6.90]; P = 0.025); Low LAEF (fourth quartile vs. first quartile: hazard ratio [HR], 2.41 [95% CI, 1.01-5.79]; P = 0.045); Elevated CASP8 (fourth quartile vs. first quartile: HR 12.198 95% CI 2.216-67.129; P = 0.004); Elevated NT-3 (fourth quartile vs. first quartile: HR 7.485 95% CI 1.353-41.402; P = 0.021). In a receiver operating characteristic curve analysis, the combination of MR-proANP, CASP8, and NT3 produced an area under the curve of 0.819; CI 95% (0.710-0.928). Conclusions: Patients with better LA mechanical function and lower levels of atrial neurohormones as well as of proteins related to fibrosis and apoptosis, have a better outcome after an RFA procedure.

Purpose: Hemodynamic atlases can add to the pathophysiological understanding of cardiac diseases. This study proposes a method to create hemodynamic atlases using 4D Flow magnetic resonance imaging (MRI). The method is demonstrated for kinetic energy (KE) and helicity density (Hd). Materials and Methods: Thirteen healthy subjects underwent 4D Flow MRI at 3T. Phase-contrast magnetic resonance cardioangiographies (PC-MRCAs) and an average heart were created and segmented. The PC-MRCAs, KE, and Hd were nonrigidly registered to the average heart to create atlases. The method was compared with 1) rigid, 2) affine registration of the PC-MRCAs, and 3) affine registration of segmentations. The peak and mean KE and Hd before and after registration were calculated to evaluate interpolation error due to nonrigid registration. Results: The segmentations deformed using nonrigid registration overlapped (median: 92.3%) more than rigid (23.1%, P amp;lt; 0.001), and affine registration of PC-MRCAs (38.5%, P amp;lt; 0.001) and affine registration of segmentations (61.5%, P amp;lt; 0.001). The peak KE was 4.9 mJ using the proposed method and affine registration of segmentations (P50.91), 3.5 mJ using rigid registration (P amp;lt; 0.001), and 4.2 mJ using affine registration of the PC-MRCAs (P amp;lt; 0.001). The mean KE was 1.1 mJ using the proposed method, 0.8 mJ using rigid registration (P amp;lt; 0.001), 0.9 mJ using affine registration of the PC-MRCAs (P amp;lt; 0.001), and 1.0 mJ using affine registration of segmentations (P50.028). The interpolation error was 5.262.6% at mid-systole, 2.863.8% at early diastole for peak KE; 9.669.3% at mid-systole, 4.064.6% at early diastole, and 4.964.6% at late diastole for peak Hd. The mean KE and Hd were not affected by interpolation. Conclusion: Hemodynamic atlases can be obtained with minimal user interaction using nonrigid registration of 4D Flow MRI. Level of Evidence: 2 Technical Efficacy: Stage 1

Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR) enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored. Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2-3 h (Time-1) and 4 weeks (Time-2) following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed. Results: From Time-1 to Time-2: Heart rate decreased (61 +/- 7 vs. 56 +/- 8 bpm, p = 0.01); Maximum change in left atrial volume increased (8 +/- 4 vs. 22 +/- 15%, p = 0.009); The duration of stasis (68 +/- 11 vs. 57 +/- 8%, p = 0.002) and the volume of stasis (14 +/- 9 vs. 9 +/- 7%, p = 0.04) decreased; Thrombin-antithrombin complex (TAT) decreased (5.2 +/- 3.3 vs. 3.3 +/- 2.2it.g/L, p = 0.008). A significant correlation was found between TAT and the volume of stasis (r(2) = 0.69, p amp;lt; 0.001) at Time-1 and between TAT and the duration of stasis (r(2) = 0.34, p = 0.04) at Time-2. Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation related atrial stunning.

Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

The right ventricle has an important role in cardiovascular disease. However, because of the complex geometry and the sensitivity to the respiratory cycle, imaging of the right ventricle is challenging. We investigated whether 3D cine phase-contrast MRI can provide data with sufficient accuracy for visualizations of the 4D blood flow in the right ventricle. Whole-heart 4D flow measurements with optimized imaging parameters and post-processing tools were made in healthy volunteers. Pathlines emitted from the right atrium could be traced through the right ventricle to the pulmonary artery without leaving the blood pool and thereby met our criteria for sufficient accuracy.

Purpose: Mitral regurgitation creates a high velocity jet into the left atrium (LA), contributing both volume andpressure; we hypothesized that the severity of regurgitation would be reflected in the degree of LA flowdistortion.

Material and Methods: Three-dimensional cine PC-MRI was applied to determine LA flow patterns andturbulent kinetic energy (TKE) in seven subjects (five patients with posterior mitral leaflet prolapse, two normalsubjects). In addition, the regurgitant volume and the time-velocity profiles in the pulmonary veins weremeasured.

Results: The LA flow in the mitral regurgitation patients was highly disturbed with elevated values of TKE.Peak TKE occurred consistently at late systole. The total LA TKE was closely related to the regurgitant volume.LA flow patterns were characterized by a pronounced vortex in proximity to the regurgitant jet. In some patients,pronounced discordances were observed between individual pulmonary venous inflows, but these could not berelated to the direction of the flow jet or parameters describing global LA hemodynamics.

Conclusion: PC-MRI permits investigations of atrial and pulmonary vein flow patterns and TKE in significantmitral regurgitation, reflecting the impact of the highly disturbed blood flow that accompanies this importantvalve disease.

Blood flow throughout the cardiovascular system is driven by pressure differences generated by the contraction and relaxation of the heart, where blood accelerates from high to low pressure areas. Absolute intracardiac pressure cannot be measured noninvasively, but relative pressure can be calculated. The aim of this study was to assess the spatial heterogeneity of the 4D relative pressure fields in the human left ventricle (LV).

Twelve healthy subjects underwent MRI examination where 4D flow as well as morphological data were acquired. The morphological data were segmented, and the segmentation used as boundary condition when computing relative pressure fields from the pressure Poisson equation using a multi grid solver. The LV lumen was divided according to a seventeen segment model in order to assess spatial heterogeneity and present the extensive amount of data in a comprehensive manner.

The basal anteroseptal segment shows a significantly lower median pressure than the opposite basal inferolateral segment during both early and late diastolic filling (p<0.0005 and p=0.0024, respectively). Along the long axis, the relative pressure in the apical segments are significantly higher relative to the basal segments (p<0.0005) along both the anteroseptal and inferolateral sides at and after the peaks of E-wave and A-wave.

During diastole the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences can also be found in the short-axis direction, and may also reflect important aspects of atrioventricular coupling.

Purpose: To assess the spatial heterogeneity of the four-dimensional (4D) relative pressure fields in the healthy human left ventricle (LV) and provide reference data for normal LV relative pressure. Methods: Twelve healthy subjects underwent a cardiac MRI examination where 4D flow and morphological data were acquired. The latter data were segmented and used to define the borders of the LV for computation of relative pressure fields using the pressure Poisson equation. The LV lumen was divided into 17 pie-shaped segments. Results: In the normal left ventricle, the relative pressure in the apical segments was significantly higher relative to the basal segments (P &lt; 0.0005) along both the anteroseptal and inferolateral sides after the peaks of early (E-wave) and late (A-wave) diastolic filling. The basal anteroseptal segment showed significantly lower median pressure than the opposite basal inferolateral segment during both E-wave (P &lt; 0.0005) and A-wave (P = 0.0024). Conclusion: Relative pressure in the left ventricle is heterogeneous. During diastole, the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences were also found in the short axis direction and may reflect important aspects of atrioventricular coupling. Additionally, this study provides reference data on LV pressure dynamics for a group of healthy subjects. (C) 2014 Wiley Periodicals, Inc.

Aims : Patients with mild heart failure (HF) who are clinically compensated may have normal left ventricular (LV) stroke volume (SV). Despite this, altered intra-ventricular flow patterns have been recognized in these subjects. We hypothesized that, compared with normal LVs, flow in myopathic LVs would demonstrate a smaller proportion of inflow volume passing directly to ejection and diminished the end-diastolic preservation of the inflow kinetic energy (KE).

Methods and results : In 10 patients with dilated cardiomyopathy (DCM) (49 ± 14 years, six females) and 10 healthy subjects (44 ± 17 years, four females), four-dimensional MRI velocity and morphological data were acquired. A previously validated method was used to separate the LV end-diastolic volume (EDV) into four flow components based on the blood's locations at the beginning and end of the cardiac cycle. KE was calculated over the cardiac cycle for each component. The EDV was larger (P = 0.021) and the ejection fraction smaller (P < 0.001) in DCM compared with healthy subjects; the SV was equivalent (DCM: 77 ± 19, healthy: 79 ± 16 mL). The proportion of the total LV inflow that passed directly to ejection was smaller in DCM (P = 0.000), but the end-diastolic KE/mL of the direct flow was not different in the two groups (NS).

Conclusion : Despite equivalent LVSVs, HF patients with mild LV remodelling demonstrate altered diastolic flow routes through the LV and impaired preservation of inflow KE at pre-systole compared with healthy subjects. These unique flow-specific changes in the flow route and energetics are detectable despite clinical compensation, and may prove useful as subclinical markers of LV dysfunction.

Background: The beating heart is the generator of blood flow through the cardiovascular system. Within the hearts own chambers, normal complex blood flow patterns can be disturbed by diseases. Methods for the quantification of intra-cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to develop and validate a novel semi-automatic analysis approach that integrates flow and morphological data. Method: In six healthy subjects and three patients with dilated cardiomyopathy, three-directional, three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) velocity data and balanced steady-state free-precession long- and short-axis images were acquired. The LV endocardium was segmented from the short-axis images at the times of isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards and backwards in time until IVR, thus including the entire cardiac cycle. The IVR volume was used to determine if and where the pathlines left the LV. This information was used to automatically separate the pathlines into four different components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and Residual Volume. Blood volumes were calculated for every component by multiplying the number of pathlines with the blood volume represented by each pathline. The accuracy and inter- and intra-observer reproducibility of the approach were evaluated by analyzing volumes of LV inflow and outflow, the four flow components, and the end-diastolic volume. Results: The volume and distribution of the LV flow components were determined in all subjects. The calculated LV outflow volumes [ml] (67 +/- 13) appeared to fall in between those obtained by through-plane phase-contrast CMR (77 +/- 16) and Doppler ultrasound (58 +/- 10), respectively. Calculated volumes of LV inflow (68 +/- 11) and outflow (67 +/- 13) were well matched (NS). Low inter- and intra-observer variability for the assessment of the volumes of the flow components was obtained. Conclusions: This semi-automatic analysis approach for the quantification of 4D blood flow resulted in accurate LV inflow and outflow volumes and a high reproducibility for the assessment of LV flow components.

Intracardiac blood flow patterns are potentially important to cardiac pumping efficiency. However, these complex flow patterns remain incompletely characterized both in health and disease. We hypothesized that normal left ventricular (LV) blood flow patterns would preferentially optimize a portion of the end-diastolic volume (LVEDV) for effective and rapid systolic ejection by virtue of location near and motion towards the LV outflow tract (LVOT). Three-dimensional cine velocity and morphological data were acquired in 12 healthy persons and 1 patient with dilated cardiomyopathy using MRI. A previously validated method was used for analysis in which the LVEDV was separated into four functional flow components based on the bloods locations at the beginning and end of the cardiac cycle. Each components volume, kinetic energy (KE), site, direction, and linear momentum relative to the LVOT were calculated. Of the four components, the LV inflow that passes directly to outflow in a single cardiac cycle (Direct Flow) had the largest volume. At the time of isovolumic contraction, Direct Flow had the greatest amount of KE and the most favorable combination of distance, angle, and linear momentum relative to the LVOT. Atrial contraction boosted the late diastolic KE of the ejected components. We conclude that normal diastolic LV flow creates favorable conditions for ensuing ejection, defined by proximity and energetics, for the Direct Flow, and that atrial contraction augments the end-diastolic KE of the ejection volume. The correlation of Direct Flow characteristics with ejection efficiency might be a relevant investigative target in cardiac failure.

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

[No abstract available]

Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 +/- 0.3 mJ) than the other flow components (P andlt; 0.001 and P andlt; 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P andlt; 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.

PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.

CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling.

Materials and Methods: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. Assessment: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC).

Results: The higher PR fraction group had more remodeled RVs (140 6 25 vs. 107 6 22 [lower PR fraction, P < 0.01] and 93 6 15 ml/m2[healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 6 3.15 vs. 2.23 6 0.81 [lower PR fraction, P < 0.01] and 1.91 6 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R25 0.47, P 5 0.002).

Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair.

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

PurposeAssessment of blood flow in the left ventricle using four-dimensional flow MRI requires accurate left ventricle segmentation that is often hampered by the low contrast between blood and the myocardium. The purpose of this work is to improve left-ventricular segmentation in four-dimensional flow MRI for reliable blood flow analysis. MethodThe left ventricle segmentations are first obtained using morphological cine-MRI with better in-plane resolution and contrast, and then aligned to four-dimensional flow MRI data. This alignment is, however, not trivial due to inter-slice misalignment errors caused by patient motion and respiratory drift during breath-hold based cine-MRI acquisition. A robust image registration based framework is proposed to mitigate such errors automatically. Data from 20 subjects, including healthy volunteers and patients, was used to evaluate its geometric accuracy and impact on blood flow analysis. ResultsHigh spatial correspondence was observed between manually and automatically aligned segmentations, and the improvements in alignment compared to uncorrected segmentations were significant (Pamp;lt;0.01). Blood flow analysis from manual and automatically corrected segmentations did not differ significantly (Pamp;gt;0.05). ConclusionOur results demonstrate the efficacy of the proposed approach in improving left-ventricular segmentation in four-dimensional flow MRI, and its potential for reliable blood flow analysis. Magn Reson Med 79:554-560, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 +/- 3.0 y.o.) and 20 old normal males (70.9 +/- 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3-19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 +/- 1.8 mJ, old = 6.4 +/- 2.4 mJ, p amp;lt; 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.

Itoh A, Stephens EH, Ennis DB, Carlhall CJ, Bothe W, Nguyen TC, Swanson JC, Miller DC, Ingels NB Jr. Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation. Am J Physiol Heart Circ Physiol 302: H180-H187, 2012. First published October 28, 2011; doi:10.1152/ajpheart.00687.2011.-Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.

Background: Atrial fibrillation (AF) is a prevalent cause of cardiovascular morbidity, including thromboembolism and heart failure. Left ventricular dysfunction (LVD) detected in AF patients may be either precursor or consequence of the arrythmia. Successful cardioversion of chronic AF is often followed by a transient period of left atrial (LA) stunning, where depressed mechanical atrial contraction persists despite reinstitution of sinus rhythm. To determine if AF-associated LVD would improve with resolution of LA dysfunction, AF patients were examined immediately and 4 weeks after cardioversion to sinus rhythm. 4D flow cardiovascular magnetic resonance (CMR) assesses ventricular function according to the volumes and energetics of functional components of the LV volume. Previously, described 4D CMR markers of LVD include decreased volume and end-diastolic kinetic energy (KE) of the Direct flow, which is the portion of LV volume that passes directly from inflow to outflow in a single cycle. We hypothesize that impaired LV flow patterns and energetics will be found immediately after cardioversion during atrial stunning, and that those parameters will improve as atrial function returns. Methods: Ten patients with a history of AF underwent CMR 2-3 h (Time-1) and 4 weeks (time-2), following electrical cardioversion to sinus rhythm. 4D phase-contrast velocity data and morphological images were acquired at a 3T CMR system. Using a previously evaluated method, pathlines were emitted from the LV end diastolic volume (LVEDV) and traced forward and backward in time until end-systole. The LVEDV was automatically separated into four functional flow components whose volume and KE were calculated. Results: Left atrial fractional area change increased over the follow-up period (P = 0.001), indicating recovery of LA mechanical function. LVEF increased between Time-1 and Time-2 (P = 0.003); LVEDVI did not change (P = 0.319). Over that interval, the ratios of Direct flow/LVEDV volume and KE increased (P = 0.001 and P = 0.003, respectively), while the ratios of Residual volume/LVEDV volume and KE decreased (P = 0.001 and P = 0.005, respectively). Conclusion: Post-cardioversion recovery of LA function was associated with improvements in conventional and 4D CMR markers of LV function. Flow-specific measures demonstrate the negative but potentially reversible impact of LA dysfunction on volume and energetic aspects of LV function.

Rapid early diastolic left ventricular (LV) filling requires a highly compliant chamber immediately after systole, allowing inflow at low driving pressures. The transmural LV deformations associated with such filling are not completely understood. We sought to characterize regional transmural LV strains during diastole, with focus on early filling, in ovine hearts at 1 week and 8 weeks after myocardial marker implantation. In seven normal sheep hearts, 13 radiopaque markers were inserted to silhouette the LV chamber and a transmural beadset was implanted into the lateral equatorial LV wall to measure transmural strains. Four-dimensional marker dynamics were obtained 1 week and 8 weeks thereafter with biplane videofluoroscopy in closed-chest, anesthetized animals. LV transmural strains in both cardiac and fiber-sheet coordinates were studied from filling onset to the end of early filling (EOEF, 100 ms after filling onset) and at end diastole. At the 8 week study, subepicardial circumferential strain (E-CC) had reached its final value already at EOEF, while longitudinal and radial strains were nearly zero at this time. Subepicardial E-CC and fiber relengthening (E-ff) at EOEF were reduced to 1 compared with 8 weeks after surgery (E-CC:0.02 +/- 0.01 to 0.08 +/- 0.02 and E-ff:0.00 +/- 0.01 to 0.03 +/- 0.01, respectively, both P < 0.05). Subepicardial E-CC during early LV filling was associated primarily with fiber-normal and sheet-normal shears at the 1 week study, but to all three fiber-sheet shears and fiber relengthening at the 8 week study. These changes in LV subepicardial mechanics provide a possible mechanistic basis for regional myocardial lusitropic function, and may add to our understanding of LV myocardial diastolic dysfunction.

Background: Diffuse myocardial fibrosis is associated with adverse outcomes, although detection and quantification is challenging. Cardiac MR relaxation times mapping represents a promising imaging biomarker for diffuse myocardial fibrosis. Purpose: To investigate whether relaxation times can detect longitudinal changes in myocardial tissue composition associated with diffuse fibrosis in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). Study type: Prospective longitudinal study. Population/Subjects/Phantom/Specimen/Animal Model: Fifteen patients with severe AS. Field Strength/Sequence: 3T /3(3) 3(3) 5-MOLLI, T2-GraSE, and 3D-QALAS. Assessment: Patients underwent MR examinations at three timepoints: before AVR, as well as 3 and 12 months after AVR. Data from each patient was analyzed in 16 myocardial segments. Statistical Tests: The segment-wise T1 and T2 data were analyzed over time after surgery using linear mixed models for repeated measures analysis. Results: The results showed that T1 relaxation times were significantly (Pamp;lt; 0.05) shorter 3 and 12 months postoperative than preoperative and that the T2 relaxation times were significantly (Pamp;lt; 0.05) longer 3 and 12 months postoperative than preoperative for both 3D and 2D mapping methods. No significant changes were seen between 3 and 12 months postoperative for any of the methods (P50.06/0.19 for T1 with 3D-QALAS/MOLLI and P50.09/0.25 for T2 with 3DQALAS/ GraSE). Data Conclusion: We demonstrated that changes in myocardial relaxation times and thus tissue characteristics can be observed within 3 months after AVR surgery. The significant changes in relaxation times from preoperative examinations to the follow-up may be interpreted as a reduction of interstitial fibrosis in the left ventricular wall. Level of Evidence: 1 Technical Efficacy: Stage 3