Retained Metabolic Flexibility of the Failing Human Heart.

BACKGROUND: The failing heart is traditionally described as metabolically inflexible and oxygen starved, causing energetic deficit and contractile dysfunction. Current metabolic modulator therapies aim to increase glucose oxidation to increase oxygen efficiency of adenosine triphosphate production, with mixed results. METHODS: To investigate metabolic flexibility and oxygen delivery in the failing heart, 20 patients with nonischemic heart failure with reduced ejection fraction (left ventricular ejection fraction 34.9±9.1) underwent separate infusions of insulin+glucose infusion (I+G) or Intralipid infusion. We used cardiovascular magnetic resonance to assess cardiac function and measured energetics using phosphorus-31 magnetic resonance spectroscopy. To investigate the effects of these infusions on cardiac substrate use, function, and myocardial oxygen uptake (MVo2), invasive arteriovenous sampling and pressure-volume loops were performed (n=9). RESULTS: At rest, we found that the heart had considerable metabolic flexibility. During I+G, cardiac glucose uptake and oxidation were predominant (70±14% total energy substrate for adenosine triphosphate production versus 17±16% for Intralipid; P=0.002); however, no change in cardiac function was seen relative to basal conditions. In contrast, during Intralipid infusion, cardiac long-chain fatty acid (LCFA) delivery, uptake, LCFA acylcarnitine production, and fatty acid oxidation were all increased (LCFA 73±17% of total substrate versus 19±26% total during I+G; P=0.009). Myocardial energetics were better with Intralipid compared with I+G (phosphocreatine/adenosine triphosphate 1.86±0.25 versus 2.01±0.33; P=0.02), and systolic and diastolic function were improved (LVEF 34.9±9.1 baseline, 33.7±8.2 I+G, 39.9±9.3 Intralipid; P<0.001). During increased cardiac workload, LCFA uptake and oxidation were again increased during both infusions. There was no evidence of systolic dysfunction or lactate efflux at 65% maximal heart rate, suggesting that a metabolic switch to fat did not cause clinically meaningful ischemic metabolism. CONCLUSIONS: Our findings show that even in nonischemic heart failure with reduced ejection fraction with severely impaired systolic function, significant cardiac metabolic flexibility is retained, including the ability to alter substrate use to match both arterial supply and changes in workload. Increasing LCFA uptake and oxidation is associated with improved myocardial energetics and contractility. Together, these findings challenge aspects of the rationale underlying existing metabolic therapies for heart failure and suggest that strategies promoting fatty acid oxidation may form the basis for future therapies.

Tricuspid valve flow measurement using a deep learning framework for automated valve-tracking 2D phase contrast.

PURPOSE: Tricuspid valve flow velocities are challenging to measure with cardiovascular MR, as the rapidly moving valvular plane prohibits direct flow evaluation, but they are vitally important to diastolic function evaluation. We developed an automated valve-tracking 2D method for measuring flow through the dynamic tricuspid valve. METHODS: Nine healthy subjects and 2 patients were imaged. The approach uses a previously trained deep learning network, TVnet, to automatically track the tricuspid valve plane from long-axis cine images. Subsequently, the tracking information is used to acquire 2D phase contrast (PC) with a dynamic (moving) acquisition plane that tracks the valve. Direct diastolic net flows evaluated from the dynamic PC sequence were compared with flows from 2D-PC scans acquired in a static slice localized at the end-systolic valve position, and also ventricular stroke volumes (SVs) using both planimetry and 2D PC of the great vessels. RESULTS: The mean tricuspid valve systolic excursion was 17.8 ± 2.5 mm. The 2D valve-tracking PC net diastolic flow showed excellent correlation with SV by right-ventricle planimetry (bias ± 1.96 SD = -0.2 ± 10.4 mL, intraclass correlation coefficient [ICC] = 0.92) and aortic PC (-1.0 ± 13.8 mL, ICC = 0.87). In comparison, static tricuspid valve 2D PC also showed a strong correlation but had greater bias (p = 0.01) versus the right-ventricle SV (10.6 ± 16.1 mL, ICC = 0.61). In most (8 of 9) healthy subjects, trace regurgitation was measured at begin-systole. In one patient, valve-tracking PC displayed a high-velocity jet (380 cm/s) with maximal velocity agreeing with echocardiography. CONCLUSION: Automated valve-tracking 2D PC is a feasible route toward evaluation of tricuspid regurgitant velocities, potentially solving a major clinical challenge.

Automatic Segmentation of the Fetus in 3D Magnetic Resonance Images Using Deep Learning: Accurate and Fast Fetal Volume Quantification for Clinical Use.

Magnetic resonance imaging (MRI) provides images for estimating fetal volume and weight, but manual delineations are time consuming. The aims were to (1) validate an algorithm to automatically quantify fetal volume by MRI; (2) compare fetal weight by Hadlock's formulas to that of MRI; and (3) quantify fetal blood flow and index flow to fetal weight by MRI. Forty-two fetuses at 36 (29-39) weeks gestation underwent MRI. A neural network was trained to segment the fetus, with 20 datasets for training and validation, and 22 for testing. Hadlock's formulas 1-4 with biometric parameters from MRI were compared with weight by MRI. Blood flow was measured using phase-contrast MRI and indexed to fetal weight. Bland-Altman analysis assessed the agreement between automatic and manual fetal segmentation and the agreement between Hadlock's formulas and fetal segmentation for fetal weight. Bias and 95% limits of agreement were for automatic versus manual measurements 4.5 ± 351 ml (0.01% ± 11%), and for Hadlock 1-4 vs MRI 108 ± 435 g (3% ± 14%), 211 ± 468 g (7% ± 15%), 106 ± 425 g (4% ± 14%), and 179 ± 472 g (6% ± 15%), respectively. Umbilical venous flow was 406 (range 151-650) ml/min (indexed 162 (range 52-220) ml/min/kg), and descending aortic flow was 763 (range 481-1160) ml/min (indexed 276 (range 189-386) ml/min/kg). The automatic method showed good agreement with manual measurements and saves considerable analysis time. Hadlock 1-4 generally agree with MRI. This study also illustrates the confounding effects of fetal weight on absolute blood flow, and emphasizes the benefit of indexed measurements for physiological assessment.

Early-Onset Fetal Growth Restriction Increases Left Ventricular Sphericity in Adolescents Born Very Preterm.

Left ventricular shape alterations predict cardiovascular outcomes and have been observed in children born preterm and after fetal growth restriction (FGR). The aim was to investigate whether left ventricular shape is altered in adolescents born very preterm and if FGR has an additive effect. Adolescents born very preterm due to verified early-onset FGR and two control groups with birthweight appropriate for gestational age (AGA), born at similar gestational age and at term, respectively, underwent cardiac MRI. Principal component analysis was applied to find the modes of variation best explaining shape variability for end-diastole, end-systole, and for the combination of both, the latter indicative of function. Seventy adolescents were included (13-16 years; 49% males). Sphericity was increased for preterm FGR versus term AGA for end-diastole (36[0-60] vs - 42[- 82-8]; p = 0.01) and the combined analysis (27[- 23-94] vs - 51[- 119-11]; p = 0.01), as well as for preterm AGA versus term AGA for end-diastole (30[- 56-115] vs - 42[- 82-8]; p = 0.04), for end-systole (57[- 29-89] vs - 30[- 79-34]; p = 0.03), and the combined analysis (44[- 50-145] vs - 51[- 119-11]; p = 0.02). No group differences were observed for left ventricular mass or ejection fraction (all p ≥ 0.33). Sphericity was increased after very preterm birth and exacerbated by early-onset FGR, indicating an additive effect to that of very preterm birth on left ventricular remodeling. Increased sphericity may be a prognostic biomarker of future cardiovascular disease in this cohort that as of yet shows no signs of cardiac dysfunction using standard clinical measurements.

Super-Resolution Cine Image Enhancement for Fetal Cardiac Magnetic Resonance Imaging.

BACKGROUND: Fetal cardiac magnetic resonance imaging (MRI) improves the diagnosis of congenital heart defects, but is sensitive to fetal motion due to long image acquisition time. This may be overcome with faster image acquisition with low resolution, followed by image enhancement to provide clinically useful images. PURPOSE: To combine phase-encoding undersampling with super-resolution neural networks to achieve high-resolution fetal cine cardiac MR images with short acquisition time. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight fetuses (gestational week 36 [interquartile range 33-38 weeks]). FIELD STRENGTH/SEQUENCE: 1.5 T, balanced steady-state free precession (bSSFP) cine sequence. ASSESSMENT: Images were acquired using fully sampled Doppler ultrasound-gated clinical bSSFP cine as reference, with equivalent cine sequences with decreased phase-encoding resolution (25%, 33%, and 50% of clinical standard). Two super-resolution methods based on convolutional neural networks were proposed and evaluated (phasrGAN and phasrresnet). Data were partitioned into training (36 cine slices), validation (3 cine slices), and test sets (67 cine slices) without overlap. Conventional reconstruction methods using bicubic interpolation and k-space zeropadding were used for comparison. Three blinded observers scored image quality between 1 and 10. STATISTICAL TESTS: Image scores are reported as median [interquartile range] and were compared using Mann-Whitney's nonparametric test with P < 0.05 showing statistically significant differences. RESULTS: Both proposed methods showed no significant difference in image quality compared to clinical images (8 [7-8.5]) down to 33% (phasrGAN 8 [6.5-8]; phasrresnet 8 [7-8], all P ≥ 0.19) phase-encoding resolution, i.e., up to three times faster image acquisition, whereas bicubic interpolation and k-space zeropadding showed significantly lower quality for 33% phase-encoding resolution (both 7 [6-8]). DATA CONCLUSION: Super-resolution enhancement can be used for fetal cine cardiac MRI to reduce image acquisition time while maintaining image quality. This may lead to an improved success rate for fetal cine MR imaging, as the impact of fetal motion is lessened by shortened acquisitions. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Infarct quantification with cardiovascular magnetic resonance using "standard deviation from remote" is unreliable: validation in multi-centre multi-vendor data.

BACKGROUND: The objective of the study was to investigate variability and agreement of the commonly used image processing method "n-SD from remote" and in particular for quantifying myocardial infarction by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). LGE-CMR in tandem with the analysis method "n-SD from remote" represents the current reference standard for infarct quantification. This analytic method utilizes regions of interest (ROIs) and defines infarct as the tissue with a set number of standard deviations (SD) above the signal intensity of remote nulled myocardium. There is no consensus on what the set number of SD is supposed to be. Little is known about how size and location of ROIs and underlying signal properties in the LGE images affect results. Furthermore, the method is frequently used elsewhere in medical imaging often without careful validation. Therefore, the usage of the "n-SD" method warrants a thorough validation. METHODS: Data from 214 patients from two multi-center cardioprotection trials were included. Infarct size from different remote ROI positions, ROI size, and number of standard deviations ("n-SD") were compared with reference core lab delineations. RESULTS: Variability in infarct size caused by varying ROI position, ROI size, and "n-SD" was 47%, 48%, and 40%, respectively. The agreement between the "n-SD from remote" method and the reference infarct size by core lab delineations was low. Optimal "n-SD" threshold computed on a slice-by-slice basis showed high variability, n = 5.3 ± 2.2. CONCLUSION: The "n-SD from remote" method is unreliable for infarct quantification due to high variability which depends on different placement and size of remote ROI, number "n-SD", and image signal properties related to the CMR-scanner and sequence used. Therefore, the "n-SD from remote" method should not be used, instead methods validated against an independent standard are recommended.

Non-invasive quantification of pressure-volume loops in patients with Fontan circulation.

BACKGROUND: Pressure-volume (PV) loops provide comprehensive information of cardiac function, but commonly implies an invasive procedure under general anesthesia. A novel technique has made it possible to non-invasively estimate PV loops with cardiac magnetic resonance (CMR) and brachial pressure which would enable good volume estimation of often anatomically complex ventricles without the need of anesthesia in most cases. In this study we aimed to compare how hemodynamic parameters derived from PV loops in patients with Fontan circulation differ to controls. METHODS: Patients with Fontan circulation (n = 17, median age 12 years, IQR 6-15) and healthy controls (n = 17, 14 years, IQR 13-22) were examined with CMR. Short axis balanced steady-state free-precession cine images covering the entire heart were acquired. PV loops were derived from left ventricular volumes in all timeframes and brachial blood pressure from cuff sphygmomanometry. RESULTS: Fontan patients had lower stroke work, ventricular mechanical efficiency and external power compared to controls. Fontan patients with dominant right ventricle had higher potential energy indexed to body surface area but lower contractility (Ees) compared to controls. Fontan patients had higher arterial elastance (Ea) and Ea/Ees ratio than controls. Contractility showed no correlation with ejection fraction (EF) in Fontan patients irrespective of ventricular morphology. No difference was seen in energy per ejected volume between Fontan patients and controls. CONCLUSIONS: This non-invasive PV-loop method could be used in future studies to show the potential prognostic value of these measures and if changes in ventricular function over time can be detected earlier by this method compared to changes in ventricular volumes and EF. In contrast to patients with acquired heart failure, Fontan patients had similar energy per ejected volume as controls which suggests similar ventricular oxygen consumption to deliver the same volume in Fontan patients as in controls.

Pulse Wave Velocity Measurements by Magnetic Resonance Imaging in Neonates and Adolescents: Methodological Aspects and Their Clinical Implications.

Pulse wave velocity (PWV) by cardiovascular magnetic resonance (CMR) lacks standardization. The aim of this study was to investigate methodological aspects of PWV measurements by CMR in neonates and adolescents. A computer phantom was created to validate the temporal resolution required for accurate PWV. Fifteen neonates and 71 adolescents underwent CMR with reference standard 3D angiography and phase-contrast flow acquisitions, and in a subset coronal overview images. Velocity and flow curves, transit time methods (time-to-foot (TTF), maximum upslope, and time-to-peak (TTP)), and baseline correction methods (no correction, automatic and manual) were investigated. In neonates, required timeframes per cardiac cycle for accurate PWV was 42 for the aortic arch and 41 for the thoracic aorta. In adolescents, corresponding values were 39 and 32. Aortic length differences by overview images and 3D angiography in adolescents were - 16-18 mm (aortic arch) and - 25-30 mm (thoracic aorta). Agreement in PWV between automatic and manual baseline correction was - 0.2 ± 0.3 m/s in neonates and 0.0 ± 0.1 m/s in adolescents. Velocity and flow-derived PWV measurements did not differ in either group (all p > 0.08). In neonates, transit time methods did not differ (all p > 0.19) but in adolescents PWV was higher for TTF (3.8 ± 0.5 m/s) and maximum upslope (3.7 ± 0.6 m/s) compared to TTP (2.7 ± 1.0 m/s; p < 0.0001). This study is a step toward standardization of PWV in neonates and adolescents using CMR. It provides required temporal resolution for phase-contrast flow acquisitions for typical heartrates in neonates and adolescents, and supports 3D angiography and time-to-foot with automatic baseline correction for accurate PWV measurements.

MVnet: automated time-resolved tracking of the mitral valve plane in CMR long-axis cine images with residual neural networks: a multi-center, multi-vendor study.

BACKGROUND: Mitral annular plane systolic excursion (MAPSE) and left ventricular (LV) early diastolic velocity (e') are key metrics of systolic and diastolic function, but not often measured by cardiovascular magnetic resonance (CMR). Its derivation is possible with manual, precise annotation of the mitral valve (MV) insertion points along the cardiac cycle in both two and four-chamber long-axis cines, but this process is highly time-consuming, laborious, and prone to errors. A fully automated, consistent, fast, and accurate method for MV plane tracking is lacking. In this study, we propose MVnet, a deep learning approach for MV point localization and tracking capable of deriving such clinical metrics comparable to human expert-level performance, and validated it in a multi-vendor, multi-center clinical population. METHODS: The proposed pipeline first performs a coarse MV point annotation in a given cine accurately enough to apply an automated linear transformation task, which standardizes the size, cropping, resolution, and heart orientation, and second, tracks the MV points with high accuracy. The model was trained and evaluated on 38,854 cine images from 703 patients with diverse cardiovascular conditions, scanned on equipment from 3 main vendors, 16 centers, and 7 countries, and manually annotated by 10 observers. Agreement was assessed by the intra-class correlation coefficient (ICC) for both clinical metrics and by the distance error in the MV plane displacement. For inter-observer variability analysis, an additional pair of observers performed manual annotations in a randomly chosen set of 50 patients. RESULTS: MVnet achieved a fast segmentation (<1 s/cine) with excellent ICCs of 0.94 (MAPSE) and 0.93 (LV e') and a MV plane tracking error of -0.10 ± 0.97 mm. In a similar manner, the inter-observer variability analysis yielded ICCs of 0.95 and 0.89 and a tracking error of -0.15 ± 1.18 mm, respectively. CONCLUSION: A dual-stage deep learning approach for automated annotation of MV points for systolic and diastolic evaluation in CMR long-axis cine images was developed. The method is able to carefully track these points with high accuracy and in a timely manner. This will improve the feasibility of CMR methods which rely on valve tracking and increase their utility in a clinical setting.

Regional contributions to left ventricular stroke volume determined by cardiac magnetic resonance imaging in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) restores ventricular synchrony and induces left ventricular (LV) reverse remodeling in patients with heart failure (HF) and dyssynchrony. However, 30% of treated patients are non-responders despite all efforts. Cardiac magnetic resonance imaging (CMR) can be used to quantify regional contributions to stroke volume (SV) as potential CRT predictors. The aim of this study was to determine if LV longitudinal (SVlong%), lateral (SVlat%), and septal (SVsept%) contributions to SV differ from healthy controls and investigate if these parameters can predict CRT response. METHODS: Sixty-five patients (19 women, 67 ± 9 years) with symptomatic HF (LVEF ≤ 35%) and broadened QRS (≥ 120 ms) underwent CMR. SVlong% was calculated as the volume encompassed by the atrioventricular plane displacement (AVPD) from end diastole (ED) to end systole (ES) divided by total SV. SVlat%, and SVsept% were calculated as the volume encompassed by radial contraction from ED to ES. Twenty age- and sex-matched healthy volunteers were used as controls. The regional measures were compared to outcome response defined as ≥ 15% decrease in echocardiographic LV end-systolic volume (LVESV) from pre- to 6-months post CRT (delta, Δ). RESULTS: AVPD and SVlong% were lower in patients compared to controls (8.3 ± 3.2 mm vs 15.3 ± 1.6 mm, P < 0.001; and 53 ± 18% vs 64 ± 8%, P < 0.01). SVsept% was lower (0 ± 15% vs 10 ± 4%, P < 0.01) with a higher SVlat% in the patient group (42 ± 16% vs 29 ± 7%, P < 0.01). There were no differences between responders and non-responders in neither SVlong% (P = 0.87), SVlat% (P = 0.09), nor SVsept% (P = 0.65). In patients with septal net motion towards the right ventricle (n = 28) ΔLVESV was - 18 ± 22% and with septal net motion towards the LV (n = 37) ΔLVESV was - 19 ± 23% (P = 0.96). CONCLUSIONS: Longitudinal function, expressed as AVPD and longitudinal contribution to SV, is decreased in patients with HF scheduled for CRT. A larger lateral contribution to SV compensates for the abnormal septal systolic net movement. However, LV reverse remodeling could not be predicted by these regional contributors to SV.

Automated left atrial time-resolved segmentation in MRI long-axis cine images using active contours.

BACKGROUND: Segmentation of the left atrium (LA) is required to evaluate atrial size and function, which are important imaging biomarkers for a wide range of cardiovascular conditions, such as atrial fibrillation, stroke, and diastolic dysfunction. LA segmentations are currently being performed manually, which is time-consuming and observer-dependent. METHODS: This study presents an automated image processing algorithm for time-resolved LA segmentation in cardiac magnetic resonance imaging (MRI) long-axis cine images of the 2-chamber (2ch) and 4-chamber (4ch) views using active contours. The proposed algorithm combines mitral valve tracking, automated threshold calculation, edge detection on a radially resampled image, edge tracking based on Dijkstra's algorithm, and post-processing involving smoothing and interpolation. The algorithm was evaluated in 37 patients diagnosed mainly with paroxysmal atrial fibrillation. Segmentation accuracy was assessed using the Dice similarity coefficient (DSC) and Hausdorff distance (HD), with manual segmentations in all time frames as the reference standard. For inter-observer variability analysis, a second observer performed manual segmentations at end-diastole and end-systole on all subjects. RESULTS: The proposed automated method achieved high performance in segmenting the LA in long-axis cine sequences, with a DSC of 0.96 for 2ch and 0.95 for 4ch, and an HD of 5.5 mm for 2ch and 6.4 mm for 4ch. The manual inter-observer variability analysis had an average DSC of 0.95 and an average HD of 4.9 mm. CONCLUSION: The proposed automated method achieved performance on par with human experts analyzing MRI images for evaluation of atrial size and function. Video Abstract.

Free-breathing fetal cardiac MRI with doppler ultrasound gating, compressed sensing, and motion compensation.

BACKGROUND: Fetal cardiovascular MRI complements ultrasound to assess fetal cardiovascular pathophysiology. PURPOSE: To develop a free-breathing method for retrospective fetal cine MRI using Doppler ultrasound (DUS) cardiac gating and tiny golden angle radial sampling (tyGRASP) for accelerated acquisition capable of detecting fetal movements for motion compensation. STUDY TYPE: Feasibility study. SUBJECTS: Nine volunteers (gestational week 34-40). Short-axis and four-chamber views were acquired during maternal free-breathing and breath-hold. FIELD STRENGTH/SEQUENCE: 1.5T cine balanced steady-state free precession. ASSESSMENT: A self-gated reconstruction method was improved for clinical application by using 1) retrospective DUS gating, and 2) motion detection and rejection/correction algorithms for compensating for fetal motion. The free-breathing reconstructions were qualitatively and quantitatively assessed, and DUS-gating was compared with self-gating in breath-hold reconstructions. A scoring of 1-4 for overall image quality, cardiac, and extracardiac diagnostic quality was used. STATISTICAL TESTS: Friedman's test was used to assess differences in qualitative scoring between observers. A Wilcoxon matched-pairs signed rank test was used to assess differences between breath-hold and free-breathing acquisitions and between observers' quantitative measurements. RESULTS: In all cases, 111 free-breathing and 145 breath-hold acquisitions, the automatically calculated DUS-based cardiac gating signal provided reconstructions of diagnostic quality (median score 4, range 1-4). Free-breathing did not affect the DUS-based cardiac gated retrospective radial reconstruction with respect to image or diagnostic quality (all P > 0.06). Motion detection with rejection/correction in k-space produced high-quality free-breathing DUS-based reconstructions [median 3, range (2-4)], whereas free-breathing self-gated methods failed in 80 out of 88 cases to produce a stable gating signal. DATA CONCLUSION: Free-breathing fetal cine cardiac MRI based on DUS gating and tyGRASP with motion compensation yields diagnostic images. This simplifies acquisition for the pregnant woman and thus could help increase fetal cardiac MRI acceptance in the clinic. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:260-272.

Valvular imaging in the era of feature-tracking: A slice-following cardiac MR sequence to measure mitral flow.

BACKGROUND: In mitral valve dysfunction, noninvasive measurement of transmitral blood flow is an important clinical examination. Flow imaging of the mitral valve, however, is challenging, since it moves in and out of the image plane during the cardiac cycle. PURPOSE: To more accurately measure mitral flow, a slice-following MRI phase contrast sequence is proposed. This study aimed to implement such a sequence, validate its slice-following functionality in a phantom and healthy subjects, and test its feasibility in patients with mitral valve dysfunction. STUDY TYPE: Prospective. PHANTOM AND SUBJECTS: The slice-following functionality was validated in a cone-shaped phantom by measuring the depicted slice radius. Sixteen healthy subjects and 10 mitral valve dysfunction patients were enrolled at two sites. FIELD STRENGTH/SEQUENCE: 1.5T and 3T gradient echo cine phase contrast. ASSESSMENT: A single breath-hold retrospectively gated sequence using offline feature-tracking of the mitral valve was developed. Valve displacements were measured and imported to the scanner, allowing the slice position to change dynamically based on the cardiac phase. Mitral valve imaging was performed with slice-following and static imaging planes. Validation was performed by comparing mitral stroke volume with planimetric and aortic stroke volume. STATISTICAL TESTS: Measurements were compared using linear regression, Pearson's R, parametric paired t-tests, Bland-Altman analysis, and intraclass correlation coefficient (ICC). RESULTS: Phantom experiments confirmed accurate slice displacements. Slice-following was feasible in all subjects, yielding physiologically accurate mitral flow patterns. In healthy subjects, mitral and aortic stroke volumes agreed, with ICC = 0.72 and 0.90 for static and slice-following planes; with bias ±1 SDs 23.2 ± 13.2 mls and 8.4 ± 10.8 mls, respectively. Agreement with planimetry was stronger, with ICC = 0.84 and 0.96; bias ±1 SDs 13.7 ± 13.7 mls and -2.0 ± 8.8 mls for static and slice-following planes, respectively. DATA CONCLUSION: Slice-following outperformed the conventional sequence and improved the accuracy of transmitral flow, which is important for assessment of diastolic function and mitral regurgitation. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1412-1421.

Evolution of left ventricular function among subjects with ST-elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: Atrioventricular plane displacement (AVPD) reflects longitudinal left ventricular (LV) systolic function, and wall thickening (WT) regional radial LV function. The temporal evolution of these measures after STEMI with CMR has not been evaluated. We aimed to investigate how AVPD and WT are affected globally and regionally from the sub-acute to the chronic phase after ST-elevation myocardial infarction (STEMI). METHODS: Healthy volunteers without cardiovascular disease and medication (controls, n = 20) and patients from the CHILL-MI study ( NCT01379261 ) prospectively underwent magnetic resonance imaging (MRI) 2-6 days and 6 months after STEMI (n = 77). CHILL-MI randomized STEMI-patients to cooling therapy initiated before reperfusion or standard of care. AVPD was measured at six points in three long axis cine images and wall thickening in short axis cine images. Infarction was quantified using late gadolinium enhancement (LGE) and used to define infarct and remote segments. RESULTS: There were no difference in AVPD either at acute or chronic phase (p = 0.90 and p = 0.40) or WT (p = 0.85 and p = 0.99) between patients randomized to cooling therapy and standard of care. Therefore, the results are presented for the pooled cohort. Global AVPD was decreased in both the sub-acute (12 ± 2 mm, p < 0.001) and the chronic phase (13 ± 2 mm, p < 0.001) compared to controls (15 ± 2 mm) with a partial recovery of AVPD (p < 0.001) in the chronic phase. Patients with left anterior descending (LAD) and right coronary artery (RCA) infarcts had decreased AVPD in the chronic phase in both infarcted and remote segments. Mean WT was decreased in patients with LAD infarction both in the sub-acute and the chronic phase in both infarcted and remote segments. The decrease in WT in patients with RCA and left circumflex (LCx) infarcts was more affected in the infarcted segments, especially in the chronic phase. CONCLUSION: AVPD was a global rather than regional marker of cardiac function in this STEMI study and this may explain the prognostic importance of local measurements of mitral annular plane systolic excursion (MAPSE). The decrease in WT in remote myocardium even in the chronic phase needs to be taken into consideration when combining functional measurements with infarct quantification for diagnosis of post-ischemic stunning and hibernation.

Independent validation of metric optimized gating for fetal cardiovascular phase-contrast flow imaging.

PURPOSE: To validate metric optimized gating phase-contrast MR (MOG PC-MR) flow measurements for a range of fetal flow velocities in phantom experiments. 2) To investigate intra- and interobserver variability for fetal flow measurements at an imaging center other than the original site. METHODS: MOG PC-MR was compared to timer/beaker measurements in a pulsatile flow phantom using a heart rate (∼145 bpm), nozzle diameter (∼6 mm), and flow range (∼130-700 mL/min) similar to fetal imaging. Fifteen healthy fetuses were included for intra- and interobserver variability in the fetal descending aorta and umbilical vein. RESULTS: Phantom MOG PC-MR flow bias and variability was 2% ± 23%. Accuracy of MOG PC-MR was degraded for flow profiles with low velocity-to-noise ratio. Intra- and interobserver coefficients of variation were 6% and 19%, respectively, for fetal descending aorta; and 10% and 17%, respectively, for the umbilical vein. CONCLUSION: Phantom validation showed good agreement between MOG and conventionally gated PC-MR, except for cases with low velocity-to-noise ratio, which resulted in MOG misgating and underestimated peak velocities and warranted optimization of sequence parameters to individual fetal vessels. Inter- and intraobserver variability for fetal MOG PC-MR imaging were comparable to previously reported values.

Gender but not diabetes, hypertension or smoking affects infarct evolution in ST-elevation myocardial infarction patients - data from the CHILL-MI, MITOCARE and SOCCER trials.

BACKGROUND: Infarct evolution rate and response to acute reperfusion therapy may differ between patients, which is important to consider for accurate management and treatment of patients with ST-elevation myocardial infarction (STEMI). The aim of this study was therefore to investigate the association of infarct size and myocardial salvage with gender, smoking status, presence of diabetes or history of hypertension in a cohort of STEMI-patients. METHODS: Patients (n = 301) with first-time STEMI from the three recent multi-center trials (CHILL-MI, MITOCARE and SOCCER) underwent cardiac magnetic resonance (CMR) imaging to determine myocardium at risk (MaR) and infarct size (IS). Myocardial salvage index (MSI) was calculated as MSI = 1-IS/MaR. Pain to balloon time, culprit vessel, trial treatments, age, TIMI grade flow and collateral flow by Rentrop grading were included as explanatory variables in the statistical model. RESULTS: Women (n = 66) had significantly smaller MaR (mean difference: 5.0 ± 1.5% of left ventricle (LV), p < 0.01), smaller IS (mean difference: 5.1 ± 1.4% of LV, p = 0.03), and larger MSI (mean difference: 9.6 ± 2.8% of LV, p < 0.01) compared to men (n = 238). These differences remained significant when adjusting for other explanatory variables. There were no significant effects on MaR, IS or MSI for diabetes, hypertension or smoking. CONCLUSIONS: Female gender is associated with higher myocardial salvage and smaller infarct size suggesting a pathophysiological difference in infarct evolution between men and women.

Validation and reproducibility of cardiovascular 4D-flow MRI from two vendors using 2 × 2 parallel imaging acceleration in pulsatile flow phantom and in vivo with and without respiratory gating.

BACKGROUND: 4D-flow magnetic resonance imaging (MRI) is increasingly used. PURPOSE: To validate 4D-flow sequences in phantom and in vivo, comparing volume flow and kinetic energy (KE) head-to-head, with and without respiratory gating. MATERIAL AND METHODS: Achieva dStream (Philips Healthcare) and MAGNETOM Aera (Siemens Healthcare) 1.5-T scanners were used. Phantom validation measured pulsatile, three-dimensional flow with 4D-flow MRI and laser particle imaging velocimetry (PIV) as reference standard. Ten healthy participants underwent three cardiac MRI examinations each, consisting of cine-imaging, 2D-flow (aorta, pulmonary artery), and 2 × 2 accelerated 4D-flow with (Resp+) and without (Resp-) respiratory gating. Examinations were acquired consecutively on both scanners and one examination repeated within two weeks. Volume flow in the great vessels was compared between 2D- and 4D-flow. KE were calculated for all time phases and voxels in the left ventricle. RESULTS: Phantom results showed high accuracy and precision for both scanners. In vivo, higher accuracy and precision ( P < 0.001) was found for volume flow for the Aera prototype with Resp+ (-3.7 ± 10.4 mL, r = 0.89) compared to the Achieva product sequence (-17.8 ± 18.6 mL, r = 0.56). 4D-flow Resp- on Aera had somewhat larger bias (-9.3 ± 9.6 mL, r = 0.90) compared to Resp+ ( P = 0.005). KE measurements showed larger differences between scanners on the same day compared to the same scanner at different days. CONCLUSION: Sequence-specific in vivo validation of 4D-flow is needed before clinical use. 4D-flow with the Aera prototype sequence with a clinically acceptable acquisition time (<10 min) showed acceptable bias in healthy controls to be considered for clinical use. Intra-individual KE comparisons should use the same sequence.

Hemodynamic forces using four-dimensional flow MRI: an independent biomarker of cardiac function in heart failure with left ventricular dyssynchrony?

Patients with heart failure with left ventricular (LV) dyssynchrony often do not respond to cardiac resynchronization therapy (CRT), indicating that the pathophysiology is insufficiently understood. Intracardiac hemodynamic forces computed from four-dimensional (4-D) flow MRI have been proposed as a new measure of cardiac function. We therefore aimed to investigate how hemodynamic forces are altered in LV dyssynchrony. Thirty-one patients with heart failure and LV dyssynchrony and 39 control subjects underwent cardiac MRI with the acquisition of 4-D flow. Hemodynamic forces were computed using Navier-Stokes equations and integrated over the manually delineated LV volume. The ratio between transverse (lateral-septal and inferior-anterior) and longitudinal (apical-basal) forces was calculated for systole and diastole separately and compared with QRS duration, aortic valve opening delay, global longitudinal strain, and ejection fraction (EF). Patients exhibited hemodynamic force patterns that were significantly altered compared with control subjects, including loss of longitudinal forces in diastole (force ratio, control subjects vs. patients: 0.32 vs. 0.90, P < 0.0001) and increased transverse force magnitudes. The systolic force ratio was correlated with global longitudinal strain and EF ( P < 0.01). The diastolic force ratio separated patients from control subjects (area under the curve: 0.98, P < 0.0001) but was not correlated to other dyssynchrony measures ( P > 0.05 for all). Hemodynamic forces by 4-D flow represent a new approach to the quantification of LV dyssynchrony. Diastolic force patterns separate healthy from diseased ventricles. Different force patterns in patients indicate the possible use of force analysis for risk stratification and CRT implantation guidance. NEW & NOTEWORTHY In this report, we demonstrate that patients with heart failure with left ventricular dyssynchrony exhibit significantly altered hemodynamic forces compared with normal. Force patterns in patients mechanistically reflect left ventricular dysfunction on the organ level, largely independent of traditional dyssynchrony measures. Force analysis may help clinical decision making and could potentially be used to improve therapy outcomes.

Altered biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and right ventricular volume overload because of pulmonary regurgitation.

Intracardiac hemodynamic forces have been proposed to influence remodeling and be a marker of ventricular dysfunction. We aimed to quantify the hemodynamic forces in patients with repaired tetralogy of Fallot (rToF) to further understand the pathophysiological mechanisms as this could be a potential marker for pulmonary valve replacement (PVR) in these patients. Patients with rToF and pulmonary regurgitation (PR) > 20% ( n = 18) and healthy control subjects ( n = 15) underwent MRI, including four-dimensional flow. A subset of patients ( n = 8) underwent PVR and MRI after surgery. Time-resolved hemodynamic forces were quantified using 4D-flow data and indexed to ventricular volume. Patients had higher systolic and diastolic left ventricular (LV) hemodynamic forces compared with control subjects in the lateral-septal/LV outflow tract ( P = 0.011 and P = 0.0031) and inferior-anterior ( P < 0.0001 and P < 0.0001) directions, which are forces not aligned with blood flow. Forces did not change after PVR. Patients had higher RV diastolic forces compared with control subjects in the diaphragm-right ventricular (RV) outflow tract (RVOT; P < 0.001) and apical-basal ( P = 0.0017) directions. After PVR, RV systolic forces in the diaphragm-RVOT direction decreased ( P = 0.039) to lower levels than in control subjects ( P = 0.0064). RV diastolic forces decreased in all directions ( P = 0.0078, P = 0.0078, and P = 0.039) but were still higher than in control subjects in the diaphragm-RVOT direction ( P = 0.046). In conclusion, patients with rToF and PR had LV hemodynamic forces less aligned with intraventricular blood flow compared with control subjects and higher diastolic RV forces along the regurgitant flow direction in the RVOT and that of tricuspid inflow. Remaining force differences in the LV and RV after PVR suggest that biventricular pumping does not normalize after surgery. NEW & NOTEWORTHY Biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and pulmonary regurgitation were quantified for the first time. Left ventricular hemodynamic forces were less aligned to the main blood flow direction in patients compared with control subjects. Higher right ventricular forces were seen along the pulmonary regurgitant and tricuspid inflow directions. Differences in forces versus control subjects remain after pulmonary valve replacement, suggesting that altered biventricular pumping does not normalize after surgery.

Disturbed left and right ventricular kinetic energy in patients with repaired tetralogy of Fallot: pathophysiological insights using 4D-flow MRI.

OBJECTIVES: Indications for pulmonary valve replacement (PVR) in patients with pulmonary regurgitation (PR) after repaired tetralogy of Fallot (rToF) are debated. We aimed to compare right (RV) and left ventricular (LV) kinetic energy (KE) measured by 4D-flow magnetic resonance imaging (MRI) in patients to controls, to further understand the pathophysiological effects of PR. METHODS: Fifteen patients with rToF with PR > 20% and 14 controls underwent MRI. Ventricular volumes and KE were quantified from cine MRI and 4D-flow, respectively. Lagrangian coherent structures were used to discriminate KE in the PR. Restrictive RV physiology was defined as end-diastolic forward flow. RESULTS: LV systolic peak KE was lower in rToF, 2.8 ± 1.1 mJ, compared to healthy volunteers, 4.8 ± 1.1 mJ, p < 0.0001. RV diastolic peak KE was higher in rToF (7.7 ± 4.3 mJ vs 3.1 ± 1.3 mJ, p = 0.0001) and the difference most pronounced in patients with non-restrictive RV physiology. KE was primarily located in the PR volume at the time of diastolic peak KE, 64 ± 17%. CONCLUSION: This is the first study showing disturbed KE in patients with rToF and PR, in both the RV and LV. The role of KE as a potential early marker of ventricular dysfunction to guide intervention needs to be addressed in future studies. KEY POINTS: • Kinetic energy (KE) reflects ventricular performance • KE is a potential marker of ventricular dysfunction in Fallot patients • KE is disturbed in both ventricles in patients with tetralogy of Fallot • KE contributes to the understanding of the pathophysiology of pulmonary regurgitation • Lagrangian coherent structures enable differentiation of ventricular inflows.