Muscle fiber strain rates in the lower leg during ankle dorsi-/plantarflexion exercise.

Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase-contrast MRI (PC-MRI), where strain rates are quantified. However, current two-dimensional implementations are limited in capturing the complex motion of contracting muscle in the context of its three-dimensional (3D) fiber architecture. The MR acquisitions (chemical shift-encoded water-fat separation scan, spin echo-echoplanar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) wereperformed at 3 T. PC-MRI acquisitions and performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Acquisitions (3 T, chemical shift-encoded water-fat separation scan, spin echo-echo planar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) were performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Strain rates and diffusion tensors were calculated and combined to obtain strain rates along and perpendicular to the muscle fibers in seven lower leg muscles during the dynamic dorsi-/plantarflexion movement cycle. To evaluate strain rates along the proximodistal muscle axis, muscles were divided into five equal segments. t-tests were used to test if cyclic strain rate patterns (amplitude > 0) were present along and perpendicular to the muscle fibers. The effects of proximal-distal location and load were evaluated using repeated measures ANOVAs. Cyclic temporal strain rate patterns along and perpendicular to the fiber were found in all muscles involved in dorsi-/plantarflexion movement (p < 0.0017). Strain rates along and perpendicular to the fiber were heterogeneously distributed over the length of most muscles (p < 0.003). Additional loading reduced strain rates of the extensor digitorum longus and gastrocnemius lateralis muscle (p < 0.001). In conclusion, the lower leg muscles involved in cyclic dorsi-/plantarflexion exercise showed cyclic fiber strain rate patterns with amplitudes that varied between muscles and between the proximodistal segments within the majority of muscles.

Evaluating a Phase-Specific Approach to Aortic Flow: A 4D Flow MRI Study.

BACKGROUND: Aortic flow parameters can be quantified using 4D flow MRI. However, data are sparse on how different methods of analysis influence these parameters and how these parameters evolve during systole. PURPOSE: To assess multiphase segmentations and multiphase quantification of flow-related parameters in aortic 4D flow MRI. STUDY TYPE: Prospective. POPULATION: 40 healthy volunteers (50% male, 28.9 ± 5.0 years) and 10 patients with thoracic aortic aneurysm (80% male, 54 ± 8 years). FIELD STRENGTH/SEQUENCE: 4D flow MRI with a velocity encoded turbo field echo sequence at 3 T. ASSESSMENT: Phase-specific segmentations were obtained for the aortic root and the ascending aorta. The whole aorta was segmented in peak systole. In all aortic segments, time to peak (TTP; for flow velocity, vorticity, helicity, kinetic energy, and viscous energy loss) and peak and time-averaged values (for velocity and vorticity) were calculated. STATISTICAL TESTS: Static vs. phase-specific models were assessed using Bland-Altman plots. Other analyses were performed using phase-specific segmentations for aortic root and ascending aorta. TTP for all parameters was compared to TTP of flow rate using paired t-tests. Time-averaged and peak values were assessed using Pearson correlation coefficient. P < 0.05 was considered statistically significant. RESULTS: In the combined group, velocity in static vs. phase-specific segmentations differed by 0.8 cm/sec for the aortic root, and 0.1 cm/sec (P = 0.214) for the ascending aorta. Vorticity differed by 167 sec-1 mL-1 (P = 0.468) for the aortic root, and by 59 sec-1 mL-1 (P = 0.481) for the ascending aorta. Vorticity, helicity, and energy loss in the ascending aorta, aortic arch, and descending aorta peaked significantly later than flow rate. Time-averaged velocity and vorticity values correlated significantly in all segments. DATA CONCLUSION: Static 4D flow MRI segmentation yields comparable results as multiphase segmentation for flow-related parameters, eliminating the need for time-consuming multiple segmentations. However, multiphase quantification is necessary for assessing peak values of aortic flow-related parameters. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Echo planar imaging-induced errors in intracardiac 4D flow MRI quantification.

PURPOSE: To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE). METHODS: Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume. RESULTS: In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were ≤5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 ± 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow. CONCLUSIONS: Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (≤10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers.

4D flow cardiovascular magnetic resonance derived energetics in the Fontan circulation correlate with exercise capacity and CMR-derived liver fibrosis/congestion.

AIM: This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise capacity and CMR-derived liver fibrosis/congestion. BACKGROUND: The Fontan circulation, in which both caval veins are directly connected with the pulmonary arteries (i.e. the TCPC) is the palliative approach for single ventricle patients. Blood flow efficiency in the TCPC has been associated with exercise capacity and liver fibrosis using computational fluid dynamic modelling. 4D flow CMR allows for assessment of in vivo blood flow energetics, including kinetic energy (KE) and viscous energy loss rate (EL). METHODS: Fontan patients were prospectively evaluated between 2018 and 2021 using a comprehensive cardiovascular and liver CMR protocol, including 4D flow imaging of the TCPC. Peak oxygen consumption (VO2) was determined using cardiopulmonary exercise testing (CPET). Iron-corrected whole liver T1 (cT1) mapping was performed as a marker of liver fibrosis/congestion. KE and EL in the TCPC were computed from 4D flow CMR and normalized for inflow. Furthermore, blood flow energetics were compared between standardized segments of the TCPC. RESULTS: Sixty-two Fontan patients were included (53% male, 17.3 ± 5.1 years). Maximal effort CPET was obtained in 50 patients (peak VO2 27.1 ± 6.2 ml/kg/min, 56 ± 12% of predicted). Both KE and EL in the entire TCPC (n = 28) were significantly correlated with cT1 (r = 0.50, p = 0.006 and r = 0.39, p = 0.04, respectively), peak VO2 (r = - 0.61, p = 0.003 and r = - 0.54, p = 0.009, respectively) and % predicted peak VO2 (r = - 0.44, p = 0.04 and r = - 0.46, p = 0.03, respectively). Segmental analysis indicated that the most adverse flow energetics were found in the Fontan tunnel and left pulmonary artery. CONCLUSIONS: Adverse 4D flow CMR derived KE and EL in the TCPC correlate with decreased exercise capacity and increased levels of liver fibrosis/congestion. 4D flow CMR is promising as a non-invasive screening tool for identification of patients with adverse TCPC flow efficiency.

Reproducibility of Aorta Segmentation on 4D Flow MRI in Healthy Volunteers.

BACKGROUND: Hemodynamic aorta parameters can be derived from 4D flow MRI, but this requires lumen segmentation. In both commercially available and research 4D flow MRI software tools, lumen segmentation is mostly (semi-)automatically performed and subsequently manually improved by an observer. Since the segmentation variability, together with 4D flow MRI data and image processing algorithms, will contribute to the reproducibility of patient-specific flow properties, the observer's lumen segmentation reproducibility and repeatability needs to be assessed. PURPOSE: To determine the interexamination, interobserver reproducibility, and intraobserver repeatability of aortic lumen segmentation on 4D flow MRI. STUDY TYPE: Prospective and retrospective. POPULATION: A healthy volunteer cohort of 10 subjects who underwent 4D flow MRI twice. Also, a clinical cohort of six subjects who underwent 4D flow MRI once. FIELD STRENGTH/SEQUENCE: 3T; time-resolved three-directional and 3D velocity-encoded sequence (4D flow MRI). ASSESSMENT: The thoracic aorta was segmented on the 4D flow MRI in five systolic phases. By positioning six planes perpendicular to a segmentation's centerline, the aorta was divided into five segments. The volume, surface area, centerline length, maximal diameter, and curvature radius were determined for each segment. STATISTICAL TESTS: To assess the reproducibility, the coefficient of variation (COV), Pearson correlation coefficient (r), and intraclass correlation coefficient (ICC) were calculated. RESULTS: The interexamination and interobserver reproducibility and intraobserver repeatability were comparable for each parameter. For both cohorts there was very good reproducibility and repeatability for volume, surface area, and centerline length (COV = 10-32%, r = 0.54-0.95 and ICC = 0.65-0.99), excellent reproducibility and repeatability for maximal diameter (COV = 3-11%, r = 0.94-0.99, ICC = 0.94-0.99), and good reproducibility and repeatability for curvature radius (COV = 25-62%, r = 0.73-0.95, ICC = 0.84-0.97). DATA CONCLUSION: This study demonstrated no major reproducibility and repeatability limitations for 4D flow MRI aortic lumen segmentation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Assessment of left ventricular mechanical dyssynchrony in left bundle branch block canine model: Comparison between cine and tagged MRI.

PURPOSE: To compare cine and tagged magnetic resonance imaging (MRI) for left ventricular dyssynchrony assessment in left bundle branch block (LBBB), using the time-to-peak contraction timing, and a novel approach based on cross-correlation. MATERIALS AND METHODS: We evaluated a canine model dataset (n = 10) before (pre-LBBB) and after induction of isolated LBBB (post-LBBB). Multislice short-axis tagged and cine MRI images were acquired using a 1.5 T scanner. We computed contraction time maps by cross-correlation, based on the timing of radial wall motion and of circumferential strain. Finally, we estimated dyssynchrony as the standard deviation of the contraction time over the different regions of the myocardium. RESULTS: Induction of LBBB resulted in a significant increase in dyssynchrony (cine: 13.0 ± 3.9 msec for pre-LBBB, and 26.4 ± 5.0 msec for post-LBBB, P = 0.005; tagged: 17.1 ± 5.0 msec at for pre-LBBB, and 27.9 ± 9.8 msec for post-LBBB, P = 0.007). Dyssynchrony assessed by cine and tagged MRI were in agreement (r = 0.73, P = 0.0003); differences were in the order of time difference between successive frames of 20 msec (bias: -2.9 msec; limit of agreement: 10.1 msec). Contraction time maps were derived; agreement was found in the contraction patterns derived from cine and tagged MRI (mean difference in contraction time per segment: 3.6 ± 13.7 msec). CONCLUSION: This study shows that the proposed method is able to quantify dyssynchrony after induced LBBB in an animal model. Cine-assessed dyssynchrony agreed with tagged-derived dyssynchrony, in terms of magnitude and spatial direction. J. MAGN. RESON. IMAGING 2016;44:956-963.

Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography.

BACKGROUND: The aim of this study is to investigate the inter and intra-rater reliability, repeatability, and reproducibility of pulmonary transit time (PTT) measurement in patients using contrast enhanced ultrasound (CEUS), as an indirect measure of preload and left ventricular function. METHODS: Mean transit times (MTT) were measured by drawing a region of interest (ROI) in right and left cardiac ventricle in the CEUS loops. Acoustic intensity dilution curves were obtained from the ROIs. MTTs were calculated by applying model-based fitting on the dilution curves. PTT was calculated as the difference of the MTTs. Eight raters with different levels of experience measured the PTT (time moment 1) and repeated the measurement within a week (time moment 2). Reliability and agreement were assessed using intra-class correlations (ICC) and Bland-Altman analysis. Repeatability was tested by estimating the variance of means (ANOVA) of three injections in each patient at different doses. Reproducibility was tested by the ICC of the two time moments. RESULTS: Fifteen patients with heart failure were included. The mean PTT was 11.8 ± 3.1 s at time moment 1 and 11.7 ± 2.9 s at time moment 2. The inter-rater reliability for PTT was excellent (ICC = 0.94). The intra-rater reliability per rater was between 0.81-0.99. Bland-Altman analysis revealed a bias of 0.10 s within the rater groups. Reproducibility for PTT showed an ICC = 0.94 between the two time moments. ANOVA showed no significant difference between the means of the three different doses F = 0.048 (P = 0.95). The mean and standard deviation for PTT estimates at three different doses was 11.6 ± 3.3 s. CONCLUSIONS: PTT estimation using CEUS shows a high inter- and intra-rater reliability, repeatability at three different doses, and reproducibility by ROI drawing. This makes the minimally invasive PTT measurement using contrast echocardiography ready for clinical evaluation in patients with heart failure and for preload estimation.

Volume quantification by contrast-enhanced ultrasound: an in-vitro comparison with true volumes and thermodilution.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has recently been proposed as a minimally- invasive, alternative method for blood volume measurement. This study aims at comparing the accuracy of CEUS and the classical thermodilution techniques for volume assessment in an in-vitro set-up. METHODS: The in-vitro set-up consisted of a variable network between an inflow and outflow tube and a roller pump. The inflow and outflow tubes were insonified with an ultrasound array transducer and a thermistor was placed in each tube. Indicator dilution curves were made by injecting indicator which consisted of an ultrasound-contrast-agent diluted in ice-cold saline. Both acoustic intensity- and thermo-dilution curves were used to calculate the indicator mean transit time between the inflow and outflow tube. The volumes were derived by multiplying the estimated mean transit time by the flow rate. We compared the volumes measured by CEUS with the true volumes of the variable network and those measured by thermodilution by Bland-Altman and intraclass-correlation analysis. RESULTS: The measurements by CEUS and thermodilution showed a very strong correlation (rs = 0.94) with a modest volume underestimation by CEUS of -40 ± 28 mL and an overestimation of 84 ± 62 mL by thermodilution compared with the true volumes. Both CEUS and thermodilution showed a high statistically significant correlation with the true volume (rs = 0.97 (95% CI, 0.95 - 0.98; P<0.0001) and rs = 0.96 (95% CI, 0.94 - 0.98; P<0.0001, respectively). CONCLUSIONS: CEUS volume estimation provides a strong correlation with both the true volumes in-vitro and volume estimation by thermodilution. It may therefore represent an interesting alternative to the standard, invasive thermodilution technique.

Clinical intra-cardiac 4D flow CMR: acquisition, analysis, and clinical applications.

Identification of flow patterns within the heart has long been recognized as a potential contribution to the understanding of physiological and pathophysiological processes of cardiovascular diseases. Although the pulsatile flow itself is multi-dimensional and multi-directional, current available non-invasive imaging modalities in clinical practice provide calculation of flow in only 1-direction and lack 3-dimensional volumetric velocity information. Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) has emerged as a novel tool that enables comprehensive and critical assessment of flow through encoding velocity in all 3 directions in a volume of interest resolved over time. Following technical developments, 4D flow CMR is not only capable of visualization and quantification of conventional flow parameters such as mean/peak velocity and stroke volume but also provides new hemodynamic parameters such as kinetic energy. As a result, 4D flow CMR is being extensively exploited in clinical research aiming to improve understanding of the impact of cardiovascular disease on flow and vice versa. Of note, the analysis of 4D flow data is still complex and accurate analysis tools that deliver comparable quantification of 4D flow values are a necessity for a more widespread adoption in clinic. In this article, the acquisition and analysis processes are summarized and clinical applications of 4D flow CMR on the heart including conventional and novel hemodynamic parameters are discussed. Finally, clinical potential of other emerging intra-cardiac 4D flow imaging modalities is explored and a near-future perspective on 4D flow CMR is provided.

Segmental assessment of blood flow efficiency in the total cavopulmonary connection using four-dimensional flow magnetic resonance imaging: vortical flow is associated with increased viscous energy loss rate.

Aims: To study flow-related energetics in multiple anatomical segments of the total cavopulmonary connection (TCPC) in Fontan patients from four-dimensional (4D) flow magnetic resonance imaging (MRI), and to study the relationship between adverse flow patterns and segment-specific energetics. Methods and results: Twenty-six extracardiac Fontan patients underwent 4D flow MRI of the TCPC. A segmentation of the TCPC was automatically divided into five anatomical segments [conduit, superior vena cava (SVC), right/left pulmonary artery (LPA), and the Fontan confluence]. The presence of vortical flow in the pulmonary arteries or Fontan confluence was qualitatively scored. Kinetic energy (KE), viscous energy loss rate, and vorticity were calculated from the 4D flow MRI velocity field and normalized for segment length and/or inflow. Energetics were compared between segments and the relationship between vortical flow and segment cross-sectional area (CSA) with segment-specific energetics was determined. Vortical flow in the LPA (n = 6) and Fontan confluence (n = 12) were associated with significantly higher vorticity (P = 0.001 and P = 0.015, respectively) and viscous energy loss rate (P = 0.046 and P = 0.04, respectively) compared to patients without vortical flow. The LPA and conduit segments showed the highest KE and viscous energy loss rate, while most favourable energetics were observed in the SVC. Conduit CSA inversely correlated with KE (r = -0.614, P = 0.019) and viscous energy loss rate (r = -0.652, P = 0.011). Conclusions: Vortical flow in the Fontan confluence and LPA associated with significantly increased viscous energy loss rate. Four-dimensional flow MRI-derived energetics may be used as a screening tool for direct, MRI-based assessment of flow efficiency in the TCPC.

Non-uniform mixing of hepatic venous flow and inferior vena cava flow in the Fontan conduit.

Fontan patients require a balanced hepatic blood flow distribution (HFD) to prevent pulmonary arteriovenous malformations. Currently, HFD is quantified by tracking Fontan conduit flow, assuming hepatic venous (HV) flow to be uniformly distributed within the Fontan conduit. However, this assumption may be unvalid leading to inaccuracies in HFD quantification with potential clinical impact. The aim of this study was to (i) assess the mixing of HV flow and inferior vena caval (IVC) flow within the Fontan conduit and (ii) quantify HFD by directly tracking HV flow and quantitatively comparing results with the conventional approach. Patient-specific, time-resolved computational fluid dynamic models of 15 total cavopulmonary connections were generated, including the HV and subhepatic IVC. Mixing of HV and IVC flow, on a scale between 0 (no mixing) and 1 (perfect mixing), was assessed at the caudal and cranial Fontan conduit. HFD was quantified by tracking particles from the caudal (HFDcaudal conduit) and cranial (HFDcranial conduit) conduit and from the hepatic veins (HFDHV). HV flow was non-uniformly distributed at both the caudal (mean mixing 0.66 ± 0.13) and cranial (mean 0.79 ± 0.11) level within the Fontan conduit. On a cohort level, differences in HFD between methods were significant but small; HFDHV (51.0 ± 20.6%) versus HFDcaudal conduit (48.2 ± 21.9%, p = 0.033) or HFDcranial conduit (48.0 ± 21.9%, p = 0.044). However, individual absolute differences of 8.2-14.9% in HFD were observed in 4/15 patients. HV flow is non-uniformly distributed within the Fontan conduit. Substantial individual inaccuracies in HFD quantification were observed in a subset of patients with potential clinical impact.

Characterization of Ascending Aortic Flow in Patients With Degenerative Aneurysms: A 4D Flow Magnetic Resonance Study.

OBJECTIVES: Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than 55 mm, although many patients with small aneurysms show only mild growth rates and more than half of complications occur in aneurysms below this threshold. Thus, assessment of hemodynamics using 4-dimensional flow magnetic resonance has been of interest to obtain more insights in aneurysm development. Nonetheless, the role of aberrant flow patterns in TAA patients is not yet fully understood. MATERIALS AND METHODS: A total of 25 TAA patients and 22 controls underwent time-resolved 3-dimensional phase contrast magnetic resonance imaging with 3-directional velocity encoding (ie, 4-dimensional flow magnetic resonance imaging). Hemodynamic parameters such as vorticity, helicity, and wall shear stress (WSS) were calculated from velocity data in 3 anatomical segments of the ascending aorta (root, proximal, and distal). Regional WSS distribution was assessed for the full cardiac cycle. RESULTS: Flow vorticity and helicity were significantly lower for TAA patients in all segments. The proximal ascending aorta showed a significant increase in peak WSS in the outer curvature in TAA patients, whereas WSS values at the inner curvature were significantly lower as compared with controls. Furthermore, positive WSS gradients from sinotubular junction to midascending aorta were most prominent in the outer curvature, whereas from midascending aorta to brachiocephalic trunk, the outer curvature showed negative WSS gradients in the TAA group. Controls solely showed a positive gradient at the inner curvature for both segments. CONCLUSIONS: Degenerative TAA patients show a decrease in flow vorticity and helicity, which is likely to cause perturbations in physiological flow patterns. The subsequent differing distribution of WSS might be a contributor to vessel wall remodeling and aneurysm formation.

Reduced scan time and superior image quality with 3D flow MRI compared to 4D flow MRI for hemodynamic evaluation of the Fontan pathway.

Long scan times prohibit a widespread clinical applicability of 4D flow MRI in Fontan patients. As pulsatility in the Fontan pathway is minimal during the cardiac cycle, acquiring non-ECG gated 3D flow MRI may result in a reduction of scan time while accurately obtaining time-averaged clinical parameters in comparison with 2D and 4D flow MRI. Thirty-two Fontan patients prospectively underwent 2D (reference), 3D and 4D flow MRI of the Fontan pathway. Multiple clinical parameters were assessed from time-averaged flow rates, including the right-to-left pulmonary flow distribution (main endpoint) and systemic-to-pulmonary collateral flow (SPCF). A ten-fold reduction in scan time was achieved [4D flow 15.9 min (SD 2.7 min) and 3D flow 1.6 min (SD 7.8 s), p < 0.001] with a superior signal-to-noise ratio [mean ratio of SNRs 1.7 (0.8), p < 0.001] and vessel sharpness [mean ratio 1.2 (0.4), p = 0.01] with 3D flow. Compared to 2D flow, good-excellent agreement was shown for mean flow rates (ICC 0.82-0.96) and right-to-left pulmonary flow distribution (ICC 0.97). SPCF derived from 3D flow showed good agreement with that from 4D flow (ICC 0.86). 3D flow MRI allows for obtaining time-averaged flow rates and derived clinical parameters in the Fontan pathway with good-excellent agreement with 2D and 4D flow, but with a tenfold reduction in scan time and significantly improved image quality compared to 4D flow.

Publisher Correction: Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy.

Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia. Yet, noninvasive evaluation of their efficacy has been lagging behind. Here, we report the development and longitudinal application of multiparametric cardiac magnetic resonance imaging (MRI) to evaluate a hydrogel-based cardiac regenerative therapy. A pH-switchable hydrogel was loaded with slow releasing insulin growth factor 1 and vascular endothelial growth factor, followed by intramyocardial injection in a mouse model of ischemia reperfusion injury. Longitudinal cardiac MRI assessed three hallmarks of cardiac regeneration: angiogenesis, resolution of fibrosis and (re)muscularization after infarction. The multiparametric approach contained dynamic contrast enhanced MRI that measured improved vessel features by assessing fractional blood volume and permeability*surface area product, T1-mapping that displayed reduced fibrosis, and tagging MRI that showed improved regional myocardial strain in hydrogel treated infarcts. Finally, standard volumetric MRI demonstrated improved left ventricular functioning in hydrogel treated mice followed over time. Histology confirmed MR-based vessel features and fibrotic measurements. Our novel triple-marker strategy enabled detection of ameliorated regeneration in hydrogel treated hearts highlighting the translational potential of these longitudinal MRI approaches.

Endocardial center motion for quantification of left ventricular discoordination in heart failure using cine MRI.

OBJECTIVE: To compare a novel cardiovascular magnetic resonance technique for the assessment of left ventricular (LV) mechanical discoordination by characterizing the endocardial center motion (ECM) in short-axis cine MRI in healthy volunteers and heart failure patients with left bundle branch block (HF-LBBB). APPROACH: To evaluate ECM analysis as mechanical discoordination measure, we retrospectively compared spatial and temporal features of the ECM between a group of healthy volunteers (n = 14) and conduction defect patients (HF-LBBB, n = 31). We tracked the center of the endocardial borders on short-axis view MRI cine loops during the cardiac cycle. From the ECM trajectory we calculated the overall traveled distance, the enclosed area, the eccentricity of the trajectory, and the maximum traveled distance. The ECM can be visualized in spatial coordinates as well as by its temporal behavior. We evaluated the classification performance of these measures for LBBB detection. We also quantified the coherence of the ECM on the longitudinal direction by considering the variability of the ECM measures between different short-axis slices. MAIN RESULTS: Patients with LBBB showed significantly higher traveled distance (p < 0.0001), enclosed area (p < 0.002), eccentricity (p < 0.02), and peak displacement (p < 0.02) of the endocardial center. Patients with positive late gadolinium enhancement showed a higher variability of ECM measures across different slices (p < 0.05). SIGNIFICANCE: ECM analysis is feasible and it allows the assessment of left ventricular mechanical discoordination. Differences in ECM measures permit one to distinguish between LBBB and healthy volunteers.

Comparison of cardiac magnetic resonance imaging and bio-impedance spectroscopy for the assessment of fluid displacement induced by external leg compression.

Heart failure is marked by frequent hospital admissions, often as a consequence of pulmonary congestion. Current gold standard techniques for thoracic fluid measurement require invasive heamodynamic access and therefore they are not suitable for continuous monitoring. Changes in thoracic impedance (TI) may enable non-invasive early detection of congestion and prevention of unplanned hospitalizations. However, the usefulness of TI to assess thoracic fluid status is limited by inter-subject variability and by the lack of reliable normalization methods. Indicator dilution methods allow absolute fluid volume estimation; cardiac magnetic resonance (CMR) has been recently proposed to apply indicator dilution methods in a minimally-invasive manner. In this study, we aim to compare bio-impedance spectroscopy (BIS) and CMR for the assessment of thoracic fluid status, and to determine their ability to detect fluid displacement induced by a leg compression procedure in healthy volunteers. A pressure gradient was applied across each subject's legs for 5 min (100-60 mmHg, distal to proximal). Each subject underwent a continuous TI-BIS measurement during the procedure, and repeated CMR-based indicator dilution measurements on a 1.5 T scanner at baseline, during compression, and after pressure release. The Cole-Cole and the local density random walk models were used for parameter extraction from TI-BIS and indicator dilution measurements, respectively. Intra-thoracic blood volume index (ITBI) derived from CMR, and extracellular fluid resistance (R E) from TI-BIS, were considered as thoracic fluid status measures. Eight healthy volunteers were included in this study. An increase in ITBI of 45.2 ± 47.2 ml m-2 was observed after the leg inflation (13.1 ± 15.1% w.r.t. baseline, p < 0.05), while a decrease of -0.84 ± 0.39 Ω in R E (-1.7 ± 0.9% w.r.t. baseline, p < 0.05) was observed. ITBV and R E normalized by body mass index were strongly inversely correlated (r = -0.93, p < 0.05). In conclusion, an acute fluid displacement to the thoracic circulation was induced in healthy volunteers. Significant changes were observed in the considered thoracic fluid measures derived from BIS and CMR. Good correlation was observed between the two measurement techniques. Further clinical studies will be necessary to prospectively evaluate the value of a combination of the two techniques for prediction of re-hospitalizations after admission for heart failure.

SPASM: a 3D-ASM for segmentation of sparse and arbitrarily oriented cardiac MRI data.

A new technique (SPASM) based on a 3D-ASM is presented for automatic segmentation of cardiac MRI image data sets consisting of multiple planes with arbitrary orientations, and with large undersampled regions. Model landmark positions are updated in a two-stage iterative process. First, landmark positions close to intersections with images are updated. Second, the update information is propagated to the regions without image information, such that new locations for the whole set of the model landmarks are obtained. Feature point detection is performed by a fuzzy inference system, based on fuzzy C-means clustering. Model parameters were optimized on a computer cluster and the computational load distributed by grid computing. SPASM was applied to image data sets with an increasing sparsity (from 2 to 11 slices) comprising images with different orientations and stemming from different MRI acquisition protocols. Segmentation outcomes and calculated volumes were compared to manual segmentation on a dense short-axis data configuration in a 3D manner. For all data configurations, (sub-)pixel accuracy was achieved. Performance differences between data configurations were significantly different (p<0.05) for SA data sets with less than 6 slices, but not clinically relevant (volume differences<4 ml). Comparison to results from other 3D model-based methods showed that SPASM performs comparable to or better than these other methods, but SPASM uses considerably less image data. Sensitivity to initial model placement proved to be limited within a range of position perturbations of approximately 20 mm in all directions.