Measurement of Abdominal Aortic Aneurysm Strain Using MR Deformable Image Registration: Accuracy and Relationship to Recent Aneurysm Progression.

BACKGROUND: Management of asymptomatic abdominal aortic aneurysm (AAA) based on maximum aneurysm diameter and growth rate fails to preempt many ruptures. Assessment of aortic wall biomechanical properties may improve assessment of progression and rupture risk. This study aimed to assess the accuracy of AAA wall strain measured by cine magnetic resonance imaging (MRI) deformable image registration (MR strain) and investigate its relationship with recent AAA progression. METHODS: The MR strain accuracy was evaluated in silico against ground truth strain in 54 synthetic MRIs generated from a finite element model simulation of an AAA patient's abdomen for different aortic pulse pressures, tissue motions, signal intensity variations, and image noise. Evaluation included bias with 95% confidence interval (CI) and correlation analysis. Association of MR strain with AAA growth rate was assessed in 25 consecutive patients with >6 months of prior surveillance, for whom cine balanced steady-state free-precession imaging was acquired at the level of the AAA as well as the proximal, normal-caliber aorta. Univariate and multivariate regressions were used to associate growth rate with clinical variables, maximum AAA diameter (Dmax), and peak circumferential MR strain through the cardiac cycle. The MR strain interoperator variability was assessed using bias with 95% CI, intraclass correlation coefficient, and coefficient of variation. RESULTS: In silico experiments revealed an MR strain bias of 0.48% ± 0.42% and a slope of correlation to ground truth strain of 0.963. In vivo, AAA MR strain (1.2% ± 0.6%) was highly reproducible (bias ± 95% CI, 0.03% ± 0.31%; intraclass correlation coefficient, 97.8%; coefficient of variation, 7.14%) and was lower than in the nonaneurysmal aorta (2.4% ± 1.7%). Dmax (ß = 0.087) and MR strain (ß= -1.563) were both associated with AAA growth rate. The MR strain remained an independent factor associated with growth rate (ß= -0.904) after controlling for Dmax. CONCLUSIONS: Deformable image registration analysis can accurately measure the circumferential strain of the AAA wall from standard cine MRI and may offer patient-specific insight regarding AAA progression.

Unilateral cerebral arterial tortuosity: Associated with aneurysm occurrence, but potentially inversely associated with aneurysm rupture.

PURPOSE: To investigate the association of tortuosity of the main cerebral arteries with intracranial aneurysm (IA) occurrence and rupture. To investigate the relationship between arterial tortuosity and aneurysm morphology as well as conventional risk factors of vascular diseases. METHODS: Three subject groups were analyzed in this study: Patients with ruptured IAs, patients with unruptured IAs, and healthy subjects. The groups were matched by sex and age using tendency score matching. Their intracranial magnetic resonance angiography (MRA) images were collected retrospectively. The intracranial arterial structures were segmented from the MRA images. Arterial tortuosity was measured and statistically compared between the different subject groups and different vessels. Correlation analysis was conducted between arterial tortuosity and clinical risk factors as well as aneurysm morphology. RESULTS: 120 patients were included in the study (average age: 67.5 years; 60% female), 40 for each group after matching. The tortuosity of the aneurysm-bearing artery was significantly greater than that of the contralateral artery in both the ruptured and unruptured IA groups (p < 0.001). There was no significant association between clinical risk factors (history of hypertension, hyperlipidemia, diabetes, smoking, and alcohol use) and arterial tortuosity. There were significant negative correlations between aneurysm-bearing artery tortuosity and aneurysm morphological features such as maximal diameter (p = 0.0011), neck diameter (p < 0.0001), maximum height (p = 0.0024), and size ratio (p = 0.0269). CONCLUSION: The occurrence of cerebral aneurysms correlates to increased unilateral arterial tortuosity, but the risk of aneurysm enlargement/rupturing decreases with greater arterial tortuosity. Abnormal tortuosity may be congenital as tortuosity has no clear connection with acquired common risk factors of vascular diseases.

Contrast-enhanced CT radiomics improves the prediction of abdominal aortic aneurysm progression.

OBJECTIVES: To determine if three-dimensional (3D) radiomic features of contrast-enhanced CT (CECT) images improve prediction of rapid abdominal aortic aneurysm (AAA) growth. METHODS: This longitudinal cohort study retrospectively analyzed 195 consecutive patients (mean age, 72.4 years ± 9.1) with a baseline CECT and a subsequent CT or MR at least 6 months later. 3D radiomic features were measured for 3 regions of the AAA, viz. the vessel lumen only; the intraluminal thrombus (ILT) and aortic wall only; and the entire AAA sac (lumen, ILT, and wall). Multiple machine learning (ML) models to predict rapid growth, defined as the upper tercile of observed growth (> 0.25 cm/year), were developed using data from 60% of the patients. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) in the remaining 40% of patients. RESULTS: The median AAA maximum diameter was 3.9 cm (interquartile range [IQR], 3.3-4.4 cm) at baseline and 4.4 cm (IQR, 3.7-5.4 cm) at the mean follow-up time of 3.2 ± 2.4 years (range, 0.5-9 years). A logistic regression model using 7 radiomic features of the ILT and wall had the highest AUC (0.83; 95% confidence interval [CI], 0.73-0.88) in the development cohort. In the independent test cohort, this model had a statistically significantly higher AUC than a model including maximum diameter, AAA volume, and relevant clinical factors (AUC = 0.78, 95% CI, 0.67-0.87 vs AUC = 0.69, 95% CI, 0.57-0.79; p = 0.04). CONCLUSION: A radiomics-based method focused on the ILT and wall improved prediction of rapid AAA growth from CECT imaging. KEY POINTS: • Radiomic analysis of 195 abdominal CECT revealed that an ML-based model that included textural features of intraluminal thrombus (if present) and aortic wall improved prediction of rapid AAA progression compared to maximum diameter. • Predictive accuracy was higher when radiomic features were obtained from the thrombus and wall as opposed to the entire AAA sac (including lumen), or the lumen alone. • Logistic regression of selected radiomic features yielded similar accuracy to predict rapid AAA progression as random forests or support vector machines.

Deep learning based fully automatic segmentation of the left ventricular endocardium and epicardium from cardiac cine MRI.

BACKGROUND: The segmentation of cardiac medical images is a crucial step for calculating clinical indices such as wall thickness, ventricular volume, and ejection fraction. METHODS: In this study, we introduce a method named LsUnet that combines multi-channel, fully convolutional neural network, and annular shape level-set methods for efficiently segmenting cardiac cine magnetic resonance (MR) images. In this method, the multi-channel deep learning algorithm is applied to train the segmentation task to extract the left ventricle (LV) endocardial and epicardial contours. Next, the segmentation contours from the multi-channel deep learning method are incorporated into a level-set formulation, which is dedicated explicitly to detecting annular shapes to assure the segmentation's accuracy and robustness. RESULTS: The proposed automatic approach was evaluated on 95 volumes (total 1,076 slices, ~80% as for training datasets, ~20% 2D as for testing datasets). This combined multi-channel deep learning and annular shape level-set segmentation method achieved high accuracy with average Dice values reaching 92.15% and 95.42% for LV endocardium and epicardium delineation, respectively, in comparison to the reference standard (the manual segmentation). CONCLUSIONS: A novel method for fully automatic segmentation of the LV endocardium and epicardium from different MRI datasets is presented. The proposed workflow is accurate and robust compared to the reference and other state-of-the-art methods.

Identification of intra-individual variation in intracranial arterial flow by MRI and the effect on computed hemodynamic descriptors.

OBJECTIVES: To determine the intra-individual flow variation in serially acquired studies, and the influence of this variation on subsequent hemodynamic simulations using the inlet flow as a boundary condition. Author: Kindly check and confirm whether the corresponding authors are correctly identified.Confirmed. MATERIALS AND METHODS: This prospective study included 51 patients (37 females and 14 males) with unruptured intracranial aneurysms who have received more than three times follow-up of 2D phase-contrast MR. The flow and velocity parameters were extracted to calculate the reproducibility and variation. Patient-specific computational fluid dynamics simulations were performed using the measured flows. RESULTS: Intraclass correlation coefficients for mean and maximum velocity and flow parameters ranged from 0.77 to 0.90. A 10% CV of mean flow was identified. Variations of 10% in inlet flow resulted in hemodynamic changes including 41.41% of peak systolic wall shear stress; 39.13% of end-diastolic wall shear stress; 2.79% of low shear area at peak systole; 2.12% of low shear area at end diastole: 47.57% of time-averaged wall shear stress; and 0.17% of oscillatory shear index. CONCLUSION: This study identified 10% of intra-individual mean flow variation on phase-contrast MR. Intra-individual flow variation resulted in a non-negligible variation in wall shear stress, but relatively small variation in low shear area in hemodynamic calculations.

Computer-aided quantification of non-contrast 3D black blood MRI as an efficient alternative to reference standard manual CT angiography measurements of abdominal aortic aneurysms.

BACKGROUND: Non-contrast 3D black blood MRI is a promising tool for abdominal aortic aneurysm (AAA) surveillance, permitting accurate aneurysm diameter measurements needed for patient management. PURPOSE: To evaluate whether automated AAA volume and diameter measurements obtained from computer-aided segmentation of non-contrast 3D black blood MRI are accurate, and whether they can supplant reference standard manual measurements from contrast-enhanced CT angiography (CTA). MATERIALS AND METHODS: Thirty AAA patients (mean age, 71.9 ± 7.9 years) were recruited between 2014 and 2017. Participants underwent both non-contrast black blood MRI and CTA within 3 months of each other. Semi-automatic (computer-aided) MRI and CTA segmentations utilizing deformable registration methods were compared against manual segmentations of the same modality using the Dice similarity coefficient (DSC). AAA lumen and total aneurysm volumes and AAA maximum diameter, quantified automatically from these segmentations, were compared against manual measurements using Pearson correlation and Bland-Altman analyses. Finally, automated measurements from non-contrast 3D black blood MRI were evaluated against manual CTA measurements using the Wilcoxon test, Pearson correlation and Bland-Altman analyses. RESULTS: Semi-automatic segmentations had excellent agreement with manual segmentations (lumen DSC: 0.91 ± 0.03 and 0.94 ± 0.03; total aneurysm DSC: 0.92 ± 0.02 and 0.94 ± 0.03, for black blood MRI and CTA, respectively). Automated volume and maximum diameter measurements also had excellent correlation to their manual counterparts for both black blood MRI (volume: r = 0.99, P < 0.001; diameter: r = 0.97, P < 0.001) and CTA (volume: r = 0.99, P < 0.001; diameter: r = 0.97, P < 0.001). Compared to manual CTA measurements, bias and limits of agreement (LOA) for automated MRI measurements (lumen volume: 1.49, [-4.19 7.17] cm3; outer wall volume: -2.46, [-14.05 9.13] cm3; maximal diameter: 0.08, [-6.51 6.67] mm) were largely equivalent to those of manual MRI measurements, particularly for maximum AAA diameter (lumen volume: 0.73, [-6.47 7.93] cm3; outer wall volume: 0.98, [-10.54 12.5] cm3; maximal diameter: 0.08, [-3.67 3.83] mm). CONCLUSION: Semi-automatic segmentation of non-contrast 3D black blood MRI efficiently provides reproducible morphologic AAA assessment yielding accurate AAA diameters and volumes with no clinically relevant differences compared to either automatic or manual measurements based on CTA.

Sound Measurement in Patient-Specific 3D Printed Bench Models of Venous Pulsatile Tinnitus.

HYPOTHESIS: We hypothesize patient-specific flow models to be an adequate in vitro surrogate to allow for characterization of pulsatile tinnitus (PT) that affects three to five million Americans. BACKGROUND: PT, rhythmic sounds without an extracorporeal source that patients appreciate, can be caused by aberrant blood flow in large cerebral veins near the cochlea. To investigate the sound production mechanism, we created 3D printed flow models based on patient-specific cerebral venous anatomies. METHODS: Magnetic resonance angiography datasets from two patients with PT were used to generate patient-specific 3D printed flow models. A flow circuit connecting the patient-specific models to a pulsatile, continuous flow pump simulating cardiac cycle was created. Sound recordings were made along the surface of the models using an electronic stethoscope. Peak-to-rms amplitude, and area under the power spectral density (PSD) curve values were computed to evaluate the sound measurements. Wilcoxon rank sum test was used to statistically determine the differences in measurements between the patient-specific models. RESULTS: In patient-1, the recordings (peak-to-rms) from the internal jugular vein stenosis of baseline model (4.29 ±â€Š1.26 for 146 samples) were significantly louder (p < 0.001) than that of the altered model (3.29 ±â€Š0.96 for 143 samples). In patient-2, the sound measured at the transverse sinus stenosis in the pre-lumbar puncture model (4.84 ±â€Š1.11 for 148 samples) was significantly louder (p < 0.0001) than that of the post-lumbar puncture model (3.14 ±â€Š0.87 for 135 samples). CONCLUSIONS: The models are able to generate sounds very similar to those appreciated by patients and examiners in the cases of objective PT.

Shape-appearance constrained segmentation and separation of vein and artery in pulsatile tinnitus patients based on MR angiography and flow MRI.

This study reports on the development and evaluation of a novel segmentation method for extracting the internal jugular vein and the adjacent carotid artery from magnetic resonance (MR) images of patients with pulsatile tinnitus. A narrow band level set method with combined shape and appearance constraints was developed and applied to high-resolution MR images from 17 pulsatile tinnitus patients (age 52 ±â€¯23 years, 10 females). The proposed method was validated by comparing with the manual segmentation as well as by identifying the jugular vein and carotid artery based on 4D flow MRI in which the two types of vessels have opposing flow. Our study showed that the vein and artery are in contact with each other on 30.2% of all the slices. Dice value, Peak signal-to-noise ratio (PSNR), Hausdorff distance and mean sum of square distance (MSSD) between automatic and manual segmentation were 89.13 ±â€¯2.84%, 27.36 ±â€¯2.39%, 17.2 ±â€¯6.9 mm, 7.4 ±â€¯5.5 mm, demonstrating good segmentation accuracy. The average Dice similarity coefficient and the coefficient of variation compared with 4D flow MRI was 91.42 ±â€¯1.63% and 89.28 ±â€¯4.54% for the internal jugular vein and the carotid artery. The present pipeline for automatic internal jugular vein quantification holds promise for efficient image interpretation in large-scale cohort studies.

On the Relative Impact of Intraluminal Thrombus Heterogeneity on Abdominal Aortic Aneurysm Mechanics.

Intraluminal thrombus (ILT) is present in the majority of abdominal aortic aneurysms (AAA) of a size warranting consideration for surgical or endovascular intervention. The rupture risk of AAAs is thought to be related to the balance of vessel wall strength and the mechanical stress caused by systemic blood pressure. Previous finite element analyses of AAAs have shown that ILT can reduce and homogenize aneurysm wall stress. These works have largely considered ILT to be homogeneous in mechanical character or have idealized a stiffness distribution through the thrombus thickness. In this work, we use magnetic resonance imaging (MRI) to delineate the heterogeneous composition of ILT in 7 AAAs and perform patient-specific finite element analysis under multiple conditions of ILT layer stiffness disparity. We find that explicit incorporation of ILT heterogeneity in the finite element analysis is unlikely to substantially alter major stress analysis predictions regarding aneurysm rupture risk in comparison to models assuming a homogenous thrombus, provided that the maximal ILT stiffness is the same between models. Our results also show that under a homogeneous ILT assumption, the choice of ILT stiffness from values common in the literature can result in significantly larger variations in stress predictions compared to the effects of thrombus heterogeneity.

Towards optimal flow diverter porosity for the treatment of intracranial aneurysm.

PURPOSE: Low-porosity endovascular stents, known as flow diverters (FDs), have been proposed as an effective and minimally invasive treatment for sidewall intracranial aneurysms (IAs). Although it has been reported that the efficacy of a FD is substantially influenced by its porosity, clinical doctors would clearly prefer to do their interventions optimally based on refined quantitative data. This study focuses on the association between the porosity configurations and the FD efficacy, in order to provide practical data to help the clinical doctors optimize the interventions. METHOD: Numerical simulations in fluid dynamics were performed using four patient-specific IA geometries, pulsatile velocity profiles and braided fully resolved FDs. The variation of velocity and wall shear stress within the IAs, were investigated in this study. Lattice Boltzmann method (LBM) was used to solve the main challenge centered on the diversity of spatial scales since the typical diameter of struts of FDs is only 25µm while the artery normally can be larger by a hundred times. RESULTS: Numerical simulations revealed that the blood flow within IA sac was substantially reduced when the porosity is less than 86%. In particular, the flow condition within each IA sac is favorite to initialize thrombus formation when porosity is less than 70%. CONCLUSION: Our study suggests the existence of a porosity threshold below which the efficacy of a FD will be sufficient for the patients to initialize the thrombus formation. Therefore, by estimating the porosity of FD on patient-specific information, it may be potentially to predict whether or the blood flow condition will successfully become prothrombotic after the FD intervention.

Fully automatic segmentation of 4D MRI for cardiac functional measurements.

PURPOSE: Segmentation of cardiac medical images, an important step in measuring cardiac function, is usually performed either manually or semiautomatically. Fully automatic segmentation of the left ventricle (LV), the right ventricle (RV) as well as the myocardium of three-dimensional (3D) magnetic resonance (MR) images throughout the entire cardiac cycle (four-dimensional, 4D), remains challenging. This study proposes a deformable-based segmentation methodology for efficiently segmenting 4D (3D + t) cardiac MR images. METHODS: The proposed methodology first used the Hough transform and the local Gaussian distribution method (LGD) to segment the LV endocardial contours from cardiac MR images. Following this, a novel level set-based shape prior method was applied to generate the LV epicardial contours and the RV boundary. RESULTS: This automatic image segmentation approach has been applied to studies on 17 subjects. The results demonstrated that the proposed method was efficient compared to manual segmentation, achieving a segmentation accuracy with average Dice values of 88.62 ± 5.47%, 87.35 ± 7.26%, and 82.63 ± 6.22% for the LV endocardial, LV epicardial, and RV contours, respectively. CONCLUSIONS: We have presented a method for accurate LV and RV segmentation. Compared to three existing methods, the proposed method can successfully segment the LV and yield the highest Dice value. This makes it an option for clinical assessment of the volume, size, and thickness of the ventricles.

Highly accelerated intracranial 4D flow MRI: evaluation of healthy volunteers and patients with intracranial aneurysms.

OBJECTIVES: To evaluate an accelerated 4D flow MRI method that provides high temporal resolution in a clinically feasible acquisition time for intracranial velocity imaging. MATERIALS AND METHODS: Accelerated 4D flow MRI was developed by using a pseudo-random variable-density Cartesian undersampling strategy (CIRCUS) with the combination of k-t, parallel imaging and compressed sensing image reconstruction techniques (k-t SPARSE-SENSE). Four-dimensional flow data were acquired on five healthy volunteers and eight patients with intracranial aneurysms using CIRCUS (acceleration factor of R = 4, termed CIRCUS4) and GRAPPA (R = 2, termed GRAPPA2) as the reference method. Images with three times higher temporal resolution (R = 12, CIRCUS12) were also reconstructed from the same acquisition as CIRCUS4. Qualitative and quantitative image assessment was performed on the images acquired with different methods, and complex flow patterns in the aneurysms were identified and compared. RESULTS: Four-dimensional flow MRI with CIRCUS was achieved in 5 min and allowed further improved temporal resolution of <30 ms. Volunteer studies showed similar qualitative and quantitative evaluation obtained with the proposed approach compared to the reference (overall image scores: GRAPPA2 3.2 ± 0.6; CIRCUS4 3.1 ± 0.7; CIRCUS12 3.3 ± 0.4; difference of the peak velocities: -3.83 ± 7.72 cm/s between CIRCUS4 and GRAPPA2, -1.72 ± 8.41 cm/s between CIRCUS12 and GRAPPA2). In patients with intracranial aneurysms, the higher temporal resolution improved capturing of the flow features in intracranial aneurysms (pathline visualization scores: GRAPPA2 2.2 ± 0.2; CIRCUS4 2.5 ± 0.5; CIRCUS12 2.7 ± 0.6). CONCLUSION: The proposed rapid 4D flow MRI with a high temporal resolution is a promising tool for evaluating intracranial aneurysms in a clinically feasible acquisition time.

Segmentation of lumen and outer wall of abdominal aortic aneurysms from 3D black-blood MRI with a registration based geodesic active contour model.

Segmentation of the geometric morphology of abdominal aortic aneurysm is important for interventional planning. However, the segmentation of both the lumen and the outer wall of aneurysm in magnetic resonance (MR) image remains challenging. This study proposes a registration based segmentation methodology for efficiently segmenting MR images of abdominal aortic aneurysms. The proposed methodology first registers the contrast enhanced MR angiography (CE-MRA) and black-blood MR images, and then uses the Hough transform and geometric active contours to extract the vessel lumen by delineating the inner vessel wall directly from the CE-MRA. The proposed registration based geometric active contour is applied to black-blood MR images to generate the outer wall contour. The inner and outer vessel wall are then fused presenting the complete vessel lumen and wall segmentation. The results obtained from 19 cases showed that the proposed registration based geometric active contour model was efficient and comparable to manual segmentation and provided a high segmentation accuracy with an average Dice value reaching 89.79%.

Flow patterns in the jugular veins of pulsatile tinnitus patients.

Pulsatile Tinnitus (PT) is a pulse-synchronous sound heard in the absence of an external source. PT is often related to abnormal flow in vascular structures near the cochlea. One vascular territory implicated in PT is the internal jugular vein (IJV). Using computational fluid dynamics (CFD) based on patient-specific Magnetic Resonance Imaging (MRI), we investigated the flow within the IJV of seven subjects, four symptomatic and three asymptomatic of PT. We found that there were two extreme anatomic types classified by the shape and position of the jugular bulbs: elevated and rounded. PT patients had elevated jugular bulbs that led to a distinctive helical flow pattern within the proximal internal jugular vein. Asymptomatic subjects generally had rounded jugular bulbs that neatly redirected flow from the sigmoid sinus directly into the jugular vein. These two flow patterns were quantified by calculating the length-averaged streamline curvature of the flow within the proximal jugular vein: 130.3±8.1m-1 for geometries with rounded bulbs, 260.7±29.4m-1 for those with elevated bulbs (P<0.005). Our results suggest that variations in the jugular bulb geometry lead to distinct flow patterns that are linked to PT, but further investigation is needed to determine if the vortex pattern is causal to sound generation.

The manifestation of vortical and secondary flow in the cerebral venous outflow tract: An in vivo MR velocimetry study.

Aberrations in flow in the cerebral venous outflow tract (CVOT) have been implicated as the cause of several pathologic conditions including idiopathic intracranial hypertension (IIH), multiple sclerosis (MS), and pulsatile tinnitus (PT). The advent of 4D flow magnetic resonance imaging (4D-flow MRI) has recently allowed researchers to evaluate blood flow patterns in the arterial structures with great success. We utilized similar imaging techniques and found several distinct flow characteristics in the CVOT of subjects with and without lumenal irregularities. We present the flow patterns of 8 out of 38 subjects who have varying heights of the internal jugular bulb and varying lumenal irregularities including stenosis and diverticulum. In the internal jugular vein (IJV) with an elevated jugular bulb (JB), 4Dflow MRI revealed a characteristic spiral flow that was dependent on the level of JB elevation. Vortical flow was also observed in the diverticula of the venous sinuses and IJV. The diversity of flow complexity in the CVOT illustrates the potential importance of hemodynamic investigations in elucidating venous pathologies.

Myocyte-depleted engineered cardiac tissues support therapeutic potential of mesenchymal stem cells.

The therapeutic potential of mesenchymal stem cells (MSCs) for restoring cardiac function after cardiomyocyte loss remains controversial. Engineered cardiac tissues (ECTs) offer a simplified three-dimensional in vitro model system to evaluate stem cell therapies. We hypothesized that contractile properties of dysfunctional ECTs would be enhanced by MSC treatment. ECTs were created from neonatal rat cardiomyocytes with and without bone marrow-derived adult rat MSCs in a type-I collagen and Matrigel scaffold using custom elastomer molds with integrated cantilever force sensors. Three experimental groups included the following: (1) baseline condition ECT consisting only of myocytes, (2) 50% myocyte-depleted ECT, modeling a dysfunctional state, and (3) 50% myocyte-depleted ECT plus 10% MSC, modeling dysfunctional myocardium with intervention. Developed stress (DS) and pacing threshold voltage (VT) were measured using 2-Hz field stimulation at 37°C on culture days 5, 10, 15, and 20. By day 5, DS of myocyte-depleted ECTs was significantly lower than baseline, and VT was elevated. In MSC-supplemented ECTs, DS and VT were significantly better than myocyte-depleted values, approaching baseline ECTs. Findings were similar through culture day 15, but lost significance at day 20. Trends in DS were partly explained by changes in the cell number and alignment with time. Thus, supplementing myocyte-depleted ECTs with MSCs transiently improved contractile function and compensated for a 50% loss of cardiomyocytes, mimicking recent animal studies and clinical trials and supporting the potential of MSCs for myocardial therapy.