Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

Preliminary investigation of multiparametric strain Z-score (MPZS) computation using displacement encoding with simulated echoes (DENSE) and radial point interpretation method (RPIM).

PURPOSE: To describe and assess an automated normalization method for identifying sentinel (septal) regions of myocardial dysfunction in nonischemic, nonvalvular dilated cardiomyopathy (DCM), using an unprecedented combination of the navigator-gated 3D spiral displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI), radial point interpolation (RPIM) and multiparametric strain z-score (MPZS). MATERIALS AND METHODS: Navigator-gated 3D spiral DENSE, in a 1.5T MRI machine, was used for acquiring the displacement encoded complex images, MR Analytical Software System (MASS) for automated boundary detection and automated meshfree RPIM for left-ventricular (LV) myocardial strain computation to analyze MPZS in 36 subjects (with n = 17 DCM patients). Pearson's r correlation established relations between global/sentinel MPZS and ejection fraction (EF). The time taken for combined RPIM-MPZS computations was recorded. RESULTS: Maximum MPZS differences were seen between anteroseptal and posterolateral regions in the base (2.0 ± 0.3 vs. 0.9 ± 0.5) and the mid-wall (2.1 ± 0.4 vs. 1.0 ± 0.4). These regional differences were found to be consistent with historically documented septal injury in nonischemic DCM. Correlations were 0.6 between global MPZS and EF, and 0.7 between sentinel MPZS and EF. The time taken for combined RPIM-MPZS computations per subject was 18.9 ± 5.9 seconds. CONCLUSION: Heterogeneous contractility found in the sentinel regions with the current automated MPZS computation scheme and the correlation found between MPZS and EF may lead to the creation of a new clinical metric in LV DCM surveillance. J. MAGN. RESON. IMAGING 2016;44:993-1002.

Three-dimensional regional strain computation method with displacement encoding with stimulated echoes (DENSE) in non-ischemic, non-valvular dilated cardiomyopathy patients and healthy subjects validated by tagged MRI.

PURPOSE: Fast cine displacement encoding with stimulated echoes (DENSE) MR has higher spatial resolution and enables rapid postprocessing. Thus we compared the accuracy of regional strains computation by DENSE with tagged MR in healthy and non-ischemic, non-valvular dilated cardiomyopathy (DCM) subjects. MATERIALS AND METHODS: Validation of three-dimensional regional strains computed with DENSE was conducted in reference to standard tagged MRI (TMRI) in healthy subjects and patients with DCM. Additional repeatability studies in healthy subjects were conducted to increase confidence in DENSE. A meshfree multiquadrics radial point interpolation method (RPIM) was used for computing Lagrange strains in sixteen left ventricular segments. Bland-Altman analysis and Student's t-tests were conducted to observe similarities in regional strains between sequences and in DENSE repeatability studies. RESULTS: Regional circumferential strains ranged from -0.21 ± 0.07 (Lateral-Apex) to -0.11 ± 0.05 (Posterorseptal-Base) in healthy subjects and -0.15 ± 0.04 (Anterior-Apex) to -0.02 ± 0.08 (Posterorseptal-Base) in DCM patients. Computed mean differences in regional circumferential strain from the DENSE-TMRI comparison study was 0.01 ± 0.03 (95% limits of agreement) in normal subjects, -0.01 ± 0.06 in DCM patients and 0.0 ± 0.02 in repeatability studies, with similar agreements in longitudinal and radial strains. CONCLUSION: We found agreement between DENSE and tagged MR in patients and volunteers in terms of evaluation of regional strains.

Automated segmentation of the left-ventricle from MRI with a fully convolutional network to investigate CTRCD in breast cancer patients.

Purpose: The goal of this study was to develop a fully convolutional network (FCN) tool to automatedly segment the left-ventricular (LV) myocardium in displacement encoding with stimulated echoes MRI. The segmentation results are used for LV chamber quantification and strain analyses in breast cancer patients susceptible to cancer therapy-related cardiac dysfunction (CTRCD). Approach: A DeepLabV3+ FCN with a ResNet-101 backbone was custom-designed to conduct chamber quantification on 45 female breast cancer datasets (23 training, 11 validation, and 11 test sets). LV structural parameters and LV ejection fraction (LVEF) were measured, and myocardial strains estimated with the radial point interpolation method. Myocardial classification validation was against quantization-based ground-truth with computations of accuracy, Dice score, average perpendicular distance (APD), Hausdorff-distance, and others. Additional validations were conducted with equivalence tests and Cronbach's alpha (C-α) intraclass correlation coefficients between the FCN and a vendor tool on chamber quantification and myocardial strain computations. Results: Myocardial classification results against ground-truth were Dice=0.89, APD=2.4 mm, and accuracy=97% for the validation set and Dice=0.90, APD=2.5 mm, and accuracy=97% for the test set. The confidence intervals (CI) and two one-sided t-test results of equivalence tests between the FCN and vendor-tool were CI=-1.36% to 2.42%, p-value < 0.001 for LVEF (58±5% versus 57±6%), and CI=-0.71% to 0.63%, p-value < 0.001 for longitudinal strain (-15±2% versus -15±3%). Conclusions: The validation results were found equivalent to the vendor tool-based parameter estimates, which show that accurate LV chamber quantification followed by strain analysis for CTRCD investigation can be achieved with our proposed FCN methodology.

Can global longitudinal strain (GLS) with magnetic resonance prognosticate early cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients, a prospective study?

PURPOSE: To determine if Artificial Intelligence-based computation of global longitudinal strain (GLS) from left ventricular (LV) MRI is an early prognostic factor of cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients. The main hypothesis based on the patients receiving antineoplastic chemotherapy treatment was CTRCD risk analysis with GLS that was independent of LV ejection fraction (LVEF). METHODS: Displacement Encoding with Stimulated Echoes (DENSE) MRI was acquired on 32 breast cancer patients at baseline and 3- and 6-month follow-ups after chemotherapy. Two DeepLabV3+ Fully Convolutional Networks (FCNs) were deployed to automate image segmentation for LV chamber quantification and phase-unwrapping for 3D strains, computed with the Radial Point Interpolation Method. CTRCD risk (cardiotoxicity and adverse cardiac events) was analyzed with Cox Proportional Hazards (PH) models with clinical and contractile prognostic factors. RESULTS: GLS worsened from baseline to the 3- and 6-month follow-ups (-19.1 ± 2.1%, -16.0 ± 3.1%, -16.1 ± 3.0%; P < 0.001). Univariable Cox regression showed the 3-month GLS significantly associated as an agonist (hazard ratio [HR]-per-SD: 2.1; 95% CI: 1.4-3.1; P < 0.001) and LVEF as a protector (HR-per-SD: 0.8; 95% CI: 0.7-0.9; P = 0.001) for CTRCD occurrence. Bivariable regression showed the 3-month GLS (HR-per-SD: 2.0; 95% CI: 1.2-3.4; P = 0.01) as a CTRCD prognostic factor independent of other covariates, including LVEF (HR-per-SD: 1.0; 95% CI: 0.9-1.2; P = 0.9). CONCLUSIONS: The end-point analyses proved the hypothesis that GLS is an early, independent prognosticator of incident CTRCD risk. This novel GLS-guided approach to CTRCD risk analysis could improve antineoplastic treatment with further validation in a larger clinical trial.

Direct left-ventricular global longitudinal strain (GLS) computation with a fully convolutional network.

This study's purpose was to develop a direct MRI-based, deep-learning semantic segmentation approach for computing global longitudinal strain (GLS), a known metric for detecting left-ventricular (LV) cardiotoxicity in breast cancer. Displacement Encoding with Stimulated Echoes cardiac image phases acquired from 30 breast cancer patients and 30 healthy females were unwrapped via a DeepLabV3 + fully convolutional network (FCN). Myocardial strains were directly computed from the unwrapped phases with the Radial Point Interpolation Method. FCN-unwrapped phases of a phantom's rotating gel were validated against quality-guided phase-unwrapping (QGPU) and robust transport of intensity equation (RTIE) phase-unwrapping. FCN performance on unwrapping human LV data was measured with F1 and Dice scores versus QGPU ground-truth. The reliability of FCN-based strains was assessed against RTIE-based strains with Cronbach's alpha (C-α) intraclass correlation coefficient. Mean squared error (MSE) of unwrapping the phantom experiment data at 0 dB signal-to-noise ratio were 1.6, 2.7 and 6.1 with FCN, QGPU and RTIE techniques. Human data classification accuracies were F1 = 0.95 (Dice = 0.96) with FCN and F1 = 0.94 (Dice = 0.95) with RTIE. GLS results from FCN and RTIE were -16 ± 3% vs. -16 ± 3% (C-α = 0.9) for patients and -20 ± 3% vs. -20 ± 3% (C-α = 0.9) for healthy subjects. The low MSE from the phantom validation demonstrates accuracy of phase-unwrapping with the FCN and comparable human subject results versus RTIE demonstrate GLS analysis accuracy. A deep-learning methodology for phase-unwrapping in medical images and GLS computation was developed and validated in a heterogeneous cohort.

Comprehensive enhanced methodology of an MRI-based automated left-ventricular chamber quantification algorithm and validation in chemotherapy-related cardiotoxicity.

Purpose: To comprehensively outline the methodology of a fully automated, MRI motion-guided, left-ventricular (LV) chamber quantification algorithm that enhances a similar, existing semi-automated approach. Additionally, to validate the motion-guided technique in comparison to chamber quantification with a vendor tool in post-chemotherapy breast cancer patients susceptible to cardiotoxicity. Approach: LV deformation data were acquired with the displacement encoding with stimulated echoes (DENSE) sequence on N = 21 post-chemotherapy female patients and N = 21 age-matched healthy females. The new chamber quantification algorithm consists of detecting LV boundary motion via a combination of image quantization and DENSE phase-encoded displacements. LV contractility was analyzed via chamber quantification and computations of 3D strains and torsion. For validation, estimates of chamber quantification with the motion-guided algorithm on DENSE and steady-state free precession (SSFP) acquisitions, and similar estimates with an existing vendor tool on DENSE acquisitions were compared via repeated measures analysis. Patient results were compared to healthy subjects for observing abnormalities. Results: Repeated measures analysis showed similar LV ejection fractions (LVEF), 59 % ± 6 % , 58 % ± 6 % , and 58 % ± 6 % , p = 0.2 , by applying the motion-guided algorithm on DENSE and SSFP and vendor tool on DENSE acquisitions, respectively. Differences found between patients and healthy subjects included enlarged basal diameters ( 5.0 ± 0.5 cm versus 4.4 ± 0.5 cm , p < 0.01 ), torsions ( p < 0.001 ), and longitudinal strains ( p < 0.001 ), but not LVEF ( p = 0.1 ). Conclusions: Measurement similarities between new and existing tools, and between DENSE and SSFP validated the motion-guided algorithm and differences found between subpopulations demonstrate the ability to detect contractile abnormalities.

Fully automated and comprehensive MRI-based left-ventricular contractility analysis in post-chemotherapy breast cancer patients.

OBJECTIVE: This study investigated the occurrence of cardiotoxicity-related left-ventricular (LV) contractile dysfunction in breast cancer patients following treatment with antineoplastic chemotherapy agents. METHODS: A validated and automated MRI-based LV contractility analysis tool consisting of quantization-based boundary detection, unwrapping of image phases and the meshfree Radial Point Interpolation Method was used toward measuring LV chamber quantifications (LVCQ), three-dimensional strains and torsions in patients and healthy subjects. Data were acquired with the Displacement Encoding with Stimulated Echoes (DENSE) sequence on 21 female patients and 21 age-matched healthy females. Estimates of patient LVCQs from DENSE acquisitions were validated in comparison to similar steady-state free precession measurements and their strain results validated via Bland-Altman interobserver agreements. The occurrence of LV abnormalities was investigated via significant differences in contractility measurements (LVCQs, strains and torsions) between patients and healthy subjects. RESULTS: Repeated measures analysis showed similarities between LVCQ measurements from DENSE and steady-state free precession, including cardiac output (4.7 ± 0.4 L, 4.6 ± 0.4 L, p = 0.8), and LV ejection fractions (59±6%, 58±5%, p = 0.2). Differences found between patients and healthy subjects included enlarged basal diameter (5.0 ± 0.5 cm vs 4.4 ± 0.5 cm, p < 0.01), apical torsion (6.0 ± 1.1° vs 9.7 ± 1.4°, p < 0.001) and global longitudinal strain (-0.15 ± 0.02 vs. -0.21 ± 0.04, p < 0.001), but not LV ejection fraction (59±6% vs. 63±6%, p = 0.1). CONCLUSION: The results from the statistical analysis reveal the possibility of LV abnormalities in the post-chemotherapy patients via enlarged basal diameter and reduced longitudinal strain and torsion, in comparison to healthy subjects. ADVANCES IN KNOWLEDGE: This study shows that subclinical LV abnormalities in post-chemotherapy breast cancer patients can be detected with an automated technique for the comprehensive analysis of contractile parameters.

Can post-chemotherapy cardiotoxicity be detected in long-term survivors of breast cancer via comprehensive 3D left-ventricular contractility (strain) analysis?

PURPOSE: This study applied a novel and automated contractility analysis tool to investigate possible cardiotoxicity-related left-ventricular (LV) dysfunction in breast cancer patients following treatment with anti-neoplastic chemotherapy agents (CTA). Subclinical dysfunction otherwise undetected via LV ejection fraction (LVEF) was determined. METHODS: Deformation data were acquired with the Displacement Encoding with Stimulated Echoes (DENSE) MRI sequence on 16 female patients who had CTA-based treatment. The contractility analysis tool consisting of image quantization-based boundary detection and the meshfree Radial Point Interpolation Method was used to compare chamber quantifications, 3D regional strains and torsion between patients and healthy subjects (N = 26 females with N = 14 age-matched). Quantifications of patient LVEFs from DENSE and Steady-State Free Precession (SSFP) acquisitions were compared, Bland-Altman interobserver agreements measured on their strain results and differences in contractile parameters with healthy subjects determined via Student's t-tests. RESULTS: A significant difference was not found between DENSE and SSFP-based patient LVEFs at 58 ±â€¯7% vs 57 ±â€¯9%, p = 0.6. Bland-Altman agreements were - 0.01 ±â€¯0.05 for longitudinal strain and 0.1 ±â€¯1.3° for torsion. Differences in basal diameter indicating enlargement, 5.2 ±â€¯0.5 cm vs 4.5 ±â€¯0.5 cm, p < 0.01, and torsion, 4.7 ±â€¯1.0° vs 8.1 ±â€¯1.1°, p < 0.001 in the mid-ventricle and 5.9 ±â€¯1.2° vs 10.2 ±â€¯0.9°, p < 0.001 apically, were seen between patients and age-matched healthy subjects and similarly in longitudinal strain, but not in LVEF. CONCLUSIONS: Results from the statistical analysis reveal the likelihood of LV remodeling in this patient subpopulation otherwise not indicated by LVEF measurements.

Introduction to a mechanism for automated myocardium boundary detection with displacement encoding with stimulated echoes (DENSE).

OBJECTIVE: Displacement ENcoding with Stimulated Echoes (DENSE) is an MRI technique developed to encode phase related to myocardial tissue displacements, and the displacement information directly applied towards detecting left-ventricular (LV) myocardial motion during the cardiac cycle. The purpose of this study is to present a novel, three-dimensional (3D) DENSE displacement-based and magnitude image quantization-based, semi-automated detection technique for myocardial wall motion, whose boundaries are used for rapid and automated computation of 3D myocardial strain. METHODS: The architecture of this boundary detection algorithm is primarily based on pixelwise spatiotemporal increments in LV tissue displacements during the cardiac cycle and further reinforced by radially searching for pixel-based image gradients in multithreshold quantized magnitude images. This spatiotemporal edge detection methodology was applied to all LV partitions and their subsequent timeframes that lead to full 3D LV reconstructions. It was followed by quantifications of 3D chamber dimensions and myocardial strains, whose rapid computation was the primary motivation behind developing this algorithm. A pre-existing two-dimensional (2D) semi-automated contouring technique was used in parallel to validate the accuracy of the algorithm and both methods tested on DENSE data acquired in (N = 14) healthy subjects. Chamber quantifications between methods were compared using paired t-tests and Bland-Altman analysis established regional strain agreements. RESULTS: There were no significant differences in the results of chamber quantifications between the 3D semi-automated and existing 2D boundary detection techniques. This included comparisons of ejection fractions, which were 0.62 ± 0.04 vs 0.60 ± 0.06 (p = 0.23) for apical, 0.60 ± 0.04 vs 0.59 ± 0.05 (p = 0.76) for midventricular and 0.56 ± 0.04 vs 0.58 ± 0.05 (p = 0.07) for basal segments, that were quantified using the 3D semi-automated and 2D pre-existing methodologies, respectively. Bland-Altman agreement between regional strains generated biases of 0.01 ± 0.06, -0.01 ± 0.01 and 0.0 ± 0.06 for the radial, circumferential and longitudinal directions, respectively. CONCLUSION: A new, 3D semi-automated methodology for contouring the entire LV and rapidly generating chamber quantifications and regional strains is presented that was validated in relation to an existing 2D contouring technique. Advances in knowledge: This study introduced a scientific tool for rapid, semi-automated generation of clinical information regarding shape and function in the 3D LV.

Topographic mapping of left ventricular regional contractile injury in ischemic mitral regurgitation.

OBJECTIVE: Restrictive leaflet tethering resulting from regional left ventricular (LV) contractile injury causes ischemic mitral regurgitation (MR). We hypothesized that 3-dimensional LV topographic mapping by MRI-based multiparametric strain analysis could characterize the regional contractile injury patterns that differentiate ischemic coronary artery disease patients who have ischemic MR from those who do not. METHODS: Magnetic resonance imaging-based multiparametric strain data were calculated for 15,300 LV grid points in 100 normal volunteers. Strain parameters from ischemic MR (n = 10) and ischemic no-MR (n = 36) patients were then normalized to this normal human strain database with z score quantification of standard deviation from the normal mean. Mean multiparametric strain z scores were calculated for 18 LV subregions (basilar/mid/apical levels; 6 LV regions). Mean strain z scores for papillary muscle-related (basilar/mid levels of anterolateral, posterolateral, and posterior) and nonpapillary muscle-related (all other) subregions were compared between ischemic MR and ischemic no-MR groups. RESULTS: Across all patients, contractile injury was greater in the papillary muscle-related regions compared with the nonpapillary regions (P = .007). In the papillary regions, contractile injury was greater in the ischemic MR group compared with the no-MR group (z scores, 1.91 ± 1.13 vs 1.20 ± 1.01, respectively; P < .001). Strain values in the nonpapillary muscle-related subregions were not different between the 2 groups (1.31 ± 1.04 vs 1.20 ± 1.03; P = .301). CONCLUSIONS: Multiparametric strain analysis demonstrated severe normalized contractile injury in the papillary muscle-related LV subregions in patients with ischemic MR. The mean degree of normalized injury approached 2 standard deviations and was significantly worse than the levels seen in ischemic no-MR patients.

Dilated Cardiomyopathy: Normalized Multiparametric Myocardial Strain Predicts Contractile Recovery.

BACKGROUND: Left ventricular contractile injury in dilated cardiomyopathy (DCM) may occur in a consistently heterogeneous distribution, suggesting that early-injury sentinel regions may have prognostic significance. Heightened surveillance of these regions with high-resolution contractile metrics may predict recovery in DCM. METHODS: Multiple three-dimensional strain parameters were calculated at each of 15,300 left ventricular grid points from systolic displacement data obtained from cardiac magnetic resonance imaging in 124 test subjects. In 24 DCM patients, Z-scores for two strain parameters at each grid point were calculated by comparison of patient-specific strain values to respective point-specific mean and standard deviation values from a normal human strain database (n = 100). Multiparametric strain Z-scores were averaged over six left ventricular regions at basilar, mid, and apical levels (18 subregions). Patients with DCM were stratified into three groups on the basis of a blinded review of clinical contractile recovery (complete, n = 7; incomplete, n = 7; none, n = 10). RESULTS: Basilar-septal subregions were consistently heavily injured. Basilar-septal Z-scores were significantly larger (worse) than those for the rest of the left ventricle (2.73 ± 1.27 versus 2.22 ± 0.83; p = 0.011) and lateral wall (2.73 ± 1.27 versus 1.44 ± 0.72; p < 0.001). All patients with sentinel region average multiparametric strain Z-scores less than two standard deviations (n = 6) experienced complete recovery, whereas 17 of 18 DCM patients with Z-scores greater than two standard deviations experienced incomplete or no contractile recovery. CONCLUSIONS: Contractile injury in DCM is heterogeneous, with basilar-septal regions injured more than lateral regions. The targeting of early-injury sentinel regions for heightened surveillance with high-resolution metrics of microregional contractile function may accurately predict recovery on medical therapy. A two standard deviation Z-score threshold may predict contractile recovery.

Quantifying "normalized" regional left ventricular contractile function in ischemic coronary artery disease.

OBJECTIVE: When significant coronary lesions are identified by angiography, regional left ventricular (LV) contractile function often plays a role in determining candidacy for revascularization. To improve on current subjective and nonquantitative metrics of regional LV function, we tested a z-score "normalization" of regional strain information quantified from clinically acquired high-resolution LV geometric datasets. METHODS: Test subjects (n = 120) underwent cardiac MRI with multiple 3-dimensional strain parameters calculated from tissue tag-plane displacement data. Sixty healthy volunteers contributed strain parameter data at each of 15,300 LV grid points, to form a normal human strain database. Point-specific database comparisons were made in 60 patients who had documented coronary artery disease (CAD), by angiography. Patient-specific, color-coded 3-dimensional LV maps of z-score-normalized contractile function were generated. RESULTS: Blinded clinical review indicated that 55% (33 of 60) of the patients with CAD had significant regional contractile abnormalities by 1 of 3 "gold-standard" criteria: (1) Q waves on electrocardiography (ECG); (2) infarct on radionuclide single-photon emission computed tomography (SPECT); or (3) akinesia or dyskinesia on echocardiography. Consistency among all gold-standard metrics was found for only 19% (6 of 31) of patients with CAD who had ≥2 available metrics. Blinded MRI-based, multiparametric, strain z-score localization of contractile abnormalities was accurate in 89% (ECG), 97% (SPECT), and 95% (echocardiography). CONCLUSIONS: Nonsubjective normalization of regional LV contractile function by z-score calculation from a normal human strain database can localize and quantitatively display regional wall motion abnormalities in patients with CAD. This high-resolution localization of regional wall motion abnormalities may help improve the accuracy of therapeutic intervention in patients who have CAD.

A validation of two-dimensional in vivo regional strain computed from displacement encoding with stimulated echoes (DENSE), in reference to tagged magnetic resonance imaging and studies in repeatability.

Fast cine displacement encoding with stimulated echoes (DENSE) has comparative advantages over tagged MRI (TMRI) including higher spatial resolution and faster post-processing. This study computed regional radial and circumferential myocardial strains with DENSE displacements and validated it in reference to TMRI, according to American Heart Association (AHA) guidelines for standardized segmentation of regions in the left ventricle (LV). This study was therefore novel in examining agreement between the modalities in 16 AHA recommended LV segments. DENSE displacements were obtained with spatiotemporal phase unwrapping and TMRI displacements obtained with a conventional tag-finding algorithm. A validation study with a rotating phantom established similar shear strain between modalities prior to in vivo studies. A novel meshfree nearest node finite element method (NNFEM) was used for rapid computation of Lagrange strain in both phantom and in vivo studies in both modalities. Also novel was conducting in vivo repeatability studies for observing recurring strain patterns in DENSE and increase confidence in it. Comprehensive regional strain agreements via Bland-Altman analysis between the modalities were obtained. Results from the phantom study showed similar radial-circumferential shear strains from the two modalities. Mean differences in regional in vivo circumferential strains were -0.01 ± 0.09 (95% limits of agreement) from comparing the modalities and -0.01 ± 0.07 from repeatability studies. Differences and means from comparison and repeatability studies were uncorrelated (p > 0.05) indicating no increases in differences with increased strain magnitudes. Bland-Altman analysis and similarities in regional strain distribution within the myocardium showed good agreements between DENSE and TMRI and show their interchangeability. NNFEM was also established as a common framework for computing strain in both modalities.

Early left ventricular regional contractile impairment in chronic mitral regurgitation occurs in a consistent, heterogeneous pattern.

OBJECTIVES: The clinical guidelines for asymptomatic patients with chronic mitral regurgitation (MR) use the ejection fraction (EF) to trigger surgical referral. We hypothesized that the EF is not sensitive enough to detect the earliest contractile injury in chronic MR and that the injury associated with chronic MR is not global but heterogeneous, occurring regionally and predictably, before the onset of global left ventricular (LV) dysfunction. METHODS: Fifteen patients with chronic MR and normal LVEF by echocardiography underwent cardiac magnetic resonance imaging with tissue tagging. Point-specific comparisons (at 15,300 LV grid points) of multiple strain parameters to a normal human strain database allowed normalization of patient-specific regional contractile function. Data were mapped over patient-specific 3-dimensional geometry and averaged across 6 LV regions. RESULTS: Global LV longitudinal and circumferential myocardial strains were normal for all 15 patients with MR compared with normal controls (P>.05). Despite preserved global function, the anteroseptum and posteroseptum demonstrated significantly worse contractile function compared with other LV regions (P=.003 and P=.035, respectively). Hypercontractile regions (lateral walls) appeared to compensate (P=.002) for the reduced septal contractile function, masking injury detection by global indexes. CONCLUSIONS: The earliest contractile injury seen in patients with MR is heterogeneous and consistently distributed along the LV septum. Compensatory responses include hypercontractility of other regions. These data suggest that rather than relying on global LV contractile metrics, which cannot detect early injury, patients might be better served by undergoing directed surveillance of "sentinel" LV regions (LV septum) with high-resolution metrics of regional contractile function.

A musculoskeletal modeling approach for estimating anterior cruciate ligament strains and knee anterior-posterior shear forces in stop-jumps performed by young recreational female athletes.

The central goal of this study was to contribute to the advancements being made in determining the underlying causes of anterior cruciate ligament (ACL) injuries. ACL injuries are frequently incurred by recreational and professional young female athletes during non-contact impact activities in sports like volleyball and basketball. This musculoskeletal-neuromuscular study investigated stop-jumps and factors related to ACL injury like knee valgus and internal-external moment loads, knee anterior-posterior (AP) shear forces, ACL strains and internal forces. Motion capture data was obtained from the landing phase of stop-jumps performed by eleven young recreational female athletes and electromyography (EMG) data collected from quadriceps, hamstring and gastrocnimius muscles which were then compared to numerically estimated activations. Numerical simulation tools used were Inverse Kinematics, Computed Muscle Control and Forward Dynamics and the knee modeled as a six degree of freedom joint. Results showed averaged peak strains of 12.2 ± 4.1% in the right and 11.9 ± 3.0% in the left ACL. Averaged peak knee AP shear forces were 482.3 ± 65.7 N for the right and 430.0 ± 52.4 N for the left knees, approximately equal to 0.7-0.8 times body weight across both knees. A lack of symmetry was observed between the knees for valgus angles (p < 0.04), valgus moments (p < 0.001) and muscle activations (p < 0.001), all of which can be detrimental to ACL stability during impact activities. Comparisons between recorded EMG data and estimated muscle activations show the relation between electrical signal and muscle depolarization. In summary, this study outlines a musculoskeletal simulation approach that provides numerical estimations for a number of variables associated with ACL injuries in female athletes performing stop-jumps.

A numerical simulation approach to studying anterior cruciate ligament strains and internal forces among young recreational women performing valgus inducing stop-jump activities.

Anterior cruciate ligament (ACL) injuries are commonly incurred by recreational and professional women athletes during non-contact jumping maneuvers in sports like basketball and volleyball, where incidences of ACL injury is more frequent to females compared to males. What remains a numerical challenge is in vivo calculation of ACL strain and internal force. This study investigated effects of increasing stop-jump height on neuromuscular and bio-mechanical properties of knee and ACL, when performed by young female recreational athletes. The underlying hypothesis is increasing stop-jump (platform) height increases knee valgus angles and external moments which also increases ACL strain and internal force. Using numerical analysis tools comprised of Inverse Kinematics, Computed Muscle Control and Forward Dynamics, a novel approach is presented for computing ACL strain and internal force based on (1) knee joint kinematics and (2) optimization of muscle activation, with ACL insertion into musculoskeletal model. Results showed increases in knee valgus external moments and angles with increasing stop-jump height. Increase in stop-jump height from 30 to 50 cm lead to increase in average peak valgus external moment from 40.5 ± 3.2 to 43.2 ± 3.7 Nm which was co-incidental with increase in average peak ACL strain, from 9.3 ± 3.1 to 13.7 ± 1.1%, and average peak ACL internal force, from 1056.1 ± 71.4 to 1165.4 ± 123.8 N for the right side with comparable increases in the left. In effect this study demonstrates a technique for estimating dynamic changes to knee and ACL variables by conducting musculoskeletal simulation on motion analysis data, collected from actual stop-jump tasks performed by young recreational women athletes.

OptDesign: extending optimizable k-dissimilarity selection to combinatorial library design.

Optimizable k-dissimilarity (OptiSim) selection entails drawing a series of subsamples of size k from a population and choosing the "best" candidate from each such subsample for inclusion in the selection set. By varying the size of the subsample, one can control the balance between representativeness and diversity in the selection set obtained. In the original formulation, a uniform random sampling from among valid candidates was used to draw the subsamples from a single target population. Here we describe in detail two key modifications that serve to extend the OptiSim methodology to vector selection for interdependent variables, specifically as applied to the design of combinatorial sublibraries. The first modification involves pivoting between variables: subsamples are drawn from each reagent pool in turn, with the viability of each candidate being evaluated in isolation as well as in terms of the products it will produce from complementary reagents already selected. The filters applied may be static or dynamic in nature, with molecular weight and hydrophobicity being examples of the former and structural diversity with respect to reagents already selected being an example of the latter. The second key modification is adding the ability to bias the selection of candidate reagents for inclusion in the subsamples. Taken together, these modifications support the efficient generation of multiblock and other sparse matrix designs that are both representative and diverse, and for which "backfilling" of designs edited to remove undesirable reagents or products is straightforward. The method is intrinsically fast and efficient, since enumeration of the full combinatorial is not required- only those candidates actually considered for inclusion need be evaluated. Moreover, because the subsample selection step is separate from the diversity-based selection of the "best" candidate, incorporating such bias in favor of a competing criterion such as low price provides a "natural," nonparametric mechanism for generating designs that are likely to be "good" in a double-objective, Pareto sense.