Efficient multi-fidelity computation of blood coagulation under flow.

Clot formation is a crucial process that prevents bleeding, but can lead to severe disorders when imbalanced. This process is regulated by the coagulation cascade, a biochemical network that controls the enzyme thrombin, which converts soluble fibrinogen into the fibrin fibers that constitute clots. Coagulation cascade models are typically complex and involve dozens of partial differential equations (PDEs) representing various chemical species' transport, reaction kinetics, and diffusion. Solving these PDE systems computationally is challenging, due to their large size and multi-scale nature. We propose a multi-fidelity strategy to increase the efficiency of coagulation cascade simulations. Leveraging the slower dynamics of molecular diffusion, we transform the governing PDEs into ordinary differential equations (ODEs) representing the evolution of species concentrations versus blood residence time. We then Taylor-expand the ODE solution around the zero-diffusivity limit to obtain spatiotemporal maps of species concentrations in terms of the statistical moments of residence time, [Formula: see text], and provide the governing PDEs for [Formula: see text]. This strategy replaces a high-fidelity system of N PDEs representing the coagulation cascade of N chemical species by N ODEs and p PDEs governing the residence time statistical moments. The multi-fidelity order (p) allows balancing accuracy and computational cost providing a speedup of over N/p compared to high-fidelity models. Moreover, this cost becomes independent of the number of chemical species in the large computational meshes typical of the arterial and cardiac chamber simulations. Using a coagulation network with N = 9 and an idealized aneurysm geometry with a pulsatile flow as a benchmark, we demonstrate favorable accuracy for low-order models of p = 1 and p = 2. The thrombin concentration in these models departs from the high-fidelity solution by under 20% (p = 1) and 2% (p = 2) after 20 cardiac cycles. These multi-fidelity models could enable new coagulation analyses in complex flow scenarios and extensive reaction networks. Furthermore, it could be generalized to advance our understanding of other reacting systems affected by flow.

Submillimeter diffusion tensor imaging and late gadolinium enhancement cardiovascular magnetic resonance of chronic myocardial infarction.

BACKGROUND: Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts. METHODS: We employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence. RESULTS: The SNR of non-diffusion-weighted images was >100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation (imbrication angle mean: 1.96 ± 11.03° vs. 0.84 ± 1.47°, p = 0.61, and inclination angle range: 111.0 ± 10.7° vs. 112.5 ± 6.8°, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts. CONCLUSIONS: The application of high-resolution DTI and LGE-CMR revealed the detailed organization of anisotropic infarct structure at a chronic state. This information enhances our understanding of chronic post-infarction remodeling in large animal and human hearts.

Realistic analytical polyhedral MRI phantoms.

PURPOSE: Analytical phantoms have closed form Fourier transform expressions and are used to simulate MRI acquisitions. Existing three-dimensional (3D) analytical phantoms are unable to accurately model shapes of biomedical interest. The goal of this study was to demonstrate that polyhedral analytical phantoms have closed form Fourier transform expressions and can accurately represent 3D biomedical shapes. METHODS: The Fourier transform of a polyhedron was implemented and its accuracy in representing faceted and smooth surfaces was characterized. Realistic anthropomorphic polyhedral brain and torso phantoms were constructed and their use in simulated 3D and two-dimensional (2D) MRI acquisitions was described. RESULTS: Using polyhedra, the Fourier transform of faceted shapes can be computed to within machine precision. Smooth surfaces can be approximated with increasing accuracy by increasing the number of facets in the polyhedron; the additional accumulated numerical imprecision of the Fourier transform of polyhedra with many faces remained small. Simulations of 3D and 2D brain and 2D torso cine acquisitions produced realistic reconstructions free of high frequency edge aliasing compared with equivalent voxelized/rasterized phantoms. CONCLUSION: Analytical polyhedral phantoms are easy to construct and can accurately simulate shapes of biomedical interest. Magn Reson Med 76:663-678, 2016. © 2015 Wiley Periodicals, Inc.

MR-guided sclerotherapy of low-flow vascular malformations using T2 -weighted interrupted bSSFP (T2 W-iSSFP): comparison of pulse sequences for visualization and needle guidance.

PURPOSE: Image-guided treatment of low-flow vascular (venous or lymphatic) malformations presents a challenging visualization problem, regardless of the imaging modality being used for guidance. The purpose of this study was to employ a new magnetic resonance imaging (MRI) sequence, T2 -weighted interrupted balanced steady-state free precession (T2 W-iSSFP), for real-time image guidance of needle insertion. MATERIALS AND METHODS: T2 W-iSSFP uses variable flip angle balanced steady-state free precession (bSSFP, a.k.a. SSFP) to establish T2 -weighting and fat suppression. Swine (n = 3) and patients (n = 4, three female, all with venous malformations) were enrolled in the assessment. T2 -weighted turbo spin echo (T2 -TSE) with spectral adiabatic inversion recovery (SPAIR), SPAIR-T2 -TSE or T2 -TSE for short, was used as the reference. T2 -weighted half Fourier acquired single shot turbo spin echo (T2 -HASTE) with SPAIR (SPAIR-T2 -HASTE, T2 -HASTE for short), fat saturated bSSFP (FS-SSFP), and T2 W-iSSFP were imaged. Numeric metrics, namely, contrast-to-noise ratio (CNR) efficiency (CNR divided by the square root of acquisition time) and local sharpness (the reciprocal of edge width), were used to assess image quality. MR-guided sclerotherapy was performed on the same patients using real-time T2 W-iSSFP to guide needle insertion. RESULTS: Comparing the visualization of needles in the images of swine, the local sharpness (mm(-1) ) was: 0.21 ± 0.06 (T2 -HASTE), 0.48 ± 0.02 (FS-SSFP), and 0.49 ± 0.03 (T2 W-iSSFP). T2 W-iSSFP is higher than T2 -HASTE (P < 0.001). For the patient images, their CNR efficiencies were: 797 ± 66 (T2 -HASTE), 281 ± 44 (FS-SSFP), and 860 ± 29 (T2 W-iSSFP). T2 W-iSSFP is higher than FS-SSFP (P < 0.02). The frame rate of T2 W-iSSFP was 2.5-3.5 frames per second. All MR-guided sclerotherapy procedures were successful, with all needles (six punctures) placed in the targets. CONCLUSION: T2 W-iSSFP provides effective lesion identification and needle visualization. This new pulse sequence can be used for MR-guided sclerotherapy of low-flow vascular malformations. It may have potential use in other MR-guided procedures where heavily T2 -weighted real-time images are needed.

Protocol Optimization for Functional Cardiac CT Imaging Using Noise Emulation in the Raw Data Domain.

Background: Four-dimensional (4D) wide coverage computed tomography (CT) is an effective imaging modality for measuring the mechanical function of the myocardium. However, repeated CT measurement across a number of heartbeats is still a concern. Purpose: A projection-domain noise emulation method is presented to generate accurate low-dose (mA modulated) 4D cardiac CT scans from high-dose scans, enabling protocol optimization to deliver sufficient image quality for functional cardiac analysis while using a dose level that is as low as reasonably achievable (ALARA). Methods: Given a targeted low-dose mA modulation curve, the proposed noise emulation method injects both quantum and electronic noise of proper magnitude and correlation to the high-dose data in projection domain. A spatially varying (i.e., channel-dependent) detector gain term as well as its calibration method were proposed to further improve the noise emulation accuracy. To determine the ALARA dose threshold, a straightforward projection domain image quality (IQ) metric was proposed that is based on the number of projection rays that do not fall under the non-linear region of the detector response. Experiments were performed to validate the noise emulation method with both phantom and clinical data in terms of visual similarity, contrast-to-noise ratio (CNR), and noise-power spectrum (NPS). Results: For both phantom and clinical data, the low-dose emulated images exhibited similar noise magnitude (CNR difference within 2%), artifacts, and texture to that of the real low-dose images. The proposed channel-dependent detector gain term resulted in additional increase in emulation accuracy. Using the proposed IQ metric, recommended kVp and mA settings were calculated for low dose 4D Cardiac CT acquisitions for patients of different sizes. Conclusions: A detailed method to estimate system-dependent parameters for a raw-data based low dose emulation framework was described. The method produced realistic noise levels, artifacts, and texture with phantom and clinical studies. The proposed low-dose emulation method can be used to prospectively select patient-specific minimal-dose protocols for functional cardiac CT.

Protocol optimization for functional cardiac CT imaging using noise emulation in the raw data domain.

BACKGROUND: Four-dimensional (4D) wide coverage computed tomography (CT) is an effective imaging modality for measuring the mechanical function of the myocardium. However, repeated CT measurement across a number of heartbeats is still a concern. PURPOSE: A projection-domain noise emulation method is presented to generate accurate low-dose (mA modulated) 4D cardiac CT scans from high-dose scans, enabling protocol optimization to deliver sufficient image quality for functional cardiac analysis while using a dose level that is as low as reasonably achievable (ALARA). METHODS: Given a targeted low-dose mA modulation curve, the proposed noise emulation method injects both quantum and electronic noise of proper magnitude and correlation to the high-dose data in projection domain. A spatially varying (i.e., channel-dependent) detector gain term as well as its calibration method were proposed to further improve the noise emulation accuracy. To determine the ALARA dose threshold, a straightforward projection domain image quality (IQ) metric was proposed that is based on the number of projection rays that do not fall under the non-linear region of the detector response. Experiments were performed to validate the noise emulation method with both phantom and clinical data in terms of visual similarity, contrast-to-noise ratio (CNR), and noise-power spectrum (NPS). RESULTS: For both phantom and clinical data, the low-dose emulated images exhibited similar noise magnitude (CNR difference within 2%), artifacts, and texture to that of the real low-dose images. The proposed channel-dependent detector gain term resulted in additional increase in emulation accuracy. Using the proposed IQ metric, recommended kVp and mA settings were calculated for low dose 4D Cardiac CT acquisitions for patients of different sizes. CONCLUSIONS: A detailed method to estimate system-dependent parameters for a raw-data based low dose emulation framework was described. The method produced realistic noise levels, artifacts, and texture with phantom and clinical studies. The proposed low-dose emulation method can be used to prospectively select patient-specific minimal-dose protocols for functional cardiac CT.

Motion correction of wide-detector 4DCT images for cardiac resynchronization therapy planning.

BACKGROUND: Lead placement at the latest mechanically activated left ventricle (LV) segments is strongly correlated with response to cardiac resynchronization therapy (CRT). We demonstrate the feasibility of a cardiac 4DCT motion correction algorithm (ResyncCT) in estimating LV mechanical activation for guiding lead placement in CRT. METHODS: Subjects with full cardiac cycle 4DCT images acquired using a wide-detector CT scanner for CRT planning/upgrade were included. 4DCT images exhibited motion artifact-induced false-dyssynchrony, hindering LV mechanical activation time estimation. Motion-corrupted images were processed with ResyncCT to yield motion-corrected images. Time to onset of shortening (TOS) was estimated in each of 72 endocardial segments. A false-dyssynchrony index (FDI) was used to quantify the extent of motion artifacts in the uncorrected and the ResyncCT images. After motion correction, the change in classification of LV free-wall segments as optimal target sites for lead placement was investigated. RESULTS: Twenty subjects (70.7 â€‹± â€‹13.9 years, 6 female) were analyzed. Motion artifacts in the ResyncCT-processed images were significantly reduced (FDI: 28.9 â€‹± â€‹9.3 â€‹% vs 47.0 â€‹± â€‹6.0 â€‹%, p â€‹< â€‹0.001). In 10 (50 â€‹%) subjects, ResyncCT motion correction yielded statistically different TOS estimates (p â€‹< â€‹0.05). Additionally, 43 â€‹% of LV free-wall segments were reclassified as optimal target sites for lead placement after motion correction. CONCLUSIONS: ResyncCT significantly reduced motion artifacts in wide-detector cardiac 4DCT images, yielded statistically different time to onset of shortening estimates, and changed the location of optimal target sites for lead placement. These results highlight the potential utility of ResyncCT motion correction in CRT planning when using wide-detector 4DCT imaging.

Geometric Changes in Mitral Valve Apparatus during Long-term Cardiac Resynchronization Therapy as Assessed with Cardiac CT.

Purpose To assess long-term geometric changes of the mitral valve apparatus using cardiac CT in individuals who underwent cardiac resynchronization therapy (CRT). Materials and Methods Participants from a randomized controlled trial with cardiac CT examinations before CRT implantation and at 6 months follow-up (Clinicaltrials.gov identifier NCT01323686) were invited to undergo an additional long-term follow-up cardiac CT examination. The geometry of the mitral valve apparatus, including mitral valve annulus area, A2 leaflet angle, tenting height, and interpapillary muscle distances, were assessed. Geometric changes at the long-term follow-up examination were reported as mean differences (95% CI), and the Pearson correlation test was used to assess correlation between statistically significant geometric changes and left ventricular (LV) volumes and function. Results Thirty participants (mean age, 68 years ± 9 [SD]; 25 male participants) underwent cardiac CT imaging after a median long-term follow-up of 9.0 years (IQR, 8.4-9.4). There were reductions in end-systolic A2 leaflet angle (-4° [95% CI: -7, -2]), end-systolic tenting height (-1 mm [95% CI: -2, -1]), and end-systolic and end-diastolic interpapillary muscle distances (-4 mm [95% CI: -6, -2]) compared with pre-CRT implantation values. The mitral valve annulus area remained unchanged. LV end-diastolic and end-systolic volumes decreased (-68 mL [95% CI: -99, -37] and -67 mL [95% CI: -96, -39], respectively), and LV ejection fraction increased (13% [95% CI: 7, 19]) at the long-term follow-up examination. Changes in interpapillary muscle distances showed moderate to strong correlations with LV volumes (r = 0.42-0.72; P < .05), while A2 leaflet angle and tenting height were not correlated to LV volumes or function. Conclusion Among the various geometric changes in the mitral valve apparatus after long-term CRT, the reduction in interpapillary muscle distances correlated with LV volumes while the reduced A2 leaflet angle and tenting height did not correlate with LV volumes. Keywords: Mitral Valve Apparatus, Cardiac Resynchronization Therapy, Cardiac CT Supplemental material is available for this article. © RSNA, 2024.

Rectus femoris knee muscle moment arms measured in vivo during dynamic motion with real-time magnetic resonance imaging.

Moment arms represent a muscle's ability to generate a moment about a joint for a given muscle force. The goal of this study was to develop a method to measure muscle moment arms in vivo over a large range of motion using real-time magnetic resonance (MR) imaging. Rectus femoris muscle-tendon lengths and knee joint angles of healthy subjects (N = 4) were measured during dynamic knee joint flexion and extension in a large-bore magnetic resonance imaging (MRI) scanner. Muscle-tendon moment arms were determined at the knee using the tendon-excursion method by differentiating measured muscle-tendon length with respect to joint angle. Rectus femoris moment arms were averaged across a group of healthy subjects and were found to vary similarly during knee joint flexion (mean: 3.0 (SD 0.5) cm, maximum: 3.5 cm) and extension (mean: 2.8 (SD 0.4) cm, maximum: 3.6 cm). These moment arms compare favorably with previously published dynamic tendon-excursion measurements in cadaveric specimens but were relatively smaller than moment arms from center-of-rotation studies. The method presented here provides a new approach to measure muscle-tendon moment arms in vivo and has the potential to be a powerful resource for characterizing musculoskeletal geometry during dynamic joint motion.

Quantitative analysis of small coronary artery calcium detectability with an accurate simulation and validation on a clinical CT scanner.

BACKGROUND: The absence of coronary artery calcium (CAC) measured via CT is associated with very favorable prognosis, and current guidelines recommend low-density lipoprotein cholesterol (LDL-c) lowering therapy for individuals with any CAC. This motivates early detection of small granules of CAC; however, calcium scan sensitivity for detecting very low levels of calcium has not been quantified. PURPOSE: In this work, the size limit of detectability of small calcium hydroxyapatite (CaHA) granules with clinical CAC scanning was assessed using validated simulations. METHODS: CT projections of digital 3D mathematical phantoms containing small CaHA granules were simulated analytically; images were reconstructed using a filter designed to reproduce the point spread function of a specific commercial scanner, and a relationship of HU number versus diameter was derived. These simulation results were validated with experimental measurements of HU versus diameter from phantoms containing small granules of CaHA on a GE Revolution CT scanner in the clinic; ground truth measurements of the CaHA granule diameters were obtained using a Zeiss Xradia 510 Versa high-resolution 3D micro-CT imaging system. Using experimental measurements on the clinical CT scanner, detectability was quantified with a detectability index (d') using a non-prewhitened matched filter. The effect of changes to reconstruction slice thickness and reconstruction kernel on granule detectability was evaluated. RESULTS: Under typical clinical calcium scanning and reconstruction conditions, the minimum detectable diameter of a simulated spherical calcium granule with a clinically relevant CaHA density was 0.76 mm. The minimum detectable volume was 2.4 times smaller on images reconstructed at a slice thickness of 0.625 mm compared to 2.5 mm. The detectability index d' increased by a factor of 1.7 when images were reconstructed with 0.625 mm slices compared to 2.5 mm slices. d' did not change when images were reconstructed with the high-resolution BONE filter compared to the less sharp STANDARD resolution filter on the GE Revolution CT. CONCLUSIONS: We have quantified detectability versus size of small calcium granules at the resolution limit of a widely available clinical CT scanner. Detectability increased significantly with reduced slice thickness and did not change with a sharper reconstruction kernel. The simulation can be used to calculate the trade-off between dose and CAC detectability.

Myocardial Regional Shortening from 4D Cardiac CT Angiography for the Detection of Left Ventricular Segmental Wall Motion Abnormality.

Purpose: To investigate whether endocardial regional shortening computed from four-dimensional (4D) CT angiography (RSCT) can be used as a decision classifier to detect the presence of left ventricular (LV) wall motion abnormalities (WMAs). Materials and Methods: One hundred electrocardiographically gated cardiac 4D CT studies (mean age, 59 years ± 14 [SD]; 61 male patients) conducted between April 2018 and December 2020 were retrospectively evaluated. Three experts labeled LV wall motion in each of the 16 American Heart Association (AHA) segments as normal or abnormal; they also measured peak RSCT across one heartbeat in each segment. The data set was split evenly into training and validation groups. During training, interchangeability of RSCT thresholding with experts to detect WMA was assessed using the individual equivalence index (γ), and an optimal threshold of the peak RSCT (RSCT*) that achieved maximum agreement was identified. RSCT* was then validated using the validation group, and the effect of AHA segment-specific thresholds was evaluated. Agreement was assessed using κ statistics. Results: The optimal threshold, RSCT* of -0.19, when applied to all AHA segments, led to high agreement (agreement rate = 92.17%, κ = 0.82) and interchangeability with experts (γ = -2.58%). The same RSCT* also achieved high agreement in the validation group (agreement rate = 90.29%, κ = 0.76, γ = -0.38%). The use of AHA segment-specific thresholds (range: 0.16 to -0.23 across AHA segments) slightly improved agreement (1.79% increase). Conclusion: RSCT thresholding was interchangeable with expert visual analysis in detecting segmental WMA from 4D CT and may be used as an objective decision classifier.Keywords: CT, Left Ventricle, Regional Endocardial Shortening, Wall Motion Abnormality Supplemental material is available for this article. © RSNA, 2023.

Pulmonary vein flow split effects in patient-specific simulations of left atrial flow.

Disruptions to left atrial (LA) blood flow, such as those caused by atrial fibrillation (AF), can lead to thrombosis in the left atrial appendage (LAA) and an increased risk of systemic embolism. LA hemodynamics are influenced by various factors, including LA anatomy and function, and pulmonary vein (PV) inflow conditions. In particular, the PV flow split can vary significantly among and within patients depending on multiple factors. In this study, we investigated how changes in PV flow split affect LA flow transport, focusing for the first time on blood stasis in the LAA, using a high-fidelity patient-specific computational fluid dynamics (CFD) model. We use an Immersed Boundary Method, simulating the flow in a fixed, uniform Cartesian mesh and imposing the movement of the LA walls with a moving Lagrangian mesh generated from 4D Computerized Tomography images. We analyzed LA anatomies from eight patients with varying atrial function, including three with AF and either a LAA thrombus or a history of Transient Ischemic Attacks (TIAs). Using four different flow splits (60/40% and 55/45% through right and left PVs, even flow rate, and same velocity through each PV), we found that flow patterns are sensitive to PV flow split variations, particularly in planes parallel to the mitral valve. Changes in PV flow split also had a significant impact on blood stasis and could contribute to increased risk for thrombosis inside the LAA, particularly in patients with AF and previous LAA thrombus or a history of TIAs. Our study highlights the importance of considering patient-specific PV flow split variations when assessing LA hemodynamics and identifying patients at increased risk for thrombosis and stroke. This knowledge is relevant to planning clinical procedures such as AF ablation or the implementation of LAA occluders.

Efficient multi-fidelity computation of blood coagulation under flow.

Clot formation is a crucial process that prevents bleeding, but can lead to severe disorders when imbalanced. This process is regulated by the coagulation cascade, a biochemical network that controls the enzyme thrombin, which converts soluble fibrinogen into the fibrin fibers that constitute clots. Coagulation cascade models are typically complex and involve dozens of partial differential equations (PDEs) representing various chemical species' transport, reaction kinetics, and diffusion. Solving these PDE systems computationally is challenging, due to their large size and multi-scale nature. We propose a multi-fidelity strategy to increase the efficiency of coagulation cascade simulations. Leveraging the slower dynamics of molecular diffusion, we transform the governing PDEs into ordinary differential equations (ODEs) representing the evolution of species concentrations versus blood residence time. We then Taylor-expand the ODE solution around the zero-diffusivity limit to obtain spatiotemporal maps of species concentrations in terms of the statistical moments of residence time, , and provide the governing PDEs for . This strategy replaces a high-fidelity system of N PDEs representing the coagulation cascade of N chemical species by N ODEs and p PDEs governing the residence time statistical moments. The multi-fidelity order( p ) allows balancing accuracy and computational cost, providing a speedup of over N/p compared to high-fidelity models. Using a simplified coagulation network and an idealized aneurysm geometry with a pulsatile flow as a benchmark, we demonstrate favorable accuracy for low-order models of p = 1 and p = 2. These models depart from the high-fidelity solution by under 16% ( p = 1) and 5% ( p = 2) after 20 cardiac cycles. The favorable accuracy and low computational cost of multi-fidelity models could enable unprecedented coagulation analyses in complex flow scenarios and extensive reaction networks. Furthermore, it can be generalized to advance our understanding of other systems biology networks affected by blood flow.

Four-dimensional computed tomography of the left ventricle, Part II: Estimation of mechanical activation times.

PURPOSE: We demonstrate the viability of a four-dimensional X-ray computed tomography (4DCT) imaging system to accurately and precisely estimate mechanical activation times of left ventricular (LV) wall motion. Accurate and reproducible timing estimates of LV wall motion may be beneficial in the successful planning and management of cardiac resynchronization therapy (CRT). METHODS: We developed an anthropomorphically accurate in silico LV phantom based on human CT images with programmed septal-lateral wall dyssynchrony. Twenty-six temporal phases of the in silico phantom were used to sample the cardiac cycle of 1 s. For each of the 26 phases, 1 cm thick axial slabs emulating axial CT image volumes were extracted, 3D printed, and imaged using a commercially available CT scanner. A continuous dynamic sinogram was synthesized by blending sinograms from these static phases; the synthesized sinogram emulated the sinogram that would be acquired under true continuous phantom motion. Using the synthesized dynamic sinogram, images were reconstructed at 70 ms intervals spanning the full cardiac cycle; these images exhibited expected motion artifact characteristics seen in images reconstructed from real dynamic data. The motion corrupted images were then processed with a novel motion correction algorithm (ResyncCT) to yield motion corrected images. Five pairs of motion uncorrected and motion corrected images were generated, each corresponding to a different starting gantry angle (0 to 180 degrees in 45 degree increments). Two line profiles perpendicular to the endocardial surface were used to sample local myocardial motion trajectories at the septum and the lateral wall. The mechanical activation time of wall motion was defined as the time at which the endocardial boundary crossed a fixed position defined on either of the two line profiles while moving toward the center of the LV during systolic contraction. The mechanical activation times of these myocardial trajectories estimated from the motion uncorrected and the motion corrected images were then compared with those derived from the static images of the 3D printed phantoms (ground truth). The precision of the timing estimates was obtained from the five different starting gantry angle simulations. RESULTS: The range of estimated mechanical activation times observed across all starting gantry angles was significantly larger for the motion uncorrected images than for the motion corrected images (lateral wall: 58 ± 15 ms vs 12 ± 4 ms, p < 0.005; septal wall: 61 ± 13 ms vs 13 ± 9 ms, p < 0.005). CONCLUSIONS: 4DCT images processed with the ResyncCT motion correction algorithm yield estimates of mechanical activation times of LV wall motion with significantly improved accuracy and precision. The promising results reported in this study highlight the potential utility of 4DCT in estimating the timing of mechanical events of interest for CRT guidance.

Four-dimensional computed tomography of the left ventricle, Part I: Motion artifact reduction.

PURPOSE: Standard four-dimensional computed tomography (4DCT) cardiac reconstructions typically include spiraling artifacts that depend not only on the motion of the heart but also on the gantry angle range over which the data was acquired. We seek to reduce these motion artifacts and, thereby, improve the accuracy of left ventricular wall positions in 4DCT image series. METHODS: We use a motion artifact reduction approach (ResyncCT) that is based largely on conjugate pairs of partial angle reconstruction (PAR) images. After identifying the key locations where motion artifacts exist in the uncorrected images, paired subvolumes within the PAR images are analyzed with a modified cross-correlation function in order to estimate 3D velocity and acceleration vectors at these locations. A subsequent motion compensation process (also based on PAR images) includes the creation of a dense motion field, followed by a backproject-and-warp style compensation. The algorithm was tested on a 3D printed phantom, which represents the left ventricle (LV) and on challenging clinical cases corrupted by severe artifacts. RESULTS: The results from our preliminary phantom test as well as from clinical cardiac scans show crisp endocardial edges and resolved double-wall artifacts. When viewed as a temporal series, the corrected images exhibit a much smoother motion of the LV endocardial boundary as compared to the uncorrected images. In addition, quantitative results from our phantom studies show that ResyncCT processing reduces endocardial surface distance errors from 0.9 ± 0.8 to 0.2 ± 0.1 mm. CONCLUSIONS: The ResyncCT algorithm was shown to be effective in reducing motion artifacts and restoring accurate wall positions. Some perspectives on the use of conjugate-PAR images and on techniques for CT motion artifact reduction more generally are also given.

Detection of left ventricular wall motion abnormalities from volume rendering of 4DCT cardiac angiograms using deep learning.

Background: The presence of left ventricular (LV) wall motion abnormalities (WMA) is an independent indicator of adverse cardiovascular events in patients with cardiovascular diseases. We develop and evaluate the ability to detect cardiac wall motion abnormalities (WMA) from dynamic volume renderings (VR) of clinical 4D computed tomography (CT) angiograms using a deep learning (DL) framework. Methods: Three hundred forty-three ECG-gated cardiac 4DCT studies (age: 61 ± 15, 60.1% male) were retrospectively evaluated. Volume-rendering videos of the LV blood pool were generated from 6 different perspectives (i.e., six views corresponding to every 60-degree rotation around the LV long axis); resulting in 2058 unique videos. Ground-truth WMA classification for each video was performed by evaluating the extent of impaired regional shortening visible (measured in the original 4DCT data). DL classification of each video for the presence of WMA was performed by first extracting image features frame-by-frame using a pre-trained Inception network and then evaluating the set of features using a long short-term memory network. Data were split into 60% for 5-fold cross-validation and 40% for testing. Results: Volume rendering videos represent ~800-fold data compression of the 4DCT volumes. Per-video DL classification performance was high for both cross-validation (accuracy = 93.1%, sensitivity = 90.0% and specificity = 95.1%, κ: 0.86) and testing (90.9, 90.2, and 91.4% respectively, κ: 0.81). Per-study performance was also high (cross-validation: 93.7, 93.5, 93.8%, κ: 0.87; testing: 93.5, 91.9, 94.7%, κ: 0.87). By re-binning per-video results into the 6 regional views of the LV we showed DL was accurate (mean accuracy = 93.1 and 90.9% for cross-validation and testing cohort, respectively) for every region. DL classification strongly agreed (accuracy = 91.0%, κ: 0.81) with expert visual assessment. Conclusions: Dynamic volume rendering of the LV blood pool combined with DL classification can accurately detect regional WMA from cardiac CT.

Non-Newtonian blood rheology impacts left atrial stasis in patient-specific simulations.

The lack of mechanically effective contraction of the left atrium (LA) during atrial fibrillation (AF) disturbs blood flow, increasing the risk of thrombosis and ischemic stroke. Thrombosis is most likely in the left atrial appendage (LAA), a small narrow sac where blood is prone to stagnate. Slow flow promotes the formation of erythrocyte aggregates in the LAA, also known as rouleaux, causing viscosity gradients that are usually disregarded in patient-specific simulations. To evaluate these non-Newtonian effects, we built atrial models derived from 4D computed tomography scans of patients and carried out computational fluid dynamics simulations using the Carreau-Yasuda constitutive relation. We examined six patients, three of whom had AF and LAA thrombosis or a history of transient ischemic attacks (TIAs). We modeled the effects of hematocrit and rouleaux formation kinetics by varying the parameterization of the Carreau-Yasuda relation and modulating non-Newtonian viscosity changes based on residence time. Comparing non-Newtonian and Newtonian simulations indicates that slow flow in the LAA increases blood viscosity, altering secondary swirling flows and intensifying blood stasis. While some of these effects are subtle when examined using instantaneous metrics like shear rate or kinetic energy, they are manifested in the blood residence time, which accumulates over multiple heartbeats. Our data also reveal that LAA blood stasis worsens when hematocrit increases, offering a potential new mechanism for the clinically reported correlation between hematocrit and stroke incidence. In summary, we submit that hematocrit-dependent non-Newtonian blood rheology should be considered when calculating patient-specific blood stasis indices by computational fluid dynamics.

Regional left ventricular endocardial strains estimated from low-dose 4DCT: Comparison with cardiac magnetic resonance feature tracking.

BACKGROUND: Estimates of regional left ventricular (LV) strains provide additional information to global function parameters such as ejection fraction (EF) and global longitudinal strain (GLS) and are more sensitive in detecting abnormal regional cardiac function. The accurate and reproducible assessment of regional cardiac function has implications in the management of various cardiac diseases such as heart failure, myocardial ischemia, and dyssynchrony. PURPOSE: To develop a method that yields highly reproducible, high-resolution estimates of regional endocardial strains from 4DCT images. METHODS: A method for estimating regional LV endocardial circumferential ( ε c c ) $( {{\epsilon }_{cc}} )$ and longitudinal ( ε l l ${\epsilon }_{ll}$ ) strains from 4DCT was developed. Point clouds representing the LV endocardial surface were extracted for each time frame of the cardiac cycle from 4DCT images. 3D deformation fields across the cardiac cycle were obtained by registering the end diastolic point cloud to each subsequent point cloud in time across the cardiac cycle using a 3D point-set registration technique. From these deformation fields, ε c c and ε l l ${\epsilon }_{cc}\ {\rm{and\ }}{\epsilon }_{ll}$ were estimated over the entire LV endocardial surface by fitting an affine transformation with maximum likelihood estimation. The 4DCT-derived strains were compared with strains estimated in the same subjects by cardiac magnetic resonance (CMR); twenty-four subjects had CMR scans followed by 4DCT scans acquired within a few hours. Regional LV circumferential and longitudinal strains were estimated from the CMR images using a commercially available feature tracking software (cvi42). Global circumferential strain (GCS) and global longitudinal strain (GLS) were calculated as the mean of the regional strains across the entire LV for both modalities. Pearson correlation coefficients and Bland-Altman analyses were used for comparisons. Intraclass correlation coefficients (ICC) were used to assess the inter- and intraobserver reproducibility of the 4DCT-derived strains. RESULTS: The 4DCT-derived regional strains correlated well with the CMR-derived regional strains ( ε c c ${\epsilon }_{cc}$ : r = 0.76, p < 0.001; ε l l ${\epsilon }_{ll}$ : r = 0.64, p < 0.001). A very strong correlation was found between 4DCT-derived GCS and 4DCT-derived EF (r = -0.96; p < 0.001). The 4DCT-derived strains were also highly reproducible, with very low inter- and intraobserver variability (intraclass correlation coefficients in the range of [0.92, 0.99]). CONCLUSIONS: We have developed a novel method to estimate high-resolution regional LV endocardial circumferential and longitudinal strains from 4DCT images. Except for the definition of the mitral valve and LV outflow tract planes, the method is completely user independent, thus yielding highly reproducible estimates of endocardial strain. The 4DCT-derived strains correlated well with those estimated using a commercial CMR feature tracking software. The promising results reported in this study highlight the potential utility of 4DCT in the precise assessment of regional cardiac function for the management of cardiac disease.

Prediction of Cardiac Resynchronization Therapy Response Using a Lead Placement Score Derived From 4-Dimensional Computed Tomography.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure; however, 30% of patients do not respond to the treatment. We sought to derive patient-specific left ventricle maps of lead placement scores (LPS) that highlight target pacing lead sites for achieving a higher probability of CRT response. METHODS: Eighty-two subjects recruited for the ImagingCRT trial (Empiric Versus Imaging Guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy) were retrospectively analyzed. All 82 subjects had 2 contrast-enhanced full cardiac cycle 4-dimensional computed tomography scans: a baseline and a 6-month follow-up scan. CRT response was defined as a reduction in computed tomography-derived end-systolic volume ≥15%. Eight left ventricle features derived from the baseline scans were used to train a support vector machine via a bagging approach. An LPS map over the left ventricle was created for each subject as a linear combination of the support vector machine feature weights and the subject's own feature vector. Performance for distinguishing responders was performed on the original 82 subjects. RESULTS: Fifty-two (63%) subjects were responders. Subjects with an LPS≤Q1 (lower-quartile) had a posttest probability of responding of 14% (3/21), while subjects with an LPS≥ Q3 (upper-quartile) had a posttest probability of responding of 90% (19/21). Subjects with Q1

Imaging left ventricular tissue mechanics and hemodynamics during supine bicycle exercise using a combined tagging and phase-contrast MRI pulse sequence.

Imaging the left ventricular mechanical and hemodynamic response to the stress of exercise may offer early prognosis in select patients with cardiac disease. Here, we demonstrate the feasibility of obtaining simultaneous measurements of longitudinal strain and transvalvular blood velocity during supine bicycle exercise stress in a wide bore magnetic resonance scanner. Combining information from the two datasets, we observe that although the time to peak strain (33.28 ± 1.86 versus 25.7 ± 2.12 as % of R-R interval) and time to peak mitral inflow velocity (44.37 ± 5.21 versus 35.5 ± 4.19 as % of R-R interval) from R-wave of the QRS complex occurred earlier during stress, the time from peak strain to peak mitral inflow velocity was not statistically different (16.5 ± 3.23 versus 13.4 ± 3.06). Further, the percentage of longitudinal relaxation at peak mitral inflow velocity was higher during stress (63.5 ± 7.72 versus 84.32 ± 6.24). These results suggest that although diastole is shortened, early diastolic filling efficiency is augmented during exercise stress in normal volunteers in an effort to maintain stroke volume.