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.

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.

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

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.

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.

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.

Novel 4DCT Method to Measure Regional Left Ventricular Endocardial Shortening Before and After Transcatheter Mitral Valve Implantation.

BACKGROUND: Regional left ventricular (LV) mechanics in mitral regurgitation (MR) patients, and local changes in function after transcatheter mitral valve implantation (TMVI) have yet to be evaluated. Herein, we introduce a method for creating high resolution maps of endocardial function from 4DCT images, leading to detailed characterization of changes in local LV function. These changes are particularly interesting when evaluating the effect of the Tendyne™ TMVI device in the region of the epicardial pad. METHODS: Regional endocardial shortening from CT (RSCT) was evaluated in Tendyne (Abbott Medical) TMVI patients with 4DCT exams pre- and post-implantation. Regional function was evaluated in 90 LV segments (5 longitudinal × 18 circumferential). LV volumes and ejection fraction (EF) were also computed. A reproducibility study was performed in a subset of patients to determine the precision of RSCT measurements in this population. RESULTS: Baseline and local changes in RSCT post TMVI were highly variable and extremely spatially heterogeneous. Both inter- and intra-observer variability were low and demonstrated the high precision of RSCT for evaluating regional LV function. CONCLUSION: RSCT is a reproducible metric which can be evaluated in patients with highly abnormal regional LV function and geometry. After TMVI, significant spatially heterogeneous changes in RSCT were observed in all subjects; therefore, it is unlikely that the functional state of TMVI patients can be fully described by changes in LV volume or EF. Measurement of RSCT provides precise characterization of the spatially heterogeneous effects of MR and TMVI on LV function and remodeling.

Targeted Coronary Artery Calcium Screening in High-Risk Younger Individuals Using Consumer Genetic Screening Results.

OBJECTIVES: The goal of this study was to assess the utility of a genetic risk score (GRS) in targeted coronary artery calcium (CAC) screening among young individuals. BACKGROUND: Early CAC screening and preventive therapy may reduce long-term risk of a coronary heart disease (CHD) event. However, identifying younger individuals at increased risk remains a challenge. GRS for CHD are age independent and can stratify individuals on various risk trajectories. METHODS: Using 142 variants associated with CHD events, we calculated a GRS in 1,927 individuals in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort (aged 32 to 47 years) and 6,600 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (aged 44 to 87 years). We assessed GRS utility to predict CAC presence in the CARDIA cohort and stratify individuals of varying risk for CAC presence over the lifetime in both cohorts. RESULTS: The GRS predicted CAC presence in CARDIA males. It was not predictive in CARDIA females, which had a CAC prevalence of 6.4%. In combined analysis of the CARDIA and MESA cohorts, the GRS was predictive of CAC in both males and females and was used to derive an equation for the age at which CAC probability crossed a predetermined threshold. When assessed in combination with traditional risk factors, the GRS further stratified individuals. For individuals with an equal number of traditional risk factors, probability of CAC reached 25% approximately 10 years earlier for those in the highest GRS quintile compared to the lowest. CONCLUSIONS: The GRS may be used to target high-risk younger individuals for early CAC screening.

Constructing a Human Atrial Fibre Atlas.

Atrial anisotropy affects electrical propagation patterns, anchor locations of atrial reentrant drivers, and atrial mechanics. However, patient-specific atrial fibre fields and anisotropy measurements are not currently available, and consequently assigning fibre fields to atrial models is challenging. We aimed to construct an atrial fibre atlas from a high-resolution DTMRI dataset that optimally reproduces electrophysiology simulation predictions corresponding to patient-specific fibre fields, and to develop a methodology for automatically assigning fibres to patient-specific anatomies. We extended an atrial coordinate system to map the pulmonary veins, vena cava and appendages to standardised positions in the coordinate system corresponding to the average location across the anatomies. We then expressed each fibre field in this atrial coordinate system and calculated an average fibre field. To assess the effects of fibre field on patient-specific modelling predictions, we calculated paced activation time maps and electrical driver locations during AF. In total, 756 activation time maps were calculated (7 anatomies with 9 fibre maps and 2 pacing locations, for the endocardial, epicardial and bilayer surface models of the LA and RA). Patient-specific fibre fields had a relatively small effect on average paced activation maps (range of mean local activation time difference for LA fields: 2.67-3.60 ms, and for RA fields: 2.29-3.44 ms), but had a larger effect on maximum LAT differences (range for LA 12.7-16.6%; range for RA 11.9-15.0%). A total of 126 phase singularity density maps were calculated (7 anatomies with 9 fibre maps for the LA and RA bilayer models). The fibre field corresponding to anatomy 1 had the highest median PS density map correlation coefficient for LA bilayer simulations (0.44 compared to the other correlations, ranging from 0.14 to 0.39), while the average fibre field had the highest correlation for the RA bilayer simulations (0.61 compared to the other correlations, ranging from 0.37 to 0.56). For sinus rhythm simulations, average activation time is robust to fibre field direction; however, maximum differences can still be significant. Patient specific fibres are more important for arrhythmia simulations, particularly in the left atrium. We propose using the fibre field corresponding to DTMRI dataset 1 for LA simulations, and the average fibre field for RA simulations as these optimally predicted arrhythmia properties.

M-SiSSR: Regional Endocardial Function Using Multilabel Simultaneous Subdivision Surface Registration.

Quantification of regional cardiac function is a central goal of cardiology. Multiple methods, such as Coherent Point Drift (CPD) and Simultaneous Subdivision Surface Registration (SiSSR), have been used to register meshes to the endocardial surface. However, these methods do not distinguish between cardiac chambers during registration, and consequently the mesh may "slip" across the interface between two structures during contraction, resulting in inaccurate regional functional measurements. Here, we present Multilabel-SiSSR (M-SiSSR), a novel method for registering a "labeled" cardiac mesh (with each triangle assigned to a cardiac structure). We compare our results to the original, label-agnostic version of SiSSR and find both a visual and quantitative improvement in tracking of the mitral valve plane.

Automatic estimation of aortic and mitral valve displacements in dynamic CTA with 4D graph-cuts.

The location of the mitral and aortic valves in dynamic cardiac imaging is useful for extracting functional derived parameters such as ejection fraction, valve excursions, and global longitudinal strain, and when performing anatomical structures tracking using slice following or valve intervention's planning. Completely automatic segmentation methods are still challenging tasks because of their fast movements and the different positions that prevent good visibility of the leaflets along the full cardiac cycle. In this article, we propose a processing pipeline to track the displacement of the aortic and mitral valve annuli from high-resolution cardiac four-dimensional computed tomographic angiography (4D-CTA). The proposed method is based on the dynamic separation of left ventricle, left atrium and aorta using statistical shape modeling and an energy minimization algorithm based on graph-cuts and has been evaluated on a set of 15 electrocardiography-gated 4D-CTAs. We report a mean agreement distance between manual annotations and our proposed method of 2.52±1.06 mm for the mitral annulus and 2.00±0.69 mm for the aortic valve annulus based on valve locations detected from manual anatomical landmarks. In addition, we show the effect of detecting the valvular planes on derived functional parameters (ejection fraction, global longitudinal strain, and excursions of the mitral and aortic valves).

Anthropomorphic left ventricular mesh phantom: a framework to investigate the accuracy of SQUEEZ using Coherent Point Drift for the detection of regional wall motion abnormalities.

We present an anthropomorphically accurate left ventricular (LV) phantom derived from human computed tomography (CT) data to serve as the ground truth for the optimization and the spatial resolution quantification of a CT-derived regional strain metric (SQUEEZ) for the detection of regional wall motion abnormalities. Displacements were applied to the mesh points of a clinically derived end-diastolic LV mesh to create analytical end-systolic poses with physiologically accurate endocardial strains. Normal function and regional dysfunction of four sizes [1, 2/3, 1/2, and 1/3 American Heart Association (AHA) segments as core diameter], each exhibiting hypokinesia (70% reduction in strain) and subtle hypokinesia (40% reduction in strain), were simulated. Regional shortening ( RS CT ) estimates were obtained by registering the end-diastolic mesh to each simulated end-systolic mesh condition using a nonrigid registration algorithm. Ground-truth models of normal function and of hypokinesia were used to identify the optimal parameters in the registration algorithm and to measure the accuracy of detecting regional dysfunction of varying sizes and severities. For normal LV function, RS CT values in all 16 AHA segments were accurate to within ± 5 % . For cases with regional dysfunction, the errors in RS CT around the dysfunctional region increased with decreasing size of dysfunctional tissue.

Vascular Landmark-Based Method for Highly Reproducible Measurement of Left Atrial Appendage Volume in Computed Tomography.

BACKGROUND: Modern computed tomographic scanning can produce 4-dimensional images of the left atrial appendage (LAA). LAA function and morphology can then be measured, to plan interventions such as occlusion and to evaluate LAA flow for thrombogenic risk analysis. A current problem here is defining a reproducible boundary between the LAA and the left atrium. METHODS: This study used retrospectively gated 4-dimensional computed tomographic data from 25 implantation and coronary artery imaging patients. In each patient, the LAA ostium was defined at multiple time points during the RR interval. To examine the reproducibility of the definition of the LAA ostium, 3 observers analyzed all time frames in each patient 3 times. Five nonconsecutive time frames from each patient were then compared using intraclass correlation coefficients to quantify the precision of the method across patients. The correlation of LAA volumes for each time frame of each patient was determined across the different observers (interobserver) and within each observer's own data sets (intraobserver). RESULTS: The method was successful in 92% of patients. Two-way random-effect, absolute-agreement, single-measurement intraclass correlation coefficients for interobserver measurements were 0.984, 0.990, and 0.988, with intraobserver intraclass correlation coefficients of 0.989, 0.989, and 0.995. The intraclass correlation coefficient of all observations was 0.988. CONCLUSIONS: Classification of the LAA ostium using a stepwise procedure identifying the coumadin ridge and 2 vascular landmarks in ECG-gated computed tomography provides a viable method of establishing a highly reproducible boundary between the atrium and LAA needed to obtain LAA metrics useful for procedure planning and measuring LAA function.

Regional dynamics of fractal dimension of the left ventricular endocardium from cine computed tomography images.

We present a method to leverage the high fidelity of computed tomography (CT) to quantify regional left ventricular function using topography variation of the endocardium as a surrogate measure of strain. 4DCT images of 10 normal and 10 abnormal subjects, acquired with standard clinical protocols, are used. The topography of the endocardium is characterized by its regional values of fractal dimension ( F D ), computed using a box-counting algorithm developed in-house. The average F D in each of the 16 American Heart Association segments is calculated for each subject as a function of time over the cardiac cycle. The normal subjects show a peak systolic percentage change in F D of 5.9 % ± 2 % in all free-wall segments, whereas the abnormal cohort experiences a change of 2 % ± 1.2 % ( p < 0.00001 ). Septal segments, being smooth, do not undergo large changes in F D . Additionally, a principal component analysis is performed on the temporal profiles of F D to highlight the possibility for unsupervised classification of normal and abnormal function. The method developed is free from manual contouring and does not require any feature tracking or registration algorithms. The F D values in the free-wall segments correlated well with radial strain and with endocardial regional shortening measurements.

Using a genetic risk score to calculate the optimal age for an individual to undergo coronary artery calcium screening.

BACKGROUND: Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test. METHODS: Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening. RESULTS: This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals. CONCLUSION: A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening.

Role of 3-Dimensional Architecture of Scar and Surviving Tissue in Ventricular Tachycardia: Insights From High-Resolution Ex Vivo Porcine Models.

BACKGROUND: An improved knowledge of the spatial organization of infarct structure and its contribution to ventricular tachycardia (VT) is important for designing optimal treatments. This study explores the relationship between the 3-dimensional structure of the healed infarct and the VT reentrant pathways in high-resolution models of infarcted porcine hearts. METHODS: Structurally detailed models of infarcted ventricles were reconstructed from ex vivo late gadolinium enhancement and diffusion tensor magnetic resonance imaging data of 8 chronically infarcted porcine hearts at submillimeter resolution (0.25×0.25×0.5 mm3). To characterize the 3-dimensional structure of surviving tissue in the zone of infarct, a novel scar-mapped thickness metric was introduced. Further, using the ventricular models, electrophysiological simulations were conducted to determine and analyze the 3-dimensional VT pathways that were established in each of the complex infarct morphologies. RESULTS: The scar-mapped thickness metric revealed the heterogeneous organization of infarct and enabled us to systematically characterize the distribution of surviving tissue thickness in 8 hearts. Simulation results demonstrated the involvement of a subendocardial tissue layer of varying thickness in the majority of VT pathways. Importantly, they revealed that VT pathways are most frequently established within thin surviving tissue structures of thickness ≤2.2 mm (90th percentile) surrounding the scar. CONCLUSIONS: The combination of high-resolution imaging data and ventricular simulations revealed the 3-dimensional distribution of surviving tissue surrounding the scar and demonstrated its involvement in VT pathways. The new knowledge obtained in this study contributes toward a better understanding of infarct-related VT.

Regional myocardial strain measurements from 4DCT in patients with normal LV function.

BACKGROUND: CT SQUEEZ is a new automated technique to evaluate regional endocardial strain by tracking features on the endocardium from 4D cine CT data. The objective of this study was to measure the range of endocardial regional strain (RSCT) values obtained with CT SQUEEZ in the normal human left ventricle (LV) from standard clinical 4D coronary CTA exams. METHODS: RSCT was measured over the heart cycle in 25 humans with normal LV function using cine CT from three vendors. Mean and standard deviation of RSCT values were computed in 16 AHA LV segments to estimate the range of values expected in the normal LV. RESULTS: Curves describing RSCT vs. time were consistent between subjects. There was a slight gradient of decreasing minimum RSCT value (increased shortening) from the base to the apex of the heart. Mean RSCT values at end-systole were: base = -32% ± 1%, mid = -33% ± 1%, apex = -36% ± 1%. The standard deviation of the minimum systolic RSCT in each segment over all subjects was 5%. The average time to reach maximum shortening was 34% of the RR interval. CONCLUSIONS: Regional strain (RSCT) can be rapidly obtained from standard gated coronary CCTA protocols using 4DCT SQUEEZ processing. We estimate that 95% of normal LV end-systolic RSCT values will fall between -23% and -43%; therefore, we hypothesize that an RSCT value higher than -23% will indicate a hypokinetic segment in the human heart.