[Show abstract][Hide abstract] ABSTRACT: Background:
Total atherosclerotic plaque burden assessment by CT angiography (CTA) is a promising tool for diagnosis and prognosis of coronary artery disease (CAD) but its validation is restricted to small clinical studies. We tested the feasibility of semi-automatically derived coronary atheroma burden assessment for identifying patients with hemodynamically significant CAD in a large cohort of patients with heterogenous characteristics.
This study focused on the CTA component of the CORE320 study population. A semi-automated contour detection algorithm quantified total coronary atheroma volume defined as the difference between vessel and lumen volume. Percent atheroma volume (PAV = [total atheroma volume/total vessel volume] × 100) was the primary metric for assessment (n = 374). The area under the receiver operating characteristic curve (AUC) determined the diagnostic accuracy for identifying patients with hemodynamically significant CAD defined as ≥50% stenosis by quantitative coronary angiography and associated myocardial perfusion abnormality by SPECT.
Of 374 patients, 139 (37%) had hemodynamically significant CAD. The AUC for PAV was 0.78 (95% confidence interval [CI] 0.73-0.83) compared with 0.84 [0.79-0.88] by standard expert CTA interpretation (p = 0.02). Accuracy for both CTA (0.91 [0.87, 0.96]) and PAV (0.86 [0.81-0.91]) increased after excluding patients with history of CAD (p < 0.01 for both). Bland-Altman analysis revealed good agreement between two observers (bias of 280.2 mm(3) [161.8, 398.7]).
A semi-automatically derived index of total coronary atheroma volume yields good accuracy for identifying patients with hemodynamically significant CAD, though marginally inferior to CTA expert reading. These results convey promise for rapid, reliable evaluation of clinically relevant CAD.
Full-text · Article · Jan 2016 · Journal of cardiovascular computed tomography
[Show abstract][Hide abstract] ABSTRACT: The relation between insulin resistance and coronary artery disease (CAD) in patients with HIV infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) were collected at semi-annual visits between 2003 and 2013 and used to compute the homeostatic model assessment of insulin resistance (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10 year study period) and the prevalence of coronary plaque or stenosis ≥ 50% were assessed with multivariable logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs. 2.7, P = 0.002) and when averaged over the study period (3.4 vs. 3.0, P < 0.001). The prevalence of coronary stenosis ≥ 50% was similar between both groups (17% vs. 15%, P = 0.41). Both measures of HOMA-IR were associated with greater odds of coronary stenosis ≥ 50% in models comparing men with values in the highest versus the lowest tertiles, though the effect of mean HOMA-IR was stronger than the single measurement of HOMA-IR prior to CTA (OR 2.46, 95% CI 1.95-3.11, vs. OR 1.43, 1.20-1.70). This effect was not significantly modified by HIV serostatus. In conclusion, insulin resistance over nearly a decade was greater in HIV-infected men than HIV-uninfected men, and among both groups, was associated with significant coronary artery stenosis.
No preview · Article · Dec 2015 · The American journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: The proliferation of four-dimensional imaging technologies, increasing computational speeds, improved simulation algorithms, and the widespread availability of powerful computing platforms is enabling simulations of cardiac hemodynamics with unprecedented speed and fidelity. Since cardiovascular disease is intimately linked to cardiovascular hemodynamics, accurate assessment of the patient's hemodynamic state is critical for the diagnosis and treatment of heart disease. Unfortunately, while a variety of invasive and non-invasive approaches for measuring cardiac hemodynamics are in widespread use, they still only provide an incomplete picture of the hemodynamic state of a patient. In this context, computational modeling of cardiac hemodynamics presents as a powerful non-invasive modality that can fill this information gap, and significantly impact the diagnosis as well as the treatment of cardiac disease. This article reviews the current status of this field as well as the emerging trends and challenges in cardiovascular health, computing, modeling and simulation and that are expected to play a key role in its future development. Some recent advances in modeling and simulations of cardiac flow are described by using examples from our own work as well as the research of other groups.
[Show abstract][Hide abstract] ABSTRACT: Objectives: The purpose of this study was to develop a quantitative method for myocardial blood flow (MBF)
measurement using contrast-enhanced multidetector computed tomography (MDCT) images with bolus tracking and helical scanning.
Materials and Methods: Nine canine models of left anterior descending artery stenosis were prepared and underwent MDCT perfusion imaging during adenosine infusion to study a wide range of flow parameters. Neutron-activated microspheres were injected to document MBF during adenosine infusion. Six animals underwent dynamic MDCT perfusion imaging, and K1 and k2 (which represent the first-order transfer constants from left ventricular blood to myocardium and from myocardium to the vascular system, respectively) were measured using a two-compartment model. The results were compared against microsphere MBF measurements, and the extraction fraction (E) of contrast agent and the mean value of K1/k2 were calculated. Six animals then underwent helical CT perfusion imaging, and neutron-activated microspheres were injected to document MBF during adenosine infusion. For each animal, based on E, K1/k2, time-registered helical CT myocardial data, and arterial input function data, tables of myocardial CT values versus MBF were simulated for various MBF values to create look-up tables from the myocardial CT value to MBF. The CT-derived MBF values were compared against the microsphere MBF measurements.
Results: A strong linear correlation was observed between the MDCT-derived MBF and the microsphere MBF (y =
1.065x – 0.616, R2 = 0.838).
Conclusions: Regional MBF can be measured accurately using a combination of bolus tracking and time-registered helical CT data from contrast-enhanced MDCT scanning during adenosine stress.
[Show abstract][Hide abstract] ABSTRACT: Establishing the diagnosis of coronary artery disease (CAD) in symptomatic patients allows appropriately allocating preventative measures. Single-photon emission computed tomography (CT)-acquired myocardial perfusion imaging (SPECT-MPI) is frequently used for the evaluation of CAD, but coronary CT angiography (CTA) has emerged as a valid alternative. Methods and Results-We compared the accuracy of SPECT-MPI and CTA for the diagnosis of CAD in 391 symptomatic patients who were prospectively enrolled in a multicenter study after clinical referral for cardiac catheterization. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of CTA and SPECT-MPI for identifying patients with CAD defined as the presence of ≥1 coronary artery with ≥50% lumen stenosis by quantitative coronary angiography. Sensitivity to identify patients with CAD was greater for CTA than SPECT-MPI (0.92 versus 0.62, respectively; P<0.001), resulting in greater overall accuracy (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.88-0.94] versus 0.69 [0.64-0.74]; P<0.001). Results were similar in patients without previous history of CAD (area under the receiver operating characteristic curve, 0.92 [0.89-0.96] versus 0.67 [0.61-0.73]; P<0.001) and also for the secondary end points of ≥70% stenosis and multivessel disease, as well as subgroups, except for patients with a calcium score of ≥400 and those with high-risk anatomy in whom the overall accuracy was similar because CTA's superior sensitivity was offset by lower specificity in these settings. Radiation doses were 3.9 mSv for CTA and 9.8 for SPECT-MPI (P<0.001). Conclusions-CTA is more accurate than SPECT-MPI for the diagnosis of CAD as defined by conventional angiography and may be underused for this purpose in symptomatic patients.
Full-text · Article · Oct 2015 · Circulation Cardiovascular Imaging
[Show abstract][Hide abstract] ABSTRACT: Aim:
Previous animal studies have demonstrated differences in perfusion and perfusion reserve between the subendocardium and subepicardium. 320-row computed tomography (CT) with sub-millimetre spatial resolution allows for the assessment of transmural differences in myocardial perfusion reserve (MPR) in humans. We aimed to test the hypothesis that MPR in all myocardial layers is determined by age, gender, and cardiovascular risk profile in patients with ischaemic symptoms or equivalent but without obstructive coronary artery disease (CAD).
Methods and results:
A total of 149 patients enrolled in the CORE320 study with symptoms or signs of myocardial ischaemia and absence of significant CAD by invasive coronary angiography were scanned with static rest and stress CT perfusion. Myocardial attenuation densities were assessed at rest and during adenosine stress, segmented into 3 myocardial layers and 13 segments. MPR was higher in the subepicardium compared with the subendocardium (124% interquartile range [45, 235] vs. 68% [22,102], P < 0.001). Moreover, MPR in the septum was lower than in the inferolateral and anterolateral segments of the myocardium (55% [19, 104] vs. 89% [37, 168] and 124% [54, 270], P < 0.001). By multivariate analysis, high body mass index was significantly associated with reduced MPR in all myocardial layers when adjusted for cardiovascular risk factors (P = 0.02).
In symptomatic patients without significant coronary artery stenosis, distinct differences in endocardial-epicardial distribution of perfusion reserve may be demonstrated with static CT perfusion. Low MPR in all myocardial layers was observed specifically in obese patients.
[Show abstract][Hide abstract] ABSTRACT: In the present study, we investigate the hemodynamics inside left atrium and understand its impact on the development of ventricular flow patterns. We construct the heart model using dynamic computed tomographic images and perform simulations using immersed boundary method based flow solver. The results show that the atrial hemodynamics is characterized by a circulatory flow generated by the left pulmonary veins and a direct stream from the right ones. The complex interaction of the vortex rings formed from each of the pulmonary veins leads to vortex breakup and annihilation, thereby producing a regularized flow at the mitral annulus. A comparison of the ventricular flow velocities between the physiological and a simplified pipe-based atrium model shows that the overall differences are limited to about 10% of the peak mitral flow velocity. The implications of this finding on the functional morphology of the left heart as well the computational and experimental modeling of ventricular hemodynamics are discussed.
[Show abstract][Hide abstract] ABSTRACT: Background:
We present the formulation and testing of a new CT angiography (CTA)-based method for noninvasive measurement of absolute coronary blood flow (CBF) termed transluminal attenuation flow encoding (TAFE). CTA provides assessment of coronary plaque but does not allow for detection of vessel specific ischemia. A simple and direct method to calculate absolute CBF from a standard CTA could isolate the functional consequence of disease and aid therapy decisions.
We present the theoretical framework and initial testing of TAFE. Nine canine models of ischemic heart disease were prepared and underwent CT imaging and microsphere measurements of myocardial blood flow. Additionally, 39 acute chest pain patients with normal coronary arteries underwent coronary CTA. We applied TAFE to calculate absolute CBF in the coronary arteries using 4 vessel input parameters including transluminal attenuation gradient, cross-sectional area, length, and the contrast bolus duration derived from the arterial input function.
In animal studies, TAFE-derived CBF in the left anterior descending, left circumflex, and right coronary artery was 20.8 ± 10.4 mL/min, 27.0 ± 13.4 mL/min, and 6.0 ± 3.7 mL/min, respectively. TAFE-derived CBF divided by myocardial mass strongly correlated with microsphere myocardial blood flow (R(2) = 0.90, P < .001). In human studies, TAFE-derived CBF in the left anterior descending, left circumflex, and right coronary artery was 26.4 ± 10.7 mL/min, 20.1 ± 13.0 mL/min, and 43.2 ± 40.9 mL/min, respectively. CBF per unit mass was 0.93 ± 0.48 mL/g/min in patients. Interobserver variability was minimal with excellent correlation (R = 0.96, P < .0001) and agreement (mean difference, 4.2 mL/min).
TAFE allows for quantification of absolute CBF from a standard CTA acquisition and may provide functional significance of coronary disease without complex computational methods.
No preview · Article · Jun 2015 · Journal of cardiovascular computed tomography
[Show abstract][Hide abstract] ABSTRACT: Recent computed tomography coronary angiography studies have noted higher transluminal contrast gradients in arteries with stenotic lesions, but the physical mechanism responsible for these gradients is not clear. We use computational fluid dynamics and contrast agent dispersion modeling to investigate the mechanism for the generation of these gradients and their correlation with the severity of the stenotic lesion. Simulations of blood flow and contrast agent dispersion in models of coronary artery are carried out for both steady and pulsatile flows, and axisymmetric stenoses of severities varying from 0% (unobstructed) to 80% are considered. Simulations show the presence of measurable gradients with magnitudes that increase monotonically with stenotic severity when other parameters are fixed. The present computational results enable us to examine the hypothesis that transluminal attenuation gradients are generated due to the advection of the contrast agent bolus, and that the magnitude of the gradient therefore encodes the flow velocity through the artery.
No preview · Article · Jun 2015 · Journal of Biomechanical Engineering
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to develop a method for automatic and stable determination of the optimal time range for fitting with a Patlak plot model in order to measure myocardial perfusion using coronary X-ray angiography images. A conventional two-compartment model is used to measure perfusion, and the slope of the Patlak plot is calculated to obtain a perfusion image. The model holds for only a few seconds while the contrast agent flows from artery to myocardium. Therefore, a specific time range should be determined for fitting with the model. To determine this time range, automation is needed for routine examinations. The optimal time range was determined to minimize the standard error between data points and their least-squares regression straight line in the Patlak plot. A total of 28 datasets were tested in seven porcine models. The new method successfully detected the time range when contrast agent flowed from artery to myocardium. The mean cross correlation in the linear regression analysis (R(2)) was 0.996 ± 0.004. The mean length of the optimal time range was 3.61 ± 1.29 frames (2.18 ± 1.40 s). This newly developed method can automatically determine the optimal time range for fitting with the model.
No preview · Article · Apr 2015 · The international journal of cardiovascular imaging
[Show abstract][Hide abstract] ABSTRACT: Coronary computed tomography angiography (CTA) has been used increasingly for the diagnosis of coronary artery disease over the past decade. Compared to invasive coronary angiography (ICA), coronary CTA has the ability to visualize and quantify atherosclerotic plaque both calcified and non-calcified. Traditional measures of evaluating a coronary stenosis such as diameter stenosis, area stenosis, minimal lumen diameter and minimal luminal area are limited in their ability to predict its functional significance especially when diameter stenosis ranges between 30-69% (intermediate range). Measurement of invasive fractional flow reserve (FFR) is considered the gold standard for assessment of the hemodynamic significance of a stenosis. The current study by Nakazato et al. evaluates the performance of an emerging coronary CTA-derived anatomical measure "percent aggregate plaque volume" to improve the detection of hemodynamic significant stenosis as compared with invasive FFR.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE. The purpose of this study was to comprehensively study estimated radiation doses for subjects included in the main analysis of the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (CORE320) study ( ClinicalTrials.gov identifier NCT00934037), a clinical trial comparing combined CT angiography (CTA) and perfusion CT with the reference standard catheter angiography plus myocardial perfusion SPECT. SUBJECTS AND METHODS. Prospectively acquired data on 381 CORE320 subjects were analyzed in four groups of testing related to radiation exposure. Radiation dose estimates were compared between modalities for combined CTA and perfusion CT with respect to covariates known to influence radiation exposure and for the main clinical outcomes defined by the trial. The final analysis assessed variations in radiation dose with respect to several factors inherent to the trial. RESULTS. The mean radiation dose estimate for the combined CTA and perfusion CT protocol (8.63 mSv) was significantly (p < 0.0001 for both) less than the average dose delivered from SPECT (10.48 mSv) and the average dose from diagnostic catheter angiography (11.63 mSv). There was no significant difference in estimated CTA-perfusion CT radiation dose for subjects who had false-positive or false-negative results in the CORE320 main analyses in a comparison with subjects for whom the CTA-perfusion CT findings were in accordance with the reference standard SPECT plus catheter angiographic findings. CONCLUSION. Radiation dose estimates from CORE320 support clinical implementation of a combined CT protocol for assessing coronary anatomy and myocardial perfusion.
No preview · Article · Jan 2015 · American Journal of Roentgenology