Wall thickness of coronary vessels varies transmurally in the LV but not the RV: implications for local stress distribution

Since the right and left ventricles (RV and LV) function under different loading conditions, it is not surprising that they differ in their mechanics (intramyocardial pressure), structure, and metabolism; such differences may also contribute to differences in the coronary vessel wall. Our hypothesis is that intima-media thickness (IMT), IMT-to-radius (IMT-to-R) ratio, and vessel wall stress vary transmurally in the LV, much more than in the RV. Five normal Yorkshire swine were used in this study. The major coronary arteries were cannulated through the aorta and perfusion fixed with 6.25% glutaraldehyde and casted with a catalyzed silicone-elastomer solution. Arterial and venous vessels were obtained from different transmural locations of the RV and LV, processed for histological analysis, and measured with an imaging software. A larger transmural gradient was found for IMT, IMT-to-R ratio, and diastolic circumferential stress in vessels from the LV than the nearly zero transmural slope in the RV. The IMT of arterial vessels in the LV showed a slope of 0.7 ± 0.5 compared with 0.3 ± 0.3 of arterial vessels in the RV (P ≤ 0.05). The slope for venous vessels in the LV was 0.14 ± 0.14 vs. 0.06 ± 0.05 in the RV. The present data reflect the local structure-function relation, where the significant gradient in intramyocardial pressure in the LV is associated with a significant gradient of IMT and IMT-to-R ratio, unlike the RV. This has important implications for local adaptation of transmural loading on the vessel wall and vascular remodeling when the loading is perturbed in cardiac hypertrophy or heart failure

Extraction of Morphometry and Branching Angles of Porcine Coronary Arterial Tree from CT Images

The morphometry (diameters, length, and angles) of coronary arteries is related to their function. A simple, easy, and accurate image-based method to seamlessly extract the morphometry for coronary arteries is of significant value for understanding the structure-function relation. Here, the morphometry of large (≥1 mm in diameter) coronary arteries was extracted from computed tomography (CT) images using a recently validated segmentation algorithm. The coronary arteries of seven pigs were filled with Microfil, and the cast hearts were imaged with CT. The centerlines of the extracted vessels, the vessel radii, and the vessel lengths were identified for over 700 vessel segments. The extraction algorithm was based on a topological analysis of a vector field generated by normal vectors of the extracted vessel wall. The diameters, lengths, and angles of the right coronary artery, left anterior descending coronary artery, and left circumflex artery of all vessels ≥1 mm in diameter were tabulated for the respective orders. It was found that bifurcations at orders 9–11 are planar (∼90%). The relations between volume and length and area and length were also examined and found to scale as power laws. Furthermore, the bifurcation angles follow the minimum energy hypothesis but with significant scatter. Some of the applications of the semiautomated extraction of morphometric data in applications to coronary physiology and pathophysiology are highlighted

Validation of Image-Based Method for Extraction of Coronary Morphometry

An accurate analysis of the spatial distribution of blood flow in any organ must be based on detailed morphometry (diameters, lengths, vessel numbers, and branching pattern) of the organ vasculature. Despite the significance of detailed morphometric data, there is relative scarcity of data on 3D vascular anatomy. One of the major reasons is that the process of morphometric data collection is labor intensive. The objective of this study is to validate a novel segmentation algorithm for semi-automation of morphometric data extraction. The utility of the method is demonstrated in porcine coronary arteries imaged by computerized tomography (CT). The coronary arteries of five porcine hearts were injected with a contrast-enhancing polymer. The coronary arterial tree proximal to 1 mm was extracted from the 3D CT images. By determining the centerlines of the extracted vessels, the vessel radii and lengths were identified for various vessel segments. The extraction algorithm described in this paper is based on a topological analysis of a vector field generated by normal vectors of the extracted vessel wall. With this approach, special focus is placed on achieving the highest accuracy of the measured values. To validate the algorithm, the results were compared to optical measurements of the main trunk of the coronary arteries with microscopy. The agreement was found to be excellent with a root mean square deviation between computed vessel diameters and optical measurements of 0.16 mm (\u3c10% of the mean value) and an average deviation of 0.08 mm. The utility and future applications of the proposed method to speed up morphometric measurements of vascular trees are discussed

Validation of Image-Based Method for Extraction of Coronary Morphometry

An accurate analysis of the spatial distribution of blood flow in any organ must be based on detailed morphometry (diameters, lengths, vessel numbers, and branching pattern) of the organ vasculature. Despite the significance of detailed morphometric data, there is relative scarcity of data on 3D vascular anatomy. One of the major reasons is that the process of morphometric data collection is labor intensive. The objective of this study is to validate a novel segmentation algorithm for semi-automation of morphometric data extraction. The utility of the method is demonstrated in porcine coronary arteries imaged by computerized tomography (CT). The coronary arteries of five porcine hearts were injected with a contrast-enhancing polymer. The coronary arterial tree proximal to 1 mm was extracted from the 3D CT images. By determining the centerlines of the extracted vessels, the vessel radii and lengths were identified for various vessel segments. The extraction algorithm described in this paper is based on a topological analysis of a vector field generated by normal vectors of the extracted vessel wall. With this approach, special focus is placed on achieving the highest accuracy of the measured values. To validate the algorithm, the results were compared to optical measurements of the main trunk of the coronary arteries with microscopy. The agreement was found to be excellent with a root mean square deviation between computed vessel diameters and optical measurements of 0.16 mm (\u3c10% of the mean value) and an average deviation of 0.08 mm. The utility and future applications of the proposed method to speed up morphometric measurements of vascular trees are discussed

Compensatory Enlargement of Ossabaw Miniature Swine Coronary Arteries in Diffuse Atherosclerosis

Studies in human and non-human primates have confirmed the compensatory enlargement or positive remodeling (Glagov phenomenon) of coronary vessels in the presence of focal stenosis. To our knowledge, this is the first study to document arterial enlargement in a metabolic syndrome animal model with diffuse coronary artery disease (DCAD) in the absence of severe focal stenosis. Two different groups of Ossabaw miniature pigs were fed a high fat atherogenic diet for 4 months (Group I) and 12 months (Group II), respectively. Group I (6 pigs) underwent contrast enhanced computed tomographic angiography (CCTA) and intravascular ultrasound (IVUS) at baseline and after 4 months of high fat diet, whereas Group II (7 pigs) underwent only IVUS at 12 months of high fat diet. IVUS measurements of the left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries in Group I showed an average increase in their lumen cross-sectional areas (CSA) of 25.8%, 11.4%, and 43.4%, respectively, as compared to baseline. The lumen CSA values of LAD in Group II were found to be between the baseline and 4 month values in Group I. IVUS and CCTA measurements showed a similar trend and positive correlation. Fractional flow reserve (FFR) was 0.91 ± 0.07 at baseline and 0.93 ± 0.05 at 4 months with only 2.2%, 1.6% and 1% stenosis in the LAD, LCX and RCA, respectively. The relation between percent stenosis and lumen CSA shows a classical Glagov phenomenon in this animal model of DCAD

Computed Tomography-Based Diagnosis of Diffuse Compensatory Enlargement of Coronary Arteries using Scaling Power Laws

Glagov\u27s positive remodelling in the early stages of coronary atherosclerosis often results in plaque rupture and acute events. Because positive remodelling is generally diffused along the epicardial coronary arterial tree, it is difficult to diagnose non-invasively. Hence, the objective of the study is to assess the use of scaling power law for the diagnosis of positive remodelling of coronary arteries based on computed tomography (CT) images. Epicardial coronary arterial trees were reconstructed from CT scans of six Ossabaw pigs fed on a high-fat, high-cholesterol, atherogenic diet for eight months as well as the same number of body-weight-matched farm pigs fed on a lean chow (101.9±16.1 versus 91.5±13.1 kg). The high-fat diet Ossabaw pig model showed diffuse positive remodelling of epicardial coronary arteries. Good fit of measured coronary data to the length–volume scaling power law ( where Lc and Vc are crown length and volume) were found for both the high-fat and control groups (R2 = 0.95±0.04 and 0.99±0.01, respectively). The coefficient, KLV, decreased significantly in the high-fat diet group when compared with the control (14.6±2.6 versus 40.9±5.6). The flow–length scaling power law, however, was nearly unaffected by the positive remodelling. The length–volume and flow–length scaling power laws were preserved in epicardial coronary arterial trees after positive remodelling. KLV \u3c 18 in the length–volume scaling relation is a good index of positive remodelling of coronary arteries. These findings provide a clinical rationale for simple, accurate and non-invasive diagnosis of positive remodelling of coronary arteries, using conventional CT scans

Computed Tomography-Based Diagnosis of Diffuse Compensatory Enlargement of Coronary Arteries using Scaling Power Laws

Glagov\u27s positive remodelling in the early stages of coronary atherosclerosis often results in plaque rupture and acute events. Because positive remodelling is generally diffused along the epicardial coronary arterial tree, it is difficult to diagnose non-invasively. Hence, the objective of the study is to assess the use of scaling power law for the diagnosis of positive remodelling of coronary arteries based on computed tomography (CT) images. Epicardial coronary arterial trees were reconstructed from CT scans of six Ossabaw pigs fed on a high-fat, high-cholesterol, atherogenic diet for eight months as well as the same number of body-weight-matched farm pigs fed on a lean chow (101.9±16.1 versus 91.5±13.1 kg). The high-fat diet Ossabaw pig model showed diffuse positive remodelling of epicardial coronary arteries. Good fit of measured coronary data to the length–volume scaling power law ( where Lc and Vc are crown length and volume) were found for both the high-fat and control groups (R2 = 0.95±0.04 and 0.99±0.01, respectively). The coefficient, KLV, decreased significantly in the high-fat diet group when compared with the control (14.6±2.6 versus 40.9±5.6). The flow–length scaling power law, however, was nearly unaffected by the positive remodelling. The length–volume and flow–length scaling power laws were preserved in epicardial coronary arterial trees after positive remodelling. KLV \u3c 18 in the length–volume scaling relation is a good index of positive remodelling of coronary arteries. These findings provide a clinical rationale for simple, accurate and non-invasive diagnosis of positive remodelling of coronary arteries, using conventional CT scans

Compensatory Enlargement of Ossabaw Miniature Swine Coronary Arteries in Diffuse Atherosclerosis

Studies in human and non-human primates have confirmed the compensatory enlargement or positive remodeling (Glagov phenomenon) of coronary vessels in the presence of focal stenosis. To our knowledge, this is the first study to document arterial enlargement in a metabolic syndrome animal model with diffuse coronary artery disease (DCAD) in the absence of severe focal stenosis. Two different groups of Ossabaw miniature pigs were fed a high fat atherogenic diet for 4 months (Group I) and 12 months (Group II), respectively. Group I (6 pigs) underwent contrast enhanced computed tomographic angiography (CCTA) and intravascular ultrasound (IVUS) at baseline and after 4 months of high fat diet, whereas Group II (7 pigs) underwent only IVUS at 12 months of high fat diet. IVUS measurements of the left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries in Group I showed an average increase in their lumen cross-sectional areas (CSA) of 25.8%, 11.4%, and 43.4%, respectively, as compared to baseline. The lumen CSA values of LAD in Group II were found to be between the baseline and 4 month values in Group I. IVUS and CCTA measurements showed a similar trend and positive correlation. Fractional flow reserve (FFR) was 0.91 ± 0.07 at baseline and 0.93 ± 0.05 at 4 months with only 2.2%, 1.6% and 1% stenosis in the LAD, LCX and RCA, respectively. The relation between percent stenosis and lumen CSA shows a classical Glagov phenomenon in this animal model of DCAD

CT-based Diagnosis of Diffuse Coronary Artery Disease on the Basis of Scaling Power Laws

Diffuse coronary artery disease (CAD) without severe segmental stenosis is a substrate for plaque rupture (1–3). Hence, diffuse CAD is associated with unstable coronary syndromes or myocardial infarctions, which have significant clinical implications (4–6). In contrast to severe segmental stenosis, diffuse CAD is difficult to diagnose angiographically given the absence of a “normal” reference vessel (7). Although intravascular ultrasonography (US) has been used to visualize plaque burden in the vessel wall for the diagnosis of diffuse CAD (8,9), it is an interventional tool that requires an invasive procedure. Hence, there is a need for a noninvasive method with which to quantify diffuse CAD. There have been previous attempts at applying global morphologic features of the coronary artery tree in the assessment of diffuse CAD (7,10,11). Several experimental reports have also documented a direct relationship between coronary artery lumen size and heart weight or distal myocardial bed size (12–18) and between myocardial mass and the cumulative length of the arterial branches that perfuse the region (18,19). On the basis of the principle of minimum energy, we have recently deduced scaling power laws between length and volume and between length and cross-sectional area in an entire tree structure of various organs in different species (20,21). In particular, these scaling power laws have a self-similar nature (20–22), which implies that they can be clinically applied to a partial tree (eg, an epicardial coronary artery tree obtained with angiography, computed tomography [CT], or magnetic resonance [MR] imaging). Hence, we hypothesized that the length-volume scaling power law (ie, scaling relation and power law distribution for the sum of intravascular lengths and volumes in a tree) provides the signature of “normal” vasculature and deviations from which can be used to quantify the extent of diffuse CAD. The purpose of this study was to provide proof of concept for a diagnostic method to assess diffuse CAD on the basis of coronary CT angiography