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54 2 Morphometry of Coronary Vasculature
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Fig. 2.18 Schematics of hierarchy of reconstructed tree. Epicard and endocard correspond to epicardium and endocardium, respectively. Reproduced from Kaimovitz (2001) with permission
2. Transmural networks span orders 8 to order 5 which penetrate the myocardial
wall at a right angle to the epicardium towards the endocardium.
3. Perfusion networks start with vessels of order 4 and extend to the capillary level.
Each of these perfusing networks was positioned within a specic wall layer. The following additional assumptions were made:
1. Epicardial and perfusion networks have a planar geometry in parallel to the wall
layers.
2. The networks have a diverging (arterial) and converging (venous) tree topology.
3. Collaterals (arterial) or anastomoses (venous) were not considered.
4. Each arterial tree was drained by two venal counterparts (Bassingthwaighte et al.,
1974).
5. Length of sequential segments were not correlated, nor were the lengths of sister
segments, nor were expansion ratio (VanBavel & Spaan, 1992 ).
6. Bifurcation and trifurcation branching were considered for arteries (Kassab et al.,
1993) and bifurcations up to quantications were considered for the venous
system consistent with measurements (Kassab et al., 1994b).
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2.4.5 Reconstruction Approach
The reconstruction procedure was composed of the following seven steps:
1. Partition into functional sub-networks: epicardial, transmural, and perfusion.
2. Reconstruction of a population of primitivetrees, i.e., topological trees without
geometric features by repeated stochastic generation of networks based on
Kassabs topological data (Kassab et al., 1993, 1994a, 1994b; Kassab,
Pallencaoe, et al., 1997).
3. Selection of physiologically compatible tree based on the criterion of total branch
length/depth, initial vessel homogeneity, and total number of vessels.
4. Assignment of 3D structure to the tree and geometrical optimization was based on
iterative simulated annealing scheme. During this stage, the purely topological
primitive trees were transformed into a network with spatial 2D or 3D geometric
characteristics. The optimization was performed based on criterion for transmural
span and homogeneity including boundary avoidance, local bifurcation geome-
try, and avoidance of segment intersections.
5. Diameter assignment was based on iterative algorithm by imposing monotonic
longitudinal diameter change (intra-element constraint) and Murrays law of
bifurcations (inter-element constraint).
6. Transformation from a rectangular slab geometry into prolate spheroid surface
through optimization implemented using Genetic Algorithm method.
7. Venous trees were generated based on the following princ iples:
(a) Venous tree reconstruction was similar to the arterial trees.
(b) The epicardial functional sub-network complied with criterion that each
arterial capillary was drained by two venal counterparts (Bassingthwaighte et al., 1974). The venous transmural and perfusion sub-networks were required to encompass a similar number of equivalent capillaries and to extend over similar span to their arterial counterpart.
(c) The venous tree reconstruction was subject to an additional constraint of
compatibility with the number of arterial capillaries in each of the wall layers.
2.4.6 Geometric Optimization
The geometrical optimization was done iter atively based on simulated annealing algorithm. The scheme for the annealing procedure includes random selection of a segment from an entire population of network segments, perturbation of the branching geometry, and objective function evaluation. This scheme was repeated subject to the coolingdown of the annealing ensemble. The perturbation of a bifurcation angle was subject to the following geometrical constraints:
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1. Mother and daughter vessels were positioned on the same plane (Zamir et al.,
1983).
2. Bounds on branching angles were imposed.
3. Constraints on cumulative element angle were also imposed where the upper
bound decreased with increase in element order number.
4. Avoidance of angle overlap.
2.4.7 Verication of Coronary Network
The validity of the reconstructed stochastic coronary trees was conrmed based on two criteria:
1. Overall visual similarity to native trees as observed, for example, from corrosion
casting and other methodologies (Fig. 2.19),
2. Agreement of the reconstructed tree with the statistical database of Kassab et al.
(1993, 1994b) Kassab, Pallencaoe, et al. (1997), and VanBavel and Spaan (1992)
in terms of:
(a) Statistics of segmental and elemental diameters and lengths
(b) Statistics of S/E ratio
(c) Connecti vity and longitudinal position (CM and LPM data)
(d) Adherence to Murrays law (see Chap. 7)
Once the annealing phase had been completed, the primitive trees were turned into a network having a geometrical visual appearance which resembled those of native coronary networks (Fig. 2.19a). The arterial epicardial tree shown in Fig. 2.19a is two dimensional and includes orders 11–8. The 3D transmural trees span over the entire wall and consists of vessel orders 8–4 (e.g., representative examples for arterial network is shown in Fig. 2.19b). After transformation into prolate spheroid surfaces, the results for LAD, LCx, and RCA representing the isolated crown and the major branches imposed on the left and the right ventricles are shown in Fig. 2.19c and d, respectively.
Figure 2.20 shows a fully reconstructed coronary vasculature ranging from the largest coronary arteries to the largest veins. The total number of reconstructed venous segments was about 17 million which spans orders 12 (coronary sinus) to 0v capillaries (rst segment of venous capillary). Combined with the reconstructed arterial network, the number of vessel segments for the entire coronary network adds up to about 27 million vessels. The reconstructed full coronary vascular network agrees with the gross anatomy of coronary networks in terms of structure, location of major vessels, and measured morphometric statistics of native coronary networks.
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Fig. 2.19 (a) Reconstructed arterial epicardial subtree for the LAD compared to native branch. (b) Reconstructed arterial transmural branches for the LAD. (c) Isolated crown of the three major epicardial branches: (a) Top view demonstrating the septum coverage, (b) Lateral posterior view demonstrating the RCA (c) Lateral anterior view demonstrating the LAD and LCx branches. (d) Major arterial epicardial branches imposed on the left and right ventricles: (a) Lateral posterior view demonstrating the RCA branch, (b) Lateral anterior view demonstrating the LAD and LCx branches. Reproduced from Kaimovitz et al. (2005) by permission
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Fig. 2.20 Rendering of the reconstructed arterial and venous trees (orders 1 to 11 and 1 to 12) as viewed from two different aspects (anterior and posterior). Red corresponds to veins and blue corresponds to veins. Reproduced from Kaimovitz et al. (2010) by permission
2.5 Non-tree Structures
Although tree structures are prevalent in nature for distribution and collection of nutrients, non-tree-like structures such as arcades, anastomoses, and inter­connections do exist in biological organs. Vascular trees appear to be the rules of architecture for three-dimensional (3D) organs (Kassab, 2000), while the existence of arcades seem to be restricted to 2D organs or surfaces of 3D organs, e.g., mesentery and omentum, surface of the heart, inner ear, retina, surface of the small intestine and colon, iris, diaphragm, thin skeletal muscle, surface of uterus, and surface of the elbow (see review in Kassab (2000)). A set of scaling laws that can explain the design of non-tree structures remain to be elucidated.
2.6 Labor Savings in Morphological Reconstruction
Besides the extensive morphometric data on the porcine coronary vasculature presented in this chapter, there is a paucity of data on the branching pattern and dimensions of the blood vessels in various organs including the human coronary vasculature. The reason for this lack of data is undoubtedly the tremendous effort
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needed to obtain the morphometric data. The author of this book can verify the countless hours needed over 4 years that was required to obtain a complete set of morphometric data on the porcine coronary vasculature.
For labor saving, pruning of the pulmonary vasculature has been introduced in morphometric data collection: cutting off branches at successive generations, mea­suring what remained, using the statistical data to estimate what were cut off, and adding the estimated data to the measured data to obtain the nal results (Horseld,
1978; Horseld & Gordon, 1981; Singhal, Henderson, Horseld, Harding, &
Cumming, 1973; Yen et al., 1983, 1984). In these studies, evaluation of the effects of pruning was not possible because a full set of precise data did not exist. With a complete set of unpruned coronary morphometric data is available (Kassab et al.,
1993), the effect of a pruning procedure on accuracy can be evaluated (Kassab et al., 1994a). A particular pruning procedure was found to reduce the labor by 79% when it
was applied to the LAD artery of the pig; however, it introduced the following errors based on comparison with the unpruned morphometric data (Kassab et al., 1994a):
1. The largest error incurred in the mean diameters of all orders of tree was 7.6%.
2. The corresponding maximum errors in the length and number of elements in all
orders were 9.8% and 30.0%, respectively.
3. The estimated error of the total equivalent Poiseuilles resistance for the LAD
artery computed from pruned data was 25.2% when compared with that com-
puted from unpruned data.
Since pruning of trees introduces signicant error that may not be acceptable for a particular analysis, the use of automation or semi-automation to reduce the workload may be necessary. In this regard, Spaan and colleagues (Spaan et al., 2005; van Horssen, Siebes, Hoefer, Spaan, & van den Wijngaard, 2010) have developed a cryomicrotome approach to automate the reconstruction of coronary vasculature. Their approach consists of 3D reconstruction of the coronary arterial tree from frozen sections of the myocardium whose vasculature is lled with uorescent polymer. This approach allows the reconstruction of coronary vasculature down to 20 μm. In parallel with this development, computerized tomographic (CT) imaging technology has provided important data on the three-dimensional branching patterns of vascular trees (Beighley, Thomas, Jorgensen, & Ritman, 1997; Garcia-Sanz, Rodriguez-Barbero, Bentley, Ritman, & Romero, 1998; Jorgensen, Demirkaya, & Ritman, 1998). Ritman and colleagues (1997) have successfully used μCT imaging to provide the 3D geometry of the entire coronary arterial tree of the rat heart (capillary level resolution). In conjunction with volumetric imaging, it is necessary to have accurate and reproducible algorithms to extract detailed morphometric data on the diameters, lengths, number of vessels, connectivity, and branching angles from the CT or μCT reconstructed tree.
The sections that follow discuss image processing, centerline detection, and grid generation. Image processing, particularly image segmentation, is a necessary rst step for both centerline detection and grid generation. The centerlines allow for the computation of various quantitative measurements, such as vessel length, vessel radius, and bifurcation angles.
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2.7 Automation: Segmentation and Centerline Detection
2.7.1 Image Processing
In quantify the geometry of the vasculature, CT or MRI is typically used, resulting in a volumetric image. A volumetric image consists of voxels aligned along a regular 3D grid. It is generally not likely that the boundaries of the vessels are exactly located at these voxels. Better precision can be achieved by nding the exact location in between a set of voxels. Since an accurate representation of the object boundary is crucial to any further processing of the data, improvement of the precision is an essential step. Different approaches are available depending on the need of the algorithm used to further process the result. Some algorithms for computing the centerline only require an accurate representation of individual points. On the other hand, grid generating algorithms typically require a surface representation of the boundary, i.e., the points need to be connected by some geometric primitive. The following subsections provide examples of both types of algorithms to extract morphometric data from medical images.
2.7.2 Segmentation of Vessel Boundary
The method described here uses similar techniques as described by Cannys non-maxima suppression (Canny, 1986) but extended to 3D. First, the image gradient is computed for every voxel. Using an experimentally determined thresh­old, all voxels with a gradient length below this threshold are neglected. The advantage of this gradient-based thresholding is that it is less sensitive to the selected threshold compared to intensity-based segmentation algorithms. This is particularly relevant for smaller vessels (one voxel in diameter or less) that can be missed due to partial volume effects when using intensity segmentation.
2.7.3 Segmentation Under Topological Control
In order to create a volume grid that corresponds to the medical image, it is necessary to produce a triangulated isosurface from a segmentation of the data. It is important to produce such an isosurface while preserving correct vessel topology. From a topological point of view, an arterial tree (excluding the capillary bed) is homeo­morphic with a sphere. Due to nite resolution, isosurfacing algorithms such as Marching Cubes (Lorensen & Cline, 1987) are unable to determine whether voxels that connect only by a corner or by an edge should truly be connected. This ambiguity can give rise to multiple handles that disrupt segmentations. Therefore, segmentations must be performed under topological control (Carson et al., 2010).
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To segment the data, a fuzzy connected-threshold algorithm is applied to the image in order to convert the series of grayscale images into a binary volume. Connectedness is restricted to face connectivity to prevent ambiguous representa­tions of the surface between vessels and background. Face connectivity is accom­plished both by restricting the region growing algorithm to faces and by a post­segmentation connectivity check that reassigns voxels found to possess vertex or edge connectivity. Subsequently, loops are removed to bring the face-connected segmentation into proper topology by using an automated approach based on skeletonization, loop detection, loop cutting, and cleanup. A breadth-rst search of branches in the skeleton is applied, starting at the top of the coronary ostia. To nd the optimal cutting location within the loop, a test cut is performed separately for each skeleton voxel belonging to the loop. Cuts are then affected at the region of minimum cross-sectional area and maximum path length from the ostia.
To extract the isosurface from the segmented image, the Marching Tetrahedra variant of the popular marching cubes algorithm can be applied. This produces a closed triangulated surface, without boundary patches at the inlets and outlets, and whose surface density is a function of resolution of the underlying data.
2.7.4 Centerline Detection
Numerous algorithms for extra cting centerlines from volumetric data sets are avail­able. An overview of the various techniques can be found in the paper by Cornea, Silver, and Min (2005). Some methods begin with all voxels of a volumetric image and use a thinning technique to shrink down the object to a single line (Bertrand & Aktouf, 1994; Brunner & Brunnett, 2004; Dyedov et al., 2009; Lee, Kashyap, & Chu, 1994; Lohou & Bertrand, 2004; Palágyi & Kuba, 1996; Saha, Chaudhuri, & Majumder, 1997; Tsao & Fu, 1981). Ideally, the topology of the object should be preserved (Lobregt, Verbeek, & Groen, 1980) which is the basic technique used in commercial software systems. Luboz et al. (2005) used a thinning-based technique to determine vessel radii and lengths from a CT scan. A standard deviation of
0.4 mm between the computed and the actual measurements was reported for a scan with a resolution of 0.6 mm. The disadvantage of thinning algorithms is that they can only be applied to volumetric data sets and the centerlines are described at voxel precision resulting in somewhat jagged lines, which do not allow accurate measurements of branch angles.
For extracting centerlines from volumetric images, geometry-based approaches are preferable over voxel-based approaches. Due to the discrete nature of a voxel of the volumetric image, the location of the centerline can have an error of half a voxel. Geometry-based methods do not have this shortcoming. Nordsletten, Blackett, Bentley, Ritman, and Smith (2006) determined normal vectors based on an isosurface computed using the volumetric image. These normal vectors are projected inward. The resulting point cloud is then collected and connected by a snake algorithm.
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2.7.5 Vector Field
The method for centerline detection described in the following subsections follows an algorithm developed by Wischgoll, Choy, Ritman, and Kassab (2008). A major advantage of this approach lies in the demonstrated accuracy based on actual validations between computed vessel diameters and optical measurements for por­cine hearts. This algorithm consists of several steps. Since the object is given as a volumetric CT-scanned image, the object boundary is extracted as previously described. A vector eld is then computed that is orthogonal to the object boundar y surface. Once the vector eld is computed, the centerlines can be determined by applying a topological analysis to this vector eld. As a last step, gaps between segments of the centerlin es can be closed automatically and vessel diameters can be computed. The following subsections explain these steps in detail.
The method presented above computes the centerlines by applying a topological analysis to a vector eld that is determined based on the geometric conguration of the object of which the centerlines are to be determined. The vector eld is computed at the identied points on the vessel boundary in such a way that the vectors are orthogonal to the vessel boundary surface. Based on these vectors, the vector eld inside the vessels is computed by using linear interpolation. Since the vasculature is given as a volumetric data set, the image gradients can be used to dene these vectors on the boundary surface. These image gradients are previously determined as they are needed for extracting the boundary. Since the points are only moved along the direction of the image gradient when determining the sub-voxel precision, this image gradient is still orthogonal to the boundary surface and therefore represents a good approximation for the desired vector eld.
2.7.6 Determination of Centerlines
In order to determine the centerlines of the object, a tetrahedrization of all points on the object boundary is computed rst. For this, Sis(2004) fast implementation of a Delaunay tetrahedrization algorithm is used. Tetrahedra outside of the vessels are removed based on the gradient vectors. This step also closes small gaps that may exist since tetrahedra covering these gaps will still have vectors attached to the vertices which point inward. Since vectors are known for each vertex of every tetrahedron, the complete vector eld can be computed by using this tetrahedrization by linear interpolation within each tetrahedron. This vector eld is then used to identify points of the centerlines which are then connected with each other.
Points on the centerlines can be identied by computing the singularities within the vector eld interpolated within every face of the tetrahedrization. For example, for a perfectly cylindrical object, the vector boundary points directly at the center of the cylinder. When examining the resulting vector eld at a cross section of the cylinder, a focus singularity is located at the center of the cylinder within this cross
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section. The location of this focus singularity resembles a point on the centerline of the cylinder. Hence, a singularity of type of node, focus, or spiral within a face of a tetrahedron indicates a point of the centerline. Since not all objects are cylindrical in shape and given the numerical errors and tolerances, points on the centerlines can be identied from singularities that resemble focus and spiral singularities.
After computing the center points, the vessel diameters are computed for each center point and all points within the vicinity are ident ied. From this set of points, only the ones that are within the slice of the vessel used to determine the center point are selected to describe the boundary. The radius is then computed as the average of the distances between the center points and the points on the boundary of the vessel slice.
Once individual p oints of the centerlines (including the corresponding vessel diameters) are computed by identifying the focus and spiral singularities within the faces of the tetrahedra, this set of points must be connected in order to retrieve all centerlines. Since the tetrahedrization describes the topology of the object, the connectivity information of the tetrahedra can be used. Thus, identied points of the centerlines of neighboring tetrahedra are connected with each other, forming the centerlines. In some cases, gaps will remain due to the choice of thresholds which can be closed using the method described in the next section.
2.7.7 Geometric Reconstruction
Based on the centerlines extracted from the volumetric image (Fig. 2.21), various measurements can be extracted, such as vessel radius or bifurcation angles (Wischgoll, Choy, & Kassab, 2009). A comparison of the computed radii, which were measured as the distance between centerline and vessel wall, and optical measurements of the radii for the main trunk of ve porcine hearts show an excellent accuracy with an average error of 0.7% and root mean square (rms) error of 1.1% of the radii . Using the centerline and radii information, conic cylinders can be formed to represent the individual vessel segment. By representing every segment in this way, the vascular tree can be reconstructed. Since the vasculature is represented as geometry, the visualization software not only facilitates the gathering of statistical information about the morphometry but it also allows a user to perform various measurements, such as distances or bifurcation angles.
2.8 Grid Generation
A grid or mesh generation is a mathematical process of generating a polygonal or polyhedral mesh that approximates the geometric object of interest (e.g., coronary vessel). The process of generating a grid or mesh of the segmented object is necessary to solve the conservation or eld equations on the geometric boundary of interest. Accurate grid generation is key to obtaining reliable numerical solutions