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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3787_Библиотеки_им_академика_М_И_Перельмана
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44 2 Morphometry of Coronary Vasculature
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relative to their mother (Dm) vessel) and by an area expansion ratio
AER ¼ D
2
2
l
þ D
2
=D
s
at each bifurcation (Kaimovitz et al., 2008). The mother
m
vessel order number was selected as the independent variable in order to partition the
anatomical data into three regimes (Kaimovitz, Lanir, & Kassab, 2005 ):
1. Epicardial (vessel orders 8–11, which mainly exist in the epicardium)
2. Transmural (orders 5–8, which perforate the myocardium)
3. Perfusion sub-networks (orders 1–5, which are within the sheets of myocardium
to provide local perfusion)
A distinction was made between intra-element and inter-element segments. For
the intra-element case, the branching occurs along the same element and thus the
larger daughter belongs to the element. Accordingly, the D
statistics were
l/Dm
represented as function of the element order number only for this case. For the
inter-element case, each daughter belongs to a different element and hence the D
s/Dm
ratio was formulated as asymmetry ratio mat rix (ARM) since the ratio is a function
of order of mother and daughter segments (see Appendix 5; Tables 2.23, 2.24, and
2.25 for LAD, LCx, and RCA, respectively). The former (intra-element) can be
viewed as an index of vessel taper, while the latter (inter-element) represents
branching asymmetry.
Figure 2.11a shows the relationship between D
LCx, and RCA arteries, respectively, where D
and order number for LAD,
l/Dm
and Dlare the diameters of the
m
mother and larger daughter vessels, respectively. Although there is a significant
decrease in diameter ratio in the transmural vessels and a significant increase in
diameter ratio for the perfusion vessels, the ratio is relatively constant in the
epicardial vessels. The minimum value of diameter ratio at order 5 (mean diameter
of about 70 μm) was statistically significant compared to other orders. Figure 2.11b
depicts the relationship between D
and order number, whi ch shows a monotonic
s/Dm
trend where the larger orders are more asymmetric than lower orders. Finally,
Fig. 2.11c shows the relationship between AER and order number. The data is
partitioned into two sub-regimes: Epicardial and transmural sub-networks (orders
5–11), and perfusion sub-networks (orders 1–5). In the epicardial and transmural
sub-networks, the AER is relatively uniform (no significant change based on order
number) but the AER increases significantly in the perfusion sub-networks from
order 5 towards the capillaries. These findings (Fig. 2.11a, c) imply a structure–
function relation at order 5 that may mark a hemodynamic transition from transmural
to perfusion sub-networks.
2.3.13 Counting Total Number of Elements
As with any scien tific methodology, the use of histology and casts has some
limitations. Each cut in histological section or break in cast deletes a segment or
subtree. The connectivity matrix accounts for missing or cut branches by tracking the

2.3 Reduction of Coronary Vasculature 45
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Fig. 2.11 Relationship
between mother vessel order
number and D
l/Dm
(ratio of
the diameter of larger
daughters relative to mother
vessel) (a); D
s/Dm
(ratio of
the diameter of smaller
daughters relative to mother
vessel) (b); and area
expansion ratio [
2
2
AER ¼ D
l
D
2
](c)
=D
s
m
for LAD, LCx, and RCA
arteries. Reproduced from
Kaimovitz et al. (2008) with
permission

46 2 Morphometry of Coronary Vasculature
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Fig. 2.12 Number of vessels in pig RCA, LAD, and LCx arteries (positive orders); and Thebesian
and sinusal veins (negative orders). Reproduced from Kassab et al. (1993, 1994b) by permission
order number of the elements that are cut and the total number of the cuts at each
order (Kassab et al., 1993). In counting the total number of elements, the number of
lost branches is added back as extrapolated from the connectivity matrix (see
Appendix in Kassab et al. (1993)). Figure 2.12 shows the total number of vessels
for the coronary arteries and veins. Similar to diameters, the relation is found to obey
a geometric sequence with order number. The element number ratio (ratio of
numbers of vessels between two consecutive orders) is 3.5–3.6 for arteries and
3.1–3.4 for veins. Appendix 6 summarizes the extrapolated total number of elements
for arteries (RCA, LAD, LCx, and LCCA) and veins (sinusal and coronary
Thebesian).
2.3.14 Arcade-Like Vessels: Epicardial Veins
Many arcading venules and veins are found within the epicardial surface of the
porcine heart (Fig. 2.13 ). The arcades can be classified as intra-connecti ons (between
parts of the same vein) and inter-connections (between different veins). The intraconnecting arcades may have multiple feeding vessels but a single draining vessel.
Consequently, the morphometry of these vessels can be described as a function of
the order of the draining vessels (Kassab et al., 1994b). The inter-connecting arcades
are either on the epicardial surface, or endocardial surface connecting sinusal to
Thebesian veins. These anastomotic veins may have multiple feeding vessels but
only two draining vessels. The morphometric features of the inter-connecting vessels
have been summarized in the form of a tree/anastomoses matrix as described by
Kassab et al. (1994b) and are summarized in Appendix 7. These anastomoses are
very important when considering retrograde perfusion when blood is delivered
through the coronary venous system where the arterial counterparts are too diseased
to deliver oxygen and nutrients to the myocardium (see review in Kassab, Navia,
March, and Choy (2008)).

2.3 Reduction of Coronary Vasculature 47
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Fig. 2.13 (a)
Photomicrograph of an
arcading venule at epicardial
surface of pig showing interconnections between
adjacent veins. (b)
Photomicrograph of a
venous anastomosis at
epicardial surface of pig
showing intra-connections
within the same vein. These
are intravital microscope
views of a radiopaque
Microfil perfusion of
coronary sinusal veins.
Reproduced from Kassab
et al. (1994b) with
permission
A
B
2.3.15 Network-Like Vessels: Capillaries
The capillary vessels have a non-tree-like branching pattern (Kassab & Fung, 1994).
As mentioned above, the capillaries were designated as blood vessels of order
number zero; those capillaries fed directly by arterioles as C
venules as C
, and those capillary vessels connected to C0aand C0vas C00(Kassab
0v
, those drained into
0a
& Fung, 1994). The capillaries are connected in patterns geometrically identified
as Y, T, H, or HP (hairpin) and anastomosed through transverse capillary crossconnections (C
1994) as shown in Fig. 2.14. The C
) (Bassingthwaighte, Yipintsoi, & Harvey, 1974; Kassab & Fung,
cc
vessels may connect adjacent capillaries or
cc
capillaries originating from different arterioles. The relative frequencies of H, Y, T,
and HP types in the right ventricle of the pig are 52%, 21%, 21%, and 6%,
respectively, whereas those in the left ventricle of the pig are 53%, 21%, 20%, and
6%, respectively. The connectivity of the capillaries to various arteries and veins is
captured in a connectivity matrix, as summarized in Appendix 8.
2.3.16 Diameters and Lengths of Capillary Segments
Appendix 9 summarizes the diameters and lengths of the capillaries in the right and
left ventricular free walls, respectively. The statistical data from four pigs are lumped

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Fig. 2.14 Schematic
diagram of capillary
segment branching showing
typical geometric patterns
known as Y, T, HP
(hairpin), and H types.
0, Capillaries of order 0; C
capillary cross-connection
(like the middle bar of the
letter H). Reproduced from
Kassab and Fung (1994)
with permission
cc
together. The means (in μm) SD of the capillary segment diameters and lengths
and the number of observations are shown for C
between each pair of consecutive C
vessels along the capillaries were found to be
cc
, C0v, C00, and Ccc. The distances
0a
61.2 44.0 μm(n ¼ 54) and 52.9 39.6 (n ¼ 57) μm for right and left coronary
capillaries in LV free wall ventricles, respectively.
2.3.17 Topology of Arteriolar and Venular Zones and Mean
Functional Capillary Length
The trunks of the arterial and venous trees are easily identified. The question is when
the branches divide repeatedly and become smaller and smaller, do the small twigs
distribute uniformly in space? This question is important because in order to
understand the length of the paths for the blood between an arteriole and a venule
(i.e., the effective length of capillary blood vessel linking an arteriole to a venule).
The path length of blood flow in capillaries is an important parameter in determining
the resistance to blood flow in the capillaries, which in turn determines the longitudinal distribution of blood pressure in the coronar y blood vessels.
To answer these questions, the spatial distribution of the C
must be known. If the C
distributed in space, then the effective capillary blood path length between arterioles
and venules can be as short as the average segmental capillary length. If the C
, and C0vsegments
0a
and C0vvessels are uniformly intermingled and uniformly
0a
and
0a

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Fig. 2.15 Reconstructed spatial distribution of arterioles and venules from a histological section
taken 1.7 mm from the epicardial surface of right ventricle. Solid vessels, arterioles; open vessels,
venules. Shaded regions, arteriolar zones (“islands”); unshaded regions, venular zones (“ocean”). A
and B indicate origin in the arteriolar zone and ending in the venular zone, respectively, of a vessel.
Reproduced from Kassab and Fung (1994) with permission
C0vvessels are segregated to different regions of space, then the effective capillary
length between arterioles and venules can be much longer than the average segmental length.
An overriding characteristic of the coronary capil laries is that most of them are
parallel to the myocardial musc le fibers. Therefore, a capillary originating from a
point in an arteriolar zone will carry blood to a point in the venular zone in a flow that
is parallel to the muscle fiber. An actual reconstructed case is shown in Fig. 2.15,in
which the muscle fibers are horizontal. The topological study of the arteriolar and
venular zones by Kassab and Fung (1994) has yielded the result that, in plane cross
sections (Fig. 2.15), the arteriolar zones can be concep tualized as islands in an ocean
consisting of the venular zone. The ocean (venular zone) surrounding the islands
(arteriolar zones) appear as non-overlapping regions, each of which lies in an
immediate neighborhood of an island. As can be seen in Fig. 2.15, capillary blood
vessel AB has an origin A in an island and an ending B in the ocean next to that
island. If it is assumed that every point in the island has an equal chance of being the
point A, and that every point in the ocean in a direction parallel to the muscle fiber
has an equal chance of being point B, then the average length of capillaries AB is
exactly one-half of the average length of the straight-line segments intercepted by the
island and its immediate ocean. The linear distance between the centers of mass of
adjacent arteriolar and venular domains of a capillary bed was measured, and the
average value of these measurements is defined as the mean functional capillary
length. The theoretical mean functional capillary length is the length of a straight
line.
The mean capillary path length was measured by tracing the capillary pathway
from an arteriole to a venule, the results of which were 547 μm for right ventricle and
550 μm for the left ventricles (Kassab & Fung, 1994). The functional mean capillary
length was also measured as a linear distance between the center of mass of two

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adjacent arterial and venular domains, the results of which were 501 μm for right
ventricle and 512 μm for the left ventricles. The ratios of the two measurements are
1.09 and 1.07 for right and left ventricles, respectively. These data suggest that most
capillary pathways followed the shortest path from terminal arteriole to collecting
venule.
2.4 Integration of 3D Coronary Vasculature
The reductionist process outlined above for obtaining statistical morphometric data
from a vascular tree is unique, given that the same set of rules are followed each time
(e.g., Weibel’s generation system, Strahler’s order scheme, or the diameter-defined
system). The integration process of creation of a circuit from statistical morphometric data, however, is a non-unique process. An infinite number of circuits can be
created corresponding to a set of morphometric data, but not uniquely specified by
them. Hence, it is necessary to apply a set of anatomical and physiological constraints to ensure the fidelity of the reconstruction as demonstrated below for two
approaches: (1) Node-to-node reconstruction, and (2) Statistical 3D reconstruction
of coronary vasculature.
2.4.1 Node-to-Node Computer Reconstruction of Coronary
Network
Since it is experimentally difficult to reconstruct the entire vascular circuit of any
organ because of the enormous number of vessels, Mittal et al. (2005) introduced a
method for the reconstruction of the full coronary vascular tree from partial measurements. The method includes the use of data on those parts of the tree that are
measured to extrapolate the data to those parts that are missing. Specifically, a
two-step approach was employed in the reconstruction of the entire coronary arterial
tree down to the capillary level. Vessels >40 μm were reconstructed from cast data,
while vessels < 40 μm were reconstructed from histological data. The cast data were
reconstructed one-bifurcation at a time, while histological data were reconstructed
one-subtree at a time by “cutting” and “pasting” of data from measured to missing
vessels. The reconstruction algorithm yielded a full arterial tree down to the first
capillary bifurcation with 1.9 million vessel segments for the RCA tree, 2.04 million
vessel segments for the LAD tree, and 1.15 milli on vessel segments for the LCx tree.
The node-to-node connectivity along with the diameter and length of every vessel
segment was noted (Fig. 2.16). Once the full tree was reconstructed, the assignment
of order numbers to every vessel segment in the tree was automated, according to the
diameter-defined Strahler system. Consequently, the diam eters, lengths, number of
vessels, segments-per-element ratio, connectivity and longitudinal matrices were

2.4 Integration of 3D Coronary Vasculature 51
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Fig. 2.16 A schematic of an arteriolar tree with the nodes labeled numerically and the segment
diameters and lengths specified. The first and second numbers in the parentheses correspond to the
diameter and length of the segment, respectively. The “2” denotes a broken vessel whose length is
unknown. The heavy line corresponds to the trunk of the arteriole tree. The partly “solid” and partly
“dashed” segments correspond to broken vessels >8 μm which were extrapolated using the
proposed algorithm. The entirely “dashed” segments correspond to extrapolated vessels.
Reproduced from Mittal et al. (2005) with permission
determined for every order number and were found to be consistent with measured
statistical data. The node-to-node network model lacked the 3D spatial distribution,
however, which is addressed in the model below.
2.4.2 Anatomical Input Files
The node-to-node connections of the entire cast data of each arterial tree (RCA,
LAD, or LCx) were stored as input files, while the hundreds of non-contiguous
arteriolar microvessels (LV or RV) were stored in separate files. In addition to the
node-to-node connectivity, the input files also contained diameter and length data of
each vessel segment (with the exception of cut vessels which only had diameters).
Hence, the branching pattern and vascular geometry of all the previously
reconstructed data on hard records (Kassab et al., 1993) were transformed into
digital Excel files. The data files are included as supplementary material on
SpringerLink.
A computer program adapted from CISpace: Tools for Learning Computational
Intelligence (Mittal et al., 2005) was used to enter the node-to-node connections
graphically. This Graphical Tool Kit can generate tab-delimited text files from any
tree of interest for the single main cast tree and the numerous histological arteriolar

52 2 Morphometry of Coronary Vasculature
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trees. An example of this graphical representation for an arteriolar tree is shown in
Fig. 2.16. The corresponding tabular format for the example tree is shown in
Appendix 10. The first and second columns in the table each uniquely identify a
particular vessel and specify the mother–daughter connection. The first column
refers to the vessel itself, whereas the second column refers to the mother vessel.
The third column contai ns the position of the vessel branch relative to the mother
(“r” for right and “l” for left), and the last two columns contain the diameter and
length of the vessel in micrometers (μm). A “2” in the length column signifies a
broken vessel whose length is unknow n.
2.4.3 Statistical 3D Reconstruction of Coronary Vasculature
A large-scale 3D stochastic reconstruction of the asymmetric coronary arterial and
venous trees (RCA, LAD, LCx, and sinusal veins) of the porcine heart has been
carried out by Kaimovitz et al. (2005) and Kaimovitz, Lanir, and Kassab (2010). The
model spans the entire coronary arterial tree and venous trees down to the capillary
vessels. The 3D tree structure was reconstructed initially in rectangular slab geometry by means of global geometrical optimization using parallel simulated annealing
(SA) algorithm which is a probabilistic technique for approximating the global
optimum of a given function. The SA optimization was subject to constraints
prescribed by measured morphometric features of the coronary arterial and venous
trees. Subsequently, the reconstructed trees were mapped onto a prolate spheroid
geometry of the heart. The transformed geometry was determined through least
squares minimization of the related changes in both segment lengths and their
angular characteristics. The venous network was partitioned into epicardial,
transmural, and perfusion functional sub-networks. The epicardial portion was
generated by SA search for the optimal coverage of the area perfused by the arterial
epicardial vessels. The epicardial sub-network and the coronary arterial capillary
network served as boundary conditions for the reconstruction of the in-between
transmural, and perfusion networks which were generated to optimize vascular
homogeneity. The following subsections outline some of the details of the 3D
reconstruction of the coronary vasculature.
2.4.4 Existing Database and Additional Assumptions
An asymmetrical, non-dichotomous coronary vascular network was reconstructed
based on the statistical morphological data obtained by Kassab, Lin, and Fung
(1994a), Kassab et al. (1993, 1994b), and Kassab, Pallencaoe, et al. (1997) for the
coronary arterial trees (RCA, LAD and LCx), venous trees (Thebesian and sinusal),
and capillary network (Fig. 2.17). Additional data of the coronary arterial tree were
obtained from measurements by VanBavel (1989) and VanBavel and Spaan (1992)

2.4 Integration of 3D Coronary Vasculature 53
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Databases
Morphometry, Bifurcation
Geometry
Reconstruction Procedure
Functional Sub-networks,
Geometrical Optimization,
Diameter Assignment
Fig. 2.17 General approach of 3D coronary reconstruction. Reproduced from Kaimovitz (2001)
with permission
Validation
Measurement Statistics,
Physiological Contraints
for inter-segmental diameter relation (Murray’s law; cube of mother diameter is
equal to the sum of cubes of daughter vessels) and studies of Zamir and Brown
(1982), Zamir, Phipps, and Wonnacott (1984), and Zamir, Wrigley, and Langille
(1983) on bifurcation angels. The total lengths of the coronary vessels were
constrained by the heart geometry, i.e., coronary trees were selected that have the
length span of the regions of perfusion of each tree.
Diameter correlations were achieved by adhering to the constraints of hydraulic
continuity, i.e., diameters change monotonically along the tree. This was achieved
via different methods for the intra-element and the inter-element cases. For intraelement correlations, a normal distribution was assumed for segment diameters in
the element, while for inter-element correlations, Murray’s law was imposed.
Since data on full 3D angles of coronary vasculature are lacking, construction of
3D tree structure was based on two assumptions which have been substantiated by
literature data. Based on Zamir et al. (1983), it was assumed that arterial as well as
venal bifurcations are mostly planar. This assumption satisfies the requirement for
minimum lateral drag force. It was also assumed that the angle which the larger
branch makes with the direction of the mother vessel decreases with the increase of
asymmetry ratio (Zamir, 1978). Based on these assumptions, a set of bifurcation
angular rules were implemented into the 3D tree construction.
The coronary network was partitioned into sub-networks (Fig. 2.18) as follows:
1. Epicardial trees range from order 11 to 9 (arteries) and 12 to 9 (veins) as
positioned on the epicardial surface.
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