Download Three-dimensional alignment of the aggregated myocytes in the

J Appl Physiol 107: 921–927, 2009.
First published July 23, 2009; doi:10.1152/japplphysiol.00275.2009.
Three-dimensional alignment of the aggregated myocytes in the normal and
hypertrophic murine heart
Boris Schmitt,1 Katsiaryna Fedarava,1 Jan Falkenberg,1 Kai Rothaus,2 Narendra K. Bodhey,1
Carolin Reischauer,3 Sebastian Kozerke,3 Bernhard Schnackenburg,4 Dirk Westermann,5
Paul P. Lunkenheimer,6 Robert H. Anderson,7 Felix Berger,1 and Titus Kuehne1
1
Unit of Cardiovascular Imaging—Department for Congenital Heart Disease and Pediatric Cardiology, German Heart
Institute Berlin, 2Institute for Informatics, University of Münster, Germany; 3Institute for Biomedical Engineering, Swiss
Federal Institute of Technology (ETH) Zurich and University Zurich, Switzerland; 4 Phillips Medical Systems, Hamburg,
5
Institute of Cardiology, Charité, Campus Benjamin Franklin, Berlin, 6Department of Thoracic and Cardiovascular Surgery,
University Hospital Münster, Germany; and 7Cardiac Unit, Institute of Child Health, University College, London,
United Kingdom
Submitted 13 March 2009; accepted in final form 16 July 2009
hypertrophy; orientation; magnetic resonance imaging; diffusion tensor imaging
THE PUMPING FUNCTION of the ventricular myocardium is determined by the three-dimensional arrangement of the individual
myocytes aggregated together within their supporting fibrous
matrix. The orientation of these aggregated myocytes can be
described in terms of their helical and intruding angles, the
latter also being called transverse angle (3, 6, 23). Several
recent studies have translated these three-dimensional angula-
Address for reprint requests and other correspondence: T. Kuehne, Unit of
Cardiovascular Imaging—Dept. of Congenital Heart Disease and Pediatric
Cardiology, German Heart Institute Berlin, Germany (e-mail: kuehne
@dhzb.de).
http://www. jap.org
tions of the aggregated myocytes to mechanical aspects of
cardiac function. The importance of the helical angles in
producing centripetal forces and constricting actions during
ventricular systole is well recognized (5, 11). Recent studies
also pay increasing attention to the influence of the intruding
angles. Indeed, most earlier investigators have argued that
myocytes rarely intrude by angles of ⬎10 degrees. More
current investigations, however, using circular knives and diffusion tensor magnetic resonance imaging (DT-MRI) to sample the ventricular walls, have demonstrated the existence of a
significant population of myocytes intruding from epicardium
to endocardium at even larger angles (20). Additional studies
using force probes suggest that these intruding myocytes working in conjunction with the fibrous matrix, have an impact on
myocardial mechanics (16, 17).
When assessing the mechanisms producing myocardial
function, therefore, it is important to take note of the intruding
angulation of the myocytes as well as their helical angles. To
the best of our knowledge, this three-dimensional alignment of
the myocytes has not been compared in the entirety of the
normal as opposed to the hypertrophied ventricular mass. It is
our belief that such information would help to improve the
understanding of the cardiac response to various pathological
conditions, the more so since the arrangement of the myocytes
within the supporting fibrous matrix is markedly heterogeneous
(1, 8, 9, 15).
The existence of the population of myocytes that are crossing the myocardial wall from epicardium to endocardium has
been well demonstrated histologically (7, 16). Histological
techniques, however, suffer from their restricted three-dimensional spatial resolution. The advent of DT-MRI now offers the
potential to overcome this shortcoming. The method has been
shown to be capable of displaying the alignment of the myocytes in nondestructive fashion (4, 19, 20, 22). Thus hoping to
improve knowledge about any myocardial realignment produced by mural hypertrophy, we have now used DT-MRI to
investigate the three-dimensional angulation of the ventricular
myocytes in a normal population of mice, and in a second
population with pharmacologically induced global ventricular
hypertrophy.
MATERIALS AND METHODS
We studied a total of 14 black mice (C57B16/J, Charles River,
Sulzfeld, Germany). Ventricular hypertrophy was induced in seven
8750-7587/09 $8.00 Copyright © 2009 the American Physiological Society
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Schmitt B, Fedarava K, Falkenberg J, Rothaus K, Bodhey NK,
Reischauer C, Kozerke S, Schnackenburg B, Westermann D,
Lunkenheimer PP, Anderson RH, Berger F, Kuehne T. Threedimensional alignment of the aggregated myocytes in the normal and
hypertrophic murine heart. J Appl Physiol 107: 921–927, 2009. First
published July 23, 2009; doi:10.1152/japplphysiol.00275.2009.—
Several observations suggest that the transmission of myocardial
forces is influenced in part by the spatial arrangement of the myocytes
aggregated together within ventricular mass. Our aim was to assess,
using diffusion tensor magnetic resonance imaging (DT-MRI), any
differences in the three-dimensional arrangement of these myocytes in
the normal heart compared with the hypertrophic murine myocardium.
We induced ventricular hypertrophy in seven mice by infusion of
angiotensin II through a subcutaneous pump, with seven other mice
serving as controls. DT-MRI of explanted hearts was performed at 3.0
Tesla. We used the primary eigenvector in each voxel to determine the
three-dimensional orientation of aggregated myocytes in respect to
their helical angles and their transmural courses (intruding angles).
Compared with controls, the hypertrophic hearts showed significant
increases in myocardial mass and the outer radius of the left ventricular chamber (P ⬍ 0.05). In both groups, a significant change was
noted from positive intruding angles at the base to negative angles at
the ventricular apex (P ⬍ 0.01). Compared with controls, the hypertrophied hearts had significantly larger intruding angles of the aggregated myocytes, notably in the apical and basal slices (P ⬍ 0.001). In
both groups, the helical angles were greatest in midventricular sections, albeit with significantly smaller angles in the mice with hypertrophied myocardium (P ⬍ 0.01). The use of DT-MRI revealed
significant differences in helix and intruding angles of the myocytes in
the mice with hypertrophied myocardium.
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After completion of the diffusion scans, we extracted the primary
eigenvectors in each pixel as described previously; this technique also
serving to trace chains of connected myocytes (10, 22, 26). The
pixel-to-pixel concatenation of the primary eigenvectors produced
sequences of straight segments of equal lengths. These segments,
representing the aggregation of the individual myocytes, were computed and analyzed for a 60°-wide segment of the left ventricular free
wall and the ventricular septum (Fig. 1C). We excluded the sites of
intersection with the wall of the right ventricle because of the known
interlacing, and hence criss-crossing, of the aggregated myocytes in
these regions (18).
Measurement of intruding and helical angles. In terms of biophysics, the course of the aggregated myocytes can be described in the
three-dimensional context of the ventricular walls by measuring two
different angles. The helical angle is the one made between the
aggregated myocytes and the ventricular equator, while the so-called
intruding or transverse angle measures the extent to which the aggregates angulate from the epicardium toward the endocardium as they
penetrate the ventricular wall (Fig. 1, B and C). We derived both these
angles by measuring the primary eigenvectors using a graphical user
interface on a MATLAB platform (The Mathworks, Natwick, MA).
The angles were computed in seven ventricular slices for each of the
14 hearts, numbering the basal slice as 1 and the apical slice as 7. The
angle of intrusion was then defined as the angle between the primary
eigenvector projected in the x-y plane and a tangent that was applied
at the epicardium (Fig. 1C and Fig. 2). The helical angle was defined
as the angle between projection of the primary eigenvector on the
tangential plane at the epicardium and the x-y plane (Fig. 1B and Fig.
2). We determined positive as opposed to negative direction of these
angles as shown in Fig. 2, following the precedent of Schmid et al.
(20). For the measurements we applied a local elliptically shaped
model of the epicardium (Fig. 2). The coordinate system was locally
adjusted in each slice for each separate measurement. The x-axis was
clockwise oriented parallel to the epicardium and the y-axis was
directed toward the endocardium. The z-axis was chosen as the
longitudinal direction along the long axis of the left ventricle.
Histology. Histology of the myocardium using hematoxylin and
eosin staining was performed on a total of 14 samples from each
mouse, taking the samples from seven slices of the left ventricular free
wall and seven from the septum. A total of 50 myocytes per sample
Fig. 1. Postprocessing of diffusion-tensor images. The figure shows 7 slices of a mouse heart seen from a side view (A). The equator of the heart is located at
the level of slice 4. For illustration purposes, the shown slices represent the center of the actual diffusion scans that had a slice thickness of 1 mm but no interslice
gaps. The assessment of helical angles (B) and intruding angles (C) is illustrated with the help of a representative chain of myocytes. By using a local ellipsoidally
shaped coordinate system, the helical angle was determined as the angle between the x-y plane and the z-component of the aggregated myocytes (the projection
the primary eigenvector onto the tangent plane). On the same slices, the intruding angle is defined as the angle between the direction of a chain of myocytes from
epicardium to endocardium and the corresponding tangent drawn at the epicardial border of a selected slice. The illustrated chain of myocytes shown in A, B,
and C is not color coded to improve its visibility. In contrast, the 7 diffusion-tensor images are color coded and show representative vector fields for helical angles.
Green color indicates high angles, red color represents smaller angles, positive/negative signs of the angles are not indicated. Note in C the distribution of high
angles at the subendocardial and subepicardial layers.
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mice by 2-wk infusion of angiotensin II via an osmotic minipump. For
implantation of the pump, the mice were anesthetized with pentobarbital sodium (50 mg/kg ip), and minipumps were placed subcutaneously in the intrascapular area to deliver angiotensin II at a dose of
300 ␮g/day. The control group, also of seven mice, was given saline
through the minipump. Prior to being killed, the animals were injected
with 50 units of heparin through the tail vein. The hearts were arrested
in diastole using a cardioplegic solution containing 15 mM KCl. The
hearts were extracted rapidly after death, and immediately placed into
4% formaldehyde solution. Prior to imaging, the hearts were embedded in agar gel, taking care to avoid any air bubbles in and around the
heart. We recorded the body weight and the weight of the hearts after
removal. The investigation conforms to the Guide for the Care and
Use of Laboratory Animals published by the US National Institutes of
Health (NIH Publication No. 85–23, revised 1996) and the animal
experiments were authorized by the responsible authorities at our
institution.
Imaging. Imaging was performed using a 3.0-Tesla whole body
scanner with a dedicated solenoid mouse coil (both from Philips
Medical Systems, Best, The Netherlands). Diffusion weighted scans
were acquired in the ventricular short axis, with seven slices covering
the heart from base to apex (Fig. 1A). The scan parameters were:
diffusion sensitized gradients (b ⫽ 700 s/mm2) along 15 directions,
effective TR/TE ⫽ 1,000/67 ms, matrix of 200 ⫻ 200 elements, inand through plane spatial resolution 0.2 ⫻ 0.2 ⫻ 1.0 mm3, no
interslice gap. Imaging resulted in a B0 image and diffusion weighted
images encoded in each of the optimized 15 directions. We also
acquired conventional T1 weighted images in a short-axis plane with
the following sequence parameters: TR/TE of 500/30 ms, matrix of
256 ⫻ 256, slice thickness 1.5 mm, and 0.1 mm interslice gap.
Post processing and data analysis. The myocardial mass, as well as
the endocardial and epicardial radius of the cavities and the walls,
were determined by drawing the appropriate contours. For myocardial
mass, contours were drawn on the T1 weighted images in all slices
covering the heart. The inner and outer radii were determined at the
equatorial slice of the heart. The measurements were made with View
Forum Software (Philips Medical Systems). The length of the left
ventricle and the thickness of the ventricular septum and the free walls
were also recorded to document the changes with and without infusion
of angiotensin. The values were indexed to the weight of the animal.
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DIFFUSION TENSOR IMAGING IN NORMAL AND HYPERTROPHIC HEART
Table 1. Baseline characteristics
Conventional data
Body weight, g
Total heart weight, g
MRI derived data
Myocardial mass of total LV (g)
Myocardial mass of total LV
weight/body wt, mg/g
Wall thickness of septum, mm
Wall thickness of LV free wall, mm
LV length, mm
Outer LV radius, epicardial, mm
Inner LV radius, endocardial, mm
Echocardiographic data
Fractional shortening, %
Heart rate, beats/min
were assessed by morphometry, measuring their diameter at the level
of the nucleus. In addition, all samples were inspected for signs of
disarray.
Statistical analysis. The baseline data with regard to body weight,
weight of the heart, and left ventricular size were compared between
the control and hypertrophied populations using the unpaired Student’s t-test. A P value of ⬍0.05 was considered to be significant.
Analysis of the angles. We analyzed the distribution of the angles
for the left ventricle. For this, the data for helical and intrusion angles
were analyzed in MATLAB. We then compared the transmural (from
epicardium to endocardium) distributions of the angles over the seven
acquired slices. The course of angles over the slices has been compared between both groups of mice in an ANOVA procedure for
repeated measurements (procedure GLM in SPSS, version 13) with
the number of slices as within-subject factor and the groups as
between-subject factor. For the tests of overall slice effects and of
interactions between group and slice effects the univariate test with
Greenhouse-Geisser correction has been used. The intracluster correlation coefficient was calculated to determine the source of variability
of the measured angles (13). A value of zero indicates that the main
source of variation is within the individual hearts, a value of 10
indicates that the source of variation is highest between the different
individuals.
Angiotensin-Treated
Mice (n ⫽ 7)
27.4⫾0.9
0.15⫾0.01
26.9⫾0.8
0.18⫾0.01*
0.09⫾0.01
0.12⫾0.02*
3.3⫾0.1
1.16⫾0.02
1.15⫾0.02
7.95⫾0.41
2.50⫾0.13
1.18⫾0.12
4.5⫾0.2*
1.26⫾0.05*
1.24⫾0.04*
7.32⫾0.45
2.87⫾0.19*
1.04⫾0.09
53.5⫾1.4
591⫾12
50.1⫾1.6
582⫾14
Values are means ⫾ SE. Radius was derived from short axis images at the
equatorial level of the heart. MRI-derived data that was indexed to the weight
of the animal did not change significance levels when comparing the 2
experimental groups. Immediately prior to euthenasia, fractional shortening
was obtained in conscious mice from transthoracic echocardiograms (Acuson,
Sonoma Health Products. Imaging was performed by M-mode at the midventricular level. LV, left ventricle. *P value ⬍0.05 was considered significant.
the left ventricular free wall and the septum, respectively. In
the control animals, we noted a change from the mean in
prevalence of positive angles at the base to negative angles at
the ventricular apex in the control animals that was highly
RESULTS
The baseline characteristics are summarized in Table 1.
Ventricular hypertrophy was noted in all the mice treated with
angiotensin II, the measurements obtained using magnetic
resonance imaging confirming the increase in myocardial mass
normalized to body weight (P ⬍ 0.05).For the hypertrophied
left ventricles there was a trend toward decreased length (P ⫽
0.061) and reduced endocardial radius (P ⫽ 0.067). The
epicardial radius and mural thickness was significantly increased (P ⬍ 0.05).
Intruding angles. Figures 3 and 4 show the transmural
course of the angle in basal, midventricular, and apical slices of
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Fig. 3. Transmural distribution of the helix and intruding angle in mice with
hypertrophic hearts compared with controls in the left ventricular free wall.
Endocardial surface is located at a transmural depth of 0%, epicardial surface
at transmural depth of 100%. The angles were measured at the base, midventricle, and apex in steps of 10% thickness of the wall. *Significant differences
between the control and hypertrophy (P ⬍ 0.05).
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Fig. 2. Illustration of the local coordinate system used to define the helix
angles (␤) and intruding angle (␣) in a tissue sample of the left ventricular
myocardium. The round headed arrows indicate the course of vectors that
define positive (solid line) and negative helix angles (dotted line). Additional
details to the coordinate system used are given in Measurement of intruding
and helical angles.
Control Mice
(n ⫽ 7)
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DIFFUSION TENSOR IMAGING IN NORMAL AND HYPERTROPHIC HEART
0.061 for the septum). There was no significant difference in
variability of measured angles between the two groups. The
intracluster correlation coefficient was 0.24 ⫾ 0.06 in the
control mice and 0.16 ⫾ 0.04 in the mice with hypertrophic
hearts.
Histology. In the samples from angiotensin II-treated mice,
the diameters of the myocytes were increased compared with
controls (29.8 ⫾ 4.4 vs. 40.2 ⫾ 5.7 ␮m, P ⬍ 0.05). Inspection
of the samples revealed no difference in morphology of the
aggregated myocytes between samples obtained from controls
and the hypertrophic hearts (Fig. 5). Signs of disarray were not
noted.
DISCUSSION
significant (P ⬍ 0.01). This trend was even more pronounced
in the hypertrophied hearts (Figs. 3 and 4). Intruding angles
were overall larger in the hypertrophic hearts compared with
control. In the free wall, difference between the angles reached
statistical significance for the majority of regions of the myocardial wall and this within slices obtained at the cardiac apex,
midventricle, and base (P ⬍ 0.05, Fig. 3). In the septum, these
differences were less pronounced. There was no significant
difference in variability of measured angles between the two
experimental groups. The intracluster correlation coefficient
was 0.09 ⫾ 0.09 in the control mice and 0.12 ⫾ 0.05 in the
mice with hypertrophic hearts.
Helical angles. In both groups, we noted high angles to be
particularly prominent in the endocardial and epicardial components of both the free wall and the septum, with significantly
lower angles dominating in the midmyocardial regions of the
walls (⬍0.005). At the equator of the heart, helical angles of
the hypertrophic hearts, compared with controls, were significantly smaller for transmural depths of 50 –100% for the free
wall (P ⬍ 0.05, Fig. 3) and of 80 –100% for the septum (P ⬍
0.05, Fig. 4). At the base and the apex, these differences were
less prominent, and smaller helical angles of the hypertrophic
hearts were noted only in the subepicardial layers. This observation held for both the free wall and the septum. In the
subendocardial region, helical angles were slightly larger in all
sections of the heart, albeit with the change failing to reach
statistical significance (P ⫽ 0.053 for the free wall and P ⫽
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Fig. 4. Transmural distribution of the helix and intruding angle in mice with
hypertrophic hearts compared with controls in the interventricular septum.
Endocardial surface is located at a transmural depth of 0%, epicardial surface
at transmural depth of 100%. The angles were measured at the base, midventricle, and apex in steps of 10% thickness of the wall. *Significant differences
between the control and hypertrophy group (P ⬍ 0.05).
Our findings of the three-dimensional arrangement of the
myocytes aggregated together within the walls of the murine
heart endorse, in terms of the helical angles, the descriptions of
McLean and Prothero (18). For the most part, they are also in
keeping with those described by Streeter and colleagues (24)
for the canine heart, Geerts et al. (6) for the goat heart, and
Greenbaum and associates (8) and Ingels (11) for the human
heart. Indeed, this pattern of myocardial architecture was
described by Pettigrew as early as 1864. Thus the myocytes are
aggregated together in reciprocal helixes in the subendocardial
and subepicardial parts of the walls, whereas they are aggregated predominantly in circular fashion within the middle parts
of the walls and the septum. These circular myocytes were
identified by Krehl as “Triebwerkzeug” and were considered
by him to provide the driving force for ventricular constriction.
Assessment of the geometric arrangements of the myocytes
by DT-MRI has now permitted us to demonstrate substantial
alterations in their spatial angulation within the myocardium in
hypertrophied compared with normal hearts. The changes in
angulation, however, were most marked in respect to the
transmural intrusion of chains of myocytes, the so-called intruding or transverse angles, with less marked changes noted in
the helical angles.
Recent studies have provided the basis for investigating the
entirety of the murine left ventricular mass using DT-MRI, and
have indicated the potential of using this technique to assess
cardiac architecture at different stages of induced myocardial
hypertrophy (2, 12). Other investigators have used DT-MRI to
examine porcine and goat hearts, confirming the existence of
the population of intruding myocytes, showing that around
two-fifths of the myocytes inclined at intruding angles between
10 and 35° relative to the plane of the epicardial surface (20,
21). These studies, however, had examined only selected
transmural slices. In our current study, we examined the global
distribution of angles of large segments of the left ventricular
free wall and of the septum. Our findings confirm that positive
intruding angles prevail at the base, but reveal that negative
angles exist at the apex (6), with the additional finding that the
angles of intrusion were larger in the hypertrophied hearts than
in controls.
Angiotensin II is known to mediate cardiac hypertrophy
either by its hypertensive hemodynamic action and/or by direct
action on the myocytes (27). It is also known to produce
increased synthesis of the proteins in the extracellular matrix,
such as collagen type I (28). In addition, the response of the
myocardium to the action of angiotensin II is rapid, with
DIFFUSION TENSOR IMAGING IN NORMAL AND HYPERTROPHIC HEART
925
Fig. 5. Representative histology samples
obtained from the left ventricular freewall
and the septum of control mice and mice
with ventricular hypertrophy. There are no
signs of disarray.
J Appl Physiol • VOL
capacity by a decline in inner diameter as part of myocardial
hypertrophy. Systolic constrictive force, in contrast, might
increase as a result of the reduction in helical angles as part of
outward displacement of the epicardial surface. On the other
hand, a more circular alignment of the tangential netting
component has been supposed to reduce stroke volume (11) .
This might apply if the length of the spiraling chains of serial
myocytes would not lengthen, which, however, is part of the
mechanism of hypertrophy. Another consequence of circular
realignment of the subepicardial helical structure was assumed
to be an increase in subepicardial torque relative to subendocardial torque, which ultimately should result in enhanced
global ventricular twisting (25). The concept only applies when
also taking into account the epi-endocardially intruding netting
of the myocardial wall, which means that the helical angle
alone does not provide the necessary information about the
basic mechanism of twisting. Regional distribution of angles of
intrusion might be a better key to the understanding of ventricular torque. Previous reports using force probes suggest that
the intruding netting component of the myocardial mesh has an
impact on myocardial mechanics (14). We speculate that alterations in regional distribution of intruding angles in the base
and the apex might influence the torque of the apex relative to
the ventricular base. It would be inappropriate at this stage,
however, to indulge in far-reaching inference from our observational findings to intramural mechanics. This matter must be
investigated systematically, which could involve, among others, micromechanical analysis.
When comparing the septum with the left ventricular free
wall, we found that intruding and helical angles had a similar
transmural distribution, albeit differences between the control
and hypertrophic hearts were less predominant in the septum.
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growth in size and expression of new myofibrils noted after
48 h in cultured myocytes (27). In our study we measured by
histology an increase of the diameter of the myocytes in the
angiotensin II-treated mice compared with controls. One might
speculate if such an increase in myocytic size has a direct
impact on the angle of intrusion. Any increase in angulation
will be part of a complex process of remodeling that occurs
during hypertrophy. In this respect, the myocardial mesh is
three dimensionally netted with superjacent constituents of the
mesh turning on a radial axis (24). As the myocytes increase
their size, their coupling with their neighbors, in both tangential and the endoepicardial directions, is structurally fixed. For
strictly geometrical reasons, changes in ventricular dimensions
must go along with changes in the helical angle. This remodeling process will also necessitate progressive changes in
connections of the myocytes with their neighbors. However,
future research is needed to substantiate this detail of microstructural remodeling. As mentioned, the circular realignment
in helical angle is a function of ventricular dimension. This was
recently shown on hearts of rats arrested in systole and diastole
(4). Accordingly, in the hypertrophic hearts of our study we did
not measure significant changes in helical angle in the subendocardial regions because the inner radius had slightly decreased while the outer radius had increased.
Earlier investigations of mice treated with angiotensin II
have shown preservation of systolic pump function, with impairment of diastolic function due to reduced compliance (28).
In keeping with these findings, we did not observe any alteration in left ventricular systolic function in the mice with
myocardial hypertrophy. Any diastolic dysfunction could be
the consequence of mural fibrosis, as well as an increase in
myocardial mass, and a minor reduction in ventricular volume
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DIFFUSION TENSOR IMAGING IN NORMAL AND HYPERTROPHIC HEART
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
GRANTS
This work was supported by the German Federal Ministry of Education and
Research Grant 01EV0704 and by the SFB-TR19, A2 D. W. Grant. Responsibility for the content rests with the authors. Dr. N. K. Bodhey, Department of
Radiology, Sree Chitra Tirunal Institute of Science & Technology, Trivandrum, was funded by the Ministry of Science & Technology, Government of
India.
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In the septum, angles were more heterogeneously distributed,
but our histological investigation failed to show any myocardial disarray, as is typically found in hypertrophic obstructive
cardiomyopathy.
Overall, the regional heterogeneities in myocardial alignment, such as we describe them in our study, throughout the
ventricular walls imperatively indicate the need of both global
and regional analysis of ventricular function. To speculate
about ventricular function on the base of morphological data is
hazardous. The interaction between the two highly heterogeneous matrices, namely the myocytes and the fibrous tissue,
does not allowed one to infer from the alignment of the
myocytes to the potential pathway of displacement of any
muscular segments.
Limitations. The study was based on one model of hypertrophy. Significant changes in the alignment of aggregated
myocytes were noted, although the degree of hypertrophy was
only modest. Future studies should compare various degrees
and time courses of hypertrophy to shed more light on the
functional importance of our noted architectural changes. In
our study, We arrested the hearts in diastole and did not study
the systolic arrangements. DT-MRI assessment of intruding
and helical angles were not performed in the area of the heart
where the right and left ventricle join because of its complex
histology. This interesting area should be systematically assessed in future research.
The primary eigenvector measured using DT-MRI is generated from the major pathways of diffusion that are assumed to
represent the dominating direction of chains of myocytes (22).
Recent reports supposed that the myocardial walls have a
laminar structure, interpreting the findings from examination of
secondary and tertiary eigenvectors (4). It is beyond the scope
of our present study to determine the precise global arrangement of the myocytes on the basis of the second and tertiary
eigenvectors. We suggest, nonetheless, that more work is
required relative to this important subject. It should also be
noted that, due to the extended time required for acquisition of
data, cardiac DT-MRI is currently limited to postmortem
studies.
In conclusion, we have shown that DT-MRI provides information concerning changes in the alignment of aggregated
myocytes mediated by angiotensin II-induced remodeling. The
technique is nondestructive and reproducible. It has provided
important information about the intramural arrangement of the
myocytes aggregated together in the walls of normal and
pathologic hearts. The potential implication of these changes
on intramural dynamics should be addressed in future research.
DIFFUSION TENSOR IMAGING IN NORMAL AND HYPERTROPHIC HEART
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