Introduction
Myocardial fiber and connective tissue architectures are fundamental
determinants of regional and global cardiac mechanical function.
Structural alterations in the myocardial tissue matrix are apparent within
90 minutes of mild ischemic injury[1] and gross changes in the fiber and
collagen network occur over a much longer time scale in infarcted
tissue. A method for measuring intercellular structure might therefore be
a sensitive indicator of the severity, extent and time course of ischemic
injury, while also providing a means to study myocardial structure/function
relationships.
Imaging using diffusion-sensitive MRI has recently been demonstrated
as a non-invasive method for computing fiber directions in various
tissues[2,3]. Diffusion anisotropy has also been reported in myocardial
tissue[4,5], however the relationship between the
principal directions of water diffusion and the orientation of local
myocardial fiber network has not been fully validated.
Methods
MR Diffusion Imaging:
Isolated canine hearts were imaged using diffusion sensitive MRI and a
spin-echo acquisition sequence. Six sets of biphasic gradient pulses,
with diffusion sensitivity of B~300 s/mm^2, were used to
compute the diffusion tensor at each imaging voxel. The principal directions
of diffusion and their diffusion values were then calculated in
each voxel and the voxel locations registered in 3D.
An MR diffusion eigen-image was created by displaying the principal
direction corresponding to (and scaled by) the largest eigenvalue, as shown
in Figure 1.
The principal diffusion direction with the largest diffusion in the
circumferential-longitudinal plane ({\it in-plane}) was assumed to
represent the local fiber direction.
The angle of the corresponding in-plane diffusion vector with respect to the
local circumferential direction (and local epicardial surface normal) was
then computed.
Fig. 1(Top) MRI diffusion principal eigen-value data set at
a 24x24 image resolution (3x3x5mm voxel size).
(Bottom) Picture of same heart noting locations of tissue sections
and circumferential-radial (CR) and longitudinal-radial (LR) slices.
Histological analysis:
Tissue blocks were harvested from 3 sites in the same heart
used for the diffusion-sensitive imaging experiment. Transmural blocks
of dimension ~1.5 cm^3 were excised, sectioned in orthogonal
planes at 50--200micron thickness (see Figure 1)
on a vibratome, transferred to a slide and viewed under low power (x10).
Fiber angles were observed and recorded in sections cut orthogonal to the
epicardial surface at ~1mm intervals.
Apical Anterior | Basal Anterior |
|
|
Basal Posterior |
|
Fig. 2 Estimated myocardial fiber angles versus percent wall
depth (from epicardium). Shown are measurements from histology of excised
tissue blocks (unfilled circles), and MR diffusion-sensitive imaging
(filled circles).
|
|
Results
Figure 2 shows plots of fiber angle versus percent wall depth for the
histological and MR-diffusion data.
The nearly linear variation of fiber angle with depth correlates with
previous findings[6]. Linear regression lines were fit to each data set at
each depth. The fiber angle intercepts at the epicardium and endocardium
and fitted slopes are presented in Table 1.
(histo/MR) | apical ant. | basal ant. |
basal post. |
epi int. | -45.6/-89.1 | -66.8/-53.6 |
-56.3/-30.3 |
endo int. | 127/94 | 57/108 | 59/15 |
slope | 173/183 | 124/162 | 115/46 |
Table 1 Epi- and endo-cardial intercepts and slope of fiber angle
versus wall depth from a linear regression fit. Data for both histological
sectioning and MR diffusion imaging are given for 3 LV free-wall locations.
Discussion
A correlation is observed between the computed direction of largest
in-plane diffusion and the histologically measured fiber angles in
at least 2 of the 3 regions analyzed.
The variance in the MR-based fiber angles is believed to arise from
the uncertainty
in the raw MR diffusion data, coupled with the relatively large MR voxel
size compared to the observed transmural fiber angle variations.
MR data from the extreme endo- and epi-cardial voxels are also likely
to exhibit corruption due to signal from the fluid surrounding the heart.
Fiber angle error at the intercepts is expected due to the uncertainty
in delimiting the endo- and epi-cardial borders from the MR images.
In the basal posterior site, where the slopes are least well correlated,
there is a correspondance between the histologically measured angles and
those from the MR analysis in the sub-epicardium where the distribution
of fiber angle was highly non-linear.
Future work will investigate the relationship between the fiber
laminal sheet structure[7] (perpendicular to the in-plane fiber direction)
and the remaining two principal directions of diffusion.
This knowledge is hoped to provide a formal
framework for further investigations into the structural mechanisms of
regional variations in myocardial function.
References
1. Zhao M et al,
J. Amer. College of Cardiology,
10:1322-34, 1995.
2. Wong EC, Cox RW and Song AW
Magnetic Resonance in Medicine,
34:139-143, 1995.
3. Hsu EW and Mori S,
Magentic Resonance in Medicine,
34:194--200, 1995.
4. Basser PJ, Mattiello J, and LeBihan D
Journal of Magnetic Resonance,
B103:247--254, 1994.
5. Reese TG, Weisskoff RM, Smith RN, Rosen BR
Dinsmore RE and Wedeen VJ
Proc of the SMR, 1:357, 1995.
6. Nielsen PMF, LeGrice IJ, Smaill BH, Hunter PJ
Am. J. Physiology, 260:H1365-H1378, 1991.
7. Legrice IJ, Smaill BH, Chai LZ, Edgar SG,
Gavin JB and Hunter PJ
Am. J. Physiology, 269:403-426, 1992.
Acknowledgements
This research was funded through NIH HL41603, NSF BES-9634974 and the
Whittaker Foundation.
|