Alexander Gotschy1,2, Constantin von Deuster1, Robbert J.H. van Gorkum1, Ella Vintschger1, Robert Manka2,3, Christian T. Stoeck1, and Sebastian Kozerke1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, 2Department of Cardiology, University Hospital Zurich, Zurich, Switzerland, 3Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
Synopsis
Cardiac
diffusion tensor imaging (cDTI) is a novel non-invasive method that allows assessing
changes in myocardial microstructure in various cardiomyopathies. To identify pathologies,
however, the distribution of cDTI parameters and their subject specific
dependencies in normal hearts need to be known. Therefore, we investigated age,
gender and heart rate dependencies of quantitative parameters derived from spin-echo
based cDTI in healthy subjects. Our results display the variation of cDTI
parameters in normal hearts and thereby allow gauging at which level of
expected pathological changes sex and age matched reference values will be
needed in future clinical practice.
Introduction
Cardiac
diffusion tensor imaging (cDTI) allows for the non-invasive investigation of
myocardial microstructure and tissue characterization without contrast agents[1,2]. Recent
studies have shown microstructural changes that occur during the progression of
diseases including hypertrophic, dilated and ischemic cardiomyopathies[3-5]. At
present, either spin-echo (SE) or stimulated-echo acquisition mode (STEAM)
sequences are used for cDTI. While the anthropometrics of healthy volunteers
for cDTI using STEAM sequences were already investigated[6,7], these
results cannot be transferred to SE based cDTI because quantitative measures of
DTI including mean diffusivity (MD) and fractional anisotropy (FA) are
significantly different between SE and STEAM[8]. Therefore,
the objective of the present work was to investigate age, gender and heart rate
dependencies of quantitative cDTI parameters derived from a SE based sequence in
healthy subjects.
Methods
For
this study, 36 volunteers (11 male, 31%) without known cardiovascular disease
were recruited. The study population consisted of two subgroups, one
representing young adults (20-35 yrs, n=18) while the other subgroup were
seniors (60-75 yrs, n=18). All study subjects underwent CMR on a clinical 1.5T
system (Philips Healthcare, Best, The Netherlands) equipped with a 5 channel
cardiac coil and a gradient system delivering 80mT/m@100mT/m/ms. For cDTI, we
used a diffusion-weighed second-order motion compensated spin-echo (SE)
sequence[9] to acquire
three imaging planes in short-axis orientation in mid systole. Prospective
cardiac triggering and respiratory navigator based slice tracking[10] allowed
for data acquisition during free-breathing with a spatial resolution of
2.5x2.5x8 mm3 and a FOV of 230x98 mm2. Diffusion
weighting was encoded with a b-value of 450 s/mm2 along 9 and a
b-value of 100 s/ms2 along 3 orthogonal directions[8]. To reduce
residual motion in the data series, groupwise non-rigid image registration exploiting
total variation displacement regularization and a PCA-based image similarity
metric was used[11]. On the aligned
data, MD, FA, helix, transverse and absolute E2A sheet angle (HA, TA, SA) were
computed[12]. In
addition, the transmural gradient of the HA was calculated (HA slope). All parameters
were evaluated in 4 sectors of the LV at the mid-ventricular level. Differences
in the baseline characteristics between both groups were tested using unpaired
two-tailed t-tests. The influence of age, sex and heart rate on the diffusion
parameters was evaluated using a multiple regression analysis.Results
Data
acquisition and analysis was successful in all study subjects. Global MD agreed
closely in both age groups and also the regional distribution of the segmental
MD was found to be similar in young adults and seniors (Table 1). In contrast,
global FA was the only parameter that exhibited an age-dependence that was
driven by significantly lower values in the septal and anterior segments of
seniors. For TA, TA standard deviation (SD) and the E2A sheet angle, no
differences between the groups were found. Figure 1 summarizes HA, TA and E2A for
both populations. Using a t-test, the transmural slope of the HA was
significantly lower in the older subjects but this trend could not be confirmed
in the multiple regression analysis. The investigation of differences between
sexes revealed significantly lower MD values in women while no difference could
be found for FA. All other parameter were similar in male and female subjects, except
for E2A sheet angle which also showed a trend to lower values in women that did,
however, not reach statistical significance in the multiple regression analyses
(Figure 2). No diffusion parameter exhibited a significant dependence on heart
rate.Discussion
We
report the first investigation of subject-specific determinants of quantitative
measures of SE based cDTI. The independence on heart rate (range studied 45 –
103/min) of all cDTI parameter is an important finding for future clinical
applications and an advantage compared to STEAM based sequences. STEAM based
cDTI exhibits significant heart rate dependence for FA, HA slope and E2A
measurements even with heart rate correction[7].
Furthermore, our results imply that the orientation of the myocardial fiberstructure,
represented by HA, TA and E2A is largely conserved across age and sex in
healthy hearts. In contrast, the changes found in MD and FA indicate age and
sex dependent alterations of the myocardial composition within the normal fiber
orientation. Figure 3 exemplarily depicts our findings by a direct comparison
of the results from a young woman and an elderly man. Finally, the presented
variation of cDTI parameters in normal hearts allows gauging at which level of
expected pathological changes sex and age matched reference values will be
needed in future clinical practice.
Acknowledgements
AG and CvD contributed equally to this work.References
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