Yoshiaki Morita1, Naoaki Yamada1, Emi Tateishi2, Teruo Noguchi2, Masahiro Higashi1, and Hiroaki Naito1
1Department of Radiology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan, 2Division of Cardiology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Synopsis
Diffuse interstitial fibrosis is frequently observed in dilated cardiomyopathy (DCM). A non-invasive
method that could reliably quantify fibrosis would be preferable. In this study, we demonstrated that the T1-map-derived
ECV reflects the myocardial collagen volume fraction in DCM. Therefore, the ECV could be a useful
and practical biomarker for the detection of diffuse interstitial fibrosis that
is difficult to evaluate using only conventional LGE images.Introduction
Diffuse interstitial fibrosis, represented by the
accumulation of collagen within the extracellular myocardial space, is frequently
observed in histological specimens of dilated cardiomyopathy (DCM)
1 and leads to irreversible
replacement fibrosis.
2 The late gadolinium enhancement
(LGE) method relies on the difference in signal intensity between fibrotic and
unaffected myocardium as “nulled” reference, which limits its usefulness in
diagnosis of diffuse interstitial fibrosis. Recently, myocardial T1 mapping has
been applied to quantify the extracellular
volume fraction (ECV) and has shown potential for providing a
better characterization of myocardial tissue composition.
3Purpose
The purpose of this study was to determine the usefulness of ECV measured by T1 mapping for quantification of interstitial fibrosis in DCM when compared with the histological collagen volume fraction from endomyocardial biopsy (EMB).
Methods
Fifty-two patients with DCM and 8 patients with normal
myocardium underwent cardiac MRI with 3T machine (MAGNETOM
Verio, Siemens AG Healthcare
Sector, Erlangen, Germany). T1mapping
using the Fast MOLLI method was performed with
short-axial slices at the basal, mid-ventricular, and apical levels at
pre-contrast and post-contrast 21 minutes. Fast-MOLLI was implemented as a two-inversion
recovery (IR) sequence with the first of 3 and the second of 5 consecutive
image acquisitions, which decreased the acquisition time by about
one-third when compared with the original MOLLI method.
4 The SSFP
(True-FISP) sequence was used for readout (TE/TR=1.1/2.5msec, flip angle 35°, FOV
320×223mm, matrix 192×256, and slice thickness 8mm). The T1 map was
reconstructed using 8 source images with different inversion time. The ECV was
quantified according to the following formula : ECV=λ x (1
– hematocrit), where λ=⊿R1myocardium
/⊿R1bloodpool (⊿R1 : the change of R1(=1/T1) between pre-contrast and
post-contrast). The pre-contrast and post-contrast T1
map was used for automatic reconstruction of the ECV map with dedicated
software (MapMaker prototype®, Medis, Leiden,
Netherlands) (Figure 1). The ECV map was segmented into 16 segments. Segment-based ECV values were measured and the mean of 16 segmental
values was calculated. LGE was also performed with IR True-FISP
after gadolinium administration. In DCM patients, the presence or absence of
LGE was decided visually on 10-minute-delayed images. All DCM
patients underwent EMB within 30 days of cardiac MRI. The
amount of myocardial fibrosis (% fibrosis) was calculated using an automated
image analysis system (ImageScope®, Aperio, CA, USA). Endomyocardium and blood
vessels were manually excluded. The % fibrosis was quantified using following
formula: Number of blue dots (indicating fibrosis) / number of total myocardial
dots.
Results
Figure 2 shows the mean ECV of the normal myocardium, all
DCM patients, and LGE positive and LGE negative DCM patients. The LGE negative
patients showed higher ECVs than were seen in a normal myocardium (p<0.01).
In DCM patients, the ECV obtained by the T1 map was strongly correlated with %
fibrosis (r=0.80, p<0.0001) (Figure 3), whereas the presence of LGE was not
related to % fibrosis (p=0.30) (Figure 4). The ECV in the septal wall showed a better
correlation with % fibrosis (r=0.84, p<0.0001). The ECV values in the anterior,
inferior, and lateral walls were also significantly correlated with % fibrosis
(r=0.76, 0.74, and 0.68, respectively). The cut-off value for ECV to
differentiate between normal myocardium and DCM was 32.5 % (Specificity 87 %,
sensitivity 74%, area under the curve 0.82).
Discussion
Currently, the determination of myocardial fibrosis
in DCM patients requires EMB for evaluation by histopathology. However, EMB is
associated with some risk and discomfort due to its invasive nature and the
possibility of sampling errors. Therefore, a non-invasive method that can
reliably quantify fibrosis would be preferable. This study revealed a strong
linear relationship between the T1-map-based ECV and histological fibrosis by
EMB, which is an important finding as it means that the T1 map for measurement
of the ECV is suitable for stratifying DCM patients based on their myocardial
fibrosis volume fraction, which is difficult to detect using only conventional
LGE. Further studies are needed to put ECV to practical use, such as monitoring
of therapeutic effect and prognostic information. The histological specimen for
EMB was obtained from the septal wall; therefore, the ECV in septal wall
segments had a better correlation with % fibrosis. However, the ECV in the wall
segments other than the septum were also associated with % fibrosis, suggesting
that myocardial fibrosis in DCM exists diffusely in the extracellular
myocardial space.
Conclusion
This study provides validation of use of the T1-map-derived
ECV for measurement of the myocardial collagen volume fraction. ECV would be a useful
and practical biomarker for the detection of diffuse interstitial fibrosis that
is difficult to evaluate using only conventional LGE images.
Acknowledgements
No acknowledgement found.References
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