Myocardial extracellular volume fraction (ECV) quantified by T1 mapping can detect diffuse myocardial fibrosis in dilated cardiomyopathy (DCM): Comparison with histological collagen volume fraction by endomyocardial biopsy (EMB)
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.3

Purpose

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

1.Brooks A et al. Interstitial fibrosis in the dilated non-ischaemic myocardium. Heart. 2003;89(10):1255-6.

2.Weber KT et al. Myocardial fibrosis: functional significance and regulatory factors. Cardiovasc Res. 1993 ;27(3):341-8.

3.Ugander M et al. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J. 2012 ;33(10):1268-78.

4.Morita Y. et al. Validation of a Faster Modified Look-Locker Inversion-recovery (MOLLI) method for myocardial T1 mapping on 3T MRI. ISMRM 20th scientific meeting and exhibition 2012

Figures

Figure 1. Dedicated software for ECV mapping (MapMaker prototype®, Medis, Leiden, Netherlands).The user can drag and drop a pre-contrast and post-contrast T1 map into the viewports and the ECV map is automatically reconstructed. If a misregistration occurs, manual motion correction is needed.

Figure 2. The mean ECV of the normal myocardium, all DCM patients, LGE positive, and LGE negative patients in DCM.

Figure 3. The correlation between ECV and % fibrosis.

Figure 4. Comparison of % fibrosis between LGE positive and negative patients.

Figure 5. Representative case of DCM. The LGE showed no apparent enhancement. However, the myocardial ECV was diffusely high (40%) and the % fibrosis obtained by EMB also showed high values (32%). The blue dots indicate the diffuse interstitial fibrosis.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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