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Characterization of the ultra-short echo time magnetic resonance (UTE MR) collagen signal associated with myocardial fibrosis

Background

The homogeneous distribution of collagen in diffuse myocardial fibrosis renders the disease unsuitable for imaging using late gadolinium enhancement (LGE) [1]. More recently, the estimation of extracellular volume from T1 maps involving gadolinium agents has shown promise; however, these methods are not specific to collagen and are governed by gadolinium kinetics [2]. The diagnosis of diffuse myocardial fibrosis would benefit from an imaging method that can directly detect collagen. Notably, ultra-short echo time magnetic resonance (UTE MR) is a technique that can be used to detect short T2* species, including collagen [3]. Our objective is to characterize the UTE signal of protons in the collagen molecule, including their T2* and chemical shift. Direct isolation of a collagen signal could aid in the diagnosis of myocardial fibrosis, especially for diffuse distributions, and the assessment of disease extent.

Methods

Collagen solutions of concentrations ranging from 0 % m/v to 50 % m/v were prepared by dissolving hydrolyzed type I and III collagen powder in 0.125 mM MnCl2 , where the signal decay of MnCl2 mimicked that of cardiac muscle. Each solution was scanned using a 3D UTE pulse sequence at 7 T, acquiring TEs from 0.02 ms to 25 ms, at a resolution of 0.781 mm isotropic. Upon fitting with a model of bi-exponential T2* with oscillation, the UTE collagen signal fraction was determined and calibrated against the collagen concentration. The T2* and resonance frequency (arising from the chemical shift) of collagen were assessed in collagen solutions. Validation of the collagen signal properties was also performed in formalin-fixed canine heart tissue, imaged with TEs from 0.02 ms to 25 ms, at a resolution of 0.156 mm isotropic.

Results

For collagen concentrations of 10 % to 50 %, the mean collagen T2* was 0.75 ± 0.05 ms, and the mean collagen frequency was 1.061 ± 0.004 kHz. A linear relationship (slope = 0.40 ± 0.01, R2 = 0.99696) was determined between the UTE collagen signal fraction associated with these characteristics and the measured collagen concentration (Figure 1). Similarly in canine heart tissue, a signal with T2* of 1.1 ± 0.3 ms and resonance frequency of 1.11 ± 0.02 kHz upfield of water was determined, consistent with collagen (Figure 2). The UTE collagen signal fraction of 1.2 ± 0.2 % in tissue corresponded to a collagen concentration of 2.3 ± 0.9 %, which was within the uncertainty of the collagen area fraction determined from histology (4 ± 2 %).

Figure 1
figure 1

UTE results in collagen solutions. (a) Collagen solution calibration plot, demonstrating a linear relationship between the UTE collagen signal fraction and the collagen concentration. m = slope, b = y-intercept, R2 = correlation coefficient, sr = standard deviation about the regression. (b) T2* decay of the 50 % collagen solution, fitted using a bi-exponential T2* model with oscillation. T2*long denotes the long T2* of MnCl2 (mimicking cardiac muscle). Although not all long TEs were fitted, the focus was in the characterization of the short TEs ≤ 2 ms, where the T2* model is accurate.

Figure 2
figure 2

Histology and UTE results in canine heart tissue. (a) Histological slice of heart tissue, stained with Picrosirius Red. The 781.2 μm x 781.2 μm region-of-interest (ROI) used for analysis is delineated. The collagen area fraction in the ROI was determined to be 4 ± 2 %, based on a pixel threshold algorithm. (b) Corresponding UTE MR image at TE = 0.02 ms, with the ROI delineated. (c) T2* decay within the ROI. T2*long denotes the long T2* of cardiac muscle. TEs ≤ 2 ms were finely sampled to determine the collagen T2* and resonance frequency, where the T2* model is accurate. Based on the calibration plot in Figure 1a, the collagen signal fraction of 1.2 ± 0.2 % was equivalent to a collagen concentration of 2.3 ± 0.9 %. Hence, there was agreement between the collagen area fraction determined from histology (4 ± 2 %) and the collagen concentration.

Conclusions

The results suggest that collagen associated with myocardial fibrosis can be endogenously detected and quantified using UTE MRI. This signal is specific to protons in collagen, characterized by a T2* of ~ 0.8 ms and a resonance frequency of ~ 1.1 kHz upfield of water at 7 T. Such properties would be beneficial in the determination of collagen content due to disease.

Funding

Canadian Institutes of Health Research (CIHR).

References

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  3. De Jong et al: J Moll Cell Cardiol. 2011

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Siu, A.G., Ramadeen, A., Hu, X. et al. Characterization of the ultra-short echo time magnetic resonance (UTE MR) collagen signal associated with myocardial fibrosis. J Cardiovasc Magn Reson 17 (Suppl 1), Q7 (2015). https://doi.org/10.1186/1532-429X-17-S1-Q7

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  • DOI: https://doi.org/10.1186/1532-429X-17-S1-Q7

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