Characterization of the ultra-short echo time magnetic resonance (UTE MR) collagen signal associated with myocardial fibrosis
Journal of Cardiovascular Magnetic Resonance volume 17, Article number: Q7 (2015)
The homogeneous distribution of collagen in diffuse myocardial fibrosis renders the disease unsuitable for imaging using late gadolinium enhancement (LGE) . 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 . 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 . 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.
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.
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 %).
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.
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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