Measuring cardiomyocyte cellular characteristics in cardiac hypertrophy using diffusion-weighted MRI

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Measuring cardiomyocyte cellular characteristics in cardiac hypertrophy using diffusion-weighted MRI

Mohsen Farzi, Sam Coveney, Maryam Afzali, Marie-Christine Zdora, Craig A. Lygate, Christoph Rau, Alejandro F. Frangi, Erica Dall’Armellina, Irvin Teh, Jürgen E. Schneider

Abstract

Purpose

This paper presents a hierarchical modeling approach for estimating cardiomyocyte major and minor diameters and intracellular volume fraction (ICV) using diffusion-weighted MRI (DWI) data in ex vivo mouse hearts.

Methods

DWI data were acquired on two healthy controls and two hearts 3 weeks post transverse aortic constriction (TAC) using a bespoke diffusion scheme with multiple diffusion times (Δ), q-shells and diffusion encoding directions. Firstly, a bi-exponential tensor model was fitted separately at each diffusion time to disentangle the dependence on diffusion times from diffusion weightings, that is, b-values. The slow-diffusing component was attributed to the restricted diffusion inside cardiomyocytes. ICV was then extrapolated at Δ=0 using linear regression. Secondly, given the secondary and the tertiary diffusion eigenvalue measurements for the slow-diffusing component obtained at different diffusion times, major and minor diameters were estimated assuming a cylinder model with an elliptical cross-section (ECS). High-resolution three-dimensional synchrotron X-ray imaging (SRI) data from the same specimen was utilized to evaluate the biophysical parameters.

Results

Estimated parameters using DWI data were (control 1/control 2 vs.TAC 1/TAC 2): major diameter—17.4𝜇m/18.0𝜇m versus 19.2𝜇m/19.0𝜇m;minor diameter—10.2𝜇m/9.4𝜇m versus 12.8𝜇m/13.4𝜇m; and ICV—62%/62%versus 68%/47%. These findings were consistent with SRI measurements.

Conclusion

The proposed method allowed for accurate estimation of biophysical parameters suggesting cardiomyocyte diameters as sensitive biomarkers of hypertrophy in the heart.