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

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 ( $\Delta$ ), 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 $\Delta =0$ 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-17.4 $\mu$ m/18.0 $\mu$ m versus 19.2 $\mu$ m/19.0 $\mu$ m; minor diameter-10.2 $\mu$ m/9.4 $\mu$ m versus 12.8 $\mu$ m/13.4 $\mu$ m; 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.