Resolving myoarchitectural disarray in the mouse ventricular wall with diffusion spectrum magnetic resonance imaging

Area of Science:

• Cardiovascular Research
• Biomedical Imaging
• Molecular Cardiology

Background:

• The ventricular wall's myoarchitecture is crucial for cardiac mechanical function.
• Congenital hypertrophic cardiomyopathy (HCM) can arise from genetic mutations affecting cardiac proteins like myosin binding protein-C (MyBP-C).
• Understanding myoarchitectural changes in HCM is vital for diagnosing and treating the condition.

Purpose of the Study:

• To evaluate the efficacy of MR diffusion spectrum imaging (DSI) tractography in detecting ventricular myoarchitectural abnormalities.
• To investigate the impact of MyBP-C ablation on cardiac myofiber organization in a mouse model of congenital HCM.

Main Methods:

• Generation of homozygous MyBP-C knockout mice by deleting specific exons of the MyBP-C gene.
• Utilizing DSI tractography to image and analyze myofiber alignment in the left ventricular wall.
• Confirmation of fiber tract imaging findings using multi-slice two-photon microscopy.

Main Results:

• DSI tractography successfully depicted helical fiber structures in wild-type mouse hearts with a continuous transition of helix angles.
• MyBP-C knockout mice exhibited significant myoarchitectural disarray, particularly in the mid-myocardium and subendocardium.
• Impaired transmural progression of helix angles was observed in the MyBP-C knockout model.

Conclusions:

• DSI tractography is a valuable tool for assessing myoarchitectural disarray in cardiomyopathy models.
• A biological link exists between myofilament expression (MyBP-C), cardiac fiber alignment, and torsional rotation in congenital HCM.