Basic/Translational Science -> Intact Heart Electrophysiology (includes Pharmacology and Optical Mapping) D-AB20 - New Mechanistic Insights on Arrhythmia Initiation and Perpetuation (ID 40) Abstract

D-AB20-04 - Defining Arrhythmogenic 3D Fibrotic Architecture In Vivo With Ex Vivo-Validated Late-Gadolinium Enhanced Cardiac Magnetic Resonance In Canine Model Of Persistent Atrial Fibrillation (ID 1445)


Background: Atrial fibrosis architecture plays a significant role in atrial fibrillation (AF).
Objective: Late gadolinium enhancement (LGE) exceeding signal intensity thresholds on cardiac magnetic resonance (CMR) has been widely utilized as surrogates for fibrosis, but 3D atrial fibrosis LGE-CMR maps were never validated.
Methods: Control (n=2) and clinically-relevant canines with 4-month tachypacing-induced persistent AF (n=2) underwent in vivo LGE-CMR at 1.5T with 0.5x0.5x1.25mm3 resolution after IV injection of 0.2mmol/kg gadolinium contrast. The hearts were then explanted and scanned at 9.4T with 154-180µm3 resolution. The atria were also mapped in vivo and ex vivo by simultaneous multi-electrode and near-infrared optical mapping. Regional histology was correlated to ex vivo LGE-CMR slices to validate biatrial fibrosis thresholds (Figure). In vivo LGE thresholds were tuned to match the histologically-validated fibrotic content.
Results: Histological validation defined in vivo scan-specific LGE thresholds of 0.8+/-0.3 standard deviations (SD) above the mean atrial tissue intensity. Thus, generic in vivo LGE-CMR thresholds (2SD) significantly underestimated biatrial fibrosis. Scan-specific thresholds revealed fibrotic 3D architecture of functionally validated arrhythmogenic regions of interest (sinoatrial node and AF reentrant substrates) poorly seen with the generic threshold.
Conclusion: Our unique validated in vivo-ex vivo LGE-CMR-histology approach together with functional mapping, utilizing a clinically-relevant canine model, can improve clinical LGE-CMR visualization of 3D arrhythmogenic fibrosis architecture for targeted AF treatment.