Introduction: Persistent (per) AF may be maintained by localized extra-PV drivers (DRs). Regional fibrosis can serve as a substrate for AF DRs, but its visualization by delayed enhancement (DE)-MRI lacks proper validation for driver substrates. The objective of this study is to evaluate if histology-validated normalized (HVN) DE-MRI thresholds can define arrhythmogenic fibrotic content in multielectrode mapping (MEM)-defined DRs from perAF patients’ (Pts) DE-MRI. Methods: PerAF Pts (n=14, 71% male; 63±10 y/o) had DE-MRI at 3T (0.63x0.63x0.63mm 3 , 0.2mmol/kg Gd) before their perAF ablation procedure. Chamber-specific DE-MRI intensity was normalized to the healthy atria (mean lowest 5% intensity, 0 AU) and mitral (LA) or tricuspid (RA) valve (100 AU). 3 control and 5 perAF canines had DE-MRI and regional histology to validate DE-MRI fibrotic thresholds for the LA and RA, which were defined as standard deviations (SD) above 40% of the mean healthy atrial tissue intensity (LA: 3.7 SD, RA: 2.7 SD). Fibrosis-enhancement of segmented MEM-defined DRs (LA: n=25, RA: n=11) were analyzed using conventional, non-normalized 3 SD and HVN thresholds and compared to 5 random regions (non-DRs) within the same anatomical region(s). Results: Only our HVN approach could reveal arrhythmogenic fibrotic substrates in LA DR regions, but not the conventional approach. Both approaches could not provide significant differences for RA DR vs non-DR fibrosis regions. The cut-off of 33.6% of LA DE-MRI fibrotic enhancement using the HVN approach allowed to distinguish LA DR vs. non-DR regions with 56% sensitivity and 70% specificity. At 12 months follow-up, 10 Pts remained free of AF. Conclusion: MEM-defined DRs within fibrotic regions, identified by HVN DE-MRI, may represent efficient targets for ablation of LA arrhythmogenic perAF substrates. Integration of MEM and MRI may lead to improved targeted ablation and long-term AF freedom.