Detection of Coronary Microvascular Dysfunction in Diabetic Mice Using Arterial Spin Labeling Cardiac <scp>MRI</scp> : A Multimodality Imaging Comparison

BACKGROUND: Coronary microvascular dysfunction (CMD) is a major contributor to cardiovascular complications in diabetes. Although noninvasive techniques such as arterial spin labeling cardiac MRI (ASL-MRI) and transthoracic echocardiography (TTE) are available, their comparative performance for CMD remains unclear. PURPOSE: To compare ASL-MRI and TTE for CMD assessment in type 1 and type 2 (T1DM, T2DM) mouse models and relate functional indices to histological microvascular and myocardial remodeling, including early-stage T2DM (8w-T2DM). STUDY TYPE: Prospective. ANIMAL MODEL: Forty 8-week-old male C57BL/6J mice allocated to five groups: control, T1DM, and T2DM (n = 10 per group, imaged 16 weeks postinduction), and early-stage T2DM (8w-T2DM) and age-matched controls (n = 5 per group, imaged 8 weeks post-induction). FIELD STRENGTH/SEQUENCE: Segmented FLASH cine, steady-pulsed labeling ASL, and inversion-recovery segmented FLASH (T1 mapping) sequences at 9.4 T. ASSESSMENT: Rest/stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were derived from ASL data using a model-based approach incorporating native T1 (from segmented FLASH data). Coronary flow velocity (CFV) and reserve (CFVR) were measured by TTE at rest (1.5% isoflurane) and stress (2.5% isoflurane). Histology included assessment of hematoxylin-eosin (myocyte area), Masson (collagen), and IB4 (capillary density). STATISTICAL TESTS: Group comparisons used t-tests, Mann-Whitney U tests, and one-/two-way ANOVA with Bonferroni correction; correlations were assessed with Pearson or Spearman coefficients (r). p < 0.05 was considered significant. RESULTS: 38 animals completed MR and TTE imaging. At 16 weeks, stress diastolic MBF was significantly lower in T1DM (14.67 ± 1.62 mL/g/min) and T2DM (13.42 ± 2.44 mL/g/min) vs. controls (22.19 ± 0.25 mL/g/min), with significantly reduced MPR in T2DM (1.53 ± 0.17 vs. 2.27 ± 0.15). TTE showed significantly reduced CFVR only in T2DM (2.16 ± 0.24 vs. 2.75 ± 0.24). In 8w-T2DM, ASL-MRI detected significantly reduced MPR (1.87 ± 0.16 vs. 2.26 ± 0.13), whereas TTE showed no significant CFVR change (p = 0.900). Capillary density significantly decreased in 16-week and 8-week T2DM. IB4-positive area correlated with CFVR (r = 0.673) and more strongly with MPR (r = 0.810). CONCLUSION: ASL-MRI detected CMD in diabetic mice, outperforming TTE in early-stage disease and showing a strong association with microvascular injury. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.