Hypointensity on Carotid Plaque MRI and Its Relationship to Calcification: Histopathologic Validation With Quantitative Susceptibility Mapping

BACKGROUND: On conventional carotid plaque MRI, calcification is commonly defined as a region that is hypointense across multiple contrast weightings. However, iron-containing components such as hemosiderin may exhibit similar signal characteristics, raising concerns regarding substrate specificity. PURPOSE: To evaluate whether quantitative susceptibility mapping (QSM) can distinguish hemosiderin from calcification in carotid atherosclerotic plaques using ex vivo MRI with direct histopathologic correlation. STUDY TYPE: Ex vivo specimen study. SPECIMEN: Twenty-four carotid endarterectomy specimens obtained between October 2017 and August 2021. FIELD STRENGTH/SEQUENCE: 3T MRI including spin-echo T1-weighted, spin-echo T2-weighted, time-of-flight-equivalent gradient-echo (FLASH) imaging, and multi-echo FLASH-based QSM reconstruction. ASSESSMENT: Histologic sections were stained with hematoxylin-eosin, von Kossa (calcification), and Berlin blue (hemosiderin). With histopathologic findings as reference, two radiologists defined corresponding regions of interest on MRI for substrate-level signal characterization. Contrast-to-noise ratios (CNR) were measured on conventional sequences, and relative susceptibility values (rSV) were measured on QSM. STATISTICAL TEST: Group comparisons were performed using the Wilcoxon rank-sum test. A two-sided p < 0.05 was considered statistically significant. RESULTS: Seventy-nine matched cross-sections yielded 41 calcifications and 25 hemosiderin deposits, including 16 sections with both components. On T1-, T2-, and FLASH imaging, CNR values did not differ significantly between calcification and hemosiderin (p = 0.12, p = 0.096, and p = 0.67, respectively), with substantial signal overlap. On QSM, hemosiderin exhibited positive rSVs (mean ± SD: 506.8 ± 320.5 ppb), whereas calcification exhibited negative rSVs (-440.5 ± 296.3 ppb), without polarity overlap in this dataset and with a significant group difference. Hemosiderin deposition was identified in 25 of 79 matched sections, and calcification and hemosiderin coexisted in 16 sections. DATA CONCLUSIONS: Hypointensity on conventional carotid plaque MRI may not reliably indicate calcification at the substrate level. QSM enables robust differentiation between diamagnetic calcium and paramagnetic iron with histopathologic validation. TECHNICAL EFFICACY: Stage 2.