Quantitative Susceptibility Mapping for Differentiating Hydroxyapatite and Calcium Oxalate Breast Calcifications at 3T: A Phantom Study

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Abstract

Purpose

Breast microcalcifications trigger 70–80% of unnecessary biopsies because current imaging cannot distinguish malignancy-associated hydroxyapatite (HA) from benign-associated calcium oxalate (CaOx). Quantitative susceptibility mapping (QSM) could exploit the susceptibility contrast between these minerals (HA: Δχ ≈ −7 ppm; CaOx: Δχ ≈ −1 ppm relative to water), but no study has demonstrated compositional differentiation at clinical field strength. This work assessed susceptibility and R2* relaxation rate maps for microcalcification differentiation at 3 T using tissue-mimicking phantoms.

Methods

A phantom comprising 12 tubes, each containing co-embedded HA and CaOx particles in BaCl 2 -crosslinked alginate gels (pure alginate, adipose-mimicking, and fibroglandular tissue-mimicking relaxation properties; n = 4 per type), were scanned at 0.70 mm and 0.86 mm isotropic resolution using a multi-echo gradient echo sequence. A consensus-aligned QSM pipeline and mono-exponential R2* fitting was developed. A digital twin phantom simulation quantified the contributions of partial volume effects and Total Variation (TV) regularisation to susceptibility underestimation.

Results

QSM detected HA in 18/24 measurements (Δχpeak = −0.37 ± 0.07 ppm in alginate at 0.70 mm) and CaOx in 0/24. R2* mapping detected HA in 23/24 and CaOx in 22/24. The digital twin identified TV regularisation as the dominant signal loss mechanism (57.5% loss), exceeding partial volume effects (24.3% loss). Combined parameters yielded three classification categories: QSM-positive with elevated R2* (HA), QSM-negative with moderate R2* (CaOx), and neither elevated (no calcification).

Conclusion

QSM at 3 T enables categorical HA detection while R2* provides complementary CaOx sensitivity, together enabling two-parameter microcalcification classification from a single multi-echo acquisition.

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