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Coherence-based ultrasound imaging has demonstrated potential to improve breast mass diagnosis by distinguishing solid from fluid-filled masses. Harmonic imaging, which is known to reduce acoustic clutter, has the potential to offer additional improvements. However, the lack of a theoretical basis to describe these improvements precludes clinical recommendations based on physics and engineering principles. This work is the first to develop a theoretical model of coherence-based ultrasound imaging to describe both solid vs. fluid mass distinction and the effects of harmonic short-lag spatial coherence (SLSC) imaging. The scattering function and the transmit ultrasound beam of the van Cittert-Zernike theorem applied to ultrasound imaging were redefined to generate the theoretical model for solid vs. fluid mass distinction and for harmonic imaging, respectively. The derived theory was used to compare fundamental and harmonic SLSC images for hypoechoic solid, hypoechoic fluid, hyperechoic, and point targets. Theoretical simulations showed improved resolution, mitigated dark-region artifacts around hyperechoic targets, and increased spatial coherence of fluid masses in harmonic SLSC images when compared to fundamental SLSC images. Experimental data from tissue-mimicking phantoms and in vivo breast ultrasound images agreed with theoretical results. In particular, when compared to fundamental SLSC imaging, harmonic SLSC imaging improved resolution by 0.19 ± 0.25 mm, mitigated dark region artifacts by 0.55 ± 0.54 mm, and increased the spatial coherence of fluid-filled masses, resulting in a 6.50 ± 4.28 dB decrease in contrast. Results will enable future clinical recommendations supporting the use of fundamental or harmonic SLSC imaging for analyses of fluid or solid masses, respectively. These contributions establish a theoretical foundation to combine fundamental and harmonic coherence-based imaging with harmonic B-mode imaging to improve the accuracy of breast mass diagnoses.
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