Despite many uses of ultrasound, some pathologies such as breast cancer still cannot reliably be diagnosed in either conventional B-mode ultrasound imaging nor with more recent ultrasound elastography methods. Speed-of-sound (SoS) is a quantitative imaging biomarker, which is sensitive to structural changes due to pathology, and hence could facilitate diagnosis. Full-angle ultrasound computed tomography (USCT) was proposed to obtain spatially-resolved SoS images, however, its water-bath setup involves practical limitations. To increase clinical utility and for widespread use, recently, a limited-angle Fourier-domain SoS reconstruction was proposed, however, it suffers from significant image reconstruction artifacts. In this work, we present a SoS reconstruction strategy, where the forward problem is formulated using differential time-of-flight measurements based on apparent displacements along different ultrasound wave propagation paths, and the inverse problem is solved in spatial-domain using a proposed total-variation scheme with spatially-varying anisotropic weighting to compensate for geometric bias from limited angle imaging setup. This is shown to be robust to missing displacement data and easily allow for incorporating any prior geometric information. In numerical simulations, SoS values in inclusions are accurately reconstructed with 90% accuracy up to a noise level of 50%. With respect to Fourier-domain reconstruction, our proposed method improved contrast ratio from 0.37 to 0.67 for even high noise levels such as 50%. Numerical full-wave simulation and our preliminary in vivo results illustrate the clinical applicability of our method in a breast cancer imaging setting. Our proposed method requires single-sided access to the tissue and can be implemented as an add-on to conventional ultrasound equipment, applicable to a range of transducers and applications.
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