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Time delay estimation (TDE) lies at the heart of signal processing algorithms in a broad range of application areas, including communications, coherent imaging, speech processing, and acoustics. In medical ultrasound for example, TDE is used in blood flow estimation, tissue motion measurement, tissue elasticity estimation, phase aberration correction, and a number of other algorithms. Because of its central significance, TDE accuracy, precision, and computational cost are of critical importance. Furthermore, because TDE is typically performed au sampled signals—and delay estimates are usually desired over a continuous domain—time delay estimator performance should be considered in conjunction with associated interpolation. In this paper we present a new time-delay estimator that directly determines continuous time-delay estimates from sampled data. The technique forms a spline-based, piecewise continuous representation of the reference signal then solves for the minimum of the sum squared error between the reference and the delayed signals to determine their relative time delay. Computer simulation results clearly show that the proposed algorithm significantly outperforms other algorithms in terms of jitter and bias over a broad range of conditions. We also describe a modified version of the algorithm that includes companding with only a minor increase in computational cost. [ABSTRACT FROM AUTHOR]