Contrast-enhanced imaging has grown significantly in the past two decades. Technology has evolved from imaging based on linear principles to elaborate pulsing and microbubble-specific detection strategies. This review provides a broad overview of the research published on these topics, emphasizing the progress made, current challenges, and future research considerations. We cover the physical and conceptual underpinnings of imaging based on ultrasound contrast agents, focused on pulsing and detection strategies. The techniques proposed are categorized according to the underlying fundamental physical and signal processing principles. We revisit methods that were previously only of academic interest and may now be clinically feasible with advances in computation and hardware. We discuss unmet challenges and opportunities originating from developments in other sub-fields of ultrasound imaging to enable wider clinical adoption of contrast-enhanced ultrasound.
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