A Systematized Review of Quantitative Ultrasound Techniques for Brain Tissue Characterization

Since 1968, acoustic characterization has been used to assess brain tissue properties. This modality has provided critical insights into microstructural characteristics that have not yet been widely translated into clinical practice. This systematized literature review synthesizes advancements in quantitative ultrasound (QUS) techniques for brain tissue characterization, focusing on their potential and current limitations as neuroimaging tools. A comprehensive search of PubMed, Scopus and digital libraries identified 115 publications; after applying the inclusion criteria, 35 were analyzed. The studies were categorized by QUS feature: speed of sound, attenuation, backscatter and speckle statistics, and by experimental model (phantoms, preclinical, human ex vivo and in vivo). Attenuation was the most frequently investigated feature (40% of the total dataset), followed by speed of sound, backscatter and speckle statistics. For the 4 QUS features, most studies were conducted in preclinical settings, highlighting the limited clinical translation of QUS for the brain. Beyond summarizing current evidence, this review examines the methodological and practical barriers to reproducibility, including variability in acquisition protocols, system-dependent signal processing and beamformer assumptions, the lack of reference standards and the absence of calibration frameworks. It also identifies future research opportunities, such as developing traceable phantoms, establishing open repositories of reference phantoms and clinical data and coordinating efforts among research, clinicians, industry and regulatory agencies. This review contextualizes the potential and significance of QUS in brain characterization and outlines the steps needed to establish it as a reliable, quantitative and clinically meaningful neuroimaging modality.