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Quantitative ultrasound (QUS) applies a set of techniques to estimate tissue acoustic parameters independent of the imaging platform. Many useful medical and laboratory applications for QUS have been reported, but challenges remain for deployment in vivo, especially for heterogeneous tissues. Several phenomena introduce variability in attenuation estimates, which may influence the estimation of other QUS parameters. For example, estimating the backscatter coefficient (BSC) requires compensation for the attenuation of overlying tissues between the transducer and the underlying tissue of interest. The purpose of this study is to extend prior studies by investigating the efficacy of several analytical methods of estimating attenuation compensation on QUS outcomes in the human median nerve.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Median nerves were imaged at the volar wrist in vivo and beam\u2010formed radiofrequency (RF) data were acquired. Six analytical approaches for attenuation compensation were compared: 1\u20132) attenuation estimated by applying spectral difference method (SDM) and spectral log difference method (SLDM) independently to regions of interest (ROIs) overlying the nerve and to the nerve ROI itself; 3\u20134) attenuation estimation by applying SDM and SLDM to ROIs overlying the nerve, and transferring these properties to the nerve ROI; and 5\u20136) methods that apply previously published values of tissue attenuation to the measured thickness of each overlying tissue. Mean between\u2010subject estimates of BSC\u2010related outcomes as well as within\u2010subject variability of these outcomes were compared among the 6 methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compensating for attenuation using SLDM and values from the literature reduced variability in BSC\u2010based outcomes, compared to SDM. Variability in attenuation coefficients contributes substantially to variability in backscatter measurements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This work has implications for the application of QUS to in vivo diagnostic assessments in peripheral nerves and possibly other heterogeneous tissues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jum.16585","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T13:40:42Z","timestamp":1728481242000},"page":"97-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influences of Variability in Attenuation Compensation on the Estimation of Backscatter Coefficient of Median Nerves in Vivo"],"prefix":"10.1002","volume":"44","author":[{"given":"Yuanshan","family":"Wu","sequence":"first","affiliation":[{"name":"Research Service VA San Diego Healthcare System  San Diego California USA"},{"name":"Department of 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