Attenuation Measuring Ultrasound Shearwave Elastography (AMUSE) as Noninvasive Imaging Biomarker for Liver Acute Cellular Rejection

Objective: There are over 9000 liver transplants in the United States per year, with acute cellular rejection (ACR) being a prevalent early post-transplant complication (20%–40%) treated using corticosteroids. Ischemia-reperfusion injury (IRI), another early post-transplant pathology, has similar laboratory results but typically resolves without therapy. ACR confirmation requires invasive liver biopsy, bearing risks like hemorrhage and pneumothorax. Attenuation Measuring Ultrasound Shearwave Elastography (AMUSE) assesses shear wave velocity (c) and attenuation (α) without rheological models and have shown potential for noninvasive tissue characterization. Methods: We analyzed 58 transplanted livers suspected for ACR by comparing AMUSE measurements to biopsy findings. Thirteen patients underwent longitudinal tracking from ACR diagnosis on day 7 to therapy initiation and repeat biopsy on day 14. Statistical methods and support vector machine (SVM) were used for performance analysis. Results: AMUSE measurements at 100, 200, and 300 Hz showed statistical significance (p < 0.001) for ACR presence, with 200 Hz exhibiting the highest Spearman correlation coefficients for c and α (0.68 and -0.83). High c (> 2.2 m/s) and low α (< 130 Np/m) at 200 Hz correlated with ACR diagnostic, while low c and high α indicated no ACR. Combining c and α into a single biomarker α/c improved patient differentiation, yielding an F1-score of 0.97. SVM was used to evaluate AMUSE ACR staging capabilities using all available frequencies, reaching 0.95 F1-score for categorical classification, with an AUROC of 0.99. When evaluating the presence of ACR the SVM reached 0.99 F1-score, with 1.00 sensitivity/recall. Conclusion: These findings support the use of AMUSE potential for detection and staging of liver ACR.