Clinical acceptance testing and scanner comparison of ultrasound shear wave elastography.

Because of the rapidly growing use of ultrasound shear wave elastography (SWE) in clinical practices, there is a significant need for development of clinical physics performance assessment methods for this technology. This study aims to report two clinical medical physicists' tasks: (a) acceptance testing (AT) of SWE function on ten commercial ultrasound systems for clinical liver application and (b) comparison of SWE measurements of targets across vendors for clinical musculoskeletal application. For AT, ten GE LOGIQ E9 XDclear 2.0 scanners with ten C1-6-D and ten 9L-D transducers were studied using two commercial homogenous phantoms. Five measurements were acquired at two depths for each scanner/transducer pair by two operators. Additional tests were performed to access effects of different coupling media, phantom locations and operators. System deviations were less than 5% of group mean or three times standard deviation; therefore, all systems passed AT. A test protocol was provided based on results that no statistically significant difference was observed between using ultrasound gel and salt water for coupling, among different phantom locations, and that interoperator and intraoperator coefficient of variation was less than 3%. For SWE target measurements, two systems were compared - a Supersonic Aixplorer scanner with a SL10-2 and a SL15-4 transducer, and an abovementioned GE scanner with 9L-D transducer. Two stepped cylinders with diameters of 4.05-10.40 mm were measured both longitudinally and transaxially. Target shear wave speed quantification was performed using an in-house MATLAB program. Using the target shear wave speed deduced from phantom specs as a reference, SL15-4 performed the best at the measured depth. However, it was challenging to reliably measure a 4.05 mm target for either system. The reported test methods and results could provide important information when dealing with SWE-related tasks in the clinical environment.

Utility of free and total target measurements as target engagement and efficacy biomarkers in biotherapeutic development--opportunities and challenges.

For biotherapeutics directed against soluble targets, most often monoclonal antibodies (mAbs), their therapeutic efficacy theoretically is driven by the magnitude and duration of free target suppression. However, for soluble targets of rapid turnover and low abundance, it can be technically challenging to directly measure the lowering of free target following treatment with biologics. The opportunities, challenges, and practical approaches to assess free and bound soluble targets and the utility of free and bound target measurements as biomarkers for target engagement and efficacy are covered in this review. In particular, case examples are presented to illustrate the interplay between drug and free/bound target, and how an integrated bioanalytical and pharmacokinetic/target engagement/pharmacodynamic (PK/TE/PD) modeling approach can be used to assess the target engagement for biologics directed against soluble targets with rapid turnover. Important caveats of the modeling approach in the absence of free target measurements are also discussed.