Liver iron quantification in children and young adults: comparison of a volumetric multi-echo 3-D Dixon sequence with conventional 2-D T2* relaxometry.

BACKGROUND: Magnetic resonance imaging (MRI)-based liver iron quantification is the standard of care to guide chelation therapy in children at risk of hemochromatosis. T2* relaxometry is the most widely used technique but requires third-party software for post-processing. Vendor-provided three-dimensional (3-D) multi-echo Dixon techniques are now available that allow inline/automated post-processing. OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of a volumetric multi-echo Dixon technique using conventional T2* relaxometry as the reference standard in a pediatric and young adult population. MATERIALS AND METHODS: In this retrospective study, we queried the radiology information system to identify all MRIs performed for liver iron quantification from July 2015 to January 2020. All patients had undergone T2* relaxometry on a 1.5-tesla (T) scanner for liver iron concentration (LIC) estimation. In addition, a 3-D multi-echo Dixon was performed using Siemens Healthineers LiverLab (Erlangen, Germany). Two readers independently estimated liver R2* and T2* on the multi-echo Dixon by drawing free-hand regions of interest on the scanner-generated R2* and T2* maps. Conventional T2*-relaxometry-based LIC was the reference standard. We estimated interobserver agreement by concordance correlation coefficient (CCC). We used Bland-Altman analysis and Pearson correlation coefficient (r) to compare LIC by the two methods. RESULTS: Fifty-four MRIs on 38 patients (22 females) were available for analysis. Mean patient age was 11.8 years (standard deviation [SD] 5.3 years). Reference standard LIC ranged 1.1-21.1 (median 6.8) mg/g dry weight of liver. The concordance between readers for T2* estimation using 3-D multi-echo Dixon was substantial (CCC 0.99, confidence interval 0.99-1.00). Bland-Altman plot showed that all observations were clustered around the zero bias line if the LIC average was ≤8 mg/g, and r was very strong (reader 1 r=0.93, reader 2 r=0.92, both P-values <0.001). With increasing LIC, there was a pattern of poor agreement on the Bland-Altman plot, with observations crossing the lower limits of agreement, and r was very weak (reader 1 r=0.05, P-value 0.84; reader 2 r=0.17, P-value 0.44). CONCLUSION: Vendor-based 3-D multi-echo Dixon allows for excellent interobserver correlation in liver T2* estimation. LIC estimated by this method has a very strong correlation with conventional T2* relaxometry if liver iron overload is mild-moderate (LIC ≤8 mg/g).

A scalable approach to combinatorial library design for drug discovery.

In this paper, we propose an algorithm for the design of lead generation libraries required in combinatorial drug discovery. This algorithm addresses simultaneously the two key criteria of diversity and representativeness of compounds in the resulting library and is computationally efficient when applied to a large class of lead generation design problems. At the same time, additional constraints on experimental resources are also incorporated in the framework presented in this paper. A computationally efficient scalable algorithm is developed, where the ability of the deterministic annealing algorithm to identify clusters is exploited to truncate computations over the entire data set to computations over individual clusters. An analysis of this algorithm quantifies the tradeoff between the error due to truncation and computational effort. Results applied on test data sets corroborate the analysis and show improvement by factors as large as 10 or more, depending on the data sets.