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A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases.

ABSTRACT: Apparent Diffusion Coefficient (ADC) is a potential quantitative imaging biomarker for tumour cell density and is widely used to detect early treatment changes in cancer therapy. We propose a strategy to improve confidence in the interpretation of measured changes in ADC using a data-driven model that describes sources of measurement error. Observed ADC is then standardised against this estimation of uncertainty for any given measurement. 20 patients were recruited prospectively and equitably across 4 sites, and scanned twice (test-retest) within 7 days. Repeatability measurements of defined regions (ROIs) of tumour and normal tissue were quantified as percentage change in mean ADC (test vs. re-test) and then standardised against an estimation of uncertainty. Multi-site reproducibility, (quantified as width of the 95% confidence bound between the lower confidence interval and higher confidence interval for all repeatability measurements), was compared before and after standardisation to the model. The 95% confidence interval width used to determine a statistically significant change reduced from 21.1 to 2.7% after standardisation. Small tumour volumes and respiratory motion were found to be important contributors to poor reproducibility. A look up chart has been provided for investigators who would like to estimate uncertainty from statistical error on individual ADC measurements.

SUBMITTER: Pathak R

PROVIDER: S-EPMC5658431 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases.

Pathak Ryan R Ragheb Hossein H Thacker Neil A NA Morris David M DM Amiri Houshang H Kuijer Joost J deSouza Nandita M NM Heerschap Arend A Jackson Alan A

Scientific reports 20171026 1

Apparent Diffusion Coefficient (ADC) is a potential quantitative imaging biomarker for tumour cell density and is widely used to detect early treatment changes in cancer therapy. We propose a strategy to improve confidence in the interpretation of measured changes in ADC using a data-driven model that describes sources of measurement error. Observed ADC is then standardised against this estimation of uncertainty for any given measurement. 20 patients were recruited prospectively and equitably ac ...[more]

PMID: 29075009

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Project description:UnlabelledBackgroundCost-effective production of lignocellulosic biofuels remains a major financial and technical challenge at the industrial scale. A critical tool in biofuels process development is the techno-economic (TE) model, which calculates biofuel production costs using a process model and an economic model. The process model solves mass and energy balances for each unit, and the economic model estimates capital and operating costs from the process model based on economic assumptions. The process model inputs include experimental data on the feedstock composition and intermediate product yields for each unit. These experimental yield data are calculated from primary measurements. Uncertainty in these primary measurements is propagated to the calculated yields, to the process model, and ultimately to the economic model. Thus, outputs of the TE model have a minimum uncertainty associated with the uncertainty in the primary measurements.ResultsWe calculate the uncertainty in the Minimum Ethanol Selling Price (MESP) estimate for lignocellulosic ethanol production via a biochemical conversion process: dilute sulfuric acid pretreatment of corn stover followed by enzymatic hydrolysis and co-fermentation of the resulting sugars to ethanol. We perform a sensitivity analysis on the TE model and identify the feedstock composition and conversion yields from three unit operations (xylose from pretreatment, glucose from enzymatic hydrolysis, and ethanol from fermentation) as the most important variables. The uncertainty in the pretreatment xylose yield arises from multiple measurements, whereas the glucose and ethanol yields from enzymatic hydrolysis and fermentation, respectively, are dominated by a single measurement: the fraction of insoluble solids (fIS) in the biomass slurries.ConclusionsWe calculate a $0.15/gal uncertainty in MESP from the TE model due to uncertainties in primary measurements. This result sets a lower bound on the error bars of the TE model predictions. This analysis highlights the primary measurements that merit further development to reduce the uncertainty associated with their use in TE models. While we develop and apply this mathematical framework to a specific biorefinery scenario here, this analysis can be readily adapted to other types of biorefining processes and provides a general framework for propagating uncertainty due to analytical measurements through a TE model.

Project description:Purpose To assess the reproducibility of ADC, T1, T2, and proton density (PD) measurements on the cortex across the entire brain using high-resolution pseudo-3D diffusion-weighted imaging using echo-planar imaging with compressed SENSE (EPICS-DWI) and 3D quantification with an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) in normal healthy adults. Methods Twelve healthy participants (median age, 33 years; range, 28–51 years) were recruited to evaluate the reproducibility of whole-brain EPICS-DWI and synthetic MRI. EPICS-DWI utilizes a compressed SENSE reconstruction framework while maintaining the EPI sampling pattern. The 3D-QALAS sequence is based on multi-acquisition 3D gradient echo, with five acquisitions equally spaced in time, interleaved with a T2 preparation pulse and an inversion pulse. EPICS-DWI (b values, 0 and 1000 s/mm2) and 3D-QALAS sequence with identical voxel size on a 3.0-T MR system were performed twice (for test-retest scan). Intraclass correlation coefficients (ICCs) for ADC, T1, T2, and PD for all parcellated volume of interest (VOI) per subject on scan-rescan tests were calculated to assess reproducibility. Bland-Altman plots were used to investigate discrepancies in ADCs, T1s, T2s, and PDs obtained from the two MR scans. Results The ICC of ADCs was 0.785, indicating “good” reproducibility. The ICCs of T1s, T2s, and PDs were 0.986, 0.978, and 0.968, indicating “excellent” reproducibility. Conclusion The combination of EPICS-DWI and 3D-QALAS sequences with identical voxel size could reproducible ADC, T1, T2, and PD measurements for the cortex across the entire brain in healthy adults. Highlights • In this pilot study, the ICCs for ADC, T1, T2, and PD were 0.785, 0.986, 0.978, and 0.968, indicating high reproducibility.• Cerebral cortices showed relatively high ADC, T1, T2, and PD in the mean than white matter regions and subcortical nuclei.• Combination of EPICS-DWI and 3D-QALAS displayed the high reproducibility of ADC, T1, T2, and PD for cerebral cortices.

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A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases.

Publications

A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases.

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