Dataset Information

Replication and generalization in applied neuroimaging.

ABSTRACT: There is much interest in translating neuroimaging findings into meaningful clinical diagnostics. The goal of scientific discoveries differs from clinical diagnostics. Scientific discoveries must replicate under a specific set of conditions; to translate to the clinic we must show that findings using purpose-built scientific instruments will be observable in clinical populations and instruments. Here we describe and evaluate data and computational methods designed to translate a scientific observation to a clinical setting. Using diffusion weighted imaging (DWI), Wahl et al. (2010) observed that across subjects the mean fractional anisotropy (FA) of homologous pairs of tracts is highly correlated. We hypothesize that this is a fundamental biological trait that should be present in most healthy participants, and deviations from this assessment may be a useful diagnostic metric. Using this metric as an illustration of our methods, we analyzed six pairs of homologous white matter tracts in nine different DWI datasets with 44 subjects each. Considering the original FA measurement as a baseline, we show that the new metric is between 2 and 4 times more precise when used in a clinical context. Our framework to translate research findings into clinical practice can be applied, in principle, to other neuroimaging results.

SUBMITTER: Lerma-Usabiaga G

PROVIDER: S-EPMC6819246 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Replication and generalization in applied neuroimaging.

Lerma-Usabiaga Garikoitz G Mukherjee Pratik P Ren Zhimei Z Perry Michael L ML Wandell Brian A BA

NeuroImage 20190726

There is much interest in translating neuroimaging findings into meaningful clinical diagnostics. The goal of scientific discoveries differs from clinical diagnostics. Scientific discoveries must replicate under a specific set of conditions; to translate to the clinic we must show that findings using purpose-built scientific instruments will be observable in clinical populations and instruments. Here we describe and evaluate data and computational methods designed to translate a scientific obser ...[more]

PMID: 31356879

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Project description:To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n=101) from healthy controls (n=51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n=97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC=75.4%, 95%CI=67.0%-83.3%; in non-affective psychosis AUC=80.5%, 95%CI=72.1-88.0%, and in affective psychosis AUC=58.7%, 95%CI=44.2-72.0%). Test-retest reliability ranged between ICC=0.48 (95%CI=0.35-0.59) and ICC=0.22 (95%CI=0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC=0.51 (95%CI=0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 minutes, diagnostic classification of the FSA increased from AUC=71.7% (95%CI=63.1%-80.3%) to 75.4% (95%CI=67.0%-83.3%) and phase encoding direction reliability from ICC=0.29 (95%CI=0.14-0.43) to ICC=0.51 (95%CI=0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data.

Dataset Information

Replication and generalization in applied neuroimaging.

Publications

Replication and generalization in applied neuroimaging.

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