title: Reliability of infarct volumetry: Its relevance and the improvement by a software-assisted approach.
abstract: Despite the efficacy of neuroprotective approaches in animal models of stroke, their translation has so far failed from bench to bedside. One reason is presumed to be a low quality of preclinical study design, leading to bias and a low a priori power. In this study, we propose that the key read-out of experimental stroke studies, the volume of the ischemic damage as commonly measured by free-handed planimetry of TTC-stained brain sections, is subject to an unrecognized low inter-rater and test-retest reliability with strong implications for statistical power and bias. As an alternative approach, we suggest a simple, open-source, software-assisted method, taking advantage of automatic-thresholding techniques. The validity and the improvement of reliability by an automated method to tMCAO infarct volumetry are demonstrated. In addition, we show the probable consequences of increased reliability for precision, p-values, effect inflation, and power calculation, exemplified by a systematic analysis of experimental stroke studies published in the year 2015. Our study reveals an underappreciated quality problem in translational stroke research and suggests that software-assisted infarct volumetry might help to improve reproducibility and therefore the robustness of bench to bedside translation.
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Friedländer
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Bohmann
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Brunkhorst
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Chae
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Kavi
authors.initials: K
authors.lastname: Devraj
authors.affiliation: 2 Department of General Pharmacology and Toxicology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Köhler
authors.affiliation: 3 Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kuhn
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lucaciu
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Luger
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Waltraud
authors.initials: W
authors.lastname: Pfeilschifter
authors.affiliation: 4 Institute for Stroke and Dementia Research, Hospital of the Ludwig-Maximilians-University, München, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sadler
authors.affiliation: 4 Institute for Stroke and Dementia Research, Hospital of the Ludwig-Maximilians-University, München, Germany.|5 Munich Cluster for Systems Neurology (SyNergy), München, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Liesz
authors.affiliation: 3 Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Scholtyschik
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Stolz
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.|2 Department of General Pharmacology and Toxicology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Vutukuri
authors.affiliation: 1 Department of Neurology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.|2 Department of General Pharmacology and Toxicology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Brunkhorst
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D020520:Brain Infarction / Q000000981:diagnostic imaging* / Q000209:etiology; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000000981:diagnostic imaging*; D008297:Male; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software; D057170:Translational Research, Biomedical
keywords: Neuroprotection; experimental stroke; image analysis; middle cerebral artery occlusion; power