Indexed distribution analysis for improved significance testing of spatially heterogeneous parameter maps: Application to dynamic contrast‐enhanced MRI biomarkers. Issue 3 (10th May 2013)

• Record Type: Journal Article
• Authors: Rose, Chris J.; O'Connor, James P. B.; Cootes, Tim F.; Taylor, Chris J.; Jayson, Gordon C.; Parker, Geoff J. M.; Waterton, John C.
• Is Part Of: Magnetic resonance in medicine. Volume 71:Issue 3(2014:Mar.)
• Page Start: 1299
• Page End: 1311
• Publication Date: 2013-05-10
• Subjects: Nuclear magnetic resonance -- Periodicals; Electron paramagnetic resonance -- Periodicals; 616.07548
• DOI: 10.1002/mrm.24755
• Languages: English
• ISSNs: 0740-3194

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mrm24755-sec-0001" sec-type="section"> <title>Purpose</title> <p>To develop significance testing methodology applicable to spatially heterogeneous parametric maps of biophysical and physiological measurements arising from imaging studies.</p> </sec> <sec id="mrm24755-sec-0002" sec-type="section"> <title>Theory</title> <p>Heterogeneity can confound statistical analyses. Indexed distribution analysis (IDA) transforms a reference distribution, establishing correspondences across parameter maps to which significance tests are applied.</p> </sec> <sec id="mrm24755-sec-0003" sec-type="section"> <title>Methods</title> <p>Well‐controlled simulated and clinical <italic>K</italic><sup>trans</sup> data from a dynamic contrast‐enhanced magnetic resonance imaging study of bevacizumab were analyzed using conventional significance tests of parameter averages, histogram analysis, and IDA. Repeated pretreatment scans provided negative control; a post treatment scan provided positive control.</p> </sec> <sec id="mrm24755-sec-0004" sec-type="section"> <title>Results</title> <p>Histogram analysis was insensitive to simulated and known effects. Simulation: conventional analysis identified treatment effect (<italic>P</italic> ≈ 5 × 10<sup>−4</sup>) and direction, but underestimated magnitude (relative error 67–81%); IDA identified treatment effect (<italic>P</italic> = 0.001), magnitude, direction, and spatial extent (100% accuracy). Bevacizumab: conventional analysis was sensitive to treatment effect (<italic>P</italic> = 0.01; 95% confidence interval on <italic>K</italic><sup>trans</sup> decrease: 23–37%); IDA was sensitive to treatment effect (<italic>P</italic> < 0.05; <italic>K</italic><sup>trans</sup> decrease approximately 25%), inferred its spatial extent to be 94–96%, and inferred that <italic>K</italic><sup>trans</sup> decrease is independent of baseline value, an inference that conventional and histogram analyses cannot make.</p> </sec> <sec id="mrm24755-sec-0005" sec-type="section"> <title>Conclusions</title> <p>In the presence of heterogeneity, IDA can accurately infer the magnitude, direction, and spatial extent of between samples of parametric maps, which can be visualized spatially with respect to the original parameter maps. <bold>Magn Reson Med 71:1299–1311, 2014. © 2013 Wiley Periodicals, Inc.</bold></p> </sec> </abstract>