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      DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans

      research-article
      a , b , c , * , a , d , e , f , a , d , g , d , d , a , a , d , d , a , d , a , d , d , d , h , i
      NeuroImage : Clinical
      Elsevier
      TBI, traumatic brain injury, DTI, diffusion tensor imaging, ROC, receiver operating characteristic, DAI, diffuse axonal injury, PTSD, post-traumatic stress disorder, FA, fractional anisotropy, MD, mean diffusivity, RD, radial diffusivity, AD, axial diffusivity, LAT, left anterior thalamic tract, RAT, right anterior thalamic tract, LCG, left cingulum, RCG, right cingulum, LCH, left cingulum – hippocampus, RCH, right cingulum – Hippocampus, LCS, left cortico-spinal tract, RCS, right cortico-spinal tract, LIF, left inferior fronto-occipital fasciculus, RIF, right inferior fronto-occipital fasciculus, LIL, left inferior longitudinal fasciculus, RIL, right inferior longitudinal fasciculus, LSL, left superior longitudinal fasciculus, RSL, right superior longitudinal fasciculus, LST, left superior longitudinal fasciculus – temporal, RST, right superior longitudinal fasciculus – temporal, LUN, left uncinate, RUN, right uncinate, GN, genu, SP, splenium, CC, corpus callosum, Traumatic brain injury, Concussion, Imaging, Axon degeneration, Neurodegeneration

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          Abstract

          Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.

          Highlights

          • We conducted ROC analyses using DTI data from veterans with and without traumatic brain injury.

          • For each participant, DTI analysis identified measures (FA, MD, RD, AD) from twenty fiber tracts.

          • ROC analyses determined which fiber tracts best predict TBI status for each measure.

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          Most cited references171

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          Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

          The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
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            Measuring the accuracy of diagnostic systems.

            J Swets (1988)
            Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.
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              Hemispheric asymmetry reduction in older adults: the HAROLD model.

              A model of the effects of aging on brain activity during cognitive performance is introduced. The model is called HAROLD (hemispheric asymmetry reduction in older adults), and it states that, under similar circumstances, prefrontal activity during cognitive performances tends to be less lateralized in older adults than in younger adults. The model is supported by functional neuroimaging and other evidence in the domains of episodic memory, semantic memory, working memory, perception, and inhibitory control. Age-related hemispheric asymmetry reductions may have a compensatory function or they may reflect a dedifferentiation process. They may have a cognitive or neural origin, and they may reflect regional or network mechanisms. The HAROLD model is a cognitive neuroscience model that integrates ideas and findings from psychology and neuroscience of aging.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                24 June 2017
                2017
                24 June 2017
                : 16
                : 1-16
                Affiliations
                [a ]War Related Illness and Injury Study Center, Veterans Affairs, Palo Alto Health Care System (VAPAHCS), Palo Alto, CA, United States
                [b ]Defense and Veterans Brain Injury Center (DVBIC), Silver Spring, MD, United States
                [c ]General Dynamics Health Solutions (GDHS), Fairfax, VA, United States
                [d ]Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
                [e ]Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
                [f ]Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States
                [g ]Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
                [h ]Department of Neurosurgery, Stanford School of Medicine, Stanford, CA, United States
                [i ]Defense and Veterans Brain Injury Center (DVBIC), Veterans Affairs, Palo Alto Health Care System (VAPAHCS), Palo Alto, CA, United States
                Author notes
                [* ]Corresponding author at: Defense and Veterans Brain Injury Center, 1335 East-West Highway, Suite 4-100, Silver Spring, MD 20910, United States.Defense and Veterans Brain Injury Center1335 East-West Highway, Suite 4-100Silver SpringMD20910United States keith.l.main3.ctr@ 123456mail.mil
                Article
                S2213-1582(17)30162-6
                10.1016/j.nicl.2017.06.031
                5503837
                f750c558-d175-4ade-bd42-2889a950fae0
                © 2017 Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 August 2016
                : 10 June 2017
                : 23 June 2017
                Categories
                Regular Article

                tbi, traumatic brain injury,dti, diffusion tensor imaging,roc, receiver operating characteristic,dai, diffuse axonal injury,ptsd, post-traumatic stress disorder,fa, fractional anisotropy,md, mean diffusivity,rd, radial diffusivity,ad, axial diffusivity,lat, left anterior thalamic tract,rat, right anterior thalamic tract,lcg, left cingulum,rcg, right cingulum,lch, left cingulum – hippocampus,rch, right cingulum – hippocampus,lcs, left cortico-spinal tract,rcs, right cortico-spinal tract,lif, left inferior fronto-occipital fasciculus,rif, right inferior fronto-occipital fasciculus,lil, left inferior longitudinal fasciculus,ril, right inferior longitudinal fasciculus,lsl, left superior longitudinal fasciculus,rsl, right superior longitudinal fasciculus,lst, left superior longitudinal fasciculus – temporal,rst, right superior longitudinal fasciculus – temporal,lun, left uncinate,run, right uncinate,gn, genu,sp, splenium,cc, corpus callosum,traumatic brain injury,concussion,imaging,axon degeneration,neurodegeneration

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