Abstract
Gulf War illness (GWI) refers to the multitude of chronic health symptoms, spanning from fatigue, musculoskeletal pain, and neurological complaints to respiratory, gastrointestinal, and dermatologic symptoms experienced by about 250,000 GW veterans who served in the 1991 Gulf War (GW). Longitudinal studies showed that the severity of these symptoms often remain unchanged even years after the GW, and these veterans with GWI continue to have poorer general health and increased chronic medical conditions than their non-deployed counterparts. For better management and treatment of this condition, there is an urgent need for developing objective biomarkers that can help with simple and accurate diagnosis of GWI. In this study, we applied multiple neuroimaging techniques, including T1-weighted magnetic resonance imaging (T1W-MRI), diffusion tensor imaging (DTI), and novel neurite density imaging (NDI) to perform both a group-level statistical comparison and a single-subject level machine learning (ML) analysis to identify diagnostic imaging features of GWI. Our results supported NDI as the most sensitive in defining GWI characteristics. In particular, our classifier trained with white matter NDI features achieved an accuracy of 90% and F-score of 0.941 for classifying GWI cases from controls after the cross-validation. These results are consistent with our previous study which suggests that NDI measures are sensitive to the microstructural and macrostructural changes in the brain of veterans with GWI, which can be valuable for designing better diagnosis method and treatment efficacy studies.
Highlights
Gulf War illness (GWI) refers to the variety of chronic symptoms experienced by about250,000 United States veterans who served in the 1991 Gulf War (GW) [1]
The greatest significant group differences between GWI cases and controls were seen in the bilateral corticospinal tract (CST, t = −3.119 false discovery rate (FDR)-p = 0.017, t = −3.129, FDR-corrected p-values (FDR-p) = 0.017) and the bilateral anterior thalamic radiations (ATR, t = −2.891, FDR-p = 0.017, t = −2.808, FDR-p = 0.017) for white matter (WM) neurite density (ND), and in the bilateral cingulum cingulate gyrus bundle (CCG, t = −4.041 FDR-p = 0.002, t = −3.384, FDR-p = 0.007) for WM orientation dispersion (OD)
We used various neuroimaging techniques (NDI, diffusion tensor imaging (DTI), structural T1-weighted magnetic resonance imaging (T1W-MRI)) to identify important features that may help to differentiate between veterans with GWI and control veterans
Summary
Gulf War illness (GWI) refers to the variety of chronic symptoms experienced by about250,000 United States veterans who served in the 1991 Gulf War (GW) [1]. Gulf War illness (GWI) refers to the variety of chronic symptoms experienced by about. Brain Sci. 2020, 10, 884 case criteria, symptoms of GWI fall into six categories: fatigue (fatigue and sleep problems), pain (joint and muscle), neurological (cognitive, mood, headache, and dizziness), respiratory (persistent cough and wheezing), gastrointestinal (diarrhea and nausea), and skin (rashes and other) problems. Exposure to neurotoxicant chemicals (organophosphate pesticides and sarin) during the war and other central nervous system (CNS) damage, such as mild traumatic brain injury (mTBI), are thought to have caused an innate immune over-response in the CNS, resulting in the development of these chronic. In order to meet the Kansas criteria for GWI, veterans must display chronic symptoms in at least three of the six categories, without presenting concurrent psychiatric and medical disorders [8]. To improve management and treatment of GWI, there is an urgent need for defining sensitive and objective biomarkers of the disorder
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