Identification of Objective Brain Imaging Biomarkers for Gulf War Illness (GWI): Exposure- and Symptom-Specific Markers, GW Subtypes, and Longitudinal Patterns
Abstract
At least 25%-30% of the nearly 700,000 U.S. Veterans who served in the 1991 Gulf War continue to suffer from a complex, multisystem disorder called Gulf War Illness (GWI). Affected individuals reported a wide variety of health problems, including pain, fatigue, poor sleep quality, and have higher rates of health conditions including hypertension, respiratory and gastrointestinal conditions. The current diagnostic criteria for GWI, the Kansas and Centers for Disease Control and Prevention (CDC) definitions, are primarily based on clusters of self-reported symptoms, such as pain, fatigue, etc. However, 30 years post-war, these definitions are in need of biological markers to assist in understanding why some people develop some symptoms and others do not. These biological markers will also help in developing effective treatments for GWI. For example, although we know that hazardous chemical exposures likely have caused many of the symptoms of GWI, we are not sure which exposures are directly related to which symptoms. With careful examination of brain imaging, we have an increased capability of doing just that. Preliminary work from the Principal Investigator’s group studied magnetic resonance imaging (MRI) pictures of the brain and looked at the structures in the brain and the functional or inner workings of the brain and revealed significant structural and functional alterations in the brain of GWI cases (with GWI) compared to deployed non-ill controls. In addition, subgroup analyses (defining GWI case subgroups based on chemical exposures) showed that distinct patterns were associated with each exposure factor. In fact, we were able to predict who had GWI versus who did not have GWI by looking at these MRI pictures above 90% accuracy level. The next step of this work is to combine datasets for reliability of what was found previously in our computer models. This has much promise for the field of GWI in that we can predict with great certainty who has GWI with a noninvasive (causing least amount of psychological and physical harm/stress towards the participants) technique. Using multimodal MRI scans obtained from a larger GWI database, the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN), necessary data harmonization steps can be first performed on this multisite database to account for technical biases (e.g., MRI scanner, site differences) to produce generalized data elements. In this project, we propose to further validate neuroimaging markers and expand our works based on following steps: (i) harmonization/generalization of multisite BBRAIN imaging data using a cutting-edge computational method, (ii) testing reliability of suggested imaging markers for classifying GWI in the generalized data, (iii) defining subgroups of GWI to test exposure or symptom specificity, (iv) determining the prognostic value of suggested imaging markers using a brain aging prediction model trained using the large Human Connectome Project dataset. Successful outcome of this project will not only help us understand the complex interactions of the brain and immune system underlying GWI pathology, but will also serve as a basis for the development of a personalized medicine approach to treating this debilitating disorder. Moreover, the generalized imaging data, which will be added into BBRAIN from this project, can be used by future investigators to generate more valuable findings from the same database. Therefore, the current project will address the FY21 GWIRP Overarching Challenges including Diagnosis, Subtyping, and Determinants at the Qualification phase. Successful execution of the project in this qualification phase will lead us to clinical translation trials (minimum 3 years of projected time to move onto Confirmation phase of biomarkers).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210488
Entities
People
- Bang-Bon Koo
Organizations
- Boston University Medical Campus
- United States Army