Biomarker levels and neuroimaging for detecting, monitoring and treating brain injury or trauma

Inventors

VAN METER, Timothy E. • Mirshahi, Nazanin

Abstract

Methods, compositions and kits useful in the detection, assessment, diagnosis, prognosis and/or treatment of brain injuries, especially mild traumatic brain injury (mTBI) or concussion, are based upon detection of changes in levels of certain protein biomarkers in a subject undergoing testing, or upon detection of changes in levels of certain protein biomarkers in conjunction with neuroimaging analyses to detect changes in vascular or blood brain barrier (BBB) permeability in the brain, or to detect damage to fiber tracts in the brain, in which changes in biomarker levels correlate with detection of changes in BBB permeability or in brain fiber tract or white matter damage in a subject with brain injury such as mTBI or concussion.

Core Innovation

The invention provides a method of measuring one or more biomarkers and neuroimaging one or more fiber tracts in the brain of an individual suspected to have brain injury. Biomarker measurement is performed using brain specific protein biomarkers selected from Neurogranin (NRGN) and/or Glial Fibrillary Acidic Protein (GFAP) measured in a biological sample obtained from the individual. The neuroimaging is performed to visualize fiber tracts when the biomarker protein levels in the sample are altered relative to respective control levels, and changes in one or more fiber tracts are detected relative to a control.

The described approach links biomarker alterations to neuroimaging changes in brain fiber tracts. It includes multi-biomarker profiling with additional biomarkers including ALDOC, NRGN, NSE, BDNF, OMG, SNCB, and GFAP, and relates these biomarker associations to BBB permeability metrics on DCE-MRI and to injury-related findings. The framework also ties biomarker changes to CT-defined hemorrhage types and certain non-hemorrhage CT findings described in the partial content.

The neuroimaging component includes specialized neuroimaging techniques to visualize fiber tracts and detect tract changes relative to a control. The partial content specifies correlation of biomarker measures with DCE-MRI BBB permeability metrics and fiber tract lesions identified using DTI-based metrics, including lesions affecting the inferior fronto-occipital fasciculus (IFOF). It further describes that the biomarker response includes robust elevations for ALDOC in mild TBI/concussion and limited or variable GFAP elevation depending on CT status and injury severity.

Claims Coverage

One independent claim is identified. It specifies the core framework of measuring selected brain-specific protein biomarkers in a biological sample, neuroimaging to visualize fiber tracts when biomarker levels are altered versus controls, and detecting fiber-tract changes versus a control.

The inventive concept centers on selecting specific brain-specific protein biomarkers, using biomarker level alterations relative to controls as the trigger for specialized neuroimaging of brain fiber tracts, and then detecting tract changes relative to a control. Dependent refinements expand biomarker selections, define allowable neuroimaging modalities, and identify particular fiber tracts such as IFOF.

Stated Advantages

Documented Applications