Biomarker levels and neuroimaging for detecting, monitoring and treating brain injury or trauma
Inventors
VAN METER, Timothy E. • Mirshahi, Nazanin
Assignees
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Publication Number
US-11709168-B2
Publication Date
2023-07-25
Expiration Date
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 relates to methods of neuroimaging an individual suspected of having mild traumatic brain injury (mTBI) or a concussion by measuring levels of one or more biomarkers associated with brain injury in a biological sample obtained from the individual. The biomarkers include Aldolase C (ALDOC) and/or Neurogranin (NRGN), and detecting an altered level relative to respective control levels triggers neuroimaging of the blood brain barrier (BBB) for changes.
The BBB neuroimaging is for changes in vascular permeability and/or damage to the fiber tracts relative to the BBB vascular permeability and/or the fiber tracts, respectively, of a healthy brain. This links biomarker alteration to imaging readouts focused on vascular permeability and fiber tract changes.
The invention also extends to monitoring a patient over time by repeating biomarker measurement at a first time point and a second time point subsequent to the first. Neuroimaging of the BBB is performed at the second time point if the levels of one or more biomarkers at the second time point are altered relative to the levels of the same biomarkers at the first time point.
Claims Coverage
Two independent claims are present. Both claims are centered on using altered biomarker levels (ALDOC and/or NRGN) as a trigger for neuroimaging the blood brain barrier (BBB) for vascular permeability and/or fiber tract damage, with the second independent claim adding a longitudinal monitoring workflow using first and second time points.
Biomarker-triggered BBB neuroimaging for vascular permeability and/or fiber tract damage
A method of neuroimaging the brain of an individual suspected of having mild traumatic brain injury (mTBI) or a concussion comprising measuring levels of one or more biomarkers selected from Aldolase C (ALDOC) and/or Neurogranin (NRGN) in a biological sample; detecting an altered level of the one or more biomarkers relative to respective control levels; and when the levels of one or more of the biomarkers are altered relative to respective control levels, neuroimaging the blood brain barrier (BBB) of the individual for changes in vascular permeability and/or damage to the fiber tracts relative to the BBB vascular permeability and/or the fiber tracts, respectively, of a healthy brain.
Longitudinal monitoring with BBB neuroimaging at a second time point when biomarkers change
A method of monitoring the brain of a patient who has sustained mTBI or a concussion comprising measuring the level of one or more biomarkers selected from Aldolase C (ALDOC) and Neurogranin (NRGN) in a sample obtained from the patient at a first time point; measuring the level of the one or more biomarkers in a sample obtained from the patient at a second time point subsequent to the first time point; and neuroimaging the blood brain barrier (BBB) of the brain of the patient at the second time point if the levels of one or more of the biomarkers at the second timepoint are altered relative to the levels of the same biomarkers at the first timepoint.
Across both independent claims, altered levels of ALDOC and/or NRGN relative to control levels or relative to a first time point trigger BBB neuroimaging focused on vascular permeability and/or fiber tract damage. The second independent claim further requires biomarker measurement at two time points and restricts BBB neuroimaging to the second time point when biomarker levels change.
Stated Advantages
Documented Applications
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