Methods for aiding in the determination of whether to perform imaging on a human subject who has sustained or may have sustained an injury to the head using early biomarkers
Inventors
McQuiston, Beth • Rogers, Justin • Marino, Jaime • CHANDRAN, RAJ • Zhang, Tianming • Datwyler, Saul
Assignees
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Publication Number
US-12092647-B2
Publication Date
2024-09-17
Expiration Date
Abstract
Disclosed herein are methods that aid in the determination of whether to perform imaging, such as magnetic resonance imaging (MRI) or computerized tomography (CT) scan, on a human subject that has sustained or may have sustained an injury to the head using an early biomarker, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or a combination thereof. These methods involve detecting levels and changes in levels of UCH-L1 in samples taken from a human subject at time points within 24 hours after the subject has sustained or may have sustained an injury to the head.
Core Innovation
The invention provides a method to aid imaging decisions in a subject after an actual or suspected injury to the head by assaying at least one early biomarker selected from ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or both UCH-L1 and GFAP. The method uses a sample that is whole blood, serum, plasma, or cerebrospinal fluid, obtained within about 24 hours after the head injury.
The method performs a magnetic resonance imaging (MRI) procedure on the subject and treats the subject for a moderate, severe, or a moderate to severe TBI when the level of UCH-L1, GFAP, or UCH-L1 and GFAP is higher than a reference level of UCH-L1, GFAP, or UCH-L1 and GFAP. The reference level is between at least about 20 pg/mL to about 200 pg/mL. The method links biomarker level versus the reference level to whether MRI is performed and to treatment selection for TBI severity.
In another implementation, the method performs at least one assay for at least one early biomarker on at least a first sample and a second sample obtained from the subject after the head injury. The first time point is within about 24 hours after the head injury, and the second time point is within about 3 to about 6 hours after the first sample is taken. The method then treats for a moderate, severe, or a moderate to severe TBI when the level of UCH-L1, GFAP, or UCH-L1 and GFAP decreases or increases from the first sample to the second sample by an amount between at least about 10 pg/mL and at least about 150 pg/mL.
Claims Coverage
The document includes two independent claims. Across these claims, the independent methods cover early biomarker level compared to a reference level for deciding treatment alongside MRI, and early biomarker change between first and second time points compared to a change amount for deciding treatment alongside MRI.
Early biomarker assay on a time-limited head injury sample with MRI-linked treatment threshold
Performing at least one assay for at least one early biomarker selected from ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or both on at least one sample that is whole blood, serum, plasma, or cerebrospinal fluid, obtained from a human subject within about 24 hours after an actual or suspected injury to the head; performing a magnetic resonance imaging (MRI) procedure on the subject; and treating the subject for a moderate, severe, or a moderate to severe TBI when the level of UCH-L1, GFAP, or UCH-L1 and GFAP in the sample is higher than a reference level between at least about 20 pg/mL to about 200 pg/mL.
MRI with two-sample early biomarker change threshold for moderate-to-severe TBI treatment
Performing at least one assay for at least one early biomarker selected from ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or both on at least a first sample taken at a first time point and a second sample taken at a second time point obtained from a human subject after an actual or suspected injury to the head; performing a magnetic resonance imaging (MRI) procedure on the subject; and treating the subject for a moderate, severe, or a moderate to severe TBI when the level of UCH-L1, GFAP, or UCH-L1 and GFAP decreases or increases from the first sample to the second sample in an amount between at least about 10 pg/mL and at least about 150 pg/mL.
Overall, the claim coverage focuses on using early biomarkers UCH-L1 and/or GFAP measured from blood, serum, plasma, or CSF soon after head injury, then using either a biomarker reference level or a biomarker change amount between two time points to determine treatment for moderate, severe, or moderate to severe TBI, in conjunction with an MRI procedure.
Stated Advantages
Provides assay performance parameter ranges and quantitative reference/threshold frameworks for early TBI biomarkers linked to imaging-relevant cutoffs.
Supports treatment selection for moderate, severe, or moderate to severe TBI using early biomarker reference levels or biomarker change between time points in conjunction with MRI.
Documented Applications
No documented applications found
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