CSF biomarker dilution factor corrections by MRI imaging and algorithm

Abstract

A method is disclosed for providing a correcting factor for the dilution of measurements of at least one biomarker in cerebrospinal fluid (CSF). The method comprises providing semi-automated measurements of the ventricular system by MRI scans using quantitative anatomical protocols, determining a measurement of biomarker levels in CSF that has been extracted, correcting the measurement of the level of said at least one biomarker'according to the ventricular size, and providing a corrected result of the measurement determined in step (b), said corrected result accounting for concentration dilution due to the change in ventricular size. The method is particularly suited for the measurement of all biomarkers found in the CSF, such as those associated with mild cognitive impairment (MCI) and Alzheimer's Disease.

1 . A method for providing a correcting factor for at least one biomarker in cerebrospinal fluid (CSF) obtained from a patient suffering from a neurological disease, said method comprising:
 (a) providing measurements of the ventricular system using quantitative anatomical protocols;   (b) determining a measurement of biomarker levels in CSF that has been extracted;   (c) correcting the measurement of the level of said at least one biomarker by an algorithm according to the ventricular size; and   (d) providing a corrected result of the measurement determined in step (b).   
     
     
         2 . The method according to  claim 1 , wherein said at least one biomarker is a Tau protein. 
     
     
         3 . The method according to  claim 2 , wherein the Tau protein is P tau231. 
     
     
         4 . The method according to  claim 1 , wherein said at least one biomarker is an amyloid beta peptide. 
     
     
         5 . The method according to  claim 4 , wherein the amyloid beta peptide is Aβ42. 
     
     
         6 . The method according to  claim 4 , wherein the amyloid beta peptide is Aβ40. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . A method for providing a cerebrospinal fluid (CSF) correction factor for CSF obtained from a patient suffering from a neurological disease for at least one biomarker, comprising the steps of:
 (a) measuring levels of biotmarkers in CSF samples obtained from the patient;   (b) providing measurements of the ventricular system using quantitative anatomical protocols; and   (c) correcting the concentration dilution level in the CSF of said at least one biomarker tested for in step (a) by a using a computer algorithm that analyzes the absolute volume and the longitudinal changes in CSF measurements obtained in step (b); and   (d) providing the CSF correction factor for the level of concentration of said at least one biomarker due to increased ventricular volume of CSF caused by the increase in ventricular size.   
     
     
         10 . The method according to  claim 9 , wherein said at least one biomarker is a Tau protein. 
     
     
         11 . The method according to  claim 10 , wherein the Tau protein is P-tau231. 
     
     
         12 . The method according to  claim 9 , wherein said at least one biomarker is an amyloid beta peptide. 
     
     
         13 . The method according to  claim 12 , wherein the amyloid beta peptide is Aβ42. 
     
     
         14 . The method according to  claim 12 , wherein the amyloid beta peptide is Aβ40. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . A method for providing a cerebrospinal fluid (CSF) correction factor for CSF obtained from a patient suffering from a neurological disease, comprising the steps of:
 (a) scanning a brain for measurements of ventricular size;   (b) testing the CSF for a level of at least one predetermined biomarker that has been extracted within a predetermined amount of time before or after the scanning in step (a);   (c) correcting the concentration dilution level in the CSF of said at least one biomarker tested for in step (b) by using a computer algorithm that compares the measurements from the scans in step (a) with a range of predetermined baseline values for a particular head size to determine ventricular size; and   (d) providing the corrected level of concentration dilution in the CSF of said at least one biomarker due to increased ventricular volume of CSF caused by an increase in ventricular size measured in step (b).   
     
     
         18 . The method according to  claim 17 , wherein said at least one biomarker is a Tau protein. 
     
     
         19 . The method according to  claim 18  wherein the Tau protein is P-tau231. 
     
     
         20 . The method according to  claim 17 , wherein said at least one biomarker is an amyloid beta peptide. 
     
     
         21 . The method according to  claim 20 , wherein the amyloid beta peptide is Aβ42. 
     
     
         22 . The method according to  claim 20 , wherein the amyloid beta peptide is Aβ40. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled)