Brain imaging

Abstract

The present disclosure relates generally to medical imaging and, more particularly, it relates to methods and systems for performing processing of magnetic resonance (MR) imaging of the brain which may be useful in the diagnosis of cognitive disorders. More specifically, the invention includes methods for processing cortical diffusion data from a region of a subject's brain, comprising determining values for the Axial Columnar Refraction (ACR) using values for AngleR and Axial Diffusivity.

1 . A method for processing cortical diffusion data from a region of a subject's brain, the method comprising:
 (a) obtaining a value for the angle of deviation (AngleR) between the principal diffusion direction and the columnar direction (ColD) of the minicolumns in a first voxel in a region of grey matter in a subject's brain;   (b) obtaining a value for the Axial Diffusivity in a second voxel which is present in the white matter underlying the region of grey matter; and   (c) determining a value for the Axial Columnar Refraction (ACR) for the voxels using values for AngleR and Axial Diffusivity.   
     
     
         2 . A method as claimed in  claim 1 , wherein Step (a) comprises:
 (a1) determining the principal diffusion direction in a voxel in the region of grey matter in a subject's brain;   (a2) determining the columnar direction (ColD) of the minicolumns in the voxel; and   (a3) obtaining a value for the angle of deviation (AngleR) between the principal diffusion direction and ColD.   
     
     
         3 . A method of obtaining an indication of the level of a cognitive disorder in a subject, the method comprising the steps:
 (a) obtaining values of ACR by a method as claimed in  claim 1  or  claim 2  for a plurality of voxels in a region of the subject's brain,   
       wherein the magnitude of the values of ACR for those voxels provides an indication of the level of a cognitive disorder in that subject. 
     
     
         4 . A method of obtaining an indication of the number of microsegment breaks in a region of a subject's brain, the method comprising the steps:
 (a) obtaining values of ACR by a method as claimed in  claim 1  or  claim 2  for a plurality of voxels in a region of the subject's brain,   
       wherein the magnitude of the values of ACR for those voxels provides an indication of the number of microsegment breaks in that region. 
     
     
         5 . A method for processing cortical diffusion data from a region of a subject's brain, the method comprising:
 (a) obtaining a value for the perpendicular diffusivity (Perp) in a first voxel in a region of grey matter in a subject's brain;   (b) obtaining a value for the Axial Diffusivity in a second voxel which is present in the white matter underlying the region of grey matter; and   (c) determining a value for the Perpendicular Columnar Refraction (PerpCR) for the voxels using values for Perp and Axial Diffusivity.   
     
     
         6 . A method as claimed in  claim 5 , wherein Step (a) comprises the steps:
 (a1) obtaining a measurement for cortical diffusion in the first voxel;   (a2) determining, from the measurement for cortical diffusion obtained in Step (a1), the principal diffusion vector (D PDD ) in the voxel;   (a3) determining the columnar direction (ColD) of the minicolumns in the voxel; and   (a4) determining a value for the perpendicular diffusivity (Perp) for the voxel by projecting D PDD  onto the plane which is orthogonal to ColD in that voxel and determining the magnitude of the projection.   
     
     
         7 . A method of obtaining an indication of the level of a cognitive disorder in a subject, the method comprising the steps:
 (a) obtaining values of Perpendicular Columnar Refraction (PerpCR) by a method as claimed in  claim 5  or  claim 6  for a plurality of voxels in a region of a subject's brain,   
       wherein the magnitude of the values of Perpendicular Columnar Refraction (PerpCR) for those voxels provides an indication of the level of a cognitive disorder in that subject. 
     
     
         8 . A method of obtaining an indication of the number of microsegment breaks in a region of a subject's brain, the method comprising the steps:
 (a) obtaining values of Perpendicular Columnar Refraction (PerpCR) by a method as claimed in  claim 5  or  claim 6  for a plurality of voxels in a region of a subject's brain,   
       wherein the magnitude of the values of Perpendicular Columnar Refraction (PerpCR) for those voxels provides an indication of the number of microsegment breaks in that region. 
     
     
         9 . A method of obtaining an indication of the level of a cognitive disorder in a subject, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, values for the angle of deviation (AngleR) between the principal diffusion direction and the average columnar direction (ColD) of the minicolumns,   wherein the brain region is cortical area 9, the PHG or the entorhinal cortex,   
       wherein the magnitude of the values of AngleR from the plurality of voxels provides an indication of the level of a cognitive disorder in that subject. 
     
     
         10 . A method of obtaining an indication of the level of MS in a subject, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, values for the angle of deviation (AngleR) between the principal diffusion direction and the average columnar direction (ColD) of the minicolumns,   preferably wherein the brain region is cortical area 9, area 41, or V1 (primary visual cortex)   
       wherein the magnitude of the values of AngleR from the plurality of voxels provides an indication of the level of MS in that subject. 
     
     
         11 . A method of obtaining an indication of the number of microsegment breaks in a region of a subject's brain, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, values for the angle of deviation (AngleR) between the principal diffusion direction and the average columnar direction (ColD) of the minicolumns, wherein the brain region is preferably cortical area 9, the PHG or the entorhinal cortex,   
       wherein the magnitude of the values of AngleR from the plurality of voxels provides an indication of the number of microsegment breaks in that region. 
     
     
         12 . A method of obtaining an indication of the level of a cognitive disorder in a subject, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, values for the axial diffusivity,   wherein the brain region is cortical area 9, the PHG or the entorhinal cortex,   
       wherein the magnitude of the values of axial diffusivity from the plurality of voxels provides an indication of the level of a cognitive disorder in that subject. 
     
     
         13 . A method of obtaining an indication of the number of microsegment breaks in a region of a subject's brain, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, values for the axial diffusivity, wherein the brain region is preferably cortical area 9, the PHG or the entorhinal cortex,   
       wherein the magnitude of the values of axial diffusivity from the plurality of voxels provides an indication of the number of microsegment breaks in that region. 
     
     
         14 . A method of obtaining an indication of the level of a cognitive disorder in a subject, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, a value for the perpendicular diffusivity (Perp), wherein the brain region is cortical area 9, the PHG or the entorhinal cortex,   
       wherein the magnitude of the values of Perp from the plurality of voxels provides an indication of the level of a cognitive disorder in that subject. 
     
     
         15 . A method of obtaining an indication of the number of microsegment breaks in a region of a subject's brain, the method comprising the steps:
 (a) obtaining, in a plurality of voxels in a region of a subject's brain, a value for the perpendicular diffusivity (Perp), wherein the brain region is preferably cortical area 9, the PHG or the entorhinal cortex,   
       wherein the magnitude of the values of Perp from the plurality of voxels provides an indication of the number of microsegment breaks in that region. 
     
     
         16 . A method as claimed in any one of the preceeding claims, wherein the value for AngleR, Axial Diffusivity and/or Perp is obtained by a neuro-imaging method, preferably by magnetic resonance imaging (MRI), most preferably by diffusion MRI. 
     
     
         17 . A method as claimed in any one of the preceeding claims, wherein the value for AngleR, Axial Diffusivity and/or Perp is obtained from or derived from one or more regions of the cortex of the brain, preferably a region of the cortex comprising grey matter with underlying (subcortical) white matter. 
     
     
         18 . A method as claimed in  claim 17 , wherein the region of the brain is selected from the group consisting of parahippocampal gyrus (PHG), fusiform gyrus (Fusi), dorsolateral prefrontal cortex area 9 (dIPFC), area 41, Heschl's gyrus (HG), planum temporale (PT), inferior parietal lobule (IPL), middle temporal gyrus (MTG), primary visual cortex (V1; area 17) and entorhinal cortex, and preferably selected from cortical area 9, the PHG or the entorhinal cortex. 
     
     
         19 . A method as claimed in any one of the preceding claims, wherein the subject is one who has a cognitive disorder selected from the group consisting of Alzheimer's Disease (AD), cerebrovascular dementia (CVD), mild cognitive impairment (MCI), frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), autism, multiple sclerosis (MS), epilepsy, amyotrophic lateral sclerosis (ALS), Parkinson's disease, schizophrenia, bipolar disorder, dyslexia, Down's syndrome, Huntington's disease, prion disease, depression, obsessive-compulsive disorder or attention deficit hyperactivity disorder (ADHD), Subjective Cognitive Impairment, preMCI, and prodromal AD, Posterior Cortical Atrophy (subset of AD), behavioural, semantic, or progressive non-fluent aphasia (subsets of FTD), encephalopathy, hepatic encephalopathy, stroke, ischaemia, ischaemic hypoxia, neuro-inflammation, traumatic brain injury (TBI), mild TBI, chronic traumatic encephalopathy, concussion and delirium. 
     
     
         20 . A method of treatment of a subject, wherein the method comprises a method as claimed in any one of  claims 1 - 3 ,  5 - 7 ,  9 ,  12  or  14 , wherein, if the subject is found have a level of a cognitive disorder beyond (above or below) a specified reference level or is found to have a value for ACR or PerpCR above a specified reference level, a cognitive-disorder treating medicament is administered to the subject. 
     
     
         21 . A method of treatment of a subject, wherein the method comprises obtaining or receiving results of a method for determining ACR or PerpCR as defined in any one of  claims 1 - 3 ,  5 - 7 ,  9 ,  12  or  14 , and if the ACR or PerpCR value is higher than a reference level, thereby providing an indication of the presence of a cognitive disorder in the subject, administering a treatment to the subject appropriate for treating the cognitive disorder. 
     
     
         22 . A system or apparatus comprising at least one processing means arranged to carry out the steps of a method as claimed in any one of  claims 1  to  19 . 
     
     
         23 . A carrier bearing software comprising instructions for configuring a processor to carry out the steps of a method as claimed in any one of  claims 1  to  19 .