Determination of magnetic resonance imaging biomarkers for multiple sclerosis treatment effects

Abstract

I denne afhandling beskrives metoder til udledning af biomarkrer for multipel sklerose (MS) baseret på magnetiske resonans billeder (MRI).Multipel sklerose resulterer i et neuro-degenerativt sygdomsforløb med en sygdomspatologi som kan måles med MRI. Diusions MRI (dMRI) som afspejler hjernevævets mikro-strukturelle egenskaber, har vist udtalt følsomhed overfor sygdoms patologien af MS. I afhandlingen præsenteres tre metoder til at analysere MRI/dMRI i hjernens hvid substans strukturer hos MS patienter. Den første metode paviser struktur-specifikke forskelle mellem en MS patient gruppe og en rask kontrol gruppe baseret pa egenskaber ved diffusionsprocessen. Den anden metode, anatomical connectivity mapping (ACM) afspejler voxel-vise, hel-hjerne forbindelser og benyttes som input til et tværstudie af MS populationen. Den tredje metode er en voxel-baseret segmenterings metode som gr brug af traditionel strukturel MRI til at segmenterer anormaliteter i den hvide substans (læsioner). Læsions segmenteringer benyttes ofte til at kvantificerer patienters læsions byrde i kliniske studier.Hoved resultatet for den første metode er, at der findes statistiske signifikante forskelle mellem raske kontroller og MS patienter i 11 hvid substans strukturer. Ved brug af ACM metoden findes desuden statistiske signikante forskelle mellem to kliniske patientgrupper, recidiverende remitterende og sekundrt progressive patienter, hvor forskellene primært findes i bilaterale motor-relaterede hvid substans strukturer. Det mest interessante fund i relation til læsion segmenterings metoden, er at metoden viser sig at vre bedre end to konkurrerende metoder, sammenlignet med manuelt indtegnede segmenteringer. Ud over at kunne bruges til at studerer MS, forventes metoderne præsenteret i afhandlingen at have generelle anvendelses muligheder indenfor neurovidenskab.This thesis describes methods for deriving multiple sclerosis (MS) biomarkers from Magnetic resonance images (MRI). MS results in a neurodegenerative disease course to which MRI has proven sensitive. In particular diusion MRI (dMRI), a modality reflecting microstructural properties of brain tissue has shown sensitivity towards the disease pathology of MS. We introduce three different methods for analysing MRI/dMRI in the white matter (WM) tracts, of an MS population. One method detects groupwise, tract-oriented differences based on features of the local diffusion tensor model. The next method, anatomical connectivity mapping (ACM) reflects voxel-wise whole-brain connectivity and is used to investigate cross sectional disease-related connectivity alterations. The third method presented is a voxelbased segmentation method able to detect WM abnormalities (WM lesions), with the potential of being used as lesion load markers often reported in clinical studies.The main result of the first method is statistical differences between healthy controls and MS patients in 11 WM tracts. The ability to distinguish the clinically defined subtypes of relapse remitting and secondary progressive MS patients is found based on the ACM method. Using ACM, localized statistical differences were detected in the bilateral motor tracts. The most interesting result of the lesion segmentation method study, was that it achieved a segmentation performance which was batter than two competing methods relative to the manual segmentations of the radiographers.The methods presented in the thesis are useful in studies of MS and are expected to have widespread applications in neuroscience