title: Characterizing the microstructural basis of "unidentified bright objects" in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis.
abstract: BACKGROUND
  The histopathological basis of "unidentified bright objects" (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1.
  
  
  METHODS
  3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO-cNAWM pairs.
  
  
  RESULTS
  No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered.
  
  
  CONCLUSIONS
  Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in 'extracellular-like', intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.
authors.affiliation: Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven 3000, Belgium ; Department of Radiology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium ; Medical Imaging Research Center (MIRC), Herestraat 49, Leuven 3000, Belgium ; Leuven Research Institute for Neuroscience & Disease (LIND), Herestraat 49, Leuven 3000, Belgium.
authors.forename: Thibo
authors.initials: T
authors.lastname: Billiet
authors.affiliation: Department of Neurosurgery, University of Bonn, Sigmund-Freud-Straße 25, Bonn 53105, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Mädler
authors.affiliation: Department of Diagnostic Imaging and Radiotherapy, University Federico II of Naples, Via de Filippis 107, Salerno 84013, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: D'Arco
authors.affiliation: Department of Radiology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium ; Leuven Research Institute for Neuroscience & Disease (LIND), Herestraat 49, Leuven 3000, Belgium.
authors.forename: Ronald
authors.initials: R
authors.lastname: Peeters
authors.affiliation: Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven 3000, Belgium ; Department of Radiology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium ; Medical Imaging Research Center (MIRC), Herestraat 49, Leuven 3000, Belgium ; Leuven Research Institute for Neuroscience & Disease (LIND), Herestraat 49, Leuven 3000, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Deprez
authors.affiliation: Department of Human Genetics, KU Leuven, Herestraat 49, Leuven 3000, Belgium ; Department of Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Plasschaert
authors.affiliation: Image Sciences Institute, University Medical Center, Heidelberglaan 100, Utrecht 3584 CX, Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Department of Computer Science & Centre for Medical Image Computing, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychology, Tilburg University, Tilburg 5000 LE, Netherlands ; Department of Health Psychology, KU Leuven, Tiensestraat 102, Leuven 3000, Belgium.
authors.forename: Bea Van
authors.initials: BV
authors.lastname: den Bergh
authors.affiliation: Leuven Research Institute for Neuroscience & Disease (LIND), Herestraat 49, Leuven 3000, Belgium ; Research Group Psychiatry, KU Leuven, Kapucijnenvoer 33, Leuven 3000, Belgium ; Department of Psychiatry, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: Department of Human Genetics, KU Leuven, Herestraat 49, Leuven 3000, Belgium ; Department of Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.affiliation: Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven 3000, Belgium ; Department of Radiology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium ; Medical Imaging Research Center (MIRC), Herestraat 49, Leuven 3000, Belgium ; Leuven Research Institute for Neuroscience & Disease (LIND), Herestraat 49, Leuven 3000, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sunaert
authors.affiliation: Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven 3000, Belgium ; Department of Radiology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium ; Medical Imaging Research Center (MIRC), Herestraat 49, Leuven 3000, Belgium ; Leuven Research Institute for Neuroscience & Disease (LIND), Herestraat 49, Leuven 3000, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Emsell
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D009456:Neurofibromatosis 1 / Q000473:pathology*; D012063:Relaxation; D066127:White Matter / Q000473:pathology*
keywords: Diffusion kurtosis imaging (DKI); Diffusion tensor imaging (DTI); Myelin water imaging (MWI); Neurite orientation dispersion and density imaging (NODDI); Neurofibromatosis type 1 (NF1); Unidentified bright objects (UBOs)