title: Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema.
abstract: The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA) and increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Chiang
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Physics, Washington University, St. Louis, MO 63130, USA.
authors.forename: Tsen-Hsuan
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: ssong@wustl.edu.
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000818:Animals; D003198:Computer Simulation; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004487:Edema / Q000473:pathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009010:Monte Carlo Method; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009444:Neuritis, Autoimmune, Experimental / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology; D019047:Phantoms, Imaging; D014276:Trigeminal Nerve / Q000473:pathology; D066127:White Matter / Q000473:pathology*
keywords: Diffusion basis spectrum imaging; Diffusion tensor imaging; Experimental autoimmune encephalomyelitis (EAE); Immunohistochemistry (IHC); Inflammation; Magnetic resonance imaging; Monte-Carlo simulation; Multiple tensor model; Restricted diffusion; White matter injury