title: In vivo detection of microscopic anisotropy using quadruple pulsed-field gradient (qPFG) diffusion MRI on a clinical scanner.
abstract: We report our design and implementation of a quadruple pulsed-field gradient (qPFG) diffusion MRI pulse sequence on a whole-body clinical scanner and demonstrate its ability to non-invasively detect restriction-induced microscopic anisotropy in human brain tissue. The microstructural information measured using qPFG diffusion MRI in white matter complements that provided by diffusion tensor imaging (DTI) and exclusively characterizes diffusion of water trapped in microscopic compartments with unique measures of average cell geometry. We describe the effect of white matter fiber orientation on the expected MR signal and highlight the importance of incorporating such information in the axon diameter measurement using a suitable mathematical framework. Integration of qPFG diffusion-weighted images (DWI) with fiber orientations measured using high-resolution DTI allows the estimation of average axon diameters in the corpus callosum of healthy human volunteers. Maps of inter-hemispheric average axon diameters reveal an anterior-posterior variation in good topographical agreement with anatomical measurements reported in previous post-mortem studies. With further technical refinements and additional clinical validation, qPFG diffusion MRI could provide a quantitative whole-brain histological assessment of white and gray matter, enabling a wide range of neuroimaging applications for improved diagnosis of neurodegenerative pathologies, monitoring neurodevelopmental processes, and mapping brain connectivity.
authors.affiliation: Section on Tissue Biophysics and Biomimetics, PPITS, NICHD, National Institutes of Health, Bethesda, MD 20892, USA. alexandru.avram@nih.gov
authors.forename: Alexandru V
authors.initials: AV
authors.lastname: Avram
authors.forename: Evren
authors.initials: E
authors.lastname: Özarslan
authors.forename: Joelle E
authors.initials: JE
authors.lastname: Sarlls
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Basser
mesh_terms: D000465:Algorithms; D016880:Anisotropy; D001921:Brain / Q000166:cytology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure*; D010363:Pattern Recognition, Automated / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity