title: Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: applications in healthy volunteers and in brain tumors.
abstract: The anisotropy of water diffusion in brain tissue is affected by both disease and development. This change can be detected using diffusion MRI and is often quantified by the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Although FA is sensitive to anisotropic cell structures, such as axons, it is also sensitive to their orientation dispersion. This is a major limitation to the use of FA as a biomarker for "tissue integrity", especially in regions of complex microarchitecture. In this work, we seek to circumvent this limitation by disentangling the effects of microscopic diffusion anisotropy from the orientation dispersion. The microscopic fractional anisotropy (μFA) and the order parameter (OP) were calculated from the contrast between signal prepared with directional and isotropic diffusion encoding, where the latter was achieved by magic angle spinning of the q-vector (qMAS). These parameters were quantified in healthy volunteers and in two patients; one patient with meningioma and one with glioblastoma. Finally, we used simulations to elucidate the relation between FA and μFA in various micro-architectures. Generally, μFA was high in the white matter and low in the gray matter. In the white matter, the largest differences between μFA and FA were found in crossing white matter and in interfaces between large white matter tracts, where μFA was high while FA was low. Both tumor types exhibited a low FA, in contrast to the μFA which was high in the meningioma and low in the glioblastoma, indicating that the meningioma contained disordered anisotropic structures, while the glioblastoma did not. This interpretation was confirmed by histological examination. We conclude that FA from DTI reflects both the amount of diffusion anisotropy and orientation dispersion. We suggest that the μFA and OP may complement FA by independently quantifying the microscopic anisotropy and the level of orientation coherence.
authors.affiliation: Clinical Sciences, Lund, Department of Medical Radiation Physics, Lund University, Lund, Sweden. Electronic address: filip.szczepankiewicz@med.lu.se.
authors.forename: Filip
authors.initials: F
authors.lastname: Szczepankiewicz
authors.affiliation: CR Development, AB, Lund, Sweden.
authors.forename: Samo
authors.initials: S
authors.lastname: Lasič
authors.affiliation: Diagnostic Radiology, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden; Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.affiliation: Diagnostic Radiology, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden; Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
authors.affiliation: Laboratory for Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Westin
authors.affiliation: Clinical Sciences, Lund, Department of Medical Radiation Physics, Lund University, Lund, Sweden; Diagnostic Radiology, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden; Lund University Bioimaging Center, Lund University, Lund, Sweden.
authors.forename: Freddy
authors.initials: F
authors.lastname: Ståhlberg
authors.affiliation: Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lätt
authors.affiliation: Division of Physical Chemistry, Department of Chemistry, Lund University, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Topgaard
authors.affiliation: Lund University Bioimaging Center, Lund University, Lund, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000033:anatomy & histology* / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D003198:Computer Simulation; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D066128:Gray Matter / Q000033:anatomy & histology / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008579:Meningioma / Q000473:pathology*; D008875:Middle Aged; D066127:White Matter / Q000033:anatomy & histology / Q000473:pathology
keywords: Diffusion weighted imaging; Magic angle spinning of the q-vector; Microscopic anisotropy; Microscopic fractional anisotropy; Order parameter