Search

Purpose: To evaluate the feasibility of using diffusion tensor imaging (DTI) to characterize the temporospatial profile of axonal degeneration and its relation to blood-brain barrier (BBB) permeability.Materials and Methods: Longitudinal DTI was performed in Wallerian degeneration slow (WldS) mice following retinal ischemia. In parallel, gadolinium (Gd)-enhanced T1 -weighted imaging (Gd-T1 WI) was performed to evaluate BBB permeability in white matter during axonal degeneration. To confirm the in vivo findings, immunohistochemistry using SMI-31 and myelin basic protein (MBP) was performed to examine the axons and myelin, respectively, and Evans blue was used to evaluate the permeability of the BBB.Results: Reduced axial diffusivity was found in the optic nerve (ON, -15%, P = 0.0063) 1 week and optic tact (OT, -18%, P = 0.0077) 2 weeks after retinal ischemia, which were respectively associated with an 11% (P = 0.0116) and 25% (P = 0.0001) axonal loss. Increased radial diffusivity was found 1-2 weeks after the colocated decrease of axial diffusivity (35% increase, P = 0.0388 in the ON at week 2 and an 80% increase, P = 0.0015 in the OT at week 4). No significant changes were observed using Gd-T1 WI (P = 0.13-0.75), although an approximately 1-fold increase in Evans blue staining intensity was found in the injured ON and OT starting 1 week after retinal ischemia.Conclusion: We demonstrated the utility of DTI to characterize anterograde-propagating axonal degeneration through the ON and OT following retinal damage. Evans blue staining revealed serum albumin accumulation at injured sites, although there was no BBB leakage detectable using Gd-T1 WI.Level Of Evidence: 2 J. Magn. Reson. Imaging 2017;45:482-491. [ABSTRACT FROM AUTHOR]

Highlights • Early changes to DTI in ON are detectable before OCT-detectable alterations to retinal thicknesses. • Gradual reductions in GCC thickness detectable by OCT are associated with co-evaluated DTI-detected white matter integrity changes in the ON. • Alterations in OCT-GCC thickness after EAE can be predominantly accounted for by shrinkage within the RNFL/GCL sublayers. These changes include both loss and shrinkage of RGC cell bodies. • After 8 weeks of EAE, there was disproportionate axon loss compared with cell body loss. We found an average of 54% of axons lost in the ON, compared with 23% loss of RGCs in the retina. Abstract Background Clinical imaging modalities including optical coherence tomography (OCT) and diffusion tensor imaging (DTI) are vital in Multiple Sclerosis (MS), but their relationships during the different phases of Retinal ganglion cell (RGC) degeneration are not clear. We hypothesize that initial injury in optic nerve causes axonal degeneration leading to RGC loss in retina, which can be characterized by a combination of DTI and OCT. Our objective was to examine the correlation between noninvasive and histological data to chronicle the degeneration profile of RGCs in the retina and optic nerve in a mouse model of MS. Materials and methods Experimental Autoimmune Encephalomyelitis (EAE) was induced in 11 C57Bl/6 mice, with 8 mice reserved as controls. OCT and DTI was conducted 2–8 weeks after induction of EAE. The thickness of the retinal ganglion cell complex (GCC) was measured using OCT and compared to DTI indices measured in optic nerves. End-stage histology was used to quantify axon/myelin loss in the optic nerve and retinal thinning/RGC loss in the retina. Results Significant changes in DTI-derived Axial Diffusivity (AD, −17.2%) and Trace Diffusivity (TR, −18.3%) began after 2 weeks of EAE. Later significant reductions in Fractional Anisotropy (FA) and AD, with increases in Radial Diffusion (RD) were apparent after 4 and 8 weeks. OCT-derived measures of GCC thickness were reduced after 4 weeks, and reached significant reduction after 8 weeks. Among EAE mice, DTI (FA, AD and RD measures) and OCT measures were all significantly correlated after 4 and 8 weeks. Among histology measures, RGC density (−23%), RGC size (−27%), and the number of SMI31+ axons (−54%) were reduced significantly. DTI measures of FA and AD along with GCC thinning were the best independent predictors of axon loss. Conclusions DTI and OCT measures are tightly correlated during the chronic phase of axonal degeneration (4–8 weeks) in EAE mice. After 8 weeks of EAE, both OCT and DTI measures are strong predictors of axon loss in the Optic Nerve. [ABSTRACT FROM AUTHOR]

Abstract: Using magnetic resonance diffusion tensor imaging (DTI), the present study investigates changes in both gray and white matter in the APPsw transgenic mouse (Tg2576), a model of β-amyloid plaque deposition associated with Alzheimer''s disease (AD). DTI analyses were performed in cross-sectional groups of transgene-positive and -negative mice at 8, 12, 16, and 18 months of age to assess the magnitude of water diffusion in gray matter (i.e., Tr(D)) and changes in diffusion in white matter that may be indicative of axonal degeneration (i.e., reduced water diffusion parallel to axonal tracts, λ‖) and myelin degradation (i.e., increased water diffusion perpendicular to axonal tracts, λ⊥). No appreciable changes in gray or white matter were observed between the APPsw and the age-matched control mice at 8 months of age. Reduced Tr(D) and λ‖ were observed in gray and white matter, respectively, for the APPsw mice at ages greater than 8 months, which coincides with the time period when appreciable amyloid plaque accumulation was confirmed by ex vivo histopathological studies. The decreases in λ‖ suggest the presence of axonal injury in multiple white matter tracts of APPsw mice. Unlike λ‖, λ⊥was unaltered between control and APPsw mice in most white matter tracts. However, in the corpus collosum (CC), λ⊥ increased at 16 and 18 months of age, suggesting the possibility of myelin damage in the CC at these later ages. This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues. [Copyright &y& Elsevier]

• Correlation between MEMRI and DTI was found in P301L tau mice. • Axonal transport deficits in tauopathy were correlated with the loss of myelin. • Myelin loss may contribute to the axonal degeneration in tauopathy. Diffusion Tensor Imaging (DTI) and Manganese Enhanced MRI (MEMRI) are noninvasive tools to characterize neural fiber microstructure and axonal transport. A combination of both may provide novel insights into the progress of neurodegeneration. To investigate the relationship of DTI and MEMRI in white matter of tauopathy, twelve optic nerves of 11-month-old p301L tau mice were imaged and finished with postmortem immunohistochemistry. MEMRI was used to quantify Mn2+ accumulation rates in the optic nerve (ON, termed ONAR) and the Superior Colliculus (SC, termed SCAR), the primary terminal site of ON in mice. We found that both ONAR and SCAR revealed a significant linear correlation with mean diffusion (mD) and radial diffusion (rD) but not with other DTI quantities. Immunohistochemistry findings showed that ONAR, mD, and rD are significantly correlated with the myelin content (Myelin Basic Protein, p < 0.05) but not with the axonal density (SMI-31), tubulin density, or tau aggregates (AT8 staining). In summary, slower axonal transport appeared to have less myelinated axons and thinner remaining axons, associated with reduced rD and mD of in vivo DTI. A combination of in vivo MEMRI and DTI can provide critical information to delineate the progress of white matter deficits in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]