The DBSI derived ||significantly decreased by 28% (2.05 0.17 versus 1.47 0.09 m2/ms) while no difference was observed in that derived using DTI (1.14 0.09 versus 1.11 0.03 m2/ms) in the cuprizone-treated mice compared with that of the control. In the control corpus callosum, the DAPI nucleus count from your caudal, middle and rostral corpus callosum regions suggested no rostrocaudal inhomogeneity (Table 1). performed within the corpus callosum of cuprizone treated mice. Results demonstrate thatin vivodiffusion basis spectrum imaging can efficiently separate the confounding Rabbit Polyclonal to ANKRD1 effects of increased cellularity and/or gray matter contamination, permitting successful detection of immunohistochemistry confirmed axonal injury and/or demyelination in middle and rostral corpus callosum that were missed by diffusion tensor imaging. In addition, diffusion basis spectrum imaging-derived cellularity strongly correlated with numbers of cell nuclei identified using immunohistochemistry. Our findings suggest that diffusion basis spectrum imaging CAY10505 offers great potential to provide non-invasive biomarkers for neuroinflammation, axonal injury and demyelination coexisting in multiple sclerosis. Keywords:magnetic resonance imaging, diffusion tensor imaging, multiple tensor model, white matter injury, swelling == Intro == Inflammation is an important pathological component of complicated CNS disorders such as multiple sclerosis. While the presence of gadolinium-enhancing lesions has been regarded as CAY10505 a surrogate marker of swelling in multiple sclerosis (Grossmanet al.,1988), this is probably an oversimplification given a recent MRI study on ultra-small particles of iron oxide that showed that cell infiltration occurs earlier and continues longer than lesions defined by gadolinium-enhancement in individuals with relapsingremitting multiple sclerosis (Vellingaet al.,2008). In addition to the less than ideal response to swelling, gadolinium-enhancement also does not reflect axon or myelin pathologies. An imaging modality capable of distinguishing and quantifying co-existing swelling, axon injury and myelin damage is required to accurately assess multiple sclerosis progression and efficacy of disease-modifying interventions. The directional diffusivities derived from diffusion tensor imaging (DTI) describe water CAY10505 motions parallel to (||, axial diffusivity) and perpendicular to (, radial diffusivity) axon tracts. We have previously proposed and exhibited that decreased ||is associated with axonal injury and dysfunction, and increased is associated with myelin injury in mouse models of white matter injury (Songet al.,2002,2003,2005). Regrettably, the current DTI model does not address effects of inflammation-associated vasogenic oedema or increased cellularity. Vasogenic oedema, manifested like a non-restricted isotropic diffusion, has long been recognized to result in the increased apparent diffusion coefficient, and the underestimated white matter tract diffusion anisotropy (Kuroiwaet al.,1999;Pasternaket al.,2009;Naismithet al.,2010). In contrast, effects of increased cellularity on DTI-derived indices have not been adequately investigated in multiple sclerosis or additional CNS white matter disorders. With increased cell content, we expect that restricted isotropic diffusion resulting from cells would lead to a decreased apparent diffusion coefficient and underestimated diffusion anisotropy in the white matter (Andersonet al.,2000). Therefore, in addition to complications from crossing fibre complications (Wheeler-Kingshott and Cercignani, 2009), DTI of CNS white matter pathology is also significantly confounded by a spectrum of isotropic diffusion tensor parts resulting from swelling (Lodygenskyet al.,2010), chronic tissue loss (Kimet al.,2007) and the partial volume effect from CSF or gray matter contamination (Karampinoset al.,2008). The diffusion properties derived using DTI shed specificity and level of sensitivity with increasing pathological and anatomical complexity. Herein, diffusion basis spectrum imaging (DBSI) is definitely proposed to address DTI limitations by resolving multiple-tensor water diffusion resulting from axon injury, demyelination and swelling. Custom-designed realistic cells phantoms made of fixed mouse trigeminal nerves (consisting of non-crossing fibres and Schwann cells) with and without gel (mimicking oedema, CSF contamination or tissue loss) were 1st employed to evaluate whether DBSI is definitely capable of separating axon fibres from baseline cellularity and oedema. Crossing nerve phantoms were constructed also using trigeminal nerves to test the feasibility of DBSI to resolve crossing fibres in the presence of vasogenic oedema. After the proof-of-concept checks using phantoms, DBSI was applied to the cuprizone-treated mouse model of CNS white matter de- and remyelination (Harsanet al.,2008;Irvine and Blakemore, 2008;Wuet CAY10505 al.,2008). Axonal injury, swelling, gliosis and demyelination have been reported to coexist at 4 weeks of continuous cuprizone feeding (Matsushima and Morell, 2001;Liuet al.,2010). Our earlier DTI studies on this model failed to detect corpus CAY10505 callosum demyelination seen by immunohistochemistry at 34 weeks of cuprizone feeding (Songet al.,2005;Sunet al.,2006). With this study, we compared DBSI and DTI using a rostrocaudal analysis of axonal injury, demyelination and swelling in the corpus callosum of 4-week cuprizone-treated mice followed by immunohistochemistry. == Materials and methods.