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In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The roles of inflammation and degeneration as well as of gray matter abnormalities in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are controversial. We analyzed the pathological manifestations in two EAE models, the chronic oligodendrocyte glycoprotein (MOG)-induced versus the relapsing-remitting proteolipid protein (PLP)-induced, along the disease progression, using advanced magnetic resonance imaging (MRI) parameters. The emphasis of this study was the overall assessment of the whole brain by histogram analysis, as well as the detection of specific affected regions by voxel based analysis (VBA) using quantitative T2, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Brains of EAE-inflicted mice from both models revealed multiple white and gray matter areas with significant changes from naïve mice for all MRI parameters. Ventricle swelling was more characteristic to the PLP-induced model. Decreased MTR values and increased apparent diffusion coefficient (ADC) were observed mainly in MOG-induced EAE, indicative of macromolecular loss and structural CNS damage involvement in the chronic disease. The MS drug glatiramer acetate (GA), applied either as prevention or therapeutic treatment, affected all the MRI pathological manifestations, resulting in reduced T2 values and ventricle volume, elevated MTR and decreased ADC, in comparison to untreated EAE-inflicted mice. In accord, immunohistochemical analysis indicated less histological damage and higher amount of proliferating oligodendrocyte progenitor cells after GA treatment. The higher brain tissue integrity reflected by the MRI parameters on the level of the whole brain and in specific regions supports the in situ anti-inflammatory and neuroprotective consequences of GA treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Nijmegen breakage syndrome (NBS) is a genomic instability disease caused by hypomorphic mutations in the NBS1 gene encoding the Nbs1 (nibrin) protein. Nbs1 is a component of the Mre11/Rad50/Nbs1 (MRN) complex that acts as a sensor of double strand breaks (DSBs) in the DNA and is critical for proper activation of the broad cellular response to DSBs. Conditional disruption of the murine ortholog of NBS1, Nbn, in the CNS of mice was previously reported to cause microcephaly, severe cerebellar atrophy and ataxia. In this study we used MRI to study the brain morphology and organization of Nbn deleted mice. Using conventional T(2)-weighted magnetic resonance, we found that the brains of the mutant mice (Nbs1-CNS-del) were significantly smaller than those of the wild-type animals, with marked mal-development of the cerebellum. Region of interest analysis of the T(2) maps revealed significant T(2) increase in the areas of white matter (corpus callosum, internal capsule and midbrain), with minor changes, if any, in gray matter. Diffusion tensor imaging (DTI) data confirmed that fractional anisotropy values were significantly reduced in these areas, mainly due to increased radial diffusivity (water diffusion perpendicular to neuronal fibers). Biochemical analysis showed low and dispersed staining for MBP and GalC in Nbs1-CNS-del brains, indicating defects in myelin formation and oligodendrocyte development. Myelin index and protein levels were significantly reduced in these brains. Our results point to a novel function of Nbs1 in the development and organization of the white matter.