Efrat Sasson

White matter correlates of cognitive domains in normal aging with diffusion tensor imaging

The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25–82 years), we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory) with white matter integrity, as measured by diffusion tensor imaging (DTI) fiber tracking in the temporal lobe projections [uncinate fasciculus (UF), fornix, cingulum, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF)]. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA) in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest (ROI) for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.

Structural correlates of memory performance with diffusion tensor imaging

Aging is associated with a variety of structural and pathological brain changes. Memory, or the ability to store and retrieve information, declines significantly during aging. In order to characterize the brain micro-structural correlates of memory performance, 52 healthy subjects, age 25-82 years, completed a computerized non-verbal memory test and were scanned using magnetic resonance diffusion tensor imaging. Partial correlation was conducted between DTI parameters and memory performance (accuracy and reaction time (RT) for different learning stages) controlling for age. A similar correlation pattern was found for apparent diffusion coefficient (ADC), FA, and radial and axial diffusivities, but correlations between ADC and memory performance were the most informative and are therefore reported here. While ADC was correlated with accuracy mainly in temporal and frontal cortical regions, it was correlated with RT in temporal and frontal white matter pathways, including the inferior longitudinal fasciculus and uncinate fasciculus. The task was repeated four times, performance in the first repetition was correlated with ADC in frontal white matter and in the fourth repetition with ADC in temporal gray matter structures mainly the parahippocapus and in the middle temporal gyrus. The localization of the correlations of ADC with the different task parameters is in line with previous studies. Thus, inter-subject variability in memory performance and tissue morphology, as expressed by diffusion tensor magnetic resonance imaging, can be used to relate tissue microstructures with cognitive performance, and to provide information to corroborate other functional localization techniques.

Magnetic resonance imaging characterization of different experimental autoimmune encephalomyelitis models and the therapeutic effect of glatiramer acetate

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.

High‐Level Gait Disorder: Associations with Specific White Matter Changes Observed on Advanced Diffusion Imaging

High‐level gait disorder (HLGD) is a debilitating disorder causing mobility decline in the elderly. Although its clinical characteristics are well described, its anatomical and pathophysiological underpinnings are poorly understood. This study examined the anatomical distribution of white matter (WM) changes in patients with mild to moderate HLGD of the cautious/disequilibrium type, using advanced magnetic resonance imaging (MRI) methods.

The Effect of Electromagnetic Field Treatment on Recovery from Spinal CordInjury in a Rat Model Clinical and Imaging Findings

Background: Spinal cord injury (SCI) refers to spinal cord damage arising from trauma, disease or degeneration. At present, there is still no treatment for any paraplegia resulting from SCI. We have previously shown that very low intensity, low frequency, electromagnetic field treatment (VLIFE) promotes neuronal plasticity after stroke and as a result, improves clinical recovery. Objective: In this paper we studied an innovative electromagnetic field treatment for SCI in an animal model. Methods: SCI was caused to 20 rats by hemi crush. The animals were divided into three groups, 7 animals were not treated, two groups received VLIFE treatment for two months, 7 rats received 15.72 Hz, and 6 rats received a dedicated treatment of 26 Hz. Clinical evaluation was performed weekly, and imaging assessment monthly. Results: Clinical performance assessed by a locomotor test, show significant clinical improvement of the neurological function following treatment with VLIFE (p < 0.05). Imaging results after two months of treatment, by MRI including DTI analysis, show that the non-treated (sham) spinal cord has not recovered, while in the treated animal the fibers of the spinal cord were preserved and rewired. VLIFE treatment has major benefits on injured spinal cord: preservation of the spinal cord from further degradation caused by the edema and internal cord scars, and rewiring of the spinal cord resulting with rehabilitation and improved clinical performance. Conclusions: Low intensity low frequency electromagnetic field treatment may be beneficial for rehabilitation from SCI, human clinical trials are planned.

P2-081: Brain localization of cognitive domains with diffusion MRI

Background: Aging is a complex heterogeneous process accompanied by cognitive decline. Diffusion-tensor imaging (DTI) measures the displacement of water molecules in vivo non-invasively. This technique has demonstrated that aging is associated with an increase in the apparent diffusion coefficient (ADC), most prominently in the frontal lobe. Methods: MRI was performed on a 3T (GE) MRI system in 51 healthy volunteers (25-82 y). DTI analysis and construction of ADC maps was performed followed by normalization to the standard Montreal Neurological Institute template and spatial smoothing. Subjects completed a battery of computerized tests (Mindstreams®, NeuroTrax Corp., NJ) assessing cognitive performance in multiple domains. Factor analysis of 55 cognitive scores resulted in three cognitive domains: memory, verbal function and processing speed. DTI using voxel-based analysis (VBA) was used to quantify regional brain changes due to age-related cognitive decline in these domains controlling for age. Results: Negative partial correlation between memory accuracy and ADC was found mainly in temporal and frontal gray and white matter, including the parahippocampus, orbitofrontal, inferior frontal gyrus, middle frontal gyrus, anterior cingulate, broca’s area, and insula (Figure 1, red). Negative partial correlation between verbal accuracy and ADC was found mainly in white matter, in frontal white matter, in the superior longitudinal fasciculus (SLF) and in the cingulum (Figure 1, blue). Positive partial correlation between processing speed and ADC was mainly in the white matter, in the posterior parts of the SLF, cingulum, posterior corona radiata and postcentral gyrus (Figure 1, green). Conclusions: Partial correlation of the cognitive domains with ADC revealed a region-specific pattern, with regions exhibiting substantial correlation playing an important role in the corresponding functional domain. ADC in the hippocampus, orbitofrontal cortex, and Broca’s area, memory related areas, was correlated with memory performance. ADC in the SLF, which connects the language areas (Wernicke’s and Broca’s), was significantly correlated with verbal performance. ADC in the posterior corona radiata, related to motor speed, and parietal white matter, involved in calculation tasks, were correlated with the processing speed. Correlating cognitive performance and quantitative measures of brain morphology can be used for indirect functional localization of cognitive domains. P2-082 VALIDATION OF A FULLY-AUTOMATED MEDICAL DEVICE FOR QUANTIFYING REGIONAL BRAIN ATROPHY FROM MRIs OF PATIENTS WITH ALZHEIMER’S DISEASE AND RELATED DISORDERS