Traditional poster

Mild traumatic brain injury (mTBI) is associated with long term cognitive and affective symptoms. Findings on conventional MRI often do not account for the duration and severity of these symptoms. The aim of this study was to ascertain whether MR relaxometry and diffusion tensor imaging would reveal abnormalities in normal appearing white matter (NAWM) in patients with mTBI. Whole group analysis showed no significant differences, but after grouping the patients according to the side of the visible lesion, a significant increase in the mean diffusivity (MD) of ipsilateral frontal lobe NAWM was demonstrated.

Diffusion tensor imaging (DTI) was performed within 7 days and after 6 months of injury in 21 traumatic brain injury (TBI) patients with frontal lobe injury and 21 age/sex matched controls. Diffusion tensor tractography (DTT) was proposed for quantification of various white matter (WM) tracts in patients with frontal lobe injury to assess diffuse axonal injury (DAI) and to look for correlation of these fiber bundles measures with various neuropsychological tests (NPT). We found reduced fractional anisotropy (FA) and increased mean diffusivity (MD) values in all WM tracts in TBI patients compared to controls, NPT scores were found to be significantly impaired in follow-up patients compare to controls and some of these tests showed significant correlation with DTI indices with different WM tracts. WM tracts which show significant difference on DTT were also correlated with those NPT which are associated with main function of frontal lobe such as memory, attention, visual and motor function. It appears more realistic methods for DAI quantification in TBI patients and provides information about structural integrity and connectivity of whole fiber tracts.

Fornix is one of the primary white matter structures of the limbic system, and its damage in mild traumatic brain injury (TBI) may explain the memory and learning dysfunctions in the post-concussion syndrome. N=24 TBI patients were longitudinally studied in two time points using T1 anatomical imaging and diffusion tensor imaging (DTI) to measure the fornix-to-brain ratio (FBR) and WM integrity of fornix, and compared with matched healthy controls. Our data show that the WM degradation in fornix onset in the acute stage after mild TBI, and that this degradation continued during the following 6-month period of recovery.

Traumatic head injury is one of the major causes of neurological morbidity and mortality in the UK with more than 0.1 million admissions per year with primary diagnosis of head injury. This constitutes a huge drain on medical resources. Majority of these patients have ongoing symptoms which do not correlate with MRI or CT findings. Here we investigated a cohort of patients with mild TBI using multi-parametric real space analysis. Our results show that a fully automatic real space method of analysing quantitative MR parameters can be used to detect changes in normal appearing tissues in patients suffering mild TBI.

Atrophy is common post traumatic brain injury (TBI) and may correlate with outcome. We hypothesised that quantification of Jacobian determinants could assess progressive changes in brain volume in within subject analyses, even in contexts that produce major problems with comparative analyses. We show implementation of the approach in a single TBI subject with serial scans before and up to 12 months after decompressive craniectomy, compared to results from healthy controls. The results indicate it is possible to monitor the changes in brain volume over time post TBI in an individual.

The natural course of radiation induced brain injury still remains poorly understood. Among the abnormalities white matter edema-like lesions (WML) and contrast enhanced necrotic lesions (CEL) have been most commonly reported. It was recently reported that radiation induced brain injury was not always an irreversible and progressive process, but one that could show regression and resolution. In total 22 nasopharyngeal carcinoma patients with 36 lobes displaying WML and CEL were analysed in this study. The preliminary results of this study suggest the development of WML and CEL tend to follow the same pattern, and not develop in the opposite direction.

Dynamic Susceptibility Contrast (DSC) MR perfusion was used to characterize the perfusion abnormalities in patients with adrenoleukodystrophy and adrenomyeloneuropathy. This study demonstrates that the combination of conventional MR and DSC perfusion MR techniques allows the definition of five different zones with characteristic profiles of abnormal signal and perfusion in patients with adrenoleukodystrophy that correspond to the zonal anatomy previously described on pathological studies. These findings can be helpful in predicting disease progression, selecting patients for therapeutic interventions and elucidating the pathophysiology of this disorder.

Adrenomyeloneuropathy (AMN) is characterized by primary distal axonopathy with secondary demyelination. In this study we performed diffusion tensor imaging (DTI) at 1.5T on 29 healthy volunteers and 39 AMN patients. Tractography of the left and right corticospinal tracts (CST) were performed and diffusion anisotropy and diffusivity were computed. A significant change in FA and perpendicular diffusivity was found from the pons to mid-brain (p<0.01) and mid-brain to thalamus (p<0.001) regions in AMN patients. This suggests that DTI can quantify the pathway-specific abnormalities in AMN, and results are in corroboration with knowledge that cerebral damage is present in AMN.

Bone marrow transplantation (BMT) has been advocated as treatment of juvenile metachromatic leukodystrophy (MLD). The effectiveness of this high-risk treatment is still questionable due to the rarity of follow-up reports. We carried out a 7 years MRI follow-up on a boy with juvenile MLD who had received BMT treatment in the presymptomatic phase and remained free of MLD symptoms during the observation. Conventional morphological MRI showed minor stable white matter lesions while quantitative T2-mapping and MR spectroscopy evidenced a stagnancy of the demyelination process and an ongoing maturation of the brain.

In this study, tract based spatial statistics (TBSS) approach is used for the investigation of Pelizeaus-Merzbacher Disease (PMD), which is a rare X-linked disease characterized by defective central nervous system myelination due to a mutation in the proteolipid protein 1 gene.

Adenylosuccinate lyase (ADSL) deficiency is an inherited metabolic disorder and characterized by the accumulation of succinylaminoimidazolecarboxamide riboside and succinyladenosine (S-Ado) in tissue and body fluids. In three children, presenting with psychomotor delay, autistic features, and white matter changes on brain MRI, screening for inborn errors of metabolism included in vitro proton MRS. It revealed resonances at 8.27 and 8.29ppm that correspond to S-Ado. In vivo proton MRS showed a signal at 8.3ppm in gray and white matter brain regions of all three patients, which was undetectable in controls. In vivo proton MRS provides a conclusive finding in ADSL deficiency.

Recently, our group showed for the first time cerebral accumulation of 3-hydroxyisovaleric acid (3HIVA) in a pediatric patient with 3-Methylcrotonyl-CoA Carboxylase deficiency (MCCD). 3HIVA has been considered to have neurotoxic effects, but this is under debate. The present study reports on cerebral accumulation of 3HIVA detected by 3T proton MRS in two adult women with MCCD, whom deficiency was discovered by a positive neonatal screening of their healthy new-born babies. As the women had not been aware of having this disorder before and they have no or limited complaints, 3HIVA is postulated to have no or minor neurotoxic effect.

Type 2 diabetes (DM2) is a known risk factor for white matter lesions (WML) in elderly subjects. In this study, we used voxel-based morphometry (VBM) to analyse the common distribution of WML in 215 subjects with DM2 (average age 76.1 years) compared to 1675 non-diabetic controls (average age 75.8 years). Our main finding is that DM2 subjects have commonly large WML areas in the brain that extend from the frontal lobe to the parietal lobe.

Type 2 DM is a major risk factor for both large and small vessel atherosclerosis, stroke, and vascular dementia. Hyperglycemia is a common mechanism of endothelial dysfunction and neuronal cell damage. Microvascular disease manifests as white matter hyperintesities on MRI, regional atrophy and functional decline. Inflammation further affects microcirculatory regulation and contributes to arteriolosclerosis. We investigated the effects of inflammation on regional perfusion and neurodegenerative changes in grey and white matter on MRI. Inflammatory markers had different effects on regional brain volumes. sICAM was associated with atrophy across all regions in the DM group, with the most significant effects in the frontal and parietal regions. In the control group, regional perfusion on both sides in the parietal lobe is positively correlated with sICAM, and perfusion in the right occipital lobe is positive with sVCAM. Associations between regional brain volumes and other inflammatory markers were not prominent. Frontal and parietal regions with high energy demands are more vulnerable to the effects of DM in the brain.

Despite successful treatment of HIV and AIDS, neuroimaging and neurospectroscopy abnormalities persist suggesting residual viral effects or unwanted neurological side effects of effective therapies. Elucidation of the recently described reduction in frontal lobe glutamate concentration in white matter of HIV-affected individuals requires independent 13C MRS measurement of glutamate turnover neurotransmitter rates in neurons and glia. This study develops the necessary frontal lobe assay of neuronal and axonal glutamate turnover by infusion of 2-13C glucose followed by low-power nOe 13C MRS in HIV and normal control subjects. Preliminary results indicate reduced 13C glutamate turnover in successfully treated HIV.

Abnormal metabolite levels were found in 3/3 patients with a diagnosis a post Lyme disease syndrome using 1H-MRS.

Vascular endothelial growth factor (VEGF) has been investigated as a potential treatment for spinal cord injury (SCI) due to its vascular-promoting and neuroprotective effects; however, studies have provided conflicting information about the post-SCI effects of VEGF. In this study, VEGF was delivered immediately after SCI and longitudinal MRI and behavioral studies were performed into the chronic phase of injury. It was found that VEGF treatment results in tissue sparing and increased markers of neurofilament, but many animals also displayed a higher incidence of mechanical allodynia. VEGF may spare tissue, but may also encourage non-specific sprouting of axons into pain pathways.

MRE is an innovative imaging technique developed to non-invasively map and quantify the viscoelastic properties of tissue in vivo. As pathological alterations cause changes in elasticity and viscosity, MRE might be applied to characterize the structural integrity of given tissues and could be employed for diagnosis and clinical monitoring of neurodegenerative diseases such as multiple sclerosis. Therefore it appears to be essential to evaluate the effect of pathological processes occurring in multiple sclerosis on the viscoelastic properties of cerebral tissue with the help of experimental rodent models. We introduced the cuprizone mouse-model (C57/black6) which depicts key features of multiple sclerosis.

The shaking pup (shp) is a canine mutant model of dysmyelination, and suffers from severe myelin deficiency. In a previous study of shp brain, Po was shown to differentiate between a control and diseased pup with respect to myelin content. In this study, WM integrity is examined in the spinal cord of shp using both DTI and DSI measurements acquired from a HYDI approach. Standard DTI measures and Po are compared to see if one or both are sensitive to changes in myelin content between shp and control, as well as to more subtle differences between two diseased pups.

Cortical pathology is an important feature of MS. However visualization with MRI is poor although sensitivity is increased using FLAIR and Double Inversion Recovery (suppression of CSF and white matter) experiments. Various inversion recovery experiments were tested ex vivo on brains of marmoset with MS, which develop cortical lesions, in their ability to improve cortical lesion detection. Experiments included settings of inversion times in which CSF, white or grey matter was suppressed and a DIR experiment in which both white and grey matter was suppressed. Cortical lesions were best visualized after suppression of white matter or in the DIR experiment.

The sensitivities of detecting white matter injury using 6 ms and 38 ms diffusion time were examined in the present study. We demonstrated that increased diffusion time in diffusion tensor imaging measurements improves the sensitivity of detecting axonal injury and myelin damage in cuprizone treated mice. In the cuprizone model of demyelination, axonal injury was seen as significantly decreased axial diffusivity at both 6 and 38 ms diffusion time with more significantly decreased axial diffusivity observed at longer diffusion time.

Natural killer (NK) cells of the innate immune system can profoundly impact the development of adaptive immune responses against foreign invaders, as well as self-antigens. In this study a combination of in vivo MRI and bioluminescence imaging was used to investigate effects of systemic depletion of NK cells on lesion development in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. The results of this study suggest organ-specific activity of NK cells on the magnitude of CNS inflammation.