Gd-DTPA enhanced MRI revealed leakage at aqueous-vitreous interface upon ocular hypertension

Session 75: Perfusion & Diffusion: Animal Models - Oral presentationThis study aims to employ in vivo contrast-enhanced MRI to evaluate the ocular transport upon an induction of ocular hypertension in the right eye in a rat model of chronic glaucoma. Following systemic administration of Gd-DTPA solution, our results showed a progressive T1-weighted signal increase in the anterior vitreous body of the glaucomatous eye but not the control eye, suggestive of the leakage of Gd-DTPA at the aqueous-vitreous interface. These findings may explain the sources of changing biochemical compositions in the glaucomatous chamber components, which may implicate the cascades of neurodegenerative processes in the retina and the optic nerve. Our findings of the early Gd-DTPA signal enhancements in the anterior vitreous body than the preretinal vitreous provided a noninvasive marker for the disease. More importantly, this approach could have direct clinical applications and can be readily translated to humans.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 74

Dynamic contrast-enhanced MRI of ocular biotransport in normal and hypertensive eyes

Proceedings of the IEEE Engineering in Medicine and Biology Society Conference, 2008, p. 835-838This study aims to employ in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate the ocular transport following an induction of ocular hypertension in a rat model of chronic glaucoma. Upon systemic administration of Gd-DTPA solution, T1-weighted signal increase was observed in the vitreous body of the glaucomatous eye but not the control eye. This increase occurred earlier in the anterior vitreous body than the preretinal vitreous. Further, there was an earlier Gd-DTPA transport into the anterior chamber in the majority of glaucomatous eyes. Our DCE-MRI findings revealed the leakage of Gd-DTPA at the aqueous-vitreous interface, which was likely resulted from increased permeability of blood-aqueous or aqueous-vitreous barrier. These may explain the sources of changing biochemical compositions in the chamber components, which may implicate the neurodegenerative processes in the glaucomatous visual components. © 2008 IEEE.published_or_final_versio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Evaluation of the visual system in a rat model of chronic glaucoma using manganese-enhanced magnetic resonance imaging

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to evaluate dynamically the Mn2+ enhancements along the visual pathway following an induction of ocular hypertension in a rat model of chronic glaucoma. Results showed an accumulation of Mn2+ ions in the vitreous humor of the glaucomatous eye, with no statistical changes in the total retinal thickness but a possible occlusion of the ions at the optic nerve head. Meanwhile, there was a reduction in Mn2+ transport in the glaucomatous optic nerve in the later stage of our model. Fewer enhancements in the visual cortex projected from the glaucomatous eye were also detectable. These may help understand the disease mechanisms, monitor the effect of drug interventions to glaucoma models, and complement the conventional techniques in examining the visual components. © 2007 IEEE.link_to_subscribed_fulltex

Ultrahigh-field magnetic resonance imaging of normal and hypertensive eyes

Poster - Track 2 Biomedical Imaging, Signal Processing, and Health Informatics: P2.28The 4th World Congress on Bioengineering (WACBE 2009), Hong Kong, 26-29 July 2009. In Proceedings of the 4th WACBE World Congress on Bioengineering, 2009, p. 14

In vivo longitudinal assessment of optic nerve degeneration in rat model of glaucoma using diffusion tensor imaging

invited for special sessio

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Diffusion tensor MR study of optic nerve degeneration in glaucoma

Axonal degeneration has been known to occur in the optic nerve (ON) of rat glaucoma model. Recently, quantitative diffusion tensor imaging (DTI) has been developed to investigate various white matter diseases in vivo. In this study, longitudinal DTI was thus employed to study such animal model in the present study. The results showed that radial diffusivity (λ⊥) and fractional anisotropy (FA) of the glaucomatous ON (gON) was increasing and decreasing respectively with time after glaucoma induction, whereas there was no significant change in the axial diffusivity (λ//). Supported by the histological staining of the ON, such changes in the two DTI-derived parameters were attributed to the 10% decrease in the axonal density of the gON as compared to nON. It was shown for the first time that DTI can be sensitive enough to detect axonal degeneration in rat glaucoma model. DTI therefore holds promise for reliable diagnoses and assessment of the glaucoma disease in human upon careful interpretation of the DTI-derived directional diffusivities. © 2007 IEEE.link_to_subscribed_fulltex