Decreased axial (λ||) and increased radial (λ⊥) diffusivity have been shown to reflect axonal and... more Decreased axial (λ||) and increased radial (λ⊥) diffusivity have been shown to reflect axonal and myelin injury respectively. In the present study, evolving white matter injury within the optic nerves of mice with retinal ischemia was examined by in vivo and ex vivo measurements of λ|| and λ⊥. The results show that at 3 days after retinal ischemia, a 33% decrease in vivo and a 38% decrease ex vivo in λ|| without change in λ⊥ was observed in the injured optic nerve compared to the control, suggestive of axonal damage without myelin injury. At 14 days, both in vivo and ex vivo measured λ⊥ increased significantly to 220–240% of the control level in the injured optic nerve suggestive of myelin damage. In contrast, the axonal injury that was clearly detected in vivo as a significantly decreased λ|| (33% decrease) was not as clearly detected by ex vivo λ|| (17% decrease). The current findings suggest that ex vivo λ⊥ is comparable to in vivo λ⊥ in detecting myelin injury. However, the structural changes resulting from axonal damage causing the decreased in vivo λ|| may not be preserved ex vivo in the fixed tissues. Despite the accurate depiction of the pathology using λ|| and λ⊥ in vivo, the use of ex vivo λ|| to extrapolate the status of axonal injury in vivo would require further investigation.
Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axona... more Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axonal conduction and can also be associated with axonal degeneration. Accurate assessments of these conditions may be highly beneficial in evaluating and selecting therapeutic strategies for patient management. Recently, an analytical approach examining diffusion tensor imaging (DTI) derived parameters has been proposed to assess the extent of axonal damage, demyelination, or both. The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability of DTI parameters to detect the progression of myelin degeneration and regeneration. Our results demonstrate that the extent of increased radial diffusivity reflects the severity of demyelination in corpus callosum of mouse brain affected by cuprizone treatment. Subsequently, radial diffusivity decreases with the progression of remyelination. Furthermore, radial diffusivity changes were specific to the time course of changes in myelin integrity as distinct from axonal injury, which was detected by βAPP immunostaining and shown to be most extensive prior to demyelination. Radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage.
Repair of myelin damage in the adult CNS requires oligodendrocyte progenitor (OP) proliferation a... more Repair of myelin damage in the adult CNS requires oligodendrocyte progenitor (OP) proliferation and subsequent differentiation into remyelinating oligodendrocytes. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF2) have been predicted to act individually and/or cooperatively to generate remyelinating oligodendrocytes. Analysis of PDGF alpha receptor (PDGFαR) heterozygous (+/−) mice indicates that PDGFαR expression modulates oligodendrocyte density in non-lesioned adult CNS. Analysis of cuprizone demyelination and recovery in PDGFαR+/− mice, FGF2 knockout (−/−) mice, and PDGFαR+/− FGF2−/− mice demonstrated that:( 1) OP proliferation and oligodendrocyte regeneration is impaired in PDGFαR heterozygotes, (2) PDGFαR+/− and FGF2−/− deletions do not act cooperatively to impair OP amplification, (3) oligodendrocyte differentiation is more frequent in FGF2−/− mice, and (4) FGF2 deletion in combination with the PDGFαR+/− genotype rescues impaired oligodendrocyte regeneration of PDGFαR heterozygotes. These findings demonstrate distinct roles for PDGF and FGF2 in vivo in the context of a demyelinating disease with spontaneous remyelination.
Proceedings of the 20th ACM SIGKDD international conference on Knowledge discovery and data mining - KDD '14, 2014
ABSTRACT Visualization of high-dimensional data such as text documents is widely applicable. The ... more ABSTRACT Visualization of high-dimensional data such as text documents is widely applicable. The traditional means is to find an appropriate embedding of the high-dimensional representation in a low-dimensional visualizable space. As topic modeling is a useful form of dimensionality reduction that preserves the semantics in documents, recent approaches aim for a visualization that is consistent with both the original word space, as well as the semantic topic space. In this paper, we address the semantic visualization problem. Given a corpus of documents, the objective is to simultaneously learn the topic distributions as well as the visualization coordinates of documents. We propose to develop a semantic visualization model that approximates L2-normalized data directly. The key is to associate each document with three representations: a coordinate in the visualization space, a multinomial distribution in the topic space, and a directional vector in a high-dimensional unit hypersphere in the word space. We join these representations in a unified generative model, and describe its parameter estimation through variational inference. Comprehensive experiments on real-life text datasets show that the proposed method outperforms the existing baselines on objective evaluation metrics for visualization quality and topic interpretability.
Decreased axial (λ||) and increased radial (λ⊥) diffusivity have been shown to reflect axonal and... more Decreased axial (λ||) and increased radial (λ⊥) diffusivity have been shown to reflect axonal and myelin injury respectively. In the present study, evolving white matter injury within the optic nerves of mice with retinal ischemia was examined by in vivo and ex vivo measurements of λ|| and λ⊥. The results show that at 3 days after retinal ischemia, a 33% decrease in vivo and a 38% decrease ex vivo in λ|| without change in λ⊥ was observed in the injured optic nerve compared to the control, suggestive of axonal damage without myelin injury. At 14 days, both in vivo and ex vivo measured λ⊥ increased significantly to 220–240% of the control level in the injured optic nerve suggestive of myelin damage. In contrast, the axonal injury that was clearly detected in vivo as a significantly decreased λ|| (33% decrease) was not as clearly detected by ex vivo λ|| (17% decrease). The current findings suggest that ex vivo λ⊥ is comparable to in vivo λ⊥ in detecting myelin injury. However, the structural changes resulting from axonal damage causing the decreased in vivo λ|| may not be preserved ex vivo in the fixed tissues. Despite the accurate depiction of the pathology using λ|| and λ⊥ in vivo, the use of ex vivo λ|| to extrapolate the status of axonal injury in vivo would require further investigation.
Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axona... more Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axonal conduction and can also be associated with axonal degeneration. Accurate assessments of these conditions may be highly beneficial in evaluating and selecting therapeutic strategies for patient management. Recently, an analytical approach examining diffusion tensor imaging (DTI) derived parameters has been proposed to assess the extent of axonal damage, demyelination, or both. The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability of DTI parameters to detect the progression of myelin degeneration and regeneration. Our results demonstrate that the extent of increased radial diffusivity reflects the severity of demyelination in corpus callosum of mouse brain affected by cuprizone treatment. Subsequently, radial diffusivity decreases with the progression of remyelination. Furthermore, radial diffusivity changes were specific to the time course of changes in myelin integrity as distinct from axonal injury, which was detected by βAPP immunostaining and shown to be most extensive prior to demyelination. Radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage.
Repair of myelin damage in the adult CNS requires oligodendrocyte progenitor (OP) proliferation a... more Repair of myelin damage in the adult CNS requires oligodendrocyte progenitor (OP) proliferation and subsequent differentiation into remyelinating oligodendrocytes. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF2) have been predicted to act individually and/or cooperatively to generate remyelinating oligodendrocytes. Analysis of PDGF alpha receptor (PDGFαR) heterozygous (+/−) mice indicates that PDGFαR expression modulates oligodendrocyte density in non-lesioned adult CNS. Analysis of cuprizone demyelination and recovery in PDGFαR+/− mice, FGF2 knockout (−/−) mice, and PDGFαR+/− FGF2−/− mice demonstrated that:( 1) OP proliferation and oligodendrocyte regeneration is impaired in PDGFαR heterozygotes, (2) PDGFαR+/− and FGF2−/− deletions do not act cooperatively to impair OP amplification, (3) oligodendrocyte differentiation is more frequent in FGF2−/− mice, and (4) FGF2 deletion in combination with the PDGFαR+/− genotype rescues impaired oligodendrocyte regeneration of PDGFαR heterozygotes. These findings demonstrate distinct roles for PDGF and FGF2 in vivo in the context of a demyelinating disease with spontaneous remyelination.
Proceedings of the 20th ACM SIGKDD international conference on Knowledge discovery and data mining - KDD '14, 2014
ABSTRACT Visualization of high-dimensional data such as text documents is widely applicable. The ... more ABSTRACT Visualization of high-dimensional data such as text documents is widely applicable. The traditional means is to find an appropriate embedding of the high-dimensional representation in a low-dimensional visualizable space. As topic modeling is a useful form of dimensionality reduction that preserves the semantics in documents, recent approaches aim for a visualization that is consistent with both the original word space, as well as the semantic topic space. In this paper, we address the semantic visualization problem. Given a corpus of documents, the objective is to simultaneously learn the topic distributions as well as the visualization coordinates of documents. We propose to develop a semantic visualization model that approximates L2-normalized data directly. The key is to associate each document with three representations: a coordinate in the visualization space, a multinomial distribution in the topic space, and a directional vector in a high-dimensional unit hypersphere in the word space. We join these representations in a unified generative model, and describe its parameter estimation through variational inference. Comprehensive experiments on real-life text datasets show that the proposed method outperforms the existing baselines on objective evaluation metrics for visualization quality and topic interpretability.
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Papers by Tuan Le