Nyoman Kurniawan | The University of Queensland, Australia (original) (raw)

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Papers by Nyoman Kurniawan

Research paper thumbnail of Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder

Background: Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorder... more Background: Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have
increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological
basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR)
strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete
agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is
known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor
functions in these mice that may also contribute to their behavioural phenotype.
Results: In this study, we performed diffusion tensor imaging and tractography, together with histological analyses
to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and
age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal
commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical
connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical
areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered
in BTBR mice between cortical areas and throughout development.
Conclusions: We demonstrate that interhemispheric connectivity and cortical area formation are altered in an
age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in
this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating
the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.
Keywords: Autism spectrum disorders (ASD), BTBR mice, Agenesis of the corpus callosum, Cortical area patterning,
Diffusion imaging

Research paper thumbnail of Brain tissue compartment density estimated using diffusion-weighted MRI yields tissue parameters consistent with histology

Human Brain Mapping, 2015

We examined whether quantitative density measures of cerebral tissue consistent with histology ca... more We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intracellular and intraneurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different subregions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (diffusion MRI: 42 ± 6%, 36 ± 4%, and 43 ± 5%; electron microscopy: 41 ± 10%, 36 ± 8%, and 44 ± 12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

Research paper thumbnail of Renal developmental defects resulting from in utero hypoxia are associated with suppression of ureteric β-catenin signaling

Kidney international, Jan 14, 2015

Gestational stressors, including glucocorticoids and protein restriction, can affect kidney devel... more Gestational stressors, including glucocorticoids and protein restriction, can affect kidney development and hence final nephron number. Since hypoxia is a common insult during pregnancy, we studied the influence of oxygen tension on kidney development in models designed to represent a pathological hypoxic insult. In vivo mouse models of moderate, transient, midgestational (12% O2, 48 h, 12.5 dpc) or severe, acute, early-gestational (5.5-7.5% O2, 8 h, 9.5-10.5 dpc) hypoxia were developed. The embryo itself is known to mature under hypoxic conditions with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models generated phenotypes seen in patients with congenital anomalies of the kidney and urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney, while moderate, transient, midgestational hypoxia permanently reduced ureteric branching and nephron formation. Both models disp...

Research paper thumbnail of Production and packaging of a biological arsenal: Evolution of centipede venoms under morphological constraint

Proceedings of the National Academy of Sciences, 2015

Research paper thumbnail of lop-DWI: A Novel Scheme for Pre-Processing of Diffusion-Weighted Images in the Gradient Direction Domain

Frontiers in neurology, 2014

We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion... more We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion-gradient directions for high angular resolution diffusion magnetic resonance imaging. Our pre-processing method incorporates prior knowledge about the acquired diffusion-weighted signal, facilitating noise reduction. Periodic spiral sampling of gradient direction encodings results in an acquired signal in each voxel that is pseudo-periodic with characteristics that allow separation of low-frequency signal from high frequency noise. Consequently, it enhances local reconstruction of the orientation distribution function used to define fiber tracks in the brain. Denoising with periodic spiral sampling was tested using synthetic data and in vivo human brain images. The level of improvement in signal-to-noise ratio and in the accuracy of local reconstruction of fiber tracks was significantly improved using our method.

Research paper thumbnail of A proteomics and transcriptomics investigation of the venom from the barychelid spider Trittame loki (brush-foot trapdoor)

Toxins, 2013

Although known for their potent venom and ability to prey upon both invertebrate and vertebrate s... more Although known for their potent venom and ability to prey upon both invertebrate and vertebrate species, the Barychelidae spider family has been entirely neglected by toxinologists. In striking contrast, the sister family Theraphosidae (commonly known as tarantulas), which last shared a most recent common ancestor with Barychelidae over 200 million years ago, has received much attention, accounting for 25% of all the described spider toxins while representing only 2% of all spider species. In this study, we evaluated for the first time the venom arsenal of a barychelid spider, Trittame loki, using transcriptomic, proteomic, and bioinformatic methods. The venom was revealed to be dominated by extremely diverse inhibitor cystine knot (ICK)/knottin peptides, accounting for 42 of the 46 full-length toxin precursors recovered in the transcriptomic sequencing. In addition to documenting differential rates of evolution adopted by different ICK/knottin toxin lineages, we discovered homologu...

Research paper thumbnail of Microscopic diffusion properties of fixed breast tissue: Preliminary findings

Magnetic Resonance in Medicine, 2014

To investigate the microscopic diffusion properties of formalin-fixed breast tissue. Diffusion mi... more To investigate the microscopic diffusion properties of formalin-fixed breast tissue. Diffusion microimaging was performed at 16.4T with 40-μm isotropic voxels on two normal and two cancer tissue samples from four patients. Results were correlated with histology of the samples. Diffusion-weighted images and mean diffusivity maps demonstrated distinct diffusivity differences between breast tissue components. Mean diffusivity (MD) in normal tissue was 0.59 ± 0.24 μm(2) /ms for gland lobule (voxels containing epithelium and intralobular stroma) and 1.23 ± 0.34 μm(2) /ms for interlobular fibrous stroma. In the cancer samples, MD = 0.45 ± 0.23 μm(2) /ms for invasive ductal carcinoma (voxels contain epithelium and intralobular stroma) and 0.61 ± 0.35 μm(2) /ms for ductal carcinoma in situ. There were significant MD differences between all tissue components (P < 0.005), except between gland lobule and ductal carcinoma in situ (P = 0.71). The low diffusivity of epithelium-rich cancer tissue and of normal epithelium relative to its supporting fibrous stroma was similar to that reported for prostate tissue and the esophageal wall. Diffusion microimaging demonstrates distinct diffusivity differences between breast tissue glandular structures. Low diffusivity may be a distinctive feature of mammalian epithelia. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Research paper thumbnail of Visualization of mouse barrel cortex using ex-vivo track density imaging

NeuroImage, 2014

We describe the visualization of the barrel cortex of the primary somatosensory area (S1) of ex v... more We describe the visualization of the barrel cortex of the primary somatosensory area (S1) of ex vivo adult mouse brain with short-tracks track density imaging (stTDI). stTDI produced much higher definition of barrel structures than conventional fractional anisotropy (FA), directionally-encoded color FA maps, spin-echo T1- and T2-weighted imaging and gradient echo T1/T2*-weighted imaging. 3D high angular resolution diffusion imaging (HARDI) data were acquired at 48 micron isotropic resolution for a (3mm)(3) block of cortex containing the barrel field and reconstructed using stTDI at 10 micron isotropic resolution. HARDI data were also acquired at 100 micron isotropic resolution to image the whole brain and reconstructed using stTDI at 20 micron isotropic resolution. The 10 micron resolution stTDI maps showed exceptionally clear delineation of barrel structures. Individual barrels could also be distinguished in the 20 micron stTDI maps but the septa separating the individual barrels appeared thicker compared to the 10 micron maps, indicating that the ability of stTDI to produce high quality structural delineation is dependent upon acquisition resolution. Close homology was observed between the barrel structure delineated using stTDI and reconstructed histological data from the same samples. stTDI also detects barrel deletions in the posterior medial barrel sub-field in mice with infraorbital nerve cuts. The results demonstrate that stTDI is a novel imaging technique that enables three-dimensional characterization of complex structures such as the barrels in S1 and provides an important complementary non-invasive imaging tool for studying synaptic connectivity, development and plasticity of the sensory system.

Research paper thumbnail of lop-DWI: A Novel Scheme for Pre-Processing of Diffusion-Weighted Images in the Gradient Direction Domain

Frontiers in Neurology, 2015

We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion... more We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion-gradient directions for high angular resolution diffusion magnetic resonance imaging. Our pre-processing method incorporates prior knowledge about the acquired diffusion-weighted signal, facilitating noise reduction. Periodic spiral sampling of gradient direction encodings results in an acquired signal in each voxel that is pseudo-periodic with characteristics that allow separation of low-frequency signal from high frequency noise. Consequently, it enhances local reconstruction of the orientation distribution function used to define fiber tracks in the brain. Denoising with periodic spiral sampling was tested using synthetic data and in vivo human brain images. The level of improvement in signal-to-noise ratio and in the accuracy of local reconstruction of fiber tracks was significantly improved using our method.

Research paper thumbnail of Super-resolution track-density imaging studies of mouse brain: Comparison to histology

Research paper thumbnail of Segmentation of the mouse hippocampal formation in magnetic resonance images

Research paper thumbnail of Longitudinal assessment of white matter pathology in the injured mouse spinal cord through ultra-high field (16.4T) in vivo diffusion tensor imaging

Research paper thumbnail of Segmentation of the C57BL/6J mouse cerebellum in magnetic resonance images

Research paper thumbnail of Microscopic diffusivity compartmentation in formalin-fixed prostate tissue

Magnetic Resonance in Medicine, 2012

Research paper thumbnail of Microscopic diffusion anisotropy in formalin fixed prostate tissue: Preliminary findings

Magnetic Resonance in Medicine, 2012

Research paper thumbnail of Acute delivery of EphA4-Fc improves functional recovery after contusive spinal cord injury in rats

Journal of Neurotrauma, 2013

Research paper thumbnail of MRI changes and complement activation correlate with epileptogenicity in a mouse model of temporal lobe epilepsy

Brain Structure and Function, 2014

Research paper thumbnail of Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder

Background: Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorder... more Background: Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have
increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological
basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR)
strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete
agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is
known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor
functions in these mice that may also contribute to their behavioural phenotype.
Results: In this study, we performed diffusion tensor imaging and tractography, together with histological analyses
to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and
age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal
commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical
connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical
areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered
in BTBR mice between cortical areas and throughout development.
Conclusions: We demonstrate that interhemispheric connectivity and cortical area formation are altered in an
age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in
this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating
the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.
Keywords: Autism spectrum disorders (ASD), BTBR mice, Agenesis of the corpus callosum, Cortical area patterning,
Diffusion imaging

Research paper thumbnail of Brain tissue compartment density estimated using diffusion-weighted MRI yields tissue parameters consistent with histology

Human Brain Mapping, 2015

We examined whether quantitative density measures of cerebral tissue consistent with histology ca... more We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intracellular and intraneurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different subregions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (diffusion MRI: 42 ± 6%, 36 ± 4%, and 43 ± 5%; electron microscopy: 41 ± 10%, 36 ± 8%, and 44 ± 12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

Research paper thumbnail of Renal developmental defects resulting from in utero hypoxia are associated with suppression of ureteric β-catenin signaling

Kidney international, Jan 14, 2015

Gestational stressors, including glucocorticoids and protein restriction, can affect kidney devel... more Gestational stressors, including glucocorticoids and protein restriction, can affect kidney development and hence final nephron number. Since hypoxia is a common insult during pregnancy, we studied the influence of oxygen tension on kidney development in models designed to represent a pathological hypoxic insult. In vivo mouse models of moderate, transient, midgestational (12% O2, 48 h, 12.5 dpc) or severe, acute, early-gestational (5.5-7.5% O2, 8 h, 9.5-10.5 dpc) hypoxia were developed. The embryo itself is known to mature under hypoxic conditions with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models generated phenotypes seen in patients with congenital anomalies of the kidney and urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney, while moderate, transient, midgestational hypoxia permanently reduced ureteric branching and nephron formation. Both models disp...

Research paper thumbnail of Production and packaging of a biological arsenal: Evolution of centipede venoms under morphological constraint

Proceedings of the National Academy of Sciences, 2015

Research paper thumbnail of lop-DWI: A Novel Scheme for Pre-Processing of Diffusion-Weighted Images in the Gradient Direction Domain

Frontiers in neurology, 2014

We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion... more We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion-gradient directions for high angular resolution diffusion magnetic resonance imaging. Our pre-processing method incorporates prior knowledge about the acquired diffusion-weighted signal, facilitating noise reduction. Periodic spiral sampling of gradient direction encodings results in an acquired signal in each voxel that is pseudo-periodic with characteristics that allow separation of low-frequency signal from high frequency noise. Consequently, it enhances local reconstruction of the orientation distribution function used to define fiber tracks in the brain. Denoising with periodic spiral sampling was tested using synthetic data and in vivo human brain images. The level of improvement in signal-to-noise ratio and in the accuracy of local reconstruction of fiber tracks was significantly improved using our method.

Research paper thumbnail of A proteomics and transcriptomics investigation of the venom from the barychelid spider Trittame loki (brush-foot trapdoor)

Toxins, 2013

Although known for their potent venom and ability to prey upon both invertebrate and vertebrate s... more Although known for their potent venom and ability to prey upon both invertebrate and vertebrate species, the Barychelidae spider family has been entirely neglected by toxinologists. In striking contrast, the sister family Theraphosidae (commonly known as tarantulas), which last shared a most recent common ancestor with Barychelidae over 200 million years ago, has received much attention, accounting for 25% of all the described spider toxins while representing only 2% of all spider species. In this study, we evaluated for the first time the venom arsenal of a barychelid spider, Trittame loki, using transcriptomic, proteomic, and bioinformatic methods. The venom was revealed to be dominated by extremely diverse inhibitor cystine knot (ICK)/knottin peptides, accounting for 42 of the 46 full-length toxin precursors recovered in the transcriptomic sequencing. In addition to documenting differential rates of evolution adopted by different ICK/knottin toxin lineages, we discovered homologu...

Research paper thumbnail of Microscopic diffusion properties of fixed breast tissue: Preliminary findings

Magnetic Resonance in Medicine, 2014

To investigate the microscopic diffusion properties of formalin-fixed breast tissue. Diffusion mi... more To investigate the microscopic diffusion properties of formalin-fixed breast tissue. Diffusion microimaging was performed at 16.4T with 40-μm isotropic voxels on two normal and two cancer tissue samples from four patients. Results were correlated with histology of the samples. Diffusion-weighted images and mean diffusivity maps demonstrated distinct diffusivity differences between breast tissue components. Mean diffusivity (MD) in normal tissue was 0.59 ± 0.24 μm(2) /ms for gland lobule (voxels containing epithelium and intralobular stroma) and 1.23 ± 0.34 μm(2) /ms for interlobular fibrous stroma. In the cancer samples, MD = 0.45 ± 0.23 μm(2) /ms for invasive ductal carcinoma (voxels contain epithelium and intralobular stroma) and 0.61 ± 0.35 μm(2) /ms for ductal carcinoma in situ. There were significant MD differences between all tissue components (P < 0.005), except between gland lobule and ductal carcinoma in situ (P = 0.71). The low diffusivity of epithelium-rich cancer tissue and of normal epithelium relative to its supporting fibrous stroma was similar to that reported for prostate tissue and the esophageal wall. Diffusion microimaging demonstrates distinct diffusivity differences between breast tissue glandular structures. Low diffusivity may be a distinctive feature of mammalian epithelia. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Research paper thumbnail of Visualization of mouse barrel cortex using ex-vivo track density imaging

NeuroImage, 2014

We describe the visualization of the barrel cortex of the primary somatosensory area (S1) of ex v... more We describe the visualization of the barrel cortex of the primary somatosensory area (S1) of ex vivo adult mouse brain with short-tracks track density imaging (stTDI). stTDI produced much higher definition of barrel structures than conventional fractional anisotropy (FA), directionally-encoded color FA maps, spin-echo T1- and T2-weighted imaging and gradient echo T1/T2*-weighted imaging. 3D high angular resolution diffusion imaging (HARDI) data were acquired at 48 micron isotropic resolution for a (3mm)(3) block of cortex containing the barrel field and reconstructed using stTDI at 10 micron isotropic resolution. HARDI data were also acquired at 100 micron isotropic resolution to image the whole brain and reconstructed using stTDI at 20 micron isotropic resolution. The 10 micron resolution stTDI maps showed exceptionally clear delineation of barrel structures. Individual barrels could also be distinguished in the 20 micron stTDI maps but the septa separating the individual barrels appeared thicker compared to the 10 micron maps, indicating that the ability of stTDI to produce high quality structural delineation is dependent upon acquisition resolution. Close homology was observed between the barrel structure delineated using stTDI and reconstructed histological data from the same samples. stTDI also detects barrel deletions in the posterior medial barrel sub-field in mice with infraorbital nerve cuts. The results demonstrate that stTDI is a novel imaging technique that enables three-dimensional characterization of complex structures such as the barrels in S1 and provides an important complementary non-invasive imaging tool for studying synaptic connectivity, development and plasticity of the sensory system.

Research paper thumbnail of lop-DWI: A Novel Scheme for Pre-Processing of Diffusion-Weighted Images in the Gradient Direction Domain

Frontiers in Neurology, 2015

We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion... more We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion-gradient directions for high angular resolution diffusion magnetic resonance imaging. Our pre-processing method incorporates prior knowledge about the acquired diffusion-weighted signal, facilitating noise reduction. Periodic spiral sampling of gradient direction encodings results in an acquired signal in each voxel that is pseudo-periodic with characteristics that allow separation of low-frequency signal from high frequency noise. Consequently, it enhances local reconstruction of the orientation distribution function used to define fiber tracks in the brain. Denoising with periodic spiral sampling was tested using synthetic data and in vivo human brain images. The level of improvement in signal-to-noise ratio and in the accuracy of local reconstruction of fiber tracks was significantly improved using our method.

Research paper thumbnail of Super-resolution track-density imaging studies of mouse brain: Comparison to histology

Research paper thumbnail of Segmentation of the mouse hippocampal formation in magnetic resonance images

Research paper thumbnail of Longitudinal assessment of white matter pathology in the injured mouse spinal cord through ultra-high field (16.4T) in vivo diffusion tensor imaging

Research paper thumbnail of Segmentation of the C57BL/6J mouse cerebellum in magnetic resonance images

Research paper thumbnail of Microscopic diffusivity compartmentation in formalin-fixed prostate tissue

Magnetic Resonance in Medicine, 2012

Research paper thumbnail of Microscopic diffusion anisotropy in formalin fixed prostate tissue: Preliminary findings

Magnetic Resonance in Medicine, 2012

Research paper thumbnail of Acute delivery of EphA4-Fc improves functional recovery after contusive spinal cord injury in rats

Journal of Neurotrauma, 2013

Research paper thumbnail of MRI changes and complement activation correlate with epileptogenicity in a mouse model of temporal lobe epilepsy

Brain Structure and Function, 2014