ORCID Profile
0000-0001-6340-182X
Current Organisations
Public Health Authority
,
University of Queensland
,
University of Sydney
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Animal Physiology - Systems | Clinical Sciences | Radiology and Organ Imaging | Knowledge Representation and Machine Learning | Biological psychology | Biological sciences | Psychology | Biomedical and clinical sciences | Genetics | Neurosciences
Expanding Knowledge in the Information and Computing Sciences | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology |
Publisher: Wiley
Date: 18-05-2023
DOI: 10.1002/NBM.4964
Abstract: Multiple sclerosis (MS) is an autoimmune disease involving demyelination and axonal damage in the central nervous system (CNS). In this study, we investigated pathological changes in the lumbar spinal cord of C57BL/6 mice induced with progressive experimental autoimmune encephalomyelitis (EAE) disease using 9.4‐T magnetic resonance imaging (MRI). Multiparametric MRI measurements including MR spectroscopy, diffusion tensor imaging (DTI) and volumetric analyses were applied to detect metabolic changes in the CNS of EAE mice. Compared with healthy mice, EAE mice showed a significant reduction in N ‐acetyl aspartate and increases in choline, glycine, taurine and lactate. DTI revealed a significant reduction in fractional anisotropy and axial diffusivity and an increase in radial diffusivity in the lumbar spinal cord white matter (WM), while in the grey matter (GM), fractional anisotropy increased. High‐resolution structural imaging also revealed lumbar spinal cord WM hypertrophy and GM atrophy. Importantly, these MRI changes were strongly correlated with EAE disease scoring and pathological changes in the lumbar (L2–L6), particularly WM demyelination lesions and aggregation of immune cells (microglia/macrophages and astrocytes) in this region. This study identified changes in MRI biomarker signatures that can be useful for evaluating the efficacy of novel drugs using EAE models in vivo.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2021
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.MRI.2017.06.012
Abstract: Fetal Alcohol Spectrum Disorders encompass a wide range of birth defects in children born to mothers who consumed alcohol during pregnancy. Typical mental impairments in FASD include difficulties in life adaptation and learning and memory, deficits in attention, visuospatial skills, language and speech disabilities, mood disorders and motor disabilities. Multimodal imaging methods have enabled in vivo studies of the teratogenic effects of alcohol on the central nervous system, giving more insight into the FASD phenotype. This paper offers an up-to-date comprehensive review of radiological findings in the central nervous system in studies of prenatal alcohol exposure in both humans and translational animal models, including Magnetic Resonance Imaging, Computed Tomography, Positron Emission Tomography, Single Photon Emission Tomography and Ultrasonography.
Publisher: Wiley
Date: 20-12-2018
DOI: 10.1002/NBM.3877
Abstract: The availability of high-field-strength magnetic resonance imaging (MRI) systems has brought about the development of techniques that aim to map myelination via the exploitation of various contrast mechanisms. Myelin mapping techniques have the potential to provide tools for the diagnosis and treatment of diseases, such as multiple sclerosis. In this study, we evaluated the sensitivity of T
Publisher: MDPI AG
Date: 13-12-2013
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.NEUROIMAGE.2011.06.003
Abstract: Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Current imaging studies have concentrated on areas of the brain and spinal cord that contain mixed populations of sensory and motor neurons. In this study, ex vivo magnetic resonance microimaging (MRM) was used to separate motor and sensory components by visualizing in idual dorsal and ventral roots in fixed spinal cords. MRM at 15μm in plane resolution enabled the axons of pure populations of sensory and motor neurons to be measured in the lumbar region of the SOD1 mouse model of ALS. MRM signal intensity increased by 38.3% (p<0.05) exclusively in the ventral motor nerve roots of the lumbar spinal cord of ALS-affected SOD1 mice compared to wildtype littermates. The hyperintensity was therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were unchanged. Significant decreases in ventral nerve root volume were also detected in the SOD1 mice, which correlated with the axonal degeneration observed by microscopy. These results demonstrate the usefulness of MRM in visualizing the ultrastructure of the mouse spinal cord. The detailed 3D anatomy allowed the processes of pure populations of sensory and motor neurons to be compared.
Publisher: BMJ
Date: 11-2015
Publisher: Elsevier BV
Date: 2023
Publisher: Springer Science and Business Media LLC
Date: 10-09-2021
Publisher: Springer Science and Business Media LLC
Date: 16-08-2021
DOI: 10.1038/S41597-021-00941-8
Abstract: In a companion paper by Cohen-Adad et al . we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at spine-generic.rtfd.io/ . The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.NEURAD.2017.03.007
Abstract: This study aims to compare the cortical and subcortical deep gray matter (GM) and white matter (WM) of ALS subjects and controls and to compare ALS subjects with (ALScog) and without (ALSnon-cog) cognitive impairment. The study was performed in 30 ALS subjects, and 19 healthy controls. Structural T1- and diffusion-weighted MRI data were analyzed using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). All DTI measures and GM volume differed significantly between ALS subjects and controls. Compared to controls, greater DTI changes were present in ALScog than ALSnon-cog subjects. GM results showed reduction in the caudate nucleus volume in ALScog subjects compared to ALSnon-cog. and comparing all ALS with controls, there were changes on the right side and in a small region in the left middle frontal gyrus. This combined DTI and VBM study showed changes in motor and extra-motor regions. The DTI changes were more extensive in ALScog than ALSnon-cog subjects. It is likely that the inclusion of ALS subjects with cognitive impairment in previous studies resulted in extra-motor WM abnormalities being reported in ALS subjects.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.NEUROIMAGE.2014.07.048
Abstract: In this study we combined ultra-high field diffusion MRI fiber tracking and super-resolution track density imaging (TDI) to map the relay locations and connectivity of the somatosensory pathway in paraformaldehyde fixed, C57Bl/6J mouse brains. Super-resolution TDI was used to achieve 20 μm isotropic resolution to inform the 3D topography of the relay locations including thalamic barreloids and brainstem barrelettes, not described previously using MRI methodology. TDI-guided mapping results for thalamo-cortical connectivity were consistent with thalamo-cortical projections labeled using virus mediated fluorescent protein expression. Trigemino-thalamic TDI connectivity maps were concordant with results obtained using anterograde dye tracing from brainstem to thalamus. Importantly, TDI mapping overcame the constraint of tissue distortion observed in mechanically sectioned tissue, enabling 3D reconstruction and long-range connectivity data. In conclusion, our results showed that diffusion micro-imaging at ultra-high field MRI revealed the stereotypical pattern of somatosensory connectivity and is a valuable tool to complement histologic methods, achieving 3D spatial preservation of whole brain networks for characterization in mouse models of human disease.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1PY00602A
Abstract: Switching on of the 19 F MRI signal via stimuli-responsive release of hydrophobic drug from PEG-based partly-fluorinated polymers due to change in thermoresponsive properties.
Publisher: Wiley
Date: 2009
DOI: 10.1002/NBM.1465
Abstract: Magnetic resonance histology (MRH) has become a widespread tool to examine brain morphology in situ or ex vivo. S les are routinely fixed and stained to allow for longer scan times with increased contrast and resolution. Although the zebrafish is an important model for neuroscience, to date most MRH studies have focused almost exclusively on mice. In this paper, we examined, for the first time, the zebrafish brain using MRH. We compared a range of fixatives, contrast agents, and fixation/staining durations to determine optimal imaging of the zebrafish brain. By quantifying the T(1), T(2), and T(2)* relaxation values, we demonstrated that ethanol and potassium permanganate are unviable for imaging and significant differences exist between mono and di-aldehydes. Furthermore, we compared two commercially available gadolinium-based contrast agents, Magnevist® and Optimark®, at five different concentrations. For both contrast agents, a concentration of 0.5% was determined to be ideal as it significantly shortened the T(1) but maintained a relatively long T(2) and T(2)*. Subsequently, we analyzed the duration of fixation/staining and established a period of 12 h, which best minimized T(1) values but maintained T(2) and T(2)* values. Finally, using this optimized fixation and staining protocol, we performed a gradient-echo T(2)*-weighted imaging to obtain an image set of the adult zebrafish brain at an isotropic resolution of 10 µm.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.NEUROIMAGE.2012.10.075
Abstract: Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. To cause selective basal forebrain cholinergic degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor antibody (mu-p75-SAP) was used. This resulted in ~25% loss of the basal forebrain cholinergic neurons and significant loss of terminal cholinergic projections in the hippoc us, as determined by histology. To test whether lesion of cholinergic neurons caused basal forebrain, hippoc al, or whole brain atrophy, we performed manual segmentation analysis, which revealed no significant atrophy in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI of the basal forebrain area revealed a significant increase in fractional anisotropy (FA +7.7%), mean diffusivity (MD +6.1%), axial diffusivity (AD +8.5%) and radial diffusivity (RD +4.0%) in lesioned mice compared to control animals. These parameters strongly inversely correlated with the number of choline acetyl transferase-positive neurons, with FA showing the greatest association (r(2)=0.72), followed by MD (r(2)=0.64), AD (r(2)=0.64) and RD (r(2)=0.61). Moreover, probabilistic tractography analysis of the septo-hippoc al tracts originating from the basal forebrain revealed an increase in streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates that moderate loss of basal forebrain cholinergic neurons (representing only a minor proportion of all septo-hippoc al axons) can be detected by measuring either DTI parameters of the basal forebrain nuclei or tractography parameters of the basal forebrain tracts. These findings provide increased support for using DTI and probabilistic tractography as non-invasive tools for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer's disease.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Wiley
Date: 06-06-2017
Abstract: Recently, Mn(II)-containing nanoparticles have been explored widely as an attractive alternative to Gd(III)-based T
Publisher: Wiley
Date: 22-12-2022
Abstract: Novel sonosensitizers with intrinsic characteristics for tumor diagnosis, efficient therapy, and tumor microenvironment regulation are appealing in current sonodynamic therapy. Herein, a manganese (Mn)‐layered double hydroxide‐based defect‐rich nanoplatform is presented as a new type of sono‐chemo sensitizer, which allows ultrasound to efficiently trigger reactive oxygen species generation for enhanced sono/chemo‐dynamic therapy. Moreover, such a nanoplatform is able to relieve tumor hypoxia and achieve augmented singlet oxygen production via catalyzing endogenous H 2 O 2 into O 2 . On top of these actions, the released Mn 2+ ions and immune‐modulating agent significantly intensify immune activation and reverse the immunosuppressive tumor microenvironment to the immunocompetent one. Consequently, this nanoplatform exhibits excellent anti‐tumor efficacy and effectively suppresses both primary and distant tumor growth, demonstrating a new strategy to functionalize nanoparticles as sono‐chemo sensitizers for synergistic combination cancer therapy.
Publisher: Frontiers Media SA
Date: 26-05-2016
Publisher: American Chemical Society (ACS)
Date: 29-06-2004
DOI: 10.1021/BI0492105
Abstract: Protein S interacts with activated protein C to play a crucial role in blood anticoagulation, and protein S deficiency is associated with increased risk of thrombosis. Despite the large volume of functional data available for this protein, no atomic resolution structure data have yet been reported. This is due at least in part to difficulties encountered when trying to produce fragments dissected from the intact protein however, a few successful strategies have been described. In this research we have expressed a number of constructs containing protein S epidermal growth factor-like (EGF) domains 1 and 2 in Escherichia coli and Pichia pastoris. None of the proteins produced was stably folded as assayed by solution nuclear magnetic resonance spectroscopy. We therefore constructed a series of non-native protein S EGF concatemers to investigate the role of pairwise domain linkage in domain folding. Our results demonstrate that N-terminal domain linkage can either positively or negatively impact on the refolding of an adjacent domain. Furthermore, analysis of the NMR data for EGF3-4 reveals the expected interdomain NOEs that are characteristic of an extended arrangement of calcium-binding EGF domains and a similar average [(1)H]-(15)N heteronuclear NOE value for each of the two domains. These results provide the first data in support of protein S EGF3-4 adopting the same extended domain orientation as observed for the functionally distinct proteins fibrillin-1 and the low-density lipoprotein receptor. The results also have important implications for future studies, particularly when a dissection approach is used, of tandem EGF domains from protein S and other proteins.
Publisher: Wiley
Date: 23-06-2013
DOI: 10.1002/NBM.2829
Abstract: The main aim of this study was to employ high-resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.4-T small-animal MR system was employed for nondestructive imaging of post-mortem, fixed spinal cord specimens at the subacute (7 days) and more chronic (28-35 days) stages post-injury. Routine histological techniques were used for subsequent investigation of the observed neuropathology at the microscopic level. The central core of the lesion appeared as a dark hypo-intense area on MR images at all time points investigated. Small focal hypo-intense spots were also observed spreading through the dorsal funiculi proximal and distal to the site of impact, an area that is known to undergo gliosis and Wallerian degeneration in response to injury. Histological examination revealed these hypo-intense spots to be high in iron content as determined by Prussian blue staining. Quantitative image analysis confirmed the increased presence of iron deposits at all post-injury time points investigated (p<0.05). Distant iron deposits were also detectable through live imaging without the use of contrast-enhancing agents, enabling the longitudinal investigation of this pathology in in idual animals. Further immunohistochemical evaluation showed that intracellular iron deposits localised to macrophages/microglia, astrocytes and oligodendrocytes in the subacute phase of SCI, but predominantly to glial fibrillary acidic protein-positive, CC-1-positive astrocytes at later stages of recovery. Progressive, widespread intracellular iron accumulation is thus a normal feature of SCI in mice, and high-resolution MRI can be effectively used to detect and monitor these neuropathological changes with time.
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.CUB.2021.10.070
Abstract: Octopods are masters of camouflage and solve complex tasks, and their cognitive ability is said to approach that of some small mammals. Despite intense interest and some research progress, much of our knowledge of octopus neuroanatomy and its links to behavior and ecology comes from one coastal species, the European common octopus, Octopus vulgaris. Octopod species are found in habitats including complex coral reefs and the relatively featureless mid-water. There they encounter different selection pressures, may be nocturnal or diurnal, and are mostly solitary or partially social. How these different ecologies and behavioral differences influence the octopus central nervous system (CNS) remains largely unknown. Here we present a phylogenetically informed comparison between diurnal and nocturnal coastal and a deep-sea species using brain imaging techniques. This study shows that characteristic neuroanatomical changes are linked to their habits and habitats. Enlargement and ision of the optic lobe as well as structural foldings and complexity in the underlying CNS are linked to behavioral adaptation (diurnal versus nocturnal social versus solitary) and ecological niche (reef versus deep sea), but phylogeny may play a part also. The difference between solitary and social life is mirrored within the brain including the formation of multiple compartments (gyri) in the vertical lobe, which is likened to the vertebrate cortex. These findings continue the case for convergence between cephalopod and vertebrate brain structure and function. Notably, within the current push toward comparisons of cognitive abilities, often with unashamed anthropomorphism at their root, these findings provide a firm grounding from which to work.
Publisher: MDPI AG
Date: 15-09-2021
DOI: 10.3390/NU13093199
Abstract: Background: We aimed to estimate the burden and underlying risk factors of malnutrition among children and adolescents with cerebral palsy in Arabic-speaking countries. Methods: OVID Medline, OVID Embase, CINAHL via EBSCO, Cochrane Library, and SCOPUS databases were searched up to 3 July 2021. Publications were reviewed to identify relevant papers following pre-defined inclusion/exclusion criteria. Two reviewers independently assessed the studies for inclusion. Data extraction was independently completed by two reviewers. Descriptive and pooled analysis has been reported. Results: From a total of 79 records screened, nine full-text articles were assessed for eligibility, of which seven studies met the inclusion criteria. Study characteristics, anthropometric measurements used, and nutritional outcome reported varied between the studies. The included studies contained data of total 400 participants aged 1–18 years. Overall, (mean: 71.46%, 95% confidence interval: 55.52–85.04) of children with cerebral palsy had at least one form of malnutrition. Severe gross motor function limitation, feeding difficulties, cognitive impairment and inadequate energy intake were the commonly reported underlying risk factors for malnutrition among children with cerebral palsy. Conclusions: The burden of malnutrition is high among children with cerebral palsy in Arabic-speaking countries. More research is needed for better understanding of this public health issue in these countries.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.NEUROIMAGE.2013.06.019
Abstract: This study examined the sensitivity of ultra-high field (16.4 T) diffusion tensor imaging (DTI 70 μm in-plane resolution, 1mm slice thickness) to evaluate the spatiotemporal development of severe mid-thoracic contusive spinal cord injury (SCI) in mice. In vivo imaging was performed prior to SCI, then again at 2h, 1 day, 3 days, 7 days, and 30 days post-SCI using a Bruker 16.4 T small animal nuclear magnetic resonance spectrometer. Cross-sectional spinal cord areas were measured in axial slices and various DTI parameters, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ||) and radial diffusivity (λ⊥), were calculated for the total spared white matter (WM), ventral funiculi (VF), lateral funiculi (LF) and dorsal columns (DCs) and then correlated with histopathology. Cross-sectional area measurements revealed significant atrophy (32% reduction) of the injured spinal cord at the lesion epicentre in the chronic phase of injury. Analysis of diffusion tensor parameters further showed that tissue integrity was most severely affected in the DCs, i.e. the site of immediate impact, which demonstrated a rapid and permanent decrease in FA and λ||. In contrast, DTI parameters for the ventrolateral white matter changed more gradually with time, suggesting that these regions are undergoing more delayed degeneration in a manner that may be amenable to therapeutic intervention. Of all the DTI parameters, λ⊥ was most closely correlated to myelin content whereas changes in FA and λ|| appeared more indicative of axonal integrity, Wallerian degeneration and associated presence of macrophages. We conclude that longitudinal DTI at 16.4T provides a clinically relevant, objective measure for assessing white matter pathology following contusive SCI in mice that may aid the translation of putative neuroprotective strategies into the clinic.
Publisher: Springer Science and Business Media LLC
Date: 12-02-2021
DOI: 10.1038/S41598-021-81362-W
Abstract: The subiculum is the major output component of the hippoc al formation and one of the major brain structures most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippoc al longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.NEUROIMAGE.2011.06.025
Abstract: The hippoc al formation plays an important role in cognition, spatial navigation, learning, and memory. High resolution magnetic resonance (MR) imaging makes it possible to study in vivo changes in the hippoc us over time and is useful for comparing hippoc al volume and structure in wild type and mutant mice. Such comparisons demand a reliable way to segment the hippoc al formation. We have developed a method for the systematic segmentation of the hippoc al formation using the perfusion-fixed C57BL/6 mouse brain for application in longitudinal and comparative studies. Our aim was to develop a guide for segmenting over 40 structures in an adult mouse brain using 30 μm isotropic resolution images acquired with a 16.4 T MR imaging system and combined using super-resolution reconstruction.
Publisher: Oxford University Press (OUP)
Date: 14-11-2020
Abstract: Genetic association studies have identified many factors associated with neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the way these genes shape neuroanatomical structure and connectivity is poorly understood. Recent research has focused on proteins that act as points of convergence for multiple factors, as these may provide greater insight into understanding the biology of neurodevelopmental disorders. USP9X, a deubiquitylating enzyme that regulates the stability of many ASD-related proteins, is one such point of convergence. Loss of function variants in human USP9X lead to brain malformations, which manifest as a neurodevelopmental syndrome that frequently includes ASD, but the underlying structural and connectomic abnormalities giving rise to patient symptoms is unknown. Here, we analyzed forebrain-specific Usp9x knockout mice (Usp9x−/y) to address this knowledge gap. Usp9x−/y mice displayed abnormal communication and social interaction behaviors. Moreover, the absence of Usp9x culminated in reductions to the size of multiple brain regions. Diffusion tensor magnetic resonance imaging revealed deficits in all three major forebrain commissures, as well as long-range hypoconnectivity between cortical and subcortical regions. These data identify USP9X as a key regulator of brain formation and function, and provide insights into the neurodevelopmental syndrome arising as a consequence of USP9X mutations in patients.
Publisher: Wiley
Date: 25-05-2016
DOI: 10.1002/ACN3.318
Publisher: Wiley
Date: 09-12-2012
DOI: 10.1002/MRM.23291
Abstract: Magnetic resonance microimaging was used to measure diffusion decay over an extended b-factor range in a formalin-fixed normal prostate s le and a Gleason pattern 3+4 cancer tissue s le. The coefficients of biexponential fits to diffusion decay data from 1600 voxels of dimension 160 × 160 × 160 μm(3) in each s le were correlated with underlying epithelial and stromal compartment partial volumes estimated from high-resolution apparent diffusion coefficient (ADC) data (40 × 40 × 40 μm(3) voxels) from the same tissue. In the normal tissue s le, the signal fractions of the low and high ADC components of the biexponential fits correlated linearly with partial volumes of epithelial tissue (R(2) = 0.6) and stromal tissue (R(2) = 0.5), respectively. Similar but weaker correlations were observed in the cancer s le. Epithelium-containing high spatial resolution voxels appeared to be composed of ∼60% low ADC and ∼40% high ADC component. Stromal voxels appeared to be composed of ∼20% low ADC and ∼80% high ADC component. This preliminary report suggests that distinctly different diffusion properties in microscopically adjacent cell types contribute to the multiexponential diffusion decay phenomenon in prostate tissue.
Publisher: Elsevier BV
Date: 2019
Publisher: Frontiers Media SA
Date: 21-04-2023
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.NEUROIMAGE.2013.09.030
Abstract: 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. In idual barrels could also be distinguished in the 20 micron stTDI maps but the septa separating the in idual 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 s les. 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.
Publisher: Wiley
Date: 05-2018
DOI: 10.14814/PHY2.13699
Publisher: Wiley
Date: 05-03-2006
DOI: 10.1002/0470028637.MET048
Abstract: Epidermal growth factor‐like (EGF) domains are one of the more abundant modules found in functionally erse extracellular proteins. The domain is characterized by six cysteine residues, which normally disulphide bond in a 1–3, 2–4, 5–6 pattern. A particular subset (cbEGF) contains the consensus sequence [DEQN]‐x‐[DEQN] 2 ‐x m ‐[DN]*‐x n ‐[YF] (where m and n are variables and * indicates possible β‐hydroxylation) associated with the ability to bind calcium. At present, cbEGFs have three main functional roles, as a spacer unit, in protein–protein interactions, and in structural stabilization. High‐resolution structures of cbEGF domains have identified a common fold, comprising a major and a minor double‐stranded β‐hairpin, stabilized by the three consensus disulphide bonds. A single calcium ion binds to the amino terminus and is coordinated by a pentagonal bipyramidal arrangement of oxygen atoms. Each in idual cbEGF domain contains a calcium‐binding site, whose affinity may be considerably enhanced by N‐terminal linkage to another domain. A number of inherited diseases caused by missense mutations within cbEGFs highlight the importance of the domain.
Publisher: MDPI AG
Date: 22-10-2018
DOI: 10.3390/MOLECULES23102715
Abstract: μ-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution structure of μ-conotoxin GIIIC was determined using 2D NMR spectroscopy and simulated annealing calculations. Despite high sequence similarity, GIIIC adopts a three-dimensional structure that differs from the previously observed conformation of μ-conotoxins GIIIA and GIIIB due to the presence of a bulky, non-polar leucine residue at position 18. The side chain of L18 is oriented towards the core of the molecule and consequently the N-terminus is re-modeled and located closer to L18. The functional characterization of GIIIC defines it as a canonical μ-conotoxin that displays substantial selectivity towards skeletal muscle sodium channels (NaV), albeit with ~2.5-fold lower potency than GIIIA. GIIIC exhibited a lower potency of inhibition of NaV1.4 channels, but the same NaV selectivity profile when compared to GIIIA. These observations suggest that single amino acid differences that significantly affect the structure of the peptide do in fact alter its functional properties. Our work highlights the importance of structural factors, beyond the disulfide pattern and electrostatic interactions, in the understanding of the functional properties of bioactive peptides. The latter thus needs to be considered when designing analogues for further applications.
Publisher: Elsevier BV
Date: 12-2023
Publisher: Springer Science and Business Media LLC
Date: 02-02-2019
DOI: 10.1007/S00429-019-01840-W
Abstract: Converging evidence from human and animal studies support an association between vitamin D deficiency and cognitive impairment. Previous studies have shown that hippoc al volume is reduced in adults with vitamin D deficiency as well as in a range of disorders, such as schizophrenia. The aim of the current study was to examine the effect of adult vitamin D (AVD) deficiency on hippoc al-dependent spatial learning, and hippoc al volume and connectivity in healthy adult mice. Ten-week-old male BALB/c mice were fed a control (vitamin D 1500 IU/kg) or vitamin D-depleted (vitamin D 0 IU/kg) diet for a minimum of 10 weeks. The mice were then tested for hippoc al-dependent spatial learning using active place avoidance (APA) and on tests of muscle and motor coordination (rotarod and grip strength). The mice were perfused and brains collected to acquire ex vivo structural and diffusion-weighted images using a 16.4 T MRI scanner. We also performed immunohistochemistry to quantify perineuronal nets (PNNs) and parvalbumin (PV) interneurons in various brain regions. AVD-deficient mice had a lower latency to enter the shock zone on APA, compared to control mice, suggesting impaired hippoc al-dependent spatial learning. There were no differences in rotarod or grip strength, indicating that AVD deficiency did not have an impact on muscle or motor coordination. AVD deficiency did not have an impact on hippoc al volume. However, AVD-deficient mice displayed a disrupted network centred on the right hippoc us with abnormal connectomes among 29 nodes. We found a reduction in PNN positive cells, but no change in PV, centred on the hippoc us. Our results provide compelling evidence to show that AVD deficiency in otherwise healthy adult mice may play a key role in hippoc al-dependent learning and memory formation. We suggest that the spatial learning deficits could be due to the disruption of right hippoc al structural connectivity.
Publisher: Wiley
Date: 08-02-2011
DOI: 10.1002/MRM.22778
Abstract: Diffusion tensor microimaging was used to investigate the water diffusion properties of formalin-fixed prostate tissue at spatial resolution approaching the cellular scale. Diffusion tensor microimaging was performed at 16.4 T with 40 μm isotropic voxels. Diffusion tensor microimaging clearly demonstrated distinct microscopic diffusion environments and tissue architecture consistent with that seen on light microscopy of the same tissue. The most restricted diffusion environment is the secretory epithelial cell layer (voxel bulk mean diffusivity, D = 0.4 ± 0.1 × 10(-3) mm(2)/sec). Diffusion in the fibromuscular stromal matrix is relatively less restricted (D = 0.7 ± 0.1 × 10(-3) mm(2)/sec). In tumor tissue (Gleason pattern 4+4) distinct glandular and ductal structures are absent in the diffusion-weighted images and diffusivity is low (D = 0.5 ± 0.1 × 10(-3) mm(2)/sec). Distinct stromal and epithelial diffusion compartments are the most likely origin of biexponential diffusion decay observed in vivo.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.NEUROIMAGE.2013.04.008
Abstract: The neocortex is the largest component of the mammalian cerebral cortex. It integrates sensory inputs with experiences and memory to produce sophisticated responses to an organism's internal and external environment. While areal patterning of the mouse neocortex has been mapped using histological techniques, the neocortex has not been comprehensively segmented in magnetic resonance images. This study presents a method for systematic segmentation of the C57BL/6J mouse neocortex. We created a minimum deformation atlas, which was hierarchically segmented into 74 neocortical and cortical-related regions, making it the most detailed atlas of the mouse neocortex currently available. In addition, we provide mean volumes and relative intensities for each structure as well as a nomenclature comparison between the two most cited histological atlases of the mouse brain. This MR atlas is available for download, and it should enable researchers to perform automated segmentation in genetic models of cortical disorders.
Publisher: Oxford University Press (OUP)
Date: 05-2016
DOI: 10.1093/JTM/TAW046
Publisher: Public Library of Science (PLoS)
Date: 25-06-2015
Publisher: Springer Science and Business Media LLC
Date: 10-03-2014
DOI: 10.1007/S00429-013-0528-4
Abstract: The complex pathogenesis of temporal lobe epilepsy includes neuronal and glial pathology, synaptic reorganization, and an immune response. However, the spatio-temporal pattern of structural changes in the brain that provide a substrate for seizure generation and modulate the seizure phenotype is yet to be completely elucidated. We used quantitative magnetic resonance imaging (MRI) to study structural changes triggered by status epilepticus (SE) and their association with epileptogenesis and with activation of complement component 3 (C3). SE was induced by injection of pilocarpine in CD1 mice. Quantitative diffusion-weighted imaging and T2 relaxometry was performed using a 16.4-Tesla MRI scanner at 3 h and 1, 2, 7, 14, 28, 35, and 49 days post-SE. Following longitudinal MRI examinations, spontaneous recurrent seizures and interictal spikes were quantified using continuous video-EEG monitoring. Immunohistochemical analysis of C3 expression was performed at 48 h, 7 days, and 4 months post-SE. MRI changes were dynamic, reflecting different outcomes in relation to the development of epilepsy. Apparent diffusion coefficient changes in the hippoc us at 7 days post-SE correlated with the severity of the evolving epilepsy. C3 activation was found in all stages of epileptogenesis within the areas with significant MRI changes and correlated with the severity of epileptic condition.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-03-2013
Publisher: Public Library of Science (PLoS)
Date: 11-06-2013
Publisher: Wiley
Date: 07-09-2010
Publisher: The Company of Biologists
Date: 2019
DOI: 10.1242/DEV.181933
Abstract: During development, the p75 neurotrophin receptor (p75NTR) is widely expressed in the nervous system where it regulates neuronal differentiation, migration and axonal outgrowth. p75NTR also mediates the survival and death of newly born neurons, with functional outcomes being dependent on both timing and cellular context. Here we show that knockout of p75NTR from embryonic day 10 (E10) in neural progenitors using a conditional Nestin-Cre p75NTR floxed mouse causes increased apoptosis of progenitor cells. By E14.5, the number of Tbr2-positive progenitor cells was significantly reduced and the rate of neurogenesis was halved. Furthermore, in adult knockout mice, there were fewer cortical pyramidal neurons, interneurons, cholinergic basal forebrain neurons, and striatal neurons, corresponding to a relative reduction in volume of these structures. Thalamic midline fusion during early postnatal development was also impaired in Nestin-Cre p75NTR floxed mice, indicating a novel role of p75NTR in the formation of this structure. The phenotype of this strain demonstrates that p75NTR regulates multiple aspects of brain development, including cortical progenitor cell survival, and that expression during early neurogenesis is required for appropriate formation of telencephalic structures.
Publisher: Informa UK Limited
Date: 23-03-2013
DOI: 10.1271/BBB.120682
Abstract: Because sucrose stored in mature stalks (in excess of 40% of stalk dry weight) can be wholly mobilized to supply carbon for the growth of heterotrophic tissues, we propose that sucrose mobilization requires a net sink-to-source transition that acts in toto within sett internode storage parenchyma. Based on our data we propose that mobilization of sucrose from culm storage parenchyma requires minimal investment of metabolic resources, and that the mechanism of sucrose mobilization is metabolically neutral. By magnetic resonance spectroscopy and phloem-specific tracer dyes, strong evidence was found that sucrose is mobilized from sett storage parenchyma via phloem to the growing shoot tissue. An analysis of the enzyme activities involved in sucrose metabolism and glycolysis suggested that sucrose synthase activity is downregulated due to the effects of sucrose mobilization. Overall, metabolism in storage parenchyma shifts from futile cycling to a more quiescent state during sucrose mobilization.
Publisher: Elsevier BV
Date: 08-2001
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.NEUROIMAGE.2010.01.086
Abstract: In the past three decades, the zebrafish has become a vital animal model in a range of biological sciences. To augment current neurobiological research, we have developed the first three-dimensional digital atlas of the zebrafish brain from T2-weighted magnetic resonance histology (MRH) images acquired on a 16.4-T superconducting magnet. We achieved an isotropic resolution of 10 microm, which is the highest resolution achieved in a vertebrate brain and, for the first time, is comparable in slice thickness to conventional histology. By using manual segmentation, 53 anatomical structures, including fiber tracts as small as 40 microm, were delineated. Using Amira software, structures were also in idually segmented and reconstructed to create three-dimensional animations. Additional quantitative information including, volume, surface areas, and mean gray scale intensities were also determined. Finally, we established a stereotaxic coordinate system as a framework in which maps created from other modalities can be incorporated into the atlas.
Publisher: MDPI AG
Date: 29-06-2022
Abstract: Background: Studies on cerebral palsy among children and adolescents in Arabic-speaking countries are scarce. In this systematic review, we aimed to describe the epidemiology of cerebral palsy among children and adolescents in Arabic-speaking countries in terms of prevalence, risk factors, motor types, and rehabilitation. Methods: Six key bibliographic databases were searched for relevant literature published to 17 July 2021. Titles and abstracts were screened for potential inclusion and two independent reviewers screened the full texts of potential articles following pre-defined inclusion/exclusion criteria. The included studies were evaluated independently by three reviewers. The risk of bias was assessed, and data were extracted and analysed. Results: A total of 32 studies from 7 countries met our inclusion criteria. The prevalence of cerebral palsy in Arabic-speaking countries was 1.8/1000 live births (95% CI: 1.2–2.5). Spastic cerebral palsy was the most common motor type, representing 59.8% (95% CI: 46.2–72.7) of pooled estimates. This included children with spastic quadriplegia, diplegia, and hemiplegia 25.1% (95% CI: 18.2–32.8), 16.2% (95% CI: 11.4–23.3), and 10.4% (95% CI: 7.3–13.8), respectively. Consanguinity was high and represented 37.7% (95% CI: 29.3–46.6). Only one included study reported the types of rehabilitation received (e.g., physiotherapy and assistance devices). Conclusions: This paper provides a summary of the epidemiology of cerebral palsy in Arabic-speaking countries and highlights areas for future research. There is still a substantial knowledge gap on the epidemiology of cerebral palsy in these regions. Countries in the Arab region should follow ex les of countries that have successfully established cerebral palsy registries to generate evidence on epidemiology of cerebral palsy and opportunities for prevention.
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 07-2020
Publisher: Mary Ann Liebert Inc
Date: 15-04-2018
Abstract: Traumatic brain injury (TBI) is associated with gray and white matter alterations in brain tissue. Gray matter alterations are not yet as well studied as those of the white matter counterpart. This work utilized T2-weighted structural imaging, diffusion tensor imaging (DTI), and diffusion kurtosis imaging to unveil the gray matter changes induced in a controlled cortical impact (CCI) mouse model of TBI at 5 h, 1 day, 3 days, 7 days, 14 days, and 30 days post-CCI. A cross-sectional histopathology approach was used to confer validity of the magnetic resonance imaging (MRI) data by performing cresyl violet staining and glial fibrillary acidic protein (GFAP) immunohistochemistry. The results demonstrated a significant increase in lesion volume up to 3 days post-injury followed by a significant decrease in the cavity volume for the period of 1 month. GFAP signals peaked on Day 7 and persisted until Day 30 in both ipsilateral and contralateral hippoc us, ipsilateral cortex, and thalamic areas. An increase in fractional anisotropy (FA) was seen at Day 7 in the pericontusional area but decreased FA in the contralateral cortex, hippoc us, and thalamus. Mean diffusivity (MD) was significantly lower in the pericontusional cortex. Increased MD and decreased mean kurtosis were limited to the injury site on Days 7 to 30 and to the contralateral hippoc us and thalamus on Days 3 and 7. This work is one of the few cross-sectional studies to demonstrate a link between MRI measures and histopathological readings to track gray matter changes in the progression of TBI.
Publisher: MDPI AG
Date: 19-05-2017
Publisher: Springer Science and Business Media LLC
Date: 06-07-2010
DOI: 10.1186/BCR2603
Publisher: Springer New York
Date: 2018
DOI: 10.1007/978-1-4939-7531-0_21
Abstract: Magnetic Resonance Imaging (MRI) is an important tool to study various animal models of degenerative diseases. This chapter describes routine protocols of T
Publisher: Springer Science and Business Media LLC
Date: 22-02-2019
Publisher: Wiley
Date: 11-06-2015
DOI: 10.1002/HBM.22872
Publisher: Informa UK Limited
Date: 03-10-2019
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BIOMATERIALS.2018.05.055
Abstract: Non-invasive imaging-guided tumor therapy requires new-generation bio-nanomaterials to sensitively respond to the unique tumor microenvironment for precise diagnosis and efficient treatment. Here, we report such a theranostic nanoplatform by engineering defect-rich multifunctional Cu-doped layered double hydroxide (Cu-LDH) nanoparticles, which integrates pH-sensitive T
Publisher: sPage.direcT
Date: 21-04-2022
DOI: 10.36959/524/331
Publisher: BMJ
Date: 06-2016
Publisher: Proceedings of the National Academy of Sciences
Date: 05-11-2013
Abstract: The gene responsible for the X-linked form of Opitz syndrome (OS), Midline-1 ( MID1 ), encodes an E3 ubiquitin ligase and was reported to guide the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). But whether and how it is involved in neural development is unclear. We demonstrate here that Mid1-dependent PP2Ac turnover is involved in axon development. Knocking down or knocking out Mid1 not only promotes axon growth and branching in vitro, but also accelerates axon elongation and disrupts the pattern of callosal projection in mouse cortex. These defects can be reversed by down-regulating the accumulated PP2Ac in Mid1-depleted cells. Dysfunction of this Mid1–PP2Ac pathway may underlie neural symptoms of OS patients.
Publisher: Wiley
Date: 16-03-2007
Abstract: In this paper we report the preparation and characterization of [Gd(dtpa)](2-) intercalated layered double hydroxide (LDH) nanomaterials. [Gd(dtpa)](2-) (gadolinium(III) diethylene triamine pentaacetate) was transferred into LDH by anionic exchange. The intercalation of [Gd(dtpa)](2-) into LDH was confirmed by X-ray diffraction for the new phase with the interlayer spacing of 3.5-4.0 nm and by FTIR for the characteristic vibration peaks of [Gd(dtpa)](2-). The morphology of the nanoparticles was influenced by the extent of [Gd(dtpa)](2-) loading, in which the poly-dispersity quality decreased as the [Gd(dtpa)](2-) loading was increased. Compared with the morphology of the original Mg(2)Al-Cl-LDH nanoparticles (hexagonal plate-like sheets of 50-200 nm), the modified LDH-Gd(dtpa) nanoparticles are bar-like with a width of 30-60 nm and a length of 50-150 nm. LDH-Gd(dtpa) was expected to have an increased water proton magnetic resonance relaxivity due to the intercalation of [Gd(dtpa)](2-) into the LDH interlayer that led to slower molecular anisotropic tumbling compared with free [Gd(dtpa)](2-) in solution. Indeed, LDH-nanoparticle suspension containing approximately 1.6 mM [Gd(dtpa)](2-) exhibits a longitudinal proton relaxivity r(1) of approximately 16 mM(-1) s(-1) and a transverse proton relaxivity r(2) of approximately 50 mM(-1) s(-1) at room temperature and a magnetic field of 190 MHz, which represents an enhancement four times (r(1)) and 12 times (r(2)) that of free [Gd(dtpa)](2-) in solution under the same reaction conditions. We have thus tailored LDH-nanoparticles into a novel contrast agent with strong relaxivity, promising for great potential applications in magnetic resonance imaging.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.BBR.2012.02.007
Abstract: Evidence from epidemiology suggests that developmental vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in rats is associated with altered brain morphology and enhanced hyperlocomotion in response to MK-801 and hetamine. The aim of this study was to determine if similar phenotypes were associated with DVD deficiency in two strains of mice (C57BL/6J, 129/X1SvJ). Brains from neonatal (P0) and adult (P70) mice were imaged using MRI and the volumes of the cerebrum, hippoc us, striatum, septum, cortex and ventricles measured, as well as the widths of white matter tracts. Locomotor sensitivity to 5mg/kg d- hetamine, 0.5mg/kg MK-801 or saline was examined in a separate group of mice in an open field. DVD deficiency altered brain morphology in C57BL6/J mice, such that C57BL/6J female DVD-deficient neonatal mice had a smaller hippoc us compared to female controls. In addition, adult C57BL/6J male DVD-deficient mice had smaller lateral ventricles compared to controls, which may have been compressed by the enlarged striatum seen in these DVD-deficient mice. However, in contrast to the behavioural phenotypes found in DVD-deficient rats, there was no significant effect of maternal diet on hetamine or MK-801-induced locomotion in either strain. These data indicate that not only species, but also strain of mouse, moderates the impact of DVD deficiency on neuroanatomical and behavioural phenotypes in rodent animal models.
Publisher: Future Medicine Ltd
Date: 07-2014
DOI: 10.2217/FNL.14.33
Abstract: ABSTRACT: MRI is a key radiological imaging technique that plays an important role in the diagnosis and characterization of heterogeneous multiple sclerosis (MS) lesions. Various MRI methodologies such as conventional T 1 /T 2 contrast, contrast agent enhancement, diffusion-weighted imaging, magnetization transfer imaging and susceptibility weighted imaging have been developed to determine the severity of MS pathology, including demyelination/remyelination and brain connectivity impairment from axonal loss. The broad spectrum of MS pathology manifests in erse patient MRI presentations and affects the accuracy of patient diagnosis. To study specific pathological aspects of the disease, rodent models such as experimental autoimmune encephalomyelitis, virus-induced and toxin-induced demyelination have been developed. This review aims to present key developments in MRI methodology for better characterization of rodent models of MS.
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.NTT.2019.106849
Abstract: This study investigated the effects of early moderate prenatal ethanol exposure (PEE) on the brain in a mouse model that mimics a scenario in humans, whereby moderate daily drinking ceases after a woman becomes aware of her pregnancy. C57BL/6J pregnant mice were given 10% v/v ethanol from gestational day 0-8 in the drinking water. The male offspring were used for imaging. Anatomical and diffusion Magnetic Resonance Imaging were performed in vivo at postnatal day 28 (P28, adolescence) and P80 (adulthood). Micro-Computed Tomography was performed on fixed whole heads at P80. Tensor-based morphometry (TBM) was applied to detect alterations in brain structure and voxel-based morphometry (VBM) for skull morphology. Diffusion tensor and neurite orientation dispersion and density imaging models were used to detect microstructural changes. Neurofilament (NF) immunohistochemistry was used to validate findings by in vivo diffusion MRI. TBM showed that PEE mice exhibited a significantly smaller third ventricle at P28 (family-wise error rate (FWE), p < 0.05). All other macro-structural alterations did not survive FWE corrections but when displayed with an uncorrected p < 0.005 showed multiple regional volume reductions and expansions, more prominently in the right hemisphere. PEE-induced gross volume changes included a bigger thalamus, hypothalamus and ventricles at P28, and bigger total brain volumes at both P28 and P80 (2-s le t-tests). Disproportionately smaller olfactory bulbs following PEE were revealed at both time-points. No alterations in diffusion parameters were detected, but PEE animals exhibited reduced NF positive staining in the thalamus and striatum and greater bone density in various skull regions. Our results show that early moderate PEE can cause alterations in the brain that are detectable during development and adulthood.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.NEUROIMAGE.2016.06.037
Abstract: Social experience is essential for adolescent development and plasticity of social animals. Deprivation of the experience by social isolation impairs white matter microstructures in the prefrontal cortex. However, the effect of social isolation may involve highly distributed brain networks, and therefore cannot be fully explained by a change of a single region. Here, we compared the connectomes of adolescent socially-isolated mice and normal-housed controls via diffusion magnetic resonance imaging. The isolated mice displayed an abnormal connectome, characterized by an increase in degree and reductions in measures such as modularity, small-worldness, and betweenness. The increase in degree was most evident in the dorsolateral orbitofrontal cortex, entorhinal cortex, and perirhinal cortex. In a connection-wise comparison, we revealed that most of the abnormal edges were inter-modular and inter-hemispheric connections of the dorsolateral orbitofrontal cortex. Further tractography-based analyses and histological examinations revealed microstructural changes in the forceps minor and lateral-cortical tracts that were associated with the dorsolateral orbitofrontal cortex. These changes of connectomes were correlated with fear memory deficits and hyper-locomotion activities induced by social isolation. Considering the key role of the orbitofrontal cortex in social behaviors, adolescent social isolation may primarily disrupt the orbitofrontal cortex and its neural pathways thereby contributing to an abnormal structural connectome.
Publisher: Proceedings of the National Academy of Sciences
Date: 04-09-2018
Abstract: The neocortex is a hallmark of mammalian evolution, and connections between both hemispheres integrate bilateral functions. In eutherians (e.g., rodents and humans), interhemispheric circuits course via the corpus callosum and share a similar connectome throughout species. Noneutherian mammals (i.e., monotremes and marsupials), however, did not evolve a corpus callosum therefore, whether the eutherian connectome arose as consequence of callosal evolution or instead reflects ancient connectivity principles remains unknown. We studied monotreme and marsupial interhemispheric neocortical connectomes and compared these with eutherian datasets. This revealed interhemispheric connectivity features shared across mammals, with or without a corpus callosum, suggesting that an ancient connectome originated at least 80 million years before callosal evolution.
Publisher: Wiley
Date: 2000
DOI: 10.1110/PS.9.7.1282
Abstract: The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40-45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB(1-2)) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB(1-2) has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and H alpha chemical shifts and the low phi and psi angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB(1-2) structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.
Publisher: Wiley
Date: 05-03-2011
DOI: 10.1002/9781119951438.EIBC0513
Abstract: Epidermal growth factor‐like (EGF) domains are one of the more abundant modules found in functionally erse extracellular proteins. The domain is characterized by six cysteine residues, which normally disulphide bond in a 1–3, 2–4, 5–6 pattern. A particular subset (cbEGF) contains the consensus sequence [DEQN]‐x‐[DEQN] 2 ‐x m ‐[DN]*‐x n ‐[YF] (where m and n are variables and * indicates possible β‐hydroxylation) associated with the ability to bind calcium. At present, cbEGFs have three main functional roles, as a spacer unit, in protein–protein interactions, and in structural stabilization. High‐resolution structures of cbEGF domains have identified a common fold, comprising a major and a minor double‐stranded β‐hairpin, stabilized by the three consensus disulphide bonds. A single calcium ion binds to the amino terminus and is coordinated by a pentagonal bipyramidal arrangement of oxygen atoms. Each in idual cbEGF domain contains a calcium‐binding site, whose affinity may be considerably enhanced by N‐terminal linkage to another domain. A number of inherited diseases caused by missense mutations within cbEGFs highlight the importance of the domain.
Publisher: Springer Science and Business Media LLC
Date: 07-11-2013
Publisher: Frontiers Media SA
Date: 2014
Publisher: Elsevier BV
Date: 09-2020
DOI: 10.1016/J.NUCMEDBIO.2020.07.005
Abstract: Prenatal ethanol exposure (PEE) has been shown to alter the level and function of receptors in the brain, one of which is GABA C57BL/6J mice were given 10% v/v ethanol during the first 8 gestational days. Male offspring were studied using in-vivo Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI), biodistribution, in-vitro autoradiography using [ In vivo PET and biodistribution did not detect alteration in brain tracer uptake. In vitro radiotracer studies detected significantly reduced GABA Early moderate PEE may induce long-term alterations in the GABA
Publisher: Springer Science and Business Media LLC
Date: 03-04-2015
Publisher: American Chemical Society (ACS)
Date: 02-09-2021
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.NEUROIMAGE.2011.07.014
Abstract: The recently proposed track-density imaging (TDI) technique was introduced as a means to achieve super-resolution using diffusion MRI. This technique is able to increase the spatial resolution of the reconstructed images beyond the acquired MRI resolution by incorporating information from whole-brain fibre-tracking results. It not only achieves super-resolution, but also provides very high anatomical contrast with a new MRI contrast mechanism. However, the anatomical information-content of this novel contrast mechanism has not yet been assessed. In this work, we perform such a study using diffusion MRI of ex vivo mouse brains acquired at 16.4 T, to compare the results of the super-resolution TDI technique with histological staining (myelin and Nissl stains) in the same brains. Furthermore, a modified version of the directionally-encoded colour TDI map using short-tracks is introduced, which reduces the TDI intensity dynamic range, and therefore enhances the directionality colour-contrast. Good agreement was observed between structures visualised in the super-resolution TDI maps and in the histological sections, supporting the anatomical information-content of the images generated using the TDI technique. The results therefore show that the TDI methodology does provide meaningful and rich anatomical contrast, in addition to achieving super-resolution. Furthermore, this study is the first to show the application of TDI to mouse brain imaging: the high-resolution, high-quality images demonstrate the useful complementary information that can be achieved using super-resolution TDI.
Publisher: Wiley
Date: 28-12-2012
DOI: 10.1002/MRM.23244
Abstract: MR microimaging at 16.4 T with 40-μm isotropic voxels was used to investigate compartmentation of water diffusion in formalin-fixed prostate tissue. Ten tissue s les (~ 28 mm(3) each) from five organs were imaged. The mean diffusivity of epithelial, stromal, and ductal/acinar compartments was estimated by two methods: (1) manual region of interest selection and (2) Gaussian fitting of voxel diffusivity histograms. For the region of interest-method, the means of the tissue s le compartment diffusivities were significantly different (P < 0.001): 0.54 ± 0.05 μm(2)/ms for epithelium-containing voxels, 0.91 ± 0.17 μm(2)/ms for stroma, and 2.20 ± 0.04 μm(2)/ms for saline-filled ducts. The means from the histogram method were also significantly different (P < 0.001): 0.45 ± 0.08 μm(2)/ms for epithelium-containing voxels, 0.83 ± 0.16 μm(2)/ms for stroma, 2.21 ± 0.02 μm(2)/ms for duct. Estimated partial volumes of epithelial, stromal, and ductal/acinar compartments in a "tissue only" subvolume of each s le were significantly different (P < 0.02) between cancer and normal tissue for all three compartments. It is concluded that the negative correlation between apparent diffusion coefficient and cancer Gleason grade observed in vivo results from an increase of partial volume of epithelial tissue and concomitant decrease of stromal tissue and ductal space.
Publisher: Wiley
Date: 27-01-2012
DOI: 10.1002/MRM.24179
Abstract: Diffusion tensor microimaging at 16.4 T with 40 μm isotropic voxels was used to investigate anisotropic water diffusion in prostate tissue at spatial resolution approaching the cellular scale. Nine normal glandular tissue s les were collected from the peripheral zone of six formalin fixed radical prostatectomy specimens. Fibromuscular stromal tissue exhibited microscopic diffusion anisotropy (mean fractional anisotropy range 0.47-0.66) significantly higher (P < 0.01, Student's t-test) than in epithelium-containing voxels (mean fractional anisotropy range 0.31-0.54) in six of the seven normal tissue s les in which both compartments could be measured. Fiber tracking demonstrated principle stromal fiber directions consistent with myocyte orientation seen on light microscopy of the same s le. Diffusion tensor microimaging may be valuable for investigation of variable results from attempts to measure diffusion anisotropy in the prostate in vivo.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2014
DOI: 10.1007/S00429-013-0572-0
Abstract: The basal ganglia are a group of subpallial nuclei that play an important role in motor, emotional, and cognitive functions. Morphological changes and disrupted afferent/efferent connections in the basal ganglia have been associated with a variety of neurological disorders including psychiatric and movement disorders. While high-resolution magnetic resonance imaging has been used to characterize changes in brain structure in mouse models of these disorders, no systematic method for segmentation of the C57BL/6 J mouse basal ganglia exists. In this study we have used high-resolution MR images of ex vivo C57BL/6 J mouse brain to create a detailed protocol for segmenting the basal ganglia. We created a three-dimensional minimum deformation atlas, which includes the segmentation of 35 striatal, pallidal, and basal ganglia-related structures. In addition, we provide mean volumes, mean T2 contrast intensities and mean FA and ADC values for each structure. This MR atlas is available for download, and enables researchers to perform automated segmentation in genetic models of basal ganglia disorders.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2021
DOI: 10.1038/S41467-021-22888-5
Abstract: Intellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders and are characterized by substantial impairment in intellectual and adaptive functioning, with their genetic and molecular basis remaining largely unknown. Here, we identify biallelic variants in the gene encoding one of the Elongator complex subunits, ELP2, in patients with ID and ASD. Modelling the variants in mice recapitulates the patient features, with brain imaging and tractography analysis revealing microcephaly, loss of white matter tract integrity and an aberrant functional connectome. We show that the Elp2 mutations negatively impact the activity of the complex and its function in translation via tRNA modification. Further, we elucidate that the mutations perturb protein homeostasis leading to impaired neurogenesis, myelin loss and neurodegeneration. Collectively, our data demonstrate an unexpected role for tRNA modification in the pathogenesis of monogenic ID and ASD and define Elp2 as a key regulator of brain development.
Publisher: Springer International Publishing
Date: 2019
Publisher: Society for Neuroscience
Date: 14-03-2012
DOI: 10.1523/JNEUROSCI.3679-11.2012
Abstract: Disruption of the potassium/chloride cotransporter 3 (KCC3), encoded by the SLC12A6 gene, causes hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder affecting both the peripheral nervous system and CNS. However, the precise role of KCC3 in the maintenance of ion homeostasis in the nervous system and the pathogenic mechanisms leading to HMSN/ACC remain unclear. We established two Slc12a6 Cre/LoxP transgenic mouse lines expressing C-terminal truncated KCC3 in either a neuron-specific or ubiquitous fashion. Our results suggest that neuronal KCC3 expression is crucial for axon volume control. We also demonstrate that the neuropathic features of HMSN/ACC are predominantly due to a neuronal KCC3 deficit, while the auditory impairment is due to loss of non-neuronal KCC3 expression. Furthermore, we demonstrate that KCC3 plays an essential role in inflammatory pain pathways. Finally, we observed hypoplasia of the corpus callosum in both mouse mutants and a marked decrease in axonal tracts serving the auditory cortex in only the general deletion mutant. Together, these results establish KCC3 as an important player in both central and peripheral nervous system maintenance.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JNEUMETH.2012.08.021
Abstract: A method is presented for three-dimensional reconstruction of the mouse brain from histological sections with the guidance of magnetic resonance images (MRI). A major focus of the method is dealing with sections in which anatomical structures have been separated or distorted as a result of histological processing. Although histology has superb resolution with the ability to discriminate cell types and anatomical structures, misalignment between sections and distortion within sections renders 3D reconstruction of the histology volume simply by stacking 2D sections inadequate. In contrast, MRI preserves the spatial and geometric information about structures at a cost of cellular detail. To utilize the information from MRI in reconstructing volumetric histological data, we developed a procedure consisting of a series of segmentation and registration operations. The method is iterative and first identifies the corresponding MRI slices for each histological section. Piecewise rigid registration is then employed to deal with tissue distortion caused by histological processing. Quantitative validation of the method's accuracy was performed on four reconstructed mouse brains by comparing a set of manually selected anatomical landmarks on pairs of MRI and histological volumes. The procedure is highly automated and amenable to high throughput.
Publisher: Springer Science and Business Media LLC
Date: 23-09-2021
Publisher: Elsevier BV
Date: 12-2021
Publisher: IOP Publishing
Date: 31-08-2018
Publisher: Wiley
Date: 17-12-2015
DOI: 10.1002/MRM.25555
Abstract: 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 s les from four patients. Results were correlated with histology of the s les. 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 s les, 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.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2020
DOI: 10.1186/S12880-020-00489-W
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of upper and lower motor neurons. There is a need for an imaging biomarker to track disease progression. Previously, magnetic resonance imaging (MRI) has shown loss of grey and white matter in the brain of patients with ALS compared to controls. We performed serial diffusion tractography imaging (DTI) study of patients with ALS looking for changes over time. On all subjects ( n = 15), we performed three MRI studies at 6 month intervals. DTI changes were assessed with tract-based spatial statistics (TBSS) and region of interest (ROI) studies. Cortic-spinal tract (CST) was selected for our ROI at the upper level the posterior limb of internal capsule (PLIC), and a lower level in the pons. There was no significant change in DTI measures over 12 months of observation. Better correlation of manual and atlas-based ROI methods was found in the posterior limb of the internal capsule than the pons. While previous DTI studies showed significant differences between ALS subjects and controls, within in idual subjects there is little evidence of progression over 12 months. This suggests that DTI is not a suitable biomarker to assess disease progression in ALS.
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 08-01-2016
DOI: 10.1002/NBM.3462
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.NEUROIMAGE.2010.12.044
Abstract: Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal cord damage in vivo. Fractional anisotropy (FA) values were reduced exclusively in the ventral white matter tracts of the lumbar spinal cord of ALS-affected SOD1 mice compared to wild-type littermates, with this effect becoming more pronounced with disease progression. The reduced FA values were therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were preserved. Significant decreases in water diffusion parallel to the white matter fibers or axial diffusivity were observed in the SOD1 mice, which can be attributed to the axonal degeneration observed by electron microscopy. At the same time, radial diffusivity perpendicular to the spinal column increased in the SOD1 mice, reflecting reduced myelination. These results demonstrate the usefulness of MRI in tracking disease progression in live animals and will aid in the assessment of treatment efficacy. This method could also potentially be adapted to aid the diagnosis and assessment of ALS progression in humans.
Publisher: Proceedings of the National Academy of Sciences
Date: 16-03-2015
Abstract: Venom peptides have attracted considerable attention because of their value as pharmacological tools and their potential for development as novel pharmaceuticals and bioinsecticides. There is also a growing interest in venoms as model evolutionary systems, particularly for understanding antagonistic coevolutionary processes. We previously demonstrated that although centipede venoms are rich in novel proteins and peptides, there are considerable differences in venom complexity between high-order taxa. We show that this disparity appears to stem from morphological limitations of the venom gland, and that most centipede venoms likely evolve under constraints imposed by low-complexity toxin production facilities. Thus, the centipede venom apparatus should be a useful model system for gaining insight into the impact of morphological constraints on venom evolution.
Publisher: American Chemical Society
Date: 2011
Publisher: Wiley
Date: 25-09-2019
DOI: 10.1002/HBM.24380
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ALCOHOL.2018.04.008
Abstract: We examined whether an early-life event - ethanol exposure in the initial stages of pregnancy - affected offspring brain structure, energy metabolism, and body composition in later life. Consumption of 10% (v/v) ethanol by inbred C57BL/6J female mice from 0.5 to 8.5 days post coitum was used to model alcohol exposure during the first 3-4 weeks of gestation in humans, when pregnancy is not typically recognized. At adolescence (postnatal day [P] 28) and adulthood (P64), the brains of male offspring were scanned ex vivo using ultra-high field (16.4 T) magnetic resonance imaging and diffusion tensor imaging. Energy metabolism and body composition were measured in adulthood by indirect calorimetry and dual-energy X-ray absorptiometry (DXA), respectively. Ethanol exposure had no substantial impact on white matter organization in the anterior commissure, corpus callosum, hippoc al commissure, internal capsule, optic tract, or thalamus. Whole brain volume and the volumes of the neocortex, cerebellum, and caudate putamen were also unaffected. Subtle, but non-significant, effects were observed on the hippoc us and the hypothalamus in adult ethanol-exposed male offspring. Ethanol exposure was additionally associated with a trend toward decreased oxygen consumption, carbon dioxide production, and reduced daily energy expenditure, as well as significantly increased adiposity, albeit with normal body weight and food intake, in adult male offspring. In summary, ethanol exposure restricted to early gestation had subtle long-term effects on the structure of specific brain regions in male offspring. The sensitivity of the hippoc us to ethanol-induced damage is reminiscent of that reported by other studies - despite differences in the level, timing, and duration of exposure - and likely contributes to the cognitive impairment that characteristically results from prenatal ethanol exposure. The hypothalamus plays an important role in regulating metabolism and energy homeostasis. Our finding of altered daily energy expenditure and adiposity in adult ethanol-exposed males is consistent with the idea that central nervous system abnormalities also underpin some of the metabolic phenotypes associated with ethanol exposure in pregnancy.
Publisher: Elsevier BV
Date: 07-2010
Publisher: Elsevier BV
Date: 09-2207
DOI: 10.1016/J.NEUROPHARM.2016.04.035
Abstract: Adolescence is a period of dynamic remodeling and maturation in the brain. Exposure to psychotropic drugs during adolescence can potentially alter neural maturation in the adolescent brain subsequently altering neural function at maturity. In this regard, antipsychotic drugs (APDs) are important given a notable global increase in prescription of these APDs to adolescents for a variety of behavioural symptoms and conditions over the past twenty years. However, there is a paucity of data on the long-term consequences of APDs on the adolescent brain. In this preclinical study, we have examined whether the adolescent brain is more susceptible than the adult brain to long-term neural changes induced by risperidone, which is the APD most frequently prescribed to adolescents. Rats were chronically treated (21 days) with 1.3 mg/kg/day risperidone or vehicle either as adolescents (postnatal day (PND) 36-56)) or adults (PND80-100). Behaviour was assessed using the well-described suppression of the conditioned avoidance response (CAR) by APDs. We examined CAR after all animals had reached maturity (PND127). We show that mature rats treated with risperidone as adolescents had increased CAR suppression compared to adults when rechallenged with this same drug. In the nucleus accumbens, significant downregulation of serotonergic 5HT2A receptors and catechol-o-methyl transferase mRNA levels was observed only in the adolescent treated animals. Impaired 5HT2A receptor signaling may explain the increased CAR suppression observed in rats treated with risperidone as adolescents. Magnetic resonance imaging (MRI), however, did not detect any risperidone-induced long-term brain structural change at maturity. These findings confirm that APD administration during adolescence may produce long-term behavioural and neurochemical alterations.
Publisher: Wiley
Date: 12-04-2011
DOI: 10.1002/DVDY.22636
Abstract: The fibroblast growth factor receptor 3 (Fgfr3) is expressed in a rostral(low) to caudal(high) gradient in the developing cerebral cortex. Therefore, we hypothesized that Fgfr3 contributes to the correct morphology and connectivity of the caudal cortex. Overall, the forebrain structures appeared normal in Fgfr3(-/-) mice. However, cortical and hippoc al volumes were reduced by 26.7% and 16.3%, respectively. Hypoplasia was particularly evident in the caudo-ventral region of the telencephalon where proliferation was mildly decreased at embryonic day 18.5. Dysplasia of GABAergic neurons in the amygdala and piriform cortex was seen following GAD67 immunohistochemistry. Dye-tracing studies and diffusion magnetic resonance imaging and tractography detected a subtle thalamocortical tract deficit, and significant decreases in the stria terminalis and lateral arms of the anterior commissure. These results indicate the subtle role of Fgfr3 in formation of caudal regions of the telencephalon affecting some brain projections.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.NEUROIMAGE.2012.05.061
Abstract: The C57BL mouse is the centerpiece of efforts to use gene-targeting technology to understand cerebellar pathology, thus creating a need for a detailed magnetic resonance imaging (MRI) atlas of the cerebellum of this strain. In this study we present a methodology for systematic delineation of the vermal and hemispheric lobules of the C57BL/6J mouse cerebellum in magnetic resonance images. We have successfully delineated 38 cerebellar and cerebellar-related structures. The higher signal-to-noise ratio achieved by group averaging facilitated the identification of anatomical structures. In addition, we have calculated average region volumes and created probabilistic maps for each structure. The segmentation method and the probabilistic maps we have created will provide a foundation for future studies of cerebellar disorders using transgenic mouse models.
Publisher: Frontiers Media SA
Date: 12-01-2015
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 06-2022
End Date: 05-2025
Summary: Advancing the visualisation and quantification of nephrons with MRI. . This project aims to characterise key components of nephrons, the glomeruli and tubules, using magnetic resonance imaging without contrast agents, in combination with Deep Learning and super-resolution techniques. Nephrons, the basic functional unit of the kidney, are critical to the maintenance of the body’s homeostasis. Their number and architecture are critical determinants of kidney function. The expected outcomes are inn .... Advancing the visualisation and quantification of nephrons with MRI. . This project aims to characterise key components of nephrons, the glomeruli and tubules, using magnetic resonance imaging without contrast agents, in combination with Deep Learning and super-resolution techniques. Nephrons, the basic functional unit of the kidney, are critical to the maintenance of the body’s homeostasis. Their number and architecture are critical determinants of kidney function. The expected outcomes are innovative semi-automated nephron visualisation and quantitation tools that enable efficient renal phenotyping. Techniques tailored to widely accessible preclinical research scanners are expected to accelerate research into genetic and environmental factors affecting kidney microstructure in embryonic and post-natal life. Read more Read less
Funder: Australian Research Council
View Funded ActivityStart Date: 2011
End Date: 2015
Funder: National Institute of Neurological Disorders and Stroke
View Funded ActivityStart Date: 06-2022
End Date: 05-2025
Amount: $485,575.00
Summary: Advancing the visualisation and quantification of nephrons with MRI. . This project aims to characterise key components of nephrons, the glomeruli and tubules, using magnetic resonance imaging without contrast agents, in combination with Deep Learning and super-resolution techniques. Nephrons, the basic functional unit of the kidney, are critical to the maintenance of the body’s homeostasis. Their number and architecture are critical determinants of kidney function. The expected outcomes are inn .... Advancing the visualisation and quantification of nephrons with MRI. . This project aims to characterise key components of nephrons, the glomeruli and tubules, using magnetic resonance imaging without contrast agents, in combination with Deep Learning and super-resolution techniques. Nephrons, the basic functional unit of the kidney, are critical to the maintenance of the body’s homeostasis. Their number and architecture are critical determinants of kidney function. The expected outcomes are innovative semi-automated nephron visualisation and quantitation tools that enable efficient renal phenotyping. Techniques tailored to widely accessible preclinical research scanners are expected to accelerate research into genetic and environmental factors affecting kidney microstructure in embryonic and post-natal life. Read more Read less
Funder: Australian Research Council
View Funded Activity