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Kay L Richards,
Nyoman D Kurniawan, Zhengyi Yang,
Tae Hwan Kim,
Marianne D Keller,
Jun Low,
Jeremy F P Ullmann,
Stacey Cole,
Samuel Foong,
Graham J Galloway,
Christopher A Reid,
George Paxinos,
David C Reutens,
Steven Petrou
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ABSTRACT: OBJECTIVE: The human γ-aminobutyric acid type A (GABAA)γ2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile seizures. R43Q mice in the C57Bl/6J background do not display spontaneous seizures, but are significantly more susceptible to hyperthermic seizures, providing a model with enhanced seizure susceptibility without the confounding influence of ongoing epileptic activity. Because of GABA's role in brain development, we sought to determine whether the R43Q mutation alters brain structure before the appearance of seizures. METHODS: We used 16.4-tesla, high-field MRI to determine the volumes of hippocampal subregions. Histologic analysis of the same brains allowed stereology-based estimates of neuron counts to be obtained in CA1-3 and the dentate gyrus. RESULTS: Morphologic changes were evident in seizure-naive hippocampi of susceptible mice. Dentate granule cell MRI determined that volume was 5% greater in R43Q mice compared with controls (0.628 mm3, 95% confidence interval [CI] 0.611-0.645 vs 0.595 mm3, 95% CI 0.571-0.619). The dentate granule cell density was 30% higher in R43Q compared with control mice (553 × 103 cells/mm3, 95% CI 489-616 vs 427 × 103 cells/mm3, 95% CI 362-491). CONCLUSIONS: In a genetic epilepsy model that is both seizure-naive and carries an allele for febrile seizure susceptibility, we have determined hippocampal structural changes that may be applied as a biomarker for seizure susceptibility.
Neurology 03/2013; · 8.31 Impact Factor
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ABSTRACT: HSQC spectra are routinely acquired for chemical structure analysis based on hydrogen and carbon chemical environments. Two fast HSQC peak matching algorithms have been developed; a nearest neighbour approach and a probabilistic method based on an existing discrete genetic algorithm. Both of these techniques are intended to find HSQC spectra matches that supplement information generated by established molecular fingerprint methods. Our results are compared to those calculated using a specific implementation of molecular fingerprints. The nearest neighbour and genetic algorithm-based methods ranked highly particular structures missed by molecular fingerprints. Our analysis shows that by complementing molecular fingerprint matches with our findings, a comprehensive list of matches can be identified. The refined list of compounds could be used to improve the quality of compounds used in screening libraries in the pharmaceutical industry.
Journal of Cheminformatics 10/2012; 4(1):25. · 3.42 Impact Factor
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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.
Journal of neuroscience methods 09/2012; 211(2):210-217. · 2.30 Impact Factor
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Jeremy F P Ullmann,
Marianne D Keller,
Charles Watson,
Andrew L Janke,
Nyoman D Kurniawan, Zhengyi Yang,
Kay Richards,
George Paxinos,
Gary F Egan,
Steven Petrou,
Perry Bartlett,
Graham J Galloway,
David C Reutens
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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.
NeuroImage 05/2012; 62(3):1408-14. · 5.89 Impact Factor
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ABSTRACT: Lumbar spine kinematics was studied in subjects with normal bone mineral density, osteopenia and osteoporosis to determine
the effect of bone mineral density and morphology on the flexion–extension movement patterns of the lumbar spine. Lateral
radiographs and skin-mounted electromagnetic motion tracking sensors were employed to study lumbar spine kinematics using
a Bayesian Belief Network model. The predicted angular displacement of the vertebrae had a high correlation (r=0.91, p<0.001) with the actual movements. The overall mean error was −0.51°±3.11°. Intervertebral angular displacement and velocity
consistently increased from L1/L2 to L5/S1. Differences were observed in the movement pattern between normal subjects and
those with decreased bone density. In normal subjects, vertebral angular acceleration consistently decreased from the upper
to the lower vertebrae but the same consistent predictable pattern was not observed in the subjects with decreased bone mineral
density. It is possible that these changes in kinematic behaviours are related to morphological changes as well as altered
neuromuscular functions.
Medical & Biological Engineering & Computing 04/2012; 47(7):783-789. · 1.88 Impact Factor
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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.
NeuroImage 07/2011; 59(1):286-96. · 5.89 Impact Factor
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Kay Richards,
Charles Watson,
Rachel F Buckley,
Nyoman D Kurniawan, Zhengyi Yang,
Marianne D Keller,
Richard Beare,
Perry F Bartlett,
Gary F Egan,
Graham J Galloway,
George Paxinos,
Steven Petrou,
David C Reutens
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ABSTRACT: The hippocampal 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 hippocampus over time and is useful for comparing hippocampal volume and structure in wild type and mutant mice. Such comparisons demand a reliable way to segment the hippocampal formation. We have developed a method for the systematic segmentation of the hippocampal 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.
NeuroImage 06/2011; 58(3):732-40. · 5.89 Impact Factor
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2011 International Conference on Digital Image Computing: Techniques and Applications (DICTA), Noosa, QLD, Australia, December 6-8, 2011; 01/2011
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2011 International Conference on Digital Image Computing: Techniques and Applications (DICTA), Noosa, QLD, Australia, December 6-8, 2011; 01/2011
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4th International Conference on Biomedical Engineering and Informatics, BMEI 2011, Shanghai, China, October 15-17, 2011; 01/2011
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ABSTRACT: An approach to image registration is outlined based on a new stochastic differential equation optimization method. The proposed method requires the use of the numerical solution of a particular stochastic differential equation to determine the iterative update of the transformation variables. A comparison to Differential Evolution optimization was carried out to establish the rate of convergence and the quality of result, as measured by the number of cost function evaluations and the size of the standard deviation of the optimal variables. Experimental data shows that the new technique is robust in terms of computational speed and convergence. The method is validated on magnetic resonance and histology images of mouse brain.
Image Processing (ICIP), 2010 17th IEEE International Conference on; 10/2010
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Proceedings of the International Conference on Image Processing, ICIP 2010, September 26-29, Hong Kong, China; 01/2010
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ABSTRACT: Cross-sectional study.
The purpose of this study was to examine disc morphology and spinal mobility in subjects with varying degrees of osteoporosis.
There was limited information on the effect of osteoporosis on lumbar morphology and spinal mobility. It was also unclear how osteoporosis affects the nonosseous tissues such as the intervertebral disc.
Ninety elderly subjects with varying bone mineral densities (22 normal, 28 osteopenia, 40 osteoporosis) were recruited from an osteoporosis clinic. Lateral radiographs and magnetic resonance images of their lumbar spines were obtained. An electromagnetic tracking device was employed to measure the ranges of motion of the whole lumbar spine.
Although the thoracic spine had been shown to have decreased anterior vertebral body height in subjects with osteoporosis, this study revealed that the anterior height was increased in the lumbar region. Osteoporosis was associated with expansion of the middle of the disc with corresponding collapse of vertebral bodies, but osteoporosis was found not to be related to either disc preservation or degeneration. No significant change in spinal mobility was observed in patients with osteoporosis.
Osteoporosis does not only affect the bone but also the nonosseous tissues. It was found to be associated with expansion of the intervertebral disc, which was likely to be secondary to changes in the vertebral endplate.
Spine 03/2009; 34(3):E115-21. · 2.08 Impact Factor
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ABSTRACT: Correlation between kinematics and morphological characteristics of lumbar spine was studied in subjects with varying bone mineral density. Effect of morphological characteristics and bone mineral density on the lumbar spine movement was investigated. Morphology parameters were measured from radiographs and a high-frequency motion tracking device were employed to detect surface movement of lumbar spine. Multiple regression analysis identified factors influencing lumbar kinematics while ANOVA examined differences in morphology with normal bone mineral density, osteopenia and osteoporosis. The results show that morphological characteristics, such as wedging deformity, are indeed influential to the kinematics. Related to our previous report, abnormal lumbar kinematic pattern in the subjects with osteoporosis, this study shows although morphological characteristics were found significantly different among normal, osteopenia, and osteoporosis subjects, the change in lumbar kinematic pattern could not be fully explained by the altered vertebral or disc morphology.
Engineering in Medicine and Biology Society, 2008. EMBS 2008. 30th Annual International Conference of the IEEE; 09/2008
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ABSTRACT: Measurement errors of skin-mounted sensors in measuring forward bending movement of the lumbar spines are investigated. In this investigation, radiographic images capturing the entire lumbar spines' positions were acquired and used as a “gold” standard. Seventeen young male volunteers (21 (SD 1) years old) agreed to participate in the study. Light-weight miniature sensors of the electromagnetic tracking systems-Fastrak® were attached to the skin overlying the spinous processes of the lumbar spine. With the sensors attached, the subjects were requested to take lateral radiographs in two postures: neutral upright and full flexion. The ranges of motions of lumbar spine were calculated from two sets of digitized data: the bony markers of vertebral bodies and the sensors and compared. The differences between the two sets of results were then analyzed. The relative movement between sensor and vertebrae was decomposed into sensor sliding and titling, from which sliding error and titling error were introduced. Gross motion range of forward bending of lumbar spine measured from bony markers of vertebrae is 67.8° (SD 10.6°) and that from sensors is 62.8° (SD 12.8°). The error and absolute error for gross motion range were 5.0° (SD 7.2°) and 7.7° (SD 3.9°). The contributions of sensors placed on S1 and L1 to the absolute error were 3.9° (SD 2.9°) and 4.4° (SD 2.8°), respectively.
Engineering in Medicine and Biology Society, 2008. EMBS 2008. 30th Annual International Conference of the IEEE; 09/2008
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ABSTRACT: Lumbar spine kinematics were assessed and studied in subjects with normal bone mineral density, osteopenia, and osteoporosis to examine the extension-flexion movement pattern and determine the effect of bone mineral density on the movement pattern of lumbar spine. Both radiographs and surface motion tracking were employed to measure lumbar spine kinematics. Several movement patterns were consistently observed on all subjects, while subjects with osteopenia or osteoporosis do not possess the same ordered vertebral acceleration seen in subjects with normal bone density. This is the first study showing altered kinematic pattern during lumbar spine movement in subjects with osteoporosis. The results provide new insight in the pathology of osteoporotic patients, which would help clinical applications as well.
Information Technology and Applications in Biomedicine, 2008. ITAB 2008. International Conference on; 06/2008
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ABSTRACT: SMACKER is a method of calculating sensitivity maps from k-space reconstruction coefficients using only a few lines of inner k-space. In this method the problem of sensitivities ending at object boundaries is eliminated, unlike in other established methods. The method allows for the rapid calculation of sensitivity profiles from images, and it is proposed here that the approach can be used in functional MRI to obtain reconstructed images in little time. Functional MRI relying on fast parallel reconstruction techniques naturally lends itself to a method that can generate and use sensitivity maps directly from images.
Biomedical Imaging: From Nano to Macro, 2008. ISBI 2008. 5th IEEE International Symposium on; 06/2008
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ABSTRACT: A Bayesian network dynamic model was developed to determine the kinematics of the intervertebral joints of the lumbar spine. Radiographic images in flexion and extension postures were used as input data for modeling, together with movement information from the skin surface using an electromagnetic motion tracking system. Intervertebral joint movements were then estimated by the graphic network. The validity of the model was tested by comparing the predicted position of the vertebrae in the neutral position with those obtained from the radiographic image in the neutral posture. The correlation between the measured and predicted movements was 0.99 (p<0.01) with a mean error of less than 1.5 degrees. The movement sequence of the various vertebrae was examined based on the model output, and wide variations in the kinematic patterns were observed. The technique is non-invasive and has potential to be used clinically to measure the kinematics of lumbar intervertebral movement.
Medical & Biological Engineering & Computing 04/2008; 46(4):333-40. · 1.88 Impact Factor
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ABSTRACT: The use of polynomial functions for modeling geometric distortion in magnetic resonance imaging (MRI) that arises from scanner's hardware imperfection is studied in detail. In this work, the geometric distortion data from four representative MRI systems were used. Modeling of these data using polynomial functions of the fourth, fifth, sixth, and seventh orders was carried out. In order to investigate how this modeling performed for different size and shape of the volume of interest, the modeling was carried out for three different volumes of interest (VOI): a cube, a cylinder, and a sphere. The modeling's goodness was assessed using both the maximum and mean absolute errors. The modeling results showed that (i) for the cube VOI there appears to be an optimal polynomial function that gives the least modeling errors and the sixth order polynomial was found to be the optimal polynomial function for the size of the cubic VOI considered in the present work; (ii) for the cylinder VOI, all four polynomials performed approximately equally well but a trend of a slight decrease in the mean absolute error with the increasing order of the polynomial was noted; and (iii) for the sphere VOI, the maximum absolute error showed some variations with the order of the polynomial, with the fourth order polynomial producing the smallest maximum absolute errors. It is further noted that extrapolation could lead to very large errors so any extrapolation needs to be avoided. A detailed analysis on the modeling errors is presented.
Medical Physics 04/2008; 35(3):908-16. · 2.83 Impact Factor
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Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2008;
