Gary F. Egan

YNIMG Journal 2021 Journal Article

A gyrification analysis approach based on Laplace Beltrami eigenfunction level sets

• Rosita Shishegar
• Fabrizio Pizzagalli
• Nellie Georgiou-Karistianis
• Gary F. Egan
• Neda Jahanshad
• Leigh A. Johnston

An accurate measure of the complexity of patterns of cortical folding or gyrification is necessary for understanding normal brain development and neurodevelopmental disorders. Conventional gyrification indices (GIs) are calculated based on surface curvature (curvature-based GI) or an outer hull surface of the cortex (outer surface-based GI). The latter is dependent on the definition of the outer hull surface and a corresponding function between surfaces. In the present study, we propose the Laplace Beltrami-based gyrification index (LB-GI). This is a new curvature-based local GI computed using the first three Laplace Beltrami eigenfunction level sets. As with outer surface-based GI methods, this method is based on the hypothesis that gyrification stems from a flat surface during development. However, instead of quantifying gyrification with reference to corresponding points on an outer hull surface, LB-GI quantifies the gyrification at each point on the cortical surface with reference to their surrounding gyral points, overcoming several shortcomings of existing methods. The LB-GI was applied to investigate the cortical maturation profile of the human brain from preschool to early adulthood using the PING database. The results revealed more detail in patterns of cortical folding than conventional curvature-based methods, especially on frontal and posterior tips of the brain, such as the frontal pole, lateral occipital, lateral cuneus, and lingual. Negative associations of cortical folding with age were observed at cortical regions, including bilateral lingual, lateral occipital, precentral gyrus, postcentral gyrus, and superior frontal gyrus. The results also indicated positive significant associations between age and the LB-GI of bilateral insula, the medial orbitofrontal, frontal pole and rostral anterior cingulate regions. It is anticipated that the LB-GI will be advantageous in providing further insights in the understanding of brain development and degeneration in large clinical neuroimaging studies.

YNIMG Journal 2021 Journal Article

Incorporation of anatomical MRI knowledge for enhanced mapping of brain metabolism using functional PET

• Viswanath P. Sudarshan
• Shenpeng Li
• Sharna D. Jamadar
• Gary F. Egan
• Suyash P. Awate
• Zhaolin Chen

Functional positron emission tomography (fPET) imaging using continuous infusion of [18F]-fluorodeoxyglucose (FDG) is a novel neuroimaging technique to track dynamic glucose utilization in the brain. In comparison to conventional static or dynamic bolus PET, fPET maintains a sustained supply of glucose in the blood plasma which improves sensitivity to measure dynamic glucose changes in the brain, and enables mapping of dynamic brain activity in task-based and resting-state fPET studies. However, there is a trade-off between temporal resolution and spatial noise due to the low concentration of FDG and the limited sensitivity of multi-ring PET scanners. Images from fPET studies suffer from partial volume errors and residual scatter noise that may cause the cerebral metabolic functional maps to be biased. Gaussian smoothing filters used to denoise the fPET images are suboptimal, as they introduce additional partial volume errors. In this work, a post-processing framework based on a magnetic resonance (MR) Bowsher-like prior was used to improve the spatial and temporal signal to noise characteristics of the fPET images. The performance of the MR guided method was compared with conventional denosing methods using both simulated and in vivo task fPET datasets. The results demonstrate that the MR-guided fPET framework denoises the fPET images and improves the partial volume correction, consequently enhancing the sensitivity to identify brain activation, and improving the anatomical accuracy for mapping changes of brain metabolism in response to a visual stimulation task. The framework extends the use of functional PET to investigate the dynamics of brain metabolic responses for faster presentation of brain activation tasks, and for applications in low dose PET imaging.

YNIMG Journal 2020 Journal Article

Analysis of continuous infusion functional PET (fPET) in the human brain

• Shenpeng Li
• Sharna D. Jamadar
• Phillip G.D. Ward
• Malin Premaratne
• Gary F. Egan
• Zhaolin Chen

Functional positron emission tomography (fPET) is a neuroimaging method involving continuous infusion of 18-F-fluorodeoxyglucose (FDG) radiotracer during the course of a PET examination. Compared with the conventional bolus administration of FDG in a static PET scan, which provides an average glucose uptake into the brain over an extended period of up to 30 ​min, fPET offers a significantly higher temporal resolution to study the dynamics of glucose uptake. Several earlier studies have applied fPET to investigate brain FDG uptake and study its relationship with functional magnetic resonance imaging (fMRI). However, due to the unique characteristics of fPET signals, modelling of the fPET signal is a complex task and poses challenges for accurate interpretation of the results from fPET experiments. This study applied independent component analysis (ICA) to analyse resting state fPET data, and to compare the performance of ICA and the general linear model (GLM) for estimation of brain activation in response to tasks. The fPET signal characteristics were compared using GLM and ICA methods to model fPET data from a visual activation experiment. Our aim was to evaluate GLM and ICA methods for analysing task fPET datasets, and to apply ICA methods to the analysis of resting state fPET datasets. Using both simulation and in-vivo experimental datasets, we show that both ICA and GLM methods can successfully identify task related brain activation. We report fPET metabolic resting state brain networks revealed by application of the fPET ICA method to a cohort of 28 healthy subjects. Functional PET provides a unique method to map dynamic changes of glucose uptake in the resting human brain and in response to extrinsic stimulation.

YNIMG Journal 2020 Journal Article

Individual differences in haemoglobin concentration influence bold fMRI functional connectivity and its correlation with cognition

• Phillip G.D. Ward
• Edwina R. Orchard
• Stuart Oldham
• Aurina Arnatkevičiūtė
• Francesco Sforazzini
• Alex Fornito
• Elsdon Storey
• Gary F. Egan

Resting-state connectivity measures the temporal coherence of the spontaneous neural activity of spatially distinct regions, and is commonly measured using BOLD-fMRI. The BOLD response follows neuronal activity, when changes in the relative concentration of oxygenated and deoxygenated haemoglobin cause fluctuations in the MRI T2* signal. Since the BOLD signal detects changes in relative concentrations of oxy/deoxy-haemoglobin, individual differences in haemoglobin levels may influence the BOLD signal-to-noise ratio in a manner independent of the degree of neural activity. In this study, we examined whether group differences in haemoglobin may confound measures of functional connectivity. We investigated whether relationships between measures of functional connectivity and cognitive performance could be influenced by individual variability in haemoglobin. Finally, we mapped the neuroanatomical distribution of the influence of haemoglobin on functional connectivity to determine where group differences in functional connectivity are manifest. In a cohort of 518 healthy elderly subjects (259 men), each sex group was median-split into two groups with high and low haemoglobin concentration. Significant differences were obtained in functional connectivity between the high and low haemoglobin groups for both men and women (Cohen's d 0. 17 and 0. 03 for men and women respectively). The haemoglobin connectome in males showed a widespread systematic increase in functional connectivity correlation values, whilst the female connectome showed predominantly parietal and subcortical increases and temporo-parietal decreases. Despite the haemoglobin groups having no differences in cognitive measures, significant differences in the linear relationships between cognitive performance and functional connectivity were obtained for all 5 cognitive tests in males, and 4 out of 5 tests in females. Our findings confirm that individual variability in haemoglobin levels that give rise to group differences are an important confounding variable in BOLD-fMRI-based studies of functional connectivity. Controlling for haemoglobin variability as a potentially confounding variable is crucial to ensure the reproducibility of human brain connectome studies, especially in studies that compare groups of individuals, compare sexes, or examine connectivity-cognition relationships.

YNIMG Journal 2019 Journal Article

Simultaneous task-based BOLD-fMRI and [18-F] FDG functional PET for measurement of neuronal metabolism in the human visual cortex

• Sharna D. Jamadar
• Phillip GD. Ward
• Shenpeng Li
• Francesco Sforazzini
• Jakub Baran
• Zhaolin Chen
• Gary F. Egan

Studies of task-evoked brain activity are the cornerstone of cognitive neuroscience, and unravel the spatial and temporal brain dynamics of cognition in health and disease. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is one of the most common methods of studying brain function in humans. BOLD-fMRI indirectly infers neuronal activity from regional changes in blood oxygenation and is not a quantitative metric of brain function. Regional variation in glucose metabolism, measured using [18-F] fluorodeoxyglucose positron emission tomography (FDG-PET), provides a more direct and interpretable measure of neuronal activity. However, while the temporal resolution of BOLD-fMRI is in the order of seconds, standard FDG-PET protocols provide a static snapshot of glucose metabolism. Here, we develop a novel experimental design for measurement of task-evoked changes in regional blood oxygenation and glucose metabolism with high temporal resolution. Over a 90-min simultaneous BOLD-fMRI/FDG-PET scan, [18F] FDG was constantly infused to 10 healthy volunteers, who viewed a flickering checkerboard presented in a hierarchical block design. Dynamic task-related changes in blood oxygenation and glucose metabolism were examined with temporal resolution of 2. 5sec and 1-min, respectively. Task-related, temporally coherent brain networks of haemodynamic and metabolic connectivity were jointly coupled in the visual cortex, as expected. Results demonstrate that the hierarchical block design, together with the infusion FDG-PET technique, enabled both modalities to track task-related neural responses with high temporal resolution. The simultaneous MR-PET approach has the potential to provide unique insights into the dynamic haemodynamic and metabolic interactions that underlie cognition in health and disease.

YNIMG Journal 2018 Journal Article

Combining images and anatomical knowledge to improve automated vein segmentation in MRI

• Phillip G.D. Ward
• Nicholas J. Ferris
• Parnesh Raniga
• David L. Dowe
• Amanda C.L. Ng
• David G. Barnes
• Gary F. Egan

Purpose To improve the accuracy of automated vein segmentation by combining susceptibility-weighted images (SWI), quantitative susceptibility maps (QSM), and a vein atlas to produce a resultant image called a composite vein image (CV image). Method An atlas was constructed in common space from manually traced MRI images from ten volunteers. The composite vein image was derived for each subject as a weighted sum of three inputs; an SWI image, a QSM image and the vein atlas. The weights for each input and each anatomical location, called template priors, were derived by assessing the accuracy of each input over an independent data set. The accuracy of vein segmentations derived automatically from each of the CV image, SWI, and QSM image sets was assessed by comparison with manual tracings. Three different automated vein segmentation techniques were used, and ten performance metrics evaluated. Results Vein segmentations using the CV image were comprehensively better than those derived from SWI or QSM images (mean Cohen's d = 1. 1). Sixty permutations of performance metric, benchmark image, and automated segmentation technique were evaluated. Vein identification improvements that were both large and significant (Cohen's d > 0. 80, p < 0. 05) were found in 77% of the permutations, compared to no improvement in 5%. Conclusion The accuracy of automated vein segmentations derived from the composite vein image was overwhelmingly superior to segmentations derived from SWI or QSM alone.

YNIMG Journal 2014 Journal Article

Functional size of human visual area V1: A neural correlate of top–down attention

• Ashika Verghese
• Scott C. Kolbe
• Andrew J. Anderson
• Gary F. Egan
• Trichur R. Vidyasagar

Heavy demands are placed on the brain's attentional capacity when selecting a target item in a cluttered visual scene, or when reading. It is widely accepted that such attentional selection is mediated by top–down signals from higher cortical areas to early visual areas such as the primary visual cortex (V1). Further, it has also been reported that there is considerable variation in the surface area of V1. This variation may impact on either the number or specificity of attentional feedback signals and, thereby, the efficiency of attentional mechanisms. In this study, we investigated whether individual differences between humans performing attention-demanding tasks can be related to the functional area of V1. We found that those with a larger representation in V1 of the central 12° of the visual field as measured using BOLD signals from fMRI were able to perform a serial search task at a faster rate. In line with recent suggestions of the vital role of visuo-spatial attention in reading, the speed of reading showed a strong positive correlation with the speed of visual search, although it showed little correlation with the size of V1. The results support the idea that the functional size of the primary visual cortex is an important determinant of the efficiency of selective spatial attention for simple tasks, and that the attentional processing required for complex tasks like reading are to a large extent determined by other brain areas and inter-areal connections.

YNIMG Journal 2014 Journal Article

Regional reproducibility of calibrated BOLD functional MRI: Implications for the study of cognition and plasticity

• Steffen N. Krieger
• Claudine J. Gauthier
• Dimo Ivanov
• Laurentius Huber
• Elisabeth Roggenhofer
• Bernhard Sehm
• Robert Turner
• Gary F. Egan

Calibrated BOLD fMRI is a promising alternative to the classic BOLD contrast due to its reduced venous sensitivity and greater physiological specificity. The delayed adoption of this technique for cognitive studies may stem partly from a lack of information on the reproducibility of these measures in the context of cognitive tasks. In this study we have explored the applicability and reproducibility of a state-of-the-art calibrated BOLD technique using a complex functional task at 7 tesla. Reproducibility measures of BOLD, CBF, CMRO2 flow-metabolism coupling n and the calibration parameter M were compared and interpreted for three ROIs. We found an averaged intra-subject variation of CMRO2 of 8% across runs and 33% across days. BOLD (46% across runs, 36% across days), CBF (33% across runs, 46% across days) and M (41% across days) showed significantly higher intra-subject variability. Inter-subject variability was found to be high for all quantities, though CMRO2 was the most consistent across brain regions. The results of this study provide evidence that calibrated BOLD may be a viable alternative for longitudinal and cognitive MRI studies.

YNIMG Journal 2014 Journal Article

Using carbogen for calibrated fMRI at 7Tesla: Comparison of direct and modelled estimation of the M parameter

• Steffen N. Krieger
• Dimo Ivanov
• Laurentius Huber
• Elisabeth Roggenhofer
• Bernhard Sehm
• Robert Turner
• Gary F. Egan
• Claudine J. Gauthier

Task-evoked changes in cerebral oxygen metabolism can be measured using calibrated functional Magnetic Resonance Imaging (fMRI). This technique requires the use of breathing manipulations such as hypercapnia, hyperoxia or a combination of both to determine a calibration factor M. The M-value is usually obtained by extrapolating the BOLD signal measured during the gas manipulation to its upper theoretical physiological limit using a biophysical model. However, a recently introduced technique uses a combination of increased inspired concentrations of O2 and CO2 to saturate the BOLD signal completely. In this study, we used this BOLD saturation technique to measure M directly at 7Tesla (T). Simultaneous carbogen-7 (7% CO2 in 93% O2) inhalation and visuo-motor task performance were used to elevate venous oxygen saturation in visual and motor areas close to their maximum, and the BOLD signal measured during this manipulation was used as an estimate of M. As accurate estimation of M is crucial for estimation of valid oxidative metabolism values, these directly estimated M-values were assessed and compared with M-values obtained via extrapolation modelling using the generalized calibration model (GCM) on the same dataset. Average M-values measured using both methods were 10. 4±3. 9% (modelled) and 7. 5±2. 2% (direct) for a visual-related ROI, and 11. 3±5. 2% (modelled) and 8. 1±2. 6% (direct) for a motor-related ROI. Results from this study suggest that, for the CO2 concentration used here, modelling is necessary for the accurate estimation of the M parameter. Neither gas inhalation alone, nor gas inhalation combined with a visuo-motor task, was sufficient to completely saturate venous blood in most subjects. Calibrated fMRI studies should therefore rely on existing models for gas inhalation-based calibration of the BOLD signal.

YNIMG Journal 2013 Journal Article

Filtering induces correlation in fMRI resting state data

• Catherine E. Davey
• David B. Grayden
• Gary F. Egan
• Leigh A. Johnston

Correlation-based functional MRI connectivity methods typically impose a temporal sample independence assumption on the data. However, the conventional use of temporal filtering to address the high noise content of fMRI data may introduce sample dependence. Violation of the independence assumption has ramifications for the distribution of sample correlation which, if unaccounted for, may invalidate connectivity results. To enable the use of temporal filtering for noise suppression while maintaining the integrity of connectivity results, we derive the distribution of sample correlation between filtered timeseries as a function of the filter frequency response. Corrected distributions are also derived for statistical inference tests of sample correlation between filtered timeseries, including Fisher's z-transformation and the Student's t-test. Crucially, the proposed corrections are valid for any unknown true correlation and arbitrary filter specifications. Empirical simulations demonstrate the potential for temporal filtering to artificially induce connectivity by introducing sample dependence, and verify the utility of the proposed corrections in mitigating this effect. The importance of our corrections is exemplified in a resting state fMRI connectivity analysis: seed–voxel correlation maps generated from filtered data using uncorrected test variates yield an unfeasible number of connections to the left primary motor cortex, suggesting artificially induced connectivity, while maps acquired from filtered data using corrected test variates exhibit bilateral connectivity in the primary motor cortex, in conformance with expected results as seen in the literature.

YNIMG Journal 2013 Journal Article

Hippocampal shape variations at term equivalent age in very preterm infants compared with term controls: Perinatal predictors and functional significance at age 7

• Deanne K. Thompson
• Christopher Adamson
• Gehan Roberts
• Nathan Faggian
• Stephen J. Wood
• Simon K. Warfield
• Lex W. Doyle
• Peter J. Anderson

The hippocampus undergoes rapid growth and development in the perinatal months. Infants born very preterm (VPT) are vulnerable to hippocampal alterations, and can provide a model of disturbed early hippocampal development. Hippocampal shape alterations have previously been associated with memory impairment, but have never been investigated in infants. The aims of this study were to determine hippocampal shape differences between 184 VPT infants (<30weeks' gestation or <1250g at birth) and 32 full-term infants, effects of perinatal factors, and associations between infant hippocampal shape and volume, and 7year verbal and visual memory (California Verbal Learning Test — Children's Version and Dot Locations). Infants underwent 1. 5T magnetic resonance imaging at term equivalent age. Hippocampi were segmented, and spherical harmonics-point distribution model shape analysis was undertaken. VPT infants' hippocampi were less infolded than full-term infants, being less curved toward the midline and less arched superior-inferiorly. Straighter hippocampi were associated with white matter injury and postnatal corticosteroid exposure. There were no significant associations between infant hippocampal shape and 7year memory measures. However, larger infant hippocampal volumes were associated with better verbal memory scores. Altered hippocampal shape in VPT infants at term equivalent age may reflect delayed or disrupted development. This study provides further insight into early hippocampal development and the nature of hippocampal abnormalities in prematurity.

YNIMG Journal 2012 Journal Article

Corpus callosum alterations in very preterm infants: Perinatal correlates and 2year neurodevelopmental outcomes

• Deanne K. Thompson
• Terrie E. Inder
• Nathan Faggian
• Simon K. Warfield
• Peter J. Anderson
• Lex W. Doyle
• Gary F. Egan

The aim of this study was to relate altered corpus callosum (CC) integrity in 106 very preterm (VPT) infants (<30weeks' gestational age or <1250g birth weight) at term equivalent to perinatal predictors and neurodevelopmental outcomes at two years. T1 and diffusion magnetic resonance images were obtained. The CC was traced, and divided into six sub-regions for cross-sectional area and shape analyses. Fractional anisotropy, mean, axial and radial diffusivity were sampled within the CC, and probabilistic tractography was performed. Perinatal predictors were explored. The Bayley Scales of Infant Development (BSID-II) was administered at two years. Intraventricular hemorrhage was associated with a smaller genu and altered diffusion values within the anterior and posterior CC of VPT infants. White matter injury was associated with widespread alterations to callosal diffusion values, especially posteriorly, and radial diffusivity was particularly elevated, indicating altered myelination. Reduced CC tract volume related to lower gestational age, particularly posteriorly. Reduced posterior callosal skew was associated with postnatal corticosteroid exposure. This more circular CC was associated with delayed cognitive development. Higher diffusivity, particularly in splenium tracts, was associated with impaired motor development. This study elucidates perinatal predictors and adverse neurodevelopmental outcomes associated with altered callosal integrity in VPT infants.

YNIMG Journal 2012 Journal Article

Neural correlates coding stimulus level and perception of capsaicin-evoked urge-to-cough in humans

• Michael J. Farrell
• Leonie J. Cole
• David Chiapoco
• Gary F. Egan
• Stuart B. Mazzone

The perception of airways irritation is represented in a distributed brain network. However, the functional roles of sub-regions of this network are yet to be determined. The aim of this study was to measure brain activation in healthy participants as they inhaled two doses of capsaicin to identify dose-dependent and dose-independent responses. Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measures of brain responses during inhalation of saline, and a low and high dose of capsaicin were made from 16 healthy participants. Subjective ratings of the urge-to-cough were also made during capsaicin challenges. The majority of brain regions that were activated during capsaicin inhalation, including insula and mid cingulate cortex, showed graduated responses to the two doses of capsaicin. Prefrontal and parietal regions had dose-independent activation, whereas premotor regions and the cerebellum activated exclusively at the high dose of capsaicin. Activation in the somatosensory and mid-cingulate cortices correlated with ratings of urge-to-cough. In the brainstem, capsaicin produced dose-dependent activations in respiratory-related regions of the dorsal pons and lateral medulla. These data show dissociable response patterns to capsaicin inhalation that may represent different regional processes involved in monitoring and assessing stimulus intensity, determining the spatial localization of the stimulus and suppressing motor responses.

YNIMG Journal 2012 Journal Article

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

• Jeremy F.P. Ullmann
• Marianne D. Keller
• Charles Watson
• Andrew L. Janke
• Nyoman D. Kurniawan
• Zhengyi Yang
• Kay Richards
• George Paxinos

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.

YNIMG Journal 2011 Journal Article

Characterization of the corpus callosum in very preterm and full-term infants utilizing MRI

• Deanne K. Thompson
• Terrie E. Inder
• Nathan Faggian
• Leigh Johnston
• Simon K. Warfield
• Peter J. Anderson
• Lex W. Doyle
• Gary F. Egan

The corpus callosum is the largest white matter tract, important for interhemispheric communication. The aim of this study was to investigate and compare corpus callosum size, shape and diffusion characteristics in 106 very preterm infants and 22 full-term infants. Structural and diffusion magnetic resonance images were obtained at term equivalent. The corpus callosum was segmented, cross-sectional areas were calculated, and shape was analyzed. Fractional anisotropy, mean, axial and radial diffusivity measures were obtained from within the corpus callosum, with additional probabilistic tractography analysis. Very preterm infants had significantly reduced callosal cross-sectional area compared with term infants (p =0. 004), particularly for the mid-body and posterior sub-regions. Very preterm callosi were more circular (p =0. 01). Fractional anisotropy was lower (p =0. 007) and mean (p =0. 006) and radial (p =0. 001) diffusivity values were higher in very preterm infants’ callosi, particularly at the anterior and posterior ends. The volume of tracts originating from the corpus callosum was reduced in very preterm infants (p =0. 001), particularly for anterior mid-body (p =0. 01) and isthmus tracts (p =0. 04). This study characterizes callosal size, shape and diffusion in typically developing infants at term equivalent age, and reports macrostructural and microstructural abnormalities as a result of prematurity.

YNIMG Journal 2011 Journal Article

Segmentation of the mouse hippocampal formation in magnetic resonance images

• Kay Richards
• Charles Watson
• Rachel F. Buckley
• Nyoman D. Kurniawan
• Zhengyi Yang
• Marianne D. Keller
• Richard Beare
• Perry F. Bartlett

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 30μm isotropic resolution images acquired with a 16. 4T MR imaging system and combined using super-resolution reconstruction.

YNIMG Journal 2010 Journal Article

An optimised framework for reconstructing and processing MR phase images

• Zhaolin Chen
• Leigh A. Johnston
• Dae Hyuk Kwon
• Se Hong Oh
• Zang-Hee Cho
• Gary F. Egan

Phase contrast imaging holds great potential for in vivo biodistribution studies of paramagnetic molecules and materials. However, in vivo quantification of iron storage and other paramagnetic materials requires improvements in reconstruction and processing of MR complex images. To achieve this, we have developed a framework including (i) an optimal coil sensitivity smoothing filter for phase imaging determined at the maximal signal to noise ratio, (ii) a phase optimised and a complex image optimised reconstruction approach, and (iii) a magnitude and phase correlation test criterion to determine the low pass filter parameter for background phase removal. The method has been evaluated using 3T and 7T MRI data containing cortical regions, the basal ganglia including the caudate, and the midbrain including the substantia nigra. The optimised reconstruction improves phase image contrast and noise suppression compared with conventional reconstruction approaches, and the correlation test criterion provides an objective method for separation of the local phase signal from the background phase measurements. Phase values of several brain regions of interest have been calculated, including gray matter (−1. 23 Hz at 7T and −0. 55 Hz at 3T), caudate (−3. 8 Hz at 7T), and the substantia nigra (−6. 2 Hz at 7T).

YNIMG Journal 2010 Journal Article

Dynamic subcortical blood flow during male sexual activity with ecological validity: A perfusion fMRI study

• Janniko R. Georgiadis
• Michael J. Farrell
• Ruud Boessen
• Derek A. Denton
• Maria Gavrilescu
• Rudie Kortekaas
• Remco J. Renken
• Johannes M. Hoogduin

This study used arterial spin labeling (ASL) fMRI to measure brain perfusion in a group of healthy men under conditions that closely resembled customary sexual behavior. Serial perfusion measures for 30 min during two self-limited periods of partnered penis stimulation, and during post-stimulatory periods, revealed novel sexual activity-related cerebral blood flow (rCBF) changes, mainly in subcortical parts of the brain. Ventral pallidum rCBF was highest during the onset of penile erection, and lowest after the termination of penis stimulation. The perceived level of sexual arousal showed the strongest positive association with rCBF in the right basal forebrain. In addition, our results demonstrate that distinct subregions of the hypothalamus and cingulate cortex subserve opposite functions during human male sexual behavior. The lateral hypothalamus and anterior part of the middle cingulate cortex showed increased rCBF correlated with penile erection. By contrast, the anteroventral hypothalamus and subgenual anterior cingulate cortex exhibited rCBF changes correlated with penile detumescence after penile stimulation. Continuous rapid and high-resolution brain perfusion imaging during normal sexual activity has provided novel insights into the central mechanisms that control male sexual arousal.

YNIMG Journal 2010 Journal Article

Retrograde axonal tracing using manganese enhanced magnetic resonance imaging

• Ken Matsuda
• Hong X. Wang
• Chao Suo
• David McCombe
• Malcolm K. Horne
• Wayne A. Morrison
• Gary F. Egan

Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate retrograde axonal tracing in the rat sciatic nerve model to assess its potential to examine peripheral nerve injury. The right sciatic nerve was exposed and crushed. After each recovery period, the distal part of the right sciatic nerve was injected with manganese (400 mM, 15 μl). After allowing 3 days for manganese transport the animals were subsequently scanned to visualize the sciatic nerve and its corresponding spinal cord and dorsal root ganglia with T1-weighted MRI. Thirty-four animals were randomly divided into 4 experimental groups according to their recovery period post-crush injury: 3 days (n =6), 2 weeks (n=6), 4 weeks (n=6) and 12 weeks (n=6); and two control groups: a non-crushed group (n=6) and a nerve cut group (n=4). In the no-injury group, the right sciatic nerve tract including its corresponding spinal cord and dorsal root ganglia showed significant T1 signal enhancement. In the animals with crush injury, the MR signal intensity was significantly reduced proximal to the injured site but gradually reappeared with increasing recovery period. The signal intensity of the sciatic tract was compared to the results of behavioral functional testing, retrograde axonal tracing with neural tracer fluorogold and histomorphometric analysis of the distal nerve. Significant correlations were observed between the MR signal intensity and the behavioral functional test (r =0. 50, p <0. 05), and the retrograde axonal tracing (r =0. 88; p <0. 05). Retrograde neuronal tract tracing with MEMRI can be used for the assessment of peripheral nerve damage and regeneration.

YNIMG Journal 2009 Journal Article

Long-term motor training induced changes in regional cerebral blood flow in both task and resting states

• Jinhu Xiong
• Liangsuo Ma
• Binquan Wang
• Shalini Narayana
• Eugene P. Duff
• Gary F. Egan
• Peter T. Fox

Neuroimaging studies of functional activation often only reflect differentiated involvement of brain regions compared between task performance and control states. Signals common for both states are typically not revealed. Previous motor learning studies have shown that extensive motor skill training can induce profound changes in regional activity in both task and control states. To address the issue of brain activity changes in the resting-state, we explored long-term motor training induced neuronal and physiological changes in normal human subjects using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Ten healthy subjects performed a finger movement task daily for four weeks, during which three sessions of fMRI images and two sessions of PET images were acquired. Using a classical data analysis strategy, we found that the brain activation increased first and then returned to the pre-training, replicating previous findings. Interestingly, we also observed that motor skill training induced significant increases in regional cerebral blood flow (rCBF) in both task and resting states as the practice progressed. The apparent decrease in activation may actually result from a greater increase in activity in the resting state, rather than a decrease in the task state. By showing that training can affect the resting state, our findings have profound implications for the interpretation of functional activations in neuroimaging studies. Combining changes in resting state with activation data should greatly enhance our understanding of the mechanisms of motor-skill learning.

YNIMG Journal 2009 Journal Article

Morphometric abnormalities and hyperanxiety in genetically epileptic rats: A model of psychiatric comorbidity?

• Viviane Bouilleret
• R. Edward Hogan
• Dennis Velakoulis
• Michael R. Salzberg
• Lei Wang
• Gary F. Egan
• Terence J. O'Brien
• Nigel C. Jones

Background Imaging studies of epilepsy patients with comorbid affective disturbance demonstrate morphometric changes in limbic brain regions implicated in psychiatric disease. Genetic Absence Epilepsy Rats from Strasbourg (GAERS), specifically bred for their epilepsy phenotype, also exhibit elevated anxiety-like behaviors suggesting a common causality. Here we examined whether relevant cerebral morphological alterations exist in this rat strain using volumetric measurements and large deformation high dimensional mapping (HDM-LD), a tool recently validated to produce accurate three-dimensional surface representations of the hippocampus. Methods Volumetric MRI and the Open Field test of anxiety were performed in adult female GAERS (n =12) and Non-Epileptic Controls (NEC; n =11). The volumes of selected brain regions, including cortex, hippocampus, amygdala, thalamus, hypothalamus and lateral ventricles, were measured using Region-Of-Interest analysis from the MRI data and total volumes compared between the two strains. Results GAERS had increased amygdala (right: p =0. 003; left p <0. 001), cortices (right: p =0. 006; left p =0. 012) and ventricular volumes (p =0. 002) when compared with NEC rats. Further, HDM-LD showed GAERS to have hippocampal volume loss in two regions: the medial hippocampal surface immediately caudal to the hippocampal commissure, and the lateral hippocampal surface over the mid-portion of the septotemporal axis. GAERS exhibited increased anxiety in the Open Field compared with NEC rats: reduced distance traveled (p <0. 001) and reduced time in the centre area (p =0. 042). Conclusions Morphometric brain changes in GAERS could be relevant to their hyperanxious and epileptic phenotypes. This model may be useful in illuminating the pathogenesis of affective disorders generally, as well as modeling psychiatric comorbidities of epilepsy.

YNIMG Journal 2008 Journal Article

Nonlinear estimation of the BOLD signal

• Leigh A. Johnston
• Eugene Duff
• Iven Mareels
• Gary F. Egan

Signal variations in functional Magnetic Resonance Imaging experiments essentially reflect the vascular system response to increased demand for oxygen caused by neuronal activity, termed the blood oxygenation level dependent (BOLD) effect. The most comprehensive model to date of the BOLD signal is formulated as a mixed continuous-discrete-time system of nonlinear stochastic differential equations. Previous approaches to the analysis of this system have been based on linearised approximations of the dynamics, which are limited in their ability to capture the inherent nonlinearities in the physiological system. In this paper we present a nonlinear filtering method for simultaneous estimation of the hidden physiological states and the system parameters, based on an iterative coordinate descent framework. State estimates of the cerebral blood flow, cerebral blood volume and deoxyhaemoglobin content are determined using a particle filter, demonstrated via simulation to be accurate, robust and efficient in comparison to linearisation-based techniques. The adaptive state and parameter estimation algorithm generates physiologically reasonable parameter estimates for experimental fMRI data. It is anticipated that signal processing techniques for modelling and estimation will become increasingly important in fMRI analyses as limitations of linear and linearised modelling are reached.

YNIMG Journal 2008 Journal Article

Reproducible activation in BA2, 1 and 3b associated with texture discrimination in healthy volunteers over time

• Leeanne M. Carey
• David F. Abbott
• Gary F. Egan
• Geoffrey A. Donnan

We aimed to quantify specific location and reproducibility of brain activation associated with discrimination of a moving textured surface in adult healthy volunteers over a 6-month interval. A sensory stimulation device was developed to provide a texture stimulus to the fingertips at a controlled speed and pressure. Repeat measurements of regional cerebral blood flow, using positron emission tomography (PET), were obtained in 10 healthy individuals, aged 33 to 80 years (mean=55. 8 years), at scanning sessions separated by 6 months. Stimulation and rest conditions were presented to either the right, dominant (n =5) or left non-dominant (n =5) hand. Activation location was objectively quantified with reference to probabilistic cytoarchitectonic maps. Differences in activation over time and regions of common activation were also quantified. Participants consistently activated Brodmann areas (BA) 2, 3b and 1, somatosensory areas of postcentral gyrus, at initial and 6-month studies: 93. 1% of common activation for the right-hand (RH) and 60. 6% for left-hand (LH) stimulation group were in these areas. Reproducible activation in BA6, 4a and 4p was also observed for the RH group (6. 8% of common activation) and LH group (39. 4%). There were no sites of significant difference over time for either hand. Highly consistent location of activation over time suggests that changes in loci of activation may be confidently monitored in adults using this paradigm. Use of probabilistic cytoarchitectonic maps permitted objective quantification of the anatomical location of the core of reproducible activation.

YNIMG Journal 2007 Journal Article

MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve

• Qizhu Wu
• Helmut Butzkueven
• Melissa Gresle
• Frank Kirchhoff
• Anna Friedhuber
• Qing Yang
• Hong Wang
• Ke Fang

Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are widely used to investigate central nervous system (CNS) white matter structure and pathology. Changes in principal diffusivities parallel and perpendicular to nerve fibers or axonal tracts have been associated with axonal pathology and de/dysmyelination respectively. However, the ultra-structural properties and the pathological alterations of white matter responsible for diffusivity changes have not been fully elucidated. We examined the relationship between the directional diffusivities and ultra-structural properties in mouse optic nerve using healthy animals, and mice with optic neuritis (ON) that exhibited marked inflammatory changes and moderately severe axonal pathology. Progressive axonal degeneration in ON resulted in a 23% reduction of parallel diffusivity as detected by diffusion MRI (P <10−5), but no change in perpendicular diffusivity. Parallel diffusion changes were highly correlated with the total axolemmal cross-sectional area in the pre-chiasmal portion of the optic nerve (r =0. 86, P <0. 001). This study provides quantitative evidence that reduced parallel diffusivity in the optic nerve correlates significantly with axolemmal cross-sectional area reductions. MRI-based assessment of axonal degeneration in murine ON is feasible and potentially useful for monitoring of neuro-protective therapies in preclinical trials in animals.

YNIMG Journal 2005 Journal Article

Functional connectivity during Stroop task performance

• Ben J. Harrison
• Marnie Shaw
• Murat Yücel
• Rosemary Purcell
• Warrick J. Brewer
• Stephen C. Strother
• Gary F. Egan
• James S. Olver

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2 15O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two “parallel” networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

YNIMG Journal 2002 Journal Article

Abnormal Functional Connectivity in Posttraumatic Stress Disorder

• Marnie E. Shaw
• Stephen C. Strother
• Alexander C. McFarlane
• Philip Morris
• Jon Anderson
• C.Richard Clark
• Gary F. Egan

This study investigated the efficacy of a combined multivariate/resampling procedure for the analysis of PET activation studies. The covariance-based multivariate analysis was used to investigate distributed brain systems in posttraumatic stress disorder (PTSD) patients and matched controls during performance of a working memory task. The results were compared to univariate results obtained in an earlier study. We also examined whether the PTSD patients demonstrated a breakdown in functional connectivity that may be associated with working memory difficulties often experienced by these patients. A resampling procedure was used specifically to test the reliability of measured between-group effects, to avoid mistaken inference on the basis of random intersubject differences. Significant and reproducible differences in network connectivity were obtained for the two groups. The functional connectivity pattern of the patient group was characterized by relatively more activation in the bilateral inferior parietal lobes and the left precentral gyrus than the control group, and less activation in the inferior medial frontal lobe, bilateral middle frontal gyri and right inferior temporal gyrus. The resampling procedure provided direct evidence that working memory updating was abnormal in PTSD patients relative to matched controls. This work focuses on the need to identify extended brain networks (in addition to regionally specific changes) for the full characterization of brain responses in neuroimaging experiments. Our multivariate analysis explicitly measures the reliability of the patterns of functional connectivity we obtain and demonstrates the potential of such analyses for the study of brain network dysfunction in psychopathology.

YNIMG Journal 2002 Journal Article

Simulation of the Effects of Global Normalization Procedures in Functional MRI

• Maria Gavrilescu
• Marnie E. Shaw
• Geoffrey W. Stuart
• Peter Eckersley
• Imants D. Svalbe
• Gary F. Egan

We report on differences in sensitivity and false-positive rate across five methods of global normalization using resting-state fMRI data embedded with simulated activation. These methods were grand mean session scaling, proportional scaling, ANCOVA, a masking method, and an orthogonalization method. We found that global normalization by proportional scaling and ANCOVA decreased the sensitivity of the statistical analysis and induced artifactual deactivation even when the correlation between the global signal and the experimental paradigm was relatively low. The masking method and the orthogonalization method performed better from this perspective but are both restricted to certain experimental conditions. Based on the results of these simulations, we offer practical guidelines for the choice of global normalization method least likely to bias the experimental results.

YNIMG Journal 2002 Journal Article

Widespread Dorsal Stream Activation during a Parametric Mental Rotation Task, Revealed with Functional Magnetic Resonance Imaging

• Katherine Podzebenko
• Gary F. Egan
• John D.G. Watson

Following a parametrically modulated mental rotation task, in which 10 healthy subjects were instructed to determine whether alphanumeric characters were normal or mirror-reversed, bilateral dorsal stream activations culminating in the intraparietal region were revealed with functional magnetic resonance imaging. Although the parietal activations were bilateral, we observed a right hemispheric dominance for the task, consistent with our previous findings (I. M. Harris et al. , 2000). By studying individual activation maps in response to the paradigm, we discerned parcellation of the intraparietal region into discrete subdivisions. In this paper, we address the involvement of structures surrounding the intraparietal sulcus in mental rotation, as well as describing a wider visuospatial attentional network, encompassing neural substrates within the dorsal stream.

YNIMG Journal 2001 Journal Article

A longitudinal PET study of motor recovery and neural plasticity in stroke

• Leeanne Carey
• David Abbott
• Gary F. Egan
• Graeme O'Keefe
• Graeme Jackson
• Geoffrey Donnan

YNIMG Journal 2001 Journal Article

A simulation of the effects of global normalization techniques in fMRI

• Maria Gavrilescu
• Marnie Shaw
• Peter Eckersley
• Imants Svalbe
• Hong Wang
• Gary F. Egan

YNIMG Journal 2001 Journal Article

Abnormal functional connectivity in post-traumatic stress disorder: insight from multivariate analysis

• Marnie Shaw
• Stephen Strother
• Jon Anderson
• Gary F. Egan
• Richard Ciark

YNIMG Journal 2001 Journal Article

Comparison of detection of fast and slow motion revealed by fMRI

• Nathan Walters
• Katherine Podzebenko
• Gary F. Egan
• John D.G. Watson

YNIMG Journal 2001 Journal Article

Cortical localisation of externalized-moving and internalized-stationary auditory percepts: a PET correlation study

• Gary F. Egan
• Marc Seal
• Johannes Leung
• Recep Ulusoy
• Simon Carlisle
• David Copolov

YNIMG Journal 2001 Journal Article

Parametric modulation of the dorsal stream during mental rotation, revealed with fMRI

• Katherine Podzebenko
• Nathan Walters
• Michael Kean
• Gary F. Egan
• John D.G. Watson

YNIMG Journal 2001 Journal Article

Selective attention for motor action: An fMRI study

• Heidi Chapman
• Maria Gavrilescu
• Hong Wang
• Michael Kean
• Gary F. Egan
• Umberto Castiello

YNIMG Journal 2000 Journal Article

Correlational studies of auditory stimulation and auditory hallucinations in schizophrenic subjects using PET

• Gary F. Egan
• Marc L. Seal
• Paul Maruff
• Matthew Waite
• Michael Wong
• Recep Ulsoy
• David L. Copolov

YNIMG Journal 2000 Journal Article

The Functional Neuroanatomy and Long-Term Reproducibility of Brain Activation Associated with a Simple Finger Tapping Task in Older Healthy Volunteers: A Serial PET Study

• Leeanne M. Carey
• David F. Abbott
• Gary F. Egan
• Henri J. Tochon-Danguy
• Geoffrey A. Donnan

We examined long-term reproducibility of the functional organization of the brain associated with a simple finger tapping movement using positron emission tomography (PET). Repeat measurements of regional cerebral blood flow were obtained in 10 individuals, ages 35 to 82 years (mean 52 years), at scanning sessions separated by 6 months. Although the functional neuroanatomy of hand movements has previously been investigated with PET by a number of groups, none has reported systematic investigation of the consistency of brain activation over an extended time. As expected, we found significant activation in the left precentral gyrus [Talairach coordinate (−32, −34, 52)], postcentral gyrus (−22, −48, 56), and supplementary motor area (SMA) (−2, −18, 52) at the initial study, consistent with previous studies in younger subjects. For the follow-up study we also found significant activation in the left precentral (−36, −28, 52) and postcentral (−28, −36, 52) gyri and in the SMA (2, −16, 56). Our group results demonstrate consistent anatomical location and extent of motor activation over time. More importantly, analysis of individuals confirmed the presence of consistent sites of activation in primary sensorimotor cortex and SMA over the 6-month interval in most subjects. A high degree of consistency in location of activation in the group, and within individuals, over time suggests that changes in loci of activation may be confidently monitored using the PET method. Evidence of individual differences in extent of activation over time highlights the need for caution when interpreting similar changes in patient studies.