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Christian Beaulieu

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22 papers

1 author row

YNICL Journal 2024 Journal Article

Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study

Hans-Peter Müller
Agessandro Abrahao
Christian Beaulieu
Michael Benatar
Annie Dionne
Angela Genge
Richard Frayne
Simon J. Graham

OBJECTIVE: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS. METHODS: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses. RESULTS: FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts. CONCLUSIONS: Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.

YNICL Journal 2022 Journal Article

Diffusion tensor tractography of the fornix in cerebral amyloid angiopathy, mild cognitive impairment and Alzheimer’s disease

Ibrahim Shaikh
Christian Beaulieu
Myrlene Gee
Cheryl R. McCreary
Andrew E. Beaudin
Diana Valdés-Cabrera
Eric E. Smith
Richard Camicioli

PURPOSE: Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls. METHODS: Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI. RESULTS: Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was ∼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group. CONCLUSION: There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.

YNIMG Journal 2021 Journal Article

A simple estimate of axon size with diffusion MRI

Kevin D Harkins
Christian Beaulieu
Junzhong Xu
John C Gore
Mark D Does

Noninvasive estimation of mean axon diameter presents a new opportunity to explore white matter plasticity, development, and pathology. Several diffusion-weighted MRI (DW-MRI) methods have been proposed to measure the average axon diameter in white matter, but they typically require many diffusion encoding measurements and complicated mathematical models to fit the signal to multiple tissue compartments, including intra- and extra-axonal spaces. Here, Monte Carlo simulations uncovered a straightforward DW-MRI metric of axon diameter: the change in radial apparent diffusion coefficient estimated at different effective diffusion times, ΔD⊥. Simulations indicated that this metric increases monotonically within a relevant range of effective mean axon diameter while being insensitive to changes in extra-axonal volume fraction, axon diameter distribution, g-ratio, and influence of myelin water. Also, a monotonic relationship was found to exist for signals coming from both intra- and extra-axonal compartments. The slope in ΔD⊥ with effective axon diameter increased with the difference in diffusion time of both oscillating and pulsed gradient diffusion sequences.

YNIMG Journal 2021 Journal Article

Automated cerebral cortex segmentation based solely on diffusion tensor imaging for investigating cortical anisotropy

Graham Little
Christian Beaulieu

To extract Diffusion Tensor Imaging (DTI) parameters from the human cortex, the inner and outer boundaries of the cortex are usually defined on 3D-T1-weighted images and then applied to the co-registered DTI. However, this analysis requires the acquisition of an additional high-resolution structural image that may not be practical in various imaging studies. Here an automatic cortical boundary segmentation method was developed to work directly only on the native DTI images by using fractional anisotropy (FA) maps and mean diffusion weighted images (DWI), the latter with acceptable gray-white matter image contrast. This new method was compared to the conventional cortical segmentations generated from high-resolution T1 structural images in 5 participants. In addition, the proposed method was applied to 15 healthy young adults (10 cross-sectional, 5 test-retest) to measure FA, MD, and radiality of the primary eigenvector across the cortex on whole-brain 1. 5 mm isotropic images acquired in 3. 5 min at 3T. The proposed method generated reasonable segmentations of the cortical boundaries for all individuals and large proportions of the proposed method segmentations (more than 85%) were within ±1 mm from those generated with the conventional approach on higher resolution T1 structural images. Both FA (~0. 15) and MD (~0. 77 × 10−3 mm2/s) extracted halfway between the cortical boundaries were relatively stable across the cortex, although focal regions such as the posterior bank of the central sulcus, anterior insula, and medial temporal lobe showed higher FA. The primary eigenvectors were primarily oriented radially to the middle cortical surface, but there were tangential orientations in the sulcal fundi as well as in the posterior bank of the central sulcus. The proposed method demonstrates the feasibility and accuracy of cortical analysis in native DTI space while avoiding the acquisition of other imaging contrasts like 3D T1-weighted scans.

YNICL Journal 2021 Journal Article

Examining brain white matter after pediatric mild traumatic brain injury using neurite orientation dispersion and density imaging: An A-CAP study

Ayushi Shukla
Ashley L. Ware
Sunny Guo
Bradley Goodyear
Miriam H. Beauchamp
Roger Zemek
William Craig
Quynh Doan

BACKGROUND: Pediatric mild traumatic brain injury (mTBI) affects millions of children annually. Diffusion tensor imaging (DTI) is sensitive to axonal injuries and white matter microstructure and has been used to characterize the brain changes associated with mild traumatic brain injury (mTBI). Neurite orientation dispersion and density imaging (NODDI) is a diffusion model that can provide additional insight beyond traditional DTI metrics, but has not been examined in pediatric mTBI. The goal of this study was to employ DTI and NODDI to gain added insight into white matter alterations in children with mTBI compared to children with mild orthopedic injury (OI). METHODS: Children (mTBI n = 320, OI n = 176) aged 8-16.99 years (12.39 ± 2.32 years) were recruited from emergency departments at five hospitals across Canada and underwent 3 T MRI on average 11 days post-injury. DTI and NODDI metrics were calculated for seven major white matter tracts and compared between groups using univariate analysis of covariance controlling for age, sex, and scanner type. False discovery rate (FDR) was used to correct for multiple comparisons. RESULTS: Univariate analysis revealed no significant group main effects or interactions in DTI or NODDI metrics. Fractional anisotropy and neurite density index in all tracts exhibited a significant positive association with age and mean diffusivity in all tracts exhibited a significant negative association with age in the whole sample. CONCLUSIONS: Overall, there were no significant differences between mTBI and OI groups in brain white matter microstructure from either DTI or NODDI in the seven tracts. This indicates that mTBI is associated with relatively minor white matter differences, if any, at the post-acute stage. Brain differences may evolve at later stages of injury, so longitudinal studies with long-term follow-up are needed.

YNIMG Journal 2020 Journal Article

Diffusion time dependency along the human corpus callosum and exploration of age and sex differences as assessed by oscillating gradient spin-echo diffusion tensor imaging

Pascal Tétreault
Kevin D. Harkins
Corey A. Baron
Rob Stobbe
Mark D. Does
Christian Beaulieu

Conventional diffusion imaging uses pulsed gradient spin echo (PGSE) waveforms with diffusion times of tens of milliseconds (ms) to infer differences of white matter microstructure. The combined use of these long diffusion times with short diffusion times (<10 ms) enabled by oscillating gradient spin echo (OGSE) waveforms can enable more sensitivity to changes of restrictive boundaries on the scale of white matter microstructure (e. g. membranes reflecting the axon diameters). Here, PGSE and OGSE images were acquired at 4. 7 T from 20 healthy volunteers aged 20–73 years (10 males). Mean, radial, and axial diffusivity, as well as fractional anisotropy were calculated in the genu, body and splenium of the corpus callosum (CC). Monte Carlo simulations were also conducted to examine the relationship of intra- and extra-axonal radial diffusivity with diffusion time over a range of axon diameters and distributions. The results showed elevated diffusivities with OGSE relative to PGSE in the genu and splenium (but not the body) in both males and females, but the OGSE-PGSE difference was greater in the genu for males. Females showed positive correlations of OGSE-PGSE diffusivity difference with age across the CC, whereas there were no such age correlations in males. Simulations of radial diffusion demonstrated that for axon sizes in human brain both OGSE and PGSE diffusivities were dominated by extra-axonal water, but the OGSE-PGSE difference nonetheless increased with area-weighted outer-axon diameter. Therefore, the lack of OGSE-PGSE difference in the body is not entirely consistent with literature that suggests it is composed predominantly of axons with large diameter. The greater OGSE-PGSE difference in the genu of males could reflect larger axon diameters than females. The OGSE-PGSE difference correlation with age in females could reflect loss of smaller axons at older ages. The use of OGSE with short diffusion times to sample the microstructural scale of restriction implies regional differences of axon diameters along the corpus callosum with preliminary results suggesting a dependence on age and sex.

YNICL Journal 2020 Journal Article

Involvement of the dentate nucleus in the pathophysiology of amyotrophic lateral sclerosis: A multi-center and multi-modal neuroimaging study

Komal Bharti
Muhammad Khan
Christian Beaulieu
Simon J. Graham
Hannah Briemberg
Richard Frayne
Angela Genge
Lawrence Korngut

Amyotrophic lateral sclerosis (ALS) is characterized primarily by motor neuron but also frontotemporal lobar degeneration. Although the cerebellum is involved in both motor and cognitive functions, little is known of its role in ALS. We targeted the dentate nucleus (DN) in the cerebellum and the associated white matter fibers tracts connecting the DN to the rest of the brain using multimodal imaging techniques to examine the cerebellar structural and functional connectivity patterns in ALS patients and hypothesized that the DN is implicated in the pathophysiology of ALS. A cohort of 127 participants (56 healthy subjects (HS); 71 ALS patients) were recruited across Canada through the Canadian ALS Neuroimaging Consortium (CALSNIC). Resting state functional MRI, diffusion tensor imaging (DTI), and 3D weighted T1 structural images were acquired on a 3-tesla scanner. The DN in the cerebellum was used as a seed to evaluate the whole brain cerebral resting-state functional connectivity (rsFC). The superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP) and inferior cerebellar peduncle (ICP) were used as a region of interest in DTI to evaluate the structural integrity of the DN with the cortex and brain stem. Cerebellar volumetric analysis was done to examine the lobular and DN grey matter (GM) changes in ALS patients. Lastly, an association between DN rsFC and structural alterations were explored. DN rsFC was reduced with cerebrum (supplementary motor area, precentral gyrus, frontal, posterior parietal, temporal), lobule IV, and brain stem, and increased with parieto-occipital region. DN rsFC and white matter (WM) diffusivity alterations at SCP, MCP, and ICP were accompanied by correlations with ALSFRS-R. There were no DN volumetric changes. Notably, DN rsFC correlated with WM abnormalities at superior cerebellar peduncle. The DN plays a pathophysiological role in ALS. Impaired rsFC is likely due to the observed cerebellar peduncular WM damage given the lack of GM atrophy of the DN. This study demonstrates altered cerebellar rsFC connectivity with motor and extra-motor regions in ALS, and impaired rsFC is likely due to the observed cerebellar peduncular WM damage given the lack of GM atrophy of the DN. The correlation between the altered DN connectivity, and the behavioral data support the hypothesis that the DN plays a pathophysiological role in ALS.

YNIMG Journal 2018 Journal Article

High resolution in-vivo diffusion imaging of the human hippocampus

Sarah Treit
Trevor Steve
Donald W. Gross
Christian Beaulieu

The human hippocampus is a key target of many imaging studies given its capacity for neurogenesis, role in long term potentiation and memory, and nearly ubiquitous involvement in neurological and psychiatric conditions. Diffusion tensor imaging (DTI) has detected microstructural abnormalities of the human hippocampus associated with various disorders, but acquisitions have typically been limited to low spatial resolution protocols designed for whole brain (e. g. > 2 mm isotropic, >8 mm3 voxels), limiting regional specificity and worsening partial volume effects. The purpose here was to develop a simple DTI protocol using readily available standard single-shot EPI at 3T, capable of yielding much higher spatial resolution images (1 x 1 x 1 mm3) of the human hippocampus in a ‘clinically feasible’ scan time of ~6 min. A thin slab of twenty 1 mm slices oriented along the long axis of the hippocampus enabled efficient coverage and a shorter repetition time, allowing more diffusion weighted images (DWIs) per slice per unit time. In combination with this strategy, a low b value of 500 s/mm2 was chosen to help overcome the very low SNR of a 1 x 1 x 1 mm3 EPI acquisition. 1 mm isotropic mean DWIs (averaged over 120–128 DWIs) showed excellent detail of the hippocampal architecture (e. g. morphology and digitations, sub-regions, stratum lacunosum moleculare - SLM) that was not readily visible on 2 mm isotropic diffusion images. Diffusion parameters within the hippocampus were consistent across subjects and fairly homogenous across sub-regions of the hippocampus (with the exception of the SLM and tail). However, it is expected that DTI parameters will be sensitive to microstructural changes associated with a number of clinical disorders (e. g. epilepsy, dementia) and that this practical, translatable approach for high resolution acquisition will facilitate localized detection of hippocampal pathology.

YNICL Journal 2017 Journal Article

Sexual dimorphism of volume reduction but not cognitive deficit in fetal alcohol spectrum disorders: A combined diffusion tensor imaging, cortical thickness and brain volume study

Sarah Treit
Zhang Chen
Dongming Zhou
Lauren Baugh
Carmen Rasmussen
Gail Andrew
Jacqueline Pei
Christian Beaulieu

Quantitative magnetic resonance imaging (MRI) has revealed abnormalities in brain volumes, cortical thickness and white matter microstructure in fetal alcohol spectrum disorders (FASD); however, no study has reported all three measures within the same cohort to assess the relative magnitude of deficits, and few studies have examined sex differences. Participants with FASD (n = 70; 30 females; 5-32 years) and healthy controls (n = 74; 35 females; 5-32 years) underwent cognitive testing and MRI to assess cortical thickness, regional brain volumes and fractional anisotropy (FA)/mean diffusivity (MD) of white matter tracts. A significant effect of group, age-by-group, or sex-by-group was found for 9/9 volumes, 7/39 cortical thickness regions, 3/9 white matter tracts, and 9/10 cognitive tests, indicating group differences that in some cases differ by age or sex. Volume reductions for several structures were larger in males than females, despite similar deficits of cognition in both sexes. Correlations between brain structure and cognitive scores were found in females of both groups, but were notably absent in males. Correlations within a given MRI modality (e.g. total brain volume and caudate volume) were prevalent in both the control and FASD groups, and were more numerous than correlations between measurement types (e.g. volumes and diffusion tensor imaging) in either cohort. This multi-modal MRI study finds widespread differences of brain structure in participants with prenatal alcohol exposure, and to a greater extent in males than females which may suggest attenuation of the expected process of sexual dimorphism of brain structure during typical development.

YNIMG Journal 2016 Journal Article

Amygdala subnuclei response and connectivity during emotional processing

Stanislau Hrybouski
Arash Aghamohammadi-Sereshki
Christopher R. Madan
Andrea T. Shafer
Corey A. Baron
Peter Seres
Christian Beaulieu
Fraser Olsen

The involvement of the human amygdala in emotion-related processing has been studied using functional magnetic resonance imaging (fMRI) for many years. However, despite the amygdala being comprised of several subnuclei, most studies investigated the role of the entire amygdala in processing of emotions. Here we combined a novel anatomical tracing protocol with event-related high-resolution fMRI acquisition to study the responsiveness of the amygdala subnuclei to negative emotional stimuli and to examine intra-amygdala functional connectivity. The greatest sensitivity to the negative emotional stimuli was observed in the centromedial amygdala, where the hemodynamic response amplitude elicited by the negative emotional stimuli was greater and peaked later than for neutral stimuli. Connectivity patterns converge with extant findings in animals, such that the centromedial amygdala was more connected with the nuclei of the basal amygdala than with the lateral amygdala. Current findings provide evidence of functional specialization within the human amygdala.

YNIMG Journal 2015 Journal Article

Accelerated longitudinal cortical thinning in adolescence

Dongming Zhou
Catherine Lebel
Sarah Treit
Alan Evans
Christian Beaulieu

It remains unclear if changes of the cerebral cortex occur gradually from childhood to adulthood, or if adolescence marks a differential period of cortical development. In the current study of 90 healthy volunteers aged 5–32years (48 females, 85 right handed) with 180 scans (2 scans for each participant with ~4year gaps), thinning of overall mean thickness and across the four major cortical lobes bilaterally was observed across this full age span. However, the thinning rate, calculated as Δcortical thickness/Δage (mm/year) between scans of each participant, revealed an accelerated cortical thinning during adolescence, which was preceded by less thinning in childhood and followed by decelerated thinning in young adulthood. Males and females showed similarly faster thinning rates during adolescence relative to young adults. The underlying basis and role of accelerated cortical thinning during adolescence for cognition, behaviour and disorders that appear at such a stage of development remains to be determined in future work.

YNICL Journal 2014 Journal Article

Response inhibition deficits in children with Fetal Alcohol Spectrum Disorder: Relationship between diffusion tensor imaging of the corpus callosum and eye movement control

Angelina Paolozza
Sarah Treit
Christian Beaulieu
James N. Reynolds

Response inhibition is the ability to suppress irrelevant impulses to enable goal-directed behavior. The underlying neural mechanisms of inhibition deficits are not clearly understood, but may be related to white matter connectivity, which can be assessed using diffusion tensor imaging (DTI). The goal of this study was to investigate the relationship between response inhibition during the performance of saccadic eye movement tasks and DTI measures of the corpus callosum in children with or without Fetal Alcohol Spectrum Disorder (FASD). Participants included 43 children with an FASD diagnosis (12.3 ± 3.1 years old) and 35 typically developing children (12.5 ± 3.0 years old) both aged 7-18, assessed at three sites across Canada. Response inhibition was measured by direction errors in an antisaccade task and timing errors in a delayed memory-guided saccade task. Manual deterministic tractography was used to delineate six regions of the corpus callosum and calculate fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity, and perpendicular diffusivity. Group differences in saccade measures were assessed using t-tests, followed by partial correlations between eye movement inhibition scores and corpus callosum FA and MD, controlling for age. Children with FASD made more saccade direction errors and more timing errors, which indicates a deficit in response inhibition. The only group difference in DTI metrics was significantly higher MD of the splenium in FASD compared to controls. Notably, direction errors in the antisaccade task were correlated negatively to FA and positively to MD of the splenium in the control, but not the FASD group, which suggests that alterations in connectivity between the two hemispheres of the brain may contribute to inhibition deficits in children with FASD.

YNIMG Journal 2013 Journal Article

Cortical thickness asymmetry from childhood to older adulthood

Dongming Zhou
Catherine Lebel
Alan Evans
Christian Beaulieu

Age-related thinning of the cortical mantle varies regionally, leading to hemispheric asymmetries in cortical thickness that may emerge at various stages of development and aging. Cortical asymmetry may play a role in modulating the functional maturation (or degradation) of language and cognition in humans, but its evolution over the lifespan is unknown. Here cortical thickness was negatively correlated with age in 274 5–59year old, right-handed healthy participants. Pre-adolescents showed limited regions of cortical asymmetry focused on medial occipital lobe (R>L) and inferior frontal gyrus (R>L), namely vision and language relevant areas. More extensive frontal (lateral R>L, medial L>R) and parietal lobe (lateral L>R, medial R>L) asymmetries emerged after adolescence, and increased during aging. Changes of cortical asymmetry in these regions may be linked to specialization of the brain with maturity.

YNIMG Journal 2013 Journal Article

The acute phase of Wallerian degeneration: Longitudinal diffusion tensor imaging of the fornix following temporal lobe surgery

Min Liu
Donald W. Gross
B. Matt Wheatley
Luis Concha
Christian Beaulieu

Numerous animal studies have shown the applicability of diffusion tensor imaging (DTI) to track Wallerian degeneration that occurs after injury to the neural fiber. Non-invasive biomarkers that may differentiate the early axonal breakdown and later myelin degradation have been attributed to either reduced parallel and elevated perpendicular diffusivity, respectively. While several human DTI studies have shown this potential at subacute and chronic time points, the diffusion changes that occur within the first week are unknown. Anterior temporal lobectomy (i. e. resection of hippocampus) is the standard surgical treatment of medically refractory temporal lobe epilepsy. The concomitant transection of the fimbria-fornix serves as a unique opportunity to examine the process of Wallerian degeneration since the timing is known. Six temporal lobe epilepsy patients underwent brain DTI before the surgery, three to four times within the first week post-operatively, and at one to four months following surgery. Both parallel and perpendicular diffusivities decreased markedly by a similar amount in the ipsilateral fornix within the first two days post-surgery. Approaching the end of the first week, perpendicular (but not parallel) diffusivity pseudo-recovered towards its pre-surgical value, but then increased dramatically months later. Fractional anisotropy, as a result of the combined action of the parallel and perpendicular diffusivities, stayed relatively stable within the first week and only reduced drastically at the chronic stage. DTI demonstrated acute water diffusion changes within days of transection that are not just limited to parallel diffusivity. While the chronic diffusion changes in the fornix are compatible with myelin degradation, the acute changes may reflect beading and swelling of axolemma, granular disintegration of the axonal neurofilaments, ischemia induced cytotoxic edema, and/or changes in the extra-axonal space including inflammatory changes and gliosis.

YNICL Journal 2012 Journal Article

Mesial temporal sclerosis is linked with more widespread white matter changes in temporal lobe epilepsy

Min Liu
Luis Concha
Catherine Lebel
Christian Beaulieu
Donald W. Gross

Temporal lobe epilepsy patients with unilateral mesial temporal sclerosis (TLE + uMTS) have been demonstrated to have extensive white matter abnormalities both ipsilateral and contralateral to the seizure onset zone. However, comparatively less is known about the white matter integrity of TLE patients without MTS (non-lesional TLE, nl-TLE). The purpose of the study was to investigate the diffusion properties of thirteen major white matter tracts in patients with TLE + uMTS and nl-TLE. Diffusion tensor imaging (DTI) was performed on 23 TLE + uMTS (15 left MTS and 8 right MTS), 15 nl-TLE and 21 controls. Thirteen tracts were delineated by tractography and their diffusion parameters compared for the two TLE groups relative to controls, with left and right hemispheres combined per tract. A subgroup analysis investigated left and right MTS separately. Compared to controls, reduced anisotropy was detected in ten tracts for TLE + uMTS, but only the parahippocampal cingulum and tapetum for nl-TLE. Right MTS subgroup showed reduced anisotropy in 7 tracts bilaterally (3 limbic, 3 association, 1 projection) and 2 tracts ipsilaterally (1 association, 1 projection) and the body of the corpus callosum whereas the left MTS subgroup showed reduced anisotropy in 4 tracts bilaterally (2 limbic, 1 association, 1 projection) and 2 tracts ipsilaterally (1 limbic, 1 association). Diffusion abnormalities in tracts were observed within and beyond the temporal lobe in TLE + uMTS and were more widespread than in nl-TLE. Patients with right MTS had more extensive, bilateral abnormalities in comparison to left MTS. These findings suggest different dysfunctional networks in TLE patients with and without MTS.

YNIMG Journal 2011 Journal Article

Developmental cortical thinning in fetal alcohol spectrum disorders

Dongming Zhou
Catherine Lebel
Claude Lepage
Carmen Rasmussen
Alan Evans
Katy Wyper
Jacqueline Pei
Gail Andrew

Regional cortical thickness was evaluated using CIVET processing of 3D T1-weighted images (i) to compare the variation in cortical thickness between 33 participants with fetal alcohol spectrum disorders (FASD) aged 6–30years (mean age 12. 3years) versus 33 age/sex/hand-matched controls, and (ii) to examine developmental changes in cortical thickness with age from children to young adults in both groups. Significant cortical thinning was found in the participants with FASD in large areas of the bilateral middle frontal lobe, pre- and post- central areas, lateral and inferior temporal and occipital lobes compared to controls. No significant cortical thickness increases were observed for the FASD group. Cortical thinning with age in a linear model was observed in both groups, but the locations were different for each group. FASD participants showed thinning with age in the left middle frontal, bilateral precentral, bilateral precuneus and paracingulate, left inferior occipital and bilateral fusiform gyri; while controls showed decreases with age in the bilateral middle frontal gyrus, right inferior frontal gyrus, bilateral precuneus gyrus, and bilateral occipital gyrus. A battery of cognitive assessments of memory, attention, motor, and verbal abilities was conducted with many of the FASD participants, but no significant correlations were found between these cognitive scores and regional cortical thickness. Non-invasive measurements of cortical thickness in children to young adults with FASD have identified both key regions of cortex that may be more deleteriously affected by prenatal alcohol exposure as well as cortical changes with age that differ from normal developmental thinning.

YNIMG Journal 2010 Journal Article

Age-related regional variations of the corpus callosum identified by diffusion tensor tractography

Catherine Lebel
Saul Caverhill-Godkewitsch
Christian Beaulieu

The corpus callosum is the largest white matter connection in the human brain, and an understanding of its evolution with age in healthy individuals is one crucial aspect for determining its role in cognition and disease. Diffusion tensor imaging (DTI) allows for investigation of age-related callosal changes since tractography can both virtually reconstruct the segments of the corpus callosum in vivo based on unique target cortical regions, and provide quantitative diffusion parameters reflecting tissue microstructure. DTI tractography was used to subdivide the corpus callosum into seven distinct sections based on unique target areas (i. e. , orbital frontal, anterior frontal, superior frontal, superior parietal, posterior parietal, temporal, and occipital) in a very large number of healthy volunteers (n =315) across a wide age range (5–59years). Both fractional anisotropy (FA) and mean diffusivity (MD) changes with respect to age were fit with Poisson curves, showing increasing FA and decreasing MD during childhood and adolescence and slightly slower decreases of FA and increases of MD at older ages. Age at peak FA values and minimum MD values varied from 21 to 44years, and an overall “outer-to-inner” trend was observed in which the anterior and posterior regions peaked earlier than central areas. In addition to these maturational trends of diffusion parameters reflecting the microstructural changes in the healthy corpus callosum over a large age range spanning childhood to older adulthood, these results can provide a baseline for identifying the presence and timing of callosal abnormalities in various brain disorders.

YNIMG Journal 2007 Journal Article

Voxel based versus region of interest analysis in diffusion tensor imaging of neurodevelopment

Lindsay Snook
Chris Plewes
Christian Beaulieu

There are two main methods of quantitative analysis in diffusion tensor imaging (DTI) studies: manual region of interest (ROI) and automated voxel based. The purpose of this study is to compare the results of each of these methods applied to the same data set. Linear correlative analysis was performed for mean diffusivity (Trace/3 ADC) and for fractional anisotropy (FA) versus age within 8–12 years (N =32) and within 21–27 years (N =28), as well as a group comparison. SPM analysis identified more structures changing with age, partly due to the limited regions measured with ROI analysis. In general, ROI and voxel-based analysis methods produced comparable results for widespread reductions of Trace/3 ADC and increases of FA with age, particularly for group comparison. The discrepancies (i. e. , missed regions) were likely related to problems of spatial normalization for SPM analysis, and masking localized changes by averaging all the voxels within a region of interest for ROI analysis. These two analysis methods for DTI offer complementary results, but neither one yields the complete story of neurodevelopment.

YNIMG Journal 2006 Journal Article

Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients

Luis Concha
Donald W. Gross
B. Matt Wheatley
Christian Beaulieu

Axonal degeneration of white matter fibers is a key consequence of neuronal or axonal injury. It is characterized by a series of time-related events with initial axonal membrane collapse followed by myelin degradation being its major hallmarks. Standard imaging cannot differentiate these phenomena, which would be useful for clinical investigations of degeneration, regeneration and plasticity. Animal models suggest that diffusion tensor magnetic resonance imaging (DTI) is capable of making such distinction. The applicability of this technique in humans would permit inferences on white matter microanatomy using a non-invasive technique. The surgical bisection of the anterior 2/3 of the corpus callosum for the palliative treatment of certain types of epilepsy serves as a unique opportunity to assess this method in humans. DTI was performed on three epilepsy patients before corpus callosotomy and at two time points (1 week and 2–4 months) after surgery. Tractography was used to define voxels of interest for analysis of mean diffusivity, fractional anisotropy and eigenvalues. Diffusion anisotropy was reduced in a spatially dependent manner in the genu and body of the corpus callosum at 1 week and remained low 2–4 months after the surgery. Decreased anisotropy at 1 week was due to a reduction in parallel diffusivity (consistent with axonal fragmentation), whereas at 2–4 months, it was due to an increase in perpendicular diffusivity (consistent with myelin degradation). DTI is capable of non-invasively detecting, staging and following the microstructural degradation of white matter following axonal injury.

YNIMG Journal 2005 Journal Article

Diffusion tensor imaging of neurodevelopment in children and young adults

Lindsay Snook
Lori-Anne Paulson
Dawne Roy
Linda Phillips
Christian Beaulieu

Diffusion tensor magnetic resonance imaging (DTI) was used to study regional changes in the brain's development from childhood (8–12 years, mean 11. 1 ± 1. 3, N = 32) to young adulthood (21–27 years, mean 24. 4 ± 1. 8, N = 28). Mean diffusivity (Trace/3 apparent diffusion coefficient, ADC) and fractional anisotropy (FA) were measured in 30 regions of interest (ROIs) in 13 distinct brain structures. Correlational analysis was performed to detect changes within 8–12 years and within 21–27 years, and group analysis to compare childhood diffusion properties with young adult values. Increases of fractional anisotropy were seen in the genu of the corpus callosum, splenium of the corpus callosum, corona radiata, putamen, and head of the caudate nucleus within 8–12 years, and also between childhood and young adulthood. Reductions in Trace/3 ADC were observed in 9 of 13 structures within 8–12 years and into young adulthood as well. DTI demonstrates more widespread changes in the brain's microstructure with maturation than previous reports using conventional T1-weighted MRI scans. These findings suggest a continuation of the brain's microstructural development through adolescence.

YNIMG Journal 2005 Journal Article

Imaging brain connectivity in children with diverse reading ability

Christian Beaulieu
Christopher Plewes
Lori Anne Paulson
Dawne Roy
Lindsay Snook
Luis Concha
Linda Phillips

Reading is a complex cognitive skill that requires the coordination of multiple brain regions. Although functional neuroimaging studies highlight the cortical brain regions associated with a specific cognitive task like reading, they do not directly address the underlying neural connections necessary for efficient performance of this task. Adults with reading disability have demonstrated lower regional white matter connectivity, but it is not known whether this relationship between neuronal wiring and reading performance also holds in younger readers. Using diffusion tensor magnetic resonance imaging (DTI) that highlights the structural integrity of the brain wiring, we show that regional brain connectivity in the left temporo-parietal white matter correlates with a wide range of reading ability in children as young as 8–12 years old. Diffusion tensor tractography suggests that the posterior limb of the internal capsule is consistent with the location of the largest cluster of correlation between reading ability (Word Identification subtest) and fractional anisotropy. The maturation of the white matter may play a key role in the development of cognitive processes such as reading.

YNIMG Journal 2004 Journal Article

Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke

Götz Thomalla
Volkmar Glauche
Martin A Koch
Christian Beaulieu
Cornelius Weiller
Joachim Röther

We used diffusion tensor imaging (DTI) to assess Wallerian degeneration of the pyramidal tract within the first 2 weeks after ischemic stroke, and correlated the extent of Wallerian degeneration with the motor deficit. Nine patients with middle cerebral artery stroke were examined 2–16 days after stroke by DTI and T2-weighted MRI. We measured fractional anisotropy (FA), averaged diffusivity (Dav), eigenvalues of the diffusion tensor and T2-weighted signal in the cerebral peduncle and compared these values between the affected and the unaffected side and between patients and six controls. FA was significantly reduced on the affected side compared to the unaffected side and compared to the control group. The largest eigenvalue was reduced, whereas the smallest eigenvalue was elevated on the affected side. There was no significant difference in T2-weighted signal and Dav. The decrease of anisotropy correlated positively with the motor deficit at the time of DTI study and 90 days after stroke. The reduction of anisotropy mirrors the disintegration of axonal structures, as it occurs in the early phase of Wallerian degeneration. DTI detects changes of water diffusion related to beginning pyramidal tract degeneration within the first 2 weeks after stroke that are not yet visible in conventional T2-weighted or orientationally averaged diffusion weighted MRI. We demonstrated for the first time a correlation of early DTI findings of pyramidal tract damage with the motor deficit. DTI can help prognosing recovery of motor function after stroke within the early subacute phase.