Academic Appointments

Boards, Advisory Committees, Professional Organizations

  • ad hoc reviewer, Journal of Magnetic Resonance Imaging (1999 - Present)
  • ad hoc reviewer, Magnetic Resonance in Medicine (2013 - Present)
  • ad hoc reviewer, Stroke (2004 - 2007)
  • ad hoc reviewer, Int. Journal of Developmental Neuroscience (2009 - Present)
  • ad hoc reviewer, The Open Neuroimaging Journal (2010 - Present)
  • ad hoc reviewer, Journal of Neuroscience Methods (2011 - Present)
  • ad hoc reviewer, Journal of Cerebral Blood Flow and Metabolism (2012 - Present)
  • ad hoc reviewer, Neuroradiology (2012 - Present)
  • ad hoc reviewer, Neuroimage (2012 - Present)

Research & Scholarship

Current Research and Scholarly Interests

Characterization of Diffusion, Perfusion and Resting State fMRI methods for Assessment of Neuro-regeneration during Stroke Rehabilitation. I have implemented an MRI imaging protocol in humans, using ferumoxytol (an iron containing compound) as a contrast agent, to characterize the brain’s resting state FMRI and cerebral blood volume metrics.


Journal Articles

  • Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain. NeuroImage D'Arceuil, H., Coimbra, A., Triano, P., Dougherty, M., Mello, J., Moseley, M., Glover, G., Lansberg, M., Blankenberg, F. 2013; 83: 200-209


    The brain demonstrates spontaneous low-frequency (<0.1Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.5 at 3T in primates and humans. We evaluated the use of ferumoxytol for steady state, resting state FMRI (CBV-rs-fMRI) and relative cerebral blood volume (rCBV) mapping, at 3T, in healthy volunteers. All standard resting state networks (RSNs) were identified in all subjects. On average the RSN Z statistics (MELODIC independent components) and volumes of the visual and default mode (DMN) networks were comparable. rCBV values were averaged for the visual (Vis) and DMN networks and correlated with the corresponding DMN and visual network Z statistics. There was a negative correlation between the rCBV and the Z statistics for the DMN, for both BOLD and CBV-rs-fMRI contrast (R(2)=0.63, 0.76). A similar correlation was not found for the visual network. Short repetition time rs-fMRI data were Fourier transformed to evaluate the effect of ferumoxytol on cardiac and respiratory fluctuations in the brain rs-BOLD, CBV signals. Cardiac and respiratory fluctuations decreased to baseline within large vessels post ferumoxytol. Robust rs-fMRI and CBV mapping is possible in normal human brain.

    View details for DOI 10.1016/j.neuroimage.2013.06.066

    View details for PubMedID 23831413

  • Probing tissue microstructure with restriction spectrum imaging: Histological and theoretical validation HUMAN BRAIN MAPPING White, N. S., Leergaard, T. B., D'Arceuil, H., Bjaalie, J. G., Dale, A. M. 2013; 34 (2): 327-346


    Water diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying biological tissue microarchitectures in vivo. Recently, there has been increased effort to develop quantitative dMRI methods to probe both length scale and orientation information in diffusion media. Diffusion spectrum imaging (DSI) is one such approach that aims to resolve such information based on the three-dimensional diffusion propagator at each voxel. However, in practice, only the orientation component of the propagator function is preserved when deriving the orientation distribution function. Here, we demonstrate how a straightforward extension of the linear spherical deconvolution (SD) model can be used to probe tissue orientation structures over a range (or "spectrum") of length scales with minimal assumptions on the underlying microarchitecture. Using high b-value Cartesian q-space data on a rat brain tissue sample, we demonstrate how this "restriction spectrum imaging" (RSI) model allows for separating the volume fraction and orientation distribution of hindered and restricted diffusion, which we argue stems primarily from diffusion in the extraneurite and intraneurite water compartment, respectively. Moreover, we demonstrate how empirical RSI estimates of the neurite orientation distribution and volume fraction capture important additional structure not afforded by traditional DSI or fixed-scale SD-like reconstructions, particularly in gray matter. We conclude that incorporating length scale information in geometric models of diffusion offers promise for advancing state-of-the-art dMRI methods beyond white matter into gray matter structures while allowing more detailed quantitative characterization of water compartmentalization and histoarchitecture of healthy and diseased tissue.

    View details for DOI 10.1002/hbm.21454

    View details for Web of Science ID 000313115000007

    View details for PubMedID 23169482

  • Ferumoxytol Enhanced Resting State fMRI and relative cerebral blood volume, rCBV, mapping in Normal Human Brain Neuroimage D'Arceuil, H. E. 2013; 3: 200-209
  • Imaging Stroke Evolution after Middle Cerebral Artery Occlusion in Non-human Primates. The open neuroimaging journal D'Arceuil, H. E., de Crespigny, A. J. 2011; 5: 216-224


    This article reviews imaging approaches applied to the study of stroke in nonhuman primates. We briefly survey the various surgical and minimally invasive experimental stroke models in nonhuman primates, followed by a summary of studies using computed tomography, positron emission tomography and magnetic resonance imaging and spectroscopy to monitor stroke from the hyperacute phase (within minutes of the onset of cerebral ischemia) to the chronic phase (1 month and beyond).

    View details for DOI 10.2174/1874440001105010216

    View details for PubMedID 22253663

  • Dynamic Diffusion Magnetic Resonance Imaging of Infarct Formation and Peri-infarct Spreading Depression after Middle Cerebral Artery Occlusion (MCAO) in macacca fasicularis. The open neuroimaging journal D'Arceuil, H. E., de Crespigny, A. 2011; 5: 153-159


    Dynamic diffusion MRI was used to visualize hyperacute stroke formation in the brain of a cynomolgus macaque. Under fluoroscopic guidance, a microcatheter was placed into the middle cerebral artery (MCA). The animal was immediately transferred to a 1.5T clinical scanner. Dynamic T2-weighted imaging during bolus injection of Oxygen-17 enriched water through the microcatheter mapped out the territory perfused by the MCA segment. Serial diffusion measurements were made using diffusion-weighted echo-planar imaging, with a temporal resolution of 15 seconds, during injection of a glue embolus into the microcatheter. The apparent diffusion coefficient declined within the lesion core. A wave of transient diffusion decline spread through peripheral uninvolved brain immediately following stroke induction. The propagation speed and pattern is consistent with spreading peri-infarct depolarizations (PID). The detection of PIDs following embolic stroke in a higher nonhuman primate brain supports the hypothesis that spreading depressions may occur following occlusive stroke in humans.

    View details for DOI 10.2174/1874440001105010153

    View details for PubMedID 22253657

  • Topography of connections between human prefrontal cortex and mediodorsal thalamus studied with diffusion tractography NEUROIMAGE Klein, J. C., Rushworth, M. F., Behrens, T. E., Mackay, C. E., de Crespigny, A. J., D'Arceuil, H., Johansen-Berg, H. 2010; 51 (2): 555-564


    Studies in monkeys show clear anatomical and functional distinctions among networks connecting with subregions within the prefrontal cortex. Three such networks are centered on lateral orbitofrontal cortex, medial frontal and cingulate cortex, and lateral prefrontal cortex and all have been identified with distinct cognitive roles. Although these areas differ in a number of their cortical connections, some of the first anatomical evidence for these networks came from tracer studies demonstrating their distinct patterns of connectivity with the mediodorsal (MD) nucleus of the thalamus. Here, we present evidence for a similar topography of MD thalamus prefrontal connections, using non-invasive imaging and diffusion tractography (DWI-DT) in human and macaque. DWI-DT suggested that there was a high probability of interconnection between medial MD and lateral orbitofrontal cortex, between caudodorsal MD and medial frontal/cingulate cortex, and between lateral MD and lateral prefrontal cortex, in both species. Within the lateral prefrontal cortex a dorsolateral region (the principal sulcus in the macaque and middle frontal gyrus in the human) was found to have a high probability of interconnection with the MD region between the regions with a high probability of interconnection with other parts of the lateral prefrontal cortex and with the lateral orbitofrontal cortex. In addition to suggesting that the thalamic connectivity in the macaque is a good guide to human prefrontal cortex, and therefore that there are likely to be similarities in the cognitive roles played by the prefrontal areas in both species, the present results are also the first to provide insight into the topography of projections of an individual thalamic nucleus in the human brain.

    View details for DOI 10.1016/j.neuroimage.2010.02.062

    View details for Web of Science ID 000277141200006

    View details for PubMedID 20206702

  • Quantitative Histological Validation of Diffusion MRI Fiber Orientation Distributions in the Rat Brain PLOS ONE Leergaard, T. B., White, N. S., de Crespigny, A., Bolstad, I., D'Arceuil, H., Bjaalie, J. G., Dale, A. M. 2010; 5 (1)


    Diffusion MRI (dMRI) is widely used to measure microstructural features of brain white matter, but commonly used dMRI measures have limited capacity to resolve the orientation structure of complex fiber architectures. While several promising new approaches have been proposed, direct quantitative validation of these methods against relevant histological architectures remains missing. In this study, we quantitatively compare neuronal fiber orientation distributions (FODs) derived from ex vivo dMRI data against histological measurements of rat brain myeloarchitecture using manual recordings of individual myelin stained fiber orientations. We show that accurate FOD estimates can be obtained from dMRI data, even in regions with complex architectures of crossing fibers with an intrinsic orientation error of approximately 5-6 degrees in these regions. The reported findings have implications for both clinical and research studies based on dMRI FOD measures, and provide an important biological benchmark for improved FOD reconstruction and fiber tracking methods.

    View details for DOI 10.1371/journal.pone.0008595

    View details for Web of Science ID 000273414100005

    View details for PubMedID 20062822

  • Cortical depth-specific microvascular dilation underlies laminar differences in BOLD fMRI response PNAS Tian, P. 2010; 107 (34): 15246-51
  • Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers NEUROIMAGE Wedeen, V. J., Wang, R. P., Schmahmann, J. D., Benner, T., Tseng, W. Y., Dai, G., Pandya, D. N., Hagmann, P., D'Arceuil, H., de Crespignya, A. J. 2008; 41 (4): 1267-1277


    MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.

    View details for DOI 10.1016/j.neuroimage.2008.03.036

    View details for Web of Science ID 000256620400010

    View details for PubMedID 18495497

  • 3D micro-CT imaging of the postmortem brain JOURNAL OF NEUROSCIENCE METHODS de Crespigny, A., Bou-Reslan, H., Nishimura, M. C., Phillips, H., Carano, R. A., D'Arceuil, H. E. 2008; 171 (2): 207-213


    Magnetic resonance microscopy (microMRI) is becoming an important tool for non-destructive analysis of fixed brain tissue. However, unlike MRI, X-ray computed tomography (CT) scans show little native soft tissue contrast. In this paper, we explored the use of contrast enhanced (brains immersion stained in iodinated CT contrast media) micro-CT (microCT) for high resolution 3D imaging of fixed normal and pathological brains, compared to microMRI and standard histopathology. An optimum iodine concentration of 0.27 M resulted in excellent contrast between gray and white matter in normal brain and a wide range of anatomical structures were identified. In glioma bearing mouse brains, there was clear deliniation of tumor margin which closely matched that seen on histopathology sections. microCT tumor volume was strongly correlated with histopathology volume. Our data suggests that microCT image contrast in the immersion-stained brains is related to axonal density and myelin content. Compared to traditional histopathology, our microCT approach is relatively rapid and less labor intensive. In addition, compared to microMRI, microCT is robust and requires much lower equipment and maintenance costs. For simple measurements, such as tumor volume and non-destructive postmortem brain screening, microCT may prove to be a valuable alternative to standard histopathology or microMRI.

    View details for Web of Science ID 000256859800004

    View details for PubMedID 18462802

  • Three-dimensional high-resolution diffusion tensor imaging and tractography of the developing rabbit brain DEVELOPMENTAL NEUROSCIENCE D'Arceuil, H., Liu, C., Levitt, P., Thompson, B., Kosofsky, B., de Crespigny, A. 2008; 30 (4): 262-275


    Diffusion tensor imaging (DTI) is sensitive to structural ordering in brain tissue particularly in the white matter tracts. Diffusion anisotropy changes with disease and also with neural development. We used high-resolution DTI of fixed rabbit brains to study developmental changes in regional diffusion anisotropy and white matter fiber tract development. Imaging was performed on a 4.7-tesla Bruker Biospec Avance scanner using custom-built solenoid coils and DTI was performed at various postnatal ages. Trace apparent diffusion coefficient, fractional diffusion anisotropy maps and fiber tracts were generated and compared across the ages. The brain was highly anisotropic at birth and white matter anisotropy increased with age. Regional DTI tractography of the internal capsule showed refinement in regional tract architecture with maturation. Interestingly, brains with congenital deficiencies of the callosal commissure showed selectively strikingly different fiber architecture compared to age-matched brains. There was also some evidence of subcortical to cortical fiber connectivity. DTI tractography of the anterior and posterior limbs of the internal capsule showed reproducibly coherent fiber tracts corresponding to known corticospinal and corticobulbar tract anatomy. There was some minor interanimal tract variability, but there was remarkable similarity between the tracts in all animals. Therefore, ex vivo DTI tractography is a potentially powerful tool for neuroscience investigations and may also reveal effects (such as fiber tract pruning during development) which may be important targets for in vivo human studies.

    View details for DOI 10.1159/000110503

    View details for Web of Science ID 000255586600006

    View details for PubMedID 17962716

  • MRI of spontaneous fluctuations after acute cerebral ischemia in nonhuman primates JOURNAL OF MAGNETIC RESONANCE IMAGING Liu, Y., D'Arceuil, H., He, J., Duggan, M., Gonzalez, G., Pryor, J., de Crespigny, A. 2007; 26 (4): 1112-1116


    To study the spontaneous low-frequency blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal fluctuations during hyperacute focal cerebral ischemia.A stroke model in nonhuman primates (macaques) was used in this study. Spontaneous fluctuations were recorded using a series of gradient-recalled echo (GRE) echo-planar imaging (EPI) images. Fast Fourier transformation (FFT) was performed on the serial EPI data to calculate the frequency and magnitude of the spontaneous fluctuations. Diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) were preformed to detect the ischemic lesion.The frequency of these fluctuations decreased in the periinfarct tissue in the ipsilateral hemisphere, while their magnitude increased. This area of abnormal signal fluctuations often extended beyond the hyperacute diffusion/perfusion abnormality.This study suggests that measurement of the spontaneous fMRI signal fluctuations provides different information than is available from diffusion/perfusion or T2-weighted MRI.

    View details for DOI 10.1002/jmri.21131

    View details for Web of Science ID 000249898800037

    View details for PubMedID 17896395

  • Superselective intracerebral catheterization of a branch of the internal carotid artery coupled with magnetic resonance Imaging INTERVENTIONAL NEURORADIOLOGY Pryor, J., D'Arceuil, H., Phil, M., Liu, J., He, J., Gonzalez, R. G., Duggan, M., De Crespigny, A. 2007; 13 (3): 277-280


    Summary: We used fluoroscopic guidance and over-thewire techniques to superselectively place a microcatheter into a branch of the MCA of three macaques and MRI bolus tracking techniques to measure perfusion within the selected brain region. Such techniques are likely to be useful in the assessment and treatment of ischemic infarction, cerebral vasospasm, and monitoring local delivery of drugs into the brain.

    View details for Web of Science ID 000251377200007

    View details for PubMedID 20566119

  • The effects of brain tissue decomposition on diffusion tensor imaging and tractography NEUROIMAGE D'Arceuil, H., de Crespigny, A. 2007; 36 (1): 64-68


    There have been numerous high resolution diffusion tensor imaging studies in fixed animal brains, but relatively few studies in human brains. While animal tissues are generally fixed pre-mortem or directly postmortem, this is not possible for human tissue, therefore there is always some delay between death and tissue fixation. The elapsed time between death and tissue fixation, the postmortem interval (PMI), will most likely adversely affect the tissue's diffusion properties. We studied the effects of PMI on the diffusion properties of rodent brain. Eight mice were euthanized and the brains (kept in the skull) were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography was also performed. The temporal changes in regional ADC and FA values were analyzed statistically using a one-way ANOVA, followed by individual Student's T-tests. Regional FA and ADC of gray and white matter decreased significantly with time (p<0.05). DTI tractography showed a decrease in the number and coherence of reconstructed fiber pathways between PMIs 0 and 14. Elapsed time between death and tissue fixation has a major effect upon the brain's diffusion properties and should be born in mind when interpreting fixed brain DTI.

    View details for DOI 10.1016/j.neuroimage.2007.02.039

    View details for Web of Science ID 000246559500007

    View details for PubMedID 17433879

  • An approach to high resolution diffusion tensor imaging in fixed primate brain NEUROIMAGE D'Arceuil, H. E., Westmoreland, S., de Crespigny, A. J. 2007; 35 (2): 553-565


    High resolution ex vivo diffusion tensor imaging (DTI) studies of neural tissues can improve our understanding of brain structure. In these studies we can modify the tissue relaxation properties of the fixed tissues to better suite the scanner hardware. We investigated the use of Gd-DTPA contrast agent to provide the optimum signal-to-noise (SNR) ratio in 3D DTI scans of formalin fixed nonhuman primate brains at 4.7 T. Relaxivity measurements in gray and white matter allowed us to optimize the Gd concentration for soaking the brains, resulting in a 2 fold improvement in SNR for the 3D scans. FA changed little with Gd concentrations up to 10 mM although ADC was reduced at 5 and 10 mM. Comparison of in vivo, fresh ex vivo and fixed brains showed no significant FA changes but reductions in ADC of about 50% in fresh ex vivo, and 64% and 80% in fixed gray and white matter respectively. Studies of the temperature dependence of diffusion in these tissues suggested that a 30 degrees increase in sample temperature may yield an improvement of up to 55% in SNR-efficiency for a given diffusion weighting. Our Gd soaking regimen appeared to have no detrimental effect on standard histology of the fixed brain sections. Our methods yield both high SNR and spatial resolution DTI data in fixed primate brains, allowing us to perform high resolution tractography which will facilitate the process of 'validation' of DTI fiber tracts against traditional measures of brain fiber architecture.

    View details for DOI 10.1016/j.neuroimage.2006.12.028

    View details for Web of Science ID 000245293100011

    View details for PubMedID 17292630

  • Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography BRAIN Schmahmann, J. D., Pandya, D. N., Wang, R., Dai, G., D'Arceuil, H. E., de Crespigny, A. J., Wedeen, V. J. 2007; 130: 630-653


    Understanding the long association pathways that convey cortical connections is a critical step in exploring the anatomic substrates of cognition in health and disease. Diffusion tensor imaging (DTI) is able to demonstrate fibre tracts non-invasively, but present approaches have been hampered by the inability to visualize fibres that have intersecting trajectories (crossing fibres), and by the lack of a detailed map of the origins, course and terminations of the white matter pathways. We therefore used diffusion spectrum imaging (DSI) that has the ability to resolve crossing fibres at the scale of single MRI voxels, and identified the long association tracts in the monkey brain. We then compared the results with available expositions of white matter pathways in the monkey using autoradiographic histological tract tracing. We identified 10 long association fibre bundles with DSI that match the observations in the isotope material: emanating from the parietal lobe, the superior longitudinal fasciculus subcomponents I, II and III; from the occipital-parietal region, the fronto-occipital fasciculus; from the temporal lobe, the middle longitudinal fasciculus and from rostral to caudal, the uncinate fasciculus, extreme capsule and arcuate fasciculus; from the occipital-temporal region, the inferior longitudinal fasciculus; and from the cingulate gyrus, the cingulum bundle. We suggest new interpretations of the putative functions of these fibre bundles based on the cortical areas that they link. These findings using DSI and validated with reference to autoradiographic tract tracing in the monkey represent a considerable advance in the understanding of the fibre pathways in the cerebral white matter. By replicating the major features of these tracts identified by histological techniques in monkey, we show that DSI has the potential to cast new light on the organization of the human brain in the normal state and in clinical disorders.

    View details for DOI 10.1093/brain/awl359

    View details for Web of Science ID 000244840000006

    View details for PubMedID 17293361

  • Serial diffusion tensor MRI after transient and permanent cerebral ischemia in nonhuman primates STROKE Liu, Y., D'Arceuil, H. E., Westmoreland, S., He, J., Duggan, M., Gonzalez, R. G., Pryor, J., de Crespigny, A. J. 2007; 38 (1): 138-145


    We measured the temporal evolution of the T2 and diffusion tensor imaging parameters after transient and permanent cerebral middle cerebral artery occlusion (MCAo) in macaques, and compared it to standard histological analysis at the study end point.Stroke was created in adult male macaques by occluding a middle cerebral artery branch for 3 hours (transient MCAo, n=4 or permanent occlusion, n=3). Conventional MRI and diffusion tensor imaging scans were performed 0 (acute day), 1, 3, 7, 10, 17, and 30 days after MCAo. Animals were euthanized after the final scan and the brains removed for histological analysis.Apparent diffusion coefficient in the lesion was decreased acutely, fractional anisotropy was elevated, and T2 remained normal. Thereafter, apparent diffusion coefficient increased above normal, fractional anisotropy decreased to below normal, T2 increased to a maximum and then declined. Reperfusion at 3 hours accelerated these MRI changes. Only the fractional anisotropy value was significantly different between transient and permanent groups at 30 days. Final MRI-defined fractional lesion volumes were well correlated with corresponding histological lesion volumes. Permanent MCAO animals showed more severe histological damage than their transient MCAO counterparts, especially myelin damage and axonal swelling.Overall, the MRI evolution of stroke in macaques was closer to what has been observed in humans than in rodent models. This work supports the use of serial MRI in stroke studies in nonhuman primates.

    View details for DOI 10.1161/01.STR.0000252127.07428.9c

    View details for Web of Science ID 000243359200031

    View details for PubMedID 17122422

  • Long-term monitoring of post-stroke plasticity after transient cerebral ischemia in mice using in vivo and ex vivo diffusion tensor MRI. The open neuroimaging journal Granziera, C., D'Arceuil, H., Zai, L., Magistretti, P. J., Sorensen, A. G., de Crespigny, A. J. 2007; 1: 10-17


    WE USED A MURINE MODEL OF TRANSIENT FOCAL CEREBRAL ISCHEMIA TO STUDY: 1) in vivo DTI long-term temporal evolution of the apparent diffusion coefficient (ADC) and diffusion fractional anisotropy (FA) at days 4, 10, 15 and 21 after stroke 2) ex vivo distribution of a plasticity-related protein (GAP-43) and its relationship with the ex vivo DTI characteristics of the striato-thalamic pathway (21 days). All animals recovered motor function. In vivo ADC within the infarct was significantly increased after stroke. In the stroke group, GAP-43 expression and FA values were significantly higher in the ipsilateral (IL) striatum and contralateral (CL) hippocampus compared to the shams. DTI tractography showed fiber trajectories connecting the CL striatum to the stroke region, where increased GAP43 and FA were observed and fiber tracts from the CL striatum terminating in the IL hippocampus.Our data demonstrate that DTI changes parallel histological remodeling and recovery of function.

    View details for DOI 10.2174/1874440000701010010

    View details for PubMedID 19018310

  • A nonlinear mesh-warping technique for correcting brain deformation after stroke MAGNETIC RESONANCE IMAGING Liu, Y., D'Arceuil, H., He, J., Duggan, M., Gonzalez, G., Pryor, J., de Crespigny, A. 2006; 24 (8): 1069-1075


    This article presents a warping technique for correcting brain tissue distortion on magnetic resonance imaging (MRI) scans due to stroke lesion growth and for mapping MRI scans to histological sections. Meshes are imposed upon the images for feature specification, and these features are exactly matched in the different images to be mapped, while the other voxels are matched by interpolation. This technique was tested on serial MR images and histological sections that were acquired in a nonhuman primate model of stroke. This technique was able to deliver satisfactory warping results. It is simple and robust and can be utilized in many applications for comparison of multimodality medical images and histological sections.

    View details for DOI 10.1016/j.mri.2006.07.007

    View details for Web of Science ID 000241253500011

    View details for PubMedID 16997077

  • Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution JOURNAL OF MEDICAL PRIMATOLOGY D'Arceuil, H. E., Duggan, M., He, J. L., Pryor, J., de Crespigny, A. 2006; 35 (2): 78-86


    An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model.Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil.Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression.Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.

    View details for DOI 10.1111/j.1600-0684.2006.00147.x

    View details for Web of Science ID 000235842000003

    View details for PubMedID 16556294

  • A comparison of CH3-DTPA-GD (NMS60) and GD-DTPA for evaluation of acute myocardial ischemia INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING D'Arceuil, H. E., de Crespigny, A. J., Pelc, L., Howard, D., Seri, S., Hashiguchi, Y., Nakatani, A., Moseley, M. E. 2005; 21 (5): 539-547


    Our objective was to evaluate the use of a new medium weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd-complex containing three Gd(3+) atoms, molecular weight 2158 Da) compared to gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in a pig myocardial ischemia model.We used 13 male white hybrid pigs. Animals were scanned in the acute phase 2-3 h after the onset of myocardial ischemia. Scans were acquired on a 1.5T GE Signa with dynamic T1-weighted imaging during a bolus injection of 0.1 mmol(gd)/kg of either NMS60 or Gd-DTPA, 2D CINE at 5 min after injection, and T1-weighted spin-echo imaging up to 60 min.The postcontrast CINE scans showed improved contrast-to-noise ratio after NMS60 injection, compared to Gd-DTPA. There was significantly greater enhancement with NMS60 in both normal myocardium and in the ischemic lesion on T1-weighted spin-echo scans up to 60 min after injection. The dose ranging study shows a 24% greater enhancement with NMS60 compared to Gd-DTPA.This new medium weighted contrast agent offers improved enhancement for cardiac MRI, compared to Gd-DTPA, with similar washout kinetics and lower toxicity, and may prove useful for better detection of myocardial ischemia as well as delayed or hyperenhancement after reperfusion.

    View details for DOI 10.1007/s10554-005-2103-4

    View details for Web of Science ID 000232030800012

    View details for PubMedID 16175444

  • Dynamic susceptibility contrast perfusion imaging of cerebral ischemia in nonhuman primates: Comparison of Gd-DTPA and NMS60 JOURNAL OF MAGNETIC RESONANCE IMAGING Liu, Y. T., D'Arceuil, H., He, J. L., Duggan, M., Seri, S., Hashiguchi, Y., Nakatani, A., Gonzalez, R. G., Pryor, J., de Crespigny, A. 2005; 22 (4): 461-466


    To study a new gadolinium (Gd) contrast agent-NMS60-for MR perfusion-weighted imaging (PWI) of brain tissue.NMS60 is a Gd3+ trimer with a molecular weight of 2158 Daltons, and a T2 relaxivity almost three times higher than that of Gd-DTPA. Middle cerebral artery (MCA) occlusion was induced in nine nonhuman primates. The animals were scanned acutely and for up to six follow-up time points. PWI peak, and time-to-peak maps were generated, and perfusion deficit volumes were measured from these maps. The values of peak, time-to-peak, and perfusion deficit volume were compared between NMS60 and GD-DTPA.These results demonstrate that there was no significant difference in our calculated perfusion parameters between the two contrast agents.The two agents were found to be equally effective for PWI for acute and chronic stroke in primates. Along with its previously demonstrated advantage for T1-enhanced imaging, the current results show that NMS60 is a viable contrast agent for use in stroke patients.

    View details for DOI 10.1002/jmri.20403

    View details for Web of Science ID 000232317700003

    View details for PubMedID 16142700

  • Acute studies of a new primate model of reversible middle cerebral artery occlusion. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association de Crespigny, A. J., D'Arceuil, H. E., Maynard, K. I., He, J., McAuliffe, D., Norbash, A., Sehgal, P. K., Hamberg, L., Hunter, G., Budzik, R. F., Putman, C. M., Gonzalez, R. G. 2005; 14 (2): 80-87


    The recent failure of many clinical trials of neuroprotective compounds may be due in part to poor animal models of human stroke. We have developed an endovascular stroke model in nonhuman primates that is compatible with serial magnetic resonance imaging (MRI) monitoring. Using cynomologous macaques (n = 4), a microcatheter was navigated transarterially (under fluoroscopic guidance) from the femoral artery to the middle cerebral artery (MCA). The microcatheter was wedged in a branch of the MCA for 3 hours to cause focal cerebral ischemia, as verified angiographically. During occlusion and/or reperfusion, animals were scanned with MRI, and imaging findings were compared with the stained brain sections. All animals demonstrated small stroke lesions in the expected vascular territory, as seen on diffusion-weighted MRI and confirmed by postmortem examination. Reperfusion after 3 hours was confirmed angiographically (n = 2) and also by MRI (n = 4). The mean initial lesion volume, measured on the postreperfusion MRI scans, was 2.3 +/- 1.3 mL (n = 4). There was good agreement between anatomic location of the lesion on MRI and postmortem histological staining (n = 3). A "minimally invasive" primate model of focal cerebral ischemia was developed that is ideally suited to MRI studies of both acute and chronic stroke. By using serial MRI scans to measure changes in lesion size over time, we will be able to control for variability in lesion size/location. This model should prove useful as a test bed for new stroke therapies, in which noninvasive imaging findings are readily comparable to human stroke.

    View details for PubMedID 17904005

  • Near-infrared frequency-domain optical spectroscopy and magnetic resonance imaging: a combined approach to studying cerebral maturation in neonatal rabbits JOURNAL OF BIOMEDICAL OPTICS D'Arceuil, H. E., Hotakainen, M. P., Liu, C., Themelis, G., de Crespigny, A. J., Franceschini, M. A. 2005; 10 (1)


    The neonatal rabbit brain shows prolonged postnatal development both structurally and physiologically. We use noninvasive near-IR frequency-domain optical spectroscopy (NIRS) and magnetic resonance imaging (MRI) to follow early developmental changes in cerebral oxygenation and anatomy, respectively. Four groups of animals are measured: NIRS in normals, MRI in normals, and both NIRS and MRI with hypoxia-ischemia (HI) (diffusion MRI staging). NIRS and/or MRI are performed from P3 (postnatal day=P) up to P76. NIRS is performed on awake animals with a frequency-domain tissue photometer. Absolute values of oxyhemoglobin concentration ([HbO2]), deoxyhemoglobin concentration ([HbR]), total hemoglobin concentration (HbT), and hemoglobin saturation (StO2) are calculated. The brains of all animals appeared to be maturing as shown in the diffusion tensor MRI. Mean optical coefficients (reduced scattering) remained unchanged in all animals throughout. StO2 increased in all animals (40% at P9 to 65% at P43) and there are no differences between normal, HI controls, and HI brains. The measured increase in StO2 is in agreement with the reported increase in blood flow during the first 2 months of life in rabbits. HbT, which reflects blood volume, peaked at postnatal day P17, as expected since the capillary density increases up to P17 when the microvasculature matures.

    View details for DOI 10.1117/1.1852554

    View details for Web of Science ID 000229208100011

    View details for PubMedID 15847577

  • An MRA study of vascular stenosis in a pig model using CH3-DTPA-Gd (NMS60) and Gd-DTPA MAGNETIC RESONANCE IMAGING D'Arceuil, H. E., de Crespigny, A. J., Pelc, L., Howard, D., Alley, M., Seric, S., Hashiguchi, Y., Nakatani, A., Moseley, M. E. 2004; 22 (9): 1243-1248


    This study used an experimental arterial stenosis model in pigs to evaluate the utility of a new medium-weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd complex containing three Gd(3+) atoms, molecular weight of 2158 Da) compared to Gd-DTPA for contrast-enhanced MRA.We used six male white hybrid pigs. Under anesthesia, one femoral artery was exposed and an inflatable cuff placed around it. The cuff was tightened around the vessel until 80-90% stenosis was achieved using digital subtraction angiography as a guide. Animals were then immediately transferred to the MRI scanner and images acquired pre- and postcontrast injection (0.1 or 0.2 mmol Gd/kg Gd-DTPA or NMS60, as a rapid bolus) using high-resolution and dynamic MRA.The dynamic MRA scans acquired during contrast bolus injection clearly showed the stenosed femoral artery as a segment of close to zero enhancement during the arterial phase of the bolus transit, while on the high-resolution scans the stenosis was difficult to detect due to venous signal contamination. The signal-to-noise at peak enhancement on the dynamic scans was significantly greater with 0.1 mmol Gd/kg NMS60 compared to 0.1 mmol Gd/kg Gd-DTPA (14.6 vs. 9.9, P < .05) and not significantly greater than 0.2 mmol Gd/kg (14.6 vs. 12.8).This new medium-weight contrast agent demonstrated significantly greater enhancement than Gd-DTPA and may be valuable to aid detection of vascular stenosis in humans.

    View details for DOI 10.1016/j.mri.2004.08.021

    View details for Web of Science ID 000226065100009

    View details for PubMedID 15607095

  • Direct CSF injection of MnCl2 for dynamic manganese-enhanced MRI MAGNETIC RESONANCE IN MEDICINE Liu, C. H., D'Arceuil, H. E., de Crespigny, A. J. 2004; 51 (5): 978-987


    MnCl(2) was injected intrathecally through the cisterna magna in rats, allowing infusion of divalent manganese ions (Mn(++)) into the CSF space and thence into the brain, without breaking the blood-brain barrier (BBB). Mn(++) uptake and washout dynamics in the brain were measured by serial T(1)-weighted MRI and EPI T(1) and T(2) mapping for up to 3 weeks after injection. Observations within the first 6 hr after injection demonstrated anterograde and bilateral distribution of the Mn(++) within the CSF space, from the olfactory bulb and frontal cortex to the brain stem. Enhancement increased in most brain areas up to 4 days after injection, and then slowly decreased. Relaxation maps at each time point demonstrated higher concentrations of Mn in basal ganglia. Residual concentrations were still observable after 3 weeks in all brain regions. With the use of MnCl(2) calibration phantoms, the maximum Mn concentration in the brain was estimated to be approximately 27 +/- 16 microM, corresponding to changes in relaxation rates of 0.49 +/- 0.30 s(-1) for R(1) and 3.9 +/- 2.4 s(-1) for R(2). For comparison, an intrathecal GdDTPA injection was performed. This injection showed different distribution dynamics: it remained chiefly within the CSF spaces, and was largely washed out after 1 day. This method shows promise as a means of supplying Mn(++) uniformly to the whole brain for a variety of chronic functional activation studies.

    View details for DOI 10.1002/mrm.20047

    View details for Web of Science ID 000221239000014

    View details for PubMedID 15122680

  • Tc-99m annexin V imaging of neonatal hypoxic brain injury STROKE D'Arceuil, H., Rhine, W., de Crespigny, A., Yenari, M., Tait, J. F., Strauss, W. H., Engelhorn, T., Kastrup, A., Moseley, M., Blankenberg, F. G. 2000; 31 (11): 2692-2699


    Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII.Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (n=17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with (99m)Tc annexin V. Radionuclide images were recorded 2 hours later.Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier.Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.

    View details for Web of Science ID 000165107100026

    View details for PubMedID 11062296

  • MRI of focal cerebral ischemia using O-17-labeled water MAGNETIC RESONANCE IN MEDICINE de Crespigny, A. J., D'Arceuil, H. E., Engelhorn, T., Moseley, M. E. 2000; 43 (6): 876-883


    This work presents a novel approach for quantifying low concentrations of H(2)(17)O in vivo and explores its utility for assessing cerebral ischemia. Oxygen-17 enriched water acts as a T(2) shortening contrast agent whose effect can be suppressed by decoupling at the (17)O frequency during TE interval in a spin-echo MR image. Serial T(2)-weighted echo planar images were acquired in phantoms and rat brain with decoupler power alternated every eight images. The resulting periodic signal change (proportional to H(2)(17)O concentration) was detected by cross-correlating the square-wave decoupler power timecourse with the signal intensity in each voxel. Natural abundance (0.037 atom%) images of H(2)(17)O in rat brain were generated. The transverse relaxivity of H(2)(17)O in brain was estimated, R(2) = 2.4+/-0.5 s(-1)(atom%)(-1). After bolus injection of 1 ml of 10 atom% H(2)(17)O, brain H(2)(17)O concentration was estimated at 0.06+/-0.01 atom%. In the rat focal ischemia model, (17)O cross-correlation maps compared well with diffusion and Gd-DTPA perfusion images to indicate infarct location. Magn Reson Med 43:876-883, 2000.

    View details for Web of Science ID 000087430000014

    View details for PubMedID 10861883

  • Sonography, CT, and MR imaging: A prospective comparison of neonates with suspected intracranial ischemia and hemorrhage AMERICAN JOURNAL OF NEURORADIOLOGY Blankenberg, F. G., Loh, N. N., Bracci, P., D'Arceuil, H. E., Rhine, W. D., Norbash, A. M., Lane, B., Berg, A., Person, B., Coutant, M., Enzmann, D. R. 2000; 21 (1): 213-218


    Sonography, CT, and MR imaging are commonly used to screen for neonatal intracranial ischemia and hemorrhage, yet few studies have attempted to determine which imaging technique is best suited for this purpose. The goals of this study were to compare sonography with CT and MR imaging prospectively for the detection of intracranial ischemia or hemorrhage and to determine the prognostic value(s) of neuroimaging in neonates suspected of having hypoxic-ischemic injury (HII).Forty-seven neonates underwent CT (n = 26) or MR imaging (n = 24) or both (n = 3) within the first month of life for suspected HII. Sonography was performed according to research protocol within an average of 14.4 +/- 9.6 hours of CT or MR imaging. A kappa analysis of interobserver agreement was conducted using three independent observers. Infants underwent neurodevelopmental assessment at ages 2 months (n = 47) and 2 years (n = 26).CT and MR imaging had significantly higher interobserver agreement (P < .001) for cortical HII and germinal matrix hemorrhage (GMH) (Grades I and II) compared with sonography. MR imaging and CT revealed 25 instances of HII compared with 13 identified by sonography. MR imaging and CT also revealed 10 instances of intraparenchymal hemorrhage (>1 cm, including Grade IV GMH) compared with sonography, which depicted five. The negative predictive values of neuroimaging, irrespective of technique used, were 53.3% and 58.8% at the 2-month and 2-year follow-up examinations, respectively.CT and MR imaging have significantly better interobserver agreement for cortical HII and GMH/intraventricular hemorrhage and can reveal more instances of intraparenchymal hemorrhage compared with sonography. The absence of neuroimaging findings on sonograms, CT scans, or MR images does not rule out later neurologic dysfunction.

    View details for Web of Science ID 000085055900042

    View details for PubMedID 10669253

  • 99mTc Annexin V Imaging of Neonatal Hypoxic Brain Injury Stroke D'Arceuil, H. 2000; 32: 2692-2700
  • Serial magnetic resonance diffusion and hemodynamic imaging in a neonatal rabbit model of hypoxic-ischemic encephalopathy NMR IN BIOMEDICINE D'Arceuil, H. E., de Crespigny, A. J., Rother, J., Moseley, M., Rhine, W. 1999; 12 (8): 505-514


    Dynamic changes in relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were investigated, using high speed magnetic resonance imaging (MRI) in an acute neonatal rabbit model of hypoxic-ischemic encephalopathy (HIE). Serial rCBV imaging used a magnetic susceptibility blood pool contrast agent. Interleaved ADC and rCBV images were acquired with 9 s temporal resolution. Rabbits received unilateral common carotid artery (CCA) ligation followed by hypoxia. rCBV increased bilaterally within 1-2 min after the onset of hypoxia. A biphasic ADC decline was observed: a slowly declining phase (84 +/- 18% of baseline) followed by a rapid, focal drop to 55 +/- 8% of baseline in the ipsilateral cortex, which was paralleled by a rapid focal rCBV drop to 70 +/- 17% of baseline. ADC decline generally began in a small region of ipsilateral cortex and spread over the ipsilateral cortex, ipsilateral subcortical tissue and contralateral cortex. The initial ADC drop usually preceded the initial rCBV drop by approximately 60 s, however at later timepoints rCBV decline sometimes preceded ADC decline. Upon normoxia, rCBV recovered to about baseline values while ADC recovered to baseline or above. This method provides a sensitive means of non-invasively visualizing acute hemodynamic- and metabolic-related changes in HIE with good temporal and spatial resolution.

    View details for Web of Science ID 000085232300004

    View details for PubMedID 10668043

  • Dynamic contrast-enhanced MRI of implanted VX2 tumors in rabbit muscle: Comparison of Gd-DTPA and NMS60 MAGNETIC RESONANCE IMAGING de Crespigny, A. J., Howard, D., D'Arceuil, H., Muller, H., Agoston, A. T., Seri, S., Hashiguchi, Y., Fujimoto, C., Nakatani, A., Moseley, M. E. 1999; 17 (9): 1297-1305


    We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.

    View details for Web of Science ID 000083588800008

    View details for PubMedID 10576715

  • Study of focused ultrasound tissue damage using MRI and histology JOURNAL OF MAGNETIC RESONANCE IMAGING Chen, L., Bouley, D., Yuh, E., D'Arceuil, H., Butts, K. 1999; 10 (2): 146-153


    This paper reports on an experimental study of in vivo tissue damage in the rabbit brain with focused ultrasound (FUS) using magnetic resonance imaging (MRI) and histopathological analysis. Ten ultrasonic lesions (tissue damage) were created in five rabbits using a focused ultrasound beam of 1.5 MHz, electrical power input to the transducer of 70-85 W, and an exposure duration of 15-20 seconds. T1- and T2-weighted fast spin-echo (FSE) and Fluid attenuated inversion recovery (FLAIR) sequences were used to detect the ultrasonic lesions after treatment. Imaging was performed for 4-8 hours after treatment, after which the animals were immediately sacrificed. Ultrasonic lesion diameter was measured on MRI and histological sections after correction for tissue shrinkage during the histological processing. The T1-weighted images showed lesions poorly, whereas both T2-weighted and FLAIR images showed lesions clearly. The lesion diameters on both T2 and FLAIR imaging correlated well with measurements from histology. The time delay before lesions appeared on T2-weighted imaging was 15 minutes to 1 hour, depending on the exposure location in the brain. J. Magn. Reson. Imaging 1999;10:146-153.

    View details for Web of Science ID 000084567000006

    View details for PubMedID 10441017

  • Diffusion-weighted magnetic resonance imaging: theory and potential applications to child neurology. Seminars in pediatric neurology Beaulieu, C., D'Arceuil, H., Hedehus, M., de Crespigny, A., Kastrup, A., Moseley, M. E. 1999; 6 (2): 87-100


    Magnetic resonance imaging (MRI) is an excellent tool for the investigation of neurological disorders in children. Diffusion-weighted MRI (DWI) is sensitive to the diffusion (or molecular displacement) of water in tissue. The purpose of this article is to describe briefly the basic theory behind DWI and to discuss its potential applications to neurological disorders in children. We demonstrate that DWI is a sensitive technique for the detection of acute brain injury, and that it is well suited for monitoring brain development, particularly myelination and white matter changes.

    View details for PubMedID 10404563

  • Diffusion and perfusion magnetic resonance imaging of the evolution of hypoxic ischemic encephalopathy in the neonatal rabbit JOURNAL OF MAGNETIC RESONANCE IMAGING D'Arceuil, H. E., de Crespigny, A. J., Rother, J., Seri, S., Moseley, M. E., Stevenson, D. K., Rhine, W. 1998; 8 (4): 820-828


    Hypoxic-ischemic encephalopathy (HIE) can result from neonatal asphyxia, the pathophysiology of which is poorly understood. We studied the acute evolution of this disease, using magnetic resonance imaging in an established animal model. HIE was induced in neonatal rabbits by a combination of common carotid artery (CCA) ligation and hypoxia. Serial diffusion and perfusion-weighted magnetic resonance images were acquired before, during, and after the hypoxic interval. Focal areas of decreased apparent diffusion coefficient (ADC) were detected initially in the cortex ipsilateral to CCA ligation within 62 +/- 48 min from the onset of hypoxia. Subsequently, these areas of decreased ADC spread to the subcortical white matter, basal ganglia (ipsilateral side), and then to the contralateral side. Corresponding perfusion-weighted images showed relative cerebral blood volume deficits which closely matched those regions of ADC change. Our results show that MRI diffusion and perfusion-weighted imaging can detect acute cell swelling post-hypoxia in this HIE model.

    View details for Web of Science ID 000080143600010

    View details for PubMedID 9702883

  • Recovery of apparent diffusion coefficient after ischemia-induced spreading depression relates to cerebral perfusion gradient STROKE Rother, J., DECRESPIGNY, A. J., DArceuil, H., Iwai, K., Moseley, M. E. 1996; 27 (5): 980-986


    Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression. DWI and dynamic contrast-enhanced MRI were applied to study the characteristics of spreading depression and the correlation between ADC recovery time and tissue perfusion in focal ischemia.Serial DWI was performed during remote middle cerebral artery occlusion in rats (n = 5) with an echo-planar imaging technique. ADC maps were calculated and ADC values displayed as a function of time in user-defined regions of interest with a time resolution of 12 to 16 seconds. Dynamic contrast-enhanced MRI was performed for qualitative correlation of ADC changes with tissue perfusion.Recovery time of transient ADC decreases correlated with the degree of the perfusion deficit (r = .81, P < .001). Slowly recovering ADC declines were found close to the ischemic core and correlated with severe perfusion deficit, while short-lasting ADC declines were typically found in moderately malperfused or normal tissue. Transient ADC decreases originated in the subcortical and cortical ischemic border zones and propagated along the cortex with a velocity of 2.9 +/- 0.9 mm/min.The variation in the recovery time of transient ADC decreases in the ischemic periphery reflects the gradient of the tissue perfusion. Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.

    View details for Web of Science ID A1996UJ68500037

    View details for PubMedID 8623122

  • MRI Detection of Cortical Spreading Depression Immediately Following Focal Ischemia in the Rat JCBFM Rother, J. 1996; 16: 214-220

Books and Book Chapters

  • Section V11 Diffusion MRI Beyond White Matter, 39: “Diffusion Imaging in Cerebral Gray Matter” Diffusion MRI: Theory, Methods and Applications D'Arceuil, H. Oxford University Press. 2011: 647-660

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