pubmed, ally years; Van der Linden

1: Phys Med Biol. 2008 May 21;53(10):2457-70. Epub 2008 Apr 18.

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Measuring brain hemodynamic changes in a songbird: responses to hypercapnia measured with functional MRI and near-infrared spectroscopy.

Vignal C, Boumans T, Montcel B, Ramstein S, Verhoye M, Van Audekerke J, Mathevon N, Van der Linden A, Mottin S.

ENES EA 3988, Université Jean Monnet, Saint-Etienne, France. Clementine.Vignal@univ-st-etienne.fr

Songbirds have been evolved into models of choice for the study of the cerebral underpinnings of vocal communication. Nevertheless, there is still a need for in vivo methods allowing the real-time monitoring of brain activity. Functional Magnetic Resonance Imaging (fMRI) has been applied in anesthetized intact songbirds. It relies on blood oxygen level-dependent (BOLD) contrast revealing hemodynamic changes. Non-invasive near-infrared spectroscopy (NIRS) is based on the weak absorption of near-infrared light by biological tissues. Time-resolved femtosecond white laser NIRS is a new probing method using real-time spectral measurements which give access to the local variation of absorbing chromophores such as hemoglobins. In this study, we test the efficiency of our time-resolved NIRS device in monitoring physiological hemodynamic brain responses in a songbird, the zebra finch (Taeniopygia guttata), using a hypercapnia event (7% inhaled CO(2)). The results are compared to those obtained using BOLD fMRI. The NIRS measurements clearly demonstrate that during hypercapnia the blood oxygen saturation level increases (increase in local concentration of oxyhemoglobin, decrease in deoxyhemoglobin concentration and total hemoglobin concentration). Our results provide the first correlation in songbirds of the variations in total hemoglobin and oxygen saturation level obtained from NIRS with local BOLD signal variations.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 18424882 [PubMed - indexed for MEDLINE]

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2: Neuroimage. 2008 May 15;41(1):1-6. Epub 2008 Mar 10.

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A three-dimensional MRI atlas of the zebra finch brain in stereotaxic coordinates.

Poirier C, Vellema M, Verhoye M, Van Meir V, Wild JM, Balthazart J, Van Der Linden A.

Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, 2020 Antwerp, Belgium. Colline.Poirier@ua.ac.be

The neurobiology of birdsong, as a model for human speech, is a fast growing area of research in the neurosciences and involves electrophysiological, histological and more recently magnetic resonance imaging (MRI) approaches. Many of these studies require the identification and localization of different brain areas (nuclei) involved in the sensory and motor control of song. Until now, the only published atlases of songbird brains consisted in drawings based on histological slices of the canary and of the zebra finch brain. Taking advantage of high-magnetic field (7 Tesla) MRI technique, we present the first high-resolution (80 x 160 x 160 microm) 3-D digital atlas in stereotaxic coordinates of a male zebra finch brain, the most widely used species in the study of birdsong neurobiology. Image quality allowed us to discern most of the song control, auditory and visual nuclei. The atlas can be freely downloaded from our Web site and can be interactively explored with MRIcro. This zebra finch MRI atlas should become a very useful tool for neuroscientists working on birdsong, especially for co-registrating MRI data but also for determining accurately the optimal coordinates and angular approach for injections or electrophysiological recordings.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov’t

PMID: 18358743 [PubMed - indexed for MEDLINE]

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3: J Neurophysiol. 2008 Feb;99(2):931-8. Epub 2007 Sep 19.

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Functional magnetic resonance imaging in zebra finch discerns the neural substrate involved in segregation of conspecific song from background noise.

Boumans T, Vignal C, Smolders A, Sijbers J, Verhoye M, Van Audekerke J, Mathevon N, Van der Linden A.

Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium. Tiny.Boumans@ua.ac.be

Recently, fMRI was introduced in a well-documented animal model for vocal learning, the songbird. Using fMRI and conspecific signals mixed with different levels of broadband noise, we now demonstrate auditory-induced activation representing discriminatory properties of auditory forebrain regions in anesthetized male zebra finches (Taeniopygia guttata). Earlier behavioral tests showed comparable calling responses to the original conspecific song stimulus heard outside and inside the magnet. A significant fMRI response was elicited by conspecific song in the primary auditory thalamo-recipient subfield L2a; in neighboring subareas L2b, L3, and L; and in the rostral part of the higher-order auditory area NCM (caudomedial nidopallium). Temporal BOLD response clustering revealed rostral and caudal clusters that we defined as “cluster Field L” and “cluster NCM”, respectively. However, because the actual border between caudal Field L subregions and NCM cannot be seen in the structural MR image and is not precisely reported elsewhere, the cluster NCM might also contain subregion L and the medial extremes of the subregions L2b and L3. Our results show that whereas in cluster Field L the response was not reduced by added noise, in cluster NCM the response was reduced and finally disappeared with increasing levels of noise added to the song stimulus. The activation in cluster NCM was significant for only two experimental stimuli that showed significantly more behavioral responses than the more degraded stimuli, suggesting that the first area within the auditory system where the ability to discern song from masking noise emerges is located in cluster NCM.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 17881485 [PubMed - indexed for MEDLINE]

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4: Eur J Neurosci. 2007 Nov;26(9):2613-26. Epub 2007 Oct 23.

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Neural representation of spectral and temporal features of song in the auditory forebrain of zebra finches as revealed by functional MRI.

Boumans T, Theunissen FE, Poirier C, Van Der Linden A.

Bio-Imaging Laboratory, University of Antwerp, Belgium.

Song perception in songbirds, just as music and speech perception in humans, requires processing the spectral and temporal structure found in the succession of song-syllables. Using functional magnetic resonance imaging and synthetic songs that preserved exclusively either the temporal or the spectral structure of natural song, we investigated how vocalizations are processed in the avian forebrain. We found bilateral and equal activation of the primary auditory region, field L. The more ventral regions of field L showed depressed responses to the synthetic songs that lacked spectral structure. These ventral regions included subarea L3, medial-ventral subarea L and potentially the secondary auditory region caudal medial nidopallium. In addition, field L as a whole showed unexpected increased responses to the temporally filtered songs and this increase was the largest in the dorsal regions. These dorsal regions included L1 and the dorsal subareas L and L2b. Therefore, the ventral region of field L appears to be more sensitive to the preservation of both spectral and temporal information in the context of song processing. We did not find any differences in responses to playback of the bird’s own song vs other familiar conspecific songs. We also investigated the effect of three commonly used anaesthetics on the blood oxygen level-dependent response: medetomidine, urethane and isoflurane. The extent of the area activated and the stimulus selectivity depended on the type of anaesthetic. We discuss these results in the context of what is known about the locus of action of the anaesthetics, and reports of neural activity measured in electrophysiological experiments.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov’t

PMID: 17970728 [PubMed - indexed for MEDLINE]

PMCID: PMC2228391

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5: Neurobiol Dis. 2007 Aug;27(2):190-206. Epub 2007 May 18.

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Overexpression of human wildtype torsinA and human DeltaGAG torsinA in a transgenic mouse model causes phenotypic abnormalities.

Grundmann K, Reischmann B, Vanhoutte G, Hübener J, Teismann P, Hauser TK, Bonin M, Wilbertz J, Horn S, Nguyen HP, Kuhn M, Chanarat S, Wolburg H, Van der Linden A, Riess O.

Department of Medical Genetics, University of Tuebingen, Calwerstr. 7, 72076 Tuebingen, Germany. Kathrin.Grundmann@med.uni-tuebingen.de

Primary torsion dystonia is an autosomal-dominant inherited movement disorder. Most cases are caused by an in-frame deletion (GAG) of the DYT1 gene encoding torsinA. Reduced penetrance and phenotypic variability suggest that alteration of torsinA amino acid sequence is necessary but not sufficient for development of clinical symptoms and that additional factors must contribute to the factual manifestation of the disease. We generated 4 independent transgenic mouse lines, two overexpressing human mutant torsinA and two overexpressing human wildtype torsinA using a strong murine prion protein promoter. Our data provide for the first time in vivo evidence that not only mutant torsinA is detrimental to neuronal cells but that also wildtype torsinA can lead to neuronal dysfunction when overexpressed at high levels. This hypothesis is supported by (i) neuropathological findings, (ii) neurochemistry, (iii) behavioral abnormalities and (iv) DTI-MRI analysis.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 17601741 [PubMed - indexed for MEDLINE]

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6: NMR Biomed. 2007 Aug;20(5):522-45.

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Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition.

Van der Linden A, Van Camp N, Ramos-Cabrer P, Hoehn M.

Bio-Imaging Laboratory, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. Annemie.vanderlinden@ua.ac.be

This review aims to make the reader aware of the potential of functional MRI (fMRI) in brain activation studies in small animal models. As small animals generally require anaesthesia for immobilization during MRI protocols, this is believed to be a serious limitation to the type of question that can be addressed with fMRI. We intend to introduce a fresh view with an in-depth overview of the surprising number of fMRI applications in a wide range of important research domains in neuroscience. These include the pathophysiology of brain functioning, the basic science of activity, and functional connectivity of different sensory circuits, including sensory brain mapping, the challenges when studying the hypothalamus as the major control centre in the central nervous system, and the limbic system as neural substrate for emotions and reward. Finally the contribution of small animal fMRI research to cognitive neuroscience is outlined. This review avoids focusing exclusively on traditional small laboratory animals such as rodents, but rather aims to broaden the scope by introducing alternative lissencephalic animal models such as songbirds and fish, as these are not yet well recognized as neuroimaging study subjects. These models are well established in many other neuroscience disciplines, and this review will show that their investigation with in vivo imaging tools will open new doors to cognitive neuroscience and the study of the autonomous nervous system in experimental animals. Copyright 2007 John Wiley & Sons, Ltd.

Publication Types:

• Research Support, Non-U.S. Gov’t
• Review

PMID: 17315146 [PubMed - indexed for MEDLINE]

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7: Neuroimage. 2006 Jul 1;31(3):981-92. Epub 2006 Mar 10.

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In vivo MR imaging of the seasonal volumetric and functional plasticity of song control nuclei in relation to song output in a female songbird.

Van Meir V, Pavlova D, Verhoye M, Pinxten R, Balthazart J, Eens M, Van der Linden A.

Bio-Imaging Lab, University of Antwerp, Groenenborgerlaan 171-Gebouw V, B-2020 Antwerp, Belgium. vincent.vanmeir@ua.ac.be

In temperate zone songbird species, seasonal plasticity in the morphological and functional state of brain regions involved in song production occurs in association with seasonal changes in song output. Following MnCl(2)-injections in HVC (used as proper name) of female starlings, in vivo tract-tracing by Manganese Enhanced-Magnetic Resonance Imaging (ME-MRI) provided repeated measures of the volume of two HVC targets, the nucleus robustus arcopallii (RA) and area X, along with measures of the activity of the caudal motor pathway and rostral basal-ganglia pathway that control singing. Mn(2+)-labeling (volume labeled and signal intensity) of both nuclei was dramatically reduced in July (post-breeding season) when birds did not sing, compared to March (breeding season) when birds produced song. Seasonal changes in telencephalon volume did not exceed 4% and were not significant but were surprisingly correlated with individual measures of song rate and song bout length. Although individual song rates were variable in March, all MnCl(2)-injections led to a reliable labeling of area X and RA. In July, delineation of area X was only possible in two birds and RA could be delineated in 50% of the population; its volume had decreased by 46% as compared to March. The birds in which RA could be delineated in July had in March a higher activity of the HVC to area X projection as reflected by the total amount of Mn(2+) accumulated in area X, which suggests unexpected relationships between the two types of HVC projection neurons.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov’t

PMID: 16529952 [PubMed - indexed for MEDLINE]

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8: J Exp Biol. 2006 Jun;209(Pt 11):2015-24.

Related Articles, 

Activation of a sensorimotor pathway in response to a water temperature drop in a teleost fish.

van den Burg EH, Verhoye M, Peeters RR, Meek J, Flik G, Van der Linden A.

Department of Organismal Animal Physiology, Faculty of Science, Radboud University Nijmegen, Toernooiveld 1, 6525 ED, Nijmegen, The Netherlands. E.vandenBurg@science.ru.nl

When common carp, Cyprinus carpio L., experience a rapid temperature drop, the cerebral blood volume is strongly reduced to dampen the temperature drop in the brain. Simultaneously, the preoptic area and pituitary gland are activated to launch whole-body adaptive responses. However, the preferred reaction of fish to a temperature change is an escape reaction, which implies activation of a sensorimotor pathway. Here, we used blood oxygenation level-dependent (BOLD)- and cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) to identify a sensorimotor pathway, during a 10 degrees C temperature drop in common carp. Transient activation was observed in the region where the sensory root of the trigeminal nerve enters the brain, and in the valvula cerebelli. In both regions, metabolic activity increased (increased deoxyhemoglobin content demonstrated by a decreased BOLD signal) within 30 s after the onset of the temperature drop, peaked after 2-3 min, and then decreased, even though the temperature continued to drop for another 2 min. These brain structures appear to respond to temperature change, rather than to the absolute temperature. Thus, during a temperature drop, the sensorimotor pathway consisting of the trigeminal nerve, the primary sensory trigeminal nucleus, the valvula cerebelli and some motornuclei, is active, in line with perception of temperature change in the buccal cavity, leading to motor activity for escape. This pathway operates in parallel to an acclimation pathway, which involves the preoptic area to pituitary gland pathway.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 16709904 [PubMed - indexed for MEDLINE]

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9: J Neurophysiol. 2006 May;95(5):3164-70. Epub 2006 Jan 4.

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Light stimulus frequency dependence of activity in the rat visual system as studied with high-resolution BOLD fMRI.

Van Camp N, Verhoye M, De Zeeuw CI, Van der Linden A.

Bio-Imaging Lab, University of Antwerp, Campus Middelheim, Groenenborgerlaan 171, 2020 Antwerp, Belgium. nadja.vancamp@ua.ac.be

The neurophysiology of the rodent visual system has mainly been investigated by invasive and ex-vivo techniques providing fragmented data. This area of research has been deprived of functional MRI studies based on blood oxygenation level dependent (BOLD) contrast, which allows a whole brain approach with a high spatial and temporal resolution. In the present study, we looked at the neurovascular response properties of the visual system of the pigmented rat, focusing on the visual cortex (VC), the superior colliculus (SC) and the flocculus-paraflocculus of the cerebellum (FL-PFL), using BOLD fMRI under domitor anesthesia. Visual stimulation was performed monocularly or binocularly while flashing light from a strobe unit was presented. For each structure, we assessed the flashing frequency that evoked the optimal BOLD response: Neither the VC nor the FL-PFL displayed frequency dependence during monocular visual stimulation, but were most sensitive to low frequencies (1-5 Hz) when flashing light was provided binocularly. The SC responded optimally to high flashing rates (8-12 Hz) during both monocular and binocular stimulation. The signal intensity changes in the VC and FL-PFL were locked to the stimulation period, whereas the BOLD response in the SC showed a similar onset but a very slow recovery at offset. The VC and FL-PFL, but not the SC, showed signs of binocular competition. The observed correlation between frequency-dependent responses of different visual areas during binocular visual presentation suggests a functional relationship between the VC and FL-PFL rather than between the SC and FL-PFL.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov’t

PMID: 16394078 [PubMed - indexed for MEDLINE]

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10: Magn Reson Med. 2006 May;55(5):1006-12.

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Changing body temperature affects the T2* signal in the rat brain and reveals hypothalamic activity.

Vanhoutte G, Verhoye M, Van der Linden A.

Bio-Imaging Laboratory, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. Greetje.Vanhoutte@ua.ac.be

This study was designed to determine brain activity in the hypothalamus-in particular the thermoregulatory function of the hypothalamic preoptic area (PO). We experimentally changed the body temperature in rats within the physiological range (37-39 degrees C) and monitored changes in blood oxygenation level-dependent (BOLD) MR signal. To explore PO activity we had to deal with general signal changes caused by temperature-dependent alterations in the affinity of oxygen for hemoglobin, which contributes to BOLD contrast because it is partly sensitive to the amount of paramagnetic deoxyhemoglobin in the voxel. To reduce these overall temperature-induced effects, we corrected the BOLD data using brain-specific correction algorithms. The results showed activity of the PO during body warming from 38 degrees C to 39 degrees C, supported by an increased BOLD signal after correction. This is the first fMRI study on the autonomous nervous system in which hypothalamic activity elicited by changes in the internal environment (body temperature) was monitored. In this study we also demonstrate 1) that any fMRI study of anesthetized small animals should guard against background BOLD signal drift, since animals are vulnerable to body temperature fluctuations; and 2) the existence of a link between PO activity and the sympathetically-mediated opening of the arteriovenous anastomoses in a parallel study on the rat tail, a peripheral thermoregulatory organ.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 16598718 [PubMed - indexed for MEDLINE]

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11: Neuroimage. 2006 Feb 1;29(3):754-63. Epub 2005 Oct 19.

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In vivo diffusion tensor imaging (DTI) of brain subdivisions and vocal pathways in songbirds.

De Groof G, Verhoye M, Van Meir V, Tindemans I, Leemans A, Van der Linden A.

Bio-Imaging Laboratory, University of Antwerp, CGB, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. Geert.DeGroof@ua.ac.be

The neural substrate for song behavior in songbirds, the song control system (SCS), is thus far the best-documented brain circuit in which to study neuroplasticity and adult neurogenesis. Not only does the volume of the key song control nuclei change in size, but also the density of the connections between them changes as a function of seasonal and hormonal influences. This study explores the potentials of in vivo Diffusion-Tensor MRI (DT-MRI or DTI) to visualize the distinct, concentrated connections of the SCS in the brain of the starling (Sturnus vulgaris). In vivo DTI on starling was performed on a 7T MR system using sagittal and coronal slices. DTI was accomplished with diffusion gradients applied in seven non-collinear directions. Fractional Anisotropy (FA)-maps allowed us to distinguish most of the grey matter and white matter-tracts, including the laminae subdividing the avian telencephalon and the tracts connecting the major song control nuclei (e.g., HVC with RA and X). The FA-maps also allowed us to discern a number of song control, auditory and visual nuclei. Fiber tracking was implemented to illustrate the discrimination of all tracts running from and to RA. Because of the remarkable plasticity inherent to the songbird brain, the successful implementation of DTI in this model could represent a useful tool for the in vivo exploration of fiber degeneration and regeneration and the biological mechanisms involved in brain plasticity.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 16242349 [PubMed - indexed for MEDLINE]

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12: NMR Biomed. 2006 Feb;19(1):18-29.

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IR-SE and IR-MEMRI allow in vivo visualization of oscine neuroarchitecture including the main forebrain regions of the song control system.

Tindemans I, Boumans T, Verhoye M, Van der Linden A.

Bio-Imaging Lab, Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

Songbirds share with humans the capacity to produce learned vocalizations (song). Recently, two major regions within the songbird’s neural substrate for song learning and production; nucleus robustus arcopallii (RA) and area X (X) are visualized in vivo using Manganese Enhanced MRI (MEMRI). The aim of this study is to extend this to all main interconnected forebrain Song Control Nuclei. The ipsilateral feedback circuits allow Mn2+ to reach all main Song Control Nuclei after stereotaxic injection of very small doses of MnCl2 (10 nl of 10 mM) into HVC of one and MAN (nucleus magnocellularis nidopallii anterioris) of the other hemisphere. Application of a high resolution (80 micron) Spin Echo Inversion Recovery sequence instead of conventional T1-weighted Spin Echo images improves the image contrast dramatically such that some Song Control Nuclei, ventricles, several laminae, fibre tracts and other specific brain regions can be discerned. The combination of this contrast-rich IR-SE sequence with the transsynaptic transport property of Manganese (Inversion Recovery based MEMRI (IR-MEMRI)) enables the visualization of all main interconnected components of the Song Control System in telencephalon and thalamus. 2006 John Wiley & Sons, Ltd.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 16411167 [PubMed - indexed for MEDLINE]

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13: NMR Biomed. 2006 Feb;19(1):10-7.

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Stimulation of the rat somatosensory cortex at different frequencies and pulse widths.

Van Camp N, Verhoye M, Van der Linden A.

Bio-Imaging Laboratory, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.

Functional MRI (fMRI) during electrical somatosensory stimulation of the rat forepaw is a widely used model to investigate the functional organization of the somatosensory cortex or to study the underlying mechanisms of the blood oxygen level-dependent (BOLD) response. In reality, somatosensory stimuli have complex timing relationships and are of long duration. However, by default electrical sensory stimulation seems to be performed at an extremely short pulse width (0.3 ms). As the pulse duration may alter the neuronal response, our aim was to investigate the influence of a much longer stimulus pulse width (10 ms) using BOLD fMRI during electrical forepaw stimulation. The optimal neuronal response was investigated by varying the stimulus frequency at a fixed pulse duration (10 ms) and amplitude (1 mA). In a parallel experiment we measured the neuronal response directly by recording the somatosensory evoked potentials (SEPs). Quantification of the BOLD data revealed a shift in the optimal response frequencies to 8-10 Hz compared with 1 Hz at 0.3 ms. The amplitude of the recorded SEPs decreased with increasing stimulation frequency and did not display any correlation with the BOLD data. Nevertheless, the summated SEPs, which are a measure of the integrated neuronal activity as a function of time, displayed a similar response profile, with a similar maximum as observed by relative BOLD changes. This shift in optimal excitation frequencies might be related to the fact that an increased pulse width of an electrical stimulus alters the nature of the stimulation, generating also sensorimotor instead of merely somatosensory input. This may influence or alter the activated pathways, resulting in a shift in the optimal response profile. 2006 John Wiley & Sons, Ltd.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 16408324 [PubMed - indexed for MEDLINE]

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14: J Magn Reson Imaging. 2005 Oct;22(4):483-91.

Related Articles, 

A comparison between blood oxygenation level-dependent and cerebral blood volume contrast in the rat cerebral and cerebellar somatosensoric cortex during electrical paw stimulation.

Van Camp N, Peeters RR, Van der Linden A.

Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium. nadja.vancamp@ua.ac.be

PURPOSE: To implement and optimize cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) in the rat cerebral and cerebellar cortex during electrical paw stimulation. MATERIALS AND METHODS: fMRI of the cerebral and cerebellar cortex was performed during electrical paw stimulation on a 7-T MRI system (MRRS, Guilford, UK) comparing the blood oxygenation level-dependent (BOLD) and CBV-weighted contrast with different ultrasmall particles of iron oxide (USPIO) contrast doses (NC100150, 30 mg Fe/mL; Amersham Health, Oslo, Norway) and different TE. RESULTS: Doses of 15 and 20 mg/kg USPIO at TE = T*2 or TE = 14 msec almost doubled the contrast-to-noise ratio (CNR) of the activated areas in the cerebral cortex without affecting the overall signal-to-noise ratio (SNR) or the incidence of activation (100%). In the cerebellum the SNR decreased significantly with an increasing contrast dose. At a dose of 15 mg/kg, the CNR was slightly smaller than the CNR measured in the BOLD images, but the activation incidence seemed to be doubled. At 20 mg/kg, the CNR was slightly increased, but the activation incidence was lower. At both contrast doses the venous artifacts disappeared. CONCLUSION: A USPIO contrast dose of 20 mg/kg proved to be beneficial for fMRI in the rat, even though it affected the CNR and SNR in the cerebral and the cerebellar cortex differentially. (c) 2005 Wiley-Liss, Inc.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov’t

PMID: 16161082 [PubMed - indexed for MEDLINE]

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15: Aquat Toxicol. 2005 Aug 15;74(1):32-46.

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Ammonia affects brain nitrogen metabolism but not hydration status in the Gulf toadfish (Opsanus beta).

Veauvy CM, McDonald MD, Van Audekerke J, Vanhoutte G, Van Camp N, Van der Linden A, Walsh PJ.

Division of Marine Biology and Fisheries, NIEHS Marine and Freshwater Biomedical Sciences Center, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Miami, FL 33149-1098, USA. cveauvy@rsmas.miami.edu

Laboratory rodents made hyperammonemic by infusing ammonia into the blood show symptoms of brain cell swelling and increased intracranial pressure. These symptoms could be caused in part by an increase in brain glutamine formed when brain glutamine synthetase (GS) naturally detoxifies ammonia to glutamine. Previous studies on the Gulf toadfish (Opsanus beta) demonstrated that it is resistant to high ammonia exposure (HAE) (96 h LC(50)=10mM) despite an increase in brain glutamine. This study attempts to resolve whether the resistance of O. beta is mediated by special handling of brain water in the face of changing glutamine concentrations. Methionine sulfoximine (MSO), an inhibitor of GS, was used to pharmacologically manipulate glutamine concentrations, and magnetic resonance imaging (MRI) was used to assess the status of brain water. Ammonia or MSO treatment did not substantially affect blood acid-base parameters. Exposure to 3.5mM ammonium chloride in seawater for 16 or 40 h resulted in a parallel increase in brain ammonia (3-fold) and glutamine (2-fold) and a decrease in brain glutamate (1.3-fold). Pre-treatment with MSO prevented ammonia-induced changes in glutamine and glutamate concentrations. HAE also induced an increase in plasma osmolality (by 7%) which was probably due to a disturbance of osmoregulatory processes but which did not result in broader whole body dehydration as indicated by muscle water analysis. The increase in brain glutamine was not associated with any changes in brain water in toadfish exposed to 3.5 mM ammonia for up to 40 h or even at 10, 20 and 30 mM ammonia consecutively and for one hour in each concentration. The lack of brain water accumulation implies that ammonia toxicity in toadfish appears to be via pathways other than cerebral swelling. Furthermore, toadfish pre-treated with MSO did not survive a normally sub-lethal exposure to 3.5 mM ammonia for 40 h. The enhancement of ammonia toxicity by MSO suggests that GS function is critical to ammonia tolerance in this species.

Publication Types:

• Comparative Study
• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, P.H.S.

PMID: 15927282 [PubMed - indexed for MEDLINE]

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16: J Neurophysiol. 2005 May;93(5):2849-55. Epub 2004 Dec 22.

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Brain responses to ambient temperature fluctuations in fish: reduction of blood volume and initiation of a whole-body stress response.

van den Burg EH, Peeters RR, Verhoye M, Meek J, Flik G, Van der Linden A.

Department of Animal Physiology, University of Nijmegen, Nijmegen, The Netherlands. Annemie.VanderLinden@ua.ac.be

Spatial and temporal ambient temperature variations directly influence cellular biochemistry and thus the physiology of ectotherms. However, many aquatic ectothermic species maintain coordinated sensorimotor function during large acute body-temperature changes, which points to a compensatory mechanism within the neural system. Here we used high-resolution functional magnetic resonance imaging to study brain responses to a drop of 10 degrees C of ambient water temperature in common carp. We observed a strong drainage of blood out of the brain as of 90 s after the onset of the temperature drop, which would be expected to reduce entry of cold blood arriving from the gills so that the change in brain temperature would be slower. Although oxygen content in the brain thus decreased, we still found specific activation in the preoptic area (involved in temperature detection and stress responses), the pituitary pars distalis (stress response), and inactivation of the anterior part of the midbrain tegmentum and the pituitary pars intermedia. We propose that the blood drainage from the brain slows down the cooling of the brain during an acute temperature drop. This could help to maintain proper brain functioning including sensorimotor activity, initiation of the stress response, and the subsequent behavioral responses.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov’t

PMID: 15615828 [PubMed - indexed for MEDLINE]

---

17: Neuroimage. 2005 May 1;25(4):1242-55.

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–>Links

Spatiotemporal properties of the BOLD response in the songbirds’ auditory circuit during a variety of listening tasks.

Van Meir V, Boumans T, De Groof G, Van Audekerke J, Smolders A, Scheunders P, Sijbers J, Verhoye M, Balthazart J, Van der Linden A.

Bio-Imaging Laboratory, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. vincent.vanmeir@ua.ac.be

Auditory fMRI in humans has recently received increasing attention from cognitive neuroscientists as a tool to understand mental processing of learned acoustic sequences and analyzing speech recognition and development of musical skills. The present study introduces this tool in a well-documented animal model for vocal learning, the songbird, and provides fundamental insight in the main technical issues associated with auditory fMRI in these songbirds. Stimulation protocols with various listening tasks lead to appropriate activation of successive relays in the songbirds’ auditory pathway. The elicited BOLD response is also region and stimulus specific, and its temporal aspects provide accurate measures of the changes in brain physiology induced by the acoustic stimuli. Extensive repetition of an identical stimulus does not lead to habituation of the response in the primary or secondary telencephalic auditory regions of anesthetized subjects. The BOLD signal intensity changes during a stimulation and subsequent rest period have a very specific time course which shows a remarkable resemblance to auditory evoked BOLD responses commonly observed in human subjects. This observation indicates that auditory fMRI in the songbird may establish a link between auditory related neuro-imaging studies done in humans and the large body of neuro-ethological research on song learning and neuro-plasticity performed in songbirds.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, Non-P.H.S.
• Research Support, U.S. Gov’t, P.H.S.

PMID: 15850742 [PubMed - indexed for MEDLINE]

---

18: Magn Reson Med. 2005 Apr;53(4):944-53.

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]
–>Links

Mathematical framework for simulating diffusion tensor MR neural fiber bundles.

Leemans A, Sijbers J, Verhoye M, Van der Linden A, Van Dyck D.

Vision Laboratory, Department of Physics, University of Antwerp, B-2020 Antwerp, Belgium. alexander.leemans@ua.ac.be

White matter (WM) fiber tractography (i.e., the reconstruction of the 3D architecture of WM fiber pathways) is known to be an important application of diffusion tensor magnetic resonance imaging (DT-MRI). For the quantitative evaluation of several fiber-tracking properties, such as accuracy, noise sensitivity, and robustness, synthetic ground-truth DT-MRI data are required. Moreover, an accurate simulated phantom is also required for optimization of the user-defined tractography parameters, and objective comparisons between fiber-tracking algorithms. Therefore, in this study a mathematical framework for simulating DT-MRI data, based on the physical properties of WM fiber bundles, is presented. We obtained a model of a WM fiber bundle by parameterizing the various features that characterize this bundle. We then evaluated three different synthetic DT-MRI models using experimental data in order to test the proposed methodology, and to determine the optimum model and parameter settings for constructing a realistic simulated DT-MRI phantom. Several examples of how the mathematical framework can be applied to compare fiber-tracking algorithms are presented. Copyright 2005 Wiley-Liss, Inc.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 15799061 [PubMed - indexed for MEDLINE]

---

19: Magn Reson Med. 2005 Mar;53(3):607-13.

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–>Links

Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer’s disease.

Vanhoutte G, Dewachter I, Borghgraef P, Van Leuven F, Van der Linden A.

Bio-Imaging Lab, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. Greetje.Vanhoutte@ua.ac.be

Transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP[V717I]) in neurons develop amyloid plaques in the brain, thus demonstrating the most prominent neuropathological hallmark of Alzheimer’s disease. In vivo 3D T2*-weighted MRI on these mice (24 months of age) revealed hypointense brain inclusions that affected the thalamus almost exclusively. Upon correlating these MRI observations with a panel of different histologic staining techniques, it appeared that only plaques that were positive for both thioflavin-S and iron were visible on the MR images. Numerous thioflavin-S-positive plaques in the cortex that did not display iron staining remained invisible to MRI. The in vivo detection of amyloid plaques in this mouse model, using the intrinsic MRI contrast arising from the iron associated with the plaques, creates an unexpected opportunity for the noninvasive investigation of the longitudinal development of the plaques in the same animal. Thus, this work provides further research opportunities for analyzing younger APP[V717I] mouse models with the knowledge of the final outcome at 24 months of age. (c) 2005 Wiley-Liss, Inc.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 15723413 [PubMed - indexed for MEDLINE]

---

20: MAGMA. 2004 Dec;17(3-6):236-48. Epub 2004 Dec 20.

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]
–>Links

The strengths of in vivo magnetic resonance imaging (MRI) to study environmental adaptational physiology in fish.

Van der Linden A, Verhoye M, Pörtner HO, Bock C.

Bio-Imaging Lab, Department, Biomedical Sciences, University of Antwerp, Middelheim Campus, Groenenborgerlaan 171, 2020, Antwerp, Belgium. annemie.vanderlinden@ua.ac.be

Adaptational physiology studies how animals cope with their environment, even if this environment is subject to permanent fluctuations such as tidal or seasonal variations. Aquatic organisms are generally more prone to be exposed to osmotic, hypoxic and temperature challenges than terrestrial animals. Some of these challenges are more restraining in an aquatic environment. To date, very few studies have used in vivo magnetic resonance imaging (MRI) to uncover the physiological mechanisms that respond to or compensate for these challenges. This paper provides an overview of what has been accomplished thus far by using MRI to study the environmental physiology of fish. It introduces the reader to the use of small teleost fish such as carp (12 cm, 60 g) and eelpout (25 cm, 50 g) as models for such research and to provide new perceptions into the applicability of MRI tools based on new insights into the nature of MRI contrast. Representative MRI studies have made contributions to the identification of the lack of cell volume repair in stenohaline fish during osmotic stress. They have studied the underlying physiological mechanisms of brain anoxia tolerance in fish and have qualified the role of the cardio-circulatory system in setting thermal tolerance windows of fish.

Publication Types:

• Review

PMID: 15614515 [PubMed - indexed for MEDLINE]

---

21: NMR Biomed. 2004 Dec;17(8):602-12.

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]
–>Links

Applications of manganese-enhanced magnetic resonance imaging (MEMRI) to image brain plasticity in song birds.

Van der Linden A, Van Meir V, Tindemans I, Verhoye M, Balthazart J.

Bio-Imaging Laboratory, Department of Biomedical Sciences, University of Antwerp, Campus Middelheim, Groenenborgerlaan 171, 2020 Antwerp, Belgium. Annemie.Vanderlinden@ua.ac.be

The song control system of song birds is an excellent model for studying brain plasticity and has thus far been extensively analyzed by histological and electrophysiological methods. However, these approaches do not provide a global view of the brain and/or do not allow repeated measures, which are necessary to establish correlations between alterations in neural substrate and behavior. Application of in vivo manganese-enhanced MRI enabled us for the first time to visualize the song control system repeatedly in the same bird, making it possible to quantify dynamically the volume changes in this circuit as a function of seasonal and hormonal influences. In this review, we introduce and explore the song control system of song birds as a natural model for brain plasticity to validate a new cutting edge technique, which we called ‘repeated dynamic manganese enhanced MRI’ or D-MEMRI. This technique is based on the use of implanted permanent cannulae–for accurate repeated manganese injections in a defined target area–and the subsequent MRI acquisition of the dynamics of the accumulation of manganese in projection brain targets. A compilation of the D-MEMRI data obtained thus far in this system demonstrates the usefulness of this new method for studying brain plasticity. In particular it is shown to be a perfect tool for long-term studies of morphological and functional responses of specific brain circuits to changes in endocrine conditions. The method was also successfully applied to obtain quantitative measures of changes in activity as a function of auditory stimuli in different neuronal populations of a same nucleus that project to different targets. D-MEMRI, combined with other MRI techniques, clearly harbors potential for unraveling seasonal, hormonal, pharmacological or even genetically driven changes in a neuronal circuit, by simultaneously measuring changes in morphology, activity and connectivity. Copyright 2004 John Wiley & Sons, Ltd.

Publication Types:

• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, P.H.S.
• Review

PMID: 15761949 [PubMed - indexed for MEDLINE]

---

22: Neuroimage. 2004 Mar;21(3):914-23.

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]
–>Links

Differential effects of testosterone on neuronal populations and their connections in a sensorimotor brain nucleus controlling song production in songbirds: a manganese enhanced-magnetic resonance imaging study.

Van Meir V, Verhoye M, Absil P, Eens M, Balthazart J, Van der Linden A.

Bio-Imaging Laboratory, Department of Biomedical Sciences, University of Antwerp, B-2020 Antwerp, Belgium. vincent.vanmeir@ua.ac.be

Nucleus HVC (formerly called high vocal center) of songbirds contains two types of projecting neurons connecting HVC respectively to the nucleus robustus archistriatalis, RA, or to area X. These two neuron classes exhibit multiple neurochemical differences and are differentially replaced by new neurons during adult life: high rates of neuronal replacement are observed in RA-projecting neurons only. The activity of these two types of neurons may also be modulated differentially by steroids. We analyzed by magnetic resonance imaging the effect of testosterone on the volume of RA and area X and on the dynamics of Mn(2+) accumulation in RA and area X of female starlings that had been injected with MnCl(2) through a permanent cannula implanted in HVC. Repeated visualization 6 weeks apart (before and after testosterone treatment) identified a volume increase of both nuclei in testosterone-treated birds associated with a concomitant decrease in controls. Following testosterone treatment, the total amount of Mn(2+) transported to RA and area X increased but the dynamics of accumulation, reflecting in part the activity of HVC neurons, was specifically altered in area X but not in RA. These data indicate that testosterone differentially affects the RA- and area X-projecting neurons in HVC. Manganese-enhanced magnetic resonance imaging (ME-MRI) thus provides repeated measures of connected brain areas and demonstrates testosterone-dependent regionally specific changes in brain activity and functional connectivity. The slow time scales investigated by this technique (compared to functional MRI) appear ideally suited for characterizing slow processes such as those involved in brain plasticity and learning.

Publication Types:

• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, Non-P.H.S.
• Research Support, U.S. Gov’t, P.H.S.

PMID: 15006658 [PubMed - indexed for MEDLINE]

---

23: Eur J Neurosci. 2003 Dec;18(12):3352-60.

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]
–>Links

In vivo dynamic ME-MRI reveals differential functional responses of RA- and area X-projecting neurons in the HVC of canaries exposed to conspecific song.

Tindemans I, Verhoye M, Balthazart J, Van Der Linden A.

Bio-Imaging Laboratory, University of Antwerp, Groenenborgerlaan 171 – Gebouw V, B-2020 Antwerp, Belgium. ilsetee@ruca.ua.ac.be

HVC (nidopallial area, formerly known as hyperstriatum ventrale pars caudalis), a key centre for song control in oscines, responds in a selective manner to conspecific songs as indicated by electrophysiology. However, immediate-early gene induction cannot be detected in this nucleus following song stimulation. HVC contains neurons projecting either towards the nucleus robustus archistriatalis (RA; motor pathway) or area X (anterior forebrain pathway). Both RA- and area X-projecting cells show auditory responses. The present study analysed these responses separately in the two types of HVC projection neurons of canaries by a new in vivo approach using manganese as a calcium analogue which can be transported anterogradely and used as a paramagnetic contrast agent for magnetic resonance imaging (MRI). Manganese was stereotaxically injected into HVC and taken up by HVC neurons. The anterograde axonal transport of manganese from HVC to RA and area X was then followed by MRI during approximately 8 h and changes in signal intensity in these targets were fitted to sigmoid functions. Data comparing birds exposed or not to conspecific songs revealed that song stimulation specifically affected the activity of the two types of HVC projection neurons (increase in the sigmoid slope in RA and in its maximum signal intensity in area X). Dynamic manganese-enhanced MRI thus allows assessment of the functional state of specific neuronal populations in the song system of living canaries in a manner reminiscent of functional MRI (but with higher resolution) or of 2-deoxyglucose autoradiography (but in living subjects).

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, Non-P.H.S.
• Research Support, U.S. Gov’t, P.H.S.

PMID: 14686908 [PubMed - indexed for MEDLINE]

---

24: Neuroimage. 2003 Jul;19(3):627-36.

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]
–>Links

Simultaneous electroencephalographic recording and functional magnetic resonance imaging during pentylenetetrazol-induced seizures in rat.

Van Camp N, D’Hooge R, Verhoye M, Peeters RR, De Deyn PP, Van der Linden A.

Bio Imaging Lab, RUCA, 2020 Antwerp, Belgium.

Truly simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) were registered in curarized rats injected with convulsive doses of pentylenetetrazol (PTZ, 65 mg/kg, sc). Rigorous control of physiological parameters like body temperature and ventilation with control of blood gasses helped to avoid potential interference between systemic parameters, and central PTZ-induced blood oxygenation level-dependent (BOLD) changes. Simultaneous EEG/fMRI recordings demonstrated progressive epileptiform EEG discharges with concomitant BOLD changes, the latter gradually affecting most of the fore- and midbrain. Approximately 15 min after PTZ injection, the first BOLD contrast changes mainly occurred in neocortex, and coincided with the first minor EEG alterations. Most regions that displayed BOLD changes were regions with reportedly high GABA(A) receptor densities. Full-blown epileptiform discharges occurred on the EEG tracing, approximately 30 min after PTZ injection, and coincided with bilateral positive and/or negative BOLD contrast changes in cortical and subcortical regions. Behavioral observations demonstrated the first of several generalized clonic or clonic-tonic seizure episodes to occur also around this time. Approximately 90 min after injection, the electrographic paroxysms gradually decreased in amplitude and duration, whereas the BOLD signal changes still extended with alternating positive and negative traces, and spread to subcortical regions like caudate-putamen and globus pallidus.

Publication Types:

• Clinical Trial
• Research Support, Non-U.S. Gov’t

PMID: 12880793 [PubMed - indexed for MEDLINE]

---

25: Magn Reson Imaging. 2002 Jul;20(6):503-10.

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]
–>Links

A data post-processing protocol for dynamic MRI data to discriminate brain activity from global physiological effects.

Peeters RR, Van der Linden A.

Bio Imaging Lab, University of Antwerp, RUCA, Antwerp, Belgium.

All fMRI techniques measure stimulus induced focal metabolic and physiological changes in activated brain areas. During the entire fMRI experiment it is necessary to maintain the general physiological condition of the subject as stable as possible. This is not always an easy task. The typical block design in standard fMRI experiments minimizes most of the problems related with these general physiological changes. However in some fMRI experiments, like pharmacological MRI, the experimental setup makes the use of a blocked design impossible. Therefore signal correction algorithms have been developed to correct for these physiological signal instabilities. These algorithms often require elaborate calculation efforts and the data interpretation is often very difficult if no prior knowledge on the nature of the changes exists.In this work we present an algorithm, which has the advantage of being low in calculation effort and the resulting data after correction are easy to interpret. It makes use of a datafit between the general physiological and focal activation related signal changes to eliminate the generalized effects. This algorithm has been tested on simulated and experimentally obtained signal traces suffering both from substantial general signal changes overwhelming the smaller focal activation induced signal changes.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 12361798 [PubMed - indexed for MEDLINE]

---

26: NMR Biomed. 2002 Jun;15(4):263-9.

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]
–>Links

In-vivo non-invasive study of the thermoregulatory function of the blood vessels in the rat tail using magnetic resonance angiography.

Vanhoutte G, Verhoye M, Raman E, Roberts M, Van der Linden A.

Bio Imaging Lab, University of Antwerp, Antwerp, Belgium. grevaho@ruca.ac.be

In rats, a significant portion of total body heat loss occurs through sympathetically mediated changes in tail blood flow, making the rat tail a convenient model to study vasomotor activity during thermoregulation. Our aim was to perform a non-invasive study of the mechanisms of blood vessel control in the rat tail upon increasing body temperature. In anaesthetized rats, blood vessel temperature was monitored using non-invasive thermistors positioned on the skin surface, covering the ventral artery (Ta) and lateral vein (Tv), and changes in blood vessel size were measured using in-vivo magnetic resonance angiography (MRA). Two important regions of the tail (base and middle) were studied during a gradual rise of rectal temperature (Tr) from 37 to 40 degrees C. MRA data show that increasing Tr causes increased diameter of both arteries and veins of the tail, that venous diameter changes are greater than arterial diameter changes, and that diameter changes of both types of vessel are greater at the base of the tail than in the middle. Temperature data allowed calculation of (Ta – Tv), which we used as an index of flow through arteriovenous anastomoses (AVAs). The data suggest that AVAs near the base of the tail are important in heat exchange, and that they remain open only for Tr values between 38 and 39 degrees C. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 12112608 [PubMed - indexed for MEDLINE]

---

27: Magn Reson Med. 2002 Feb;47(2):305-13.

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–>Links

Assessment of the neovascular permeability in glioma xenografts by dynamic T(1) MRI with Gadomer-17.

Verhoye M, van der Sanden BP, Rijken PF, Peters HP, Van der Kogel AJ, Pée G, Vanhoutte G, Heerschap A, Van der Linden A.

Bio Imaging Lab, RUCA, Antwerp, Belgium. maver@ruca.ua.ac.be

The uptake of Gadomer-17, as probed by fast dynamic T(1) measurements, was used to assess the vascular permeability surface-area product per leakage volume of tissue (k(Tofts)) of human glioma xenografts implanted in mice. With this approach we could discriminate between two types of glioma xenograft lines with a known difference in the perfused vascular architecture and degree of hypoxia. The T(1) data were analyzed according to the Tofts-Kermode compartment model. The fast-growing E102 tumor demonstrated a homogeneous distribution of the vascular permeability surface area across the tumor (mean k(Tofts) value = 0.18 +/- 0.05 min(-1)). The slowly growing E106 tumor showed a more heterogeneous pattern. Three perfused tumor areas with differences in vascular permeability surface area could be distinguished: a well-perfused periphery with high k(Tofts) values (0.24 +/- 0.04 min(-1)), perfused capillaries inside the tumor with low k(Tofts) values (0.108 +/- 0.026 min(-1)), and perfused capillaries adjacent to necrotic regions with high k(Tofts) values (0.29 +/- 0.10 min(-1)). On a different series of tumors, the hypoxic fractions were measured, and these were significantly higher in E106 tumors (0.14 +/- 0.05) compared to tumors of the E102 line (0.03 +/- 0.02). Copyright 2002 Wiley-Liss, Inc.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 11810674 [PubMed - indexed for MEDLINE]

---

28: Neuroscience. 2002;113(4):797-808.

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Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice.

Spittaels K, Van den Haute C, Van Dorpe J, Terwel D, Vandezande K, Lasrado R, Bruynseels K, Irizarry M, Verhoye M, Van Lint J, Vandenheede JR, Ashton D, Mercken M, Loos R, Hyman B, Van der Linden A, Geerts H, Van Leuven F.

Experimental Genetics Group, Department of Human Genetics, KU Leuven, Campus Gasthuisberg O&N 06, B-3000 Leuven, Belgium.

Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20% reduction in wet brain weight. The reduced volume was most prominent for the cerebral cortex, without however, disturbing the normal cortical layering. The resulting compacted architecture was further demonstrated by an increased neuronal density, by reduced size of neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons in the cortex. No evidence for apoptosis was obtained. The marked overall reduction in the level of the microtubule-associated protein 2 in brain and in spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton in the proximal apical dendrites. The overall reduction in size of the entire CNS induced by constitutive active GSK-3beta caused only very subtle changes in the psychomotoric ability of adult and ageing GSK-3beta transgenic mice. Copyright 2002 IBRO

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 12182887 [PubMed - indexed for MEDLINE]

---

29: Neuroscience. 2002;112(2):467-74.

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–>Links

In vivo manganese-enhanced magnetic resonance imaging reveals connections and functional properties of the songbird vocal control system.

Van der Linden A, Verhoye M, Van Meir V, Tindemans I, Eens M, Absil P, Balthazart J.

Bio-Imaging Laboratory, RUCA, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. avadelin@ruca.ua.ac.be

Injection of manganese (Mn(2+)), a paramagnetic tract tracing agent and calcium analogue, into the high vocal center of starlings labeled within a few hours the nucleus robustus archistriatalis and area X as observed by in vivo magnetic resonance imaging. Structures highlighted by Mn(2+) accumulation assumed the expected tri-dimensional shape of the nucleus robustus archistriatalis and area X as identified by classical histological or neurochemical methods. The volume of these nuclei could be accurately calculated by segmentation of the areas highlighted by Mn(2+). Besides confirming previously established volumetric sex differences, Mn(2+) uptake into these nuclei revealed new functional sex differences affecting Mn(2+) transport. A faster transport was observed in males than in females and different relative amounts of Mn(2+) were transported to nucleus robustus archistriatalis and area X in males as compared to females.This new in vivo approach, allowing repeated measures, opens new vistas to study the remarkable seasonal plasticity in size and activity of song-control nuclei and correlate neuronal activity with behavior. It also provides new insights on in vivo axonal transport and neuronal activity in song-control nuclei of oscines.

Publication Types:

• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, Non-P.H.S.
• Research Support, U.S. Gov’t, P.H.S.

PMID: 12044464 [PubMed - indexed for MEDLINE]

---

30: Magn Reson Imaging. 2001 Jul;19(6):821-6.

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–>Links

Comparing BOLD fMRI signal changes in the awake and anesthetized rat during electrical forepaw stimulation.

Peeters RR, Tindemans I, De Schutter E, Van der Linden A.

Bio Imaging Lab, University of Antwerp, RUCA, Groenenborgerlaan 171, B2020, Antwerp, Belgium. rope@ruca.ua.ac.be

The difference between awake curarized and alpha-chloralose anesthetized animals was studied with respect to the BOLD signal response in an fMRI experiment. By studying the activation of the cortex upon electrical forepaw stimulation in the same rat, but following consecutively applied curarization and alpha-chloralose anesthesia protocols, it was possible to compare quantitatively the effect of both immobilization protocols on the fMRI data. The largest BOLD signal change as a result of forepaw stimulation was found in the awake condition, however the activated areas are less specific than those in the anesthetized state leaving it more difficult to interpret.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov’t

PMID: 11551722 [PubMed - indexed for MEDLINE]

---

31: Eur J Hum Genet. 2001 Mar;9(3):153-9.

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–>Links

Brain studies of mouse models for neurogenetic disorders using in vivo magnetic resonance imaging (MRI).

Kooy RF, Verhoye M, Lemmon V, Van Der Linden A.

Department of Medical Genetics, University of Antwerp, Antwerp, Belgium. fkooy@uia.ac.be

Magnetic resonance imaging (MRI) is a technique commonly used to detect neural abnormalities in routine clinical practice. It is perhaps less well known that the technique can be adapted to measure various anatomical and physiological features of small laboratory rodents. This review focuses on the potential of the MRI technique to image the brain of (transgenic) mouse models for neurological diseases, and aims to introduce these exciting new technological developments to the non-specialist reader.

Publication Types:

• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, P.H.S.
• Review

PMID: 11313752 [PubMed - indexed for MEDLINE]

---

32: J Neurophysiol. 2001 Jan;85(1):125-33.

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–>Links

Does anoxia induce cell swelling in carp brains? In vivo MRI measurements in crucian carp and common carp.

Van der Linden A, Verhoye M, Nilsson GE.

Bio-Imaging Lab, University Center Antwerp, University of Antwerp, 2020 Antwerp, Belgium. avadelin@ruca.ua.ac.be

Although both common and crucian carp survived 2 h of anoxia at 18 degrees C, the response of their brains to anoxia was quite different and indicative of the fact that the crucian carp is anoxia tolerant while the common carp is not. Using in vivo T(2) and diffusion-weighted magnetic resonance imaging (MRI), we studied anoxia induced changes in brain volume, free water content (T(2)), and water homeostasis (water diffusion coefficient). The anoxic crucian carp showed no signs of brain swelling or changes in brain water homeostasis even after 24 h except for the optic lobes, where cellular edema was indicated. The entire common carp brain suffered from cellular edema, net water gain, and a volume increase (by 6.5%) that proceeded during 100 min normoxic recovery (by 10%). The common carp recovered from this insult, proving that the changes were reversible and suggesting that the oversized brain cavity allows brain swelling during energy deficiency without a resultant increase in intracranial pressure and global ischemia. It is tempting to suggest that this is a function of the large brain cavity seen in many ectothermic vertebrates.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 11152713 [PubMed - indexed for MEDLINE]

---

33: MAGMA. 1998 Aug;6(1):22-7.

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Imaging birds in a bird cage: in-vivo FSE 3D MRI of bird brain.

Verhoye M, Van der Linden A, Van Audekerke J, Sijbers J, Eens M, Balthazart J.

Bio-Imaging Laboratory, RUCA, University of Antwerp, Belgium.

An in-vivo magnetic resonance imaging (MRI) procedure is described that allows one to obtain three-dimensional high quality images of the entire brain of small birds such as the canary (20 g) and the starling (75 g) with an image resolution of 0.1 mm (58-113 microm, dependent on the size of the imaged bird). The entire imaging procedure took about 2 h after which the birds recovered from anaesthesia uneventfully and could be reused for subsequent additional imaging. This non invasive MRI technique enables to correlate brain measures with behavioural or physiological data that are dynamic in nature and could permit significant progress for bird neurological research.

Publication Types:

• Research Support, Non-U.S. Gov’t
• Research Support, U.S. Gov’t, P.H.S.

PMID: 9794286 [PubMed - indexed for MEDLINE]

---

34: J Neurosci Methods. 1998 Jun 1;81(1-2):45-52.

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Non invasive in vivo anatomical studies of the oscine brain by high resolution MRI microscopy.

Van der Linden A, Verhoye M, Van Auderkerke J, Peeters R, Eens M, Newman SW, Smulders T, Balthazart J, DeVoogd TJ.

Bio-Imaging Lab, RUCA, Univ. Antwerp, Belgium. avadelin@ruca.ua.ac.be

We describe in this paper an in vivo Magnetic Resonance Imaging (MRI) procedure that allows one to obtain three-dimensional high quality images of the entire brain of small passerine birds such as the canary with a slice thickness of 58 micron and an image resolution of 78 microns. This imaging procedure was completed in 70 min on anaesthetised birds that later recovered uneventfully and could be reused for subsequent additional imaging. To illustrate the high resolution and anatomical detail that can be achieved, examples of coronal images through the entire hypothalamus are provided in the same sectioning plane as the previously published canary brain atlas. The data set can be used to create sections in any desired plane and the entire data set can be viewed from any point of view in a volume rendered image. This provides a useful tool in understanding the three-dimensional organisation of the brain. Similar procedures can also be applied on fixed brains and might allow an even better anatomical resolution of images because time constrains no longer limit the duration of image acquisition. The non-invasive MRI technique enables to study neuroanatomical features with a high resolution and without killing the animal subjects so that measures can be obtained in a same individual both before and after an experimental treatment.

Explore posts in the same categories: MRI, RAT, auditory, bird, brain, metabolism, mice