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Purpose To introduce a novel imaging and parameter estimation framework for accurate multi-shot diffusion MRI. Theory and Methods We propose a new framework called ADEPT (Accurate Diffusion Echo-Planar imaging with multi-contrast shoTs) that enables fast diffusion MRI by allowing diffusion contrast settings to change between shots in a multi-shot EPI acquisition (i.e., intra-scan modulation). The framework estimates diffusion parameter maps directly from the acquired intra-scan modulated k-space data, while simultaneously accounting for shot-to-shot phase inconsistencies. The performance of the estimation framework is evaluated using Monte Carlo simulation studies and in-vivo experiments and compared to that of reference methods that rely on parallel imaging for shot-to-shot phase correction. Results Simulation and real-data experiments show that ADEPT yields more accurate and more precise estimates of the diffusion metrics in multi-shot EPI data in comparison with the reference methods. Conclusion ADEPT allows fast multi-shot EPI diffusion MRI without significantly degrading the accuracy and precision of the estimated diffusion maps.

Premenopausal bilateral ovariectomy is considered to be one of the risk factors of Alzheimer's disease (AD). However, the underlying mechanisms remain unclear. Here, we aimed to investigate long-term neurological consequences of ovariectomy in a rodent AD model, TG2576 (TG), and wild-type mice (WT) that underwent an ovariectomy or sham-operation, using in vivo MRI biomarkers. An increase in osmoregulation and energy metabolism biomarkers in the hypothalamus, a decrease in white matter integrity, and a decrease in the resting-state functional connectivity was observed in ovariectomized TG mice compared to sham-operated TG mice. In addition, we observed an increase in functional connectivity in ovariectomized WT mice compared to sham-operated WT mice. Furthermore, genotype (TG vs. WT) effects on imaging markers and GFAP immunoreactivity levels were observed, but there was no effect of interaction (Genotype xSurgery) on amyloid-beta-and GFAP immunoreactivity levels. Taken together, our results indicated that both genotype and ovariectomy alters imaging biomarkers associated with AD. (C) 2021 Elsevier Inc. All rights reserved.

Purpose Echo planar imaging (EPI) is commonly used to acquire the many volumes needed for high angular resolution diffusion Imaging (HARDI), posing a higher risk for artifacts, such as distortion and deformation. An alternative to EPI is fast spin echo (FSE) imaging, which has fewer artifacts but is inherently slower. The aim is to accelerate FSE such that a HARDI data set can be acquired in a time comparable to EPI using compressed sensing. Methods Compressed sensing was applied in either q-space or simultaneously in k-space and q-space, by undersampling the k-space in the phase-encoding direction or retrospectively eliminating diffusion directions for different degrees of undersampling. To test the replicability of the acquisition and reconstruction, brain data were acquired from six mice, and a numerical phantom experiment was performed. All HARDI data were analyzed individually using constrained spherical deconvolution, and the apparent fiber density and complexity metric were evaluated, together with whole-brain tractography. Results The apparent fiber density and complexity metric showed relatively minor differences when only q-space undersampling was used, but deteriorate when k-space undersampling was applied. Likewise, the tract density weighted image showed good results when only q-space undersampling was applied using 15 directions or more, but information was lost when fewer volumes or k-space undersampling were used. Conclusion It was found that acquiring 15 to 20 diffusion directions with a full k-space and reconstructed using compressed sensing could suffice for a replicable measurement of quantitative measures in mice, where areas near the sinuses and ear cavities are untainted by signal loss.

Background: Although effective in reducing relapse rate and delaying progression, current therapies for multiple sclerosis (MS) do not completely halt disease progression. T cell autoimmunity to myelin antigens is considered one of the main mechanisms driving MS. It is characterized by autoreactivity to disease-initiating myelin antigen epitope(s), followed by a cascade of epitope spreading, which are both strongly patient-dependent. Targeting a variety of MSassociated antigens by myelin antigen-presenting tolerogenic dendritic cells (tolDC) is a promising treatment strategy to re-establish tolerance in MS. Electroporation with mRNA encoding myelin proteins is an innovative technique to load tolDC with the full spectrum of naturally processed myelin-derived epitopes. Methods: In this study, we generated murine tolDC presenting myelin oligodendrocyte glycoprotein (MOG) using mRNA electroporation and we assessed the efficacy of MOG mRNA-electroporated tolDC to dampen pathogenic T cell responses in experimental autoimmune encephalomyelitis (EAE). For this, MOG35–55- immunized C57BL/6 mice were injected intravenously at days 13, 17, and 21 post-disease induction with 1α, 25-dihydroxyvitamin D3-treated tolDC electroporated with MOG-encoding mRNA. Mice were scored daily for signs of paralysis. At day 25, myelin reactivity was evaluated following restimulation of splenocytes with myelin-derived epitopes. Ex vivo magnetic resonance imaging (MRI) was performed to assess spinal cord inflammatory lesion load.Results: Treatment of MOG35–55-immunized C57BL/6 mice with MOG mRNA-electroporated or MOG35–55- pulsed tolDC led to a stabilization of the EAE clinical score from the first administration onwards, whereas it worsened in mice treated with non-antigen-loaded tolDC or with vehicle only. In addition, MOG35–55-specific pro-inflammatory pathogenic T cell responses and myelin antigen epitope spreading were inhibited in the peripheral immune system of tolDC-treated mice. Finally, magnetic resonance imaging analysis of hyperintense spots along the spinal cord was in line with the clinical score. Conclusions: Electroporation with mRNA is an efficient and versatile tool to generate myelin-presenting tolDC that are capable to stabilize the clinical score in EAE. These results pave the way for further research into mRNA-electroporated tolDC treatment as a patient-tailored therapy for MS. This work was supported by the Methusalem Funding Program from the University of Antwerp, by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWTTBM 140191), and by the Belgian Charcot Foundation. Furthermore, the authors received research funding from Roche Belgium. Judith Derdelinckx holds a PhD fellowship from the Research Foundation Flanders (FWO)

How do intrinsic brain dynamics interact with processing of external sensory stimuli? We sought new insights using functional magnetic resonance imaging to track spatiotemporal activity patterns at the whole brain level in lightly anesthetized mice, during both resting conditions and visual stimulation trials. Our results provide evidence that quasiperiodic patterns (QPPs) are the most prominent component of mouse resting brain dynamics. These QPPs captured the temporal alignment of anticorrelation between the default mode (DMN)- and task-positive (TPN)-like networks, with global brain fluctuations, and activity in neuromodulatory nuclei of the reticular formation. Specifically, the phase of QPPs prior to stimulation could significantly stratify subsequent visual response magnitude, suggesting QPPs relate to brain state fluctuations. This is the first observation in mice that dynamics of the DMN- and TPN-like networks, and particularly their anticorrelation, capture a brain state dynamic that affects sensory processing. Interestingly, QPPs also displayed transient onset response properties during visual stimulation, which covaried with deactivations in the reticular formation. We conclude that QPPs appear to capture a brain state fluctuation that may be orchestrated through neuromodulation. Our findings provide new frontiers to understand the neural processes that shape functional brain states and modulate sensory input processing.

The first months of life are characterized by massive neuroplastic processes that parallel the acquisition of skills and abilities vital for proper functioning in later life. Likewise, juvenile songbirds learn the song sung by their tutor during the first months after hatching. To date, most studies targeting brain development in songbirds exclusively focus on the song control and auditory pathways. To gain a comprehensive insight into structural developmental plasticity of the entire zebra finch brain throughout the different subphases of song learning, we designed a longitudinal study in a group of male (16) and female (19) zebra finches. We collected T2-weighted 3-dimensional anatomical scans at six developmental milestones throughout the process of song learning, i.e. 20, 30, 40, 65, 90 and 120 days post hatching (dph), and one additional time point well after song crystallization, i.e. 200 dph. We observed that the total brain volume initially increases, peaks around 3040 dph and decreases towards the end of the study. Further, we performed brain-wide voxel-based volumetric analyses to create spatio-temporal maps indicating when specific brain areas increase or decrease in volume, relative to the subphases of song learning. These maps informed (1) that most areas implicated in song control change early, i.e. between 20 and 65 dph, and are embedded in large clusters that cover major subdivisions of the zebra finch brain, (2) that volume changes between consecutive subphases of vocal learning appear highly similar in males and females, and (3) that only more rostrally situated brain regions change in volume towards later ages. Lastly, besides detecting sex differences in local tissue volume that align with previous studies, we uncovered two additional brain loci that are larger in male compared to female zebra finches. These volume differences co-localize with areas related to the song control and auditory pathways and can therefore be associated to the behavioral difference as only male zebra finches sing. In sum, our data point to clear heterochronous patterns of brain development similar to brain development in mammalian species and this work can serve as a reference for future neurodevelopmental imaging studies in zebra finches.

Substantial knowledge of auditory processing within mammalian nervous systems emerged from neurophysiological studies of the mustached bat (Pteronotus parnellii). This highly social and vocal species retrieves precise information about the velocity and range of its targets through echolocation. Such high acoustic processing demands were likely the evolutionary pressures driving the over-development at peripheral (cochlea), metencephalic (cochlear nucleus), mesencephalic (inferior colliculus), diencephalic (medial geniculate body of the thalamus), and telencephalic (auditory cortex) auditory processing levels in this species. Auditory researchers stand to benefit from a three dimensional brain atlas of this species, due to its considerable contribution to auditory neuroscience. Our MRI-based atlas was generated from 2 sets of image data of an ex-vivo male mustached bat's brain: a detailed 3D-T2-weighted-RARE scan [(59 ׫202F»63 x 85) μm3] and track density images based on super resolution diffusion tensor images [(78) μm3] reconstructed from a set of low resolution diffusion weighted images using Super-Resolution-Reconstruction (SRR). By surface-rendering these delineations and extrapolating from cortical landmarks and data from previous studies, we generated overlays that estimate the locations of classic functional subregions within mustached bat auditory cortex. This atlas is freely available from our website and can simplify future electrophysiological, microinjection, and neuroimaging studies in this and related species.

Time-resolved 'dynamic' over whole-period 'static' analysis of low frequency (LF) blood-oxygen level dependent (BOLD) fluctuations provides many additional insights into the macroscale organization and dynamics of neural activity. Although there has been considerable advancement in the development of mouse resting state fMRI (rsfMRI), very little remains known about its dynamic repertoire. Here, we report for the first time the detection of a set of recurring spatiotemporal Quasi-Periodic Patterns (QPPs) in mice, which show spatial similarity with known resting state networks. Furthermore, we establish a close relationship between several of these patterns and the global signal. We acquired high temporal rsfMRI scans under conditions of low (LA) and high (HA) medetomidine-isoflurane anesthesia. We then employed the algorithm developed by Majeed etal. (2011), previously applied in rats and humans, which detects and averages recurring spatiotemporal patterns in the LF BOLD signal. One type of observed patterns in mice was highly similar to those originally observed in rats, displaying propagation from lateral to medial cortical regions, which suggestively pertain to a mouse Task-Positive like network (TPN) and Default Mode like network (DMN). Other QPPs showed more widespread or striatal involvement and were no longer detected after global signal regression (GSR). This was further supported by diminished detection of subcortical dynamics after GSR, with cortical dynamics predominating. Observed QPPs were both qualitatively and quantitatively determined to be consistent across both anesthesia conditions, with GSR producing the same outcome. Under LA, QPPs were consistently detected at both group and single subject level. Under HA, consistency and pattern occurrence rate decreased, whilst cortical contribution to the patterns diminished. These findings confirm the robustness of QPPs across species and demonstrate a new approach to study mouse LF BOLD spatiotemporal dynamics and mechanisms underlying functional connectivity. The observed impact of GSR on QPPs might help better comprehend its controversial role in conventional resting state studies. Finally, consistent detection of QPPs at single subject level under LA promises a step forward towards more reliable mouse rsfMRI and further confirms the importance of selecting an optimal anesthesia regime.

Similar to human speech, bird song is controlled by several pathways including a cortico-basal ganglia-thalamo-cortical (C-BG-T-C) loop. Neurotoxic disengagement of the basal ganglia component, i.e. Area X, induces long-term changes in song performance, while most of the lesioned area regenerates within the first months. Importantly however, the timing and spatial extent of structural neuroplastic events potentially affecting other constituents of the C-BG-T-C loop is not clear. We designed a longitudinal MRI study where changes in brain structure were evaluated relative to the time after neurotoxic lesioning or to vocal performance. By acquiring both Diffusion Tensor Imaging and 3-dimensional anatomical scans, we were able to track alterations in respectively intrinsic tissue properties and local volume. Voxel-based statistical analyses revealed structural remodeling remote to the lesion, i.e. in the thalamus and, surprisingly, the cerebellum, both peaking within the first two months after lesioning Area X. Voxel-wise correlations between song performance and MRI parameters uncovered intriguing brain-behavior relationships in several brain areas pertaining to the C-BG-T-C loop supervising vocal motor control. Our results clearly point to structural neuroplasticity in the cerebellum induced by basal ganglia (striatal) damage and might point to the existence of a human-like cerebello-thalamic-basal ganglia pathway capable of modifying vocal motor output.

BACKGROUND: Amyloid-related imaging abnormalities (ARIA) have been reported with some anti-amyloid-β (Aβ) immunotherapy trials. They are detected with magnetic resonance imaging (MRI) and thought to represent transient accumulation of fluid/edema (ARIA-E) or microhemorrhages (ARIA-H). Although the clinical significance and pathophysiology are unknown, it has been proposed that anti-Aβimmunotherapy may affect blood-brain barrier (BBB) integrity. OBJECTIVE: To examine vascular integrity in aged (12-16 months) PDAPP and wild type mice (WT), we performed a series of longitudinal in vivo MRI studies. METHODS: Mice were treated on a weekly basis using anti-Aβimmunotherapy (3D6) and follow up was done longitudinally from 1-12 weeks after treatment. BBB-integrity was assessed using both visual assessment of T1-weighted scans and repeated T1 mapping in combination with gadolinium (Gd-DOTA). RESULTS: A subset of 3D6 treated PDAPP mice displayed numerous BBB disruptions, whereas WT and saline-treated PDAPP mice showed intact BBB integrity under the conditions tested. In addition, the contrast induced decrease in T1 value was observed in the meningeal and midline area. BBB disruption events occurred early during treatment (between 1 and 5 weeks), were transient, and resolved quickly. Finally, BBB-leakages associated with microhemorrhages were confirmed by Perls'Prussian blue histopathological analysis. CONCLUSION: Our preclinical findings support the hypothesis that 3D6 leads to transient leakage from amyloid-positive vessels. The current study has provided valuable insights on the time course of vascular alterations during immunization treatment and supports further research in relation to the nature of ARIA and the utility of in vivo repeated T1 MRI as a translational tool.

Zebra finches are an excellent model to study the process of vocal learning, a complex socially-learned tool of communication that forms the basis of spoken human language. So far, structural investigation of the zebra finch brain has been performed ex vivo using invasive methods such as histology. These methods are highly specific, however, they strongly interfere with performing whole-brain analyses and exclude longitudinal studies aimed at establishing causal correlations between neuroplastic events and specific behavioral performances. Therefore, the aim of the current study was to implement an in vivo Diffusion Tensor Imaging (DTI) protocol sensitive enough to detect structural sex differences in the adult zebra finch brain. Voxel-wise comparison of male and female DTI parameter maps shows clear differences in several components of the song control system (i.e. Area X surroundings, the high vocal center (HVC) and the lateral magnocellular nucleus of the anterior nidopallium (LMAN)), which corroborate previous findings and are in line with the clear behavioral difference as only males sing. Furthermore, to obtain additional insights into the 3-dimensional organization of the zebra finch brain and clarify findings obtained by the in vivo study, ex vivo DTI data of the male and female brain were acquired as well, using a recently established super-resolution reconstruction (SRR) imaging strategy. Interestingly, the SRR-DTI approach led to a marked reduction in acquisition time without interfering with the (spatial and angular) resolution and SNR which enabled to acquire a data set characterized by a 78 μm isotropic resolution including 90 diffusion gradient directions within 44 h of scanning time. Based on the reconstructed SRR-DTI maps, whole brain probabilistic Track Density Imaging (TDI) was performed for the purpose of super resolved track density imaging, further pushing the resolution up to 40 μm isotropic. The DTI and TDI maps realized atlas-quality anatomical maps that enable a clear delineation of most components of the song control and auditory systems. In conclusion, this study paves the way for longitudinal in vivo and high-resolution ex vivo experiments aimed at disentangling neuroplastic events that characterize the critical period for vocal learning in zebra finch ontogeny.

In this paper, we propose a method to denoise magnitude magnetic resonance (MR) images, which are Rician distributed. Conventionally, maximum likelihood methods incorporate the Rice distribution to estimate the true, underlying signal from a local neighborhood within which the signal is assumed to be constant. However, if this assumption is not met, such filtering will lead to blurred edges and loss of fine structures. As a solution to this problem, we put forward the concept of restricted local neighborhoods where the true intensity for each noisy pixel is estimated from a set of preselected neighboring pixels. To this end, a reference image is created from the noisy image using a recently proposed nonlocal means algorithm. This reference image is used as a prior for further noise reduction. A scheme is developed to locally select an appropriate subset of pixels from which the underlying signal is estimated. Experimental results based on the peak signal to noise ratio, structural similarity index matrix, Bhattacharyya coefficient and mean absolute difference from synthetic and real MR images demonstrate the superior performance of the proposed method over other state-of-the-art methods.

In magnetic resonance imaging the spin-lattice relaxation time (T 1 ) of tissues is estimated from a set of T 1 -weighted images. As the T 1 estimation is a voxel-wise estimation, correct alignment of the T 1 -weighted images is crucial for T 1 mapping. Therefore, to correct for motion, the T 1 -weighted images are often registered prior to the T 1 estimation. This two-step approach, however, does not provide an accurate motion detection due to the high dynamic contrast changes in the series of images. Moreover, interpolation effects during registration, propagate to the T 1 estimation. In this work, we propose a unified approach, where the motion estimation is integrated into the T 1 estimation procedure. The motion model parameters and T 1 parameters are jointly estimated using a Maximum Likelihood (ML) approach. Results on simulation and real data experiments show a substantial improvement in the precision and accuracy of the estimated T 1 map compared to the conventional two-step approach.

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.

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.

Review of the literature reveals that the relationship between the extensor digitorum muscle tendon to the proximal phalanx and the metacarpophalangeal joint capsule remains unclear. The present study presents data about these relationships and consists of three parts: dissection of the region, high-gradient magnetic resonance imaging, and functional study. A total of 50 hands were used. Dissection was performed on 30, magnetic resonance studies were performed on 10, and the remaining 10 hands were used for the functional analysis. Dissection did not reveal an insertion of the extensor digitorum tendon on the base of the proximal phalanx. An extension of the dorsal part of the metacarpophalangeal joint capsule running proximally toward the palmar side of the extensor tendon was observed in eight hands. In the remaining 22 hands, only loose connective tissue was found between the articular capsule and the tendon. The development of this tissue was variable. These observations were correlated using a 7T magnetic resonance installation. The results of the functional study showed that hyperextension of the proximal phalanx increased after resection of the metacarpophalangeal structures lying under the extensor tendon. In conclusion, no real tendinous insertion of the extensor digitorum tendon on the base of the proximal phalanx could be found. Loose connective tissue was observed between the metacarpophalangeal joint capsule and the palmar aspect of the tendon, which seemed to play a secondary role in the extension of the proximal phalanx.

Effective denoising is vital for proper analysis and accurate quantitative measurements from Magnetic Resonance (MR) images. Apart from following the general criteria for denoising, the algorithms that deal with MR images should also take into account the bias generated due to the Rician nature of the noise in the magnitude MR images. Maximum Likelihood (ML) estimation methods were proved to be very effective in denoising MR images. However, one drawback of the existing non local ML estimation method is the usage of a fixed sample size for ML estimation. As a result, optimal results cannot be achieved because of over or under smoothing. In this work, we propose an adaptive non local ML estimation method for denoising MR images in which the samples are selected in an adaptive way for the ML estimation of the true underlying signal. The method has been tested both on simulated and real data, showing its effectiveness.

Effective denoising is vital for proper analysis and accurate quantitative measurements from magnetic resonance (MR) images. Even though many methods were proposed to denoise MR images, only few deal with the estimation of true signal from MR images acquired with phased-array coils. If the magnitude data from phased array coils are reconstructed as the root sum of squares, in the absence of noise correlations and subsampling, the data is assumed to follow a non central-χ distribution. However, when the k-space is subsampled to increase the acquisition speed (as in GRAPPA like methods), noise becomes spatially varying. In this note, we propose a method to denoise multiple-coil acquired MR images. Both the non central-χ distribution and the spatially varying nature of the noise is taken into account in the proposed method. Experiments were conducted on both simulated and real data sets to validate and to demonstrate the effectiveness of the proposed method.

An important focus of Huntington Disease (HD) research is the identification of symptom-independent biomarkers of HD neuropathology. There is an urgent need for reproducible, sensitive and specific outcome measures, which can be used to track disease onset as well as progression. Neuroimaging studies, in particular diffusion-based MRI methods, are powerful probes for characterizing the effects of disease and aging on tissue microstructure. We report novel diffusional kurtosis imaging (DKI) findings in aged transgenic HD rats. We demonstrate altered diffusion metrics in the (pre)frontal cerebral cortex, external capsule and striatum. Presence of increased diffusion complexity and restriction in the striatum is confirmed by an increased fiber dispersion in this region. Immunostaining of the same specimens reveals decreased number of microglia in the (pre)frontal cortex, and increased numbers of oligodendrocytes in the striatum. We conclude that DKI allows sensitive and specific characterization of altered tissue integrity in this HD rat model, indicating a promising potential for diagnostic imaging of gray and white matter pathology.

Huntington Disease (HD) is a fatal neurodegenerative disorder, caused by a mutation in the Huntington gene. Although HD is most often diagnosed in mid-life, the key to its clinical expression may be found during brain maturation. In the present work, we performed in vivo diffusion kurtosis imaging (DKI) in order to study brain microstructure alterations in developing transgenic HD rat pups. Several developing brain regions, relevant for HD pathology (caudate putamen, cortex, corpus callosum, external capsule and anterior commissure anterior), were examined at postnatal days 15 (P15) and 30 (P30), and DKI results were validated with histology. At P15, we observed higher mean (MD) and radial (RD) diffusivity values in the cortex of transgenic HD rat pups. In addition, at the age of P30, lower axial kurtosis (AK) values in the caudate putamen of transgenic HD pups were found. At the level of the external capsule, higher MD values at P15 but lower MD and AD values at P30 were detected. The observed DKI results have been confirmed by myelin basic protein immunohistochemistry, which revealed a reduced fiber staining as well as less ordered fibers in transgenic HD rat pups. These results indicate that neuronal development in young transgenic HD rat pups occurs differently compared to controls and that the presence of mutant huntingtin has an influence on postnatal brain development. In this context, various diffusivity parameters estimated by the DKI model are a powerful tool to assess changes in tissue microstructure and detect developmental changes in young transgenic HD rat pups.

Background Repeated exposure to mild stressors induces anhedonia—a core symptom of major depressive disorder—in up to 70% of the stress-exposed rats, whereas the remaining show resilience to stress. This chronic mild stress (CMS) model is well documented as an animal model of major depressive disorder. We examined the morphological, microstructural, and metabolic characteristics of the hippocampus in anhedonic and stress resilient rats that may mark the differential behavioral outcome. Methods Anhedonic ( n = 8), resilient ( n = 8), and control ( n = 8) rats were subjected to in vivo diffusion kurtosis imaging, high-resolution three-dimensional magnetic resonance imaging and proton magnetic resonance spectroscopy. Results Diffusion kurtosis parameters were decreased in both CMS-exposed groups. A significant inward displacement in the ventral part of the right hippocampus was apparent in the resilient subjects and an increase of the glutamate:total creatine ratio and N-acetylaspartylglutamate:total creatine was observed in the anhedonic subjects. Conclusions Diffusion kurtosis imaging discloses subtle substructural changes in the hippocampus of CMS-exposed animals irrespective of their anhedonic or resilient nature. In contrast, proton magnetic resonance spectroscopy and magnetic resonance imaging-based shape change analysis of the hippocampus allowed discrimination of these two subtypes of stress sensitivity. Although the precise mechanism discriminating their behavior is yet to be elucidated, the present study underlines the role of the hippocampus in the etiology of depression and the induction of anhedonia. Our results reflect the potency of noninvasive magnetic resonance methods in preclinical settings with key translational benefit to and from the clinic.

At present, resting state functional MRI (rsfMRI) is increasingly used in human neuropathological research. The present study aims at implementing rsfMRI in mice, a species that holds the widest variety of neurological disease models. Moreover, by acquiring rsfMRI data with a comparable protocol for anesthesia, scanning and analysis, in both rats and mice we were able to compare findings obtained in both species. The outcome of rsfMRI is different for rats and mice and depends strongly on the applied number of components in the Independent Component Analysis (ICA). The most important difference was the appearance of unilateral cortical components for the mouse resting state data compared to bilateral rat cortical networks. Furthermore, a higher number of components was needed for the ICA analysis to separate different cortical regions in mice as compared to rats.

International audience; 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.

Songbirds' vocal communication behaviour has been a favourite research domain for years. In order to study brain activation in response to acoustic stimuli, two different in-vivo methods that are able to assess neuronal activity based on detection of haemodynamic changes were compared within identical experimental settings. Optical imaging (non-invasive in-vivo broadband time-resolved spectroscopy) and functional magnetic resonance imaging (Blood Oxygenation Level Dependent MRI) were both performed in zebra finch brain upon a hypercapnic challenge known to induce a standard haemodynamic response. The use of these two methods offers the opportunity to compare their sensitivity and to correlate local variations in CBV and haemoglobin saturation level (obtained from optical data) with local BOLD signal variations (providing overall information on CBF, CBV and haemoglobin oxygenation). Both for optical imaging and fMRI, four adult female zebra finches (Taeniopygia guttata) were anaesthetized with 2% isoflurane while spontaneously breathing, and immobilized in a stereotactical device equipped with essential monitoring devices. Each bird underwent three runs of 5 minute hypercapnia (600 ml/min 7% CO2, 21% O2, 72% N2), interleaved by 20 minutes normocapnia (600 ml/min 21% O2, 79% N2). Optical imaging was performed with an ultrafast white laser and time-resolved spectrometer. With the 95% PL (i.e. mean path length of the light detected by the camera at 95% of the measured temporal profile) at 2 spectral windows centered at 748 nm and 793 nm, we quantify respectively the haemoglobin saturation level and CBV. MR imaging was performed at 300 MHz on a 7 Tesla in-vivo NMR microscope with horizontal bore and actively shielded gradient-insert (210 mT/m). The optical imaging data demonstrated that hypercapnia induced a significant increase of the hemoglobin saturation level in run1 (p=.01) and run2 (p=.01). No significant CBV changes were observed during run1 (p=.1), run2 (p=.75) and run3 (p=.5). The fMRI data demonstrated the existence of significant BOLD signal changes for run1 (p

Simultaneously acquired EEG and BOLD (Blood Oxygenation level dependent contrast) MRI allowed to study on line the neurophysiological changes in rat brain during epileptic seizures. MRI and EEG data were acquired with a specially designed high quality MR RF-antenna with incorporated non- invasive carbon EEG electrodes. The problem of severe pollution of the EEG data due to MR gradient switching during simultaneous EEG/MRI acquisitions was solved by a specially designed automated effective filtering algorithm. We measured continuously EEG data, and T2*-weighted coronal MRI sections of rat brain before and after the injection of pentetrazol (43 mg/(kg body weight) PTZ; convulsive dose 97%), an epilepsy inductor. In this way, we could correlate the abnormalities in the EEG traces, with changes in the MRI BOLD signal intensities. Immediately after PTZ induction and before epileptic discharges were observed on the EEG traces, the cortex displayed an increase in BOLD signal intensity (increase in blood flow). Much later and correlated with epileptic discharges on the EEG traces, the ventromedial hypothalamic nuclei showed an increased BOLD signal while the BOLD signal intensity dropped in the entire brain, except for the hypothalamus. The decreased BOLD signal reflected general hypoxia and subsequent ischemia as a consequence of the sustained depolarization of neurons during the seizure.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We determined the effects of a mild hypoxic challenge on the energy metabolism of the common carp, Cyprinus carpio, under different temperature conditions, by P-31-nuclear magnetic resonance spectroscopy (P-31-NMR). Fish were acclimated to the optimal temperature of 25 degrees C or the acute sublethal temperature of 33 degrees C. A group of the 25 degrees C acclimated fish was also exposed to a temperature shock of 33 degrees C. The resting levels of phosphocreatine (PCr) and inorganic phosphate (P-i) were comparable between the three groups. The level of ATP remained unchanged under all experimental conditions. Submission to a short hypoxic challenge resulted in acidosis and a depletion of PCr, while Pi increased. The recovery of the PCr levels after hypoxia was independent of the temperature to which the fish were acclimated, but when submitted to an acute temperature shock, the recovery was much slower. Resting intracellular pH (pH(i)) decreased under increasing temperature and the recovery of pH, was independent of the temperature condition. The extent of acidosis under the hypoxic challenge was more severe in carp exposed to both the acute and the chronic sublethal temperature stress. This study revealed that shortly after exposure to a sublethal acute temperature stress, significant differences in the capacity to recover from an hypoxic challenge had occurred. After a period of 4 weeks exposure to a sustained sublethal high temperature, carp regain the capacity to recover fully from the hypoxia, indicating that acclimation had occurred. (C) 1998 Elsevier Science Inc. All rights reserved.