Johan Van Audekerke

Functional connectivity fMRI of the rodent brain : comparison of functional connectivity networks in rat and mouse

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.

Magnetic Resonance Imaging and Spectroscopy Reveal Differential Hippocampal Changes in Anhedonic and Resilient Subtypes of the Chronic Mild Stress Rat Model

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.

Maximum likelihood estimation-based denoising of magnetic resonance images using restricted local neighborhoods

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.

Microstructural changes observed with DKI in a transgenic Huntington rat model: evidence for abnormal neurodevelopment.

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.

Nonlocal maximum likelihood estimation method for denoising multiple-coil magnetic resonance images.

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.

Identification and characterization of Huntington related pathology: an in vivo DKI imaging study.

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.

An adaptive non local maximum likelihood estimation method for denoising magnetic resonance images

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.

Recovery of the energy metabolism after a hypoxic challenge at different temperature conditions: a 31P-nuclear magnetic resonance spectroscopy study with common carp

Abstract We determined the effects of a mild hypoxic challenge on the energy metabolism of the common carp, Cyprinus carpio , under different temperature conditions, by 31 P-nuclear magnetic resonance spectroscopy ( 31 P-NMR). Fish were acclimated to the optimal temperature of 25°C or the acute sublethal temperature of 33°C. A group of the 25°C acclimated fish was also exposed to a temperature shock of 33°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 P i 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 i 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.

The insertion of the extensor digitorum tendon on the proximal phalanx

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.

Functional Magnetic Resonance Imaging (fMRI) with Auditory Stimulation in Songbirds

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and molecular approaches allow the investigation of either different stimuli on few neurons, or one stimulus in large parts of the brain, blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows combining both advantages, i.e. compare the neural activation induced by different stimuli in the entire brain at once. fMRI in songbirds is challenging because of the small size of their brains and because their bones and especially their skull comprise numerous air cavities, inducing important susceptibility artifacts. Gradient-echo (GE) BOLD fMRI has been successfully applied to songbirds (1-5) (for a review, see (6)). These studies focused on the primary and secondary auditory brain areas, which are regions free of susceptibility artifacts. However, because processes of interest may occur beyond these regions, whole brain BOLD fMRI is required using an MRI sequence less susceptible to these artifacts. This can be achieved by using spin-echo (SE) BOLD fMRI (7,8) . In this article, we describe how to use this technique in zebra finches (Taeniopygia guttata), which are small songbirds with a bodyweight of 15-25 g extensively studied in behavioral neurosciences of birdsong. The main topic of fMRI studies on songbirds is song perception and song learning. The auditory nature of the stimuli combined with the weak BOLD sensitivity of SE (compared to GE) based fMRI sequences makes the implementation of this technique very challenging.