Xavier Helluy

• PhD
• Researcher at Ruhr University Bochum

Quantitative muscle MRI is increasingly important in the non-invasive evaluation of neuromuscular disorders and their progression. Underlying histopathotological alterations, leading to changes in qMRI parameters are incompletely unraveled. Early microstructural differences of unknown origin reflected by Diffusion MRI in non-fat infiltrated muscles...

Functional magnetic resonance imaging (fMRI) in awake small animals such as pigeons or songbirds opens a new window into the neural fundaments of cognitive behavior. However, high-field fMRI in the avian brain is challenging due to strong local magnetic field inhomogeneities caused by air cavities in the skull. A spoiled gradient-echo fMRI sequence...

Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of toxic proteins, which the glymphatic system is thought to clear by flushing cerebral spinal fluid (CSF) through the brain. In mice, this process occurs during non-rapid eye movement...

Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of toxic proteins implicated in Alzheimer’s disease. The glymphatic system is thought to clear these proteins by flushing cerebral spinal fluid (CSF) through the brain. In mice, this pr...

Functional magnetic resonance imaging, as a non-invasive technique, offers unique opportunities to assess brain function and connectivity under a broad range of applications, ranging from passive sensory stimulation to high-level cognitive abilities, in awake animals. This approach is confounded, however, by the fact that physical restraint and lou...

Animal-fMRI is a powerful method to understand neural mechanisms of cognition, but it remains a major challenge to scan actively participating small animals under low-stress conditions. Here, we present an event-related functional MRI platform in awake pigeons using single-shot RARE fMRI to investigate the neural fundaments for visually-guided deci...

The Alzheimer disease‐associated multifunctional low‐density lipoprotein receptor‐related protein‐1 is expressed in the brain. Recent studies uncovered a role of this receptor for the appropriate functioning of neural stem cells, oligodendrocytes, and neurons. The constitutive knock‐out (KO) of the receptor is embryonically lethal. To unravel the r...

The phylogenetic position of crocodilians in relation to birds and mammals makes them an interesting animal model for investigating the evolution of the nervous system in amniote vertebrates. A few neuroanatomical atlases are available for reptiles, but with a growing interest in these animals within the comparative neurosciences, a need for these...

The number of human embryology collections is very limited worldwide. Some of these comprise the Carnegie Collection, Kyoto Collection, and the Blechschmidt Collection. One further embryonic collection is the Hinrichsen Collection of the Ruhr University Bochum, Germany, which also contains very well-preserved embryos/fetuses, along with approximate...

Purpose To investigate the association of inflammation and brain edema in a cerebral malaria (CM) mouse model with a combination of bis-5-hydroxy-tryptamide-diethylenetriaminepentaacetate gadolinium, referred to as MPO-Gd, and cross-linked iron oxide nanoparticle (CLIO-NP) imaging. Materials and Methods Female wild-type (n = 23) and myeloperoxidase...

Background and purpose: Detection and localization of the early phase of blood-brain barrier disruption (BBBD) in vivo during cerebral ischemia/reperfusion injury remain a major challenge but may be a relevant outcome parameter in stroke. Methods: We studied early BBBD in mice after transient middle cerebral artery occlusion by multimodal, high-...

Crocodilians are important for understanding the evolutionary history of amniote neural systems as they are the nearest extant relatives of modern birds and share a stem amniote ancestor with mammals. Although the crocodilian brain has been investigated anatomically, functional studies are rare. Here, we employed functional magnetic resonance imagi...

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of cerebral malaria can be difficult. We present an experimental mouse model of cerebral malaria that shares multiple features of the human disease, including edema and microvascular pathology. Using...

Purpose: Establishment of regional longitudinal (T1 ) and transverse (T2 ) relaxation times in awake pigeons and rats at 7T field strength. Regional differences in relaxation times between species and between two different pigeon breeds (homing pigeons and Figurita pigeons) were investigated. Methods: T1 and T2 relaxation times were determined f...

Non-invasive detection of 2-hydroxyglutarate (2HG) by magnetic resonance spectroscopy is attractive since it is related to tumor metabolism. Here, we compare the detection accuracy of 2HG in a controlled phantom setting via widely used localized spectroscopy sequences quantified by linear combination of metabolite signals vs. a more complex approac...

Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac in...

Ex vivo T2*w 3D animated vizualization of cardiac lesions in a ABY mouse 14 d.p.i. at 17.6T with 20um resolution. (MPG)

Vizualization of cardiac lesions in a short axis Cine movie of an infected ABY mouse at 17.6T. (AVI)

Vizualization of cardiac lesions in a long axis Cine movie of an infected ABY mouse at 17.6T. (AVI)

Ex vivo T2*w 3D animated vizualization of cardiac lesions in a ABY mouse 9 d.p.i. at 17.6T. (MPG)

Vizualization of cardiac lesions in a short axis Cine movie of an infected ABY mouse at 17.6T. Higher spatial resolution. (AVI)

It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation...

Automated and quantitative assessment of neuroblast migration. Representative source images of neuroblast alignment within the olfactory bulb in an uninfected control (first row, left) and an ECM mouse (second row, left) are displayed. To assess linearity and orientation of neuroblasts quantitatively and in an automated fashion binary masks were cr...

Automated and quantitative lacunarity analysis of microglial activation. A, Representative Iba-1 image stacks (1024x1024 pixels in-plane, five 1μm thick images stacked by maximum-intensity-projection) at the level of the brainstem from a control (left), an animal with moderate disease (RMCBS 14, middle) and a severely sick animal (RMCBS 3, right) a...

Histological proof of microhemorrhages. A sagittal 1 μm HE section of one representative ECM mouse is displayed. Squares 1–4 are magnified on the right. Boxes 1 and 2 show microhemorrhages in the olfactory bulb, boxes 3 and 4 in the brain parenchyma in close vicinity to the RMS. Please note the extravasation of erythrocytes into the perivascular sp...

Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% ox...

Representative T2* datasets of one representative mouse 3 days prior to hypoxic exposure, 48h after hypoxia and 24h after reoxygenation are displayed. Note the drastic increase of microhemorrhages 24h after reoxygenation compared to 48h after hypoxia. (MP4)

Purpose: An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs. Methods: A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial pr...

This work presents a spectroscopic method to measure slow flow. Within a single shot the velocity distribution is acquired. This allows distinguishing rapidly between single velocities within the sampled volume with a high sensitivity. The technique is based on signal acquisition in the presence of a periodic gradient and a train of refocussing RF...

A method for the quantification of perfusion in murine myocardium is demonstrated. The method allows for the reconstruction of perfusion maps on arbitrary time points in the heart cycle while addressing problems that arise due to the irregular heart beat of mice. A flow-sensitive alternating inversion recovery arterial spin labeling method using an...

We thank Jansen and van Royen for their interest in our publication.1 They questioned whether the widely used contrast-enhanced MRI method indeed detects microvascular obstruction (MVO), because the incidence of MRI-defined intramyocardial hemorrhage (IMH) without MVO (isolated IMH) in our rat model was higher than those reported in large animals a...

The quantification of myocardial perfusion using a Look-Locker flow-sensitive alternating inversion recovery- arterial spin labeling experiment is considered. Due to the anatomy of the heart, a substantial but unintended partial inversion of the inflowing blood occurs during the slice-selective inversion. Both, the partial inversion as well as the...

The present work introduces an alternative to the conventional [Formula: see text]-gradient spatial phase encoding technique. By applying far off-resonant radiofrequency (RF) pulses, a spatially dependent phase shift is introduced to the on-resonant transverse magnetization. This so-called Bloch-Siegert (BS) phase shift has been recently used for [...

The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the...

Monocytes and macrophages are indispensable in the healing process of myocardial infarction (MI). However, the spatiotemporal distribution of monocyte infiltration and its correlation to prognostic indicators of reperfused MI have not been well described. With combined fluorine-19/proton-MRI ((19)F/(1)H-MRI), we non-invasively visualized the spatio...

Introduction: Using ultra-high-field contrast-enhanced magnetic resonance imaging (MRI), an increase of field strength is associated with a decrease of T 1 relaxivity. Yet, the impact of this effect on signal characteristics and contrast-enhanced pathology remains unclear. Hence, we evaluated the potential of a 17.6-T MRI to assess contrast-enhanc...

Introduction Myocarditis is a challenging disease for diagnosis and treatment. Recently, we have established a non-invasive cellular 19F-MR method to visualize inflammation of myocarditis in mice [1]. In this study, we correlated detection of inflammation by 19F-MR and tissue characterization by 1H-MR in viral myocarditis mouse model. Methods Viral...

104 Background and objective High molecular weight kininogen (HK) is an abundant plasma protein that serves as an important component of the intrinsic pathway of coagulation. Recent studies have suggested an important role for the intrinsic coagulation pathway in pathologic thrombosis. We have previously described the production of kininogen defic...

We have recently identified T cells as important mediators of ischemic brain damage but the contribution of the different T cell subsets is unclear. Forkheadbox P3 (FoxP3)+ regulatory T lymphocytes (Treg) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-m...

Aims: The purpose of this clinical trial was to investigate whether cardiovascular magnetic resonance imaging (CMR) using ferumoxytol (Feraheme™, FH), an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO), allows more detailed characterization of infarct pathology compared with conventional gadolinium-based necrosis/fibrosis imaging in p...

Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High molecular weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng(-/-) mice are protecte...

Yuxiang Ye, 2011 Finalist and Presenting Author

Objectives: Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction. The purpose of this clinical trial was to investigate whether magnetic resonance imaging (MRI) of macrophages using ferucarbotran (Resovist®) allow...

Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb) protects mice from ischemic stroke. To elucidate underlying mechanisms in-vivo, infarct development was followed by ultra-high field MRI at 17.6 Tesla. Cerebral infarction was induced by transient-middle-cerebral-artery-occlusion (tMCAO) for 1 hour in C57/BL6 control mice (...

Introduction: Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction.

A switchable contrast mechanism, flow enhanced off-resonance saturation, is presented. This technique combines the effects of flow and off-resonance saturation for remote detection of iron oxide contrast agents incorporated into a vessel wall. Initial results from phantom experiments are presented and show the feasibility of this method. A specific...

Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle c...

Intrinsic coagulation factor XII deficient (FXII(-/-)) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla. Cerebral ischemia was induced by either transient (60 min) or permanent occlusion of the middle cerebral ar...

As Larmor frequencies for high-resolution NMR spectroscopy and microimaging approach 1 GHz, effects such as dielectric resonance and sample-induced spatial inhomogeneities in the radiofrequency transmission and reception fields become more prominent. These effects have been studied extensively for high field human imaging, but have received less at...

The temperature dependence of the crystal structure of TrMA2HgCl4 (TrMA=trimethylammonium) is studied by single-crystal and powder X-ray diffraction between 161 and 373K. Below room temperature, we did not find significant changes of the crystal structure. The phase transition at 325K is described by a rotation of one of the two independent TrMA+ c...

We consider 29Si and 19F MAS NMR spectra of isolated 29Si(19F)2 and 29Si(19F)3 spin systems in two organosilicon compounds of the type RR'SiF2 and RSiF3(R,R' = organic ligands). Experimental spectra are analysed by means of numerical simulations. It is found that the SiF3 group in RSiF3 is reorienting rapidly around the molecular Si-C bond directio...

13C MAS NMR experiments on solid l-tyrosine-ethylester with 13C in low natural abundance and in fully 13C enriched form are reported. The phenyl rings are found to undergo π flips with a rather low activation energy Ea = 50 ± 12 kJ mol-1. In addition, the ester groups are afflicted by dynamic disorder at all temperatures accessible to MAS NMR exper...

We discuss the dynamic solid-state properties of crystalline phases E(XMe3)4 as seen by solid-state NMR and powder X-ray diffraction. In the first part we will qualitatively describe some of the NMR tools suitable for such investigations. In the second part we will give examples from the group of solid compounds E(XMe3)4 with E = C, Si, Ge and X = ...

Double-quantum filtered MAS NMR spectra of an isolated homonuclear spin-1/2 pair are considered, at and away from rotational resonance conditions. The pulse sequence used is the solid-state NMR equivalent of double-quantum filtered COSY, known from solution-state NMR. The 119Sn spin pair in [(chex3Sn)2S] is characterized by a difference in isotropi...

The compounds tetrakis(trimethylstannyl)germane, Ge(SnMe3)4 (1), and tetrakis(trimethylstannyl)silane, Si(SnMe3)4 (2), have crystal structures with the quasispherical molecules in a closed-packed stacking. At room temperature both structures have the space group P (Z = 2) with a = 9.94457 (5), b = 14.52927 (8), c = 9.16021 (5) Å, α = 90.53390 (30),...

Double-quantum filtration under rotational resonance MAS NMR conditions where the chemical shielding anisotropies involved exceed the differences in isotropic chemical shielding is considered by means of numerical simulations and (13)C MAS NMR experiments. The responses of two different pulse sequences, suitable for double-quantum filtration specif...

Characterizing the orientation and molecular conformation of small organic molecules bound to the inner or outer surfaces of proteins represents an important step in drug design and in understanding the mechanisms of biochemical reactions, and similarly, of non-biological catalytic reactions. In a biochemical context, such molecular units or subuni...

A 31P solid-state NMR study of TiP2O7 is reported. The combined constraints from one-dimensional 31P MAS NMR experiments and from 31P 2D MAS NMR experiments probing through-bond P−O−P connectivities via homonuclear J coupling interactions (TOBSY experiments), positively identify the cubic space group Pa3̄ with a 3 × 3 × 3 superstructure. Additional...

The compounds tetrakis(trimethylsilyl)methane C[Si(CH(3))(3)](4) (TC) and tetrakis(trimethylsilyl)silane Si[Si(CH(3))(3)](4) (TSi) have crystal structures with the molecules in a cubic closed-packed (c.c.p.) stacking. At room temperature both structures have space group Fm{\bar 3}m (Z = 4) with a = 13.5218 (1) Å, V = 2472.3 (1) Å(3) for TSi, and a...

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...

The compounds tetrakis(trimethylsilyl)methane C[Si(CH3)3]4 (TC) and tetrakis(trimethylsilyl)silane Si[Si(CH3)3]4 (TSi) have crystal structures with the molecules in a cubic closed-packed (c.c.p.) stacking. At room temperature both structures have space group (Z = 4) with a = 13.5218 (1) Å, V = 2472.3 (1) Å3 for TSi, and a = 12.8902 (2) Å, V = 2141....

The dynamic hydrogen disorder in yttrium-dihydride phases as observed by variable-temperature yttrium cross polarization magic angle spinning nuclear magnetic resonance (Y CP MAS NMR) was discussed. Y CP MAS NMR techniques were used to investigate order-disorder phenomena in yttrium metal hydrides. The dihydride phases display electric conductivity...

Modes of molecular reorientation in solid tetrakis(trimethylstannyl)methane, C(SnMe3)4, have been investigated by one- and two-dimensional13C and119Sn static and magic-angle spinning nuclear magnetic resonance spectroscopy (NMR) in the temperature range from 150 to 290 K. Spectral lineshape fitting of one- and two-dimensional119Sn NMR experiments s...

One- and two-dimensional C-13 and Si-29 solid-state NMR experiments at variable temperature demonstrate that crystalline (Ph3Si)Si(SiMe3)(3) lacks all molecular symmetry and that internal 2 pi/3 reorientation of all three crystallographically inequivalent SiMe3 groups in the molecule occurs. Quantitative analysis of one-dimensional MAS NMR spectra...

One- and two-dimensional 13C and 29Si solid-state NMR experiments at variable temperature demonstrate that crystalline (Ph3Si)Si(SiMe3)3 lacks all molecular symmetry and that internal 2π/3 reorientation of all three crystallographically inequivalent SiMe3 groups in the molecule occurs. Quantitative analysis of one-dimensional MAS NMR spectra and of...

Variable-temperature 13C and 29Si one- and two-dimensional MAS NMR experiments are reported for the low-temperature phases of Si(SiMe3)4 (1) and C(SiMe3)4 (2). Quantitative determination of exchange rate constants from 13C and 29Si NMR spectra of 1 and 2 proves considerable dissimilarities of the molecular solid-state dynamic properties of 1 and 2,...

Variable-temperature solid-state NMR studies (13C, 29Si) of polycrystalline (Me3Si)3C−CC−C(SiMe3)3 (1) are reported. These studies prove the simultaneous occurrence of two different reorientational modes in solid 1 in the temperature range T ≈ 150−240 K: reorientation around the molecular C−CC−C axis and internal reorientation of the Me3Si groups....