Marzena Arridge - Academia.edu (original) (raw)

Papers by Marzena Arridge

Brain Communications

Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism.... more Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism. In Huntington’s disease, altered proton magnetic resonance spectroscopy-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. Proton magnetic resonance spectroscopy metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardized collection of CSF, blood, phenotypic and volumetric imaging data, we used 3 T proton magnetic resonance spectroscopy in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of...

2696. Molecular NMR and EPR in Vivo Detection of Cell Death Using Specific Phosphatidylserine-Tar... more 2696. Molecular NMR and EPR in Vivo Detection of Cell Death Using Specific Phosphatidylserine-Targeted Iron Oxide Particles. Kim Anne Radermacher, Sébastien Boutry, Isabelle Mahieu, Sophie Laurent, Luce Vander Elst, Caroline Bouzin, Julie Magat, Vincent Grégoire, Olivier Feron, Robert N. Muller, Bénédicte F. Jordan, Bernard Gallez Biomedical Magnetic Resonance Unit, Catholic University of Louvain, Bruxelles, Belgium; NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium; Unit of Pharmacology and Therapeutics, Catholic University of Louvain, Bruxelles, Belgium; Center for Molecular Imaging and Experimental Radiotherapy, Catholic University of Louvain, Bruxelles, Belgium

Magnetic resonance spectroscopy (MRS) is a non-invasive method of exploring cerebral metabolism. ... more Magnetic resonance spectroscopy (MRS) is a non-invasive method of exploring cerebral metabolism. In Huntington’s disease, altered MRS-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies of metabolite trajectory are lacking. MRS metabolites may represent a valuable source of biomarkers, thus their relationship with established biofluid and structural imaging markers of disease progression require further exploration to assess prognostic value and elucidate biochemical pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardised collection of CSF, blood, phenotypic and imaging data, we used MRS to evaluate metabolic profiles in the putamen of 56 participants at baseline (15 healthy controls, 15 premanifest and 26 manifest gene expansion carriers) and at 2-year follow-up. Intergroup differences and associations with established measures were assessed c...

Science Translational Medicine, 2020

Longitudinal analysis in 80 patients shows that mutant huntingtin and neurofilament light could p... more Longitudinal analysis in 80 patients shows that mutant huntingtin and neurofilament light could predict Huntington’s disease progression.

The longitudinal dynamics of the most promising biofluid biomarker candidates for Huntington’s di... more The longitudinal dynamics of the most promising biofluid biomarker candidates for Huntington’s disease (HD) – mutant huntingtin (mHTT) and neurofilament light (NfL) – are incompletely defined, but could help understand the natural history of the disease and how these biomarkers might help in therapeutic development and the clinic. In an 80-participant cohort over 24 months, mHTT in cerebrospinal fluid (CSF), and NfL in CSF and blood, had distinct longitudinal trajectories in HD mutation carriers compared with controls. Baseline analyte values predicted clinical disease status and subsequent clinical progression and brain atrophy, better than did the rate of change in analytes. Overall NfL was a stronger monitoring and prognostic biomarker for HD than mHTT. Nonetheless, mHTT possesses prognostic value and is a valuable pharmacodynamic marker for huntingtin-lowering trials.

Journal of vascular surgery, May 22, 2017

Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but ess... more Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and a prelude to clinical sequelae. There are currently no clinical imaging tools to assess the inflammatory activity within plaques. This study characterized inflammation in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) as a magnetic resonance imaging (MRI) probe. DT-MPIO were used to detect and characterize inflammatory markers, vascular cell adhesion molecule 1 (VCAM-1). and P-selectin on (1) tumor necrosis factor-α-treated cells by immunocytochemistry and (2) aortic root plaques of apolipoprotein-E deficient mice by in vivo MRI. Furthermore, apolipoprotein E-deficient mice with focal carotid plaques of different phenotypes were developed by means of periarterial cuff placement to allow in vivo molecular MRI using these probes. The association between biomarkers and t...

PloS one, 2017

Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medicatio... more Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC) and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies s...

Alimentary pharmacology & therapeutics, Jan 8, 2016

Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestat... more Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and (1) H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No (1) H magnetic resonance spectroscopy abnormalities were seen. Serum manganese le...

Metabolic brain disease, Feb 3, 2016

The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and fu... more The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was sign...

Thrombosis and Haemostasis, 2016

SummaryBlood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. ... more SummaryBlood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated car...

Thesis (Ph. D.)--University of London, 1997.

Biomedical optics express, 2011

Förster resonance energy transfer (FRET) is a powerful biological tool for reading out cell signa... more Förster resonance energy transfer (FRET) is a powerful biological tool for reading out cell signaling processes. In vivo use of FRET is challenging because of the scattering properties of bulk tissue. By combining diffuse fluorescence tomography with fluorescence lifetime imaging (FLIM), implemented using wide-field time-gated detection of fluorescence excited by ultrashort laser pulses in a tomographic imaging system and applying inverse scattering algorithms, we can reconstruct the three dimensional spatial localization of fluorescence quantum efficiency and lifetime. We demonstrate in vivo spatial mapping of FRET between genetically expressed fluorescent proteins in live mice read out using FLIM. Following transfection by electroporation, mouse hind leg muscles were imaged in vivo and the emission of free donor (eGFP) in the presence of free acceptor (mCherry) could be clearly distinguished from the fluorescence of the donor when directly linked to the acceptor in a tandem (eGFP-...

EJNMMI Research, 2011

Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis ... more Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy.

Angewandte Chemie (International ed. in English), 2014

MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivi... more MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these 'smart' self-assembli...

Radiology, 2008

Research ethics committee approval was obtained for this study, and written informed consent was ... more Research ethics committee approval was obtained for this study, and written informed consent was obtained from all participants. The purpose was to prospectively evaluate the feasibility of breath-hold multiecho in-and out-ofphase magnetic resonance (MR) imaging for simultaneous lipid quantification and T2* measurement. A spoiled gradient-echo sequence with seven echo times alternately in phase and out of phase was used at 3.0 T. Imaging was performed in a lipid phantom, in five healthy volunteers (all men; mean age, 37 years), and in five obese individuals with hyperlipidemia or diabetes (four men, one woman; mean age, 53 years). A biexponential curve-fitting model was used to derive the relative signal contributions from fat and water, and these results were compared with results of liver proton MR spectroscopy, the reference standard. There was a significant correlation between multiecho and spectroscopic measurements of hepatic lipid concentration (r 2 ϭ 0.99, P Ͻ .001). In vivo, the T2* of water was consistently longer than that of fat and reliably enabled the signal components to be correctly assigned. In the lipid phantom, the multiecho method could be used to determine the fat-to-water ratio and the T2* values of fat and water throughout the entire range of fat concentrations. Multiecho imaging shows promise as a method of simultaneous fat and T2* quantification.

Psychopharmacology, 2011

Rationale Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are increasingly use... more Rationale Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are increasingly used for the treatment of depression in children. Limited data are however available on their effects on brain development and their efficacy remains debated. Moreover, previous experimental studies are seriously hampered in their clinical relevance. Objectives The aim of the present study was to investigate putative age-related effects of a chronic treatment with fluoxetine (5 mg/kg, either orally or i.p. for 3 weeks, 1 week washout) using conventional methods (behavioral testing and binding assay using [ 123 I]β-CIT) and a novel Magnetic Resonance Imaging (MRI) approach. Methods Behavior was assessed, as well as serotonin transporter (SERT) availability and function through ex vivo binding assays and in vivo pharmacological MRI (phMRI) with an acute fluoxetine challenge (10 mg/kg oral or 5 mg/kg i.v.) in adolescent and adult rats. Results Fluoxetine caused an increase in anxiety-like behavior in adult-, but not adolescent treated rats. On the binding assays, we observed increased SERT densities in most cortical brain regions and hypothalamus in adolescent-, but not adult-treated rats. Finally, reductions in brain activation were observed with phMRI following treatment, in both the adult-and adolescent-treated animals. Conclusion Collectively, our data indicate that the short-term effects of fluoxetine on the 5-HT system may be age-dependent. These findings could reflect structural and functional rearrangements in the developing brain that do not occur in the matured rat brain. phMRI possibly will be well suited to study this important issue in the pediatric population.

Proceedings of the National Academy of Sciences, 2012

The blood–brain barrier (BBB), a critical guardian of communication between the periphery and the... more The blood–brain barrier (BBB), a critical guardian of communication between the periphery and the brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting in the inappropriate passage of molecules and leukocytes into the brain. Here we show that the glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) is expressed in brain microvascular endothelial cells, where it regulates BBB integrity. In particular, ANXA1 −/− mice exhibit significantly increased BBB permeability as a result of disrupted interendothelial cell tight junctions, essentially related to changes in the actin cytoskeleton, which stabilizes tight and adherens junctions. This situation is reminiscent of early MS pathology, a relationship confirmed by our detection of a selective loss of ANXA1 in the plasma and cerebrovascular endothelium of patients with MS. Importantly, this loss is swiftly restored by i.v. administration of human recombinant ANXA1. Analysis in vitro c...

Journal of Materials Chemistry, 2012