Marzena Wylezinska

Imperial College London, Londinium, England, United Kingdom

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Publications (52)218.8 Total impact

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    ABSTRACT: Myo-inositol (Myo-ins) is a marker of neuroglial cells, being present in the astrocytes of brain tissue, but also functions as an osmolyte. Numbers of astrocytes are known to increase following injury to the brain. Growth-restricted fetuses are at increased risk of later neurodevelopmental impairments even in the absence of overt lesions and despite preserved/increased cerebral blood flow. This study aims to investigate brain Myo-ins metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution using magnetic resonance spectroscopy (MRS) at a short echo time. Biometry and Doppler assessment of blood flow was assessed using ultrasound in 28 fetuses with IUGR and 47 appropriately grown control subjects. MRI was used to exclude overt brain injury. Proton magnetic resonance spectroscopy of the fetal brain was then performed at an echo time of 42ms to examine the Myo-ins:Choline (Cho), Myo-ins:Creatine (Cr) and Cho:Cr ratios. No alterations in brain Myo-ins:Cho, Myo-ins:Cr or Cho:Cr ratios were detected between appropriately grown and growth restricted fetuses. IUGR is not associated with a measureable difference in brain myo-inositol ratios. This may be due to the protective effects of preserved cerebral blood flow in growth restriction and comparable astrocyte numbers when compared to controls.
    European journal of obstetrics, gynecology, and reproductive biology 06/2013; 170(1). DOI:10.1016/j.ejogrb.2013.05.006
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    ABSTRACT: Mice are widely used to investigate atherogenesis, which is known to be influenced by stresses related to blood flow. However, numerical characterization of the haemodynamic environment in the commonly studied aortic arch has hitherto been based on idealizations of inflow into the aorta. Our purpose in this work was to numerically characterize the haemodynamic environment in the mouse aortic arch using measured inflow velocities, and to relate the resulting shear stress patterns to known locations of high- and low-lesion prevalence. Blood flow velocities were measured in the aortic root of C57/BL6 mice using phase-contrast MRI. Arterial geometries were obtained by micro-CT of corrosion casts. These data were used to compute blood flow and wall shear stress (WSS) patterns in the arch. WSS profiles computed using realistic and idealized aortic root velocities differed significantly. An unexpected finding was that average WSS in the high-lesion-probability region on the inner wall was actually higher than the WSS in the low-probability region on the outer wall. Future studies of mouse aortic arch haemodynamics should avoid the use of idealized inflow velocity profiles. Lesion formation does not seem to uniquely associate with low or oscillating WSS in this segment, suggesting that other factors may also play a role in lesion localization.
    Journal of The Royal Society Interface 07/2012; 9(76):2834-44. DOI:10.1098/rsif.2012.0295
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    ABSTRACT: Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, (11)C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers. Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment. PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls (P = 0.03). The caudate and thalamic binding potential were more significantly increased in six patients with genotype 1 infection (P = 0.007) and positively correlated with viraemia (r = 0.77, P = 0.005). Basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls (P = 0.0004 and P = 0.01, respectively). Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C. This provides further in vivo evidence for a neurotropic role for HCV.
    Journal of Viral Hepatitis 02/2012; 19(2):e89-96. DOI:10.1111/j.1365-2893.2011.01510.x
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    ABSTRACT: Magnetic Resonance Imaging (MRI) has become an established technique in fetal medicine, providing complementary information to ultrasound in studies of the brain. MRI can provide detailed structural information irrespective of the position of the fetal head or maternal habitus. Proton Magnetic Resonance Spectroscopy ((1)HMRS) is based on the same physical principles as MRI but data are collected as a spectrum, allowing the biochemical and metabolic status of in vivo tissue to be studied in a non-invasive manner. (1)HMRS has been used to assess metabolic function in the neonatal brain but fetal studies have been limited, primarily due to fetal motion. This review will assess the technique and findings from fetal studies to date.
    European journal of obstetrics, gynecology, and reproductive biology 09/2011; 158(1):3-8. DOI:10.1016/j.ejogrb.2010.03.003
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    ABSTRACT: With the growing prevalence of psychotropic drug prescriptions among children and adolescents, the need for studies on lasting effects of drug exposure on the developing brain rises. Fluoxetine is the only selective serotonin reuptake inhibitor (SSRI) officially registered to treat major depressive disorder in children. Although various (pre)clinical studies have assessed the (long-term) effects of fluoxetine exposure in the perinatal period and in adulthood, limited data is available on its effects on the developing brain later in life, i.e. during adolescence. The present study aimed at investigating the effects of age following chronic SSRI treatment on the central serotonin (5-HT) system. To this end, pharmacological MRI (phMRI) was performed in chronic fluoxetine-treated (5 mg/kg, oral gavage for 3 weeks) juvenile (PND25) and adult rats (PND65) after a 1-week washout period, using an acute fluoxetine challenge (5 mg/kg, i.v.) to trigger the 5-HT system. We observed a diminished brain response to the acute challenge in adult treated animals when compared to control animals, whereas this response was increased in juvenile treated rats. As a result, a significant age by treatment interaction effect was seen in several (subcortical) 5-HT related brain regions. An opposite effect of chronic fluoxetine treatment was seen in the developing brain compared to that in matured brain, as assessed non-invasively using phMRI. These findings most likely reflect neuronal imprinting effects of juvenile SSRI treatment and may underlie emotional disturbances seen in animals and children treated with this drug. Also, our findings suggest that phMRI might be ideally suited to study this important issue in the pediatric population.
    NeuroImage 08/2011; 59(1):218-26. DOI:10.1016/j.neuroimage.2011.07.082
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    ABSTRACT: The purpose of this study was to investigate alterations in brain metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution of blood flow. Biometry and Doppler assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and cerebral redistribution and in 41 appropriately grown control subjects. Proton magnetic resonance spectroscopy of the fetal brain was then performed to determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr. Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and creatine peaks were identified in all these spectra; lactate was present in 5 IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were significantly lower in IUGR fetuses with cerebral redistribution. Cerebral redistribution is associated with altered brain metabolism that is evidenced by a reduction in NAA:Cho and NAA:Cr ratios.
    American journal of obstetrics and gynecology 06/2011; 205(5):483.e1-8. DOI:10.1016/j.ajog.2011.06.032
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    ABSTRACT: With the increasing availability of human MR scanners at various field strengths, the optimal field strength for in vivo clinical MR studies of the liver has become a focus of attention. Comparison between results at 3.0 and 1.5 T is of particular clinical interest, especially for multicentre studies. For MRS studies, higher field strengths should be advantageous, because improved sensitivity and chemical shift dispersion are expected. We report a comparison between single-voxel hepatic proton-decoupled (31)P MRS performed at 1.5 and 3.0 T in the same subjects using similar methodologies. Twelve healthy volunteers and 15 patients with chronic liver disease were studied. Improved spectral resolution was achieved using proton decoupling, and there was an improvement (21%) in the signal-to-noise ratio (SNR) of the phosphomonoester (PME) resonance at 3.0 T relative to 1.5 T. There was no significant change in nuclear Overhauser effects for PME or phosphodiesters (PDEs) between the two field strengths. The T(1) value of PDE was significantly longer at 3 T, although there was no significant change in the T(1) value of PME. There was no significant difference in the mean PME/PDE ratios for either the control or patient groups at both 1.5 and 3.0 T, but there was a small positive mean difference in PME/PDE at 3.0 T on pairwise testing between field strengths (+ 0.05, p < 0.01). There were significant correlations between PME/PDE values at the two magnetic field strengths (r = 0.806, p < 0.001). The underlying broad resonance was reduced at 3.0 T relative to 1.5 T, related to line broadening of the phospholipid bilayer signal. In conclusion, there was an improvement in hepatic (31)P MR signal quality at 3.0 T relative to 1.5 T. Broadly similar hepatic (31)P MR parameters were obtained at 1.5 and 3.0 T. The modest difference noted in the PME/PDE ratio between field strengths for patients with chronic liver disease should inform multicentre study design involving these field strengths.
    NMR in Biomedicine 04/2011; 24(3):231-7. DOI:10.1002/nbm.1578
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    ABSTRACT: INTRODUCTION Atherosclerotic lesions have a highly non-uniform distribution in regions of arterial branching and curvature, consistent with hemodynamic factors, in particular wall shear stress (WSS), controlling their development. The widespread and increasing use of the mouse as a model for studying atherosclerosis has encouraged investigation of the hemodynamics of the mouse aortic arch [1-3], in which previous studies have revealed areas of high and low lesion prevalence and variation in the expression of pro-atherogenic molecules [4]. Our previous computational simulations [1-2] did not produce distributions of WSS that explain the pattern of lesions. We are currently investigating whether incorporation of more realistic aortic root velocity measurements, obtained using phase-contrast magnetic resonance imaging (PC-MRI), into these simulations can improve the correlation with disease. Here we present velocities obtained by PC-MRI and preliminary simulations employing the data. MATERIALS AND METHODS A 9.4T DirectDrive Varian MRI system (Oxford Instrument, UK) with 100G/cm gradients and a Rapid bird-cage RF coil was used for in-vivo quantification of aortic root blood flow in mice. Ten C57/BL6 male mice aged 7.5 ± 0.5 weeks and weighing 22.5 ± 2.5 g were anesthetized using 1.5% isoflurane in 1.5 L/min O 2 ; body temperature was maintained at 36.7 ± 0.2 o C using a hot air system (SA Instruments, USA). Cardiac-and respiratory-gated phase-contrast PC-MR sequences were used to obtain temporally-and spatially-resolved blood flow velocity components, measured during systole at intervals of 6 msec over 50 msec. The onset of systole was defined as 4 µs after the peak of the R wave. The average respiratory rate during acquisition was 32.8 ± 15 breaths/min and the average heart rate was 525 ± 62 bpm. A velocity encoding (V enc) value of 140 cm/sec was used for through-plane velocities, while for in-plane velocities V enc was varied between 30 and 50 cm/sec. The imaging plane at the root of the aortic arch was selected from high-resolution anatomical coronal images (Fig. 1). The in-plane image resolution was 0.117 mm and the slice thickness was 1 mm. After heparinization (500 IU) via the tail vein, mice were sacrificed and corrosion casts of the arterial system were prepared by injection of methyl methacrylate resin (Batson's No 17) at 100 mmHg. The tissue was dissolved in potassium hydroxide and the cast imaged with an isotropic spatial resolution of 11-13 µm using a Metris micro-CT scanner (X-Tek HMX ST 225) at 80 kV and 140-190 µA. Images of the aortic arch were segmented in Amira (Visage Imaging, San Diego, CA). The VMTK (open-source, vmtk.org) and ICEM CFD (ANSYS, Canonsburg, PA) packages were used for surface smoothing, surface triangulation and tetrahedral mesh generation, before numerically solving the steady and unsteady Navier-Stokes equations using a validated finite element code [5]. Newtonian blood rheology and rigid arterial walls were assumed.
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    ABSTRACT: Hepatic steatosis is an important factor in pathogenesis, progression and response to treatment in hepatitis C. We aimed to investigate differences in hepatic lipid composition in liver biopsies from patients with chronic hepatitis C using proton magnetic resonance spectroscopy ((1)H MRS) and to translate these findings to the in vivo clinical setting. Two cohorts of patients with histologically defined chronic hepatitis C were studied. High-resolution MR spectra were obtained from 47 liver biopsy samples. These data were used to derive biologically relevant prior knowledge for the assignment and interpretation of lower-resolution in vivo hepatic MRS data acquired at 1.5T from a second cohort of 59 patients. MRS data were obtained both in vitro and in vivo from a subset of 11 patients. Multivariate factor analysis demonstrated characteristic MR spectral differences by fibrosis stage and genotype. Total lipid increased with fibrosis stage (r=0.43, p=0.003) and was higher in genotype 3 compared to genotype 1 (p=0.03), while lipid polyunsaturation decreased with increasing fibrosis stage (r=-0.55, p<0.0005) and, independently, with increasing steatosis. Non-invasive assessment using in vivo hepatic (1)H MRS corroborated in vitro findings, but the signal-to-noise ratio was insufficient for reliable assessment of lipid polyunsaturation in vivo. Hepatic lipid composition was analysed using MRS in patients with chronic hepatitis C in vitro and in vivo, demonstrating significant differences in indices by disease severity. High-resolution data informed the analysis and interpretation of in vivo spectra, but further improvements in spectral quality in vivo are required.
    Journal of Hepatology 10/2009; 52(1):16-24. DOI:10.1016/j.jhep.2009.10.006
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    ABSTRACT: Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.
    Journal of Viral Hepatitis 09/2009; 17(6):419-26. DOI:10.1111/j.1365-2893.2009.01198.x
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    ABSTRACT: Continuous theta burst stimulation (cTBS) is a novel transcranial stimulation technique that causes significant inhibition of synaptic transmission for <or=1 h when applied over the primary motor cortex (M1) in humans. Here we use magnetic resonance spectroscopy to define mechanisms mediating this inhibition by noninvasively measuring local changes in the cortical concentrations of gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx). cTBS to the left M1 led to an increase in GABA compared with stimulation at a control site without significant change in Glx. This direct evidence for increased GABAergic interneuronal activity is framed in terms of a new hypothesis regarding mechanisms underlying cTBS.
    Journal of Neurophysiology 05/2009; 101(6):2872-7. DOI:10.1152/jn.91060.2008
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    ABSTRACT: Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 05/2009; 29(16):5202-6. DOI:10.1523/JNEUROSCI.4432-08.2009
  • Journal of Hepatology 04/2009; 50. DOI:10.1016/S0168-8278(09)60402-5
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    ABSTRACT: Studies using proton magnetic resonance spectroscopy (1H-MRS) indicate that unmedicated, acutely depressed patients have decreased levels of gamma-aminobutyric acid (GABA) in the occipital cortex. The aim of this study was to use 1H-MRS to determine if changes in occipital and frontal cortical GABA levels were present in patients with a history of depression who had recovered and were no longer taking medication. We used 1H-MRS to measure levels of GABA in both occipital cortex and anterior cingulate cortex/prefrontal cortex in medication-free, fully recovered subjects with a history of recurrent unipolar depression. Levels of GABA in both occipital and anterior cingulate cortex were significantly lower in recovered depressed subjects than healthy controls. Our data provide preliminary evidence that a history of recurrent depression is associated with decreased GABA levels in anterior cingulate cortex and occipital cortex. These changes could represent part of the neurobiological vulnerability to recurrent depressive episodes.
    The International Journal of Neuropsychopharmacology 04/2008; 11(2):255-60. DOI:10.1017/S1461145707007924
  • Journal of Hepatology 01/2008; 48. DOI:10.1016/S0168-8278(08)60738-2
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    ABSTRACT: Diffusion MRI and magnetic resonance spectroscopic measurements of selectively neuronally localised N-acetylaspartate (NAA) both have been used widely to assess white matter integrity and axonal loss. We have tested directly the relationship between changes in diffusion MRI parameters and NAA concentrations in the corpus callosum (CC) in an in vivo study of patients with MS. Fifteen MS patients (median EDSS 2.5, range 1-4) were studied with T(1) anatomical, T(2)-weighted, and diffusion-sensitised MRI and PRESS single-voxel MRS. A recently described method, tract-based spatial statistics (TBSS) [Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E. et al., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505] also was used to perform exploratory voxelwise whole-brain analysis of white matter diffusion fractional anisotropy (FA). We found a strong correlation between callosal size and both mean FA (r=0.68, p<0.005) (related specifically to changes in the radial tensor component) and mean inter-hemispheric motor tract connectivity probability (r=0.74, p<0.001). TBSS confirmed that the diffusion anisotropies of white matter voxels specifically within the callosum were correlated with the callosal size. Individual patient global T(2) lesion volumes were correlated with both the probability of callosal connectivity (r=-0.69, p<0.005) and fractional anisotropy across the callosum (r=-0.76, p<0.001). However, absolute concentrations of NAA from the voxel showed no correlation with callosal cross-sectional area, mean connectivity or fractional anisotropy within the callosal pathway. We conclude that diffusion MRI shows changes consistent with sensitivity to axonal loss, but that relative NAA changes are not necessarily related directly to this. Axonal metabolic function, independent of structural integrity, may be a major determinant of NAA measures in MS.
    NeuroImage 05/2007; 36(1):19-27. DOI:10.1016/j.neuroimage.2007.02.036
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    ABSTRACT: Studies using proton magnetic resonance spectroscopy (MRS) have indicated that unmedicated, acutely depressed patients have decreased levels of gamma-aminobutyric acid (GABA) in occipital cortex. Cortical levels of glutamate (Glu) may be increased, although these data are less consistent. The aim of this study was to use MRS to determine whether changes in GABA and Glu levels were present in patients with mood disorders who had recovered and were no longer taking medication. An [1H]-MRS was used to measure levels of GABA, of the combined concentration of Glu and glutamine (Gln), and of N-acetylaspartate (NAA) in occipital cortex in medication-free, fully recovered subjects with a history of recurrent unipolar depression (n = 15), bipolar disorder (n = 16), and a group of healthy controls (n = 18). Occipital levels of GABA and NAA were significantly lower in recovered depressed and bipolar subjects than in healthy controls, whereas Glu +Gln concentrations were higher. Our data suggest that recovered unmedicated subjects with a history of mood disorder have changes in cortical concentrations of GABA, NAA, and Glu +Gln. These biochemical abnormalities may be markers of a trait vulnerability to mood disorder, rather than neurochemical correlates of an abnormal mood state.
    Biological Psychiatry 04/2007; 61(6):806-12. DOI:10.1016/j.biopsych.2006.08.048
  • European Neuropsychopharmacology 03/2007; 17. DOI:10.1016/S0924-977X(07)70090-1
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    Gut 12/2006; 55(11):1670; author reply 1670.
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    Psychopharmacology 08/2006; 187(1):131-2. DOI:10.1007/s00213-006-0407-2

Publication Stats

2k Citations
218.80 Total Impact Points

Institutions

  • 2006–2013
    • Imperial College London
      • Department of Imaging Sciences
      Londinium, England, United Kingdom
  • 2006–2008
    • Oxford University Hospitals NHS Trust
      • Department of Clinical Neurology
      Oxford, England, United Kingdom
  • 2003–2007
    • University of Oxford
      • Department of Psychiatry
      Oxford, ENG, United Kingdom
  • 1994–2003
    • University College London Hospitals NHS Foundation Trust
      • Department of Medical Physics
      Londinium, England, United Kingdom
  • 1994–1996
    • University College London
      • • Division of Medicine
      • • Department of Medical Physics and Bioengineering
      London, ENG, United Kingdom