Xavier Helluy

Publications of Xavier Helluy

• Magnetic resonance imaging (MRI) of inflamed myocardium using iron oxide nanoparticles in patients with acute myocardial infarction - Preliminary results.

  Authors: Ali Yilmaz, Sabine Rösch, Karin Klingel, Reinhard Kandolf, Xavier Helluy, Karl-Heinz Hiller, Peter M Jakob, Udo Sechtem

  International journal of cardiology. 06/2011;

  OBJECTIVES: Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardialOBJECTIVES: 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®) allows improved visualisation of the myocardial (peri-)infarct zone compared to conventional gadolinium-based necrosis/fibrosis imaging in patients with acute myocardial infarction. MATERIAL AND METHODS: The clinical study NIMINI-1 was performed as a prospective, non-randomised, non-blinded, single agent phase III clinical trial (NCT0088644). Twenty patients who had experienced either an acute ST-elevation or non-ST-elevation myocardial infarction (STEMI/NSTEMI) were included to this study. Following coronary angiography, a first baseline cardiovascular magnetic resonance (CMR) study (pre-SPIO) was performed within seven days after onset of cardiac symptoms. A second CMR study (post-SPIO) was performed either 10min, 4h, 24h or 48h after ferucarbotran administration. The CMR studies comprised cine-CMR, T2-weighted "edema" imaging, T2*-weighted cardiac imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. RESULTS: The median extent of short-axis in-plane LGE was 28% (IQR 19-31%). Following Resovist® administration the median extent of short-axis in-plane T2*-weighted hypoenhancement (suggestive of intramyocardial haemorrhage and/or SPIO accumulation) was 0% (IQR 0-9%; p=0.68 compared to pre-SPIO). A significant in-slice increase (>3%) in the extent of T2*-weighted "hypoenhancement" (post-SPIO compared to pre-SPIO) was seen in 6/16 patients (38%). However, no patient demonstrated "hypoenhancement" in T2*-weighted images following Resovist® administration that exceeded the area of LGE. CONCLUSIONS: T2/T2*-weighted MRI aiming at non-invasive myocardial macrophage imaging using the approved dose of ferucarbotran does not allow improved visualisation of the myocardial (peri-) infarct zone compared to conventional gadolinium-based necrosis/fibrosis imaging.

• Molecular magnetic resonance imaging (MRI) of inflamed myocardium using ferucarbotran in patients with acute myocardial infarction

  Authors: Ali Yilmaz, Sabine Rösch, Karin Klingel, Reinhard Kandolf, Xavier Helluy, Karl-Heinz Hiller, Peter Jakob, Udo Sechtem

  Journal of Cardiovascular Magnetic Resonance. 01/2011;

• Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia: an MRI study at 17.6 Tesla.

  Authors: Mirko Pham, Xavier Helluy, Christoph Kleinschnitz, Peter Kraft, Andreas J Bartsch, Peter Jakob, Bernhard Nieswandt, Martin Bendszus, Guido Stoll

  PloS one. 01/2011; 6(4):e18386.

  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 byInhibition 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 (N = 10) and mice treated with 100 µg Fab-fragments of the GPIb blocking antibody p0p/B 1 h after tMCAO (N = 10). To control for the effect of reperfusion, additional mice underwent permanent occlusion and received anti-GPIb treatment (N = 6; pMCAO) or remained without treatment (N = 3; pMCAO). MRI 2 h and 24 h after MCAO measured cerebral-blood-flow (CBF) by continuous arterial-spin labelling, the apparent-diffusion-coefficient (ADC), quantitative-T2 and T2-weighted imaging. All images were registered to a standard mouse brain MRI atlas and statistically analysed voxel-wise, and by cortico-subcortical ROI analysis. Anti-GPIb treatment led to a relative increase of postischemic CBF vs. controls in the cortical territory of the MCA (2 h: 44.2±6.9 ml/100 g/min versus 24 h: 60.5±8.4; p = 0.0012, F((1,18)) = 14.63) after tMCAO. Subcortical CBF 2 h after tMCAO was higher in anti-GPIb treated animals (45.3±5.9 vs. controls: 33.6±4.3; p = 0.04). In both regions, CBF findings were clearly related to a lower probability of infarction (Cortex/Subcortex of treated group: 35%/65% vs. controls: 95%/100%) and improved quantitative-T2 and ADC. After pMCAO, anti-GPIb treated mice developed similar infarcts preceded by severe irreversible hypoperfusion as controls after tMCAO indicating dependency of stroke protection on reperfusion. Blockade of platelet adhesion by anti-GPIb-Fab-fragments results in substantially improved CBF early during reperfusion. This finding was in exact spatial correspondence with the prevention of cerebral infarction and indicates in-vivo an increased patency of the microcirculation. Thus, progression of infarction during early ischemia and reperfusion can be mitigated by anti-platelet treatment.

• Flow-enhanced off-resonance saturation for remote detection of iron-based contrast agents.

  Authors: Philipp Krämer, Xavier Helluy, Thomas Kampf, Esra Lang, Peter M Jakob

  Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 06/2010; 63(6):1708-15.

  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 oxideA 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 saturation contrast could be observed. This contrast mechanism is highly dependent on field homogeneity and spectral selectivity of the off-resonance saturation pulses. The contrast scales directly with the pulse offset of the used saturation pulses, the flow velocity in the vessel, and the duration of the off-resonance saturation module prior to the imaging sequence. This technique has the potential to detect iron-loaded atherosclerotic plaques in future in vivo applications.

• Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI.

  Authors: Mirko Pham, Xavier Helluy, Stefan Braeuninger, Peter Jakob, Guido Stoll, Christoph Kleinschnitz, Martin Bendszus

  Experimental & translational stroke medicine. 03/2010; 2:6.

  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 influenceTransgenic 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 cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI).C57Bl/6 and Sv/129 mice underwent 60 min of tMCAO and were analyzed by MRI 2 h and 24 h afterwards. Structural and functional images were registered to a standard anatomical template. Probability maps of infarction were rendered by automated segmentation from quantitative T2-relaxometric images. Whole-brain segmentation of infarction was accomplished manually on high-resolution T2-weighted (T2-w) RARE images. Cerebral perfusion (cerebral blood flow, CBF) was measured quantitatively by modified continuous arterial-spin-labeling (CASL) and apparent diffusion coefficients (ADC) by spin-echo diffusion-weighted imaging (DWI).Probabilities of cortical (95.1% +/- 3.1 vs. 92.1% +/- 2.5; p > 0.05) and subcortical (100% vs. 100%; p > 0.05) infarctions at 24 h were similar in both groups as was the whole-brain volumetric extent of cerebral infarction. In addition, CBF and ADC values did not differ between C57Bl/6 and Sv/129 mice at any time point or region of interest.The C57Bl/6 and Sv/129 genetic background is no major confounding factor of infarct size and cerebral perfusion in the tMCAO model.