Marlène Wiart

Clinical and imaging predictors of intracerebral haemorrhage in stroke patients treated with intravenous tissue plasminogen activator

Objective: To evaluate clinical, biological, and pretreatment imaging variables for predictors of tissue plasminogen activator (tPA) related intracerebral haemorrhage (ICH) in stroke patients. Methods: 48 consecutive patients with hemispheric stroke were given intravenous tPA within seven hours of symptom onset, after computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Baseline diffusion weighted (DWI) and perfusion weighted (PWI) imaging volumes, time to peak, mean transit time, regional cerebral blood flow index, and regional cerebral blood volume were evaluated. The distribution of apparent diffusion coefficient (ADC) values was determined within each DWI lesion. Results: The symptomatic ICH rate was 8.3% (four of 48); the rate for any ICH was 43.8% (21 of 48). Univariate analysis showed that age, weight, history of hyperlipidaemia, baseline NIHSS score, glucose level, red blood cell count, and lacunar state on MRI were associated with ICH. However, mean 24 hour systolic blood pressure and a hyperdense artery sign on pretreatment CT were the only independent predictors of ICH. Patients with a hyperdense artery sign had larger pretreatment PWI and DWI lesion volumes and a higher NIHSS score. Analysis of the distribution of ADC values within DWI lesions showed that a greater percentage of pixels had lower ADCs (<400×10−6 mm2/s) in patients who experienced ICH than in those who did not. Conclusion: Key clinical and biological variables, pretreatment CT signs, and MRI indices are associated with tPA related intracerebral haemorrhage.

Inflammatory Response After Ischemic Stroke A USPIO-Enhanced MRI Study in Patients

Background and Purpose— The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume. Methods— We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests. Results— The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test (P=0.39) or Spearman test (P=0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement. Conclusions— USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.

Prospective comparison of MR lung perfusion and lung scintigraphy

This study attempted to assess the accuracy and potential of lung magnetic resonance (MR) perfusion imaging compared with perfusion scintigraphy in the evaluation of patients with suspected lung perfusion defects. The technique, which uses an inversion recovery turbo‐FLASH sequence with ultra‐short TE (1.4 msec), was tested in 24 patients suspected clinically of having acute pulmonary embolism (n = 19) and in patients with severe pulmonary emphysema (n = 5). Perfusion lung scintigraphy was performed within 48 hours prior to the MRI examination in both groups of patients. The dynamic study was acquired in the coronal plane and consisted of 10 images of 6 slices (a total of 60 images per series). Gadopentetate dimeglumine (0.1 mmol/kg) was manually injected as a compact bolus during the acquisition of the first image. Three senior radiologists reviewed all unprocessed two‐dimensional coronal sections. They were blinded to clinical data and other imaging modalities. For the three observers, the average sensitivity and specificity of MR were 69% and 91%, respectively. The overall agreement between MR and scintigraphy appears to be good, with a good correlation between the two modalities (kappa = 0.63). However, the data showed variability depending on the location of the perfusion defect, with higher accuracy in the upper lobes. The agreement between MR perfusion and scintigraphy appears to be moderate in the left inferior lobe (kappa = 0.48). The data showed an overall good interobsever agreement (kappa = 0.66). MR perfusion of the lung is a promising technique in detecting lung perfusion defects. J. Magn. Reson. Imaging 1999;9:61–68

Laser-polarized 3He as a probe for dynamic regional measurements of lung perfusion and ventilation using magnetic resonance imaging

Magnetic resonance imaging (MRI) using laser‐polarized noble gases, such as 129Xe and 3He, allows unparalleled noninvasive information on gas distribution in lung airways and distal spaces. In addition to pulmonary ventilation, lung perfusion assessment is crucial for proper diagnosis of pathological conditions, such as pulmonary embolism. Magnetic resonance perfusion imaging usually can be performed using techniques based on the detection of water protons in tissues. However, lung proton imaging is extremely difficult due to the low proton density and the magnetically inhomogeneous structure of the lung parenchyma. Here we show that laser‐polarized 3He can be used as a noninvasive probe to image, in a single MRI experiment, not only the ventilation but also the perfusion state of the lungs. Blood volume maps of the lungs were generated based on the 3He signal depletion during the first pass of a superparamagnetic contrast agent bolus. The combined and simultaneous lung ventilation and perfusion assessments are demonstrated in normal rat lungs and are applied to an experimental animal model of pulmonary embolism. Magn Reson Med 44:1–4, 2000.

Hypointense transcerebral veins at T2^*-weighted MRI : A marker of hemorrhagic transformation risk in patients treated with intravenous tissue plasminogen activator

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2∗-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week (r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).

Early-Stage Investigations of Ultrasmall Superparamagnetic Iron Oxide-Induced Signal Change After Permanent Middle Cerebral Artery Occlusion in Mice

BACKGROUND AND PURPOSE MR signal changes after intravenous ultrasmall superparamagnetic iron oxide (USPIO) injection are related to inflammatory cells at the subacute stages after focal cerebral injury. However, at the early stages, the interpretation of USPIO-related MR signal alterations remains controversial. Here, we compared MR signal changes after intravenous USPIO injection with the histological iron and macrophage distribution during the first 24 hours in a rodent model of acute stroke. METHODS Multiparametric MRI at 7T and histological USPIO distribution were confronted from 6 to 24 hours after permanent middle cerebral artery occlusion in mice. Blood-brain barrier disruption was assessed using gadolinium MRI and immunoglobulin staining. Prussian blue staining was performed to depict the USPIO brain distribution. USPIO uptake by phagocytes was assessed by immunochemistry on brain tissue, peripheral blood cells, and monocyte cells derived from bone marrow culture. RESULTS After USPIO injection, 4 areas of early signal change were observed on every MRI. In all these areas, iron particles were mostly free whether detected in the vascular and cerebrospinal fluid compartments or in the interstitium. Within the first 24 hours, USPIO-loaded cells were not detected in the blood of injured mice or in cultured monocytic cells incubated with USPIO at plasmatic concentration. CONCLUSIONS These results suggest that, in this model, early reproducible USPIO-related MR signal changes are mainly caused by passive diffusion of free USPIO after blood-brain barrier leakage and by intravascular trapping rather than by peripheral phagocyte infiltration.

Characterization of hepatocellular carcinoma and colorectal liver metastasis by means of perfusion MRI.

To characterize and compare hepatocellular carcinoma and liver metastases of colorectal metastatic cancer (CMC) by means of quantitative liver perfusion MRI.

Hypointense leptomeningeal vessels at T2*-weighted MRI in acute ischemic stroke

Susceptibility-weighted sequences may improve our understanding of the pathophysiology of acute cerebral ischemia.1–4 At the acute stage of ischemic stroke, a signal loss, attributed to intravascular deoxygenation, has been identified with T2*-weighted gradient echo (GRE) MRI along the course of leptomeningeal vessels.5 We sought to detect any difference between clinical and MRI parameters according to the presence of this imaging feature. Consecutive patients with acute (<6 hours) hemispheric stroke were recruited between March 2002 and September 2003. Neurologic impairment was assessed using the NIH Stroke Scale (NIHSS) score. MRI was performed with a 1.5 T imager (Siemens Vision, Erlangen, Germany). MRI protocol included6 the following: three-dimensional time-of-flight MR angiography (MRA); T2*-weighted GRE sequence; diffusion-weighted imaging (DWI); and perfusion-weighted MRI (PWI) with an echo-planar imaging sequence, using the bolus passage of contrast agent. The abnormal visualization of leptomeningeal vessels (AVLV) was defined at baseline T2*-weighted GRE sequence as a serpiginous signal loss along the course of the juxtacortical vessels5 (figure). The …

In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages.

The inflammatory response following ischemic stroke is dominated by innate immune cells: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1) and alternatively activated (M2) macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle) were intravenously administered during the subacute stage of ischemia (D4) in a model of transient middle cerebral artery occlusion. Functional neuroscores and magnetic resonance imaging endpoints (infarct volumes, blood-brain barrier integrity, phagocytic activity assessed by iron oxide uptake) were longitudinally monitored for 2 weeks. This cell-based treatment did not significantly improve any outcome measure compared with vehicle, suggesting that this strategy is not relevant to stroke therapy.

Influence of perfusion on high‐intensity focused ultrasound prostate ablation: A first‐pass MRI study

Our aim was to evaluate the influence of regional prostate blood flow (rPBF) on high‐intensity focused ultrasound (HIFU) treatment outcome. A total of 48 patients with clinically localized prostate cancer were examined by dynamic contrast‐enhanced (DCE)‐MRI prior to HIFU therapy. A prostate‐specific antigen (PSA) nadir threshold of 0.2 ng/ml was used to define the populations of responders and nonresponders. A dedicated tracer kinetic model, namely “monoexponential plus constant” (MPC) deconvolution, was implemented to provide quantitative estimates of rPBF. The results were compared with those obtained by semiquantitative (steepest slope, mean gradient) and quantitative (Fermi deconvolution) approaches. Of the four methods studied, quantitative rPBF obtained by MPC deconvolution proved the most sensitive to the perfusion changes encountered in this study. Furthermore, blood‐flow values obtained with MPC deconvolution in the prostate and muscle (12 ± 8 and 5 ± 3 ml/min/100 g, respectively) were in good agreement with literature data. The mean pretreatment rPBF obtained with MPC deconvolution was significantly higher in nonresponders compared to responders (16 ± 9 vs. 10 ± 6 ml/min/100 g), suggesting a correlation between baseline perfusion and treatment outcome. The present work describes and validates the use of dynamic MRI to estimate rPBF in patients, which in the future may help to refine the conduct of HIFU therapy. Magn Reson Med 58:119–127, 2007.